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Sample records for crossing over genetic

  1. Linkage of genetics and ethics: more crossing over is needed.

    PubMed

    Lissemore, James L

    2005-07-01

    Since the development of recombinant DNA technology in the mid 1970s, there has been increasing interest in the ethical, legal, and social implications of genetics and related fields. The web sites of five different organizations (government, academic, and independent not-for-profit) that deal explicitly with genetics and ethics are reviewed here. Some of the sites cover genetics and other issues in bioethics while others cover human genetics exclusively. The target audiences for the sites include medical and scientific professionals, students, and the general public. Among the issues examined are genetic testing, genetic discrimination in employment and health insurance, genetically modified foods, stem cells and DNA patenting. Resources for those interested in legal issues are particularly well-represented on these sites.

  2. Genetic Background, Maternal Age, and Interaction Effects Mediate Rates of Crossing Over in Drosophila melanogaster Females.

    PubMed

    Hunter, Chad M; Robinson, Matthew C; Aylor, David L; Singh, Nadia D

    2016-05-03

    Meiotic recombination is a genetic process that is critical for proper chromosome segregation in many organisms. Despite being fundamental for organismal fitness, rates of crossing over vary greatly between taxa. Both genetic and environmental factors contribute to phenotypic variation in crossover frequency, as do genotype-environment interactions. Here, we test the hypothesis that maternal age influences rates of crossing over in a genotypic-specific manner. Using classical genetic techniques, we estimated rates of crossing over for individual Drosophila melanogaster females from five strains over their lifetime from a single mating event. We find that both age and genetic background significantly contribute to observed variation in recombination frequency, as do genotype-age interactions. We further find differences in the effect of age on recombination frequency in the two genomic regions surveyed. Our results highlight the complexity of recombination rate variation and reveal a new role of genotype by maternal age interactions in mediating recombination rate.

  3. DNA double-strand break repair: Genetic determinants of flanking crossing-over

    SciTech Connect

    Kusano, Kohji; Sunohara, Yukari; Kobayashi, Ichizo; Takahashi, Noriko; Yoshikura, Hiroshi )

    1994-02-01

    Whether or not homologous interaction of two DNA molecules results in crossing-over of the flanking sequences is an important decision in view of genome organization. Several homologous recombination models, including the double-strand break repair models, explain this decision as choice between two alternative modes of resolution of Holliday-type intermediates. The authors have demonstrated that a double-strand gap can be repaired through gene conversion copying a homologous duplex, as predicted by the double-strand break repair models, in the RecE pathway of Escherichia coli. This gap repair is often accompanied by crossing-over of the flanking sequences. Mutations in ruvC and recG, whose products interact with Holliday structures in vitro, do not block double-strand gap repair or its association with flanking crossing-over. However, two mutations in the recJ gene, which encodes a single-strand 5[prime][yields]3[prime] exonuclease, severely decrease association of flanking crossing-over. Two mutations in the recQ gene, which encodes a helicase, moderately decrease association of flanking crossing-over by themselves and suppress the severe effect of a recJ mutation. Similar relationships of recJ and recQ mutations are observed in cell survival after ultraviolet light irradiation, [gamma]-ray irradiation, and H[sub 2]O[sub 2] treatment. The authors discuss how cooperation of the recQ gene product and the recJ gene product brings about double-strand break repair accompanied by flanking crossing-over. They also discuss how this reaction is related to repair of chromosome damages.

  4. [Cross-over studies].

    PubMed

    Bonten, Tobias N; Siegerink, Bob; van der Bom, Johanna G

    2013-01-01

    Randomized, parallel group clinical trials often require large groups of patients; this is expensive and takes time. A randomized cross-over trial can be an efficient and more affordable alternative. A cross-over design can be used to study chronic disorders in which treatments have temporary effects. Participants receive all treatments in consecutive periods and outcomes are measured after every period. In general, only a quarter of the total group size is needed for cross-over studies compared with parallel group studies. Results can be affected by period-effects and carry-over-effects, which can be prevented through randomization and a wash-out period of sufficient length. The dropping-out of participants has more negative consequences for cross-over studies than for parallel group studies.

  5. A novel approach to genetic and environmental analysis of cross-lagged associations over time: the cross-lagged relationship between self-perceived abilities and school achievement is mediated by genes as well as the environment.

    PubMed

    Luo, Yu L L; Haworth, Claire M A; Plomin, Robert

    2010-10-01

    Using longitudinal cross-lagged analysis to infer causal directions of reciprocal effects is one of the most important tools in the developmental armamentarium. The strength of these analyses can be enhanced by analyzing the genetic and environmental aetiology underlying cross-lagged relationships, for which we present a novel approach here. Our approach is based on standard Cholesky decomposition. Standardized path coefficients are employed to assess genetic and environmental contributions to cross-lagged associations. We indicate how our model differs importantly from another approach that does not in fact analyze genetic and environmental contributions to cross-lagged associations. As an illustration, we apply our approach to the analysis of the cross-lagged relationships between self-perceived abilities and school achievement from age 9 to age 12. Self-perceived abilities of 3852 pairs of twins from the UK Twins Early Development Study were assessed using a self-report scale. School achievement was assessed by teachers based on UK National Curriculum criteria. The key cross-lagged association between self-perceived abilities at age 9 and school achievement at age 12 was mediated by genetic influences (28%) as well as shared (55%) and non-shared (16%) environment. The reverse cross-lagged association from school achievement at 9 to self-perceived abilities at 12 was primarily genetically mediated (73%). Unlike the approach to cross-lagged genetic analysis used in recent research, our approach assesses genetic and environmental contributions to cross-lagged associations per se. We discuss implications of finding that genetic factors contribute to the cross-lag between self-perceived abilities at age 9 and school achievement at age 12.

  6. Bridge over Troubled Water: Guidance Crosses

    ERIC Educational Resources Information Center

    Amundson, Norm

    2008-01-01

    This article is based on a keynote presentation at an international conference where the focus was cross-over career guidance. Simon and Garfunkel's popular song, "Bridge over troubled water", was used as a metaphor for exploring the cross-over theme. Some of the concepts under consideration included the working alliance, the importance of a…

  7. Cedarwood: cross-over pressure research

    USDA-ARS?s Scientific Manuscript database

    A series of experiments were conducted to determine the cross-over pressure for cedarwood oil in carbon dioxide. A closed stirrer reactor with an in-line loop connected to the injector of a GC was used to measure the concentration of cedarwood oil in the carbon dioxide. Both neat cedarwood oil as ...

  8. Transreplication and crossing over in Sordaria fimicola.

    PubMed

    KITANI, Y; OLIVE, L S; EL-ANI, A S

    1961-09-08

    A study of the segregation of markers closely linked to the gray ascospore color locus in Sordaria fimicola reveals that there is a high incidence of crossing over very near the locus when it transreplicates, which is much more pronounced in 5:3 than in 6:2 asci. Also, a single 7:1 and several aberrant 4:4 asci are described. At a different spore color locus, transreplication yields only 6:2 ratios, while other spore color loci fail to transreplicate altogether

  9. French Crossings: II. Laughing Over Boundaries.

    PubMed

    Jones, Colin

    Under the generic title, 'French Crossings', this Presidential Address explores the history of laughter in French society, and humour's potential for trangressing boundaries. It focuses on the irreverent and almost entirely unknown book of comic drawings entitled Livre de caricatures tant Bonnes que mauvaises (Book of Caricatures, both Good and Bad), that was composed between the 1740s and the mid-1770s by the luxury Parisian embroiderer and designer, Charles-Germain de Saint-Aubin, and his friends and family. The bawdy laughter that the book seems intended to provoke gave it its nickname of the Livre de culs (Book of Arses). Yet despite the scatological character of many of the drawings, the humour often conjoined lower body functions with rather cerebral and erudite wit. The laughter provoked unsparingly targeted and exposed to ridicule the social elite, cultural celebrities and political leaders of Ancien Regime France. This made it a dangerous object, which was kept strictly secret. Was this humour somehow pre- or proto-Revolutionary? In fact, the work is so embedded in the culture of the Ancien Regime that 1789 was one boundary that the work signally fails to cross.

  10. French Crossings: II. Laughing Over Boundaries

    PubMed Central

    Jones, Colin

    2016-01-01

    Under the generic title, ‘French Crossings’, this Presidential Address explores the history of laughter in French society, and humour’s potential for trangressing boundaries. It focuses on the irreverent and almost entirely unknown book of comic drawings entitled Livre de caricatures tant Bonnes que mauvaises (Book of Caricatures, both Good and Bad), that was composed between the 1740s and the mid-1770s by the luxury Parisian embroiderer and designer, Charles-Germain de Saint-Aubin, and his friends and family. The bawdy laughter that the book seems intended to provoke gave it its nickname of the Livre de culs (Book of Arses). Yet despite the scatological character of many of the drawings, the humour often conjoined lower body functions with rather cerebral and erudite wit. The laughter provoked unsparingly targeted and exposed to ridicule the social elite, cultural celebrities and political leaders of Ancien Regime France. This made it a dangerous object, which was kept strictly secret. Was this humour somehow pre- or proto-Revolutionary? In fact, the work is so embedded in the culture of the Ancien Regime that 1789 was one boundary that the work signally fails to cross. PMID:27630375

  11. The Relationship between Chiasmata and Crossing over in TRITICUM AESTIVUM

    PubMed Central

    Fu, T. K.; Sears, E. R.

    1973-01-01

    Telocentrics for the β arm of chromosome 4A and the long arm of 6B were used as cytological markers for the determination of chiasma frequency. In concomitant studies of recombination, terminal segments of rye and T. umbellulatum chromatin carrying Hp (Hairy peduncle) and Lr9 (Leaf-rust resistance), respectively, marked 4A and 6B. Two temperatures, 21° and 32°, were used for both the 4A and 6B experiments.—Only one chiasma was observed in each heteromorphic bivalent. Because there was a substantial reduction in pairing between diakinesis and metaphase I, all determinations of chiasma frequency were made at diakinesis. In the 21° experiments, agreement was good between genetic recombination and cytological prediction on the basis of the partial chiasmatypy hypothesis that each chiasma represents a crossover. At 32° both chiasma frequency and crossing over, but particularly the latter, were strongly reduced. The fewer crossovers than expected are explained in part by stickiness of chromosomes at the high temperature, sometimes resulting in adjacent chromosomes being wrongly scored as having a chiasma, and in part by premetaphase disjunction of some recombined bivalents and subsequent independent behavior of the two resulting univalents.—Male transmission of the 4A telocentric from the heteromorphic bivalent was unusually high: 51% at 21° and 31% at 32°. PMID:17248642

  12. DNA repair and crossing over favor similar chromosome regions as discovered in radiation hybrid of Triticum

    USDA-ARS?s Scientific Manuscript database

    The uneven distribution of recombination across the length of chromosomes results in inaccurate estimates of genetic to physical distances. In wheat (Triticum aestivum L.) chromosome 3B, it has been estimated that 90% of the cross over occurs in distal sub-telomeric regions representing 40% of the...

  13. 4. END OF RAILWAY SUPERSTRUCTURE, WHERE IT CROSSES NORTH OVER ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. END OF RAILWAY SUPERSTRUCTURE, WHERE IT CROSSES NORTH OVER MARKET STREET AND DESCENDS TO MEET SUBWAY AT 44TH STREET. - Market Street Elevated Railway, Market Street between Sixty-ninth & Forty-sixth Streets, Philadelphia, Philadelphia County, PA

  14. View of Steel Flume Bridge #2 crossing over wash. Looking ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View of Steel Flume Bridge #2 crossing over wash. Looking downstream, southwest - Childs-Irving Hydroelectric Project, Childs System, Flume Bridge No. 2, Forest Service Road 708/502, Camp Verde, Yavapai County, AZ

  15. View of Steel Flume Bridge #3 crossing over Sally May ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View of Steel Flume Bridge #3 crossing over Sally May Wash. Looking northwest - Childs-Irving Hydroelectric Project, Childs System, Flume Bridge No. 3, Forest Service Road 708/502, Camp Verde, Yavapai County, AZ

  16. Genetic crossing vs cloning by computer simulation

    SciTech Connect

    Dasgupta, S.

    1997-06-01

    We perform Monte Carlo simulation using Penna`s bit string model, and compare the process of asexual reproduction by cloning with that by genetic crossover. We find them to be comparable as regards survival of a species, and also if a natural disaster is simulated.

  17. Genetic Crossing vs Cloning by Computer Simulation

    NASA Astrophysics Data System (ADS)

    Dasgupta, Subinay

    We perform Monte Carlo simulation using Penna's bit string model, and compare the process of asexual reproduction by cloning with that by genetic crossover. We find them to be comparable as regards survival of a species, and also if a natural disaster is simulated.

  18. Genetic Diversity of Natural Crossing in Cotton

    USDA-ARS?s Scientific Manuscript database

    We have shown previously genetic diversity in mature cotton pollen sensitivity to low humidity. This study investigated the impact of pollen sensitivity to low humidity on the amount of outcrossing to neighboring plants. We utilized “red” and “green” pigmented cotton, in addition to gossypol glan...

  19. Power to detect clinically relevant carry-over in a series of cross-over studies.

    PubMed

    Putt, Mary E

    2006-08-15

    The potential for carry-over effects is an important consideration in the design of any cross-over study, and can cause an investigator to abandon the design altogether. In cross-over studies, carry-over is the lingering effect of a treatment into the subsequent period. Carry-over effects are differences in the extent of the carry-over between the treatments under consideration. It is well known that the test for carry-over effects in individual studies has low power. Empirical evidence of carry-over effects, or the absence of carry-over effects, could be useful for investigators considering the design. Here we develop methods for expressing the power to detect carry-over as a function of the power to detect a clinically relevant treatment effect. Our results suggest that for two-treatment, two-period cross-over studies the power to detect clinically relevant carry-over effects is often less than 15 per cent, and the number of studies needed to differentiate this effect from the type I error rate of 10 per cent is prohibitive. For the three-treatment three-period cross-over design, the power to detect carry-over effects was larger than for the two-period study, but still approached the type I error rate in a number of cases. Unequivocal conclusions about the absence of carry-over effects based on collections of hypothesis tests appear unlikely. Similar findings are presented for bioequivalence studies. For bioequivalence studies, small carry-over effects (e.g. 12.5 per cent of the treatment effect) can seriously inflate the type I error rate, particularly when the power to detect equivalence is high.

  20. Plasmodium falciparum genetic crosses in a humanized mouse model

    PubMed Central

    Vaughan, Ashley M.; Pinapati, Richard S.; Cheeseman, Ian H.; Camargo, Nelly; Fishbaugher, Matthew; Checkley, Lisa A.; Nair, Shalini; Hutyra, Carolyn A.; Nosten, François H.; Anderson, Timothy J. C.; Ferdig, Michael T.; Kappe, Stefan H. I.

    2015-01-01

    Genetic crosses of phenotypically distinct strains of the human malaria parasite Plasmodium falciparum are a powerful tool for identifying genes controlling drug resistance and other key phenotypes. Previous studies relied on the isolation of recombinant parasites from splenectomized chimpanzees, a research avenue that is no longer available. Here, we demonstrate that human-liver chimeric mice support recovery of recombinant progeny for the identification of genetic determinants of parasite traits and adaptations. PMID:26030447

  1. A genetic algorithm to reduce stream channel cross section data

    USGS Publications Warehouse

    Berenbrock, C.

    2006-01-01

    A genetic algorithm (GA) was used to reduce cross section data for a hypothetical example consisting of 41 data points and for 10 cross sections on the Kootenai River. The number of data points for the Kootenai River cross sections ranged from about 500 to more than 2,500. The GA was applied to reduce the number of data points to a manageable dataset because most models and other software require fewer than 100 data points for management, manipulation, and analysis. Results indicated that the program successfully reduced the data. Fitness values from the genetic algorithm were lower (better) than those in a previous study that used standard procedures of reducing the cross section data. On average, fitnesses were 29 percent lower, and several were about 50 percent lower. Results also showed that cross sections produced by the genetic algorithm were representative of the original section and that near-optimal results could be obtained in a single run, even for large problems. Other data also can be reduced in a method similar to that for cross section data.

  2. Before crossing over: the advantages of eukaryotic sex in genomes lacking chiasmatic recombination.

    PubMed

    Antezana, M A; Hudson, R R

    1997-08-01

    Non-recombining populations should suffer from four classic population genetic disadvantages: (1) they cannot reverse Muller's Ratchet, the accumulation of deleterious mutations caused by genetic drift and mutation; (2) whenever the fix a favourable mutation they lose all unlinked favourable variants; (3) they tend to lose favourable mutations that are linked to deleterious mutations; and (4) their genetic loads can be quite high when deleterious mutations have synergistic effects. It is commonly assumed that inter-chromosomal recombination (independent assortment) can counter these phenomena, but this has been studied only for the genetic load case. In contrast, many studies have shown that recombination via crossing over can counter these phenomena. Here we first show that segregation alone can strongly decelerate Muller's Ratchet in diploids, i.e. that recombination is not the only way to do so. We then show that inter-chromosomal recombination can indeed deal with phenomena (1) to (3) above very effectively if the genome consists of a moderate number of chromosomes. Therefore, if the above advantages of genetic recombination played a large role in the initial success of eukaryotic sex, the crucial moment in the origin of sex might have been the evolution of inter-chromosomal recombination, i.e. the evolution of genome segmentation, segregation, and syngamy. Crossing over might have become established as a major recombinational device only later, eliminating the disadvantages of extensively segmented genomes.

  3. Mutagenesis and interchromosomal effect on crossing-over in Drosophila

    SciTech Connect

    Chadov, B.F.; Chadova, E.V.

    1994-12-01

    The possibility of mutational consequences of interchromosomal effect on crossing-over was studied in Drosophila melanogaster females with four genotypes: (1) structurally normal (control); (2) heterozygous at In(1)Muller-5 inversion (X chromosome); (3) heterozygous at In(3LR)CxD inversion (chromosome 3); and (4) heterozygous at both inversions. The mutational effect was determined through the loss of autosome 2 and formation of arm compounds C(2L) and C(2R). In females with recombinations, the rate of mutational events did not exceed that of the control. It was concluded that interchromosomal effect on crossing-over is of a regulatory character and disturbs neither recombination itself nor chromosome pairing. Coorientation X-3 leading to the appearance of intersexes in the progeny occurred in meiosis in females with two inversions.

  4. [Genetical analysis on cross incubation of Beauveria bassiana].

    PubMed

    Wang, C; Ding, D; Wang, S; Li, Z

    2000-10-01

    Heterokaryon of Beauveria bassiana was formed during the cross incubation of two vegetative compatible strains with genetic markers of actidione resistance and 34 degrees C tolerance. The chromosome(s) or its fragment successive losses, recombination and segreation led to haploidization during the conidia formation period. After at least 4 generations of parasexual cycle, the genetic character of heterokayon could get to relative stable. Genetic marker and RAPD analysis indicated that the combinants showed the phenomenon of preferential selection of one parental type by unrandom chromosome lossing and the gene of the other parental strain was suppressed or lost completely. Different culture medium, in vivo or in vitro, and different mixture ratio of original strain spores could affect parasexual process and then the preferential selection. The results also demonstrated the heterosis effect of cross culture.

  5. Etoposide exposure during male mouse pachytene has complex effects on crossing-over and causes nondisjunction.

    PubMed

    Russell, Liane B; Hunsicker, Patricia R; Kerley, Marilyn; Pyle, April; Saxton, Arnold M

    2004-12-31

    In experiments involving different germ-cell stages, we had previously found meiotic prophase of the male mouse to be vulnerable to the induction of several types of genetic damage by the topoisomerase-II inhibitor etoposide. The present study of etoposide effects involved two end points of meiotic events known to occur in primary spermatocytes--chromosomal crossing-over and segregation. By following assortment of 13 microsatellite markers in two chromosomes (Ch 7 and Ch 15) it was shown that etoposide significantly affected crossing-over, but did not do so in a uniform fashion. Treatment generally changed the pattern for each chromosome, leading to local decreases in recombination, a distal shift in locations of crossing-over, and an overall decrease in double crossovers; at least some of these results might be interpreted as evidence for increased interference. Two methods were used to explore etoposide effects on chromosome segregation: a genetic experiment capable of detecting sex-chromosome nondisjunction in living progeny; and the use of FISH (fluorescence in situ hybridization) technology to score numbers of Chromosomes X, Y, and 8 in spermatozoa. Taken together these two approaches indicated that etoposide exposure of pachytene spermatocytes induces malsegregation, and that the findings of the genetic experiment probably yielded a marked underestimate of nondisjunction. As indicated by certain segregants, at least part of the etoposide effect could be due to disrupted pairing of achiasmatic homologs, followed by precocious sister-centromere separation. It has been shown for several organisms that absent or reduced levels of recombination, as well as suboptimally positioned recombination events, may be associated with abnormal segregation. Etoposide is the only chemical tested to date for which living progeny indicates an effect on both male meiotic crossing-over and chromosome segregation. Whether, however, etoposide-induced changes in recombination

  6. Genetic analysis of complex traits in the emerging Collaborative Cross

    PubMed Central

    Aylor, David L.; Valdar, William; Foulds-Mathes, Wendy; Buus, Ryan J.; Verdugo, Ricardo A.; Baric, Ralph S.; Ferris, Martin T.; Frelinger, Jeff A.; Heise, Mark; Frieman, Matt B.; Gralinski, Lisa E.; Bell, Timothy A.; Didion, John D.; Hua, Kunjie; Nehrenberg, Derrick L.; Powell, Christine L.; Steigerwalt, Jill; Xie, Yuying; Kelada, Samir N.P.; Collins, Francis S.; Yang, Ivana V.; Schwartz, David A.; Branstetter, Lisa A.; Chesler, Elissa J.; Miller, Darla R.; Spence, Jason; Liu, Eric Yi; McMillan, Leonard; Sarkar, Abhishek; Wang, Jeremy; Wang, Wei; Zhang, Qi; Broman, Karl W.; Korstanje, Ron; Durrant, Caroline; Mott, Richard; Iraqi, Fuad A.; Pomp, Daniel; Threadgill, David; Pardo-Manuel de Villena, Fernando; Churchill, Gary A.

    2011-01-01

    The Collaborative Cross (CC) is a mouse recombinant inbred strain panel that is being developed as a resource for mammalian systems genetics. Here we describe an experiment that uses partially inbred CC lines to evaluate the genetic properties and utility of this emerging resource. Genome-wide analysis of the incipient strains reveals high genetic diversity, balanced allele frequencies, and dense, evenly distributed recombination sites—all ideal qualities for a systems genetics resource. We map discrete, complex, and biomolecular traits and contrast two quantitative trait locus (QTL) mapping approaches. Analysis based on inferred haplotypes improves power, reduces false discovery, and provides information to identify and prioritize candidate genes that is unique to multifounder crosses like the CC. The number of expression QTLs discovered here exceeds all previous efforts at eQTL mapping in mice, and we map local eQTL at 1-Mb resolution. We demonstrate that the genetic diversity of the CC, which derives from random mixing of eight founder strains, results in high phenotypic diversity and enhances our ability to map causative loci underlying complex disease-related traits. PMID:21406540

  7. Analysis of cross-over studies with missing data.

    PubMed

    Rosenkranz, Gerd K

    2015-08-01

    This paper addresses some aspects of the analysis of cross-over trials with missing or incomplete data. A literature review on the topic reveals that many proposals provide correct results under the missing completely at random assumption while only some consider the more general missing at random situation. It is argued that mixed-effects models have a role in this context to recover some of the missing intra-subject from the inter-subject information, in particular when missingness is ignorable. Eventually, sensitivity analyses to deal with more general missingness mechanisms are presented.

  8. Genetic analysis in the Collaborative Cross breeding population

    PubMed Central

    Philip, Vivek M.; Sokoloff, Greta; Ackert-Bicknell, Cheryl L.; Striz, Martin; Branstetter, Lisa; Beckmann, Melissa A.; Spence, Jason S.; Jackson, Barbara L.; Galloway, Leslie D.; Barker, Paul; Wymore, Ann M.; Hunsicker, Patricia R.; Durtschi, David C.; Shaw, Ginger S.; Shinpock, Sarah; Manly, Kenneth F.; Miller, Darla R.; Donohue, Kevin D.; Culiat, Cymbeline T.; Churchill, Gary A.; Lariviere, William R.; Palmer, Abraham A.; O'Hara, Bruce F.; Voy, Brynn H.; Chesler, Elissa J.

    2011-01-01

    Genetic reference populations in model organisms are critical resources for systems genetic analysis of disease related phenotypes. The breeding history of these inbred panels may influence detectable allelic and phenotypic diversity. The existing panel of common inbred strains reflects historical selection biases, and existing recombinant inbred panels have low allelic diversity. All such populations may be subject to consequences of inbreeding depression. The Collaborative Cross (CC) is a mouse reference population with high allelic diversity that is being constructed using a randomized breeding design that systematically outcrosses eight founder strains, followed by inbreeding to obtain new recombinant inbred strains. Five of the eight founders are common laboratory strains, and three are wild-derived. Since its inception, the partially inbred CC has been characterized for physiological, morphological, and behavioral traits. The construction of this population provided a unique opportunity to observe phenotypic variation as new allelic combinations arose through intercrossing and inbreeding to create new stable genetic combinations. Processes including inbreeding depression and its impact on allelic and phenotypic diversity were assessed. Phenotypic variation in the CC breeding population exceeds that of existing mouse genetic reference populations due to both high founder genetic diversity and novel epistatic combinations. However, some focal evidence of allele purging was detected including a suggestive QTL for litter size in a location of changing allele frequency. Despite these inescapable pressures, high diversity and precision for genetic mapping remain. These results demonstrate the potential of the CC population once completed and highlight implications for development of related populations. PMID:21734011

  9. The evolutionary stability of cross-sex, cross-trait genetic covariances.

    PubMed

    Gosden, Thomas P; Chenoweth, Stephen F

    2014-06-01

    Although knowledge of the selective agents behind the evolution of sexual dimorphism has advanced considerably in recent years, we still lack a clear understanding of the evolutionary durability of cross-sex genetic covariances that often constrain its evolution. We tested the relative stability of cross-sex genetic covariances for a suite of homologous contact pheromones of the fruit fly Drosophila serrata, along a latitudinal gradient where these traits have diverged in mean. Using a Bayesian framework, which allowed us to account for uncertainty in all parameter estimates, we compared divergence in the total amount and orientation of genetic variance across populations, finding divergence in orientation but not total variance. We then statistically compared orientation divergence of within-sex (G) to cross-sex (B) covariance matrices. In line with a previous theoretical prediction, we find that the cross-sex covariance matrix, B, is more variable than either within-sex G matrix. Decomposition of B matrices into their symmetrical and nonsymmetrical components revealed that instability is linked to the degree of asymmetry. We also find that the degree of asymmetry correlates with latitude suggesting a role for spatially varying natural selection in shaping genetic constraints on the evolution of sexual dimorphism.

  10. Internal tidal currents over the summit of cross seamount

    USGS Publications Warehouse

    Noble, M.; Mullineaux, Lauren S.

    1989-01-01

    Spectral analysis of 46 days of record from a current meter deployed above the summit of Cross Seamount (approximately 300 km west of the Hawaiian Islands) indicates that the strongest current fluctuations were driven by the semidiurnal tide. The tides accounted for 28% of the variance in the current spectrum, were mainly baroclinic in character, and were propagated towards the west-northwest. The amplitude of the S2 current flowing parallel to the major axis of the current ellipse ranged between 4 and 9 cm-1 s. The S2 current was 1.5 times larger than the M2 current. This ratio is 4 times larger than is expected for this region of the Pacific and is not a general characteristics of flows over seamounts. Instantaneous current speeds over the seamount often exceeded 20 cm s-1 and were probably responsible for the small ripples observed on the sediment-covered regions of the summit. ?? 1990.

  11. Twinning and mitotic crossing-over: some possibilities and their implications.

    PubMed Central

    Côté, G B; Gyftodimou, J

    1991-01-01

    Mitotic crossing-over does occur in man and is much more frequent and important than generally assumed. Its postzygotic occurrence before an embryo differentiates into MZ twins is theoretically predicted to have disrupting effects on genomic imprinting and cis-acting sequences, with consequences ranging from early lethality to MZ twin discordance. Some predictions are at odds with classical views on twinning and include a high discordance rate of MZ twins for some genetic diseases. A review of MZ twin discordance and an attempt at explaining some of the data lead one to hypothesize both the existence of a sex differences in the rate of mitotic crossing-over and the impossibility for crossed X chromosomes to undergo inactivation. The close interrelationship of twinning and midline malformations further suggests a major role of mitotic crossing-over in the induction of the twinning process itself. The model can be tested with molecular methods and provides a new approach for the gene mapping of so-called multifactorial diseases and of rarer disorders with apparently irregular inheritance. PMID:2063864

  12. Ploidy, sex and crossing over in an evolutionary aging model

    NASA Astrophysics Data System (ADS)

    Lobo, Matheus P.; Onody, Roberto N.

    2006-02-01

    Nowadays, many forms of reproduction coexist in nature: Asexual, sexual, apomictic and meiotic parthenogenesis, hermaphroditism and parasex. The mechanisms of their evolution and what made them successful reproductive alternatives are very challenging and debated questions. Here, using a simple evolutionary aging model, we give a possible scenario. By studying the performance of populations where individuals may have diverse characteristics-different ploidies, sex with or without crossing over, as well as the absence of sex-we find an evolution sequence that may explain why there are actually two major or leading groups: Sexual and asexual. We also investigate the dependence of these characteristics on different conditions of fertility and deleterious mutations. Finally, if the primeval organisms on Earth were, in fact, asexual individuals we conjecture that the sexual form of reproduction could have more easily been set and found its niche during a period of low-intensity mutations.

  13. Genetic analysis in the Collaborative Cross breeding population

    SciTech Connect

    Philip, Vivek; Sokoloff, Greta; Ackert-Bicknell, Cheryl; Striz, Martin; Branstetter, Lisa R; Beckmann, Melissa; Spence, Jason S; Jackson, Barbara L; Galloway, Leslie D; Barker, Gene; Wymore, Ann M; Hunsicker, Patricia R; Durtschi, David W; Shaw, Ginger S; Shinpock, Sarah G; Manly, Kenneth F; Miller, Darla R; Donahue, Kevin; Culiat, Cymbeline T; Churchill, Gary A; Lariviere, William R; Palmer, Abraham; O'Hara, Bruce; Voy, Brynn H; Chesler, Elissa J

    2011-01-01

    Genetic reference populations in model organisms are critical resources for systems genetic analysis of disease related phenotypes. The breeding history of these inbred panels may influence detectable allelic and phenotypic diversity. The existing panel of common inbred strains reflects historical selection biases, and existing recombinant inbred panels have low allelic diversity. All such populations may be subject to consequences of inbreeding depression. The Collaborative Cross (CC) is a mouse reference population with high allelic diversity that is being constructed using a randomized breeding design that systematically outcrosses eight founder strains, followed by inbreeding to obtain new recombinant inbred strains. Five of the eight founders are common laboratory strains, and three are wild-derived. Since its inception, the partially inbred CC has been characterized for physiological, morphological, and behavioral traits. The construction of this population provided a unique opportunity to observe phenotypic variation as new allelic combinations arose through intercrossing and inbreeding to create new stable genetic combinations. Processes including inbreeding depression and its impact on allelic and phenotypic diversity were assessed. Phenotypic variation in the CC breeding population exceeds that of existing mouse genetic reference populations due to both high founder genetic diversity and novel epistatic combinations. However, some focal evidence of allele purging was detected including a suggestive QTL for litter size in a location of changing allele frequency. Despite these inescapable pressures, high diversity and precision for genetic mapping remain. These results demonstrate the potential of the CC population once completed and highlight implications for development of related populations. Supplementary material consists of Supplementary Table 1 Phenotypic means, variances, ranges and heritabilities for all traits and generations, Supplementary Table

  14. Governmentality, biopower, and the debate over genetic enhancement.

    PubMed

    McWhorter, Ladelle

    2009-08-01

    Although Foucault adamantly refused to make moral pronouncements or dictate moral principles or political programs to his readers, his work offers a number of tools and concepts that can help us develop our own ethical views and practices. One of these tools is genealogical analysis, and one of these concepts is "biopower." Specifically, this essay seeks to demonstrate that Foucault's concept of biopower and his genealogical method are valuable as we consider moral questions raised by genetic enhancement technologies. First, it examines contemporary debate over the development, marketing, and application of such technologies, suggesting that what passes for ethical deliberation is often little more than political maneuvering in a field where stakes are very high and public perceptions will play a crucial role in decisions about which technologies will be funded or disallowed. It goes on to argue that genuine ethical deliberation on these issues requires some serious investigation of their historical context. Accordingly, then, it takes up the oft-heard charge from critics that genetic enhancement technologies are continuous with twentieth-century eugenic projects or will usher in a new age of eugenics. Foucault explicitly links twentieth-century eugenics with the rise of biopower. Through review of some aspects of the twentieth-century eugenics movement alongside some of the rhetoric and claims of enhancement's modern-day proponents, the essay shows ways in which deployment of genetic enhancement technologies is and is not continuous with earlier deployments of biopower.

  15. Detecting Major Genetic Loci Controlling Phenotypic Variability in Experimental Crosses

    PubMed Central

    Rönnegård, Lars; Valdar, William

    2011-01-01

    Traditional methods for detecting genes that affect complex diseases in humans or animal models, milk production in livestock, or other traits of interest, have asked whether variation in genotype produces a change in that trait’s average value. But focusing on differences in the mean ignores differences in variability about that mean. The robustness, or uniformity, of an individual’s character is not only of great practical importance in medical genetics and food production but is also of scientific and evolutionary interest (e.g., blood pressure in animal models of heart disease, litter size in pigs, flowering time in plants). We describe a method for detecting major genes controlling the phenotypic variance, referring to these as vQTL. Our method uses a double generalized linear model with linear predictors based on probabilities of line origin. We evaluate our method on simulated F2 and collaborative cross data, and on a real F2 intercross, demonstrating its accuracy and robustness to the presence of ordinary mean-controlling QTL. We also illustrate the connection between vQTL and QTL involved in epistasis, explaining how these concepts overlap. Our method can be applied to a wide range of commonly used experimental crosses and may be extended to genetic association more generally. PMID:21467569

  16. Modelling and design of cross-over trials.

    PubMed

    Jones, B; Donev, A N

    1996-07-15

    There are many diseases and conditions that can be studied using a cross-over clinical trial, where the subjects receive sequences of treatments. The treatments are then compared using the repeated measurements taken 'within' subjects. The actual plan or design of the trial is usually obtained by consulting a published table of designs or by applying relatively simple rules such as using all possible permutations of the treatments. However, there is a danger is this approach because the model assumed for the data when the tables or rules were constructed may not be appropriate for the new trial being planned. Also, there may be restrictions in the new trial on the number of treatment sequences that can be used or on the number of periods of treatment particular subjects can be given. Such restrictions may mean that a published design of the ideal size cannot be found unless compromises are made. A better approach is to make the design satisfy the objectives of the trial rather than vice versa. In this paper we describe an approach to constructing such tailor-made designs which we hope will lead to ill-fitting 'off the peg' designs being a thing of the past. We use a computer algorithm to search for optimal designs and illustrate it using a number of examples. The criterion of optimality used in this paper is A-optimality but our approach is not restricted to one particular criterion. The model used in the search for the optimal design is chosen to suit the nature of the trial at hand and as an example a variety of models for three treatments are considered. We also illustrate the construction of designs for the comparison of two active treatments and a placebo where it can be assumed that the carry-over effects of the active treatments are similar. Finally, we illustrate an augmentation of a design that could arise when the objectives of a trial change.

  17. Vertical, Bubbly, Cross-Flow Characteristics over Tube Bundles

    NASA Astrophysics Data System (ADS)

    Iwaki, C.; Cheong, K. H.; Monji, H.; Matsui, G.

    2005-12-01

    Two-phase flow over tube bundles is commonly observed in shell and tube-type heat exchangers. However, only limited amount of data concerning flow pattern and void fraction exists due to the flow complexity and the difficulties in measurement. The detailed flow structure in tube bundles needs to be understood for reliable and effective design. Therefore, the objective of this study was to clarify the two-phase structure of cross-flow in tube bundles by PIV. Experiments were conducted using two types of models, namely in-line and staggered arrays with a pitch-to-diameter ratio of 1.5. Each test section contains 20 rows of five 15 mm O.D. tubes in each row. The experiment’s data were obtained under very low void fraction (α<0.02). Liquid and gas velocity data in the whole flow field were measured successfully by optical filtering and image processing. The structures of bubbly flow in the two different configurations of tube bundles were described in terms of the velocity vector field, turbulence intensity and void fraction.

  18. Randomised cross-over study of oral appliances for snoring.

    PubMed

    Maguire, J; Steele, J G; Gibson, G J; Wilson, J A; Steen, N; McCracken, G I

    2010-06-01

    To compare a mandibular advancement splint to a control bite raising appliance in the treatment of snoring with or without mild obstructive sleep apnoea syndrome. A prospective two-treatment randomised cross-over clinical trial. Single centre secondary care Dental Hospital. Fifty-two subjects (36 men, 16 women) diagnosed with non-apnoeic snoring or mild obstructive sleep apnoea syndrome (apnoea/hypopnoea index < or =15 events/h), were recruited from Departments of Respiratory Medicine and ENT surgery, Newcastle upon Tyne Hospitals NHS Foundation Trust. The Snoring Symptoms Inventory questionnaire (SSI) and the Epworth Sleepiness Score (ESS) were used to evaluate changes in symptoms. Patient reported outcomes (compliance, adverse events, splint preference) were recorded by questionnaire. Subjects attended for five study visits and used a mandibular advancement splint and a bite raising appliance at home each for 4 weeks, with a 3-week washout period between devices. Thirty-eight subjects completed the study. Both the mandibular advancement splint and bite raising appliance significantly reduced the SSI compared to the baseline scores: mandibular advancement splint 5.5, P = 0.013; bite raising appliance 3.1, P = 0.005. No statistically significant difference between the two treatment periods was detected (P > 0.05). The reduction in the Epworth Sleepiness Score was: mandibular advancement splint 1.0, P = 0.02; bite raising appliance 0.3, P = 0.4. The change in the Epworth Sleepiness Score was not statistically significantly different between the mandibular advancement splint and bite raising appliance treatment periods (P > 0.05). In this cohort of patients diagnosed with snoring +/- mild OSA: 1 both the mandibular advancement splint and bite raising appliance designs of splint appeared to reduce the symptoms of snoring; 2 no difference in the magnitude of this effect was detected in favour of one design of splint.

  19. The utility of empirically assigning ancestry groups in cross-population genetic studies of addiction.

    PubMed

    Peterson, Roseann E; Edwards, Alexis C; Bacanu, Silviu-Alin; Dick, Danielle M; Kendler, Kenneth S; Webb, Bradley T

    2017-08-01

    Given moderate heritability and significant heterogeneity among addiction phenotypes, successful genome-wide association studies (GWAS) are expected to need very large samples. As sample sizes grow, so can genetic diversity leading to challenges in analyzing these data. Methods for empirically assigning individuals to genetically informed ancestry groups are needed. We describe a strategy for empirically assigning ancestry groups in ethnically diverse GWAS data including extensions of principal component analysis (PCA) and population matching through minimum Mahalanobis distance. We apply these methods to data from Spit for Science (S4S): the University Student Survey, a study following college students longitudinally that includes genetic and environmental data on substance use and mental health (n = 7,603). The genetic-based population assignments for S4S were 48.7% European, 22.5% African, 10.4% Americas, 9.2% East Asian, and 9.2% South Asian descent. Self-reported census categories "More than one race" and "Unknown"as well as "Hawaiian/Pacific Islander" and "American-Indian/Native Alaskan" were empirically assigned representing a +9% sample retention over conventional methods. Although there was high concordance between self-reported race and empirical population-match (+.924), there was reduction in variance for most ancestry PCs for genetic-based population assignments. We were able to create more genetically homogenous groups and reduce sample and marker loss through cross-ancestry meta-analysis, potentially increasing power to detect etiologically relevant variation. Our approach provides a framework for empirically assigning genetic ancestry groups which can be applied to other ethnically diverse genetic studies. Given the important public health impact and demonstrable gains in statistical power from studying diverse populations, empirically sound practices for genetic studies are needed. (Am J Addict 2017;26:494-501). © 2017 American Academy of

  20. Optimized protocols for improving the likelihood of cloning recombinant progeny from Plasmodium yoelii genetic crosses

    PubMed Central

    Qi, Yanwei; Zhu, Feng; Li, Jian; Fu, Yong; Pattaradilokrat, Sittiporn; Hong, Linxian; Liu, Shengfa; Huang, Fusheng; Xu, Wenyue; Su, Xin-zhuan

    2012-01-01

    Genetic cross is a powerful tool for studying malaria genes contributing to drug resistance, parasite development, and pathogenesis. Cloning and identification of recombinant progeny (RP) is laborious and expensive, especially when a large proportion of progeny derived from self-fertilization are present in the uncloned progeny of a genetic cross. Since the frequency of cross-fertilization affects the number of recombinant progeny in a genetic cross, it is important to optimize the procedure of a genetic cross to maximize the cross-fertilization. Here we investigated the factors that might influence the chances of obtaining RP from a genetic cross and showed that different Plasmodium yoelii strains/subspecies/clones had unique abilities in producing oocysts in a mosquito midgut. When a genetic cross is performed between two parents producing different numbers of functional gametocytes, the ratio of parental parasites must be adjusted to improve the chance of obtaining RP. An optimized parental ratio could be established based on oocyst counts from single infection of each parent before crossing experiments, which may reflect the efficiency of gametocyte production and/or fertilization. The timing of progeny cloning is also important; cloning of genetic cross progeny from mice directly infected with sporozoites (vs. frozen blood after needle passage) at a time when parasitemia is low (usually <1%) could improve the chance of obtaining RP. This study provides an optimized protocol for efficiently cloning RPs from a genetic cross of malaria parasites. PMID:23116600

  1. The Collaborative Cross at Oak Ridge National Laboratory: developing a powerful resource for systems genetics

    SciTech Connect

    Chesler, Elissa J; Branstetter, Lisa R; Churchill, Gary A; Culiat, Cymbeline T; Galloway, Leslie D; Jackson, Barbara L; Johnson, Dabney K; Miller, Darla R; Philip, Vivek M; Threadgill, David; Voy, Brynn H; Williams, Robert; Manly, Kenneth

    2008-01-01

    Complex traits and disease co-morbidity in humans and in model organisms are the result of naturally occurring polymorphisms that interact with each other and with the environment. To ensure the availability of the resources needed to investigate biomolecular networks and ultimately systems level phenotypes, we have initiated breeding of a new genetic reference population of mice, the Collaborative Cross. This population has been designed to optimally support systems genetics analysis. Its novel and important features include high levels of genetic diversity, a large population size to ensure sufficient power in high-dimensional studies, and high mapping precision through accumulation of independent recombination events. Implementation of the Collaborative Cross has been in progress at the Oak Ridge National Laboratory (ORNL) since May 2005. This is achieved through a software assisted breeding program with fully traceable lineages, performed in a uniform environment. Currently, there are 650 lines in production with almost 200 lines over seven generations of inbreeding. Retired breeders enter a high-throughput phenotyping protocol and DNA samples are banked for analysis of recombination history, allele loss, and population structure. Herein we present a progress report of the Collaborative Cross breeding program at ORNL and a description of the kinds of investigations that this resource will support.

  2. Prenatal genetic counseling in cross-cultural medicine

    PubMed Central

    Bhogal, Ashvinder K.; Brunger, Fern

    2010-01-01

    Abstract OBJECTIVE To help family physicians practise effective genetic counseling and offer practical strategies for cross-cultural communication in the context of prenatal genetic counseling. SOURCES OF INFORMATION PubMed and the Cochrane Database of Systematic Reviews were searched. Most evidence was level II and some was level III. MAIN MESSAGE The values and beliefs of practitioners, no less than those of patients, are shaped by culture. In promoting a patient’s best interest, the assumptions of both the patient and the provider must be held up for examination and discussed in the attempt to arrive at a consensus. Through the explicit discussion and formation of trust, the health professionals, patients, and family members who are involved can develop a shared understanding of appropriate therapeutic goals and methods. CONCLUSION Reflecting on the cultural nature of biomedicine’s ideas about risk, disability, and normality helps us to realize that there are many valid interpretations of what is in a patient’s best interest. Self-reflection helps to ensure that respectful communication with the specific family and patient is the basis for health care decisions. Overall, this helps to improve the quality of care. PMID:20944039

  3. Primary care patient willingness for genetic testing for salt-sensitive hypertension: a cross sectional study

    PubMed Central

    2013-01-01

    Background The current research into single nucleotide polymorphisms has extended the role of genetic testing to the identification of increased risk for common medical conditions. Advances in genetic research may soon necessitate preparation for the role of genetic testing in primary care medicine. This study attempts to determine what proportion of patients would be willing to undergo genetic testing for salt-sensitive hypertension in a primary care setting, and what factors are related to this willingness. Methods A cross-sectional study using a self-report questionnaire was conducted among outpatients in primary care clinics and hospitals in Japan. The main characteristics measured were education level, family medical history, personal medical history, concern about hypertension, salt preference, reducing salt intake, and willingness to undergo genetic testing for salt-sensitive hypertension. Results Of 1,932 potential participants, 1,457 (75%) responded to the survey. Of the respondents, 726 (50%) indicated a willingness to undergo genetic testing. Factors related to this willingness were being over 50 years old (adjusted odds ratio [ad-OR] = 1.42, 95% Confidence interval = 1.09 – 1.85), having a high level of education (ad-OR: 1.83, 1.38 – 2.42), having a family history of hypertension (ad-OR: 1.36, 1.09 – 1.71), and worrying about hypertension (ad-OR: 2.06, 1.59 – 2.68). Conclusions Half of the primary care outpatients surveyed in this study wanted to know their genetic risk for salt-sensitive hypertension. Those who were worried about hypertension or had a family history of hypertension were more likely to be interested in getting tested. These findings suggest that primary care physicians should provide patients with advice on genetic testing, as well as address their anxieties and concerns related to developing hypertension. PMID:24103405

  4. Cross-fertilization between genetically modified and non-genetically modified maize crops in Uruguay.

    PubMed

    Galeano, Pablo; Debat, Claudio Martínez; Ruibal, Fabiana; Fraguas, Laura Franco; Galván, Guillermo A

    2010-01-01

    The cultivation of genetically modified (GM) Bt maize (Zea mays L.) events MON810 and Bt11 is permitted in Uruguay. Local regulations specify that 10% of the crop should be a non-GM cultivar as refuge area for biodiversity, and the distance from other non-GM maize crops should be more than 250 m in order to avoid cross-pollination. However, the degree of cross-fertilization between maize crops in Uruguay is unknown. The level of adventitious presence of GM material in non-GM crops is a relevant issue for organic farming, in situ conservation of genetic resources and seed production. In the research reported here, the occurrence and frequency of cross-fertilization between commercial GM and non-GM maize crops in Uruguay was assessed. The methodology comprised field sampling and detection using DAS-ELISA and PCR. Five field-pair cases where GM maize crops were grown near non-GM maize crops were identified. These cases had the potential to cross-fertilize considering the distance between crops and the similarity of the sowing dates. Adventitious presence of GM material in the offspring of non-GM crops was found in three of the five cases. Adventitious presence of event MON810 or Bt11 in non-GM maize, which were distinguished using specific primers, matched the events in the putative sources of transgenic pollen. Percentages of transgenic seedlings in the offspring of the non-GM crops were estimated as 0.56%, 0.83% and 0.13% for three sampling sites with distances of respectively 40, 100 and 330 m from the GM crops. This is a first indication that adventitious presence of transgenes in non-GM maize crops will occur in Uruguay if isolation by distance and/or time is not provided. These findings contribute to the evaluation of the applicability of the "regulated coexistence policy" in Uruguay.

  5. Mitotic Crossing over and Nondisjunction in Translocation Heterozygotes of Aspergillus

    PubMed Central

    Käfer, Etta

    1976-01-01

    To analyze mitotic recombination in translocation heterozygotes of A. nidulans two sets of well-marked diploids were constructed, homo- or heterozygous for the reciprocal translocations T1(IL;VIIR) or T2(IL;VIIIR) and heterozygous for selective markers on IL. It was found that from all translocation heterozygotes some of the expected mitotic crossover types could be selected. Such crossovers are monosomic for one translocated segment and trisomic for the other and recovery depends on the relative viabilities of these unbalanced types. The obtained segregants show characteristically reduced growth rates and conidiation dependent on sizes and types of mono- and trisomic segments, and all spontaneously produce normal diploid sectors. Such secondary diploid types either arose in one step of compensating crossing over in the other involved arm, or—more conspicuously—in two steps of nondisjunction via a trisomic intermediate.—In both of the analyzed translocations the segments translocated to IL were extremely long, while those translocated from IL were relatively short. The break in I for T1(I;VII) was located distal to the main selective marker in IL, while that of T2(I;VIII) had been mapped proximal but closely linked to it. Therefore, as expected, the selected primary crossover from the two diploids with T2( I;VIII) in coupling or in repulsion to the selective marker, showed the same chromosomal imbalance and poor growth. These could however be distinguished visually because they spontaneously produced different trisomic intermediates in the next step, in accordance with the different arrangement of the aneuploid segments. On the other hand, from diploids heterozygous for T1( I;VII) mitotic crossovers could only be selected when the selective markers were in coupling with the translocation; these crossovers were relatively well-growing and produced frequent secondary segregants of the expected trisomic, 2n+VII, type. For both translocations it was impossible to

  6. Cross-referencing yeast genetics and mammalian genomes

    SciTech Connect

    Hieter, P.; Basset, D.; Boguski, M.

    1994-09-01

    We have initiated a project that will systematically transfer information about yeast genes onto the genetic maps of mice and human beings. Rapidly expanding human EST data will serve as a source of candidate human homologs that will be repeatedly searched using yeast protein sequence queries. Search results will be automatically reported to participating labs. Human cDNA sequences from which the ESTs are derived will be mapped at high resolution in the human and mouse genomes. The comparative mapping information cross-references the genomic position of novel human cDNAs with functional information known about the cognate yeast genes. This should facilitate the initial identification of genes responsible for mammalian mutant phenotypes, including human disease. In addition, the identification of mammalian homologs of yeast genes provides reagents for determining evolutionary conservation and for performing direct experiments in multicellular eukaryotes to enhance study of the yeast protein`s function. For example, ESTs homologous to CDC27 and CDC16 were identified, and the corresponding cDNA clones were obtained from ATTC, completely sequenced, and mapped on human and mouse chromosomes. In addition, the CDC17hs cDNA has been used to raise antisera to the CDC27Hs protein and used in subcellular localization experiments and junctional studies in mammalian cells. We have received funding from the National Center for Human Genome Research to provide a community resource which will establish comprehensive cross-referencing among yeast, human, and mouse loci. The project is set up as a service and information on how to communicate with this effort will be provided.

  7. Cross-over limb replantation: a case report.

    PubMed

    Holmes, W J M; Williams, A; Everitt, K J M; Kay, S P J; Bourke, G

    2013-10-01

    Following traumatic bilateral arm amputation in a 46-year-old woman, orthotopic replantation was not possible. The patient underwent replantation of the left forearm to the right proximal forearm. At two years she has a sensate hand, with good recovery of her long flexors of the hand and wrist extensors. DASH score is 93.9 and Chen's score is III (medium). We demonstrate a high level of function compared to the contralateral prosthetic limb. There have only been four similar cases described. Although a rare circumstance, a cross-limb replant can provide a level of function and independence superior to a simple prosthesis. Cross-limb transfer should be considered in situations where bilateral arm amputation is present and neither can be orthotopically replanted.

  8. Control of cross-over by single-strand DNA resection.

    PubMed

    Prado, Félix; Aguilera, Andrés

    2003-08-01

    Control of DNA cross-overs is necessary for meiotic recombination and genome integrity. The frequency of cross-overs is dependent on homology length and the conversion tract, but the mechanisms underlying the regulation of cross-overs remain unknown. We propose that 5'-end resection, a key intermediate in double-strand break repair, could determine the formation of cross-overs. Extensive DNA resection might favor gene conversion without cross-over by channeling recombination events through synthesis-dependent strand-annealing. In reactions with short regions of homology, resection beyond the homologous sequence would impede Holliday junction formation and, consequently, cross-over. Extensive DNA resection could be an effective mechanism to prevent reciprocal exchanges between dispersed DNA sequences, and thus contribute to the genome stability.

  9. Elective cross-over transfer of the foot: case report.

    PubMed

    Cavadas, Pedro C; Thione, Alessandro; Landín, Luis

    2010-10-01

    The case of a patient with sequels of a right Syme amputation and a left replanted upper tibial amputation was treated with elective cross-transfer of the left foot and ankle to the right distal tibial stump, and the left below-knee (BK) stump was resurfaced with a latissimus dorsi free flap. The patient regained independent walking capacity with a left BK prosthesis at 8 months postoperatively. Copyright © 2010 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  10. Designing a Unique Single Point Cross Over Method

    NASA Technical Reports Server (NTRS)

    Wilson, Richard Phillip

    2002-01-01

    The idea behind genetic algorithms is to extract optimization strategies nature uses successfully - known as Darwinian Evolution - and transform them for application in mathematical optimization theory to find the global optimum in a defined phase space. One could imagine a population of individual 'explorers' sent into the optimization phase-space. Each explorer is defined by its genes, what means, its position inside the phase-space is coded in his genes. Every explorer has the duty to find a value of the quality of his position in the phase space. (Consider the phase-space being a number of variables in some technological process, the value of quality of any position in the phase space - in other words: any set of the variables - can be expressed by the yield of the desired chemical product.) Then the struggle of 'life' begins. The three fundamental principles are selection, mating/crossover, and mutation. Only explorers (= genes) sitting on the best places will reproduce and create a new population. This is performed in the second step (mating/crossover). The 'hope' behind this part of the algorithm is, that 'good' sections of two parents will be recombined to yet better fitting children. In fact, many of the created children will not be successful (as in biological evolution), but a few children will indeed fulfill this hope. These good sections are named in some publications as building blocks. Now there appears a problem. Repeating these steps, no new area would be explored. The two former steps would only exploit the already known regions in the phase space, which could lead to premature convergence of the algorithm with the consequence of missing the global optimum by exploiting some local optimum. The third step, mutation, ensures the necessary accidental effects. One can imagine the new population being mixed up a little bit to bring some new information into this set of genes. Whereas in biology a gene is described as a macro-molecule with four

  11. Genetic connectivity for two bear species at wildlife crossing structures in Banff National Park.

    PubMed

    Sawaya, Michael A; Kalinowski, Steven T; Clevenger, Anthony P

    2014-04-07

    Roads can fragment and isolate wildlife populations, which will eventually decrease genetic diversity within populations. Wildlife crossing structures may counteract these impacts, but most crossings are relatively new, and there is little evidence that they facilitate gene flow. We conducted a three-year research project in Banff National Park, Alberta, to evaluate the effectiveness of wildlife crossings to provide genetic connectivity. Our main objective was to determine how the Trans-Canada Highway and crossing structures along it affect gene flow in grizzly (Ursus arctos) and black bears (Ursus americanus). We compared genetic data generated from wildlife crossings with data collected from greater bear populations. We detected a genetic discontinuity at the highway in grizzly bears but not in black bears. We assigned grizzly bears that used crossings to populations north and south of the highway, providing evidence of bidirectional gene flow and genetic admixture. Parentage tests showed that 47% of black bears and 27% of grizzly bears that used crossings successfully bred, including multiple males and females of both species. Differentiating between dispersal and gene flow is difficult, but we documented gene flow by showing migration, reproduction and genetic admixture. We conclude that wildlife crossings allow sufficient gene flow to prevent genetic isolation.

  12. Genetic connectivity for two bear species at wildlife crossing structures in Banff National Park

    PubMed Central

    Sawaya, Michael A.; Kalinowski, Steven T.; Clevenger, Anthony P.

    2014-01-01

    Roads can fragment and isolate wildlife populations, which will eventually decrease genetic diversity within populations. Wildlife crossing structures may counteract these impacts, but most crossings are relatively new, and there is little evidence that they facilitate gene flow. We conducted a three-year research project in Banff National Park, Alberta, to evaluate the effectiveness of wildlife crossings to provide genetic connectivity. Our main objective was to determine how the Trans-Canada Highway and crossing structures along it affect gene flow in grizzly (Ursus arctos) and black bears (Ursus americanus). We compared genetic data generated from wildlife crossings with data collected from greater bear populations. We detected a genetic discontinuity at the highway in grizzly bears but not in black bears. We assigned grizzly bears that used crossings to populations north and south of the highway, providing evidence of bidirectional gene flow and genetic admixture. Parentage tests showed that 47% of black bears and 27% of grizzly bears that used crossings successfully bred, including multiple males and females of both species. Differentiating between dispersal and gene flow is difficult, but we documented gene flow by showing migration, reproduction and genetic admixture. We conclude that wildlife crossings allow sufficient gene flow to prevent genetic isolation. PMID:24552834

  13. Genetic control of agronomically important traits of pepper fruits analyzed by Hayman's partial diallel cross scheme.

    PubMed

    Schuelter, A R; Pereira, G M; Amaral, A T; Casali, V W D; Scapim, C A; Barros, W S; Finger, F L

    2010-01-01

    Pepper species of the genus Capsicum have been cultivated over centuries, producing both pungent and sweet fruit; the pungency is caused by alkaloids called capsaicinoids. Among the five cultivated species, Capsicum chinense is one of the most popular, being native to the Amazon basin. This species is characterized by a wide variety of fruit sizes, shapes and colors, with different capsaicinoid content. In addition, fruits are rich in vitamins A and C. Despite the importance of this plant as a spice and its medicinal uses, research on its genetic variability and potential for breeding programs is still incipient. We investigated the genetic control of some traits through diallel analysis with the objective of introgressing these traits into cultivated varieties. For the diallel analysis, the progeny of crosses between peppers with pungent and sweet fruits, together with the parents, were grown in pots under greenhouse conditions. The fruits were harvested and analyzed for the traits total fresh fruit mass, total dry fruit mass, percentage dry matter, total soluble solids, vitamin C content, fruit pungency, and number of seeds per fruit. Genetic variability was detected for all traits. In the diallel analysis, the additive-dominant model was considered to be adequate for total fresh fruit mass, percentage dry matter, total soluble solids, and vitamin C content. Additive genetic effects and dominance were found for all traits; consequently, breeding for improvement of these fruit traits would be viable.

  14. Sex-Related Differences in Crossing over in Caenorhabditis Elegans

    PubMed Central

    Zetka, M. C.; Rose, A. M.

    1990-01-01

    In the nematode Caenorhabditis elegans, hermaphrodite recombination has been characterized and is the basis of the genetic map used in this organism. In this study we have examined male recombination on linkage group I and have found it to be approximately one-third less than that observed in the hermaphrodite. This decrease was interval-dependent and nonuniform. We observed less recombination in the male in 5 out of 6 intervals examined, and no observable difference in one interval on the right end of LG I. Hermaphrodite recombination frequencies are the result of recombination in two germlines; oocyte and hermaphrodite spermatocytes. We have measured recombination in the oocyte and have found it to be approximately twofold lower than that calculated for hermaphrodite spermatocytes and not significantly different from the male spermatocyte frequency. Thus, recombination frequencies appear to be a function of gonad physiology rather than the sex of the germline. Evidence from experiments examining the effect of karyotype on recombination in males sexually transformed by the her-1 mutation into XO hermaphrodites (normally XX), suggests the sexual phenotype rather than genotype determines the recombination frequency characteristic of a particular sex. Hermaphrodite recombination is known to be affected by temperature, maternal age, and the rec-1 mutation. We have examined the effect of these parameters on recombination in the male and have found male recombination frequency increased with elevated temperatures and in the presence of Rec-1, and decreased with paternal age. PMID:2245915

  15. Nineteenth century French rose (Rosa sp.) germplasm shows a shift over time from a European to an Asian genetic background

    PubMed Central

    Liorzou, Mathilde; Pernet, Alix; Li, Shubin; Chastellier, Annie; Thouroude, Tatiana; Michel, Gilles; Malécot, Valéry; Gaillard, Sylvain; Briée, Céline; Foucher, Fabrice; Oghina-Pavie, Cristiana; Clotault, Jérémy; Grapin, Agnès

    2016-01-01

    Hybridization with introduced genetic resources is commonly practiced in ornamental plant breeding to introgress desired traits. The 19th century was a golden age for rose breeding in France. The objective here was to study the evolution of rose genetic diversity over this period, which included the introduction of Asian genotypes into Europe. A large sample of 1228 garden roses encompassing the conserved diversity cultivated during the 18th and 19th centuries was genotyped with 32 microsatellite primer pairs. Its genetic diversity and structure were clarified. Wide diversity structured in 16 genetic groups was observed. Genetic differentiation was detected between ancient European and Asian accessions, and a temporal shift from a European to an Asian genetic background was observed in cultivated European hybrids during the 19th century. Frequent crosses with Asian roses throughout the 19th century and/or selection for Asiatic traits may have induced this shift. In addition, the consistency of the results with respect to a horticultural classification is discussed. Some horticultural groups, defined according to phenotype and/or knowledge of their pedigree, seem to be genetically more consistent than others, highlighting the difficulty of classifying cultivated plants. Therefore, the horticultural classification is probably more appropriate for commercial purposes rather than genetic relatedness, especially to define preservation and breeding strategies. PMID:27406785

  16. Nineteenth century French rose (Rosa sp.) germplasm shows a shift over time from a European to an Asian genetic background.

    PubMed

    Liorzou, Mathilde; Pernet, Alix; Li, Shubin; Chastellier, Annie; Thouroude, Tatiana; Michel, Gilles; Malécot, Valéry; Gaillard, Sylvain; Briée, Céline; Foucher, Fabrice; Oghina-Pavie, Cristiana; Clotault, Jérémy; Grapin, Agnès

    2016-08-01

    Hybridization with introduced genetic resources is commonly practiced in ornamental plant breeding to introgress desired traits. The 19th century was a golden age for rose breeding in France. The objective here was to study the evolution of rose genetic diversity over this period, which included the introduction of Asian genotypes into Europe. A large sample of 1228 garden roses encompassing the conserved diversity cultivated during the 18th and 19th centuries was genotyped with 32 microsatellite primer pairs. Its genetic diversity and structure were clarified. Wide diversity structured in 16 genetic groups was observed. Genetic differentiation was detected between ancient European and Asian accessions, and a temporal shift from a European to an Asian genetic background was observed in cultivated European hybrids during the 19th century. Frequent crosses with Asian roses throughout the 19th century and/or selection for Asiatic traits may have induced this shift. In addition, the consistency of the results with respect to a horticultural classification is discussed. Some horticultural groups, defined according to phenotype and/or knowledge of their pedigree, seem to be genetically more consistent than others, highlighting the difficulty of classifying cultivated plants. Therefore, the horticultural classification is probably more appropriate for commercial purposes rather than genetic relatedness, especially to define preservation and breeding strategies.

  17. A Cross-Over Experimental Design for Testing Audiovisual Training Materials.

    ERIC Educational Resources Information Center

    Stolovitch, Harold D.; Bordeleau, Pierre

    This paper contains a description of the cross-over type of experimental design as well as a case study of its use in field testing audiovisual materials related to teaching handicapped children. Increased efficiency is an advantage of the cross-over design, while difficulty in selecting similar format audiovisual materials for field testing is a…

  18. Idealized Quasi-Linear Convective Storms Crossing Over Coastlines

    NASA Astrophysics Data System (ADS)

    Lombardo, K.

    2015-12-01

    As organized coastal convective storms develop over land and move over a coastal ocean, their storm-scale structures, intensity, and associated weather threats evolve. This study aims to identify and quantify the fundamental mechanisms controlling the evolution of coastal quasi-linear convective systems (QLCSs) as they move offshore, as well as characterize the environmental conditions that support a phase space of life cycles. Results from this work will contribute to the improved predictability of these potentially severe warm season storms. The current work uses the Cloud Model 1 (CM1; Bryan and Fritsch 2002) to systematically study the interaction between QLCSs and marine atmospheric boundary layers (MABLs) associated with the coastal ocean in an idealized numerical framework. The initial simulations are run in 2-dimensions, with a 250 m horizontal resolution and a vertical resolution ranging from 100 m in the lowest 3000 m stretched to 250 m at the top of the 20 km domain. All simulations use the Weisman-Klemp analytic sounding as the base-state sounding profile in conjunction with an RKW-type wind profile. To create a numerical environment representative of a coastal region, the western half of the 800 km domain is configured to represent a land surface, while the eastern half represents a water surface. A series of sensitivity experiments are conducted to explore the influence of sea surface temperature and the associated marine atmospheric boundary layer on coastal QLCSs. Sea surface temperature values are selected to represent values observed within the Mid-Atlantic Bight coastal waters during the warm season, ranging from 14oC ('early summer') to 23oC ('late summer'). The numerical MABL is allowed to develop in time through surface heat fluxes. This presentation will discuss preliminary results from the 'early summer' and 'late summer' SST sensitivity experiments. Preliminary simulations indicate that the 'early summer' QLCS moves more quickly than the

  19. Genomic compatibility occurs over a wide range of parental genetic similarity in an outcrossing plant

    PubMed Central

    Willi, Yvonne; Van Buskirk, Josh

    2005-01-01

    The theory of inbreeding and outbreeding suggests that there is a hump-shaped relationship between the genetic similarity of sexually reproducing parents and the performance of their offspring. Inbreeding depression occurs when genetic similarity is high, whereas hybrid breakdown is expected when genetic similarity is low. Between these extremes, the effect of genetic similarity on fitness is unclear. We studied the shape of this relationship by crossing 65 target genotypes of the clonal, self-incompatible Ranunculus reptans with partner genotypes spanning a broad scale of genetic similarity, ranging from crosses within populations to between-population crosses and hybridisation with a closely related species. Offspring were raised in outdoor tubs. Results revealed a quadratic relationship between parental genetic distance and offspring performance, with the clonal component of fitness more strongly hump-shaped than the sexual component. Optimal genetic similarity encompassed a broad range of within-population and between-population crosses. This pattern of genomic compatibility has important implications for the evolution of mating systems and mate choice. PMID:16006327

  20. Complex genetic diseases: controversy over the Croesus code.

    PubMed

    Wright, A F; Hastie, N D

    2001-01-01

    The polarization of views on how best to exploit new information from the Human Genome Project for medicine reflects our ignorance of the genetic architecture underlying common diseases: are susceptibility alleles common or rare, neutral or deleterious, few or many? Single-nucleotide polymorphism (SNP) technology is almost in place to dissect such diseases and to create a personalized medicine, but success is critically dependent on the biology and "Nature to be commanded must be obeyed" (Francis Bacon, 1620, Novum Organum).

  1. Controversy over genetically modified organisms: the governing laws and regulations.

    PubMed

    Keatley, K L

    2000-01-01

    Genetically Modified Organisms (GMOs) are increasingly becoming a topic of controversy in the U.S. and abroad. The public is questioning their safety and wanting the products labeled as genetically modified. There are other concerns from some of the scientific world and some government officials and organizations such as the Food & Agricultural Organization (FAO) that question whether adequate research has been done to qualify GMOs as safe for long-term use. Of particular concern are the allergenic properties, a GMO may impart, possible transfer effects of antibiotic resistance (given that antibiotic resistant marker genes are used for many GMOs), the expression of previously unexpressed traits, and the drift of pollen from genetically modified crops. It has also been noted that the laws and regulations governing the biotechnology world are outdated, are not comprehensive, and span too many agencies. The primary agencies currently regulating biotechnology are the U.S. Department of Agriculture (USDA), the Food and Drug Administration (FDA), and the Environmental Protection Agency (EPA).

  2. Genetic programming over context-free languages with linear constraints for the knapsack problem: first results.

    PubMed

    Bruhn, Peter; Geyer-Schulz, Andreas

    2002-01-01

    In this paper, we introduce genetic programming over context-free languages with linear constraints for combinatorial optimization, apply this method to several variants of the multidimensional knapsack problem, and discuss its performance relative to Michalewicz's genetic algorithm with penalty functions. With respect to Michalewicz's approach, we demonstrate that genetic programming over context-free languages with linear constraints improves convergence. A final result is that genetic programming over context-free languages with linear constraints is ideally suited to modeling complementarities between items in a knapsack problem: The more complementarities in the problem, the stronger the performance in comparison to its competitors.

  3. Comparative genetic analysis of lint yield and fiber quality among single, three-way, and double crosses in upland cotton

    USDA-ARS?s Scientific Manuscript database

    Decisions on the appropriate crossing systems to employ for genetic improvement of quantitative traits are critical in cotton breeding. Determination of genetic variance for lint yield and fiber quality in three different crossing schemes, i.e., single cross (SC), three-way cross (TWC), and double ...

  4. Formation of interference-sensitive meiotic cross-overs requires sufficient DNA leading-strand elongation

    PubMed Central

    Huang, Jiyue; Cheng, Zhihao; Wang, Cong; Hong, Yue; Su, Hang; Wang, Jun; Copenhaver, Gregory P.; Ma, Hong; Wang, Yingxiang

    2015-01-01

    Meiosis halves diploid genomes to haploid and is essential for sexual reproduction in eukaryotes. Meiotic recombination ensures physical association of homologs and their subsequent accurate segregation and results in the redistribution of genetic variations among progeny. Most organisms have two classes of cross-overs (COs): interference-sensitive (type I) and -insensitive (type II) COs. DNA synthesis is essential for meiotic recombination, but whether DNA synthesis has a role in differentiating meiotic CO pathways is unknown. Here, we show that Arabidopsis POL2A, the homolog of the yeast DNA polymerase-ε (a leading-strand DNA polymerase), is required for plant fertility and meiosis. Mutations in POL2A cause reduced fertility and meiotic defects, including abnormal chromosome association, improper chromosome segregation, and fragmentation. Observation of prophase I cell distribution suggests that pol2a mutants likely delay progression of meiotic recombination. In addition, the residual COs in pol2a have reduced CO interference, and the double mutant of pol2a with mus81, which affects type II COs, displayed more severe defects than either single mutant, indicating that POL2A functions in the type I pathway. We hypothesize that sufficient leading-strand DNA elongation promotes formation of some type I COs. Given that meiotic recombination and DNA synthesis are conserved in divergent eukaryotes, this study and our previous study suggest a novel role for DNA synthesis in the differentiation of meiotic recombination pathways. PMID:26392549

  5. Formation of interference-sensitive meiotic cross-overs requires sufficient DNA leading-strand elongation.

    PubMed

    Huang, Jiyue; Cheng, Zhihao; Wang, Cong; Hong, Yue; Su, Hang; Wang, Jun; Copenhaver, Gregory P; Ma, Hong; Wang, Yingxiang

    2015-10-06

    Meiosis halves diploid genomes to haploid and is essential for sexual reproduction in eukaryotes. Meiotic recombination ensures physical association of homologs and their subsequent accurate segregation and results in the redistribution of genetic variations among progeny. Most organisms have two classes of cross-overs (COs): interference-sensitive (type I) and -insensitive (type II) COs. DNA synthesis is essential for meiotic recombination, but whether DNA synthesis has a role in differentiating meiotic CO pathways is unknown. Here, we show that Arabidopsis POL2A, the homolog of the yeast DNA polymerase-ε (a leading-strand DNA polymerase), is required for plant fertility and meiosis. Mutations in POL2A cause reduced fertility and meiotic defects, including abnormal chromosome association, improper chromosome segregation, and fragmentation. Observation of prophase I cell distribution suggests that pol2a mutants likely delay progression of meiotic recombination. In addition, the residual COs in pol2a have reduced CO interference, and the double mutant of pol2a with mus81, which affects type II COs, displayed more severe defects than either single mutant, indicating that POL2A functions in the type I pathway. We hypothesize that sufficient leading-strand DNA elongation promotes formation of some type I COs. Given that meiotic recombination and DNA synthesis are conserved in divergent eukaryotes, this study and our previous study suggest a novel role for DNA synthesis in the differentiation of meiotic recombination pathways.

  6. Somatic nonhomologous crossing-over between neuropeptide genes in rat hypothalamic neurons.

    PubMed Central

    Mohr, E; Peters, A; Morris, J F; Richter, D

    1994-01-01

    Molecular biological and immunocytochemical data demonstrate nonhomologous crossing-over between the closely linked vasopressin (VP) and oxytocin (OT) genes in rat hypothalamic neuroendocrine neurons. Reverse transcription of hypothalamic total RNA from wild-type or homozygous Brattleboro aged rats combined with polymerase chain reaction (PCR) amplifications in the presence of appropriate 5' forward and 3' reverse primers deduced from the VP and OT cDNA sequences yielded PCR products that, upon cloning and sequencing, revealed several hybrid transcripts. They encode the N-terminal part of the VP precursor fused to the C-terminal part of the OT precursor (VP/OT transcripts) and vice versa (OT/VP transcripts). VP/OT hybrid precursor proteins have been identified immunocytochemically in enlarged cisternae of the rough endoplasmic reticulum, yet there is no evidence that the products can be secreted from affected cells. Recombination appears to be a rather frequent genetic event affecting about 0.06-0.1% of the rat vasopressinergic magnocellular neurons in aged rats. Images PMID:7972073

  7. Predicting Phenotypes from Genetic Crosses: A Mathematical Concept to Help Struggling Biology Students

    ERIC Educational Resources Information Center

    Baurhoo, Neerusha; Darwish, Shireef

    2012-01-01

    Predicting phenotypic outcomes from genetic crosses is often very difficult for biology students, especially those with learning disabilities. With our mathematical concept, struggling students in inclusive biology classrooms are now better equipped to solve genetic problems and predict phenotypes, because of improved understanding of dominance…

  8. Predicting Phenotypes from Genetic Crosses: A Mathematical Concept to Help Struggling Biology Students

    ERIC Educational Resources Information Center

    Baurhoo, Neerusha; Darwish, Shireef

    2012-01-01

    Predicting phenotypic outcomes from genetic crosses is often very difficult for biology students, especially those with learning disabilities. With our mathematical concept, struggling students in inclusive biology classrooms are now better equipped to solve genetic problems and predict phenotypes, because of improved understanding of dominance…

  9. Bridge No. 1601, Third B&O Crossing, over CSX (former B&O) ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Bridge No. 1601, Third B&O Crossing, over CSX (former B&O) tracks and North Branch Road, looking northwest. - Western Maryland Railway, Cumberland Extension, Pearre to North Branch, from WM milepost 125 to 160, Pearre, Washington County, MD

  10. Cross-over: a generalizable phenomenon necessary for secondary intraneural ganglion cyst formation.

    PubMed

    Spinner, Robert J; Amrami, Kimberly K; Wang, Huan; Kliot, Michel; Carmichael, Stephen W

    2008-03-01

    The appearances of intraneural ganglion cysts are being elucidated. We previously introduced the cross-over phenomenon to explain how a fibular (peroneal) or tibial intraneural ganglion cyst arising from the superior tibiofibular joint could give rise to multiple cysts: cyst fluid ascending up the primarily affected nerve could reach the level of the sciatic nerve, fill its common epineurial sheath and spread circumferentially (cross over), at which time pressure fluxes could result in further ascent up the sciatic or descent down the same parent nerve or the opposite, previously unaffected fibular or tibial nerves. In this study, we hypothesized that cross-over could occur in other nerves, potentially leading to the formation of more than one intraneural ganglion cyst in such situations. We analyzed the literature and identified a single case that we could review where proximal extension of an intraneural ganglion cyst involving a nerve at a different site could theoretically undergo cross-over in another major nerve large enough for available magnetic resonance images to resolve this finding. A case of a suprascapular intraneural ganglion cyst previously reported by our group that arose from the glenohumeral joint and extended to the neck was reanalyzed for the presence or absence of cross-over. An injection of dye into the outer epineurium of the suprascapular nerve in a fresh cadaveric specimen was performed to test for cross-over experimentally. Retrospective review of this case of suprascapular intraneural ganglion cyst demonstrated evidence to support previously unrecognized cross-over at the level of the upper trunk, with predominant ascent up the C5 and the C6 nerve roots and subtle descent down the anterior and posterior divisions of the upper trunk as well as the proximal portion of the suprascapular nerve. This appearance gave rise to multiple interconnected intraneural ganglion cysts arising from a single distant connection to the glenohumeral joint

  11. A mixed effects model for the analysis of repeated measures cross-over studies.

    PubMed

    Putt, M; Chinchilli, V M

    1999-11-30

    A mixed effects model is developed for cross-over trials in which the response is measured repeatedly within each time period. Relative to previous work on repeated measures cross-overs, the methodology synthesizes two important features. First, our procedure eliminates preliminary testing for carry-over, defined loosely as the component of a response that is due to treatment in the preceding period. This is achieved by generalizing the methodology to cross-over designs in which preliminary testing for carry-over is unnecessary. We focus largely on 'simple' carry-over, that is, carry-over that lasts for exactly one period and is independent of the treatment administered in the period in which the carry-over occurs. However, we also illustrate a modification of the procedure for a repeated measures cross-over design which uses a more complicated model of carry-over. Second, the model allows both the between- and within-subject variance to differ among treatments. Conditions are described wherein closed-form (CF) solutions to the variance components as well as closed-form hypothesis tests of the treatment differences exist. Flexibility in the model is illustrated with an example in which inference based on the CF likelihood-based estimates of the variance, and estimates formed using an iterative routine (PROC MIXED) are compared. Copyright 1999 John Wiley & Sons, Ltd.

