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Sample records for loci controls resistance

  1. QTL meta-analysis provides a comprehensive view of loci controlling partial resistance to Aphanomyces euteiches in four sources of resistance in pea

    Technology Transfer Automated Retrieval System (TEKTRAN)

    More knowledge about diversity of Quantitative Trait Loci (QTL) controlling polygenic disease resistance in natural genetic variation of crop species is required for durably improving plant genetic resistances to pathogens. Polygenic partial resistance to Aphanomyces root rot, due to Aphanomcyces eu...

  2. Identification of quantitative trait loci controlling resistance to maize chlorotic dwarf virus.

    PubMed

    Jones, Mark W; Redinbaugh, Margaret G; Anderson, Robert J; Louie, R

    2004-12-01

    Ineffective screening methods and low levels of disease resistance have hampered genetic analysis of maize (Zea mays L.) resistance to disease caused by maize chlorotic dwarf virus (MCDV). Progeny from a cross between the highly resistant maize inbred line Oh1VI and the susceptible inbred line Va35 were evaluated for MCDV symptoms after multiple virus inoculations, using the viral vector Graminella nigrifrons. Symptom severity scores from three rating dates were used to calculate area under the disease progress curve (AUDPC) scores for vein banding, leaf twist and tear, and whorl chlorosis. AUDPC scores for the F(2) population indicated that MCDV resistance was quantitatively inherited. Genotypic and phenotypic analyses of 314 F(2) individuals were compared using composite interval mapping (CIM) and analysis of variance. CIM identified two major quantitative trait loci (QTL) on chromosomes 3 and 10 and two minor QTL on chromosomes 4 and 6. Resistance was additive, with alleles from Oh1VI at the loci on chromosomes 3 and 10 contributing equally to resistance.

  3. Genotyping-by-sequencing markers facilitate the identification of quantitative trait loci controlling resistance to Penicillium expansum in Malus sieversii.

    PubMed

    Norelli, John L; Wisniewski, Michael; Fazio, Gennaro; Burchard, Erik; Gutierrez, Benjamin; Levin, Elena; Droby, Samir

    2017-01-01

    Blue mold caused by Penicillium expansum is the most important postharvest disease of apple worldwide and results in significant financial losses. There are no defined sources of resistance to blue mold in domesticated apple. However, resistance has been described in wild Malus sieversii accessions, including plant introduction (PI)613981. The objective of the present study was to identify the genetic loci controlling resistance to blue mold in this accession. We describe the first quantitative trait loci (QTL) reported in the Rosaceae tribe Maleae conditioning resistance to P. expansum on genetic linkage group 3 (qM-Pe3.1) and linkage group 10 (qM-Pe10.1). These loci were identified in a M.× domestica 'Royal Gala' X M. sieversii PI613981 family (GMAL4593) based on blue mold lesion diameter seven days post-inoculation in mature, wounded apple fruit inoculated with P. expansum. Phenotypic analyses were conducted in 169 progeny over a four year period. PI613981 was the source of the resistance allele for qM-Pe3.1, a QTL with a major effect on blue mold resistance, accounting for 27.5% of the experimental variability. The QTL mapped from 67.3 to 74 cM on linkage group 3 of the GMAL4593 genetic linkage map. qM-Pe10.1 mapped from 73.6 to 81.8 cM on linkage group 10. It had less of an effect on resistance, accounting for 14% of the experimental variation. 'Royal Gala' was the primary contributor to the resistance effect of this QTL. However, resistance-associated alleles in both parents appeared to contribute to the least square mean blue mold lesion diameter in an additive manner at qM-Pe10.1. A GMAL4593 genetic linkage map composed of simple sequence repeats and 'Golden Delicious' single nucleotide polymorphism markers was able to detect qM-Pe10.1, but failed to detect qM-Pe3.1. The subsequent addition of genotyping-by-sequencing markers to the linkage map provided better coverage of the PI613981 genome on linkage group 3 and facilitated discovery of qM-Pe3.1. A DNA

  4. Genotyping-by-sequencing markers facilitate the identification of quantitative trait loci controlling resistance to Penicillium expansum in Malus sieversii

    PubMed Central

    Wisniewski, Michael; Fazio, Gennaro; Burchard, Erik; Gutierrez, Benjamin; Levin, Elena; Droby, Samir

    2017-01-01

    Blue mold caused by Penicillium expansum is the most important postharvest disease of apple worldwide and results in significant financial losses. There are no defined sources of resistance to blue mold in domesticated apple. However, resistance has been described in wild Malus sieversii accessions, including plant introduction (PI)613981. The objective of the present study was to identify the genetic loci controlling resistance to blue mold in this accession. We describe the first quantitative trait loci (QTL) reported in the Rosaceae tribe Maleae conditioning resistance to P. expansum on genetic linkage group 3 (qM-Pe3.1) and linkage group 10 (qM-Pe10.1). These loci were identified in a M.× domestica ‘Royal Gala’ X M. sieversii PI613981 family (GMAL4593) based on blue mold lesion diameter seven days post-inoculation in mature, wounded apple fruit inoculated with P. expansum. Phenotypic analyses were conducted in 169 progeny over a four year period. PI613981 was the source of the resistance allele for qM-Pe3.1, a QTL with a major effect on blue mold resistance, accounting for 27.5% of the experimental variability. The QTL mapped from 67.3 to 74 cM on linkage group 3 of the GMAL4593 genetic linkage map. qM-Pe10.1 mapped from 73.6 to 81.8 cM on linkage group 10. It had less of an effect on resistance, accounting for 14% of the experimental variation. ‘Royal Gala’ was the primary contributor to the resistance effect of this QTL. However, resistance-associated alleles in both parents appeared to contribute to the least square mean blue mold lesion diameter in an additive manner at qM-Pe10.1. A GMAL4593 genetic linkage map composed of simple sequence repeats and ‘Golden Delicious’ single nucleotide polymorphism markers was able to detect qM-Pe10.1, but failed to detect qM-Pe3.1. The subsequent addition of genotyping-by-sequencing markers to the linkage map provided better coverage of the PI613981 genome on linkage group 3 and facilitated discovery of q

  5. Comparative analysis of quantitative trait loci controlling glucosinolates, myrosinase and insect resistance in Arabidopsis thaliana.

    PubMed Central

    Kliebenstein, Daniel; Pedersen, Deana; Barker, Bridget; Mitchell-Olds, Thomas

    2002-01-01

    Evolutionary interactions among insect herbivores and plant chemical defenses have generated systems where plant compounds have opposing fitness consequences for host plants, depending on attack by various insect herbivores. This interplay complicates understanding of fitness costs and benefits of plant chemical defenses. We are studying the role of the glucosinolate-myrosinase chemical defense system in protecting Arabidopsis thaliana from specialist and generalist insect herbivory. We used two Arabidopsis recombinant inbred populations in which we had previously mapped QTL controlling variation in the glucosinolate-myrosinase system. In this study we mapped QTL controlling resistance to specialist (Plutella xylostella) and generalist (Trichoplusia ni) herbivores. We identified a number of QTL that are specific to one herbivore or the other, as well as a single QTL that controls resistance to both insects. Comparison of QTL for herbivory, glucosinolates, and myrosinase showed that T. ni herbivory is strongly deterred by higher glucosinolate levels, faster breakdown rates, and specific chemical structures. In contrast, P. xylostella herbivory is uncorrelated with variation in the glucosinolate-myrosinase system. This agrees with evolutionary theory stating that specialist insects may overcome host plant chemical defenses, whereas generalists will be sensitive to these same defenses. PMID:12019246

  6. QTL meta-analysis provides a comprehensive view of loci controlling partial resistance to Aphanomyces euteiches in four sources of resistance in pea

    PubMed Central

    2013-01-01

    the moderately low diversity of loci controlling partial resistance to A. euteiches in four main sources of resistance in pea. Seven highly consistent genomic regions with potential use in marker-assisted-selection were identified. Confidence intervals at several main QTL regions were reduced and co-segregation among resistance and morphological/phenological alleles was identified. Further work will be required to identify the best combinations of QTL for durably increasing partial resistance to A. euteiches. PMID:23497245

  7. Multiple Avirulence Loci and Allele-Specific Effector Recognition Control the Pm3 Race-Specific Resistance of Wheat to Powdery Mildew[OPEN

    PubMed Central

    Roffler, Stefan; Stirnweis, Daniel; Treier, Georges; Herren, Gerhard; Korol, Abraham B.; Wicker, Thomas

    2015-01-01

    In cereals, several mildew resistance genes occur as large allelic series; for example, in wheat (Triticum aestivum and Triticum turgidum), 17 functional Pm3 alleles confer agronomically important race-specific resistance to powdery mildew (Blumeria graminis). The molecular basis of race specificity has been characterized in wheat, but little is known about the corresponding avirulence genes in powdery mildew. Here, we dissected the genetics of avirulence for six Pm3 alleles and found that three major Avr loci affect avirulence, with a common locus_1 involved in all AvrPm3-Pm3 interactions. We cloned the effector gene AvrPm3a2/f2 from locus_2, which is recognized by the Pm3a and Pm3f alleles. Induction of a Pm3 allele-dependent hypersensitive response in transient assays in Nicotiana benthamiana and in wheat demonstrated specificity. Gene expression analysis of Bcg1 (encoded by locus_1) and AvrPm3 a2/f2 revealed significant differences between isolates, indicating that in addition to protein polymorphisms, expression levels play a role in avirulence. We propose a model for race specificity involving three components: an allele-specific avirulence effector, a resistance gene allele, and a pathogen-encoded suppressor of avirulence. Thus, whereas a genetically simple allelic series controls specificity in the plant host, recognition on the pathogen side is more complex, allowing flexible evolutionary responses and adaptation to resistance genes. PMID:26452600

  8. Chlamydomonas reinhardtii strains expressing nitrate reductase under control of the cabII-1 promoter: isolation of chlorate resistant mutants and identification of new loci for nitrate assimilation.

    PubMed

    Navarro, María Teresa; Mariscal, Vicente; Macías, María Isabel; Fernández, Emilio; Galván, Aurora

    2005-01-01

    The Chlamydomonas reinhardtii strain Tx11-8 is a transgenic alga that bears the nitrate reductase gene (Nia1) under control of the CabII-1 gene promoter (CabII-1-Nia1). Approximately nine copies of the chimeric CabII-1-Nia1 gene were found to be integrated in this strain and to confer a phenotype of chlorate sensitivity in the presence of ammonium. We have used this strain for the isolation of spontaneous chlorate resistant mutants in the presence of ammonium that were found to be defective at loci involved in MoCo metabolism and light-dependent growth in nitrate media. Of a total of 45 mutant strains analyzed first, 44 were affected in the MoCo activity (16 Nit(-), unable to grow in nitrate, and 28 Nit(+), able to grow in nitrate). All the Nit(-) strains lacked MoCo activity. Diploid complementation of Nit(-), MoCo(-) strains with C. reinhardtii MoCo mutants and genetic analysis indicated that some strains were defective at known loci for MoCo biosynthesis, while three strains were defective at two new loci, hereafter named Nit10 and Nit11. The other 28 Nit(+) strains showed almost undetectable MoCo activity or activity was below 20% of the parental strain. Second, only one strain (named 23c(+)) showed MoCo and NR activities comparable to those in the parental strain. Strain 23c(+) seems to be affected in a locus, Nit12, required for growth in nitrate under continuous light. It is proposed that this locus is required for nitrate/chlorate transport activity. In this work, mechanisms of chlorate toxicity are reviewed in the light of our results.

  9. Quantitative trait loci associated with anthracnose resistance in sorghum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    With an aim to develop a durable resistance to the fungal disease anthracnose, two unique genetic sources of resistance were selected to create genetic mapping populations to identify regions of the sorghum genome that encode anthracnose resistance. A series of quantitative trait loci were identifi...

  10. The Red Queen lives: Epistasis between linked resistance loci.

    PubMed

    Metzger, César M J A; Luijckx, Pepijn; Bento, Gilberto; Mariadassou, Mahendra; Ebert, Dieter

    2016-02-01

    A popular theory explaining the maintenance of genetic recombination (sex) is the Red Queen Theory. This theory revolves around the idea that time-lagged negative frequency-dependent selection by parasites favors rare host genotypes generated through recombination. Although the Red Queen has been studied for decades, one of its key assumptions has remained unsupported. The signature host-parasite specificity underlying the Red Queen, where infection depends on a match between host and parasite genotypes, relies on epistasis between linked resistance loci for which no empirical evidence exists. We performed 13 genetic crosses and tested over 7000 Daphnia magna genotypes for resistance to two strains of the bacterial pathogen Pasteuria ramosa. Results reveal the presence of strong epistasis between three closely linked resistance loci. One locus masks the expression of the other two, while these two interact to produce a single resistance phenotype. Changing a single allele on one of these interacting loci can reverse resistance against the tested parasites. Such a genetic mechanism is consistent with host and parasite specificity assumed by the Red Queen Theory. These results thus provide evidence for a fundamental assumption of this theory and provide a genetic basis for understanding the Red Queen dynamics in the Daphnia-Pasteuria system.

  11. Temporal and multiple quantitative trait loci analyses of resistance to bacterial wilt in tomato permit the resolution of linked loci.

    PubMed Central

    Mangin, B; Thoquet, P; Olivier, J; Grimsley, N H

    1999-01-01

    Ralstonia solanacearum is a soil-borne bacterium that causes the serious disease known as bacterial wilt in many plant species. In tomato, several QTL controlling resistance have been found, but in different studies, markers spanning a large region of chromosome 6 showed strong association with the resistance. By using two different approaches to analyze the data from a field test F3 population, we show that at least two separate loci approximately 30 cM apart on this chromosome are most likely involved in the resistance. First, a temporal analysis of the progression of symptoms reveals a distal locus early in the development of the disease. As the disease progresses, the maximum LOD peak observed shifts toward the proximal end of the chromosome, obscuring the distal locus. Second, although classical interval mapping could only detect the presence of one locus, a statistical "two-QTL model" test, specifically adapted for the resolution of linked QTL, strongly supported the hypothesis for the presence of two loci. These results are discussed in the context of current molecular knowledge about disease resistance genes on chromosome 6 and observations made by tomato breeders during the production of bacterial wilt-resistant varieties. PMID:10049932

  12. Temporal and multiple quantitative trait loci analyses of resistance to bacterial wilt in tomato permit the resolution of linked loci.

    PubMed

    Mangin, B; Thoquet, P; Olivier, J; Grimsley, N H

    1999-03-01

    Ralstonia solanacearum is a soil-borne bacterium that causes the serious disease known as bacterial wilt in many plant species. In tomato, several QTL controlling resistance have been found, but in different studies, markers spanning a large region of chromosome 6 showed strong association with the resistance. By using two different approaches to analyze the data from a field test F3 population, we show that at least two separate loci approximately 30 cM apart on this chromosome are most likely involved in the resistance. First, a temporal analysis of the progression of symptoms reveals a distal locus early in the development of the disease. As the disease progresses, the maximum LOD peak observed shifts toward the proximal end of the chromosome, obscuring the distal locus. Second, although classical interval mapping could only detect the presence of one locus, a statistical "two-QTL model" test, specifically adapted for the resolution of linked QTL, strongly supported the hypothesis for the presence of two loci. These results are discussed in the context of current molecular knowledge about disease resistance genes on chromosome 6 and observations made by tomato breeders during the production of bacterial wilt-resistant varieties.

  13. Genome-wide Association Study Identifies New Loci for Resistance to Leptosphaeria maculans in Canola

    PubMed Central

    Raman, Harsh; Raman, Rosy; Coombes, Neil; Song, Jie; Diffey, Simon; Kilian, Andrzej; Lindbeck, Kurt; Barbulescu, Denise M.; Batley, Jacqueline; Edwards, David; Salisbury, Phil A.; Marcroft, Steve

    2016-01-01

    Key message “We identified both quantitative and quantitative resistance loci to Leptosphaeria maculans, a fungal pathogen, causing blackleg disease in canola. Several genome-wide significant associations were detected at known and new loci for blackleg resistance. We further validated statistically significant associations in four genetic mapping populations, demonstrating that GWAS marker loci are indeed associated with resistance to L. maculans. One of the novel loci identified for the first time, Rlm12, conveys adult plant resistance in canola.” Blackleg, caused by Leptosphaeria maculans, is a significant disease which affects the sustainable production of canola (Brassica napus). This study reports a genome-wide association study based on 18,804 polymorphic SNPs to identify loci associated with qualitative and quantitative resistance to L. maculans. Genomic regions delimited with 694 significant SNP markers, that are associated with resistance evaluated using 12 single spore isolates and pathotypes from four canola stubble were identified. Several significant associations were detected at known disease resistance loci including in the vicinity of recently cloned Rlm2/LepR3 genes, and at new loci on chromosomes A01/C01, A02/C02, A03/C03, A05/C05, A06, A08, and A09. In addition, we validated statistically significant associations on A01, A07, and A10 in four genetic mapping populations, demonstrating that GWAS marker loci are indeed associated with resistance to L. maculans. One of the novel loci identified for the first time, Rlm12, conveys adult plant resistance and mapped within 13.2 kb from Arabidopsis R gene of TIR-NBS class. We showed that resistance loci are located in the vicinity of R genes of Arabidopsis thaliana and Brassica napus on the sequenced genome of B. napus cv. Darmor-bzh. Significantly associated SNP markers provide a valuable tool to enrich germplasm for favorable alleles in order to improve the level of resistance to L. maculans in

  14. Small brown planthopper resistance loci in wild rice (Oryza officinalis).

    PubMed

    Zhang, Weilin; Dong, Yan; Yang, Ling; Ma, Bojun; Ma, Rongrong; Huang, Fudeng; Wang, Changchun; Hu, Haitao; Li, Chunshou; Yan, Chengqi; Chen, Jianping

    2014-06-01

    Host-plant resistance is the most practical and economical approach to control the rice planthoppers. However, up to date, few rice germplasm accessions that are resistant to the all three kinds of planthoppers (1) brown planthopper (BPH; Nilaparvata lugens Stål), (2) the small brown planthopper (SBPH; Laodelphax striatellus Fallen), and (3) the whitebacked planthopper (WBPH, Sogatella furcifera Horvath) have been identified; consequently, the genetic basis for host-plant broad spectrum resistance to rice planthoppers in a single variety has been seldom studied. Here, one wild species, Oryza officinalis (Acc. HY018, 2n = 24, CC), was detected showing resistance to the all three kinds of planthoppers. Because resistance to WBPH and BPH in O. officinalis has previously been reported, the study mainly focused on its SBPH resistance. The SBPH resistance gene(s) was (were) introduced into cultivated rice via asymmetric somatic hybridization. Three QTLs for SBPH resistance detected by the SSST method were mapped and confirmed on chromosomes 3, 7, and 12, respectively. The allelic/non-allelic relationship and relative map positions of the three kinds of planthopper resistance genes in O. officinalis show that the SBPH, WBPH, and BPH resistance genes in O. officinalis were governed by multiple genes, but not by any major gene. The data on the genetics of host-plant broad spectrum resistance to planthoppers in a single accession suggested that the most ideally practical and economical approach for rice breeders is to screen the sources of broad spectrum resistance to planthoppers, but not to employ broad spectrum resistance gene for the management of planthoppers. Pyramiding these genes in a variety can be an effective way for the management of planthoppers.

  15. Quantitative trait loci for broomrape (Orobanche cumana Wallr.) resistance in sunflower.

    PubMed

    Pérez-Vich, B; Akhtouch, B; Knapp, S J; Leon, A J; Velasco, L; Fernández-Martínez, J M; Berry, S T

    2004-06-01

    Broomrape (Orobanche cumana Wallr.) is a root parasite of sunflower that is regarded as one of the most important constraints of sunflower production in the Mediterranean region. Breeding for resistance is the most effective method of control. P-96 is a sunflower line which shows dominant resistance to broomrape race E and recessive resistance to the very new race F. The objective of this study was to map and characterize quantitative trait loci (QTL) for resistance to race E and to race F of broomrape in P-96. A population from a cross between P-96 and the susceptible line P-21 was phenotyped for broomrape resistance in four experiments, two for race E and two for race F, by measuring different resistance parameters (resistance or susceptibility, number of broomrape per plant, and proportion of resistant plants per F(3) family). This population was also genotyped with microsatellite and RFLP markers. A linkage map comprising 103 marker loci distributed on 17 linkage groups was developed, and composite interval mapping analyses were performed. In total, five QTL ( or1.1, or3.1, or7.1 or13.1 and or13.2) for resistance to race E and six QTL ( or1.1, or4.1, or5.1, or13.1, or13.2 and or16.1) for resistance to race F of broomrape were detected on 7 of the 17 linkage groups. Phenotypic variance for race E resistance was mainly explained by the major QTL or3.1 associated to the resistance or susceptibility character ( R(2)=59%), while race F resistance was explained by QTL with a small to moderate effect ( R(2) from 15.0% to 38.7%), mainly associated with the number of broomrape per plant. Or3.1 was race E-specific, while or1.1, or13.1 and or13.2 of were non-race specific. Or13.1, and or13.2 were stable across the four experiments. Or3.1, and or7.1 were stable over the two race E experiments and or1.1 and or5.1 over the two race F experiments. The results from this study suggest that resistance to broomrape in sunflower is controlled by a combination of qualitative, race

  16. Confirming and identifying new loci for rice blast disease resistance using magnaporthe oryzae field isolates in the US

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Quantitative trait loci (QTL) in rice play important roles in controlling rice blast disease. In the present study, 10 field isolates of the races IA1, IB1, IB17, and IC1 of U.S. rice blast fungus Magnaporthe oryzae collected in 1996 and 2009 were used to identify blast resistance QTL with a recombi...

  17. Reappraisal of known malaria resistance loci in a large multicenter study.

    PubMed

    2014-11-01

    Many human genetic associations with resistance to malaria have been reported, but few have been reliably replicated. We collected data on 11,890 cases of severe malaria due to Plasmodium falciparum and 17,441 controls from 12 locations in Africa, Asia and Oceania. We tested 55 SNPs in 27 loci previously reported to associate with severe malaria. There was evidence of association at P < 1 × 10(-4) with the HBB, ABO, ATP2B4, G6PD and CD40LG loci, but previously reported associations at 22 other loci did not replicate in the multicenter analysis. The large sample size made it possible to identify authentic genetic effects that are heterogeneous across populations or phenotypes, with a striking example being the main African form of G6PD deficiency, which reduced the risk of cerebral malaria but increased the risk of severe malarial anemia. The finding that G6PD deficiency has opposing effects on different fatal complications of P. falciparum infection indicates that the evolutionary origins of this common human genetic disorder are more complex than previously supposed.

  18. Genome-wide search of stem rust resistance loci at the seedling stage in durum wheat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Puccinia graminis f. sp. tritici, the causative agent of stem rust in wheat, is known to rapidly evolve new virulence to resistance genes. While more than 50 stem rust resistance (Sr) loci have been identified in wheat, only a few remain effective, particularly against the highly virulent race Ug99 ...

  19. Genome-wide association study indicates two novel resistance loci for severe malaria.

    PubMed

    Timmann, Christian; Thye, Thorsten; Vens, Maren; Evans, Jennifer; May, Jürgen; Ehmen, Christa; Sievertsen, Jürgen; Muntau, Birgit; Ruge, Gerd; Loag, Wibke; Ansong, Daniel; Antwi, Sampson; Asafo-Adjei, Emanuel; Nguah, Samuel Blay; Kwakye, Kingsley Osei; Akoto, Alex Osei Yaw; Sylverken, Justice; Brendel, Michael; Schuldt, Kathrin; Loley, Christina; Franke, Andre; Meyer, Christian G; Agbenyega, Tsiri; Ziegler, Andreas; Horstmann, Rolf D

    2012-09-20

    Malaria causes approximately one million fatalities per year, mostly among African children. Although highlighted by the strong protective effect of the sickle-cell trait, the full impact of human genetics on resistance to the disease remains largely unexplored. Genome-wide association (GWA) studies are designed to unravel relevant genetic variants comprehensively; however, in malaria, as in other infectious diseases, these studies have been only partly successful. Here we identify two previously unknown loci associated with severe falciparum malaria in patients and controls from Ghana, West Africa. We applied the GWA approach to the diverse clinical syndromes of severe falciparum malaria, thereby targeting human genetic variants influencing any step in the complex pathogenesis of the disease. One of the loci was identified on chromosome 1q32 within the ATP2B4 gene, which encodes the main calcium pump of erythrocytes, the host cells of the pathogenic stage of malaria parasites. The second was indicated by an intergenic single nucleotide polymorphism on chromosome 16q22.2, possibly linked to a neighbouring gene encoding the tight-junction protein MARVELD3. The protein is expressed on endothelial cells and might therefore have a role in microvascular damage caused by endothelial adherence of parasitized erythrocytes. We also confirmed previous reports on protective effects of the sickle-cell trait and blood group O. Our findings underline the potential of the GWA approach to provide candidates for the development of control measures against infectious diseases in humans.

  20. Reappraisal of known malaria resistance loci in a large multi-centre study

    PubMed Central

    Rockett, Kirk A.; Clarke, Geraldine M.; Fitzpatrick, Kathryn; Hubbart, Christina; Jeffreys, Anna E.; Rowlands, Kate; Craik, Rachel; Jallow, Muminatou; Conway, David J.; Bojang, Kalifa A.; Pinder, Margaret; Usen, Stanley; Sisay-Joof, Fatoumatta; Sirugo, Giorgio; Toure, Ousmane; Thera, Mahamadou A.; Konate, Salimata; Sissoko, Sibiry; Niangaly, Amadou; Poudiougou, Belco; Mangano, Valentina D.; Bougouma, Edith C.; Sirima, Sodiomon B.; Modiano, David; Amenga-Etego, Lucas N.; Ghansah, Anita; Koram, Kwadwo A.; Wilson, Michael D.; Enimil, Anthony; Evans, Jennifer; Amodu, Olukemi; Olaniyan, Subulade; Apinjoh, Tobias; Mugri, Regina; Ndi, Andre; Ndila, Carolyne M.; Uyoga, Sophie; Macharia, Alexander; Peshu, Norbert; Williams, Thomas N.; Manjurano, Alphaxard; Riley, Eleanor; Drakeley, Chris; Reyburn, Hugh; Nyirongo, Vysaul; Kachala, David; Molyneux, Malcolm; Dunstan, Sarah J.; Phu, Nguyen Hoan; Ngoc Quyen, Nguyen Thi; Thai, Cao Quang; Hien, Tran Tinh; Manning, Laurens; Laman, Moses; Siba, Peter; Karunajeewa, Harin; Allen, Steve; Allen, Angela; Davis, Timothy M. E.; Michon, Pascal; Mueller, Ivo; Green, Angie; Molloy, Sile; Johnson, Kimberly J.; Kerasidou, Angeliki; Cornelius, Victoria; Hart, Lee; Vanderwal, Aaron; SanJoaquin, Miguel; Band, Gavin; Le, Si Quang; Pirinen, Matti; Sepúlveda, Nuno; Spencer, Chris C.A.; Clark, Taane G.; Agbenyega, Tsiri; Achidi, Eric; Doumbo, Ogobara; Farrar, Jeremy; Marsh, Kevin; Taylor, Terrie; Kwiatkowski, Dominic P.

    2015-01-01

    Many human genetic associations with resistance to malaria have been reported but few have been reliably replicated. We collected data on 11,890 cases of severe malaria due to Plasmodium falciparum and 17,441 controls from 12 locations in Africa, Asia and Oceania. There was strong evidence of association with the HBB, ABO, ATP2B4, G6PD and CD40LG loci but previously reported associations at 22 other loci did not replicate in the multi-centre analysis. The large sample size made it possible to identify authentic genetic effects that are heterogeneous across populations or phenotypes, a striking example being the main African form of G6PD deficiency, which reduced the risk of cerebral malaria but increased the risk of severe malarial anaemia. The finding that G6PD deficiency has opposing effects on different fatal complications of P. falciparum infection indicates that the evolutionary origins of this common human genetic disorder are more complex than previously supposed. PMID:25261933

  1. Quantitative trait Loci mapping for bacterial blight resistance in rice using bulked segregant analysis.

    PubMed

    Han, Xueying; Yang, Yong; Wang, Xuming; Zhou, Jie; Zhang, Wenhao; Yu, Chulang; Cheng, Chen; Cheng, Ye; Yan, Chengqi; Chen, Jianping

    2014-07-03

    Oryza meyeriana is highly resistant to rice bacterial blight (BB) and this resistance trait has been transferred to cultivated rice (O. sativa) using asymmetric somatic hybridization. However, no resistance genes have yet been cloned. In the present study, a progeny of the somatic hybridization with high BB resistance was crossed with a rice cultivar with high BB susceptibility to develop an F2 population. Using bulked segregant analysis (BSA), 17 polymorphic markers that were linked to rice BB resistance were obtained through scanning a total of 186 simple sequence repeats (SSR) and sequence-tagged site (STS) markers, evenly distributed on 12 chromosomes. A genetic linkage map was then constructed based on the 17 linkage markers and the F2 segregating population, which was followed by mapping for quantitative trait loci (QTLs) for BB resistance. Three QTLs were identified on chromosomes 1, 3 and 5, respectively, and the alleles of the resistant parent at any of the QTLs increased BB resistance. All of the three QTLs had a strong effect on resistance, explaining about 21.5%, 12.3% and 39.2% of the resistance variance, respectively. These QTLs were different from the loci of the BB resistance genes that have been identified in previous studies. The QTLs mapped in this work will facilitate the isolation of novel BB resistance genes and their utilization in rice resistance breeding.

  2. Quantitative trait Loci for resistance to the congenital nephropathy in tensin 2-deficient mice.

    PubMed

    Sasaki, Hayato; Sasaki, Nobuya; Nishino, Tomohiro; Nagasaki, Ken-Ichi; Kitamura, Hiroshi; Torigoe, Daisuke; Agui, Takashi

    2014-01-01

    The ICR-derived glomerulonephritis (ICGN) mouse is a chronic kidney disease (CKD) model that is characterized histologically by glomerulosclerosis, vascular sclerosis and tubulointerstitial fibrosis, and clinically by proteinuria and anemia, which are common symptoms and pathological changes associated with a variety of kidney diseases. Previously, we performed a quantitative trait locus (QTL) analysis to identify the causative genes for proteinuria in ICGN mice, and found a deletion mutation of the tensin 2 gene (Tns2nph, MGI no: 2447990). Interestingly, the congenic strain carrying the Tns2nph mutation on a C57BL/6J (B6) genetic background exhibited milder phenotypes than did ICGN mice, indicating the presence of several modifier genes controlling the disease phenotype. In this study, to identify the modifier/resistant loci for CKD progression in Tns2-deficient mice, we performed QTL analysis using backcross progenies from susceptible ICGN and resistant B6 mice. We identified a significant locus on chromosome (Chr) 2 (LOD = 5.36; 31 cM) and two suggestive loci on Chrs 10 (LOD = 2.27; 64 cM) and X (LOD = 2.65; 67 cM) with linkage to the severity of tubulointerstitial injury. One significant locus on Chr 13 (LOD = 3.49; approximately 14 cM) and one suggestive locus on Chr 2 (LOD = 2.41; 51 cM) were identified as QTLs for the severity of glomerulosclerosis. Suggestive locus in BUN was also detected in the same Chr 2 region (LOD = 2.34; 51 cM). A locus on Chr 2 (36 cM) was significantly linked with HGB (LOD = 4.47) and HCT (LOD = 3.58). Four novel epistatic loci controlling either HGB or tubulointerstitial injury were discovered. Further genetic analysis should lead to identification of CKD modifier gene(s), aiding early diagnosis and providing novel approaches to the discovery of drugs for the treatment and possible prevention of kidney disease.

  3. A joint analysis to identify loci underlying variation in nematode resistance in three European sheep populations.

    PubMed

    Riggio, V; Pong-Wong, R; Sallé, G; Usai, M G; Casu, S; Moreno, C R; Matika, O; Bishop, S C

    2014-12-01

    Gastrointestinal nematode infections are one of the main health/economic issues in sheep industries, worldwide. Indicator traits for resistance such as faecal egg count (FEC) are commonly used in genomic studies; however, published results are inconsistent among breeds. Meta (or joint)-analysis is a tool for aggregating information from multiple independent studies. The aim of this study was to identify loci underlying variation in FEC, as an indicator of nematode resistance, in a joint analysis using data from three populations (Scottish Blackface, Sarda × Lacaune and Martinik Black-Belly × Romane), genotyped with the ovine 50k SNP chip. The trait analysed was the average animal effect for Strongyles and Nematodirus FEC data. Analyses were performed with regional heritability mapping (RHM), fitting polygenic effects with either the whole genomic relationship matrix or matrices excluding the chromosome being interrogated. Across-population genomic covariances were set to zero. After quality control, 4123 animals and 38 991 SNPs were available for the analysis. RHM identified genome-wide significant regions on OAR4, 12, 14, 19 and 20, with the latter being the most significant. The OAR20 region is close to the major histocompatibility complex, which has often been proposed as a functional candidate for nematode resistance. This region was significant only in the Sarda × Lacaune population. Several other regions, on OAR1, 3, 4, 5, 7, 12, 19, 20 and 24, were significant at the suggestive level.

  4. Quantitative trait loci for aluminum resistance in Chinese wheat landrace FSW.

    PubMed

    Cai, Shibin; Bai, Gui-Hua; Zhang, Dadong

    2008-06-01

    Aluminum (Al) toxicity is a major constraint for wheat production in acid soils worldwide. Chinese landrace FSW demonstrates a high level of Al resistance. A population of recombinant inbred lines (RILs) was developed from a cross between FSW and an Al-sensitive Chinese line, ND35, using single seed descent, to map quantitative trait loci (QTLs) for Al resistance. Wheat reaction to Al stress was measured by net root growth (NRG) in a nutrient solution culture containing Al(3+) and hematoxylin staining score (HSS) of root after Al stress. After 1,437 simple sequence repeats (SSRs) were screened using bulk segregant analysis, three QTLs were identified to control Al resistance in FSW. One major QTL (Qalt.pser-4DL) was mapped on chromosome 4DL that co-segregated with Xups4, a marker for the promoter of the Al-activated malate transporter (ALMT1) gene. The other two QTLs (Qalt.pser-3BL, Qalt.pser-2A) were located on chromosomes 3BL and 2A, respectively. Together, the three QTLs accounted for up to 81.9% of the phenotypic variation for HSS and 78.3% of the variation for NRG. The physical positions of flanking markers for Qalt.pser-4DL and Qalt.pser-3BL were determined by analyzing these markers in corresponding nulli-tetrasomic, ditelosomic, and 3BL deletion lines of Chinese Spring. Qalt.pser-3BL is a novel QTL with a major effect on Al resistance discovered in this study. The two major QTLs on 4DL and 3BL demonstrated an additive effect. The SSR markers closely linked to the QTLs have potential to be used for marker-assisted selection (MAS) to improve Al resistance of wheat cultivars in breeding programs.

  5. Evaluation and Quantitative trait loci mapping of resistance to powdery mildew in lettuce

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lettuce (Lactuca sativa L.) is the major leafy vegetable that is susceptible to powdery mildew disease under greenhouse and field conditions. We mapped quantitative trait loci (QTLs) for resistance to powdery mildew under greenhouse conditions in an interspecific population derived from a cross betw...

  6. A consensus map for Ug99 stem rust resistance loci in wheat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The global effort to identify new sources of resistance to wheat stem rust, caused by Puccinia graminis f. sp. tritici race group Ug99, has resulted in numerous studies reporting both qualitative genes and quantitative trait loci (QTLs). The purpose of our study was to assemble all available informa...

  7. Genetic analysis of durable resistance to Magnaporthe oryzae in the rice accession Gigante Vercelli identified two blast resistance loci.

    PubMed

    Urso, Simona; Desiderio, Francesca; Biselli, Chiara; Bagnaresi, Paolo; Crispino, Laura; Piffanelli, Pietro; Abbruscato, Pamela; Assenza, Federica; Guarnieri, Giada; Cattivelli, Luigi; Valè, Giampiero

    2016-02-01

    Rice cultivars exhibiting durable resistance to blast, the most important rice fungal disease provoking up to 30 % of rice losses, are very rare and searching for sources of such a resistance represents a priority for rice-breeding programs. To this aim we analyzed Gigante Vercelli (GV) and Vialone Nano (VN), two temperate japonica rice cultivars in Italy displaying contrasting response to blast, with GV showing a durable and broad-spectrum resistance, whereas VN being highly susceptible. An SSR-based genetic map developed using a GV × VN population segregating for blast resistance identified two blast resistance loci, localized to the long arm of chromosomes 1 and 4 explaining more than 78 % of the observed phenotypic variation for blast resistance. The pyramiding of two blast resistance QTLs was therefore involved in the observed durable resistance in GV. Mapping data were integrated with information obtained from RNA-seq expression profiling of all classes of resistance protein genes (resistance gene analogs, RGAs) and with the map position of known cloned or mapped blast resistance genes to search candidates for the GV resistant response. A co-localization of RGAs with the LOD peak or the marker interval of the chromosome 1 QTL was highlighted and a valuable tool for selecting the resistance gene during breeding programs was developed. Comparative analysis with known blast resistance genes revealed co-positional relationships between the chromosome 1 QTL with the Pi35/Pish blast resistance alleles and showed that the chromosome 4 QTL represents a newly identified blast resistance gene. The present genetic analysis has therefore allowed the identification of two blast resistance loci in the durable blast-resistant rice cultivar GV and tools for molecular selection of these resistance genes.

  8. Resisting Mind Control.

    ERIC Educational Resources Information Center

    Anderson, Susan M.; Zimbardo, Philip G.

    1980-01-01

    Provides conceptual analyses of mind control techniques along with practical advice on how to resist these techniques. The authors stress that effective mind control stems more from everyday social relations than from exotic technological gimmicks. Suggestions are given for resisting persuasion, resisting systems, and challenging the system.…

  9. Using Genotyping by Sequencing to Map Two Novel Anthracnose Resistance Loci in Sorghum bicolor

    PubMed Central

    J. Felderhoff, Terry; M. McIntyre, Lauren; Saballos, Ana; Vermerris, Wilfred

    2016-01-01

    Colletotrichum sublineola is an aggressive fungal pathogen that causes anthracnose in sorghum [Sorghum bicolor (L.) Moench]. The obvious symptoms of anthracnose are leaf blight and stem rot. Sorghum, the fifth most widely grown cereal crop in the world, can be highly susceptible to the disease, most notably in hot and humid environments. In the southeastern United States the acreage of sorghum has been increasing steadily in recent years, spurred by growing interest in producing biofuels, bio-based products, and animal feed. Resistance to anthracnose is, therefore, of paramount importance for successful sorghum production in this region. To identify anthracnose resistance loci present in the highly resistant cultivar ‘Bk7’, a biparental mapping population of F3:4 and F4:5 sorghum lines was generated by crossing ‘Bk7’ with the susceptible inbred ‘Early Hegari-Sart’. Lines were phenotyped in three environments and in two different years following natural infection. The population was genotyped by sequencing. Following a stringent custom filtering protocol, totals of 5186 and 2759 informative SNP markers were identified in the two populations. Segregation data and association analysis identified resistance loci on chromosomes 7 and 9, with the resistance alleles derived from ‘Bk7’. Both loci contain multiple classes of defense-related genes based on sequence similarity and gene ontologies. Genetic analysis following an independent selection experiment of lines derived from a cross between ‘Bk7’ and sweet sorghum ‘Mer81-4’ narrowed the resistance locus on chromosome 9 substantially, validating this QTL. As observed in other species, sorghum appears to have regions of clustered resistance genes. Further characterization of these regions will facilitate the development of novel germplasm with resistance to anthracnose and other diseases. PMID:27194807

  10. Genome-wide association analysis identifies resistance loci for bacterial blight in a diverse collection of indica rice germplasm.

    PubMed

    Zhang, Fan; Wu, Zhi-Chao; Wang, Ming-Ming; Zhang, Fan; Dingkuhn, Michael; Xu, Jian-Long; Zhou, Yong-Li; Li, Zhi-Kang

    2017-01-01

    Bacterial blight, which is caused by Xanthomonas oryzae pv. oryzae (Xoo), is one of the most devastating rice diseases worldwide. The development and use of disease-resistant cultivars have been the most effective strategy to control bacterial blight. Identifying the genes mediating bacterial blight resistance is a prerequisite for breeding cultivars with broad-spectrum and durable resistance. We herein describe a genome-wide association study involving 172 diverse Oryza sativa ssp. indica accessions to identify loci influencing the resistance to representative strains of six Xoo races. Twelve resistance loci containing 121 significantly associated signals were identified using 317,894 single nucleotide polymorphisms, which explained 13.3-59.9% of the variability in lesion length caused by Xoo races P1, P6, and P9a. Two hotspot regions (L11 and L12) were located within or nearby two cloned R genes (xa25 and Xa26) and one fine-mapped R gene (Xa4). Our results confirmed the relatively high resolution of genome-wide association studies. Moreover, we detected novel significant associations on chromosomes 2, 3, and 6-10. Haplotype analyses of xa25, the Xa26 paralog (MRKc; LOC_Os11g47290), and a Xa4 candidate gene (LOC_11g46870) revealed differences in bacterial blight resistance among indica subgroups. These differences were responsible for the observed variations in lesion lengths resulting from infections by Xoo races P1 and P9a. Our findings may be relevant for future studies involving bacterial blight resistance gene cloning, and provide insights into the genetic basis for bacterial blight resistance in indica rice, which may be useful for knowledge-based crop improvement.

  11. Genome-wide association analysis identifies resistance loci for bacterial blight in a diverse collection of indica rice germplasm

    PubMed Central

    Wang, Ming-Ming; Zhang, Fan; Dingkuhn, Michael; Xu, Jian-Long; Zhou, Yong-Li; Li, Zhi-Kang

    2017-01-01

    Bacterial blight, which is caused by Xanthomonas oryzae pv. oryzae (Xoo), is one of the most devastating rice diseases worldwide. The development and use of disease-resistant cultivars have been the most effective strategy to control bacterial blight. Identifying the genes mediating bacterial blight resistance is a prerequisite for breeding cultivars with broad-spectrum and durable resistance. We herein describe a genome-wide association study involving 172 diverse Oryza sativa ssp. indica accessions to identify loci influencing the resistance to representative strains of six Xoo races. Twelve resistance loci containing 121 significantly associated signals were identified using 317,894 single nucleotide polymorphisms, which explained 13.3–59.9% of the variability in lesion length caused by Xoo races P1, P6, and P9a. Two hotspot regions (L11 and L12) were located within or nearby two cloned R genes (xa25 and Xa26) and one fine-mapped R gene (Xa4). Our results confirmed the relatively high resolution of genome-wide association studies. Moreover, we detected novel significant associations on chromosomes 2, 3, and 6–10. Haplotype analyses of xa25, the Xa26 paralog (MRKc; LOC_Os11g47290), and a Xa4 candidate gene (LOC_11g46870) revealed differences in bacterial blight resistance among indica subgroups. These differences were responsible for the observed variations in lesion lengths resulting from infections by Xoo races P1 and P9a. Our findings may be relevant for future studies involving bacterial blight resistance gene cloning, and provide insights into the genetic basis for bacterial blight resistance in indica rice, which may be useful for knowledge-based crop improvement. PMID:28355306

  12. A Genome-Wide Association Study Reveals New Loci for Resistance to Clubroot Disease in Brassica napus

    PubMed Central

    Li, Lixia; Luo, Yujie; Chen, Biyun; Xu, Kun; Zhang, Fugui; Li, Hao; Huang, Qian; Xiao, Xin; Zhang, Tianyao; Hu, Jihong; Li, Feng; Wu, Xiaoming

    2016-01-01

    Rapeseed (Brassica napus L.) is one of the most important oil crops in the world. However, the yield and quality of rapeseed were largely decreased by clubroot (Plasmodiophora brassicae Woronin). Therefore, it is of great importance for screening more resistant germplasms or genes and improving the resistance to P. brassicae in rapeseed breeding. In this study, a massive resistant identification for a natural global population was conducted in two environments with race/pathotype 4 of P. brassicae which was the most predominant in China, and a wide range of phenotypic variation was found in the population. In addition, a genome-wide association study of 472 accessions for clubroot resistance (CR) was performed with 60K Brassica Infinium SNP arrays for the first time. In total, nine QTLs were detected, seven of which were novel through integrative analysis. Furthermore, additive effects in genetic control of CR in rapeseed among the above loci were found. By bioinformatic analyses, the candidate genes of these loci were predicted, which indicated that TIR-NBS gene family might play an important role in CR. It is believable that the results presented in our study could provide valuable information for understanding the genetic mechanism and molecular regulation of CR. PMID:27746804

  13. Identification of genetic loci that control mammary tumor susceptibility through the host microenvironment

    DOE PAGES

    Zhang, Pengju; Lo, Alvin; Huang, Yurong; ...

    2015-03-09

    The interplay between host genetics, tumor microenvironment and environmental exposure in cancer susceptibility remains poorly understood. Here we assessed the genetic control of stromal mediation of mammary tumor susceptibility to low dose ionizing radiation (LDIR) using backcrossed F1 into BALB/c (F1Bx) between cancer susceptible (BALB/c) and resistant (SPRET/EiJ) mouse strains. Tumor formation was evaluated after transplantation of non-irradiated Trp53-/- BALB/c mammary gland fragments into cleared fat pads of F1Bx hosts. Genome-wide linkage analysis revealed 2 genetic loci that constitute the baseline susceptibility via host microenvironment. However, once challenged with LDIR, we discovered 13 additional loci that were enriched for genesmore » involved in cytokines, including TGFβ1 signaling. Surprisingly, LDIR-treated F1Bx cohort significantly reduced incidence of mammary tumors from Trp53-/- fragments as well as prolonged tumor latency, compared to sham-treated controls. We demonstrated further that plasma levels of specific cytokines were significantly correlated with tumor latency. Using an ex vivo 3-D assay, we confirmed TGFβ1 as a strong candidate for reduced mammary invasion in SPRET/EiJ, which could explain resistance of this strain to mammary cancer risk following LDIR. Our results open possible new avenues to understand mechanisms of genes operating via the stroma that affect cancer risk from external environmental exposures.« less

  14. Identification of genetic loci that control mammary tumor susceptibility through the host microenvironment

    SciTech Connect

    Zhang, Pengju; Lo, Alvin; Huang, Yurong; Huang, Ge; Liang, Guozhou; Mott, Joni; Karpen, Gary H.; Blakely, Eleanor A.; Bissell, Mina J.; Barcellos-Hoff, Mary Helen; Snijders, Antoine M.; Mao, Jian-Hua

    2015-03-09

    The interplay between host genetics, tumor microenvironment and environmental exposure in cancer susceptibility remains poorly understood. Here we assessed the genetic control of stromal mediation of mammary tumor susceptibility to low dose ionizing radiation (LDIR) using backcrossed F1 into BALB/c (F1Bx) between cancer susceptible (BALB/c) and resistant (SPRET/EiJ) mouse strains. Tumor formation was evaluated after transplantation of non-irradiated Trp53-/- BALB/c mammary gland fragments into cleared fat pads of F1Bx hosts. Genome-wide linkage analysis revealed 2 genetic loci that constitute the baseline susceptibility via host microenvironment. However, once challenged with LDIR, we discovered 13 additional loci that were enriched for genes involved in cytokines, including TGFβ1 signaling. Surprisingly, LDIR-treated F1Bx cohort significantly reduced incidence of mammary tumors from Trp53-/- fragments as well as prolonged tumor latency, compared to sham-treated controls. We demonstrated further that plasma levels of specific cytokines were significantly correlated with tumor latency. Using an ex vivo 3-D assay, we confirmed TGFβ1 as a strong candidate for reduced mammary invasion in SPRET/EiJ, which could explain resistance of this strain to mammary cancer risk following LDIR. Our results open possible new avenues to understand mechanisms of genes operating via the stroma that affect cancer risk from external environmental exposures.

  15. Using genotyping by sequencing to map two novel anthracnose resistance Loci in Sorghum bicolor

    DOE PAGES

    Felderhoff, Terry J.; McIntyre, Lauren M.; Saballos, Ana; ...

    2016-05-18

    Colletotrichum sublineola is an aggressive fungal pathogen that causes anthracnose in sorghum [Sorghum bicolor (L.) Moench]. The obvious symptoms of anthracnose are leaf blight and stem rot. Sorghum, the fifth most widely grown cereal crop in the world, can be highly susceptible to the disease, most notably in hot and humid environments. In the southeastern United States the acreage of sorghum has been increasing steadily in recent years, spurred by growing interest in producing biofuels, bio-based products, and animal feed. Resistance to anthracnose is, therefore, of paramount importance for successful sorghum production in this region. To identify anthracnose resistance locimore » present in the highly resistant cultivar ‘Bk7’, a biparental mapping population of F3:4 and F4:5 sorghum lines was generated by crossing ‘Bk7’ with the susceptible inbred ‘Early Hegari-Sart’. Lines were phenotyped in three environments and in two different years following natural infection. The population was genotyped by sequencing. Following a stringent custom filtering protocol, totals of 5186 and 2759 informative SNP markers were identified in the two populations. Segregation data and association analysis identified resistance loci on chromosomes 7 and 9, with the resistance alleles derived from ‘Bk7’. Both loci contain multiple classes of defense-related genes based on sequence similarity and gene ontologies. In addition, genetic analysis following an independent selection experiment of lines derived from a cross between ‘Bk7’ and sweet sorghum ‘Mer81-4’ narrowed the resistance locus on chromosome 9 substantially, validating this QTL. As observed in other species, sorghum appears to have regions of clustered resistance genes. Further characterization of these regions will facilitate the development of novel germplasm with resistance to anthracnose and other diseases.« less

  16. Proactive control of proactive interference using the method of loci.

    PubMed

    Bass, Willa S; Oswald, Karl M

    2014-01-01

    Proactive interferencebuilds up with exposure to multiple lists of similar items with a resulting reduction in recall. This study examined the effectiveness of using a proactive strategy of the method of loci to reduce proactive interference in a list recall paradigm of categorically similar words. While all participants reported using some form of strategy to recall list words, this study demonstrated that young adults were able to proactively use the method of loci after 25 min of instruction to reduce proactive interference as compared with other personal spontaneous strategies. The implications of this study are that top-down proactive strategies such as the method of loci can significantly reduce proactive interference, and that the use of image and sequence or location are especially useful in this regard.

  17. Simultaneous estimation of the locations and effects of multiple disease loci in case-control studies.

    PubMed

    Chien, Li-Chu; Chiu, Yen-Feng; Liang, Kung-Yee; Chuang, Lee-Ming

    2015-04-01

    The genetic basis of complex diseases often involves multiple causative loci. Under such a disease etiology, assuming one disease locus in linkage disequilibrium mapping is likely to induce bias and lead to efficiency loss in disease locus estimation. An approach is needed for simultaneously localizing multiple functional loci within the same region. However, due to the increasing number of parameters accompanying disease loci, these estimates can be computationally infeasible. To circumvent this problem, we propose to estimate the main and two-adjacent-locus joint effects and a nuisance parameter at the disease loci separately through a linear approximation. Estimates of the genetic effects are entered into a generalized estimating equation to estimate disease loci, and the procedure is conducted iteratively until convergence. The proposed method provides estimates and confidence intervals (CIs) for the disease loci, the genetic main effects, and the joint effects of two adjacent disease loci, with the CIs for the disease loci providing useful regions for further fine-mapping. We apply the proposed approach to a data example of case-control studies. Results of the simulations and data example suggest that the developed method performs well in terms of bias, variance, and coverage probability under scenarios with up to three disease loci.

  18. Mapping and quantitative trait loci analysis of verticillium wilt resistance genes in cotton.

    PubMed

    Wang, Hong-Mei; Lin, Zhong-Xu; Zhang, Xian-Long; Chen, Wei; Guo, Xiao-Ping; Nie, Yi-Chun; Li, Yun-Hai

    2008-02-01

    Verticillium wilt is one of the most serious constraints to cotton production in almost all of the cotton-growing countries. In this study, "XinLuZao1" (XLZ1), a susceptible cultivar Gossypium hirsutum L. and "Hai7124" (H7124), a resistant line G. barbadense, and their F(2:3) families were used to map and study the disease index induced by verticillium wilt. A total of 430 SSR loci were mapped into 41 linkage groups; the map spanned 3,745.9 cM and the average distance between adjacent loci was 8.71 cM. Four and five quantitative trait loci (QTLs) were detected based on the disease index investigated on July 22 and August 24 in 2004, respectively. These nine QTLs explained 10.63-28.83% of the phenotypic variance, six of them were located on the D sub-genome. Two QTLs located in the same marker intervals may partly explain the significant correlation of the two traits. QTLs explaining large phenotypic variation were identified in this study, which may be quite useful in cotton anti-disease breeding.

  19. Genetic mapping and transcription analyses of resistance gene loci in potato using NBS profiling.

    PubMed

    Brugmans, Bart; Wouters, Doret; van Os, Hans; Hutten, Ronald; van der Linden, Gerard; Visser, Richard G F; van Eck, Herman J; van der Vossen, Edwin A G

    2008-11-01

    NBS profiling is a method for the identification of resistance gene analog (RGA) derived fragments. Here we report the use of NBS profiling for the genome wide mapping of RGA loci in potato. NBS profiling analyses on a minimal set of F1 genotypes of the diploid mapping population previously used to generate the ultra dense (UHD) genetic map of potato, allowed us to efficiently map polymorphic RGA fragments relative to 10,000 existing AFLP markers. In total, 34 RGA loci were mapped, of which only 13 contained RGA sequences homologous to RGAs genetically positioned at approximately similar positions in potato or tomato. The remaining RGA loci mapped either at approximate chromosomal regions previously shown to contain RGAs in potato or tomato without sharing homology to these RGAs, or mapped at positions not yet identified as RGA-containing regions. In addition to markers representing RGAs with unknown functions, segregating markers were detected that were closely linked to four functional R genes that segregate in the UHD mapping population. To explore the potential of NBS profiling in RGA transcription analyses, RNA isolated from different tissues was used as template for NBS profiling. Of all the fragments amplified approximately 15% showed putative intensity or absent/present differences between different tissues suggesting putative tissue specific RGA or R gene transcription. Putative absent/present differences between individuals were also found. In addition to being a powerful tool for generating candidate gene markers linked to R gene loci, NBS profiling, when applied to cDNA, can be instrumental in identifying those members of an R gene cluster that are transcribed, and thus putatively functional.

  20. Identification of genomic loci associated with crown rust resistance in perennial ryegrass (Lolium perenne L.) divergently selected populations.

    PubMed

    Brazauskas, Gintaras; Xing, Yongzhong; Studer, Bruno; Schejbel, Britt; Frei, Ursula; Berg, Paul Ragnar; Lübberstedt, Thomas

    2013-07-01

    The inheritance of crown rust resistance in perennial ryegrass is complex with both major and minor quantitative trait loci (QTL) being detected on all seven linkage groups. However, QTL mapping populations have only few segregating alleles, limiting the transferability of results to other materials. In this study, a synthetic population was developed from four crown rust resistant and susceptible parents as starting material for a divergent selection experiment of crown rust resistance to be closer to practice in plant breeding programs, and to identify genome regions relevant across a broader range of genotypes. Following three cycles of directional selection, perennial ryegrass populations were produced with a two-fold difference in average rust resistance. Divergently selected populations were genotyped at 7 resistance gene analog-derived expressed sequence tag (RGA-derived EST) as well as 15 simple sequence repeat (SSR) loci. A test for selective neutrality (Waples test), which tests the hypothesis of genetic drift versus selection, identified significant differences in allele frequencies for 7 loci (32%). The selection effect was bidirectional with the same loci showing significant response in both positively and negatively selected populations. A region under selection represented by markers LpSSR006 and EST13 on linkage group (LG) 4 was further confirmed by colocation with two separate QTL for crown rust resistance in a VrnA, a two-way pseudo-testcross mapping population. This suggests suitability of alleles identified for introgression into perennial ryegrass germplasm, where quantitative resistance to crown rust is desired.

  1. Blood and Intestine eQTLs from an Anti-TNF-Resistant Crohn's Disease Cohort Inform IBD Genetic Association Loci

    PubMed Central

    Di Narzo, Antonio F; Peters, Lauren A; Argmann, Carmen; Stojmirovic, Aleksandar; Perrigoue, Jacqueline; Li, Katherine; Telesco, Shannon; Kidd, Brian; Walker, Jennifer; Dudley, Joel; Cho, Judy; Schadt, Eric E; Kasarskis, Andrew; Curran, Mark; Dobrin, Radu; Hao, Ke

    2016-01-01

    OBJECTIVES: Genome-wide association studies (GWAS) have identified loci reproducibly associated with inflammatory bowel disease (IBD) and other immune-mediated diseases; however, the molecular mechanisms underlying most of genetic susceptibility remain undefined. Expressional quantitative trait loci (eQTL) of disease-relevant tissue can be employed in order to elucidate the genes and pathways affected by disease-specific genetic variance. METHODS: In this study, we derived eQTLs for human whole blood and intestine tissues of anti-tumor necrosis factor-resistant Crohn's disease (CD) patients. We interpreted these eQTLs in the context of published IBD GWAS hits to inform on the disease process. RESULTS: At 10% false discovery rate, we discovered that 5,174 genes in blood and 2,063 genes in the intestine were controlled by a nearby single-nucleotide polymorphism (SNP) (i.e., cis-eQTL), among which 1,360 were shared between the two tissues. A large fraction of the identified eQTLs were supported by the regulomeDB database, showing that the eQTLs reside in regulatory elements (odds ratio; OR=3.44 and 3.24 for blood and intestine eQTLs, respectively) as opposed to protein-coding regions. Published IBD GWAS hits as a whole were enriched for blood and intestine eQTLs (OR=2.88 and 2.05; and P value=2.51E-9 and 0.013, respectively), thereby linking genetic susceptibility to control of gene expression in these tissues. Through a systematic search, we used eQTL data to inform 109 out of 372 IBD GWAS SNPs documented in National Human Genome Research Institute catalog, and we categorized the genes influenced by eQTLs according to their functions. Many of these genes have experimentally validated roles in specific cell types contributing to intestinal inflammation. CONCLUSIONS: The blood and intestine eQTLs described in this study represent a powerful tool to link GWAS loci to a regulatory function and thus elucidate the mechanisms underlying the genetic loci associated with IBD

  2. Inheritance of partial resistance against Colletotrichum lindemuthianum in Phaseolus vulgaris and co-localization of quantitative trait loci with genes involved in specific resistance.

    PubMed

    Geffroy, V; Sévignac, M; De Oliveira, J C; Fouilloux, G; Skroch, P; Thoquet, P; Gepts, P; Langin, T; Dron, M

    2000-03-01

    Anthracnose, one of the most important diseases of common bean (Phaseolus vulgaris), is caused by the fungus Colletotrichum lindemuthianum. A "candidate gene" approach was used to map anthracnose resistance quantitative trait loci (QTL). Candidate genes included genes for both pathogen recognition (resistance genes and resistance gene analogs [RGAs]) and general plant defense (defense response genes). Two strains of C. lindemuthianum, identified in a world collection of 177 strains, displayed a reproducible and differential aggressiveness toward BAT93 and JaloEEP558, two parental lines of P. vulgaris representing the two major gene pools of this crop. A reliable test was developed to score partial resistance in aerial organs of the plant (stem, leaf, petiole) under controlled growth chamber conditions. BAT93 was more resistant than JaloEEP558 regardless of the organ or strain tested. With a recombinant inbred line (RIL) population derived from a cross between these two parental lines, 10 QTL were located on a genetic map harboring 143 markers, including known defense response genes, anthracnose-specific resistance genes, and RGAs. Eight of the QTL displayed isolate specificity. Two were co-localized with known defense genes (phenylalanine ammonia-lyase and hydroxyproline-rich glycoprotein) and three with anthracnose-specific resistance genes and/or RGAs. Interestingly, two QTL, with different allelic contribution, mapped on linkage group B4 in a 5.0 cM interval containing Andean and Mesoamerican specific resistance genes against C. lindemuthianum and 11 polymorphic fragments revealed with a RGA probe. The possible relationship between genes underlying specific and partial resistance is discussed.

  3. Identification of genetic loci associated with fire blight resistance in Malus through combined use of QTL and association mapping.

    PubMed

    Khan, M Awais; Zhao, Youfu Frank; Korban, Schuyler S

    2013-07-01

    Fire blight, incited by the enterobacterium Erwinia amylovora, is a destructive disease of Rosaceae, particularly of apples and pears. There are reports on the molecular mechanisms underlying E. amylovora pathogenesis and how the host activates its resistance mechanism. The host's resistance mechanism is quantitatively controlled, although some major genes might also be involved. Thus far, quantitative trait loci (QTL) mapping and differential expression studies have been used to elucidate those genes and/or genomic regions underlying quantitative resistance present in the apple genome. In this study, an effort is undertaken to dissect the genetic basis of fire blight resistance in apple using both QTL and genome-wide association mapping. On the basis of an F1 pedigree of 'Coop 16' × 'Coop 17' and a genome-wide association study (GWAS) mapping population of Malus accessions (species, old and new cultivars and selections), new QTLs and associations have been identified. A total of three QTLs for resistance to fire blight, with above 95% significant logarithm of odds threshold value of 2.5, have been identified on linkage groups (LGs) 02, 06, and 15 of the apple genome with phenotypic variation explained values of 14.7, 20.1 and 17.4, respectively. Although elevated P-values with signals for marker-trait associations are observed for some LGs, these are not found to be significant. However, a total of 34 significant associations, with P-values ≥0.02, have been detected including 8 for lesion length at 7 days following inoculation (PL1), 14 for lesion length at 14 days following inoculation (PL2), and 12 for shoot length.

  4. Using early flowering transgenic apple to accelerate the breeding of donor parents with multiple loci for disease resistance (Malus x domestica)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    One of the goals of the USDA-NIFA-SCRI RosBREED project is to develop donor parents with multiple loci for disease resistance. Due to the long generation time of tree fruit crops, the accumulation of pyramided resistance loci for multiple diseases by conventional breeding methods could require deca...

  5. Identifying Loci Contributing to Natural Variation in Xenobiotic Resistance in Drosophila

    PubMed Central

    Najarro, Michael A.; Hackett, Jennifer L.; Smith, Brittny R.; Highfill, Chad A.; King, Elizabeth G.; Long, Anthony D.; Macdonald, Stuart J.

    2015-01-01

    Natural populations exhibit a great deal of interindividual genetic variation in the response to toxins, exemplified by the variable clinical efficacy of pharmaceutical drugs in humans, and the evolution of pesticide resistant insects. Such variation can result from several phenomena, including variable metabolic detoxification of the xenobiotic, and differential sensitivity of the molecular target of the toxin. Our goal is to genetically dissect variation in the response to xenobiotics, and characterize naturally-segregating polymorphisms that modulate toxicity. Here, we use the Drosophila Synthetic Population Resource (DSPR), a multiparent advanced intercross panel of recombinant inbred lines, to identify QTL (Quantitative Trait Loci) underlying xenobiotic resistance, and employ caffeine as a model toxic compound. Phenotyping over 1,700 genotypes led to the identification of ten QTL, each explaining 4.5–14.4% of the broad-sense heritability for caffeine resistance. Four QTL harbor members of the cytochrome P450 family of detoxification enzymes, which represent strong a priori candidate genes. The case is especially strong for Cyp12d1, with multiple lines of evidence indicating the gene causally impacts caffeine resistance. Cyp12d1 is implicated by QTL mapped in both panels of DSPR RILs, is significantly upregulated in the presence of caffeine, and RNAi knockdown robustly decreases caffeine tolerance. Furthermore, copy number variation at Cyp12d1 is strongly associated with phenotype in the DSPR, with a trend in the same direction observed in the DGRP (Drosophila Genetic Reference Panel). No additional plausible causative polymorphisms were observed in a full genomewide association study in the DGRP, or in analyses restricted to QTL regions mapped in the DSPR. Just as in human populations, replicating modest-effect, naturally-segregating causative variants in an association study framework in flies will likely require very large sample sizes. PMID:26619284

  6. Scab resistance in 'Geneva' apple is conditioned by a resistance gene cluster with complex genetic control.

    PubMed

    Bastiaanse, Héloïse; Bassett, Heather C M; Kirk, Christopher; Gardiner, Susan E; Deng, Cecilia; Groenworld, Remmelt; Chagné, David; Bus, Vincent G M

    2016-02-01

    Apple scab, caused by the fungal pathogen Venturia inaequalis, is one of the most severe diseases of apple worldwide. It is the most studied plant-pathogen interaction involving a woody species using modern genetic, genomic, proteomic and bioinformatic approaches in both species. Although 'Geneva' apple was recognized long ago as a potential source of resistance to scab, this resistance has not been characterized previously. Differential interactions between various monoconidial isolates of V. inaequalis and six segregating F1 and F2 populations indicate the presence of at least five loci governing the resistance in 'Geneva'. The 17 chromosomes of apple were screened using genotyping-by-sequencing, as well as single marker mapping, to position loci controlling the V. inaequalis resistance on linkage group 4. Next, we fine mapped a 5-cM region containing five loci conferring both dominant and recessive scab resistance to the distal end of the linkage group. This region corresponds to 2.2 Mbp (from 20.3 to 22.5 Mbp) on the physical map of 'Golden Delicious' containing nine candidate nucleotide-binding site leucine-rich repeat (NBS-LRR) resistance genes. This study increases our understanding of the complex genetic basis of apple scab resistance conferred by 'Geneva', as well as the gene-for-gene (GfG) relationships between the effector genes in the pathogen and resistance genes in the host.

  7. Identification of New Resistance Loci to African Stem Rust Race TTKSK in Tetraploid Wheats Based on Linkage and Genome-Wide Association Mapping

    PubMed Central

    Laidò, Giovanni; Panio, Giosuè; Marone, Daniela; Russo, Maria A.; Ficco, Donatella B. M.; Giovanniello, Valentina; Cattivelli, Luigi; Steffenson, Brian; de Vita, Pasquale; Mastrangelo, Anna M.

    2015-01-01

    Stem rust, caused by Puccinia graminis Pers. f. sp. tritici Eriks. and E. Henn. (Pgt), is one of the most destructive diseases of wheat. Races of the pathogen in the “Ug99 lineage” are of international concern due to their virulence for widely used stem rust resistance genes and their spread throughout Africa. Disease resistant cultivars provide one of the best means for controlling stem rust. To identify quantitative trait loci (QTL) conferring resistance to African stem rust race TTKSK at the seedling stage, we evaluated an association mapping (AM) panel consisting of 230 tetraploid wheat accessions under greenhouse conditions. A high level of phenotypic variation was observed in response to race TTKSK in the AM panel, allowing for genome-wide association mapping of resistance QTL in wild, landrace, and cultivated tetraploid wheats. Thirty-five resistance QTL were identified on all chromosomes, and seventeen are of particular interest as identified by multiple associations. Many of the identified resistance loci were coincident with previously identified rust resistance genes; however, nine on chromosomes 1AL, 2AL, 4AL, 5BL, and 7BS may be novel. To validate AM results, a biparental population of 146 recombinant inbred lines was also considered, which derived from a cross between the resistant cultivar “Cirillo” and susceptible “Neodur.” The stem rust resistance of Cirillo was conferred by a single gene on the distal region of chromosome arm 6AL in an interval map coincident with the resistance gene Sr13, and confirmed one of the resistance loci identified by AM. A search for candidate resistance genes was carried out in the regions where QTL were identified, and many of them corresponded to NBS-LRR genes and protein kinases with LRR domains. The results obtained in the present study are of great interest as a high level of genetic variability for resistance to race TTKSK was described in a germplasm panel comprising most of the tetraploid wheat sub

  8. Location of Vibrio anguillarum resistance-associated trait loci in half-smooth tongue sole Cynoglossus semilaevis at its microsatellite linkage map

    NASA Astrophysics Data System (ADS)

    Tang, Zhihong; Guo, Li; Liu, Yang; Shao, Changwei; Chen, Songlin; Yang, Guanpin

    2016-11-01

    A cultured female half-smooth tongue sole ( Cynoglossus semilaevis) was crossed with a wild male, yielding the first filial generation of pseudo-testcrossing from which 200 fish were randomly selected to locate the Vibrio anguillarum resistance trait in half-smooth tongue sole at its microsatellite linkage map. In total, 129 microsatellites were arrayed into 18 linkage groups, ≥4 each. The map reconstructed was 852.85 cM in length with an average spacing of 7.68 cM, covering 72.07% of that expected (1 183.35 cM). The V. anguillarum resistance trait was a composite rather than a unit trait, which was tentatively partitioned into Survival time in Hours After V. anguillarum Infection (SHAVI) and Immunity of V. Anguillarum Infection (IVAI). Above a logarithm of the odds (LOD) threshold of 2.5, 18 loci relative to SHAVI and 3 relative to IVAI were identified. The 3 loci relative to IVAI explained 18.78%, 5.87% and 6.50% of the total phenotypic variation in immunity. The microsatellites bounding the 3 quantitative trait loci (QTLs) of IVAI may in future aid to the selection of V. anguillarum-immune half-smooth tongue sole varieties, and facilitate cloning the gene(s) controlling such immunity.

  9. Novel loci control variation in reproductive timing in Arabidopsis thaliana in natural environments.

    PubMed Central

    Weinig, Cynthia; Ungerer, Mark C; Dorn, Lisa A; Kane, Nolan C; Toyonaga, Yuko; Halldorsdottir, Solveig S; Mackay, Trudy F C; Purugganan, Michael D; Schmitt, Johanna

    2002-01-01

    Molecular biologists are rapidly characterizing the genetic basis of flowering in model species such as Arabidopsis thaliana. However, it is not clear how the developmental pathways identified in controlled environments contribute to variation in reproductive timing in natural ecological settings. Here we report the first study of quantitative trait loci (QTL) for date of bolting (the transition from vegetative to reproductive growth) in A. thaliana in natural seasonal field environments and compare the results with those obtained under typical growth-chamber conditions. Two QTL specific to long days in the chamber were expressed only in spring-germinating cohorts in the field, and two loci specific to short days in the chamber were expressed only in fall-germinating cohorts, suggesting differential involvement of the photoperiod pathway in different seasonal environments. However, several other photoperiod-specific QTL with large effects in controlled conditions were undetectable in natural environments, indicating that expression of allelic variation at these loci was overridden by environmental factors specific to the field. Moreover, a substantial number of QTL with major effects on bolting date in one or more field environments were undetectable under controlled environment conditions. These novel loci suggest the involvement of additional genes in the transition to flowering under ecologically relevant conditions. PMID:12524356

  10. Using genotyping by sequencing to map two novel anthracnose resistance Loci in Sorghum bicolor

    SciTech Connect

    Felderhoff, Terry J.; McIntyre, Lauren M.; Saballos, Ana; Vermerris, Wilfred

    2016-05-18

    Colletotrichum sublineola is an aggressive fungal pathogen that causes anthracnose in sorghum [Sorghum bicolor (L.) Moench]. The obvious symptoms of anthracnose are leaf blight and stem rot. Sorghum, the fifth most widely grown cereal crop in the world, can be highly susceptible to the disease, most notably in hot and humid environments. In the southeastern United States the acreage of sorghum has been increasing steadily in recent years, spurred by growing interest in producing biofuels, bio-based products, and animal feed. Resistance to anthracnose is, therefore, of paramount importance for successful sorghum production in this region. To identify anthracnose resistance loci present in the highly resistant cultivar ‘Bk7’, a biparental mapping population of F3:4 and F4:5 sorghum lines was generated by crossing ‘Bk7’ with the susceptible inbred ‘Early Hegari-Sart’. Lines were phenotyped in three environments and in two different years following natural infection. The population was genotyped by sequencing. Following a stringent custom filtering protocol, totals of 5186 and 2759 informative SNP markers were identified in the two populations. Segregation data and association analysis identified resistance loci on chromosomes 7 and 9, with the resistance alleles derived from ‘Bk7’. Both loci contain multiple classes of defense-related genes based on sequence similarity and gene ontologies. In addition, genetic analysis following an independent selection experiment of lines derived from a cross between ‘Bk7’ and sweet sorghum ‘Mer81-4’ narrowed the resistance locus on chromosome 9 substantially, validating this QTL. As observed in other species, sorghum appears to have regions of clustered resistance genes. Further characterization of these regions will facilitate the development of novel germplasm with resistance to anthracnose and other diseases.

  11. Induction and expression of mutations at multiple drug-resistance marker loci in Chinese hamster ovary cells

    SciTech Connect

    Adair, G.M.; Carver, J.H.

    1983-01-01

    We observed quantitative and qualitative differences in the mutability and mutagen-specificity of various drug-resistance marker loci in Chinese hamster ovary (THO) cells, which suggest that mammalian gene loci may differ in their relative mutability by a given mutagenic agent. We have used the CHO-AT3-2 multiple-marker mutagenesis assay system to examine the dose-dependent induction and kinetics of expression of mutations at four well-characterized, drug-resistance marker loci, after treatment with chemical agents which produce various types of DNA damage. The CHO-AT3-2 subline allows simultaneous quantitation and direct comparison of induced mutation frequencies at the hgprt, oua (Na/sup +//K/sup +/ ATPase), aprt, and tk loci. The agents tested in this study included ethyl methanesulfonate, methyl methanesulfonate, mitomycin C, ICR-191, benzo(a)pyrene, and dimethylnitrosamine. The expression kinetics and optimal expression times for each drug-resistance marker were determined in dose-response experiments in which cells from mutagen-treated populations were plated at 1-2-day intervals over a period of 10 days following mutagenesis. Comparison of induced mutation frequencies for each drug-resistance marker after mutagen treatments yielding equivalent cell survivals (equitoxic doses resulting in relative cell survivals of 0.37) revealed locus-specific differences in the relative mutagenicities of the agents tested. These results indicate that the apparent mutagenicity of a particular agent at a single genetic locus may not necessarily be an accurate indicator of that agent's mutagenic potential for the genome as a whole.

  12. Effective resist profile control

    NASA Astrophysics Data System (ADS)

    Liu, Chen-Yu; Wang, Chien-Wei; Huang, Chun-Ching; Chang, Ching-Yu; Ku, Yao-Ching

    2014-03-01

    To meet Moore's law, resist resolution improvement has become more and more important. However, it is difficult to improve resist resolution and keep vertical sidewall profile. For example, a high contrast hole resist may cause trench scum, due to very T-top profile. This paper reports several concepts for resist profile tuning without losing performance for lithographic factor , including mask error enhancement factor (MEEF), depth of focus (DOF), and critical dimension uniformity (CDU). To quantitative analysis the resist profile improvement, we define a new factor, Scum fail ratio (F/R%) for new techniques evaluation. The new techniques, including floatable additive, floatable PAG, and new monomer, are discussed. From X-SEM and CD-SEM data, former three concepts could improve resist sidewall profile quantitatively evaluated by Scum fail F/R% and keep lithographic factors. In addition, another key factor, resist residue defect, is also discussed. The high contrast resist with higher receding contact angle (RCA) easily generates more residue defect after development. With the new monomer composition, RCA of Resist E is decreased from 54 to 48 degree after development. Therefore, the residue defect is improved one order.

  13. Interaction of common bacterial blight bacteria with disease resistance quantitative trait loci in common bean.

    PubMed

    Duncan, Robert W; Singh, Shree P; Gilbertson, Robert L

    2011-04-01

    . fuscans subsp. fuscans genotypes were inoculated onto 28 common bean genotypes having various combinations of known CBB resistance quantitative trait loci (QTL) and associated sequence-characterized amplified region markers. Different levels of virulence were observed for X. campestris pv. phaseoli strains, whereas X. fuscans subsp. fuscans strains were similar in virulence. The typical X. campestris pv. phaseoli strain from Wisconsin was most virulent, whereas X. campestris pv. phaseoli genotypes from East Africa were the least virulent. Host genotypes having the SU91 marker-associated resistance and one or more other QTL (i.e., pyramided resistance), such as the VAX lines, were highly resistant to all genotypes of common blight bacteria tested. This information will help in the development of CBB resistance-breeding strategies for different common bean market classes in different geographical regions, as well as the identification of appropriate pathogen genotypes for screening for resistance.

  14. Regional heritability mapping and genome-wide association identify loci for complex growth, wood and disease resistance traits in Eucalyptus.

    PubMed

    Resende, Rafael Tassinari; Resende, Marcos Deon Vilela; Silva, Fabyano Fonseca; Azevedo, Camila Ferreira; Takahashi, Elizabete Keiko; Silva-Junior, Orzenil Bonfim; Grattapaglia, Dario

    2017-02-01

    Although genome-wide association studies (GWAS) have provided valuable insights into the decoding of the relationships between sequence variation and complex phenotypes, they have explained little heritability. Regional heritability mapping (RHM) provides heritability estimates for genomic segments containing both common and rare allelic effects that individually contribute too little variance to be detected by GWAS. We carried out GWAS and RHM for seven growth, wood and disease resistance traits in a breeding population of 768 Eucalyptus hybrid trees using EuCHIP60K. Total genomic heritabilities accounted for large proportions (64-89%) of pedigree-based trait heritabilities, providing additional evidence that complex traits in eucalypts are controlled by many sequence variants across the frequency spectrum, each with small contributions to the phenotypic variance. RHM detected 26 quantitative trait loci (QTLs) encompassing 2191 single nucleotide polymorphisms (SNPs), whereas GWAS detected 13 single SNP-trait associations. RHM and GWAS QTLs individually explained 5-15% and 4-6% of the genomic heritability, respectively. RHM was superior to GWAS in capturing larger proportions of genomic heritability. Equated to previously mapped QTLs, our results highlighted genomic regions for further examination towards gene discovery. RHM-QTLs bearing a combination of common and rare variants could be useful enhancements to incorporate prior knowledge of the underlying genetic architecture in genomic prediction models.

  15. Method to detect differentially methylated loci with case-control designs using Illumina arrays.

    PubMed

    Wang, Shuang

    2011-11-01

    It is now understood that many human cancer types are the result of the accumulation of both genetic and epigenetic changes. DNA methylation is a molecular modification of DNA that is crucial for normal development. Genes that are rich in CpG dinucleotides are usually not methylated in normal tissues, but are frequently hypermethylated in cancer. With the advent of high-throughput platforms, large-scale structure of genomic methylation patterns is available through genome-wide scans and tremendous amount of DNA methylation data have been recently generated. However, sophisticated statistical methods to handle complex DNA methylation data are very limited. Here, we developed a likelihood based Uniform-Normal-mixture model to select differentially methylated loci between case and control groups using Illumina arrays. The idea is to model the data as three types of methylation loci, one unmethylated, one completely methylated, and one partially methylated. A three-component mixture model with two Uniform distributions and one truncated normal distribution was used to model the three types. The mixture probabilities and the mean of the normal distribution were used to make inference about differentially methylated loci. Through extensive simulation studies, we demonstrated the feasibility and power of the proposed method. An application to a recently published study on ovarian cancer identified several methylation loci that are missed by the existing method.

  16. Quantitative trait loci controlling light and hormone response in two accessions of Arabidopsis thaliana.

    PubMed Central

    Borevitz, Justin O; Maloof, Julin N; Lutes, Jason; Dabi, Tsegaye; Redfern, Joanna L; Trainer, Gabriel T; Werner, Jonathan D; Asami, Tadao; Berry, Charles C; Weigel, Detlef; Chory, Joanne

    2002-01-01

    We have mapped quantitative trait loci (QTL) responsible for natural variation in light and hormone response between the Cape Verde Islands (Cvi) and Landsberg erecta (Ler) accessions of Arabidopsis thaliana using recombinant inbred lines (RILs). Hypocotyl length was measured in four light environments: white, blue, red, and far-red light and in the dark. In addition, white light plus gibberellin (GA) and dark plus the brassinosteroid biosynthesis inhibitor brassinazole (BRZ) were used to detect hormone effects. Twelve QTL were identified that map to loci not previously known to affect light response, as well as loci where candidate genes have been identified from known mutations. Some QTL act in all environments while others show genotype-by-environment interaction. A global threshold was established to identify a significant epistatic interaction between two loci that have few main effects of their own. LIGHT1, a major QTL, has been confirmed in a near isogenic line (NIL) and maps to a new locus with effects in all light environments. The erecta mutation can explain the effect of the HYP2 QTL in the blue, BRZ, and dark environments, but not in far-red. LIGHT2, also confirmed in an NIL, has effects in white and red light and shows interaction with GA. The phenotype and map position of LIGHT2 suggest the photoreceptor PHYB as a candidate gene. Natural variation in light and hormone response thus defines both new genes and known genes that control light response in wild accessions. PMID:11861571

  17. Comparative mapping of Raphanus sativus genome using Brassica markers and quantitative trait loci analysis for the Fusarium wilt resistance trait.

    PubMed

    Yu, Xiaona; Choi, Su Ryun; Ramchiary, Nirala; Miao, Xinyang; Lee, Su Hee; Sun, Hae Jeong; Kim, Sunggil; Ahn, Chun Hee; Lim, Yong Pyo

    2013-10-01

    Fusarium wilt (FW), caused by the soil-borne fungal pathogen Fusarium oxysporum is a serious disease in cruciferous plants, including the radish (Raphanus sativus). To identify quantitative trait loci (QTL) or gene(s) conferring resistance to FW, we constructed a genetic map of R. sativus using an F2 mapping population derived by crossing the inbred lines '835' (susceptible) and 'B2' (resistant). A total of 220 markers distributed in 9 linkage groups (LGs) were mapped in the Raphanus genome, covering a distance of 1,041.5 cM with an average distance between adjacent markers of 4.7 cM. Comparative analysis of the R. sativus genome with that of Arabidopsis thaliana and Brassica rapa revealed 21 and 22 conserved syntenic regions, respectively. QTL mapping detected a total of 8 loci conferring FW resistance that were distributed on 4 LGs, namely, 2, 3, 6, and 7 of the Raphanus genome. Of the detected QTL, 3 QTLs (2 on LG 3 and 1 on LG 7) were constitutively detected throughout the 2-year experiment. QTL analysis of LG 3, flanked by ACMP0609 and cnu_mBRPGM0085, showed a comparatively higher logarithm of the odds (LOD) value and percentage of phenotypic variation. Synteny analysis using the linked markers to this QTL showed homology to A. thaliana chromosome 3, which contains disease-resistance gene clusters, suggesting conservation of resistance genes between them.

  18. Quantitative Trait Loci for High-Temperature Adult-Plant Resistance to Stripe Rust (Puccinia Striiformis f. sp. tritici) in a Hard Red Winter Wheat Germplasm IDO444

    Technology Transfer Automated Retrieval System (TEKTRAN)

    High-temperature adult-plant (HTAP) resistance to stripe rust (Puccinia striiformis f. sp. tritici) is a durable type of resistance in wheat. The objective of this study was to identify quantitative trait loci (QTL) conferring the HTAP resistance to stripe rust in a population consisted of 179 F7:8...

  19. Quantitative trait loci detection of Edwardsiella tarda resistance in Japanese flounder Paralichthys olivaceus using bulked segregant analysis

    NASA Astrophysics Data System (ADS)

    Wang, Xiaoxia; Xu, Wenteng; Liu, Yang; Wang, Lei; Sun, Hejun; Wang, Lei; Chen, Songlin

    2016-11-01

    In recent years, Edwardsiella tarda has become one of the most deadly pathogens of Japanese flounder ( Paralichthys olivaceus), causing serious annual losses in commercial production. In contrast to the rapid advances in the aquaculture of P. olivaceus, the study of E. tarda resistance-related markers has lagged behind, hindering the development of a disease-resistant strain. Thus, a marker-trait association analysis was initiated, combining bulked segregant analysis (BSA) and quantitative trait loci (QTL) mapping. Based on 180 microsatellite loci across all chromosomes, 106 individuals from the F1333 (♀: F0768 ×♂: F0915) (Nomenclature rule: F+year+family number) were used to detect simple sequence repeats (SSRs) and QTLs associated with E. tarda resistance. After a genomic scan, three markers (Scaffold 404-21589, Scaffold 404-21594 and Scaffold 270-13812) from the same linkage group (LG)-1 exhibited a significant difference between DNA, pooled/bulked from the resistant and susceptible groups (P <0.001). Therefore, 106 individuals were genotyped using all the SSR markers in LG1 by single marker analysis. Two different analytical models were then employed to detect SSR markers with different levels of significance in LG1, where 17 and 18 SSR markers were identified, respectively. Each model found three resistance-related QTLs by composite interval mapping (CIM). These six QTLs, designated qE1-6, explained 16.0%-89.5% of the phenotypic variance. Two of the QTLs, qE-2 and qE-4, were located at the 66.7 cM region, which was considered a major candidate region for E. tarda resistance. This study will provide valuable data for further investigations of E. tarda resistance genes and facilitate the selective breeding of disease-resistant Japanese flounder in the future.

  20. Mapping quantitative trait loci conferring resistance to rice black-streaked virus in maize (Zea mays L.).

    PubMed

    Luan, Junwen; Wang, Fei; Li, Yujie; Zhang, Bin; Zhang, Juren

    2012-08-01

    Maize rough dwarf disease (MRDD) is one of the most serious virus diseases of maize worldwide, and it causes great reduction of maize production. In China, the pathogen was shown to be rice black-streaked virus (RBSDV). Currently, MRDD has spread broadly and leads to significant loss in China. However, there has been little research devoted to this disease. Our aims were to identify the markers and loci underlying resistance to this virus disease. In this study, segregation populations were constructed from two maize elite lines '90110', which is highly resistant to MRDD and 'Ye478', which is highly susceptible to MRDD. The F(2) and BC(1) populations were used for bulk sergeant analysis (BSA) to identify resistance-related markers. One hundred and twenty F(7:9) RILs were used for quantitative trait loci (QTL) mapping through the experiment of multiple environments over 3 years. Natural occurrence and artificial inoculation were both used and combined to determine the phenotype of plants. Five QTL, qMRD2, qMRD6, qMRD7, qMRD8 and qMRD10 were measured in the experiments. The qMRD8 on chromosome 8 was proved to be one major QTL conferring resistance to RBSDV disease in almost all traits and environments, which explained 12.0-28.9 % of the phenotypic variance for disease severity in this present study.

  1. Mapping Quantitative Trait Loci Controlling Milk Production in Dairy Cattle by Exploiting Progeny Testing

    PubMed Central

    Georges, M.; Nielsen, D.; Mackinnon, M.; Mishra, A.; Okimoto, R.; Pasquino, A. T.; Sargeant, L. S.; Sorensen, A.; Steele, M. R.; Zhao, X.; Womack, J. E.; Hoeschele, I.

    1995-01-01

    We have exploited ``progeny testing'' to map quantitative trait loci (QTL) underlying the genetic variation of milk production in a selected dairy cattle population. A total of 1,518 sires, with progeny tests based on the milking performances of > 150,000 daughters jointly, was genotyped for 159 autosomal microsatellites bracketing 1645 centimorgan or approximately two thirds of the bovine genome. Using a maximum likelihood multilocus linkage analysis accounting for variance heterogeneity of the phenotypes, we identified five chromosomes giving very strong evidence (LOD score >/= 3) for the presence of a QTL controlling milk production: chromosomes 1, 6, 9, 10 and 20. These findings demonstrate that loci with considerable effects on milk production are still segregating in highly selected populations and pave the way toward marker-assisted selection in dairy cattle breeding. PMID:7713441

  2. The Utilization during Mitotic Cell Division of Loci Controlling Meiotic Recombination and Disjunction in DROSOPHILA MELANOGASTER

    PubMed Central

    Baker, Bruce S.; Carpenter, Adelaide T. C.; Ripoll, P.

    1978-01-01

    are in a nondividing (G2) state.—Mitotic recombination is at or above control levels in the presence of each of the recombination-defective meiotic mutants examined, suggesting that meiotic and mitotic recombination are under separate genetic control in Drosophila.—Of the six mutants examined that are defective in processes required for regular meiotic chromosome segregation, four (l(1)TW-6cs, cand, mei-S332, ord) affect mitotic chromosome behavior. At semi-restrictive temperatures, the cold sensitive lethal l(1)TW-6cs causes very frequent somatic spots, a substantial proportion of which are attributable to nondisjunction or loss. Thus, this locus specifies a function essential for chromosome segregation at mitosis as well as at the first meiotic division in females. The patterns of mitotic effects caused by cand, mei-S332, and ord suggest that they may be leaky alleles at essential loci that specify functions common to meiosis and mitosis. Mutants at the two remaining loci (nod, pal) do not affect mitotic chromosome stability. PMID:17248870

  3. Identification and mapping of leaf, stem and stripe rust resistance quantitative trait loci and their interactions in durum wheat.

    PubMed

    Singh, A; Pandey, M P; Singh, A K; Knox, R E; Ammar, K; Clarke, J M; Clarke, F R; Singh, R P; Pozniak, C J; Depauw, R M; McCallum, B D; Cuthbert, R D; Randhawa, H S; Fetch, T G

    2013-02-01

    Leaf rust (Puccinia triticina Eriks.), stripe rust (Puccinia striiformis f. tritici Eriks.) and stem rust (Puccinia graminis f. sp. tritici) cause major production losses in durum wheat (Triticum turgidum L. var. durum). The objective of this research was to identify and map leaf, stripe and stem rust resistance loci from the French cultivar Sachem and Canadian cultivar Strongfield. A doubled haploid population from Sachem/Strongfield and parents were phenotyped for seedling reaction to leaf rust races BBG/BN and BBG/BP and adult plant response was determined in three field rust nurseries near El Batan, Obregon and Toluca, Mexico. Stripe rust response was recorded in 2009 and 2011 nurseries near Toluca and near Njoro, Kenya in 2010. Response to stem rust was recorded in field nurseries near Njoro, Kenya, in 2010 and 2011. Sachem was resistant to leaf, stripe and stem rust. A major leaf rust quantitative trait locus (QTL) was identified on chromosome 7B at Xgwm146 in Sachem. In the same region on 7B, a stripe rust QTL was identified in Strongfield. Leaf and stripe rust QTL around DArT marker wPt3451 were identified on chromosome 1B. On chromosome 2B, a significant leaf rust QTL was detected conferred by Strongfield, and at the same QTL, a Yr gene derived from Sachem conferred resistance. Significant stem rust resistance QTL were detected on chromosome 4B. Consistent interactions among loci for resistance to each rust type across nurseries were detected, especially for leaf rust QTL on 7B. Sachem and Strongfield offer useful sources of rust resistance genes for durum rust breeding.

  4. Quantitative trait loci for resistance to Haemonchus contortus artificial challenge in Red Maasai and Dorper sheep of East Africa.

    PubMed

    Marshall, K; Mugambi, J M; Nagda, S; Sonstegard, T S; Van Tassell, C P; Baker, R L; Gibson, J P

    2013-06-01

    A genome-wide scan was performed to detect quantitative trait loci (QTL) for resistance to the gastrointestinal nematode Haemonchus contortus in a double backcross population of Red Maasai and Dorper sheep. The mapping population comprised six sire families, with 1026 lambs in total. The lambs were artificially challenged with H. contortus at about 6.5 months of age, and nine phenotypes were measured: fecal egg count, packed cell volume decline, two weight traits and five worm traits. A subset of the population (342 lambs) was selectively genotyped for 172 microsatellite loci covering 25 of the 26 autosomes. QTL mapping was performed for models which assumed that the QTL alleles were either fixed or segregating within each breed, combined with models with only an additive QTL effect fitted or both additive and dominance QTL effects fitted. Overall, QTL significant at the 1% chromosome-wide level were identified for 22 combinations of trait and chromosome. Of particular interest are a region of chromosome 26 with putative QTL for all nine traits and a region of chromosome 2 with putative QTL for three traits. Favorable QTL alleles for disease resistance originated in both the Red Maasai and Dorper breeds, were not always fixed within breed and had significant dominance effects in some cases. We anticipate that this study, in combination with follow-up work and other relevant studies, will help elucidate the biology of disease resistance.

  5. Signatures of balancing selection are maintained at disease resistance loci following mating system evolution and a population bottleneck in the genus Capsella

    PubMed Central

    2012-01-01

    Background Population bottlenecks can lead to a loss of variation at disease resistance loci, which could have important consequences for the ability of populations to adapt to pathogen pressure. Alternatively, current or past balancing selection could maintain high diversity, creating a strong heterogeneity in the retention of polymorphism across the genome of bottlenecked populations. We sequenced part of the LRR region of 9 NBS-LRR disease resistance genes in the outcrossing Capsella grandiflora and the recently derived, bottlenecked selfing species Capsella rubella, and compared levels and patterns of nucleotide diversity and divergence with genome-wide reference loci. Results In strong contrast with reference loci, average diversity at resistance loci was comparable between C. rubella and C. grandiflora, primarily due to two loci with highly elevated diversity indicative of past or present balancing selection. Average between-species differentiation was also reduced at the set of R-genes compared with reference loci, which is consistent with the maintenance of ancestral polymorphism. Conclusions Historical or ongoing balancing selection on plant disease resistance genes is a likely contributor to the retention of ancestral polymorphism in some regions of the bottlenecked Capella rubella genome. PMID:22909344

  6. Genome-wide association analysis identifies genetic loci associated with resistance to multiple antimalarials in Plasmodium falciparum from China-Myanmar border

    PubMed Central

    Wang, Zenglei; Cabrera, Mynthia; Yang, Jingyun; Yuan, Lili; Gupta, Bhavna; Liang, Xiaoying; Kemirembe, Karen; Shrestha, Sony; Brashear, Awtum; Li, Xiaolian; Porcella, Stephen F.; Miao, Jun; Yang, Zhaoqing; Su, Xin-zhuan; Cui, Liwang

    2016-01-01

    Drug resistance has emerged as one of the greatest challenges facing malaria control. The recent emergence of resistance to artemisinin (ART) and its partner drugs in ART-based combination therapies (ACT) is threatening the efficacy of this front-line regimen for treating Plasmodium falciparum parasites. Thus, an understanding of the molecular mechanisms that underlie the resistance to ART and the partner drugs has become a high priority for resistance containment and malaria management. Using genome-wide association studies, we investigated the associations of genome-wide single nucleotide polymorphisms with in vitro sensitivities to 10 commonly used antimalarial drugs in 94 P. falciparum isolates from the China-Myanmar border area, a region with the longest history of ART usage. We identified several loci associated with various drugs, including those containing pfcrt and pfdhfr. Of particular interest is a locus on chromosome 10 containing the autophagy-related protein 18 (ATG18) associated with decreased sensitivities to dihydroartemisinin, artemether and piperaquine – an ACT partner drug in this area. ATG18 is a phosphatidylinositol-3-phosphate binding protein essential for autophagy and recently identified as a potential ART target. Further investigations on the ATG18 and genes at the chromosome 10 locus may provide an important lead for a connection between ART resistance and autophagy. PMID:27694982

  7. Modular Skeletal Evolution in Sticklebacks Is Controlled by Additive and Clustered Quantitative Trait Loci

    PubMed Central

    Miller, Craig T.; Glazer, Andrew M.; Summers, Brian R.; Blackman, Benjamin K.; Norman, Andrew R.; Shapiro, Michael D.; Cole, Bonnie L.; Peichel, Catherine L.; Schluter, Dolph; Kingsley, David M.