  12. Calculation of linearized supersonic flow over slender cones of arbitrary cross section

    NASA Technical Reports Server (NTRS)

    Mascitti, V. R.

    1972-01-01

    Supersonic linearized conical-flow theory is used to determine the flow over slender pointed cones having horizontal and vertical planes of symmetry. The geometry of the cone cross sections and surface velocities are expanded in Fourier series. The symmetry condition permits the uncoupling of lifting and nonlifting solutions. The present method reduces to Ward's theory for flow over a cone of elliptic cross section. Results are also presented for other shapes. Results by this method diverge for cross-sectional shapes where the maximum thickness is large compared with the minimum thickness. However, even for these slender-body shapes, lower order solutions are good approximations to the complete solution.

  13. Genetic Gains Through Testing and Crossing Longleaf Pine Plus Trees

    Treesearch

    Calvin F. Bey; E. Bayne Snyder

    1978-01-01

    A progeny test of 226 superior tree selections from nine geographic sources across the South confirmed earlier results that showed the Gulf Coast source superior in survival and growth. Family variation within a region was large and provided additional genetic gain. Control-pollinated tests of elite x elite trees yielded even more gains. Progeny of the elite x elite...

  14. Experimental evolution of phenotypic plasticity: how predictive are cross-environment genetic correlations?

    PubMed

    Czesak, Mary Ellen; Fox, Charles W; Wolf, Jason B

    2006-09-01

    Genetic correlations are often predictive of correlated responses of one trait to selection on another trait. There are examples, however, in which genetic correlations are not predictive of correlated responses. We examine how well a cross-environment genetic correlation predicts correlated responses to selection and the evolution of phenotypic plasticity in the seed beetle Stator limbatus. This beetle exhibits adaptive plasticity in egg size by laying large eggs on a resistant host and small eggs on a high-quality host. From a half-sib analysis, the cross-environment genetic correlation estimate was large and positive (rA=0.99). However, an artificial-selection experiment on egg size found that the realized genetic correlations were positive but asymmetrical; that is, they depended on both the host on which selection was imposed and the direction of selection. The half-sib estimate poorly predicted the evolution of egg size plasticity; plasticity evolved when selection was imposed on one host but did not evolve when selection was imposed on the other host. We use a simple two-locus additive genetic model to explore the conditions that can generate the observed realized genetic correlation and the observed pattern of plasticity evolution. Our model and experimental results indicate that the ability of genetic correlations to predict correlated responses to selection depends on the underlying genetic architecture producing the genetic correlation.

  15. Sex-specific genetic variance and the evolution of sexual dimorphism: a systematic review of cross-sex genetic correlations.

    PubMed

    Poissant, Jocelyn; Wilson, Alastair J; Coltman, David W

    2010-01-01

    The independent evolution of the sexes may often be constrained if male and female homologous traits share a similar genetic architecture. Thus, cross-sex genetic covariance is assumed to play a key role in the evolution of sexual dimorphism (SD) with consequent impacts on sexual selection, population dynamics, and speciation processes. We compiled cross-sex genetic correlations (r(MF)) estimates from 114 sources to assess the extent to which the evolution of SD is typically constrained and test several specific hypotheses. First, we tested if r(MF) differed among trait types and especially between fitness components and other traits. We also tested the theoretical prediction of a negative relationship between r(MF) and SD based on the expectation that increases in SD should be facilitated by sex-specific genetic variance. We show that r(MF) is usually large and positive but that it is typically smaller for fitness components. This demonstrates that the evolution of SD is typically genetically constrained and that sex-specific selection coefficients may often be opposite in sign due to sub-optimal levels of SD. Most importantly, we confirm that sex-specific genetic variance is an important contributor to the evolution of SD by validating the prediction of a negative correlation between r(MF) and SD.

  16. Inherited differences in crossing over and gene conversion frequencies between wild strains of Sordaria fimicola from "Evolution Canyon".

    PubMed

    Saleem, M; Lamb, B C; Nevo, E

    2001-12-01

    Recombination generates new combinations of existing genetic variation and therefore may be important in adaptation and evolution. We investigated whether there was natural genetic variation for recombination frequencies and whether any such variation was environment related and possibly adaptive. Crossing over and gene conversion frequencies often differed significantly in a consistent direction between wild strains of the fungus Sordaria fimicola isolated from a harsher or a milder microscale environment in "Evolution Canyon," Israel. First- and second-generation descendants from selfing the original strains from the harsher, more variable, south-facing slope had higher frequencies of crossing over in locus-centromere intervals and of gene conversion than those from the lusher north-facing slopes. There were some significant differences between strains within slopes, but these were less marked than between slopes. Such inherited variation could provide a basis for natural selection for optimum recombination frequencies in each environment. There were no significant differences in meiotic hybrid DNA correction frequencies between strains from the different slopes. The conversion analysis was made using only conversions to wild type, because estimations of conversion to mutant were affected by a high frequency of spontaneous mutation. There was no polarized segregation of chromosomes at meiosis I or of chromatids at meiosis II.

  17. Inherited differences in crossing over and gene conversion frequencies between wild strains of Sordaria fimicola from "Evolution Canyon".

    PubMed Central

    Saleem, M; Lamb, B C; Nevo, E

    2001-01-01

    Recombination generates new combinations of existing genetic variation and therefore may be important in adaptation and evolution. We investigated whether there was natural genetic variation for recombination frequencies and whether any such variation was environment related and possibly adaptive. Crossing over and gene conversion frequencies often differed significantly in a consistent direction between wild strains of the fungus Sordaria fimicola isolated from a harsher or a milder microscale environment in "Evolution Canyon," Israel. First- and second-generation descendants from selfing the original strains from the harsher, more variable, south-facing slope had higher frequencies of crossing over in locus-centromere intervals and of gene conversion than those from the lusher north-facing slopes. There were some significant differences between strains within slopes, but these were less marked than between slopes. Such inherited variation could provide a basis for natural selection for optimum recombination frequencies in each environment. There were no significant differences in meiotic hybrid DNA correction frequencies between strains from the different slopes. The conversion analysis was made using only conversions to wild type, because estimations of conversion to mutant were affected by a high frequency of spontaneous mutation. There was no polarized segregation of chromosomes at meiosis I or of chromatids at meiosis II. PMID:11779798

  18. Handling Arabidopsis plants: growth, preservation of seeds, transformation, and genetic crosses.

    PubMed

    Rivero, Luz; Scholl, Randy; Holomuzki, Nicholas; Crist, Deborah; Grotewold, Erich; Brkljacic, Jelena

    2014-01-01

    Growing healthy plants is essential for the advancement of Arabidopsis thaliana (Arabidopsis) research. Over the last 20 years, the Arabidopsis Biological Resource Center (ABRC) has collected and developed a series of best-practice protocols, some of which are presented in this chapter. Arabidopsis can be grown in a variety of locations, growth media, and environmental conditions. Most laboratory accessions and their mutant or transgenic derivatives flower after 4-5 weeks and set seeds after 7-8 weeks, under standard growth conditions (soil, long day, 23 ºC). Some mutant genotypes, natural accessions, and Arabidopsis relatives require strict control of growth conditions best provided by growth rooms, chambers, or incubators. Other lines can be grown in less-controlled greenhouse settings. Although the majority of lines can be grown in soil, certain experimental purposes require utilization of sterile solid or liquid growth media. These include the selection of primary transformants, identification of homozygous lethal individuals in a segregating population, or bulking of a large amount of plant material. The importance of controlling, observing, and recording growth conditions is emphasized and appropriate equipment required to perform monitoring of these conditions is listed. Proper conditions for seed harvesting and preservation, as well as seed quality control, are also described. Plant transformation and genetic crosses, two of the methods that revolutionized Arabidopsis genetics, are introduced as well.

  19. Crossing-over in rearranging chromosomes of Drosophila: The role of delayed pairing

    SciTech Connect

    Chadov, B.F.; Chadova, E.V.; Khotskina, E.A.

    1995-11-01

    A Df(2R)MS2-10 deletion of pericentromeric heterochromatin and an Is(Y;2L)419 insertion of Y material in the region 34A, as well as nondisjunction of chromosomes 2 in 2/F(2L); F(2R) females did not directly prevent chromosome arms in chromosome 2 of Drosophila from pairing. However, these events resulted in (1) two- to four-fold decrease in the rate of crossing-over in chromosome 2; (2) a decreased proportion of exchange tetrads two to three times greater for multiple-exchange tetrads than for single-exchange ones; and (3) a decreased rate of crossing-over throughout the entire chromosome arm enhanced in a proximal direction. An In(1)dl-49+B{sup M1}inversion in the X chromosome cancelled the suppression of crossing-over. Crossing-over increased due to an increasing proportion of single-exchange tretrads. The changes in crossing-over found cannot be explained by asynapsis in the chromosomes with rearrangements. According to the authors, these changes are probably accounted for by a delayed pairing of these chromosomes. The delayed pairing of individual chromosome regions or the whole chromosome is considered the most common type of pairing disturbance. It effects on meiosis are discussed. 39 refs., 6 figs., 1 tab.

  20. A Cross-Sectional Study of Ageing and Cardiovascular Function over the Baboon Lifespan

    PubMed Central

    Yeung, Kristen R.; Pears, Suzanne; Heffernan, Scott J.; Makris, Angela; Hennessy, Annemarie; Lind, Joanne M.

    2016-01-01

    Background Ageing is associated with changes at the molecular and cellular level that can alter cardiovascular function and ultimately lead to disease. The baboon is an ideal model for studying ageing due to the similarities in genetic, anatomical, physiological and biochemical characteristics with humans. The aim of this cross-sectional study was to investigate the changes in cardiovascular profile of baboons over the course of their lifespan. Methods Data were collected from 109 healthy baboons (Papio hamadryas) at the Australian National Baboon Colony. A linear regression model, adjusting for sex, was used to analyse the association between age and markers of ageing with P < 0.01 considered significant. Results Male (n = 49, 1.5–28.5 years) and female (n = 60, 1.8–24.6 years) baboons were included in the study. Age was significantly correlated with systolic (R2 = 0.23, P < 0.001) and diastolic blood pressure (R2 = 0.44, P < 0.001), with blood pressure increasing with age. Age was also highly correlated with core augmentation index (R2 = 0.17, P < 0.001) and core pulse pressure (R2 = 0.30, P < 0.001). Creatinine and urea were significantly higher in older animals compared to young animals (P < 0.001 for both). Older animals (>12 years) had significantly shorter telomeres when compared to younger (<3 years) baboons (P = 0.001). Conclusion This study is the first to demonstrate that cardiovascular function alters with age in the baboon. This research identifies similarities within cardiovascular parameters between humans and baboon even though the length of life differs between the two species. PMID:27427971

  1. Tryptophan depletion in chronic fatigue syndrome, a pilot cross-over study.

    PubMed

    The, Gerard K H; Verkes, Robbert J; Fekkes, Durk; Bleijenberg, Gijs; van der Meer, Jos W M; Buitelaar, Jan K

    2014-09-16

    Chronic fatigue syndrome (CFS) is still an enigmatic disorder. CFS can be regarded as a complex disorder with tremendous impact on lives of CFS-patients. Full recovery without treatment is rare. A somatic explanation for the fatigue is lacking. There is clinical and experimental evidence implicating enhanced serotonergic neurotransmission in CFS. Genetic studies and imaging studies support the hypothesis of upregulated serotonin system in CFS. In line with the hypothesis of an increased serotonergic state in CFS, we performed a randomised clinical trial investigated the effect of 5-HT3 receptor antagonism in CFS. No benefit was found of the 5-HT3 receptor antagonist ondansetron compared to placebo.To further investigate the involvement of serotonin in CFS we performed a placebo controlled cross over pilot study investigating the effect of Acute Tryptophan Depletion. Five female CFS-patients who met the US Center for Disease Control and Prevention criteria for CFS were recruited. There were two test days, one week apart. Each participant received placebo and ATD. To evaluate the efficacy of the ATD procedure tryptophan and the large neutral amino acids were measured. The outcome measures were fatigue severity, concentration and mood states. ATD resulted in a significant plasma tryptophan to large neutral amino acid ratio reduction of 96%. There were no significant differences in fatigue-, depression and concentration between the placebo- and ATD condition. These first five CFS-patients did not respond to the ATD procedure. However, a much larger sample size is needed to draw final conclusions on the hypothesis of an increased serotonergic state in the pathophysiology of CFS. ISRCTN07518149.

  2. Bi- and multivariate analyses of diallel crosses: a tool for the genetic dissection of neurobehavioral phenotypes.

    PubMed

    Crusio, W E

    1993-01-01

    The genetic-correlational approach provides a very powerful tool for the analysis of causal relationships between phenotypes. It appears to be particularly appropriate for investigating the functional organization of behavior and/or causal relationships between brain and behavior. A method for the bivariate analysis of diallel crosses that permits the estimation of correlations due to environmental effects, additive-genetic effects, and/or dominance deviations is described, together with a worked-out example stemming from a five times replicated 4 x 4 diallel cross between inbred mouse strains. The phenotypes chosen to illustrate the analysis were locomotor activity and rearing frequency in an open field. Large, positive additive-genetic and dominance correlations between these two phenotypes were obtained. This finding was replicated in another, independently executed, diallel cross.

  3. CRISPR-directed mitotic recombination enables genetic mapping without crosses.

    PubMed

    Sadhu, Meru J; Bloom, Joshua S; Day, Laura; Kruglyak, Leonid

    2016-05-27

    Linkage and association studies have mapped thousands of genomic regions that contribute to phenotypic variation, but narrowing these regions to the underlying causal genes and variants has proven much more challenging. Resolution of genetic mapping is limited by the recombination rate. We developed a method that uses CRISPR (clustered, regularly interspaced, short palindromic repeats) to build mapping panels with targeted recombination events. We tested the method by generating a panel with recombination events spaced along a yeast chromosome arm, mapping trait variation, and then targeting a high density of recombination events to the region of interest. Using this approach, we fine-mapped manganese sensitivity to a single polymorphism in the transporter Pmr1. Targeting recombination events to regions of interest allows us to rapidly and systematically identify causal variants underlying trait differences. Copyright © 2016, American Association for the Advancement of Science.

  4. A Genetic Map of the Mouse Suitable for Typing Intraspecific Crosses

    PubMed Central

    Dietrich, W.; Katz, H.; Lincoln, S. E.; Shin, H. S.; Friedman, J.; Dracopoli, N. L.; Lander, E. S.

    1992-01-01

    We report the construction of a genetic linkage map of the mouse, consisting entirely of genetic markers that can be rapidly typed by polymerase chain reaction and that show a high degree of polymorphism among inbred laboratory strains. Specifically, the map contains 317 simple sequence length polymorphisms at an average spacing of 4.3 cM and is detectably linked to approximately 99% of the mouse genome. In typical crosses between inbred laboratory strains, about 50% of the markers are polymorphic, making it straightforward to follow inheritance in almost any cross. PMID:1353738

  5. Peri-event cross-correlation over time for analysis of interactions in neuronal firing.

    PubMed

    Paiva, António R C; Park, Il; Sanchez, Justin C; Príncipe, José C

    2008-01-01

    Several methods have been described in the literature to verify the presence of couplings between neurons in the brain. In this paper we introduce the peri-event cross-correlation over time (PECCOT) to describe the interaction among the two neurons as a function of the event onset. Instead of averaging over time, the PECCOT averages the cross-correlation over instances of the event. As a consequence, the PECCOT is able to characterize with high temporal resolution the interactions over time among neurons. To illustrate the method, the PECCOT is applied to a simulated dataset and for analysis of synchrony in recordings of a rat performing a go/no go behavioral lever press task. We verify the presence of synchrony before the lever press time and its suppression afterwards.

  6. The Collaborative Cross Resource for Systems Genetics Research of Infectious Diseases.

    PubMed

    Maurizio, Paul L; Ferris, Martin T

    2017-01-01

    An increasing body of evidence highlights the role of host genetic variation in driving susceptibility to severe disease following pathogen infection. In order to fully appreciate the importance of host genetics on infection susceptibility and resulting disease, genetically variable experimental model systems should be employed. These systems allow for the identification, characterization, and mechanistic dissection of genetic variants that cause differential disease responses. Herein we discuss application of the Collaborative Cross (CC) panel of recombinant inbred strains to study viral pathogenesis, focusing on practical considerations for experimental design, assessment and analysis of disease responses within the CC, as well as some of the resources developed for the CC. Although the focus of this chapter is on viral pathogenesis, many of the methods presented within are applicable to studies of other pathogens, as well as to case-control designs in genetically diverse populations.

  7. Double blind cross-over study of a new appetite suppressant AN 448.

    PubMed

    Haugen, H N

    1975-01-01

    The effects of a new appetite suppressant, AN 448, and a placebo have been compared in 30 obese individuals using a fully randomized double-blind cross-over design. 1 mg of AN 448 t.i.d. produced a significant degree of appetite suppression and a mean weight loss of more than 4 kg per individual over a 6 week period. Side effects were few and no haematological, renal or hepatic damage was observed.

  8. Kinematic head and trunk strategies used by hemiplegic stroke patients crossing over obstacles of different heights

    PubMed Central

    Han, Jin-Tae; Lee, Jung-Hoon; Fell, Dennis W.

    2017-01-01

    [Purpose] The purpose of this study was to compare kinematic data regarding the head, trunk, and pelvis strategies used by individuals with hemiplegia when crossing over obstacles of different heights. [Subjects and Methods] Nine adults with hemiplegia from stroke (7 males and 2 females) participated in this study. A motion analysis system with six infrared cameras was used to measure the kinematic data of the head, trunk, and pelvis while the subjects crossed over obstacles of different heights. Repeated measures ANOVA analysis was performed to compare the resulting kinematic data. [Results] An increase in the magnitude of the kinematic data of the head, trunk, and pelvis of the hemiparetic stroke patients was observed when the height of the obstacles, which they crossed over, increased. [Conclusion] This study described the kinematic strategies, with regard to the head, trunk, and pelvis, used by hemiplegic patients crossing over obstacles of different heights. The results indicate that these kinematic strategies primarily change when the obstacle height was 20% of the height of the subjects. PMID:28210053

  9. Bridge No. 1601, Third B&O Crossing, over CSX tracks in ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Bridge No. 1601, Third B&O Crossing, over CSX tracks in North Branch, Maryland, looking northwest. The Pittsburgh Plate Glass Plant can be seen in the background. NPS property boundary is out of view at lower right. - Western Maryland Railway, Cumberland Extension, Pearre to North Branch, from WM milepost 125 to 160, Pearre, Washington County, MD

  10. High genetic differentiation and cross-shelf patterns of genetic diversity among Great Barrier Reef populations of Symbiodinium

    NASA Astrophysics Data System (ADS)

    Howells, E. J.; van Oppen, M. J. H.; Willis, B. L.

    2009-03-01

    The resilience of Symbiodinium harboured by corals is dependent on the genetic diversity and extent of connectivity among reef populations. This study presents genetic analyses of Great Barrier Reef (GBR) populations of clade C Symbiodinium hosted by the alcyonacean coral, Sinularia flexibilis. Allelic variation at four newly developed microsatellite loci demonstrated that Symbiodinium populations are genetically differentiated at all spatial scales from 16 to 1,360 km (pairwise ΦST = 0.01-0.47, mean = 0.22); the only exception being two neighbouring populations in the Cairns region separated by 17 km. This indicates that gene flow is restricted for Symbiodinium C hosted by S. flexibilis on the GBR. Patterns of population structure reflect longshore circulation patterns and limited cross-shelf mixing, suggesting that passive transport by currents is the primary mechanism of dispersal in Symbiodinium types that are acquired horizontally. There was no correlation between the genetic structure of Symbiodinium populations and their host S. flexibilis, most likely because different factors affect the dispersal and recruitment of each partner in the symbiosis. The genetic diversity of these Symbiodinium reef populations is on average 1.5 times lower on inshore reefs than on offshore reefs. Lower inshore diversity may reflect the impact of recent bleaching events on Sinularia assemblages, which have been more widespread and severe on inshore reefs, but may also have been shaped by historical sea level fluctuations or recent migration patterns.

  11. Approaching the Functional Annotation of Fungal Virulence Factors Using Cross-Species Genetic Interaction Profiling

    PubMed Central

    Brown, Jessica C. S.; Madhani, Hiten D.

    2012-01-01

    In many human fungal pathogens, genes required for disease remain largely unannotated, limiting the impact of virulence gene discovery efforts. We tested the utility of a cross-species genetic interaction profiling approach to obtain clues to the molecular function of unannotated pathogenicity factors in the human pathogen Cryptococcus neoformans. This approach involves expression of C. neoformans genes of interest in each member of the Saccharomyces cerevisiae gene deletion library, quantification of their impact on growth, and calculation of the cross-species genetic interaction profiles. To develop functional predictions, we computed and analyzed the correlations of these profiles with existing genetic interaction profiles of S. cerevisiae deletion mutants. For C. neoformans LIV7, which has no S. cerevisiae ortholog, this profiling approach predicted an unanticipated role in the Golgi apparatus. Validation studies in C. neoformans demonstrated that Liv7 is a functional Golgi factor where it promotes the suppression of the exposure of a specific immunostimulatory molecule, mannose, on the cell surface, thereby inhibiting phagocytosis. The genetic interaction profile of another pathogenicity gene that lacks an S. cerevisiae ortholog, LIV6, strongly predicted a role in endosome function. This prediction was also supported by studies of the corresponding C. neoformans null mutant. Our results demonstrate the utility of quantitative cross-species genetic interaction profiling for the functional annotation of fungal pathogenicity proteins of unknown function including, surprisingly, those that are not conserved in sequence across fungi. PMID:23300468

  12. Approaching the functional annotation of fungal virulence factors using cross-species genetic interaction profiling.

    PubMed

    Brown, Jessica C S; Madhani, Hiten D

    2012-01-01

    In many human fungal pathogens, genes required for disease remain largely unannotated, limiting the impact of virulence gene discovery efforts. We tested the utility of a cross-species genetic interaction profiling approach to obtain clues to the molecular function of unannotated pathogenicity factors in the human pathogen Cryptococcus neoformans. This approach involves expression of C. neoformans genes of interest in each member of the Saccharomyces cerevisiae gene deletion library, quantification of their impact on growth, and calculation of the cross-species genetic interaction profiles. To develop functional predictions, we computed and analyzed the correlations of these profiles with existing genetic interaction profiles of S. cerevisiae deletion mutants. For C. neoformans LIV7, which has no S. cerevisiae ortholog, this profiling approach predicted an unanticipated role in the Golgi apparatus. Validation studies in C. neoformans demonstrated that Liv7 is a functional Golgi factor where it promotes the suppression of the exposure of a specific immunostimulatory molecule, mannose, on the cell surface, thereby inhibiting phagocytosis. The genetic interaction profile of another pathogenicity gene that lacks an S. cerevisiae ortholog, LIV6, strongly predicted a role in endosome function. This prediction was also supported by studies of the corresponding C. neoformans null mutant. Our results demonstrate the utility of quantitative cross-species genetic interaction profiling for the functional annotation of fungal pathogenicity proteins of unknown function including, surprisingly, those that are not conserved in sequence across fungi.

  13. Genetic changes of survival traits over the past 25 yr in Dutch dairy cattle.

    PubMed

    van Pelt, M L; Ducrocq, V; de Jong, G; Calus, M P L; Veerkamp, R F

    2016-12-01

    Genetic correlations and heritabilities for survival were investigated over a period of 25 yr to evaluate if survival in first lactation has become a different trait and if this is affected by adjusting for production level. Survival after first calving until 12mo after calving (surv_12mo) and survival of first lactation (surv_1st_lac) were analyzed in Dutch black-and-white cows. The data set contained 1,108,745 animals for surv_12mo and 1,062,276 animals for surv_1st_lac, with first calving between 1989 and 2013. The trait survival as recorded over 25 yr was split in five 5-yr intervals to enable a multitrait analysis. Bivariate models using subsets of the full data set and multitrait and autoregressive models using the full data set were used. Survival and functional survival were analyzed. Functional survival was defined as survival adjusted for within-herd production level for 305-d yield of combined kilograms of fat and protein. Mean survival increased over time, whereas genetic variances and heritability decreased. Bivariate models yielded large standard errors on genetic correlations due to poor connectedness between the extreme 5-yr intervals. The more parsimonious models using the full data set gave nonunity genetic correlations. Genetic correlations for survival were below 0.90 between intervals separated by 1 or more 5-yr intervals. Genetic correlations for functional survival did not indicate that definition of survival changed (≥0.90). The difference in genetic correlations between survival and functional survival is likely explained by lower emphasis of dairy farmers on culling in first lactation for low yield in more recent years. This suggests that genetic evaluation for longevity using historical data should analyze functional survival rather than survival. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  14. Genetic and QTL analysis of resistance to Xiphinema index in a grapevine cross.

    PubMed

    Xu, K; Riaz, S; Roncoroni, N C; Jin, Y; Hu, R; Zhou, R; Walker, M A

    2008-01-01

    Resistance to the dagger nematode Xiphinema index has been an important objective in grape rootstock breeding programs. This nematode not only causes severe feeding damage to the root system, but it also vectors grapevine fanleaf virus (GFLV), the causal agent of fanleaf degeneration and one of the most severe viral diseases of grape. The established screening procedures for dagger nematode resistance are time consuming and can produce inconsistent results. A fast and reliable greenhouse-based system for screening resistance to X. index that is suitable for genetic studies and capable of evaluating breeding populations is needed. In this report, the dynamics of nematode numbers, gall formation, and root weight loss were investigated using a variety of soil mixes and pot sizes over a 52-week period. Results indicated that the number of galls formed was correlated with the size of the nematode population and with the degree of root weight loss. After inoculation with 100 nematodes, gall formation could be reliably evaluated in 4-8 weeks in most plant growth conditions and results were obtained 6 months more rapidly than past evaluation methods. This modified X. index resistance screening method was successfully applied to 185 of the 188 F(1) progeny from a cross of D8909-15 x F8909-17 (the 9621 population), which segregates for a form of X. index resistance originally derived from Vitis arizonica. Quantitative trait loci (QTL) analysis was carried out on both parental genetic maps of 255 markers using MapQTL 4.0. Results revealed that X. index resistance is controlled by a major QTL, designated Xiphinema index Resistance 1 (XiR1), near marker VMC5a10 on chromosome 19. The XiR1 QTL was supported by a LOD score of 36.9 and explained 59.9% of the resistance variance in the mapping population.

  15. Using the Collaborative Cross to Study the Role of Genetic Diversity in Cancer-Related Phenotypes.

    PubMed

    Reilly, Karlyne M

    2016-03-01

    Human populations are genetically diverse and often a single mouse model can only represent a small subset of the human population. Studying genetic diversity directly can improve the predictive value of mouse models of cancer biology and research on the effects of carcinogens and therapeutics in humans. The collaborative cross is a panel of inbred mouse lines that captures 90% of the genetic diversity of the Mus musculus strain and can help identify regions of the genome that are responsible for variation in cancer phenotypes across the population. The appropriate procedure will depend on the mouse model used; here, three mouse cross designs are described as examples. © 2016 Cold Spring Harbor Laboratory Press.

  16. GACD: Integrated Software for Genetic Analysis in Clonal F1 and Double Cross Populations.

    PubMed

    Zhang, Luyan; Meng, Lei; Wu, Wencheng; Wang, Jiankang

    2015-01-01

    Clonal species are common among plants. Clonal F1 progenies are derived from the hybridization between 2 heterozygous clones. In self- and cross-pollinated species, double crosses can be made from 4 inbred lines. A clonal F1 population can be viewed as a double cross population when the linkage phase is determined. The software package GACD (Genetic Analysis of Clonal F1 and Double cross) is freely available public software, capable of building high-density linkage maps and mapping quantitative trait loci (QTL) in clonal F1 and double cross populations. Three functionalities are integrated in GACD version 1.0: binning of redundant markers (BIN); linkage map construction (CDM); and QTL mapping (CDQ). Output of BIN can be directly used as input of CDM. After adding the phenotypic data, the output of CDM can be used as input of CDQ. Thus, GACD acts as a pipeline for genetic analysis. GACD and example datasets are freely available from www.isbreeding.net. © The American Genetic Association. 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Frequency of nonallelic homologous recombination is correlated with length of homology: evidence that ectopic synapsis precedes ectopic crossing-over.

    PubMed

    Liu, Pengfei; Lacaria, Melanie; Zhang, Feng; Withers, Marjorie; Hastings, P J; Lupski, James R

    2011-10-07

    Genomic disorders constitute a class of diseases that are associated with DNA rearrangements resulting from region-specific genome instability, that is, genome architecture incites genome instability. Nonallelic homologous recombination (NAHR) or crossing-over in meiosis between sequences that are not in allelic positions (i.e., paralogous sequences) can result in recurrent deletions or duplications causing genomic disorders. Previous studies of NAHR have focused on description of the phenomenon, but it remains unclear how NAHR occurs during meiosis and what factors determine its frequency. Here we assembled two patient cohorts with reciprocal genomic disorders; deletion associated Smith-Magenis syndrome and duplication associated Potocki-Lupski syndrome. By assessing the full spectrum of rearrangement types from the two cohorts, we find that complex rearrangements (those with more than one breakpoint) are more prevalent in copy-number gains (17.7%) than in copy-number losses (2.3%); an observation that supports a role for replicative mechanisms in complex rearrangement formation. Interestingly, for NAHR-mediated recurrent rearrangements, we show that crossover frequency is positively associated with the flanking low-copy repeat (LCR) length and inversely influenced by the inter-LCR distance. To explain this, we propose that the probability of ectopic chromosome synapsis increases with increased LCR length, and that ectopic synapsis is a necessary precursor to ectopic crossing-over. Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  18. Testing Predictions of the Double-Strand Break Repair Model Relating to Crossing Over in Mammalian Cells

    PubMed Central

    Birmingham, Erin C.; Lee, Shauna A.; McCulloch, Richard D.; Baker, Mark D.

    2004-01-01

    In yeast, four-stranded, biparental “joint molecules” containing a pair of Holliday junctions are demonstrated intermediates in the repair of meiotic double-strand breaks (DSBs). Genetic and physical evidence suggests that when joint molecules are resolved by the cutting of each of the two Holliday junctions, crossover products result at least most of the time. The double-strand break repair (DSBR) model is currently accepted as a paradigm for acts of DSB repair that lead to crossing over. In this study, a well-defined mammalian gene-targeting assay was used to test predictions that the DSBR model makes about the frequency and position of hDNA in recombinants generated by crossing over. The DSBR model predicts that hDNA will frequently form on opposite sides of the DSB in the two homologous sequences undergoing recombination [half conversion (HC); 5:3, 5:3 segregation]. By examining the segregation patterns of poorly repairable small palindrome genetic markers, we show that this configuration of hDNA is rare. Instead, in a large number of recombinants, full conversion (FC) events in the direction of the unbroken chromosomal sequence (6:2 segregation) were observed on one side of the DSB. A conspicuous fraction of the unidirectional FC events was associated with normal 4:4 marker segregation on the other side of the DSB. In addition, a large number of recombinants displayed evidence of hDNA formation. In several, hDNA was symmetrical on one side of the DSB, suggesting that the two homologous regions undergoing recombination swapped single strands of the same polarity. These data are considered within the context of modified versions of the DSBR model. PMID:15579705

  19. A novel Lie algebra of the genetic code over the Galois field of four DNA bases.

    PubMed

    Sánchez, Robersy; Grau, Ricardo; Morgado, Eberto

    2006-07-01

    Starting from the four DNA bases order in the Boolean lattice, a novel Lie Algebra of the genetic code is proposed. Here, the main partitions of the genetic code table were obtained as equivalent classes of quotient spaces of the genetic code vector space over the Galois field of the four DNA bases. The new algebraic structure shows strong connections among algebraic relationships, codon assignments and physicochemical properties of amino acids. Moreover, a distance defined between codons expresses a physicochemical meaning. It was also noticed that the distance between wild type and mutant codons tends to be small in mutational variants of four genes: human phenylalanine hydroxylase, human beta-globin, HIV-1 protease and HIV-1 reverse transcriptase. These results strongly suggest that deterministic rules in genetic code origin must be involved.

  20. SPECIFIC AND CROSS-OVER EFFECTS OF FOAM ROLLING ON ANKLE DORSIFLEXION RANGE OF MOTION

    PubMed Central

    Beardsley, Chris

    2016-01-01

    ABSTRACT Background Flexibility is an important physical quality. Self-myofascial release (SMFR) methods such as foam rolling (FR) increase flexibility acutely but how long such increases in range of motion (ROM) last is unclear. Static stretching (SS) also increases flexibility acutely and produces a cross-over effect to contralateral limbs. FR may also produce a cross-over effect to contralateral limbs but this has not yet been identified. Purpose To explore the potential cross-over effect of SMFR by investigating the effects of a FR treatment on the ipsilateral limb of 3 bouts of 30 seconds on changes in ipsilateral and contralateral ankle DF ROM and to assess the time-course of those effects up to 20 minutes post-treatment. Methods A within- and between-subject design was carried out in a convenience sample of 26 subjects, allocated into FR (n=13) and control (CON, n=13) groups. Ankle DF ROM was recorded at baseline with the in-line weight-bearing lunge test for both ipsilateral and contralateral legs and at 0, 5, 10, 15, 20 minutes following either a two-minute seated rest (CON) or 3 3 30 seconds of FR of the plantar flexors of the dominant leg (FR). Repeated measures ANOVA was used to examine differences in ankle DF ROM. Results No significant between-group effect was seen following the intervention. However, a significant within-group effect (p<0.05) in the FR group was seen between baseline and all post-treatment time-points (0, 5, 10, 15 and 20 minutes). Significant within-group effects (p<0.05) were also seen in the ipsilateral leg between baseline and at all post-treatment time-points, and in the contralateral leg up to 10 minutes post-treatment, indicating the presence of a cross-over effect. Conclusions FR improves ankle DF ROM for at least 20 minutes in the ipsilateral limb and up to 10 minutes in the contralateral limb, indicating that FR produces a cross-over effect into the contralateral limb. The mechanism producing these cross-over effects is

  1. Cross-layer restoration with software defined networking based on IP over optical transport networks

    NASA Astrophysics Data System (ADS)

    Yang, Hui; Cheng, Lei; Deng, Junni; Zhao, Yongli; Zhang, Jie; Lee, Young

    2015-10-01

    The IP over optical transport network is a very promising networking architecture applied to the interconnection of geographically distributed data centers due to the performance guarantee of low delay, huge bandwidth and high reliability at a low cost. It can enable efficient resource utilization and support heterogeneous bandwidth demands in highly-available, cost-effective and energy-effective manner. In case of cross-layer link failure, to ensure a high-level quality of service (QoS) for user request after the failure becomes a research focus. In this paper, we propose a novel cross-layer restoration scheme for data center services with software defined networking based on IP over optical network. The cross-layer restoration scheme can enable joint optimization of IP network and optical network resources, and enhance the data center service restoration responsiveness to the dynamic end-to-end service demands. We quantitatively evaluate the feasibility and performances through the simulation under heavy traffic load scenario in terms of path blocking probability and path restoration latency. Numeric results show that the cross-layer restoration scheme improves the recovery success rate and minimizes the overall recovery time.

  2. Genetic analysis of albuminuria in collaborative cross and multiple mouse intercross populations

    PubMed Central

    Thaisz, Jill; Tsaih, Shirng-Wern; Feng, Minjie; Philip, Vivek M.; Zhang, Yunyu; Yanas, Liane; Sheehan, Susan; Xu, Lingfei; Miller, Darla R.; Paigen, Beverly; Chesler, Elissa J.; Churchill, Gary A.

    2012-01-01

    Albuminuria is an important marker of nephropathy that increases the risk of progressive renal and chronic cardiovascular diseases. The genetic basis of kidney disease is well-established in humans and rodent models, but the causal genes remain to be identified. We applied several genetic strategies to map and refine genetic loci affecting albuminuria in mice and translated the findings to human kidney disease. First, we measured albuminuria in mice from 33 inbred strains, used the data for haplotype association mapping (HAM), and detected 10 genomic regions associated with albuminuria. Second, we performed eight F2 intercrosses between genetically diverse strains to identify six loci underlying albuminuria, each of which was concordant to kidney disease loci in humans. Third, we used the Oak Ridge National Laboratory incipient Collaborative Cross subpopulation to detect an additional novel quantitative trait loci (QTL) underlying albuminuria. We also performed a ninth intercross, between genetically similar strains, that substantially narrowed an albuminuria QTL on Chromosome 17 to a region containing four known genes. Finally, we measured renal gene expression in inbred mice to detect pathways highly correlated with albuminuria. Expression analysis also identified Glcci1, a gene known to affect podocyte structure and function in zebrafish, as a strong candidate gene for the albuminuria QTL on Chromosome 6. Overall, these findings greatly enhance our understanding of the genetic basis of albuminuria in mice and may guide future studies into the genetic basis of kidney disease in humans. PMID:22859403

  3. Anomalous compressibility of ferropericlase throughout the iron spin cross-over

    PubMed Central

    Wentzcovitch, R. M.; Justo, J. F.; Wu, Z.; da Silva, C. R. S.; Yuen, D. A.; Kohlstedt, D.

    2009-01-01

    The thermoelastic properties of ferropericlase Mg1−xFexO (x = 0.1875) throughout the iron high-to-low spin cross-over have been investigated by first principles at Earth's lower mantle conditions. This cross-over has important consequences for elasticity such as an anomalous bulk modulus (KS) reduction. At room temperature the anomaly is somewhat sharp in pressure but broadens with increasing temperature. Along a typical geotherm it occurs across most of the lower mantle with a more significant KS reduction at ≈1,400–1,600 km depth. This anomaly might also cause a reduction in the effective activation energy for diffusion creep and lead to a viscosity minimum in the mid-lower mantle, in apparent agreement with results from inversion of data related with mantle convection and postglacial rebound. PMID:19439661

  4. A Two-Pathway Analysis of Meiotic Crossing Over and Gene Conversion in Saccharomyces cerevisiae

    PubMed Central

    Stahl, Franklin W.; Foss, Henriette M.

    2010-01-01

    Several apparently paradoxical observations regarding meiotic crossing over and gene conversion are readily resolved in a framework that recognizes the existence of two recombination pathways that differ in mismatch repair, structures of intermediates, crossover interference, and the generation of noncrossovers. One manifestation of these differences is that simultaneous gene conversion on both sides of a recombination-initiating DNA double-strand break (“two-sidedness”) characterizes only one of the two pathways and is promoted by mismatch repair. Data from previous work are analyzed quantitatively within this framework, and a molecular model for meiotic double-strand break repair based on the concept of sliding D-loops is offered as an efficient scheme for visualizing the salient results from studies of crossing over and gene conversion, the molecular structures of recombination intermediates, and the biochemical competencies of the proteins involved. PMID:20679514

  5. [Homologue pairing: initiation sites and effects on crossing over and chromosome disjunction in Drosophila melanogaster].

    PubMed

    Chubykin, V L

    1996-01-01

    The role of homologue pairing and chromocentral association of chromosomes in recombination and segregation during cell division is discussed. Peculiarities of mitotic and meiotic chromosome pairing in Drosophila males and females are considered. On the basis of our own and published data, the presence and localization of sites of homologue pairing initiation in euchromatin are substantiated. The effects of transfer of initiation sites along a chromosome (exemplified by inversions) on chromosome pairing (asynapsis), crossing over (intrachromosomal, interchromosomal, and centromeric effects), and segregation are discussed. To record the effects of pairing sites on crossing over, a method of comparing crossing-over frequencies in an inverted region with those in a region of the same size and position with regard to the centromere on cytological maps was proposed. Chromosomes orient toward opposite division poles during paracentromeric heterochromatin pairing. This occurs after successful euchromatin pairing, during which the chromocentral circular structure is reorganized. If heterochromatin pairing is disrupted because of structural or locus mutations, nonexchange bivalents segregate randomly. In this case, chromosome coordination may occur due to proximal chiasmata or chromocentral associations between homologues.

  6. RNF212 is a dosage-sensitive regulator of crossing-over during mammalian meiosis

    PubMed Central

    Reynolds, April; Qiao, Huanyu; Yang, Ye; Chen, Jefferson K; Jackson, Neil; Biswas, Kajal; Holloway, J Kim; Baudat, Frédéric; de Massy, Bernard; Wang, Jeremy; Höög, Christer; Cohen, Paula E; Hunter, Neil

    2013-01-01

    Crossing-over ensures accurate chromosome segregation during meiosis, and every pair of chromosomes obtains at least one crossover, even though the majority of recombination sites yield non-crossovers. A putative regulator of crossing-over is RNF212, which is associated with variation in crossover rates in humans. We show that mouse RNF212 is essential for crossing-over, functioning to couple chromosome synapsis to the formation of crossover-specific recombination complexes. Selective localization of RNF212 to a subset of recombination sites is shown to be a key early step in the crossover designation process. RNF212 acts at these sites to stabilize meiosis-specific recombination factors, including the MutSγ complex (MSH4-MSH5). We infer that selective stabilization of key recombination proteins is a fundamental feature of meiotic crossover control. Haploinsufficiency indicates that RNF212 is a limiting factor for crossover control and raises the possibility that human alleles may alter the amount or stability of RNF212 and be risk factors for aneuploid conditions. PMID:23396135

  7. Genetic and phenotypic stability of measures of neuroticism over 22 years.

    PubMed

    Wray, Naomi R; Birley, Andrew J; Sullivan, Patrick F; Visscher, Peter M; Martin, Nicholas G

    2007-10-01

    People meeting diagnostic criteria for anxiety or depressive disorders tend to score high on the personality scale of neuroticism. Studying this dimension of personality can therefore give insights into the etiology of important psychiatric disorders. Neuroticism can be assessed easily via self-report questionnaires in large population samples. We have examined the genetic and phenotypic stability of neuroticism, measured up to 4 times over 22 years, on different scales, on a data set of 4,999 families with over 20,000 individuals completing at least 1 neuroticism questionnaire. The neuroticism scales used were the Eysenck Personality Questionnaire revised (EPQ-R), the EPQ-R shortened form, and the NEO 5 factor inventory personality questionnaire. The estimates of heritability of the individual measures ranged from .26 +/- .04 to .36 +/- .03. Genetic, environmental, and phenotypic correlations averaged .91, .42, and .57 respectively. Despite the range in heritabilities, a more parsimonious 'repeatability model' of equal additive genetic variances and genetic correlations of unity could not be rejected. Use of multiple measures increases the effective heritability from .33 for a single measure to .43 for mean score because of the reduction in the estimate of the environmental variance, and this will increase power in genetic linkage or association studies of neuroticism.

  8. Reading self-perceived ability, enjoyment and achievement: A genetically informative study of their reciprocal links over time.

    PubMed

    Malanchini, Margherita; Wang, Zhe; Voronin, Ivan; Schenker, Victoria J; Plomin, Robert; Petrill, Stephen A; Kovas, Yulia

    2017-04-01

    Extant literature has established a consistent association between aspects of reading motivation, such as enjoyment and self-perceived ability, and reading achievement, in that more motivated readers are generally more skilled readers. However, the developmental etiology of this relation is yet to be investigated. The present study explores the development of the motivation-achievement association and its genetic and environmental underpinnings. Applying cross-lagged design in a sample of 13,825 twins, we examined the relative contribution of genetic and environmental factors to the association between reading enjoyment and self-perceived ability and reading achievement. Children completed a reading comprehension task and self-reported their reading enjoyment and perceived ability twice in middle childhood: when they were 9-10 and 12 years old. Results showed a modest reciprocal association over time between reading motivation (enjoyment and perceived ability) and reading achievement. Reading motivation at age 9-10 statistically predicted the development of later achievement, and similarly, reading achievement at age 9-10 predicted the development of later motivation. This reciprocal association was observed beyond the stability of the variables and their contemporaneous correlation and was largely explained by genetic factors. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  9. Reading Self-Perceived Ability, Enjoyment and Achievement: A Genetically Informative Study of Their Reciprocal Links Over Time

    PubMed Central

    2017-01-01

    Extant literature has established a consistent association between aspects of reading motivation, such as enjoyment and self-perceived ability, and reading achievement, in that more motivated readers are generally more skilled readers. However, the developmental etiology of this relation is yet to be investigated. The present study explores the development of the motivation–achievement association and its genetic and environmental underpinnings. Applying cross-lagged design in a sample of 13,825 twins, we examined the relative contribution of genetic and environmental factors to the association between reading enjoyment and self-perceived ability and reading achievement. Children completed a reading comprehension task and self-reported their reading enjoyment and perceived ability twice in middle childhood: when they were 9–10 and 12 years old. Results showed a modest reciprocal association over time between reading motivation (enjoyment and perceived ability) and reading achievement. Reading motivation at age 9–10 statistically predicted the development of later achievement, and similarly, reading achievement at age 9–10 predicted the development of later motivation. This reciprocal association was observed beyond the stability of the variables and their contemporaneous correlation and was largely explained by genetic factors. PMID:28333527

  10. Development of genetic diversity, differentiation and structure over 500 years in four ponderosa pine populations.

    PubMed

    Lesser, M R; Parchman, T L; Jackson, S T

    2013-05-01

    Population history plays an important role in shaping contemporary levels of genetic variation and geographic structure. This is especially true in small, isolated range-margin populations, where effects of inbreeding, genetic drift and gene flow may be more pronounced than in large continuous populations. Effects of landscape fragmentation and isolation distance may have implications for persistence of range-margin populations if they are demographic sinks. We studied four small, disjunct populations of ponderosa pine over a 500-year period. We coupled demographic data obtained through dendroecological methods with microsatellite data to discern how and when contemporary levels of allelic diversity, among and within-population levels of differentiation, and geographic structure, arose. Alleles accumulated rapidly following initial colonization, demonstrating proportionally high levels of gene flow into the populations. At population sizes of approximately 100 individuals, allele accumulation saturated. Levels of genetic differentiation among populations (F(ST) and Jost's D(est)) and diversity within populations (F(IS)) remained stable through time. There was no evidence of geographic genetic structure at any time in the populations' history. Proportionally, high gene flow in the early stages of population growth resulted in rapid accumulation of alleles and quickly created relatively homogenous genetic patterns among populations. Our study demonstrates that contemporary levels of genetic diversity were formed quickly and early in population development. How contemporary genetic diversity accumulates over time is a key facet of understanding population growth and development. This is especially relevant given the extent and speed at which species ranges are predicted to shift in the coming century.

  11. Effects of strains, strain crosses and environments on additive genetic and phenotypic variances in Drosophila melanogaster.

    PubMed

    Noor, R R; Barker, J S; Kinghorn, B P

    1993-01-12

    The stability of phenotypic, additive genetic and environmental variances of thorax length of Drosophila melanogaster in pure and synthetic strains was examined in two different environments. Two pure strains from different geographic locations (Melbourne and Townsville) were used, together with three synthetic populations formed from them. The existence of differences in thorax length between the Melbourne and Townsville populations, genotype by environment interaction, and heterosis in crosses between these populations indicate that they are genetically different. Thus geographic separation can cause differences in mean thorax length of flies from different populations. Both the difference in selection histories between the two localities and drift could lead to these differences. Up to the thirty fifth generation there was no evidence of any reduction in the difference between the Melbourne and Townsville populations, in either laboratory environment. The genetic differentiation of strains therefore may be maintained over many generations under new environmental conditions. The fluctuation over generations of heterosis of thorax length is possibly caused by the fluctuation of the rate of loss of favourable epistatic interaction in crossbred genotypes in combination with natural selection effects. V(p) was significantly higher in poor than in the good environment. This higher V(p) in the poor environment is most likly due to higher non additive genetic variance. V(p) was also significantly influenced by strain. In general, V(p) values of synthetic strains were higher than those of pure strains in both environments. Finally, the additive and environmental variances of thorax length were relatively stable across strains, generations and environments. ZUSAMMENFASSUNG: Wirkung von Herkünften, Kreuzungen und Umwelten auf additiv-genetische und phänotypische Varianzen in Drosophila melanogaster Die Stabilität phänotypischer, additiv-genetischer und umweltbedingter

  12. Genetics of murine craniofacial morphology: Diallel analysis of the eight founders of the Collaborative Cross

    PubMed Central

    Percival, Christopher J.; Liberton, Denise K.; de Villena, Fernando Pardo-Manuel; Spritz, Richard; Marcucio, Ralph

    2016-01-01

    Summary Using eight inbred founder strains of the mouse Collaborative Cross (CC) project and their reciprocal F1 hybrids, we quantified variation in craniofacial morphology across mouse strains, explored genetic contributions to craniofacial variation that distinguish the founder strains, and tested whether specific or summary measures of craniofacial shape display stronger additive genetic contributions. This study thus provides critical information about phenotypic diversity among CC founder strains and about the genetic contributions to this phenotypic diversity, which is relevant to understanding the basis of variation in standard laboratory strains and natural populations. Craniofacial shape was quantified as a series of size-adjusted linear dimensions (RDs) and by principal components (PC) analysis of morphological landmarks captured from computed tomography images from 62 out of the 64 reciprocal crosses of the CC founder strains. We first identified aspects of skull morphology that vary between these phenotypically ‘normal’ founder strains and that are defining characteristics of these strains. We estimated the contributions of additive and various non-additive genetic factors to phenotypic variation using diallel analyses of a subset of these strongly differing RDs and the first 8 PCs of skull shape variation. We find little difference in the genetic contributions to RD measures and PC scores, suggesting fundamental similarities in the magnitude of genetic contributions to both specific and summary measures of craniofacial phenotypes. Our results indicate that there are stronger additive genetic effects associated with defining phenotypic characteristics of specific founder strains, suggesting these distinguishing measures are good candidates for use in genotype-phenotype association studies of CC mice. Our results add significantly to understanding of genotype-phenotype associations in the skull, which serve as a foundation for modeling the origins of

  13. Probing Protein-Protein Interactions with Genetically Encoded Photoactivatable Cross-Linkers.

    PubMed

    Cooley, Richard B; Sondermann, Holger

    2017-01-01

    Fundamental to all living organisms is the ability of proteins to interact with other biological molecules at the right time and location, with the proper affinity, and to do so reversibly. One well-established technique to study protein interactions is chemical cross-linking, a process in which proteins in close spatial proximity are covalently tethered together. An emerging technology that overcomes many limitations of traditional cross-linking methods is one in which photoactivatable cross-linking noncanonical amino acids are genetically encoded into a protein of interest using the cell's native translational machinery. These proteins can then be used to trap interacting biomolecules upon UV illumination. Here, we describe a method for the site-specific incorporation of photoactivatable cross-linking amino acids into fluorescently tagged proteins of interest in E. coli. Photo-cross-linking and analysis by SDS-PAGE using in-gel fluorescence detection, which provides rapid, highly sensitive, and specific detection of cross-linked adducts even in impure systems, are also described. An example expression and cross-linking experiment involving transmembrane signaling of a bacterial second messenger receptor system that controls biofilm formation is shown. All reagents needed to carry out these experiments are commercially available, and do not require special or unique technology to perform, making this method tractable to a broad community studying protein structure and function.

  14. 43 CFR 4300.80 - How can I get a permit to cross reindeer over public lands?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false How can I get a permit to cross reindeer over public lands? 4300.80 Section 4300.80 Public Lands: Interior Regulations Relating to Public Lands... ADMINISTRATION; ALASKA; REINDEER; GENERAL Reindeer Crossing Permits § 4300.80 How can I get a permit to cross...

  15. 43 CFR 4300.80 - How can I get a permit to cross reindeer over public lands?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false How can I get a permit to cross reindeer over public lands? 4300.80 Section 4300.80 Public Lands: Interior Regulations Relating to Public Lands... ADMINISTRATION; ALASKA; REINDEER; GENERAL Reindeer Crossing Permits § 4300.80 How can I get a permit to cross...

  16. 43 CFR 4300.80 - How can I get a permit to cross reindeer over public lands?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false How can I get a permit to cross reindeer over public lands? 4300.80 Section 4300.80 Public Lands: Interior Regulations Relating to Public Lands... ADMINISTRATION; ALASKA; REINDEER; GENERAL Reindeer Crossing Permits § 4300.80 How can I get a permit to cross...

  17. 43 CFR 4300.80 - How can I get a permit to cross reindeer over public lands?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false How can I get a permit to cross reindeer over public lands? 4300.80 Section 4300.80 Public Lands: Interior Regulations Relating to Public Lands... ADMINISTRATION; ALASKA; REINDEER; GENERAL Reindeer Crossing Permits § 4300.80 How can I get a permit to cross...

  18. A portable expression resource for engineering cross-species genetic circuits and pathways

    PubMed Central

    Kushwaha, Manish; Salis, Howard M.

    2015-01-01

    Genetic circuits and metabolic pathways can be reengineered to allow organisms to process signals and manufacture useful chemicals. However, their functions currently rely on organism-specific regulatory parts, fragmenting synthetic biology and metabolic engineering into host-specific domains. To unify efforts, here we have engineered a cross-species expression resource that enables circuits and pathways to reuse the same genetic parts, while functioning similarly across diverse organisms. Our engineered system combines mixed feedback control loops and cross-species translation signals to autonomously self-regulate expression of an orthogonal polymerase without host-specific promoters, achieving nontoxic and tuneable gene expression in diverse Gram-positive and Gram-negative bacteria. Combining 50 characterized system variants with mechanistic modelling, we show how the cross-species expression resource's dynamics, capacity and toxicity are controlled by the control loops' architecture and feedback strengths. We also demonstrate one application of the resource by reusing the same genetic parts to express a biosynthesis pathway in both model and non-model hosts. PMID:26184393

  19. The Collaborative Cross at Oak Ridge National Laboratory: developing a powerful resource for systems genetics

    PubMed Central

    Miller, Darla R.; Branstetter, Lisa R.; Galloway, Leslie D.; Jackson, Barbara L.; Philip, Vivek M.; Voy, Brynn H.; Culiat, Cymbeline T.; Threadgill, David W.; Williams, Robert W.; Churchill, Gary A.; Johnson, Dabney K.; Manly, Kenneth F.

    2009-01-01

    Complex traits and disease comorbidity in humans and in model organisms are the result of naturally occurring polymorphisms that interact with each other and with the environment. To ensure the availability of resources needed to investigate biomolecular networks and systems-level phenotypes underlying complex traits, we have initiated breeding of a new genetic reference population of mice, the Collaborative Cross. This population has been designed to optimally support systems genetics analysis. Its novel and important features include a high level of genetic diversity, a large population size to ensure sufficient power in high-dimensional studies, and high mapping precision through accumulation of independent recombination events. Implementation of the Collaborative Cross has been ongoing at the Oak Ridge National Laboratory (ORNL) since May 2005. Production has been systematically managed using a software-assisted breeding program with fully traceable lineages, performed in a controlled environment. Currently, there are 650 lines in production, and close to 200 lines are now beyond their seventh generation of inbreeding. Retired breeders enter a high-throughput phenotyping protocol and DNA samples are banked for analyses of recombination history, allele drift and loss, and population structure. Herein we present a progress report of the Collaborative Cross breeding program at ORNL and a description of the kinds of investigations that this resource will support. PMID:18716833

  20. The Collaborative Cross at Oak Ridge National Laboratory: developing a powerful resource for systems genetics.

    PubMed

    Chesler, Elissa J; Miller, Darla R; Branstetter, Lisa R; Galloway, Leslie D; Jackson, Barbara L; Philip, Vivek M; Voy, Brynn H; Culiat, Cymbeline T; Threadgill, David W; Williams, Robert W; Churchill, Gary A; Johnson, Dabney K; Manly, Kenneth F

    2008-06-01

    Complex traits and disease comorbidity in humans and in model organisms are the result of naturally occurring polymorphisms that interact with each other and with the environment. To ensure the availability of resources needed to investigate biomolecular networks and systems-level phenotypes underlying complex traits, we have initiated breeding of a new genetic reference population of mice, the Collaborative Cross. This population has been designed to optimally support systems genetics analysis. Its novel and important features include a high level of genetic diversity, a large population size to ensure sufficient power in high-dimensional studies, and high mapping precision through accumulation of independent recombination events. Implementation of the Collaborative Cross has been ongoing at the Oak Ridge National Laboratory (ORNL) since May 2005. Production has been systematically managed using a software-assisted breeding program with fully traceable lineages, performed in a controlled environment. Currently, there are 650 lines in production, and close to 200 lines are now beyond their seventh generation of inbreeding. Retired breeders enter a high-throughput phenotyping protocol and DNA samples are banked for analyses of recombination history, allele drift and loss, and population structure. Herein we present a progress report of the Collaborative Cross breeding program at ORNL and a description of the kinds of investigations that this resource will support.

  1. Genetic analysis of intestinal polyp development in Collaborative Cross mice carrying the Apc (Min/+) mutation.

    PubMed

    Dorman, Alexandra; Baer, Daria; Tomlinson, Ian; Mott, Richard; Iraqi, Fuad A

    2016-02-19

    Colorectal cancer is an abnormal tissue development in the colon or rectum. Most of CRCs develop due to somatic mutations, while only a small proportion is caused by inherited mutations. Familial adenomatous polyposis is an inherited genetic disease, which is characterized by colorectal polyps. It is caused by inactivating mutations in the Adenomatous polyposis coli gene. Mice carrying and non-sense mutation in Adenomatous polyposis coli gene at site R850, which designated Apc (R850X/+) (Min), develop intestinal adenomas, while the bulk of the disease is in the small intestine. A number of genetic modifier loci of Min have been mapped, but so far most of the underlying genes have not been identified. In our previous studies, we have shown that Collaborative Cross mice are a powerful tool for mapping loci responsible for phenotypic variation. As a first step towards identification of novel modifiers of Min, we assessed the phenotypic variation between 27 F1 crosses between different Collaborative cross mice and C57BL/6-Min lines. Here, C57BL/6-Min male mice were mated with females from 27 Collaborative cross lines. F1 offspring were terminated at 23 weeks old and multiple phenotypes were collected: polyp counts, intestine length, intestine weight, packed cell volume and spleen weight. Additionally, in eight selected F1 Collaborative cross-C57BL/6-Min lines, body weight was monitored and compared to control mice carry wildtype Adenomatous polyposis coli gene. We found significant (p < 0.05) phenotypic variation between the 27 F1 Collaborative cross-C57BL/6-Min lines for all the tested phenotypes, and sex differences with traits; Colon, body weight and intestine length phenotypes, only. Heritability calculation showed that these phenotypes are mainly controlled by genetic factors. Variation in polyp development is controlled, an appreciable extent, by genetic factors segregating in the Collaborative cross population and suggests that it is suited for identifying

  2. Partitioning of resources: the evolutionary genetics of sexual conflict over resource acquisition and allocation.

    PubMed

    Zajitschek, F; Connallon, T

    2017-04-01

    Fitness depends on both the resources that individuals acquire and the allocation of those resources to traits that influence survival and reproduction. Optimal resource allocation differs between females and males as a consequence of their fundamentally different reproductive strategies. However, because most traits have a common genetic basis between the sexes, conflicting selection between the sexes over resource allocation can constrain the evolution of optimal allocation within each sex, and generate trade-offs for fitness between them (i.e. 'sexual antagonism' or 'intralocus sexual conflict'). The theory of resource acquisition and allocation provides an influential framework for linking genetic variation in acquisition and allocation to empirical evidence of trade-offs between distinct life-history traits. However, these models have not considered the emergence of trade-offs within the context of sexual dimorphism, where they are expected to be particularly common. Here, we extend acquisition-allocation theory and develop a quantitative genetic framework for predicting genetically based trade-offs between life-history traits within sexes and between female and male fitness. Our models demonstrate that empirically measurable evidence of sexually antagonistic fitness variation should depend upon three interacting factors that may vary between populations: (1) the genetic variances and between-sex covariances for resource acquisition and allocation traits, (2) condition-dependent expression of resource allocation traits and (3) sex differences in selection on the allocation of resource to different fitness components.

  3. Climatology of cross-tropopause mass exchange over the Tibetan Plateau and its surroundings

    NASA Astrophysics Data System (ADS)

    Tian, Hongying; Tian, Wenshou; Luo, Jiali; Zhang, Jiankai; Zhang, Min

    2017-04-01

    The cross-tropopause mass flux (CTMF) and long-term trends in stratosphere-troposphere exchange (STE) over the Tibetan Plateau(TP) and its surroundings were analyzed using European Centre for Medium-Range Weather Forecasts reanalysis data. The gross CTMF (the sum of upward and downward mass flux) shows an evident wave train structure over the TP, which is mainly related to the horizontal exchange of air masses along the tropopause associated with the sharp meridional gradient in tropopause pressure or vertical discontinuity of the thermal tropopause in winter. The seasonal cycle of the STE over the TP shows that the gross mass flux is downwards in Northern Hemisphere (NH) winter and upwards in NH summer. The gross CTMF over the TP accounts for 2.96% of the global total CTMF arising from STE processes resolved by Wei method. Both the upward and downward CTMF over the TP exhibit statistically significant positive trends in winter during the period 1979-2009. The strong positive trends of STE in winter over the TP are resulted from the combined effects of the rising tropopause height, enhanced westerlies and decreasing plateau winter monsoon. In summer, both the upward and downward CTMF exhibit statistically significant negative trends over the northern TP, while the trend in upward CTMF is positive over the southern TP, in accordance with the increasing intensity of Asian summer monsoon in recent decades. The sensitivity simulations with a climate model confirm that changes in the Asian monsoon can significantly affect the tropopause and the CTMF over the TP.

  4. Increased frequency of mitotic crossing-over in heterochromatin during the first cleavage division in Drosophila melanogaster

    SciTech Connect

    Omel`yanchuk, L.V.; Volkova, E.I.

    1995-06-01

    It is shown that, although no compaction of paracentromeric heterochromatin occurs during the first cleavage division in Drosophila melanogaster, the frequency of mitotic crossing-over in corresponding chromosome regions is increased, as compared to that in euchromatin. Because a similar situation is observed at later stages of Drosophila development, at which compact chromatin regions become well-manifested, it is concluded that the effect of heterochromatin on the frequency of crossing-over does not depend on its packing. A positive correlation between crossing-over events in paracentromeric heterochromatin and euchromatin was observed. This effect is probably due to the formation of a continuous region of somatic synapsis, which facilitates the process of mitotic crossing-over. On this basis, it is proposed that the effect of heterochromatin on mitotic crossing-over is associated with preferential chromosome pairing in the corresponding regions. 10 refs., 1 fig.

  5. SRLVs: a genetic continuum of lentiviral species in sheep and goats with cumulative evidence of cross species transmission.

    PubMed

    Leroux, Caroline; Cruz, Juliano Cezar Minardi; Mornex, Jean-François

    2010-01-01

    Lentiviruses from distinct animal species have in common their genomic organization, the induction of slowly progressive diseases over months or years, the large spectrum of induced symptoms and concerned organs, the frequent inapparent infection without any detectable clinical signs, their ability to persist into their hosts despite an often strong and mature immune response. Lentiviruses are also characterized by their genomic plasticity and the rapid evolution of the viral species. SRLVs infecting goats and sheep follow a genomic evolution pattern similar to that observed in HIV or in other lentiviruses. Based on limited number of complete sequences, they have been initially described as two distinct genetic groups evolving independently in sheep or goats, the ovine strains being closely related to each other and distinct from the caprine ones. Over the last 2 decades, the description of many partial or complete sequences of caprine and ovine field isolates from various geographical regions and their phylogenetic studies clearly evidenced the existence of a genetic continuum with viruses that did not simply clustered according to the animal species they were isolated from. Three classifications have been successively proposed and allowed to refine the SRLV phylogeny over time. Phylogenetic reconstructions support the existence of SRLV cross-species transmission in domestic and wild small ruminants.

  6. Cortisol reactivity to stress among youth: Stability over time and genetic variants for stress sensitivity

    PubMed Central

    Hankin, Benjamin L.; Badanes, Lisa S.; Smolen, Andrew; Young, Jami F.

    2015-01-01

    Stress sensitivity may be one process that can explain why some genetically at-risk individuals are more susceptible to some types of stress-reactive psychopathologies. Dysregulation of the Limbic Hypothalamic Pituitary Adrenal (LHPA) axis, including cortisol reactivity to challenge, represents a key aspect of stress sensitivity. However, the degree of stability over time among youth, especially differential stability as a function of particular genetic variants, has not been investigated. A general community sample of children and adolescents (mean age = 11.4; 56% girls) provided a DNA sample and completed two separate laboratory stress challenges, across an 18-month follow-up (N =224 at Time 1; N = 194 at Time 2), with repeated measures of salivary cortisol. Results showed that test-retest stability for several indices of cortisol reactivity across the laboratory challenge visits were significant and of moderate magnitude for the whole sample. Moreover, gene variants of several biologically plausible systems relevant for stress sensitivity (especially 5-HTTLPR and CRHR1) demonstrated differential stability of cortisol reactivity over 18-months, such that carriers of genotypes conferring enhanced environmental susceptibility exhibited greater stability of cortisol levels over time for some LHPA axis indices. Findings suggest that LHPA axis dysregulation may exhibit some trait-like aspects underlying stress sensitivity in youth, especially for those who carry genes related to greater genetic susceptibility to environmental stress. PMID:25688432

  7. Cross-over to quasi-condensation: mean-field theories and beyond

    NASA Astrophysics Data System (ADS)

    Henkel, Carsten; Sauer, Tim-O.; Proukakis, N. P.

    2017-06-01

    We analyze the cross-over of a homogeneous, weakly interacting Bose gas in one dimension from the ideal gas into the dense quasi-condensate phase. We review a number of mean-field theories, perturbative or self-consistent, and provide accurate evaluations of equation of state, density fluctuations, and correlation functions. A smooth crossover is reproduced by classical-field simulations based on the stochastic Gross-Pitaevskii equation and the Yang-Yang solution to the one-dimensional Bose gas.

  8. Photosensitivity of germanosilicate fibres and preforms doped with nitrogen inhomogeneously over the cross section

    SciTech Connect

    Yatsenko, Yu P; Mashinsky, V M; Medvedkov, O I; Sazhin, O D; Dianov, Evgenii M; Khopin, V F; Vechkanov, N N; Gur'yanov, A N

    2003-03-31

    The effect of the inhomogeneous distribution of nitrogen impurity on the photosensitivity of germanosilicate fibres is studied. For this purpose, single-mode fibres with different alternations of the core layers sintered in nitrogen and oxygen atmospheres were specially prepared by the MCVD technique. Photoinduced variations in the quadratic nonlinear susceptibility and refractive index of these fibres were recorded. It is shown that the recording efficiency depends on the radial distribution of germanium oxygen-deficient centres, which can be controlled at the stage of sintering through a nonuniform doping by nitrogen over the cross-section. (fibre optics)

  9. Identification of genetic factors that modify motor performance and body weight using Collaborative Cross mice

    DOE PAGES

    Mao, Jian -Hua; Langley, Sasha A.; Huang, Yurong; ...

    2015-11-09

    Evidence has emerged that suggests a link between motor deficits, obesity and many neurological disorders. However, the contributing genetic risk factors are poorly understood. Here we used the Collaborative Cross (CC), a large panel of newly inbred mice that captures 90% of the known variation among laboratory mice, to identify the genetic loci controlling rotarod performance and its relationship with body weight in a cohort of 365 mice across 16 CC strains. Body weight and rotarod performance varied widely across CC strains and were significantly negatively correlated. Genetic linkage analysis identified 14 loci that were associated with body weight. However,more » 45 loci affected rotarod performance, seven of which were also associated with body weight, suggesting a strong link at the genetic level. As a result, we show that genes identified in this study overlap significantly with those related to neurological disorders and obesity found in human GWA studies. In conclusion, our results provide a genetic framework for studies of the connection between body weight, the central nervous system and behavior.« less

  10. Identification of genetic factors that modify motor performance and body weight using Collaborative Cross mice

    SciTech Connect

    Mao, Jian -Hua; Langley, Sasha A.; Huang, Yurong; Hang, Michael; Bouchard, Kristofer E.; Celniker, Susan E.; Brown, James B.; Jansson, Janet K.; Karpen, Gary H.; Snijders, Antoine M.

    2015-11-09

    Evidence has emerged that suggests a link between motor deficits, obesity and many neurological disorders. However, the contributing genetic risk factors are poorly understood. Here we used the Collaborative Cross (CC), a large panel of newly inbred mice that captures 90% of the known variation among laboratory mice, to identify the genetic loci controlling rotarod performance and its relationship with body weight in a cohort of 365 mice across 16 CC strains. Body weight and rotarod performance varied widely across CC strains and were significantly negatively correlated. Genetic linkage analysis identified 14 loci that were associated with body weight. However, 45 loci affected rotarod performance, seven of which were also associated with body weight, suggesting a strong link at the genetic level. As a result, we show that genes identified in this study overlap significantly with those related to neurological disorders and obesity found in human GWA studies. In conclusion, our results provide a genetic framework for studies of the connection between body weight, the central nervous system and behavior.

  11. Effects of crossing distance and genetic relatedness on pollen performance in Alstroemeria aurea (Alstroemeriaceae).

    PubMed

    Souto, Cintia P; Aizen, Marcelo A; Premoli, Andrea C

    2002-03-01

    Prezygotic barriers may represent effective mechanisms to avoid the deleterious effects of inbreeding. This study reports the existence of distance-dependent prezygotic barriers in self-compatible Alstroemeria aurea, a clonal herb native to temperate forests of the southern Andes. We analyzed pollen germination and tube growth as indicators of donor-recipient affinity using crossing distances of 1, 10, and 100 m. We used allozyme electrophoresis to determine the actual genetic relatedness between donor and recipient ramets. Pollen germination was not affected by distance between mates, but the number of pollen tubes reaching the base of the style increased strongly with distance between donor and recipient. This pattern was related to an increase in genetic dissimilarity with distance between mates. In contrast, pollen tube-style interactions did not change with distance when we restricted analysis to individuals at different distances that appeared to be genetically identical. This test implied genetic dissimilarity as the critical factor affecting pollen performance. We propose that the existence of prezygotic barriers might contribute to the high degree of genetic mixing exhibited by some clonal species.

  12. Areas of intervention for genetic counselling of dementia: cross-cultural comparison between Italians and Americans.

    PubMed

    Binetti, Giuliano; Benussi, Luisa; Roberts, Scott; Villa, Aldo; Pasqualetti, Patrizio; Sheu, Ching-Fan; Gigola, Lara; Lussignoli, Giulia; Dal Forno, Gloria; Barbiero, Laura; Corbellini, Gilberto; Green, Robert C; Rossini, Paolo M; Ghidoni, Roberta

    2006-12-01

    Purposes of this study are: (1) to evaluate attitudes, beliefs and experiences towards dementia among relatives of Italian familial cases; (2) to perform a cross-cultural comparison between Italian and American samples; (3) to identify predictors of intentions to undergo hypothetical genetic testing. Participants were 134 relatives of patients affected by familial forms of dementia. We administered tests measuring health psychological styles, social variables, illness perceptions, intentions regarding genetic testing, and perceptions of the pros and cons of genetic testing. Respondents had a poor Alzheimer's disease knowledge and a low perceived dementia threat. When compared to Americans, Italians reported greater willingness to undergo genetic testing and perceived a different subset of benefits and risks. The strongest predictors of test intention were decisional balance, homemaker status and two beliefs concerning dementia causes. Italians had a poor knowledge of the disease and a low awareness of personal risk of developing dementia. As compared to Americans, they expressed higher intentions to undergo genetic testing and they have a different perception of benefits and risks. Understanding of cultural differences in knowledge, attitudes and perception of the disease is important to design optimal health services and education programs for dementia.

  13. Genetic and cellular analysis of cross-incompatibility in Zea mays.

    PubMed

    Lu, Yongxian; Kermicle, Jerry L; Evans, Matthew M S

    2014-03-01

    Three genetic systems conferring cross-incompatibility have been described in Zea mays: Teosinte crossing barrier1-strong (Tcb1-s) found in teosinte, and Gametophyte factor1-strong (Ga1-s) and Ga2-s found in maize and teosinte. The reproductive barrier between maize and some weedy teosintes is controlled by the Tcb1-s locus. Multi-generation inheritance experiments on two independent Tcb1-s lineages show that the Tcb1-s barrier is unstable in some maize lines. Reciprocal crosses between Tcb1-s tester plants and three recombinants in the Tcb1-s mapping region demonstrate that the Tcb1-s haplotype contains separable male and female components. In vivo assays of the dynamics of pollen tube growth and pollen tube morphology during rejection of incompatible pollen in silks carrying the Tcb1-s, Ga1-s, or Ga2-s barriers showed that, in all three, pollen tube growth is slower than in compatible crosses at early stages and had ceased by 24 h after pollination. In all three crossing barrier systems, incompatible pollen tubes have clustered callose plugs in contrast to pollen tubes of compatible crosses. Incompatible pollen tubes growing in the Tcb1-s, Ga1-s, and Ga2-s silks have different morphologies: straight, curved, and kinked, respectively. The distinct morphologies suggest that these crossing barriers block incompatible pollen through different mechanisms. This study lays the foundation for cloning the Tcb1 genes and provides clues about the cellular mechanisms involved in pollen rejection in the Tcb1-s, Ga1-s, and Ga2-s crossing barriers.

  14. Drinking motives and drinking behavior over time: a full cross-lagged panel study among adults.

    PubMed

    Crutzen, Rik; Kuntsche, Emmanuel; Schelleman-Offermans, Karen

    2013-03-01

    Drinking motives are among the most proximal factors for drinking behavior and serve as a mechanism through which more distal factors are mediated. However, it is less clear whether drinking motives are precursors of drinking or, in contrast, shaped by previous drinking experiences (reciprocal effects), or both. Moreover, in adults it is unclear whether drinking motives, usually shaped in adolescence, influence each other over time. In this longitudinal study (N = 2440, 47% women, average age 53 years), drinking motives and drinking behavior (i.e., number of drinks on the heaviest drinking day and number of drinking days; both during the past week) were assessed at 2 time points, separated by 3 months. Full cross-lagged regression models revealed that drinking motives were positively associated with drinking behavior over time and that drinking motives are shaped by the number of drinking days (i.e., reciprocal effects). Furthermore, coping and enhancement motives, as well as social and conformity motives, positively reinforced each other. Moreover, social motives were positively associated with enhancement motives over time. In conclusion, drinking motives influence each other over a 3-month period in adulthood and predict drinking behavior over time, making them important candidates for prevention efforts. Drinking motives are likely to be modifiable and might be used to stimulate drinking decrease. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

  15. Obstacle crossing following stroke improves over one month when the unaffected limb leads, but not when the affected limb leads.

    PubMed

    Said, Catherine M; Galea, Mary; Lythgo, Noel

    2014-01-01

    While it is well established that obstacle crossing is impaired following stroke, it is not known whether obstacle crossing improves as gait improves following stroke. The purpose of this study was to determine whether obstacle crossing changed over a one month time period in people with a recent stroke. Twenty participants receiving rehabilitation following a recent stroke were tested on two occasions one month apart. Participants received usual care rehabilitation, including physiotherapy, between the tests. The main outcome measure was obstacle crossing speed as participants stepped over a 4-cm high obstacle. Secondary measures were spatiotemporal variables. Data were collected via a three dimensional motion analysis system. When leading with the affected limb no changes in obstacle crossing speed or spatiotemporal variables were observed over the one month period. When leading with the unaffected limb, crossing speed significantly increased (p=.002), and affected trail limb swing time (p=.03) and crossing step double support time reduced (p=.016). While not significant, the lead and trail limb pre-obstacle distance increased (p=.08), and lead swing time (p=.052) reduced. Change in obstacle crossing speed did not correlate with change in level gait speed. Obstacle crossing does not necessarily improve over a one month time period in people receiving rehabilitation following stroke. These findings suggest that there may be a need for more targeted training of obstacle crossing, particularly when leading with the affected limb.