    2014-01-01

    Understanding the genetic architecture of evolutionary change remains a long-standing goal in biology. In vertebrates, skeletal evolution has contributed greatly to adaptation in body form and function in response to changing ecological variables like diet and predation. Here we use genome-wide linkage mapping in threespine stickleback fish to investigate the genetic architecture of evolved changes in many armor and trophic traits. We identify >100 quantitative trait loci (QTL) controlling the pattern of serially repeating skeletal elements, including gill rakers, teeth, branchial bones, jaws, median fin spines, and vertebrae. We use this large collection of QTL to address long-standing questions about the anatomical specificity, genetic dominance, and genomic clustering of loci controlling skeletal differences in evolving populations. We find that most QTL (76%) that influence serially repeating skeletal elements have anatomically regional effects. In addition, most QTL (71%) have at least partially additive effects, regardless of whether the QTL controls evolved loss or gain of skeletal elements. Finally, many QTL with high LOD scores cluster on chromosomes 4, 20, and 21. These results identify a modular system that can control highly specific aspects of skeletal form. Because of the general additivity and genomic clustering of major QTL, concerted changes in both protective armor and trophic traits may occur when sticklebacks inherit either marine or freshwater alleles at linked or possible “supergene” regions of the stickleback genome. Further study of these regions will help identify the molecular basis of both modular and coordinated changes in the vertebrate skeleton. PMID:24652999

  8. Targeted Sequencing of Lung Function Loci in Chronic Obstructive Pulmonary Disease Cases and Controls

    PubMed Central

    Wain, Louise V.; Shrine, Nick; McKeever, Tricia M.; Sayers, Ian; Hall, Ian P.

    2017-01-01

    Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide; smoking is the main risk factor for COPD, but genetic factors are also relevant contributors. Genome-wide association studies (GWAS) of the lung function measures used in the diagnosis of COPD have identified a number of loci, however association signals are often broad and collectively these loci only explain a small proportion of the heritability. In order to examine the association with COPD risk of genetic variants down to low allele frequencies, to aid fine-mapping of association signals and to explain more of the missing heritability, we undertook a targeted sequencing study in 300 COPD cases and 300 smoking controls for 26 loci previously reported to be associated with lung function. We used a pooled sequencing approach, with 12 pools of 25 individuals each, enabling high depth (30x) coverage per sample to be achieved. This pooled design maximised sample size and therefore power, but led to challenges during variant-calling since sequencing error rates and minor allele frequencies for rare variants can be very similar. For this reason we employed a rigorous quality control pipeline for variant detection which included the use of 3 independent calling algorithms. In order to avoid false positive associations we also developed tests to detect variants with potential batch effects and removed them before undertaking association testing. We tested for the effects of single variants and the combined effect of rare variants within a locus. We followed up the top signals with data available (only 67% of collapsing methods signals) in 4,249 COPD cases and 11,916 smoking controls from UK Biobank. We provide suggestive evidence for the combined effect of rare variants on COPD risk in TNXB and in sliding windows within MECOM and upstream of HHIP. These findings can lead to an improved understanding of the molecular pathways involved in the development of COPD. PMID:28114305

  9. Targeted Sequencing of Lung Function Loci in Chronic Obstructive Pulmonary Disease Cases and Controls.

    PubMed

    Artigas, María Soler; Wain, Louise V; Shrine, Nick; McKeever, Tricia M; Sayers, Ian; Hall, Ian P; Tobin, Martin D

    2017-01-01

    Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide; smoking is the main risk factor for COPD, but genetic factors are also relevant contributors. Genome-wide association studies (GWAS) of the lung function measures used in the diagnosis of COPD have identified a number of loci, however association signals are often broad and collectively these loci only explain a small proportion of the heritability. In order to examine the association with COPD risk of genetic variants down to low allele frequencies, to aid fine-mapping of association signals and to explain more of the missing heritability, we undertook a targeted sequencing study in 300 COPD cases and 300 smoking controls for 26 loci previously reported to be associated with lung function. We used a pooled sequencing approach, with 12 pools of 25 individuals each, enabling high depth (30x) coverage per sample to be achieved. This pooled design maximised sample size and therefore power, but led to challenges during variant-calling since sequencing error rates and minor allele frequencies for rare variants can be very similar. For this reason we employed a rigorous quality control pipeline for variant detection which included the use of 3 independent calling algorithms. In order to avoid false positive associations we also developed tests to detect variants with potential batch effects and removed them before undertaking association testing. We tested for the effects of single variants and the combined effect of rare variants within a locus. We followed up the top signals with data available (only 67% of collapsing methods signals) in 4,249 COPD cases and 11,916 smoking controls from UK Biobank. We provide suggestive evidence for the combined effect of rare variants on COPD risk in TNXB and in sliding windows within MECOM and upstream of HHIP. These findings can lead to an improved understanding of the molecular pathways involved in the development of COPD.

  10. Rapid generation of drug-resistance alleles at endogenous loci using CRISPR-Cas9 indel mutagenesis

    PubMed Central

    Ipsaro, Jonathan J.; Shen, Chen; Arai, Eri; Xu, Yali; Kinney, Justin B.; Joshua-Tor, Leemor; Vakoc, Christopher R.

    2017-01-01

    Genetic alterations conferring resistance to the effects of chemical inhibitors are valuable tools for validating on-target effects in cells. Unfortunately, for many therapeutic targets such alleles are not available. To address this issue, we evaluated whether CRISPR-Cas9-mediated insertion/deletion (indel) mutagenesis can produce drug-resistance alleles at endogenous loci. This method takes advantage of the heterogeneous in-frame alleles produced following Cas9-mediated DNA cleavage, which we show can generate rare alleles that confer resistance to the growth-arrest caused by chemical inhibitors. We used this approach to identify novel resistance alleles of two lysine methyltransferases, DOT1L and EZH2, which are each essential for the growth of MLL-fusion leukemia cells. We biochemically characterized the DOT1L mutation, showing that it is significantly more active than the wild-type enzyme. These findings validate the on-target anti-leukemia activities of existing DOT1L and EZH2 inhibitors and reveal a simple method for deriving drug-resistance alleles for novel targets, which may have utility during early stages of drug development. PMID:28231254

  11. Rapid generation of drug-resistance alleles at endogenous loci using CRISPR-Cas9 indel mutagenesis.

    PubMed

    Ipsaro, Jonathan J; Shen, Chen; Arai, Eri; Xu, Yali; Kinney, Justin B; Joshua-Tor, Leemor; Vakoc, Christopher R; Shi, Junwei

    2017-01-01

    Genetic alterations conferring resistance to the effects of chemical inhibitors are valuable tools for validating on-target effects in cells. Unfortunately, for many therapeutic targets such alleles are not available. To address this issue, we evaluated whether CRISPR-Cas9-mediated insertion/deletion (indel) mutagenesis can produce drug-resistance alleles at endogenous loci. This method takes advantage of the heterogeneous in-frame alleles produced following Cas9-mediated DNA cleavage, which we show can generate rare alleles that confer resistance to the growth-arrest caused by chemical inhibitors. We used this approach to identify novel resistance alleles of two lysine methyltransferases, DOT1L and EZH2, which are each essential for the growth of MLL-fusion leukemia cells. We biochemically characterized the DOT1L mutation, showing that it is significantly more active than the wild-type enzyme. These findings validate the on-target anti-leukemia activities of existing DOT1L and EZH2 inhibitors and reveal a simple method for deriving drug-resistance alleles for novel targets, which may have utility during early stages of drug development.

  12. Barbarea vulgaris linkage map and quantitative trait loci for saponins, glucosinolates, hairiness and resistance to the herbivore Phyllotreta nemorum.

    PubMed

    Kuzina, Vera; Nielsen, Jens Kvist; Augustin, Jörg Manfred; Torp, Anna Maria; Bak, Søren; Andersen, Sven Bode

    2011-02-01

    Combined genomics and metabolomics approaches were used to unravel molecular mechanisms behind interactions between winter cress (Barbarea vulgaris) and flea beetle (Phyllotreta nemorum). B. vulgaris comprises two morphologically, biochemically and cytologically deviating types, which differ in flea beetle resistance, saponin and glucosinolate profiles, as well as leaf pubescence. An F2 population generated from a cross between the two B. vulgaris types was used to construct a B. vulgaris genetic map based on 100 AFLP and 31 microsatellite markers. The map was divided into eight linkage groups. QTL (quantitative trait loci) analysis revealed a total of 15 QTL affecting eight traits, including nine QTL for four saponins, two QTL for two glucosinolates, two QTL for hairiness, and two QTL for flea beetle resistance. The two QTL for resistance towards flea beetles in B. vulgaris co-localized with QTL for the four saponins associated with resistance. Furthermore, global QTL analysis of B. vulgaris metabolites identified QTL for a number of flavonoid glycosides and additional saponins from both resistant and susceptible types. The transcriptome of the resistant B. vulgaris type was sequenced by pyrosequencing, and sequences containing microsatellites were identified. Microsatellite types in B. vulgaris were similar to Arabidopsis thaliana but different from Oryza sativa. Comparative analysis between B. vulgaris and A. thaliana revealed a remarkable degree of synteny between a large part of linkage groups 1 and 4 of B. vulgaris harboring the two QTL for flea beetle resistance and Arabidopsis chromosomes 3 and 1. Gene candidates that may underlie QTL for resistance and saponin biosynthesis are discussed.

  13. Identification of quantitative trait loci conditioning partial resistance to Phytophthora sojae in soybean PI 407861A

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Improving resistance for Phytophthora root and stem rot is an important goal in soybean [Glycine max (L.) Merr.] breeding. Partial resistance can be as effective in managing this disease as single-gene (Rps) mediated resistance and is more durable. The objective of this study was to identify QTL con...

  14. Quantitative trait loci meta-analysis of Plum pox virus resistance in apricot (Prunus armeniaca L.): new insights on the organization and the identification of genomic resistance factors.

    PubMed

    Marandel, Grégoire; Salava, Jaroslav; Abbott, Albert; Candresse, Thierry; Decroocq, Véronique

    2009-05-01

    Plum pox virus (PPV) is responsible for sharka disease, one of the most detrimental stone fruit diseases affecting Prunus trees worldwide. Only a few apricot cultivars have been described as resistant, most originating from North American breeding programmes. Several PPV resistance quantitative trait loci (QTLs) have been mapped in various progenies, consistently highlighting the contribution to the resistance of the upper part of linkage group 1 (LG1). However, to date, no consensus has been reached on the precise number of QTLs linked to the resistance to PPV in apricot and P. davidiana or on their accurate position on the genetic linkage map. In the present study, the quantitative resistance of cultivar 'Harlayne' was analysed over five growth periods in a large F1 population. Four QTLs were identified, three mapping on LG1, explaining between 5% and 39% of the observed phenotypic variance. In an effort to further this analysis of PPV resistance in apricot, these results were merged in a single QTL meta-analysis with those of five other PPV resistance analyses available in the literature. Three consensus QTL regions were identified on LG1 and a putative fourth region on LG3. QTL meta-analysis also revealed the contribution of each resistant cultivar to metaQTLs, providing interesting comparative data on the resistance factors shared between the resistance sources used in the various studies. Finally, it was shown that one of the metaQTLs co-localizes with the eukaryotic translation initiation factor eIF4E, thus providing new hypotheses on the mechanisms of PPV resistance in apricot.

  15. Association mapping utilizing diverse barley lines reveals net form net blotch seedling resistance/susceptibility loci

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pyrenophora teres f. teres is a necrotrophic fungal pathogen and the causal agent of the economically important foliar disease net form net blotch (NFNB) of barley. The deployment of effective and durable resistance against P. teres f. teres has been hindered by the complexity of quantitative resist...

  16. Quantitative trait loci for Fusarium head blight resistance in Huangcandou x 'Jagger' wheat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fusarium head blight (FHB) is a devastating disease in wheat (Triticum aestivum), and growing resistant cultivars is one of the most effective strategies to minimize its damage. Huangcandou (HCD) is a Chinese wheat landrace that shows a high level of resistance to FHB spread within a spike (type II)...

  17. Quantitative trait loci from two genotypes of oat (Avena sativa L.) conditioning resistance to Puccinia coronata

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Developing oat cultivars with partial resistance to crown rust would be beneficial for disease management. Two recombinant inbred line (RIL) populations were derived by crossing the susceptible cultivar ‘Provena’ with two partially resistant sources, ‘CDC Boyer’ and breeding line 94197A1-9-2-2-2-5. ...

  18. Novel quantitative trait loci for partial resistance to Phytophthora sojae in soybean PI 398841

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phytophthora root and stem rot caused by Phytophthora sojae Kaufmann and Gerdmann is one of the most severe soybean [Glycine max (L.) Merr] diseases in the US. Partial resistance is as effective in managing this disease as single-gene (Rps) mediated resistance and is more durable. The objective of t...

  19. New consistent QTL in pea associated with partial resistance to Aphanomyces euteiches in multiple field and controlled environments from France and the United States

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Partial resistances, often controlled by QTL (Quantitative Trait Loci), are considered to be more durable than monogenic resistances. Prior to develop efficient breeding programs for polygenic resistance to pathogens, a higher understanding of genetic diversity and stability of resistance QTL in pla...

  20. Linkage and mapping of quantitative trait loci associated with angular leaf spot and powdery mildew resistance in common beans.

    PubMed

    Bassi, Denis; Briñez, Boris; Rosa, Juliana Santa; Oblessuc, Paula Rodrigues; Almeida, Caléo Panhoca de; Nucci, Stella Maris; Silva, Larissa Chariel Domingos da; Chiorato, Alisson Fernando; Vianello, Rosana Pereira; Camargo, Luis Eduardo Aranha; Blair, Matthew Wohlgemuth; Benchimol-Reis, Luciana Lasry

    2017-02-20

    Angular leaf spot (ALS) and powdery mildew (PWM) are two important fungi diseases causing significant yield losses in common beans. In this study, a new genetic linkage map was constructed using single sequence repeats (SSRs) and single nucleotide polymorphisms (SNPs), in a segregating population derived from the AND 277 x SEA 5 cross, with 105 recombinant inbred lines. Phenotypic evaluations were performed in the greenhouse to identify quantitative trait loci (QTLs) associated with resistance by means of the composite interval mapping analysis. Four QTLs were identified for ALS resistance. The QTL ALS11AS, linked on the SNP BAR 5054, mapped on chromosome Pv11, showed the greatest effect (R2 = 26.5%) on ALS phenotypic variance. For PWM resistance, two QTLs were detected, PWM2AS and PWM11AS, on Pv2 and Pv11, explaining 7% and 66% of the phenotypic variation, respectively. Both QTLs on Pv11 were mapped on the same genomic region, suggesting that it is a pleiotropic region. The present study resulted in the identification of new markers closely linked to ALS and PWM QTLs, which can be used for marker-assisted selection, fine mapping and positional cloning.

  1. Two alternative recessive quantitative trait loci influence resistance to spring black stem and leaf spot in Medicago truncatula

    PubMed Central

    Kamphuis, Lars G; Lichtenzveig, Judith; Oliver, Richard P; Ellwood, Simon R

    2008-01-01

    is tightly linked to a cluster of Toll/Interleukin1 receptor-nucleotide binding site-leucine-rich repeat (TIR-NBS-LRR) genes and disease resistance protein-like genes, while no resistance gene analogues (RGAs) are apparent in the genomic sequence of the reference accession A17 at the rnpm2 locus. Conclusion The induction of defence responses and cell death in the susceptible interaction following infection by P. medicaginis suggested this pathogen is not negatively affected by these responses and may promote them. A QTL for resistance was revealed in each of two populations derived from crosses between a resistant accession and two different susceptible accessions. Both loci are recessive in nature, and the simplest explanation for the existence of two separate QTLs is the occurrence of host genotype-specific susceptibility loci that may interact with undetermined P. medicaginis virulence factors. PMID:18366746

  2. Putative resistance gene markers associated with quantitative trait loci for fire blight resistance in Malus 'Robusta 5' accessions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Breeding of fire blight resistant scions and rootstocks is a goal of several international apple breeding programs, as options are limited for management of this destructive disease caused by the bacterial pathogen Erwinia amylovora. A broad, large effect QTL for fire blight resistance has been pre...

  3. A native QTL for Fusarium head blight resistance in North American barley (Hordeum vulgare L.) independent of height, maturity, and spike type loci.

    PubMed

    Yu, G T; Franckowiak, J D; Neate, S M; Zhang, B; Horsley, R D

    2010-02-01

    Fusarium head blight (FHB), caused by Fusarium graminearum Schwabe (teleomorph Gibberella zeae (Schwein.) Petch), is one of the major diseases of barley (Hordeum vulgare L.) in eastern China, the Upper Midwest of the USA, and the eastern Prairie Provinces of Canada. To identify quantitative trait loci (QTL) controlling FHB resistance, a recombinant inbred line population (F6:7) was developed from the cross Zhenongda 7/PI 643302. The population was phenotyped for resistance to FHB in two experiments in China and four experiments in North Dakota. Accumulation of the mycotoxin deoxynivalenol was determined in one experiment in China and two in North Dakota. Simplified composite interval mapping was performed on the whole genome level using the software MQTL. The QTL FHB-2 from PI 643302 for FHB resistance was found on the distal portion of chromosome 2HL in all six FHB screening environments. This QTL accounted for 14% of phenotypic variation over six environments and was not associated with heading date or plant height. The FHB resistance QTL FHB-2 detected near the end of chromosome 2HL is in a different location from those found previously and is therefore probably unique. Because the QTL was not contributed by the Chinese cultivar Zhenongda 7, it is likely a native QTL present in North American barley. The QTL FHB-2 represents the first reported QTL for native FHB resistance in North American germ plasm and has been given the provisional name Qrgz-2H-14. This QTL should be considered for pyramiding with other FHB QTL previously mapped.

  4. Identification of quantitative trait loci affecting resistance to gastro-intestinal parasites in a double backcross population of Red Maasai and Dorper sheep

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A genome-wide scan for quantitative trait loci (QTL) affecting gastrointestinal (GI) nematode resistance was completed using a double backcross sheep population derived from Red Maasai and Dorper ewes bred to F1 rams. These breeds were chosen, because Red Maasai sheep are known to be more tolerant ...

  5. Compact, Controlled Resistance Exercise Device

    NASA Technical Reports Server (NTRS)

    Paulus, David C.; DeWitt, John K.; Reich, Alton J.; Shaw, James E.; Deaconu, Stelu S.

    2011-01-01

    Spaceflight leads to muscle and bone atrophy. Isoinertial (free-weight) exercises provide a sufficient stimulus to elicit increases in both muscle strength and bone mineral density in Earth-based studies. While exercise equipment is in use on the International Space Station for crewmember health maintenance, current devices are too large to place in a transport vehicle or small spacecraft. Therefore, a portable computer controlled resistance exercise device is being developed that is able to simulate the inertial loading experienced when lifting a mass on Earth. This portable device weighs less than 50 lb and can simulate the resistance of lifting and lowering up to 600 lb of free-weights. The objective is to allow crewmembers to perform resistance exercise with loads capable of maintaining muscle and bone health. The device is reconfigurable and allows for the performance of typical Earth-based free-weight exercises. Forces exerted, volume of work, range of motion, time-under-tension, and speed/ acceleration of movement are recorded and can be remotely monitored to track progress and modify individual protocols based on exercise session data. A performance evaluation will be completed and data will be presented that include ground-reaction force comparisons between the device and free-weight dead-lifts over a spectrum of resistance levels. Movement biomechanics will also be presented.

  6. Grapevine powdery mildew resistance and susceptibility loci identified on a high-resolution SNP map.

    PubMed

    Barba, Paola; Cadle-Davidson, Lance; Harriman, James; Glaubitz, Jeffrey C; Brooks, Siraprapa; Hyma, Katie; Reisch, Bruce

    2014-01-01

    Improved efficacy and durability of powdery mildew resistance can be enhanced via knowledge of the genetics of resistance and susceptibility coupled with the development of high-resolution maps to facilitate the stacking of multiple resistance genes and other desirable traits. We studied the inheritance of powdery mildew (Erysiphe necator) resistance and susceptibility of wild Vitis rupestris B38 and cultivated V. vinifera 'Chardonnay', finding evidence for quantitative variation. Molecular markers were identified using genotyping-by-sequencing, resulting in 16,833 single nucleotide polymorphisms (SNPs) based on alignment to the V. vinifera 'PN40024' reference genome sequence. With an average density of 36 SNPs/Mbp and uniform coverage of the genome, this 17K set was used to identify 11 SNPs on chromosome 7 associated with a resistance locus from V. rupestris B38 and ten SNPs on chromosome 9 associated with a locus for susceptibility from 'Chardonnay' using single marker association and linkage disequilibrium analysis. Linkage maps for V. rupestris B38 (1,146 SNPs) and 'Chardonnay' (1,215 SNPs) were constructed and used to corroborate the 'Chardonnay' locus named Sen1 (Susceptibility to Erysiphe necator 1), providing the first insight into the genetics of susceptibility to powdery mildew from V. vinifera. The identification of markers associated with a susceptibility locus in a V. vinifera background can be used for negative selection among breeding progenies. This work improves our understanding of the nature of powdery mildew resistance in V. rupestris B38 and 'Chardonnay', while applying next-generation sequencing tools to advance grapevine genomics and breeding.

  7. Identification of QTL controlling high levels of partial resistance to Fusarium solani f. sp. pisi in pea

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fusarium root rot is a common biotic restraint on pea yields worldwide and genetic resistance is the most feasible method for improving pea production. This study was conducted to discover quantitative trait loci (QTL) controlling genetic partial resistance to Fusarium root rot caused by Fusarium s...

  8. Yield effecgs of two southern leaf blight resistance loci in maize hybrids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plants need to balance resources between yield and defense. This phenomenon has rarely been investigated in the context of naturally-occurring quantitative resistance alleles in an agricultural production environment. B73-3B and B73-6A are two near-isogenic lines (NILs) in the background of the mai...

  9. Using genotyping by sequencing (GBS) to identify Loci in Colocasiae esculenta linked to Phytophthora colocasiae resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    One of the most significant threats to taro production is taro leaf blight (TLB) caused by the oomycete pathogen Phytophthora colocasiae. Therefore, one of the primary selection criteria for the University of Hawaii taro breeding program is TLB resistance. Some cultivars from Palau, Micronesia and o...

  10. Fusarium head blight resistance loci in a stratified population of wheat landraces and varieties

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To determine if Chinese and Japanese wheat landraces and varieties have unique sources of Fusarium head blight (FHB) resistance, an association mapping panel of 195 wheat accessions including both commercial varieties and landraces was genotyped with 364 genome-wide simple sequence repeat (SSR) and ...

  11. Quantitative Trait Loci for Aluminum Resistance in Chinese Wheat Landrace FSW

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aluminum (Al) toxicity is a major constraint for wheat production in acid soils worldwide. Chinese landrace FSW demonstrates a high level of Al resistance. A population of 170 F6 recombinant inbred lines (RILs) was developed from a cross between FSW and an Al-sensitive Chinese line, ND35, using sing...

  12. Quantitative Trait Loci for Partial Resistance to Phytophthora Sojaei in Soybean [Glycine Max (L.) Merr.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phytophthora root and stem rot of soybean, caused by the oomycete, Phytophthora sojae, is one of the most destructive diseases to limit soybean production in the US. Although fourteen resistance genes (Rps) to P. sojae have been identified, adaptation of by the pathogen has made many of these ineffe...

  13. Confirming QTLs and finding additional Loci responsible for resistance to Sheath Blight in Rice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rice sheath blight (ShB) caused by the soil borne pathogen Rhizoctonia solani, is one of the most destructive diseases of rice around the globe, causing severe losses in rice yield and quality annually. Major genes governing resistance to ShB have not been found in cultivated rice worldwide; however...

  14. Quantitative trait loci for resistance to common scab and cold-induced sweetening in diploid potato

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The development of germplasm with resistance to common scab and cold-induced sweetening is a high priority for the potato industry. A mapping population was developed from mating two individuals from a diploid family generated by crossing the susceptible cultivated potato (Solanum tuberosum) clone U...

  15. Mapping the Rust Resistant Loci MXC3 and MER in P. trichocarpa and Assessing the Intermarker Linkage Disequilibrium in MXC3 Region

    SciTech Connect

    Yin, Tongming; Difazio, Stephen P.; Gunter, Lee E; Tuskan, Gerald A

    2004-01-01

    In an attempt to elucidate the molecular mechanisms of Melampsora rust resistance in Populus trichocarpa, we have mapped two resistance loci, MXC3 and MER, and intensively characterized the flanking genomic sequence for the MXC3 locus and the level of linkage disequilibrium (LD) in natural populations. We used an interspecific backcross pedigree and a genetic map that was highly saturated with AFLP and SSR markers, and assembled shotgun-sequence data in the region containing markers linked to MXC3. The two loci were mapped to different linkage groups. Linkage disequilibrium for MXC3 was confined to two closely linked regions spanning 34 and 16 kb, respectively. The MXC3 region also contained six disease-resistance candidate genes. The MER and MXC3 loci are clearly distinct, and may have different mechanisms of resistance, as different classes of putative resistance genes were present near each locus. The suppressed recombination previously observed in the MXC3 region was possibly caused by extensive hemizygous rearrangements confined to the original parent tree. The relatively low observed LD may facilitate association studies using candidate genes for rust resistance, but will probably inhibit marker-aided selection.

  16. Genome-Wide Association Study and QTL Mapping Reveal Genomic Loci Associated with Fusarium Ear Rot Resistance in Tropical Maize Germplasm

    PubMed Central

    Chen, Jiafa; Shrestha, Rosemary; Ding, Junqiang; Zheng, Hongjian; Mu, Chunhua; Wu, Jianyu; Mahuku, George

    2016-01-01

    Fusarium ear rot (FER) incited by Fusarium verticillioides is a major disease of maize that reduces grain quality globally. Host resistance is the most suitable strategy for managing the disease. We report the results of genome-wide association study (GWAS) to detect alleles associated with increased resistance to FER in a set of 818 tropical maize inbred lines evaluated in three environments. Association tests performed using 43,424 single-nucleotide polymorphic (SNPs) markers identified 45 SNPs and 15 haplotypes that were significantly associated with FER resistance. Each associated SNP locus had relatively small additive effects on disease resistance and accounted for 1–4% of trait variation. These SNPs and haplotypes were located within or adjacent to 38 candidate genes, 21 of which were candidate genes associated with plant tolerance to stresses, including disease resistance. Linkage mapping in four biparental populations to validate GWAS results identified 15 quantitative trait loci (QTL) associated with F. verticillioides resistance. Integration of GWAS and QTL to the maize physical map showed eight colocated loci on chromosomes 2, 3, 4, 5, 9, and 10. QTL on chromosomes 2 and 9 are new. These results reveal that FER resistance is a complex trait that is conditioned by multiple genes with minor effects. The value of selection on identified markers for improving FER resistance is limited; rather, selection to combine small effect resistance alleles combined with genomic selection for polygenic background for both the target and general adaptation traits might be fruitful for increasing FER resistance in maize. PMID:27742723

  17. Genetic Architecture of Resistance to Alternaria brassicae in Arabidopsis thaliana: QTL Mapping Reveals Two Major Resistance-Conferring Loci

    PubMed Central

    Rajarammohan, Sivasubramanian; Kumar, Amarendra; Gupta, Vibha; Pental, Deepak; Pradhan, Akshay K.; Kaur, Jagreet

    2017-01-01

    Alternaria brassicae, a necrotrophic fungal pathogen, causes Alternaria blight, one of the most important diseases of oleiferous Brassica crops. The current study utilized Arabidopsis as a model to decipher the genetic architecture of defense against A. brassicae. Significant phenotypic variation that was largely genetically determined was observed among Arabidopsis accessions in response to pathogen challenge. Three biparental mapping populations were developed from three resistant accessions viz. CIBC-5, Ei-2, and Cvi-0 and two susceptible accessions – Gre-0 and Zdr-1 (commonly crossed to CIBC-5 and Ei-2). A total of six quantitative trait locus (QTLs) governing resistance to A. brassicae were identified, five of which were population-specific while one QTL was common between all the three mapping populations. Interestingly, the common QTL had varying phenotypic contributions in different populations, which can be attributed to the genetic background of the parental accessions. The presence of both common and population-specific QTLs indicate that resistance to A. brassicae is quantitative, and that different genes may mediate resistance to the pathogen in different accessions. Two of the QTLs had moderate-to-large effects, one of which explained nearly 50% of the variation. The large effect QTLs may therefore contain genes that could play a significant role in conferring resistance even in heterologous hosts. PMID:28286515

  18. Genetic bases of estrogen-induced tumorigenesis in the rat: mapping of loci controlling susceptibility to mammary cancer in a Brown Norway x ACI intercross.

    PubMed

    Schaffer, Beverly S; Lachel, Cynthia M; Pennington, Karen L; Murrin, Clare R; Strecker, Tracy E; Tochacek, Martin; Gould, Karen A; Meza, Jane L; McComb, Rodney D; Shull, James D

    2006-08-01

    Exposure to estrogens is associated with an increased risk of breast cancer. Our laboratory has shown that the ACI rat is uniquely susceptible to 17beta-estradiol (E2)-induced mammary cancer. We previously mapped two loci, Emca1 and Emca2 (estrogen-induced mammary cancer), that act independently to determine susceptibility to E2-induced mammary cancer in crosses between the susceptible ACI rat strain and the genetically related, but resistant, Copenhagen (COP) rat strain. In this study, we evaluate susceptibility to E2-induced mammary cancer in a cross between the ACI strain and the unrelated Brown Norway (BN) rat strain. Whereas nearly 100% of the ACI rats developed mammary cancer when treated continuously with E2, BN rats did not develop palpable mammary cancer during the 196-day course of E2 treatment. Susceptibility to E2-induced mammary cancer segregated as a dominant or incompletely dominant trait in a cross between BN females and ACI males. In a population of 251 female (BN x ACI)F(2) rats, we observed evidence for a total of five genetic determinants of susceptibility. Two loci, Emca4 and Emca5, were identified when mammary cancer status at sacrifice was evaluated as the phenotype, and three additional loci, Emca6, Emca7, and Emca8, were identified when mammary cancer number was evaluated as the phenotype. A total of three genetic interactions were identified. These data indicate that susceptibility to E2-induced mammary cancer in the BN x ACI cross behaves as a complex trait controlled by at least five loci and multiple gene-gene interactions.

  19. Unique genetic loci identified for emotional behavior in control and chronic stress conditions

    PubMed Central

    Carhuatanta, Kimberly A. K.; Shea, Chloe J. A.; Herman, James P.; Jankord, Ryan

    2014-01-01

    An individual's genetic background affects their emotional behavior and response to stress. Although studies have been conducted to identify genetic predictors for emotional behavior or stress response, it remains unknown how prior stress history alters the interaction between an individual's genome and their emotional behavior. Therefore, the purpose of this study is to identify chromosomal regions that affect emotional behavior and are sensitive to stress exposure. We utilized the BXD behavioral genetics mouse model to identify chromosomal regions that predict fear learning and emotional behavior following exposure to a control or chronic stress environment. 62 BXD recombinant inbred strains and C57BL/6 and DBA/2 parental strains underwent behavioral testing including a classical fear conditioning paradigm and the elevated plus maze. Distinct quantitative trait loci (QTLs) were identified for emotional learning, anxiety and locomotion in control and chronic stress populations. Candidate genes, including those with already known functions in learning and stress were found to reside within the identified QTLs. Our data suggest that chronic stress history reveals novel genetic predictors of emotional behavior. PMID:25374516

  20. Towards Positional Isolation of Three Quantitative Trait Loci Conferring Resistance to Powdery Mildew in Two Spanish Barley Landraces

    PubMed Central

    Silvar, Cristina; Perovic, Dragan; Nussbaumer, Thomas; Spannagl, Manuel; Usadel, Björn; Casas, Ana; Igartua, Ernesto; Ordon, Frank

    2013-01-01

    Three quantitative trait loci (QTL) conferring broad spectrum resistance to powdery mildew, caused by the fungus Blumeria graminis f. sp. hordei, were previously identified on chromosomes 7HS, 7HL and 6HL in the Spanish barley landrace-derived lines SBCC097 and SBCC145. In the present work, a genome-wide putative linear gene index of barley (Genome Zipper) and the first draft of the physical, genetic and functional sequence of the barley genome were used to go one step further in the shortening and explicit demarcation on the barley genome of these regions conferring resistance to powdery mildew as well as in the identification of candidate genes. First, a comparative analysis of the target regions to the barley Genome Zippers of chromosomes 7H and 6H allowed the development of 25 new gene-based molecular markers, which slightly better delimit the QTL intervals. These new markers provided the framework for anchoring of genetic and physical maps, figuring out the outline of the barley genome at the target regions in SBCC097 and SBCC145. The outermost flanking markers of QTLs on 7HS, 7HL and 6HL defined a physical area of 4 Mb, 3.7 Mb and 3.2 Mb, respectively. In total, 21, 10 and 16 genes on 7HS, 7HL and 6HL, respectively, could be interpreted as potential candidates to explain the resistance to powdery mildew, as they encode proteins of related functions with respect to the known pathogen defense-related processes. The majority of these were annotated as belonging to the NBS-LRR class or protein kinase family. PMID:23826271

  1. The making of a bell pepper-shaped tomato fruit: identification of loci controlling fruit morphology in Yellow Stuffer tomato.

    PubMed

    van der Knaap, E; Tanksley, S D

    2003-06-01

    The heirloom tomato cultivar Yellow Stuffer produces fruit that are similar in shape and structure to fruit produced by the bell pepper varieties of garden pepper. To determine the genetic basis of this extreme fruit type in tomato, quantitative trait loci (QTL) analysis was performed on an F(2) population derived from a cross between Yellow Stuffer and the related species, Lycopersicon pimpinellifolium, which produces a small, round fruit typical of most wild species. F(2) plants were analyzed for both fruit size and the degree to which their fruit resembled the bell pepper. Three QTL were determined to influence bell pepper shape and seven QTL influenced fruit mass. The map positions of all three bell shape and six out of seven fruit size QTL appear to be allelic to components of fruit morphology analyzed in this population and to major fruit morphology QTL reported previously, adding support to the hypothesis that the majority of fruit size and shape variation in cultivated tomato is attributable to allelic variation at a limited number of loci. However, novel loci controlling components of fruit morphology, such as elongated fruit shape, bumpiness, number of seed per fruit and flowers per inflorescence were identified in this study as well. The three bell shape loci involved are: bell2.1, bell2.2 and bell8.1, and appear to correspond to locule number2.1 ( lcn2.1) and fruit weight 2.2 ( fw2.2) and fruit shape 8.1 ( fs8.1), respectively. The Yellow Stuffer alleles at lcn2.1 and fw2.2 increase locule number and fruit size, respectively, hence contributing to the overall bell pepper shape. The Yellow Stuffer allele at fs8.1 causes convex locule walls, giving the extended, bumpy shape characteristic of bell peppers. In addition, most fruit size QTL correspond to loci controlling number of flowers per inflorescence and/or stem-end blockiness. Comparisons among previously identified fruit morphology loci in tomato, eggplant and pepper suggest that loci affecting

  2. Quantitative trait loci associated with longevity of lettuce seeds under conventional and controlled deterioration storage conditions.

    PubMed

    Schwember, Andrés R; Bradford, Kent J

    2010-10-01

    Lettuce (Lactuca sativa L.) seeds have poor shelf life and exhibit thermoinhibition (fail to germinate) above ∼25°C. Seed priming (controlled hydration followed by drying) alleviates thermoinhibition by increasing the maximum germination temperature, but reduces lettuce seed longevity. Controlled deterioration (CD) or accelerated ageing storage conditions (i.e. elevated temperature and relative humidity) are used to study seed longevity and to predict potential seed lifetimes under conventional storage conditions. Seeds produced in 2002 and 2006 of a recombinant inbred line (RIL) population derived from a cross between L. sativa cv. Salinas×L. serriola accession UC96US23 were utilized to identify quantitative trait loci (QTLs) associated with seed longevity under CD and conventional storage conditions. Multiple longevity-associated QTLs were identified under both conventional and CD storage conditions for control (non-primed) and primed seeds. However, seed longevity was poorly correlated between the two storage conditions, suggesting that deterioration processes under CD conditions are not predictive of ageing in conventional storage conditions. Additionally, the same QTLs were not identified when RIL populations were grown in different years, indicating that lettuce seed longevity is strongly affected by production environment. Nonetheless, a major QTL on chromosome 4 [Seed longevity 4.1 (Slg4.1)] was responsible for almost 23% of the phenotypic variation in viability of the conventionally stored control seeds of the 2006 RIL population, with improved longevity conferred by the Salinas allele. QTL analyses may enable identification of mechanisms responsible for the sensitivity of primed seeds to CD conditions and breeding for improved seed longevity.

  3. Genetic linkage analysis of the lesser grain borer Rhyzopertha dominica identifies two loci that confer high-level resistance to the fumigant phosphine.

    PubMed Central

    Schlipalius, David I; Cheng, Qiang; Reilly, Paul E B; Collins, Patrick J; Ebert, Paul R

    2002-01-01

    High levels of inheritable resistance to phosphine in Rhyzopertha dominica have recently been detected in Australia and in an effort to isolate the genes responsible for resistance we have used random amplified DNA fingerprinting (RAF) to produce a genetic linkage map of R. dominica. The map consists of 94 dominant DNA markers with an average distance between markers of 4.6 cM and defines nine linkage groups with a total recombination distance of 390.1 cM. We have identified two loci that are responsible for high-level resistance. One provides approximately 50x resistance to phosphine while the other provides 12.5x resistance and in combination, the two genes act synergistically to provide a resistance level 250x greater than that of fully susceptible beetles. The haploid genome size has been determined to be 4.76 x 10(8) bp, resulting in an average physical distance of 1.2 Mbp per map unit. No recombination has been observed between either of the two resistance loci and their adjacent DNA markers in a population of 44 fully resistant F5 individuals, which indicates that the genes are likely to reside within 0.91 cM (1.1 Mbp) of the DNA markers. PMID:12072472

  4. Mapping Quantitative Trait Loci of Resistance to Tomato Spotted Wilt Virus and Leaf Spots in a Recombinant Inbred Line Population of Peanut (Arachis hypogaea L.) from SunOleic 97R and NC94022

    PubMed Central

    Feng, Suping; Qiao, Lixian; Culbreath, Albert K.; Kale, Sandip; Wang, Jianping; Holbrook, C. Corley; Zhuang, Weijian; Varshney, Rajeev K.; Guo, Baozhu

    2016-01-01

    Peanut is vulnerable to a range of diseases, such as Tomato spotted wilt virus (TSWV) and leaf spots which will cause significant yield loss. The most sustainable, economical and eco-friendly solution for managing peanut diseases is development of improved cultivars with high level of resistance. We developed a recombinant inbred line population from the cross between SunOleic 97R and NC94022, named as the S-population. An improved genetic linkage map was developed for the S-population with 248 marker loci and a marker density of 5.7 cM/loci. This genetic map was also compared with the physical map of diploid progenitors of tetraploid peanut, resulting in an overall co-linearity of about 60% with the average co-linearity of 68% for the A sub-genome and 47% for the B sub-genome. The analysis using the improved genetic map and multi-season (2010–2013) phenotypic data resulted in the identification of 48 quantitative trait loci (QTLs) with phenotypic variance explained (PVE) from 3.88 to 29.14%. Of the 48 QTLs, six QTLs were identified for resistance to TSWV, 22 QTLs for early leaf spot (ELS) and 20 QTLs for late leaf spot (LLS), which included four, six, and six major QTLs (PVE larger than 10%) for each disease, respectively. A total of six major genomic regions (MGR) were found to have QTLs controlling more than one disease resistance. The identified QTLs and resistance gene-rich MGRs will facilitate further discovery of resistance genes and development of molecular markers for these important diseases. PMID:27427980

  5. Identification of quantitative trait loci controlling fibre length and lignin content in Arabidopsis thaliana stems.

    PubMed

    Capron, Arnaud; Chang, Xue Feng; Hall, Hardy; Ellis, Brian; Beatson, Rodger P; Berleth, Thomas

    2013-01-01

    Fibre properties and the biochemical composition of cell walls are important traits in many applications. For example, the lengths of fibres define the strength and quality of paper, and lignin content is a critical parameter for the use of biomass in biofuel production. Identifying genes controlling these traits is comparatively difficult in woody species, because of long generation times and limited amenability to high-resolution genetic mapping. To address this problem, this study mapped quantitative trait loci (QTLs) defining fibre length and lignin content in the Arabidopsis recombinant inbred line population Col-4 × Ler-0. Adapting high-throughput phenotyping techniques for both traits for measurements in Arabidopsis inflorescence stems identified significant QTLs for fibre length on chromosomes 2 and 5, as well as one significant QTL affecting lignin content on chromosome 2. For fibre length, total variation within the population was 208% higher than between parental lines and the identified QTLs explained 50.58% of the observed variation. For lignin content, the values were 261 and 26.51%, respectively. Bioinformatics analysis of the associated intervals identified a number of candidate genes for fibre length and lignin content. This study demonstrates that molecular mapping of QTLs pertaining to wood and fibre properties is possible in Arabidopsis, which substantially broadens the use of Arabidopsis as a model species for the functional characterization of plant genes.

  6. A repressor-antirepressor pair links two loci controlling light-induced carotenogenesis in Myxococcus xanthus.

    PubMed

    López-Rubio, José Juan; Elías-Arnanz, Montserrat; Padmanabhan, S; Murillo, Francisco José

    2002-03-01

    The light-inducible carB operon encodes all but one of the structural genes for carotenogenesis in Myxococcus xanthus. It is transcriptionally controlled by two proteins expressed from two unlinked genetic loci: CarS from the light-inducible carQRS operon, and CarA from the light-independent carA operon. CarA represses transcription from the carB promoter (P(B)) in the dark, and CarS counteracts this on illumination. The CarA sequence revealed a helix-turn-helix DNA-binding motif of the type found in bacterial MerR transcriptional factors, whereas CarS contains no known DNA-binding motif. Here, we examine the molecular interplay between CarA and CarS. We demonstrate the following. (i) Whereas CarS exhibits no DNA binding in vitro, CarA binds specifically to a region encompassing P(B) to form at least two distinct complexes. (ii) A palindrome located between positions -46 and -63 relative to the transcription start point is essential but not sufficient for the formation of the two CarA-DNA complexes observed. (iii) CarS abrogates the specific DNA binding of CarA. CarA is therefore a repressor and CarS an antirepressor. (iv) CarS physically interacts with CarA; thus, the functional interaction between them is mediated by protein-protein interactions.

  7. Insecticide resistance and vector control.

    PubMed Central

    Brogdon, W. G.; McAllister, J. C.

    1998-01-01

    Insecticide resistance has been a problem in all insect groups that serve as vectors of emerging diseases. Although mechanisms by which insecticides become less effective are similar across all vector taxa, each resistance problem is potentially unique and may involve a complex pattern of resistance foci. The main defense against resistance is close surveillance of the susceptibility of vector populations. We describe the mechanisms of insecticide resistance, as well as specific instances of resistance emergence worldwide, and discuss prospects for resistance management and priorities for detection and surveillance. PMID:9866736

  8. QTL Mapping of Genome Regions Controlling Temephos Resistance in Larvae of the Mosquito Aedes aegypti

    PubMed Central

    Reyes-Solis, Guadalupe del Carmen; Saavedra-Rodriguez, Karla; Suarez, Adriana Flores; Black, William C.

    2014-01-01

    Introduction The mosquito Aedes aegypti is the principal vector of dengue and yellow fever flaviviruses. Temephos is an organophosphate insecticide used globally to suppress Ae. aegypti larval populations but resistance has evolved in many locations. Methodology/Principal Findings Quantitative Trait Loci (QTL) controlling temephos survival in Ae. aegypti larvae were mapped in a pair of F3 advanced intercross lines arising from temephos resistant parents from Solidaridad, México and temephos susceptible parents from Iquitos, Peru. Two sets of 200 F3 larvae were exposed to a discriminating dose of temephos and then dead larvae were collected and preserved for DNA isolation every two hours up to 16 hours. Larvae surviving longer than 16 hours were considered resistant. For QTL mapping, single nucleotide polymorphisms (SNPs) were identified at 23 single copy genes and 26 microsatellite loci of known physical positions in the Ae. aegypti genome. In both reciprocal crosses, Multiple Interval Mapping identified eleven QTL associated with time until death. In the Solidaridad×Iquitos (SLD×Iq) cross twelve were associated with survival but in the reciprocal IqxSLD cross, only six QTL were survival associated. Polymorphisms at acetylcholine esterase (AchE) loci 1 and 2 were not associated with either resistance phenotype suggesting that target site insensitivity is not an organophosphate resistance mechanism in this region of México. Conclusions/Significance Temephos resistance is under the control of many metabolic genes of small effect and dispersed throughout the Ae. aegypti genome. PMID:25330200

  9. Quantitative trait loci (QTL) mapping of resistance to strongyles and coccidia in the free-living Soay sheep (Ovis aries).

    PubMed

    Beraldi, Dario; McRae, Allan F; Gratten, Jacob; Pilkington, Jill G; Slate, Jon; Visscher, Peter M; Pemberton, Josephine M

    2007-01-01

    A genome-wide scan was performed to detect quantitative trait loci (QTL) for resistance to gastrointestinal parasites and ectoparasitic keds segregating in the free-living Soay sheep population on St. Kilda (UK). The mapping panel consisted of a single pedigree of 882 individuals of which 588 were genotyped. The Soay linkage map used for the scans comprised 251 markers covering the whole genome at average spacing of 15cM. The traits here investigated were the strongyle faecal egg count (FEC), the coccidia faecal oocyst count (FOC) and a count of keds (Melophagus ovinus). QTL mapping was performed by means of variance component analysis so that the genetic parameters of the study traits were also estimated and compared with previous studies in Soay and domestic sheep. Strongyle FEC and coccidia FOC showed moderate heritability (h(2)=0.26 and 0.22, respectively) in lambs but low heritability in adults (h(2)<0.10). Ked count appeared to have very low h(2) in both lambs and adults. Genome scans were performed for the traits with moderate heritability and two genomic regions reached the level of suggestive linkage for coccidia FOC in lambs (logarithm of the odds=2.68 and 2.21 on chromosomes 3 and X, respectively). We believe this is the first study to report a QTL search for parasite resistance in a free-living animal population and therefore may represent a useful reference for similar studies aimed at understanding the genetics of host-parasite co-evolution in the wild.

  10. White mold resistance-associated quantitative trait loci in the Jalo x Small White common bean population.

    PubMed

    Souza, D A; Balestre, M; Pamplona, A K A; Leite, M E; Dias, J A; Santos, J B

    2016-08-26

    We aimed to identify simple sequence repeat (SSR) markers linked to quantitative trait loci (QTLs) associated with white mold resistance in a segregating population derived from a cross between common bean cultivars Jalo and Small White, in the Southern State of Minas Gerais. Parents were crossed to obtain the F2 generation of 190 plants. From these, F2:3 and F2:4 progenies were obtained for phenotypic evaluation. DNA was extracted from F2 plants and parents for genotyping with SSR primers. For phenotypic assessment by the straw test, we used 190 F2:3 progenies and six lines in a triple-lattice design of 14 x 14 m. Nine trials were conducted for phenotyping by the oxalic acid method to evaluate 177 F2:4 progenies, in addition to the two parents and two common treatments represented by the Jalo and Corujinha lines. The experimental design for the oxalic acid method was completely randomized with three replicates. Adjusted means of evaluations related to F2:3 and F2:4 were used to identify QTLs by using the moving away method from the marker under Bayesian analysis. The markers GATS91, BM197, and X60000 stood out with high heritability and with effects on disease reduction by the straw test; therefore, these markers are promising for selection. The markers BM183, BM189, and SSR-IAC143 were associated with the QTLs identified by oxalic acid, providing greater effects in white mold resistance with high heritability. Based on the oxalic acid and straw test methods, the most prominent marker was PVBR189.

  11. Multiplex SSR-PCR approaches for semi-automated genotyping and characterization of loci linked to blast disease resistance genes in rice.

    PubMed

    Ashkani, Sadegh; Rafii, Mohd Yusop; Shabanimofrad, Mahmoodreza; Foroughi, Majid; Azizia, Parisa; Akhtar, Mohd Sayeed; Sahebi, Mahbod; Harun, Abd Rahim; Nasehi, Abbas

    2015-11-01

    In the present study, 63 polymorphic microsatellite markers related to rice blast resistance genes were fluorescently labelled at the 5'-end with either 6-FAM or HEX using the G5 dye set and incorporated into a multiplex SSR-PCR for the detection of fragments using an automated system. For rice F3 families obtained from crosses between Pongsu Seribu 2 (Malaysian blast resistant cultivar) and Mahsuri (a susceptible rice cultivar), the genotypes for 13 designated multiplex SSR panels were determined. The genotyping assays were performed using a capillary-based ABIPRISM 3100 genetic analyser. The sizes of the SSRs alleles observed in the range from 79 to 324 bp. The observed marker segregation data were analysed using the Chi(2) test. A genetic linkage map covering ten chromosomes and comprising 63 polymorphic SSR markers was constructed, and the distorted loci were localised to linkage groups. The results indicated that distorted loci are presented on eight chromosomes.

  12. Multi-ethnic genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis

    PubMed Central

    Waage, Johannes; Baurecht, Hansjörg; Hotze, Melanie; Strachan, David P; Curtin, John A; Bønnelykke, Klaus; Tian, Chao; Takahashi, Atsushi; Esparza-Gordillo, Jorge; Alves, Alexessander Couto; Thyssen, Jacob P; den Dekker, Herman T; Ferreira, Manuel A; Altmaier, Elisabeth; Sleiman, Patrick MA; Xiao, Feng Li; Gonzalez, Juan R; Marenholz, Ingo; Kalb, Birgit; Yanes, Maria Pino; Xu, Cheng-Jian; Carstensen, Lisbeth; Groen-Blokhuis, Maria M; Venturini, Cristina; Pennell, Craig E; Barton, Sheila J; Levin, Albert M; Curjuric, Ivan; Bustamante, Mariona; Kreiner-Møller, Eskil; Lockett, Gabrielle A; Bacelis, Jonas; Bunyavanich, Supinda; Myers, Rachel A; Matanovic, Anja; Kumar, Ashish; Tung, Joyce Y; Hirota, Tomomitsu; Kubo, Michiaki; McArdle, Wendy L; Henderson, A J; Kemp, John P; Zheng, Jie; Smith, George Davey; Rüschendorf, Franz; Bauerfeind, Anja; Lee-Kirsch, Min Ae; Arnold, Andreas; Homuth, Georg; Schmidt, Carsten O; Mangold, Elisabeth; Cichon, Sven; Keil, Thomas; Rodríguez, Elke; Peters, Annette; Franke, Andre; Lieb, Wolfgang; Novak, Natalija; Fölster-Holst, Regina; Horikoshi, Momoko; Pekkanen, Juha; Sebert, Sylvain; Husemoen, Lise L; Grarup, Niels; de Jongste, Johan C; Rivadeneira, Fernando; Hofman, Albert; Jaddoe, Vincent WV; Pasmans, Suzanne GMA; Elbert, Niels J; Uitterlinden, André G; Marks, Guy B; Thompson, Philip J; Matheson, Melanie C; Robertson, Colin F; Ried, Janina S; Li, Jin; Zuo, Xian Bo; Zheng, Xiao Dong; Yin, Xian Yong; Sun, Liang Dan; McAleer, Maeve A; O'Regan, Grainne M; Fahy, Caoimhe MR; Campbell, Linda E; Macek, Milan; Kurek, Michael; Hu, Donglei; Eng, Celeste; Postma, Dirkje S; Feenstra, Bjarke; Geller, Frank; Hottenga, Jouke Jan; Middeldorp, Christel M; Hysi, Pirro; Bataille, Veronique; Spector, Tim; Tiesler, Carla MT; Thiering, Elisabeth; Pahukasahasram, Badri; Yang, James J; Imboden, Medea; Huntsman, Scott; Vilor-Tejedor, Natàlia; Relton, Caroline L; Myhre, Ronny; Nystad, Wenche; Custovic, Adnan; Weiss, Scott T; Meyers, Deborah A; Söderhäll, Cilla; Melén, Erik; Ober, Carole; Raby, Benjamin A; Simpson, Angela; Jacobsson, Bo; Holloway, John W; Bisgaard, Hans; Sunyer, Jordi; Hensch, Nicole M Probst; Williams, L Keoki; Godfrey, Keith M; Wang, Carol A; Boomsma, Dorret I; Melbye, Mads; Koppelman, Gerard H; Jarvis, Deborah; McLean, WH Irwin; Irvine, Alan D; Zhang, Xue Jun; Hakonarson, Hakon; Gieger, Christian; Burchard, Esteban G; Martin, Nicholas G; Duijts, Liesbeth; Linneberg, Allan; Jarvelin, Marjo-Riitta; Noethen, Markus M; Lau, Susanne; Hübner, Norbert; Lee, Young-Ae; Tamari, Mayumi; Hinds, David A; Glass, Daniel; Brown, Sara J; Heinrich, Joachim; Evans, David M; Weidinger, Stephan

    2015-01-01

    Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, African, Japanese and Latino ancestry, followed by replication in 32,059 cases and 228,628 controls from 18 studies. We identified 10 novel risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with novel secondary signals at 4 of these). Notably, the new loci include candidate genes with roles in regulation of innate host defenses and T-cell function, underscoring the important contribution of (auto-)immune mechanisms to atopic dermatitis pathogenesis. PMID:26482879

  13. Analysis techniques for multivariate root loci. [a tool in linear control systems

    NASA Technical Reports Server (NTRS)

    Thompson, P. M.; Stein, G.; Laub, A. J.

    1980-01-01

    Analysis and techniques are developed for the multivariable root locus and the multivariable optimal root locus. The generalized eigenvalue problem is used to compute angles and sensitivities for both types of loci, and an algorithm is presented that determines the asymptotic properties of the optimal root locus.

  14. Two – three loci control scleral ossicle formation via epistasis in the cavefish Astyanax mexicanus

    PubMed Central

    Lyon, Anastasia; Powers, Amanda K.; Gross, Joshua B.; O’Quin, Kelly E.

    2017-01-01

    The sclera is the protective outer layer of the eye. In fishes, birds, and reptiles, the sclera may be reinforced with additional bony elements called scleral ossicles. Teleost fish vary in the number and size of scleral ossicles; however, the genetic mechanisms responsible for this variation remain poorly understood. In this study, we examine the inheritance of scleral ossicles in the Mexican tetra, Astyanax mexicanus, which exhibits both a cave morph and a surface fish morph. As these morphs and their hybrids collectively exhibit zero, one, and two scleral ossicles, they represent a microcosm of teleost scleral ossicle diversity. Our previous research in F2 hybrids of cavefish from Pachón cave and surface fish from Texas suggested that three genes likely influence the formation of scleral ossicles in this group through an epistatic threshold model of inheritance, though our sample size was small. In this study, we expand our sample size using additional hybrids of Pachón cavefish and Mexican surface fish to (1) confirm the threshold model of inheritance, (2) refine the number of genes responsible for scleral ossicle formation, and (3) increase our power to detect quantitative trait loci (QTL) for this trait. To answer these three questions, we scored surface fish and cavefish F2 hybrids for the presence of zero, one, or two scleral ossicles. We then analyzed their distribution among the F2 hybrids using a chi-square (χ2) test, and used a genetic linkage map of over 100 microsatellite markers to identify QTL responsible for scleral ossicle number. We found that inheritance of scleral ossicles follows an epistatic threshold model of inheritance controlled by two genes, which contrasts the three-locus model estimated from our previous study. Finally, the combined analysis of hybrids from both crosses identified two strong QTL for scleral ossicle number on linkage groups 4.2 and 21, and a weaker QTL on linkage group 4.1. Scleral ossification remains a complex

  15. Identification of Loci Associated with Drought Resistance Traits in Heterozygous Autotetraploid Alfalfa (Medicago sativa L.) Using Genome-Wide Association Studies with Genotyping by Sequencing

    PubMed Central

    Li, Yajun; Rivera, Martha; Main, Dorrie; Greene, Stephanie L.

    2015-01-01

    Drought resistance is an important breeding target for enhancing alfalfa productivity in arid and semi-arid regions. Identification of genes involved in drought tolerance will facilitate breeding for improving drought resistance and water use efficiency in alfalfa. Our objective was to use a diversity panel of alfalfa accessions comprised of 198 cultivars and landraces to identify genes involved in drought tolerance. The panel was selected from the USDA-ARS National Plant Germplasm System alfalfa collection and genotyped using genotyping by sequencing. A greenhouse procedure was used for phenotyping two important traits associated with drought tolerance: drought resistance index (DRI) and relative leaf water content (RWC). Marker-trait association identified nineteen and fifteen loci associated with DRI and RWC, respectively. Alignments of target sequences flanking to the resistance loci against the reference genome of M. truncatula revealed multiple chromosomal locations. Markers associated with DRI are located on all chromosomes while markers associated with RWC are located on chromosomes 1, 2, 3, 4, 5, 6 and 7. Co-localizations of significant markers between DRI and RWC were found on chromosomes 3, 5 and 7. Most loci associated with DRI in this work overlap with the reported QTLs associated with biomass under drought in alfalfa. Additional significant markers were targeted to several contigs with unknown chromosomal locations. BLAST search using their flanking sequences revealed homology to several annotated genes with functions in stress tolerance. With further validation, these markers may be used for marker-assisted breeding new alfalfa varieties with drought resistance and enhanced water use efficiency. PMID:26406473

  16. Identification of Loci Associated with Drought Resistance Traits in Heterozygous Autotetraploid Alfalfa (Medicago sativa L.) Using Genome-Wide Association Studies with Genotyping by Sequencing.

    PubMed

    Zhang, Tiejun; Yu, Long-Xi; Zheng, Ping; Li, Yajun; Rivera, Martha; Main, Dorrie; Greene, Stephanie L

    2015-01-01

    Drought resistance is an important breeding target for enhancing alfalfa productivity in arid and semi-arid regions. Identification of genes involved in drought tolerance will facilitate breeding for improving drought resistance and water use efficiency in alfalfa. Our objective was to use a diversity panel of alfalfa accessions comprised of 198 cultivars and landraces to identify genes involved in drought tolerance. The panel was selected from the USDA-ARS National Plant Germplasm System alfalfa collection and genotyped using genotyping by sequencing. A greenhouse procedure was used for phenotyping two important traits associated with drought tolerance: drought resistance index (DRI) and relative leaf water content (RWC). Marker-trait association identified nineteen and fifteen loci associated with DRI and RWC, respectively. Alignments of target sequences flanking to the resistance loci against the reference genome of M. truncatula revealed multiple chromosomal locations. Markers associated with DRI are located on all chromosomes while markers associated with RWC are located on chromosomes 1, 2, 3, 4, 5, 6 and 7. Co-localizations of significant markers between DRI and RWC were found on chromosomes 3, 5 and 7. Most loci associated with DRI in this work overlap with the reported QTLs associated with biomass under drought in alfalfa. Additional significant markers were targeted to several contigs with unknown chromosomal locations. BLAST search using their flanking sequences revealed homology to several annotated genes with functions in stress tolerance. With further validation, these markers may be used for marker-assisted breeding new alfalfa varieties with drought resistance and enhanced water use efficiency.

  17. Genome Sequence of the Thermotolerant Foodborne Pathogen Salmonella enterica Serovar Senftenberg ATCC 43845 and Phylogenetic Analysis of Loci Encoding Increased Protein Quality Control Mechanisms.

    PubMed

    Nguyen, Scott V; Harhay, Gregory P; Bono, James L; Smith, Timothy P L; Harhay, Dayna M

    2017-01-01

    Salmonella enterica subsp. enterica bacteria are important foodborne pathogens with major economic impact. Some isolates exhibit increased heat tolerance, a concern for food safety. Analysis of a finished-quality genome sequence of an isolate commonly used in heat resistance studies, S. enterica subsp. enterica serovar Senftenberg 775W (ATCC 43845), demonstrated an interesting observation that this strain contains not just one, but two horizontally acquired thermotolerance locus homologs. These two loci reside on a large 341.3-kbp plasmid that is similar to the well-studied IncHI2 R478 plasmid but lacks any antibiotic resistance genes found on R478 or other IncHI2 plasmids. As this historical Salmonella isolate has been in use since 1941, comparative analysis of the plasmid and of the thermotolerance loci contained on the plasmid will provide insight into the evolution of heat resistance loci as well as acquisition of resistance determinants in IncHI2 plasmids. IMPORTANCE Thermal interventions are commonly used in the food industry as a means of mitigating pathogen contamination in food products. Concern over heat-resistant food contaminants has recently increased, with the identification of a conserved locus shown to confer heat resistance in disparate lineages of Gram-negative bacteria. Complete sequence analysis of a historical isolate of Salmonella enterica serovar Senftenberg, used in numerous studies because of its novel heat resistance, revealed that this important strain possesses two distinct copies of this conserved thermotolerance locus, residing on a multireplicon IncHI2/IncHI2A plasmid. Phylogenetic analysis of these loci in comparison with homologs identified in various bacterial genera provides an opportunity to examine the evolution and distribution of loci conferring resistance to environmental stressors, such as heat and desiccation.

  18. Genome Sequence of the Thermotolerant Foodborne Pathogen Salmonella enterica Serovar Senftenberg ATCC 43845 and Phylogenetic Analysis of Loci Encoding Increased Protein Quality Control Mechanisms

    PubMed Central

    Nguyen, Scott V.; Harhay, Gregory P.; Bono, James L.; Smith, Timothy P. L.

    2017-01-01

    ABSTRACT Salmonella enterica subsp. enterica bacteria are important foodborne pathogens with major economic impact. Some isolates exhibit increased heat tolerance, a concern for food safety. Analysis of a finished-quality genome sequence of an isolate commonly used in heat resistance studies, S. enterica subsp. enterica serovar Senftenberg 775W (ATCC 43845), demonstrated an interesting observation that this strain contains not just one, but two horizontally acquired thermotolerance locus homologs. These two loci reside on a large 341.3-kbp plasmid that is similar to the well-studied IncHI2 R478 plasmid but lacks any antibiotic resistance genes found on R478 or other IncHI2 plasmids. As this historical Salmonella isolate has been in use since 1941, comparative analysis of the plasmid and of the thermotolerance loci contained on the plasmid will provide insight into the evolution of heat resistance loci as well as acquisition of resistance determinants in IncHI2 plasmids. IMPORTANCE Thermal interventions are commonly used in the food industry as a means of mitigating pathogen contamination in food products. Concern over heat-resistant food contaminants has recently increased, with the identification of a conserved locus shown to confer heat resistance in disparate lineages of Gram-negative bacteria. Complete sequence analysis of a historical isolate of Salmonella enterica serovar Senftenberg, used in numerous studies because of its novel heat resistance, revealed that this important strain possesses two distinct copies of this conserved thermotolerance locus, residing on a multireplicon IncHI2/IncHI2A plasmid. Phylogenetic analysis of these loci in comparison with homologs identified in various bacterial genera provides an opportunity to examine the evolution and distribution of loci conferring resistance to environmental stressors, such as heat and desiccation. PMID:28293682

  19. Mapping of quantitative trait loci for a new source of resistance to bruchids in the wild species Vigna nepalensis Tateishi & Maxted (Vigna subgenus Ceratotropis).

    PubMed

    Somta, Prakit; Kaga, Akito; Tomooka, Norihiko; Isemura, Takehisa; Vaughan, Duncan A; Srinives, Peerasak

    2008-08-01

    Azuki bean breeders have long been interested in producing azuki bean [Vigna angularis (Willd.) Ohwi & Ohashi] varieties with bruchid resistance. A new bruchid (Callosobruchus spp.) resistance source was found in V. nepalensis Tateishi & Maxted, a species that is cross compatible with azuki bean. Quantitative trait loci (QTLs) analysis for resistance to C. chinensis (L.) and C. maculatus (F.) was conducted using F2 (V. nepalensisxV. angularis) and BC1F1 [(V. nepalensisxV. angularis)xV. angularis] populations derived from crosses between the bruchid resistant species V. nepalensis and bruchid susceptible species V. angularis. Resistance was measured using two traits, percentage of seeds damaged by bruchids and the time taken for adult bruchids to emerge from seeds. Based on the results from both populations seven QTLs were detected for bruchid resistance; five QTLs for resistance to C. chinensis and two QTLs for resistance to C. maculatus. The different locations found for some resistance QTL to the two bruchid species suggests different resistance mechanisms. QTLs on linkage group (LG) 1 and LG2 for bruchid resistance to C. chinensis co-localized with seed size QTLs suggesting that incremental increase in seed size accompanied susceptibility to C. chinensis. Based on linked markers the QTL on these two linkage groups appear to be the same as previously reported in other Asian Vigna. However, several other QTLs were newly detected including one on LG4 that appears unrelated to seed size. Transfer of these new sources of bruchid resistance from V. nepalensis to azuki bean will be aided by the progress being made in azuki genome mapping.

  20. Mapping of quantitative trait loci associated with partial resistance to phytophthora sojae and flooding tolerance in soybean

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phytophthora root rot (PRR) caused by Phytophthora sojae Kaufm. & Gerd. and flooding can limit growth and productivity, of soybean [Glycine max (L.) Merr.], especially on poorly drained soils. The primary objective of this research project was to map quantitative trait loci (QTL) associated with f...

  1. Identification of quantitative trait loci for resistance to Verticillium wilt and yield parameters in hop (Humulus lupulus L.).

    PubMed

    Jakse, Jernej; Cerenak, Andreja; Radisek, Sebastjan; Satovic, Zlatko; Luthar, Zlata; Javornik, Branka

    2013-06-01

    Verticillium wilt (VW) can cause substantial yield loss in hop particularly with the outbreaks of the lethal strain of Verticillium albo-atrum. To elucidate genetic control of VW resistance in hop, an F1 mapping population derived from a cross of cultivar Wye Target, with the predicted genetic basis of resistance, and susceptible male breeding line BL2/1 was developed to assess wilting symptoms and to perform QTL mapping. The genetic linkage map, constructed with 203 markers of various types using a pseudo-testcross strategy, formed ten major linkage groups (LG) of the maternal and paternal maps, covering 552.98 and 441.1 cM, respectively. A significant QTL for VW resistance was detected at LOD 7 on a single chromosomal region on LG03 of both parental maps, accounting for 24.2-26.0 % of the phenotypic variance. QTL analysis for alpha-acid content and yield parameters was also performed on this map. QTLs for these traits were also detected and confirmed our previously detected QTLs in a different pedigree and environment. The work provides the basis for exploration of QTL flanking markers for possible use in marker-assisted selection.

  2. Genetic dissection of milk yield traits and mastitis resistance quantitative trait loci on chromosome 20 in dairy cattle.

    PubMed

    Kadri, Naveen K; Guldbrandtsen, Bernt; Lund, Mogens S; Sahana, Goutam

    2015-12-01

    Intense selection to increase milk yield has had negative consequences for mastitis incidence in dairy cattle. Due to low heritability of mastitis resistance and an unfavorable genetic correlation with milk yield, a reduction in mastitis through traditional breeding has been difficult to achieve. Here, we examined quantitative trait loci (QTL) that segregate for clinical mastitis and milk yield on Bos taurus autosome 20 (BTA20) to determine whether both traits are affected by a single polymorphism (pleiotropy) or by multiple closely linked polymorphisms. In the latter but not the former situation, undesirable genetic correlation could potentially be broken by selecting animals that have favorable variants for both traits. First, we performed a within-breed association study using a haplotype-based method in Danish Holstein cattle (HOL). Next, we analyzed Nordic Red dairy cattle (RDC) and Danish Jersey cattle (JER) with the goal of determining whether these QTL identified in Holsteins were segregating across breeds. Genotypes for 12,566 animals (5,966 HOL, 5,458 RDC, and 1,142 JER) were determined by using the Illumina Bovine SNP50 BeadChip (50K; Illumina, San Diego, CA), which identifies 1,568 single nucleotide polymorphisms on BTA20. Data were combined, phased, and clustered into haplotype states, followed by within- and across-breed haplotype-based association analyses using a linear mixed model. Association signals for both clinical mastitis and milk yield peaked in the 26- to 40-Mb region on BTA20 in HOL. Single-variant association analyses were carried out in the QTL region using whole sequence level variants imputed from references of 2,036 HD genotypes (BovineHD BeadChip; Illumina) and 242 whole-genome sequences. The milk QTL were also segregating in RDC and JER on the BTA20-targeted region; however, an indication of differences in the causal factor(s) was observed across breeds. A previously reported F279Y mutation (rs385640152) within the growth hormone

  3. Characterization of disease resistance loci in the USDA soybean germplasm collection using genome-wide association studies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetic resistance is a key strategy for soybean disease management. In past decades, soybean germplasm has been phenotyped for resistance to many different pathogens and genes for resistance have been incorporated into elite breeding lines often resulting in commercial cultivars with disease resist...

  4. Flavonoid-deficient mutants in grass pea (Lathyrus sativus L.): genetic control, linkage relationships, and mapping with aconitase and S-nitrosoglutathione reductase isozyme loci.

    PubMed

    Talukdar, Dibyendu

    2012-01-01

    Two flavonoid-deficient mutants, designated as fldL-1 and fldL-2, were isolated in EMS-mutagenized (0.15%, 10 h) M(2) progeny of grass pea (Lathyrus sativus L.). Both the mutants contained total leaf flavonoid content only 20% of their mother varieties. Genetic analysis revealed monogenic recessive inheritance of the trait, controlled by two different nonallelic loci. The two mutants differed significantly in banding patterns of leaf aconitase (ACO) and S-nitrosoglutathione reductase (GSNOR) isozymes, possessing unique bands in Aco 1, Aco 2, and Gsnor 2 loci. Isozyme loci inherited monogenically showing codominant expression in F(2) (1:2:1) and backcross (1:1) segregations. Linkage studies and primary trisomic analysis mapped Aco 1 and fld 1 loci on extra chromosome of trisomic-I and Aco 2, fld 2, and Gsnor 2 on extra chromosome of trisomic-IV in linked associations.

  5. Molecular Mapping of Stem Rust Resistance Loci Effective Against the Ug99 Race Group of the Stem Rust Pathogen and Validation of a Single Nucleotide Polymorphism Marker Linked to Stem Rust Resistance Gene Sr28.

    PubMed

    Babiker, E M; Gordon, T C; Chao, S; Rouse, M N; Wanyera, R; Acevedo, M; Brown-Guedira, G; Bonman, J M

    2017-02-01

    Wheat landrace PI 177906 has seedling resistance to stem rust caused by Puccinia graminis f. sp. tritici races TTKSK, TTKST, and BCCBC and field resistance to the Ug99 race group. Parents, 140 recombinant inbred lines, and 138 double haploid (DH) lines were evaluated for seedling resistance to races TTKSK and BCCBC. Parents and the DH population were evaluated for field resistance to Ug99 in Kenya. The 90K wheat single nucleotide polymorphism (SNP) genotyping platform was used to genotype the parents and populations. Goodness-of-fit tests indicated that two dominant genes in PI 177906 conditioned seedling resistance to TTKSK. Two major loci for seedling resistance were consistently mapped to the chromosome arms 2BL and 6DS. The BCCBC resistance was mapped to the same location on 2BL as the TTKSK resistance. Using field data from the three seasons, two major QTL were consistently detected at the same regions on 2BL and 6DS. Based on the mapping result, race specificity, and the infection type observed in PI 177906, the TTKSK resistance on 2BL is likely due to Sr28. One SNP marker (KASP_IWB1208) was found to be predictive for the presence of the TTKSK resistance locus on 2BL and Sr28.

  6. Urban Graffiti: Crime, Control, and Resistance.

    ERIC Educational Resources Information Center

    Ferrell, Jeff

    1995-01-01

    Explores the ways in which producers of contemporary urban graffiti resist the increasing segregation and control of urban environments, and shows how graffiti participants undermine efforts at control. Data come from four years of field work in Denver (Colorado) and research in other cities. (SLD)

  7. Rapid identification of resistance loci effective against Puccinia graminis f. sp. tritici race TTKSK in 33 spring wheat landraces

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Wheat breeders worldwide are seeking new sources of resistance to Puccinia graminis f. sp tritici race TTKSK. To prioritize field-resistant landraces for follow-up genetic studies to test for the presence of new resistance genes, seedling response to Pgt race TTKSK, molecular markers linked to speci...

  8. Quantitative trait loci and underlying candidate genes controlling agronomical and fruit quality traits in octoploid strawberry (Fragaria × ananassa).

    PubMed

    Zorrilla-Fontanesi, Yasmín; Cabeza, Amalia; Domínguez, Pedro; Medina, Juan Jesús; Valpuesta, Victoriano; Denoyes-Rothan, Beatrice; Sánchez-Sevilla, José F; Amaya, Iraida

    2011-09-01

    Breeding for fruit quality traits in strawberry (Fragaria × ananassa, 2n = 8x = 56) is complex due to the polygenic nature of these traits and the octoploid constitution of this species. In order to improve the efficiency of genotype selection, the identification of quantitative trait loci (QTL) and associated molecular markers will constitute a valuable tool for breeding programs. However, the implementation of these markers in breeding programs depends upon the complexity and stability of QTLs across different environments. In this work, the genetic control of 17 agronomical and fruit quality traits was investigated in strawberry using a F(1) population derived from an intraspecific cross between two contrasting selection lines, '232' and '1392'. QTL analyses were performed over three successive years based on the separate parental linkage maps and a pseudo-testcross strategy. The integrated strawberry genetic map consists of 338 molecular markers covering 37 linkage groups, thus exceeding the 28 chromosomes. 33 QTLs were identified for 14 of the 17 studied traits and approximately 37% of them were stable over time. For each trait, 1-5 QTLs were identified with individual effects ranging between 9.2 and 30.5% of the phenotypic variation, indicating that all analysed traits are complex and quantitatively inherited. Many QTLs controlling correlated traits were co-located in homoeology group V, indicating linkage or pleiotropic effects of loci. Candidate genes for several QTLs controlling yield, anthocyanins, firmness and L-ascorbic acid are proposed based on both their co-localization and predicted function. We also report conserved QTLs among strawberry and other Rosaceae based on their syntenic location.

  9. Deletions of multidrug resistance gene loci in breast cancer leads to the down-regulation of its expression and predict tumor response to neoadjuvant chemotherapy

    PubMed Central

    Litviakov, Nikolai V.; Cherdyntseva, Nadezhda V.; Tsyganov, Matvey M.; Slonimskaya, Elena M.; Ibragimova, Marina K.; Kazantseva, Polina V.; Kzhyshkowska, Julia; Choinzonov, Eugeniy L.

    2016-01-01

    Neoadjuvant chemotherapy (NAC) is intensively used for the treatment of primary breast cancer. In our previous studies, we reported that clinical tumor response to NAC is associated with the change of multidrug resistance (MDR) gene expression in tumors after chemotherapy. In this study we performed a combined analysis of MDR gene locus deletions in tumor DNA, MDR gene expression and clinical response to NAC in 73 BC patients. Copy number variations (CNVs) in biopsy specimens were tested using high-density microarray platform CytoScanTM HD Array (Affymetrix, USA). 75%–100% persons having deletions of MDR gene loci demonstrated the down-regulation of MDR gene expression. Expression of MDR genes was 2–8 times lower in patients with deletion than in patients having no deletion only in post-NAC tumors samples but not in tumor tissue before chemotherapy. All patients with deletions of ABCB1 ABCB 3 ABCC5 gene loci – 7q21.1, 6p21.32, 3q27 correspondingly, and most patients having deletions in ABCC1 (16p13.1), ABCC2 (10q24), ABCG1 (21q22.3), ABCG2 (4q22.1), responded favorably to NAC. The analysis of all CNVs, including both amplification and deletion showed that the frequency of 13q14.2 deletion was 85% among patients bearing tumor with the deletion at least in one MDR gene locus versus 9% in patients with no deletions. Differences in the frequency of 13q14.2 deletions between the two groups were statistically significant (p = 2.03 ×10−11, Fisher test, Bonferroni-adjusted p = 1.73 × 10−8). In conclusion, our study for the first time demonstrates that deletion MDR gene loci can be used as predictive marker for tumor response to NAC. PMID:26799285

  10. Transcriptomic characterization of two major Fusarium resistance quantitative trait loci (QTLs), Fhb1 and Qfhs.ifa-5A, identifies novel candidate genes

    PubMed Central

    Schweiger, Wolfgang; Steiner, Barbara; Ametz, Christian; Siegwart, Gerald; Wiesenberger, Gerlinde; Berthiller, Franz; Lemmens, Marc; Jia, Haiyan; Adam, Gerhard; Muehlbauer, Gary J; Kreil, David P; Buerstmayr, Hermann

    2013-01-01

    Fusarium head blight, caused by Fusarium graminearum, is a devastating disease of wheat. We developed near-isogenic lines (NILs) differing in the two strongest known F. graminearum resistance quantitative trait loci (QTLs), Qfhs.ndsu-3BS (also known as resistance gene Fhb1) and Qfhs.ifa-5A, which are located on the short arm of chromosome 3B and on chromosome 5A, respectively. These NILs showing different levels of resistance were used to identify transcripts that are changed significantly in a QTL-specific manner in response to the pathogen and between mock-inoculated samples. After inoculation with F. graminearum spores, 16 transcripts showed a significantly different response for Fhb1 and 352 for Qfhs.ifa-5A. Notably, we identified a lipid transfer protein which is constitutively at least 50-fold more abundant in plants carrying the resistant allele of Qfhs.ifa-5A. In addition to this candidate gene associated with Qfhs.ifa-5A, we identified a uridine diphosphate (UDP)-glycosyltransferase gene, designated TaUGT12887, exhibiting a positive difference in response to the pathogen in lines harbouring both QTLs relative to lines carrying only the Qfhs.ifa-5A resistance allele, suggesting Fhb1 dependence of this transcript. Yet, this dependence was observed only in the NIL with already higher basal resistance. The complete cDNA of TaUGT12887 was reconstituted from available wheat genomic sequences, and a synthetic recoded gene was expressed in a toxin-sensitive strain of Saccharomyces cerevisiae. This gene conferred deoxynivalenol resistance, albeit much weaker than that observed with the previously characterized barley HvUGT13248. PMID:23738863

  11. Resistance gene enrichment sequencing (RenSeq) enables reannotation of the NB-LRR gene family from sequenced plant genomes and rapid mapping of resistance loci in segregating populations.

    PubMed

    Jupe, Florian; Witek, Kamil; Verweij, Walter; Sliwka, Jadwiga; Pritchard, Leighton; Etherington, Graham J; Maclean, Dan; Cock, Peter J; Leggett, Richard M; Bryan, Glenn J; Cardle, Linda; Hein, Ingo; Jones, Jonathan D G

    2013-11-01

    RenSeq is a NB-LRR (nucleotide binding-site leucine-rich repeat) gene-targeted, Resistance gene enrichment and sequencing method that enables discovery and annotation of pathogen resistance gene family members in plant genome sequences. We successfully applied RenSeq to the sequenced potato Solanum tuberosum clone DM, and increased the number of identified NB-LRRs from 438 to 755. The majority of these identified R gene loci reside in poorly or previously unannotated regions of the genome. Sequence and positional details on the 12 chromosomes have been established for 704 NB-LRRs and can be accessed through a genome browser that we provide. We compared these NB-LRR genes and the corresponding oligonucleotide baits with the highest sequence similarity and demonstrated that ~80% sequence identity is sufficient for enrichment. Analysis of the sequenced tomato S. lycopersicum 'Heinz 1706' extended the NB-LRR complement to 394 loci. We further describe a methodology that applies RenSeq to rapidly identify molecular markers that co-segregate with a pathogen resistance trait of interest. In two independent segregating populations involving the wild Solanum species S. berthaultii (Rpi-ber2) and S. ruiz-ceballosii (Rpi-rzc1), we were able to apply RenSeq successfully to identify markers that co-segregate with resistance towards the late blight pathogen Phytophthora infestans. These SNP identification workflows were designed as easy-to-adapt Galaxy pipelines.

  12. Using crossover breakpoints in recombinant inbred lines to identify quantitative trait loci controlling the global recombination frequency.

    PubMed

    Esch, Elisabeth; Szymaniak, Jessica M; Yates, Heather; Pawlowski, Wojciech P; Buckler, Edward S

    2007-11-01

    Recombination is a crucial component of evolution and breeding, producing new genetic combinations on which selection can act. Rates of recombination vary tremendously, not only between species but also within species and for specific chromosomal segments. In this study, by examining recombination events captured in recombinant inbred mapping populations previously created for maize, wheat, Arabidopsis, and mouse, we demonstrate that substantial variation exists for genomewide crossover rates in both outcrossed and inbred plant and animal species. We also identify quantitative trait loci (QTL) that control this variation. The method that we developed and employed here holds promise for elucidating factors that regulate meiotic recombination and for creation of hyperrecombinogenic lines, which can help overcome limited recombination that hampers breeding progress.

  13. Additive effects of two quantitative trait loci that confer Rhopalosiphum maidis (corn leaf aphid) resistance in maize inbred line Mo17

    PubMed Central

    Betsiashvili, Mariam; Ahern, Kevin R.; Jander, Georg

    2015-01-01

    Plants show considerable within-species variation in their resistance to insect herbivores. In the case of Zea mays (cultivated maize), Rhopalosiphum maidis (corn leaf aphids) produce approximately twenty times more progeny on inbred line B73 than on inbred line Mo17. Genetic mapping of this difference in maize aphid resistance identified quantitative trait loci (QTL) on chromosomes 4 and 6, with the Mo17 allele reducing aphid reproduction in each case. The chromosome 4 QTL mapping interval includes several genes involved in the biosynthesis of DIMBOA (2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one), a maize defensive metabolite that also is required for callose accumulation in response to aphid feeding. Consistent with the known association of callose with plant defence against aphids, R. maidis reproduction on B73×Mo17 recombinant inbred lines was negatively correlated with both DIMBOA content and callose formation. Further genetic mapping, as well as experiments with near-isogenic lines, confirmed that the Mo17 allele causes increased DIMBOA accumulation relative to the B73 allele. The chromosome 6 aphid resistance QTL functions independently of DIMBOA accumulation and has an effect that is additive to that of the chromosome 4 QTL. Thus, at least two separate defence mechanisms account for the higher level of R. maidis resistance in Mo17 compared with B73. PMID:25249072

  14. Genetic diversity of rhg1 and Rhg4 loci in wild soybeans resistant to soybean cyst nematode race 3.

    PubMed

    Yuan, C P; Wang, Y J; Zhao, H K; Zhang, L; Wang, Y M; Liu, X D; Zhong, X F; Dong, Y S

    2016-06-10

    Over-utilization of germplasms that are resistant to the soybean cyst nematode (SCN) in soybean breeding programs can lead to genetic vulnerability in resistant cultivars. Resistant wild soybean (Glycine soja) is considered an invaluable gene source for increasing the genetic diversity of SCN resistance. In this study, we genotyped 23 G. soja accessions that are resistant to SCN race 3 for polymorphisms in the resistance genes, rhg1, Rhg4, and SHMT, and investigated their genetic relationship with eight Glycine max resistant cultivars. We identified 89 single nucleotide polymorphisms (SNPs) and 11 DNA insertion-deletions (InDels), of which 70 SNPs and 8 InDels were found in rhg1, 9 SNPs were found in Rhg4, and 10 SNPs and 3 InDels were found in SHMT. Nucleotide diversity was π = 0.00238 and θ = 0.00235, and haplotype diversity was 1.000. A phylogenetic tree comprising four clusters was constructed using sequence variations of the 23 G. soja and 8 G. max resistant accessions. Five G. soja accessions in subcluster A2, and four G. soja accessions in cluster B were genetically distant from G. max genotypes. Eight resistance-associated SNPs in the three resistance genes formed nine haplotypes in total. G. soja resistant accessions had different haplotypes (H2, H4, H5, H6, H7, and H8) compared with those of G. max (H1, H3, and H9). These results provide vital information on the use of wild soybeans for broadening the genetic base of SCN resistance.

  15. Identifying quantitative trait loci (QTL) for resistance to Fusarium crown rot (Fusarium pseudograminearum) in two spring wheat populations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fusarium crown rot (FCR), caused by F. pseudograminearum and F. culmorum, reduces wheat yields in the Pacific Northwest (PNW) of the U.S. by as much as 35%. Currently there is no consistent durable resistance to FCR in PNW wheat cultivars. Significant QTL for crown rot resistance have been documente...

  16. Mapping of iron and zinc quantitative trait loci in soybean for association to iron deficiency chlorosis resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Iron deficiency chlorosis (IDC) is a nutritional disease of soybean (Glycine max (L.) Merr.) which when left unchecked can result in a severe yield penalty or even death in the most extreme cases. In order to curb these effects, resistance to the disease is needed. Breeding for resistance has been ...

  17. Lessons from a phenotyping center revealed by the genome-guided mapping of powdery mildew resistance loci

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The genomics era brought unprecedented tools for genetic analysis of host resistance, but careful attention is needed on obtaining accurate and reproducible phenotypes so that genomic results appropriately reflect biology. Phenotyping host resistance by natural infection in the field can produce var...

  18. Susceptibility of Adult Cat Fleas (Siphonaptera: Pulicidae) to Insecticides and Status of Insecticide Resistance Mutations at the Rdl and Knockdown Resistance Loci.

    PubMed

    Rust, Michael K; Vetter, Richard; Denholm, Ian; Blagburn, Byron; Williamson, Martin S; Kopp, Steven; Coleman, Glen; Hostetler, Joe; Davis, Wendell; Mencke, Norbert; Rees, Robert; Foit, Sabrina; Böhm, Claudia; Tetzner, Kathrin

    2015-08-01

    The susceptibility of 12 field-collected isolates and 4 laboratory strains of cat fleas, Ctenocephalides felis was determined by topical application of some of the insecticides used as on-animal therapies to control them. In the tested field-collected flea isolates the LD50 values for fipronil and imidacloprid ranged from 0.09 to 0.35 ng/flea and 0.02 to 0.19 ng/flea, respectively, and were consistent with baseline figures published previously. The extent of variation in response to four pyrethroid insecticides differed between compounds with the LD50 values for deltamethrin ranging from 2.3 to 28.2 ng/flea, etofenprox ranging from 26.7 to 86.7 ng/flea, permethrin ranging from 17.5 to 85.6 ng/flea, and d-phenothrin ranging from 14.5 to 130 ng/flea. A comparison with earlier data for permethrin and deltamethrin implied a level of pyrethroid resistance in all isolates and strains. LD50 values for tetrachlorvinphos ranged from 20.0 to 420.0 ng/flea. The rdl mutation (conferring target-site resistance to cyclodiene insecticides) was present in most field-collected and laboratory strains, but had no discernible effect on responses to fipronil, which acts on the same receptor protein as cyclodienes. The kdr and skdr mutations conferring target-site resistance to pyrethroids but segregated in opposition to one another, precluding the formation of genotypes homozygous for both mutations.

  19. Adhesion Control between Resist and Photomask Blank

    NASA Astrophysics Data System (ADS)

    Kurihara, Masaaki; Hatakeyama, Sho; Yoshida, Kouji; Abe, Makoto; Totsukawa, Daisuke; Morikawa, Yasutaka; Mohri, Hiroshi; Hoga, Morihisa; Hayashi, Naoya; Ohtani, Hiroyuki; Fujihira, Masamichi

    2009-06-01

    Most problems in photomask fabrication such as pattern collapse, haze, and cleaning damage are related to the behavior of surfaces and interfaces of resists, opaque layers, and quartz substrates. Therefore, it is important to control the corresponding surface and interface energies in photomask fabrication processes. In particular, adhesion analysis in microscopic regions is strongly desirable to optimize material and process designs in photomask fabrication. We applied the direct peeling (DP) method with a scanning probe microscope (SPM) tip and measured the adhesion of resist patterns on Cr and quartz surfaces for photomask process optimization. We also studied the effect of tip shape on the reproducibility of adhesion measurements and the dependence of collapse behavior on the resist profile. We measured lateral forces between the resulting collapsed resist pillar and the Cr or the quartz surface before and after the sliding and related these observed lateral forces to the static and kinetic frictional forces, respectively. We also studied the effect of surface modification of the Cr and quartz surfaces with silanization reagents on adhesion measured with the DP method. Resist adhesion could be controlled by surface modification using silanes. We also discuss the relationship between the adhesion observed with the DP method and the properties of the modified surfaces including water contact angles and local adhesive forces measured from force-distance curves with an SPM.

  20. Reflections on Speech Motor Control Based on Phonatory and DDK Tasks in Dysarthric Subjects with Lesions in Different Cerebellar Loci

    ERIC Educational Resources Information Center

    Vandana, V. P.

    2007-01-01

    There are very few acoustic studies reflecting on the localization of speech function within the different loci of the cerebellum. Task based performance profile of subjects with lesion in different cerebellar loci is not reported. Also, the findings on nonfocal cerebellar lesions cannot be generalized to lesions restricted to the cerebellum.…

  1. Characterization of Quantitative Trait Loci Controlling Genetic Variation for Preharvest Sprouting in Synthetic Backcross-Derived Wheat Lines

    PubMed Central

    Imtiaz, Muhammad; Ogbonnaya, Francis C.; Oman, Jason; van Ginkel, Maarten

    2008-01-01

    Aegilops tauschii, the wild relative of wheat, has stronger seed dormancy, a major component of preharvest sprouting resistance (PHSR), than bread wheat. A diploid Ae. tauschii accession (AUS18836) and a tetraploid (Triticum turgidum L. ssp. durum var. Altar84) wheat were used to construct a synthetic wheat (Syn37). The genetic architecture of PHS was investigated in 271 BC1F7 synthetic backcross lines (SBLs) derived from Syn37/2*Janz (resistant/susceptible). The SBLs were evaluated in three environments over 2 years and PHS was assessed by way of three measures: the germination index (GI), which measures grain dormancy, the whole spike assay (SI), which takes into account all spike morphology, and counted visually sprouted seeds out of 200 (VI). Grain color was measured using both Chroma Meter- and NaOH-based approaches. QTL for PHSR and grain color were mapped and their additive and epistatic effects as well as their interactions with environment were estimated by a mixed linear-model approach. Single-locus analysis following composite interval mapping revealed four QTL for GI, two QTL for SI, and four QTL for VI on chromosomes 3DL and 4AL. The locus QPhs.dpiv-3D.1 on chromosome 3DL was tightly linked to the red grain color (RGC) at a distance of 5 cM. The other locus on chromosome 3D, “QPhs.dpiv-3D.2” was independent of RGC locus. Two-locus analysis detected nine QTL with main effects and 18 additive × additive interactions for GI, SI, and VI. Two of the nine main effects QTL and two epistatic QTL showed significant interactions with environments. Both additive and epistatic effects contributed to phenotypic variance in PHSR and the identified markers are potential candidates for marker-assisted selection of favorable alleles at multiple loci. SBLs derived from Ae. tauschii proved to be a promising tool to dissect, introgress, and pyramid different PHSR genes into adapted wheat genetic backgrounds. The enhanced expression of PHS resistance in SBLs enabled

  2. Identification of Quantitative Trait Loci Conditioning the Main Biomass Yield Components and Resistance to Melampsora spp. in Salix viminalis × Salix schwerinii Hybrids

    PubMed Central

    Sulima, Paweł; Przyborowski, Jerzy A.; Kuszewska, Anna; Załuski, Dariusz; Jędryczka, Małgorzata; Irzykowski, Witold

    2017-01-01

    The biomass of Salix viminalis is the most highly valued source of green energy, followed by S. schwerinii, S. dasyclados and other species. Significant variability in productivity and leaf rust resistance are noted both within and among willow species, which creates new opportunities for improving willow yield parameters through selection of desirable recombinants supported with molecular markers. The aim of this study was to identify quantitative trait loci (QTLs) linked with biomass yield-related traits and the resistance/susceptibility of Salix mapping population to leaf rust. The experimental material comprised a mapping population developed based on S. viminalis × S. schwerinii hybrids. Phenotyping was performed on plants grown in a field experiment that had a balanced incomplete block design with 10 replications. Based on a genetic map, 11 QTLs were identified for plant height, 9 for shoot diameter, 3 for number of shoots and 11 for resistance/susceptibility to leaf rust. The QTLs identified in our study explained 3%–16% of variability in the analyzed traits. Our findings make significant contributions to the development of willow breeding programs and research into shrubby willow crops grown for energy. PMID:28327519

  3. Hypertension: issues in control and resistance.

    PubMed

    Wofford, Marion R; Minor, Deborah S

    2009-10-01

    Hypertension remains uncontrolled in more than 50% of treated patients. Barriers to hypertension control include those that are patient-related, physician-related, and related to the health system. Identification of uncontrolled hypertension, pseudoresistant hyper-tension, and resistant hypertension require thoughtful attention to accurate blood pressure measurement, lifestyle factors, evaluation for secondary causes of hypertension, and proper treatment. Recent guidelines emphasize the importance of aggressive treatment and referral to hypertension specialists for patients with resistant hypertension, defined as blood pressure that remains above goal despite the use of three appropriate anti-hypertensive agents.