  16. Hypervariable minisatellite regions are sites for crossing-over at meiosis in man.

    PubMed

    Chandley, A C; Mitchell, A R

    1988-01-01

    In situ hybridization to human meiotic metaphase I (MI) preparations, using the labeled minisatellite core sequence lambda 33.15, showed clustering of autoradiographic grains principally at or around chiasmata, autosomal sites where crossing-over had occurred. For the XY bivalent, the pairing region formed between the terminal regions of the two short arms (Xpter Ypter), was also a principal site of labeling; in addition, the terminal region of the X long arm (Xqter) was labeled. Control experiments using a member of the human Alu family of dispersed repeated DNA sequences showed a much more randomized grain distribution, with clustering over chiasmata being far less obvious. The data provide support for the suggestion that polymorphic minisatellite regions within the human genome might play a significant role in pairing and/or recombination.

  17. Population genetics of the aquatic fungus Tetracladium marchalianum over space and time.

    PubMed

    Anderson, Jennifer L; Shearer, Carol A

    2011-01-14

    Aquatic hyphomycete fungi are fundamental mediators of energy flow and nutrient spiraling in rivers. These microscopic fungi are primarily dispersed in river currents, undergo substantial annual fluctuations in abundance, and reproduce either predominantly or exclusively asexually. These aspects of aquatic hyphomycete biology are expected to influence levels and distributions of genetic diversity over both spatial and temporal scales. In this study, we investigated the spatiotemporal distribution of genotypic diversity in the representative aquatic hyphomycete Tetracladium marchalianum. We sampled populations of this fungus from seven sites, three sites each in two rivers in Illinois, USA, and one site in a Wisconsin river, USA, and repeatedly sampled one population over two years to track population genetic parameters through two seasonal cycles. The resulting fungal isolates (N = 391) were genotyped at eight polymorphic microsatellite loci. In spite of seasonal reductions in the abundance of this species, genotypic diversity was consistently very high and allele frequencies remarkably stable over time. Likewise, genotypic diversity was very high at all sites. Genetic differentiation was only observed between the most distant rivers (∼450 km). Clear evidence that T. marchalianum reproduces sexually in nature was not observed. Additionally, we used phylogenetic analysis of partial β-tubulin gene sequences to confirm that the fungal isolates studied here represent a single species. These results suggest that populations of T. marchalianum may be very large and highly connected at local scales. We speculate that large population sizes and colonization of alternate substrates in both terrestrial and aquatic environments may effectively buffer the aquatic populations from in-stream population fluctuations and facilitate stability in allele frequencies over time. These data also suggest that overland dispersal is more important for structuring populations of T

  18. Population Genetics of the Aquatic Fungus Tetracladium marchalianum over Space and Time

    PubMed Central

    Anderson, Jennifer L.; Shearer, Carol A.

    2011-01-01

    Aquatic hyphomycete fungi are fundamental mediators of energy flow and nutrient spiraling in rivers. These microscopic fungi are primarily dispersed in river currents, undergo substantial annual fluctuations in abundance, and reproduce either predominantly or exclusively asexually. These aspects of aquatic hyphomycete biology are expected to influence levels and distributions of genetic diversity over both spatial and temporal scales. In this study, we investigated the spatiotemporal distribution of genotypic diversity in the representative aquatic hyphomycete Tetracladium marchalianum. We sampled populations of this fungus from seven sites, three sites each in two rivers in Illinois, USA, and one site in a Wisconsin river, USA, and repeatedly sampled one population over two years to track population genetic parameters through two seasonal cycles. The resulting fungal isolates (N = 391) were genotyped at eight polymorphic microsatellite loci. In spite of seasonal reductions in the abundance of this species, genotypic diversity was consistently very high and allele frequencies remarkably stable over time. Likewise, genotypic diversity was very high at all sites. Genetic differentiation was only observed between the most distant rivers (∼450 km). Clear evidence that T. marchalianum reproduces sexually in nature was not observed. Additionally, we used phylogenetic analysis of partial β-tubulin gene sequences to confirm that the fungal isolates studied here represent a single species. These results suggest that populations of T. marchalianum may be very large and highly connected at local scales. We speculate that large population sizes and colonization of alternate substrates in both terrestrial and aquatic environments may effectively buffer the aquatic populations from in-stream population fluctuations and facilitate stability in allele frequencies over time. These data also suggest that overland dispersal is more important for structuring populations of T

  19. Genetic engineering in agriculture and corporate engineering in public debate: risk, public relations, and public debate over genetically modified crops.

    PubMed

    Patel, Rajeev; Torres, Robert J; Rosset, Peter

    2005-01-01

    Corporations have long influenced environmental and occupational health in agriculture, doing a great deal of damage, making substantial profits, and shaping public debate to make it appear that environmental misfortunes are accidents of an otherwise well-functioning system, rather than systemic. The debate over the genetically modified (GM) crops is an example. The largest producer of commercial GM seeds, Monsanto, exemplifies the industry's strategies: the invocation of poor people as beneficiaries, characterization of opposition as technophobic or anti-progress, and portrayal of their products as environmentally beneficial in the absence of or despite the evidence. This strategy is endemic to contemporary market capitalism, with its incentives to companies to externalize health and environmental costs to increase profits.

  20. Reducing cross-sectional data using a genetic algorithm method and effects on cross-section geometry and steady-flow profiles

    USGS Publications Warehouse

    Berenbrock, Charles E.

    2015-01-01

    The effects of reduced cross-sectional data points on steady-flow profiles were also determined. Thirty-five cross sections of the original steady-flow model of the Kootenai River were used. These two methods were tested for all cross sections with each cross section resolution reduced to 10, 20 and 30 data points, that is, six tests were completed for each of the thirty-five cross sections. Generally, differences from the original water-surface elevation were smaller as the number of data points in reduced cross sections increased, but this was not always the case, especially in the braided reach. Differences were smaller for reduced cross sections developed by the genetic algorithm method than the standard algorithm method.

  1. Gene conversion and crossing over along the 405-kb left arm of Saccharomyces cerevisiae chromosome VII.

    PubMed

    Malkova, Anna; Swanson, Johanna; German, Miriam; McCusker, John H; Housworth, Elizabeth A; Stahl, Franklin W; Haber, James E

    2004-09-01

    Gene conversions and crossing over were analyzed along 10 intervals in a 405-kb region comprising nearly all of the left arm of chromosome VII in Saccharomyces cerevisiae. Crossover interference was detected in all intervals as measured by a reduced number of nonparental ditypes. We have evaluated interference between crossovers in adjacent intervals by methods that retain the information contained in tetrads as opposed to single segregants. Interference was seen between intervals when the distance in the region adjacent to a crossover was < approximately 35 cM (90 kb). At the met13 locus, which exhibits approximately 9% gene conversions, those gene conversions accompanied by crossing over exerted interference in exchanges in an adjacent interval, whereas met13 gene conversions without an accompanying exchange did not show interference. The pattern of exchanges along this chromosome arm can be represented by a counting model in which there are three nonexchange events between adjacent exchanges; however, maximum-likelihood analysis suggests that approximately 8-12% of the crossovers on chromosome VII arise by a separate, noninterfering mechanism.

  2. Recombination and Gene Flux Caused by Gene Conversion and Crossing over in Inversion Heterokaryotypes

    PubMed Central

    Navarro, A.; Betran, E.; Barbadilla, A.; Ruiz, A.

    1997-01-01

    A theoretical analysis of the effects of inversions on recombination and gene flux between arrangements caused by gene conversion and crossing over was carried out. Two different mathematical models of recombination were used: the Poisson model (without interference) and the Counting model (with interference). The main results are as follows. (1) Recombination and gene flux are highly site-dependent both inside and outside the inverted regions. (2) Crossing over overwhelms gene conversion as a cause of gene flux in large inversions, while conversion becomes relatively significant in short inversions and in regions around the breakpoints. (3) Under the Counting model the recombination rate between two markers depends strongly on the position of the markers along the inverted segment. Two equally spaced markers in the central part of the inverted segment have less recombination than if they are in a more extreme position. (4) Inversions affect recombination rates in the uninverted regions of the chromosome. Recombination increases in the distal segment and decreases in the proximal segment. These results provide an explanation for a number of observations reported in the literature. Because inversions are ubiquitous in the evolutionary history of many Drosophila species, the effects of inversions on recombination are expected to influence DNA variation patterns. PMID:9178017

  3. “Slalom”: Microsurgical Cross-Over Decompression for Multilevel Degenerative Lumbar Stenosis

    PubMed Central

    2016-01-01

    Objective. Selective, bilateral multisegmental microsurgical decompression of lumbar spinal canal stenosis through separate, alternating cross-over approaches. Indications. Two-segmental and multisegmental degenerative central and lateral lumbar spinal stenosis. Contraindications. None. Surgical Technique. Minimally invasive, muscle, and facet joint-sparing bilateral decompression of the lumbar spinal canal through 2 or more alternating microsurgical cross-over approaches from one side. Results. From December 2010 until December 2015 we operated on 202 patients with 2 or multisegmental stenosis (115 f; 87 m; average age 69.3 yrs, range 51–91 yrs). All patients were suffering from symptoms typical of a degenerative lumbar spinal stenosis. All patients complained about back pain; however the leg symptoms were dominant in all cases. Per decompressed segment, the average OR time was 36 min and the blood loss 45.7 cc. Patients were mobilized 6 hrs postop and hospitalization averaged 5.9 days. A total of 116/202 patients did not need submuscular drainage. 27/202 patients suffered from a complication (13.4%). Dural tears occurred in 3.5%, an epidural hematoma in 5.5%, a deep wound infection in 1.98%, and a temporary radiculopathy postop in 1.5%. Postop follow-up ranged from 12 to 24 months. There was a significant improvement of EQ 5 D, Oswestry Disability Index (ODI), VAS for Back and Leg Pain, and preoperative standing times and walking distances. PMID:27504456

  4. "Slalom": Microsurgical Cross-Over Decompression for Multilevel Degenerative Lumbar Stenosis.

    PubMed

    Mayer, H Michael; Heider, Franziska

    2016-01-01

    Objective. Selective, bilateral multisegmental microsurgical decompression of lumbar spinal canal stenosis through separate, alternating cross-over approaches. Indications. Two-segmental and multisegmental degenerative central and lateral lumbar spinal stenosis. Contraindications. None. Surgical Technique. Minimally invasive, muscle, and facet joint-sparing bilateral decompression of the lumbar spinal canal through 2 or more alternating microsurgical cross-over approaches from one side. Results. From December 2010 until December 2015 we operated on 202 patients with 2 or multisegmental stenosis (115 f; 87 m; average age 69.3 yrs, range 51-91 yrs). All patients were suffering from symptoms typical of a degenerative lumbar spinal stenosis. All patients complained about back pain; however the leg symptoms were dominant in all cases. Per decompressed segment, the average OR time was 36 min and the blood loss 45.7 cc. Patients were mobilized 6 hrs postop and hospitalization averaged 5.9 days. A total of 116/202 patients did not need submuscular drainage. 27/202 patients suffered from a complication (13.4%). Dural tears occurred in 3.5%, an epidural hematoma in 5.5%, a deep wound infection in 1.98%, and a temporary radiculopathy postop in 1.5%. Postop follow-up ranged from 12 to 24 months. There was a significant improvement of EQ 5 D, Oswestry Disability Index (ODI), VAS for Back and Leg Pain, and preoperative standing times and walking distances.

  5. Population genetic structuring in Opisthorchis viverrini over various spatial scales in Thailand and Lao PDR.

    PubMed

    Laoprom, Nonglak; Sithithaworn, Paiboon; Andrews, Ross H; Ando, Katsuhiko; Laha, Thewarach; Klinbunga, Sirawut; Webster, Joanne P; Petney, Trevor N

    2012-01-01

    Khon Kaen Province in northeast Thailand is known as a hot spot for opisthorchiasis in Southeast Asia. Preliminary allozyme and mitochondrial DNA haplotype data from within one endemic district in this Province (Ban Phai), indicated substantial genetic variability within Opisthorchis viverrini. Here, we used microsatellite DNA analyses to examine the genetic diversity and population structure of O. viverrini from four geographically close localities in Khon Kaen Province. Genotyping based on 12 microsatellite loci yielded a mean number of alleles per locus that ranged from 2.83 to 3.7 with an expected heterozygosity in Hardy-Weinberg equilibrium of 0.44-0.56. Assessment of population structure by pairwise F(ST) analysis showed inter-population differentiation (P<0.05) which indicates population substructuring between these localities. Unique alleles were found in three of four localities with the highest number observed per locality being three. Our results highlight the existence of genetic diversity and population substructuring in O. viverrini over a small spatial scale which is similar to that found at a larger scale. This provides the basis for the investigation of the role of parasite genetic diversity and differentiation in transmission dynamics and control of O. viverrini.

  6. Transcriptional profiles of WNV neurovirulence in a genetically diverse Collaborative Cross population.

    PubMed

    Green, Richard; Wilkins, Courtney; Thomas, Sunil; Sekine, Aimee; Ireton, Renee C; Ferris, Martin T; Hendrick, Duncan M; Voss, Kathleen; Pardo-Manuel de Villena, Fernando; Baric, Ralph S; Heise, Mark T; Gale, Michael

    2016-12-01

    West Nile Virus (WNV) is a mosquito-transmitted virus from the Flaviviridae family that causes fever in 1 in 5 infected people. WNV can also become neuro-invasive and cross the blood-brain barrier leading to severe neurological symptoms in a subset of WNV infected individuals [1]. WNV neuro-invasion is believed to be influenced by a number of factors including host genetics. In order to explore these effects and recapitulate the complex immune genetic differences among individuals, we studied gene expression following WNV infection in the Collaborative Cross (CC) model. The CC is a mouse genetics resource composed of > 70 independently bred, octo-parental recombinant inbred mouse lines [2]. To identify the individual host gene expression signatures influencing protection or susceptibility to WNV disease and WNV neuroinvasion, we used the nanostring nsolver platform to quantify gene expression in brain tissue isolated from WNV-infected CC mice at days 4, 7 and 12 post-infection [3]. This nanostring technology provided a high throughput, non-amplification based mRNA quantitation method to detect immune genes involved in neuro-invasion. Data was deposited into the Gene Expression Omnibus (GEO) under accession GSE85999.

  7. A Genetic Test for Whether Pairs of Hermaphrodites Can Cross-Fertilize in a Selfing Killifish.

    PubMed

    Furness, Andrew I; Tatarenkov, Andrey; Avise, John C

    2015-01-01

    Kryptolebias marmoratus, a small killifish that lives in mangrove habitat from southern Florida to Brazil, is one of the planet's only known self-fertilizing hermaphroditic vertebrates. Generation after generation, hermaphroditic individuals simultaneously produce sperm and eggs and internally self-fertilize to produce what are, in effect, highly inbred clones of themselves. Although populations are composed primarily of hermaphrodites, they also contain some true males. The frequency of males in a population varies geographically, from <2% in Florida to as high as 25% in Belize. Males are known to mate occasionally with hermaphrodites, thereby releasing genetic variation that has profound consequences for population genetic structure. However, it is unknown whether hermaphrodites can or do sporadically mate with each other also. Here, we test whether hermaphroditic individuals of the killifish Kryptolebias marmoratus are capable of crossing with one another, in addition to their much more common habits of self-fertilization and occasional outcrossing with pure males. We employ an experimental design in which replicate hermaphrodite pairs were housed together and allowed to reproduce naturally. Among 173 embryos screened at diagnostic microsatellite loci, all were found to result from selfing (i.e., no embryos were the product of a hermaphrodite cross). We thus conclude that hermaphrodite pairs are unlikely to cross, or do so exceedingly rarely.

  8. Efficient Replication of over 180 Genetic Associations with Self-Reported Medical Data

    PubMed Central

    Tung, Joyce Y.; Do, Chuong B.; Hinds, David A.; Kiefer, Amy K.; Macpherson, J. Michael; Chowdry, Arnab B.; Francke, Uta; Naughton, Brian T.; Mountain, Joanna L.; Wojcicki, Anne; Eriksson, Nicholas

    2011-01-01

    While the cost and speed of generating genomic data have come down dramatically in recent years, the slow pace of collecting medical data for large cohorts continues to hamper genetic research. Here we evaluate a novel online framework for obtaining large amounts of medical information from a recontactable cohort by assessing our ability to replicate genetic associations using these data. Using web-based questionnaires, we gathered self-reported data on 50 medical phenotypes from a generally unselected cohort of over 20,000 genotyped individuals. Of a list of genetic associations curated by NHGRI, we successfully replicated about 75% of the associations that we expected to (based on the number of cases in our cohort and reported odds ratios, and excluding a set of associations with contradictory published evidence). Altogether we replicated over 180 previously reported associations, including many for type 2 diabetes, prostate cancer, cholesterol levels, and multiple sclerosis. We found significant variation across categories of conditions in the percentage of expected associations that we were able to replicate, which may reflect systematic inflation of the effects in some initial reports, or differences across diseases in the likelihood of misdiagnosis or misreport. We also demonstrated that we could improve replication success by taking advantage of our recontactable cohort, offering more in-depth questions to refine self-reported diagnoses. Our data suggest that online collection of self-reported data from a recontactable cohort may be a viable method for both broad and deep phenotyping in large populations. PMID:21858135

  9. Genetic Similarities between Compulsive Overeating and Addiction Phenotypes: A Case for "Food Addiction"?

    PubMed

    Carlier, Nina; Marshe, Victoria S; Cmorejova, Jana; Davis, Caroline; Müller, Daniel J

    2015-12-01

    There exists a continuous spectrum of overeating, where at the extremes there are casual overindulgences and at the other a 'pathological' drive to consume palatable foods. It has been proposed that pathological eating behaviors may be the result of addictive appetitive behavior and loss of ability to regulate the consumption of highly processed foods containing refined carbohydrates, fats, salt, and caffeine. In this review, we highlight the genetic similarities underlying substance addiction phenotypes and overeating compulsions seen in individuals with binge eating disorder. We relate these similarities to findings from neuroimaging studies on reward processing and clinical diagnostic criteria based on addiction phenotypes. The abundance of similarities between compulsive overeating and substance addictions puts forth a case for a 'food addiction' phenotype as a valid, diagnosable disorder.

  10. Compact and efficient large cross-section SOI rib waveguide taper optimized by a genetic algorithm

    NASA Astrophysics Data System (ADS)

    Liu, Yujin; Wang, Xi; Dong, Ying; Wang, Xiaohao

    2016-01-01

    A genetic algorithm is applied to optimize a taper between a large cross-section silicon-on-insulator (SOI) rib waveguide and a single-mode fiber to achieve an ultra-compact and highly efficient coupling structure. The coupling efficiency is taken as the objective function of the genetic algorithm in the taper optimization process. To apply the optimization algorithm, the taper is segmented into several sections. Three encoding forms and a two-step optimization strategy are adopted in the optimization process, resulting in a 10μm long taper with a coupling efficiency of 93.30% in quasi-TE mode at 1550nm. The characteristics of the optimized taper including the field profile, spectrum and fabrication tolerances in both horizontal and vertical directions are investigated via a three dimensional eigenmode expansion (EME) method, indicating that the optimized taper is compatible with the prevailing integrated circuit (IC) processing technology.

  11. The Collaborative Cross, a community resource for the genetic analysis of complex traits.

    PubMed

    Churchill, Gary A; Airey, David C; Allayee, Hooman; Angel, Joe M; Attie, Alan D; Beatty, Jackson; Beavis, William D; Belknap, John K; Bennett, Beth; Berrettini, Wade; Bleich, Andre; Bogue, Molly; Broman, Karl W; Buck, Kari J; Buckler, Ed; Burmeister, Margit; Chesler, Elissa J; Cheverud, James M; Clapcote, Steven; Cook, Melloni N; Cox, Roger D; Crabbe, John C; Crusio, Wim E; Darvasi, Ariel; Deschepper, Christian F; Doerge, R W; Farber, Charles R; Forejt, Jiri; Gaile, Daniel; Garlow, Steven J; Geiger, Hartmut; Gershenfeld, Howard; Gordon, Terry; Gu, Jing; Gu, Weikuan; de Haan, Gerald; Hayes, Nancy L; Heller, Craig; Himmelbauer, Heinz; Hitzemann, Robert; Hunter, Kent; Hsu, Hui-Chen; Iraqi, Fuad A; Ivandic, Boris; Jacob, Howard J; Jansen, Ritsert C; Jepsen, Karl J; Johnson, Dabney K; Johnson, Thomas E; Kempermann, Gerd; Kendziorski, Christina; Kotb, Malak; Kooy, R Frank; Llamas, Bastien; Lammert, Frank; Lassalle, Jean-Michel; Lowenstein, Pedro R; Lu, Lu; Lusis, Aldons; Manly, Kenneth F; Marcucio, Ralph; Matthews, Doug; Medrano, Juan F; Miller, Darla R; Mittleman, Guy; Mock, Beverly A; Mogil, Jeffrey S; Montagutelli, Xavier; Morahan, Grant; Morris, David G; Mott, Richard; Nadeau, Joseph H; Nagase, Hiroki; Nowakowski, Richard S; O'Hara, Bruce F; Osadchuk, Alexander V; Page, Grier P; Paigen, Beverly; Paigen, Kenneth; Palmer, Abraham A; Pan, Huei-Ju; Peltonen-Palotie, Leena; Peirce, Jeremy; Pomp, Daniel; Pravenec, Michal; Prows, Daniel R; Qi, Zhonghua; Reeves, Roger H; Roder, John; Rosen, Glenn D; Schadt, Eric E; Schalkwyk, Leonard C; Seltzer, Ze'ev; Shimomura, Kazuhiro; Shou, Siming; Sillanpää, Mikko J; Siracusa, Linda D; Snoeck, Hans-Willem; Spearow, Jimmy L; Svenson, Karen; Tarantino, Lisa M; Threadgill, David; Toth, Linda A; Valdar, William; de Villena, Fernando Pardo-Manuel; Warden, Craig; Whatley, Steve; Williams, Robert W; Wiltshire, Tim; Yi, Nengjun; Zhang, Dabao; Zhang, Min; Zou, Fei

    2004-11-01

    The goal of the Complex Trait Consortium is to promote the development of resources that can be used to understand, treat and ultimately prevent pervasive human diseases. Existing and proposed mouse resources that are optimized to study the actions of isolated genetic loci on a fixed background are less effective for studying intact polygenic networks and interactions among genes, environments, pathogens and other factors. The Collaborative Cross will provide a common reference panel specifically designed for the integrative analysis of complex systems and will change the way we approach human health and disease.

  12. SPECIFIC AND CROSS OVER EFFECTS OF MASSAGE FOR MUSCLE SORENESS: RANDOMIZED CONTROLLED TRIAL

    PubMed Central

    Sundstrup, Emil; Søndergaard, Stine D.; Behm, David; Brandt, Mikkel; Særvoll, Charlotte A.; Jakobsen, Markus D.; Andersen, Lars L.

    2014-01-01

    Purpose/Background: Muscle soreness can negatively interfere with the activities of daily living as well as sports performance. In the working environment, a common problem is muscle tenderness, soreness and pain, especially for workers frequently exposed to unilateral high repetitive movements tasks. The aim of the study is therefore to investigate the acute effect of massage applied using a simple device Thera‐band roller Massager on laboratory induced hamstring muscle soreness, and the potential cross over effect to the non‐massaged limb. Methods: 22 healthy untrained men (Mean age 34 +/− 7 years; mean height 181.7 +/− 6.9 cm; mean weight 80.6 +/− 6.4 kg; BMI: 24.5 +/− 1.3) with no prior history of knee, low back or neck injury or other adverse health issues were recruited. Participants visited the researchers on two separate occasions, separated by 48 hours, each time providing a soreness rating (modified visual analog scale 0‐10), and being tested for pressure pain threshold (PPT) and active range of motion (ROM) of the hamstring muscles. During the first visit, delayed onset muscular soreness of the hamstring muscles was induced by 10 x 10 repetitions of the stiff‐legged dead‐lift. On the second visit participants received either 1) 10 minutes of roller massage on one leg, while the contralateral leg served as a cross over control, or 2) Resting for 10 minutes with no massage at all. Measurement of soreness, PPT and ROM were taken immediately before and at 0, 10, 30 and 60 min. after treatment. Results: There was a significant group by time interaction for soreness (p < 0.0001) and PPT (p = 0.0007), with the massage group experiencing reduced soreness and increasing PPT compared with the control group. There was no group by time interaction for ROM (p = 0.18). At 10 min. post massage there was a significant reduction in soreness of the non‐massaged limb in the cross over control group compared to controls but this effect was lost 30

  13. Impact of melanoma genetic test reporting on perceived control over melanoma prevention

    PubMed Central

    Aspinwall, Lisa G.; Stump, Tammy K.; Taber, Jennifer M.; Kohlmann, Wendy; Leaf, Samantha L.; Leachman, Sancy A.

    2015-01-01

    To determine whether receiving melanoma genetic test results undermines perceived control over melanoma prevention, control-related beliefs were examined among 60 adults from melanoma-prone families receiving CDKN2A/p16 test results (27 unaffected noncarriers, 15 unaffected carriers, 18 affected carriers; response rate at 2 years=64.9% of eligible respondents). Multilevel modeling of perceived control ratings over a 2-year period revealed significant variation in individual trajectories: most participants showed increases (45%) or no change (38.3%), while 16.7% showed decreases. At the group level, noncarriers reported sustained increases through the 2-year follow-up (ps<.05); unaffected carriers reported significant short-term increases (ps<.05); and affected carriers reported no change. Participants in all groups continued to rate photoprotection as highly effective in reducing melanoma risk and reported decreased belief that carrying the p16 mutation would inevitably lead to the development of melanoma. Qualitative responses immediately following counseling and test reporting corroborated these findings, as 93% indicated it was possible to either prevent (64.9%) or decrease the likelihood (28.1%) of future melanomas. Thus, genetic test reporting does not generally undermine perceived control over melanoma prevention, though variability in response to positive results warrants future study. PMID:25822116

  14. Impact of melanoma genetic test reporting on perceived control over melanoma prevention.

    PubMed

    Aspinwall, Lisa G; Stump, Tammy K; Taber, Jennifer M; Kohlmann, Wendy; Leaf, Samantha L; Leachman, Sancy A

    2015-10-01

    To determine whether receiving melanoma genetic test results undermines perceived control over melanoma prevention, control-related beliefs were examined among 60 adults from melanoma-prone families receiving CDKN2A/p16 test results (27 unaffected noncarriers, 15 unaffected carriers, 18 affected carriers; response rate at 2 years = 64.9 % of eligible respondents). Multilevel modeling of perceived control ratings over a 2-year period revealed significant variation in individual trajectories: most participants showed increases (45 %) or no change (38.3 %), while 16.7 % showed decreases. At the group level, noncarriers reported sustained increases through the 2-year follow-up (ps < .05); unaffected carriers reported significant short-term increases (ps < .05); and affected carriers reported no change. Participants in all groups continued to rate photoprotection as highly effective in reducing melanoma risk and reported decreased beliefs that carrying the p16 mutation would inevitably lead to the development of melanoma. Qualitative responses immediately following counseling and test reporting corroborated these findings, as 93 % indicated it was possible to either prevent (64.9 %) or decrease the likelihood (28.1 %) of future melanomas. Thus, genetic test reporting does not generally undermine perceived control over melanoma prevention, though variability in response to positive results warrants future study.

  15. European Invasion of North American Pinus strobus at Large and Fine Scales: High Genetic Diversity and Fine-Scale Genetic Clustering over Time in the Adventive Range

    PubMed Central

    Mandák, Bohumil; Hadincová, Věroslava; Mahelka, Václav; Wildová, Radka

    2013-01-01

    Background North American Pinus strobus is a highly invasive tree species in Central Europe. Using ten polymorphic microsatellite loci we compared various aspects of the large-scale genetic diversity of individuals from 30 sites in the native distribution range with those from 30 sites in the European adventive distribution range. To investigate the ascertained pattern of genetic diversity of this intercontinental comparison further, we surveyed fine-scale genetic diversity patterns and changes over time within four highly invasive populations in the adventive range. Results Our data show that at the large scale the genetic diversity found within the relatively small adventive range in Central Europe, surprisingly, equals the diversity found within the sampled area in the native range, which is about thirty times larger. Bayesian assignment grouped individuals into two genetic clusters separating North American native populations from the European, non-native populations, without any strong genetic structure shown over either range. In the case of the fine scale, our comparison of genetic diversity parameters among the localities and age classes yielded no evidence of genetic diversity increase over time. We found that SGS differed across age classes within the populations under study. Old trees in general completely lacked any SGS, which increased over time and reached its maximum in the sapling stage. Conclusions Based on (1) the absence of difference in genetic diversity between the native and adventive ranges, together with the lack of structure in the native range, and (2) the lack of any evidence of any temporal increase in genetic diversity at four highly invasive populations in the adventive range, we conclude that population amalgamation probably first happened in the native range, prior to introduction. In such case, there would have been no need for multiple introductions from previously isolated populations, but only several introductions from

  16. Beliefs in genetic determinism and attitudes towards psychiatric genetic research: psychometric scale properties, construct associations, demographic correlates, and cross-cultural comparisons.

    PubMed

    Voracek, Martin; Swami, Viren; Loibl, Lisa Mariella; Furnham, Adrian

    2007-12-01

    Using two new scales, this study examined beliefs in genetic determinism and attitudes towards psychiatric genetic research in student samples from Austria, Malaysia, Romania, and the United Kingdom. For both constructs, effects of culture were detectable, whereas those related to key demographics were either small and inconsistent across samples (political orientation and religiosity) or zero (sex and age). Judged from factorial dimensionality and internal consistency, the psychometric properties of both scales were satisfactory. Belief in genetic determinism had lower prevalence and corresponded only modestly to positive attitudes towards psychiatric genetic research which had higher prevalence. The correlations of both constructs with a preference of inequality among social groups (social dominance orientation) were modest and inconsistent across samples. Both scales appear appropriate for cross-cultural applications, in particular for research into lay theories and public perceptions regarding genetic vs environmental effects on human behavior, mental disorders, and behavioral and psychiatric genetic research related to these.

  17. Bioorthogonally cross-linked hydrogel network with precisely controlled disintegration time over a broad range.

    PubMed

    Xu, Jianwen; Feng, Ellva; Song, Jie

    2014-03-19

    Hydrogels with predictable degradation are highly desired for biomedical applications where timely disintegration of the hydrogel (e.g., drug delivery, guided tissue regeneration) is required. However, precisely controlling hydrogel degradation over a broad range in a predictable manner is challenging due to limited intrinsic variability in the degradation rate of liable bonds and difficulties in modeling degradation kinetics for complex polymer networks. More often than not, empirical tuning of the degradation profile results in undesired changes in other properties. Here we report a simple but versatile hydrogel platform that allows us to formulate hydrogels with predictable disintegration time from 2 to >250 days yet comparable macroscopic physical properties. This platform is based on a well-defined network formed by two pairs of four-armed polyethylene glycol macromers terminated with azide and dibenzocyclooctyl groups, respectively, via labile or stable linkages. The high-fidelity bioorthogonal reaction between the symmetric hydrophilic macromers enables robust cross-linking in water, phosphate-buffered saline, and cell culture medium to afford tough hydrogels capable of withstanding >90% compressive strain. Strategic placement of labile ester linkages near the cross-linking site within this superhydrophilic network, accomplished by adjustments of the ratio of the macromers used, enables broad tuning of the disintegration rates precisely matching with the theoretical predictions based on first-order linkage cleavage kinetics. This platform can be exploited for applications where a precise degradation rate is targeted.

  18. Bioorthogonally Cross-Linked Hydrogel Network with Precisely Controlled Disintegration Time over a Broad Range

    PubMed Central

    2015-01-01

    Hydrogels with predictable degradation are highly desired for biomedical applications where timely disintegration of the hydrogel (e.g., drug delivery, guided tissue regeneration) is required. However, precisely controlling hydrogel degradation over a broad range in a predictable manner is challenging due to limited intrinsic variability in the degradation rate of liable bonds and difficulties in modeling degradation kinetics for complex polymer networks. More often than not, empirical tuning of the degradation profile results in undesired changes in other properties. Here we report a simple but versatile hydrogel platform that allows us to formulate hydrogels with predictable disintegration time from 2 to >250 days yet comparable macroscopic physical properties. This platform is based on a well-defined network formed by two pairs of four-armed polyethylene glycol macromers terminated with azide and dibenzocyclooctyl groups, respectively, via labile or stable linkages. The high-fidelity bioorthogonal reaction between the symmetric hydrophilic macromers enables robust cross-linking in water, phosphate-buffered saline, and cell culture medium to afford tough hydrogels capable of withstanding >90% compressive strain. Strategic placement of labile ester linkages near the cross-linking site within this superhydrophilic network, accomplished by adjustments of the ratio of the macromers used, enables broad tuning of the disintegration rates precisely matching with the theoretical predictions based on first-order linkage cleavage kinetics. This platform can be exploited for applications where a precise degradation rate is targeted. PMID:24597638

  19. Cross over of recurrence networks to random graphs and random geometric graphs

    NASA Astrophysics Data System (ADS)

    Jacob, Rinku; Harikrishnan, K. P.; Misra, R.; Ambika, G.

    2017-02-01

    Recurrence networks are complex networks constructed from the time series of chaotic dynamical systems where the connection between two nodes is limited by the recurrence threshold. This condition makes the topology of every recurrence network unique with the degree distribution determined by the probability density variations of the representative attractor from which it is constructed. Here we numerically investigate the properties of recurrence networks from standard low-dimensional chaotic attractors using some basic network measures and show how the recurrence networks are different from random and scale-free networks. In particular, we show that all recurrence networks can cross over to random geometric graphs by adding sufficient amount of noise to the time series and into the classical random graphs by increasing the range of interaction to the system size. We also highlight the effectiveness of a combined plot of characteristic path length and clustering coefficient in capturing the small changes in the network characteristics.

  20. Egos inflating over time: a cross-temporal meta-analysis of the Narcissistic Personality Inventory.

    PubMed

    Twenge, Jean M; Konrath, Sara; Foster, Joshua D; Campbell, W Keith; Bushman, Brad J

    2008-07-01

    A cross-temporal meta-analysis found that narcissism levels have risen over the generations in 85 samples of American college students who completed the 40-item forced-choice Narcissistic Personality Inventory (NPI) between 1979 and 2006 (total n=16,475). Mean narcissism scores were significantly correlated with year of data collection when weighted by sample size (beta=.53, p<.001). Since 1982, NPI scores have increased 0.33 standard deviation. Thus, almost two-thirds of recent college students are above the mean 1979-1985 narcissism score, a 30% increase. The results complement previous studies finding increases in other individualistic traits such as assertiveness, agency, self-esteem, and extraversion.

  1. A double-blind cross-over trial of fenoprofen and phenylbutazone in ankylosing spondylitis.

    PubMed

    Wordsworth, B P; Ebringer, R W; Coggins, E; Smith, S

    1980-11-01

    Fenoprofen, 600 mg, three times daily, was compared with phenylbutazone, 100 mg, three times daily, in 30 patients suffering from ankylosing spondylitis in a double-blind cross-over study. Assessments were made after an initial washout period and after each month-long treatment period. Phenylbutazone significantly improved morning stiffness, finger-to-floor distance, chest expansion, overall joint pain, spinal pain, the physician's assessment of disease activity and ESR. Only chest expansion was significantly improved by fenoprofen, and phenylbutazone was significantly better than fenoprofen in its effects on finger-to-floor distance, morning stiffness, overall joint pain, spinal pain and the physician's assessment of disease activity. Side-effects were of a minor nature apart from one patient who developed rectal bleeding on phenylbutazone which recurred on rechallenging.

  2. [Intraluminal Aspect of Femoro-femoral Cross-over Bypass Graft Mimics Bladder Stone].

    PubMed

    Sonak, I; Wiedemann, A; Heppner, H J

    2016-04-01

    Iatrogenic bladder perforation with delayed diagnosis and treatment in the context of the placement of a vascular prosthesis, e.g. a femoro-femoral cross-over bypass graft, is extremely rare. This is emphasised by the present publication, which is the second published case study worldwide. To identify such a situation is very important because there is a risk of inappropriate treatment if such a bypass complication remains undetected, and the potential complications of an improperly intended "treatment of a bladder stone" may be deleterious or even lethal. Therefore, the involved disciplines should be aware of this possibility in order to initiate relevant diagnostic measures, especially diagnostic cystoscopy, without any delay if symptoms such as voiding disorders or alguria coincide with vascular bypass grafting.

  3. Assessing individual bioequivalence with high-order cross-over designs: a unified procedure.

    PubMed

    Hsuan, Francis C; Reeve, Russell

    2003-09-30

    The U.S. FDA's newly issued guidance on bioequivalence recommends the use of individual bioequivalence (IBE) for highly variable drugs and possibly for modified release dosage forms. The recommended approach to the analysis is to follow the methodology of Hyslop, Hsuan and Holder (HHH), based on a linear mixed model. A limitation of the HHH method is that it works only for uniform designs, such as RTRT/TRTR. In this paper, we present an alternative approach based on a multivariate model. The multivariate model is shown to be a strict superset of the linear mixed model and can successfully model data where the mixed model fails. Our multivariate approach coincides with the HHH method where the HHH method applies, but generalizes to any high-order cross-over design, such as the Balaam design, RTR/TRT, and TRSS/RSTT/STRR. We present numerical examples to demonstrate the proposed method, and examine its properties with a simulation study.

  4. Molecular-scale dynamics of light-induced spin cross-over in a two-dimensional layer

    PubMed Central

    Bairagi, Kaushik; Iasco, Olga; Bellec, Amandine; Kartsev, Alexey; Li, Dongzhe; Lagoute, Jérôme; Chacon, Cyril; Girard, Yann; Rousset, Sylvie; Miserque, Frédéric; Dappe, Yannick J; Smogunov, Alexander; Barreteau, Cyrille; Boillot, Marie-Laure; Mallah, Talal; Repain, Vincent

    2016-01-01

    Spin cross-over molecules show the unique ability to switch between two spin states when submitted to external stimuli such as temperature, light or voltage. If controlled at the molecular scale, such switches would be of great interest for the development of genuine molecular devices in spintronics, sensing and for nanomechanics. Unfortunately, up to now, little is known on the behaviour of spin cross-over molecules organized in two dimensions and their ability to show cooperative transformation. Here we demonstrate that a combination of scanning tunnelling microscopy measurements and ab initio calculations allows discriminating unambiguously between both states by local vibrational spectroscopy. We also show that a single layer of spin cross-over molecules in contact with a metallic surface displays light-induced collective processes between two ordered mixed spin-state phases with two distinct timescale dynamics. These results open a way to molecular scale control of two-dimensional spin cross-over layers. PMID:27425776

  5. The cross-over to magnetostrophic convection in planetary dynamo systems

    PubMed Central

    King, E. M.

    2017-01-01

    Global scale magnetostrophic balance, in which Lorentz and Coriolis forces comprise the leading-order force balance, has long been thought to describe the natural state of planetary dynamo systems. This argument arises from consideration of the linear theory of rotating magnetoconvection. Here we test this long-held tenet by directly comparing linear predictions against dynamo modelling results. This comparison shows that dynamo modelling results are not typically in the global magnetostrophic state predicted by linear theory. Then, in order to estimate at what scale (if any) magnetostrophic balance will arise in nonlinear dynamo systems, we carry out a simple scaling analysis of the Elsasser number Λ, yielding an improved estimate of the ratio of Lorentz and Coriolis forces. From this, we deduce that there is a magnetostrophic cross-over length scale, LX≈(Λo2/Rmo)D, where Λo is the linear (or traditional) Elsasser number, Rmo is the system scale magnetic Reynolds number and D is the length scale of the system. On scales well above LX, magnetostrophic convection dynamics should not be possible. Only on scales smaller than LX should it be possible for the convective behaviours to follow the predictions for the magnetostrophic branch of convection. Because LX is significantly smaller than the system scale in most dynamo models, their large-scale flows should be quasi-geostrophic, as is confirmed in many dynamo simulations. Estimating Λo≃1 and Rmo≃103 in Earth’s core, the cross-over scale is approximately 1/1000 that of the system scale, suggesting that magnetostrophic convection dynamics exists in the core only on small scales below those that can be characterized by geomagnetic observations. PMID:28413338

  6. The cross-over to magnetostrophic convection in planetary dynamo systems.

    PubMed

    Aurnou, J M; King, E M

    2017-03-01

    Global scale magnetostrophic balance, in which Lorentz and Coriolis forces comprise the leading-order force balance, has long been thought to describe the natural state of planetary dynamo systems. This argument arises from consideration of the linear theory of rotating magnetoconvection. Here we test this long-held tenet by directly comparing linear predictions against dynamo modelling results. This comparison shows that dynamo modelling results are not typically in the global magnetostrophic state predicted by linear theory. Then, in order to estimate at what scale (if any) magnetostrophic balance will arise in nonlinear dynamo systems, we carry out a simple scaling analysis of the Elsasser number Λ, yielding an improved estimate of the ratio of Lorentz and Coriolis forces. From this, we deduce that there is a magnetostrophic cross-over length scale, [Formula: see text], where Λo is the linear (or traditional) Elsasser number, Rmo is the system scale magnetic Reynolds number and D is the length scale of the system. On scales well above [Formula: see text], magnetostrophic convection dynamics should not be possible. Only on scales smaller than [Formula: see text] should it be possible for the convective behaviours to follow the predictions for the magnetostrophic branch of convection. Because [Formula: see text] is significantly smaller than the system scale in most dynamo models, their large-scale flows should be quasi-geostrophic, as is confirmed in many dynamo simulations. Estimating Λo ≃1 and Rmo ≃10(3) in Earth's core, the cross-over scale is approximately 1/1000 that of the system scale, suggesting that magnetostrophic convection dynamics exists in the core only on small scales below those that can be characterized by geomagnetic observations.

  7. The cross-over to magnetostrophic convection in planetary dynamo systems

    NASA Astrophysics Data System (ADS)

    Aurnou, J. M.; King, E. M.

    2017-03-01

    Global scale magnetostrophic balance, in which Lorentz and Coriolis forces comprise the leading-order force balance, has long been thought to describe the natural state of planetary dynamo systems. This argument arises from consideration of the linear theory of rotating magnetoconvection. Here we test this long-held tenet by directly comparing linear predictions against dynamo modelling results. This comparison shows that dynamo modelling results are not typically in the global magnetostrophic state predicted by linear theory. Then, in order to estimate at what scale (if any) magnetostrophic balance will arise in nonlinear dynamo systems, we carry out a simple scaling analysis of the Elsasser number Λ, yielding an improved estimate of the ratio of Lorentz and Coriolis forces. From this, we deduce that there is a magnetostrophic cross-over length scale, LX≈(Λo2/ R mo)D , where Λo is the linear (or traditional) Elsasser number, Rmo is the system scale magnetic Reynolds number and D is the length scale of the system. On scales well above LX, magnetostrophic convection dynamics should not be possible. Only on scales smaller than LX should it be possible for the convective behaviours to follow the predictions for the magnetostrophic branch of convection. Because LX is significantly smaller than the system scale in most dynamo models, their large-scale flows should be quasi-geostrophic, as is confirmed in many dynamo simulations. Estimating Λo≃1 and Rmo≃103 in Earth's core, the cross-over scale is approximately 1/1000 that of the system scale, suggesting that magnetostrophic convection dynamics exists in the core only on small scales below those that can be characterized by geomagnetic observations.

  8. Melatonin improves sleep in children with epilepsy: randomized, double-blind cross-over study

    PubMed Central

    Jain, Sejal V; Horn, Paul S; Simakajornboon, Narong; Beebe, Dean W; Holland, Katherine; Byars, Anna W; Glauser, Tracy A

    2015-01-01

    Objective Insomnia, especially maintenance insomnia is widely prevalent in epilepsy. Although melatonin is commonly used, limited data address its efficacy. We performed a randomized, double-blind, placebo-controlled, cross-over study to identify the effects of melatonin on sleep and seizure control in children with epilepsy. Methods Eleven pre-pubertal, developmentally normal children aged 6–11 years with epilepsy were randomized by software algorithm to receive placebo or 9 mg sustained release melatonin for 4 weeks, followed by a 1-week washout and 4-week crossover condition. The pharmacy performed blinding; patients, parents and study staff other than a statistician were blinded. Primary outcomes were sleep onset latency and wakefulness after sleep onset (WASO) measured on polysomnography. Secondary outcomes included seizure frequency, epileptiform spike density per hour of sleep on EEG and reaction time measures on psychomotor vigilance task. Statistical tests appropriate for cross-over designs were used for analysis. Results Data were analyzed from ten subjects who completed the study. Melatonin decreased sleep latency (Mean difference (MD): 11.4 min, p= 0.02) and WASO (MD 22 min, p=0.04) as compared to placebo. No worsening of spike density or seizure frequency was seen. Additionally, Slow-wave sleep duration and REM latency were increased with melatonin and REM sleep duration was decreased. These changes were statistically significant. Worsening of headache was noted in one subject with migraine on melatonin. Conclusion Sustained-release melatonin resulted in statistically significant decreases in sleep latency and WASO. No clear effects on seizures were observed but the study was too small to allow any conclusions to be drawn in this regard. PMID:25862116

  9. Genetical studies on dieldrin-resistance in Aëdes aegypti and its cross-resistance to DDT

    PubMed Central

    Khan, N. H.; Brown, A. W. A.

    1961-01-01

    A strain of Aëdes aegypti was recently found in Puerto Rico which proved to be resistant to both DDT and dieldrin. This paper reports on genetical studies of this strain to determine whether a single entity is involved or two distinct resistances. Tests carried out by repeated back-crossing combined with selection pressure from DDT and dieldrin and by crossing with a strain with marker genes indicate that a single entity is responsible (dieldrin-resistance with cross-resistance to DDT) and that its genetic factor is located on chromosome 2 at a distance of 25 from locus ”yellow”. PMID:13755610

  10. High recombination rates and hotspots in a Plasmodium falciparum genetic cross

    PubMed Central

    2011-01-01

    Background The human malaria parasite Plasmodium falciparum survives pressures from the host immune system and antimalarial drugs by modifying its genome. Genetic recombination and nucleotide substitution are the two major mechanisms that the parasite employs to generate genome diversity. A better understanding of these mechanisms may provide important information for studying parasite evolution, immune evasion and drug resistance. Results Here, we used a high-density tiling array to estimate the genetic recombination rate among 32 progeny of a P. falciparum genetic cross (7G8 × GB4). We detected 638 recombination events and constructed a high-resolution genetic map. Comparing genetic and physical maps, we obtained an overall recombination rate of 9.6 kb per centimorgan and identified 54 candidate recombination hotspots. Similar to centromeres in other organisms, the sequences of P. falciparum centromeres are found in chromosome regions largely devoid of recombination activity. Motifs enriched in hotspots were also identified, including a 12-bp G/C-rich motif with 3-bp periodicity that may interact with a protein containing 11 predicted zinc finger arrays. Conclusions These results show that the P. falciparum genome has a high recombination rate, although it also follows the overall rule of meiosis in eukaryotes with an average of approximately one crossover per chromosome per meiosis. GC-rich repetitive motifs identified in the hotspot sequences may play a role in the high recombination rate observed. The lack of recombination activity in centromeric regions is consistent with the observations of reduced recombination near the centromeres of other organisms. PMID:21463505

  11. High recombination rates and hotspots in a Plasmodium falciparum genetic cross.

    PubMed

    Jiang, Hongying; Li, Na; Gopalan, Vivek; Zilversmit, Martine M; Varma, Sudhir; Nagarajan, Vijayaraj; Li, Jian; Mu, Jianbing; Hayton, Karen; Henschen, Bruce; Yi, Ming; Stephens, Robert; McVean, Gilean; Awadalla, Philip; Wellems, Thomas E; Su, Xin-zhuan

    2011-01-01

    The human malaria parasite Plasmodium falciparum survives pressures from the host immune system and antimalarial drugs by modifying its genome. Genetic recombination and nucleotide substitution are the two major mechanisms that the parasite employs to generate genome diversity. A better understanding of these mechanisms may provide important information for studying parasite evolution, immune evasion and drug resistance. Here, we used a high-density tiling array to estimate the genetic recombination rate among 32 progeny of a P. falciparum genetic cross (7G8 × GB4). We detected 638 recombination events and constructed a high-resolution genetic map. Comparing genetic and physical maps, we obtained an overall recombination rate of 9.6 kb per centimorgan and identified 54 candidate recombination hotspots. Similar to centromeres in other organisms, the sequences of P. falciparum centromeres are found in chromosome regions largely devoid of recombination activity. Motifs enriched in hotspots were also identified, including a 12-bp G/C-rich motif with 3-bp periodicity that may interact with a protein containing 11 predicted zinc finger arrays. These results show that the P. falciparum genome has a high recombination rate, although it also follows the overall rule of meiosis in eukaryotes with an average of approximately one crossover per chromosome per meiosis. GC-rich repetitive motifs identified in the hotspot sequences may play a role in the high recombination rate observed. The lack of recombination activity in centromeric regions is consistent with the observations of reduced recombination near the centromeres of other organisms. © 2011 Jiang et al.; licensee BioMed Central Ltd.

  12. Mammalian Reverse Genetics without Crossing Reveals Nr3a as a Short-Sleeper Gene.

    PubMed

    Sunagawa, Genshiro A; Sumiyama, Kenta; Ukai-Tadenuma, Maki; Perrin, Dimitri; Fujishima, Hiroshi; Ukai, Hideki; Nishimura, Osamu; Shi, Shoi; Ohno, Rei-ichiro; Narumi, Ryohei; Shimizu, Yoshihiro; Tone, Daisuke; Ode, Koji L; Kuraku, Shigehiro; Ueda, Hiroki R

    2016-01-26

    The identification of molecular networks at the system level in mammals is accelerated by next-generation mammalian genetics without crossing, which requires both the efficient production of whole-body biallelic knockout (KO) mice in a single generation and high-performance phenotype analyses. Here, we show that the triple targeting of a single gene using the CRISPR/Cas9 system achieves almost perfect KO efficiency (96%-100%). In addition, we developed a respiration-based fully automated non-invasive sleep phenotyping system, the Snappy Sleep Stager (SSS), for high-performance (95.3% accuracy) sleep/wake staging. Using the triple-target CRISPR and SSS in tandem, we reliably obtained sleep/wake phenotypes, even in double-KO mice. By using this system to comprehensively analyze all of the N-methyl-D-aspartate (NMDA) receptor family members, we found Nr3a as a short-sleeper gene, which is verified by an independent set of triple-target CRISPR. These results demonstrate the application of mammalian reverse genetics without crossing to organism-level systems biology in sleep research.

  13. Is Sensory Over-Responsivity Distinguishable from Childhood Behavior Problems? A Phenotypic and Genetic Analysis

    PubMed Central

    Van Hulle, Carol A.; Schmidt, Nicole L.; Goldsmith, H. Hill

    2011-01-01

    Background Although impaired sensory processing accompanies various clinical conditions, the question of its status as an independent disorder remains open. Our goal was to delineate the comorbidity (or lack thereof) between childhood psychopathology and sensory over-responsivity (SOR) in middle childhood using phenotypic and behavior genetic analyses. Method Participants (N=970) were drawn from the Wisconsin Twin Project, a population-based sample of twins and their families. Mothers completed a sensory responsivity checklist when their offspring were on average 7 years old, followed by a diagnostic interview (Diagnostic Interview Schedule for Children; DISC) within 6 – 12 months. We examined the incidence of DISC diagnoses - ADHD, Conduct Disorder, Oppositional Defiance Disorder, Agoraphobia, General Anxiety, OCD, Panic disorder, Separation Anxiety, Social Phobia, Specific Phobia, Depression, Enuresis, Trichtolloma, Tics, selective mutism, and Pica -among children with SOR, and vice-versa. Children with Autism or PDD were excluded from the present study. Additionally, we examined parent reported physical health diagnoses among non-diagnosed children and three groups of children with SOR and/or DISC diagnoses. Biometric models explored common underlying genetic and environmental influences on symptoms of SOR and psychopathology. Results A majority of individuals who screened positive for SOR did not qualify for a DISC diagnosis (58.2%), and vice versa (68.3%). Children who screened positive for SOR only and typical children had similar rates of physical health problems. Turning to a dimensional approach, multivariate twin models of demonstrated that modest covariation between SOR and DISC symptoms could be entirely accounted for by common underlying genetic effects. Conclusions Our results suggest that SOR occurs independently of recognized childhood psychiatric diagnoses but is also a relatively frequent comorbid condition with recognized diagnoses. Genetic

  14. An information-theoretic approach to estimating the composite genetic effects contributing to variation among generation means: Moving beyond the joint-scaling test for line cross analysis.

    PubMed

    Blackmon, Heath; Demuth, Jeffery P

    2016-02-01

    The pace and direction of evolution in response to selection, drift, and mutation are governed by the genetic architecture that underlies trait variation. Consequently, much of evolutionary theory is predicated on assumptions about whether genes can be considered to act in isolation, or in the context of their genetic background. Evolutionary biologists have disagreed, sometimes heatedly, over which assumptions best describe evolution in nature. Methods for estimating genetic architectures that favor simpler (i.e., additive) models contribute to this debate. Here we address one important source of bias, model selection in line cross analysis (LCA). LCA estimates genetic parameters conditional on the best model chosen from a vast model space using relatively few line means. Current LCA approaches often favor simple models and ignore uncertainty in model choice. To address these issues we introduce Software for Analysis of Genetic Architecture (SAGA), which comprehensively assesses the potential model space, quantifies model selection uncertainty, and uses model weighted averaging to accurately estimate composite genetic effects. Using simulated data and previously published LCA studies, we demonstrate the utility of SAGA to more accurately define the components of complex genetic architectures, and show that traditional approaches have underestimated the importance of epistasis.

  15. Attitudes to genetically modified food over time: How trust in organizations and the media cycle predict support.

    PubMed

    Marques, Mathew D; Critchley, Christine R; Walshe, Jarrod

    2015-07-01

    This research examined public opinion toward genetically modified plants and animals for food, and how trust in organizations and media coverage explained attitudes toward these organisms. Nationally representative samples (N=8821) over 10 years showed Australians were less positive toward genetically modified animals compared to genetically modified plants for food, especially in years where media coverage was high. Structural equation modeling found that positive attitudes toward different genetically modified organisms for food were significantly associated with higher trust in scientists and regulators (e.g. governments), and with lower trust in watchdogs (e.g. environmental movement). Public trust in scientists and watchdogs was a stronger predictor of attitudes toward the use of genetically modified plants for food than animals, but only when media coverage was low. Results are discussed regarding the moral acceptability of genetically modified organisms for food, the media's role in shaping public opinion, and the role public trust in organizations has on attitudes toward genetically modified organisms.

  16. Ecological change predicts population dynamics and genetic diversity over 120 000 years.

    PubMed

    Horreo, Jose Luis; Jiménez-Valverde, Alberto; Fitze, Patrick S

    2016-05-01

    While ecological effects on short-term population dynamics are well understood, their effects over millennia are difficult to demonstrate and convincing evidence is scant. Using coalescent methods, we analysed past population dynamics of three lizard species (Psammodromus hispanicus, P. edwardsianus, P. occidentalis) and linked the results with climate change data covering the same temporal horizon (120 000 years). An increase in population size over time was observed in two species, and in P. occidentalis, no change was observed. Temporal changes in temperature seasonality and the maximum temperature of the warmest month were congruent with changes in population dynamics observed for the three species and both variables affected population density, either directly or indirectly (via a life-history trait). These results constitute the first solid link between ecological change and long-term population dynamics. The results moreover suggest that ecological change leaves genetic signatures that can be retrospectively traced, providing evidence that ecological change is a crucial driver of genetic diversity and speciation.

  17. Cross-correlation of bio-signals using continuous wavelet transform and genetic algorithm.

    PubMed

    Sukiennik, Piotr; Białasiewicz, Jan T

    2015-05-30

    Continuous wavelet transform allows to obtain time-frequency representation of a signal and analyze short-lived temporal interaction of concurrent processes. That offers good localization in both time and frequency domain. Scalogram and coscalogram analysis of two signal interaction dynamics gives an indication of the cross-correlation of analyzed signals in both domains. We have used genetic algorithm with a fitness function based on signals convolution to find time delay between investigated signals. Two methods of cross-correlation are proposed: one that finds single delay for analyzed signals, and one returns a vector of delay values for each of wavelet transform sub-band center frequencies. Algorithms were implemented using MATLAB. We have extracted the data of simultaneously recorded encephalogram and arterial blood pressure and have investigated their interaction dynamics. We found time delay whose value cannot be precisely determined by scalograms and coscalogram inspection. The biomedical signals used come from MIMIC database. Cross-correlation of two complex signals is commonly performed using fast Fourier transform. It works well for signals with invariant frequency content. We have determined the time delay between analyzed signals using wavelet scalograms and we have accordingly shifted one of them, aligning associated events. Their coscalogram indicates the cross-correlation of the associated events. Introducing new methods of wavelet transform in cross-correlation analysis has proven to be beneficial to the gain of the information about process interaction. Introduced solutions could be used to reason about causality between processes and gain bigger insight regarding analyzed systems. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Eulerian models for particle trajectory crossing in turbulent flows over a large range of Stokes numbers

    NASA Astrophysics Data System (ADS)

    Fox, Rodney O.; Vie, Aymeric; Laurent, Frederique; Chalons, Christophe; Massot, Marc

    2012-11-01

    Numerous applications involve a disperse phase carried by a gaseous flow. To simulate such flows, one can resort to a number density function (NDF) governed a kinetic equation. Traditionally, Lagrangian Monte-Carlo methods are used to solve for the NDF, but are expensive as the number of numerical particles needed must be large to control statistical errors. Moreover, such methods are not well adapted to high-performance computing because of the intrinsic inhomogeneity of the NDF. To overcome these issues, Eulerian methods can be used to solve for the moments of the NDF resulting in an unclosed Eulerian system of hyperbolic conservation laws. To obtain closure, in this work a multivariate bi-Gaussian quadrature is used, which can account for particle trajectory crossing (PTC) over a large range of Stokes numbers. This closure uses up to four quadrature points in 2-D velocity phase space to capture large-scale PTC, and an anisotropic Gaussian distribution around each quadrature point to model small-scale PTC. Simulations of 2-D particle-laden isotropic turbulence at different Stokes numbers are employed to validate the Eulerian models against results from the Lagrangian approach. Good agreement is found for the number density fields over the entire range of Stokes numbers tested. Research carried out at the Center for Turbulence Research 2012 Summer Program.

  19. Quantitative study of ruthenium cross-over in direct methanol fuel cells during early operation hours

    NASA Astrophysics Data System (ADS)

    Schoekel, A.; Melke, J.; Bruns, M.; Wippermann, K.; Kuppler, F.; Roth, C.

    2016-01-01

    In direct methanol fuel cells (DMFC), ruthenium cross-over is an important degradation phenomenon. The loss of ruthenium from the anode, its transport through the membrane and its deposition onto the cathode are detrimental to the fuel cell performance and limit the fuel cell's lifetime. Here we present a quantitative study on the fraction of ruthenium being transferred from the anode to the cathode during early operation hours (0-100 h) of a DMFC. Already during fabrication of the MEA ruthenium is transferred to the cathode. In our pristine MEAs about 0.024 wt% Ru could be found in the cathode catalyst. The cell potential during operation seems to have only a minor influence on the dissolution process. In contrast, the operation time appears to be much more important. Our data hint at two dissolution processes: a fast process dominating the first hours of operation and a slower process, which is responsible for the ongoing ruthenium transfer during the fuel cell lifetime. After 2 h held at open circuit conditions the Ru content of the cathode side was 10 times higher than in the pristine MEA. In contrast, the slower process increased that amount only by a factor of two over the course of another 100 h.

  20. The collaborative cross: a recombinant inbred mouse population for the systems genetic era.

    PubMed

    Threadgill, David W; Miller, Darla R; Churchill, Gary A; de Villena, Fernando Pardo-Manuel

    2011-01-01

    The mouse is the most extensively used mammalian model for biomedical and aging research, and an extensive catalogue of laboratory resources is available to support research using mice: classical inbred lines, genetically modified mice (knockouts, transgenics, and humanized mice), selectively bred lines, consomics, congenics, recombinant inbred panels, outbred and heterogeneous stocks, and an expanding set of wild-derived strains. However, these resources were not designed or intended to model the heterogeneous human population or for a systematic analysis of phenotypic effects due to random combinations of uniformly distributed natural variants. The Collaborative Cross (CC) is a large panel of recently established multiparental recombinant inbred mouse lines specifically designed to overcome the limitations of existing mouse genetic resources for analysis of phenotypes caused by combinatorial allele effects. The CC models the complexity of the human genome and supports analyses of common human diseases with complex etiologies originating through interactions between allele combinations and the environment. The CC is the only mammalian resource that has high and uniform genomewide genetic variation effectively randomized across a large, heterogeneous, and infinitely reproducible population. The CC supports data integration across environmental and biological perturbations and across space (different labs) and time.

  1. Heritability and coefficient of genetic variation analyses of phenotypic traits provide strong basis for high-resolution QTL mapping in the Collaborative Cross mouse genetic reference population.

    PubMed

    Iraqi, Fuad A; Athamni, Hanifa; Dorman, Alexandra; Salymah, Yasser; Tomlinson, Ian; Nashif, Aysar; Shusterman, Ariel; Weiss, Ervin; Houri-Haddad, Yael; Mott, Richard; Soller, Morris

    2014-04-01

    Most biological traits of human importance are complex in nature; their manifestation controlled by the cumulative effect of many genetic factors interacting with one another and with the individual's life history. Because of this, mouse genetic reference populations (GRPs) consisting of collections of inbred lines or recombinant inbred lines (RIL) derived from crosses between inbred lines are of particular value in analysis of complex traits, since massive amounts of data can be accumulated on the individual lines. However, existing mouse GRPs are derived from inbred lines that share a common history, resulting in limited genetic diversity, and reduced mapping precision due to long-range gametic disequilibrium. To overcome these limitations, the Collaborative Cross (CC) a genetically highly diverse collection of mouse RIL was established. The CC, now in advanced stages of development, will eventually consist of about 500 RIL derived from reciprocal crosses of eight divergent founder strains of mice, including three wild subspecies. Previous studies have shown that the CC indeed contains enormous diversity at the DNA level, that founder haplotypes are inherited in expected frequency, and that long-range gametic disequilibrium is not present. We here present data, primarily from our own laboratory, documenting extensive genetic variation among CC lines as expressed in broad-sense heritability (H(2)) and by the well-known "coefficient of genetic variation," demonstrating the ability of the CC resource to provide unprecedented mapping precision leading to identification of strong candidate genes.

  2. Explorations of ABO-Rh antigen expressions on erythrocyte dielectrophoresis: changes in cross-over frequency.

    PubMed

    Leonard, Kaela M; Minerick, Adrienne R

    2011-09-01

    A quadrupole dielectrophoretic microdevice was utilized to examine the ABO-Rh dependencies on erythrocyte polarizations. This important step toward medical microdevice technology would transform key clinical blood tests from the laboratory into the field. Previous work in dielectrophoretic microdevices demonstrated that the large number of ABO antigens on erythrocyte membranes impacts their dielectrophoretic signature at 1 MHz. This work explores the dielectrophoretic behavior of native human erythrocytes categorized by their ABO-Rh blood types and directly compares these responses to the same erythrocyte sample modified to remove the A and B antigens. A β(1-3)-galactosidase enzyme was utilized to cleave the ABO polysaccharide backbone at the galactosidase bonds. The enzymatic reaction was optimized by comparing agglutination of the native and modified blood cells in addition to UV-Vis and HPLC analysis of the reaction effluent for saccharide residues. Next, the dielectrophoretic behaviors of the native and modified erythrocytes were visually verified in a quadrupole electrode microdevice over a frequency range from 100 kHz to 80 MHz. The lower cross-over frequency (COF), which transitions from negative to positive dielectrophoresis, for ABO blood types tested (A+, A-, B+, B-, AB+, O+ and O-) differed over the range from 17 to 47 MHz. The COFs of the corresponding enzyme-modified erythrocytes were also determined and the range narrowed to 29-41 MHz. A second COF in the 70-80 MHz range was observed and was reduced in the presence of the transmembrane Rhesus factor. These results suggest that antigen expression on erythrocyte membrane surfaces influence cell polarizations in nonuniform AC fields. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Monte Carlo integration over stepping stone models for spatial genetic inference using approximate Bayesian computation.

    PubMed

    Baird, Stuart J E; Santos, Filipe

    2010-09-01

    Approximate Bayesian computation (ABC) substitutes simulation for analytic models in Bayesian inference. Simulating evolutionary scenarios under Kimura's stepping stone model (KSS) might therefore allow inference over spatial genetic process where analytical results are difficult to obtain. ABC first creates a reference set of simulations and would proceed by comparing summary statistics over KSS simulations to summary statistics from localities sampled in the field, but: comparison of which localities and stepping stones? Identical stepping stones can be arranged so two localities fall in the same stepping stone, nearest or diagonal neighbours, or without contact. None is intrinsically correct, yet some choice must be made and this affects inference. We explore a Bayesian strategy for mapping field observations onto discrete stepping stones. We make Sundial, for projecting field data onto the plane, available. We generalize KSS over regular tilings of the plane. We show Bayesian averaging over the mapping between a continuous field area and discrete stepping stones improves the fit between KSS and isolation by distance expectations. We make Tiler Durden available for carrying out this Bayesian averaging. We describe a novel parameterization of KSS based on Wright's neighbourhood size, placing an upper bound on the geographic area represented by a stepping stone and make it available as m Vector. We generalize spatial coalescence recursions to continuous and discrete space cases and use these to numerically solve for KSS coalescence previously examined only using simulation. We thus provide applied and analytical resources for comparison of stepping stone simulations with field observations.

  4. Effects of habitat fragmentation, population size and demographic history on genetic diversity: the Cross River gorilla in a comparative context.

    PubMed

    Bergl, Richard A; Bradley, Brenda J; Nsubuga, Anthony; Vigilant, Linda

    2008-09-01

    In small and fragmented populations, genetic diversity may be reduced owing to increased levels of drift and inbreeding. This reduced diversity is often associated with decreased fitness and a higher threat of extinction. However, it is difficult to determine when a population has low diversity except in a comparative context. We assessed genetic variability in the critically endangered Cross River gorilla (Gorilla gorilla diehli), a small and fragmented population, using 11 autosomal microsatellite loci. We show that levels of diversity in the Cross River population are not evenly distributed across the three genetically identified subpopulations, and that one centrally located subpopulation has higher levels of variability than the others. All measures of genetic variability in the Cross River population were comparable to those of the similarly small mountain gorilla (G. beringei beringei) populations (Bwindi and Virunga). However, for some measures both the Cross River and mountain gorilla populations show lower levels of diversity than a sample from a large, continuous western gorilla population (Mondika, G. gorilla gorilla). Finally, we tested for the genetic signature of a bottleneck in each of the four populations. Only Cross River showed strong evidence of a reduction in population size, suggesting that the reduction in size of this population was more recent or abrupt than in the two mountain gorilla populations. These results emphasize the need for maintaining connectivity in fragmented populations and highlight the importance of allowing small populations to expand.

  5. A haemodynamic evaluation of the femoro-femoral cross-over bypass.

    PubMed

    Lee, R E; Baird, R N

    1990-04-01

    The femoro-femoral cross-over bypass has become a popular choice for the management of unilateral iliac artery disease, being used in preference to aorto-femoral or extraperitoneal ilio-femoral bypasses. It is a relatively minor procedure and associated with a small incidence of side effects, the main one being the risk of development of a steal of blood from the donor limb by the bypass. Although this problem has been widely discussed, haemodynamic studies have been limited by the use of indirect measurements of blood flow, such as ankle systolic pressures or by the use of electromagnetic flowmetry at the time of surgery. No study employing volumetric blood flow measurements to identify and quantify blood steal in the postoperative patient has been reported to date. With aims of studying the haemodynamic effects of a femoro-femoral cross-over bypass on the circulation in both the recipient and donor limbs, and of identifying preoperatively, problems likely to lead to haemodynamic problems or to graft failure, the present study of 31 patients undergoing femoro-femoral bypass was undertaken. The patients, 18 of whom had rest pain and 13 intermittent claudication, were studied preoperatively using arteriography and a non-invasive assessment. At 3 months from the operation, all received a clinical assessment and a further non-invasive assessment, including a measurement of blood volume flow. Flow measurements were made in the bypass at rest and during a reactive hyperaemia test. In addition, flow measurements were made in the donor limb below the bypass origin at rest and during hyperaemic testing of the recipient limb in order to assess any steal effect the bypass might cause to the donor limb circulation. All 31 patients were improved by surgery, but five developed donor limb claudication which was attributed to steal in three cases. Resting blood flow in the bypasses, 161 (65-282)ml/min [median (range)], rose by 116% (5-428%) to 300 (82-1114)ml/min after hyperaemic

  6. 78 FR 58382 - Notice of Final Federal Agency Actions on the Proposed U.S. 50 Study Crossing Over Sinepauxent...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-23

    ... Crossing over Sinepauxent Bay Study from MD 611 to MD 378 and 5th Street to Somerset Street located in the... over Sinepauxent Bay Study from MD 611 to MD 378 and 5th Street to Somerset Street in Ocean City,...

  7. Soil water capture trends over 50 years of single-cross maize (Zea mays L.) breeding in the US corn-belt

    PubMed Central

    Reyes, Andres; Messina, Carlos D.; Hammer, Graeme L.; Liu, Lu; van Oosterom, Erik; Lafitte, Renee; Cooper, Mark

    2015-01-01

    Breeders have successfully improved maize (Zea mays L.) grain yield for the conditions of the US corn-belt over the past 80 years, with the past 50 years utilizing single-cross hybrids. Long-term improvement for grain yield under water-limited conditions has also been reported. Grain yield under water-limited conditions depends on water use, water use efficiency, and harvest index. It has been hypothesized that long-term genetic gain for yield could be due, in part, to increased water capture from the soil. This hypothesis was tested using a set of elite single-cross hybrids that were released by DuPont Pioneer between 1963 and 2009. Eighteen hybrids were grown in the field during 2010 and 2011 growing seasons at Woodland, CA, USA. Crops grew predominantly on stored soil water and drought stress increased as the season progressed. Soil water content was measured to 300cm depth throughout the growing season. Significant water extraction occurred to a depth of 240–300cm and seasonal water use was calculated from the change in soil water over this rooting zone. Grain yield increased significantly with year of commercialization, but no such trend was observed for total water extraction. Therefore, the measured genetic gain for yield for the period represented by this set of hybrids must be related to either increased efficiency of water use or increased carbon partitioning to the grain, rather than increased soil water uptake. PMID:26428065

  8. Measurement of the tt[over] production cross section in pp[over] collisions at sqrt(s)=1.96 TeV.

    PubMed

    Abazov, V M; Abbott, B; Abolins, M; Acharya, B S; Adams, M; Adams, T; Aguilo, E; Ahn, S H; Ahsan, M; Alexeev, G D; Alkhazov, G; Alton, A; Alverson, G; Alves, G A; Anastasoaie, M; Ancu, L S; Andeen, T; Anderson, S; Andrieu, B; Anzelc, M S; Aoki, M; Arnoud, Y; Arov, M; Arthaud, M; Askew, A; Asman, B; Assis Jesus, A C S; Atramentov, O; Avila, C; Ay, C; Badaud, F; Baden, A; Bagby, L; Baldin, B; Bandurin, D V; Banerjee, P; Banerjee, S; Barberis, E; Barfuss, A-F; Bargassa, P; Baringer, P; Barreto, J; Bartlett, J F; Bassler, U; Bauer, D; Beale, S; Bean, A; Begalli, M; Begel, M; Belanger-Champagne, C; Bellantoni, L; Bellavance, A; Benitez, J A; Beri, S B; Bernardi, G; Bernhard, R; Bertram, I; Besançon, M; Beuselinck, R; Bezzubov, V A; Bhat, P C; Bhatnagar, V; Biscarat, C; Blazey, G; Blekman, F; Blessing, S; Bloch, D; Bloom, K; Boehnlein, A; Boline, D; Bolton, T A; Borissov, G; Bose, T; Brandt, A; Brock, R; Brooijmans, G; Bross, A; Brown, D; Buchanan, N J; Buchholz, D; Buehler, M; Buescher, V; Bunichev, V; Burdin, S; Burke, S; Burnett, T H; Buszello, C P; Butler, J M; Calfayan, P; Calvet, S; Cammin, J; Carvalho, W; Casey, B C K; Castilla-Valdez, H; Chakrabarti, S; Chakraborty, D; Chan, K; Chan, K M; Chandra, A; Charles, F; Cheu, E; Chevallier, F; Cho, D K; Choi, S; Choudhary, B; Christofek, L; Christoudias, T; Cihangir, S; Claes, D; Coadou, Y; Cooke, M; Cooper, W E; Corcoran, M; Couderc, F; Cousinou, M-C; Crépé-Renaudin, S; Cutts, D; Cwiok, M; da Motta, H; Das, A; Davies, G; De, K; de Jong, S J; De La Cruz-Burelo, E; De Oliveira Martins, C; Degenhardt, J D; Déliot, F; Demarteau, M; Demina, R; Denisov, D; Denisov, S P; Desai, S; Diehl, H T; Diesburg, M; Dominguez, A; Dong, H; Dudko, L V; Duflot, L; Dugad, S R; Duggan, D; Duperrin, A; Dyer, J; Dyshkant, A; Eads, M; Edmunds, D; Ellison, J; Elvira, V D; Enari, Y; Eno, S; Ermolov, P; Evans, H; Evdokimov, A; Evdokimov, V N; Ferapontov, A V; Ferbel, T; Fiedler, F; Filthaut, F; Fisher, W; Fisk, H E; Fortner, M; Fox, H; Fu, S; Fuess, S; Gadfort, T; Galea, C F; Gallas, E; Garcia, C; Garcia-Bellido, A; Gavrilov, V; Gay, P; Geist, W; Gelé, D; Gerber, C E; Gershtein, Y; Gillberg, D; Ginther, G; Gollub, N; Gómez, B; Goussiou, A; Grannis, P D; Greenlee, H; Greenwood, Z D; Gregores, E M; Grenier, G; Gris, Ph; Grivaz, J-F; Grohsjean, A; Grünendahl, S; Grünewald, M W; Guo, F; Guo, J; Gutierrez, G; Gutierrez, P; Haas, A; Hadley, N J; Haefner, P; Hagopian, S; Haley, J; Hall, I; Hall, R E; Han, L; Harder, K; Harel, A; Harrington, R; Hauptman, J M; Hauser, R; Hays, J; Hebbeker, T; Hedin, D; Hegeman, J G; Heinmiller, J M; Heinson, A P; Heintz, U; Hensel, C; Herner, K; Hesketh, G; Hildreth, M D; Hirosky, R; Hobbs, J D; Hoeneisen, B; Hoeth, H; Hohlfeld, M; Hong, S J; Hossain, S; Houben, P; Hu, Y; Hubacek, Z; Hynek, V; Iashvili, I; Illingworth, R; Ito, A S; Jabeen, S; Jaffré, M; Jain, S; Jakobs, K; Jarvis, C; Jesik, R; Johns, K; Johnson, C; Johnson, M; Jonckheere, A; Jonsson, P; Juste, A; Kajfasz, E; Kalinin, A M; Kalk, J M; Kappler, S; Karmanov, D; Kasper, P A; Katsanos, I; Kau, D; Kaushik, V; Kehoe, R; Kermiche, S; Khalatyan, N; Khanov, A; Kharchilava, A; Kharzheev, Y M; Khatidze, D; Kim, T J; Kirby, M H; Kirsch, M; Klima, B; Kohli, J M; Konrath, J-P; Korablev, V M; Kozelov, A V; Kraus, J; Krop, D; Kuhl, T; Kumar, A; Kupco, A; Kurca, T; Kvita, J; Lacroix, F; Lam, D; Lammers, S; Landsberg, G; Lebrun, P; Lee, W M; Leflat, A; Lellouch, J; Leveque, J; Li, J; Li, L; Li, Q Z; Lietti, S M; Lima, J G R; Lincoln, D; Linnemann, J; Lipaev, V V; Lipton, R; Liu, Y; Liu, Z; Lobodenko, A; Lokajicek, M; Love, P; Lubatti, H J; Luna, R; Lyon, A L; Maciel, A K A; Mackin, D; Madaras, R J; Mättig, P; Magass, C; Magerkurth, A; Mal, P K; Malbouisson, H B; Malik, S; Malyshev, V L; Mao, H S; Maravin, Y; Martin, B; McCarthy, R; Melnitchouk, A; Mendoza, L; Mercadante, P G; Merkin, M; Merritt, K W; Meyer, A; Meyer, J; Millet, T; Mitrevski, J; Molina, J; Mommsen, R K; Mondal, N K; Moore, R W; Moulik, T; Muanza, G S; Mulders, M; Mulhearn, M; Mundal, O; Mundim, L; Nagy, E; Naimuddin, M; Narain, M; Naumann, N A; Neal, H A; Negret, J P; Neustroev, P; Nilsen, H; Nogima, H; Novaes, S F; Nunnemann, T; O'Dell, V; O'Neil, D C; Obrant, G; Ochando, C; Onoprienko, D; Oshima, N; Osman, N; Osta, J; Otec, R; Otero Y Garzón, G J; Owen, M; Padley, P; Pangilinan, M; Parashar, N; Park, S-J; Park, S K; Parsons, J; Partridge, R; Parua, N; Patwa, A; Pawloski, G; Penning, B; Perfilov, M; Peters, K; Peters, Y; Pétroff, P; Petteni, M; Piegaia, R; Piper, J; Pleier, M-A; Podesta-Lerma, P L M; Podstavkov, V M; Pogorelov, Y; Pol, M-E; Polozov, P; Pope, B G; Popov, A V; Potter, C; Prado da Silva, W L; Prosper, H B; Protopopescu, S; Qian, J; Quadt, A; Quinn, B; Rakitine, A; Rangel, M S; Ranjan, K; Ratoff, P N; Renkel, P; Reucroft, S; Rich, P; Rieger, J; Rijssenbeek, M; Ripp-Baudot, I; Rizatdinova, F; Robinson, S; Rodrigues, R F; Rominsky, M; Royon, C; Rubinov, P; Ruchti, R; Safronov, G; Sajot, G; Sánchez-Hernández, A; Sanders, M P; Santoro, A; Savage, G; Sawyer, L; Scanlon, T; Schaile, D; Schamberger, R D; Scheglov, Y; Schellman, H; Schliephake, T; Schwanenberger, C; Schwartzman, A; Schwienhorst, R; Sekaric, J; Severini, H; Shabalina, E; Shamim, M; Shary, V; Shchukin, A A; Shivpuri, R K; Siccardi, V; Simak, V; Sirotenko, V; Skubic, P; Slattery, P; Smirnov, D; Snow, G R; Snow, J; Snyder, S; Söldner-Rembold, S; Sonnenschein, L; Sopczak, A; Sosebee, M; Soustruznik, K; Spurlock, B; Stark, J; Steele, J; Stolin, V; Stoyanova, D A; Strandberg, J; Strandberg, S; Strang, M A; Strauss, E; Strauss, M; Ströhmer, R; Strom, D; Stutte, L; Sumowidagdo, S; Svoisky, P; Sznajder, A; Tamburello, P; Tanasijczuk, A; Taylor, W; Temple, J; Tiller, B; Tissandier, F; Titov, M; Tokmenin, V V; Toole, T; Torchiani, I; Trefzger, T; Tsybychev, D; Tuchming, B; Tully, C; Tuts, P M; Unalan, R; Uvarov, L; Uvarov, S; Uzunyan, S; Vachon, B; van den Berg, P J; Van Kooten, R; van Leeuwen, W M; Varelas, N; Varnes, E W; Vasilyev, I A; Vaupel, M; Verdier, P; Vertogradov, L S; Verzocchi, M; Villeneuve-Seguier, F; Vint, P; Vokac, P; Von Toerne, E; Voutilainen, M; Wagner, R; Wahl, H D; Wang, L; Wang, M H L S; Warchol, J; Watts, G; Wayne, M; Weber, G; Weber, M; Welty-Rieger, L; Wenger, A; Wermes, N; Wetstein, M; White, A; Wicke, D; Wilson, G W; Wimpenny, S J; Wobisch, M; Wood, D R; Wyatt, T R; Xie, Y; Yacoob, S; Yamada, R; Yan, M; Yasuda, T; Yatsunenko, Y A; Yip, K; Yoo, H D; Youn, S W; Yu, J; Zatserklyaniy, A; Zeitnitz, C; Zhao, T; Zhou, B; Zhu, J; Zielinski, M; Zieminska, D; Zieminski, A; Zivkovic, L; Zutshi, V; Zverev, E G

    2008-05-16

    We measure the tt[over] production cross section in pp[over] collisions at sqrt(s)=1.96 TeV in the lepton + jets channel. Two complementary methods discriminate between signal and background: b tagging and a kinematic likelihood discriminant. Based on 0.9 fb(-1) of data collected by the D0 detector at the Fermilab Tevatron Collider, we measure sigma(tt[over])=7.62+/-0.85 pb, assuming the current world average m(t)=172.6 GeV. We compare our cross section measurement with theory predictions to determine a value for the top-quark mass of 170+/-7 GeV.