  4. Linkage disequilibrium between two distinct loci in chromosomes 5 and 7 of Plasmodium falciparum and in vivo chloroquine resistance in Southwest Nigeria.

    PubMed

    Happi, C T; Gbotosho, G O; Folarin, O A; Sowunmi, A; Bolaji, O M; Fateye, B A; Kyle, D E; Milhous, W; Wirth, D F; Oduola, A M J

    2006-12-01

    Chloroquine (CQ) resistance in Plasmodium falciparum is associated with polymorphisms in loci on pfcrt and pfmdr1 genes. In this study, we determined the association and linkage disequilibrium between in vivo CQ resistance and P. falciparum polymorphisms in pfcrt gene at codon 76 and pfmdr1 gene at codon 86 in isolates obtained from 111 children with acute uncomplicated falciparum malaria in Nigeria. Patients were treated with standard dosage of CQ and followed up for 28 days. Filter paper samples were collected at enrollment and during follow-up for parasites genotypes and identification of pfcrt and pfmdr1 mutations. Association and linkage disequilibrium between mutant pfcrtT76 and pfmdr1Y86 alleles in pretreatment isolates of P. falciparum was determined. Fifty-five out of the 111 patients (49.5%) failed treatment. Single mutant pfcrtT76 or pfmdr1Y86 alleles were found in 55 out of 111 P. falciparum isolates screened at enrollment. Of these 55 isolates, the mutant pfcrtT76 and pfmdr1Y86 alleles were found in 84%. Both mutant pfcrtT76 (p=0.0196) and pfmdr1Y86 (p=0.000042) alleles were associated with in vivo CQ resistance. In addition, the mutant pfcrtT76 (p=0.047) and pfmdr1Y86 (p=0.006) alleles were significantly selected by CQ in patients who failed treatment. Association analysis between paired single alleles at pfcrt and pfmdr1 loci showed a significant association (p=0.0349 and chi(2)=4.45) between the pfcrt T76 allele on chromosome 7 and the pfmdr1Y86 allele on chromosome 5 and that these two mutant alleles were in linkage disequilibrium (p=0.000, D'=0.64, and r(2)=0.28). Considering the high level of CQ resistance and drug use in the study area, the observed linkage disequilibrium between the mutant pfcrtT76 and pfmdr1Y86 alleles is maintained epistatically through directional CQ selective pressure.

  5. Genes and quantitative trait loci (QTL) controlling trace element concentrations in perennial grasses grown on phytotoxic soil contaminated with heavy metals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Perennial grasses cover diverse soils throughout the world, including sites contaminated with heavy metals, producing forages that must be safe for livestock and wildlife. Chromosome regions known as quantitative trait loci (QTLs) controlling forage mineral concentrations were mapped in a populatio...

  6. Identification of quantitative trait loci (QTL) for resistance to Fusarium crown rot (Fusarium pseudograminearum) in multiple assay environments in the Pacific Northwestern US.

    PubMed

    Poole, G J; Smiley, R W; Paulitz, T C; Walker, C A; Carter, A H; See, D R; Garland-Campbell, K

    2012-06-01

    Fusarium crown rot (FCR), caused by Fusarium pseudograminearum and F. culmorum, reduces wheat (Triticum aestivum L.) yields in the Pacific Northwest (PNW) of the US by as much as 35%. Resistance to FCR has not yet been discovered in currently grown PNW wheat cultivars. Several significant quantitative trait loci (QTL) for FCR resistance have been documented on chromosomes 1A, 1D, 2B, 3B, and 4B in resistant Australian cultivars. Our objective was to identify QTL and tightly linked SSR markers for FCR resistance in the partially resistant Australian spring wheat cultivar Sunco using PNW isolates of F. pseudograminerarum in greenhouse and field based screening nurseries. A second objective was to compare heritabilities of FCR resistance in multiple types of disease assaying environments (seedling, terrace, and field) using multiple disease rating methods. Two recombinant inbred line (RIL) mapping populations were derived from crosses between Sunco and PNW spring wheat cultivars Macon and Otis. The Sunco/Macon population comprised 219 F(6):F(7) lines and the Sunco/Otis population comprised 151 F(5):F(6) lines. Plants were inoculated with a single PNW F. pseudograminearum isolate (006-13) in growth room (seedling), outdoor terrace (adult) and field (adult) assays conducted from 2008 through 2010. Crown and lower stem tissues of seedling and adult plants were rated for disease severity on several different scales, but mainly on a numeric scale from 0 to 10 where 0 = no discoloration and 10 = severe disease. Significant QTL were identified on chromosomes 2B, 3B, 4B, 4D, and 7A with LOD scores ranging from 3 to 22. The most significant and consistent QTL across screening environments was located on chromosome 3BL, inherited from the PNW cultivars Macon and Otis, with maximum LOD scores of 22 and 9 explaining 36 and 23% of the variation, respectively for the Sunco/Macon and Sunco/Otis populations. The SSR markers Xgwm247 and Xgwm299 flank these QTL and are being

  7. Resistance of Mice of the 129 Background to Yersinia pestis Maps to Multiple Loci on Chromosome 1

    PubMed Central

    Tencati, Michael

    2016-01-01

    Yersinia pestis is a Gram-negative bacterium that is the causative agent of bubonic and pneumonic plague. It is commonly acquired by mammals such as rodents and humans via the bite of an infected flea. We previously reported that multiple substrains of the 129 mouse background are resistant to pigmentation locus-negative (pgm−) Yersinia pestis and that this phenotype maps to a 30-centimorgan (cM) region located on chromosome 1. In this study, we have further delineated this plague resistance locus to a region of less than 20 cM through the creation and phenotyping of recombinant offspring arising from novel crossovers in this region. Furthermore, our experiments have revealed that there are at least two alleles in this initial locus, both of which are required for resistance on a susceptible C57BL/6 background. These two alleles work in trans since resistance is restored in offspring possessing one allele contributed by each parent. Our studies also indicated that the Slc11a1 gene (formerly known as Nramp1) located within the chromosome1 locus is not responsible for conferring resistance to 129 mice. PMID:27481241

  8. Mapping of genomic regions (quantitative trait loci) controlling production and quality in industrial cultures of the edible basidiomycete Pleurotus ostreatus.

    PubMed

    Larraya, Luis M; Alfonso, Mikel; Pisabarro, Antonio G; Ramírez, Lucía

    2003-06-01

    Industrial production of the edible basidiomycete Pleurotus ostreatus (oyster mushroom) is based on a solid fermentation process in which a limited number of selected strains are used. Optimization of industrial mushroom production depends on improving the culture process and breeding new strains with higher yields and productivities. Traditionally, fungal breeding has been carried out by an empirical trial and error process. In this study, we used a different approach by mapping quantitative trait loci (QTLs) controlling culture production and quality within the framework of the genetic linkage map of P. ostreatus. Ten production traits and four quality traits were studied and mapped. The production QTLs identified explain nearly one-half of the production variation. More interestingly, a single QTL mapping to the highly polymorphic chromosome VII appears to be involved in control of all the productivity traits studied. Quality QTLs appear to be scattered across the genome and to have less effect on the variation of the corresponding traits. Moreover, some of the new hybrid strains constructed in the course of our experiments had production or quality values higher than those of the parents or other commercial strains. This approach opens the possibility of marker-assisted selection and breeding of new industrial strains of this fungus.

  9. Mapping of Genomic Regions (Quantitative Trait Loci) Controlling Production and Quality in Industrial Cultures of the Edible Basidiomycete Pleurotus ostreatus

    PubMed Central

    Larraya, Luis M.; Alfonso, Mikel; Pisabarro, Antonio G.; Ramírez, Lucía

    2003-01-01

    Industrial production of the edible basidiomycete Pleurotus ostreatus (oyster mushroom) is based on a solid fermentation process in which a limited number of selected strains are used. Optimization of industrial mushroom production depends on improving the culture process and breeding new strains with higher yields and productivities. Traditionally, fungal breeding has been carried out by an empirical trial and error process. In this study, we used a different approach by mapping quantitative trait loci (QTLs) controlling culture production and quality within the framework of the genetic linkage map of P. ostreatus. Ten production traits and four quality traits were studied and mapped. The production QTLs identified explain nearly one-half of the production variation. More interestingly, a single QTL mapping to the highly polymorphic chromosome VII appears to be involved in control of all the productivity traits studied. Quality QTLs appear to be scattered across the genome and to have less effect on the variation of the corresponding traits. Moreover, some of the new hybrid strains constructed in the course of our experiments had production or quality values higher than those of the parents or other commercial strains. This approach opens the possibility of marker-assisted selection and breeding of new industrial strains of this fungus. PMID:12788770

  10. Identification of quantitative trait loci(QTL) controlling important fatty acids in peanut (Arachis hypogaea L.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fatty acids play important role in controlling oil quality of peanut. In addition to the major fatty acids, oleic acid (C18:1) and linoleic acid (C18:2) accounting for about 80%, there are several minor fatty acids accounting for about 20% in peanut oil, such as palmitic acid (PA, C16:0), stearic (S...

  11. Molecular mapping of greenbug resistance loci Gb6 and Gb2 in 1AL.1RS wheat-rye translocations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The greenbug, Schizaphis graminum (Rondani), is an economically important aphid pest of wheat worldwide. The greenbug resistance genes Gb2 and Gb6, derived from the same donor rye line 'Insave', are presented in wheat germplasm lines 'Amigo' and 'GRS1201' respectively as 1AL.1RS wheat-rye transloca...

  12. Mapping Fusarium solani and Aphanomyces euteiches root rot resistance and root architecture quantitative trait loci in common bean (Phaseolus vulgaris)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Root rot diseases of bean (Phaseolus vulgaris L.) are a constraint to dry and snap bean production. We developed the RR138 RIL mapping population from the cross of OSU5446, a susceptible line that meets current snap bean processing industry standards, and RR6950, a root rot resistant dry bean in th...

  13. Association mapping of quantitative trait loci responsible for resistance to Bacterial Leaf Streak and Spot Blotch in spring wheat landraces

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacterial leaf streak (BLS), caused by Xanthomonas translucens pv. undulosa, and spot blotch (SB), caused by Cochliobolus sativus are two major diseases of wheat (Triticum aestivum L.). Planting resistant cultivars is the best approach to manage these diseases and identifying new sources of resistan...

  14. Genome-wide association studies identify 25 genetic loci associated with resistance to Bacterial Cold Water Disease in rainbow trout

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacterial cold water disease (BCWD) causes significant mortality and economic losses in salmonids aquaculture. In previous studies we have identified moderate-large effect QTL for BCWD resistance in rainbow trout (Oncorhynchus mykiss). However, the recent availability of a high density SNP array and...

  15. Mapping quantitative trait loci for plant adaptation and morphology traits in wheat using single nucleotide polymorphisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Wheat (Triticum aestivum L.) morphological and adaptation-related traits that are controlled by quantitative traits loci (QTL) define potential growing areas of a wheat cultivar. To dissect the QTL for heading date (HD), lodging resistance (LR), shattering resistance (SR), cold tolerance (CT), plant...

  16. Identification of Novel Loci Associated with Gastrointestinal Parasite Resistance in a Red Maasai x Dorper Backcross Population

    PubMed Central

    Kemp, Stephen; Mugambi, John M.; Gibson, John P.; Baker, Robert Leyden; Hanotte, Olivier; Marshall, Karen

    2015-01-01

    Gastrointestinal (GI) parasitic infection is the main health constraint for small ruminant production, causing loss of weight and/or death. Red Maasai sheep have adapted to a tropical environment where extreme parasite exposure is a constant, especially with highly pathogenic Haemonchus contortus. This breed has been reported to be resistant to gastrointestinal parasite infection, hence it is considered an invaluable resource to study associations between host genetics and resistance. The aim of this study was to identify polymorphisms strongly associated with host resistance in a double backcross population derived from Red Maasai and Dorper sheep using a SNP-based GWAS analysis. The animals that were genotyped represented the most resistant and susceptible individuals based on the tails of phenotypic distribution (10% each) for average faecal egg counts (AVFEC). AVFEC, packed cell volume (AVPCV), and live weight (AVLWT) were adjusted for fixed effects and co-variables, and an association analysis was run using EMMAX. Revised significance levels were calculated using 100,000 permutation tests. The top five significant SNP markers with - log10 p-values >3.794 were observed on five different chromosomes for AVFEC, and BLUPPf90/PostGSf90 results confirmed EMMAX significant regions for this trait. One of these regions included a cluster of significant SNP on chromosome (Chr) 6 not in linkage disequilibrium to each other. This genomic location contains annotated genes involved in cytokine signalling, haemostasis and mucus biosynthesis. Only one association detected on Chr 7 was significant for both AVPCV and AVLWT. The results generated here reveal candidate immune variants for genes involved in differential response to infection and provide additional SNP marker information that has potential to aid selection of resistance to gastrointestinal parasites in sheep of a similar genetic background to the double backcross population. PMID:25867089

  17. Tomato mutants altered in bacterial disease resistance provide evidence for a new locus controlling pathogen recognition.

    PubMed Central

    Salmeron, J M; Barker, S J; Carland, F M; Mehta, A Y; Staskawicz, B J

    1994-01-01

    We have employed a genetic approach to study the resistance of tomato to the phytopathogenic bacterium Pseudomonas syringae pv tomato. Resistance to P. s. tomato depends upon expression of the Pto locus in tomato, which encodes a protein with similarity to serine/threonine protein kinases and recognizes pathogen strains expressing the avirulence gene avrPto. Eleven tomato mutants were isolated with altered resistance to P. s. tomato strains expressing avrPto. We identified mutations both in the Pto resistance locus and in a new locus designated Prf (for Pseudomonas resistance and fenthion sensitivity). The genetic approach allowed us to dissect the roles of these loci in signal transduction in response to pathogen attack. Lines carrying mutations in the Pto locus vary 200-fold in the degree to which they are susceptible to P. s. tomato strains expressing avrPto. The pto mutants retain sensitivity to the organophosphate insecticide fenthion; this trait segregates with Pto in genetic crosses. This result suggested that contrary to previous hypotheses, the Pto locus controls pathogen recognition but not fenthion sensitivity. Interestingly, mutations in the prf locus result in both complete susceptibility to P. s. tomato and insensitivity to fenthion, suggesting that Prf plays a role in tomato signaling in response to both pathogen elicitors and fenthion. Because pto and prf mutations do not alter recognition of Xanthomonas campestris strains expressing avrBsP, an avirulence gene recognized by all tested tomato cultivars, Prf does not play a general role in disease resistance but possibly functions specifically in resistance against P. s. tomato. Genetic analysis of F2 populations from crosses of pto and prf homozygotes indicated that the Pto and Prf loci are tightly linked. PMID:7911348

  18. Major quantitative trait loci control divergence in critical photoperiod for flowering between selfing and outcrossing species of monkeyflower (Mimulus).

    PubMed

    Fishman, Lila; Sweigart, Andrea L; Kenney, Amanda M; Campbell, Samantha

    2014-03-01

    • Divergence in flowering time is a key contributor to reproductive isolation between incipient species, as it enforces habitat specialization and causes assortative mating even in sympatry. Understanding the genetic basis of flowering time divergence illuminates the origins and maintenance of species barriers. • We investigated the genetics of divergence in critical photoperiod for flowering between yellow monkeyflowers Mimulus guttatus (outcrosser, summer flowering) and Mimulus nasutus (selfer, spring flowering). We used quantitative trait locus (QTL) mapping of F2 hybrids and fine-mapping in nearly isogenic lines to characterize the genomic regions underlying a > 2 h critical photoperiod difference between allopatric populations, and then tested whether the same QTLs control flowering time in sympatry. • We identified two major QTLs that almost completely explain M. nasutus's ability to flower in early spring; they are shared by allopatric and sympatric population pairs. The smaller QTL is coincident with one that differentiates ecotypes within M. guttatus, but the larger effect QTL appears unique to M. nasutus. • Unlike floral traits associated with mating system divergence, large interspecific differences in flowering phenology depend on only a few loci. Major critical photoperiod QTLs may be 'speciation genes' and also restrict interspecific gene flow in secondary sympatry.

  19. Mapping quantitative trait loci controlling early growth in a (longleaf pine x slash pine) x slash pine BC(1) family.

    PubMed

    Weng, C.; Kubisiak, L.; Nelson, D.; Stine, M.

    2002-04-01

    Random amplified polymorphic DNA (RAPD) markers were employed to map the genome and quantitative trait loci controlling the early growth of a pine hybrid F(1) tree ( Pinus palustris Mill. x P. elliottii Engl.) and a recurrent slash pine tree ( P. elliottii Engl.) in a (longleaf pine x slash pine) x slash pine BC(1) family consisting of 258 progeny. Of the 150 hybrid F(1) parent-specific RAPD markers, 133 were mapped into 17 linkage groups covering a genetic distance of 1,338.2 cM. Of the 116 slash pine parent-specific RAPD markers, 83 were mapped into 19 linkage groups covering a genetic distance of 994.6 cM. A total of 11 different marker intervals were found to be significantly associated with 13 of the 20 traits on height and diameter growth using MAPMAKER/QTL. Nine of the eleven marker intervals were unique to the hybrid parent 488 genome, and two were unique to the recurrent parent 18-27 genome. The amount of phenotypic variance explained by the putative QTLs ranged from 3.6% to 11.0%. Different QTLs were detected at different ages. Two marker intervals from the hybrid parent 488 were found to have QTL by environment interactions.

  20. Orthogonal control of expression mean and variance by epigenetic features at different genomic loci

    SciTech Connect

    Dey, Siddharth S.; Foley, Jonathan E.; Limsirichai, Prajit; Schaffer, David V.; Arkin, Adam P.

    2015-05-05

    While gene expression noise has been shown to drive dramatic phenotypic variations, the molecular basis for this variability in mammalian systems is not well understood. Gene expression has been shown to be regulated by promoter architecture and the associated chromatin environment. However, the exact contribution of these two factors in regulating expression noise has not been explored. Using a dual-reporter lentiviral model system, we deconvolved the influence of the promoter sequence to systematically study the contribution of the chromatin environment at different genomic locations in regulating expression noise. By integrating a large-scale analysis to quantify mRNA levels by smFISH and protein levels by flow cytometry in single cells, we found that mean expression and noise are uncorrelated across genomic locations. Furthermore, we showed that this independence could be explained by the orthogonal control of mean expression by the transcript burst size and noise by the burst frequency. Finally, we showed that genomic locations displaying higher expression noise are associated with more repressed chromatin, thereby indicating the contribution of the chromatin environment in regulating expression noise.

  1. Orthogonal control of expression mean and variance by epigenetic features at different genomic loci

    DOE PAGES

    Dey, Siddharth S.; Foley, Jonathan E.; Limsirichai, Prajit; ...

    2015-05-05

    While gene expression noise has been shown to drive dramatic phenotypic variations, the molecular basis for this variability in mammalian systems is not well understood. Gene expression has been shown to be regulated by promoter architecture and the associated chromatin environment. However, the exact contribution of these two factors in regulating expression noise has not been explored. Using a dual-reporter lentiviral model system, we deconvolved the influence of the promoter sequence to systematically study the contribution of the chromatin environment at different genomic locations in regulating expression noise. By integrating a large-scale analysis to quantify mRNA levels by smFISH andmore » protein levels by flow cytometry in single cells, we found that mean expression and noise are uncorrelated across genomic locations. Furthermore, we showed that this independence could be explained by the orthogonal control of mean expression by the transcript burst size and noise by the burst frequency. Finally, we showed that genomic locations displaying higher expression noise are associated with more repressed chromatin, thereby indicating the contribution of the chromatin environment in regulating expression noise.« less

  2. What controls aqueous humour outflow resistance?

    PubMed Central

    Johnson, Mark

    2010-01-01

    The bulk of aqueous humour outflow resistance is generated in or near the inner wall endothelium of Schlemm's canal in normal eyes, and probably also in glaucomatous eyes. Fluid flow through this region is controlled by the location of the giant vacuoles and pores found in cells of the endothelium of Schlemm's canal, but the flow resistance itself is more likely generated either in the extracellular matrix of the juxtacanalicular connective tissue or the basement membrane of Schlemm's canal. Future studies utilizing in vitro perfusion studies of inner wall endothelial cells may give insights into the process by which vacuoles and pores form in this unique endothelium and why inner wall pore density is greatly reduced in glaucoma. PMID:16386733

  3. Two Loci Control Phytoglycogen Production in the Monocellular Green Alga Chlamydomonas reinhardtii1

    PubMed Central

    Dauvillée, David; Colleoni, Christophe; Mouille, Gregory; Buléon, Alain; Gallant, Daniel J.; Bouchet, Brigitte; Morell, Matthew K.; d'Hulst, Christophe; Myers, Alan M.; Ball, Steven G.

    2001-01-01

    The STA8 locus of Chlamydomonas reinhardtii was identified in a genetic screen as a factor that controls starch biosynthesis. Mutations of STA8 cause a significant reduction in the amount of granular starch produced during nutrient limitation and accumulate phytoglycogen. The granules remaining in sta8 mutants are misshapen, and the abundance of amylose and long chains in amylopectin is altered. Mutations of the STA7 locus, which completely lack isoamylase activity, also cause accumulation of phytoglycogen, although sta8 and sta7 mutants differ in that there is a complete loss of granular starch in the latter. This is the first instance in which mutations of two different genetic elements in one plant species have been shown to cause phytoglycogen accumulation. An analytical procedure that allows assay of isoamylase in total extracts was developed and used to show that sta8 mutations cause a 65% reduction in the level of this activity. All other enzymes known to be involved in starch biosynthesis were shown to be unaffected in sta8 mutants. The same amount of total isoamylase activity (approximately) as that present in sta8 mutants was observed in heterozygous triploids containing two sta7 mutant alleles and one wild-type allele. This strain, however, accumulates normal levels of starch granules and lacks phytoglycogen. The total level of isoamylase activity, therefore, is not the major determinant of whether granule production is reduced and phytoglycogen accumulates. Instead, a qualitative property of the isoamylase that is affected by the sta8 mutation is likely to be the critical factor in phytoglycogen production. PMID:11299352

  4. Active control of multiple resistive wall modes

    NASA Astrophysics Data System (ADS)

    Brunsell, P. R.; Yadikin, D.; Gregoratto, D.; Paccagnella, R.; Liu, Y. Q.; Bolzonella, T.; Cecconello, M.; Drake, J. R.; Kuldkepp, M.; Manduchi, G.; Marchiori, G.; Marrelli, L.; Martin, P.; Menmuir, S.; Ortolani, S.; Rachlew, E.; Spizzo, G.; Zanca, P.

    2005-12-01

    A two-dimensional array of saddle coils at Mc poloidal and Nc toroidal positions is used on the EXTRAP T2R reversed-field pinch (Brunsell P R et al 2001 Plasma Phys. Control. Fusion 43 1457) to study active control of resistive wall modes (RWMs). Spontaneous growth of several RWMs with poloidal mode number m = 1 and different toroidal mode number n is observed experimentally, in agreement with linear MHD modelling. The measured plasma response to a controlled coil field and the plasma response computed using the linear circular cylinder MHD model are in quantitive agreement. Feedback control introduces a linear coupling of modes with toroidal mode numbers n, n' that fulfil the condition |n - n'| = Nc. Pairs of coupled unstable RWMs are present in feedback experiments with an array of Mc × Nc = 4 × 16 coils. Using intelligent shell feedback, the coupled modes are generally not controlled even though the field is suppressed at the active coils. A better suppression of coupled modes may be achieved in the case of rotating modes by using the mode control feedback scheme with individually set complex gains. In feedback with a larger array of Mc × Nc = 4 × 32 coils, the coupling effect largely disappears, and with this array, the main internal RWMs n = -11, -10, +5, +6 are all simultaneously suppressed throughout the discharge (7 8 wall times). With feedback there is a two-fold extension of the pulse length, compared to discharges without feedback.

  5. Natural resistance to Meningococcal Disease related to CFH loci: Meta-analysis of genome-wide association studies.

    PubMed

    Martinón-Torres, Federico; Png, Eileen; Khor, Chiea Chuen; Davila, Sonia; Wright, Victoria J; Sim, Kar Seng; Vega, Ana; Fachal, Laura; Inwald, David; Nadel, Simon; Carrol, Enitan D; Martinón-Torres, Nazareth; Alonso, Sonia Marcos; Carracedo, Angel; Morteruel, Elvira; López-Bayón, Julio; Torre, Andrés Concha; Monge, Cristina Calvo; de Aguilar, Pilar Azcón González; Torné, Elisabeth Esteban; Martínez-Padilla, María Del Carmen; Martinón-Sánchez, José María; Levin, Michael; Hibberd, Martin L; Salas, Antonio

    2016-11-02

    Meningococcal disease (MD) remains an important infectious cause of life threatening infection in both industrialized and resource poor countries. Genetic factors influence both occurrence and severity of presentation, but the genes responsible are largely unknown. We performed a genome-wide association study (GWAS) examining 5,440,063 SNPs in 422 Spanish MD patients and 910 controls. We then performed a meta-analysis of the Spanish GWAS with GWAS data from the United Kingdom (combined cohorts: 897 cases and 5,613 controls; 4,898,259 SNPs). The meta-analysis identified strong evidence of association (P-value ≤ 5 × 10(-8)) in 20 variants located at the CFH gene. SNP rs193053835 showed the most significant protective effect (Odds Ratio (OR) = 0.62, 95% confidence interval (C.I.) = 0.52-0.73; P-value = 9.62 × 10(-9)). Five other variants had been previously reported to be associated with susceptibility to MD, including the missense SNP rs1065489 (OR = 0.64, 95% C.I.) = 0.55-0.76, P-value = 3.25 × 10(-8)). Theoretical predictions point to a functional effect of rs1065489, which may be directly responsible for protection against MD. Our study confirms the association of CFH with susceptibility to MD and strengthens the importance of this link in understanding pathogenesis of the disease.

  6. Natural resistance to Meningococcal Disease related to CFH loci: Meta-analysis of genome-wide association studies

    PubMed Central

    Martinón-Torres, Federico; Png, Eileen; Khor, Chiea Chuen; Davila, Sonia; Wright, Victoria J.; Sim, Kar Seng; Vega, Ana; Fachal, Laura; Inwald, David; Nadel, Simon; Carrol, Enitan D.; Martinón-Torres, Nazareth; Alonso, Sonia Marcos; Carracedo, Angel; Morteruel, Elvira; López-Bayón, Julio; Torre, Andrés Concha; Monge, Cristina Calvo; de Aguilar, Pilar Azcón González; Torné, Elisabeth Esteban; Martínez-Padilla, María del Carmen; Martinón-Sánchez, José María; Levin, Michael; Hibberd, Martin L.; Salas, Antonio; Gómez-Carballa, Alberto; Cebey, Miriam; Sánchez, Natalia García; Calle, Irene Rivero; Grande, Antonio Justicia; Pardo-Seco, Jacobo; Barral-Arca, Ruth; Pischedda, Sara; Currás-Tuala, María-José; Rodriguez-Tenreiro, Carmen; Redondo-Collazo, Lorenzo; Sánchez, Fernanda Pardo; de la Cruz Moreno, Jesús; Millán Miralles, Mª. Leticia; García Rodríguez, José Luis; García, Susana Rey; Doce, Ana Hurtado; Barba, Ángela Ferrer; Pallares, Manuel Ortiz; Romero, Alfredo Reparaz; Muñoz Bonet, Juan Ignacio; Cancela, Manuel Silveira; Bergara, Eider Oñate; Arriortua, Amaya Bustinza; Navarro Gómez, María Luisa; Fernández, Mario Sánchez; Martínez, Xavier Allué; Ortega, Álvaro Castellanos; Rosso, Servando Pantoja; Caballero Macarrón, César Pérez; Menchón, Natalia Molini; Sánchez, Francisco Giménez; Garzón, Manuel González-Ripoll; García, María del Mar Ballesteros; Sánchez Granados, José Manuel; Ayestarán, Olga Serrano; Payo, Roman; Palazón, Sonia Cañadas; León León, Maria Cruz; Dominguez, Susana Reyes; Villanueba, David Arjona; Alonso Martín, J. Antonio; Orayen, Concepción Goñi; Iturbe, Enrique Bernaola; Alonso Salas, María Teresa; Fernández, Isabel Quintela; Booy, Robert; Coin, Lachlan J. M.; Eleftherohorinou, Hariklia; Faust, Saul; Galassini, Rachel; Habibi, Parviz; Haralambous, Elene; Kroll, Simon; Langford, Paul; Pathan, Nazima; Pollard, Andrew J.; Abdulla, Farhana; Agapow, Paul; Bellos, Evangelos; Hamilton, Shea; Herberg, Jethro A.; Hoggart, Clive; Kaforou, Myrsini; Mashbat, Meg; Mustafa, Sobia; Sancho-Shimizu, Vanessa

    2016-01-01

    Meningococcal disease (MD) remains an important infectious cause of life threatening infection in both industrialized and resource poor countries. Genetic factors influence both occurrence and severity of presentation, but the genes responsible are largely unknown. We performed a genome-wide association study (GWAS) examining 5,440,063 SNPs in 422 Spanish MD patients and 910 controls. We then performed a meta-analysis of the Spanish GWAS with GWAS data from the United Kingdom (combined cohorts: 897 cases and 5,613 controls; 4,898,259 SNPs). The meta-analysis identified strong evidence of association (P-value ≤ 5 × 10−8) in 20 variants located at the CFH gene. SNP rs193053835 showed the most significant protective effect (Odds Ratio (OR) = 0.62, 95% confidence interval (C.I.) = 0.52–0.73; P-value = 9.62 × 10−9). Five other variants had been previously reported to be associated with susceptibility to MD, including the missense SNP rs1065489 (OR = 0.64, 95% C.I.) = 0.55–0.76, P-value = 3.25 × 10−8). Theoretical predictions point to a functional effect of rs1065489, which may be directly responsible for protection against MD. Our study confirms the association of CFH with susceptibility to MD and strengthens the importance of this link in understanding pathogenesis of the disease. PMID:27805046

  7. Species-specific differences in tissue-specific expression of alcohol dehydrogenase are under the control of complex cis-acting loci: Evidence from Drosophila hybrids

    SciTech Connect

    Ranganayakulu, G.; Reddy, A.R. ); Kirkpatrick, R.B.; Martin, P.F. )

    1991-12-01

    Differences in the expression of alcohol dehydrogenase in the hindgut and testis of adult Drosophila virilis, D. texana, D. novamexicana and D. borealis flies were observed. These heritable differences do not arise due to chromosomal rearrangements, since the polytene chromosome banding patterns did not reveal any such gross chromosomal rearrangements near the Adh locus in any of the tested species. Analysis of the interspecific hybrids revealed that these differences are controlled by complex cis-acting genetic loci. Further, the cis-acting locus controlling the expression of ADH in testis was found to be separable by crossing-over.

  8. Epigenomic analysis of the HOX gene loci reveals mechanisms that may control canonical expression patterns in AML and normal hematopoietic cells.

    PubMed

    Spencer, D H; Young, M A; Lamprecht, T L; Helton, N M; Fulton, R; O'Laughlin, M; Fronick, C; Magrini, V; Demeter, R T; Miller, C A; Klco, J M; Wilson, R K; Ley, T J

    2015-06-01

    HOX genes are highly expressed in many acute myeloid leukemia (AML) samples, but the patterns of expression and associated regulatory mechanisms are not clearly understood. We analyzed RNA sequencing data from 179 primary AML samples and normal hematopoietic cells to understand the range of expression patterns in normal versus leukemic cells. HOX expression in AML was restricted to specific genes in the HOXA or HOXB loci, and was highly correlated with recurrent cytogenetic abnormalities. However, the majority of samples expressed a canonical set of HOXA and HOXB genes that was nearly identical to the expression signature of normal hematopoietic stem/progenitor cells. Transcriptional profiles at the HOX loci were similar between normal cells and AML samples, and involved bidirectional transcription at the center of each gene cluster. Epigenetic analysis of a subset of AML samples also identified common regions of chromatin accessibility in AML samples and normal CD34(+) cells that displayed differences in methylation depending on HOX expression patterns. These data provide an integrated epigenetic view of the HOX gene loci in primary AML samples, and suggest that HOX expression in most AML samples represents a normal stem cell program that is controlled by epigenetic mechanisms at specific regulatory elements.

  9. Genome-Wide Interaction with Insulin Secretion Loci Reveals Novel Loci for Type 2 Diabetes in African Americans

    PubMed Central

    Keaton, Jacob M.; Hellwege, Jacklyn N.; Ng, Maggie C. Y.; Palmer, Nicholette D.; Pankow, James S.; Fornage, Myriam; Wilson, James G.; Correa, Adolfo; Rasmussen-Torvik, Laura J.; Rotter, Jerome I.; Chen, Yii-Der I.; Taylor, Kent D.; Rich, Stephen S.; Wagenknecht, Lynne E.; Freedman, Barry I.; Bowden, Donald W.

    2016-01-01

    Type 2 diabetes (T2D) is the result of metabolic defects in insulin secretion and insulin sensitivity, yet most T2D loci identified to date influence insulin secretion. We hypothesized that T2D loci, particularly those affecting insulin sensitivity, can be identified through interaction with insulin secretion loci. To test this hypothesis, single nucleotide polymorphisms (SNPs) associated with acute insulin response to glucose (AIRg), a dynamic measure of first-phase insulin secretion, were identified in African Americans from the Insulin Resistance Atherosclerosis Family Study (IRASFS; n = 492 subjects). These SNPs were tested for interaction, individually and jointly as a genetic risk score (GRS), using genome-wide association study (GWAS) data from five cohorts (ARIC, CARDIA, JHS, MESA, WFSM; n = 2,725 cases, 4,167 controls) with T2D as the outcome. In single variant analyses, suggestively significant (Pinteraction<5×10−6) interactions were observed at several loci including LYPLAL1 (rs10746381), CHN2 (rs7796525), and EXOC1 (rs4289500). Notable AIRg GRS interactions were observed with SAMD4A (rs11627203) and UTRN (rs17074194). These data support the hypothesis that additional genetic factors contributing to T2D risk can be identified by interactions with insulin secretion loci. PMID:27448167

  10. The role of self-control in resistance to persuasion.

    PubMed

    Burkley, Edward

    2008-03-01

    Four studies investigated a self-control theory of resistance to persuasion. This theory asserts that resistance to persuasion requires and consumes self-control resources. Study 1 showed that resistance to a persuasive message reduced the ability to engage in a subsequent self-control task. Studies 2 and 3 showed that self-control depletion leads to increased persuasion. Study 4 showed that self-control depletion increased persuasion, particularly under effortful resistance (i.e., strong arguments). Together, these findings suggest that self-control plays a vital role in the process of resistance to persuasion. People must have self-control resources to fend off persuasive appeals; without them, they become susceptible to influence.

  11. Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways.

    PubMed

    Scott, Robert A; Lagou, Vasiliki; Welch, Ryan P; Wheeler, Eleanor; Montasser, May E; Luan, Jian'an; Mägi, Reedik; Strawbridge, Rona J; Rehnberg, Emil; Gustafsson, Stefan; Kanoni, Stavroula; Rasmussen-Torvik, Laura J; Yengo, Loïc; Lecoeur, Cecile; Shungin, Dmitry; Sanna, Serena; Sidore, Carlo; Johnson, Paul C D; Jukema, J Wouter; Johnson, Toby; Mahajan, Anubha; Verweij, Niek; Thorleifsson, Gudmar; Hottenga, Jouke-Jan; Shah, Sonia; Smith, Albert V; Sennblad, Bengt; Gieger, Christian; Salo, Perttu; Perola, Markus; Timpson, Nicholas J; Evans, David M; Pourcain, Beate St; Wu, Ying; Andrews, Jeanette S; Hui, Jennie; Bielak, Lawrence F; Zhao, Wei; Horikoshi, Momoko; Navarro, Pau; Isaacs, Aaron; O'Connell, Jeffrey R; Stirrups, Kathleen; Vitart, Veronique; Hayward, Caroline; Esko, Tõnu; Mihailov, Evelin; Fraser, Ross M; Fall, Tove; Voight, Benjamin F; Raychaudhuri, Soumya; Chen, Han; Lindgren, Cecilia M; Morris, Andrew P; Rayner, Nigel W; Robertson, Neil; Rybin, Denis; Liu, Ching-Ti; Beckmann, Jacques S; Willems, Sara M; Chines, Peter S; Jackson, Anne U; Kang, Hyun Min; Stringham, Heather M; Song, Kijoung; Tanaka, Toshiko; Peden, John F; Goel, Anuj; Hicks, Andrew A; An, Ping; Müller-Nurasyid, Martina; Franco-Cereceda, Anders; Folkersen, Lasse; Marullo, Letizia; Jansen, Hanneke; Oldehinkel, Albertine J; Bruinenberg, Marcel; Pankow, James S; North, Kari E; Forouhi, Nita G; Loos, Ruth J F; Edkins, Sarah; Varga, Tibor V; Hallmans, Göran; Oksa, Heikki; Antonella, Mulas; Nagaraja, Ramaiah; Trompet, Stella; Ford, Ian; Bakker, Stephan J L; Kong, Augustine; Kumari, Meena; Gigante, Bruna; Herder, Christian; Munroe, Patricia B; Caulfield, Mark; Antti, Jula; Mangino, Massimo; Small, Kerrin; Miljkovic, Iva; Liu, Yongmei; Atalay, Mustafa; Kiess, Wieland; James, Alan L; Rivadeneira, Fernando; Uitterlinden, Andre G; Palmer, Colin N A; Doney, Alex S F; Willemsen, Gonneke; Smit, Johannes H; Campbell, Susan; Polasek, Ozren; Bonnycastle, Lori L; Hercberg, Serge; Dimitriou, Maria; Bolton, Jennifer L; Fowkes, Gerard R; Kovacs, Peter; Lindström, Jaana; Zemunik, Tatijana; Bandinelli, Stefania; Wild, Sarah H; Basart, Hanneke V; Rathmann, Wolfgang; Grallert, Harald; Maerz, Winfried; Kleber, Marcus E; Boehm, Bernhard O; Peters, Annette; Pramstaller, Peter P; Province, Michael A; Borecki, Ingrid B; Hastie, Nicholas D; Rudan, Igor; Campbell, Harry; Watkins, Hugh; Farrall, Martin; Stumvoll, Michael; Ferrucci, Luigi; Waterworth, Dawn M; Bergman, Richard N; Collins, Francis S; Tuomilehto, Jaakko; Watanabe, Richard M; de Geus, Eco J C; Penninx, Brenda W; Hofman, Albert; Oostra, Ben A; Psaty, Bruce M; Vollenweider, Peter; Wilson, James F; Wright, Alan F; Hovingh, G Kees; Metspalu, Andres; Uusitupa, Matti; Magnusson, Patrik K E; Kyvik, Kirsten O; Kaprio, Jaakko; Price, Jackie F; Dedoussis, George V; Deloukas, Panos; Meneton, Pierre; Lind, Lars; Boehnke, Michael; Shuldiner, Alan R; van Duijn, Cornelia M; Morris, Andrew D; Toenjes, Anke; Peyser, Patricia A; Beilby, John P; Körner, Antje; Kuusisto, Johanna; Laakso, Markku; Bornstein, Stefan R; Schwarz, Peter E H; Lakka, Timo A; Rauramaa, Rainer; Adair, Linda S; Smith, George Davey; Spector, Tim D; Illig, Thomas; de Faire, Ulf; Hamsten, Anders; Gudnason, Vilmundur; Kivimaki, Mika; Hingorani, Aroon; Keinanen-Kiukaanniemi, Sirkka M; Saaristo, Timo E; Boomsma, Dorret I; Stefansson, Kari; van der Harst, Pim; Dupuis, Josée; Pedersen, Nancy L; Sattar, Naveed; Harris, Tamara B; Cucca, Francesco; Ripatti, Samuli; Salomaa, Veikko; Mohlke, Karen L; Balkau, Beverley; Froguel, Philippe; Pouta, Anneli; Jarvelin, Marjo-Riitta; Wareham, Nicholas J; Bouatia-Naji, Nabila; McCarthy, Mark I; Franks, Paul W; Meigs, James B; Teslovich, Tanya M; Florez, Jose C; Langenberg, Claudia; Ingelsson, Erik; Prokopenko, Inga; Barroso, Inês

    2012-09-01

    Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.

  12. Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

    PubMed Central

    Scott, Robert A; Lagou, Vasiliki; Welch, Ryan P; Wheeler, Eleanor; Montasser, May E; Luan, Jian’an; Mägi, Reedik; Strawbridge, Rona J; Rehnberg, Emil; Gustafsson, Stefan; Kanoni, Stavroula; Rasmussen-Torvik, Laura J; Yengo, Loïc; Lecoeur, Cecile; Shungin, Dmitry; Sanna, Serena; Sidore, Carlo; Johnson, Paul C D; Jukema, J Wouter; Johnson, Toby; Mahajan, Anubha; Verweij, Niek; Thorleifsson, Gudmar; Hottenga, Jouke-Jan; Shah, Sonia; Smith, Albert V; Sennblad, Bengt; Gieger, Christian; Salo, Perttu; Perola, Markus; Timpson, Nicholas J; Evans, David M; Pourcain, Beate St; Wu, Ying; Andrews, Jeanette S; Hui, Jennie; Bielak, Lawrence F; Zhao, Wei; Horikoshi, Momoko; Navarro, Pau; Isaacs, Aaron; O’Connell, Jeffrey R; Stirrups, Kathleen; Vitart, Veronique; Hayward, Caroline; Esko, Tönu; Mihailov, Evelin; Fraser, Ross M; Fall, Tove; Voight, Benjamin F; Raychaudhuri, Soumya; Chen, Han; Lindgren, Cecilia M; Morris, Andrew P; Rayner, Nigel W; Robertson, Neil; Rybin, Denis; Liu, Ching-Ti; Beckmann, Jacques S; Willems, Sara M; Chines, Peter S; Jackson, Anne U; Kang, Hyun Min; Stringham, Heather M; Song, Kijoung; Tanaka, Toshiko; Peden, John F; Goel, Anuj; Hicks, Andrew A; An, Ping; Müller-Nurasyid, Martina; Franco-Cereceda, Anders; Folkersen, Lasse; Marullo, Letizia; Jansen, Hanneke; Oldehinkel, Albertine J; Bruinenberg, Marcel; Pankow, James S; North, Kari E; Forouhi, Nita G; Loos, Ruth J F; Edkins, Sarah; Varga, Tibor V; Hallmans, Göran; Oksa, Heikki; Antonella, Mulas; Nagaraja, Ramaiah; Trompet, Stella; Ford, Ian; Bakker, Stephan J L; Kong, Augustine; Kumari, Meena; Gigante, Bruna; Herder, Christian; Munroe, Patricia B; Caulfield, Mark; Antti, Jula; Mangino, Massimo; Small, Kerrin; Miljkovic, Iva; Liu, Yongmei; Atalay, Mustafa; Kiess, Wieland; James, Alan L; Rivadeneira, Fernando; Uitterlinden, Andre G; Palmer, Colin N A; Doney, Alex S F; Willemsen, Gonneke; Smit, Johannes H; Campbell, Susan; Polasek, Ozren; Bonnycastle, Lori L; Hercberg, Serge; Dimitriou, Maria; Bolton, Jennifer L; Fowkes, Gerard R; Kovacs, Peter; Lindström, Jaana; Zemunik, Tatijana; Bandinelli, Stefania; Wild, Sarah H; Basart, Hanneke V; Rathmann, Wolfgang; Grallert, Harald; Maerz, Winfried; Kleber, Marcus E; Boehm, Bernhard O; Peters, Annette; Pramstaller, Peter P; Province, Michael A; Borecki, Ingrid B; Hastie, Nicholas D; Rudan, Igor; Campbell, Harry; Watkins, Hugh; Farrall, Martin; Stumvoll, Michael; Ferrucci, Luigi; Waterworth, Dawn M; Bergman, Richard N; Collins, Francis S; Tuomilehto, Jaakko; Watanabe, Richard M; de Geus, Eco J C; Penninx, Brenda W; Hofman, Albert; Oostra, Ben A; Psaty, Bruce M; Vollenweider, Peter; Wilson, James F; Wright, Alan F; Hovingh, G Kees; Metspalu, Andres; Uusitupa, Matti; Magnusson, Patrik K E; Kyvik, Kirsten O; Kaprio, Jaakko; Price, Jackie F; Dedoussis, George V; Deloukas, Panos; Meneton, Pierre; Lind, Lars; Boehnke, Michael; Shuldiner, Alan R; van Duijn, Cornelia M; Morris, Andrew D; Toenjes, Anke; Peyser, Patricia A; Beilby, John P; Körner, Antje; Kuusisto, Johanna; Laakso, Markku; Bornstein, Stefan R; Schwarz, Peter E H; Lakka, Timo A; Rauramaa, Rainer; Adair, Linda S; Smith, George Davey; Spector, Tim D; Illig, Thomas; de Faire, Ulf; Hamsten, Anders; Gudnason, Vilmundur; Kivimaki, Mika; Hingorani, Aroon; Keinanen-Kiukaanniemi, Sirkka M; Saaristo, Timo E; Boomsma, Dorret I; Stefansson, Kari; van der Harst, Pim; Dupuis, Josée; Pedersen, Nancy L; Sattar, Naveed; Harris, Tamara B; Cucca, Francesco; Ripatti, Samuli; Salomaa, Veikko; Mohlke, Karen L; Balkau, Beverley; Froguel, Philippe; Pouta, Anneli; Jarvelin, Marjo-Riitta; Wareham, Nicholas J; Bouatia-Naji, Nabila; McCarthy, Mark I; Franks, Paul W; Meigs, James B; Teslovich, Tanya M; Florez, Jose C; Langenberg, Claudia; Ingelsson, Erik; Prokopenko, Inga; Barroso, Inês

    2012-01-01

    Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have raised the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional follow-up of these newly discovered loci will further improve our understanding of glycemic control. PMID:22885924

  13. Occurrence, genetic control and evolution of non-target-site based resistance to herbicides inhibiting acetolactate synthase (ALS) in the dicot weed Papaver rhoeas.

    PubMed

    Scarabel, Laura; Pernin, Fanny; Délye, Christophe

    2015-09-01

    Non-target-site resistance (NTSR) to herbicides is a major issue for the chemical control of weeds. Whilst predominant in grass weeds, NTSR remains largely uninvestigated in dicot weeds. We investigated the occurrence, inheritance and genetic control of NTSR to acetolactate synthase (ALS) inhibitors in Papaver rhoeas (corn poppy) using progenies from plants with potential NTSR to the imidazolinone herbicide imazamox. NTSR to imazamox was inherited from parents over two successive generations. NTSR to tritosulfuron (a sulfonylurea) was observed in F1 generations and inherited in F2 generations. NTSR to florasulam (a triazolopyrimidine) emerged in F2 generations. Our findings suggest NTSR was polygenic and gradually built-up by accumulation over generations of loci with moderate individual effects in single plants. We also demonstrated that ALS alleles conferring herbicide resistance can co-exist with NTSR loci in P. rhoeas plants. Previous research focussed on TSR in P. rhoeas, which most likely caused underestimation of NTSR significance in this species. This may also apply to other dicot species. From our data, resistance to ALS inhibitors in P. rhoeas appears complex, and involves well-known mutant ALS alleles and a set of unknown NTSR loci that confer resistance to ALS inhibitors from different chemical families.

  14. Vanadate-resistant mutants of Saccharomyces cerevisiae show alterations in protein phosphorylation and growth control.

    PubMed Central

    Kanik-Ennulat, C; Neff, N

    1990-01-01

    This work describes two spontaneous vanadate-resistant mutants of Saccharomyces cerevisiae with constitutive alterations in protein phosphorylation, growth control, and sporulation. Vanadate has been shown by a number of studies to be an efficient competitor of phosphate in biochemical reactions, especially those that involve phosphoproteins as intermediates or substrates. Resistance to toxic concentrations of vanadate can arise in S. cerevisiae by both recessive and dominant spontaneous mutations in a large number of loci. Mutations in two of the recessive loci, van1-18 and van2-93, resulted in alterations in the phosphorylation of a number of proteins. The mutant van1-18 gene also showed an increase in plasma membrane ATPase activity in vitro and a lowered basal phosphatase activity under alkaline conditions. Cells containing the van2-93 mutant allele had normal levels of plasma membrane ATPase activity, but this activity was not inhibited by vanadate. Both of these mutants failed to enter stationary phase, were heat shock sensitive, showed lowered long-term viability, and sporulated on rich medium in the presence of 2% glucose. The wild-type VAN1 gene was isolated and sequenced. The open reading frame predicts a protein of 522 amino acids, with no significant homology to any genes that have been identified. Diploid cells that contained two mutant alleles of this gene demonstrated defects in spore viability. These data suggest that the VAN1 gene product is involved in regulation of the phosphorylation of a number of proteins, some of which appear to be important in cell growth control. Images PMID:2137555

  15. Identification of sex-specific quantitative trait loci controlling alcohol preference in C57BL/ 6 mice.

    PubMed

    Melo, J A; Shendure, J; Pociask, K; Silver, L M

    1996-06-01

    Mice from various inbred strains consume alcoholic beverages at highly reproducible and strain-specific levels. While most mice consume alcohol in moderate amounts, C57BL/6J animals exhibit sustained oral ingestion of high levels of alcohol in the presence of competing water and food. We now report a genetic investigation of this phenotype as one potential model for alcoholism. An intercross-backcross breeding protocol was used to identify two recessive alcohol preference quantitative trait loci (QTLs) that are both sex-restricted in expression. A comparison of our results with those of an earlier morphine preference study argues against the hypothesis of a single unified phenotype defined by a preference for all euphoria-producing drugs.

  16. An Image-Based Genetic Assay Identifies Genes in T1D Susceptibility Loci Controlling Cellular Antiviral Immunity in Mouse

    PubMed Central

    Liao, Juan; Jijon, Humberto B.; Kim, Ira R.; Goel, Gautam; Doan, Aivi; Sokol, Harry; Bauer, Hermann; Herrmann, Bernhard G.; Lassen, Kara G.; Xavier, Ramnik J.

    2014-01-01

    The pathogenesis of complex diseases, such as type 1 diabetes (T1D), derives from interactions between host genetics and environmental factors. Previous studies have suggested that viral infection plays a significant role in initiation of T1D in genetically predisposed individuals. T1D susceptibility loci may therefore be enriched in previously uncharacterized genes functioning in antiviral defense pathways. To identify genes involved in antiviral immunity, we performed an image-based high-throughput genetic screen using short hairpin RNAs (shRNAs) against 161 genes within T1D susceptibility loci. RAW 264.7 cells transduced with shRNAs were infected with GFP-expressing herpes simplex virus type 1 (HSV-1) and fluorescent microscopy was performed to assess the viral infectivity by fluorescence reporter activity. Of the 14 candidates identified with high confidence, two candidates were selected for further investigation, Il27 and Tagap. Administration of recombinant IL-27 during viral infection was found to act synergistically with interferon gamma (IFN-γ) to activate expression of type I IFNs and proinflammatory cytokines, and to enhance the activities of interferon regulatory factor 3 (IRF3). Consistent with a role in antiviral immunity, Tagap-deficient macrophages demonstrated increased viral replication, reduced expression of proinflammatory chemokines and cytokines, and decreased production of IFN-β. Taken together, our unbiased loss-of-function genetic screen identifies genes that play a role in host antiviral immunity and delineates roles for IL-27 and Tagap in the production of antiviral cytokines. PMID:25268627

  17. Genome-wide association and regional heritability mapping to identify loci underlying variation in nematode resistance and body weight in Scottish Blackface lambs.

    PubMed

    Riggio, V; Matika, O; Pong-Wong, R; Stear, M J; Bishop, S C

    2013-05-01

    The genetic architecture underlying nematode resistance and body weight in Blackface lambs was evaluated comparing genome-wide association (GWA) and regional heritability mapping (RHM) approaches. The traits analysed were faecal egg count (FEC) and immunoglobulin A activity against third-stage larvae from Teladorsagia circumcincta, as indicators of nematode resistance, and body weight in a population of 752 Scottish Blackface lambs, genotyped with the 50k single-nucleotide polymorphism (SNP) chip. FEC for both Nematodirus and Strongyles nematodes (excluding Nematodirus), as well as body weight were collected at approximately 16, 20 and 24 weeks of age. In addition, a weighted average animal effect was estimated for both FEC and body weight traits. After quality control, 44 388 SNPs were available for the GWA analysis and 42 841 for the RHM, which utilises only mapped SNPs. The same fixed effects were used in both analyses: sex, year, management group, litter size and age of dam, with day of birth as covariate. Some genomic regions of interest for both nematode resistance and body weight traits were identified, using both GWA and RHM approaches. For both methods, strong evidence for association was found on chromosome 14 for Nematodirus average animal effect, chromosome 6 for Strongyles FEC at 16 weeks and chromosome 6 for body weight at 16 weeks. Across the entire data set, RHM identified more regions reaching the suggestive level than GWA, suggesting that RHM is capable of capturing some of the variation not detected by GWA analyses.

  18. Rehabilitation device with variable resistance and intelligent control

    PubMed Central

    Dong, Shufang; Lu, Ke-Qian; Sun, J.Q.; Rudolph, Katherine

    2008-01-01

    Resistance exercise has been widely reported to have positive rehabilitation effects for patients with neuromuscular and orthopaedic conditions. This paper presents an optimal design of magneto-rheological fluid dampers for variable resistance exercise device in the form of a knee brace. An intelligent supervisory control for regulating the resistive force or torque of the knee brace has also been studied. The device provides both isometric and isokinetic strength training for the knee. PMID:15694609

  19. Additional rabbit IgA allotypes, f69, f70, g76,g77: control by the C alphaf and C alphag loci.

    PubMed

    Lammert, J M; Dray, S; Knight, K L; Hanly, W C

    1977-04-01

    Genetic and immunochemical studies have led to the identification of four additional rabbit IgA allotypes controlled by the Calphaf and Calphag loci. The folowing linkage combinations of the VHa and the 'new' alleles were observed among the populations of rabbits studied: a1f70g76, a1f69g77, and a2f69g77. Cross-reactions among g74, g76, and g77 molecules with various anti-g anti-allotype antisera indicate that the IgA-g allotypic specificities are comprised of multiple antigenic determinants. These studies provide a basis for further understanding of the evolution and gnetic control of the immunoglobulin heavy chain chromosomal region.

  20. Major Quantitative Trait Loci and Putative Candidate Genes for Powdery Mildew Resistance and Fruit-Related Traits Revealed by an Intraspecific Genetic Map for Watermelon (Citrullus lanatus var. lanatus)

    PubMed Central

    Kim, Kwang-Hwan; Hwang, Ji-Hyun; Han, Dong-Yeup; Park, Minkyu; Kim, Seungill; Choi, Doil; Kim, Yongjae; Lee, Gung Pyo; Kim, Sun-Tae; Park, Young-Hoon

    2015-01-01

    An intraspecific genetic map for watermelon was constructed using an F2 population derived from ‘Arka Manik’ × ‘TS34’ and transcript sequence variants and quantitative trait loci (QTL) for resistance to powdery mildew (PMR), seed size (SS), and fruit shape (FS) were analyzed. The map consists of 14 linkage groups (LGs) defined by 174 cleaved amplified polymorphic sequences (CAPS), 2 derived-cleaved amplified polymorphic sequence markers, 20 sequence-characterized amplified regions, and 8 expressed sequence tag-simple sequence repeat markers spanning 1,404.3 cM, with a mean marker interval of 6.9 cM and an average of 14.6 markers per LG. Genetic inheritance and QTL analyses indicated that each of the PMR, SS, and FS traits is controlled by an incompletely dominant effect of major QTLs designated as pmr2.1, ss2.1, and fsi3.1, respectively. The pmr2.1, detected on chromosome 2 (Chr02), explained 80.0% of the phenotypic variation (LOD = 30.76). This QTL was flanked by two CAPS markers, wsb2-24 (4.00 cM) and wsb2-39 (13.97 cM). The ss2.1, located close to pmr2.1 and CAPS marker wsb2-13 (1.00 cM) on Chr02, explained 92.3% of the phenotypic variation (LOD = 68.78). The fsi3.1, detected on Chr03, explained 79.7% of the phenotypic variation (LOD = 31.37) and was flanked by two CAPS, wsb3-24 (1.91 cM) and wsb3-9 (7.00 cM). Candidate gene-based CAPS markers were developed from the disease resistance and fruit shape gene homologs located on Chr.02 and Chr03 and were mapped on the intraspecific map. Colocalization of these markers with the major QTLs indicated that watermelon orthologs of a nucleotide-binding site-leucine-rich repeat class gene containing an RPW8 domain and a member of SUN containing the IQ67 domain are candidate genes for pmr2.1 and fsi3.1, respectively. The results presented herein provide useful information for marker-assisted breeding and gene cloning for PMR and fruit-related traits. PMID:26700647

  1. Major Quantitative Trait Loci and Putative Candidate Genes for Powdery Mildew Resistance and Fruit-Related Traits Revealed by an Intraspecific Genetic Map for Watermelon (Citrullus lanatus var. lanatus).

    PubMed

    Kim, Kwang-Hwan; Hwang, Ji-Hyun; Han, Dong-Yeup; Park, Minkyu; Kim, Seungill; Choi, Doil; Kim, Yongjae; Lee, Gung Pyo; Kim, Sun-Tae; Park, Young-Hoon

    2015-01-01

    An intraspecific genetic map for watermelon was constructed using an F2 population derived from 'Arka Manik' × 'TS34' and transcript sequence variants and quantitative trait loci (QTL) for resistance to powdery mildew (PMR), seed size (SS), and fruit shape (FS) were analyzed. The map consists of 14 linkage groups (LGs) defined by 174 cleaved amplified polymorphic sequences (CAPS), 2 derived-cleaved amplified polymorphic sequence markers, 20 sequence-characterized amplified regions, and 8 expressed sequence tag-simple sequence repeat markers spanning 1,404.3 cM, with a mean marker interval of 6.9 cM and an average of 14.6 markers per LG. Genetic inheritance and QTL analyses indicated that each of the PMR, SS, and FS traits is controlled by an incompletely dominant effect of major QTLs designated as pmr2.1, ss2.1, and fsi3.1, respectively. The pmr2.1, detected on chromosome 2 (Chr02), explained 80.0% of the phenotypic variation (LOD = 30.76). This QTL was flanked by two CAPS markers, wsb2-24 (4.00 cM) and wsb2-39 (13.97 cM). The ss2.1, located close to pmr2.1 and CAPS marker wsb2-13 (1.00 cM) on Chr02, explained 92.3% of the phenotypic variation (LOD = 68.78). The fsi3.1, detected on Chr03, explained 79.7% of the phenotypic variation (LOD = 31.37) and was flanked by two CAPS, wsb3-24 (1.91 cM) and wsb3-9 (7.00 cM). Candidate gene-based CAPS markers were developed from the disease resistance and fruit shape gene homologs located on Chr.02 and Chr03 and were mapped on the intraspecific map. Colocalization of these markers with the major QTLs indicated that watermelon orthologs of a nucleotide-binding site-leucine-rich repeat class gene containing an RPW8 domain and a member of SUN containing the IQ67 domain are candidate genes for pmr2.1 and fsi3.1, respectively. The results presented herein provide useful information for marker-assisted breeding and gene cloning for PMR and fruit-related traits.

  2. Surveillance and Control of Antibiotic Resistance in the Mediterranean Region

    PubMed Central

    Ricciardi, Walter; Giubbini, Gabriele; Laurenti, Patrizia

    2016-01-01

    Antibiotic resistance is one of the most relevant problems in the healthcare: the growth of resistant microorganisms in healthcare settings is a worrisome threat, raising length to stay (LOS), morbidity and mortality in those patients. The importance of the antibiotic resistance and its spread around the world, gave rise to the activation of several surveillance systems, based especially on the collection of laboratory data to local or national level. The objective of this work is to carry out a review of the scientific literature existing on the topic and scientific activities related to surveillance of antibiotic resistance in the countries bordering the Mediterranean Sea. Recent Data from European Centre for Disease Prevention and Control (November 2015) show, for different combinations bacterium-drug, an increase of resistance from North to South and from West to East of Europe. It is of particular concern the phenomenon of resistance carried out by some gram-negative, specifically Klebsiella pneumoniae and Escherichia coli to third-generation cephalosporin, often combined in opposition to fluoroquinolones and aminoglycosides. Is particularly high the incidence of resistance to carbapenems by strains of Enterobacteriaceae (Klebsiella included). The resistance exerted by MRSA (Methicillin-resistant Staphylococcus aureus) continues to be relevant, albeit showing some decline in recent years. The incidence of resistance carried on by Streptococcus pneumoniae is stable and is mainly relevant to macrolides. Finally, a significant increase in recording relatively exercised by Enterococcus faecium to Vancomycin. Detecting, preventing, and controlling antibiotic resistance requires strategic, coordinated, and sustained efforts. It also depends on the engagement of governments, academia, industry, healthcare providers, the general public, and the agricultural community, as well as international partners. Committing to combating antibiotic-resistant microbes does support

  3. Genetic control of T cell responsiveness to the Friend murine leukemia virus envelope antigen. Identification of class II loci of the H-2 as immune response genes

    PubMed Central

    1988-01-01

    T cells primed specifically for the envelope glycoprotein of Friend murine leukemia helper virus (F-MuLV) were prepared by immunizing mice with a recombinant vaccinia virus that expressed the entire env gene of F-MuLV. Significant proliferative responses of F-MuLV envelope- specific, H-2a/b T cells were observed when the T cells were stimulated with antigen-pulsed peritoneal exudate cells (PEC) having the b allele at the K, A beta, A alpha, and E beta loci of the H-2. On the other hand, PEC having only the kappa allele at these loci did not induce the envelope-specific T cell proliferation, even when the PEC had the b allele at the E alpha, S, or D loci. F-MuLV envelope-specific proliferation of H-2a/b T cells under the stimulation of antigen- pulsed, H-2a/b PEC was specifically blocked with anti-I-Ab and anti-I- Ek mAbs but not with anti-Kb, anti-Kk, or anti-I-Ak mAbs. Moreover, (B10.MBR x A/WySn)F1 mice that have the b allele only at the K locus but not in I-A subregion were nonresponders to the envelope glycoprotein, and the bm12 mutation at the A beta locus completely abolished the T cell responsiveness to this antigen. These results indicate that proliferative T cells recognize a limited number of epitopes on F-MuLV envelope protein in the context of I-Ab, hybrid I- Ak/b, and/or hybrid I-Ek/b class II MHC molecules but fail to recognize the same envelope protein in the context of I-Ak or I-Ek molecules. This influence of the H-2I region on T cell recognition of the envelope glycoprotein appeared to control in vivo induction of protective immunity against Friend virus complex after immunization with the vaccinia-F-MuLV env vaccine. Thus, these results provide, for the first time, direct evidence for Ir gene-controlled responder/nonresponder phenotypes influencing the immune response to a pathogenic virus of mice. PMID:3141552

  4. Insecticide resistance in the horn fly: alternative control strategies.

    PubMed

    Oyarzún, M P; Quiroz, A; Birkett, M A

    2008-09-01

    The horn fly, Haematobia irritans (Linnaeus 1758) (Diptera: Muscidae) is one of the most widespread and economically important pests of cattle. Although insecticides have been used for fly control, success has been limited because of the development of insecticide resistance in all countries where the horn fly is found. This problem, along with public pressure for insecticide-free food and the prohibitive cost of developing new classes of compounds, has driven the investigation of alternative control methods that minimize or avoid the use of insecticides. This review provides details of the economic impact of horn flies, existing insecticides used for horn fly control and resistance mechanisms. Current research on new methods of horn fly control based on resistant cattle selection, semiochemicals, biological control and vaccines is also discussed.

  5. Mapping four quantitative trait loci associated with type I Fusarium head blight resistance in winter wheat ‘INW0412’

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fusarium head blight (FHB) has become one of the most damaging wheat diseases in humid and semi-humid regions around the world. Breeding efforts have focused on resistance mechanisms that limit the spread once a spike is infected, or type II resistance. But resistance to initial infection, type I re...

  6. Automatic control and detector for three-terminal resistance measurement

    DOEpatents

    Fasching, George E.

    1976-10-26

    A device is provided for automatic control and detection in a three-terminal resistance measuring instrument. The invention is useful for the rapid measurement of the resistivity of various bulk material with a three-terminal electrode system. The device maintains the current through the sample at a fixed level while measuring the voltage across the sample to detect the sample resistance. The three-electrode system contacts the bulk material and the current through the sample is held constant by means of a control circuit connected to a first of the three electrodes and works in conjunction with a feedback controlled amplifier to null the voltage between the first electrode and a second electrode connected to the controlled amplifier output. An A.C. oscillator provides a source of sinusoidal reference voltage of the frequency at which the measurement is to be executed. Synchronous reference pulses for synchronous detectors in the control circuit and an output detector circuit are provided by a synchronous pulse generator. The output of the controlled amplifier circuit is sampled by an output detector circuit to develop at an output terminal thereof a D.C. voltage which is proportional to the sample resistance R. The sample resistance is that segment of the sample between the area of the first electrode and the third electrode, which is connected to ground potential.

  7. Dual Cry2Ab and Vip3A resistant strains of Helicoverpa armigera and Helicoverpa punctigera (Lepidoptera: Noctuidae); testing linkage between loci and monitoring of allele frequencies.

    PubMed

    Walsh, T K; Downes, S J; Gascoyne, J; James, W; Parker, T; Armstrong, J; Mahon, R J

    2014-08-01

    Considerable attention has been given to delaying the evolution of insect resistance to toxins produced by transgenic crops. The major pests of cotton in Australia are the Lepidoptera Helicoverpa armigera (Hubner, 1805) and Helicoverpa punctigera (Wallengren), and the toxins deployed in current and imminent transgenic cotton varieties are Cry1Ac, Cry2Ab and Vip3A from Bacillus thuringiensis. In this study, lines that carry alleles conferring resistance to Cry2Ab and Vip3A were isolated using F2 tests. Extensive work on the Cry2Ab resistant lines, and preliminary work on the Vip3A resistant lines, suggested a single common resistance to each toxin in both species thereby justifying the use of more efficient F1 tests as the primary means for monitoring changes over time. A potential further efficiency could be gained by developing a single resistant line that carries both types of Bt resistance. Herein we report on work with both H. armigera and H. punctigera that tests whether dual Cry2Ab-Vip3A resistant lines can be developed and, if so, whether they can be used to effectively monitor resistance frequencies. Furthermore, the creation of dual resistant lines allowed linkage between the Cry2Ab and Vip3A resistances to be investigated for H. punctigera. We show that dual resistant lines can be used to increase the efficiency of the F1 screen for recessive alleles, and that in H. punctigera there is no linkage between Cry2Ab and Vip3A resistance.

  8. Salmonella and Campylobacter: Antimicrobial resistance and bacteriophage control in poultry.

    PubMed

    Grant, Ar'Quette; Hashem, Fawzy; Parveen, Salina

    2016-02-01

    Salmonella and Campylobacter are major causes of foodborne related illness and are traditionally associated with consuming undercooked poultry and/or consuming products that have been cross contaminated with raw poultry. Many of the isolated Salmonella and Campylobacter that can cause disease have displayed antimicrobial resistance phenotypes. Although poultry producers have reduced on-the-farm overuse of antimicrobials, antimicrobial resistant Salmonella and Campylobacter strains still persist. One method of bio-control, that is producing promising results, is the use of lytic bacteriophages. This review will highlight the current emergence and persistence of antimicrobial resistant Salmonella and Campylobacter recovered from poultry as well as bacteriophage research interventions and limitations.

  9. A design of tamper resistant prescription RFID access control system.

    PubMed

    Chen, Yu-Yi; Huang, Der-Chen; Tsai, Meng-Lin; Jan, Jinn-Ke

    2012-10-01

    In this paper, we propose a tamper resistant prescription RFID access control protocol for different authorized readers. Not only the authentication mechanism but also the access right authorization mechanism is designed in our scheme. Only the specific doctor, usually the patient's doctor, can access the tag. Moreover, some related information of patient's prescription is attached to a RFID tag for tamper resistance. The patients' rights will be guaranteed.

  10. Control of ideal and resistive magnetohydrodynamic modes in reversed field pinches with a resistive wall

    SciTech Connect

    Richardson, A. S.; Finn, J. M.; Delzanno, G. L.

    2010-11-15

    Numerical studies of magnetohydrodynamic (MHD) instabilities with feedback control in reversed field pinches (RFPs) are presented. Specifically, investigations are performed of the stability of m=1 modes in RFPs with control based on sensing the normal and tangential magnetic fields at the resistive wall and applying two-parameter feedback proportional to these fields. The control scheme is based on that of [J. M. Finn, Phys. Plasmas 13, 082504 (2006)], which is here modified to use a more realistic plasma model. The plasma model now uses full resistive MHD rather than reduced MHD, and it uses three realistic classes of equilibrium parallel current density profiles appropriate to RFPs. Results with these modifications are in qualitative agreement with [J. M. Finn, Phys. Plasmas 13, 082504 (2006)]: the feedback can stabilize tearing modes (with resistive or ideal-wall) and resistive wall ideal modes. The limit for stabilization is again found to be near the threshold for ideal modes with an ideal-wall. In addition to confirming these predictions, the nature of the instabilities limiting the range of feedback stabilization near the ideal-wall ideal-plasma threshold are studied, and the effects of viscosity, resistive wall time, and plasma resistivity are reported.

  11. Identification of loci associated with drought resistance traits in heterozygous autotetraploid alfalfa (Medicago sativa L.) using genome-wide association studies with genotyping by sequencing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Developing molecular markers associated with drought resistance would be helpful for improving the accuracy in selecting resistant alfalfa, and accelerating the breeding process. A panel of accessions comprised of 200 alfalfa cultivars and landraces with potential drought tolerance were selected fro...

  12. Unlinked genetic loci control the reduced transcription of aminopeptidase N 1 and 3 in the European corn borer and determine tolerance to Bacillus thuringiensis Cry1Ab toxin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Crystalline (Cry) toxins from Bacillus thuringiensis (Bt) control insect feeding damage on crop plants via foliar applications or by expression within transgenic plants, but continued Bt use is threatened by the buildup of insect resistance traits. Aminopeptidase N (apn) gene family members encode m...

  13. Genetic Mapping of Quantitative Trait Loci Controlling Growth and Wood Quality Traits in Eucalyptus Grandis Using a Maternal Half-Sib Family and Rapd Markers

    PubMed Central

    Grattapaglia, D.; Bertolucci, FLG.; Penchel, R.; Sederoff, R. R.

    1996-01-01

    Quantitative trait loci (QTL) mapping of forest productivity traits was performed using an open pollinated half-sib family of Eucalyptus grandis. For volume growth, a sequential QTL mapping approach was applied using bulk segregant analysis (BSA), selective genotyping (SG) and cosegregation analysis (CSA). Despite the low heritability of this trait and the heterogeneous genetic background employed for mapping. BSA detected one putative QTL and SG two out of the three later found by CSA. The three putative QTL for volume growth were found to control 13.7% of the phenotypic variation, corresponding to an estimated 43.7% of the genetic variation. For wood specific gravity five QTL were identified controlling 24.7% of the phenotypic variation corresponding to 49% of the genetic variation. Overlapping QTL for CBH, WSG and percentage dry weight of bark were observed. A significant case of digenic epistasis was found, involving unlinked QTL for volume. Our results demonstrate the applicability of the within half-sib design for QTL mapping in forest trees and indicate the existence of major genes involved in the expression of economically important traits related to forest productivity in Eucalyptus grandis. These findings have important implications for marker-assisted tree breeding. PMID:8913761

  14. Genetic mapping of quantitative trait loci controlling growth and wood quality traits in Eucalyptus grandis using a maternal half-sib family and RAPD markers.

    PubMed

    Grattapaglia, D; Bertolucci, F L; Penchel, R; Sederoff, R R

    1996-11-01

    Quantitative trait loci (QTL) mapping of forest productivity traits was performed using an open pollinated half-sib family of Eucalyptus grandis. For volume growth, a sequential QTL mapping approach was applied using bulk segregant analysis (BSA), selective genotyping (SG) and cosegregation analysis (CSA). Despite the low heritability of this trait and the heterogeneous genetic background employed for mapping, BSA detected one putative QTL and SG two out of the three later found by CSA. The three putative QTL for volume growth were found to control 13.7% of the phenotypic variation, corresponding to an estimated 43.7% of the genetic variation. For wood specific gravity five QTL were identified controlling 24.7% of the phenotypic variation corresponding to 49% of the genetic variation. Overlapping QTL for CBH, WSG and percentage dry weight of bark were observed. A significant case of digenic epistasis was found, involving unlinked QTL for volume. Our results demonstrate the applicability of the within half-sib design for QTL mapping in forest trees and indicate the existence of major genes involved in the expression of economically important traits related to forest productivity in Eucalyptus grandis. These findings have important implications for marker-assisted tree breeding.

  15. Averting a malaria disaster: will insecticide resistance derail malaria control?

    PubMed

    Hemingway, Janet; Ranson, Hilary; Magill, Alan; Kolaczinski, Jan; Fornadel, Christen; Gimnig, John; Coetzee, Maureen; Simard, Frederic; Roch, Dabiré K; Hinzoumbe, Clément Kerah; Pickett, John; Schellenberg, David; Gething, Peter; Hoppé, Mark; Hamon, Nicholas

    2016-04-23

    World Malaria Day 2015 highlighted the progress made in the development of new methods of prevention (vaccines and insecticides) and treatment (single dose drugs) of the disease. However, increasing drug and insecticide resistance threatens the successes made with existing methods. Insecticide resistance has decreased the efficacy of the most commonly used insecticide class of pyrethroids. This decreased efficacy has increased mosquito survival, which is a prelude to rising incidence of malaria and fatalities. Despite intensive research efforts, new insecticides will not reach the market for at least 5 years. Elimination of malaria is not possible without effective mosquito control. Therefore, to combat the threat of resistance, key stakeholders need to rapidly embrace a multifaceted approach including a reduction in the cost of bringing new resistance management methods to market and the streamlining of associated development, policy, and implementation pathways to counter this looming public health catastrophe.

  16. A genetic map of cucumber composed of RAPDs, RFLPs, AFLPs, and loci conditioning resistance to papaya ringspot and zucchini yellow mosaic viruses.

    PubMed

    Park, Y H; Sensoy, S; Wye, C; Antonise, R; Peleman, J; Havey, M J

    2000-12-01

    The watermelon strain of papaya ringspot virus (PRSV-W) and zucchini yellow mosaic virus (ZYMV) are potyviruses that cause significant disease losses in cucumber. Resistances have been identified primarily in exotic germplasm that require transfer to elite cultivated backgrounds. To select more efficiently for virus resistances, we identified molecular markers tightly linked to PRSV-W and ZYMV resistances in cucumber. We generated F6 recombinant inbred lines (RILs) from a cross between Cucumis sativus L. 'Straight 8' and a line from 'Taichung Mou Gua', TMG1 (susceptible and resistant, respectively, to both viruses), and studied the segregations of amplified fragment length polymorphism (AFLP) markers, randomly amplified polymorphic DNAs (RAPDs), restriction fragment length polymorphisms (RFLPs), and resistances to PRSV-W and ZYMV. A 353-point map of cucumber was generated, delineating 12 linkage groups at LOD 3.5. Linkage arrangements among RFLPs were consistent with previously published maps; however linkages among RAPDs in our map did not agree with a previously published map. Resistances to PRSV-W and ZYMV were tightly linked (2.2 cM) and mapped to the end of one linkage group. One AFLP cosegregated with resistance to ZYMV.

  17. Relationship of Antimicrobial Control Policies and Hospital and Infection Control Characteristics to Antimicrobial Resistance Rates

    PubMed Central

    Larson, Elaine L.; Quiros, Dave; Giblin, Tara; Lin, Susan

    2007-01-01

    Background Antibiotic misuse and noncompliance with infection control precautions have contributed to increasing levels of antimicrobial resistance in hospitals. Objectives To assess the extent to which resistance is monitored in infection control programs and to correlate resistance rates with characteristics of antimicrobial control policies, provider attitudes and practices, and systems-level indicators of implementation of the hand hygiene guideline of the Centers for Disease Control and Prevention. Methods An on-site survey of intensive care unit staff and infection control directors of 33 hospitals in the United States was conducted. The following data were collected: antimicrobial control policies; rates during the previous 12 months of methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and ceftazidime-resistant Klebsiella pneumoniae; an implementation score of systems-level efforts to implement the guideline; staff attitudes toward practice guidelines; and observations of staff hand hygiene. Variables associated with resistance rates were examined for independent effects by using logistic regression. Results Resistance rates for S aureus, enterococci, and K pneumoniae were 52.5%, 18.2%, and 16.0%, respectively. Ten (30.3%) hospitals had an antibiotic control policy. No statistically significant correlation was observed between staff attitudes toward practice guidelines, observed hand hygiene behavior, or having an antibiotic use policy and resistance rates. In logistic regression analysis, higher scores on measures of systems-level efforts to implement the guideline were associated with lower rates of resistant S aureus and enterococci (P=.046). Conclusions Organizational-level factors independent of the practices of individual clinicians may be associated with rates of antimicrobial resistance. PMID:17322010

  18. Selection of multiple-antibiotic-resistant (mar) mutants of Escherichia coli by using the disinfectant pine oil: roles of the mar and acrAB loci.

    PubMed Central

    Moken, M C; McMurry, L M; Levy, S B

    1997-01-01

    Mutants of Escherichia coli selected for resistance to the disinfectant pine oil or to a household product containing pine oil also showed resistance to multiple antibiotics (tetracycline, ampicillin, chloramphenicol, and nalidixic acid) and overexpressed the marA gene. Likewise, antibiotic-selected Mar mutants, which also overexpress marA, were resistant to pine oil. Deletion of the mar or acrAB locus, the latter encoding a multidrug efflux pump positively regulated in part by MarA, increased the susceptibility of wild-type and mutant strains to pine oil. PMID:9420057

  19. Aod1 controlling day 3 thymectomy-induced autoimmune ovarian dysgenesis in mice encompasses two linked quantitative trait loci with opposing allelic effects on disease susceptibility.

    PubMed

    Roper, Randall J; McAllister, Ryan D; Biggins, Julia E; Michael, Sandra D; Min, Soo Hong; Tung, Kenneth S K; Call, Stanford B; Gao, Jianfeng; Teuscher, Cory

    2003-06-15

    Day 3 thymectomy (D3Tx) leads to a paucity of CD4(+)CD25(+) suppressor T cells, a loss of peripheral tolerance, and the development of organ-specific autoimmune disease in adult mice. Importantly, D3Tx does not lead to autoimmune disease in all mouse strains, indicating that this process is genetically controlled. Previously, we reported linkage of D3Tx-induced autoimmune ovarian dysgenesis (AOD) and its intermediate phenotypes, antiovarian autoantibody responsiveness, oophoritis, and atrophy, to five quantitative trait loci (QTL), designated Aod1 through Aod5. We also showed interaction between these QTL and H2 as well as Gasa2, a QTL controlling susceptibility to D3Tx-induced autoimmune gastritis. To physically map Aod1, interval-specific bidirectional recombinant congenic strains of mice were generated and studied for susceptibility to D3Tx-induced AOD. Congenic mapping studies revealed that Aod1 controls susceptibility to oophoritis and comprises two linked QTL with opposing allelic effects. Aod1a resides between D16Mit211 (23.3 cM) and D16Mit51 (66.75 cM) on chromosome 16. Aod1b maps proximal of Aod1a between D16Mit89 (20.9 cM) and D16Mit211 (23.3 cM) and includes the candidate genes stefin A1, A2, and A3 (Stfa1-Stfa3), inhibitors of cathepsin S, a cysteine protease required for autoantigen presentation, and the development of autoimmune disease of the salivary and lacrimal glands following D3Tx. cDNA sequencing revealed the existence of structural polymorphisms for both Stfa1 and Stfa2. Given the roles of cathepsins in Ag processing and presentation, Stfa1 and Stfa2 alleles have the potential to control susceptibility to autoimmune disease at the level of both CD4(+)CD25(+) suppressor and CD4(+)CD25(-) effector T cells.

  20. Detection of quantitative trait loci for mungbean yellow mosaic India virus (MYMIV) resistance in mungbean (Vigna radiata (L.) Wilczek) in India and Pakistan

    PubMed Central

    Kitsanachandee, Ratanakorn; Somta, Prakit; Chatchawankanphanich, Orawan; Akhtar, Khalid P.; Shah, Tariq Mahmud; Nair, Ramakrishnan M.; Bains, Tejinderjit S.; Sirari, Asmita; Kaur, Livinder; Srinives, Peerasak

    2013-01-01

    Yellow mosaic disease (YMD) is one of the major diseases affecting mungbean (Vigna radiata (L.) Wilczek). In this study, we report the mapping of the quantitative trait locus (QTL) for mungbean yellow mosaic India virus (MYMIV) resistance in mungbean. An F8 recombinant inbred line (RIL) mapping population was generated in Thailand from a cross between NM10-12-1 (MYMIV resistance) and KPS2 (MYMIV susceptible). One hundred and twenty-two RILs and their parents were evaluated for MYMIV resistance in infested fields in India and Pakistan. A genetic linkage map was developed for the RIL population using simple sequence repeat (SSR) markers. Composite interval mapping identified five QTLs for MYMIV resistance: three QTLs for India (qYMIV1, qYMIV2 and qYMIV3) and two QTLs for Pakistan (qYMIV4 and qYMIV5). qYMIV1, qYMIV2, qYMIV3, qYMIV4 and qYMIV5 explained 9.33%, 10.61%, 12.55%, 21.93% and 6.24% of variation in disease responses, respectively. qYMIV1 and qYMIV4 appeared to be the same locus and were common to a major QTL for MYMIV resistance in India identified previously using a different resistant mungbean. PMID:24399908

  1. A Cluster of Nucleotide-Binding Site-Leucine-Rich Repeat Genes Resides in a Barley Powdery Mildew Resistance Quantitative Trait Loci on 7HL.

    PubMed

    Cantalapiedra, Carlos P; Contreras-Moreira, Bruno; Silvar, Cristina; Perovic, Dragan; Ordon, Frank; Gracia, María Pilar; Igartua, Ernesto; Casas, Ana M

    2016-07-01

    Powdery mildew causes severe yield losses in barley production worldwide. Although many resistance genes have been described, only a few have already been cloned. A strong QTL (quantitative trait locus) conferring resistance to a wide array of powdery mildew isolates was identified in a Spanish barley landrace on the long arm of chromosome 7H. Previous studies narrowed down the QTL position, but were unable to identify candidate genes or physically locate the resistance. In this study, the exome of three recombinant lines from a high-resolution mapping population was sequenced and analyzed, narrowing the position of the resistance down to a single physical contig. Closer inspection of the region revealed a cluster of closely related NBS-LRR (nucleotide-binding site-leucine-rich repeat containing protein) genes. Large differences were found between the resistant lines and the reference genome of cultivar Morex, in the form of PAV (presence-absence variation) in the composition of the NBS-LRR cluster. Finally, a template-guided assembly was performed and subsequent expression analysis revealed that one of the new assembled candidate genes is transcribed. In summary, the results suggest that NBS-LRR genes, absent from the reference and the susceptible genotypes, could be functional and responsible for the powdery mildew resistance. The procedure followed is an example of the use of NGS (next-generation sequencing) tools to tackle the challenges of gene cloning when the target gene is absent from the reference genome.

  2. Asymptotic unbounded root loci - Formulas and computation

    NASA Technical Reports Server (NTRS)

    Sastry, S. S.; Desoer, C. A.

    1983-01-01

    A new geometric way of computing the asymptotic behavior of unbounded root loci of a strictly proper linear time-invariant control system as loop gain goes to infinity is presented. Properties of certain restricted linear maps and nested restrictions of linear maps are developed, and formulas are obtained for the leading coefficient of the asymptotic values of the unbounded multivariable root loci are obtained in terms of eigenvalues of those maps. Published results and a certain simple null structure assumption are used to relate these asymptotic values to the structure at infinity of the Smith-McMillan form of the open loop transfer function. Explicit matrix formulas for the more abstract derived formulas are given and additional geometric insights are developed with orthogonal projections and singular value decomposition. Formulas for the pivots of the unbounded root loci are calculated and shown to have the same form as the coefficients of the unbounded asymptotic root loci.

  3. Resistance to genetic insect control: Modelling the effects of space.

    PubMed

    Watkinson-Powell, Benjamin; Alphey, Nina

    2017-01-21

    Genetic insect control, such as self-limiting RIDL(2) (Release of Insects Carrying a Dominant Lethal) technology, is a development of the sterile insect technique which is proposed to suppress wild populations of a number of major agricultural and public health insect pests. This is achieved by mass rearing and releasing male insects that are homozygous for a repressible dominant lethal genetic construct, which causes death in progeny when inherited. The released genetically engineered ('GE') insects compete for mates with wild individuals, resulting in population suppression. A previous study modelled the evolution of a hypothetical resistance to the lethal construct using a frequency-dependent population genetic and population dynamic approach. This found that proliferation of resistance is possible but can be diluted by the introgression of susceptible alleles from the released homozygous-susceptible GE males. We develop this approach within a spatial context by modelling the spread of a lethal construct and resistance trait, and the effect on population control, in a two deme metapopulation, with GE release in one deme. Results show that spatial effects can drive an increased or decreased evolution of resistance in both the target and non-target demes, depending on the effectiveness and associated costs of the resistant trait, and on the rate of dispersal. A recurrent theme is the potential for the non-target deme to act as a source of resistant or susceptible alleles for the target deme through dispersal. This can in turn have a major impact on the effectiveness of insect population control.

  4. Control of volume resistivity in inorganic organic separators

    NASA Technical Reports Server (NTRS)

    Sheibley, D. W.; Manzo, M. A.

    1979-01-01

    Control of resistivity in NASA inorganic-organic separators is achieved by incorporating small percentages of high surface area, fine particle silica with other ingredients in the separator coating. The volume resistivity is predictable from the surface area of filler particles in the coating. The approach is applied to two polymer- plasticizer -filler coating systems, where the filler content of each is below the generally acknowledged critical pigment volume concentration of the coating. Application of these coating systems to 0.0254 cm thick (10-mil) fuel cell grade asbestos sheet produces inexpensive, flexible, microporous separators that perform as well as the original inorganic-organic concept, the Astropower separator.

  5. Deciphering the conserved genetic loci implicated in plant disease control through comparative genomics of Bacillus amyloliquefaciens subsp. plantarum

    PubMed Central

    Hossain, Mohammad J.; Ran, Chao; Liu, Ke; Ryu, Choong-Min; Rasmussen-Ivey, Cody R.; Williams, Malachi A.; Hassan, Mohammad K.; Choi, Soo-Keun; Jeong, Haeyoung; Newman, Molli; Kloepper, Joseph W.; Liles, Mark R.

    2015-01-01

    To understand the growth-promoting and disease-inhibiting activities of plant growth-promoting rhizobacteria (PGPR) strains, the genomes of 12 Bacillus subtilis group strains with PGPR activity were sequenced and analyzed. These B. subtilis strains exhibited high genomic diversity, whereas the genomes of B. amyloliquefaciens strains (a member of the B. subtilis group) are highly conserved. A pairwise BLASTp matrix revealed that gene family similarity among Bacillus genomes ranges from 32 to 90%, with 2839 genes within the core genome of B. amyloliquefaciens subsp. plantarum. Comparative genomic analyses of B. amyloliquefaciens strains identified genes that are linked with biological control and colonization of roots and/or leaves, including 73 genes uniquely associated with subsp. plantarum strains that have predicted functions related to signaling, transportation, secondary metabolite production, and carbon source utilization. Although B. amyloliquefaciens subsp. plantarum strains contain gene clusters that encode many different secondary metabolites, only polyketide biosynthetic clusters that encode difficidin and macrolactin are conserved within this subspecies. To evaluate their role in plant pathogen biocontrol, genes involved in secondary metabolite biosynthesis were deleted in a B. amyloliquefaciens subsp. plantarum strain, revealing that difficidin expression is critical in reducing the severity of disease, caused by Xanthomonas axonopodis pv. vesicatoria in tomato plants. This study defines genomic features of PGPR strains and links them with biocontrol activity and with host colonization. PMID:26347755

  6. Intensified agriculture favors evolved resistance to biological control.

    PubMed

    Tomasetto, Federico; Tylianakis, Jason M; Reale, Marco; Wratten, Steve; Goldson, Stephen L

    2017-03-13

    Increased regulation of chemical pesticides and rapid evolution of pesticide resistance have increased calls for sustainable pest management. Biological control offers sustainable pest suppression, partly because evolution of resistance to predators and parasitoids is prevented by several factors (e.g., spatial or temporal refuges from attacks, reciprocal evolution by control agents, and contrasting selection pressures from other enemy species). However, evolution of resistance may become more probable as agricultural intensification reduces the availability of refuges and diversity of enemy species, or if control agents have genetic barriers to evolution. Here we use 21 y of field data from 196 sites across New Zealand to show that parasitism of a key pasture pest (Listronotus bonariensis; Argentine stem weevil) by an introduced parasitoid (Microctonus hyperodae) was initially nationally successful but then declined by 44% (leading to pasture damage of c. 160 million New Zealand dollars per annum). This decline was not attributable to parasitoid numbers released, elevation, or local climatic variables at sample locations. Rather, in all locations the decline began 7 y (14 host generations) following parasitoid introduction, despite releases being staggered across locations in different years. Finally, we demonstrate experimentally that declining parasitism rates occurred in ryegrass Lolium perenne, which is grown nationwide in high-intensity was significantly less than in adjacent plots of a less-common pasture grass (Lolium multiflorum), indicating that resistance to parasitism is host plant-dependent. We conclude that low plant and enemy biodiversity in intensive large-scale agriculture may facilitate the evolution of host resistance by pests and threaten the long-term viability of biological control.

  7. Quantitative trait loci mapping of resistance to Fusarium oxysporum f. sp. niveum race 2 in Citrullus lanatus var. citroides using genotyping-by-sequencing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    One of the most devastating watermelon diseases worldwide, Fusarium wilt, is caused by Fusarium oxysporum f. sp. niveum (Fon). Spread of the particularly virulent Fon race 2 in the United States, coupled with the lack of resistance in edible cultivars of the sweet cultivated watermelon Citrullus lan...

  8. Quantitative Trait Loci for Resistance to Aspergillus Ear Rot: Analysis by Linkage Mapping, Characterization of Near-Isogenic Lines and Meta-Analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    High levels of aflatoxin contamination of maize can be deadly for exposed human populations. Resistance to aflatoxin accumulation in maize has been reported in multiple studies and acts at multiple steps where there is fungal-plant interaction. In this study, we report the identification and mapping...

  9. Identification of quantitative trait loci (QTL) for resistance to Fusarium crown rot (Fusarium pseudograminearum) in multiple assay environments in the Pacific Northwestern US

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fusarium crown rot (FCR), caused by F. pseudograminearum and F. culmorum, reduces wheat (Triticum aestivum L.) yields in the Pacific Northwest (PNW) of the U.S. by as much as 35%. Resistance to FCR has not yet been discovered in currently grown PNW wheat cultivars. Several significant quantitative t...

  10. Association mapping of North American spring wheat breeding germplasm reveals loci conferring resistance to Ug99 and other African stem rust races

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The recently identified Puccinia graminis f. sp. tritici (Pgt) race TTKSK (Ug99) poses a severe threat to global wheat production because of its broad virulence on several widely deployed resistance genes. Additional concerning virulences have been detected in the Ug99 group of races, and spread of ...

  11. Identification of quantitative trait loci (QTLs) responsible for sheath blight resistance in rice using recombinant inbred line population of Lemont X Jasmine 85

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rice sheath blight (RSB) caused by the soil borne pathogen Rhizoctonia solani, is one of the most destructive diseases of rice, causing severe losses in rice yield and quality annually. The major gene (s) governing the resistance to RSB have not been found in cultivated rice worldwide. However, ri...

  12. Mapping of two loci conferring resistance to wheat stem rust pathogen races TTKSK (Ug99) and TRTTF in the elite hard red spring wheat line SD4279

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Since its identification in the late 1990's, the stem rust pathogen (Puccinia graminis. f. sp. tritici (Pgt)) strain Ug99 (race TTKSK) has represented a worldwide wheat production threat due to its ability to overcome most of the resistance genes present in commercial cultivars. In order to address ...

  13. Multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis: epidemiology and control.

    PubMed

    Matteelli, Alberto; Migliori, Giovanni Battista; Cirillo, Daniela; Centis, Rosella; Girard, Enrico; Raviglion, Mario

    2007-10-01

    The emergence of multidrug-resistant (MDR)-TB and, more recently, of extensively drug-resistant (XDR)-TB is a real threat to achieve TB control and elimination. Over 400,000 new cases of MDR-TB occur each year and, although their number is currently unknown, XDR cases are recognized in every setting where there has been the capacity to detect them. The long-term vision for the full control of MDR-TB requires the scaling-up of culture and drug-susceptibility testing capacity, which is very limited in disease-endemic countries, and the expanded use of high-technology assays for rapid determination of resistance. MDR cases are treatable and well designed regimens, largely based on second-line anti-TB drugs, can considerably improve cure rates. However, treatment regimens need to be markedly improved through the introduction of less toxic and more powerful drugs, thus reducing duration of treatment and tolerability. This is of utmost importance for XDR-TB cases. The prevalence of MDR-TB and XDR-TB are inversely correlated with the quality of TB control and the proper use of second-line anti-TB drugs. Adherence to proper standards of care and control is imperative and a top priority of all TB control efforts. However, the risk of an uncontrollable epidemic of MDR- and XDR-TB is real considering current levels of financing and commitment to care.