  9. Choosing appropriate analysis methods for cluster randomised cross-over trials with a binary outcome.

    PubMed

    Morgan, Katy E; Forbes, Andrew B; Keogh, Ruth H; Jairath, Vipul; Kahan, Brennan C

    2017-01-30

    In cluster randomised cross-over (CRXO) trials, clusters receive multiple treatments in a randomised sequence over time. In such trials, there is usual correlation between patients in the same cluster. In addition, within a cluster, patients in the same period may be more similar to each other than to patients in other periods. We demonstrate that it is necessary to account for these correlations in the analysis to obtain correct Type I error rates. We then use simulation to compare different methods of analysing a binary outcome from a two-period CRXO design. Our simulations demonstrated that hierarchical models without random effects for period-within-cluster, which do not account for any extra within-period correlation, performed poorly with greatly inflated Type I errors in many scenarios. In scenarios where extra within-period correlation was present, a hierarchical model with random effects for cluster and period-within-cluster only had correct Type I errors when there were large numbers of clusters; with small numbers of clusters, the error rate was inflated. We also found that generalised estimating equations did not give correct error rates in any scenarios considered. An unweighted cluster-level summary regression performed best overall, maintaining an error rate close to 5% for all scenarios, although it lost power when extra within-period correlation was present, especially for small numbers of clusters. Results from our simulation study show that it is important to model both levels of clustering in CRXO trials, and that any extra within-period correlation should be accounted for. Copyright © 2016 John Wiley & Sons, Ltd.

  10. Diagnostic Value of Lumbar Facet Joint Injection: A Prospective Triple Cross-Over Study

    PubMed Central

    Schütz, Uwe; Cakir, Balkan; Dreinhöfer, Karsten; Richter, Marcus; Koepp, Holger

    2011-01-01

    The diagnosis “lumbar facet syndrome” is common and often indicates severe lumbar spine surgery procedures. It is doubtful whether a painful facet joint (FJ) can be identified by a single FJ block. The aim of this study was to clarify the validity of a single and placebo controlled bilateral FJ blocks using local anesthetics. A prospective single blinded triple cross-over study was performed. 60 patients (31 f, 29 m, mean age 53.2 yrs (22–73)) with chronic low back pain (mean pain persistance 31 months, 6 months of conservative treatment without success) admitted to a local orthopaedic department for surgical or conservative therapy of chronic LBP, were included in the study. Effect on pain reduction (10 point rating scale) was measured. The 60 subjects were divided into six groups with three defined sequences of fluoroscopically guided bilateral monosegmental lumbar FJ test injections in “oblique needle” technique: verum-(local anaesthetic-), placebo-(sodium chloride-) and sham-injection. Carry-over and periodic effects were evaluated and a descriptive and statistical analysis regarding the effectiveness, difference and equality of the FJ injections and the different responses was performed. The results show a high rate of non-response, which documents the lack of reliable and valid predictors for a positive response towards FJ blocks. There was a high rate of placebo reactions noted, including subjects who previously or later reacted positively to verum injections. Equivalence was shown among verum vs. placebo and partly vs. sham also. With regard to test validity criteria, a single intraarticular FJ block with local anesthetics is not useful to detect the pain-responsible FJ and therefore is no valid and reliable diagostic tool to specify indication of lumbar spine surgery. Comparative FJ blocks with local anesthetics and placebo-controls have to be interpretated carefully also, because they solely give no proper diagnosis on FJ being main pain

  11. A randomised cross-over pharmacokinetic bioavailability study of synthetic versus kiwifruit-derived vitamin C.

    PubMed

    Carr, Anitra C; Bozonet, Stephanie M; Vissers, Margreet C M

    2013-11-11

    Kiwifruit are a rich source of vitamin C and also contain numerous phytochemicals, such as flavonoids, which may influence the bioavailability of kiwifruit-derived vitamin C. The aim of this study was to compare the relative bioavailability of synthetic versus kiwifruit-derived vitamin C using a randomised cross-over pharmacokinetic study design. Nine non-smoking males (aged 18-35 years) received either a chewable tablet (200 mg vitamin C) or the equivalent dose from gold kiwifruit (Actinidia chinensis var. Sungold). Fasting blood and urine were collected half hourly to hourly over the eight hours following intervention. The ascorbate content of the plasma and urine was determined using HPLC with electrochemical detection. Plasma ascorbate levels increased from 0.5 h after the intervention (P = 0.008). No significant differences in the plasma time-concentration curves were observed between the two interventions (P = 0.645). An estimate of the total increase in plasma ascorbate indicated complete uptake of the ingested vitamin C tablet and kiwifruit-derived vitamin C. There was an increase in urinary ascorbate excretion, relative to urinary creatinine, from two hours post intervention (P < 0.001). There was also a significant difference between the two interventions, with enhanced ascorbate excretion observed in the kiwifruit group (P = 0.016). Urinary excretion was calculated as ~40% and ~50% of the ingested dose from the vitamin C tablet and kiwifruit arms, respectively. Overall, our pharmacokinetic study has shown comparable relative bioavailability of kiwifruit-derived vitamin C and synthetic vitamin C.

  12. Genetic data from algae sedimentary DNA reflect the influence of environment over geography.

    PubMed

    Stoof-Leichsenring, Kathleen R; Herzschuh, Ulrike; Pestryakova, Luidmila A; Klemm, Juliane; Epp, Laura S; Tiedemann, Ralph

    2015-08-11

    Genetic investigations on eukaryotic plankton confirmed the existence of modern biogeographic patterns, but analyses of palaeoecological data exploring the temporal variability of these patterns have rarely been presented. Ancient sedimentary DNA proved suitable for investigations of past assemblage turnover in the course of environmental change, but genetic relatedness of the identified lineages has not yet been undertaken. Here, we investigate the relatedness of diatom lineages in Siberian lakes along environmental gradients (i.e. across treeline transects), over geographic distance and through time (i.e. the last 7000 years) using modern and ancient sedimentary DNA. Our results indicate that closely-related Staurosira lineages occur in similar environments and less-related lineages in dissimilar environments, in our case different vegetation and co-varying climatic and limnic variables across treeline transects. Thus our study reveals that environmental conditions rather than geographic distance is reflected by diatom-relatedness patterns in space and time. We tentatively speculate that the detected relatedness pattern in Staurosira across the treeline could be a result of adaptation to diverse environmental conditions across the arctic boreal treeline, however, a geographically-driven divergence and subsequent repopulation of ecologically different habitats might also be a potential explanation for the observed pattern.

  13. Genetic data from algae sedimentary DNA reflect the influence of environment over geography

    PubMed Central

    Stoof-Leichsenring, Kathleen R.; Herzschuh, Ulrike; Pestryakova, Luidmila A.; Klemm, Juliane; Epp, Laura S.; Tiedemann, Ralph

    2015-01-01

    Genetic investigations on eukaryotic plankton confirmed the existence of modern biogeographic patterns, but analyses of palaeoecological data exploring the temporal variability of these patterns have rarely been presented. Ancient sedimentary DNA proved suitable for investigations of past assemblage turnover in the course of environmental change, but genetic relatedness of the identified lineages has not yet been undertaken. Here, we investigate the relatedness of diatom lineages in Siberian lakes along environmental gradients (i.e. across treeline transects), over geographic distance and through time (i.e. the last 7000 years) using modern and ancient sedimentary DNA. Our results indicate that closely-related Staurosira lineages occur in similar environments and less-related lineages in dissimilar environments, in our case different vegetation and co-varying climatic and limnic variables across treeline transects. Thus our study reveals that environmental conditions rather than geographic distance is reflected by diatom-relatedness patterns in space and time. We tentatively speculate that the detected relatedness pattern in Staurosira across the treeline could be a result of adaptation to diverse environmental conditions across the arctic boreal treeline, however, a geographically-driven divergence and subsequent repopulation of ecologically different habitats might also be a potential explanation for the observed pattern. PMID:26261899

  14. First principles study of thermal conductivity cross-over in nanostructured zinc-chalcogenides

    SciTech Connect

    Katre, Ankita; Madsen, Georg K. H.; Togo, Atsushi; Tanaka, Isao

    2015-01-28

    Systematic first principles studies of zinc-chalcogenides have been performed to understand their thermal transport behaviour. We have applied the Boltzmann transport equation in the relaxation time approximation to calculate the thermal conductivity of ZnS, ZnSe, and ZnTe. We find a thermal conductivity cross-over between ZnS and ZnSe at nanostructure sizes around 0.1–0.2 μm and explain this in terms of the different contributions of phonon modes in these materials. We study the effect of nanostructuring using both the diffusive boundary scattering and confined mean free path limit and discuss the variations in the results. Furthermore, we show the strong influence of isotope scattering on the thermal conductivity. The calculated thermal conductivity is found to be strongly dependent on the volume and we explain the observed differences between local density and generalized gradient approximation calculations. We compare further calculated thermal properties, such as the thermal expansion coefficient, to experiment to validate our approach.

  15. Naltrexone augmentation in OCD: a double-blind placebo-controlled cross-over study.

    PubMed

    Amiaz, Revital; Fostick, Leah; Gershon, Ari; Zohar, Joseph

    2008-06-01

    Current treatments for Obsessive Compulsive Disorder (OCD) rely primarily on serotonergic mechanisms. However, approximately 30% of patients do not respond to serotonin reuptake inhibitors and remain chronically ill. Given the behavioral similarities between some of the compulsive behaviors in OCD and addiction, we hypothesized that the opioid antagonist naltrexone might attenuate compulsions in OCD as well. The effect of naltrexone augmentation to SRI was compared to placebo in 10 OCD outpatients who had not responded to an adequate dose of SSRI or clomipramine for at least 2 months. Participants underwent 5 weeks of treatment with naltrexone or placebo (and 1 week of tapering) in a randomized, double-blind, cross-over design. Patients were evaluated weekly using the Y-BOCS, CGI, HAM-A, and MADRS scales. A two-way repeated measures MANOVA revealed no significant effect for Y-BOCS. However, while receiving naltrexone, patients had significantly higher scores on CGI, MADRS and HAM-A as compared to placebo. The lack of significant findings on OC symptoms could be due to either ceiling effect or alternatively, due to a non-specific exacerbation on anxiety and depression but not on OC symptoms.

  16. Parametric representation of open quantum systems and cross-over from quantum to classical environment.

    PubMed

    Calvani, Dario; Cuccoli, Alessandro; Gidopoulos, Nikitas I; Verrucchi, Paola

    2013-04-23

    The behavior of most physical systems is affected by their natural surroundings. A quantum system with an environment is referred to as open, and its study varies according to the classical or quantum description adopted for the environment. We propose an approach to open quantum systems that allows us to follow the cross-over from quantum to classical environments; to achieve this, we devise an exact parametric representation of the principal system, based on generalized coherent states for the environment. The method is applied to the s = 1/2 Heisenberg star with frustration, where the quantum character of the environment varies with the couplings entering the Hamiltonian H. We find that when the star is in an eigenstate of H, the central spin behaves as if it were in an effective magnetic field, pointing in the direction set by the environmental coherent-state angle variables (θ, ϕ), and broadened according to their quantum probability distribution. Such distribution is independent of ϕ, whereas as a function of θ is seen to get narrower as the quantum character of the environment is reduced, collapsing into a Dirac-δ function in the classical limit. In such limit, because ϕ is left undetermined, the Von Neumann entropy of the central spin remains finite; in fact, it is equal to the entanglement of the original fully quantum model, a result that establishes a relation between this latter quantity and the Berry phase characterizing the dynamics of the central spin in the effective magnetic field.

  17. The effects of ankle supports on gait in adults: A randomized cross-over study.

    PubMed

    Keene, David J; Willett, Keith; Lamb, Sarah E

    2015-12-01

    We aimed to compare the effects of different ankle supports used after ankle injury/surgery on temporo-spatial gait characteristics. We conducted a randomized cross-over study including adult participants with no previous lower limb or neurological pathology, who underwent gait analysis on an electronic walkway in three different ankle supports, Tubigrip(®), a stirrup brace and a walker boot. The 18 participants were an average age of 42 (SD 13, range 24-62) years and 14 (88%) were female. Compared to Tubigrip(®), gait in the walker boot was slower (-0.19 m/s, 95%CI -0.23 to -0.16, P < 0.001), step length asymmetry was 10% (95%CI 9-12, P < 0.001) worse, single support time asymmetry was 5% (95%CI 3-7, P < 0.001) worse and participants also adopted a wider step width (4.1 cm, 95%CI 3.7-4.5, P < 0.001). There were no important differences in gait between the Tubigrip(®) and stirrup brace. The findings of this study suggest that there is a limit to the degree of normal walking characteristics in a walker boot in the absence of lower limb impairment. Further research is required to directly compare the effects of these ankle supports in clinical populations.

  18. A randomised cross-over study assessing the "blue pyjama syndrome" in major depressive episode.

    PubMed

    Delmas, Hélèna; Batail, Jean-Marie; Falissard, Bruno; Robert, Gabriel; Rangé, Maxence; Brousse, Stéphane; Soulabaille, Jacques; Drapier, Dominique; Naudet, Florian

    2017-06-01

    This paper introduces a "blue pyjama syndrome" (whereby wearing hospital pyjamas results in an exaggerated impression of severity). We performed a 5-day, prospective, randomized, cross-over study in a French mood disorder unit for inpatients. At Day 1 (D1) and Day 5 (D5), two 5-minute video interviews were recorded with patients in pyjamas or in day clothes (the sequence was randomly allocated). Psychiatrists unaware of the study objective assessed the videos and scored their clinical global impressions (CGI, with scores ranging from 1 to 7). Of 30 participants with major depressive episode selected for inclusion, 26 participants (69% women) provided useable data for an evaluation by 10 psychiatrists. Pyjamas significantly increased the psychiatrists' CGI ratings of disease severity by 0·65 [0·27; 1·02] points. The psychiatrists' global impressions also rated patients as significantly less severe at D5 in comparison with D1 by -0·66 [-1·03; -0·29] points. The "blue pyjama syndrome" is in the same order of magnitude as the difference observed after a week of hospitalisation. This potentially calls into question the reliability and validity of observer ratings of depression.

  19. Oral Solubilized Ursodeoxycholic Acid Therapy in Amyotrophic Lateral Sclerosis: A Randomized Cross-Over Trial

    PubMed Central

    Min, Ju-Hong; Hong, Yoon-Ho; Sung, Jung-Joon; Kim, Sung-Min; Lee, Jung Bok

    2012-01-01

    To evaluate the efficacy and safety of ursodeoxycholic acid (UDCA) with oral solubilized formula in amyotrophic lateral sclerosis (ALS) patients, patients with probable or definite ALS were randomized to receive oral solubilized UDCA (3.5 g/140 mL/day) or placebo for 3 months after a run-in period of 1 month and switched to receive the other treatment for 3 months after a wash-out period of 1 month. The primary outcome was the rate of progression, assessed by the Appel ALS rating scale (AALSRS), and the secondary outcomes were the revised ALS functional rating scale (ALSFRS-R) and forced vital capacity (FVC). Fifty-three patients completed either the first or second period of study with only 16 of 63 enrolled patients given both treatments sequentially. The slope of AALSRS was 1.17 points/month lower while the patients were treated with UDCA than with placebo (95% CI for difference 0.08-2.26, P = 0.037), whereas the slopes of ALSFRS-R and FVC did not show significant differences between treatments. Gastrointestinal adverse events were more common with UDCA (P < 0.05). Oral solubilized UDCA seems to be tolerable in ALS patients, but we could not make firm conclusion regarding its efficacy, particularly due to the high attrition rate in this cross-over trial. PMID:22323869

  20. Over the border--the problems of uncontrolled radioactive materials crossing national borders.

    PubMed

    Duftschmid, K E

    2002-03-01

    Cross-border movement of radioactive materials and contaminated items, in particular metallurgical scrap, has become a problem of increasing importance. Radioactive sources out of regulatory control, now often called 'orphan sources', have frequently caused serious, even deadly, radiation exposures and widespread contamination. The United States Nuclear Regulatory Commission reported over 2,300 incidents of radioactive materials found in recycled metal scrap and more than 50 accidental smeltings of radioactive sources. A further potentially serious problem is illicit trafficking in nuclear and other radioactive materials. In 1995 the International Atomic Energy Agency (IAEA) started a programme to combat illicit trafficking in nuclear and other radioactive materials, which includes an international database on incidents of illicit trafficking, receiving reports from some 80 member states. For the period 1993-2000 the IAEA database includes 345 confirmed incidents. While from 1994-1996 the frequency declined significantly, this trend has been reversed since 1997, largely due to radioactive sources rather than nuclear material. This paper compares monitoring techniques for radioactive materials in scrap applied at steel plants and scrap yards with monitoring at borders, a completely different situation. It discusses the results of the 'Illicit Trafficking Radiation Detection Assessment Program', a large international pilot study, conducted in cooperation between the IAEA, the Austrian Government and the Austrian Research Centre Seibersdorf. The aim of this exercise was to derive realistic and internationally agreed requirements for border monitoring instrumentation. Finally the present extent of border monitoring installations is discussed.

  1. Cold Dialysis Solution for Hemodialysis Patients With Fatigue: a Cross-over Study.

    PubMed

    Sajadi, Mahbobeh; Gholami, Zohreh; Hekmatpou, Davood; Soltani, Parvin; Haghverdi, Farshid

    2016-09-01

    The purpose of this study was to explore the effect of cold dialysis on fatigue in hemodialysis patients. In a double-blinded cross-over clinical trial, 46 participants were recruited from a hemodialysis unit in Iran. The participants were allocated into 2 groups through simple random sampling method. Each group received 3 sessions of hemodialysis with a dialysis solution temperature of either 37°C 3 or 35.5°C during the first week and then with for another week with the other temperature.  The self-report Piper Fatigue Scale questionnaire was filled out by the participants. The Piper Fatigue Scale scores in the cold dialysis groups were significantly lower than those in the conventional dialysis solution temperature (P < .001). Reducing the temperature of hemodialysis solution brought a 31.3% reduction in the fatigue score. Cold dialysis can be used for all hemodialysis patients as a routine intervention, and in particular, it is recommended dialysis patients who have severe fatigue as a convenient and inexpensive therapeutic option.

  2. HTP-3 links DSB formation with homolog pairing and crossing over during C. elegans meiosis.

    PubMed

    Goodyer, William; Kaitna, Susanne; Couteau, Florence; Ward, Jordan D; Boulton, Simon J; Zetka, Monique

    2008-02-01

    Repair of the programmed meiotic double-strand breaks (DSBs) that initiate recombination must be coordinated with homolog pairing to generate crossovers capable of directing chromosome segregation. Chromosome pairing and synapsis proceed independently of recombination in worms and flies, suggesting a paradoxical lack of coregulation. Here, we find that the meiotic axis component HTP-3 links DSB formation with homolog pairing and synapsis. HTP-3 forms complexes with the DSB repair components MRE-11/RAD-50 and the meiosis-specific axis component HIM-3. Loss of htp-3 or mre-11 recapitulates meiotic phenotypes consistent with a failure to generate DSBs, suggesting that HTP-3 associates with MRE-11/RAD-50 in a complex required for meiotic DSB formation. Loss of HTP-3 eliminates HIM-3 localization to axes and HIM-3-dependent homolog alignment, synapsis, and crossing over. Our study reveals a mechanism for coupling meiotic DSB formation with homolog pairing through the essential participation of an axis component with complexes mediating both processes.

  3. A randomized cross-over study comparing cabergoline and quinagolide in the treatment of hyperprolactinemic patients.

    PubMed

    De Luis, D A; Becerra, A; Lahera, M; Botella, J I; Valero; Varela, C

    2000-01-01

    Quinagolide (QUI) and cabergoline (CAB) are dopamine agonists recently introduced for the treatment of hyperprolactinemia. In the present study, these drugs have been compared in terms of effectiveness and tolerability. Twenty patients (18 females and 2 males) with hyperprolactinemia (8 with microprolactinomas, 6 with idiopathic hyperprolactinemia and 6 with empty sella turcica syndrome) were treated with oral QUI (75 microg once daily) and CAB (0,5 mg twice weekly), in a randomized cross-over trial with placebo between both drugs. Each drug was administered for 12 weeks, separated by other 12 weeks with placebo. PRL levels decreased with both drugs at 2 or 4 weeks of starting the treatment, without differences between both drugs at weeks 4, 8 and 12. At week 12, normal PRL levels (<20 ng/ml) were attained in 90% patients with CAB and only in 75% patients with QUI (p<0.05). After discontinuation of treatment, significant increase in serum PRL was higher after QUI withdrawal than after CAB. Clinical efficacy of both treatments was similar in terms of improvement amenorrhea, oligomenorrhea, galactorrhea, and impotence. All patients completed both cycles of treatment, and the most frequent side-effects were nausea, headache and dizziness, without significant differences between CAB (30%) and QUI (55%). Our study indicates that, at the doses employed here, CAB showed a high percentage of patients with normal PRL at the end of treatment and long-lasting efficacy in the levels of PRL. Clinical response and side-effects were similar in both drugs.

  4. Smoking Behavior and Exposure: Results of a Menthol Cigarette Cross-over Study.

    PubMed

    Watson, Christina Vaughan; Richter, Patricia; de Castro, B Rey; Sosnoff, Connie; Potts, Jennifer; Clark, Pamela; McCraw, Joan; Yan, Xizheng; Chambers, David; Watson, Clifford

    2017-05-01

    Our objective was to improve understanding of the differences in use behavior and exposure when smoking menthol and non-menthol cigarettes using a 2-part cross-over design. Adult daily smokers were assigned randomly to alternate between 2 weeks of exclusively smoking a menthol test cigarette or a non-menthol test cigarette. Urine and saliva were collected for biomarker measurements; carbon monoxide (CO) was measured, and participants smoked test cigarettes through a CreSS® smoking topography device during 3 clinic visits. Participants turned in their cigarette butts from the test periods for determination of mouth level nicotine and completed subjective questionnaires related to the test cigarettes. Regardless of cigarette preference, participants had higher salivary cotinine when smoking the non-menthol test cigarette, but there were no significant differences detected in urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol between the 2 test cigarettes. Mouth level nicotine, puff volume, and puff duration were significantly higher when smoking the menthol brand. Both menthol and non-menthol smokers reported significantly lower enjoyment and satisfaction scores for test cigarettes compared with their brand of choice. Our results suggest that mentholation has an effect on measures of smoking behavior and that mouth level nicotine is a useful indicator of between-brand smoke exposure.

  5. Crossing Over from Attractive to Repulsive Interactions in a Tunneling Bosonic Josephson Junction

    NASA Astrophysics Data System (ADS)

    Spagnolli, G.; Semeghini, G.; Masi, L.; Ferioli, G.; Trenkwalder, A.; Coop, S.; Landini, M.; Pezzè, L.; Modugno, G.; Inguscio, M.; Smerzi, A.; Fattori, M.

    2017-06-01

    We explore the interplay between tunneling and interatomic interactions in the dynamics of a bosonic Josephson junction. We tune the scattering length of an atomic K 39 Bose-Einstein condensate confined in a double-well trap to investigate regimes inaccessible to other superconducting or superfluid systems. In the limit of small-amplitude oscillations, we study the transition from Rabi to plasma oscillations by crossing over from attractive to repulsive interatomic interactions. We observe a critical slowing down in the oscillation frequency by increasing the strength of an attractive interaction up to the point of a quantum phase transition. With sufficiently large initial oscillation amplitude and repulsive interactions, the system enters the macroscopic quantum self-trapping regime, where we observe coherent undamped oscillations with a self-sustained average imbalance of the relative well population. The exquisite agreement between theory and experiments enables the observation of a broad range of many body coherent dynamical regimes driven by tunable tunneling energy, interactions and external forces, with applications spanning from atomtronics to quantum metrology.

  6. Double blind cross-over studies on phototoxicity to three tetracycline derivatives in human volunteers.

    PubMed

    Bjellerup, M; Ljunggren, B

    1987-12-01

    A double blind cross-over phototoxicity study using demethylchlortetracycline (DMCT) 0.3 g x 2, doxycycline 0.1 g x 2, lymecycline 0.6 g x 2 and placebo was performed on 8 healthy human volunteers. Drugs were given for 3 consecutive days, and on the third day the volunteers were tested with different modalities of artificial long-wave ultraviolet radiation (UVA) and assessed 24 h later for objective as well as subjective abnormal photoreactions. All 4 substances were tested in each individual at weekly intervals and serum concentrations of tetracycline were determined. It was found most convenient to irradiate relatively large skin areas using fluorescent tubes emitting mainly UVA but also a small proportion of UVB. Using this type of irradiation, weak erythemal reactions were obtained with all 3 derivatives. Taking only stronger reactions and stinging sensations into account, 0/8 reacted to lymecycline, 0/8 to DMCT and 4/8 to doxycycline. There was no significant difference in serum concentration among the 3 derivatives. It is concluded that doxycycline is the most potent photosensitizer at the dosage tested.

  7. Cross-layer optimization for video transmission over multirate GMC-CDMA wireless links.

    PubMed

    Bandyopadhyay, Saurav K; Partasides, George; Kondi, Lisimachos P

    2008-06-01

    In this paper, we consider the problem of video transmission over wireless generalized multicarrier code division multiple access (GMC-CDMA) systems. Such systems offer deterministic elimination of multiple access interference. A scalable video source codec is used and a multirate setup is assumed, i.e., each video user is allowed to occupy more than one GMC-CDMA channels. Furthermore, each of these channels can utilize a different number of subcarriers. We propose a cross-layer optimization method to select the source coding rate, channel coding rate, number of subcarriers per GMC-CDMA channel and transmission power per GMC-CDMA channel given a maximum transmission power for each video user and an available chip rate. Universal rate distortion characteristics (URDC) are used to approximate the expected distortion at the receiver. The proposed algorithm is optimal in the operational rate distortion sense, subject to the specific setup used and the approximation caused by the use of the URDC. Experimental results are presented and conclusions are drawn.

  8. Aggregation of population-based genetic variation over protein domain homologues and its potential use in genetic diagnostics.

    PubMed

    Wiel, Laurens; Venselaar, Hanka; Veltman, Joris A; Vriend, Gert; Gilissen, Christian

    2017-08-16

    Whole exomes of patients with a genetic disorder are nowadays routinely sequenced but interpretation of the identified genetic variants remains a major challenge. The increased availability of population-based human genetic variation has given rise to measures of genetic tolerance that have been used, for example, to predict disease-causing genes in neurodevelopmental disorders. Here, we investigated whether combining variant information from homologous protein domains can improve variant interpretation. For this purpose, we developed a framework that maps population variation and known pathogenic mutations onto 2,750 "meta-domains." These meta-domains consist of 30,853 homologous Pfam protein domain instances that cover 36% of all human protein coding sequences. We find that genetic tolerance is consistent across protein domain homologues, and that patterns of genetic tolerance faithfully mimic patterns of evolutionary conservation. Furthermore, for a significant fraction (68%) of the meta-domains high-frequency population variation re-occurs at the same positions across domain homologues more often than expected. In addition, we observe that the presence of pathogenic missense variants at an aligned homologous domain position is often paired with the absence of population variation and vice versa. The use of these meta-domains can improve the interpretation of genetic variation. © 2017 The Authors. Human Mutation published by Wiley Periodicals, Inc.

  9. Two phase genetic algorithm for vehicle routing and scheduling problem with cross-docking and time windows considering customer satisfaction

    NASA Astrophysics Data System (ADS)

    Baniamerian, Ali; Bashiri, Mahdi; Zabihi, Fahime

    2017-04-01

    Cross-docking is a new warehousing policy in logistics which is widely used all over the world and attracts many researchers attention to study about in last decade. In the literature, economic aspects has been often studied, while one of the most significant factors for being successful in the competitive global market is improving quality of customer servicing and focusing on customer satisfaction. In this paper, we introduce a vehicle routing and scheduling problem with cross-docking and time windows in a three-echelon supply chain that considers customer satisfaction. A set of homogeneous vehicles collect products from suppliers and after consolidation process in the cross-dock, immediately deliver them to customers. A mixed integer linear programming model is presented for this problem to minimize transportation cost and early/tardy deliveries with scheduling of inbound and outbound vehicles to increase customer satisfaction. A two phase genetic algorithm (GA) is developed for the problem. For investigating the performance of the algorithm, it was compared with exact and lower bound solutions in small and large-size instances, respectively. Results show that there are at least 86.6% customer satisfaction by the proposed method, whereas customer satisfaction in the classical model is at most 33.3%. Numerical examples results show that the proposed two phase algorithm could achieve optimal solutions in small-size instances. Also in large-size instances, the proposed two phase algorithm could achieve better solutions with less gap from the lower bound in less computational time in comparison with the classic GA.

  10. Genetic diversity of Elaeis oleifera (HBK) Cortes populations using cross species SSRs: implication's for germplasm utilization and conservation.

    PubMed

    Ithnin, Maizura; Teh, Chee-Keng; Ratnam, Wickneswari

    2017-04-19

    The Elaeis oleifera genetic materials were assembled from its center of diversity in South and Central America. These materials are currently being preserved in Malaysia as ex situ living collections. Maintaining such collections is expensive and requires sizable land. Information on the genetic diversity of these collections can help achieve efficient conservation via maintenance of core collection. For this purpose, we have applied fourteen unlinked microsatellite markers to evaluate 532 E. oleifera palms representing 19 populations distributed across Honduras, Costa Rica, Panama and Colombia. In general, the genetic diversity decreased from Costa Rica towards the north (Honduras) and south-east (Colombia). Principle coordinate analysis (PCoA) showed a single cluster indicating low divergence among palms. The phylogenetic tree and STRUCTURE analysis revealed clusters based on country of origin, indicating considerable gene flow among populations within countries. Based on the values of the genetic diversity parameters, some genetically diverse populations could be identified. Further, a total of 34 individual palms that collectively captured maximum allelic diversity with reduced redundancy were also identified. High pairwise genetic differentiation (Fst > 0.250) among populations was evident, particularly between the Colombian populations and those from Honduras, Panama and Costa Rica. Crossing selected palms from highly differentiated populations could generate off-springs that retain more genetic diversity. The results attained are useful for selecting palms and populations for core collection. The selected materials can also be included into crossing scheme to generate offsprings that capture greater genetic diversity for selection gain in the future.

  11. Anxiety genetics – findings from cross-species genome-wide approaches

    PubMed Central

    2013-01-01

    Anxiety disorders are complex diseases, which often occur in combination with major depression, alcohol use disorder, or general medical conditions. Anxiety disorders were the most common mental disorders within the EU states in 2010 with 14% prevalence. Anxiety disorders are triggered by environmental factors in genetically susceptible individuals, and therefore genetic research offers a great route to unravel molecular basis of these diseases. As anxiety is an evolutionarily conserved response, mouse models can be used to carry out genome-wide searches for specific genes in a setting that controls for the environmental factors. In this review, we discuss translational approaches that aim to bridge results from unbiased genome-wide screens using mouse models to anxiety disorders in humans. Several methods, such as quantitative trait locus mapping, gene expression profiling, and proteomics, have been used in various mouse models of anxiety to identify genes that regulate anxiety or play a role in maintaining pathological anxiety. We first discuss briefly the evolutionary background of anxiety, which justifies cross-species approaches. We then describe how several genes have been identified through genome-wide methods in mouse models and subsequently investigated in human anxiety disorder samples as candidate genes. These studies have led to the identification of completely novel biological pathways that regulate anxiety in mice and humans, and that can be further investigated as targets for therapy. PMID:23659354

  12. Genetic analysis of dyslexia candidate genes in the European cross-linguistic NeuroDys cohort

    PubMed Central

    Becker, Jessica; Czamara, Darina; Scerri, Tom S; Ramus, Franck; Csépe, Valéria; Talcott, Joel B; Stein, John; Morris, Andrew; Ludwig, Kerstin U; Hoffmann, Per; Honbolygó, Ferenc; Tóth, Dénes; Fauchereau, Fabien; Bogliotti, Caroline; Iannuzzi, Stéphanie; Chaix, Yves; Valdois, Sylviane; Billard, Catherine; George, Florence; Soares-Boucaud, Isabelle; Gérard, Christophe-Loïc; van der Mark, Sanne; Schulz, Enrico; Vaessen, Anniek; Maurer, Urs; Lohvansuu, Kaisa; Lyytinen, Heikki; Zucchelli, Marco; Brandeis, Daniel; Blomert, Leo; Leppänen, Paavo HT; Bruder, Jennifer; Monaco, Anthony P; Müller-Myhsok, Bertram; Kere, Juha; Landerl, Karin; Nöthen, Markus M; Schulte-Körne, Gerd; Paracchini, Silvia; Peyrard-Janvid, Myriam; Schumacher, Johannes

    2014-01-01

    Dyslexia is one of the most common childhood disorders with a prevalence of around 5–10% in school-age children. Although an important genetic component is known to have a role in the aetiology of dyslexia, we are far from understanding the molecular mechanisms leading to the disorder. Several candidate genes have been implicated in dyslexia, including DYX1C1, DCDC2, KIAA0319, and the MRPL19/C2ORF3 locus, each with reports of both positive and no replications. We generated a European cross-linguistic sample of school-age children – the NeuroDys cohort – that includes more than 900 individuals with dyslexia, sampled with homogenous inclusion criteria across eight European countries, and a comparable number of controls. Here, we describe association analysis of the dyslexia candidate genes/locus in the NeuroDys cohort. We performed both case–control and quantitative association analyses of single markers and haplotypes previously reported to be dyslexia-associated. Although we observed association signals in samples from single countries, we did not find any marker or haplotype that was significantly associated with either case–control status or quantitative measurements of word-reading or spelling in the meta-analysis of all eight countries combined. Like in other neurocognitive disorders, our findings underline the need for larger sample sizes to validate possibly weak genetic effects. PMID:24022301

  13. Genetic analysis of dyslexia candidate genes in the European cross-linguistic NeuroDys cohort.

    PubMed

    Becker, Jessica; Czamara, Darina; Scerri, Tom S; Ramus, Franck; Csépe, Valéria; Talcott, Joel B; Stein, John; Morris, Andrew; Ludwig, Kerstin U; Hoffmann, Per; Honbolygó, Ferenc; Tóth, Dénes; Fauchereau, Fabien; Bogliotti, Caroline; Iannuzzi, Stéphanie; Chaix, Yves; Valdois, Sylviane; Billard, Catherine; George, Florence; Soares-Boucaud, Isabelle; Gérard, Christophe-Loïc; van der Mark, Sanne; Schulz, Enrico; Vaessen, Anniek; Maurer, Urs; Lohvansuu, Kaisa; Lyytinen, Heikki; Zucchelli, Marco; Brandeis, Daniel; Blomert, Leo; Leppänen, Paavo H T; Bruder, Jennifer; Monaco, Anthony P; Müller-Myhsok, Bertram; Kere, Juha; Landerl, Karin; Nöthen, Markus M; Schulte-Körne, Gerd; Paracchini, Silvia; Peyrard-Janvid, Myriam; Schumacher, Johannes

    2014-05-01

    Dyslexia is one of the most common childhood disorders with a prevalence of around 5-10% in school-age children. Although an important genetic component is known to have a role in the aetiology of dyslexia, we are far from understanding the molecular mechanisms leading to the disorder. Several candidate genes have been implicated in dyslexia, including DYX1C1, DCDC2, KIAA0319, and the MRPL19/C2ORF3 locus, each with reports of both positive and no replications. We generated a European cross-linguistic sample of school-age children - the NeuroDys cohort - that includes more than 900 individuals with dyslexia, sampled with homogenous inclusion criteria across eight European countries, and a comparable number of controls. Here, we describe association analysis of the dyslexia candidate genes/locus in the NeuroDys cohort. We performed both case-control and quantitative association analyses of single markers and haplotypes previously reported to be dyslexia-associated. Although we observed association signals in samples from single countries, we did not find any marker or haplotype that was significantly associated with either case-control status or quantitative measurements of word-reading or spelling in the meta-analysis of all eight countries combined. Like in other neurocognitive disorders, our findings underline the need for larger sample sizes to validate possibly weak genetic effects.

  14. Limitations to estimating bacterial cross-speciestransmission using genetic and genomic markers: inferencesfrom simulation modeling

    USGS Publications Warehouse

    Julio Andre, Benavides; Cross, Paul C.; Luikart, Gordon; Scott, Creel

    2014-01-01

    Cross-species transmission (CST) of bacterial pathogens has major implications for human health, livestock, and wildlife management because it determines whether control actions in one species may have subsequent effects on other potential host species. The study of bacterial transmission has benefitted from methods measuring two types of genetic variation: variable number of tandem repeats (VNTRs) and single nucleotide polymorphisms (SNPs). However, it is unclear whether these data can distinguish between different epidemiological scenarios. We used a simulation model with two host species and known transmission rates (within and between species) to evaluate the utility of these markers for inferring CST. We found that CST estimates are biased for a wide range of parameters when based on VNTRs and a most parsimonious reconstructed phylogeny. However, estimations of CST rates lower than 5% can be achieved with relatively low bias using as low as 250 SNPs. CST estimates are sensitive to several parameters, including the number of mutations accumulated since introduction, stochasticity, the genetic difference of strains introduced, and the sampling effort. Our results suggest that, even with whole-genome sequences, unbiased estimates of CST will be difficult when sampling is limited, mutation rates are low, or for pathogens that were recently introduced.

  15. A reciprocal cross design to map the genetic architecture of complex traits in apomictic plants.

    PubMed

    Yin, Danni; Zhu, Xuli; Jiang, Libo; Zhang, Jian; Zeng, Yanru; Wu, Rongling

    2015-02-01

    Many higher plants of economic and biological importance undergo apomixis in which the maternal tissue of the ovule forms a seed, without experiencing meiosis and fertilization. This feature of apomixis has made it difficult to perform linkage mapping which relies on meiotic recombination. Here, we describe a computational model for mapping quantitative trait loci (QTLs) that control complex traits in apomictic plants. The model is founded on the mixture model-based likelihood in which maternal genotypes are dissolved into two possible components generated by meiotic and apomictic processes, respectively. The EM algorithm was implemented to discern meiotic and apomictic genotypes and, therefore, allow the marker-QTL linkage relationship to be estimated. By capitalizing on reciprocal crosses, the model is renovated to estimate and test imprinting effects of QTLs, providing a better gateway to characterize the genetic architecture of complex traits. The model was validated through computer simulation and further demonstrated for its usefulness by analyzing a real data for an apomictic woody plant. The model has for the first time provided a unique tool for genetic mapping in apomictic plants.

  16. First measurement of the tt[over ] differential cross section dsigma/dM_{tt[over ]} in pp[over ] collisions at sqrt[s]=1.96 TeV.

    PubMed

    Aaltonen, T; Adelman, J; Akimoto, T; Alvarez González, B; Amerio, S; Amidei, D; Anastassov, A; Annovi, A; Antos, J; Apollinari, G; Apresyan, A; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Aurisano, A; Azfar, F; Azzurri, P; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Bartsch, V; Bauer, G; Beauchemin, P-H; Bedeschi, F; Beecher, D; Behari, S; Bellettini, G; Bellinger, J; Benjamin, D; Beretvas, A; Beringer, J; Bhatti, A; Binkley, M; Bisello, D; Bizjak, I; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Bridgeman, A; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Burke, S; Burkett, K; Busetto, G; Bussey, P; Buzatu, A; Byrum, K L; Cabrera, S; Calancha, C; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carls, B; Carlsmith, D; Carosi, R; Carrillo, S; Carron, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavaliere, V; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, K; Chokheli, D; Chou, J P; Choudalakis, G; Chuang, S H; Chung, K; Chung, W H; Chung, Y S; Chwalek, T; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Compostella, G; Convery, M E; Conway, J; Cordelli, M; Cortiana, G; Cox, C A; Cox, D J; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Cully, J C; Dagenhart, D; Datta, M; Davies, T; de Barbaro, P; De Cecco, S; Deisher, A; De Lorenzo, G; Dell'orso, M; Deluca, C; Demortier, L; Deng, J; Deninno, M; Derwent, P F; di Giovanni, G P; Dionisi, C; Di Ruzza, B; Dittmann, J R; D'Onofrio, M; Donati, S; Dong, P; Donini, J; Dorigo, T; Dube, S; Efron, J; Elagin, A; Erbacher, R; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Ferrazza, C; Field, R; Flanagan, G; Forrest, R; Frank, M J; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garberson, F; Garcia, J E; Garfinkel, A F; Genser, K; Gerberich, H; Gerdes, D; Gessler, A; Giagu, S; Giakoumopoulou, V; Giannetti, P; Gibson, K; Gimmell, J L; Ginsburg, C M; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Grinstein, S; Grosso-Pilcher, C; Grundler, U; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, K; Hahn, S R; Halkiadakis, E; Han, B-Y; Han, J Y; Happacher, F; Hara, K; Hare, D; Hare, M; Harper, S; Harr, R F; Harris, R M; Hartz, M; Hatakeyama, K; Hays, C; Heck, M; Heijboer, A; Heinrich, J; Henderson, C; Herndon, M; Heuser, J; Hewamanage, S; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Hou, S; Houlden, M; Hsu, S-C; Huffman, B T; Hughes, R E; Husemann, U; Hussein, M; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ivanov, A; James, E; Jang, D; Jayatilaka, B; Jeon, E J; Jha, M K; Jindariani, S; Johnson, W; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Kar, D; Karchin, P E; Kato, Y; Kephart, R; Keung, J; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, H W; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Knuteson, B; Ko, B R; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kreps, M; Kroll, J; Krop, D; Krumnack, N; Kruse, M; Krutelyov, V; Kubo, T; Kuhr, T; Kulkarni, N P; Kurata, M; Kwang, S; Laasanen, A T; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; Lecompte, T; Lee, E; Lee, H S; Lee, S W; Leone, S; Lewis, J D; Lin, C-S; Linacre, J; Lindgren, M; Lipeles, E; Liss, T M; Lister, A; Litvintsev, D O; Liu, C; Liu, T; Lockyer, N S; Loginov, A; Loreti, M; Lovas, L; Lucchesi, D; Luci, C; Lueck, J; Lujan, P; Lukens, P; Lungu, G; Lyons, L; Lys, J; Lysak, R; Macqueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maki, T; Maksimovic, P; Malde, S; Malik, S; Manca, G; Manousakis-Katsikakis, A; Margaroli, F; Marino, C; Marino, C P; Martin, A; Martin, V; Martínez, M; Martínez-Ballarín, R; Maruyama, T; Mastrandrea, P; Masubuchi, T; Mathis, M; Mattson, M E; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzione, A; Merkel, P; Mesropian, C; Miao, T; Miladinovic, N; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyake, H; Moggi, N; Moon, C S; Moore, R; Morello, M J; Morlock, J; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Mussini, M; Nachtman, J; Nagai, Y; Nagano, A; Naganoma, J; Nakamura, K; Nakano, I; Napier, A; Necula, V; Nett, J; Neu, C; Neubauer, M S; Neubauer, S; Nielsen, J; Nodulman, L; Norman, M; Norniella, O; Nurse, E; Oakes, L; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Orava, R; Osterberg, K; Pagan Griso, S; Palencia, E; Papadimitriou, V; Papaikonomou, A; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Peiffer, T; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Pianori, E; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Poukhov, O; Pounder, N; Prakoshyn, F; Pronko, A; Proudfoot, J; Ptohos, F; Pueschel, E; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ramakrishnan, V; Ranjan, N; Redondo, I; Renton, P; Renz, M; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rodriguez, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Roy, P; Ruiz, A; Russ, J; Rusu, V; Rutherford, B; Saarikko, H; Safonov, A; Sakumoto, W K; Saltó, O; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savoy-Navarro, A; Schlabach, P; Schmidt, A; Schmidt, E E; Schmidt, M A; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sforza, F; Sfyrla, A; Shalhout, S Z; Shears, T; Shepard, P F; Shimojima, M; Shiraishi, S; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Sinervo, P; Sisakyan, A; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soha, A; Somalwar, S; Sorin, V; Spalding, J; Spreitzer, T; Squillacioti, P; Stanitzki, M; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Strycker, G L; Stuart, D; Suh, J S; Sukhanov, A; Suslov, I; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Tanaka, R; Tecchio, M; Teng, P K; Terashi, K; Thom, J; Thompson, A S; Thompson, G A; Thomson, E; Tipton, P; Ttito-Guzmán, P; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Totaro, P; Tourneur, S; Trovato, M; Tsai, S-Y; Tu, Y; Turini, N; Ukegawa, F; Vallecorsa, S; van Remortel, N; Varganov, A; Vataga, E; Vázquez, F; Velev, G; Vellidis, C; Vidal, M; Vidal, R; Vila, I; Vilar, R; Vine, T; Vogel, M; Volobouev, I; Volpi, G; Wagner, P; Wagner, R G; Wagner, R L; Wagner, W; Wagner-Kuhr, J; Wakisaka, T; Wallny, R; Wang, S M; Warburton, A; Waters, D; Weinberger, M; Weinelt, J; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Wilbur, S; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Würthwein, F; Xie, S; Yagil, A; Yamamoto, K; Yamaoka, J; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zhang, X; Zheng, Y; Zucchelli, S

    2009-06-05

    We present a measurement of the tt[over ] differential cross section with respect to the tt[over ] invariant mass, dsigma/dM_{tt[over ]}, in pp[over ] collisions at sqrt[s]=1.96 TeV using an integrated luminosity of 2.7 fb;{-1} collected by the CDF II experiment. The tt[over ] invariant mass spectrum is sensitive to a variety of exotic particles decaying into tt[over ] pairs. The result is consistent with the standard model expectation, as modeled by PYTHIA with CTEQ5L parton distribution functions.

  17. Evidence of cross-contamination by Campylobacter spp. of broiler carcasses using genetic characterization of isolates.

    PubMed

    Normand, Valérie; Boulianne, Martine; Quessy, Sylvain

    2008-10-01

    Campylobacter is recognized as one of the leading cause of gastroenteritis worldwide, and is frequently isolated from the small intestines and ceca microflora of chickens. Twenty-one out of 81 Campylobacter-positive poultry flocks were selected to evaluate the genetic diversity of Campylobacter isolates and to study the distribution of genotypes among flocks. Campylobacter isolates recovered from chicken carcasses and ceca were analyzed by pulsed-field gel electrophoresis (PFGE). Little diversity was found among Campylobacter strains isolated from a given carcass, with a maximum of 2 different genotypes being present. However, at flock level, as many as 4 different profiles were observed. Typing of strains showed that most strains isolated from ceca were similar to those isolated from corresponding broiler carcasses. A total of 39 different macrorestriction profiles were observed, with evidence of Campylobacter cross-contamination among broiler flocks in Quebec slaughterhouses. Surprisingly, some flocks shared related genotypes both with and without sharing similar rearing practices. Existence of such cross-contamination must be considered to in developing strategies to control Campylobacter in chickens, and to avoid bacteria contamination of noncolonized flocks. Further typing studies of Campylobacter found in hatcheries, farm environment, and crates or trucks in Quebec might be helpful in elucidating the kinetics of broiler chicken Campylobacter contamination.

  18. Evidence of cross-contamination by Campylobacter spp. of broiler carcasses using genetic characterization of isolates

    PubMed Central

    Normand, Valérie; Boulianne, Martine; Quessy, Sylvain

    2008-01-01

    Campylobacter is recognized as one of the leading cause of gastroenteritis worldwide, and is frequently isolated from the small intestines and ceca microflora of chickens. Twenty-one out of 81 Campylobacter-positive poultry flocks were selected to evaluate the genetic diversity of Campylobacter isolates and to study the distribution of genotypes among flocks. Campylobacter isolates recovered from chicken carcasses and ceca were analyzed by pulsed-field gel electrophoresis (PFGE). Little diversity was found among Campylobacter strains isolated from a given carcass, with a maximum of 2 different genotypes being present. However, at flock level, as many as 4 different profiles were observed. Typing of strains showed that most strains isolated from ceca were similar to those isolated from corresponding broiler carcasses. A total of 39 different macrorestriction profiles were observed, with evidence of Campylobacter cross-contamination among broiler flocks in Quebec slaughterhouses. Surprisingly, some flocks shared related genotypes both with and without sharing similar rearing practices. Existence of such cross-contamination must be considered to in developing strategies to control Campylobacter in chickens, and to avoid bacteria contamination of noncolonized flocks. Further typing studies of Campylobacter found in hatcheries, farm environment, and crates or trucks in Quebec might be helpful in elucidating the kinetics of broiler chicken Campylobacter contamination. PMID:19086371

  19. Maternal and genetic factors in stress-resilient and -vulnerable rats: a cross-fostering study.

    PubMed

    Uchida, Shusaku; Hara, Kumiko; Kobayashi, Ayumi; Otsuki, Koji; Hobara, Teruyuki; Yamagata, Hirotaka; Watanabe, Yoshifumi

    2010-02-26

    Early environmental factors can modulate the development of the hypothalamic-pituitary-adrenal (HPA) axis response to stress, together with subsequent brain functions and emotional behaviors. Two rat strains, Sprague-Dawley (SD) and Fischer 344 (F344), are known to exhibit differences in HPA axis reactivity and anxiety behavior in response to restraint stress in adulthood. To investigate the contribution of maternal influences in determining HPA axis and behavioral responses to stress, a cross-fostering study was performed using stress-resilient (SD) or stress-susceptible (F344) strains. We found that SD rats adopted by either an SD (in-fostered) or an F344 (cross-fostered) dam and F344 rats adopted by an SD dam (cross-fostered) showed a suppression of the HPA axis response following 14 days of repeated restraint stress. In contrast, F344 rats adopted by an F344 dam (in-fostered) did not show such HPA axis habituation. We also found that F344 rats adopted by an F344 dam showed increased anxiety-related behaviors in social interaction and novelty-suppressed feeding tests as a result of the 14 days of restraint stress, while SD rats adopted by either an SD or an F344 dam and F344 rats adopted by an SD dam showed normal anxiety-related behaviors under the same experimental conditions. These results suggest that while genetic differences between SD and F344 strains account for some of the variations in stress vulnerability, maternal factors also contribute. (c) 2009 Elsevier B.V. All rights reserved.

  20. [Nephrolithiasis in "disk-variant" cross-over renal dystopia. Report of a case].

    PubMed

    Gebauer, B; Meyer, D R; Friedrich, M

    1998-01-01

    Renal dystopia is a frequent urogenital anomality. Renal dystopia encloses pelvic kidney or malascending kidney, but also rare anomalities like renal duplication or crossed renal dystopia. These allotopias are often diagnosed on routine examination of the urogenital system. We report a case with fused crossed renal dystopia on the left with atypical symptoms of nephrolithiasis and give a summery of the embryological origin.

  1. Computer-assisted instruction in parasitology: a cross-over design.

    PubMed

    Sanprasert, Vivornpun; Jaratsing, Pornpun; Nuchprayoon, Issarang; Nuchprayoon, Surang

    2005-09-01

    We report here the results of the study using CAI compared to the hard copy for study of lessons in parasitology. We evaluated the CAI compared to hard copy lessons in 60 students, attending the third-year parasitology course at Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. The students were randomly divided into two groups (30 each). The lessons tested were Ascaris lumbricoides and Enterobius vermicularis, which were prepared as CAI and hard copy form. Using a cross-over design, the first group was provided CAI form on the topic of A. lumbricoides, then switched to hard copy form on the topic of E. vermicularis. The second group was provided hard copy form on the topic of A. lumbricoides, then switched to CAI form on the topic of E. vermicularis. After 30 minute reading, the 10-multiple choice question test was provided for each topic. There was no significant difference of the scores between 2 groups. The most students (91.67%) had more satisfaction when using CAI compared to hard copy in terms of easy to use, convenient to use, less time consuming, more understandable, more attractive to read, and less stress for study. There were 32.8% students complaining that reading hard copy was boring. Other comments were stress when reading (2%), more difficult (17.2%) and more time needed to search specific information (17.2%), and wasting papers (17.2%). However 58.6% still complained problems when using CAL. About 25% had physical discomfort (e.g. Headache, eye pain), and 25% had difficulty to access to use CAI (e.g. no computers available, problems with computer or network error). We suggested that instructors should create and improve CAI lessons in biomedical sciences both in quantity and quality (e.g. content with details, pictures, narrations).

  2. Where and When To Inject Low Molecular Weight Heparin in Hemodiafiltration? A Cross Over Randomised Trial

    PubMed Central

    Dhondt, Annemieke; Pauwels, Ruben; Devreese, Katrien; Eloot, Sunny; Glorieux, Griet; Vanholder, Raymond

    2015-01-01

    Background and Objective Low molecular weight heparins (LMWHs) are small enough to pass large pore dialysis membranes. Removal of LMWH if injected before the start of the session is possible during high-flux dialysis and hemodiafiltration. The aim of this study was to determine the optimal mode (place and time) of tinzaparin administration during postdilution hemodiafiltration. Study Design, Setting, Patients In 13 chronic hemodiafiltration patients, 3 approaches of injection were compared in a randomised cross over trial: i) before the start of the session at the inlet blood line filled with rinsing solution (IN0), ii) 5 min after the start at the inlet line filled with blood (IN5) and iii) before the start of the session at the outlet blood line (OUT0). Anti-Xa activity, thrombin generation, visual clotting score and reduction ratios of urea and beta2microglobulin were measured. Results Anti-Xa activity was lower with IN0 compared with IN5 and OUT0, and also more thrombin generation was observed with IN0. No differences were observed in visual clotting scores and no clinically relevant differences were observed in solute reduction ratio. An anti-Xa of 0.3 IU/mL was discriminative for thrombin generation. Anti-Xa levels below 0.3 IU/mL at the end of the session were associated with worse clotting scores and lower reduction ratio of urea and beta2microglobulin. Conclusions Injection of tinzaparin at the inlet line before the start of postdilution hemodiafiltration is associated with loss of anticoagulant activity and can therefore not be recommended. Additionally, we found that an anti-Xa above 0.3 IU/mL at the end of the session is associated with less clotting and higher dialysis adequacy. Trial Registration Clinicaltrials.gov NCT00756145 PMID:26076014

  3. A cross-assessment of CCI-ECVs and RCSM simulations over the Mediterranean area

    NASA Astrophysics Data System (ADS)

    D'Errico, Miriam; Planton, Serge; Nabat, Pierre

    2017-04-01

    A first objective of this study, conducted in the framework of the Climate Modelling Users Group (CMUG), one of the projects of the European Space Agency Climate Change Initiative (ESA CCI) program, is a cross-assessment of simulations of a Med-CORDEX regional climate system model (CNRM-RCSM5) and a sub-set of atmosphere, marine and surface interrelated Satellite-Derived Essential Climate Variables (CCI-ECVs) (i.e. sea surface temperature, sea level, aerosols and soil moisture content) over the Mediterranean area. The consistency between the model and the CCI-ECVs is evaluated through the analysis of a climate specific event that can be observed with the CCI-ECVs, in atmospheric reanalysis and reproduced in the RCSM simulations. In this presentation we focus on the July 2006 heat wave that affected the western part of the Mediterranean continental and marine area. The application of a spectral nudging method using ERA-Interim reanalysis in our simulation allows to reproduce this event with a proper chronology. As a result we show that the consistency between the simulated model aerosol optical depth and the ECV products (being produced by the ESA Aerosol CCI project consortium) depends on the choice of the algorithm used to infer the variable from the satellite observations. In particular the heat wave main characteristics become consistent between the model and the satellite-derived observations for sea surface temperature, soil moisture and sea level. The link between the atmospheric circulation and the aerosols distribution is also investigated.

  4. Conditional Poisson models: a flexible alternative to conditional logistic case cross-over analysis.

    PubMed

    Armstrong, Ben G; Gasparrini, Antonio; Tobias, Aurelio

    2014-11-24

    The time stratified case cross-over approach is a popular alternative to conventional time series regression for analysing associations between time series of environmental exposures (air pollution, weather) and counts of health outcomes. These are almost always analyzed using conditional logistic regression on data expanded to case-control (case crossover) format, but this has some limitations. In particular adjusting for overdispersion and auto-correlation in the counts is not possible. It has been established that a Poisson model for counts with stratum indicators gives identical estimates to those from conditional logistic regression and does not have these limitations, but it is little used, probably because of the overheads in estimating many stratum parameters. The conditional Poisson model avoids estimating stratum parameters by conditioning on the total event count in each stratum, thus simplifying the computing and increasing the number of strata for which fitting is feasible compared with the standard unconditional Poisson model. Unlike the conditional logistic model, the conditional Poisson model does not require expanding the data, and can adjust for overdispersion and auto-correlation. It is available in Stata, R, and other packages. By applying to some real data and using simulations, we demonstrate that conditional Poisson models were simpler to code and shorter to run than are conditional logistic analyses and can be fitted to larger data sets than possible with standard Poisson models. Allowing for overdispersion or autocorrelation was possible with the conditional Poisson model but when not required this model gave identical estimates to those from conditional logistic regression. Conditional Poisson regression models provide an alternative to case crossover analysis of stratified time series data with some advantages. The conditional Poisson model can also be used in other contexts in which primary control for confounding is by fine

  5. Variation and Evolution of the Meiotic Requirement for Crossing Over in Mammals

    PubMed Central

    2017-01-01

    The segregation of homologous chromosomes at the first meiotic division is dependent on the presence of at least one well-positioned crossover per chromosome. In some mammalian species, however, the genomic distribution of crossovers is consistent with a more stringent baseline requirement of one crossover per chromosome arm. Given that the meiotic requirement for crossing over defines the minimum frequency of recombination necessary for the production of viable gametes, determining the chromosomal scale of this constraint is essential for defining crossover profiles predisposed to aneuploidy and understanding the parameters that shape patterns of recombination rate evolution across species. Here, I use cytogenetic methods for in situ imaging of crossovers in karyotypically diverse house mice (Mus musculus domesticus) and voles (genus Microtus) to test how chromosome number and configuration constrain the distribution of crossovers in a genome. I show that the global distribution of crossovers in house mice is thresholded by a minimum of one crossover per chromosome arm, whereas the crossover landscape in voles is defined by a more relaxed requirement of one crossover per chromosome. I extend these findings in an evolutionary metaanalysis of published recombination and karyotype data for 112 mammalian species and demonstrate that the physical scale of the genomic crossover distribution has undergone multiple independent shifts from one crossover per chromosome arm to one per chromosome during mammalian evolution. Together, these results indicate that the chromosomal scale constraint on crossover rates is itself a trait that evolves among species, a finding that casts light on an important source of crossover rate variation in mammals. PMID:27838628

  6. Cross-Spectra Over the Sea from Observations and Mesoscale Modelling

    NASA Astrophysics Data System (ADS)

    Vincent, C. L.; Larsén, X. G.; Larsen, S. E.; Sørensen, P.

    2013-02-01

    Cospectra and quadrature spectra are calculated for six pairs of tall offshore measurement masts near the Horns Rev I wind farm in the Danish North Sea and the Nysted wind farm in the Baltic sea. The mast-pairs are separated from one another by horizontal distances of 2.13-12.4 km. Cospectra and quadrature spectra for the two sites are classified in terms of the angle between the mean wind direction and the line connecting each pair of masts. The frequency axes of the spectra are normalized to remove the effect of mean wind speed and separation distance. Results indicate a larger contribution to the quadrature spectrum for flow from the sea than for flow from the land, and the patterns in the spectra are clearer and better defined for Horns Rev I (which has a long uninterrupted sea-fetch from the west) than for Nysted (which is surrounded by a more complicated coastline). The analysis is replicated based on 3-month simulations using the weather research and forecasting (WRF) numerical model with a horizontal grid spacing of 2 km. For the sea-fetch directions, good agreement in spectral properties between the model and observations is found. Analytical expressions based on the properties of the cross-correlation function and an exponentially decaying coherence function are fitted to the normalized cospectra and quadrature spectra. The expressions are shown to be a good fit to the spectra calculated from the WRF simulations and to the observed spectra for directions with a long sea-fetch, which suggests that to a good approximation, the average cospectra and quadrature spectra over the sea can be written as functions of frequency, mean wind speed, separation distance and the angle between the wind direction and the orientation of the masts.

  7. Cardiovascular Effects of Energy Drinks in Familial Long QT Syndrome: A Randomized Cross-Over Study.

    PubMed

    Gray, Belinda; Ingles, Jodie; Medi, Caroline; Driscoll, Timothy; Semsarian, Christopher

    2017-03-15

    Caffeinated energy drinks may trigger serious cardiac effects. The aim of this study was to determine the cardiovascular effects of caffeinated energy drink consumption in patients with familial long QT syndrome (LQTS). From 2014-2016, 24 LQTS patients aged 16-50 years were recruited to a randomized, double-blind, cross-over study of energy drink (ED) versus control (CD) with participants acting as their own controls (one week washout). The primary study outcome was an increase in corrected QT interval (QTc) by >20ms. Secondary outcomes were changes in systolic and diastolic blood pressure. In 24 patients with LQTS (no dropout), mean age was 29±9 years, 13/24 (54%) were female, and 8/24 (33%) were probands. Intention to treat analysis revealed no significant change in QTc with ED compared with CD (12±28ms vs 16±27ms, 3% vs 4%, p=0.71). The systolic and diastolic blood pressure significantly increased with ED compared to CD (peak change 7±16mmHg vs 1±16mmHg, 6% vs 0.8%, p=0.046 and 8±10 vs 2±9mmHg, 11% vs 3% p=0.01 respectively). These changes correlated with significant increases in serum caffeine (14.6±11.3 vs 0.5±0.1μmol/L, p<0.001) and serum taurine (737±199 vs -59±22μmol/L, p<0.001). There were three patients with dangerous QTc prolongation of ≥50ms following energy drink consumption. Caffeinated energy drinks have significant haemodynamic effects in patients with LQTS, especifically an acute increase in blood pressure. Since dangerous QTc prolongation was seen in some LQTS patients, we recommend caution in young patients with LQTS consuming energy drinks. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Antibiotics in periodontal surgeries: A prospective randomised cross over clinical trial

    PubMed Central

    Oswal, Sheetal; Ravindra, Shivamurthy; Sinha, Aditya; Manjunath, Shaurya

    2014-01-01

    Aims and Objectives: (1) To evaluate the need of antibiotics in periodontal surgeries in reducing postsurgical infections and explore if antibiotics have any key role in reducing or eliminating inflammatory complications. (2) To establish the incidence of postoperative infections in relation to type of surgery and determine those factors, which may affect infection rates. Materials and Methods: A prospective randomized double-blind cross over clinical study was carried out for a period of 1-year with predefined inclusion and exclusion criteria. All the patients included in the study for any periodontal surgery were randomly divided into three categories: Group A (prophylactic), Group B (therapeutic), and Group C (no antibiotics). Patients were followed up for 1-week after surgery on the day of suture removal and were evaluated for pain, swelling, fever, infection, delayed wound healing and any other significant findings. Appropriate statistical analysis was carried out to evaluate the objectives and P < 0.05 was considered as statistically significant. Results: No infection was reported in any of 90 sites. Patients reported less pain and postoperative discomfort when prophylactic antibiotics were given. However, there were no statistical significant differences between the three groups. Summary and Conclusion: There was no postoperative infection reported in all the 90 sites operated in this study. The prevalence of postoperative infections following periodontal surgery is <1% and this low risk does not justify the routine use of systemic antimicrobials just to prevent infections. Use of prophylactic antibiotics may have role in prevention of inflammatory complication, but again not infection. PMID:25425817

  9. Hematological clozapine monitoring with a point-of-care device: a randomized cross-over trial.

    PubMed

    Nielsen, Jimmi; Thode, Dorrit; Stenager, Elsebeth; Andersen, Kristian Øllegaard; Sondrup, Ulla; Hansen, Tine N; Munk, Anne Marie; Lykkegaard, Signe; Gosvig, Annette; Petrov, Igor; le Quach, Phuong

    2012-06-01

    Clozapine remains the drug of choice for patients with treatment-resistant schizophrenia, who show a response rate of about 50% despite their unresponsiveness to other antipsychotics. Although treatment with clozapine can lead to considerable savings on bed days, the drug is underutilized for several reasons, perhaps most importantly because of the mandatory hematological monitoring. The Chempaq Express Blood Counter (Chempaq XBC) is a point-of-care device providing counts of white blood cells (WBC) and granulocytes based on a capillary blood sampling. A randomized cross-over trial design was used comparing capillary blood sampling using a point-of-care device with traditional venous blood sampling. Patients were randomized to two sequences starting with either capillary or venous blood sampling followed by a repeated sequence. Primary outcome was measured on a 10-cm visual analog scale. Eighty-five patients were included in the test. Eight (9.4%) dropped out before completion. Patients indicated that they found capillary blood monitoring less painful than venous sampling (VAS ratings: 0.55 cm 25-75 percentiles: 0.1-1.4 cm vs. 1.75 cm 25-75 percentiles: 0.7-2.6, p<0.001). They also felt less inconvenienced by the point-of-care method than the traditional blood sampling, which involved traveling to the laboratory clinical (0.3 cm 25-75 percentiles: 0.05-0.7 vs. 2.3 cm 25-75 percentiles: 0.75-4.5, p<0.001). For hematological monitoring of clozapine patients a point-of-care device based on capillary blood sampling is better tolerated than traditional venous blood sampling.

  10. Variation and Evolution of the Meiotic Requirement for Crossing Over in Mammals.

    PubMed

    Dumont, Beth L

    2017-01-01

    The segregation of homologous chromosomes at the first meiotic division is dependent on the presence of at least one well-positioned crossover per chromosome. In some mammalian species, however, the genomic distribution of crossovers is consistent with a more stringent baseline requirement of one crossover per chromosome arm. Given that the meiotic requirement for crossing over defines the minimum frequency of recombination necessary for the production of viable gametes, determining the chromosomal scale of this constraint is essential for defining crossover profiles predisposed to aneuploidy and understanding the parameters that shape patterns of recombination rate evolution across species. Here, I use cytogenetic methods for in situ imaging of crossovers in karyotypically diverse house mice (Mus musculus domesticus) and voles (genus Microtus) to test how chromosome number and configuration constrain the distribution of crossovers in a genome. I show that the global distribution of crossovers in house mice is thresholded by a minimum of one crossover per chromosome arm, whereas the crossover landscape in voles is defined by a more relaxed requirement of one crossover per chromosome. I extend these findings in an evolutionary metaanalysis of published recombination and karyotype data for 112 mammalian species and demonstrate that the physical scale of the genomic crossover distribution has undergone multiple independent shifts from one crossover per chromosome arm to one per chromosome during mammalian evolution. Together, these results indicate that the chromosomal scale constraint on crossover rates is itself a trait that evolves among species, a finding that casts light on an important source of crossover rate variation in mammals.

  11. Spatio-temporal Genetic Structure of a Tropical Bee Species Suggests High Dispersal Over a Fragmented Landscape.

    PubMed

    Suni, Sevan S; Bronstein, Judith L; Brosi, Berry J

    2014-03-01

    Habitat destruction threatens biodiversity by reducing the amount of available resources and connectivity among geographic areas. For organisms living in fragmented habitats, population persistence may depend on dispersal, which maintains gene flow among fragments and can prevent inbreeding within them. It is centrally important to understand patterns of dispersal for bees living in fragmented areas given the importance of pollination systems and recently documented declines in bee populations. We used population and landscape genetic techniques to characterize patterns of dispersal over a large fragmented area in southern Costa Rica for the orchid bee species Euglossa championi. First, we estimated levels of genetic differentiation among forest fragments as φpt, an analog to the traditional summary statistic Fst, as well as two statistics that may more adequately represent levels of differentiation, G'st and Dest . Second, we used a Bayesian approach to determine the number and composition of genetic groups in our sample. Third we investigated how genetic differentiation changes with distance. Fourth, we determined the extent to which deforested areas restrict dispersal. Finally, we estimated the extent to which there were temporal differences in allele frequencies within the same forest fragments. Within years we found low levels of differentiation even over 80 km, and no effect of land use type on level of genetic differentiation. However, we found significant genetic differentiation between years. Taken together our results suggest that there are high levels of gene flow over this geographic area, and that individuals show low site fidelity over time.

  12. Spatio-temporal Genetic Structure of a Tropical Bee Species Suggests High Dispersal Over a Fragmented Landscape

    PubMed Central

    Suni, Sevan S.; Bronstein, Judith L.; Brosi, Berry J.

    2014-01-01

    Habitat destruction threatens biodiversity by reducing the amount of available resources and connectivity among geographic areas. For organisms living in fragmented habitats, population persistence may depend on dispersal, which maintains gene flow among fragments and can prevent inbreeding within them. It is centrally important to understand patterns of dispersal for bees living in fragmented areas given the importance of pollination systems and recently documented declines in bee populations. We used population and landscape genetic techniques to characterize patterns of dispersal over a large fragmented area in southern Costa Rica for the orchid bee species Euglossa championi. First, we estimated levels of genetic differentiation among forest fragments as φpt, an analog to the traditional summary statistic Fst, as well as two statistics that may more adequately represent levels of differentiation, G’st and Dest. Second, we used a Bayesian approach to determine the number and composition of genetic groups in our sample. Third we investigated how genetic differentiation changes with distance. Fourth, we determined the extent to which deforested areas restrict dispersal. Finally, we estimated the extent to which there were temporal differences in allele frequencies within the same forest fragments. Within years we found low levels of differentiation even over 80 km, and no effect of land use type on level of genetic differentiation. However, we found significant genetic differentiation between years. Taken together our results suggest that there are high levels of gene flow over this geographic area, and that individuals show low site fidelity over time. PMID:24659825

  13. Measuring the effect of enhanced cleaning in a UK hospital: a prospective cross-over study

    PubMed Central

    Dancer, Stephanie J; White, Liza F; Lamb, Jim; Girvan, E Kirsty; Robertson, Chris

    2009-01-01

    Background Increasing hospital-acquired infections have generated much attention over the last decade. There is evidence that hygienic cleaning has a role in the control of hospital-acquired infections. This study aimed to evaluate the potential impact of one additional cleaner by using microbiological standards based on aerobic colony counts and the presence of Staphylococcus aureus including meticillin-resistant S. aureus. Methods We introduced an additional cleaner into two matched wards from Monday to Friday, with each ward receiving enhanced cleaning for six months in a cross-over design. Ten hand-touch sites on both wards were screened weekly using standardised methods and patients were monitored for meticillin-resistant S. aureus infection throughout the year-long study. Patient and environmental meticillin-resistant S. aureus isolates were characterised using molecular methods in order to investigate temporal and clonal relationships. Results Enhanced cleaning was associated with a 32.5% reduction in levels of microbial contamination at hand-touch sites when wards received enhanced cleaning (P < 0.0001: 95% CI 20.2%, 42.9%). Near-patient sites (lockers, overbed tables and beds) were more frequently contaminated with meticillin-resistant S. aureus/S. aureus than sites further from the patient (P = 0.065). Genotyping identified indistinguishable strains from both hand-touch sites and patients. There was a 26.6% reduction in new meticillin-resistant S. aureus infections on the wards receiving extra cleaning, despite higher meticillin-resistant S. aureus patient-days and bed occupancy rates during enhanced cleaning periods (P = 0.032: 95% CI 7.7%, 92.3%). Adjusting for meticillin-resistant S. aureus patient-days and based upon nine new meticillin-resistant S. aureus infections seen during routine cleaning, we expected 13 new infections during enhanced cleaning periods rather than the four that actually occurred. Clusters of new meticillin-resistant S. aureus

  14. A study on the distribution of polystyrene sulfonic acid grafts over the cross-section of a PFA film

    NASA Astrophysics Data System (ADS)

    Shin, Junhwa; Ko, Beom-Seok; Kang, Sung-A.; Fei, Geng; Nho, Young-Chang; Kang, Phil-Hyun

    2009-03-01

    In this study, the distribution behaviors of polystyrene sulfonic acid (PSSA) grafts over the cross-section of grafted PFA membranes (PFA- g-PSSA) were investigated by using SEM-EDX analysis. Membranes with various degrees of grafting (DOG) and thicknesses were prepared by a simultaneous radiation grafting of styrene and a subsequent sulfonation with chlorosulfonic acid. A SEM-EDX instrument was utilized to directly observe that the distribution behaviors of the PSSA grafts over the cross-section of grafted PFA membranes and the results showed that the distribution behaviors were largely affected by the grafting conditions such as the degree of grafting, monomer concentration, and film thickness.

  15. Knowledge, attitudes and preferences regarding genetic testing for smoking cessation. A cross-sectional survey among Dutch smokers

    PubMed Central

    Smerecnik, Chris; van Schooten, Frederik J; de Vries, Hein; van Schayck, Constant P

    2012-01-01

    Objectives Recent research strongly suggests that genetic variation influences smokers' ability to stop. Therefore, the use of (pharmaco) genetic testing may increase cessation rates. This study aims to assess the intention of smokers concerning undergoing genetic testing for smoking cessation and their knowledge, attitudes and preferences about this subject. Design Online cross-sectional survey. Setting Database internet research company of which every inhabitant of the Netherlands of ≥12 years with an email address and capable of understanding Dutch can become a member. Participants 587 of 711 Dutch smokers aged ≥18 years, daily smokers for ≥5 years and smoke on average ≥10 cigarettes/day (response rate=83%). Primary and secondary outcome measures Smokers' knowledge, attitudes and preferences and their intention to undergo genetic testing for smoking cessation. Results Knowledge on the influence of genetic factors in smoking addiction and cessation was found to be low. Smokers underestimated their chances of having a genetic predisposition and the influence of this on smoking cessation. Participants perceived few disadvantages, some advantages and showed moderate self-efficacy towards undergoing a genetic test and dealing with the results. Smokers were mildly interested in receiving information and participating in genetic testing, especially when offered by their general practitioner (GP). Conclusions For successful implementation of genetic testing for smoking in general practice, several issues should be addressed, such as the knowledge on smoking cessation, genetics and genetic testing (including advantages and disadvantages) and the influence of genetics on smoking addiction and cessation. Furthermore, smokers allocate their GPs a crucial role in the provision of information and the delivery of a genetic test for smoking; however, it is unclear whether GPs will be able and willing to take on this role. PMID:22223839

  16. Low Cross-Sex Genetic Correlation in Carotenoid-Based Plumage Traits in the Blue Tit Nestlings (Cyanistes caeruleus)

    PubMed Central

    Drobniak, Szymon M.; Wiejaczka, Dariusz; Arct, Aneta; Dubiec, Anna; Gustafsson, Lars; Cichoń, Mariusz

    2013-01-01

    In some bird species, both adult and juvenile individuals are often brightly coloured. It has been commonly assumed that identical plumage colouration present in both sexes results from strong intersexual genetic correlations in colour-related traits. Here, we aimed at testing this hypothesis in juvenile individuals and looked at genetic parameters describing carotenoid-based colouration of blue tit nestlings in a wild population. To separate genetic and environmental sources of phenotypic variation we performed a cross-fostering experiment. Our analyses confirmed the existence of sexual dichromatism in blue tit nestlings and revealed a significant, although low, genetic component of carotenoid-based colouration. However, genetic effects are expressed differently across sexes as indicated by low cross-sex genetic correlations (rmf). Thus our results do not support the prediction of generally high rmf and suggest that intersexual constraints on the evolution of colouration traits may be weaker than expected. We hypothesise that observed patterns of genetic correlations result from sex-specific selective pressures acting on nestling plumage colouration. PMID:23936101

  17. Arthroscopy or ultrasound in undergraduate anatomy education: a randomized cross-over controlled trial

    PubMed Central

    2012-01-01

    Background The exponential growth of image-based diagnostic and minimally invasive interventions requires a detailed three-dimensional anatomical knowledge and increases the demand towards the undergraduate anatomical curriculum. This randomized controlled trial investigates whether musculoskeletal ultrasound (MSUS) or arthroscopic methods can increase the anatomical knowledge uptake. Methods Second-year medical students were randomly allocated to three groups. In addition to the compulsory dissection course, the ultrasound group (MSUS) was taught by eight, didactically and professionally trained, experienced student-teachers and the arthroscopy group (ASK) was taught by eight experienced physicians. The control group (CON) acquired the anatomical knowledge only via the dissection course. Exposure (MSUS and ASK) took place in two separate lessons (75 minutes each, shoulder and knee joint) and introduced standard scan planes using a 10-MHz ultrasound system as well as arthroscopy tutorials at a simulator combined with video tutorials. The theoretical anatomic learning outcomes were tested using a multiple-choice questionnaire (MCQ), and after cross-over an objective structured clinical examination (OSCE). Differences in student’s perceptions were evaluated using Likert scale-based items. Results The ASK-group (n = 70, age 23.4 (20–36) yrs.) performed moderately better in the anatomical MC exam in comparison to the MSUS-group (n = 84, age 24.2 (20–53) yrs.) and the CON-group (n = 88, 22.8 (20–33) yrs.; p = 0.019). After an additional arthroscopy teaching 1% of students failed the MC exam, in contrast to 10% in the MSUS- or CON-group, respectively. The benefit of the ASK module was limited to the shoulder area (p < 0.001). The final examination (OSCE) showed no significant differences between any of the groups with good overall performances. In the evaluation, the students certified the arthroscopic tutorial a greater advantage concerning anatomical skills

  18. Short Daily versus Conventional Hemodialysis for Hypertensive Patients: A Randomized Cross-Over Study

    PubMed Central

    Zimmerman, Deborah L.; Ruzicka, Marcel; Hebert, Paul; Fergusson, Dean; Touyz, Rhian M.; Burns, Kevin D.

    2014-01-01

    Background Treatment of end stage renal disease patients with short daily hemodialysis has been associated with an improvement in blood pressure. It is unclear from these studies if anti-hypertensive management had been optimized prior to starting short daily hemodialysis. Also, the potential mechanism(s) of blood pressure improvement remain to be fully elucidated. Study Design, Setting and Participants We undertook a randomized cross-over trial in adult hypertensive patients with ESRD treated with conventional hemodialysis to determine: 1) if short-daily hemodialysis is associated with a reduction in systolic blood pressure after a 3-month blood pressure optimization period and; 2) the potential mechanism(s) of blood pressure reduction. Blood pressure was measured using Canadian Hypertension Education Program guidelines. Extracellular fluid volume (ECFV) was assessed with bioimpedance. Serum catecholamines were used to assess the sympathetic nervous system. Interleukin-6 (IL-6) and thiobarbituric acid reactive substances (T-BARS) were used as markers of inflammation and oxidative stress respectively. Results After a 3-month run-in phase in which systolic blood pressure improved, there was no significant difference in pre-dialysis systolic pressure between short-daily and conventional hemodialysis (p = 0.39). However, similar blood pressures were achieved on fewer anti-hypertensive medications with short daily hemodialysis compared to conventional hemodialysis (p = 0.01). Short daily hemodialysis, compared to conventional hemodialysis, was not associated with a difference in dry weight or ECFV (p = 0.77). Sympathetic nervous system activity as assessed by plasma epinephrine (p = 1.0) and norepinephrine (p = 0.52) was also not different. Markers of inflammation (p = 0.42) and oxidative stress (p = 0.83) were also similar between the two treatment arms. Conclusions Patients treated with short daily, compared to conventional hemodialysis

  19. Analysis of spatial genetic structure in an expanding Pinus halepensis population reveals development of fine-scale genetic clustering over time.

    PubMed

    Troupin, D; Nathan, R; Vendramin, G G

    2006-10-01

    We analysed the change of spatial genetic structure (SGS) of reproductive individuals over time in an expanding Pinus halepensis population. To our knowledge, this is the first empirical study to analyse the temporal component of SGS by following the dynamics of successive cohorts of the same population over time, rather than analysing different age cohorts at a single time. SGS is influenced by various factors including restricted gene dispersal, microenvironmental selection, mating patterns and the spatial pattern of reproductive individuals. Several factors that affect SGS are expected to vary over time and as adult density increases. Using air photo analysis, tree-ring dating and molecular marker analysis we reconstructed the spread of reproductive individuals over 30 years beginning from five initial individuals. In the early stages, genotypes were distributed randomly in space. Over time and with increasing density, fine-scale (< 20 m) SGS developed and the magnitude of genetic clustering increased. The SGS was strongly affected by the initial spatial distribution and genetic variation of the founding individuals. The development of SGS may be explained by fine-scale environmental heterogeneity and possibly microenvironmental selection. Inbreeding and variation in reproductive success may have enhanced SGS magnitude over time.

  20. [Influences of excision repair cross complementation group 4 genetic variations on DNA damage in lymphocytes among coke oven workers].

    PubMed

    Yang, Xiao-bo; Zhen, Jin-ping; Bai, Yun; Wang, Hong; Tan, Hao; Tian, Feng-jie; Chen, Wei-hong; Wu, Tang-chun

    2007-08-01

    To investigate the relationship between excision repair cross complementation group 4 ERCC4 gene polymorphisms and DNA damage in lymphocytes of coke oven workers and controls. Two hundred and forty-six coke oven workers and one hundred and twenty-seven controls were recruited in the study, and peripheral vein blood was drawn after over night fasting. Comet assay was used to evaluate DNA damage, and TaqMan-MGB probes were used to analyze ERCC4 genetic variations including the three Tagged-single nucleotide polymorphisms (Tag SNPs), referred to rs744154, rs3136079 and rs31870 which were picked out from Hapmap database. Then haplotypes were reconstructed by PHASE2.0.2 software. The lymphocytes Olive TM value of coke oven workers was significantly higher than that of controls (1.26+/-1.12 vs 0.52+/-0.97, P<0.01). Among coke oven workers, no significant difference was found between the Olive TM of those with different genotypes or haplotype pairs at ERCC4 gene (P>0.05). However, in the control group, the TG genotype carriers had higher Olive TM than the TT and GG genotype carriers (0.26+/-0.96 vs 0.66+/-0.98 and 0.66+/-0.51, P<0.05), and the CTG/CTG haplotype pairs carriers had the highest Olive TM (0.69+/-1.01), and no CTG haplotype carriers had the lowest Olive TM (0.25+/-0.80), and the difference was borderline (P=0.08). The gene polymorphism at ERCC4 gene has no effects on the DNA damage of lymphocytes in coke oven workers, but the TG genotype carriers has lower DNA damage in the control. DNA damage is influenced by the interaction of genetic and environmental factors.

  1. Membrane tethering by the atlastin GTPase depends on GTP hydrolysis but not on forming the cross-over configuration.

    PubMed

    Saini, Simran G; Liu, Chuang; Zhang, Peijun; Lee, Tina H

    2014-12-01

    The membrane-anchored atlastin GTPase couples nucleotide hydrolysis to the catalysis of homotypic membrane fusion to form a branched endoplasmic reticulum network. Trans dimerization between atlastins anchored in opposing membranes, accompanied by a cross-over conformational change, is thought to draw the membranes together for fusion. Previous studies on the conformational coupling of atlastin to its GTP hydrolysis cycle have been carried out largely on atlastins lacking a membrane anchor. Consequently, whether fusion involves a discrete tethering step and, if so, the potential role of GTP hydrolysis and cross-over in tethering remain unknown. In this study, we used membrane-anchored atlastins in assays that separate tethering from fusion to dissect the requirements for each. We found that tethering depended on GTP hydrolysis, but, unlike fusion, it did not depend on cross-over. Thus GTP hydrolysis initiates stable head-domain contact in trans to tether opposing membranes, whereas cross-over formation plays a more pivotal role in powering the lipid rearrangements for fusion.

  2. 78 FR 59754 - Notice of Final Federal Agency Actions on the Proposed U.S. 50 Study Crossing Over Sinepauxent...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-27

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF TRANSPORTATION Federal Highway Administration Notice of Final Federal Agency Actions on the Proposed U.S. 50 Study Crossing Over Sinepauxent Bay in the Town of Ocean City, Worcester County, Maryland Correction In...

  3. Ultrasensitive detection of genetically modified plants by fluorescence cross-correlation spectroscopy

    NASA Astrophysics Data System (ADS)

    Li, Junfeng; Xing, Da; Chen, Tongsheng; Liu, Jinfeng

    2006-09-01

    In this study, a novel method for the direct detection of GMP without amplified by the general method of PCR is firstly presented and proved by experiments. In our method, fluorescence correlation spectroscopy, cleaving nucleic acid by restriction endonuclease and two nucleic acid probe hybridization techniques are combined to distinguish the caulifiower mosaic virus (CaMV) 35S promoter and determine whether samples contain genetically modified components. The detection principle is as follows: firstly two restriction endonucleases FOKI and BsrDlare used to cleave the genomic DNA and the 169bp fragments of CaMV 35S promoter are retrieved; secondly, two nucleic acid probes labeled by Rhodamine Green and y5 dyes respectively hybridize with cleaved 169bp fragments of CaMV 35S promoter; thirdly, the hybridization products simultaneously with two dye-labeled probes are detected by fluorescence cross-correlation spectroscopy and GMP is distinguished. As the detection and analysis by FCS can be performed at the level of single molecule, there is no need for any type of amplification. Genetically modified tobaccos are measured by this method. The results indicate this method can detect CaMV 35S promoter of GMP exactly and the sensitivity can be down to 3.47X10 -10M. Because no any type of amplification is involved, this method can avoid the non-specffic amplification and false-positive problems of PCR, Due to its high-sensitivity, simplicity, reliability and little need for sample amounts, this method promises to be a highly effective detection method for GMP.

  4. Population genetics of Cryptosporidium meleagridis in humans and birds: evidence for cross-species transmission.

    PubMed

    Wang, Yuanfei; Yang, Wenli; Cama, Vitaliano; Wang, Lin; Cabrera, Lilia; Ortega, Ynes; Bern, Caryn; Feng, Yaoyu; Gilman, Robert; Xiao, Lihua

    2014-07-01

    Population genetic studies have been used to understand the transmission of pathogens in humans and animals, especially the role of zoonotic infections and evolution and dispersal of virulent subtypes. In this study, we analysed the genetic diversity and population structure of Cryptosporidium meleagridis, the only known Cryptosporidium species that infects both avian and mammalian hosts and is responsible for approximately 10% of human cryptosporidiosis in some areas. A total of 62 C. meleagridis specimens from children, AIDS patients, and birds in Lima, Peru were characterised by sequence analysis of the ssrRNA gene and five minisatellite, microsatellite and polymorphic markers in chromosome 6, including the 60 kDa glycoprotein (gp60), 47 kDa glycoprotein (CP47), a serine repeat antigen (MSC6-5), retinitis pigmentosa GTPase regulator (RPGR) and thrombospondin protein 8 (TSP8). The multilocus sequence analysis identified concurrent infections with Cryptosporidium hominis in four AIDS patients and three children. Unique subtypes of C. meleagridis ranged from eight at the gp60 locus (gene diversity -Hd=0.651), three at the RPGR (Hd=0.556), three at the MSC6-5 locus (Hd=0.242), two at TSP8 (Hd=0.198), to one at CP47 (monomorphic), much lower than that of C. hominis in the same area. Intragenic linkage disequilibrium was strong and complete at all gene loci. Intergenic linkage disequilibrium was highly significant (P<0.001) for all pairs of polymorphic loci. Two major groups of subtypes were seen, with most subtypes belonging to group 1. Within group 1, there was no clear population segregation, and two of the 14 multilocus subtypes of C. meleagridis were found in both AIDS patients and birds. We believe that these results provide the first evidence of a clonal population structure of C. meleagridis and the likely occurrence of cross-species transmission of C. meleagridis between birds and humans. Published by Elsevier Ltd.

  5. Closed-loop separation control over a sharp edge ramp using genetic programming

    NASA Astrophysics Data System (ADS)

    Debien, Antoine; von Krbek, Kai A. F. F.; Mazellier, Nicolas; Duriez, Thomas; Cordier, Laurent; Noack, Bernd R.; Abel, Markus W.; Kourta, Azeddine

    2016-03-01

    We experimentally perform open and closed-loop control of a separating turbulent boundary layer downstream from a sharp edge ramp. The turbulent boundary layer just above the separation point has a Reynolds number Re_{θ }≈ 3500 based on momentum thickness. The goal of the control is to mitigate separation and early re-attachment. The forcing employs a spanwise array of active vortex generators. The flow state is monitored with skin-friction sensors downstream of the actuators. The feedback control law is obtained using model-free genetic programming control (GPC) (Gautier et al. in J Fluid Mech 770:442-457, 2015). The resulting flow is assessed using the momentum coefficient, pressure distribution and skin friction over the ramp and stereo PIV. The PIV yields vector field statistics, e.g. shear layer growth, the back-flow area and vortex region. GPC is benchmarked against the best periodic forcing. While open-loop control achieves separation reduction by locking-on the shedding mode, GPC gives rise to similar benefits by accelerating the shear layer growth. Moreover, GPC uses less actuation energy.

  6. The Drosophila over compensating males gene genetically inhibits dosage compensation in males.

    PubMed

    Lim, Chiat Koo; Kelley, Richard L

    2013-01-01

    Male Drosophila are monosomic for the X chromosome, but survive due to dosage compensation. They use the Male Specific Lethal (MSL) complex composed of noncoding roX RNA and histone modifying enzymes to hypertranscribe most genes along the X ∼1.6-1.8 fold relative to each female allele. It is not known how the MSL complex achieves this precise adjustment to a large and diverse set of target genes. We carried out a genetic screen searching for novel factors that regulate dosage compensation in flies. This strategy generated thirty alleles in a previously uncharacterized gene, over compensating males (ocm) that antagonizes some aspect of MSL activity. The mutations were initially recovered because they derepressed an MSL-dependent eye color reporter. Null ocm mutations are lethal to both sexes early in development revealing an essential function. Combinations of hypomorphic ocm alleles display a male specific lethality similar to mutations in the classic msl genes, but ocm males die due to excessive, rather than lack of dosage compensation. Males that die due to very low MSL activity can be partially rescued by ocm mutations. Likewise, males that would die from ocm mutations can be rescued by reducing the dose of various msl and roX genes. ocm encodes a large nuclear protein that shares a novel cysteine rich motif with known transcription factors.

  7. Relationships between parental negativity and childhood antisocial behavior over time: a bidirectional effects model in a longitudinal genetically informative design.

    PubMed

    Larsson, Henrik; Viding, Essi; Rijsdijk, Fruhling V; Plomin, Robert

    2008-07-01

    This study examined the direction and etiology underlying the relationships between parental negativity and early childhood antisocial behavior using a bidirectional effects model in a longitudinal genetically informative design. We analyzed parent reports of parental negativity and early childhood antisocial behavior in 6,230 pairs of twins at 4 and 7 years of age. Results from a cross-lagged twin model contribute to the understanding of the mechanisms underlying the bidirectional processes involved in parental negativity and childhood antisocial behavior. Specifically, the findings of this study suggest that the association between parenting and child antisocial behavior is best explained by both parent-driven and child-driven effects. We found support for the notion that parent's negative feelings towards their children environmentally mediate the risk for child antisocial behavior. We also found evidence of genetically mediated child effects; in which genetically influenced antisocial behavior evoke parental negativity towards the child.

  8. Genetic monitoring reveals temporal stability over 30 years in a small, lake-resident brown trout population.

    PubMed

    Charlier, J; Laikre, L; Ryman, N

    2012-10-01

    Knowledge of the degree of temporal stability of population genetic structure and composition is important for understanding microevolutionary processes and addressing issues of human impact of natural populations. We know little about how representative single samples in time are to reflect population genetic constitution, and we explore the temporal genetic variability patterns over a 30-year period of annual sampling of a lake-resident brown trout (Salmo trutta) population, covering 37 consecutive cohorts and five generations. Levels of variation remain largely stable over this period, with no indication of substructuring within the lake. We detect genetic drift, however, and the genetically effective population size (N(e)) was assessed from allele-frequency shifts between consecutive cohorts using an unbiased estimator that accounts for the effect of overlapping generation. The overall mean N(e) is estimated as 74. We find indications that N(e) varies over time, but there is no obvious temporal trend. We also estimated N(e) using a one-sample approach based on linkage disequilibrium (LD) that does not account for the effect of overlapping generations. Combining one-sample estimates for all years gives an N(e) estimate of 76. This similarity between estimates may be coincidental or reflecting a general robustness of the LD approach to violations of the discrete generations assumption. In contrast to the observed genetic stability, body size and catch per effort have increased over the study period. Estimates of annual effective number of breeders (N(b)) correlated with catch per effort, suggesting that genetic monitoring can be used for detecting fluctuations in abundance.

  9. Genetic monitoring reveals temporal stability over 30 years in a small, lake-resident brown trout population

    PubMed Central

    Charlier, J; Laikre, L; Ryman, N

    2012-01-01

    Knowledge of the degree of temporal stability of population genetic structure and composition is important for understanding microevolutionary processes and addressing issues of human impact of natural populations. We know little about how representative single samples in time are to reflect population genetic constitution, and we explore the temporal genetic variability patterns over a 30-year period of annual sampling of a lake-resident brown trout (Salmo trutta) population, covering 37 consecutive cohorts and five generations. Levels of variation remain largely stable over this period, with no indication of substructuring within the lake. We detect genetic drift, however, and the genetically effective population size (Ne) was assessed from allele-frequency shifts between consecutive cohorts using an unbiased estimator that accounts for the effect of overlapping generation. The overall mean Ne is estimated as 74. We find indications that Ne varies over time, but there is no obvious temporal trend. We also estimated Ne using a one-sample approach based on linkage disequilibrium (LD) that does not account for the effect of overlapping generations. Combining one-sample estimates for all years gives an Ne estimate of 76. This similarity between estimates may be coincidental or reflecting a general robustness of the LD approach to violations of the discrete generations assumption. In contrast to the observed genetic stability, body size and catch per effort have increased over the study period. Estimates of annual effective number of breeders (Nb) correlated with catch per effort, suggesting that genetic monitoring can be used for detecting fluctuations in abundance. PMID:22828900

  10. Estimating Typhoon Rainfall over Sea from SSM/I Satellite Data Using an Improved Genetic Programming

    NASA Astrophysics Data System (ADS)

    Yeh, K.; Wei, H.; Chen, L.; Liu, G.

    2010-12-01

    Estimating Typhoon Rainfall over Sea from SSM/I Satellite Data Using an Improved Genetic Programming Keh-Chia Yeha, Hsiao-Ping Weia,d, Li Chenb, and Gin-Rong Liuc a Department of Civil Engineering, National Chiao Tung University, Hsinchu, Taiwan, 300, R.O.C. b Department of Civil Engineering and Engineering Informatics, Chung Hua University, Hsinchu, Taiwan, 300, R.O.C. c Center for Space and Remote Sensing Research, National Central University, Tao-Yuan, Taiwan, 320, R.O.C. d National Science and Technology Center for Disaster Reduction, Taipei County, Taiwan, 231, R.O.C. Abstract This paper proposes an improved multi-run genetic programming (GP) and applies it to predict the rainfall using meteorological satellite data. GP is a well-known evolutionary programming and data mining method, used to automatically discover the complex relationships among nonlinear systems. The main advantage of GP is to optimize appropriate types of function and their associated coefficients simultaneously. This study makes an improvement to enhance escape ability from local optimums during the optimization procedure. The GP continuously runs several times by replacing the terminal nodes at the next run with the best solution at the current run. The current novel model improves GP, obtaining a highly nonlinear mathematical equation to estimate the rainfall. In the case study, this improved GP described above combining with SSM/I satellite data is employed to establish a suitable method for estimating rainfall at sea surface during typhoon periods. These estimated rainfalls are then verified with the data from four rainfall stations located at Peng-Jia-Yu, Don-Gji-Dao, Lan-Yu, and Green Island, which are four small islands around Taiwan. From the results, the improved GP can generate sophisticated and accurate nonlinear mathematical equation through two-run learning procedures which outperforms the traditional multiple linear regression, empirical equations and back-propagated network

  11. Bit error probability of trellis-coded quadrature amplitude modulation over cross-coupled multidimensional channels

    NASA Astrophysics Data System (ADS)

    Kavehrad, Mohsen; Sundberg, Carl-Erik W.

    1987-04-01

    Average bit error probabilities for M-ary quadrature amplitude modulation (MQAM) systems are evaluated using a truncated union bound to calculate an approximate upper bound on the average bit error probability. Coded BPSK and QSPK are studied in a dual-polarized channel with and without an interference compensator. Trellis-coded MQAM signals are also examined. A new technique, dual-channel polarization hopping, which provides diversity gains when applied to coded cross-coupled channels is proposed. Average bit error probabilities for convolutionally coded QAM schemes in cross-coupled interference channels are derived. It is concluded that trellis-coded QAM schemes give larger coding gains in cross-coupled interference channels than in Gaussian noise and the choice of optimum code for the trellis-coded QAM scheme depends on the expected interference level.

  12. Prediction of blood pressure changes over time and incidence of hypertension by a genetic risk score in Swedes.

    PubMed

    Fava, Cristiano; Sjögren, Marketa; Montagnana, Martina; Danese, Elisa; Almgren, Peter; Engström, Gunnar; Nilsson, Peter; Hedblad, Bo; Guidi, Gian Cesare; Minuz, Pietro; Melander, Olle

    2013-02-01

    Recent Genome-Wide Association Studies (GWAS) have pinpointed different single nucleotide polymorphisms consistently associated with blood pressure (BP) and hypertension prevalence. However, little data exist regarding single nucleotide polymorphisms predicting BP variation over time and hypertension incidence. The aim of this study was to confirm the association of a genetic risk score (GRS), based on 29 independent single nucleotide polymorphisms, with cross-sectional BP and hypertension prevalence and to challenge its prediction of BP change over time and hypertension incidence in >17 000 middle-aged Swedes participating in a prospective study, the Malmö Preventive Project, investigated at baseline and over a 23-year average period of follow-up. The GRS was associated with higher systolic and diastolic BP values both at baseline (β ± SEM, 0.968 ± 0.102 mm Hg and 0.585 ± 0.064 mm Hg; P<1E-19 for both) and at reinvestigation (β ± SEM, 1.333 ± 0.161 mm Hg and 0.724 ± 0.086 mm Hg; P<1E-15 for both) and with increased hypertension prevalence (odds ratio [95% CI], 1.192 [1.140-1.245] and 1.144 [1.107-1.183]; P<1E-15 for both). The GRS was positively associated with change (Δ) in BP (β ± SEM, 0.033 ± 0.008 mm Hg/y and 0.023 ± 0.004 mm Hg/y; P<1E-04 for both) and hypertension incidence (odds ratio [95% CI], 1.110 [1.065-1.156]; P=6.7 E-07), independently from traditional risk factors. The relative weight of the GRS was lower in magnitude than obesity or prehypertension, but comparable with diabetes mellitus or a positive family history of hypertension. A C-statistics analysis does not show any improvement in the prediction of incident hypertension on top of traditional risk factors. Our data from a large cohort study show that a GRS is independently associated with BP increase and incidence of hypertension.

  13. The cell pole: the site of cross talk between the DNA uptake and genetic recombination machinery.

    PubMed

    Kidane, Dawit; Ayora, Silvia; Sweasy, Joann B; Graumann, Peter L; Alonso, Juan C

    2012-01-01

    Natural transformation is a programmed mechanism characterized by binding of free double-stranded (ds) DNA from the environment to the cell pole in rod-shaped bacteria. In Bacillus subtilis some competence proteins, which process the dsDNA and translocate single-stranded (ss) DNA into the cytosol, recruit a set of recombination proteins mainly to one of the cell poles. A subset of single-stranded binding proteins, working as "guardians", protects ssDNA from degradation and limit the RecA recombinase loading. Then, the "mediators" overcome the inhibitory role of guardians, and recruit RecA onto ssDNA. A RecA·ssDNA filament searches for homology on the chromosome and, in a process that is controlled by "modulators", catalyzes strand invasion with the generation of a displacement loop (D-loop). A D-loop resolvase or "resolver" cleaves this intermediate, limited DNA replication restores missing information and a DNA ligase seals the DNA ends. However, if any step fails, the "rescuers" will repair the broken end to rescue chromosomal transformation. If the ssDNA does not share homology with resident DNA, but it contains information for autonomous replication, guardian and mediator proteins catalyze plasmid establishment after inhibition of RecA. DNA replication and ligation reconstitute the molecule (plasmid transformation). In this review, the interacting network that leads to a cross talk between proteins of the uptake and genetic recombination machinery will be placed into prospective.

  14. Population dynamics of a natural red deer population over 200 years detected via substantial changes of genetic variation.

    PubMed

    Hoffmann, Gunther Sebastian; Johannesen, Jes; Griebeler, Eva Maria

    2016-05-01

    Most large mammals have constantly been exposed to anthropogenic influence over decades or even centuries. Because of their long generation times and lack of sampling material, inferences of past population genetic dynamics, including anthropogenic impacts, have only relied on the analysis of the structure of extant populations. Here, we investigate for the first time the change in the genetic constitution of a natural red deer population over two centuries, using up to 200-year-old antlers (30 generations) stored in trophy collections. To the best of our knowledge, this is the oldest DNA source ever used for microsatellite population genetic analyses. We demonstrate that government policy and hunting laws may have strong impacts on populations that can lead to unexpectedly rapid changes in the genetic constitution of a large mammal population. A high ancestral individual polymorphism seen in an outbreeding population (1813-1861) was strongly reduced in descendants (1923-1940) during the mid-19th and early 20th century by genetic bottlenecks. Today (2011), individual polymorphism and variance among individuals is increasing in a constant-sized (managed) population. Differentiation was high among periods (F ST > ***); consequently, assignment tests assigned individuals to their own period with >85% probability. In contrast to the high variance observed at nuclear microsatellite loci, mtDNA (D-loop) was monomorphic through time, suggesting that male immigration dominates the genetic evolution in this population.

  15. Extreme mitochondrial variation in the Atlantic gall crab Opecarcinus hypostegus (Decapoda: Cryptochiridae) reveals adaptive genetic divergence over Agaricia coral hosts

    PubMed Central

    van Tienderen, Kaj M.; van der Meij, Sancia E. T.

    2017-01-01

    The effectiveness of migration in marine species exhibiting a pelagic larval stage is determined by various factors, such as ocean currents, pelagic larval stage duration and active habitat selection. Direct measurement of larval movements is difficult and, consequently, factors determining the gene flow patterns remain poorly understood for many species. Patterns of gene flow play a key role in maintaining genetic homogeneity in a species by dampening the effects of local adaptation. Coral-dwelling gall crabs (Cryptochiridae) are obligate symbionts of stony corals (Scleractinia). Preliminary data showed high genetic diversity on the COI gene for 19 Opecarcinus hypostegus specimens collected off Curaçao. In this study, an additional 176 specimens were sequenced and used to characterize the population structure along the leeward side of Curaçao. Extremely high COI genetic variation was observed, with 146 polymorphic sites and 187 unique haplotypes. To determine the cause of this high genetic diversity, various gene flow scenarios (geographical distance along the coast, genetic partitioning over depth, and genetic differentiation by coral host) were examined. Adaptive genetic divergence across Agariciidae host species is suggested to be the main cause for the observed high intra-specific variance, hypothesised as early signs of speciation in O. hypostegus. PMID:28079106

  16. Cross-Shelf Circulation and Momentum and Heat Balances Over the Inner Continental Shelf Near Martha’s Vineyard, Massachusetts

    DTIC Science & Technology

    2007-09-01

    T2 or AT = 0 at x = c : 0, the temperature stratification as a function of cross-shelf position in the model is AT- QS_X (.32) Poe , Uo The vertical... Poe - U o - U o x ) (4 ., The cross-shelf temperature gradient in the model is positive near shore: a(T) Uo d> 0 for x < --- (4.35) 5W3 h 153 The...Wind-driven currents over the continental shelf. In Kenneth H. Brink and Allan R. Robinson, editors, The Global Coastal Ocean: Processes and Methods

  17. Divergent selection on, but no genetic conflict over, female and male timing and rate of reproduction in a human population

    PubMed Central

    Bolund, Elisabeth; Bouwhuis, Sandra; Pettay, Jenni E.; Lummaa, Virpi

    2013-01-01

    The sexes often have different phenotypic optima for important life-history traits, and because of a largely shared genome this can lead to a conflict over trait expression. In mammals, the obligate costs of reproduction are higher for females, making reproductive timing and rate especially liable to conflict between the sexes. While studies from wild vertebrates support such sexual conflict, it remains unexplored in humans. We used a pedigreed human population from preindustrial Finland to estimate sexual conflict over age at first and last reproduction, reproductive lifespan and reproductive rate. We found that the phenotypic selection gradients differed between the sexes. We next established significant heritabilities in both sexes for all traits. All traits, except reproductive rate, showed strongly positive intersexual genetic correlations and were strongly genetically correlated with fitness in both sexes. Moreover, the genetic correlations with fitness were almost identical in men and women. For reproductive rate, the intersexual correlation and the correlation with fitness were weaker but again similar between the sexes. Thus, in this population, an apparent sexual conflict at the phenotypic level did not reflect an underlying genetic conflict over the studied reproductive traits. These findings emphasize the need for incorporating genetic perspectives into studies of human life-history evolution. PMID:24107531

  18. Divergent selection on, but no genetic conflict over, female and male timing and rate of reproduction in a human population.

    PubMed

    Bolund, Elisabeth; Bouwhuis, Sandra; Pettay, Jenni E; Lummaa, Virpi

    2013-12-07

    The sexes often have different phenotypic optima for important life-history traits, and because of a largely shared genome this can lead to a conflict over trait expression. In mammals, the obligate costs of reproduction are higher for females, making reproductive timing and rate especially liable to conflict between the sexes. While studies from wild vertebrates support such sexual conflict, it remains unexplored in humans. We used a pedigreed human population from preindustrial Finland to estimate sexual conflict over age at first and last reproduction, reproductive lifespan and reproductive rate. We found that the phenotypic selection gradients differed between the sexes. We next established significant heritabilities in both sexes for all traits. All traits, except reproductive rate, showed strongly positive intersexual genetic correlations and were strongly genetically correlated with fitness in both sexes. Moreover, the genetic correlations with fitness were almost identical in men and women. For reproductive rate, the intersexual correlation and the correlation with fitness were weaker but again similar between the sexes. Thus, in this population, an apparent sexual conflict at the phenotypic level did not reflect an underlying genetic conflict over the studied reproductive traits. These findings emphasize the need for incorporating genetic perspectives into studies of human life-history evolution.

  19. Black and white and read all over: the past, present and future of giant panda genetics.

    PubMed

    Wei, Fuwen; Hu, Yibo; Zhu, Lifeng; Bruford, Michael W; Zhan, Xiangjiang; Zhang, Lei

    2012-12-01

    Few species attract much more attention from the public and scientists than the giant panda (Ailuropoda melanoleuca), a popular, enigmatic but highly endangered species. The application of molecular genetics to its biology and conservation has facilitated surprising insights into the biology of giant pandas as well as the effectiveness of conservation efforts during the past decades. Here, we review the history of genetic advances in this species, from phylogeny, demographical history, genetic variation, population structure, noninvasive population census and adaptive evolution to reveal to what extent the current status of the giant panda is a reflection of its evolutionary legacy, as opposed to the influence of anthropogenic factors that have negatively impacted this species. In addition, we summarize the conservation implications of these genetic findings applied for the management of this high-profile species. Finally, on the basis of these advances and predictable future changes in genetic technology, we discuss future research directions that seem promising for giant panda biology and conservation.

  20. Soil water capture trends over 50 years of single-cross maize (Zea mays L.) breeding in the US corn-belt.

    PubMed

    Reyes, Andres; Messina, Carlos D; Hammer, Graeme L; Liu, Lu; van Oosterom, Erik; Lafitte, Renee; Cooper, Mark

    2015-12-01

    Breeders have successfully improved maize (Zea mays L.) grain yield for the conditions of the US corn-belt over the past 80 years, with the past 50 years utilizing single-cross hybrids. Long-term improvement for grain yield under water-limited conditions has also been reported. Grain yield under water-limited conditions depends on water use, water use efficiency, and harvest index. It has been hypothesized that long-term genetic gain for yield could be due, in part, to increased water capture from the soil. This hypothesis was tested using a set of elite single-cross hybrids that were released by DuPont Pioneer between 1963 and 2009. Eighteen hybrids were grown in the field during 2010 and 2011 growing seasons at Woodland, CA, USA. Crops grew predominantly on stored soil water and drought stress increased as the season progressed. Soil water content was measured to 300cm depth throughout the growing season. Significant water extraction occurred to a depth of 240-300cm and seasonal water use was calculated from the change in soil water over this rooting zone. Grain yield increased significantly with year of commercialization, but no such trend was observed for total water extraction. Therefore, the measured genetic gain for yield for the period represented by this set of hybrids must be related to either increased efficiency of water use or increased carbon partitioning to the grain, rather than increased soil water uptake. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  1. Regional Brain Shrinkage over Two Years: Individual Differences and Effects of Pro-Inflammatory Genetic Polymorphisms

    PubMed Central

    Persson, N.; Ghisletta, P.; Dahle, C.L.; Bender, A.R.; Yang, Y.; Yuan, P.; Daugherty, A.M.; Raz, N.

    2014-01-01

    We examined regional changes in brain volume in healthy adults (N = 167, age 19-79 years at baseline; N = 90 at follow-up) over approximately two years. With latent change score models, we evaluated mean change and individual differences in rates of change in 10 anatomically-defined and manually-traced regions of interest (ROIs): lateral prefrontal cortex (LPFC), orbital frontal cortex (OF), prefrontal white matter (PFw), hippocampus (HC), parahippocampal gyrus (PhG), caudate nucleus (Cd), putamen (Pt), insula (In), cerebellar hemispheres (CbH), and primary visual cortex (VC). Significant mean shrinkage was observed in the HC, CbH, In, OF, and the PhG, and individual differences in change were noted in all regions, except the OF. Pro-inflammatory genetic variants mediated shrinkage in PhG and CbH. Carriers of two T alleles of interleukin-1β (IL-1βC-511T, rs16944) and a T allele of methylenetetrahydrofolate reductase (MTHFRC677T, rs1801133) polymorphisms showed increased PhG shrinkage. No effects of a pro-inflammatory polymorphism for C-reactive protein (CRP-286C>A>T, rs3091244) or apolipoprotein (APOE) ε4 allele were noted. These results replicate the pattern of brain shrinkage observed in previous studies, with a notable exception of the LPFC thus casting doubt on the unique importance of prefrontal cortex in aging. Larger baseline volumes of CbH and In were associated with increased shrinkage, in conflict with the brain reserve hypothesis. Contrary to previous reports, we observed no significant linear effects of age and hypertension on regional brain shrinkage. Our findings warrant further investigation of the effects of neuroinflammation on structural brain change throughout the lifespan. PMID:25264227

  2. Regional brain shrinkage over two years: individual differences and effects of pro-inflammatory genetic polymorphisms.

    PubMed

    Persson, N; Ghisletta, P; Dahle, C L; Bender, A R; Yang, Y; Yuan, P; Daugherty, A M; Raz, N

    2014-12-01

    We examined regional changes in brain volume in healthy adults (N=167, age 19-79years at baseline; N=90 at follow-up) over approximately two years. With latent change score models, we evaluated mean change and individual differences in rates of change in 10 anatomically-defined and manually-traced regions of interest (ROIs): lateral prefrontal cortex (LPFC), orbital frontal cortex (OF), prefrontal white matter (PFw), hippocampus (Hc), parahippocampal gyrus (PhG), caudate nucleus (Cd), putamen (Pt), insula (In), cerebellar hemispheres (CbH), and primary visual cortex (VC). Significant mean shrinkage was observed in the Hc, CbH, In, OF, and PhG, and individual differences in change were noted in all regions, except the OF. Pro-inflammatory genetic variants modified shrinkage in PhG and CbH. Carriers of two T alleles of interleukin-1β (IL-1β C-511T, rs16944) and a T allele of methylenetetrahydrofolate reductase (MTHFR C677T, rs1801133) polymorphisms showed increased PhG shrinkage. No effects of a pro-inflammatory polymorphism for C-reactive protein (CRP-286C>A>T, rs3091244) or apolipoprotein (APOE) ε4 allele were noted. These results replicate the pattern of brain shrinkage observed in previous studies, with a notable exception of the LPFC, thus casting doubt on the unique importance of prefrontal cortex in aging. Larger baseline volumes of CbH and In were associated with increased shrinkage, in conflict with the brain reserve hypothesis. Contrary to previous reports, we observed no significant linear effects of age and hypertension on regional brain shrinkage. Our findings warrant further investigation of the effects of neuroinflammation on structural brain change throughout the lifespan.

  3. Landscape genetics, historical isolation and cross-Andean gene flow in the wax palm, Ceroxylon echinulatum (Arecaceae).

    PubMed

    Trénel, Philipp; Hansen, Michael M; Normand, Signe; Borchsenius, Finn

    2008-08-01

    Knowledge of the role of landscapes in shaping genetic connectivity and divergence is essential for understanding patterns of biogeography and diversity. This is particularly relevant for the Andes region, a major biodiversity hotspot of relatively recent origin. We examined the phylogeography and landscape genetics of the Andean wax palm Ceroxylon echinulatum (Arecaceae) that occurs in two narrow bands of montane forests on each side of the Andes in Ecuador and northeastern Peru. First, we tested the hypothesis of C. echinulatum being a geographic cline species crossing the Andes in the Amotape-Huancabamba zone (AHZ) of southern Ecuador/northern Peru, as indicated by observations on fruit morphology. Second, we assessed the timeframe of cross-Andean divergence, and third, we investigated the impact of contemporary and historical landscape features on observed spatio-genetic patterns. Individual-based Bayesian clustering (BC) identified a northeastern, southeastern, southwestern, and northwestern cluster, with areas of genetic discontinuity coinciding with the Andes and the Giron-Paute deflection. F-statistics derived from BC suggested an east-to-west dispersal history. Population-based analyses revealed strong genetic structuring at both small and large geographic scales. Interpopulation relationships and Mantel tests strongly supported the cline model with cross-Andean dispersal in the AHZ. Along the cline, gene flow measured as F(ST) was mainly limited by distance, with less but significant impact of climatic friction. Coalescent analysis revealed that cross-Andean divergence took place during the Quaternary. Significant historical isolation (R(ST) > F(ST)) was found in the southwestern population. The current study illustrates a joint effect of founder dynamics, divergence by distance and historical isolation on patterns of Andean diversity and distribution.

  4. Little genetic differentiation as assessed by uniparental markers in the presence of substantial language variation in peoples of the Cross River region of Nigeria

    PubMed Central

    2010-01-01

    Background The Cross River region in Nigeria is an extremely diverse area linguistically with over 60 distinct languages still spoken today. It is also a region of great historical importance, being a) adjacent to the likely homeland from which Bantu-speaking people migrated across most of sub-Saharan Africa 3000-5000 years ago and b) the location of Calabar, one of the largest centres during the Atlantic slave trade. Over 1000 DNA samples from 24 clans representing speakers of the six most prominent languages in the region were collected and typed for Y-chromosome (SNPs and microsatellites) and mtDNA markers (Hypervariable Segment 1) in order to examine whether there has been substantial gene flow between groups speaking different languages in the region. In addition the Cross River region was analysed in the context of a larger geographical scale by comparison to bordering Igbo speaking groups as well as neighbouring Cameroon populations and more distant Ghanaian communities. Results The Cross River region was shown to be extremely homogenous for both Y-chromosome and mtDNA markers with language spoken having no noticeable effect on the genetic structure of the region, consistent with estimates of inter-language gene flow of 10% per generation based on sociological data. However the groups in the region could clearly be differentiated from others in Cameroon and Ghana (and to a lesser extent Igbo populations). Significant correlations between genetic distance and both geographic and linguistic distance were observed at this larger scale. Conclusions Previous studies have found significant correlations between genetic variation and language in Africa over large geographic distances, often across language families. However the broad sampling strategies of these datasets have limited their utility for understanding the relationship within language families. This is the first study to show that at very fine geographic/linguistic scales language differences can be

  5. Little genetic differentiation as assessed by uniparental markers in the presence of substantial language variation in peoples of the Cross River region of Nigeria.

    PubMed

    Veeramah, Krishna R; Connell, Bruce A; Ansari Pour, Naser; Powell, Adam; Plaster, Christopher A; Zeitlyn, David; Mendell, Nancy R; Weale, Michael E; Bradman, Neil; Thomas, Mark G

    2010-03-31

    The Cross River region in Nigeria is an extremely diverse area linguistically with over 60 distinct languages still spoken today. It is also a region of great historical importance, being a) adjacent to the likely homeland from which Bantu-speaking people migrated across most of sub-Saharan Africa 3000-5000 years ago and b) the location of Calabar, one of the largest centres during the Atlantic slave trade. Over 1000 DNA samples from 24 clans representing speakers of the six most prominent languages in the region were collected and typed for Y-chromosome (SNPs and microsatellites) and mtDNA markers (Hypervariable Segment 1) in order to examine whether there has been substantial gene flow between groups speaking different languages in the region. In addition the Cross River region was analysed in the context of a larger geographical scale by comparison to bordering Igbo speaking groups as well as neighbouring Cameroon populations and more distant Ghanaian communities. The Cross River region was shown to be extremely homogenous for both Y-chromosome and mtDNA markers with language spoken having no noticeable effect on the genetic structure of the region, consistent with estimates of inter-language gene flow of 10% per generation based on sociological data. However the groups in the region could clearly be differentiated from others in Cameroon and Ghana (and to a lesser extent Igbo populations). Significant correlations between genetic distance and both geographic and linguistic distance were observed at this larger scale. Previous studies have found significant correlations between genetic variation and language in Africa over large geographic distances, often across language families. However the broad sampling strategies of these datasets have limited their utility for understanding the relationship within language families. This is the first study to show that at very fine geographic/linguistic scales language differences can be maintained in the presence of

  6. Changes in barley (Hordeum vulgare L. subsp. vulgare) genetic diversity and structure in Jordan over a period of 31 years

    USDA-ARS?s Scientific Manuscript database

    In many regions of the world, the cultivation of landraces is still common, in particular in centres of crop diversity. Significant effort has been put into ex situ conservation of landraces but limited data exist on the changes in genetic diversity that occur over time in farmers’ fields. We assess...

  7. Spatial Genetic Structure of Coffee-Associated Xylella fastidiosa Populations Indicates that Cross Infection Does Not Occur with Sympatric Citrus Orchards.

    PubMed

    Francisco, Carolina S; Ceresini, Paulo C; Almeida, Rodrigo P P; Coletta-Filho, Helvécio D

    2017-04-01

    Xylella fastidiosa, an economically important plant-pathogenic bacterium, infects both coffee and citrus trees in Brazil. Although X. fastidiosa in citrus is well studied, knowledge about the population structure of this bacterium infecting coffee remains unknown. Here, we studied the population structure of X. fastidiosa infecting coffee trees in São Paulo State, Brazil, in four regions where citrus is also widely cultivated. Genotyping of over 500 isolates from coffee plants using 14 genomic microsatellite markers indicated that populations were largely geographically isolated, as previously found with populations of X. fastidiosa infecting citrus. These results were supported by a clustering analysis, which indicated three major genetic groups among the four sampled regions. Overall, approximately 38% of isolates showed significant membership coefficients not related to their original geographical populations (i.e., migrants), characterizing a significant degree of genotype flow among populations. To determine whether admixture occurred between isolates infecting citrus and coffee plants, one site with citrus and coffee orchards adjacent to each other was selected; over 100 isolates were typed from each host plant. No signal of natural admixture between citrus- and coffee-infecting isolates was found; artificial cross-infection assays with representative isolates also yielded no successful cross infection. A comparison determined that X. fastidiosa populations from coffee have higher genetic diversity and allelic richness compared with citrus. The results showed that coffee and citrus X. fastidiosa populations are effectively isolated from each other and, although coffee populations are spatially structured, migration has an important role in shaping diversity.

  8. AN EXAMINATION OF THE OVERLAP BETWEEN GENETIC AND ENVIRONMENTAL RISK FACTORS FOR INTENTIONAL WEIGHT LOSS AND OVEREATING

    PubMed Central

    Wade, Tracey D.; Treloar, Susan A.; Heath, Andrew C.; Martin, Nicholas G

    2009-01-01

    Objective In order to further our understanding of how intentional weight loss (IWL) and overeating are related, we examined the shared genetic and environmental variance between lifetime IWL and overeating. Methods Interview data were available for 1976 female twins (both members of 439 and 264 pairs of monozygotic and dizygotic twins respectively), mean age=40.61, SD=4.72. We used lifetime diagnostic data for eating disorders obtained from a semi-structured psychiatric telephone interview, examined in a bivariate twin analysis. Both lifetime behaviours were measured on a 3-point scale, where absence of IWL or overeating formed one anchor on the scale and lifetime anorexia nervosa (AN) and bulimia nervosa (BN) formed the opposite anchors respectively. Results In line with previous findings, a higher body mass index was significantly associated with the lifetime presence of IWL and/or overeating (odds ratio=1.13, 95% confidence interval (CI): 1.08–1.19). The best fitting twin model contained additive genetic and non-shared environmental influence influencing both IWL and overeating, with correlations between these influences of 0.61 (95% CI: 0.35–0.92) and 0.24 (95% CI: 0.07–0.42) respectively. Conclusion About 37% of genetic risk factors were considered to overlap between IWL and overeating, and with only 6% of overlap between environmental risk factors. Thus considerable independence of risk factors was indicated. PMID:19235851

  9. Is all fair in biological warfare? The controversy over genetically engineered biological weapons.

    PubMed

    Appel, J M

    2009-07-01

    Advances in genetics may soon make possible the development of ethnic bioweapons that target specific ethnic or racial groups based upon genetic markers. While occasional published reports of such research generate public outrage, little has been written about the ethical distinction (if any) between the development of such weapons and ethnically neutral bioweapons. The purpose of this paper is to launch a debate on the subject of ethnic bioweapons before they become a scientific reality.

  10. Feasibility demonstration of booster cross-over system for 3 1/2 inch SRB/MLP frangible nut system

    NASA Technical Reports Server (NTRS)

    1983-01-01

    Recent testing of the SRB/MLP Frangible Nut System (SOS Part Number 114850-9/Boosters P/N 114848-3) at NASA indicated a need to reduce the function time between boosters (2) within a single frangible nut. These boosters are initiated separately by electrical impulse(s). Coupling the output of each detonator with an explosive cross-over would reduce the function time between boosters (independent of electrical impulse) while providing additional redundancy to the system. The objectives of this program were to: provide an explosive cross-over between boosters, reduce function time between boosters to less than one (1) millisecond within a given nut, reduce cost of boosters, be compatible with the existing frangible nut system, and meet requirements of USBI Spec's (nut 10SPC-0030, booster 10SPC-0031).

  11. Application of random regression models for genetic analysis of 305-d milk yield over different lactations of Iranian Holsteins.

    PubMed

    Torshizi, Mahdi Elahi; Farhangfar, Homayoun; Mashhadi, Mojtaba Hosseinpour

    2017-10-01

    During the last decade, genetic evaluation of dairy cows using longitudinal data (test day milk yield or 305- day milk yield) using random regression method has been officially adopted in several countries. The objectives of this study were to estimate covariance functions for genetic and permanent environmental effects and to obtain genetic parameters of 305-day milk yield over seven parities. Data including 60,279 total 305-day milk yield of 17,309 Iranian Holstein dairy cows in 7 parities calved between 20 to 140 months between 2004 and 2011. Residual variances were modeled by homogeneous and step functions with 7 and 10 classes. The results showed that a third order polynomial for additive genetic and permanent environmental effects plus a step function with 10 classes for the residual variance was the most adequate and parsimonious model to describe the covariance structure of the data. Heritability estimates obtained by this model varied from 0.17 to 0.28. The performance of this model was better than repeatability model. Moreover, 10 classes of residual variance produce the more accurate result than 7 classes or homogeneous residual effect. A quadratic Legendre polynomial for additive genetic and permanent environmental effects with 10 step function residual classes are sufficient to produce a parsimonious model that explained the change in 305-day milk yield over consecutive parities of Iranian Holstein cows.

  12. External chest compressions using a mechanical feedback device : cross-over simulation study.

    PubMed

    Skorning, M; Derwall, M; Brokmann, J C; Rörtgen, D; Bergrath, S; Pflipsen, J; Beuerlein, S; Rossaint, R; Beckers, S K

    2011-08-01

    External chest compressions (ECC) are essential components of resuscitation and are usually performed without any adjuncts in professional healthcare. Even for healthcare professionals during in-hospital and out-of-hospital resuscitation poor performance in ECC has been reported in recent years. Although several stand-alone devices have been developed none has been implemented as a standard in patient care. The aim of this study was to examine if the use of a mechanical device providing visual feedback and audible assistance during ECC improves performance of healthcare professionals following minimal and simplified instructions. In a prospective, randomized cross-over study 81 healthcare professionals performed ECC for 3 min (in the assumed setting of a secured airway) twice on a manikin (Skillreporter ResusciAnne®, with PC-Skillreporting System Version 1.3.0, Laerdal, Stavanger, Norway) in a mock cardiac arrest scenario. Group 1 (n=40) performed ECC with the device first followed by classic ECC and group 2 (n=41) in the opposite order. Minimal instructions were standardized and provided by video instruction (1 min 38 s). Endpoints were achievement of a mean compression rate between 90 and 110/min and a mean compression depth of 40-50 mm. In addition participants had to answer questionnaires about demographic data, professional experience and recent recommendations for ECC as well as their impression of the device concerning the ease of use and their personal level of confidence. Data were analyzed for group-related and inter-group differences using SAS (Version 9.1.3, SAS Institute, Cary, NC). A total of 81 healthcare professionals regularly involved in resuscitation attempts in pre-hospital or in-hospital settings took part in the study with no differences between the groups: females 35.8% (n=52), emergency medical technicians 32.1% (n=26), anesthesia nurses 32.1% (n=26), physicians (anesthesiology) 45% (n=29). In group 1 33 out of 40 (82.5%; 99.7±4

  13. The cell pole: The site of cross talk between the DNA uptake and genetic recombination machinery

    PubMed Central

    Kidane, Dawit; Ayora, Silvia; Sweasy, Joann; Graumann, Peter L.; Alonso, Juan C.

    2012-01-01

    Natural transformation is a programmed mechanism characterized by binding of free double-stranded (ds) DNA from the environment to the cell pole in rod-shaped bacteria. In Bacillus subtilis some competence proteins, which process the dsDNA and translocate single-stranded (ss) DNA into the cytosol, recruit a set of recombination proteins mainly to one of the cell poles. A subset of single-stranded binding proteins, working as “guardians”, protect ssDNA from degradation and limit the RecA recombinase loading. Then, the “mediators” overcome the inhibitory role of guardians, and recruit RecA onto ssDNA. A RecA·ssDNA filament searches for homology on the chromosome and, in a process that is controlled by “modulators”, catalyzes strand invasion with the generation of a displacement loop (D-loop). A D-loop resolvase or “resolver” cleaves this intermediate, limited DNA replication restores missing information and a DNA ligase seals the DNA ends. However, if any step fails, the “rescuers” will repair the broken end to rescue chromosomal transformation. If the ssDNA does not share homology with resident DNA, but it contains information for autonomous replication, guardian and mediator proteins catalyze plasmid establishment after inhibition of RecA. DNA replication and ligation reconstitute the molecule (plasmid transformation). In this review, the interacting network that leads to a cross talk between proteins of the uptake and genetic recombination machinery will be placed into prospective. PMID:23046409

  14. Field-induced superconducting phase of FeSe in the BCS-BEC cross-over.

    PubMed

    Kasahara, Shigeru; Watashige, Tatsuya; Hanaguri, Tetsuo; Kohsaka, Yuhki; Yamashita, Takuya; Shimoyama, Yusuke; Mizukami, Yuta; Endo, Ryota; Ikeda, Hiroaki; Aoyama, Kazushi; Terashima, Taichi; Uji, Shinya; Wolf, Thomas; von Löhneysen, Hilbert; Shibauchi, Takasada; Matsuda, Yuji

    2014-11-18

    Fermi systems in the cross-over regime between weakly coupled Bardeen-Cooper-Schrieffer (BCS) and strongly coupled Bose-Einstein-condensate (BEC) limits are among the most fascinating objects to study the behavior of an assembly of strongly interacting particles. The physics of this cross-over has been of considerable interest both in the fields of condensed matter and ultracold atoms. One of the most challenging issues in this regime is the effect of large spin imbalance on a Fermi system under magnetic fields. Although several exotic physical properties have been predicted theoretically, the experimental realization of such an unusual superconducting state has not been achieved so far. Here we show that pure single crystals of superconducting FeSe offer the possibility to enter the previously unexplored realm where the three energies, Fermi energy εF, superconducting gap Δ, and Zeeman energy, become comparable. Through the superfluid response, transport, thermoelectric response, and spectroscopic-imaging scanning tunneling microscopy, we demonstrate that εF of FeSe is extremely small, with the ratio Δ/εF ~ 1(~0.3) in the electron (hole) band. Moreover, thermal-conductivity measurements give evidence of a distinct phase line below the upper critical field, where the Zeeman energy becomes comparable to εF and Δ. The observation of this field-induced phase provides insights into previously poorly understood aspects of the highly spin-polarized Fermi liquid in the BCS-BEC cross-over regime.

  15. Field-induced superconducting phase of FeSe in the BCS-BEC cross-over

    PubMed Central

    Kasahara, Shigeru; Watashige, Tatsuya; Hanaguri, Tetsuo; Kohsaka, Yuhki; Yamashita, Takuya; Shimoyama, Yusuke; Mizukami, Yuta; Endo, Ryota; Ikeda, Hiroaki; Aoyama, Kazushi; Terashima, Taichi; Uji, Shinya; Wolf, Thomas; von Löhneysen, Hilbert; Shibauchi, Takasada; Matsuda, Yuji

    2014-01-01

    Fermi systems in the cross-over regime between weakly coupled Bardeen–Cooper–Schrieffer (BCS) and strongly coupled Bose–Einstein-condensate (BEC) limits are among the most fascinating objects to study the behavior of an assembly of strongly interacting particles. The physics of this cross-over has been of considerable interest both in the fields of condensed matter and ultracold atoms. One of the most challenging issues in this regime is the effect of large spin imbalance on a Fermi system under magnetic fields. Although several exotic physical properties have been predicted theoretically, the experimental realization of such an unusual superconducting state has not been achieved so far. Here we show that pure single crystals of superconducting FeSe offer the possibility to enter the previously unexplored realm where the three energies, Fermi energy εF, superconducting gap Δ, and Zeeman energy, become comparable. Through the superfluid response, transport, thermoelectric response, and spectroscopic-imaging scanning tunneling microscopy, we demonstrate that εF of FeSe is extremely small, with the ratio Δ/εF∼1(∼0.3) in the electron (hole) band. Moreover, thermal-conductivity measurements give evidence of a distinct phase line below the upper critical field, where the Zeeman energy becomes comparable to εF and Δ. The observation of this field-induced phase provides insights into previously poorly understood aspects of the highly spin-polarized Fermi liquid in the BCS-BEC cross-over regime. PMID:25378706

  16. Computational analysis of magnetohydrodynamic Casson and Maxwell flows over a stretching sheet with cross diffusion

    NASA Astrophysics Data System (ADS)

    Kumaran, G.; Sandeep, N.; Ali, M. E.

    This paper reports the magnetohydrodynamic chemically reacting Casson and Maxwell fluids past a stretching sheet with cross diffusion, non-uniform heat source/sink, thermophoresis and Brownian motion effects. Numerical results are obtained by employing the R-K based shooting method. Effects of pertinent parameters on flow, thermal and concentration fields are discussed with graphical illustrations. We presented the tabular results to discuss the nature of the skin friction coefficient, reduced Nusselt and Sherwood numbers. Dual nature is observed in the solution of Casson and Maxwell fluids. It is also observed a significant increase in heat and mass transfer rate of Maxwell fluid when compared with the Casson fluid.

  17. Genetics

    MedlinePlus

    ... Inheritance; Heterozygous; Inheritance patterns; Heredity and disease; Heritable; Genetic markers ... The chromosomes are made up of strands of genetic information called DNA. Each chromosome contains sections of ...

  18. Dissecting the Effect of Genetic Variation on the Hepatic Expression of Drug Disposition Genes across the Collaborative Cross Mouse Strains

    PubMed Central

    Nachshon, Aharon; Abu-Toamih Atamni, Hanifa J.; Steuerman, Yael; Sheikh-Hamed, Roa'a; Dorman, Alexandra; Mott, Richard; Dohm, Juliane C.; Lehrach, Hans; Sultan, Marc; Shamir, Ron; Sauer, Sascha; Himmelbauer, Heinz; Iraqi, Fuad A.; Gat-Viks, Irit

    2016-01-01

    A central challenge in pharmaceutical research is to investigate genetic variation in response to drugs. The Collaborative Cross (CC) mouse reference population is a promising model for pharmacogenomic studies because of its large amount of genetic variation, genetic reproducibility, and dense recombination sites. While the CC lines are phenotypically diverse, their genetic diversity in drug disposition processes, such as detoxification reactions, is still largely uncharacterized. Here we systematically measured RNA-sequencing expression profiles from livers of 29 CC lines under baseline conditions. We then leveraged a reference collection of metabolic biotransformation pathways to map potential relations between drugs and their underlying expression quantitative trait loci (eQTLs). By applying this approach on proximal eQTLs, including eQTLs acting on the overall expression of genes and on the expression of particular transcript isoforms, we were able to construct the organization of hepatic eQTL-drug connectivity across the CC population. The analysis revealed a substantial impact of genetic variation acting on drug biotransformation, allowed mapping of potential joint genetic effects in the context of individual drugs, and demonstrated crosstalk between drug metabolism and lipid metabolism. Our findings provide a resource for investigating drug disposition in the CC strains, and offer a new paradigm for integrating biotransformation reactions to corresponding variations in DNA sequences. PMID:27761138

  19. Dissecting the Effect of Genetic Variation on the Hepatic Expression of Drug Disposition Genes across the Collaborative Cross Mouse Strains.

    PubMed

    Nachshon, Aharon; Abu-Toamih Atamni, Hanifa J; Steuerman, Yael; Sheikh-Hamed, Roa'a; Dorman, Alexandra; Mott, Richard; Dohm, Juliane C; Lehrach, Hans; Sultan, Marc; Shamir, Ron; Sauer, Sascha; Himmelbauer, Heinz; Iraqi, Fuad A; Gat-Viks, Irit

    2016-01-01

    A central challenge in pharmaceutical research is to investigate genetic variation in response to drugs. The Collaborative Cross (CC) mouse reference population is a promising model for pharmacogenomic studies because of its large amount of genetic variation, genetic reproducibility, and dense recombination sites. While the CC lines are phenotypically diverse, their genetic diversity in drug disposition processes, such as detoxification reactions, is still largely uncharacterized. Here we systematically measured RNA-sequencing expression profiles from livers of 29 CC lines under baseline conditions. We then leveraged a reference collection of metabolic biotransformation pathways to map potential relations between drugs and their underlying expression quantitative trait loci (eQTLs). By applying this approach on proximal eQTLs, including eQTLs acting on the overall expression of genes and on the expression of particular transcript isoforms, we were able to construct the organization of hepatic eQTL-drug connectivity across the CC population. The analysis revealed a substantial impact of genetic variation acting on drug biotransformation, allowed mapping of potential joint genetic effects in the context of individual drugs, and demonstrated crosstalk between drug metabolism and lipid metabolism. Our findings provide a resource for investigating drug disposition in the CC strains, and offer a new paradigm for integrating biotransformation reactions to corresponding variations in DNA sequences.

  20. Genetic parameters for body weight, carcass chemical composition and yield in a broiler-layer cross developed for QTL mapping

    PubMed Central

    Nunes, Beatriz do Nascimento; Ramos, Salvador Boccaletti; Savegnago, Rodrigo Pelicioni; Ledur, Mônica Corrêa; Nones, Kátia; Klein, Claudete Hara; Munari, Danísio Prado

    2011-01-01

    The objective of this study was to estimate genetic and phenotypic correlations of body weight at 6 weeks of age (BW6), as well as final carcass yield, and moisture, protein, fat and ash contents, using data from 3,422 F2 chickens originated from reciprocal cross between a broiler and a layer line. Variance components were estimated by the REML method, using animal models for evaluating random additive genetic and fixed contemporary group (sex, hatch and genetic group) effects. The heritability estimates (h2) for BW6, carcass yield and percentage of carcass moisture were 0.31 ± 0.07, 0.20 ± 0.05 and 0.33 ± 0.07, respectively. The h2 for the percentages of protein, fat and ash on a dry matter basis were 0.48 ± 0.09, 0.55 ± 0.10 and 0.36 ± 0.08, respectively. BW6 had a positive genetic correlation with fat percentage in the carcass, but a negative one with protein and ash contents. Carcass yield, thus, appears to have only low genetic association with carcass composition traits. The genetic correlations observed between traits, measured on a dry matter basis, indicated that selection for carcass protein content may favor higher ash content and a lower percentage of carcass fat. PMID:21931515

  1. Cross-layer ultrasound video streaming over mobile WiMAX and HSUPA networks.

    PubMed

    Alinejad, Ali; Philip, Nada Y; Istepanian, Robert S H

    2012-01-01

    It is well known that the evolution of 4G-based mobile multimedia network systems will contribute significantly to future mobile healthcare (m-health) applications that require high bandwidth and fast data rates. Central to the success of such emerging applications is the compatibility of broadband networks, such as mobile Worldwide Interoperability For Microwave Access (WiMAX) and High-Speed Uplink Packet Access (HSUPA), and especially their rate adaption issues combined with the acceptable real-time medical quality of service requirements. In this paper, we address the relevant challenges of cross-layer design requirements for real-time rate adaptation of ultrasound video streaming in mobile WiMAX and HSUPA networks. A comparative performance analysis of such approach is validated in two experimental m-health test bed systems for both mobile WiMAX and HSUPA networks. The experimental results have shown an improved performance of mobile WiMAX compared to the HSUPA using the same cross-layer optimization approach.

  2. PIV measurement of the vertical cross-flow structure over tube bundles

    NASA Astrophysics Data System (ADS)

    Iwaki, C.; Cheong, K. H.; Monji, H.; Matsui, G.

    Shell and tube heat exchangers are among the most commonly used types of heat exchangers. Shell-side cross-flow in tube bundles has received considerable attention and has been investigated extensively. However, the microscopic flow structure including velocity distribution, wake, and turbulent structure in the tube bundles needs to be determined for more effective designs. Therefore, in this study, in order to clarify the detailed structure of cross-flow in tube bundles with particle image velocimetry (PIV), experiments were conducted using two types of model; in-line and staggered bundles with a pitch-to-diameter ratio of 1.5, containing 20 rows of five 15 mm O.D. tubes in each row. The velocity data in the whole flow field were measured successfully by adjusting the refractive index of the working fluid to that of the tube material. The flow features were characterized in different tube bundles with regards to the velocity vector field, vortex structure, and turbulent intensity.

  3. HcRed, a Genetically Encoded Fluorescent Binary Cross-Linking Agent for Cross-Linking of Mitochondrial ATP Synthase in Saccharomyces cerevisiae

    PubMed Central

    Gong, Lan; Ramm, Georg; Devenish, Rodney J.; Prescott, Mark

    2012-01-01

    Genetically encoded fluorescent cross-linking agents represent powerful tools useful both for visualising and modulating protein interactions in living cells. The far-red fluorescent protein HcRed, which is fluorescent only in a dimer form, can be used to promote the homo-dimerisation of target proteins, and thereby yield useful information about biological processes. We have in yeast cells expressed HcRed fused to a subunit of mitochondrial ATP synthase (mtATPase). This resulted in cross-linking of the large multi-subunit mtATPase complex within the inner-membrane of the mitochondrion. Fluorescence microscopy revealed aberrant mitochondrial morphology, and mtATPase complexes isolated from mitochondria were recovered as fluorescent dimers under conditions where complexes from control mitochondria were recovered as monomers. When viewed by electron microscopy normal cristae were absent from mitochondria in cells in which mATPase complexes were cross-linked. mtATPase dimers are believed to be the building blocks that are assembled into supramolecular mtATPase ribbons that promote the formation of mitochondrial cristae. We propose that HcRed cross-links mATPase complexes in the mitochondrial membrane hindering the normal assembly/disassembly of the supramolecular forms of mtATPase. PMID:22496895

  4. Associations between reading achievement and independent reading in early elementary school: A genetically-informative cross-lagged study

    PubMed Central

    Harlaar, Nicole; Deater-Deckard, Kirby; Thompson, Lee A.; DeThorne, Laura S.; Petrill, Stephen A.

    2013-01-01

    This study used a cross-lagged twin design to examine reading achievement and independent reading from 10 to 11 years (n = 436 twin pairs). Reading achievement at age 10 significantly predicted independent reading at age 11. The alternative path, from independent reading at age 10 to reading achievement at age 11, was not significant. Individual differences in reading achievement and independent reading at both ages were primarily due to genetic influences. Furthermore, individual differences in independent reading at age 11 partly reflected genetic influences on reading achievement at age 10. These findings suggest that genetic influences that contribute to individual differences in children’s reading abilities also influence the extent to which children actively seek out and create opportunities to read. PMID:22026450

  5. Associations between reading achievement and independent reading in early elementary school: a genetically informative cross-lagged study.

    PubMed

    Harlaar, Nicole; Deater-Deckard, Kirby; Thompson, Lee A; Dethorne, Laura S; Petrill, Stephen A

    2011-01-01

    This study used a cross-lagged twin design to examine reading achievement and independent reading from 10 to 11 years (n = 436 twin pairs). Reading achievement at age 10 significantly predicted independent reading at age 11. The alternative path, from independent reading at age 10 to reading achievement at age 11, was not significant. Individual differences in reading achievement and independent reading at both ages were primarily due to genetic influences. Furthermore, individual differences in independent reading at age 11 partly reflected genetic influences on reading achievement at age 10. These findings suggest that genetic influences that contribute to individual differences in children's reading abilities also influence the extent to which children actively seek out and create opportunities to read.

  6. Genetic loci with parent-of-origin effects cause hybrid seed lethality in crosses between Mimulus species.

    PubMed

    Garner, Austin G; Kenney, Amanda M; Fishman, Lila; Sweigart, Andrea L

    2016-07-01

    In flowering plants, F1 hybrid seed lethality is a common outcome of crosses between closely related diploid species, but the genetic basis of this early-acting and potentially widespread form of postzygotic reproductive isolation is largely unknown. We intercrossed two closely related species of monkeyflower, Mimulus guttatus and Mimulus tilingii, to characterize the mechanisms and strength of postzygotic reproductive isolation. Then, using a reciprocal backcross design, we performed high-resolution genetic mapping to determine the genetic architecture of hybrid seed lethality and directly test for loci with parent-of-origin effects. We found that F1 hybrid seed lethality is an exceptionally strong isolating barrier between Mimulus species, with reciprocal crosses producing < 1% viable seeds. This form of postzygotic reproductive isolation appears to be highly polygenic, indicating that multiple incompatibility loci have accumulated rapidly between these closely related Mimulus species. It is also primarily caused by genetic loci with parent-of-origin effects, suggesting a possible role for imprinted genes in the evolution of Mimulus hybrid seed lethality. Our findings suggest that divergence in loci with parent-of-origin effects, which is probably driven by genomic coevolution within lineages, might be an important source of hybrid incompatibilities between flowering plant species. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  7. Genetic Map Construction and Detection of Genetic Loci Underlying Segregation Distortion in an Intraspecific Cross of Populus deltoides.

    PubMed

    Zhou, Wencai; Tang, Zaixiang; Hou, Jing; Hu, Nan; Yin, Tongming

    2015-01-01

    Based on a two-way pseudo-testcross strategy, high density and complete coverage linkage maps were constructed for the maternal and paternal parents of an intraspecific F2 pedigree of Populus deltoides. A total of 1,107 testcross markers were obtained, and the mapping population consisted of 376 progeny. Among these markers, 597 were from the mother, and were assigned into 19 linkage groups, spanning a total genetic distance of 1,940.3 cM. The remaining 519 markers were from the father, and were also were mapped into 19 linkage groups, covering 2,496.3 cM. The genome coverage of both maps was estimated as greater than 99.9% at 20 cM per marker, and the numbers of linkage groups of both maps were in accordance with the 19 haploid chromosomes in Populus. Marker segregation distortion was observed in large contiguous blocks on some of the linkage groups. Subsequently, we mapped the segregation distortion loci in this mapping pedigree. Altogether, eight segregation distortion loci with significant logarithm of odds supports were detected. Segregation distortion indicated the uneven transmission of the alternate alleles from the mapping parents. The corresponding genome regions might contain deleterious genes or be associated with hybridization incompatibility. In addition to the detection of segregation distortion loci, the established genetic maps will serve as a basic resource for mapping genetic loci controlling traits of interest in future studies.

  8. Genetic Map Construction and Detection of Genetic Loci Underlying Segregation Distortion in an Intraspecific Cross of Populus deltoides

    PubMed Central

    Hou, Jing; Hu, Nan; Yin, Tongming

    2015-01-01

    Based on a two-way pseudo-testcross strategy, high density and complete coverage linkage maps were constructed for the maternal and paternal parents of an intraspecific F2 pedigree of Populus deltoides. A total of 1,107 testcross markers were obtained, and the mapping population consisted of 376 progeny. Among these markers, 597 were from the mother, and were assigned into 19 linkage groups, spanning a total genetic distance of 1,940.3 cM. The remaining 519 markers were from the father, and were also were mapped into 19 linkage groups, covering 2,496.3 cM. The genome coverage of both maps was estimated as greater than 99.9% at 20 cM per marker, and the numbers of linkage groups of both maps were in accordance with the 19 haploid chromosomes in Populus. Marker segregation distortion was observed in large contiguous blocks on some of the linkage groups. Subsequently, we mapped the segregation distortion loci in this mapping pedigree. Altogether, eight segregation distortion loci with significant logarithm of odds supports were detected. Segregation distortion indicated the uneven transmission of the alternate alleles from the mapping parents. The corresponding genome regions might contain deleterious genes or be associated with hybridization incompatibility. In addition to the detection of segregation distortion loci, the established genetic maps will serve as a basic resource for mapping genetic loci controlling traits of interest in future studies. PMID:25942445

  9. Modelling ionosphere using combined memory based and genetic algorithms over the Europe region.

    NASA Astrophysics Data System (ADS)

    Tomasik, L.

    2009-04-01

    The state of the ionosphere depends on space weather factors like the intensity of solar activity, magnetic activity, local time, season, unfortunately the dependence is not thoroughly known. Memory based method like K Nearest Neighbor algorithm allows predictions by the similarity between ionosphere states. In mostly the nearest neighbour method is a case based on statistical approach used to predict the ionospheric conditions. In this case part of KNN algorithm was modificated by genetic programming. Genetic programming is a method that permit to automatically making algorithms knowing only general definition of a problem. The paper presents the using KNN whit genetic core algorithm in space weather applications and the use of this method for forecasting and mapping of the ionosphere characteristics, as foF2, M(3000)F2. The proposed algorithm is demonstrating for European area.

  10. The European Society of Human Genetics: beginnings, early history and development over its first 25 years.

    PubMed

    Harper, Peter S

    2017-05-10

    The European Society of Human Genetics (ESHG) was founded on 15 March 1967, after preliminary discussions at the International Human Genetics Congress in Chicago the previous year and in Copenhagen in early 1967. Its initial meeting was held on 18-19 November 1967, also in Copenhagen, and annual meetings have been held from that time until the present, apart from years in which the International Congress of Human Genetics was also being held. The character of the Society during its early years was strongly influenced by its founding and permanent Secretary, Jan Mohr, head of the Copenhagen Institute of Medical Genetics, whose records are archived in the Tage Kemp/Jan Mohr Archive, now part of the Danish National Archives. These records show Jan Mohr's determination to keep the activities of the Society limited to the holding of an annual meeting to enhance contacts between European human geneticists, and to resist expansion to other activities. Pressures for a wider role of ESHG became irresistible in the late 1980s and a revised constitution, adopted in 1991, reshaped the Society into a more conventional and less restrictive structure. This has allowed it to play a wider and increasingly influential role in the development of human and medical genetics across Europe, with its own Journal, a range of committees covering different aspects of the field and a series of valuable reports on specific important topics, to be described in a forthcoming article on the Society's more recent history.European Journal of Human Genetics advance online publication, 10 May 2017; doi:10.1038/ejhg.2017.34.