  14. QTL for several metabolic traits map to loci controlling growth and body composition in an F2 intercross between high- and low-growth chicken lines.

    PubMed

    Nadaf, Javad; Pitel, Frédérique; Gilbert, Hélène; Duclos, Michel J; Vignoles, Florence; Beaumont, Catherine; Vignal, Alain; Porter, Tom E; Cogburn, Larry A; Aggrey, Samuel E; Simon, Jean; Le Bihan-Duval, Elisabeth

    2009-08-07

    Quantitative trait loci (QTL) for metabolic and body composition traits were mapped at 7 and 9 wk, respectively, in an F(2) intercross between high-growth and low-growth chicken lines. These lines also diverged for abdominal fat percentage (AFP) and plasma insulin-like growth factor-I (IGF-I), insulin, and glucose levels. Genotypings were performed with 129 microsatellite markers covering 21 chromosomes. A total of 21 QTL with genomewide level of significance were detected by single-trait analyses for body weight (BW), breast muscle weight (BMW) and percentage (BMP), AF weight (AFW) and percentage (AFP), shank length (ShL) and diameter (ShD), fasting plasma glucose level (Gluc), and body temperature (T(b)). Other suggestive QTL were identified for these parameters and for plasma IGF-I and nonesterified fatty acid levels. QTL controlling adiposity and Gluc were colocalized on GGA3 and GGA5 and QTL for BW, ShL and ShD, adiposity, and T(b) on GGA4. Multitrait analyses revealed two QTL controlling Gluc and AFP on GGA5 and Gluc and T(b) on GGA26. Significant effects of the reciprocal cross were observed on BW, ShD, BMW, and Gluc, which may result from mtDNA and/or maternal effects. Most QTL regions for Gluc and adiposity harbor genes for which alleles have been associated with increased susceptibility to diabetes and/or obesity in humans. Identification of genes responsible for these metabolic QTL will increase our understanding of the constitutive "hyperglycemia" found in chickens. Furthermore, a comparative approach could provide new information on the genetic causes of diabetes and obesity in humans.

  15. Infection control implications of heterogeneous resistance mechanisms in carbapenem-resistant Enterobacteriaceae (CRE).

    PubMed

    Goodman, K E; Simner, P J; Tamma, P D; Milstone, A M

    2016-01-01

    The Centers for Disease Control and Prevention (CDC) defines carbapenem-resistant Enterobacteriaceae (CRE) based upon a phenotypic demonstration of carbapenem resistance. However, considerable heterogeneity exists within this definitional umbrella. CRE may mechanistically differ by whether they do or do not produce carbapenemases. Moreover, patients can acquire CRE through multiple pathways: endogenously through antibiotic selective pressure on intestinal microbiota, exogenously through horizontal transmission or through a combination of these factors. Some evidence suggests that non-carbapenemase-producing CRE may be more frequently acquired by antibiotic exposure and carbapenemase-producing CRE via horizontal transmission, but definitive data are lacking. This review examines types of CRE resistance mechanisms, antibiotic exposure and horizontal transmission pathways of CRE acquisition, and the implications of these heterogeneities to the development of evidence-based CRE healthcare epidemiology policies. In our Expert Commentary & Five-Year View, we outline specific nosocomial CRE knowledge gaps and potential methodological approaches for their resolution.

  16. Impurity control and corrosion resistance of magnesium-aluminum alloy

    SciTech Connect

    Liu, M.; Song, GuangLing

    2013-01-01

    The corrosion resistance of magnesium alloys is very sensitive to the contents of impurity elements such as iron. In this study, a series of diecast AXJ530 magnesium alloy samples were prepared with additions of Mn and Fe. Through a comprehensive phase diagram calculation and corrosion evaluation, the mechanisms for the tolerance limit of Fe in magnesium alloy are discussed. This adds a new dimension to control the alloying impurity in terms of alloying composition design and casting conditions.

  17. Quantitative trait loci for CD4:CD8 lymphocyte ratio are associated with risk of type 1 diabetes and HIV-1 immune control.

    PubMed

    Ferreira, Manuel A R; Mangino, Massimo; Brumme, Chanson J; Zhao, Zhen Zhen; Medland, Sarah E; Wright, Margaret J; Nyholt, Dale R; Gordon, Scott; Campbell, Megan; McEvoy, Brian P; Henders, Anjali; Evans, David M; Lanchbury, Jerry S; Pereyra, Florencia; Walker, Bruce D; Haas, David W; Soranzo, Nicole; Spector, Tim D; de Bakker, Paul I W; Frazer, Ian H; Montgomery, Grant W; Martin, Nicholas G

    2010-01-01

    Abnormal expansion or depletion of particular lymphocyte subsets is associated with clinical manifestations such as HIV progression to AIDS and autoimmune disease. We sought to identify genetic predictors of lymphocyte levels and reasoned that these may play a role in immune-related diseases. We tested 2.3 million variants for association with five lymphocyte subsets, measured in 2538 individuals from the general population, including CD4+ T cells, CD8+ T cells, CD56+ natural killer (NK) cells, and the derived measure CD4:CD8 ratio. We identified two regions of strong association. The first was located in the major histocompatibility complex (MHC), with multiple SNPs strongly associated with CD4:CD8 ratio (rs2524054, p = 2.1 x 10(-28)). The second region was centered within a cluster of genes from the Schlafen family and was associated with NK cell levels (rs1838149, p = 6.1 x 10(-14)). The MHC association with CD4:CD8 replicated convincingly (p = 1.4 x 10(-9)) in an independent panel of 988 individuals. Conditional analyses indicate that there are two major independent quantitative trait loci (QTL) in the MHC region that regulate CD4:CD8 ratio: one is located in the class I cluster and influences CD8 levels, whereas the second is located in the class II cluster and regulates CD4 levels. Jointly, both QTL explained 8% of the variance in CD4:CD8 ratio. The class I variants are also strongly associated with durable host control of HIV, and class II variants are associated with type-1 diabetes, suggesting that genetic variation at the MHC may predispose one to immune-related diseases partly through disregulation of T cell homeostasis.

  18. Identification of Quantitative Trait Loci Controlling Root and Shoot Traits Associated with Drought Tolerance in a Lentil (Lens culinaris Medik.) Recombinant Inbred Line Population

    PubMed Central

    Idrissi, Omar; Udupa, Sripada M.; De Keyser, Ellen; McGee, Rebecca J.; Coyne, Clarice J.; Saha, Gopesh C.; Muehlbauer, Fred J.; Van Damme, Patrick; De Riek, Jan

    2016-01-01

    Drought is one of the major abiotic stresses limiting lentil productivity in rainfed production systems. Specific rooting patterns can be associated with drought avoidance mechanisms that can be used in lentil breeding programs. In all, 252 co-dominant and dominant markers were used for Quantitative Trait Loci (QTL) analysis on 132 lentil recombinant inbred lines based on greenhouse experiments for root and shoot traits during two seasons under progressive drought-stressed conditions. Eighteen QTLs controlling a total of 14 root and shoot traits were identified. A QTL-hotspot genomic region related to a number of root and shoot characteristics associated with drought tolerance such as dry root biomass, root surface area, lateral root number, dry shoot biomass and shoot length was identified. Interestingly, a QTL (QRSratioIX-2.30) related to root-shoot ratio, an important trait for drought avoidance, explaining the highest phenotypic variance of 27.6 and 28.9% for the two consecutive seasons, respectively, was detected. This QTL was closed to the co-dominant SNP marker TP6337 and also flanked by the two SNP TP518 and TP1280. An important QTL (QLRNIII-98.64) related to lateral root number was found close to TP3371 and flanked by TP5093 and TP6072 SNP markers. Also, a QTL (QSRLIV-61.63) associated with specific root length was identified close to TP1873 and flanked by F7XEM6b SRAP marker and TP1035 SNP marker. These two QTLs were detected in both seasons. Our results could be used for marker-assisted selection in lentil breeding programs targeting root and shoot characteristics conferring drought avoidance as an efficient alternative to slow and labor-intensive conventional breeding methods. PMID:27602034

  19. Identification of quantitative trait loci controlling sugar content based on an enriched genetic linkage map of sugarcane (Saccharum spp. hybrids) cultivar ‘LCP 85-384’

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Since sugarcane cultivars possess >100 chromosomes (2n = 100-130) and are genetically complex polyploid and aneuploids, identification of quantitative trait loci (QTLs) associated with sugar content is considered the best option to improve sugar content through molecular breeding. Also, improving su...

  20. Identification of quantitative trait loci controlling sucrose content based on an enriched genetic linkage map of sugarcane (saccharum spp. hybrids) cultivar ‘LCP 85-384’

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sucrose content is the most important trait in sugarcane breeding. Since sugarcane cultivars possess 100 to 130 chromosomes and are genetically complex polyploids and aneuploids, identification of quantitative trait loci (QTLs) associated with sucrose content is considered the best option to improve...

  1. Genes controlling vaccine responses and disease resistance to respiratory viral pathogens in cattle

    PubMed Central

    Glass, Elizabeth J.; Baxter, Rebecca; Leach, Richard J.; Jann, Oliver C.

    2012-01-01

    Farm animals remain at risk of endemic, exotic and newly emerging viruses. Vaccination is often promoted as the best possible solution, and yet for many pathogens, either there are no appropriate vaccines or those that are available are far from ideal. A complementary approach to disease control may be to identify genes and chromosomal regions that underlie genetic variation in disease resistance and response to vaccination. However, identification of the causal polymorphisms is not straightforward as it generally requires large numbers of animals with linked phenotypes and genotypes. Investigation of genes underlying complex traits such as resistance or response to viral pathogens requires several genetic approaches including candidate genes deduced from knowledge about the cellular pathways leading to protection or pathology, or unbiased whole genome scans using markers spread across the genome. Evidence for host genetic variation exists for a number of viral diseases in cattle including bovine respiratory disease and anecdotally, foot and mouth disease virus (FMDV). We immunised and vaccinated a cattle cross herd with a 40-mer peptide derived from FMDV and a vaccine against bovine respiratory syncytial virus (BRSV). Genetic variation has been quantified. A candidate gene approach has grouped high and low antibody and T cell responders by common motifs in the peptide binding pockets of the bovine major histocompatibility complex (BoLA) DRB3 gene. This suggests that vaccines with a minimal number of epitopes that are recognised by most cattle could be designed. Whole genome scans using microsatellite and single nucleotide polymorphism (SNP) markers has revealed many novel quantitative trait loci (QTL) and SNP markers controlling both humoral and cell-mediated immunity, some of which are in genes of known immunological relevance including the toll-like receptors (TLRs). The sequencing, assembly and annotation of livestock genomes and is continuing apace. In

  2. Resistance controllability and variability improvement in a TaO{sub x}-based resistive memory for multilevel storage application

    SciTech Connect

    Prakash, A. E-mail: amit.knp02@gmail.com Song, J.; Hwang, H. E-mail: amit.knp02@gmail.com; Deleruyelle, D.; Bocquet, M.

    2015-06-08

    In order to obtain reliable multilevel cell (MLC) characteristics, resistance controllability between the different resistance levels is required especially in resistive random access memory (RRAM), which is prone to resistance variability mainly due to its intrinsic random nature of defect generation and filament formation. In this study, we have thoroughly investigated the multilevel resistance variability in a TaO{sub x}-based nanoscale (<30 nm) RRAM operated in MLC mode. It is found that the resistance variability not only depends on the conductive filament size but also is a strong function of oxygen vacancy concentration in it. Based on the gained insights through experimental observations and simulation, it is suggested that forming thinner but denser conductive filament may greatly improve the temporal resistance variability even at low operation current despite the inherent stochastic nature of resistance switching process.

  3. Molecular mapping of stem rust resistance loci effective against the Ug99 race group of the stem rust pathogen and identification of SNP marker linked to stem rust resistance gene Sr28

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Wheat landrace PI 177906 has field resistance to the Ug99 race group and seedling resistance to stem rust caused by Puccinia graminis f. sp. tritici (Pgt) races TTKSK, TTKST, and BCCBC. Two populations were developed from a cross between PI 177906 and LMPG-6, 138 double haploid (DH) lines and 140 re...

  4. Genetic loci conditioning adult plant resistance to the Ug99 race group and seedling resistance to races TRTTF and TTTTF of the stem rust pathogen in wheat landrace CItr 15026

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Wheat landrace CItr 15026 previously showed adult plant resistance (APR) to the Ug99 stem rust race group in Kenya and seedling resistance to Puccinia graminis f. sp tritici (Pgt) races QFCSC, TTTTF, and TRTTF. CItr 15026 was crossed to susceptible accessions LMPG-6 and Red Bobs, and 180 DH lines an...

  5. Mapping QTL controlling southern leaf blight resistance by combined analysis of three related recombinant inbred line populations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Quantitative trait loci (QTL) for resistance to southern leaf blight (SLB) disease caused by Cochliobolus heterostrophus race O were identified in three maize recombinant inbred populations assed in two environments. Each population derived from a cross between a temperate and a tropical maize li...

  6. Malaria distribution, prevalence, drug resistance and control in Indonesia.

    PubMed

    Elyazar, Iqbal R F; Hay, Simon I; Baird, J Kevin

    2011-01-01

    Approximately 230 million people live in Indonesia. The country is also home to over 20 anopheline vectors of malaria which transmit all four of the species of Plasmodium that routinely infect humans. A complex mosaic of risk of infection across this 5000-km-long archipelago of thousands of islands and distinctive habitats seriously challenges efforts to control malaria. Social, economic and political dimensions contribute to these complexities. This chapter examines malaria and its control in Indonesia, from the earliest efforts by malariologists of the colonial Netherlands East Indies, through the Global Malaria Eradication Campaign of the 1950s, the tumult following the coup d'état of 1965, the global resurgence of malaria through the 1980s and 1990s and finally through to the decentralization of government authority following the fall of the authoritarian Soeharto regime in 1998. We detail important methods of control and their impact in the context of the political systems that supported them. We examine prospects for malaria control in contemporary decentralized and democratized Indonesia with multidrug-resistant malaria and greatly diminished capacities for integrated malaria control management programs.

  7. Malaria Distribution, Prevalence, Drug Resistance and Control in Indonesia

    PubMed Central

    Elyazar, Iqbal R.F.; Hay, Simon I.; Baird, J. Kevin

    2011-01-01

    Approximately 230 million people live in Indonesia. The country is also home to over 20 anopheline vectors of malaria which transmit all four of the species of Plasmodium that routinely infect humans. A complex mosaic of risk of infection across this 5000-km-long archipelago of thousands of islands and distinctive habitats seriously challenges efforts to control malaria. Social, economic and political dimensions contribute to these complexities. This chapter examines malaria and its control in Indonesia, from the earliest efforts by malariologists of the colonial Netherlands East Indies, through the Global Malaria Eradication Campaign of the 1950s, the tumult following the coup d’état of 1965, the global resurgence of malaria through the 1980s and 1990s and finally through to the decentralization of government authority following the fall of the authoritarian Soeharto regime in 1998. We detail important methods of control and their impact in the context of the political systems that supported them. We examine prospects for malaria control in contemporary decentralized and democratized Indonesia with multidrug-resistant malaria and greatly diminished capacities for integrated malaria control management programs. PMID:21295677

  8. Altered baroreflex control of forearm vascular resistance during simulated microgravity

    NASA Technical Reports Server (NTRS)

    Convertino, V. A.; Doerr, D. F.; Vernikos, J.

    1994-01-01

    Reflex peripheral vasoconstriction induced by activation of cardiopulmonary baroreceptors in response to reduced central venous pressure (CVP) is a basic mechanism for elevating systemic vascular resistance and defending arterial blood pressure during orthostatically-induced reductions in cardiac filling and output. The sensitivity of the cardiopulmonary baroreflex response [defined as the slope of the relationship between changes in forearm vascular resistance (FVR) and CVP] and the resultant vasoconstriction are closely and inversely associated with the amount of circulating blood volume. Thus, a high-gain FVR response will be elicited by a hypovolemic state. Exposure to microgravity during spaceflight results in reduced plasma volume. It is therefore reasonable to expect that the FVR response to cardiopulmonary baroreceptor unloading would be accentuated following adaptation to microgravity. Such data could provide better insight about the physiological mechanisms underlying alterations in blood pressure control following spaceflight. We therefore exposed eleven men to 6 degrees head-down bedrest for 7 days and measured specific hemodynamic responses to low levels of the lower body negative pressure to determine if there are alterations in cardiopulmonary baroreceptor stimulus-FVR reflex response relationship during prolonged exposure to an analog of microgravity.

  9. Radiation-induced mutation at minisatellite loci

    SciTech Connect

    Dubrova, Y.E. |; Nesterov, V.N.; Krouchinsky, N.G.

    1997-10-01

    We are studying the radiation-induced increase of mutation rate in minisatellite loci in mice and humans. Minisatellite mutations were scored by multilocus DNA fingerprint analysis in the progeny of {gamma}-irradiated and non-irradiated mice. The frequency of mutation in offspring of irradiated males was 1.7 higher that in the control group. Germline mutation at human minisatellite loci was studied among children born in heavily polluted areas of the Mogilev district of Belarus after the Chernobyl accident and in a control population. The frequency of mutation assayed both by DNA fingerprinting and by eight single locus probes was found to be two times higher in the exposed families than in the control group. Furthermore, mutation rate was correlated with the parental radiation dose for chronic exposure {sup 137}Cs, consistent with radiation-induction of germline mutation. The potential use of minisatellites in monitoring germline mutation in humans will be discussed.

  10. Remote Symbolic Computation of Loci

    ERIC Educational Resources Information Center

    Abanades, Miguel A.; Escribano, Jesus; Botana, Francisco

    2010-01-01

    This article presents a web-based tool designed to compute certified equations and graphs of geometric loci specified using standard Dynamic Geometry Systems (DGS). Complementing the graphing abilities of the considered DGS, the equations of the loci produced by the application are remotely computed using symbolic algebraic techniques from the…

  11. Methicillin-resistant Staphylococcus aureus. A continuing infection control challenge.

    PubMed

    Molinari, John A

    2012-04-01

    The ability of MRSA and other staphylococci to colonize, persist, and adapt to multiple environmental and tissue conditions has allowed for these bacteria to be virtually ubiquitous in their distribution. The effectiveness of commonly used antibiotics, such as penicillin, has continued to decline against infections caused by MRSA and increasingly resistant strains. The challenge for both dental and medical health professionals is to routinely apply proven, evidence-based infection control precautions. As mentioned earlier in this discussion, when compliance with effective aseptic technique practices improves, the patients and environments. Ensure that reusable equipment is not used for the care of another patient until it has been appropriately cleaned and reprocessed and that single-use items are properly discarded. Clean and disinfect clinical contact surfaces that are not barrier-protected by using an environmental protection agency-registered hospital disinfectant with a low- (ie, HIV and HBV label claims) to intermediate-level (ie, tuberculocidal claim) activity after each patient. When the surface is visibly contaminated with blood, an intermediate-incidence of detectable infections can be reduced. Microorganisms will continue to evolve and adapt in order to survive and thrive, sometimes at the expense of susceptible human hosts. The struggle is to constantly remain aware of impending infectious threats which may challenge current precautions, and maintain and improve the quality of infection control to minimize the potential for disease.

  12. Resistance to aryloxyphenoxypropionate herbicides in Amazon sprangletop: Confirmation, control, and molecular basis of resistance.

    PubMed

    Tehranchian, Parsa; Norsworthy, Jason K; Korres, Nicholas E; McElroy, Scott; Chen, Shu; Scott, Robert C

    2016-10-01

    Amazon sprangletop is problematic weed of rice in the midsouthern USA. Two biotypes of this species from rice fields approximately 100km apart in Louisiana were unaffected when sprayed with the labeled field rate of cyhalofop-butyl (314g ai ha(-1)) in 2008. Dose response studies were conducted to confirm the level of resistance to cyhalofop-butyl over a range of doses. Cross-resistance to acetyl-CoA carboxylase (ACCase)-inhibiting herbicides from two different chemical families and multiple herbicide resistance to other mechanisms of action were evaluated. Sequencing using the Illumina Hiseq platform and ACCase gene sequencing revealed two different amino acid substitutions, Trp2027-to-Cys in the first resistant biotype and Asp2078-to-Gly in the second resistant biotype, within the CT domain of the ACCase gene. Two known amino acid substitutions confirmed resistance to cyhalofop-butyl and fenoxaprop-P-ethyl in resistant Amazon sprangletop biotypes. Asp2078-to-Gly amino acid substitution that was detected in one of the resistant biotypes did not result in cross-resistance to clethodim, an ACCase-inhibiting cyclohexandione herbicide which has endowed clethodim resistance in other weed species. Based on this research, both resistant Amazon sprangletop biotypes have evolved target-site resistance to the APP herbicides; yet, alternative herbicides are still active on these plants.

  13. Inspiratory resistive loading improves cycling capacity: a placebo controlled trial

    PubMed Central

    Gething, A; Williams, M; Davies, B

    2004-01-01

    Background: Respiratory muscle training has been shown to improve both its strength and endurance. The effect of these improvements on whole-body exercise performance remains controversial. Objective: To assess the effect of a 10 week inspiratory resistive loading (IRL) intervention on respiratory muscle performance and whole-body exercise endurance. Methods: Fifteen apparently healthy subjects (10 men, 5 women) were randomly allocated to one of three groups. One group underwent IRL set at 80% of maximum inspiratory pressure with ever decreasing work/rest ratios until task failure, for three days a week for 10 weeks (IRL group). A second placebo group performed the same training procedure but with a minimal resistance (PLA group). IRL and placebo training were performed at rest. The remaining five control subjects performed no IRL during the 10 week study period (CON group). Cycling endurance capacity at 75% V·O2peak was measured before and after the intervention. Results: After the 10 week IRL intervention, respiratory muscle strength (maximum inspiratory pressure) and endurance (sum of sustained maximum inspiratory pressure) had significantly improved (by 34% and 38% respectively). An increase in diaphragm thickness was also observed. These improvements translated into a 36% increase in cycling time to exhaustion at 75% V·O2peak. During cycling trials, heart rate, ventilation, and rating of perceived exertion were attenuated in the IRL group. No changes were observed for the PLA or CON group either in the time to exhaustion or cardiorespiratory response to the same intensity of exercise. Conclusion: Ten weeks of IRL attenuated the heart rate, ventilatory, and perceptual response to constant workload exercise, and improved the cycling time to exhaustion. Familiarisation was not a factor and the placebo effect was minimal. PMID:15562168

  14. Genotyping-by-sequencing-based genome-wide association studies on Verticillium wilt resistance in autotetraploid alfalfa (Medicago sativa L.).

    PubMed

    Yu, Long-Xi; Zheng, Ping; Zhang, Tiejun; Rodringuez, Jonas; Main, Dorrie

    2017-02-01

    Verticillium wilt (VW) is a fungal disease that causes severe yield losses in alfalfa. The most effective method to control the disease is through the development and use of resistant varieties. The identification of marker loci linked to VW resistance can facilitate breeding for disease-resistant alfalfa. In the present investigation, we applied an integrated framework of genome-wide association with genotyping-by-sequencing (GBS) to identify VW resistance loci in a panel of elite alfalfa breeding lines. Phenotyping was performed by manual inoculation of the pathogen to healthy seedlings, and scoring for disease resistance was carried out according to the standard test of the North America Alfalfa Improvement Conference (NAAIC). Marker-trait association by linkage disequilibrium identified 10 single nucleotide polymorphism (SNP) markers significantly associated with VW resistance. Alignment of the SNP marker sequences to the M. truncatula genome revealed multiple quantitative trait loci (QTLs). Three, two, one and five markers were located on chromosomes 5, 6, 7 and 8, respectively. Resistance loci found on chromosomes 7 and 8 in the present study co-localized with the QTLs reported previously. A pairwise alignment (blastn) using the flanking sequences of the resistance loci against the M. truncatula genome identified potential candidate genes with putative disease resistance function. With further investigation, these markers may be implemented into breeding programmes using marker-assisted selection, ultimately leading to improved VW resistance in alfalfa.

  15. Genotyping-by-sequencing based genome-wide association studies on Verticillium wilt resistance in heterozygous autotetraploid alfalfa (Medicago sativa L.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Verticillium wilt (VW) is a fungal disease which causes severe yield loss in alfalfa. The most effective method to control the disease is through the development and use of resistant varieties. Identification of gene loci linked to VW resistance will facilitate breeding for the disease-resistant al...

  16. Antibiotic combinations for controlling colistin-resistant Enterobacter cloacae.

    PubMed

    Lima, Thais Bergamin; Silva, Osmar Nascimento; de Almeida, Keyla Caroline; Ribeiro, Suzana Meira; Motta, Dielle de Oliveira; Maria-Neto, Simone; Lara, Michelle Brizolla; Filho, Carlos Roberto Souza; Ombredane, Alicia Simalie; de Faria Junior, Celio; Parachin, Nadia Skorupa; Magalhães, Beatriz Simas; Franco, Octávio Luiz

    2017-02-01

    Enterobacter cloacae is a Gram-negative bacterium associated with high morbidity and mortality in intensive care patients due to its resistance to multiple antibiotics. Currently, therapy against multi-resistant bacteria consists of using colistin, in spite of its toxic effects at higher concentrations. In this context, colistin-resistant E. cloacae strains were challenged with lower levels of colistin combined with other antibiotics to reduce colistin-associated side effects. Colistin-resistant E. cloacae (ATCC 49141) strains were generated by serial propagation in subinhibitory colistin concentrations. After this, three colistin-resistant and three nonresistant replicates were isolated. The identity of all the strains was confirmed by MALDI-TOF MS, VITEK 2 and MicroScan analysis. Furthermore, cross-resistance to other antibiotics was checked by disk diffusion and automated systems. The synergistic effects of the combined use of colistin and chloramphenicol were observed via the broth microdilution checkerboard method. First, data here reported showed that all strains presented intrinsic resistance to penicillin, cephalosporin (except fourth generation), monobactam, and some associations of penicillin and β-lactamase inhibitors. Moreover, a chloramphenicol and colistin combination was capable of inhibiting the induced colistin-resistant strains as well as two colistin-resistant clinical strains. Furthermore, no cytotoxic effect was observed by using such concentrations. In summary, the data reported here showed for the first time the possible therapeutic use of colistin-chloramphenicol for infections caused by colistin-resistant E. cloacae.

  17. Genetic architecture of cyst nematode resistance revealed by genome-wide association study in soybean

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bi-parental mapping populations have been commonly utilized to identify and characterize quantitative trait loci (QTL) controlling resistance to soybean cyst nematode (SCN, Heterodera glycines Ichinohe). Although this approach successfully mapped a large number of SCN resistance QTL, it captures onl...

  18. Genome-wide nested association mapping of quantitative resistance to northern leaf blight in maize

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Quantitative resistance to plant pathogens, controlled by multiple loci of small effect, is important for food production, food security, and food safety but is poorly understood. To gain insights into the genetic architecture of quantitative resistance in maize, we evaluated a 5,000 inbred-line ne...

  19. Pyrethroid resistance in African anopheline mosquitoes: what are the implications for malaria control?

    PubMed

    Ranson, Hilary; N'guessan, Raphael; Lines, Jonathan; Moiroux, Nicolas; Nkuni, Zinga; Corbel, Vincent

    2011-02-01

    The use of pyrethroid insecticides in malaria vector control has increased dramatically in the past decade through the scale up of insecticide treated net distribution programmes and indoor residual spraying campaigns. Inevitably, the major malaria vectors have developed resistance to these insecticides and the resistance alleles are spreading at an exceptionally rapid rate throughout Africa. Although substantial progress has been made on understanding the causes of pyrethroid resistance, remarkably few studies have focused on the epidemiological impact of resistance on current malaria control activities. As we move into the malaria eradication era, it is vital that the implications of insecticide resistance are understood and strategies to mitigate these effects are implemented.

  20. Diminished Baroreflex Control of Forearm Vascular Resistance Following Training

    NASA Technical Reports Server (NTRS)

    Mack, G. W.; Thompson, C. A.; Doerr, D. F.; Nadel, E. R.; Convertino, V. A.

    1991-01-01

    The stimulus-response characteristics of cardiopulmonary baroreflex control of forearm vascular resistance (FVR units in mm Hg x min x I00 ml/ml) were studied in 14 volunteers before and after 10 wk of endurance training. We assessed the relationship betaleen reflex stimulus (changes in central venous pressure, CVP) and response (FVR) during unloading of cardiopulmonary baroreceptors with lower body negative pressure (LBNP, 0 to - 2O mm Hg). Changes in CVP during LBNP were estimated from pressure changes in a large peripheral vein in the dependent arm of the subject in the right lateral decubitus position. Maximal oxygen uptake (VO(sub 2max)) and total blood volume increased with endurance training from 37.8 +/- 1.4 ml/min x kg and 63.6 +/- 2.1 ml/kg to 45.3 +/- 1.4 ml/ min x kg and 69.3 +/- 2.8 ml/kg respectively (P less than 0.05). Reflex forearm vasoconstriction occurred in response to a reduction in estimated CVP, and the absolute change in FVR per unit of CVP was reduced from -5.96 +/- 0.79 to -4.06 +/- 0.52 units x mm/ Hg (P less than 0.05) following exercise training but was unchanged from -6.10 to 0.57 to -6.22 +/- 0.94 units x mm/ Hg for the time control group (N = 7). Resting values for FVR were similar before and after exercise training; however, resting estimated CVP was elevated from 9.5 +/- 0.5 mm x Hg before training to 11.3 +/- 0.6 mm x Hg after training. The reduction in sensitivity of the cardiopulmonary baroreflex control of FVR was linearly related to the increase in blood volume (r = 0.65, P less than 0.05). suggesting that diminished cardiopulmonary baroreflex control of FVR in physically fit individuals is related, in part, to a training-induced blood volume expansion.

  1. Control of linear modes in cylindrical resistive magnetohydrodynamics with a resistive wall, plasma rotation, and complex gain

    SciTech Connect

    Brennan, D. P.; Finn, J. M.

    2014-10-15

    Feedback stabilization of magnetohydrodynamic (MHD) modes in a tokamak is studied in a cylindrical model with a resistive wall, plasma resistivity, viscosity, and toroidal rotation. The control is based on a linear combination of the normal and tangential components of the magnetic field just inside the resistive wall. The feedback includes complex gain, for both the normal and for the tangential components, and it is known that the imaginary part of the feedback for the former is equivalent to plasma rotation [J. M. Finn and L. Chacon, Phys. Plasmas 11, 1866 (2004)]. The work includes (1) analysis with a reduced resistive MHD model for a tokamak with finite β and with stepfunction current density and pressure profiles, and (2) computations with a full compressible visco-resistive MHD model with smooth decreasing profiles of current density and pressure. The equilibria are stable for β = 0 and the marginal stability values β{sub rp,rw} < β{sub rp,iw} < β{sub ip,rw} < β{sub ip,iw} (resistive plasma, resistive wall; resistive plasma, ideal wall; ideal plasma, resistive wall; and ideal plasma, ideal wall) are computed for both models. The main results are: (a) imaginary gain with normal sensors or plasma rotation stabilizes below β{sub rp,iw} because rotation suppresses the diffusion of flux from the plasma out through the wall and, more surprisingly, (b) rotation or imaginary gain with normal sensors destabilizes above β{sub rp,iw} because it prevents the feedback flux from entering the plasma through the resistive wall to form a virtual wall. A method of using complex gain G{sub i} to optimize in the presence of rotation in this regime with β > β{sub rp,iw} is presented. The effect of imaginary gain with tangential sensors is more complicated but essentially destabilizes above and below β{sub rp,iw}.

  2. Controlling herbicide resistant annual bluegrass (Poa annua L.) phenotypes with methiozolin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Methiozolin is an isoxazoline herbicide being investigated for selective POST annual bluegrass control in managed turfgrass. Research was conducted to evaluate methiozolin efficacy for controlling two annual bluegrass phenotypes with target site resistance to photosystem II (PSII) or enolpyruvylshik...

  3. Light-controlled resistive switching memory of multiferroic BiMnO3 nanowire arrays.

    PubMed

    Sun, Bai; Li, Chang Ming

    2015-03-14

    A multiferroic BiMnO3 nanowire array was prepared using a hydrothermal process and its resistive switching memory behaviors were further investigated. The prominent ferroelectricity can be well controlled by white-light illumination, thus offering an excellent light-controlled resistive switching memory device using a Ag/BiMnO3/Ti structure at room temperature.

  4. [Chloroquine resistance and malaria control in Ivory Coast].

    PubMed

    Henry, M C; Koné, M; Guillet, P; Mouchet, J

    1998-01-01

    We present here data from the Ivory Coast on the susceptibility of Plasmodium falciparum to chloroquine, obtained since the first chloroquine-resistant strains were discovered in 1987. Susceptibility was assessed using the WHO 7-day field test. Almost all the tests were carried out in the capital, Adidjan, and in the southern forest zone. The frequency of chloroquine resistance was below 30% in most cases, the actual frequency differing between regions. The frequency of R3 chloroquine-resistant P. falciparum was very low. Such resistant parasites were found only on an oil-palm plantation and in the south west of the country, probably due to the free medical care available at both locations. In general, access to health care is limited. Fevers attributed to malaria are generally treated at home using plants or incomplete courses of chloroquine. Our data suggest that R3 chloroquine-resistant P. falciparum strains are selected by repeated high doses of chloroquine, rather than by low doses. Thus, symptomatic treatment of uncomplicated malaria and treatment at home with the "correct" medication may be more effective than systematic medication, for limiting the level of chloroquine resistance in the parasite. Pyrethroid-resistant Anopheles gambiae s.l. is present in West Africa and this may reduce the short-term effectiveness of impregnated mosquito nets. In the absence of R3 chloroquine-resistant P. falciparum, self-medication at home may be a practical and realistic way to treat malaria. However, more knowledge about the effectiveness of anti-malaria drugs, their use in various social, cultural and economic environments and the geographical distribution of insecticide-resistant vectors is required before effective strategies can be designed. However, it would certainly be of value to consistently check the quality of anti-malaria drugs and to try to improve the effectiveness of self-medication at home.

  5. Precise estimation of genomic regions controlling lodging resistance using a set of reciprocal chromosome segment substitution lines in rice

    PubMed Central

    Ookawa, Taiichiro; Aoba, Ryo; Yamamoto, Toshio; Ueda, Tadamasa; Takai, Toshiyuki; Fukuoka, Shuichi; Ando, Tsuyu; Adachi, Shunsuke; Matsuoka, Makoto; Ebitani, Takeshi; Kato, Yoichiro; Mulsanti, Indria Wahyu; Kishii, Masahiro; Reynolds, Matthew; Piñera, Francisco; Kotake, Toshihisa; Kawasaki, Shinji; Motobayashi, Takashi; Hirasawa, Tadashi

    2016-01-01

    Severe lodging has occurred in many improved rice varieties after the recent strong typhoons in East and Southeast Asian countries. The indica variety Takanari possesses strong culm characteristics due to its large section modulus, which indicates culm thickness, whereas the japonica variety Koshihikari is subject to substantial bending stress due to its thick cortical fibre tissue. To detect quantitative trait loci (QTLs) for lodging resistance and to eliminate the effects of genetic background, we used reciprocal chromosome segment substitution lines (CSSLs) derived from a cross between Koshihikari and Takanari. The oppositional effects of QTLs for section modulus were confirmed in both genetic backgrounds on chromosomes 1, 5 and 6, suggesting that these QTLs are not affected by the genetic background and are controlled independently by a single factor. The candidate region of a QTL for section modulus included SD1. The section modulus of NIL-sd1 was lower than that of Koshihikari, whereas the section modulus of NIL-SD1 was higher than that of Takanari. This result indicated that those regions regulate the culm thickness. The reciprocal effects of the QTLs for cortical fibre tissue thickness were confirmed in both genetic backgrounds on chromosome 9 using CSSLs. PMID:27465821

  6. Genetic control of autoantibody expression in autoimmune myasthenia gravis: role of the self-antigen and of HLA-linked loci.

    PubMed

    Giraud, M; Beaurain, G; Eymard, B; Tranchant, C; Gajdos, P; Garchon, H-J

    2004-08-01

    Autoantibodies against the muscle acetylcholine receptor (AChR) play an essential role in the pathophysiology of autoimmune myasthenia gravis (MG). Their serum titers, however, vary considerably among patients. Our aim was to investigate whether their variation might be explained by genetic factors. Using different methods, we have obtained strong evidence for a three-locus association influencing autoantibody titers in MG patients with thymus hyperplasia or with a normal thymus. Two of the loci, one encoding the AChR alpha-subunit, the other encoding the alpha-chain of the class II antigen-presentation molecule, HLA-DQ, demonstrated interaction to determine high autoantibody titers. The third locus was associated with the 8.1 ancestral HLA haplotype. It exerted an additive effect and it is postulated to have a nonantigen specific immunoregulatory function. Our study demonstrates for the first time that polymorphism of an autoantigen gene may quantitatively modify the immune response against it. Altogether, the data lend support to a three-gene model to explain autoantibody expression in a subset of MG patients.

  7. Nonequivalent Loci and the distribution of mutant effects.

    PubMed Central

    Welch, J J; Waxman, D

    2002-01-01

    It has been observed repeatedly that the distribution of new mutations of a quantitative trait has a kurtosis (a statistical measure of the distribution's shape) that is systematically larger than that of a normal distribution. Here we suggest that rather than being a property of individual loci that control the trait, the enhanced kurtosis is highly likely to be an emergent property that arises directly from the loci being mutationally nonequivalent. We present a method of incorporating nonequivalent loci into quantitative genetic modeling and give an approximate relation between the kurtosis of the mutant distribution and the degree of mutational nonequivalence of loci. We go on to ask whether incorporating the experimentally observed kurtosis through nonequivalent loci, rather than at locus level, affects any biologically important conclusions of quantitative genetic modeling. Concentrating on the maintenance of quantitative genetic variation by mutation-selection balance, we conclude that typically nonequivalent loci yield a genetic variance that is of order 10% smaller than that obtained from the previous approaches. For large populations, when the kurtosis is large, the genetic variance may be <50% of the result of equivalent loci, with Gaussian distributions of mutant effects. PMID:12072483

  8. Controlled ferrite content improves weldability of corrosion-resistant steel

    NASA Technical Reports Server (NTRS)

    Malin, C. O.

    1967-01-01

    Corrosion-resistant steel that adds restrictions on chemical composition to ensure sufficient ferrite content decreases the tendency of CRES to develop cracks during welding. The equations restricting composition are based on the Schaeffler constitution diagram.

  9. Identification and characterisation of functional expressed sequence tags-derived simple sequence repeat (eSSR) markers for genetic linkage mapping of Schistosoma mansoni juvenile resistance and susceptibility loci in Biomphalaria glabrata

    PubMed Central

    Ittiprasert, Wannaporn; Miller, André; Su, Xin-zhuan; Mu, Jianbing; Bhusudsawang, Ganlayarat; Ukoskit, Kitipat; Knight, Matty

    2013-01-01

    Biomphalaria glabrata susceptibility to Schistosoma mansoni has a strong genetic component, offering the possibility for investigating host–parasite interactions at the molecular level, perhaps leading to novel control approaches. The identification, mapping and molecular characterisation of genes that influence the outcome of parasitic infection in the intermediate snail host is, therefore, seen as fundamental to the control of schistosomiasis. To better understand the evolutionary processes driving disease resistance/susceptibility phenotypes, we previously identified polymorphic random amplification of polymorphic DNA and genomic simple sequence repeats from B. glabrata. In the present study we identified and characterised polymorphic expressed simple sequence repeats markers (Bg-eSSR) from existing B. glabrata expressed sequence tags. Using these markers, and with previously identified genomic simple sequence repeats, genetic linkage mapping for parasite refractory and susceptibility phenotypes, the first known for B. glabrata, was initiated. Data mining of 54,309 expressed sequence tag, produced 660 expressed simple sequence repeats of which dinucleotide motifs (TA)n were the most common (37.88%), followed by trinucleotide (29.55%), mononucleotide (18.64%) and tetranucleotide (10.15%). Penta- and hexanucleotide motifs represented <3% of the Bg-eSSRs identified. While the majority (71%) of Bg-eSSRs were monomorphic between resistant and susceptible snails, several were, however, useful for the construction of a genetic linkage map based on their inheritance in segregating F2 progeny snails derived from crossing juvenile BS-90 and NMRI snails. Polymorphic Bg-eSSRs assorted into six linkage groups at a logarithm of odds score of 3. Interestingly, the heritability of four markers (Prim1_910, Prim1_771, Prim6_1024 and Prim7_823) with juvenile snail resistance were, by t-test, significant (P < 0.05) while an allelic marker, Prim24_524, showed linkage with the

  10. Effect of resistance training on strength, postural control, and gait velocity among older adults.

    PubMed

    Topp, R; Mikesky, A; Dayhoff, N E; Holt, W

    1996-11-01

    The purpose of this study was to examine the effects of a 14-week resistance training program on the ankle strength, training intensity, postural control, and gait velocity of older adults. Forty-two older adults (mean age = 72), 21 in the resistance and control groups, completed the 14-week project. The resistance training group participated in 14 weeks of resistance training three times per week using elastic bands (Theraband) for resistance. Isokinetic ankle strength, training intensity, postural stability, and gait velocity were measured prior to and following the 14-week intervention. Following the training, the resistance group exhibited improved ankle dorsiflexion, training resistances, and gait velocity, but showed no change in plantar flexion or postural control. The control group also exhibited improvements in dorsiflexion, but these gains were approximately one-half of the gains observed in the resistance training group. Finally, when adjusted for baseline differences, subjects in the resistance training group demonstrated no changes in the dependent measures over the control group.

  11. Quantitative trait loci that control plasma lipid levels in an F2 intercross between C57BL/6J and DDD.Cg-A(y) inbred mouse strains.

    PubMed

    Suto, Jun-ichi

    2012-04-01

    The objectives of this study were to characterize plasma lipid phenotypes and dissect the genetic basis of plasma lipid levels in an obese DDD.Cg-A(y) mouse strain. Plasma triglyceride (TG) levels were significantly higher in the DDD.Cg-A(y) strain than in the B6.Cg-A(y) strain. In contrast, plasma total-cholesterol (CHO) levels did not substantially differ between the two strains. As a rule, the A(y) allele significantly increased TG levels, but did not increase CHO levels. Quantitative trait locus (QTL) analyses for plasma TG and CHO levels were performed in two types of F(2) female mice [F(2)A(y) (F(2) mice carrying the A(y) allele) and F(2) non- A(y) mice (F(2) mice without the A(y) allele)] produced by crossing C57BL/6J females and DDD.Cg-A(y) males. Single QTL scan identified one significant QTL for TG levels on chromosome 1, and two significant QTLs for CHO levels on chromosomes 1 and 8. When the marker nearest to the QTL on chromosome 1 was used as covariates, four additional significant QTLs for CHO levels were identified on chromosomes 5, 6, and 17 (two loci). In contrast, consideration of the agouti locus genotype as covariates did not detect additional QTLs. DDD.Cg-A(y) showed a low CHO level, although it had Apoa2(b), which was a CHO-increasing allele at the Apoa2 locus. This may have been partly due to the presence of multiple QTLs, which were associated with decreased CHO levels, on chromosome 8.

  12. Quantitative trait loci that control body weight and obesity in an F2 intercross between C57BL/6J and DDD.Cg-Ay mice.

    PubMed

    Suto, Jun-ichi

    2011-07-01

    I have developed a congenic mouse strain for the A(y) allele at the agouti locus in an inbred DDD/Sgn strain, DDD.Cg-A(y). DDD.Cg-A(y) females are extremely obese and significantly heavier than B6.Cg-A(y) females. The objectives of this study were to determine the genetic basis of obesity in DDD.Cg-A(y) mice, and to determine whether or not their high body weight was due to the presence of DDD background-specific modifiers. I performed quantitative trait locus (QTL) analyses for body weight and body mass index in two types of F(2) mice [F2 A(y) (F(2) mice carrying the A(y) allele) and F(2) non-A(y) (F2 mice without the A(y) allele)] produced by crossing C57BL/6J females and DDD.Cg-A(y) males. The results of the QTL analysis of F(2) A(y) mice were very similar to those obtained for F(2) non-A(y) mice. It was unlikely that the high body weight of DDD.Cg-A(y) mice was due to the presence of specific modifiers. When both F(2) datasets were merged and analyzed, four significant body weight QTLs were identified on chromosomes 6, 9, and 17 (2 loci) and four significant obesity QTLs were identified on chromosomes 1, 6, 9, and 17. Although the presence of DDD background-specific modifiers was not confirmed, a multifactorial basis of obesity in DDD.Cg-A(y) females was thus revealed.

  13. Mapping Quantitative Trait Loci Controlling High Iron and Zinc Content in Self and Open Pollinated Grains of Pearl Millet [Pennisetum glaucum (L.) R. Br.

    PubMed Central

    Kumar, Sushil; Hash, Charles T.; Thirunavukkarasu, Nepolean; Singh, Govind; Rajaram, Vengaldas; Rathore, Abhishek; Senapathy, Senthilvel; Mahendrakar, Mahesh D.; Yadav, Rattan S.; Srivastava, Rakesh K.

    2016-01-01

    Pearl millet is a multipurpose grain/fodder crop of the semi-arid tropics, feeding many of the world’s poorest and most undernourished people. Genetic variation among adapted pearl millet inbreds and hybrids suggests it will be possible to improve grain micronutrient concentrations by selective breeding. Using 305 loci, a linkage map was constructed to map QTLs for grain iron [Fe] and zinc [Zn] using replicated samples of 106 pearl millet RILs (F6) derived from ICMB 841-P3 × 863B-P2. The grains of the RIL population were evaluated for Fe and Zn content using atomic absorption spectrophotometer. Grain mineral concentrations ranged from 28.4 to 124.0 ppm for Fe and 28.7 to 119.8 ppm for Zn. Similarly, grain Fe and Zn in open pollinated seeds ranged between 22.4–77.4 and 21.9–73.7 ppm, respectively. Mapping with 305 (96 SSRs; 208 DArT) markers detected seven linkage groups covering 1749 cM (Haldane) with an average intermarker distance of 5.73 cM. On the basis of two environment phenotypic data, two co-localized QTLs for Fe and Zn content on linkage group (LG) 3 were identified by composite interval mapping (CIM). Fe QTL explained 19% phenotypic variation, whereas the Zn QTL explained 36% phenotypic variation. Likewise for open pollinated seeds, the QTL analysis led to the identification of two QTLs for grain Fe content on LG3 and 5, and two QTLs for grain Zn content on LG3 and 7. The total phenotypic variance for Fe and Zn QTLs in open pollinated seeds was 16 and 42%, respectively. Analysis of QTL × QTL and QTL × QTL × environment interactions indicated no major epistasis. PMID:27933068

  14. Antifungal Resistance and New Strategies to Control Fungal Infections

    PubMed Central

    Vandeputte, Patrick; Ferrari, Selene; Coste, Alix T.