  11. Children's Sleep and Cognitive Performance: A Cross-Domain Analysis of Change over Time

    ERIC Educational Resources Information Center

    Bub, Kristen L.; Buckhalt, Joseph A.; El-Sheikh, Mona

    2011-01-01

    Relations between changes in children's cognitive performance and changes in sleep problems were examined over a 3-year period, and family socioeconomic status, child race/ethnicity, and gender were assessed as moderators of these associations. Participants were 250 second- and third-grade (8-9 years old at Time 1) boys and girls. At each…

  12. Children's sleep and cognitive performance: a cross-domain analysis of change over time.

    PubMed

    Bub, Kristen L; Buckhalt, Joseph A; El-Sheikh, Mona

    2011-11-01

    Relations between changes in children's cognitive performance and changes in sleep problems were examined over a 3-year period, and family socioeconomic status, child race/ethnicity, and gender were assessed as moderators of these associations. Participants were 250 second- and third-grade (8-9 years old at Time 1) boys and girls. At each assessment, children's cognitive performance (Verbal Comprehension, Decision Speed) was measured using the Woodcock-Johnson III Tests of Cognitive Abilities, and sleep problems (Sleepiness, Sleep/Wake Problems) were collected via self-report. Individual growth models revealed that children who reported increases in Sleepiness exhibited little growth in Verbal Comprehension over time compared with their peers who reported decreases in Sleepiness, resulting in a nearly 11-point cognitive deficit by the end of the study. These associations were not found for Sleep/Wake Problems or Decision Speed. Child race/ethnicity and gender moderated these associations, with Sleepiness serving as a vulnerability factor for poor cognitive outcomes, especially among African American children and girls. Differences in cognitive performance for children with high and low Sleepiness trajectories ranged from 16 to 19 points for African American children and from 11 to 19 points for girls. Results build substantially on existing literature examining associations between sleep and cognitive functioning in children and are the first to demonstrate that children's sleep trajectories over 3 waves were associated with changes in their cognitive performance over time.

  13. Children's Sleep and Cognitive Performance: A Cross-Domain Analysis of Change over Time

    ERIC Educational Resources Information Center

    Bub, Kristen L.; Buckhalt, Joseph A.; El-Sheikh, Mona

    2011-01-01

    Relations between changes in children's cognitive performance and changes in sleep problems were examined over a 3-year period, and family socioeconomic status, child race/ethnicity, and gender were assessed as moderators of these associations. Participants were 250 second- and third-grade (8-9 years old at Time 1) boys and girls. At each…

  14. Optimal design of loudspeaker arrays for robust cross-talk cancellation using the Taguchi method and the genetic algorithm.

    PubMed

    Bai, Mingsian R; Tung, Chih-Wei; Lee, Chih-Chung

    2005-05-01

    An optimal design technique of loudspeaker arrays for cross-talk cancellation with application in three-dimensional audio is presented. An array focusing scheme is presented on the basis of the inverse propagation that relates the transducers to a set of chosen control points. Tikhonov regularization is employed in designing the inverse cancellation filters. An extensive analysis is conducted to explore the cancellation performance and robustness issues. To best compromise the performance and robustness of the cross-talk cancellation system, optimal configurations are obtained with the aid of the Taguchi method and the genetic algorithm (GA). The proposed systems are further justified by physical as well as subjective experiments. The results reveal that large number of loudspeakers, closely spaced configuration, and optimal control point design all contribute to the robustness of cross-talk cancellation systems (CCS) against head misalignment.

  15. Reasoning over genetic variance information in cause-and-effect models of neurodegenerative diseases.

    PubMed

    Naz, Mufassra; Kodamullil, Alpha Tom; Hofmann-Apitius, Martin

    2016-05-01

    The work we present here is based on the recent extension of the syntax of the Biological Expression Language (BEL), which now allows for the representation of genetic variation information in cause-and-effect models. In our article, we describe, how genetic variation information can be used to identify candidate disease mechanisms in diseases with complex aetiology such as Alzheimer's disease and Parkinson's disease. In those diseases, we have to assume that many genetic variants contribute moderately to the overall dysregulation that in the case of neurodegenerative diseases has such a long incubation time until the first clinical symptoms are detectable. Owing to the multilevel nature of dysregulation events, systems biomedicine modelling approaches need to combine mechanistic information from various levels, including gene expression, microRNA (miRNA) expression, protein-protein interaction, genetic variation and pathway. OpenBEL, the open source version of BEL, has recently been extended to match this requirement, and we demonstrate in our article, how candidate mechanisms for early dysregulation events in Alzheimer's disease can be identified based on an integrative mining approach that identifies 'chains of causation' that include single nucleotide polymorphism information in BEL models.

  16. Fine-scale spatial genetic dynamics over the life cycle of the tropical tree Prunus africana

    PubMed Central

    Berens, D G; Braun, C; González-Martínez, S C; Griebeler, E M; Nathan, R; Böhning-Gaese, K

    2014-01-01

    Studying fine-scale spatial genetic patterns across life stages is a powerful approach to identify ecological processes acting within tree populations. We investigated spatial genetic dynamics across five life stages in the insect-pollinated and vertebrate-dispersed tropical tree Prunus africana in Kakamega Forest, Kenya. Using six highly polymorphic microsatellite loci, we assessed genetic diversity and spatial genetic structure (SGS) from seed rain and seedlings, and different sapling stages to adult trees. We found significant SGS in all stages, potentially caused by limited seed dispersal and high recruitment rates in areas with high light availability. SGS decreased from seed and early seedling stages to older juvenile stages. Interestingly, SGS was stronger in adults than in late juveniles. The initial decrease in SGS was probably driven by both random and non-random thinning of offspring clusters during recruitment. Intergenerational variation in SGS could have been driven by variation in gene flow processes, overlapping generations in the adult stage or local selection. Our study shows that complex sequential processes during recruitment contribute to SGS of tree populations. PMID:24849171

  17. Reasoning over genetic variance information in cause-and-effect models of neurodegenerative diseases

    PubMed Central

    Naz, Mufassra; Kodamullil, Alpha Tom

    2016-01-01

    The work we present here is based on the recent extension of the syntax of the Biological Expression Language (BEL), which now allows for the representation of genetic variation information in cause-and-effect models. In our article, we describe, how genetic variation information can be used to identify candidate disease mechanisms in diseases with complex aetiology such as Alzheimer’s disease and Parkinson’s disease. In those diseases, we have to assume that many genetic variants contribute moderately to the overall dysregulation that in the case of neurodegenerative diseases has such a long incubation time until the first clinical symptoms are detectable. Owing to the multilevel nature of dysregulation events, systems biomedicine modelling approaches need to combine mechanistic information from various levels, including gene expression, microRNA (miRNA) expression, protein–protein interaction, genetic variation and pathway. OpenBEL, the open source version of BEL, has recently been extended to match this requirement, and we demonstrate in our article, how candidate mechanisms for early dysregulation events in Alzheimer’s disease can be identified based on an integrative mining approach that identifies ‘chains of causation’ that include single nucleotide polymorphism information in BEL models. PMID:26249223

  18. [A cross-sectional study on the industrial noise over-limit status in Guangzhou factories].

    PubMed

    Zhang, Wei-sen; DU, Wei-jia; Wang, Zhi; Mai, Shi-qi; Xu, Qi-rong; Liu, Yi-min

    2011-03-01

    To investigate the industrial noise over-limit status of the worksites in Guangzhou factories, so as to promote the prevention and control of occupational noise hazards. 211 factories in Guangzhou were monitored and investigated. The analysis and assessment were developed for the properties and size of the factories, the districts of the factories being located, the industries of the factories being classified and the date of monitoring. In this understudied factories, most of them were national-owned and joint-ventures, medium size, located in urban, and mainly involved in the industries of manufacturing of motor vehicle, shipping, electron and electric equipment, and the industries of petroleum and chemicals. The prevalence of noise over-limit was higher in joint-ventures (36.0%) and private-run enterprises (31.2%). The over-limit status mainly presented in industries of textile, food and beverage processing, and leather producing, with getting prevalence of over-limit 46.7%, 43.1% and 41.3% respectively. Subsequence were industries of manufacturing of electron and electric equipment, motor vehicle and shipping, and industries of printing and goods producing for culture and sports, with the prevalence for all > 35%. Factories monitored during spring and summer also had higher prevalence of noise over-limit. The similar results were got after adjustment for each other using multivariable regression. The most common over-limit sites mainly focused on the operation of cutting and sawing, milling and planing, pressing, riveting, drilling, jointing, assembling and quality inspecting in industries of mechanism processing and manufacturing, on quality inspecting and packing in industries of pharmacy and food and beverage manufacture, on spinning and scutching in textile industry, and on cleaning and maintaining as assistant jobs, and patrolling and inspecting air-press machine, ventilation machine, dynamotor and pump. Noise in Guangzhou factories widely exists with

  19. Genetic analysis of QTL for eye cross and eye diameter in common carp (Cyprinus carpio L.) using microsatellites and SNPs.

    PubMed

    Jin, S B; Zhang, X F; Lu, J G; Fu, H T; Jia, Z Y; Sun, X W

    2015-04-17

    A group of 107 F1 hybrid common carp was used to construct a linkage map using JoinMap 4.0. A total of 4877 microsatellite and single nucleotide polymorphism (SNP) markers isolated from a genomic library (978 microsatellite and 3899 SNP markers) were assigned to construct the genetic map, which comprised 50 linkage groups. The total length of the linkage map for the common carp was 4775.90 cM with an average distance between markers of 0.98 cM. Ten quantitative trait loci (QTL) were associated with eye diameter, corresponding to 10.5-57.2% of the total phenotypic variation. Twenty QTL were related to eye cross, contributing to 10.8-36.9% of the total phenotypic variation. Two QTL for eye diameter and four QTL for eye cross each accounted for more than 20% of the total phenotypic variation and were considered to be major QTL. One growth factor related to eye diameter was observed on LG10 of the common carp genome, and three growth factors related to eye cross were observed on LG10, LG35, and LG44 of the common carp genome. The significant positive relationship of eye cross and eye diameter with other commercial traits suggests that eye diameter and eye cross can be used to assist in indirect selection for many commercial traits, particularly body weight. Thus, the growth factor for eye cross may also contribute to the growth of body weight, implying that aggregate breeding could have multiple effects. These findings provide information for future genetic studies and breeding of common carp.

  20. Cross-over studies underestimate energy compensation: The example of sucrose-versus sucralose-containing drinks.

    PubMed

    Gadah, Nouf S; Brunstrom, Jeffrey M; Rogers, Peter J

    2016-12-01

    The vast majority of preload-test-meal studies that have investigated the effects on energy intake of disguised nutrient or other food/drink ingredient manipulations have used a cross-over design. We argue that this design may underestimate the effect of the manipulation due to carry-over effects. To test this we conducted comparable cross-over (n = 69) and parallel-groups (n = 48) studies testing the effects of sucrose versus low-calorie sweetener (sucralose) in a drink preload on test-meal energy intake. The parallel-groups study included a baseline day in which only the test meal was consumed. Energy intake in that meal was used to control for individual differences in energy intake in the analysis of the effects of sucrose versus sucralose on energy intake on the test day. Consistent with our prediction, the effect of consuming sucrose on subsequent energy intake was greater when measured in the parallel-groups study than in the cross-over study (respectively 64% versus 36% compensation for the 162 kcal difference in energy content of the sucrose and sucralose drinks). We also included a water comparison group in the parallel-groups study (n = 24) and found that test-meal energy intake did not differ significantly between the water and sucralose conditions. Together, these results confirm that consumption of sucrose in a drink reduces subsequent energy intake, but by less than the energy content of the drink, whilst drink sweetness does not increase food energy intake. Crucially, though, the studies demonstrate that study design affects estimated energy compensation.

  1. Video-game based therapy performed by children with cerebral palsy: a cross-over randomized controlled trial and a cross-sectional quantitative measure of physical activity.

    PubMed

    Zoccolillo, L; Morelli, D; Cincotti, F; Muzzioli, L; Gobbetti, T; Paolucci, S; Iosa, M

    2015-12-01

    Previous studies reported controversial results about the efficacy of video-game based therapy (VGT) in improving neurorehabilitation outcomes in children with cerebral palsy (CP). Primary aim was to investigate the effectiveness of VGT with respect to conventional therapy (CT) in improving upper limb motor outcomes in a group of children with CP. Secondary aim was to quantify if VGT leads children to perform a higher number of movements. A cross-over randomized controlled trial (RCT) for investigating the primary aim and a cross-sectional study for investigating the secondary aim of this study. Outpatients. clinical diagnosis of CP, age between 4 and 14 years, level of GMFC between I and IV. QI<35, severe comorbidities, incapacity to stand even with an external support. Twenty-two children with CP (6.89±1.91-year old) were enrolled in a cross-over RCT with 16 sessions of VGT (using Xbox with Kinect device) and then 16 of CT or vice versa. Upper limb functioning was assessed using the Quality of Upper Extremities Skills Test (QUEST) and hand abilities using Abilhand-kids score. According to the secondary aim of this study a secondary cross-sectional study has been performed. Eight children with CP (6.50±1.60-year old) were enrolled into a trial in which five wireless triaxial accelerometers were positioned on their forearms, legs and trunk for quantifying the physical activity during VGT vs. CT. QUEST scores significantly improved only after VGT (P=0.003), and not after CT (P=0.056). The reverse occurred for Abilhand-kids scores (P=0.165 vs. P=0.013, respectively). Quantity of performed movements was three times higher in VGT than in CT (+198%, P=0.027). VGT resulted effective in improving the motor functions of upper limb extremities in children with CP, conceivably for the increased quantity of limb movements, but failed in improving the manual abilities for performing activities of daily living which benefited more from CT. VGT performed using the X-Box with

  2. Terrestrial support of lake food webs: Synthesis reveals controls over cross-ecosystem resource use.

    PubMed

    Tanentzap, Andrew J; Kielstra, Brian W; Wilkinson, Grace M; Berggren, Martin; Craig, Nicola; Del Giorgio, Paul A; Grey, Jonathan; Gunn, John M; Jones, Stuart E; Karlsson, Jan; Solomon, Christopher T; Pace, Michael L

    2017-03-01

    Widespread evidence that organic matter exported from terrestrial into aquatic ecosystems supports recipient food webs remains controversial. A pressing question is not only whether high terrestrial support is possible but also what the general conditions are under which it arises. We assemble the largest data set, to date, of the isotopic composition (δ(2)H, δ(13)C, and δ(15)N) of lake zooplankton and the resources at the base of their associated food webs. In total, our data set spans 559 observations across 147 lakes from the boreal to subtropics. By predicting terrestrial resource support from within-lake and catchment-level characteristics, we found that half of all consumer observations that is, the median were composed of at least 42% terrestrially derived material. In general, terrestrial support of zooplankton was greatest in lakes with large physical and hydrological connections to catchments that were rich in aboveground and belowground organic matter. However, some consumers responded less strongly to terrestrial resources where within-lake production was elevated. Our study shows that multiple mechanisms drive widespread cross-ecosystem support of aquatic consumers across Northern Hemisphere lakes and suggests that changes in terrestrial landscapes will influence ecosystem processes well beyond their boundaries.

  3. Cross-Amplification and Validation of SNPs Conserved over 44 Million Years between Seals and Dogs

    PubMed Central

    Hoffman, Joseph I.; Thorne, Michael A. S.; McEwing, Rob; Forcada, Jaume; Ogden, Rob

    2013-01-01

    High-density SNP arrays developed for humans and their companion species provide a rapid and convenient tool for generating SNP data in closely-related non-model organisms, but have not yet been widely applied to phylogenetically divergent taxa. Consequently, we used the CanineHD BeadChip to genotype 24 Antarctic fur seal (Arctocephalus gazella) individuals. Despite seals and dogs having diverged around 44 million years ago, 33,324 out of 173,662 loci (19.2%) could be genotyped, of which 173 were polymorphic and clearly interpretable. Two SNPs were validated using KASP genotyping assays, with the resulting genotypes being 100% concordant with those obtained from the high-density array. Two loci were also confirmed through in silico visualisation after mapping them to the fur seal transcriptome. Polymorphic SNPs were distributed broadly throughout the dog genome and did not differ significantly in proximity to genes from either monomorphic SNPs or those that failed to cross-amplify in seals. However, the nearest genes to polymorphic SNPs were significantly enriched for functional annotations relating to energy metabolism, suggesting a possible bias towards conserved regions of the genome. PMID:23874599

  4. Terrestrial support of lake food webs: Synthesis reveals controls over cross-ecosystem resource use

    PubMed Central

    Tanentzap, Andrew J.; Kielstra, Brian W.; Wilkinson, Grace M.; Berggren, Martin; Craig, Nicola; del Giorgio, Paul A.; Grey, Jonathan; Gunn, John M.; Jones, Stuart E.; Karlsson, Jan; Solomon, Christopher T.; Pace, Michael L.

    2017-01-01

    Widespread evidence that organic matter exported from terrestrial into aquatic ecosystems supports recipient food webs remains controversial. A pressing question is not only whether high terrestrial support is possible but also what the general conditions are under which it arises. We assemble the largest data set, to date, of the isotopic composition (δ2H, δ13C, and δ15N) of lake zooplankton and the resources at the base of their associated food webs. In total, our data set spans 559 observations across 147 lakes from the boreal to subtropics. By predicting terrestrial resource support from within-lake and catchment-level characteristics, we found that half of all consumer observations that is, the median were composed of at least 42% terrestrially derived material. In general, terrestrial support of zooplankton was greatest in lakes with large physical and hydrological connections to catchments that were rich in aboveground and belowground organic matter. However, some consumers responded less strongly to terrestrial resources where within-lake production was elevated. Our study shows that multiple mechanisms drive widespread cross-ecosystem support of aquatic consumers across Northern Hemisphere lakes and suggests that changes in terrestrial landscapes will influence ecosystem processes well beyond their boundaries. PMID:28345035

  5. Adult criminal involvement: A cross-sectional inquiry into correlates and mechanisms over the life course

    PubMed Central

    DePadilla, Lara; Perkins, Molly M.; Elifson, Kirk W.; Sterk, Claire E.

    2013-01-01

    In this paper, we examine the relative contribution of four domains of predictors that have been linked to adult criminal involvement: (1) socio-demographic characteristics, (2) family-of-origin factors, (3) proximal processes developed during adolescence, and (4) current lifestyle and situational factors. Cross-sectional data were collected through face-to-face interviews with 242 community-recruited adults. Data analysis involved negative binomial regression. Being male, family size, juvenile delinquency, aggression, living with someone involved in illegal activity and recent violent victimization were independently associated with non-violent criminal involvement. Aggression, association with deviant peers, and recent violent victimization were independently associated with violent criminal involvement. Juvenile delinquency and aggression mediated the affect of multiple family-of-origin characteristics on non-violent criminal involvement and aggression mediated the effect of childhood physical abuse on violent criminal involvement. The results emphasize the importance of investigating both antecedents and proximal risk factors predictive of different types of criminal involvement, which, in turn, will assist in developing risk-focused prevention and intervention programs. PMID:24307752

  6. Cross-species behavioural genetics: A starting point for unravelling the neurobiology of human psychiatric disorders.

    PubMed

    de Mooij-van Malsen, Annetrude J G; Vinkers, Christiaan H; Peterse, Danielle P; Olivier, Berend; Kas, Martien J H

    2011-08-01

    Identifying the genetic and neurobiological mechanisms underlying certain behavioural traits is an important strategy to understand the aetiology of various psychiatric disorders and to find potential new treatment possibilities. It has proven a great challenge to develop paradigms that allow translational research for behavioural phenotypes that are relevant for disorders across the psychiatric spectrum. Recently, there has been increasing attention for studies that implement rodent behavioural paradigms in the home cage to assess the association between genetic backgrounds and behavioural traits. The application of interspecies genetics to unravel these traits has revealed novel insights in the genetic mechanisms that are encoding phenotypes relevant to biological processes underlying psychiatric disorders. By means of two examples, namely the stress-induced hyperthermia paradigm and the home cage environment, this review aims to show that by using individual genetic variations with phenotypes obtained from mice and across categories of neuropsychiatric disorders, novel insights in the neurobiological trajectory of psychiatric disorders can be obtained.

  7. Cross-Disorder Genetic Analysis of Tic Disorders, Obsessive-Compulsive, and Hoarding Symptoms.

    PubMed

    Zilhão, Nuno R; Smit, Dirk J; Boomsma, Dorret I; Cath, Danielle C

    2016-01-01

    Hoarding, obsessive-compulsive disorder (OCD), and Tourette's disorder (TD) are psychiatric disorders that share symptom overlap, which might partly be the result of shared genetic variation. Population-based twin studies have found significant genetic correlations between hoarding and OCD symptoms, with genetic correlations varying between 0.1 and 0.45. For tic disorders, studies examining these correlations are lacking. Other lines of research, including clinical samples and GWAS or CNV data to explore genetic relationships between tic disorders and OCD, have only found very modest if any shared genetic variation. Our aim was to extend current knowledge on the genetic structure underlying hoarding, OC symptoms (OCS), and lifetime tic symptoms and, in a trivariate analysis, assess the degree of common and unique genetic factors contributing to the etiology of these disorders. Data have been gathered from participants in the Netherlands Twin Register comprising a total of 5293 individuals from a sample of adult monozygotic (n = 2460) and dizygotic (n = 2833) twin pairs (mean age 33.61 years). The data on Hoarding, OCS, and tic symptoms were simultaneously analyzed in Mplus. A liability threshold model was fitted to the twin data, analyzing heritability of phenotypes and of their comorbidity. Following the criteria for a probable clinical diagnosis in all phenotypes, 6.8% of participants had a diagnosis of probable hoarding disorder (HD), 6.3% of OCS, and 12.8% of any probable lifetime tic disorder. Genetic factors explained 50.4, 70.1, and 61.1% of the phenotypic covariance between hoarding-OCS, hoarding-tics, and OCS-tics, respectively. Substantial genetic correlations were observed between hoarding and OCS (0.41), hoarding and tics (0.35), and between OCS and tics (0.37). These results support the contribution of genetic factors in the development of these disorders and their comorbidity. Furthermore, tics were mostly influenced by specific

  8. Crosses prior to parthenogenesis explain the current genetic diversity of tropical plant-parasitic Meloidogyne species (Nematoda: Tylenchida).

    PubMed

    Fargette, Mireille; Berthier, Karine; Richaud, Myriam; Lollier, Virginie; Franck, Pierre; Hernandez, Adan; Frutos, Roger

    2010-08-01

    The tropical and subtropical parthenogenetic plant-parasitic nematodes Meloidogyne are polyphagous major agricultural pests. Implementing proper pest management approaches requires a good understanding of mechanisms, population structure, evolutionary patterns and species identification. A comparative analysis of the mitochondrial vs nuclear diversity was conducted on a selected set of Meloidogyne lines from various geographic origins. Mitochondrial co2-16S sequences and AFLP markers of total DNA were applied because of their ability to evidence discrete genetic variation between closely related isolates. Several distinct maternal lineages were present, now associated with different genetic backgrounds. Relative discordances were found when comparing mitochondrial and nuclear diversity patterns. These patterns are most likely related to crosses within one ancestral genetic pool, followed by the establishment of parthenogenesis. In this case, they mirror the genetic backgrounds of the original individuals. Another aspect could be that species emergence was recent or on process from this original genetic pool and that the relatively short time elapsed since then and before parthenogenesis settlement did not allow for lineage sorting. This could also be compatible with the hypothesis of hybrids between closely related species. This genetic pool would correspond to a species as defined by the species interbreeding concept, but also including the grey area of species boundaries. This complex process has implications on the way genotypic and phenotypic diversity should be addressed. The phenotype of parthenogenetic lines is at least for part determined by the ancestral amphimictic genetic background. A direct consequence is, therefore, in terms of risk management, the limited confidence one can have on the direct association of an agronomic threat to a simple typing or species delineation. Risk management strategies and tools must thus consider this complexity when

  9. Genetic Background Specific Hypoxia Resistance in Rat is Correlated with Balanced Activation of a Cross-Chromosomal Genetic Network Centering on Physiological Homeostasis.

    PubMed

    Mao, Lei

    2012-01-01

    Genetic background of an individual can drastically influence an organism's response upon environmental stress and pathological stimulus. Previous studies in inbred rats showed that compared to Brown Norway (BN), Dahl salt-sensitive (SS) rat exerts strong hypoxia susceptibility. However, despite extensive narrow-down approaches via the chromosome substitution methodology, this genome-based physiological predisposition could not be traced back to distinct quantitative trait loci. Upon the completion and public data availability of PhysGen SS-BN consomic (CS) rat platform, I employed systems biology approach attempting to further our understanding of the molecular basis of genetic background effect in light of hypoxia response. I analyzed the physiological screening data of 22 CS rat strains under normoxia and 2-weeks of hypoxia, and cross-compared them to the parental strains. The analyses showed that SS-9(BN) and SS-18(BN) represent the most hypoxia-resistant CS strains with phenotype similar to BN, whereas SS-6(BN) and SS-Y(BN) segregated to the direction of SS. A meta-analysis on the transcriptomic profiles of these CS rat strains under hypoxia treatment showed that although polymorphisms on the substituted BN chromosomes could be directly involved in hypoxia resistance, this seems to be embedded in a more complex trans-chromosomal genetic regulatory network. Via information theory based modeling approach, this hypoxia relevant core genetic network was reverse engineered. Network analyses showed that the protective effects of BN chromosome 9 and 18 were reflected by a balanced activation of this core network centering on physiological homeostasis. Presumably, it is the system robustness constituted on such differential network activation that acts as hypoxia response modifier. Understanding of the intrinsic link between the individual genetic background and the network robustness will set a basis in the current scientific efforts toward personalized medicine.

  10. Temperature can shape a cline in polyandry, but only genetic variation can sustain it over time.

    PubMed

    Taylor, Michelle L; Price, Tom A R; Skeats, Alison; Wedell, Nina

    2016-01-01

    Multiple mating by females (polyandry) is a widespread behavior occurring in diverse taxa, species, and populations. Polyandry can also vary widely within species, and individual populations, so that both monandrous and polyandrous females occur together. Genetic differences can explain some of this intraspecific variation in polyandry, but environmental factors are also likely to play a role. One environmental factor that influences many fundamental biological processes is temperature. Higher temperatures have been shown to directly increase remating in laboratory studies of insects. In the longer term, high temperature could also help to drive the evolution of larger-scale patterns of behavior by changing the context-dependent balance of costs and benefits of polyandry across environments. We examined the relative influence of rearing and mating temperatures on female remating in populations of Drosophila pseudoobscura that show a latitudinal cline in polyandry in nature, using a range of ecologically relevant temperatures. We found that females of all genotypes remated more at cooler temperatures, which fits with the observation of higher average frequencies of polyandry at higher latitudes in this species. However, the impact of temperature was outweighed by the strong genetic control of remating in females in this species. It is likely that genetic factors provide the primary explanation for the latitudinal cline in polyandry in this species.

  11. Temperature can shape a cline in polyandry, but only genetic variation can sustain it over time

    PubMed Central

    Taylor, Michelle L.; Price, Tom A.R.; Skeats, Alison

    2016-01-01

    Multiple mating by females (polyandry) is a widespread behavior occurring in diverse taxa, species, and populations. Polyandry can also vary widely within species, and individual populations, so that both monandrous and polyandrous females occur together. Genetic differences can explain some of this intraspecific variation in polyandry, but environmental factors are also likely to play a role. One environmental factor that influences many fundamental biological processes is temperature. Higher temperatures have been shown to directly increase remating in laboratory studies of insects. In the longer term, high temperature could also help to drive the evolution of larger-scale patterns of behavior by changing the context-dependent balance of costs and benefits of polyandry across environments. We examined the relative influence of rearing and mating temperatures on female remating in populations of Drosophila pseudoobscura that show a latitudinal cline in polyandry in nature, using a range of ecologically relevant temperatures. We found that females of all genotypes remated more at cooler temperatures, which fits with the observation of higher average frequencies of polyandry at higher latitudes in this species. However, the impact of temperature was outweighed by the strong genetic control of remating in females in this species. It is likely that genetic factors provide the primary explanation for the latitudinal cline in polyandry in this species. PMID:27004012

  12. Effects of age on genetic influence on bone loss over 17 years in women: the Healthy Ageing Twin Study (HATS).

    PubMed

    Moayyeri, Alireza; Hammond, Christopher J; Hart, Deborah J; Spector, Timothy D

    2012-10-01

    The rate of bone loss varies across the aging period via multiple complex mechanisms. Therefore, the role of genetic factors on bone loss may also change similarly. In this study, we investigated the effect of age on the genetic component of bone loss in a large twin-based longitudinal study. During 17 years of follow-up in TwinsUK and Healthy Ageing Twin Study (HATS), 15,491 hip and lumbar spine dual-energy X-ray absorptiometry (DXA) scans were performed in 7056 twins. Out of these subjects, 2716 female twins aged >35 years with at least two scans separated for >4 years (mean follow-up 9.7 years) were included in this analysis. We used a mixed-effects random-coefficients regression model to predict hip and spine bone mineral density (BMD) values for exact ages of 40, 45, 50, 55, 60, 65, 70, 75, and 80 years, with adjustment for baseline age, weight, height, and duration of hormone replacement therapy. We then estimated heritability of the changes in BMD measures between these age ranges. Heritability estimates for cross-sectional hip and spine BMD were high (ranging between 69% and 88%) at different ages. Heritability of change of BMD was lower and more variable, generally ranging from 0% to 40% for hip and 0% to 70% for spine; between age 40 and 45 years genetic factors explained 39.9% (95% confidence interval [CI], 25%-53%) of variance of BMD loss for total hip, 46.4% (95% CI, 32%-58%) for femoral neck, and 69.5% (95% CI, 59%-77%) for lumbar spine. These estimates decreased with increasing age, and there appeared to be no heritability of BMD changes after the age of 65 years. There was some evidence at the spine for shared genetic effects between cross-sectional and longitudinal BMD. Whereas genetic factors appear to have an important role in bone loss in early postmenopausal women, nongenetic mechanisms become more important determinants of bone loss with advanced age. Copyright © 2012 American Society for Bone and Mineral Research.

  13. Cross-validation of satellite products over France through their integration into a land surface model

    NASA Astrophysics Data System (ADS)

    Calvet, Jean-Christophe; Barbu, Alina; Carrer, Dominique; Meurey, Catherine

    2014-05-01

    Long (more than 30 years) time series of satellite-derived products over land are now available. They concern Essential Climate Variables (ECV) such as LAI, FAPAR, surface albedo, and soil moisture. The direct validation of such Climate Data Records (CDR) is not easy, as in situ observations are limited in space and time. Therefore, indirect validation has a key role. It consists in comparing the products with similar preexisting products derived from satellite observations or from land surface model (LSM) simulations. The most advanced indirect validation technique consists in integrating the products into a LSM using a data assimilation scheme. The obtained reanalysis accounts for the synergies of the various upstream products and provides statistics which can be used to monitor the quality of the assimilated observations. Meteo-France develops the ISBA-A-gs generic LSM able to represent the diurnal cycle of the surface fluxes together with the seasonal, interannual and decadal variability of the vegetation biomass. The LSM is embedded in the SURFEX modeling platform together with a simplified extended Kalman filter. These tools form a Land Data Assimilation System (LDAS). The current version of the LDAS assimilates SPOT-VGT LAI and ASCAT surface soil moisture (SSM) products over France (8km x 8km), and a passive monitoring of albedo, FAPAR and Land Surface temperature (LST) is performed (i.e., the simulated values are compared with the satellite products). The LDAS-France system is used in the European Copernicus Global Land Service (http://land.copernicus.eu/global/) to monitor the quality of upstream products. The LDAS generates statistics whose trends can be analyzed in order to detect possible drifts in the quality of the products: (1) for LAI and SSM, metrics derived from the active monitoring (i.e. assimilation) such as innovations (observations vs. model forecast), residuals (observations vs. analysis), and increments (analysis vs. model forecast) ; (2

  14. The effect of the mus309 mutation, defective in DNA double-strand break repair, on crossing over in Drosophila melanogaster suggests a mechanism for the centromere effect of crossing over.

    PubMed

    Portin, Petter

    2010-03-01

    The mus309 gene in Drosophila melanogaster encodes a RecQ helicase which is involved in DNA double-strand break (DSB) repair. In a brood pattern analysis, it was observed that in mus309 mutant females, the frequency of single crossovers in the central cv-v interval of the X chromosome was reduced in young females but returned to the level of the wild type control as the females aged. In the proximal v-f interval, the frequency of single crossovers was increased during the entire experimental period. In particular, it was observed that the frequency of double crossovers, as well as the coefficient of coincidence first increased but then gradually decreased, finally reaching the level of the control flies, as the females aged. Map distances increased due to the mus309 mutation in both gene interval studies, but they did not change as the females aged, a result suggesting that the mus309 gene controls the distribution of DSBs to be repaired as crossovers instead of non-crossovers. The results suggest a mechanism for the centromere effect of crossing over in Drosophila, viz the fact the frequency of meiotic crossing over reduces with the age of the female, and that the reduction is more pronounced the closer the interval is to the proximal heterochromatin of the chromosome arm. According to the model suggested, the centromere effect is simply a matter of the balance between different pathways of the repair of the DSBs of DNA.

  15. Genetics, cross-resistance and mechanism of resistance to spinosad in a field strain of Musca domestica L. (Diptera: Muscidae).

    PubMed

    Khan, Hafiz Azhar Ali; Akram, Waseem; Shad, Sarfraz Ali

    2014-02-01

    The house fly, Musca domestica L., is a cosmopolitan insect with the ability to develop resistance to insecticides used for their management. In the present study, we investigated the genetics of spinosad resistance, and cross-resistance potential to other insecticides by selecting a field strain with a commercial spinosad formulation. Bioassays with the field strain, before selection with spinosad, gave resistance ratios (RRs) of 4, 5, 66, 21 and 5 fold for spinosad, indoxacarb, abamectin, imidacloprid and deltamethrin, respectively, in comparison to a laboratory susceptible (Lab-susceptible) strain. After continuous selection of the field strain (Spin-SEL) with spinosad, the RR was increased up to 155 fold; however, the resistance was unstable (RR decreased 1.43 fold) when this strain was not exposed to spinosad for five generations. The Spin-SEL strain did not show cross-resistance to abamectin, indoxacarb or deltamethrin, but showed negative cross-resistance to imidacloprid. Crosses between the Spin-SEL and Lab-susceptible strains revealed an autosomal and incomplete dominant mode of resistance to spinosad. A direct test using a monogenic inheritance model based on Chi-square analysis revealed that the resistance was governed by more than one gene. Moreover, the resistance was neither overcome with the insecticide synergist piperonyl butoxide nor with S,S,S-tributylphosphorotrithioate. Lack of cross-resistance and instability of resistance suggest that rotation with spinosad could be an effective resistance management strategy.

  16. Genetic structure and bio-climatic modeling support allopatric over parapatric speciation along a latitudinal gradient

    PubMed Central

    2012-01-01

    Background Four of the five species of Telopea (Proteaceae) are distributed in a latitudinal replacement pattern on the south-eastern Australian mainland. In similar circumstances, a simple allopatric speciation model that identifies the origins of genetic isolation within temporal geographic separation is considered as the default model. However, secondary contact between differentiated lineages can result in similar distributional patterns to those arising from a process of parapatric speciation (where gene flow between lineages remains uninterrupted during differentiation). Our aim was to use the characteristic distributional patterns in Telopea to test whether it reflected the evolutionary models of allopatric or parapatric speciation. Using a combination of genetic evidence and environmental niche modelling, we focused on three main questions: do currently described geographic borders coincide with genetic and environmental boundaries; are there hybrid zones in areas of secondary contact between closely related species; did species distributions contract during the last glacial maximum resulting in distributional gaps even where overlap and hybridisation currently occur? Results Total genomic DNA was extracted from 619 individuals sampled from 36 populations representing the four species. Seven nuclear microsatellites (nSSR) and six chloroplast microsatellites (cpSSR) were amplified across all populations. Genetic structure and the signature of admixture in overlap zones was described using the Bayesian clustering methods implemented in STUCTURE and NewHybrids respectively. Relationships between chlorotypes were reconstructed as a median-joining network. Environmental niche models were produced for all species using environmental parameters from both the present day and the last glacial maximum (LGM). The nSSR loci amplified a total of 154 alleles, while data for the cpSSR loci produced a network of six chlorotypes. STRUCTURE revealed an optimum number of five

  17. Genetic structure and bio-climatic modeling support allopatric over parapatric speciation along a latitudinal gradient.

    PubMed

    Rossetto, Maurizio; Allen, Chris B; Thurlby, Katie A G; Weston, Peter H; Milner, Melita L

    2012-08-20

    Four of the five species of Telopea (Proteaceae) are distributed in a latitudinal replacement pattern on the south-eastern Australian mainland. In similar circumstances, a simple allopatric speciation model that identifies the origins of genetic isolation within temporal geographic separation is considered as the default model. However, secondary contact between differentiated lineages can result in similar distributional patterns to those arising from a process of parapatric speciation (where gene flow between lineages remains uninterrupted during differentiation). Our aim was to use the characteristic distributional patterns in Telopea to test whether it reflected the evolutionary models of allopatric or parapatric speciation. Using a combination of genetic evidence and environmental niche modelling, we focused on three main questions: do currently described geographic borders coincide with genetic and environmental boundaries; are there hybrid zones in areas of secondary contact between closely related species; did species distributions contract during the last glacial maximum resulting in distributional gaps even where overlap and hybridisation currently occur? Total genomic DNA was extracted from 619 individuals sampled from 36 populations representing the four species. Seven nuclear microsatellites (nSSR) and six chloroplast microsatellites (cpSSR) were amplified across all populations. Genetic structure and the signature of admixture in overlap zones was described using the Bayesian clustering methods implemented in STUCTURE and NewHybrids respectively. Relationships between chlorotypes were reconstructed as a median-joining network. Environmental niche models were produced for all species using environmental parameters from both the present day and the last glacial maximum (LGM).The nSSR loci amplified a total of 154 alleles, while data for the cpSSR loci produced a network of six chlorotypes. STRUCTURE revealed an optimum number of five clusters

  18. Estimates for genetic variance components in reciprocal recurrent selection in populations derived from maize single-cross hybrids.

    PubMed

    dos Reis, Matheus Costa; Pádua, José Maria Villela; Abreu, Guilherme Barbosa; Guedes, Fernando Lisboa; Balbi, Rodrigo Vieira; de Souza, João Cândido

    2014-01-01

    This study was carried out to obtain the estimates of genetic variance and covariance components related to intra- and interpopulation in the original populations (C0) and in the third cycle (C3) of reciprocal recurrent selection (RRS) which allows breeders to define the best breeding strategy. For that purpose, the half-sib progenies of intrapopulation (P11 and P22) and interpopulation (P12 and P21) from populations 1 and 2 derived from single-cross hybrids in the 0 and 3 cycles of the reciprocal recurrent selection program were used. The intra- and interpopulation progenies were evaluated in a 10 × 10 triple lattice design in two separate locations. The data for unhusked ear weight (ear weight without husk) and plant height were collected. All genetic variance and covariance components were estimated from the expected mean squares. The breakdown of additive variance into intrapopulation and interpopulation additive deviations (σ τ (2)) and the covariance between these and their intrapopulation additive effects (Cov Aτ) found predominance of the dominance effect for unhusked ear weight. Plant height for these components shows that the intrapopulation additive effect explains most of the variation. Estimates for intrapopulation and interpopulation additive genetic variances confirm that populations derived from single-cross hybrids have potential for recurrent selection programs.

  19. Development of a 10,000 Locus Genetic Map of the Sunflower Genome Based on Multiple Crosses

    PubMed Central

    Bowers, John E.; Bachlava, Eleni; Brunick, Robert L.; Rieseberg, Loren H.; Knapp, Steven J.; Burke, John M.

    2012-01-01

    Genetic linkage maps have the potential to facilitate the genetic dissection of complex traits and comparative analyses of genome structure, as well as molecular breeding efforts in species of agronomic importance. Until recently, the majority of such maps was based on relatively low-throughput marker technologies, which limited marker density across the genome. The availability of high-throughput genotyping technologies has, however, made possible the efficient development of high-density genetic maps. Here, we describe the analysis and integration of genotypic data from four sunflower (Helianthus annuus L.) mapping populations to produce a consensus linkage map of the sunflower genome. Although the individual maps (which contained 3500–5500 loci each) were highly colinear, we observed localized variation in recombination rates in several genomic regions. We also observed several gaps up to 26 cM in length that completely lacked mappable markers in individual crosses, presumably due to regions of identity by descent in the mapping parents. Because these regions differed by cross, the consensus map of 10,080 loci contained no such gaps, clearly illustrating the value of simultaneously analyzing multiple mapping populations. PMID:22870395

  20. Estimates for Genetic Variance Components in Reciprocal Recurrent Selection in Populations Derived from Maize Single-Cross Hybrids

    PubMed Central

    dos Reis, Matheus Costa; Pádua, José Maria Villela; Abreu, Guilherme Barbosa; Guedes, Fernando Lisboa; Balbi, Rodrigo Vieira; de Souza, João Cândido

    2014-01-01

    This study was carried out to obtain the estimates of genetic variance and covariance components related to intra- and interpopulation in the original populations (C0) and in the third cycle (C3) of reciprocal recurrent selection (RRS) which allows breeders to define the best breeding strategy. For that purpose, the half-sib progenies of intrapopulation (P11 and P22) and interpopulation (P12 and P21) from populations 1 and 2 derived from single-cross hybrids in the 0 and 3 cycles of the reciprocal recurrent selection program were used. The intra- and interpopulation progenies were evaluated in a 10 × 10 triple lattice design in two separate locations. The data for unhusked ear weight (ear weight without husk) and plant height were collected. All genetic variance and covariance components were estimated from the expected mean squares. The breakdown of additive variance into intrapopulation and interpopulation additive deviations (σ τ 2) and the covariance between these and their intrapopulation additive effects (CovAτ) found predominance of the dominance effect for unhusked ear weight. Plant height for these components shows that the intrapopulation additive effect explains most of the variation. Estimates for intrapopulation and interpopulation additive genetic variances confirm that populations derived from single-cross hybrids have potential for recurrent selection programs. PMID:25009831

  1. Development of a 10,000 locus genetic map of the sunflower genome based on multiple crosses.

    PubMed

    Bowers, John E; Bachlava, Eleni; Brunick, Robert L; Rieseberg, Loren H; Knapp, Steven J; Burke, John M

    2012-07-01

    Genetic linkage maps have the potential to facilitate the genetic dissection of complex traits and comparative analyses of genome structure, as well as molecular breeding efforts in species of agronomic importance. Until recently, the majority of such maps was based on relatively low-throughput marker technologies, which limited marker density across the genome. The availability of high-throughput genotyping technologies has, however, made possible the efficient development of high-density genetic maps. Here, we describe the analysis and integration of genotypic data from four sunflower (Helianthus annuus L.) mapping populations to produce a consensus linkage map of the sunflower genome. Although the individual maps (which contained 3500-5500 loci each) were highly colinear, we observed localized variation in recombination rates in several genomic regions. We also observed several gaps up to 26 cM in length that completely lacked mappable markers in individual crosses, presumably due to regions of identity by descent in the mapping parents. Because these regions differed by cross, the consensus map of 10,080 loci contained no such gaps, clearly illustrating the value of simultaneously analyzing multiple mapping populations.

  2. BRAIN ABNORMALITIES IN YOUNG ADULTS AT GENETIC RISK FOR AUTOSOMAL DOMINANT ALZHEIMER’S DISEASE: A CROSS-SECTIONAL STUDY

    PubMed Central

    Reiman, Eric M.; Quiroz, Yakeel T.; Fleisher, Adam S.; Chen, Kewei; Velez-Pardo, Carlos; Jimenez-Del-Rio, Marlene; Fagan, Anne M.; Shah, Aarti R.; Alvarez, Sergio; Arbelaez, Andrés; Giraldo, Margarita; Acosta-Baena, Natalia; Sperling, Reisa A.; Dickerson, Brad; Stern, Chantal E.; Tirado, Victoria; Munoz, Claudia; Reiman, Rebecca A.; Huentelman, Matthew J.; Alexander, Gene E.; Langbaum, Jessica B.S.; Kosik, Kenneth S.; Tariot, Pierre N.; Lopera, Francisco

    2013-01-01

    Summary Background We previously detected functional brain imaging abnormalities in young adults at genetic risk for late-onset Alzheimer’s disease (AD). Here, we sought to characterize structural and functional magnetic resonance imaging (MRI), cerebrospinal fluid (CSF), and plasma biomarker abnormalities in young adults at risk for autosomal dominant early-onset AD. Biomarker measurements were characterized and compared in presenilin 1 (PSEN1) E280A mutation carriers and non-carriers from the world’s largest known autosomal dominant early-onset AD kindred, more than two decades before the carriers’ estimated median age of 44 at the onset of mild cognitive impairment (MCI) and before their estimated age of 28 at the onset of amyloid-β (Aβ) plaque deposition. Methods Biomarker data for this cross-sectional study were acquired in Antioquia, Colombia between July and August, 2010. Forty-four participants from the Colombian Alzheimer’s Prevention Initiative (API) Registry had structural MRIs, functional MRIs during associative memory encoding/novel viewing and control tasks, and cognitive assessments. They included 20 mutation carriers and 24 non-carriers, who were cognitively normal, 18-26 years old and matched for their gender, age, and educational level. Twenty of the participants, including 10 mutation carriers and 10 non-carriers, had lumbar punctures and venipunctures. Primary outcome measures included task-dependent hippocampal/parahippocampal activations and precuneus/posterior cingulate deactivations, regional gray matter reductions, CSF Aβ1-42, total tau and phospho-tau181 levels, and plasma Aβ1-42 levels and Aβ1-42/Aβ1-40 ratios. Structural and functional MRI data were compared using automated brain mapping algorithms and AD-related search regions. Cognitive and fluid biomarkers were compared using Mann-Whitney tests. Findings The mutation carrier and non-carrier groups did not differ significantly in their dementia ratings, neuropsychological

  3. Genetic structure and variability of virus populations in cross-protected grapevines superinfected by Grapevine fanleaf virus.

    PubMed

    Vigne, Emmanuelle; Marmonier, Aurélie; Komar, Véronique; Lemaire, Olivier; Fuchs, Marc

    2009-09-01

    Recombination was assessed in a vineyard site in which grapevines cross-protected with mild strains GHu of Grapevine fanleaf virus (GFLV) or Ta of Arabis mosaic virus (ArMV) were superinfected with GFLV field isolates following transmission by the nematode vector Xiphinema index. The genetic structure and variability within RNA2 of isolates from grapevines co-infected with GFLV field isolates and either GFLV-GHu or ArMV-Ta were characterized to identify intra- and interspecies recombinants. Sequence analysis and phylogenetic relationships inferred intraspecies recombination among GFLV field isolates but not between field isolates and GFLV-GHu. SISCAN analysis confirmed a mosaic structure for two GFLV field isolates for which recombination sites were located in the movement protein and coat protein genes. One of the recombinants was found in eight grapevines that were in close spatial proximity within the vineyard site, suggesting its transmission by X. index. No interspecies recombination was detected between GFLV field isolates and ArMV-Ta. Altogether, our findings suggest that mild protective strains GFLV-GHu and ArMV-Ta did not assist the emergence of viable recombinants to detectable level during a 12-year cross-protection trial. To our knowledge, this is the first extensive characterization of the genetic structure and variability of virus isolates in cross-protected plants.

  4. Further evidence that aberrant segregation and crossing over in Sordaria brevicollis may be discrete, though associated, events.

    PubMed

    Theivendirarajah, K; Whitehouse, H L

    1983-01-01

    Crosses were made between buff spore colour mutants in Sordaria brevicollis in the presence of flanking markers. Recombinant asci with one or more wild-type spores were isolated and the spores germinated and scored for buff and flanking marker genotype. The buff genotype was determined by back-crossing to each parent and looking for recombinants. It was found that the majority of the recombinant asci had aberrant segregation at one or other mutant site but not both. It was inferred that in the recombinants hybrid DNA rarely extended to both sites. When the aberrant segregation was associated with crossing-over, the crossovers were situated at either end of the gene rather than between the allelic sites where the hybrid DNA was believed to terminate. Thus, some of the crossovers were separated from the site of the aberrant segregation by a site apparently not involved in hybrid DNA and none was in the position predicted by the Meselson-Radding model, that is, where the hybrid DNA terminates.

  5. The genetic and epigenetic landscape for CNS drug discovery targeting cross-diagnostic behavioral domains.

    PubMed

    de Mooij-van Malsen, Annetrude J G; Pjetri, Eneda; Kas, Martien J

    2015-04-15

    Animal studies play a central role in the identification and testing of novel drugs for CNS disorders. In his longstanding career, Berend Olivier has significantly contributed to CNS drug discovery by applying and supporting novel views and methodologies in the fields of behavioral neuroscience, pharmacology, and (epi-) genetics. Here we review and put forward some of these integrated approaches that have led to a productive collaboration and new insights into the genetic and epigenetic regulation of neurobehavioural traits related to psychiatric disorders.

  6. Cross layer optimization for cloud-based radio over optical fiber networks

    NASA Astrophysics Data System (ADS)

    Shao, Sujie; Guo, Shaoyong; Qiu, Xuesong; Yang, Hui; Meng, Luoming

    2016-07-01

    To adapt the 5G communication, the cloud radio access network is a paradigm introduced by operators which aggregates all base stations computational resources into a cloud BBU pool. The interaction between RRH and BBU or resource schedule among BBUs in cloud have become more frequent and complex with the development of system scale and user requirement. It can promote the networking demand among RRHs and BBUs, and force to form elastic optical fiber switching and networking. In such network, multiple stratum resources of radio, optical and BBU processing unit have interweaved with each other. In this paper, we propose a novel multiple stratum optimization (MSO) architecture for cloud-based radio over optical fiber networks (C-RoFN) with software defined networking. Additionally, a global evaluation strategy (GES) is introduced in the proposed architecture. MSO can enhance the responsiveness to end-to-end user demands and globally optimize radio frequency, optical spectrum and BBU processing resources effectively to maximize radio coverage. The feasibility and efficiency of the proposed architecture with GES strategy are experimentally verified on OpenFlow-enabled testbed in terms of resource occupation and path provisioning latency.

  7. Retrospective analysis of the genetic diversity of Klebsiella oxytoca isolated in Poland over a 50-year period.

    PubMed

    Stojowska, K; Krawczyk, B; Kałuzewski, S; Kur, J

    2009-10-01

    Population genetics analyses and determination of the phylogenetic relationships between strains have proven to be extremely useful approaches, enabling deeper insights into the epidemiological pattern of bacterial species. There is no longitudinal data describing the molecular epidemiology of Klebsiella oxytoca strains that are opportunistic pathogens responsible for an increasing number of multi-resistant infections in hospitals. The aim of the present study was to assess the genetic diversity of K. oxytoca strains over a 50-year period using internal transcribed spacer polymerase chain reaction (ITS-PCR) and PCR MP (ang. PCR melting profiles) genotyping methods on a large collection of strains isolated from the patients of several hospitals in Poland. The phylogenetic analysis based on ITS-PCR exhibited six distinct branches. Two main groups, KoX and KoY, with four and two sub-groups within KoX and KoY, respectively, have been identified. Typing by the PCR MP method showed a higher level of genetic diversity. However, all K. oxytoca strains were also divided into six genotype groups (KoA, KoB, KoC, KoD, KoE and KoF). In conclusion, we found that the ITS-PCR and PCR MP methods are useful for the phylogenetic delineation of genetic groups in K. oxytoca.

  8. Sampling genetic diversity in the sympatrically and allopatrically speciating Midas cichlid species complex over a 16 year time series

    PubMed Central

    Bunje, Paul ME; Barluenga, Marta; Meyer, Axel

    2007-01-01

    Background Speciation often occurs in complex or uncertain temporal and spatial contexts. Processes such as reinforcement, allopatric divergence, and assortative mating can proceed at different rates and with different strengths as populations diverge. The Central American Midas cichlid fish species complex is an important case study for understanding the processes of speciation. Previous analyses have demonstrated that allopatric processes led to species formation among the lakes of Nicaragua as well as sympatric speciation that is occurring within at least one crater lake. However, since speciation is an ongoing process and sampling genetic diversity of such lineages can be biased by collection scheme or random factors, it is important to evaluate the robustness of conclusions drawn on individual time samples. Results In order to assess the validity and reliability of inferences based on different genetic samples, we have analyzed fish from several lakes in Nicaragua sampled at three different times over 16 years. In addition, this time series allows us to analyze the population genetic changes that have occurred between lakes, where allopatric speciation has operated, as well as between different species within lakes, some of which have originated by sympatric speciation. Focusing on commonly used genetic markers, we have analyzed both DNA sequences from the complete mitochondrial control region as well as nuclear DNA variation at ten microsatellite loci from these populations, sampled thrice in a 16 year time period, to develop a robust estimate of the population genetic history of these diversifying lineages. Conclusion The conclusions from previous work are well supported by our comprehensive analysis. In particular, we find that the genetic diversity of derived crater lake populations is lower than that of the source population regardless of when and how each population was sampled. Furthermore, changes in various estimates of genetic diversity within lakes

  9. Development of novel DNA markers for genetic analysis of grey hamsters by cross-species amplification of microsatellites.

    PubMed

    Wang, C; Zhang, S J; Du, X Y; Xu, Y M; Huo, X Y; Liao, L F; Chen, Z W

    2015-11-13

    The grey hamster has been used in biomedical research for decades. However, effective molecular methods for evaluating the genetic structure of this species are lacking, which hinders its wider usage. In this study, we employed cross-amplification of microsatellite loci of species within the same genus by polymerase chain reaction. Loci screened included 107 from the Mongolian gerbil (MG) and 60 from the Chinese hamster (CH); of these, 15 polymorphic loci were identified for the grey hamster. Of the 167 loci screened, 95 (56.9%) with clear bands on agarose gel were initially identified. After sequencing, 74 (77.9%) of these matched the criteria for microsatellite characteristics, including 41 from MG and 33 from CH. Lastly, 15 (20.3%) loci with more than two alleles for each locus were identified through capillary electrophoresis scanning. To justify the applicability of the 15 grey hamster loci, genetic indexes of grey hamsters were evaluated using 46 generations of outbred stock, established 20 years ago, from Xinjiang, China. Mean effective allele numbers and expected heterozygosity of stock were as low as, respectively, 1.2 and 0.14; these were 2.8 and 4.0 times inferior, respectively, to wild grey hamsters. This finding suggests that the genetic structure of the stock-bred population is too weak to resist artificial and natural selection, mutation and genetic drifting. In conclusion, we have developed de novo microsatellite markers for genetic analysis of the grey hamster, providing data and methodology for the enrichment of a genetic library for this species.

  10. Cross-Disorder Genetic Analysis of Tic Disorders, Obsessive–Compulsive, and Hoarding Symptoms

    PubMed Central

    Zilhão, Nuno R.; Smit, Dirk J.; Boomsma, Dorret I.; Cath, Danielle C.

    2016-01-01

    Hoarding, obsessive–compulsive disorder (OCD), and Tourette’s disorder (TD) are psychiatric disorders that share symptom overlap, which might partly be the result of shared genetic variation. Population-based twin studies have found significant genetic correlations between hoarding and OCD symptoms, with genetic correlations varying between 0.1 and 0.45. For tic disorders, studies examining these correlations are lacking. Other lines of research, including clinical samples and GWAS or CNV data to explore genetic relationships between tic disorders and OCD, have only found very modest if any shared genetic variation. Our aim was to extend current knowledge on the genetic structure underlying hoarding, OC symptoms (OCS), and lifetime tic symptoms and, in a trivariate analysis, assess the degree of common and unique genetic factors contributing to the etiology of these disorders. Data have been gathered from participants in the Netherlands Twin Register comprising a total of 5293 individuals from a sample of adult monozygotic (n = 2460) and dizygotic (n = 2833) twin pairs (mean age 33.61 years). The data on Hoarding, OCS, and tic symptoms were simultaneously analyzed in Mplus. A liability threshold model was fitted to the twin data, analyzing heritability of phenotypes and of their comorbidity. Following the criteria for a probable clinical diagnosis in all phenotypes, 6.8% of participants had a diagnosis of probable hoarding disorder (HD), 6.3% of OCS, and 12.8% of any probable lifetime tic disorder. Genetic factors explained 50.4, 70.1, and 61.1% of the phenotypic covariance between hoarding-OCS, hoarding-tics, and OCS-tics, respectively. Substantial genetic correlations were observed between hoarding and OCS (0.41), hoarding and tics (0.35), and between OCS and tics (0.37). These results support the contribution of genetic factors in the development of these disorders and their comorbidity. Furthermore, tics were mostly influenced by specific

  11. Frequency of Nonallelic Homologous Recombination Is Correlated with Length of Homology: Evidence that Ectopic Synapsis Precedes Ectopic Crossing-Over

    PubMed Central

    Liu, Pengfei; Lacaria, Melanie; Zhang, Feng; Withers, Marjorie; Hastings, P.J.; Lupski, James R.

    2011-01-01

    Genomic disorders constitute a class of diseases that are associated with DNA rearrangements resulting from region-specific genome instability, that is, genome architecture incites genome instability. Nonallelic homologous recombination (NAHR) or crossing-over in meiosis between sequences that are not in allelic positions (i.e., paralogous sequences) can result in recurrent deletions or duplications causing genomic disorders. Previous studies of NAHR have focused on description of the phenomenon, but it remains unclear how NAHR occurs during meiosis and what factors determine its frequency. Here we assembled two patient cohorts with reciprocal genomic disorders; deletion associated Smith-Magenis syndrome and duplication associated Potocki-Lupski syndrome. By assessing the full spectrum of rearrangement types from the two cohorts, we find that complex rearrangements (those with more than one breakpoint) are more prevalent in copy-number gains (17.7%) than in copy-number losses (2.3%); an observation that supports a role for replicative mechanisms in complex rearrangement formation. Interestingly, for NAHR-mediated recurrent rearrangements, we show that crossover frequency is positively associated with the flanking low-copy repeat (LCR) length and inversely influenced by the inter-LCR distance. To explain this, we propose that the probability of ectopic chromosome synapsis increases with increased LCR length, and that ectopic synapsis is a necessary precursor to ectopic crossing-over. PMID:21981782

  12. Relative Intensity of a Cross-Over Resonance to Lamb Dips Observed in Stark Spectroscopy of Methane

    NASA Astrophysics Data System (ADS)

    Okuda, Shoko; Sasada, Hiroyuki

    2017-06-01

    Last ISMS, we reported on Stark effects of the νb{3} band of methane observed with a sub-Doppler resolution spectrometer. We determined the rotation-induced permanent dipole moment (PEDM) in the vibrational ground state and the vibration-, rotation-, and Coriolis-type-interaction-induced PEDMs in the v_{3}=1 state. Figure illustrates Stark modulation spectrum of the Q(6)E with the external electric field of 31.0 kV/cm and the selection rule of Δ M=±1, where M is the magnetic quantum number. The Δ M=1 and -1 components of the Lamb dips labeled by A and B are resolved, and the central component C is identified with the cross-over resonance. The Lamb dips are assigned to the magnetic quantum numbers of the lower and upper states, (M'',M') according to the Clebsch-Gordan coefficients. We found that the relative intensity of the cross-over resonance to the associated Lamb dips depends on the P, Q, and R branches. We ascribe the dependence to the collisional relaxation processes.

  13. Cross stratum resources protection in fog-computing-based radio over fiber networks for 5G services

    NASA Astrophysics Data System (ADS)

    Guo, Shaoyong; Shao, Sujie; Wang, Yao; Yang, Hui

    2017-09-01

    In order to meet the requirement of internet of things (IoT) and 5G, the cloud radio access network is a paradigm which converges all base stations computational resources into a cloud baseband unit (BBU) pool, while the distributed radio frequency signals are collected by remote radio head (RRH). A precondition for centralized processing in the BBU pool is an interconnection fronthaul network with high capacity and low delay. However, it has become more complex and frequent in the interaction between RRH and BBU and resource scheduling among BBUs in cloud. Cloud radio over fiber network has been proposed in our previous work already. In order to overcome the complexity and latency, in this paper, we first present a novel cross stratum resources protection (CSRP) architecture in fog-computing-based radio over fiber networks (F-RoFN) for 5G services. Additionally, a cross stratum protection (CSP) scheme considering the network survivability is introduced in the proposed architecture. The CSRP with CSP scheme can effectively pull the remote processing resource locally to implement the cooperative radio resource management, enhance the responsiveness and resilience to the dynamic end-to-end 5G service demands, and globally optimize optical network, wireless and fog resources. The feasibility and efficiency of the proposed architecture with CSP scheme are verified on our software defined networking testbed in terms of service latency, transmission success rate, resource occupation rate and blocking probability.

  14. Extra virgin olive oil phenols and markers of oxidation in Greek smokers: a randomized cross-over study.

    PubMed

    Moschandreas, J; Vissers, M N; Wiseman, S; van Putte, K P; Kafatos, A

    2002-10-01

    To examine the effect of a low phenol olive oil and high phenol olive oil on markers of oxidation and plasma susceptibility to oxidation in normolipaemic smokers. Randomized single-blind cross-over trial with two intervention periods. The Medical School and University Hospital of the University of Crete, Heraklion, Crete, Greece. Twenty-five healthy males and females completed the study. Each intervention was of three weeks duration and intervention periods were separated by a two week washout. Seventy grams of extra virgin olive oil was supplied to each subject per day in the intervention periods. The olive oils supplied differed in their phenol content by 18.6 mg/day. Two fasting venous blood samples were taken at the end of each intervention period. The markers of antioxidant capacity measured in fasting plasma samples (total plasma resistance to oxidation, concentrations of protein carbonyl as a marker of protein oxidation, malondialdehyde and lipid hydroperoxides as markers of lipid oxidation and the ferric reducing ability of plasma) did not differ significantly between the low and high phenol olive oil diets. No effect of olive oil phenols on markers of oxidation in smokers was detected. It may be that the natural concentrations of phenols in olive oil are too low to produce an effect in the post-absorptive phase. Possible reasons for period effects and interactions between diet and administration period need attention to aid further cross-over trials of this kind. Unilever Research Vlaardingen, The Netherlands.

  15. Anxiety trajectories in the second half of life: Genetic and environmental contributions over age.

    PubMed

    Lee, Lewina O; Gatz, Margaret; Pedersen, Nancy L; Prescott, Carol A

    2016-02-01

    Clinically significant anxiety symptoms are prevalent among the elderly, yet knowledge about the longitudinal course of anxiety symptoms in later life remains scarce. The goals of this study were to (a) characterize age trajectories of state anxiety symptoms in the second half of life, and (b) estimate genetic and environmental contributions to individual differences in the age trajectory of state anxiety. This study was based on data from 1,482 participants in the Swedish Adoption/Twin Study of Aging who were aged 50 and older at their first occasion (512 complete twin pairs, 458 singletons) and had up to 6 measurement occasions spanning 11 years. Consistent with life span developmental theories of age-related emotional change, anxiety symptom levels declined during the transition from midlife to the mid-60s, followed by a mild increase that gradually plateaued in the 80s. There were substantial individual differences in the age trajectory of anxiety. After accounting for effects of sex, cohort, mode of testing, and proximity to death, this longitudinal variation was partitioned into biometric sources. Nonshared environmental variance was highest in the late 60s and declined thereafter, whereas genetic variance increased at an accelerated pace from approximately age 60 onward. There was no evidence for effects of rearing or other shared environment on anxiety symptoms in later life. These findings highlight how the etiology of anxiety symptoms changes from midlife to old age. (c) 2016 APA, all rights reserved).

  16. Anxiety Trajectories in the Second Half of Life: Genetic and Environmental Contributions over Age

    PubMed Central

    Lee, Lewina O.; Gatz, Margaret; Pedersen, Nancy L.; Prescott, Carol A.

    2015-01-01

    Clinically significant anxiety symptoms are prevalent among the elderly, yet knowledge about the longitudinal course of anxiety symptoms in later life remains scarce. The goals of this study were to (1) characterize age trajectories of state anxiety symptoms in the second half of life, and (2) estimate genetic and environmental contributions to individual differences in the age trajectory of state anxiety. This study was based on data from 1,482 participants in the Swedish Adoption/Twin Study of Aging who were aged 50 and older at their first occasion (512 complete twin pairs, 458 singletons) and had up to six measurement occasions spanning 11 years. Consistent with lifespan developmental theories of age-related emotional change, anxiety symptom levels declined during the transition from midlife to the mid −60s, followed by a mild increase that gradually plateaued in the 80s. There were substantial individual differences in the age trajectory of anxiety. After accounting for effects of sex, cohort, mode of testing and proximity to death, this longitudinal variation was partitioned into biometric sources. Nonshared environmental variance was highest in the late 60s and declined thereafter, whereas genetic variance increased at an accelerated pace from approximately age 60 onward. There was no evidence for effects of rearing or other shared environment on anxiety symptoms in later life. These findings highlight how the etiology of anxiety symptoms changes from midlife to old age. PMID:26751006

  17. Fatigue is Specific to Working Muscles: No Cross-over with Single-leg Cycling in Trained Cyclists

    PubMed Central

    Elmer, Steven J.; Amann, Markus; McDaniel, John; Martin, David T.; Martin, James C.

    2014-01-01

    Fatigue induced via a maximal isometric contraction of a single-limb muscle group can evoke a “cross-over” of fatigue that reduces voluntary muscle activation and maximum isometric force in the rested contralateral homologous muscle group. We asked whether a cross-over of fatigue also occurs when fatigue is induced via high-intensity endurance exercise involving a substantial muscle mass. Specifically, we used high-intensity single-leg cycling to induce fatigue and evaluated associated effects on maximum cycling power (Pmax) in the fatigued ipsilateral leg (FATleg) as well as the rested contralateral leg (RESTleg). On separate days, 12 trained cyclists performed right leg Pmax trials before and again 30s, 3, 5, and 10min after a cycling time trial (TT, 10min) performed either with their right or left leg. Fatigue was estimated by comparing exercise-induced changes in Pmax and maximum handgrip isometric force (Fmax). Mean power produced during the right and left leg TT’s did not differ (203±8 vs. 199±8W). Compared to pre-TT, FATleg Pmax was reduced by 22±3% at 30s post-TT and remained reduced by 9±2% at 5min post-TT (both P<0.05). Despite considerable power loss in the FATleg, post-TT RESTleg Pmax (596–603W) did not differ from pre-TT values (596±35W). There were no alterations in handgrip Fmax (529–547N). Our data suggest that any potential cross-over of fatigue, if present at all, was not sufficient to measurably compromise RESTleg Pmax in trained cyclists. These results along with the lack of changes in handgrip Fmax indicate that impairments in maximal voluntary neuromuscular function were specific to working muscles. PMID:22806085

  18. Developing Exon-Primed Intron-Crossing (EPIC) markers for population genetic studies in three Aedes disease vectors.

    PubMed

    White, Vanessa Linley; Endersby, Nancy Margaret; Chan, Janice; Hoffmann, Ary Anthony; Weeks, Andrew Raymond

    2015-03-01

    Aedes aegypti, Aedes notoscriptus, and Aedes albopictus are important vectors of many arboviruses implicated in human disease such as dengue fever. Genetic markers applied across vector species can provide important information on population structure, gene flow, insecticide resistance, and taxonomy, however, robust microsatellite markers have proven difficult to develop in these species and mosquitoes generally. Here we consider the utility and transferability of 15 Ribosome protein (Rp) Exon-Primed Intron-Crossing (EPIC) markers for population genetic studies in these 3 Aedes species. Rp EPIC markers designed for Ae. aegypti also successfully amplified populations of the sister species, Ae. albopictus, as well as the distantly related species, Ae. notoscriptus. High SNP and good indel diversity in sequenced alleles plus support for amplification of the same regions across populations and species were additional benefits of these markers. These findings point to the general value of EPIC markers in mosquito population studies.

  19. A self-adaptive genetic algorithm-artificial neural network algorithm with leave-one-out cross validation for descriptor selection in QSAR study.

    PubMed

    Wu, Jingheng; Mei, Juan; Wen, Sixiang; Liao, Siyan; Chen, Jincan; Shen, Yong

    2010-07-30

    Based on the quantitative structure-activity relationships (QSARs) models developed by artificial neural networks (ANNs), genetic algorithm (GA) was used in the variable-selection approach with molecule descriptors and helped to improve the back-propagation training algorithm as well. The cross validation techniques of leave-one-out investigated the validity of the generated ANN model and preferable variable combinations derived in the GAs. A self-adaptive GA-ANN model was successfully established by using a new estimate function for avoiding over-fitting phenomenon in ANN training. Compared with the variables selected in two recent QSAR studies that were based on stepwise multiple linear regression (MLR) models, the variables selected in self-adaptive GA-ANN model are superior in constructing ANN model, as they revealed a higher cross validation (CV) coefficient (Q(2)) and a lower root mean square deviation both in the established model and biological activity prediction. The introduced methods for validation, including leave-multiple-out, Y-randomization, and external validation, proved the superiority of the established GA-ANN models over MLR models in both stability and predictive power. Self-adaptive GA-ANN showed us a prospect of improving QSAR model.

  20. Development of novel microsatellite DNA markers by cross-amplification and analysis of genetic variation in gerbils.

    PubMed

    Du, Xiaoyan; Chen, Zhenwen; Li, Wei; Tan, Yuanqing; Lu, Jing; Zhu, Xiangdong; Zhao, Taiyun; Dong, Gang; Zeng, Lin

    2010-01-01

    The objectives of this study are to establish microsatellite loci for the Mongolian gerbil based on mouse microsatellite DNA sequences and to investigate genetic variation in the laboratory gerbil (Capital Medical University, CMU) and 2 wild gerbil populations (from Yin Chuan city [YIN] and the Hohehot Municipality [HOH]). In total, 536 mouse microsatellite markers were chosen to identify polymorphic dinucleotide repeat loci in the gerbil by cross-amplification. Of these markers, 313 (58.39%) have been discretely amplified from the CMU laboratory gerbil and been sequenced. Of the 313 sequenced markers, 130 were confirmed as simple sequence repeat (SSR) loci in the gerbil. In total, 6 of those newly identified loci plus 6 identified in previous reports were used to estimate the genetic polymorphism for 30 laboratory gerbils and 54 wild gerbils (27 each of the HOH and YIN groups). A total of 29 alleles were observed in the 3 populations, and 11 of 12 loci (91.67%) are polymorphic markers. Nei's standard genetic distances of 0.0592 (CMU vs. HOH) and 0.1033 (CMU vs. YIN) were observed. The averages of observed versus expected heterozygosity are 0.5231/0.4008, 0.5051/0.3882, and 0.4825/0.3665 for the YIN, HOH, and CMU populations, respectively. These results show that cross-amplification using mouse microsatellite primers is an efficient way to identify gerbil SSR loci. By using these 12 selected markers, we have demonstrated that genetic variation level within the CMU population is higher than that has been reported previously and are comparable with the levels found in 2 wild populations.

  1. Patients' decisional control over care: a cross-national comparison from both the patients' and nurses' points of view.

    PubMed

    Papastavrou, Evridiki; Efstathiou, Georgios; Tsangari, Haritini; Karlou, Chryssoula; Patiraki, Elisabeth; Jarosova, Darja; Balogh, Zoltan; Merkouris, Anastasios; Suhonen, Riitta

    2016-03-01

    Patients' decisional control over care is the ability or power for patients to decide what their involvement will be in healthcare decisions. There is evidence of limited agreement between the perceptions of patients and the perceptions of nurses and/or caregivers with regard to the degree of patient involvement in the planning and performance of their care. To analyse and compare patients' and nurses' perceptions of patients' decisional control over their own care. A multisite cross-sectional comparative survey design was employed. Data were collected from hospitalised surgical inpatients (n = 1315) and their caregivers (n = 960 nurses) in five European countries. The Individualised Care Scale part B was used for collecting data from both the patients and nurses. Ethical standards were followed throughout the study. Significant between-country differences were found between patients and nurses. In all countries, both patients and nurses regarded that decisional control over care had been actualised (ICS-B: M = 3.75-4.47 and 3.48-4.33, respectively), but there were significant differences in their perceptions regarding four of the six items of the decisional control factor of the ICS-B. The results show that there are disparities between patients' and nurses' perceptions of patient involvement in care, probably due to cultural issues that need further exploration. The disparities between patients' and nurses' perceptions on patients' decisional control over their care should be taken into consideration as a potential cause of patient dissatisfaction with nursing care. © 2015 Nordic College of Caring Science.

  2. Cross-satellite comparison of operational land surface temperature products derived from MODIS and ASTER data over bare soil surfaces

    NASA Astrophysics Data System (ADS)

    Duan, Si-Bo; Li, Zhao-Liang; Cheng, Jie; Leng, Pei

    2017-04-01

    The collection 6 (C6) MODIS land surface temperature (LST) product is publicly available for the user community. Compared to the collection 5 (C5) MODIS LST product, the C6 MODIS LST product has been refined over bare soil pixels. Assessing the accuracy of the C6 MODIS LST product will help to facilitate the use of the LST product in various applications. In this study, we present a cross-satellite comparison to evaluate the accuracy of the C6 MODIS LST product (MOD11_L2) over bare soil surfaces under various atmospheric and surface conditions using the ASTER LST product as a reference. For comparison, the C5 MODIS LST product was also used in the analysis. The absolute biases (0.2-1.5 K) of the differences between the C6 MODIS LST and ASTER LST over bare soil surfaces are approximately two times less than those (0.6-3.8 K) of the differences between the C5 MODIS LST and ASTER LST. Furthermore, the RMSEs (0.7-2.3 K) over bare soil surfaces for the C6 MODIS LST are significantly smaller than those (0.9-4.2 K) for the C5 MODIS LST. These results indicate that the accuracy of the C6 MODIS LST product is much better than that of the C5 MODIS LST product. We recommend that the user community employs the C6 MODIS LST product in their applications.

  3. The effect of intermittent training in hypobaric hypoxia on sea-level exercise: a cross-over study in humans.

    PubMed

    Hendriksen, Ingrid J M; Meeuwsen, Ted

    2003-01-01

    The purpose of this study was to examine the effect of intermittent training in a hypobaric chamber on physical exercise at sea level. Over a 10 day period, 16 male triathletes trained for 2 h each day on a cycle ergometer placed in a hypobaric chamber. Training intensity was at 60%-70% of the heart rate reserve. There were 8 subjects who trained at a simulated altitude of 2,500 m, the other 8 trained at sea level. A year later, a cross-over study took place. Baseline measurements were made on a cycle ergometer at sea level, which included an incremental test until exhaustion and a Wingate Anaerobic Test. Altogether, 12 subjects completed the cross-over study. At 9 days after training in hypoxia, significant increases were seen in maximal power output (.W(max))(5.2%), anaerobic mean power (4.1%), and anaerobic peak power (3.8%). A non-significant increase in maximal oxygen uptake (.VO(2max)) of 1.9% was observed. At 9 days after training at sea level, no significant changes were seen in .W(max)(2.1%), .VO(2max) (2.0%), anaerobic mean power (0.2%) and anaerobic peak power (0.2%). When comparing the results of the two training regimes, the anaerobic mean power was the only variable that showed a significantly larger increase as a result of training at altitude. And, although the differences in percentage change between the two training protocols were not significant, they were substantial for as well as for anaerobic peak power. The results of this study indicate that intermittent hypobaric training can improve the anaerobic energy supplying system, and also, to a lesser extent, the aerobic system. It can be concluded that the overall results of the cross-over study showed predominantly improvements in the anaerobic metabolism at variance with the previous study of our own group, where the relative .VO(2max) and .W(max) increased by 7%.

  4. Estimates of genetic parameters for total milk yield over multiple ages in Brazilian Murrah buffaloes using different models.

    PubMed

    Sesana, R C; Baldi, F; Borquis, R R A; Bignardi, A B; Hurtado-Lugo, N A; El Faro, L; Albuquerque, L G; Tonhati, H

    2014-04-14

    The objective of this study was to estimate variance components and genetic parameters for accumulated 305-day milk yield (MY305) over multiple ages, from 24 to 120 months of age, applying random regression (RRM), repeatability (REP) and multi-trait (MT) models. A total of 4472 lactation records from 1882 buffaloes of the Murrah breed were utilized. The contemporary group (herd-year-calving season) and number of milkings (two levels) were considered as fixed effects in all models. For REP and RRM, additive genetic, permanent environmental and residual effects were included as random effects. MT considered the same random effects as did REP and RRM with the exception of permanent environmental effect. Residual variances were modeled by a step function with 1, 4, and 6 classes. The heritabilities estimated with RRM increased with age, ranging from 0.19 to 0.34, and were slightly higher than that obtained with the REP model. For the MT model, heritability estimates ranged from 0.20 (37 months of age) to 0.32 (94 months of age). The genetic correlation estimates for MY305 obtained by RRM (L23.res4) and MT models were very similar, and varied from 0.77 to 0.99 and from 0.77 to 0.99, respectively. The rank correlation between breeding values for MY305 at different ages predicted by REP, MT, and RRM were high. It seems that a linear and quadratic Legendre polynomial to model the additive genetic and animal permanent environmental effects, respectively, may be sufficient to explain more parsimoniously the changes in MY305 genetic variation with age.

  5. Combining Gender, Work, and Family Identities: The Cross-Over and Spill-Over of Gender Norms into Young Adults’ Work and Family Aspirations

    PubMed Central

    Meeussen, Loes; Veldman, Jenny; Van Laar, Colette

    2016-01-01

    The current study investigates how descriptive and prescriptive gender norms that communicate work and family identities to be (in)compatible with gender identities limit or enhance young men and women’s family and career aspirations. Results show that young adults (N = 445) perceived gender norms to assign greater compatibility between female and family identities and male and work identities than vice versa, and that young men and women mirror their aspirations to this traditional division of tasks. Spill-over effects of norms across life domains and cross-over effects of norms across gender-groups indicated that young women, more than young men, aimed to ‘have it all’: mirroring their career ambitions to a male career model, while keeping their family aspirations high. Moreover, young women opposed traditional role divisions in the family domain by decreasing their family aspirations in face of norms of lower family involvement or higher career involvement of men. Conversely, in line with traditional gender roles, young men showed lower family aspirations in the face of strong male career norms; and showed increases in their career aspirations when perceiving women to take up more family roles. Young men’s family aspirations were, however, more influenced by new norms prescribing men to invest more in their family, suggesting opportunities for change. Together, these findings show that through social norms, young adults’ gender identity affects aspirations for how to manage the co-presence of their work and family identities. Altering these norms may provide leverage for change to allow both men and women to combine their multiple identities in an enriching way. PMID:27909416

  6. Combining Gender, Work, and Family Identities: The Cross-Over and Spill-Over of Gender Norms into Young Adults' Work and Family Aspirations.

    PubMed

    Meeussen, Loes; Veldman, Jenny; Van Laar, Colette

    2016-01-01

    The current study investigates how descriptive and prescriptive gender norms that communicate work and family identities to be (in)compatible with gender identities limit or enhance young men and women's family and career aspirations. Results show that young adults (N = 445) perceived gender norms to assign greater compatibility between female and family identities and male and work identities than vice versa, and that young men and women mirror their aspirations to this traditional division of tasks. Spill-over effects of norms across life domains and cross-over effects of norms across gender-groups indicated that young women, more than young men, aimed to 'have it all': mirroring their career ambitions to a male career model, while keeping their family aspirations high. Moreover, young women opposed traditional role divisions in the family domain by decreasing their family aspirations in face of norms of lower family involvement or higher career involvement of men. Conversely, in line with traditional gender roles, young men showed lower family aspirations in the face of strong male career norms; and showed increases in their career aspirations when perceiving women to take up more family roles. Young men's family aspirations were, however, more influenced by new norms prescribing men to invest more in their family, suggesting opportunities for change. Together, these findings show that through social norms, young adults' gender identity affects aspirations for how to manage the co-presence of their work and family identities. Altering these norms may provide leverage for change to allow both men and women to combine their multiple identities in an enriching way.

  7. Over production of lignocellulosic enzymes of Coriolus versicolor by genetic engineering methodology. Final report

    SciTech Connect

    Williams, A.L.

    1998-07-01

    The project seeks to understand the biological and chemical processes involved in the secretion of the enzyme polyphenol oxidase (PPO) by the hyphae, the basic unit of the filamentous fungus Coriolus versicolor. These studies are made to determine rational strategies for enhanced secretion of PPO, both with the use of recombinant DNA techniques and without. This effort focuses on recombinant DNA techniques to enhance enzyme production. The major thrust of this project was two-fold: to mass produce C. versicolor tyrosinase (polyphenol oxidase) by genetic engineering as well as cultural manipulations; and to utilize PPO as a biocatalyst in the processing of lignocellulose as a renewable energy resource. In this study, the assessment of genomic and cDNA recombinant clones with regards to the overproduction of PPO continued. Further, immunocytochemical techniques were employed to assess the mechanism(s) involved in the secretion of PPO by the hyphae. Also, factors influencing PPO secretion were examined.

  8. Etiology of Obesity Over the Life Span: Ecological and Genetic Highlights from Asian Countries.

    PubMed

    Chong, Pei Nee; Teh, Christinal Pey Wen; Poh, Bee Koon; Noor, Mohd Ismail

    2014-03-01

    Obesity is a worldwide pandemic, and the prevalence rate has doubled since the 1980s. Asian countries are also experiencing the global epidemic of obesity with its related health consequences. The prevalence of overweight and obesity are increasing at an alarming rate across all age groups in Asia. These increases are mainly attributed to rapid economic growth, which leads to socio-economic, nutrition and lifestyle transitions, resulting in a positive energy balance. In addition, fat mass and obesity-associated gene variants, copy number variants in chromosomes and epigenetic modifications have shown positive associations with the risk of obesity among Asians. In this review highlights of prevalence and related ecological and genetic factors that could influence the rapid rise in obesity among Asian populations are discussed.

  9. Genetic diversity and molecular evolution of the major human metapneumovirus surface glycoproteins over a decade.

    PubMed

    Papenburg, Jesse; Carbonneau, Julie; Isabel, Sandra; Bergeron, Michel G; Williams, John V; De Serres, Gaston; Hamelin, Marie-Ève; Boivin, Guy

    2013-11-01

    Human metapneumovirus (HMPV) is a recently discovered paramyxovirus that is a major cause of respiratory infections worldwide. We aim to describe the molecular evolution of the HMPV F (fusion) and G (attachment) surface glycoproteins because they are targets for vaccines, monoclonal antibodies and antivirals currently in development. Nasopharyngeal aspirates were collected in children <3 years old with acute respiratory infection in Quebec City during 2001-2010. HMPV-positive samples (n = 163) underwent HMPV-F and -G gene sequencing. Furthermore, HMPV-F (n = 124) and -G (n = 217) sequences were obtained from GenBank and other studies. Evolutionary analyses (phylogenetic reconstruction, sequence identity, detection of recombination and adaptive evolution) were computed. Sequences clustered into 5 genetic lineages (A1, A2a, A2b, B1 and B2). Multiple lineages circulated each year in Quebec City. With the exception of B1, each of the 5 subgroups was the predominant lineage during ≥1 season. The A1 lineage was not detected since 2002-2003 in our local cohort. There was no evidence of inter- or intragenic recombination. HMPV-F was highly conserved, whereas HMPV-G exhibited greater diversity. HMPV-F demonstrated strong evidence of purifying selection, both overall and in an abundance of negatively selected amino acid sites. In contrast, sites under diversifying selection were detected in all HMPV-G lineages (range, 4-15), all of which were located in the ectodomain. Predominant circulating HMPV lineages vary by year. HMPV-F is highly constrained and undergoes significant purifying selection. Given its high genetic variability, we found a modest number of positively selected sites in HMPV-G. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Genetics of acute inflammation: inflammatory reactions in inbred lines of mice and in their interline crosses.

    PubMed

    Stiffel, C; Ibanez, O M; Ribeiro, O G; Decreusefond, C; Mouton, D; Siqueira, M; Biozzi, G

    1990-01-01

    Acute inflammation is induced by the subcutaneous injection of swollen polyacrylamide microbeads, its intensity measured by the cell and protein concentration of the local exudates. A large and continuous range of responses is obtained in different inbred strains of mice, which suggests a polygenic control of the inflammatory response. The variable levels of the global dominance observed in F1 hybrids issued from several parental combinations indicated that the pattern of alleles controlling high or low response was different in each parental strain. Balanced intercrossing of the 8 inbred strains studied has provided a genetically heterogeneous F3 population, presenting a high variability of responses. The value of the genetic part of F3 phenotypic variance, the spread of the interstrain differences, as well as the polygenic nature of the regulation of inflammatory responses pointed out the possibility to perform a bidirectional genetic selection by using the F3 mice as the foundation population, and response to microbeads as the selective phenotypic character.

  11. Genetic background and phenotypic characterization over two farrowings of leg conformation defects in Landrace and Large White sows.

    PubMed

    de Sevilla, X Fernàndez; Fàbrega, E; Tibau, J; Casellas, J

    2009-05-01

    A Bayesian threshold animal model was applied to evaluate the prevalence over 2 farrowings and genetic background of overall leg conformation score and the presence or absence of 6 specific leg defects (abnormal hoof growth, splay footed, plantigradism, straight pasterns, sickle-hocked legs, and the presence of swelling or injuries) in purebred Landrace and Large White sows. Data sets contained phenotypic records from 2,477 and 1,550 Landrace and Large White females, respectively, at the end of the growing period. Leg conformation data from first and second farrowings were available for 223 and 191 Landrace sows and 213 and 193 Large White sows, respectively. Overall leg conformation deteriorated with age, with statistically relevant differences between females at the end of the growing period, first farrowing (FF), and second farrowing (SF). In a similar way, the prevalence of the 6 specific leg defects increased between the end of the growing period and FF (with the exception of straight pasterns in the Landrace population). Differences between FF and second farrowing were statistically relevant for hoof growth (highest posterior density regions at 95% did not overlap), plantigradism, sickle-hocked legs, and overall leg conformation score in Landrace and for sickle-hocked leg and overall leg conformation score in Large White. The statistical relevance of the genetic background was tested through the Bayes factor (BF) between the model with the additive genetic component and the model with 0 heritability (nonheritable). Heritability (h(2)) was discarded (BF < 1) for sickle-hocked leg in both breeds, whereas decisive evidence (BF > 100) of genetic background was obtained for overall leg conformation score in Landrace and Large White sows (h(2) = 0.27 and 0.38, respectively), hoof growth in both breeds (h(2) = 0.22 and 0.26, respectively), and plantigradism (h(2) = 0.34) and the presence of swelling or injuries in Landrace (h(2) = 0.27). Note that a BF > 100 implies

  12. Is Sensory Over-Responsivity Distinguishable from Childhood Behavior Problems? A Phenotypic and Genetic Analysis

    ERIC Educational Resources Information Center

    Van Hulle, Carol A.; Schmidt, Nicole L.; Goldsmith, H. Hill

    2012-01-01

    Background: Although impaired sensory processing accompanies various clinical conditions, the question of its status as an independent disorder remains open. Our goal was to delineate the comorbidity (or lack thereof) between childhood psychopathology and sensory over-responsivity (SOR) in middle childhood using phenotypic and behavior-genetic…

  13. Is Sensory Over-Responsivity Distinguishable from Childhood Behavior Problems? A Phenotypic and Genetic Analysis

    ERIC Educational Resources Information Center

    Van Hulle, Carol A.; Schmidt, Nicole L.; Goldsmith, H. Hill

    2012-01-01

    Background: Although impaired sensory processing accompanies various clinical conditions, the question of its status as an independent disorder remains open. Our goal was to delineate the comorbidity (or lack thereof) between childhood psychopathology and sensory over-responsivity (SOR) in middle childhood using phenotypic and behavior-genetic…

  14. Merging molecular data for evaluating cross country genetic diversity of pigs.

    USDA-ARS?s Scientific Manuscript database

    Integration of molecular data generated by microsatellite panels recommended by FAO around the world should be initiated in order to accomplish objectives stated in the Global Plan of Action for Animal Genetic Resources. To that end microsatellite datasets from U.S. (n=179, including imported Chines...

  15. A Cross-Sectional Behavioral Genetic Analysis of Task Persistence in the Transition to Middle Childhood

    ERIC Educational Resources Information Center

    Deater-Deckard, Kirby; Petrill, Stephen A.; Thompson, Lee A.; DeThorne, Laura S.

    2005-01-01

    Task persistence, measured by a composite score of independent teacher, tester and observer reports, was examined using behavioral genetic analysis. Participants included 92 monozygotic and 137 same-sex dizygotic twin pairs in Kindergarten or 1st grade (4.3 to 7.9 years old). Task persistence was widely distributed, higher among older children,…

  16. Migration in Afro-Brazilian rural communities: crossing demographic and genetic data.

    PubMed

    Amorim, Carlos Eduardo G; Gontijo, Carolina C; Falcão-Alencar, Gabriel; Godinho, Neide M O; Toledo, Rafaela C P; Pedrosa, Maria Angélica F; Luizon, Marcelo R; Simões, Aguinaldo L; Klautau-Guimãres, Maria N; Oliveira, Silviene F

    2011-08-01

    Many studies have used genetic markers to understand global migration patterns of our species. However, there are only few studies of human migration on a local scale. We, therefore, researched migration dynamics in three Afro-Brazilian rural communities, using demographic data and ten Ancestry Informative Markers. In addition to the description of migration and marriage structures, we carried out genetic comparisons between the three populations, as well as between locals and migrants from each community. Genetic admixture analyses were conducted according to the gene-identity method, with Sub-Saharan Africans, Amerindians, and Europeans as parental populations. The three analyzed Afro-Brazilian rural communities consisted of 16% to 30% of migrants, most of them women. The age pyramid revealed a gap in the segment of men aged between 20 to 30 yrs. While endogamous marriages predominated, exogamous marriages were mainly patrilocal. Migration dynamics are apparently associated with matrimonial customs and other social practices of such communities. The impact of migration upon the populations' genetic composition was low but showed an increase in European alleles with a concomitant decrease in the Amerindian contribution. Admixture analysis evidenced a higher African contribution to the gene pool of the studied populations, followed by the contribution of Europeans and Amerindians, respectively.

  17. A genetic anomaly of oriented collagen biosynthesis and cross-linking: Keratoconus.

    PubMed

    Bourges, J L; Robert, A M; Robert, L

    2015-02-01

    Oriented collagen biosynthesis is one of the major mechanisms involved in tissue and organ formation during development. Corneal biogenesis is one example. Defects in this process lead to anomalies in tissue structure and function. The transparency of cornea and its achievement are a good example as well as its pathological modifications. Keratoconus is one example of this type of pathologies, involving also inappropriate cross-linking of collagen fibers. Among the tentatives to correct this anomaly, the riboflavin-potentiated UV-cross-linking (CXL) of keratoconus corneas appears clinically satisfactory, although none of the experiments and clinical results published prove effective cross-linking. The published results are reviewed in this article. Copyright © 2014. Published by Elsevier SAS.

  18. The feasibility of using a double blind experimental cross-over design to study interventions for sick building syndrome.

    PubMed

    Tamblyn, R M; Menzies, R I; Tamblyn, R T; Farant, J P; Hanley, J

    1992-06-01

    Methodological problems have limited scientific investigation of the causes of and solutions for sick building syndrome. The feasibility of using an experimental double blind cross-over study to resolve many of these methodological problems was assessed in a pilot study. The experimental intervention was to vary the amount of outdoor air from 10 cubic feet per minute per person (cfmpp) to 20 cfmpp or 50 cfmpp by central manipulation of the building heating, ventilation and air-conditioning (HVAC) system. Over 6 consecutive study weeks, 2 trials of rates were administered in random order. Study subjects and investigators of the study were blinded to intervention sequence. Unblinding, office environment rating and symptom occurrence were measured weekly. Of 305 eligible workers, 254 participated. Problems were encountered in delivering the lowest dose of ventilation due to building leakage. The prevalence of symptoms diminished steadily over the 6 study weeks, time trends which could be controlled by recommended design modifications. Blinding to the intervention was successfully maintained. Weekly non-response did not introduce a response bias but reduced the number of subjects available for analysis by one-third for each trial. We conclude that this design, with certain modifications, is feasible to evaluate many proposed interventions for sick building syndrome.

  19. EBL-1, a putative erythrocyte binding protein of Plasmodium falciparum, maps within a favored linkage group in two genetic crosses.

    PubMed

    Peterson, D S; Wellems, T E

    2000-01-05

    The Duffy binding-like (DBL) superfamily of Plasmodium falciparum encompasses genes which encode ligands for host cell receptors. This superfamily includes two distinct groups of genes, the var genes which encode antigenically variant cytoadherence proteins (PfEMP1), and the eba-175 gene which encodes a glycophorin A binding protein involved in erythrocyte invasion. Here we describe another DBL superfamily member related to eba-175, the ebl-1 gene. Like the eba-175 gene, ebl-1 is a single copy gene encoding DBL domains that have sequences and an overall arrangement distinct from var genes. The inheritance of ebl-1 was found to be strongly favored in two genetic crosses in which one parental clone lacked a chromosome segment carrying the gene. A proliferation phenotype has been previously linked to the same chromosome segment in the first genetic cross. These results suggest that ebl-1 and eba-175 are related members of a multigene family involved in the invasion of erythrocytes by P. falciparum.

  20. A Cross-Species Gene Expression Marker-Based Genetic Map and QTL Analysis in Bambara Groundnut.

    PubMed

    Chai, Hui Hui; Ho, Wai Kuan; Graham, Neil; May, Sean; Massawe, Festo; Mayes, Sean

    2017-02-22

    Bambara groundnut (Vigna subterranea (L.) Verdc.) is an underutilised legume crop, which has long been recognised as a protein-rich and drought-tolerant crop, used extensively in Sub-Saharan Africa. The aim of the study was to identify quantitative trait loci (QTL) involved in agronomic and drought-related traits using an expression marker-based genetic map based on major crop resources developed in soybean. The gene expression markers (GEMs) were generated at the (unmasked) probe-pair level after cross-hybridisation of bambara groundnut leaf RNA to the Affymetrix Soybean Genome GeneChip. A total of 753 markers grouped at an LOD (Logarithm of odds) of three, with 527 markers mapped into linkage groups. From this initial map, a spaced expression marker-based genetic map consisting of 13 linkage groups containing 218 GEMs, spanning 982.7 cM (centimorgan) of the bambara groundnut genome, was developed. Of the QTL detected, 46% were detected in both control and drought treatment populations, suggesting that they are the result of intrinsic trait differences between the parental lines used to construct the cross, with 31% detected in only one of the conditions. The present GEM map in bambara groundnut provides one technically feasible route for the translation of information and resources from major and model plant species to underutilised and resource-poor crops.

  1. A Cross-Species Gene Expression Marker-Based Genetic Map and QTL Analysis in Bambara Groundnut

    PubMed Central

    Chai, Hui Hui; Ho, Wai Kuan; Graham, Neil; May, Sean; Massawe, Festo; Mayes, Sean

    2017-01-01

    Bambara groundnut (Vigna subterranea (L.) Verdc.) is an underutilised legume crop, which has long been recognised as a protein-rich and drought-tolerant crop, used extensively in Sub-Saharan Africa. The aim of the study was to identify quantitative trait loci (QTL) involved in agronomic and drought-related traits using an expression marker-based genetic map based on major crop resources developed in soybean. The gene expression markers (GEMs) were generated at the (unmasked) probe-pair level after cross-hybridisation of bambara groundnut leaf RNA to the Affymetrix Soybean Genome GeneChip. A total of 753 markers grouped at an LOD (Logarithm of odds) of three, with 527 markers mapped into linkage groups. From this initial map, a spaced expression marker-based genetic map consisting of 13 linkage groups containing 218 GEMs, spanning 982.7 cM (centimorgan) of the bambara groundnut genome, was developed. Of the QTL detected, 46% were detected in both control and drought treatment populations, suggesting that they are the result of intrinsic trait differences between the parental lines used to construct the cross, with 31% detected in only one of the conditions. The present GEM map in bambara groundnut provides one technically feasible route for the translation of information and resources from major and model plant species to underutilised and resource-poor crops. PMID:28241413

  2. Genetically Engineered Phages: a Review of Advances over the Last Decade

    PubMed Central

    Pires, Diana P.; Sillankorva, Sanna; Azeredo, Joana

    2016-01-01

    SUMMARY Soon after their discovery in the early 20th century, bacteriophages were recognized to have great potential as antimicrobial agents, a potential that has yet to be fully realized. The nascent field of phage therapy was adversely affected by inadequately controlled trials and the discovery of antibiotics. Although the study of phages as anti-infective agents slowed, phages played an important role in the development of molecular biology. In recent years, the increase in multidrug-resistant bacteria has renewed interest in the use of phages as antimicrobial agents. With the wide array of possibilities offered by genetic engineering, these bacterial viruses are being modified to precisely control and detect bacteria and to serve as new sources of antibacterials. In applications that go beyond their antimicrobial activity, phages are also being developed as vehicles for drug delivery and vaccines, as well as for the assembly of new materials. This review highlights advances in techniques used to engineer phages for all of these purposes and discusses existing challenges and opportunities for future work. PMID:27250768

  3. Changes in the genetic structure of Atlantic salmon populations over four decades reveal substantial impacts of stocking and potential resiliency

    PubMed Central

    Perrier, Charles; Guyomard, René; Bagliniere, Jean-Luc; Nikolic, Natacha; Evanno, Guillaume

    2013-01-01

    While the stocking of captive-bred fish has been occurring for decades and has had substantial immediate genetic and evolutionary impacts on wild populations, its long-term consequences have only been weakly investigated. Here, we conducted a spatiotemporal analysis of 1428 Atlantic salmon sampled from 1965 to 2006 in 25 populations throughout France to investigate the influence of stocking on the neutral genetic structure in wild Atlantic salmon (Salmo salar) populations. On the basis of the analysis of 11 microsatellite loci, we found that the overall genetic structure among populations dramatically decreased over the period studied. Admixture rates among populations were highly variable, ranging from a nearly undetectable contribution from donor stocks to total replacement of the native gene pool, suggesting extremely variable impacts of stocking. Depending on population, admixture rates either increased, remained stable, or decreased in samples collected between 1998 and 2006 compared to samples from 1965 to 1987, suggesting either rising, long-lasting or short-term impacts of stocking. We discuss the potential mechanisms contributing to this variability, including the reduced fitness of stocked fish and persistence of wild locally adapted individuals. PMID:23919174

  4. Genetic diversity of Plasmodium vivax over time and space: a community-based study in rural Amazonia.

    PubMed

    Batista, Camilla L; Barbosa, Susana; Da Silva Bastos, Melissa; Viana, Susana Ariane S; Ferreira, Marcelo U

    2015-02-01

    To examine how community-level genetic diversity of the malaria parasite Plasmodium vivax varies across time and space, we investigated the dynamics of parasite polymorphisms during the early phases of occupation of a frontier settlement in the Amazon Basin of Brazil. Microsatellite characterization of 84 isolates of P. vivax sampled over 3 years revealed a moderate-to-high genetic diversity (mean expected heterozygosity, 0.699), with a large proportion (78.5%) of multiple-clone infections (MCI), but also a strong multilocus linkage disequilibrium (LD) consistent with rare outcrossing. Little temporal and no spatial clustering was observed in the distribution of parasite haplotypes. A single microsatellite haplotype was shared by 3 parasites collected during an outbreak; all other 81 haplotypes were recovered only once. The lowest parasite diversity, with the smallest proportion of MCI and the strongest LD, was observed at the time of the outbreak, providing a clear example of epidemic population structure in a human pathogen. Population genetic parameters returned to pre-outbreak values during last 2 years of study, despite the concomitant decline in malaria incidence. We suggest that parasite genotyping can be useful for tracking the spread of new parasite strains associated with outbreaks in areas approaching malaria elimination.

  5. Changes in the genetic structure of Atlantic salmon populations over four decades reveal substantial impacts of stocking and potential resiliency.

    PubMed

    Perrier, Charles; Guyomard, René; Bagliniere, Jean-Luc; Nikolic, Natacha; Evanno, Guillaume

    2013-07-01

    While the stocking of captive-bred fish has been occurring for decades and has had substantial immediate genetic and evolutionary impacts on wild populations, its long-term consequences have only been weakly investigated. Here, we conducted a spatiotemporal analysis of 1428 Atlantic salmon sampled from 1965 to 2006 in 25 populations throughout France to investigate the influence of stocking on the neutral genetic structure in wild Atlantic salmon (Salmo salar) populations. On the basis of the analysis of 11 microsatellite loci, we found that the overall genetic structure among populations dramatically decreased over the period studied. Admixture rates among populations were highly variable, ranging from a nearly undetectable contribution from donor stocks to total replacement of the native gene pool, suggesting extremely variable impacts of stocking. Depending on population, admixture rates either increased, remained stable, or decreased in samples collected between 1998 and 2006 compared to samples from 1965 to 1987, suggesting either rising, long-lasting or short-term impacts of stocking. We discuss the potential mechanisms contributing to this variability, including the reduced fitness of stocked fish and persistence of wild locally adapted individuals.

  6. Maximal fat oxidation rate and cross-over point with respect to lactate thresholds do not have good agreement.

    PubMed

    González-Haro, C

    2011-05-01

    The present cross-sectional study was designed to assess the agreement between maximal fat oxidation rate (maxFAT (OXR)) VS. Lactate Threshold (LT), and CROSS-OVER point (CO (P)) VS. Individual Anaerobic Threshold (IAT) in well-trained athletes. 2 groups of male, well-trained endurance athletes (short-distance triathletes (ST) (n=11), and road cyclists (RC) (n=11)) performed a graded cycle ergometer test to exhaustion, with 4-min stages and 30-W increments. LT, IAT, maxFAT (OXR) and CO (P) were determined for each group. FAT (OXR) and CHO (OXR) were estimated by means of indirect calorimetry and stoichiometric equations. The agreement between maxFAT (OXR) VS. LT, and CO (P) VS. IAT were determined using the Bland-Altman methodology. In spite of the low systematic error (bias) (high accuracy) for CO (P) VS. IAT, the variable error (limits of agreement) was moderate (moderate precision). For maxFAT (OXR) VS. LT the systematic error was moderate (moderate accuracy), and the variable error was moderate to high (moderate to low precision). In conclusion, the data obtained from this study shows that maxFAT (OXR) and CO (P) do not exhibit good agreement with LT and IAT, in male endurance well-trained athletes. Consequently, it is not possible to assume that maxFAT (OXR) VS. LT and CO (P) VS. IAT occurs at the same exercise intensity.

  7. Lactase and placebo in the management of the irritable bowel syndrome: a double-blind, cross-over study.

    PubMed

    Lisker, R; Solomons, N W; Pérez Briceño, R; Ramírez Mata, M

    1989-07-01

    A double-blind, cross-over, therapeutic, clinical trial of the efficacy of exogenous, microbial beta-D-galactosidase to reduce the symptoms of the irritable bowel syndrome (IBS) was conducted in 12 patients whose customary diets regularly included milk. Eight of the 12 subjects (67%) proved to be lactase-nonpersistent, lactose-maldigesters when challenged with a aqueous dose of 12.5 g. The study lasted 4 months, with the first month a non-intervention, control period and the latter 3 months alternating in the sequence, treatment/placebo/treatment, or placebo/treatment/placebo. When symptoms during trial months were analyzed by the cumulative sum procedure, gastrointestinal symptoms were found to be independent of lactase treatment. We found a positive temporal association of the severity of both gastrointestinal and non-gastrointestinal symptomatology. In populations with a high prevalence of lactose deficiency, IBS symptoms appear to be independent of lactose maldigestion.

  8. Cross-over between discrete and continuous protein structure space: insights into automatic classification and networks of protein structures.

    PubMed

    Pascual-García, Alberto; Abia, David; Ortiz, Angel R; Bastolla, Ugo

    2009-03-01

    Structural classifications of proteins assume the existence of the fold, which is an intrinsic equivalence class of protein domains. Here, we test in which conditions such an equivalence class is compatible with objective similarity measures. We base our analysis on the transitive property of the equivalence relationship, requiring that similarity of A with B and B with C implies that A and C are also similar. Divergent gene evolution leads us to expect that the transitive property should approximately hold. However, if protein domains are a combination of recurrent short polypeptide fragments, as proposed by several authors, then similarity of partial fragments may violate the transitive property, favouring the continuous view of the protein structure space. We propose a measure to quantify the violations of the transitive property when a clustering algorithm joins elements into clusters, and we find out that such violations present a well defined and detectable cross-over point, from an approximately transitive regime at high structure similarity to a regime with large transitivity violations and large differences in length at low similarity. We argue that protein structure space is discrete and hierarchic classification is justified up to this cross-over point, whereas at lower similarities the structure space is continuous and it should be represented as a network. We have tested the qualitative behaviour of this measure, varying all the choices involved in the automatic classification procedure, i.e., domain decomposition, alignment algorithm, similarity score, and clustering algorithm, and we have found out that this behaviour is quite robust. The final classification depends on the chosen algorithms. We used the values of the clustering coefficient and the transitivity violations to select the optimal choices among those that we tested. Interestingly, this criterion also favours the agreement between automatic and expert classifications. As a domain set, we

  9. [Treatment of essential headache in developmental age with L-5-HTP (cross over double-blind study versus placebo)].

    PubMed

    Longo, G; Rudoi, I; Iannuccelli, M; Strinati, R; Panizon, F

    1984-01-01

    Thirty patients (mean age: 10.38 years) affected by primary headache were selected for a double-blind cross-over clinical trial. The patients were randomized into 2 homogeneous groups of 15 and treated for 12 weeks with L-5-HTP (100 mg/day) and placebo as per the following design: placebo - L-5-HTP (group A) and L-5-HTP - placebo (group B). Evaluation was carried out every 3 weeks by the Migraine Index supplying a general assessment of the attacks, i.e. severity, duration and frequency. The decrease in mean score values was directly proportional to L-5-HTP treatment, and statistical significance (Wilcoxon's test) was observed only for L-5-HTP in both groups, from 0.05 to 0.01. Improvement, as evaluated by CGI on percentage distribution of the patients, was homogeneous in both groups.

  10. Acceptance and usability of different sunscreen formulations among outdoor workers: a randomized, single-blind, cross-over study.

    PubMed

    Bauer, Andrea; Hault, Kathrin; Püschel, Andrea; Rönsch, Henriette; Knuschke, Peter; Beissert, Stefan

    2014-03-01

    Adequate sun protection is often neglected during occupational outdoor work. To investigate the acceptance and usability of sunscreens during outdoor work a single-blind, randomized-controlled, cross-over trial was performed in 40 subjects. Two sunscreen formulations were used daily on working days for 4 weeks at a time, with a wash-out phase before crossover. The primary outcome was overall acceptance of the products with daily application. More than 80% of the outdoor workers were fully satisfied with the cosmetic properties, sweat resistance, performance and usability of both products under outdoor working conditions. With respect to overall performance, the milk was rated slightly better than the gel. In terms of ease of application, the milk was preferred (p<0.05). Sunscreens for those working outdoors must contain very high, broad-spectrum, photostable filters for both UVB and UVA, they must be easy to apply and sweat resistant, and should not irritate the eyes.

  11. Pulmonary rehabilitation after total laryngectomy: a randomized cross-over clinical trial comparing two different heat and moisture exchangers (HMEs).

    PubMed

    Herranz, Jesús; Espiño, María Alvarez; Morado, Carolina Ogen

    2013-09-01

    Post-laryngectomy heat and moisture exchanger (HME) use is known to have a beneficial effect on tracheal climate, pulmonary symptoms and related aspects. This study aims to investigate differences in clinical effects between the first and second generation Provox HMEs. The second generation (Provox XtraHME) has better humidification properties than the first generation (Provox HME), and has been shown to further improve tracheal climate. Forty-five laryngectomized patients, who were already using an HME, participated in a prospective, randomized cross-over clinical study in which each HME was used for 6 weeks. Results showed that for most parameters studied, the second generation HME performed equally well or better than the first generation HME. The improvement in tracheal climate translated into patients reporting significantly less tracheal dryness with the second generation than with the first generation (p = 0.039). Using an HME with better humidification properties is related to a reduction in tracheal dryness in our study population.

  12. Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial.

    PubMed Central

    Rae, Caroline; Digney, Alison L; McEwan, Sally R; Bates, Timothy C

    2003-01-01

    Creatine supplementation is in widespread use to enhance sports-fitness performance, and has been trialled successfully in the treatment of neurological, neuromuscular and atherosclerotic disease. Creatine plays a pivotal role in brain energy homeostasis, being a temporal and spatial buffer for cytosolic and mitochondrial pools of the cellular energy currency, adenosine triphosphate and its regulator, adenosine diphosphate. In this work, we tested the hypothesis that oral creatine supplementation (5 g d(-1) for six weeks) would enhance intelligence test scores and working memory performance in 45 young adult, vegetarian subjects in a double-blind, placebo-controlled, cross-over design. Creatine supplementation had a significant positive effect (p < 0.0001) on both working memory (backward digit span) and intelligence (Raven's Advanced Progressive Matrices), both tasks that require speed of processing. These findings underline a dynamic and significant role of brain energy capacity in influencing brain performance. PMID:14561278

  13. Use of the repeated cross-over design in assessing bioequivalence: (within and between subjects variability - Schuirmann Confidence Intervals estimation).

    PubMed

    Le Roux, Y; Guimart, C; Tenenhaus, M

    1998-01-01

    In 1992, the Division of Bioequivalence in the Office of Generic Drugs published a guide to Statistical procedures for bioequivalence studies using a standard two-treatments cross-over design (1). This paper describes the application of the guidelines to a practical protocol and the recent Proc MIXED (SAS) will be shown to be much more convenient than the traditional Proc GLM for theoretical and practical reasons (correct estimation of residuals, analysis of the within-subjects variation, direct calculation of the Schuirmann 90% Confidence Intervals). This new procedure was applied to a study protocol on riluzole (Rilutek) including a replicate design with the within-subject and between-subject variances being estimated on Cmax and AUC biopharmaceutic parameters.

  14. Have African American men become less committed to marriage? Explaining the twentieth century racial cross-over in men's marriage timing.

    PubMed

    Koball, H

    1998-05-01

    Prior to World War II, the median age at marriage for white men was later than that for African American men. Since World War II, African American men have, on average, married later than white men. A discrete-time hazard model using data from the National Survey of Families and Households was analyzed to explain this racial cross-over in men's timing of marriage. Dramatic increases in the educational attainment of African American parents and the large movement of African Americans out of the South brought about the racial cross-over in the timing of marriage. Increased enrollment in higher education among African American men also contributed to the racial cross-over in the timing of marriage. Although lack of full-time employment and military service delayed marriage, these factors did not contribute to the racial cross-over.

  15. A randomised, double- blind, cross-over study investigating the prebiotic effect of agave fructans in healthy human subjects.

    PubMed

    Ramnani, P; Costabile, A; Bustillo, A G R; Gibson, G R

    2015-01-01

    This placebo-controlled, randomised, double-blind, cross-over human feeding study aimed to determine the prebiotic effect of agave fructans. A total of thirty-eight volunteers completed this trial. The treatment consisted of 3 weeks' supplementation with 5 g/d of prebiotic agave fructan (Predilife) or equivalent placebo (maltodextrin), followed by a 2-week washout period following which subjects were crossed over to alternate the treatment arm for 3 weeks followed by a 2-week washout. Faecal samples were collected at baseline, on the last day of treatment (days 22 and 58) and washout (days 36 and 72), respectively. Changes in faecal bacterial populations, SCFA and secretory IgA were assessed using fluorescent in situ hybridisation, GC and ELISA, respectively. Bowel movements, stool consistencies, abdominal comfort and mood changes were evaluated by a recorded daily questionnaire. In parallel, the effect of agave fructans on different regions of the colon using a three-stage continuous culture simulator was studied. Predilife significantly increased faecal bifidobacteria (log10 9·6 (sd 0·4)) and lactobacilli (log10 7·7 (sd 0·8)) compared with placebo (log10 9·2 (sd 0·4); P = 0·00) (log10 7·4 (sd 0·7); P = 0·000), respectively. No change was observed for other bacterial groups tested, SCFA, secretory IgA, and PGE2 concentrations between the treatment and placebo. Denaturing gradient gel electrophoresis analysis indicated that bacterial communities were randomly dispersed and no significant differences were observed between Predilife and placebo treatments. The in vitro models showed similar increases in bifidobacterial and lactobacilli populations to that observed with the in vivo trial. To conclude, agave fructans are well tolerated in healthy human subjects and increased bifidobacteria and lactobacilli numbers in vitro and in vivo but did not influence other products of fermentation.

  16. L-lysine as adjunctive treatment in patients with schizophrenia: a single-blinded, randomized, cross-over pilot study

    PubMed Central

    2011-01-01

    Background Accumulating evidence suggests that the brain's nitric oxide (NO) signalling system may be involved in the pathophysiology of schizophrenia and could thus constitute a novel treatment target. The study was designed to investigate the benefit of L-lysine, an amino acid that interferes with NO production, as an add-on treatment for schizophrenia. Methods L-lysine, 6 g/day, was administered to 10 patients with schizophrenia as an adjunctive to their conventional antipsychotic medication. The study was designed as a single-blinded, cross-over study where patients were randomly assigned to initial treatment with either L-lysine or placebo and screened at baseline, after four weeks when treatment was crossed over, and after eight weeks. Results L-lysine treatment caused a significant increase in blood concentration of L-lysine and was well tolerated. A significant decrease in positive symptom severity, measured by the Positive And Negative Syndrome Scale (PANSS), was detected. A certain decrease in score was also observed during placebo treatment and the effects on PANSS could not unequivocally be assigned to the L-lysine treatment. Furthermore, performance on the Wisconsin Card Sorting Test was significantly improved compared to baseline, an effect probably biased by training. Subjective reports from three of the patients indicated decreased symptom severity and enhanced cognitive functioning. Conclusions Four-week L-lysine treatment of 6 g/day caused a significant increase in blood concentration of L-lysine that was well tolerated. Patients showed a significant decrease in positive symptoms as assessed by PANSS in addition to self-reported symptom improvement by three patients. The NO-signalling pathway is an interesting, potentially new treatment target for schizophrenia; however, the effects of L-lysine need further evaluation to decide the amino acid's potentially beneficial effects on symptom severity in schizophrenia. Trial registration NCT00996242 PMID

  17. Motor effects of radio electric asymmetric conveyer in Alzheimer's disease: results from a cross-over trial.

    PubMed

    Olazarán, Javier; González, Belén; Osa-Ruiz, Emma; Felipe-Ruiz, Silvia; Boyano, Inmaculada; Fontani, Vania; Castagna, Alessandro; Mendoza, Carolina; Zea, María Ascensión; Frades, Belén; Rinaldi, Salvatore; Martínez-Martín, Pablo

    2014-01-01

    We conducted a randomized, cross-over trial to investigate the feasibility, safety, and motor effects of brain stimulation with radio electric asymmetric conveyer (REAC) technique in patients with Alzheimer's disease (AD). Neuropostural optimization (NPO) and sham protocol were administered to 60 patients from the nursing home and day care units of the Alzheimer Center Reina Sofía Foundation. The mean age was 84.1 (SD 7.9) years and 86.7% of the subjects were female. Motor measures were collected at baseline (T1), immediately (T2), seven (T3), and 11 days (T4) after treatment and, following cross-over, immediately (T5), seven (T6), and 11 (T7) days after treatment. Close safety surveillance was conducted from seven days before T1 to the end of the study (T7), with total study duration of 35 days. Wilcoxon test was utilized in the efficacy analysis, considering T1 and T5 as independent baseline assessments and using a threshold of p < 0.05 (corrected) for statistical significance. The NPO protocol was easily administered and well accepted by the participants. Axial movements improved at T3 and T4 after NPO and at T2 after sham NPO, but no significant effects were observed in axial movements in the second phase of the trial. The effects of NPO in gait performance were not consistent. There were six falls between T2 and T7, but only two of them occurred in patients who had received NPO. In light of safety and feasibility of REAC, a trial with the more intense neuropsycho-physical optimization protocol is warranted.

  18. On the cross-polarization characteristics of crooked wire antennas designed by genetic-algorithms

    NASA Technical Reports Server (NTRS)

    Rengarajan, S. R.; Rahmat-Samii, Y.

    2002-01-01

    In many modern communication applications there is a need for simple circularly polarized antennas for hemispherical coverage with good axial ratio or low value of cross polarization. We revisited the crooked wire antenna because of its simplicity. This paper presents results of our investigation on the crooked wire antennas and other elements.

  19. MutMap+: Genetic Mapping and Mutant Identification without Crossing in Rice

    PubMed Central

    Abe, Akira; Natsume, Satoshi; Yaegashi, Hiroki; Sharma, Shailendra; Sharma, Shiveta; Kanzaki, Hiroyuki; Matsumura, Hideo; Saitoh, Hiromasa; Mitsuoka, Chikako; Utsushi, Hiroe; Uemura, Aiko; Kanzaki, Eiko; Kosugi, Shunichi; Yoshida, Kentaro; Cano, Liliana; Kamoun, Sophien; Terauchi, Ryohei

    2013-01-01

    Advances in genome sequencing technologies have enabled researchers and breeders to rapidly associate phenotypic variation to genome sequence differences. We recently took advantage of next-generation sequencing technology to develop MutMap, a method that allows rapid identification of causal nucleotide changes of rice mutants by whole genome resequencing of pooled DNA of mutant F2 progeny derived from crosses made between candidate mutants and the parental line. Here we describe MutMap+, a versatile extension of MutMap, that identifies causal mutations by comparing SNP frequencies of bulked DNA of mutant and wild-type progeny of M3 generation derived from selfing of an M2 heterozygous individual. Notably, MutMap+ does not necessitate artificial crossing between mutants and the wild-type parental line. This method is therefore suitable for identifying mutations that cause early development lethality, sterility, or generally hamper crossing. Furthermore, MutMap+ is potentially useful for gene isolation in crops that are recalcitrant to artificial crosses. PMID:23874658

  20. Improved access to life insurance after genetic diagnosis of familial hypercholesterolaemia: cross-sectional postal questionnaire study

    PubMed Central

    Huijgen, Roeland; Homsma, Sietske JM; Hutten, Barbara A; Kindt, Iris; Vissers, Maud N; Kastelein, John JP; van Rijckevorsel, Jan LA

    2012-01-01

    A decade ago, in the initial stage of genetic testing for familial hypercholesterolaemia (FH) in The Netherlands, it was reported that such screening decreased access to affordable life insurance for mutation carriers. In 2003, in order to improve access to insurance for FH mutation carriers, insurers agreed to underwrite according to a set of guidelines. In this cross-sectional study, we assessed whether access to insurance has improved since the advent of these guidelines. We approached 2825 subjects that had participated in the genetic testing for FH between 1998 and 2003. We compared unconditional acceptance rates before and after FH diagnosis and before and after the guidelines were issued by means of logistic regression analysis. Our study outcome pertains to 414 FH patients who applied for life insurance. Unconditional acceptance of a policy before DNA diagnosis and before the issue of guidelines occurred in 182 out of 255 (71%) cases, versus 27 out of 35 (77%) cases after DNA diagnosis, but before the issue of guidelines. De facto, 107 out of 124 (86%) patients received unconditional acceptance after DNA diagnosis and after the issue of guidelines (P for trend=0.002). Access to life insurance improved for FH patients after molecular diagnosis and it improved even further after the guidelines were issued. Therefore, we argue that limited access to life insurance on the basis of ‘DNA discrimination' is no longer a valid argument against genetic cascade testing for FH, at least not in our country. PMID:22293687

  1. Genetic analysis of a mouse cross implicates an anti-inflammatory gene in control of atherosclerosis susceptibility.

    PubMed

    Garrett, Norman E; Grainger, Andrew T; Li, Jing; Chen, Mei-Hua; Shi, Weibin

    2017-01-23

    Nearly all genetic crosses generated from Apoe(-/-) or Lldlr(-/-) mice for genetic analysis of atherosclerosis have used C57BL/6 J (B6) mice as one parental strain, thus limiting their mapping power and coverage of allelic diversity. SM/J-Apoe (-/-) and BALB/cJ-Apoe (-/-) mice differ significantly in atherosclerosis susceptibility. 224 male F2 mice were generated from the two Apoe (-/-) strains to perform quantitative trait locus (QTL) analysis of atherosclerosis. F2 mice were fed 5 weeks of Western diet and analyzed for atherosclerotic lesions in the aortic root. Genome-wide scans with 144 informative SNP markers identified a significant locus near 20.2 Mb on chromosome 10 (LOD score: 6.03), named Ath48, and a suggestive locus near 49.5 Mb on chromosome 9 (LOD: 2.29; Ath29) affecting atherosclerotic lesion sizes. Using bioinformatics tools, we prioritized 12 candidate genes for Ath48. Of them, Tnfaip3, an anti-inflammatory gene, is located precisely underneath the linkage peak and contains two non-synonymous SNPs leading to conservative amino acid substitutions. Thus, this study demonstrates the power of forward genetics involving the use of a different susceptible strain and bioinformatics tools in finding atherosclerosis susceptibility genes.

  2. Genetic analysis of diabetes and insulitis in an interspecific cross of the nonobese diabetic mouse with Mus spretus.

    PubMed Central

    de Gouyon, B; Melanitou, E; Richard, M F; Requarth, M; Hahn, I H; Guenet, J L; Demenais, F; Julier, C; Lathrop, G M; Boitard, C

    1993-01-01

    The nonobese diabetic (NOD) mouse is a widely used model for genetic studies of insulin-dependent diabetes mellitus due to the similarities between the murine and human diseases. To aid in the localization and identification of diabetes-related susceptibility genes, we have constructed an interspecific backcross between NOD and Mus spretus (SEG/Pas) mice. Although no diabetic animals were observed in the first backcross generation of (SEG/Pas x NOD) x NOD (BC1), the incidence of insulitis (lymphocyte infiltration of the islets of Langerhans) exceeded 20% after injections of cyclophosphamide, a treatment that provokes an acute form of diabetes in NOD mice. Insulitis, a prediabetic condition, is a useful phenotype in studies of diabetes susceptibility. In the second backcross (BC2) generation, 8% of the animals became diabetic and 76% were found to have insulitis. Genetic mapping studies in the BC2 families confirmed the importance of the major histocompatibility complex region on the severity of insulitis and suggested that additional susceptibility loci were linked to markers on mouse chromosomes 3, 6, and 15. Mus spretus crosses have been an important tool in recent advances in murine genetics, and our results extend their usefulness to the study of a multifactorial disease. Images Fig. 1 PMID:8446602

  3. A steep cline in ladybird melanism has decayed over 25 years: a genetic response to climate change?

    PubMed Central

    Brakefield, P M; de Jong, P W

    2011-01-01

    A cline in the frequency of melanic morphs of the two-spot ladybird, Adalia bipunctata, was first surveyed in 1980 along a transect extending inland from the coast in the Netherlands. At that time, the frequency of melanics increased over some 40 km from 10% near the coast to nearly 60% inland. Additional surveys made in 1991 and 1995 demonstrated some progressive change in cline shape. New samples from 1998 and 2004 confirm these dynamics, and show that over a period of about 50 generations for the beetle, the cline had decayed rapidly to yield rather uniform frequencies of melanic morphs at around 20% along the whole transect by 2004. Climate data and evidence for thermal melanism in this species support our contention that these dynamics reflect a dramatic example of a rapid genetic response within populations to climate change and local selection. PMID:21792220

  4. Strategies used for genetically modifying bacterial genome: ite-directed mutagenesis, gene inactivation, and gene over-expression*

    PubMed Central

    Xu, Jian-zhong; Zhang, Wei-guo

    2016-01-01

    With the availability of the whole genome sequence of Escherichia coli or Corynebacterium glutamicum, strategies for directed DNA manipulation have developed rapidly. DNA manipulation plays an important role in understanding the function of genes and in constructing novel engineering bacteria according to requirement. DNA manipulation involves modifying the autologous genes and expressing the heterogenous genes. Two alternative approaches, using electroporation linear DNA or recombinant suicide plasmid, allow a wide variety of DNA manipulation. However, the over-expression of the desired gene is generally executed via plasmid-mediation. The current review summarizes the common strategies used for genetically modifying E. coli and C. glutamicum genomes, and discusses the technical problem of multi-layered DNA manipulation. Strategies for gene over-expression via integrating into genome are proposed. This review is intended to be an accessible introduction to DNA manipulation within the bacterial genome for novices and a source of the latest experimental information for experienced investigators. PMID:26834010

  5. Genetic analysis of hybrid seed formation ability of Brassica rapa in intergeneric crossings with Raphanus sativus.

    PubMed

    Tonosaki, K; Michiba, K; Bang, S W; Kitashiba, H; Kaneko, Y; Nishio, T

    2013-03-01

    A hybridization barrier leads to the inability of seed formation after intergeneric crossings between Brassica rapa and Raphanus sativus. Most B. rapa lines cannot set intergeneric hybrid seeds because of embryo breakdown, but a B. rapa line obtained from turnip cultivar 'Shogoin-kabu' is able to produce a large number of hybrid seeds as a maternal parent by crossings with R. sativus. In 'Shogoin-kabu' crossed with R. sativus, developments of embryos and endosperms were slower than those in intraspecific crossings, but some of them grew to mature seeds without embryo breakdown. Intergeneric hybrid seeds were obtained in a 'Shogoin-kabu' line at a rate of 0.13 per pollinated flower, while no hybrid seeds were obtained in a line developed from Chinese cabbage cultivar 'Chiifu'. F(1) hybrid plants between the lines of 'Shogoin-kabu' and 'Chiifu' set a larger number of hybrid seeds per flower, 0.68, than both the parental lines. Quantitative trait loci (QTLs) for hybrid seed formation were analyzed after intergeneric crossings using two different F(2) populations derived from the F(1) hybrids, and three QTLs with significant logarithm of odds scores were detected. Among them, two QTLs, i.e., one in linkage group A10 and the other in linkage group A01, were detected in both the F(2) populations. These two QTLs had contrary effects on the number of hybrid seeds. Epistatic interaction between these two QTLs was revealed. Possible candidate genes controlling hybrid seed formation ability in QTL regions were inferred using the published B. rapa genome sequences.

  6. Genetic and environmental influences on forced expiratory volume in midlife: a cross-cultural replication.

    PubMed

    Whitfield, K E; Grant, J; Ravich-Scherbo, I; Marytuina, T; Iboutolina, A

    1999-01-01

    Previous research has shown that forced expiratory volume (FEV) is a useful predictor of remaining life in older adults. The present analyses are an attempt to replicate results from a study of Swedish twins which demonstrated substantial heritability of FEV with a sample of middle-aged Russian adult twins. Data were collected from 116 pairs of Russian twins (monozygote = 71, dizygotic = 45, mean age = 40.9 years). Phenotypic correlations between FEV, age, gender, height, and cigarette consumption (in pack years) were all significant, ranging from -.72 to .31. After the effects of age, gender, height, and smoking were partialled out of FEV, quantitative genetic analyses were conducted. Shared environmental effects were significant, accounting for 47% of the variance in FEV. Genetic effects, which accounted for about 28% of the variance, could be dropped from the model without a significant decrease in the fit. These results are discussed in relation to previous research conducted in other countries.

  7. An evaluation of video instruction for an electric toothbrush. Comparative single-brushing cross-over study.

    PubMed

    Addy, M; Renton-Harper, P; Warren, P; Newcombe, R G

    1999-05-01

    Instructions on the use of electric toothbrushes are usually derived from the written and/or diagrammatic leaflets provided with the device or perhaps less often instruction from a professional. Videos are now widely used for information transfer and the direction of physical activities. The aim of this study was to determine whether video instruction in the use of an electric toothbrush could promote efficient use of the device. The 2-min video demonstrated the use of an oscillating, rotating electric toothbrush used by a hygienist for 15 s in each buccal and lingual quadrant. A voice-over directed the observer to follow the hygienist's movements. The study was planned as a 2-phase, single-examiner blind, randomised, cross-over study accepting there would be confounding of the 2nd period by carry-over from the 1st. A group of 24 healthy volunteers participated who had average oral hygiene and never used an electric toothbrush. 12 subjects received the video first (VN) and 12 subjects the instructional leaflet with the device (NV). Single brushings were performed after suspending tooth cleaning for 48 h. Plaque was scored before and after brushing. A 2-week washout period was permitted before the crossover. In period 1, plaque removal with the video was overall significantly greater than with written instructions. The effects for posterior teeth were greater than anterior and comparison between groups for posterior minus anterior differences were highly significant in favour of the VN group. In period 2, the effect of period was dominant with both groups achieving greater plaque removal in period 2 than period 1. Plaque removal by group VN remained considerably greater than group NV Despite the confounding influences of carry-over in this particular design of study, the results support the idea that video instruction for electric toothbrushes could be a simple and efficient way of improving plaque removal by these devices. The methodology needs to be verified in a

  8. Changes in the rumen microbiome and metabolites reveal the effect of host genetics on hybrid crosses.

    PubMed

    Li, Zhipeng; Wright, André-Denis G; Si, Huazhe; Wang, Xiaoxu; Qian, Wenxi; Zhang, Zhigang; Li, Guangyu

    2016-12-01

    The rumen microbiota plays important roles in nutrient metabolism and absorption of the host. However, it is poorly understood how host genetic variation shapes the community structure of the rumen microbiota and its metabolic phenotype. Here, we used sika deer (Cervus nippon) and elk (Cervus elaphus) to produce the following two types of hybrid offspring: sika deer ♀ × elk ♂ (SEH) and elk ♀ × sika deer ♂ (ESH). Then, we examined the rumen microbiome and metabolites in the parents and their hybrid offspring. The rumen microbiota in the hybrids differed from that in their parents, suggesting a significant effect of host genetics on the rumen microbiome that may have resulted from vertical transmission. The rumen metabolites displayed patterns similar to the structure of the rumen microbiome, with changes in the amounts of volatile fatty acids and metabolites of amino acids. The alanine, arginine, proline and phenylalanine pathways were enriched in the rumen of hybrid animals. The enriched metabolites in the above pathways were positively correlated with the bacteria Prevotella spp., Acetitomaculum spp., Quinella spp., Succinivibrio spp. and Ruminobacter spp. These results suggest that host genetics has a major impact on the rumen microbiome and metabolites in hybrid animals. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

  9. Genetic evaluation of severe male factor infertility in Turkey: a cross-sectional study.

    PubMed

    Cavkaytar, Sabri; Batioglu, Sertaç; Gunel, Mufit; Ceylaner, Serdar; Karaer, Abdullah

    2012-06-01

    To determine the frequency, types of chromosomal abnormalities and Y chromosome microdeletions in patients with severe male factor infertility, and the association between clinical background and genetic abnormality. A total of 322 infertile men; 136 men with severe oligozoospermia (sperm count <5 million/ml) and 196 with nonobstructive azoospermia were studied between April 2004 and November 2006 at the Dr. Zekai Tahir Burak Women's Health Education and Research Hospital, Ankara, Turkey. Blood, semen samples, and testicular biopsies of patients were obtained. Hormonal analysis (follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels), semen analysis, karyotype analysis, and PCR screening for Y chromosome microdeletions were performed. Forty-eight out of 332 (14%) infertile men had a genetic abnormality. Twenty-four (7.2%) cases with karyotype abnormality were detected. The frequencies of karyotype abnormalities were Klinefelter's syndrome 17/24 (71%), translocation 3/24 (12%), mix gonadal dysgenesis 2/24 (8%), XX male 1/24 (4%), and 46XYY 1/24 (4%). Twenty cases (6%) infertile men had only Y chromosome microdeletions. The frequencies of the deleted areas were azoospermia factor (AZF)c 42%, AZFb 25%, AZFa 21%, AZFb, c 8%, and AZFa, c 4%. Four of the cases with Y chromosome microdeletions also had a concurrent karyotype abnormality. All patients with nonobstructive azoospermia and severe oligozoospermia (sperm count <5 million/ml) should undergo genetic screening.

  10. Transcriptome Profiling in Rat Inbred Strains and Experimental Cross Reveals Discrepant Genetic Architecture of Genome-Wide Gene Expression

    PubMed Central

    Kaisaki, Pamela J.; Otto, Georg W.; Argoud, Karène; Collins, Stephan C.; Wallis, Robert H.; Wilder, Steven P.; Yau, Anthony C. Y.; Hue, Christophe; Calderari, Sophie; Bihoreau, Marie-Thérèse; Cazier, Jean-Baptiste; Mott, Richard; Gauguier, Dominique

    2016-01-01

    To test the impact of genetic heterogeneity on cis- and trans-mediated mechanisms of gene expression regulation, we profiled the transcriptome of adipose tissue in 20 inbred congenic strains derived from diabetic Goto–Kakizaki (GK) rats and Brown–Norway (BN) controls, which contain well-defined blocks (1–183 Mb) of genetic polymorphisms, and in 123 genetically heterogeneous rats of an (GK × BN)F2 offspring. Within each congenic we identified 73–1351 differentially expressed genes (DEGs), only 7.7% of which mapped within the congenic blocks, and which may be regulated in cis. The remainder localized outside the blocks, and therefore must be regulated in trans. Most trans-regulated genes exhibited approximately twofold expression changes, consistent with monoallelic expression. Altered biological pathways were replicated between congenic strains sharing blocks of genetic polymorphisms, but polymorphisms at different loci also had redundant effects on transcription of common distant genes and pathways. We mapped 2735 expression quantitative trait loci (eQTL) in the F2 cross, including 26% predominantly cis-regulated genes, which validated DEGs in congenic strains. A hotspot of >300 eQTL in a 10 cM region of chromosome 1 was enriched in DEGs in a congenic strain. However, many DEGs among GK, BN and congenic strains did not replicate as eQTL in F2 hybrids, demonstrating distinct mechanisms of gene expression when alleles segregate in an outbred population or are fixed homozygous across the entire genome or in short genomic regions. Our analysis provides conceptual advances in our understanding of the complex architecture of genome expression and pathway regulation, and suggests a prominent impact of epistasis and monoallelic expression on gene transcription. PMID:27646706

  11. Genome Wide SSR High Density Genetic Map Construction from an Interspecific Cross of Gossypium hirsutum × Gossypium tomentosum

    PubMed Central

    Khan, Muhammad K. R.; Chen, Haodong; Zhou, Zhongli; Ilyas, Muhammad K.; Wang, Xingxing; Cai, Xiaoyan; Wang, Chunying; Liu, Fang; Wang, Kunbo

    2016-01-01

    A high density genetic map was constructed using F2 population derived from an interspecific cross of G. hirsutum × G. tomentosum. The map consisted of 3093 marker loci distributed across all the 26 chromosomes and covered 4365.3 cM of cotton genome with an average inter-marker distance of 1.48 cM. The maximum length of chromosome was 218.38 cM and the minimum was 122.09 cM with an average length of 167.90 cM. A sub-genome covers more genetic distance (2189.01 cM) with an average inter loci distance of 1.53 cM than D sub-genome which covers a length of 2176.29 cM with an average distance of 1.43 cM. There were 716 distorted loci in the map accounting for 23.14% and most distorted loci were distributed on D sub-genome (25.06%), which were more than on A sub-genome (21.23%). In our map 49 segregation hotspots (SDR) were distributed across the genome with more on D sub-genome as compared to A genome. Two post-polyploidization reciprocal translocations of “A2/A3 and A4/A5” were suggested by seven pairs of duplicate loci. The map constructed through these studies is one of the three densest genetic maps in cotton however; this is the first dense genome wide SSR interspecific genetic map between G. hirsutum and G. tomentosum. PMID:27148280

  12. Salivary Oxytocin Concentrations in Males following Intranasal Administration of Oxytocin: A Double-Blind, Cross-Over Study

    PubMed Central

    Daughters, Katie; Manstead, Antony S. R.; Hubble, Kelly; Rees, Aled; Thapar, Anita; van Goozen, Stephanie H. M.

    2015-01-01

    The use of intranasal oxytocin (OT) in research has become increasingly important over the past decade. Although researchers have acknowledged a need for further investigation of the physiological effects of intranasal administration, few studies have actually done so. In the present double-blind cross-over study we investigated the longevity of a single 24 IU dose of intranasal OT measured in saliva in 40 healthy adult males. Salivary OT concentrations were significantly higher in the OT condition, compared to placebo. This significant difference lasted until the end of testing, approximately 108 minutes after administration, and peaked at 30 minutes. Results showed significant individual differences in response to intranasal OT administration. To our knowledge this is the largest and first all-male within-subjects design study to demonstrate the impact of intranasal OT on salivary OT concentrations. The results are consistent with previous research in suggesting that salivary OT is a valid matrix for OT measurement. The results also suggest that the post-administration ‘wait-time’ prior to starting experimental tasks could be reduced to 30 minutes, from the 45 minutes typically used, thereby enabling testing during peak OT concentrations. Further research is needed to ascertain whether OT concentrations after intranasal administration follow similar patterns in females, and different age groups. PMID:26669935

  13. Improving total field geomagnetic secular variation modeling from a new set of cross-over marine data

    NASA Astrophysics Data System (ADS)

    Pavón-Carrasco, F. Javier; Torta, J. Miquel; Catalán, Manuel; Talarn, Àngela; Ishihara, Takemi

    2013-03-01

    A new set of cross-over marine data has been used to generate a regional model for the secular variation of the total geomagnetic field, showing the potential of the suggested approach for gaining a better knowledge of the field over oceanic regions. The model, which is valid for the Northern Atlantic region during the temporal interval 1960-2000, was obtained using spherical cap harmonic analysis (SCHA) in space and penalized splines in time. The maximum spatial expansion is equivalent to degree 9 in ordinary spherical harmonic analysis. Annual mean intensity data from different geomagnetic observatories have been used to improve the spatial and temporal resolution of the original dataset. Results indicate that the regional model improves, in terms of the root mean square error, the prediction given by the 11th generation of IGRF and CM4 global models, especially for the geomagnetic observatories considered. We also provide the uncertainty of the model coefficients and the secular variation prediction given by a bootstrap algorithm. The model is available in the EarthRef. org Digital Archive at http://earthref.org/ERDA/1728/.

  14. Linkage analysis and map construction in genetic populations of clonal F1 and double cross.

    PubMed

    Zhang, Luyan; Li, Huihui; Wang, Jiankang

    2015-01-15

    In this study, we considered four categories of molecular markers based on the number of distinguishable alleles at the marker locus and the number of distinguishable genotypes in clonal F1 progenies. For two marker loci, there are nine scenarios that allow the estimation of female, male, and/or combined recombination frequencies. In a double cross population derived from four inbred lines, five categories of markers are classified and another five scenarios are present for recombination frequency estimation. Theoretical frequencies of identifiable genotypes were given for each scenario, from which the maximum likelihood estimates of one or more of the three recombination frequencies could be estimated. If there was no analytic solution, then Newton-Raphson method was used to acquire a numerical solution. We then proposed to use an algorithm in Traveling Salesman Problem to determine the marker order. Finally, we proposed a procedure to build the two haploids of the female parent and the two haploids of the male parent in clonal F1. Once the four haploids were built, clonal F1 hybrids could be exactly regarded as a double cross population. Efficiency of the proposed methods was demonstrated in simulated clonal F1 populations and one actual maize double cross. Extensive comparisons with software JoinMap4.1, OneMap, and R/qtl show that the methodology proposed in this article can build more accurate linkage maps in less time.

  15. Genetic diversity and striatal gene networks: focus on the heterogeneous stock-collaborative cross (HS-CC) mouse

    PubMed Central

    2010-01-01

    Background The current study focused on the extent genetic diversity within a species (Mus musculus) affects gene co-expression network structure. To examine this issue, we have created a new mouse resource, a heterogeneous stock (HS) formed from the same eight inbred strains that have been used to create the collaborative cross (CC). The eight inbred strains capture > 90% of the genetic diversity available within the species. For contrast with the HS-CC, a C57BL/6J (B6) × DBA/2J (D2) F2 intercross and the HS4, derived from crossing the B6, D2, BALB/cJ and LP/J strains, were used. Brain (striatum) gene expression data were obtained using the Illumina Mouse WG 6.1 array, and the data sets were interrogated using a weighted gene co-expression network analysis (WGCNA). Results Genes reliably detected as expressed were similar in all three data sets as was the variability of expression. As measured by the WGCNA, the modular structure of the transcriptome networks was also preserved both on the basis of module assignment and from the perspective of the topological overlap maps. Details of the HS-CC gene modules are provided; essentially identical results were obtained for the HS4 and F2 modules. Gene ontology annotation of the modules revealed a significant overrepresentation in some modules for neuronal processes, e.g., central nervous system development. Integration with known protein-protein interactions data indicated significant enrichment among co-expressed genes. We also noted significant overlap with markers of central nervous system cell types (neurons, oligodendrocytes and astrocytes). Using the Allen Brain Atlas, we found evidence of spatial co-localization within the striatum for several modules. Finally, for some modules it was possible to detect an enrichment of transcription binding sites. The binding site for Wt1, which is associated with neurodegeneration, was the most significantly overrepresented. Conclusions Despite the marked differences in genetic

  16. Cross-shore velocity shear, eddies and heterogeneity in water column properties over fringing coral reefs: West Maui, Hawaii

    USGS Publications Warehouse

    Storlazzi, C.D.; McManus, M.A.; Logan, J.B.; McLaughlin, B.E.

    2006-01-01

    A multi-day hydrographic survey cruise was conducted to acquire spatially extensive, but temporally limited, high-resolution, three-dimensional measurements of currents, temperature, salinity and turbidity off West Maui in the summer of 2003 to better understand coastal dynamics along a complex island shoreline with coral reefs. These data complement long-term, high-resolution tide, wave, current, temperature, salinity and turbidity measurements made at a number of fixed locations in the study area starting in 2001. Analyses of these hydrographic data, in conjunction with numerous field observations, evoke the following conceptual model of water and turbidity flux along West Maui. Wave- and wind-driven flows appear to be the primary control on flow over shallower portions of the reefs while tidal and subtidal currents dominate flow over the outer portions of the reefs and insular shelf. When the direction of these flows counter one another, which is quite common, they cause a zone of cross-shore horizontal shear and often form a front, with turbid, lower-salinity water inshore of the front and clear, higher-salinity water offshore of the front. It is not clear whether these zones of high shear and fronts are the cause or the result of the location of the fore reef, but they appear to be correlated alongshore over relatively large horizontal distances (orders of kilometers). When two flows converge or when a single flow is bathymetrically steered, eddies can be generated that, in the absence of large ocean surface waves, tend to accumulate material. Areas of higher turbidity and lower salinity tend to correlate with regions of poor coral health or the absence of well-developed reefs, suggesting that the oceanographic processes that concentrate and/or transport nutrients, contaminants, low-salinity water or suspended sediment might strongly influence coral reef ecosystem health and sustainability.

  17. A cross-sectional study of attitudes about the use of genetic testing for clinical care among patients with an alcohol use disorder.

    PubMed

    Strobel, Brittany; McManus, Lauren; Leong, Shirley; Blow, Frederic; Slaymaker, Valerie; Berrettini, Wade; Gordon, Adam J; O'Brien, Charles; Oslin, David

    2013-01-01

    Modification and individualization of medical treatments due to genetic testing has the potential to revolutionize healthcare delivery. As evidence mounts that genetic testing may improve treatment decisions for patients with alcohol use disorder (AUD), we explored patient concerns and attitudes toward genetic testing. Subjects of two USA cross-sectional AUD studies were surveyed regarding their attitudes regarding the use of genetic testing for AUD treatment. Four hundred and fifty-seven participants were surveyed. Overall, subjects showed a high degree of willingness to provide DNA for clinical use and recognized genetics as important to the pathophysiology of a number of disorders including AUD. There were, however, significant concerns expressed related to insurance denial or employment problems. We found that patients enrolled in AUD studies had some concerns about use of genetic testing. The patients in these two samples were, however, willing and knowledgeable about providing DNA samples.

  18. Botany, genetics and ethnobotany: a crossed investigation on the elusive tapir's diet in French Guiana.

    PubMed

    Hibert, Fabrice; Sabatier, Daniel; Andrivot, Judith; Scotti-Saintagne, Caroline; Gonzalez, Sophie; Prévost, Marie-Françoise; Grenand, Pierre; Chave, Jérome; Caron, Henri; Richard-Hansen, Cécile

    2011-01-01

    While the populations of large herbivores are being depleted in many tropical rainforests, the importance of their trophic role in the ecological functioning and biodiversity of these ecosystems is still not well evaluated. This is due to the outstanding plant diversity that they feed upon and the inherent difficulties involved in observing their elusive behaviour. Classically, the diet of elusive tropical herbivores is studied through the observation of browsing signs and macroscopic analysis of faeces or stomach contents. In this study, we illustrate that the original coupling of classic methods with genetic and ethnobotanical approaches yields information both about the diet diversity, the foraging modalities and the potential impact on vegetation of the largest terrestrial mammal of Amazonia, the lowland tapir. The study was conducted in the Guianan shield, where the ecology of tapirs has been less investigated. We identified 92 new species, 51 new genera and 13 new families of plants eaten by tapirs. We discuss the relative contribution of our different approaches, notably the contribution of genetic barcoding, used for the first time to investigate the diet of a large tropical mammal, and how local traditional ecological knowledge is accredited and valuable for research on the ecology of elusive animals.

  19. Botany, Genetics and Ethnobotany: A Crossed Investigation on the Elusive Tapir's Diet in French Guiana

    PubMed Central

    Hibert, Fabrice; Sabatier, Daniel; Andrivot, Judith; Scotti-Saintagne, Caroline; Gonzalez, Sophie; Prévost, Marie-Françoise; Grenand, Pierre; Chave, Jérome; Caron, Henri; Richard-Hansen, Cécile

    2011-01-01

    While the populations of large herbivores are being depleted in many tropical rainforests, the importance of their trophic role in the ecological functioning and biodiversity of these ecosystems is still not well evaluated. This is due to the outstanding plant diversity that they feed upon and the inherent difficulties involved in observing their elusive behaviour. Classically, the diet of elusive tropical herbivores is studied through the observation of browsing signs and macroscopic analysis of faeces or stomach contents. In this study, we illustrate that the original coupling of classic methods with genetic and ethnobotanical approaches yields information both about the diet diversity, the foraging modalities and the potential impact on vegetation of the largest terrestrial mammal of Amazonia, the lowland tapir. The study was conducted in the Guianan shield, where the ecology of tapirs has been less investigated. We identified 92 new species, 51 new genera and 13 new families of plants eaten by tapirs. We discuss the relative contribution of our different approaches, notably the contribution of genetic barcoding, used for the first time to investigate the diet of a large tropical mammal, and how local traditional ecological knowledge is accredited and valuable for research on the ecology of elusive animals. PMID:21991372

  20. Genetic-and-Epigenetic Interspecies Networks for Cross-Talk Mechanisms in Human Macrophages and Dendritic Cells during MTB Infection

    PubMed Central

    Li, Cheng-Wei; Lee, Yun-Lin; Chen, Bor-Sen

    2016-01-01

    Tuberculosis is caused by Mycobacterium tuberculosis (Mtb) infection. Mtb is one of the oldest human pathogens, and evolves mechanisms implied in human evolution. The lungs are the first organ exposed to aerosol-transmitted Mtb during gaseous exchange. Therefore, the guards of the immune system in the lungs, such as macrophages (Mϕs) and dendritic cells (DCs), are the most important defense against Mtb infection. There have been several studies discussing the functions of Mϕs and DCs during Mtb infection, but the genome-wide pathways and networks are still incomplete. Furthermore, the immune response induced by Mϕs and DCs varies. Therefore, we analyzed the cross-talk genome-wide genetic-and-epigenetic interspecies networks (GWGEINs) between Mϕs vs. Mtb and DCs vs. Mtb to determine the varying mechanisms of both the host and pathogen as it relates to Mϕs and DCs during early Mtb infection. First, we performed database mining to construct candidate cross-talk GWGEIN between human cells and Mtb. Then we constructed dynamic models to characterize the molecular mechanisms, including intraspecies gene/microRNA (miRNA) regulation networks (GRNs), intraspecies protein-protein interaction networks (PPINs), and the interspecies PPIN of the cross-talk GWGEIN. We applied a system identification method and a system order detection scheme to dynamic models to identify the real cross-talk GWGEINs using the microarray data of Mϕs, DCs and Mtb. After identifying the real cross-talk GWGEINs, the principal network projection (PNP) method was employed to construct host-pathogen core networks (HPCNs) between Mϕs vs. Mtb and DCs vs. Mtb during infection process. Thus, we investigated the underlying cross-talk mechanisms between the host and the pathogen to determine how the pathogen counteracts host defense mechanisms in Mϕs and DCs during Mtb H37Rv early infection. Based on our findings, we propose Rv1675c as a potential drug target because of its important defensive role in

  1. Genetic Susceptibility to Lipid Levels and Lipid Change Over Time and Risk of Incident Hyperlipidemia in Chinese Populations.

    PubMed

    Lu, Xiangfeng; Huang, Jianfeng; Mo, Zengnan; He, Jiang; Wang, Laiyuan; Yang, Xueli; Tan, Aihua; Chen, Shufeng; Chen, Jing; Gu, C Charles; Chen, Jichun; Li, Ying; Zhao, Liancheng; Li, Hongfan; Hao, Yongchen; Li, Jianxin; Hixson, James E; Li, Yunzhi; Cheng, Min; Liu, Xiaoli; Cao, Jie; Liu, Fangcao; Huang, Chen; Shen, Chong; Shen, Jinjin; Yu, Ling; Xu, Lihua; Mu, Jianjun; Wu, Xianping; Ji, Xu; Guo, Dongshuang; Zhou, Zhengyuan; Yang, Zili; Wang, Renping; Yang, Jun; Yan, Weili; Peng, Xiaozhong; Gu, Dongfeng

    2016-02-01

    Multiple genetic loci associated with lipid levels have been identified predominantly in Europeans, and the issue of to what extent these genetic loci can predict blood lipid levels increases over time and the incidence of future hyperlipidemia remains largely unknown. We conducted a meta-analysis of genome-wide association studies of lipid levels in 8344 subjects followed by replication studies including 14 739 additional individuals. We replicated 17 previously reported loci. We also newly identified 3 Chinese-specific variants in previous regions (HLA-C, LIPG, and LDLR) with genome-wide significance. Almost all the variants contributed to lipid levels change and incident hyperlipidemia >8.1-year follow-up among 6428 individuals of a prospective cohort study. The strongest associations for lipid levels change were detected at LPL, TRIB1, APOA1-C3-A4-A5, LIPC, CETP, and LDLR (P range from 4.84×10(-4) to 4.62×10(-18)), whereas LPL, TRIB1, ABCA1, APOA1-C3-A4-A5, CETP, and APOE displayed significant strongest associations for incident hyperlipidemia (P range from 1.20×10(-3) to 4.67×10(-16)). The 4 lipids genetic risk scores were independently associated with linear increases in their corresponding lipid levels and risk of incident hyperlipidemia. A C-statistics analysis showed significant improvement in the prediction of incident hyperlipidemia on top of traditional risk factors including the baseline lipid levels. These findings identified some evidence for allelic heterogeneity in Chinese when compared with Europeans in relation to lipid associations. The individual variants and those cumulative effects were independent risk factors for lipids increase and incident hyperlipidemia. © 2015 American Heart Association, Inc.

  2. The pharmacodynamic equivalence of levothyroxine and liothyronine. A randomized, double blind, cross-over study in thyroidectomized patients

    PubMed Central

    Celi, Francesco S.; Zemskova, Marina; Linderman, Joyce D.; Babar, Nabeel I.; Skarulis, Monica C.; Csako, Gyorgy; Wesley, Robert; Costello, Rene; Penzak, Scott R.; Pucino, Frank

    2009-01-01

    Summary Context The substitution of liothyronine (l-T3) for levothyroxine (l-T4) is commonly employed during thyroid hormone (TH) withdrawal in preparation for diagnostic and therapeutic interventions on thyroid cancer patients. Presently, only limited data are available on the l-T3 for l-T4 therapeutic substitution. Objective To characterize the pharmcodynamic equivalence of l-T3 and l-T4. Design Randomized, double-blind, cross-over intervention study. Setting NIH Clinical Center. Patients 10 thyroidectomized patients. Interventions Study participants were treated with l-T3 or l-T4 with a target TSH ≥0.5≤1.5 mU/l for at least 30 days before undergoing inpatient testing. Following testing, subjects crossed-over according to the same scheme. Main outcome measures Area under the serum concentration-time curve of TSH from 0 to 60 minutes (AUC 0-60) and peak TSH serum concentration (Cmax) following thyrotropin-releasing hormone (TRH) stimulation test, total l-T4 and l-T3 dose (mcg/kg), and l-T4/l-T3 ratio. Results No difference was observed for time 0 TSH values between l-T3 and l-T4 replacement phases (1.48± 0.77 vs. 1.21± 0.62 mU/l, p=0.293) at average daily doses of 40.3±11.3 mcg lT-3 and 115.2±38.5 mcg lT-4, l-T3: l-T4 ratio 0.36±0.06. TRH stimulation test resulted in similar l-T3 vs.l-T4 TSH responses with AUC 0-60 of 326.1 (95% CI 232.6-457.1) and 247.1 (95% CI 153.8-397.1) mU*min /l (p=0.285); and Cmax of 6.83 (95% CI 4.88-9.55) and 5.23 (95% CI 3.31-8.3) mU/l (p=0.383). Conclusions This is the first study addressing the equivalency between l-T3 and l-T4 therapy measured by baseline and TRH-stimulated TSH. The therapeutic substitution of l-T3 for l-T4 was achieved at approximately 1:3 ratio. PMID:20447070

  3. The VEPRO trial: A cross-over randomised controlled trial comparing 2 progressive lenses for patients with presbyopia

    PubMed Central

    Boutron, Isabelle; Touizer, Caroline; Pitrou, Isabelle; Roy, Carine; Ravaud, Philippe

    2008-01-01

    Background The aim of this trial was to compare the effectiveness of two generations of progressive lenses for presbyopia. Methods A multicenter cross-over randomized controlled trial performed in a primary care setting (5 optical dispensaries) was planned. Two categories of progressive lenses were compared: 1) a new-generation lens (i.e., VARILUX PANAMIC ORMA CRIZAL), which is expensive but a supposed improvement in comfort, and 2) an older-generation lens (i.e., VARILUX CONFORT ORMA CRIZAL), which is less expensive and is considered the reference lens. Patients were randomized to wear one generation of progressive lens for 4 weeks, then cross over to wear the other lens for 4 weeks, without knowing the sequence of lenses. Inclusion criteria were 1) age 43–60 years; 2) outpatients already wearing progressive lenses and referred to an optician ophthalmologist for optical correction prescription within the last 6 months; 3) receiving a correction of ≤3 dioptres in cases of associated myopia, hyperopia or astigmatism; 4) understanding and speaking French and able to answer a questionnaire; and 5) giving written consent to participate in the study. The primary outcome was patient preference for one progressive lens at week 8. Secondary outcomes were subjective measures of bifocal visual performance, including a) near visual acuity, b) visual field, c) kinetic visual skills, d) visual adaptability, e) visual comfort, and f) rapidity of adaptation. Results 127 patients were randomized to one of the lens groups. Two patients withdrew prematurely; 98.4% and 97.6% patients who wore the new versus older lenses, respectively, wore their progressive lenses every day during the 4-week period 1 and period 2. The number of participants in each of 5 centres varied from 16 (12.6%) to 35 (27.6%). 57.9% patients preferred the new-generation lenses, 36.5% the older-generation lenses, and 5.6% had no preference (p = 0.01). The two groups did not differ in any of the measures of

  4. Public participation in genetic databases: crossing the boundaries between biobanks and forensic DNA databases through the principle of solidarity

    PubMed Central

    Machado, Helena; Silva, Susana

    2015-01-01

    The ethical aspects of biobanks and forensic DNA databases are often treated as separate issues. As a reflection of this, public participation, or the involvement of citizens in genetic databases, has been approached differently in the fields of forensics and medicine. This paper aims to cross the boundaries between medicine and forensics by exploring the flows between the ethical issues presented in the two domains and the subsequent conceptualisation of public trust and legitimisation. We propose to introduce the concept of ‘solidarity’, traditionally applied only to medical and research biobanks, into a consideration of public engagement in medicine and forensics. Inclusion of a solidarity-based framework, in both medical biobanks and forensic DNA databases, raises new questions that should be included in the ethical debate, in relation to both health services/medical research and activities associated with the criminal justice system. PMID:26139851

  5. Public participation in genetic databases: crossing the boundaries between biobanks and forensic DNA databases through the principle of solidarity.

    PubMed

    Machado, Helena; Silva, Susana

    2015-10-01

    The ethical aspects of biobanks and forensic DNA databases are often treated as separate issues. As a reflection of this, public participation, or the involvement of citizens in genetic databases, has been approached differently in the fields of forensics and medicine. This paper aims to cross the boundaries between medicine and forensics by exploring the flows between the ethical issues presented in the two domains and the subsequent conceptualisation of public trust and legitimisation. We propose to introduce the concept of 'solidarity', traditionally applied only to medical and research biobanks, into a consideration of public engagement in medicine and forensics. Inclusion of a solidarity-based framework, in both medical biobanks and forensic DNA databases, raises new questions that should be included in the ethical debate, in relation to both health services/medical research and activities associated with the criminal justice system.

  6. Retraction of a study on genetically modified corn: Expert investigations should speak louder during controversies over safety.

    PubMed

    Xia, Jufeng; Song, Peipei; Xu, Lingzhong; Tang, Wei

    2015-04-01

    Over the past few years, genetically modified organisms (GMO) have gradually become more familiar after numerous reports of problems with GMO safety, such as genetically modified (GM) potatoes disrupting immunity, GM corn inducing tumors, and GM rice being fed to unwitting Chinese children. Every time, these reports cause panic among the population and lead to objections to GMO in various fora. After each incident, the scientific community has delivered its academic appraisal and refuted rumors through slow and cautious investigations and evaluations. Unfortunately, during each event media outlets quickly scare the public about food safety and ignore the ensuing comments from scientists. Although scientists have investigated each GMO crisis and reached scientific and rational conclusions, they have less ability to disseminate information than the media, so the public is not promptly informed of their rational and objective viewpoints as experts. Thus, scientists need greater ability to disseminate information from scientific investigations and evaluations in order to correct the intemperate reporting by attention-seeking media.

  7. Genetic Cross-Interaction between APOE and PRNP in Sporadic Alzheimer's and Creutzfeldt-Jakob Diseases

    PubMed Central

    Calero, Olga; Bullido, María J.; Clarimón, Jordi; Frank-García, Ana; Martínez-Martín, Pablo; Lleó, Alberto; Rey, María Jesús; Rábano, Alberto; Blesa, Rafael; Gómez-Isla, Teresa; Valdivieso, Fernando; de Pedro-Cuesta, Jesús; Ferrer, Isidro; Calero, Miguel

    2011-01-01

    Alzheimer's disease (AD) and Creutzfeldt-Jakob disease (CJD) represent two distinct clinical entities belonging to a wider group, generically named as conformational disorders that share common pathophysiologic mechanisms. It is well-established that the APOE ε4 allele and homozygosity at polymorphic codon 129 in the PRNP gene are the major genetic risk factors for AD and human prion diseases, respectively. However, the roles of PRNP in AD, and APOE in CJD are controversial. In this work, we investigated for the first time, APOE and PRNP genotypes simultaneously in 474 AD and 175 sporadic CJD (sCJD) patients compared to a common control population of 335 subjects. Differences in genotype distribution between patients and control subjects were studied by logistic regression analysis using age and gender as covariates. The effect size of risk association and synergy factors were calculated using the logistic odds ratio estimates. Our data confirmed that the presence of APOE ε4 allele is associated with a higher risk of developing AD, while homozygosity at PRNP gene constitutes a risk for sCJD. Opposite, we found no association for PRNP with AD, nor for APOE with sCJD. Interestingly, when AD and sCJD patients were stratified according to their respective main risk genes (APOE for AD, and PRNP for sCJD), we found statistically significant associations for the other gene in those strata at higher previous risk. Synergy factor analysis showed a synergistic age-dependent interaction between APOE and PRNP in both AD (SF = 3.59, p = 0.027), and sCJD (SF = 7.26, p = 0.005). We propose that this statistical epistasis can partially explain divergent data from different association studies. Moreover, these results suggest that the genetic interaction between APOE and PRNP may have a biological correlate that is indicative of shared neurodegenerative pathways involved in AD and sCJD. PMID:21799773

  8. Gene flow in wild chimpanzee populations: what genetic data tell us about chimpanzee movement over space and time.

    PubMed

    Gagneux, P; Gonder, M K; Goldberg, T L; Morin, P A

    2001-06-29

    The isolation of phylogenetically distinct primate immunodeficiency viruses from at least seven wild-born, captive chimpanzees indicates that viruses closely related to HIV-1 may be endemic in some wild chimpanzee populations. The search for the chimpanzee population or populations harbouring these viruses is therefore on. This paper attempts to answer the question of whether or not such populations of chimpanzees are likely to exist at all, and, if so, where they are likely to be found. We summarize what is known about gene flow in wild populations of chimpanzees, both between major phylogeographical subdivisions of the species, and within these subdivisions. Our analysis indicates that hitherto undocumented reproductively isolated chimpanzee populations may in fact exist. This conclusion is based on the observation that, despite limited geographical sampling and limited numbers of genetic loci, conventional notions of the nature and extent of chimpanzee gene flow have recently been substantially revised. Molecular genetic studies using mitochondrial DNA sequences and hypervariable nuclear microsatellite markers have indicated the existence of heretofore undocumented barriers to chimpanzee gene flow. These studies have identified at least one population of chimpanzees genetically distinct enough to be classified into a new subspecies (Pan troglodytes vellerosus). At the same time, they have called into question the long-accepted genetic distinction between eastern chimpanzees (Pan troglodytes schweinfurthii) and western equatorial chimpanzees (Pan troglodytes troglodytes). The same studies have further indicated that gene flow between local populations is more extensive than was previously thought, and follows patterns sometimes inconsistent with those documented through direct behavioural observation. Given the apparently incomplete nature of the current understanding of chimpanzee gene flow in equatorial Africa, it seems reasonable to speculate that a chimpanzee

  9. Limitations to estimating bacterial cross-species transmission using genetic and genomic markers: inferences from simulation modeling

    PubMed Central

    Benavides, Julio A; Cross, Paul C; Luikart, Gordon; Creel, Scott

    2014-01-01

    Cross-species transmission (CST) of bacterial pathogens has major implications for human health, livestock, and wildlife management because it determines whether control actions in one species may have subsequent effects on other potential host species. The study of bacterial transmission has benefitted from methods measuring two types of genetic variation: variable number of tandem repeats (VNTRs) and single nucleotide polymorphisms (SNPs). However, it is unclear whether these data can distinguish between different epidemiological scenarios. We used a simulation model with two host species and known transmission rates (within and between species) to evaluate the utility of these markers for inferring CST. We found that CST estimates are biased for a wide range of parameters when based on VNTRs and a most parsimonious reconstructed phylogeny. However, estimations of CST rates lower than 5% can be achieved with relatively low bias using as low as 250 SNPs. CST estimates are sensitive to several parameters, including the number of mutations accumulated since introduction, stochasticity, the genetic difference of strains introduced, and the sampling effort. Our results suggest that, even with whole-genome sequences, unbiased estimates of CST will be difficult when sampling is limited, mutation rates are low, or for pathogens that were recently introduced. PMID:25469159

  10. Limitations to estimating bacterial cross-species transmission using genetic and genomic markers: inferences from simulation modeling.

    PubMed

    Benavides, Julio A; Cross, Paul C; Luikart, Gordon; Creel, Scott

    2014-08-01

    Cross-species transmission (CST) of bacterial pathogens has major implications for human health, livestock, and wildlife management because it determines whether control actions in one species may have subsequent effects on other potential host species. The study of bacterial transmission has benefitted from methods measuring two types of genetic variation: variable number of tandem repeats (VNTRs) and single nucleotide polymorphisms (SNPs). However, it is unclear whether these data can distinguish between different epidemiological scenarios. We used a simulation model with two host species and known transmission rates (within and between species) to evaluate the utility of these markers for inferring CST. We found that CST estimates are biased for a wide range of parameters when based on VNTRs and a most parsimonious reconstructed phylogeny. However, estimations of CST rates lower than 5% can be achieved with relatively low bias using as low as 250 SNPs. CST estimates are sensitive to several parameters, including the number of mutations accumulated since introduction, stochasticity, the genetic difference of strains introduced, and the sampling effort. Our results suggest that, even with whole-genome sequences, unbiased estimates of CST will be difficult when sampling is limited, mutation rates are low, or for pathogens that were recently introduced.

  11. Carotenoids are more bioavailable from papaya than from tomato and carrot in humans: a randomised cross-over study

    PubMed Central

    Schweiggert, Ralf M.; Kopec, Rachel E.; Villalobos-Gutierrez, Maria G.; Högel, Josef; Quesada, Silvia; Esquivel, Patricia; Schwartz, Steven J.; Carle, Reinhold

    2014-01-01

    Carrot, tomato and papaya represent important dietary sources of β-carotene and lycopene. The main objective of the present study was to compare the bioavailability of carotenoids from these food sources in healthy human subjects. A total of sixteen participants were recruited for a randomised cross-over study. Test meals containing raw carrots, tomatoes and papayas were adjusted to deliver an equal amount of β-carotene and lycopene. For the evaluation of bioavailability, TAG-rich lipoprotein (TRL) fractions containing newly absorbed carotenoids were analysed over 9.5 h after test meal consumption. The bioavailability of β-carotene from papayas was approximately three times higher than that from carrots and tomatoes, whereas differences in the bioavailability of β-carotene from carrots and tomatoes were insignificant. Retinyl esters appeared in the TRL fractions at a significantly higher concentration after the consumption of the papaya test meal. Similarly, lycopene was approximately 2.6 times more bioavailable from papayas than from tomatoes. Furthermore, the bioavailability of β-cryptoxanthin from papayas was shown to be 2.9 and 2.3 times higher than that of the other papaya carotenoids β-carotene and lycopene, respectively. The morphology of chromoplasts and the physical deposition form of carotenoids were hypothesised to play a major role in the differences observed in the bioavailability of carotenoids from the foods investigated. Particularly, the liquid-crystalline deposition of β-carotene and the storage of lycopene in very small crystalloids in papayas were found to be associated with their high bioavailability. In conclusion, papaya was shown to provide highly bioavailable β-carotene, β-cryptoxanthin and lycopene and may represent a readily available dietary source of provitamin A for reducing the incidence of vitamin A deficiencies in many subtropical and tropical developing countries. PMID:23931131

  12. Adolescents' ability to select healthy food using two different front-of-pack food labels: a cross-over study.

    PubMed

    Babio, Nancy; Vicent, Paloma; López, Leonor; Benito, Anna; Basulto, Julio; Salas-Salvadó, Jordi

    2014-06-01

    To compare, in adolescents, two models of front-of-pack Guideline Daily Amounts (GDA) labels in terms of (i) friendliness and acceptance and (ii) the ability to choose a diet that closely follows the nutritional recommendations. A randomized cross-over study was designed to compare two simplified front-of-pack GDA nutrition labels. A Spanish secondary school. Eighty-one healthy adolescents aged between 14 and 16 years were recruited. Participants were randomly exposed to two experimental non-real food-choice conditions using multiple-traffic-light or monochrome nutritional labels. Participants had to choose options from a closed menu for 5 d on the basis of the experimental front-of-pack labelling. For each meal, three food options with different nutritional compositions were given to the participants. The contents of total energy and fat, saturated fat, sugar and salt of the chosen options were calculated. There were no significant differences in baseline sociodemographic and anthropometric characteristics between participants regardless of the experimental condition in which they started. There were no carry-over effects between the experimental sequences. It was observed that when participants used the multiple-traffic-light GDA system they chose significantly less total energy (mean -123·1 (sd 211·0) kJ (-29·4 (sd 50·4) kcal), P < 0·001), sugar (-4·5 (sd 4·6) g, P < 0·001), fat (-2·1 (sd 4·5) g, P = 0·006), saturated fat (-1·0 (sd 1·9) g, P = 0·002) and salt (-0·4 (sd 0·5) g, P < 0·001) than when they used the monochrome GDA system. Compared with the monochrome GDA front-of-pack nutritional label, the multiple-traffic-light system helped adolescents to differentiate between healthier and less healthy food, theoretically making it possible for them to choose a diet closer to dietary recommendations.

  13. Carotenoids are more bioavailable from papaya than from tomato and carrot in humans: a randomised cross-over study.

    PubMed

    Schweiggert, Ralf M; Kopec, Rachel E; Villalobos-Gutierrez, Maria G; Högel, Josef; Quesada, Silvia; Esquivel, Patricia; Schwartz, Steven J; Carle, Reinhold

    2014-02-01

    Carrot, tomato and papaya represent important dietary sources of β-carotene and lycopene. The main objective of the present study was to compare the bioavailability of carotenoids from these food sources in healthy human subjects. A total of sixteen participants were recruited for a randomised cross-over study. Test meals containing raw carrots, tomatoes and papayas were adjusted to deliver an equal amount of β-carotene and lycopene. For the evaluation of bioavailability, TAG-rich lipoprotein (TRL) fractions containing newly absorbed carotenoids were analysed over 9·5 h after test meal consumption. The bioavailability of β-carotene from papayas was approximately three times higher than that from carrots and tomatoes, whereas differences in the bioavailability of β-carotene from carrots and tomatoes were insignificant. Retinyl esters appeared in the TRL fractions at a significantly higher concentration after the consumption of the papaya test meal. Similarly, lycopene was approximately 2·6 times more bioavailable from papayas than from tomatoes. Furthermore, the bioavailability of β-cryptoxanthin from papayas was shown to be 2·9 and 2·3 times higher than that of the other papaya carotenoids β-carotene and lycopene, respectively. The morphology of chromoplasts and the physical deposition form of carotenoids were hypothesised to play a major role in the differences observed in the bioavailability of carotenoids from the foods investigated. Particularly, the liquid-crystalline deposition of β-carotene and the storage of lycopene in very small crystalloids in papayas were found to be associated with their high bioavailability. In conclusion, papaya was shown to provide highly bioavailable β-carotene, β-cryptoxanthin and lycopene and may represent a readily available dietary source of provitamin A for reducing the incidence of vitamin A deficiencies in many subtropical and tropical developing countries.

  14. A two-way cross-over bioequivalence study comparing two products of diclofenac sodium suppositories in healthy human volunteers.

    PubMed

    Hasan, Mazen; Otoom, Sameer; Najib, Naji; Sallam, El-Sayed

    2004-12-01

    This report presents the results of two treatment cross-over investigations on 20 healthy male volunteers to assess the bioequivalence of two suppository products of diclofenac sodium. The study was carried out under US Food and Drug Administration Guidelines. The two products were voltaren (100 mg) suppository (Ciba-Giegy), as a reference product, and Inflaban (100 mg) suppository (The Arab Pharmaceutical Manufacturing Company, Ltd. "APM"), as a test product. Both products were administered rectally as a single dose (100 mg) separated by a one-week wash-out period. Following drug administration, blood samples were collected over 12 hr, and serum harvested from the blood was analyzed for diclofenac sodium using a sensitive and specific high performance liquid chromatographic assay. The results of this investigation indicated that there were no statistically significant differences between the two products in either the mean concentration-time profiles or in the obtained pharmacokinetic parameters, including area under the serum concentration-time curve for 12 hr (AUC(0-12h)), lag time between product administration and first appearance of the drug in serum (T(lag)), peak serum concentration (C(max)), and time to reach this peak serum concentration (T(max)). Concerning the relative extent of absorption, assessed by the AUC ratio (Inflaban/Voltaren) for 12 hr, the average value was found to be 1.00+/-0.09 with a 95% confidence limits (C.L.) of 0.82-1.18. Thus, these findings clearly indicate that the two products are bioequivalent in terms of rate and extent of drug absorption.

  15. Prediction of testcross means and variances among F3 progenies of F1 crosses from testcross means and genetic distances of their parents in maize.

    PubMed

    Melchinger, A E; Gumber, R K; Leipert, R B; Vuylsteke, M; Kuiper, M

    1998-03-01

    Prediction of the means and genetic variances in segregating generations could help to assess the breeding potential of base populations. In this study, we investigated whether the testcross (TC) means and variances of F3 progenies from F1 crosses in European maize can be predicted from the TC means of their parents and F1 crosses and four measures of parental genetic divergence: genetic distance (GD) determined by 194 RFLP or 691 AFLP(TM) (1) markers, mid-parent heterosis (MPH), and absolute difference between the TC means of parents (∣P1-P2∣). The experimental materials comprised six sets of crosses; each set consisted of four elite inbreds from the flint or dent germplasm and the six possible F1 crosses between them, which were evaluated for mid-parent heterosis. Testcross progenies of these materials and 20 random F3 plants per F1 cross were produced with a single-cross tester from the opposite heterotic group and evaluated in two environments. The characters studied were plant height, dry matter content and grain yield. The genetic distance between parent lines ranged between 0.17 and 0.70 for RFLPs and between 0.14 and 0.57 for AFLPs in the six sets. Testcross-means of parents, F1 crosses, and F3 populations averaged across the six crosses in a particular set generally agreed well for all three traits. Bartlett's test revealed heterogeneous TC variances among the six crosses in all sets for plant height, in four sets for grain yield and in five sets for dry matter content. Correlations among the TC means of the parents, F1 crosses, and F3 populations were highly significant and positive for all traits. Estimates of the TC variance among F3 progenies for the 36 crosses showed only low correlations with the four measures of parental genetic divergence for all traits. The results demonstrated that for our material, the TC means of the parents or the parental F1 cross can be used as predictors for the TC means of F3 populations. However, the prediction of the

  16. Dark chocolate and vascular function in patients with peripheral artery disease: a randomized, controlled cross-over trial.

    PubMed

    Hammer, Alexandra; Koppensteiner, Renate; Steiner, Sabine; Niessner, Alexander; Goliasch, Georg; Gschwandtner, Michael; Hoke, Matthias

    2015-01-01

    Flavonoid-rich dark chocolate has positive effects on vascular function in healthy subjects and in patients at risk of atherosclerosis. The impact of dark chocolate on endothelial and microvascular function in patients with symptomatic peripheral artery disease (PAD) has not been investigated so far. In an investigator blinded, randomized, controlled, cross-over trial we assessed the effect of flavonoid-rich dark chocolate and cocoa-free control chocolate on flow-mediated dilatation (FMD) of the brachial artery and on microvascular function (assessed by Laser Doppler fluxmetry) in 21 patients with symptomatic (Fontaine stage II) PAD. Measurements were done in each patient on 2 single days, with an interval of 7 days, at baseline and at 2 hours after ingestion of 50 g dark chocolate or 50 g white chocolate, respectively. FMD remained unchanged after intake of dark chocolate (baseline and 2 hours after ingestion, %: 5.1 [IQR 4.4 to 7.3] and 5.5 [IQR 3.9 to 10.4]; p = 0.57, and after intake of white chocolate (baseline and 2 hours after ingestion, %: 6.4 [IQR 4.5 to 11.4] and 4.4 [IQR 2.6 to 8.7]; p = 0.14. Similarly, microcirculatory parameters were not significantly altered after intake of any chocolate compared with the respective baseline values. In conclusion, a single consumption of 50 g dark chocolate has no effect on endothelial and microvascular function in patients with symptomatic PAD.

  17. Medical professionals' perspectives on prescribed and over-the-counter medicines containing codeine: a cross-sectional study

    PubMed Central

    Foley, Michelle; Carney, Tara; Rich, Eileen; Parry, Charles; Van Hout, Marie-Claire; Deluca, Paolo

    2016-01-01

    Objectives To explore prescribing practitioners' perspectives on prescribed codeine use, their ability to identify dependence and their options for treatment in the UK. Design Cross-sectional design using a questionnaire containing closed-ended and open-ended items. Setting A nationally representative sample of prescribing professionals working in the UK. Participants 300 prescribing professionals working in primary care and pain settings. Results Participants stated that they regularly reviewed patients prescribed codeine, understood the risks of dependence and recognised the potential for codeine to be used recreationally. Over half the participants felt patients were unaware of the adverse health consequences of high doses of combination codeine medicines. One-quarter of participants experienced patient resentment when asking about medicines containing codeine. Just under 40% of participants agreed that it was difficult to identify problematic use of codeine without being informed by the patient and did not feel confident in identification of codeine dependence. Less than 45% of all participants agreed that codeine dependence could be managed effectively in general practice. Slow or gradual withdrawal was the most popular suggested treatment in managing dependence. Education and counselling was also emphasised in managing codeine-dependent patients in primary care. Conclusions Communication with patients should involve assessment of patient understanding of their medication, including the risk of dependence. There is a need to develop extra supports for professionals including patient screening tools for identifying codeine dependence. The support structure for managing codeine-dependent patients in primary care requires further examination. PMID:27417200

  18. Pavlovian conditioning and cross-sensitization studies raise challenges to the hypothesis that overeating is an addictive behavior

    PubMed Central

    Harb, M R; Almeida, O F X

    2014-01-01

    Elevated glucocorticoid levels and sign tracking (ST) in Pavlovian conditioning are potential biomarkers of compulsive behaviors such as addiction. As overeating is sometimes viewed as a form of addictive behavior, we hypothesized that murine Pavlovian sign trackers would have a greater propensity to overeat and develop obesity. Using a food reward in the classical conditioning paradigm, we show that ST behavior is a robust conditioned response but not a predictor of eating and growth trajectories in mice, thus challenging the view that the development of obesity and drug addiction depend on identical mechanisms. This interpretation was supported by experiments which showed that overweight mice do not display cross-sensitization to an addictive drug (morphine), and conversely, that overweight morphine-sensitized animals do not overconsume a highly rewarding food. Although the rewarding/motivational effects of both food and drugs of abuse are mediated by similar neurochemical mechanisms, obesity and drug addiction represent a summation of other dysfunctional input and output pathways that lead to the emergence of two distinct disorders, each of which would deserve a specific pharmacotherapeutic approach. PMID:24780921

  19. Pavlovian conditioning and cross-sensitization studies raise challenges to the hypothesis that overeating is an addictive behavior.

    PubMed

    Harb, M R; Almeida, O F X

    2014-04-29

    Elevated glucocorticoid levels and sign tracking (ST) in Pavlovian conditioning are potential biomarkers of compulsive behaviors such as addiction. As overeating is sometimes viewed as a form of addictive behavior, we hypothesized that murine Pavlovian sign trackers would have a greater propensity to overeat and develop obesity. Using a food reward in the classical conditioning paradigm, we show that ST behavior is a robust conditioned response but not a predictor of eating and growth trajectories in mice, thus challenging the view that the development of obesity and drug addiction depend on identical mechanisms. This interpretation was supported by experiments which showed that overweight mice do not display cross-sensitization to an addictive drug (morphine), and conversely, that overweight morphine-sensitized animals do not overconsume a highly rewarding food. Although the rewarding/motivational effects of both food and drugs of abuse are mediated by similar neurochemical mechanisms, obesity and drug addiction represent a summation of other dysfunctional input and output pathways that lead to the emergence of two distinct disorders, each of which would deserve a specific pharmacotherapeutic approach.

  20. Genomic identification and quantification of microbial species adhering to toothbrush bristles after disinfection: A cross-over study.

    PubMed

    do Nascimento, Cássio; Trinca, Nayara Nascimento; Pita, Murillo Sucena; Pedrazzi, Vinícius

    2015-07-01

    The aim of this clinical investigation was to identify and quantify the microbial species adhering to toothbrush bristles after controlled brushing and storage in different antimicrobial agents. Sixteen healthy participants were enrolled in this study and randomly submitted to 4 interventions in a cross-over design: brushing and toothbrush storage in (I) Periogard/(II) Periobio (Chlorhexidine gluconate 0.12%), (III) Cepacol (cetylpyridinium chloride 0.05%) and (IV) distilled water (positive control). Thirty-eight bacterial species including putative pathogens and 5 Candida spp. were assessed by Checkerboard DNA-DNA hybridization. The results of the study have shown a striking reduction of the total microbial counts, including bacteria and Candida spp., on the toothbrush bristles after storage in cetylpyridinium chloride 0.05% (p < 0.0001). Chlorhexidine gluconate 0.12% showed no differences on the total bacterial count when compared to distilled water (p > 0.05). Cetylpyridinium chloride solution also presented the lowest genome counts and frequency of detection for individual target species; distilled water showed the highest individual genome counts (p < 0.05). Potential pathogenic species were recorded in moderate to high levels for chlorhexidine gluconate and distilled water. Cetylpyridinium chloride 0.05% was the most effective storage solution in the reduction of total and individual microbial counts, including pathogenic species. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Multichannel commutators of analog signals for measurement of energy distribution over beam cross section of pulse laser

    NASA Astrophysics Data System (ADS)

    Kuznetsov, A. A.

    1984-11-01

    Instruments of measuring the energy distribution over the beam cross section of a pulse laser are checked against standards which include a primary instrument transducer, usually of the magnetic type, in the etalons as well as in reference and operating meters. Measurement of the energy distribution in the case of monopulse lasers with nonreproducible process characteristics and unknown space distributions requires a sufficiently wide dynamic range. The commutator of signals must have a dynamic range of 55 to 65 dB. Existing multichannel commutators of analog signals are inadequate for this application. A comparative design and performance evaluation of special purpose multichannel commutators for this application reveals that electromechanical ones such as ShI relays are superior in terms of low bias voltage with contactors closed, high ratio of open resistance to closed resistance, small temperature drift, wide dynamic range, low crosstalk level, and high stability, while contactless ones such optrons or transistor-diode switches excell in high speed. Accordingly, one or another type of commutator must be selected and design for a given energy distribution measuring instrument, also taking into account the required precision and sensitivity of digital voltmeters used with these instruments.

  2. Heparin versus low molecular weight heparin K 2165 in chronic hemodialysis patients: a randomized cross-over study.

    PubMed

    Borm, J J; Krediet, R; Sturk, A; ten Cate, J W

    1986-01-01

    Ten patients on chronic intermittent hemodialysis treatment received either unfractionated heparin or low molecular weight (LMW) heparin K 2165 in a single-blinded randomized cross-over study to assess: effects on hemostasis and ex vivo platelet functions, and effectiveness, i.e. prevention of fibrin formation in the extracorporeal circuit. The 20 dialysis treatments were without untoward side effects, for both drugs used. The variation in the plasma anti-Xa activities was significantly less during K 2165 treatment than during heparinization. No differences between the drugs were observed regarding the Ivy bleeding time, platelet count and platelet aggregation (spontaneous, and induced by ADP and collagen). Plasma platelet factor 4 levels did not increase under K 2165 to such an extent as under heparin. Both drugs did not influence the plasma levels of beta-thromboglobulin, thromboxane B2 and platelet serotonin content. K 2165 did not affect platelet adhesion to collagen, in contrast to heparin which substantially inhibited platelet adhesion. Under both treatments, 4 minor clots were observed in 4 artificial kidneys, despite plasma anti-Xa levels in between 0.19 and 0.46 U/ml. K 2165 may therefore be considered as effective an anticoagulant as heparin, with less effects on ex vivo platelet functions.

  3. Microwave conductance in random waveguides in the cross-over to Anderson localization and single-parameter scaling

    PubMed Central

    Shi, Zhou; Wang, Jing; Genack, Azriel Z.

    2014-01-01

    The nature of transport of electrons and classical waves in disordered systems depends upon the proximity to the Anderson localization transition between freely diffusing and localized waves. The suppression of average transport and the enhancement of relative fluctuations in conductance in one-dimensional samples with lengths greatly exceeding the localization length, , are related in the single-parameter scaling (SPS) theory of localization. However, the difficulty of producing an ensemble of statistically equivalent samples in which the electron wave function is temporally coherent has so-far precluded the experimental demonstration of SPS. Here we demonstrate SPS in random multichannel systems for the transmittance T of microwave radiation, which is the analog of the dimensionless conductance. We show that for , a single eigenvalue of the transmission matrix (TM) dominates transmission, and the distribution of the is Gaussian with a variance equal to the average of , as conjectured by SPS. For samples in the cross-over to localization, , we find a one-sided distribution for . This anomalous distribution is explained in terms of a charge model for the eigenvalues of the TM τ in which the Coulomb interaction between charges mimics the repulsion between the eigenvalues of TM. We show in the localization limit that the joint distribution of T and the effective number of transmission eigenvalues determines the probability distributions of intensity and total transmission for a single-incident channel. PMID:24516156

  4. Combining walking and relaxation for stress reduction-A randomized cross-over trial in healthy adults.

    PubMed

    Matzer, Franziska; Nagele, Eva; Lerch, Nikolaus; Vajda, Christian; Fazekas, Christian

    2017-08-25

    Both physical activity and relaxation have stress-relieving potential. This study investigates their combined impact on the relaxation response while considering participants' initial stress level. In a randomized cross-over trial, 81 healthy adults completed 4 types of short-term interventions for stress reduction, each lasting for 1 hr: (1) physical activity (walking) combined with resting, (2) walking combined with balneotherapy, (3) combined resting and balneotherapy, and (4) resting only. Saliva cortisol, blood pressure, state of mood, and relaxation were measured preintervention and postintervention. Stress levels were determined by validated questionnaires. All interventions were associated with relaxation responses in the variables saliva cortisol, blood pressure, state of mood, and subjective relaxation. No significant differences were found regarding the reduction of salivary cortisol (F = 1.30; p = .281). The systolic blood pressure was reduced best when walking was combined with balneotherapy or resting (F = 7.34; p < .001). Participants with high stress levels (n = 25) felt more alert after interventions including balneotherapy, whereas they reported an increase of tiredness when walking was combined with resting (F = 3.20; p = .044). Results suggest that combining physical activity and relaxation (resting or balneotherapy) is an advantageous short-term strategy for stress reduction as systolic blood pressure is reduced best while similar levels of relaxation can be obtained. Copyright © 2017 John Wiley & Sons, Ltd.

  5. Using acupressure and Montessori-based activities to decrease agitation for residents with dementia: a cross-over trial.

    PubMed

    Lin, Li-Chan; Yang, Man-Hua; Kao, Chieh-Chun; Wu, Shiao-Chi; Tang, Sai-Hung; Lin, Jaung-Geng

    2009-06-01

    To explore the effectiveness of acupressure and Montessori-based activities in decreasing the agitated behaviors of residents with dementia. A double-blinded, randomized (two treatments and one control; three time periods) cross-over design was used. Six special care units for residents with dementia in long-term care facilities in Taiwan were the sites for the study. One hundred thirty-three institutionalized residents with dementia. Subjects were randomized into three treatment sequences: acupressure-presence-Montessori methods, Montessori methods-acupressure-presence and presence-Montessori methods-acupressure. All treatments were done once a day, 6 days per week, for a 4-week period. The Cohen-Mansfield Agitation Inventory, Ease-of-Care, and the Apparent Affect Rating Scale. After receiving the intervention, the acupressure and Montessori-based-activities groups saw a significant decrease in agitated behaviors, aggressive behaviors, and physically nonaggressive behaviors than the presence group. Additionally, the ease-of-care ratings for the acupressure and Montessori-based-activities groups were significantly better than for the presence group. In terms of apparent affect, positive affect in the Montessori-based-activities group was significantly better than in the presence group. This study confirms that a blending of traditional Chinese medicine and a Western activities program would be useful in elderly care and that in-service training for formal caregivers in the use of these interventions would be beneficial for patients

  6. Modafinil for attentional and psychomotor dysfunction in advanced cancer: a double-blind, randomised, cross-over trial.

    PubMed

    Lundorff, L E; Jønsson, B H; Sjøgren, P

    2009-12-01

    Cognitive impairment seems to be highly prevalent in patients with advanced cancer. Modafinil, a novel vigilance and wake-promoting agent, may be an alternative treatment. We wanted to investigate this treatment on attentional and psychomotor dysfunction in cancer patients. 28 cancer patients with a tiredness score of 50 mm or more on a scale of 0 to 10 (0=no tiredness, 10=worst possible tiredness) and Karnofsky Performance Status 40-70 were included. All medications were kept stable during the trial despite short acting opioids for breakthrough pain. On day 1 the patients were randomly assigned to receive 200 mg Modafinil orally or placebo and on day 4 they crossed-over to the alternative treatment. Finger Tapping Test (FTT), Trail Making Test (TMT) and Edmonton Symptom Assessment System (ESAS) were evaluated before tablet intake and again 4, 5 hours after. FTT for the dominant hand as well as TMT were statistically significantly improved on modafinil (p-values=0.006 and 0.042, respectively). On ESAS, depression and drowsiness also improved statistically significantly (p-values=<0.001 and 0.038, respectively). Modafinil in a single dose regimen was significantly superior to placebo regarding two cognitive tests of psychomotor speed and attention. Furthermore subjective scores of depression and drowsiness were significantly improved by modafinil.

  7. Detection dog efficacy for collecting faecal samples from the critically endangered Cross River gorilla (Gorilla gorilla diehli) for genetic censusing

    PubMed Central

    Arandjelovic, Mimi; Bergl, Richard A.; Ikfuingei, Romanus; Jameson, Christopher; Parker, Megan; Vigilant, Linda

    2015-01-01

    Population estimates using genetic capture–recapture methods from non-invasively collected wildlife samples are more accurate and precise than those obtained from traditional methods when detection and resampling rates are high. Recently, detection dogs have been increasingly used to find elusive species and their by-products. Here we compared the effectiveness of dog- and human-directed searches for Cross River gorilla (Gorilla gorilla diehli) faeces at two sites. The critically endangered Cross River gorilla inhabits a region of high biodiversity and endemism on the border between Nigeria and Cameroon. The rugged highland terrain and their cryptic behaviour make them difficult to study and a precise population size for the subspecies is still lacking. Dog-directed surveys located more fresh faeces with less bias than human-directed survey teams. This produced a more reliable population estimate, although of modest precision given the small scale of this pilot study. Unfortunately, the considerable costs associated with use of the United States-based detection dog teams make the use of these teams financially unfeasible for a larger, more comprehensive survey. To realize the full potential of dog-directed surveys and increase cost-effectiveness, we recommend basing dog-detection teams in the countries where they will operate and expanding the targets the dogs are trained to detect. PMID:26064602

  8. Detection dog efficacy for collecting faecal samples from the critically endangered Cross River gorilla (Gorilla gorilla diehli) for genetic censusing.

    PubMed

    Arandjelovic, Mimi; Bergl, Richard A; Ikfuingei, Romanus; Jameson, Christopher; Parker, Megan; Vigilant, Linda

    2015-02-01

    Population estimates using genetic capture-recapture methods from non-invasively collected wildlife samples are more accurate and precise than those obtained from traditional methods when detection and resampling rates are high. Recently, detection dogs have been increasingly used to find elusive species and their by-products. Here we compared the effectiveness of dog- and human-directed searches for Cross River gorilla (Gorilla gorilla diehli) faeces at two sites. The critically endangered Cross River gorilla inhabits a region of high biodiversity and endemism on the border between Nigeria and Cameroon. The rugged highland terrain and their cryptic behaviour make them difficult to study and a precise population size for the subspecies is still lacking. Dog-directed surveys located more fresh faeces with less bias than human-directed survey teams. This produced a more reliable population estimate, although of modest precision given the small scale of this pilot study. Unfortunately, the considerable costs associated with use of the United States-based detection dog teams make the use of these teams financially unfeasible for a larger, more comprehensive survey. To realize the full potential of dog-directed surveys and increase cost-effectiveness, we recommend basing dog-detection teams in the countries where they will operate and expanding the targets the dogs are trained to detect.

  9. Appetitive traits as behavioural pathways in genetic susceptibility to obesity: a population-based cross-sectional study.

    PubMed

    Konttinen, Hanna; Llewellyn, Clare; Wardle, Jane; Silventoinen, Karri; Joensuu, Anni; Männistö, Satu; Salomaa, Veikko; Jousilahti, Pekka; Kaprio, Jaakko; Perola, Markus; Haukkala, Ari

    2015-10-01

    The mechanisms through which genes influence body weight are not well understood, but appetite has been implicated as one mediating pathway. Here we use data from two independent population-based Finnish cohorts (4632 adults aged 25-74 years from the DILGOM study and 1231 twin individuals aged 21-26 years from the FinnTwin12 study) to investigate whether two appetitive traits mediate the associations between known obesity-related genetic variants and adiposity. The results from structural equation modelling indicate that the effects of a polygenic risk score (90 obesity-related loci) on measured body mass index and waist circumference are partly mediated through higher levels of uncontrolled eating (βindirect = 0.030-0.032, P < 0.001 in DILGOM) and emotional eating (βindirect = 0.020-0.022, P < 0.001 in DILGOM and βindirect = 0.013-0.015, P = 0.043-0.044 in FinnTwin12). Our findings suggest that genetic predispositions to obesity may partly exert their effects through appetitive traits reflecting lack of control over eating or eating in response to negative emotions. Obesity prevention and treatment studies should examine the impact of targeting these eating behaviours, especially among individuals having a high genetic predisposition to obesity.

  10. Genetics

    USDA-ARS?s Scientific Manuscript database

    The genus Capsicum represents one of several well characterized Solanaceous genera. A wealth of classical and molecular genetics research is available for the genus. Information gleaned from its cultivated relatives, tomato and potato, provide further insight for basic and applied studies. Early ...

  11. Genetics

    USDA-ARS?s Scientific Manuscript database

    Maintaining genetic variation in wild populations of Arctic organisms is fundamental to the long-term persistence of high latitude biodiversity. Variability is important because it provides options for species to respond to changing environmental conditions and novel challenges such as emerging path...

  12. Over-the-counter medication use for childhood fever: a cross-sectional study of Australian parents.

    PubMed

    Walsh, Anne; Edwards, Helen; Fraser, Jenny

    2007-09-01

    To report Australian parents' medication (paracetamol, ibuprofen and homeopathic) use in childhood fever management. A cross-sectional survey of 401 Queensland parents of children aged between 6 months and 5 years recruited through advertising (48.4%), face-to-face (26.4%) and snowball (24.4%) methods was conducted. A 17-item instrument was developed; construct and content validity were determined by an expert panel; and item reliability by test-retest with nine parents. Areas targeted were medication use and influences on and barriers to medication use. Most participants were female, had tertiary education and lived in a major city (mean age 34.6 years). Reducing children's fever with over-the-counter medications was common (91%): 94% of parents reported using paracetamol and 77% reported using ibuprofen. A few (3.7%) used homeopathic remedies. Dosage was determined by weight (86.3%), age (84.3%), temperature (32.4%), illness severity (31.4%) and lethargy (20.9%). Frequency was determined by instructions on the medication label (55.3%), temperature (40.6%) and well-being (27.7%). Ibuprofen was administered too frequently by 31.5% (four hourly by 22.8%), and paracetamol by 3.8%. Fifty-two per cent had alternated medications, 65.8% of these for temperatures below 38.5 degrees C. Decisions to alternate were influenced by information from doctors/hospitals (49.5%) and children remaining febrile post-antipyretic (41.7%). Most parents reported over-the-counter medications as potentially harmful (73.2%), citing liver (38.2%), stomach (26.4%) and kidney (18.6%) damage and overdose (35.7%) as concerns. When medications were refused or spat out (44.0%), parents used force (62.4%), different methods (29.5%) or suppositories (20.8%). Most parents used over-the-counter medications to reduce fever, often below 38.5 degrees C. The belief that these medications were harmful was overridden by fears of harmful outcomes from fever.

  13. Crossing the impassable: genetic connections in 20 reef fishes across the eastern Pacific barrier

    PubMed Central

    Lessios, H.A; Robertson, D.R

    2006-01-01

    The ‘impassable’ Eastern Pacific Barrier (EPB), ca 5000 km of deep water separating the eastern from the central Pacific, is the World's widest marine biogeographic barrier. Sequencing of mitochondrial DNA in 20 reef fish morphospecies encountered on both sides of the barrier revealed cryptic speciation in two. Among the other 18 species only two showed significant differentiation (as revealed by haplotype networks and FST statistics) between the eastern and the central Pacific. Coalescence analyses indicated that genetic similarity in the 18 truly transpacific species resulted from different combinations of ages of most recent invasion and of levels of recurrent gene flow, with estimated times of initial separation ranging from approximately 30 000 to 1 Myr (ago). There is no suggestion of simultaneous interruptions of gene flow among the species. Migration across the EPB was previously thought to be exclusively eastward, but our evidence showed two invasions from east to west and eight cases in which subsequent gene flow possibly proceeded in the same direction. Thus, the EPB is sporadically permeable to propagules originating on either side. PMID:16901840

  14. Crossing the impassable: genetic connections in 20 reef fishes across the eastern Pacific barrier.

    PubMed

    Lessios, H A; Robertson, D R

    2006-09-07

    The 'impassable' Eastern Pacific Barrier (EPB), ca 5000 km of deep water separating the eastern from the central Pacific, is the World's widest marine biogeographic barrier. Sequencing of mitochondrial DNA in 20 reef fish morphospecies encountered on both sides of the barrier revealed cryptic speciation in two. Among the other 18 species only two showed significant differentiation (as revealed by haplotype networks and FST statistics) between the eastern and the central Pacific. Coalescence analyses indicated that genetic similarity in the 18 truly transpacific species resulted from different combinations of ages of most recent invasion and of levels of recurrent gene flow, with estimated times of initial separation ranging from approximately 30000 to 1 Myr (ago). There is no suggestion of simultaneous interruptions of gene flow among the species. Migration across the EPB was previously thought to be exclusively eastward, but our evidence showed two invasions from east to west and eight cases in which subsequent gene flow possibly proceeded in the same direction. Thus, the EPB is sporadically permeable to propagules originating on either side.

  15. Genetic diversity of Plasmodium Vivax in South of Iran: A cross-sectional study

    PubMed Central

    Sharifi-Sarasiabi, K; Hosseiniteshnizi, S; Dehghan, F; Madani, A

    2015-01-01

    Despite declining the number of malaria cases in Iran, increased prevalence of malaria is supposed to be due to migration from eastern neighboring countries of Iran, which are abundant in Plasmodium vivax (P. vivax). The circumsporozoite protein (CSP) of the P. vivax, is one of the candidate antigens for antimalaria vaccine. The diversity of P. vivax populations circulating in Iran has been investigated by using circumsporozoite protein (CSP) in this study. A hundred and eighteen blood samples were collected from patients diagnosed with P. vivax malaria from south of Iran during 2007-2008. All samples were analyzed by using nested PCR/ RFLP and 18 were sequenced. Genotyping of Pvcsp gene showed that VK210 type was predominant (95%) in south of Iran. Sequence analysis of Pvcsp gene revealed 6 distinct allelic variants in VK210 type. The present data indicate that there is some degree of genetic diversity among P. vivax populations in Hormozgan province of Iran. It seems that in neighbors of Iran, VK210 type is predominant, probably due to similar vector of malaria in these regions.

  16. Reporting of cross-over clinical trials of analgesic treatments for chronic pain: Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks systematic review and recommendations.

    PubMed

    Gewandter, Jennifer S; McDermott, Michael P; McKeown, Andrew; Hoang, Kim; Iwan, Katarzyna; Kralovic, Sarah; Rothstein, Daniel; Gilron, Ian; Katz, Nathaniel P; Raja, Srinivasa N; Senn, Stephen; Smith, Shannon M; Turk, Dennis C; Dworkin, Robert H

    2016-11-01

    Cross-over trials are typically more efficient than parallel group trials in that the sample size required to yield a desired power is substantially smaller. It is important, however, to consider some issues specific to cross-over trials when designing and reporting them, and when evaluating the published results of such trials. This systematic review evaluated the quality of reporting and its evolution over time in articles of cross-over clinical trials of pharmacologic treatments for chronic pain published between 1993 and 2013. Seventy-six (61%) articles reported a within-subject primary analysis, or if no primary analysis was identified, reported at least 1 within-subject analysis, which is required to achieve the gain in power associated with the cross-over design. For 39 (31%) articles, it was unclear whether analyses conducted were within-subject or between-group. Only 36 (29%) articles reported a method to accommodate missing data (eg, last observation carried forward, n = 29), and of those, just 14 included subjects in the analysis who provided data from only 1 period. Of the articles that identified a within-subject primary analysis, 21 (51%) provided sufficient information for the results to be included in a meta-analysis (ie, estimates of the within-subject treatment effect and variability). These results and others presented in this article demonstrate deficiencies in reporting of cross-over trials for analgesic treatments. Clearer reporting in future trials could improve readers' ability to critically evaluate the results, use these data in meta-analyses, and plan future trials. Recommendations for proper reporting of cross-over trials that apply to any condition are provided.

  17. The interplay of DNA methylation over time with Th2 pathway genetic variants on asthma risk and temporal asthma transition.

    PubMed

    Zhang, Hongmei; Tong, Xin; Holloway, John W; Rezwan, Faisal I; Lockett, Gabrielle A; Patil, Veeresh; Ray, Meredith; Everson, Todd M; Soto-Ramírez, Nelís; Arshad, S Hasan; Ewart, Susan; Karmaus, Wilfried

    2014-01-01

    Genetic effects on asthma of genes in the T-helper 2 (Th2) pathway may interact with epigenetic factors including DNA methylation. We hypothesized that interactions between genetic variants and methylation in genes in this pathway (IL4, IL4R, IL13, GATA3, and STAT6) influence asthma risk, that such influences are age-dependent, and that methylation of some CpG sites changes over time in accordance with asthma transition. We tested these hypotheses in subsamples of girls from a population-based birth cohort established on the Isle of Wight, UK, in 1989. Logistic regression models were applied to test the interaction effect of DNA methylation and SNP on asthma within each of the five genes. Bootstrapping was used to assess the models identified. From 1,361 models fitted at each age of 10 and 18 years, 8 models, including 4 CpGs and 8 SNPs, showed potential associations with asthma risk. Of the 4 CpGs, methylation of cg26937798 (IL4R) and cg23943829 (IL4) changes between ages 10 and 18 (both higher at 10; P = 9.14 × 10(-6) and 1.07 × 10(-5), respectively). At age 10, the odds of asthma tended to decrease as cg12405139 (GATA3) methylation increased (log-OR = -12.15; P = 0.049); this effect disappeared by age 18. At age 18, methylation of cg09791102 (IL4R) was associated with higher risk of asthma among subjects with genotype GG compared to AG (P = 0.003), increased cg26937798 methylation among subjects with rs3024685 (IL4R) genotype AA (P = 0.003) or rs8832 (IL4R) genotype GG (P = 0.01) was associated with a lower asthma risk; these CpGs had no effect at age 10. Increasing cg26937798 methylation over time possibly reduced the risk of positive asthma transition (asthma-free at age 10 → asthma at age 18; log-OR = -3.11; P = 0.069) and increased the likelihood of negative transition (asthma at age 10 → asthma-free at age 18; log-OR = 3.97; P = 0.074). The interaction of DNA methylation and SNPs in Th2 pathway

  18. Mechanisms and genetic control of interspecific crossing barriers in Lycopersicon. Final report

    SciTech Connect

    Mutschler, M.A.

    1997-04-30

    Deficiency of Lycopersicon esculentum allele (E) was observed from the RFLP and isozyme data of the F{sub 2} populations derived from the cross L. esculentum x L. pennellii. The genome composition of the F{sub 2} populations containing L. pennellii cytoplasm (F{sub 2}{sup Lp4}) has a lower proportion of the homozygous L. pennellii (PP) genotypes and a higher proportion of heterozygote (EP) genotypes than that of the F{sub 2} populations containing L. esculentum cytoplasm (F{sub 2}{sup Le}). A lower proportion of the L. pennellii alleles (P) was also observed in F{sub 2}{sup Lp4} as compared to F{sub 2}{sup Le} when each marker locus was tested individually. To study the effects of gametic and zygotic selection on segregation distortion, the expected patterns of segregation at a marker locus were derived for ten selection models with gametic or zygotic selection at a hidden linked locus. Segregation distortion caused by four of the selection models studied can be uniquely identified by the patterns of significance expected for the likelihood ratio tests at the marker loci. Comparison of the chromosomal regions associated with specific selection models across populations (of this experiment and previous publications) indicated that the segregation distortion observed in chromosome 10 is associated with zygotic selection affecting both arms of the chromosome, and cytoplasm substitution has the effect of decreasing the segregation distortion on the long arm of the chromosome.

  19. Cross-phenotype association mapping of the MHC identifies genetic variants that differentiate psoriatic arthritis from psoriasis.

    PubMed

    Bowes, John; Ashcroft, James; Dand, Nick; Jalali-Najafabadi, Farideh; Bellou, Eftychia; Ho, Pauline; Marzo-Ortega, Helena; Helliwell, Philip S; Feletar, Marie; Ryan, Anthony W; Kane, David J; Korendowych, Eleanor; Simpson, Michael A; Packham, Jonathan; McManus, Ross; Brown, Matthew A; Smith, Catherine H; Barker, Jonathan N; McHugh, Neil; FitzGerald, Oliver; Warren, Richard B; Barton, Anne

    2017-10-01

    Psoriatic arthritis (PsA) is a chronic inflammatory arthritis, with a strong heritable component, affecting patients with psoriasis. Here we attempt to identify genetic variants within the major histocompatibility complex (MHC) that differentiate patients with PsA from patients with cutaneous psoriasis alone (PsC). 2808 patients with PsC, 1945 patients with PsA and 8920 population controls were genotyped. We imputed SNPs, amino acids and classical HLA alleles across the MHC and tested for association with PsA compared to population controls and the PsC patient group. In addition we investigated the impact of the age of disease onset on associations. HLA-C*06:02 was protective of PsA compared to PsC (p=9.57×10(-66), OR 0.37). The HLA-C*06:02 risk allele was associated with a younger age of psoriasis onset in all patients (p=1.01×10(-59)). After controlling for the age of psoriasis onset no association of PsA to HLA-C*06:02 (p=0.07) was observed; instead, the most significant association was to amino acid at position 97 of HLA-B (p=1.54×10(-9)) where the presence of asparagine or serine residue increased PsA risk. Asparagine at position 97 of HLA-B defines the HLA-B*27 alleles. By controlling for the age of psoriasis onset, we show, for the first time, that HLA-C*06:02 is not associated with PsA and that amino acid position 97 of HLA-B differentiates PsA from PsC. This amino acid also represents the largest genetic effect for ankylosing spondylitis, thereby refining the genetic overlap of these two spondyloarthropathies. Correcting for bias has important implications for cross-phenotype genetic studies. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. Integrating serological and genetic data to quantify cross-species transmission: brucellosis as a case study.

    PubMed

    Viana, Mafalda; Shirima, Gabriel M; John, Kunda S; Fitzpatrick, Julie; Kazwala, Rudovick R; Buza, Joram J; Cleaveland, Sarah; Haydon, Daniel T; Halliday, Jo E B

    2016-06-01

    Epidemiological data are often fragmented, partial, and/or ambiguous and unable to yield the desired level of understanding of infectious disease dynamics to adequately inform control measures. Here, we show how the information contained in widely available serology data can be enhanced by integration with less common type-specific data, to improve the understanding of the transmission dynamics of complex multi-species pathogens and host communities. Using brucellosis in northern Tanzania as a case study, we developed a latent process model based on serology data obtained from the field, to reconstruct Brucella transmission dynamics. We were able to identify sheep and goats as a more likely source of human and animal infection than cattle; however, the highly cross-reactive nature of Brucella spp. meant that it was not possible to determine which Brucella species (B. abortus or B. melitensis) is responsible for human infection. We extended our model to integrate simulated serology and typing data, and show that although serology alone can identify the host source of human infection under certain restrictive conditions, the integration of even small amounts (5%) of typing data can improve understanding of complex epidemiological dynamics. We show that data integration will often be essential when more than one pathogen is present and when the distinction between exposed and infectious individuals is not clear from serology data. With increasing epidemiological complexity, serology data become less informative. However, we show how this weakness can be mitigated by integrating such data with typing data, thereby enhancing the inference from these data and improving understanding of the underlying dynamics.

  1. Effects of adding chymosin to milk on calcium homeostasis: a randomized, double-blind, cross-over study.

    PubMed

    Møller, Ulla Kristine; Jensen, Lars Thorbjørn; Mosekilde, Leif; Rejnmark, Lars

    2015-02-01

    Calcium intake and absorption is important for bone health. In a randomized double-blind cross-over trial, we investigated effects of adding chymosin to milk on the intestinal calcium absorption as measured by renal calcium excretion and indices of calcium homeostasis. The primary outcome of the study was 24-h renal calcium excretion that is considered a proxy measure of the amount of calcium absorbed from the intestine. We studied 125 healthy men and women, aged 34 (25-45) years on two separate days. On each day, a light breakfast was served together with 500 ml of semi-skimmed milk to which either chymosin or similar placebo was added. Compared with placebo, chymosin did not affect 24-h urinary calcium, calcium/creatinine ratio, plasma parathyroid hormone, calcitonin or ionized calcium levels. However, during the first 4 h after intake of milk with chymosin, urinary calcium-creatinine ratio was significantly increased (17%) compared with placebo. Stratification by daily calcium intake showed effect of chymosin in participant with a habitual intake above the median (>1,050 mg/day) in whom both urinary calcium and calcium/creatinine ratio were significantly increased compared with placebo. Effects did not depend on plasma 25-hydroxyvitamin D levels. Chymosin added to milk increases renal calcium excretion in the hours following intake without affecting plasma levels of calcium or calciotropic hormones. The effect most likely represents enhanced intestinal calcium absorption shortly after intake. Further studies are warranted on whether intake of milk-added chymosin may cause beneficial effects on bone. www.ClinicalTrials.gov no. NCT01370941.

  2. Glycemic Response to Black Beans and Chickpeas as Part of a Rice Meal: A Randomized Cross-Over Trial.

    PubMed

    Winham, Donna M; Hutchins, Andrea M; Thompson, Sharon V

    2017-10-04

    Legumes, such as black beans (Phaseolus vulgaris L.) and chickpeas (Cicer arietinum L.), have a low glycemic index, and may reduce the glycemic load of meals in which they are included. Although the low glycemic response of beans consumed alone has been documented, few studies have examined the glycemic response to traditional food combinations such as black beans and rice or chickpeas and rice. This randomized cross-over study examined the glycemic and insulinemic impact of 50 grams of available carbohydrate from three test meals: plain white rice (control), black beans with rice, and chickpeas with rice among healthy adult women (n = 12, 18-65 years). Treatments were consumed on different mornings, a minimum of 7 days apart. Blood samples were collected at time 0 (fasting), and at 30, 60, 90, and 120 min postprandial, and were subsequently analyzed for glucose and insulin concentrations. Glucose response based on the incremental area under the curve showed a significant difference by treatment (p = 0.027). Changes in blood glucose concentrations were significantly different for the black bean meal and the chickpea meal in comparison to rice alone at 60 min (p = 0.026 and p = 0.024), 90 min (p = 0.001 and p = 0.012) and 120 min post prandial (p = 0.024; black bean meal). Findings indicate that combinations of black beans and chickpeas with white rice improve glycemic response, providing evidence that has promising implications for dietary guidance to reduce postprandial glucose and related health risks through traditional food patterns.

  3. Postprandial effects of calcium phosphate supplementation on plasma concentration-double-blind, placebo-controlled cross-over human study.

    PubMed

    Trautvetter, Ulrike; Kiehntopf, Michael; Jahreis, Gerhard

    2013-03-08

    The aim of the present study was to examine the postprandial calcium and phosphate concentrations after supplementation with pentacalcium hydroxy-triphosphate (CaP). Ten men participated in this double-blind, placebo-controlled, cross-over study. The participants were divided into two groups. One group consumed bread enriched with CaP (plus 1 g calcium/d) and the other group a placebo product for three weeks. After a two week wash-out, the intervention was switched between the groups for another three weeks. Blood samples were drawn at the beginning (single administration) and at the end (repeated administration) of the intervention periods at 0, 30, 60, 120, 180 and 240 min. Between 0 and 30 min, a test meal, with or without CaP was consumed. The plasma concentrations of calcium and phosphate were examined. One participant dropped out due to personal reasons. CaP supplementation resulted in a significantly higher plasma calcium concentration after 240 min compared to placebo. After repeated CaP administration, the AUC for the increment in plasma calcium concentration was significantly higher compared to placebo.After single and repeated CaP supplementation, plasma phosphate concentration significantly decreased after 30, 60, 120 and 180 min compared to 0 min. The placebo administration resulted in significant decreases after 30, 60 and 120 min compared to 0 min. Our results show that CaP contributes to an adequate calcium supply, but without increasing the plasma concentration of phosphate. www.clinicaltrials.gov; NCT01296997.

  4. Postprandial effects of calcium phosphate supplementation on plasma concentration-double-blind, placebo-controlled cross-over human study

    PubMed Central

    2013-01-01

    Background The aim of the present study was to examine the postprandial calcium and phosphate concentrations after supplementation with pentacalcium hydroxy-triphosphate (CaP). Methods Ten men participated in this double-blind, placebo-controlled, cross-over study. The participants were divided into two groups. One group consumed bread enriched with CaP (plus 1 g calcium/d) and the other group a placebo product for three weeks. After a two week wash-out, the intervention was switched between the groups for another three weeks. Blood samples were drawn at the beginning (single administration) and at the end (repeated administration) of the intervention periods at 0, 30, 60, 120, 180 and 240 min. Between 0 and 30 min, a test meal, with or without CaP was consumed. The plasma concentrations of calcium and phosphate were examined. One participant dropped out due to personal reasons. Results CaP supplementation resulted in a significantly higher plasma calcium concentration after 240 min compared to placebo. After repeated CaP administration, the AUC for the increment in plasma calcium concentration was significantly higher compared to placebo. After single and repeated CaP supplementation, plasma phosphate concentration significantly decreased after 30, 60, 120 and 180 min compared to 0 min. The placebo administration resulted in significant decreases after 30, 60 and 120 min compared to 0 min. Conclusion Our results show that CaP contributes to an adequate calcium supply, but without increasing the plasma concentration of phosphate. Trial registration http://www.clinicaltrials.gov; NCT01296997 PMID:23510513

  5. Effects of almond and pistachio consumption on gut microbiota composition in a randomised cross-over human feeding study.

    PubMed

    Ukhanova, Maria; Wang, Xiaoyu; Baer, David J; Novotny, Janet A; Fredborg, Marlene; Mai, Volker

    2014-06-28

    The modification of microbiota composition to a 'beneficial' one is a promising approach for improving intestinal as well as overall health. Natural fibres and phytochemicals that reach the proximal colon, such as those present in various nuts, provide substrates for the maintenance of healthy and diverse microbiota. The effects of increased consumption of specific nuts, which are rich in fibre as well as various phytonutrients, on human gut microbiota composition have not been investigated to date. The objective of the present study was to determine the effects of almond and pistachio consumption on human gut microbiota composition. We characterised microbiota in faecal samples collected from volunteers in two separate randomised, controlled, cross-over feeding studies (n 18 for the almond feeding study and n 16 for the pistachio feeding study) with 0, 1·5 or 3 servings/d of the respective nuts for 18 d. Gut microbiota composition was analysed using a 16S rRNA-based approach for bacteria and an internal transcribed spacer region sequencing approach for fungi. The 16S rRNA sequence analysis of 528 028 sequence reads, retained after removing low-quality and short-length reads, revealed various operational taxonomic units that appeared to be affected by nut consumption. The effect of pistachio consumption on gut microbiota composition was much stronger than that of almond consumption and included an increase in the number of potentially beneficial butyrate-producing bacteria. Although the numbers of bifidobacteria were not affected by the consumption of either nut, pistachio consumption appeared to decrease the number of lactic acid bacteria (P< 0·05). Increasing the consumption of almonds or pistachios appears to be an effective means of modifying gut microbiota composition.

  6. Acute effects of beer on endothelial function and haemodynamics: a single-blind, cross-over study in healthy volunteers

    PubMed Central

    Karatzi, Kalliopi; Rontoyanni, Victoria G.; Protogerou, Athanase D.; Georgoulia, Aggeliki; Xenos, Konstantinos; Chrysou, John; Sfikakis, Petros P.; Sidossis, Labros S.

    2015-01-01

    Objective Moderate consumption of beer is associated with lower cardiovascular (CV) risk. To explore the underlying mechanisms we studied the acute effects of the constituents of beer (alcohol and antioxidants), on established predictors of CV risk: endothelial function, aortic stiffness, pressure wave reflections and aortic pressure. Research Methods & Proceedures In a randomized, single – blind, cross - over study 17 healthy, non-smoking, volunteers (28.5±5.2 years and 24.4±2.5 BMI) consumed in 3 separate days, at least one week apart: a) 400 ml of beer & 400 ml water, b) 800 ml of dealcoholized beer (same amount of polyphenols), and c) 67 ml of vodka & 733 ml water (same amount of alcohol). Each time aortic stiffness (pulse wave velocity, pressure wave reflections (Aix), aortic and brachial pressure (Sphygmocor device) and endothelial function (brachial flow mediated dilatation) were assessed at fast and 1 and 2 hours postprandial. Results Aortic stiffness was significantly and similarly reduced by all 3 interventions. However, endothelial function was significantly improved only after beer consumption (average of 1.33%, CI 0.15-2.53). Although wave reflections were significantly reduced by all 3 interventions (average of beer: 9.1%, dealcoholized beer: 2.8%, vodka 8.5%, all CI within limits of significance), the reduction was higher after beer consumption compared todealcoholized beer (p=0.018). Pulse pressure amplification (i.e. brachial/aortic) was increased by all 3 test drinks. Conclusions Beer improves acutely parameters of arterial function and structure, in healthy non-smokers. This benefit seems to be mediated by the additive or synergistic effects of alcohol and anti-oxidants and merits further investigation. PMID:23810643

  7. Effects of music therapy on pain responses induced by blood sampling in premature infants: A randomized cross-over trial

    PubMed Central

    Shabani, Fidan; Nayeri, Nahid Dehghan; Karimi, Roghiyeh; Zarei, Khadijeh; Chehrazi, Mohammad

    2016-01-01

    Background: Premature infants are subjected to many painful procedures during care and treatment. The aim of this study was to assess the effect of music therapy on physiological and behavioral pain responses of premature infants during and after blood sampling. Materials and Methods: This study was a cross-over clinical trial conducted on 20 infants in a hospital affiliated to Tehran University of Medical Sciences for a 5-month period in 2011. In the experimental group, Transitions music was played from 5 min before until 10 min after blood sampling. The infants’ facial expressions and physiological measures were recorded from 10 min before until 10 min after sampling. All steps and measurements, except music therapy, were the same for the control group. Data were analyzed using SAS and SPSS software through analysis of variance (ANOVA) and Chi-square tests. Results: There were significant differences between the experimental and control groups (P = 0.022) in terms of heart rate during needle extraction and at the first 5 min after sampling (P = 0.005). Considering the infant's sleep–wake state in the second 5 min before sampling, the statistical difference was significant (P = 0.044). Difference was significant (P = 0.045) during injection of the needle, in the first 5 min after sampling (P = 0.002), and in the second 5 min after sampling (P = 0.005). There were significant difference in infants’ facial expressions of pain in the first 5 min after sampling (P = 0.001). Conclusions: Music therapy reduces the physiological and behavioral responses of pain during and after blood sampling. PMID:27563323

  8. Randomized cross-over trial of ventilator modes during non-invasive ventilation titration in amyotrophic lateral sclerosis.

    PubMed

    Vrijsen, Bart; Buyse, Bertien; Belge, Catharina; Vanpee, Goele; Van Damme, Philip; Testelmans, Dries

    2017-08-01

    Non-invasive ventilation (NIV) improves survival, quality of life and sleep in patients with amyotrophic lateral sclerosis (ALS). Nevertheless, NIV titration is conducted in different ways. We aim to provide more insight into NIV titration by comparing the effects of a spontaneous (S) and spontaneous-timed (ST) modes on gas exchange, sleep architecture and patient-ventilator asynchronies (PVAs). After an initial night of NIV titration, patients were randomized to S or ST mode in a cross-over design. NIV was titrated using polysomnography, oximetry (oxygen saturation, SpO2 %) and transcutaneous carbon dioxide (PtcCO2 ) measurement. PVAs were analysed breath-by-breath. Thirteen patients were analysed after inclusion. ST mode showed better results in gas exchange (minimal SpO2 %: 83 (80-89)% vs 87 (84-89)%; oxygen desaturation index: 15 (5-28)/h sleep vs 7 (3-9)/h sleep; PtcCO2 >55 mm Hg: 20 (0-59)% vs 0 (0-27)% total sleep time for S and ST mode, respectively, all P < 0.05) and respiratory events (obstructive: 8.9 (1.2-18.3)/h sleep vs 1.8 (0.3-4.9)/h sleep and central: 2.6 (0.4-14.1)/h sleep vs 0.2 (0.0-1.1)/h sleep for S and ST mode, respectively, both P < 0.01). No differences in sleep architecture were found. Ineffective efforts and respiratory events were more frequently present in S mode. Nevertheless, four patients were discharged on S mode as these patients showed clinically better results for sleep architecture and PVA during the night on S mode. ST mode shows better results in gas exchange, respiratory events and PVA. Nevertheless, accurate NIV titration remains necessary as some patients show equal or better results when using the S mode. © 2017 Asian Pacific Society of Respirology.

  9. Effects of pressure applied during standardized spinal mobilizations on peripheral skin blood flow: A randomised cross-over study.

    PubMed

    Zegarra-Parodi, Rafael; Pazdernik, Vanessa K; Roustit, Matthieu; Park, Peter Yong Soo; Degenhardt, Brian F

    2016-02-01

    Peripheral skin blood flow (SBF) changes during and after spinal mobilization (SM), evaluated with laser Doppler flowmetry, may document physiological responses associated with SM. To document variations in SBF during and after application of an SM and evaluate influence of pressure on SBF by applying the same standardized SM with 3 different nonnoxious pressures. Cross-over design with 4 interventions on 4 different days: control (no touch) and 3 SMs applied rhythmically at 5%, 40%, or 80% of pain pressure threshold (sham SM, low-pressure SM, or high-pressure SM, respectively). Thirty-two individuals participated. The inspiratory gasp (IG) test was our positive control of vasoconstriction through excitation of the skin sympathetic nervous activity (SSNA). Each session comprised 5 phases: (1) baseline at the end of a 20-min acclimatization, (2) IG test, (3) post-IG phase, (4) SM phase or no manual contact for control, and (5) post-SM phase. A Biopac MP36 system collected SBF data, and a Novel Pliance-X system recorded pressure data. Equal and significant bilateral vasodilation occurred during application of unilateral sham SM, low-pressure SM, and high-pressure SM. Post-SM significant vasodilation persisted after high-pressure SM. The current study is the first to describe bilateral peripheral SBF changes occurring during and 5 min after application of standardized SMs. Our post-SM vasodilation suggests involvement of mechanisms other than the putative SSNA-excitatory mechanism proposed with skin conductance measurements. Persistence of post-SM vasodilation following only high-pressure SM suggests possible pressure-dependent mechanisms. However, further research is warranted to clarify our findings. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Effects of music therapy on pain responses induced by blood sampling in premature infants: A randomized cross-over trial.

    PubMed

    Shabani, Fidan; Nayeri, Nahid Dehghan; Karimi, Roghiyeh; Zarei, Khadijeh; Chehrazi, Mohammad

    2016-01-01

    Premature infants are subjected to many painful procedures during care and treatment. The aim of this study was to assess the effect of music therapy on physiological and behavioral pain responses of premature infants during and after blood sampling. This study was a cross-over clinical trial conducted on 20 infants in a hospital affiliated to Tehran University of Medical Sciences for a 5-month period in 2011. In the experimental group, Transitions music was played from 5 min before until 10 min after blood sampling. The infants' facial expressions and physiological measures were recorded from 10 min before until 10 min after sampling. All steps and measurements, except music therapy, were the same for the control group. Data were analyzed using SAS and SPSS software through analysis of variance (ANOVA) and Chi-square tests. There were significant differences between the experimental and control groups (P = 0.022) in terms of heart rate during needle extraction and at the first 5 min after sampling (P = 0.005). Considering the infant's sleep-wake state in the second 5 min before sampling, the statistical difference was significant (P = 0.044). Difference was significant (P = 0.045) during injection of the needle, in the first 5 min after sampling (P = 0.002), and in the second 5 min after sampling (P = 0.005). There were significant difference in infants' facial expressions of pain in the first 5 min after sampling (P = 0.001). Music therapy reduces the physiological and behavioral responses of pain during and after blood sampling.

  11. A cross-over study with the two novel dopaminergic drugs cabergoline and quinagolide in hyperprolactinemic patients.

    PubMed

    Giusti, M; Porcella, E; Carraro, A; Cuttica, M; Valenti, S; Giordano, G

    1994-01-01

    Cabergoline and quinagolide, two new dopamine agonist drugs with long-lasting activity, are currently under investigation for the treatment of hyperprolactinemia. At present, studies comparing these drugs for tolerability and efficacy in the same patients are lacking. It was our aim to make such a comparison in an open randomized cross-over trial. Cabergoline (0.5 mg twice weekly) and quinagolide (75 micrograms once daily) were given orally. Each drug was administered for 12 weeks. Treatment with the second drug was started after the recurrence of hyperprolactinemia. Twelve women with hyperprolactinemia due to idiopathic disease (n = 6), microprolactinoma (n = 5) or postsurgical empty sella (n = 1) were evaluated. Six women were amenorrheic and 6 were oligomenorrheic. Ten had spontaneous or provoked galactorrhea. Baseline characteristics (age, clinical signs and PRL levels) of patients initially allocated to the two treatment groups were similar. Nine patients completed both treatment cycles and PRL levels were lower under cabergoline (10.7 +/- 3.7 micrograms/L) than under quinagolide (25.0 +/- 7.7 micrograms/L; p < 0.05). One patient discontinued cabergoline because of dryness of the eyes after having completed the quinagolide cycle and 2 patients initially treated with cabergoline discontinued quinagolide because of gastrointestinal symptoms. After completion of the first treatment cycle, the time of recurrence of hyperprolactinemia was significantly longer after cabergoline (14 +/- 7 weeks) than after quinagolide (5 +/- 1 weeks; p < 0.05). At week 12, normal PRL levels (< 20 micrograms/L) were observed in 10 and 6 women during cabergoline and quinagolide, respectively. Only one case was resistant to both drugs. The clinical effects of the two treatments were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Health effects of green tea catechins in overweight and obese men: a randomised controlled cross-over trial.

    PubMed

    Brown, A L; Lane, J; Holyoak, C; Nicol, B; Mayes, A E; Dadd, T

    2011-12-01

    Regular consumption of green tea may be cardioprotective. In the present study we investigated the health effects of dietary supplementation with green tea catechins and the potential modifying effect of the catechol-O-methyltransferase (COMT) Val/Met genotype. Subjects (sedentary males, aged 40-69 years, with BMI ≥ 28 and ≤ 38 kg/m(2)) were randomly assigned to consume decaffeinated green tea extract (DGT; 530 mg containing about 400 mg total catechins/capsule, twice daily) and placebo in a complete cross-over design. Ambulatory blood pressure and biomarkers of metabolic function (cholesterol, TAG, glucose and insulin) were measured at weeks 0 and 6. Although a marked increase in the concentration of plasma epigallocatechin gallate (EGCG), urinary epigallocatechin (EGC) and urinary 4'-O-methyl EGC was found after DGT treatment, no effect on blood pressure or biomarkers of metabolic function was observed. However, a period × treatment interaction (P < 0·05) was detected for body-weight change. Despite a similar increase in estimated energy intake during intervention period 1, body weight decreased by 0·64 (sd 2·2) kg and increased by 0·53 (sd 1·9) kg in the DGT and placebo groups, respectively (P = 0·025), suggesting a protective effect of green tea catechins on weight gain. Additionally, the COMT Val/Met genotype influenced urinary accumulation of EGC and 4'-O-methyl EGC (P < 0·01). Mean concentrations were lower in individuals homozygous for the high-activity G-allele, possibly reflecting increased metabolic flux and a more rapid conversion to downstream metabolic species, compared with individuals carrying at least one copy of the low-activity A-allele. Additional studies are needed to confirm these findings and further explore the modifying effect of genotype.

  13. Medical professionals' perspectives on prescribed and over-the-counter medicines containing codeine: a cross-sectional study.

    PubMed

    Foley, Michelle; Carney, Tara; Rich, Eileen; Parry, Charles; Van Hout, Marie-Claire; Deluca, Paolo

    2016-07-14

    To explore prescribing practitioners' perspectives on prescribed codeine use, their ability to identify dependence and their options for treatment in the UK. Cross-sectional design using a questionnaire containing closed-ended and open-ended items. A nationally representative sample of prescribing professionals working in the UK. 300 prescribing professionals working in primary care and pain settings. Participants stated that they regularly reviewed patients prescribed codeine, understood the risks of dependence and recognised the potential for codeine to be used recreationally. Over half the participants felt patients were unaware of the adverse health consequences of high doses of combination codeine medicines. One-quarter of participants experienced patient resentment when asking about medicines containing codeine. Just under 40% of participants agreed that it was difficult to identify problematic use of codeine without being informed by the patient and did not feel confident in identification of codeine dependence. Less than 45% of all participants agreed that codeine dependence could be managed effectively in general practice. Slow or gradual withdrawal was the most popular suggested treatment in managing dependence. Education and counselling was also emphasised in managing codeine-dependent patients in primary care. Communication with patients should involve assessment of patient understanding of their medication, including the risk of dependence. There is a need to develop extra supports for professionals including patient screening tools for identifying codeine dependence. The support structure for managing codeine-dependent patients in primary care requires further examination. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-serv