    2012-01-01

    Despite improvement of antifungal therapies over the last 30 years, the phenomenon of antifungal resistance is still of major concern in clinical practice. In the last 10 years the molecular mechanisms underlying this phenomenon were extensively unraveled. In this paper, after a brief overview of currently available antifungals, molecular mechanisms of antifungal resistance will be detailed. It appears that major mechanisms of resistance are essential due to the deregulation of antifungal resistance effector genes. This deregulation is a consequence of point mutations occurring in transcriptional regulators of these effector genes. Resistance can also follow the emergence of point mutations directly in the genes coding antifungal targets. In addition we further describe new strategies currently undertaken to discover alternative therapy targets and antifungals. Identification of new antifungals is essentially achieved by the screening of natural or synthetic chemical compound collections. Discovery of new putative antifungal targets is performed through genome-wide approaches for a better understanding of the human pathogenic fungi biology. PMID:22187560

  15. Multigenic Control of Pod Shattering Resistance in Chinese Rapeseed Germplasm Revealed by Genome-Wide Association and Linkage Analyses

    PubMed Central

    Liu, Jia; Wang, Jun; Wang, Hui; Wang, Wenxiang; Zhou, Rijin; Mei, Desheng; Cheng, Hongtao; Yang, Juan; Raman, Harsh; Hu, Qiong

    2016-01-01

    The majority of rapeseed cultivars shatter seeds upon maturity especially under hot-dry and windy conditions, reducing yield and gross margin return to growers. Here, we identified quantitative trait loci (QTL) for resistance to pod shatter in an unstructured diverse panel of 143 rapeseed accessions, and two structured populations derived from bi-parental doubled haploid (DH) and inter-mated (IF2) crosses derived from R1 (resistant to pod shattering) and R2 (prone to pod shattering) accessions. Genome-wide association analysis identified six significant QTL for resistance to pod shatter located on chromosomes A01, A06, A07, A09, C02, and C05. Two of the QTL, qSRI.A09 delimited with the SNP marker Bn-A09-p30171993 (A09) and qSRI.A06 delimited with the SNP marker Bn-A06-p115948 (A06) could be repeatedly detected across environments in a diversity panel, DH and IF2 populations, suggesting that at least two loci on chromosomes A06 and A09 were the main contributors to pod shatter resistance in Chinese germplasm. Significant SNP markers identified in this study especially those that appeared repeatedly across environments provide a cost-effective and an efficient method for introgression and pyramiding of favorable alleles for pod shatter resistance via marker-assisted selection in rapeseed improvement programs. PMID:27493651

  16. Control of fluoroquinolone resistance through successful regulation, Australia.

    PubMed

    Cheng, Allen C; Turnidge, John; Collignon, Peter; Looke, David; Barton, Mary; Gottlieb, Thomas

    2012-09-01

    Fluoroquinolone antimicrobial drugs are highly bioavailable, broad-spectrum agents with activity against gram-negative pathogens, especially those resistant to other classes of antimicrobial drugs. Australia has restricted the use of quinolones in humans through its national pharmaceutical subsidy scheme; and, through regulation, has not permitted the use of quinolones in food-producing animals. As a consequence, resistance to fluoroquinolones in the community has been slow to emerge and has remained at low levels in key pathogens, such as Escherichia coli. In contrast to policies in most other countries, this policy has successfully preserved the utility of this class of antimicrobial drugs for treatment of most infections.

  17. Hydrogel control of xylem hydraulic resistance in plants.

    PubMed

    Zwieniecki, M A; Melcher, P J; Michele Holbrook, N M

    2001-02-09

    Increasing concentrations of ions flowing through the xylem of plants produce rapid, substantial, and reversible decreases in hydraulic resistance. Changes in hydraulic resistance in response to solution ion concentration, pH, and nonpolar solvents are consistent with this process being mediated by hydrogels. The effect is localized to intervessel bordered pits, suggesting that microchannels in the pit membranes are altered by the swelling and deswelling of pectins, which are known hydrogels. The existence of an ion-mediated response breaks the long-held paradigm of the xylem as a system of inert pipes and suggests a mechanism by which plants may regulate their internal flow regime.

  18. A review of control methods and resistance mechanisms in stored-product insects.

    PubMed

    Boyer, S; Zhang, H; Lempérière, G

    2012-04-01

    This review describes the major stored-product insect species and their resistance to insecticides. The economic importance of the control of those pests is highlighted with a loss of more than one billion US dollars per year worldwide. A detailed common description of species resistance throughout the world has been developed, and we observed 28 recurrent studied species involved in resistance cases disseminated on the five continents. The different mechanisms, including behavioral resistance, were studied particularly on Oryzaephilus surinamensis. The role of detoxifying enzymes and studies on the genetic resistance, involving the kdr mutation mechanisms and the transmission of the genes of resistance, are also described. A chapter clarifying definitions on cross and multiple resistance is enclosed.

  19. Footing, Resistance and Control: Negotiating a Traffic Citation

    ERIC Educational Resources Information Center

    Smith, Wendy B.

    2010-01-01

    The purpose of this article is to demonstrate the micro-interactional processes by which powerful and powerless identities are locally reconstructed. The article specifically examines the interplay between consent and resistance to law-breaking identities. Data consist of transcripts of 45 incidents in which highway patrol officers issue traffic…

  20. Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis.

    PubMed

    Hobbs, Brian D; de Jong, Kim; Lamontagne, Maxime; Bossé, Yohan; Shrine, Nick; Artigas, María Soler; Wain, Louise V; Hall, Ian P; Jackson, Victoria E; Wyss, Annah B; London, Stephanie J; North, Kari E; Franceschini, Nora; Strachan, David P; Beaty, Terri H; Hokanson, John E; Crapo, James D; Castaldi, Peter J; Chase, Robert P; Bartz, Traci M; Heckbert, Susan R; Psaty, Bruce M; Gharib, Sina A; Zanen, Pieter; Lammers, Jan W; Oudkerk, Matthijs; Groen, H J; Locantore, Nicholas; Tal-Singer, Ruth; Rennard, Stephen I; Vestbo, Jørgen; Timens, Wim; Paré, Peter D; Latourelle, Jeanne C; Dupuis, Josée; O'Connor, George T; Wilk, Jemma B; Kim, Woo Jin; Lee, Mi Kyeong; Oh, Yeon-Mok; Vonk, Judith M; de Koning, Harry J; Leng, Shuguang; Belinsky, Steven A; Tesfaigzi, Yohannes; Manichaikul, Ani; Wang, Xin-Qun; Rich, Stephen S; Barr, R Graham; Sparrow, David; Litonjua, Augusto A; Bakke, Per; Gulsvik, Amund; Lahousse, Lies; Brusselle, Guy G; Stricker, Bruno H; Uitterlinden, André G; Ampleford, Elizabeth J; Bleecker, Eugene R; Woodruff, Prescott G; Meyers, Deborah A; Qiao, Dandi; Lomas, David A; Yim, Jae-Joon; Kim, Deog Kyeom; Hawrylkiewicz, Iwona; Sliwinski, Pawel; Hardin, Megan; Fingerlin, Tasha E; Schwartz, David A; Postma, Dirkje S; MacNee, William; Tobin, Martin D; Silverman, Edwin K; Boezen, H Marike; Cho, Michael H

    2017-03-01

    Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. We performed a genetic association study in 15,256 cases and 47,936 controls, with replication of select top results (P < 5 × 10(-6)) in 9,498 cases and 9,748 controls. In the combined meta-analysis, we identified 22 loci associated at genome-wide significance, including 13 new associations with COPD. Nine of these 13 loci have been associated with lung function in general population samples, while 4 (EEFSEC, DSP, MTCL1, and SFTPD) are new. We noted two loci shared with pulmonary fibrosis (FAM13A and DSP) but that had opposite risk alleles for COPD. None of our loci overlapped with genome-wide associations for asthma, although one locus has been implicated in joint susceptibility to asthma and obesity. We also identified genetic correlation between COPD and asthma. Our findings highlight new loci associated with COPD, demonstrate the importance of specific loci associated with lung function to COPD, and identify potential regions of genetic overlap between COPD and other respiratory diseases.

  1. Weed control and yield comparisons of glyphosate- and glufosinate-resistant corn grown in rotation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A 6-yr field study was conducted from 2004 to 2009 at Stoneville, MS to examine the effects of rotating glyphosate-resistant and glufosinate-resistant corn (Zea mays L.) under reduced tillage conditions on weed control, soil weed seedbank, and yield. The four rotation systems were glyphosate-resista...

  2. Multiple resistance of horseweed to glyphosate and paraquat and its control with paraquat and metribuzin combinations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Greenhouse and field studies were conducted in 2007 and 2008 to investigate possible multiple-resistance of horseweed to paraquat and glyphosate, and to evaluate the effect of the addition of metribuzin to paraquat on control of paraquat-resistant horseweed. Results indicated that the GR50 (herbicid...

  3. Temperature control during regeneration of activated carbon fiber cloth with resistance-feedback.

    PubMed

    Johnsen, David L; Rood, Mark J

    2012-10-16

    Electrothermal swing adsorption (ESA) of organic compounds from gas streams with activated carbon fiber cloth (ACFC) reduces emissions to the atmosphere and recovers feedstock for reuse. Local temperature measurement (e.g., with a thermocouple) is typically used to monitor/control adsorbent regeneration cycles. Remote electrical resistance measurement is evaluated here as an alternative to local temperature measurement. ACFC resistance that was modeled based on its physical properties was within 10.5% of the measured resistance values during electrothermal heating. Resistance control was developed based on this measured relationship and used to control temperature to within 2.3% of regeneration set-point temperatures. Isobutane-laden adsorbent was then heated with resistance control. After 2 min of heating, the temperature of the adsorbent with isobutane was 13% less than the adsorbent without isobutane. This difference decreased to 2.1% after 9 min of heating, showing desorption of isobutane. An ACFC cartridge was also heated to 175 °C for 900 cycles with its resistance and adsorption capacity values remaining within 3% and 2%, respectively. This new method to control regeneration power application based on rapid sensing of the adsorbent's resistance removes the need for direct-contact temperature sensors providing a simple, cost-efficient, and long-term regeneration technique for ESA systems.

  4. Mapping quantitative trait loci of resistance to Tomato spotted wilt virus and leaf spots in a recombinant inbred line population of peanut (Arachis hypogae L.) from SunOleic 97R and NC94022

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Peanut is vulnerable to a range of diseases, such as Tomato spotted wilt virus (TSWV) and leaf spots. The most sustainable and economical solution for managing peanut diseases is development of resistance cultivars. The new breeding line NC94022, high resistance to TSWV and moderate resistance to le...

  5. Tailoring resistive switching in Pt/SrTiO3 junctions by stoichiometry control

    PubMed Central

    Mikheev, Evgeny; Hwang, Jinwoo; Kajdos, Adam P.; Hauser, Adam J.; Stemmer, Susanne

    2015-01-01

    Resistive switching effects in transition metal oxide-based devices offer new opportunities for information storage and computing technologies. Although it is known that resistive switching is a defect-driven phenomenon, the precise mechanisms are still poorly understood owing to the difficulty of systematically controlling specific point defects. As a result, obtaining reliable and reproducible devices remains a major challenge for this technology. Here, we demonstrate control of resistive switching based on intentional manipulation of native point defects. Oxide molecular beam epitaxy is used to systematically investigate the effect of Ti/Sr stoichiometry on resistive switching in high-quality Pt/SrTiO3 junctions. We demonstrate resistive switching with improved state retention through the introduction of Ti- and Sr-excess into the near-interface region. More broadly, the results demonstrate the utility of high quality metal/oxide interfaces and explicit control over structural defects to improve control, uniformity, and reproducibility of resistive switching processes. Unintentional interfacial contamination layers, which are present if Schottky contacts are processed at low temperature, can easily dominate the resistive switching characteristics and complicate the interpretation if nonstoichiometry is also present. PMID:26056783

  6. Control-system techniques for improved departure/spin resistance for fighter aircraft

    NASA Technical Reports Server (NTRS)

    Nguyen, L. T.; Gilbert, W. P.; Ogburn, M. E.

    1980-01-01

    Some fundamental information on control system effects on controllability of highly maneuverable aircraft at high angles of attack are summarized as well as techniques for enhancing fighter aircraft departure/spin resistance using control system design. The discussion includes: (1) a brief review of pertinent high angle of attack phenomena including aerodynamics, inertia coupling, and kinematic coupling; (2) effects of conventional stability augmentation systems at high angles of attack; (3) high angle of attack control system concepts designed to enhance departure/spin resistance; and (4) the outlook for applications of these concepts to future fighters, particularly those designs which incorporate relaxed static stability.

  7. Manipulated transformation of filamentary and homogeneous resistive switching on ZnO thin film memristor with controllable multistate.

    PubMed

    Huang, Chi-Hsin; Huang, Jian-Shiou; Lai, Chih-Chung; Huang, Hsin-Wei; Lin, Su-Jien; Chueh, Yu-Lun

    2013-07-10

    A bias polarity-manipulated transformation from filamentary to homogeneous resistive switching was demonstrated on a Pt/ZnO thin film/Pt device. Two types of switching behaviors, exhibiting different resistive switching characteristics and memory performances were investigated in detail. The detailed transformation mechanisms are systematically proposed. By controlling different compliance currents and RESET-stop voltages, controllable multistate resistances in low resistance states and a high resistance states in the ZnO thin film metal-insulator-metal structure under the homogeneous resistive switching were demonstrated. We believe that findings would open up opportunities to explore the resistive switching mechanisms and performance memristor with multistate storage.

  8. Insulin resistance in obesity and its molecular control.

    PubMed

    Noguchi, T; Tanaka, T

    1995-09-01

    The Wistar fatty rat is a model of obese non-insulin-dependent diabetes mellitus. Males, but not females, develop hyperglycemia, glucouria and polyuria within 8 weeks of age. The regulation of gene expression by insulin has been shown to be differentially impaired in the liver of the fatty rats. The genes resistant to insulin include glucokinase gene and phosphoenolpyruvate carboxykinase gene. In contrast, L-type pyruvate kinase gene responds to insulin normally, raising the possibility that the signaling pathway from the insulin receptor to the insulin-resistant genes, but not to the insulin-sensitive genes, is defective at a point beyond the receptor kinase in the fatty rats. On the other hand, female fatty rats develop hyperglycemia only when they are given sucrose for several weeks. This treatment causes a decrease in gucokinase while enzymes involved in gluconeogenesis are increased. Chronic feeding of sucrose also leads to hypertriglycemia and visceral fat accumulation, which is more frequently associated with abnormalities in glucose and lipid metabolisms. Fructose is believed to be the responsible component of sucrose for these effects. Hypertriglyceridemic effect of fructose is mainly due to an increase in hepatic production of VLDL. Most enzymes related to lipogenesis in the liver are induced by dietary fructose even in diabetes. L-type pyruvate kinase is one of such enzymes. Cis-acting element named PKL-III in the 5'-flanking region of this gene is shown to be responsive to dietary fructose as well as to dietary glucose. Thus, identification and characterization of a protein bound to this element could help in the further understanding of the molecular mechanism of the fructose actions.

  9. Risk of Classic Kaposi Sarcoma With Combinations of Killer Immunoglobulin-Like Receptor and Human Leukocyte Antigen Loci: A Population-Based Case-control Study

    PubMed Central

    Goedert, James J.; Martin, Maureen P.; Vitale, Francesco; Lauria, Carmela; Whitby, Denise; Qi, Ying; Gao, Xiaojiang; Carrington, Mary

    2016-01-01

    Background. Kaposi sarcoma (KS) is a complication of KS-associated herpesvirus (KSHV) infection. Other oncogenic viral infections and malignancies are associated with certain HLA alleles and their natural killer (NK) cell immunoglobulin-like receptor (KIR) ligands. We tested whether HLA-KIR influences the risk of KSHV infection or KS. Methods. In population-based case-control studies, we compared HLA class I and KIR gene frequencies in 250 classic (non-AIDS) KS cases, 280 KSHV-seropositive controls, and 576 KSHV-seronegative controls composing discovery and validation cohorts. Logistic regression was used to calculate sex- and age-adjusted odds ratios (ORs) and 95% confidence intervals. Results. In both the discovery and validation cohorts, KS was associated with HLA-A*11:01 (adjusted OR for the combined cohorts, 0.4; P = .002) and HLA-C*07:01 (adjusted OR, 1.6; P = .002). Consistent associations across cohorts were also observed with activating KIR3DS1 plus HLA-B Bw4-80I and homozygosity for HLA-C group 1. With KIR3DS1 plus HLA-B Bw4-80I, the KSHV seroprevalence was 40% lower (adjusted OR for the combined cohorts, 0.6; P = .01), but the KS risk was 2-fold higher (adjusted OR, 2.1; P = .002). Similarly, the KSHV seroprevalence was 40% lower (adjusted OR, 0.6; P = .01) but the KS risk 80% higher with HLA-C group 1 homozygosity (adjusted OR, 1.8; P = .005). Conclusions. KIR-mediated NK cell activation may decrease then risk of KSHV infection but enhance KSHV dissemination and progression to KS if infection occurs. PMID:26268853

  10. Identification of Klebsiella capsule synthesis loci from whole genome data

    PubMed Central

    Wick, Ryan R.; Gorrie, Claire; Jenney, Adam; Follador, Rainer; Thomson, Nicholas R.

    2016-01-01

    Klebsiella pneumoniae is a growing cause of healthcare-associated infections for which multi-drug resistance is a concern. Its polysaccharide capsule is a major virulence determinant and epidemiological marker. However, little is known about capsule epidemiology since serological typing is not widely accessible and many isolates are serologically non-typeable. Molecular typing techniques provide useful insights, but existing methods fail to take full advantage of the information in whole genome sequences. We investigated the diversity of the capsule synthesis loci (K-loci) among 2503 K. pneumoniae genomes. We incorporated analyses of full-length K-locus nucleotide sequences and also clustered protein-encoding sequences to identify, annotate and compare K-locus structures. We propose a standardized nomenclature for K-loci and present a curated reference database. A total of 134 distinct K-loci were identified, including 31 novel types. Comparative analyses indicated 508 unique protein-encoding gene clusters that appear to reassort via homologous recombination. Extensive intra- and inter-locus nucleotide diversity was detected among the wzi and wzc genes, indicating that current molecular typing schemes based on these genes are inadequate. As a solution, we introduce Kaptive, a novel software tool that automates the process of identifying K-loci based on full locus information extracted from whole genome sequences (https://github.com/katholt/Kaptive). This work highlights the extensive diversity of Klebsiella K-loci and the proteins that they encode. The nomenclature, reference database and novel typing method presented here will become essential resources for genomic surveillance and epidemiological investigations of this pathogen. PMID:28348840

  11. Characterisation of a novel panel of polymorphic microsatellite loci for the liver fluke, Fasciola hepatica, using a next generation sequencing approach.

    PubMed

    Cwiklinski, Krystyna; Allen, Katherine; LaCourse, James; Williams, Diana J; Paterson, Steve; Hodgkinson, Jane E

    2015-06-01

    The liver fluke, Fasciola hepatica is an economically important pathogen of sheep and cattle and has been described by the WHO as a re-emerging zoonosis. Control is heavily reliant on the use of drugs, particularly triclabendazole and as a result resistance has now emerged. The population structure of F. hepatica is not well known, yet it can impact on host-parasite interactions and parasite control with drugs, particularly regarding the spread of triclabendazole resistance. We have identified 2448 potential microsatellites from 83 Mb of F. hepatica genome sequence using msatfinder. Thirty-five loci were developed and optimised for microsatellite PCR, resulting in a panel of 15 polymorphic loci, with a range of three to 15 alleles. This panel was validated on genomic DNA from 46 adult F. hepatica; 38 liver flukes sourced from a Northwest abattoir, UK and 8 liver flukes from an established isolate (Shrewsbury; Ridgeway Research). Evidence for null alleles was found at four loci (Fh_1, Fh_8, Fh_13 and Fh_14), which showed markedly higher levels of homozygosity than the remaining 11 loci. Of the 38 liver flukes isolated from cattle livers (n=10) at the abattoir, 37 genotypes were identified. Using a multiplex approach all 15 loci could be amplified from several life cycle stages that typically yield low amounts of DNA, including metacercariae, the infective life cycle stage present on pasture, highlighting the utility of this multiplex microsatellite panel. This study reports the largest panel of microsatellite markers available to date for population studies of F. hepatica and the first multiplex panel of microsatellite markers that can be used for several life cycle stages.

  12. Mapping quantitative trait loci for expression abundance.

    PubMed

    Jia, Zhenyu; Xu, Shizhong

    2007-05-01

    Mendelian loci that control the expression levels of transcripts are called expression quantitative trait loci (eQTL). When mapping eQTL, we often deal with thousands of expression traits simultaneously, which complicates the statistical model and data analysis. Two simple approaches may be taken in eQTL analysis: (1) individual transcript analysis in which a single expression trait is mapped at a time and the entire eQTL mapping involves separate analysis of thousands of traits and (2) individual marker analysis where differentially expressed transcripts are detected on the basis of their association with the segregation pattern of an individual marker and the entire analysis requires scanning markers of the entire genome. Neither approach is optimal because data are not analyzed jointly. We develop a Bayesian clustering method that analyzes all expressed transcripts and markers jointly in a single model. A transcript may be simultaneously associated with multiple markers. Additionally, a marker may simultaneously alter the expression of multiple transcripts. This is a model-based method that combines a Gaussian mixture of expression data with segregation of multiple linked marker loci. Parameter estimation for each variable is obtained via the posterior mean drawn from a Markov chain Monte Carlo sample. The method allows a regular quantitative trait to be included as an expression trait and subject to the same clustering assignment. If an expression trait links to a locus where a quantitative trait also links, the expressed transcript is considered to be associated with the quantitative trait. The method is applied to a microarray experiment with 60 F(2) mice measured for 25 different obesity-related quantitative traits. In the experiment, approximately 40,000 transcripts and 145 codominant markers are investigated for their associations. A program written in SAS/IML is available from the authors on request.

  13. [A mathematical model for the chemical control of Aedes aegypti (Diptera: Culicidae) having acquired chemical resistance].

    PubMed

    Restrepo-Alape, Leonardo D; Toro-Zapata, Hernán D; Muñoz-Loaiza, Aníbal

    2010-12-01

    Dengue fever is a common vector-borne disease in tropical and subtropical areas. It is transmitted to humans by the bite of an infected female Aedes mosquito. Since no vaccines are currently available which can protect against infection, disease control relies on controlling the mosquito population. This work was aimed at modelling such mosquito's population dynamics regarding chemical control of the adult population and its acquired resistance to chemicals. The model was analysed by using classical dynamic system theory techniques and mosquito growth threshold was determined as this establishes when a particular population may prosper in the environment or when it is likely to disappear. A suitable chemical control strategy was developed from such threshold. Simulations were made in control and non-control scenarios; this determined the degree of control application effectiveness against different levels of acquired resistance.

  14. Intracellular pH and the Control of Multidrug Resistance

    NASA Astrophysics Data System (ADS)

    Simon, Sanford; Roy, Deborshi; Schindler, Melvin

    1994-02-01

    Many anticancer drugs are classified as either weak bases or molecules whose binding to cellular structures is pH dependent. Accumulation of these drugs within tumor cells should be affected by transmembrane pH gradients. Indeed, development of multidrug resistance (MDR) in tumor cells has been correlated with an alkaline shift of cytosolic pH. To examine the role of pH in drug partitioning, the distribution of two drugs, doxorubicin and daunomycin, was monitored in fibroblasts and myeloma cells. In both cell types the drugs rapidly accumulated within the cells. The highest concentrations were measured in the most acidic compartments-e.g., lysosomes. Modifying the cellular pH in drug-sensitive cells to mimic reported shifts in MDR caused an immediate change in the cellular drug concentration. Drug accumulation was enhanced by acidic shifts and reversed by alkaline shifts. All of these effects were rapid and reversible. These results demonstrate that the alkaline shift observed in MDR is sufficient to prevent the accumulation of chemotherapeutic drugs independent of active drug efflux.

  15. Intracellular pH and the control of multidrug resistance.

    PubMed Central

    Simon, S; Roy, D; Schindler, M

    1994-01-01

    Many anticancer drugs are classified as either weak bases or molecules whose binding to cellular structures is pH dependent. Accumulation of these drugs within tumor cells should be affected by transmembrane pH gradients. Indeed, development of multidrug resistance (MDR) in tumor cells has been correlated with an alkaline shift of cytosolic pH. To examine the role of pH in drug partitioning, the distribution of two drugs, doxorubicin and daunomycin, was monitored in fibroblasts and myeloma cells. In both cell types the drugs rapidly accumulated within the cells. The highest concentrations were measured in the most acidic compartments--e.g., lysosomes. Modifying the cellular pH in drug-sensitive cells to mimic reported shifts in MDR caused an immediate change in the cellular drug concentration. Drug accumulation was enhanced by acidic shifts and reversed by alkaline shifts. All of these effects were rapid and reversible. These results demonstrate that the alkaline shift observed in MDR is sufficient to prevent the accumulation of chemotherapeutic drugs independent of active drug efflux. Images PMID:8302842

  16. Antibiotic Adjuvants: Diverse Strategies for Controlling Drug-Resistant Pathogens

    PubMed Central

    Gill, Erin E; Franco, Octavio L; Hancock, Robert E W

    2015-01-01

    The growing number of bacterial pathogens that are resistant to numerous antibiotics is a cause for concern around the globe. There have been no new broad-spectrum antibiotics developed in the last 40 years, and the drugs we have currently are quickly becoming ineffective. In this article, we explore a range of therapeutic strategies that could be employed in conjunction with antibiotics and may help to prolong the life span of these life-saving drugs. Discussed topics include antiresistance drugs, which are administered to potentiate the effects of current antimicrobials in bacteria where they are no longer (or never were) effective; antivirulence drugs, which are directed against bacterial virulence factors; host-directed therapies, which modulate the host's immune system to facilitate infection clearance; and alternative treatments, which include such therapies as oral rehydration for diarrhea, phage therapy, and probiotics. All of these avenues show promise for the treatment of bacterial infections and should be further investigated to explore their full potential in the face of a postantibiotic era. PMID:25393203

  17. Alzheimer disease (AD) specific transcription, DNA methylation and splicing in twenty AD associated loci.

    PubMed

    Humphries, Crystal; Kohli, Martin A; Whitehead, Patrice; Mash, Deborah C; Pericak-Vance, Margaret A; Gilbert, John

    2015-07-01

    Genome-wide association studies have identified twenty loci associated with late-onset Alzheimer disease (LOAD). We examined each of the twenty loci, specifically the ±50kb region surrounding the most strongly associated variant, for changes in gene(s) transcription specific to LOAD. Post-mortem human brain samples were examined for expression, methylation, and splicing differences. LOAD specific differences were detected by comparing LOAD to normal and "disease" controls. Eight loci, prominently ABCA7, contain LOAD specific differences. Significant changes in the CELF1 and ZCWPW1 loci occurred in genes not located nearest the associated variant, suggesting that these genes should be investigated further as LOAD candidates.

  18. Are Herbicide Resistant Crops The Answer To Controlling Cascuta?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Herbicide tolerant crop technology could provide new management strategies for the control of parasitic plants. Three herbicide-tolerant oilseed rape genotypes were used to examine the response of attached C. campestris to glyphosate, imazamox and glufosinate. C. campestris was allowed to establi...

  19. ELECTRICAL RESISTIVITY VARIATIONS ASSOCIATED WITH CONTROLLED GASOLINE SPILLS

    EPA Science Inventory

    A number of geophysical surveys were conducted over two controlled releases of about 100 gallons each of gasoline. In order to clearly identify the responses associated with the gasoline plume, measurements were made before, during and after the injection. The two experiments we...

  20. Genetic hitchhiking and resistance evolution to transgenic Bt toxins: insights from the African stalk borer Busseola fusca (Noctuidae).

    PubMed

    Campagne, P; Capdevielle-Dulac, C; Pasquet, R; Cornell, S J; Kruger, M; Silvain, J-F; LeRü, B; Van den Berg, J

    2017-04-01

    Since transgenic crops expressing Bacillus thuringiensis (Bt) toxins were first released, resistance evolution leading to failure in control of pests populations has been observed in a number of species. Field resistance of the moth Busseola fusca was acknowledged 8 years after Bt maize was introduced in South Africa. Since then, field resistance of this corn borer has been observed at several locations, raising questions about the nature, distribution and dynamics of the resistance trait. Using genetic markers, our study identified four outlier loci clearly associated with resistance. In addition, genetic structure at neutral loci reflected extensive gene flow among populations. A realistically parameterised model suggests that resistance could travel in space at speed of several kilometres a year. Markers at outlier loci delineated a geographic region associated with resistance spread. This was an area of approximately 100 km radius, including the location where resistance was first reported. Controlled crosses corroborated these findings and showed significant differences of progeny survival on Bt plants depending on the origin of the resistant parent. Last, our study suggests diverse resistance mutations, which would explain the widespread occurrence of resistant larvae in Bt fields across the main area of maize production in South Africa.

  1. Angles of multivariable root loci

    NASA Technical Reports Server (NTRS)

    Thompson, P. M.; Stein, G.; Laub, A. J.

    1982-01-01

    A generalized eigenvalue problem is demonstrated to be useful for computing the multivariable root locus, particularly when obtaining the arrival angles to finite transmission zeros. The multivariable root loci are found for a linear, time-invariant output feedback problem. The problem is then employed to compute a closed-loop eigenstructure. The method of computing angles on the root locus is demonstrated, and the method is extended to a multivariable optimal root locus.

  2. The impact of insecticide-resistance on control of vectors and vector-borne diseases

    PubMed Central

    Busvine, J. R.; Pal, R.

    1969-01-01

    A questionnaire inquiring into the nature of schemes for the insecticidal control of disease vectors, the development of resistance in these vectors, and the effect of any such resistance on their control and on the extent of disease was sent to more than 100 health authorities throughout the world. The replies to the questionnaire are summarized in this paper. Until recently, the use of insecticides in public health has been largely based on three organochlorine compounds—DDT, HCH and dieldrin. However, in some countries resistance to these has now severely affected control both of many insect species and of the diseases they transmit (e.g., malaria, yellow fever, filariasis, typhus, plague). Certain other public health problems (onchocerciasis, Chagas' disease, trypanosomiasis, leishmaniasis) have not so far been greatly affected by resistance, but it is difficult to be sure of the continued reliability of the organochlorines. Research in the past 5 years, much of it sponsored by WHO, has shown the value of various organophosphorus and carbamate insecticides as replacements for the organochlorines, although resistance to them, too, can occur. Attention must therefore be focused on all facets of the use of these newer compounds and particular scrutiny made of possible instances of resistance to them. PMID:5307234

  3. Multiple Insecticide Resistance: An Impediment to Insecticide-Based Malaria Vector Control Program

    PubMed Central

    Steurbaut, Walter; Spanoghe, Pieter; Van Bortel, Wim; Denis, Leen; Tessema, Dejene A.; Getachew, Yehenew; Coosemans, Marc; Duchateau, Luc; Speybroeck, Niko

    2011-01-01

    Background Indoor Residual Spraying (IRS), insecticide-treated nets (ITNs) and long-lasting insecticidal nets (LLINs) are key components in malaria prevention and control strategy. However, the development of resistance by mosquitoes to insecticides recommended for IRS and/or ITNs/LLINs would affect insecticide-based malaria vector control. We assessed the susceptibility levels of Anopheles arabiensis to insecticides used in malaria control, characterized basic mechanisms underlying resistance, and evaluated the role of public health use of insecticides in resistance selection. Methodology/Principal findings Susceptibility status of An. arabiensis was assessed using WHO bioassay tests to DDT, permethrin, deltamethrin, malathion and propoxur in Ethiopia from August to September 2009. Mosquito specimens were screened for knockdown resistance (kdr) and insensitive acetylcholinesterase (ace-1R) mutations using AS-PCR and PCR-RFLP, respectively. DDT residues level in soil from human dwellings and the surrounding environment were determined by Gas Chromatography with Electron Capture Detector. An. arabiensis was resistant to DDT, permethrin, deltamethrin and malathion, but susceptible to propoxur. The West African kdr allele was found in 280 specimens out of 284 with a frequency ranged from 95% to 100%. Ace-1R mutation was not detected in all specimens scored for the allele. Moreover, DDT residues were found in soil samples from human dwellings but not in the surrounding environment. Conclusion The observed multiple-resistance coupled with the occurrence of high kdr frequency in populations of An. arabiensis could profoundly affect the malaria vector control programme in Ethiopia. This needs an urgent call for implementing rational resistance management strategies and integrated vector control intervention. PMID:21264325

  4. Two major quantitative trait loci controlling the number of seminal roots in maize co-map with the root developmental genes rtcs and rum1.

    PubMed

    Salvi, Silvio; Giuliani, Silvia; Ricciolini, Claudia; Carraro, Nicola; Maccaferri, Marco; Presterl, Thomas; Ouzunova, Milena; Tuberosa, Roberto

    2016-02-01

    The genetic dissection of root architecture and functions allows for a more effective and informed design of novel root ideotypes and paves the way to evaluate their effects on crop resilience to a number of abiotic stresses. In maize, limited attention has been devoted to the genetic analysis of root architecture diversity at the early stage. The difference in embryonic (including seminal and primary) root architecture between the maize reference line B73 (which mostly develops three seminal roots) and the landrace Gaspé Flint (with virtually no seminal roots) was genetically dissected using a collection of introgression lines grown in paper rolls and pots. Quantitative trait locus (QTL) analysis identified three QTLs controlling seminal root number (SRN) on chromosome bins 1.02, 3.07, and 8.04-8.05, which collectively explained 66% of the phenotypic variation. In all three cases, Gaspé Flint contributed the allele for lower SRN. Primary root dry weight was negatively correlated with SRN (r= -0.52), and QTLs for primary root size co-mapped with SRN QTLs, suggesting a pleiotropic effect of SRN QTLs on the primary root, most probably caused by competition for seed resources. Interestingly, two out of three SRN QTLs co-mapped with the only two known maize genes (rtcs and rum1) affecting the number of seminal roots. The strong additive effect of the three QTLs and the development of near isogenic lines for each QTL in the elite B73 background provide unique opportunities to characterize functionally the genes involved in root development and to evaluate how root architecture affects seedling establishment, early development, and eventually yield in maize.

  5. Two major quantitative trait loci controlling the number of seminal roots in maize co-map with the root developmental genes rtcs and rum1

    PubMed Central

    Salvi, Silvio; Giuliani, Silvia; Ricciolini, Claudia; Carraro, Nicola; Maccaferri, Marco; Presterl, Thomas; Ouzunova, Milena; Tuberosa, Roberto

    2016-01-01

    The genetic dissection of root architecture and functions allows for a more effective and informed design of novel root ideotypes and paves the way to evaluate their effects on crop resilience to a number of abiotic stresses. In maize, limited attention has been devoted to the genetic analysis of root architecture diversity at the early stage. The difference in embryonic (including seminal and primary) root architecture between the maize reference line B73 (which mostly develops three seminal roots) and the landrace Gaspé Flint (with virtually no seminal roots) was genetically dissected using a collection of introgression lines grown in paper rolls and pots. Quantitative trait locus (QTL) analysis identified three QTLs controlling seminal root number (SRN) on chromosome bins 1.02, 3.07, and 8.04–8.05, which collectively explained 66% of the phenotypic variation. In all three cases, Gaspé Flint contributed the allele for lower SRN. Primary root dry weight was negatively correlated with SRN (r= −0.52), and QTLs for primary root size co-mapped with SRN QTLs, suggesting a pleiotropic effect of SRN QTLs on the primary root, most probably caused by competition for seed resources. Interestingly, two out of three SRN QTLs co-mapped with the only two known maize genes (rtcs and rum1) affecting the number of seminal roots. The strong additive effect of the three QTLs and the development of near isogenic lines for each QTL in the elite B73 background provide unique opportunities to characterize functionally the genes involved in root development and to evaluate how root architecture affects seedling establishment, early development, and eventually yield in maize. PMID:26880748

  6. Plasmodium genetic loci linked to host cytokine and chemokine responses

    PubMed Central

    Pattaradilokrat, Sittiporn; Li, Jian; Wu, Jian; Qi, Yanwei; Eastman, Richard T.; Zilversmit, Martine; Nair, Sethu C.; Huaman, Maria Cecilia; Quinones, Mariam; Jiang, Hongying; Li, Na; Zhu, Jun; Zhao, Keji; Kaneko, Osamu; Long, Carole A.; Su, Xin-zhuan

    2014-01-01

    Both host and parasite factors contribute to disease severity of malaria infection; however, the molecular mechanisms responsible for the disease and the host-parasite interactions involved remain largely unresolved. To investigate effects of parasite factors on host immune responses and pathogenesis, we measured levels of plasma cytokines/chemokines (CC) and growth rates in mice infected with two Plasmodium yoelii strains having different virulence phenotypes and in progeny from a genetic cross of the two parasites. Quantitative trait loci (QTL) analysis linked levels of many CCs, particularly IL-1β, IP-10, IFN-γ, MCP-1, and MIG, and early parasite growth rate to loci on multiple parasite chromosomes, including chromosomes 7, 9, 10, 12, and 13. Comparison of the genome sequences spanning the mapped loci revealed various candidate genes. The loci on chromosome 7 and 13 had significant (p < 0.005) additive effects on IL-1β, IL-5, and IP-10 responses, and the chromosome 9 and 12 loci had significant (p = 0.017) interaction. Infection of knockout mice showed critical roles of MCP-1 and IL-10 in parasitemia control and host mortality. These results provide important information for better understanding of malaria pathogenesis and can be used to examine the role of these factors in human malaria infection. PMID:24452266

  7. Plasmodium genetic loci linked to host cytokine and chemokine responses.

    PubMed

    Pattaradilokrat, S; Li, J; Wu, J; Qi, Y; Eastman, R T; Zilversmit, M; Nair, S C; Huaman, M C; Quinones, M; Jiang, H; Li, N; Zhu, J; Zhao, K; Kaneko, O; Long, C A; Su, X-z

    2014-01-01

    Both host and parasite factors contribute to disease severity of malaria infection; however, the molecular mechanisms responsible for the disease and the host-parasite interactions involved remain largely unresolved. To investigate the effects of parasite factors on host immune responses and pathogenesis, we measured levels of plasma cytokines/chemokines (CCs) and growth rates in mice infected with two Plasmodium yoelii strains having different virulence phenotypes and in progeny from a genetic cross of the two parasites. Quantitative trait loci (QTL) analysis linked levels of many CCs, particularly IL-1β, IP-10, IFN-γ, MCP-1 and MIG, and early parasite growth rate to loci on multiple parasite chromosomes, including chromosomes 7, 9, 10, 12 and 13. Comparison of the genome sequences spanning the mapped loci revealed various candidate genes. The loci on chromosomes 7 and 13 had significant (P<0.005) additive effects on IL-1β, IL-5 and IP-10 responses, and the chromosome 9 and 12 loci had significant (P=0.017) interaction. Infection of knockout mice showed critical roles of MCP-1 and IL-10 in parasitemia control and host mortality. These results provide important information for a better understanding of malaria pathogenesis and can be used to examine the role of these factors in human malaria infection.

  8. Nosocomial infections in burn patients: etiology, antimicrobial resistance, means to control.

    PubMed

    Leseva, M; Arguirova, M; Nashev, D; Zamfirova, E; Hadzhyiski, O

    2013-03-31

    The aim of our study was to determine the etiology of nosocomial infections, their changes over a period of five years (2007-2011), and the measures for control of infections and antimicrobial resistance in the Burns Clinic of the N.I. Pirogov University Multi-Profile Hospital for Active Treatment and Emergency Medicine, Sofia, Bulgaria. The medical records for all the patients and the database of the "Clinical Microbiology and Surveillance of Infections" National Information System were reviewed and analyzed to identify the microbial pathogens isolated in our burns Clinic. The three most frequent nosocomial pathogens were S. aureus, A. baumannii and P. aeruginosa. In order to control effectively nosocomial infections, a system of anti-infective and anti- microbial resistance measures has been developed and routinely implemented in our Clinic since 2008. Since 2009, thanks to this system, there has been a significant decrease in the rates of multi-resistant Staphylococcus aureus strains. Although at present the incidence of the nosocomial infections in our burns clinic is lower than in neighboring countries, several important infection control issues still need to be solved. We mainly rely on updating and strengthening the existing anti-infective system in order to control the spread of multi-drug resistant organisms, such as A. baumannii, extended spectrum beta-lactamase-producing Enterobacteriaceae, and carbapenem-resistant P. aeruginosa.

  9. Comparative risk of renal, cardiovascular, and mortality outcomes in controlled, uncontrolled resistant, and non-resistant hypertension

    PubMed Central

    Sim, John J.; Bhandari, Simran K.; Shi, Jiaxiao; Reynolds, Kristi; Calhoun, David A.; Kalantar-Zadeh, Kamyar; Jacobsen, Steven J.

    2015-01-01

    We sought to compare the risk of end stage renal disease (ESRD), ischemic heart event (IHE), congestive heart failure (CHF), cerebrovascular accident (CVA), and all-cause mortality among 470,386 individuals with resistant and nonresistant hypertension (non-RH). Resistant hypertension (60,327 individuals) was sub-categorized into 2 groups; 23,104 patients with cRH (controlled on 4 or more medicines) and 37,223 patients with uRH (uncontrolled on 3 or more medicines) in a 5 year retrospective cohort study. Cox proportional hazard modeling was used to estimate hazard ratios adjusting for age, gender, race, body mass index, chronic kidney disease (CKD), and co-morbidities. Resistant hypertension (cRH and uRH) compared to non-RH, had multivariable adjusted hazard ratios (95% confidence intervals) of 1.32 (1.27–1.37), 1.24 (1.20–1.28), 1.46 (1.40–1.52), 1.14 (1.10–1.19), and 1.06 (1.03–1.08) for ESRD, IHE, CHF, CVA, and mortality, respectively. Comparison of uRH to cRH had hazard ratios of 1.25 (1.18–1.33), 1.04 (0.99–1.10), 0.94 (0.89–1.01), 1.23 (1.14–1.31), and 1.01 (0.97–1.05) for ESRD, IHE, CHF, CVA, and mortality, respectively. Males and Hispanics had greater risk for ESRD within all 3 cohorts. Resistant hypertension had greater risk for ESRD, IHE, CHF, CVA, and mortality. The risk of ESRD and CVA and were 25% and 23% greater, respectively, in uRH compared to cRH supporting the linkage between blood pressure and both outcomes. PMID:25945406

  10. Research on temperature control with numerical regulators in electric resistance furnaces with indirect heating

    NASA Astrophysics Data System (ADS)

    Diniş, C. M.; Popa, G. N.; Iagăr, A.

    2016-02-01

    The paper is an analysis of two-positions (hysteresis) regulators, self-tuned PID controller and PID controller for temperature control used for indirect heat resistance furnaces. For PID controller was used three methods of tuning: Ziegler-Nichols step response model, Cohen-Coon tuning rules and Ziegler-Nichols tuning rules. In experiments it used an electric furnace with indirect heating with active power of resistance of 1 kW/230V AC and a numerical temperature regulator AT-503 type (ANLY). It got a much better temperature control when using the Cohen-Coon tuning rules method than those of Ziegler-Nichols step response method and Ziegler-Nichols tuning rules method.

  11. Controllable resistive switching in Au/Nb:SrTiO3 microscopic Schottky junctions

    NASA Astrophysics Data System (ADS)

    Wang, Yuhang; Shi, Xiaolan; Zhao, Kehan; Xie, Guanlin; Huang, Siyu; Zhang, Liuwan

    2016-02-01

    The reversible resistive switching effect at oxide interface shows promising applications in information storage and artificial intelligence. However, the microscopic switching mechanism is still elusive due to the difficulty of direct observation of the electrical and chemical behavior at the buried interface, which becomes a major barrier to design reliable, scalable, and reproducible devices. Here we used a gold-coated AFM tip as a removable electrode to investigate the resistive switching effect in a microscopic Au/Nb:SrTiO3 Schottky junction. We found that unlike the inhomogeneous random resistive switching in the macroscopic Schottky junctions, the high and low resistance states can be reversibly switched in a controllable way on the Nb-doped SrTiO3 surface by the conductive tip. The switching between the high and low resistance states in vacuum is accompanied by the reversible shift of the surface Fermi level. We indicate that the transfer of the interface oxygen ion in a double-well potential is responsible for the resistive switching in both macroscopic and microscopic Schottky junctions. Our findings provide a guide to optimize the key performance parameters of a resistive switching device such as operation voltage, switching speed, on/off ratio, and state retention time by proper electrode selection and fabrication strategy.

  12. An error-resistant linguistic protocol for air traffic control

    NASA Technical Reports Server (NTRS)

    Cushing, Steven

    1989-01-01

    The research results described here are intended to enhance the effectiveness of the DATALINK interface that is scheduled by the Federal Aviation Administration (FAA) to be deployed during the 1990's to improve the safety of various aspects of aviation. While voice has a natural appeal as the preferred means of communication both among humans themselves and between humans and machines as the form of communication that people find most convenient, the complexity and flexibility of natural language are problematic, because of the confusions and misunderstandings that can arise as a result of ambiguity, unclear reference, intonation peculiarities, implicit inference, and presupposition. The DATALINK interface will avoid many of these problems by replacing voice with vision and speech with written instructions. This report describes results achieved to date on an on-going research effort to refine the protocol of the DATALINK system so as to avoid many of the linguistic problems that still remain in the visual mode. In particular, a working prototype DATALINK simulator system has been developed consisting of an unambiguous, context-free grammar and parser, based on the current air-traffic-control language and incorporated into a visual display involving simulated touch-screen buttons and three levels of menu screens. The system is written in the C programming language and runs on the Macintosh II computer. After reviewing work already done on the project, new tasks for further development are described.

  13. Mycoplasmas and Their Antibiotic Resistance: The Problems and Prospects in Controlling Infections

    PubMed Central

    Chernova, O.A.; Medvedeva, E.S.; Mouzykantov, A.A.; Baranova, N.B.; Chernov, V.M.

    2016-01-01

    The present review discusses the problem of controlling mycoplasmas (class Mollicutes), the smallest of self-replicating prokaryotes, parasites of higher eukaryotes, and main contaminants of cell cultures and vaccines. Possible mechanisms for the rapid development of resistance to antimicrobial drugs in mycoplasmas have been analyzed. Omics technologies provide new opportunities for investigating the molecular basis of bacterial adaptation to stress factors and identifying resistomes, the total of all genes and their products contributing to antibiotic resistance in microbes. The data obtained using an integrated approach with post-genomics methods show that antibiotic resistance may be caused by more complex processes than has been believed heretofore. The development of antibiotic resistance in mycoplasmas is associated with essential changes in the genome, proteome, and secretome profiles, which involve many genes and proteins related to fundamental cellular processes and virulence. PMID:27437137

  14. Beverton-Holt discrete pest management models with pulsed chemical control and evolution of pesticide resistance

    NASA Astrophysics Data System (ADS)

    Liang, Juhua; Tang, Sanyi; Cheke, Robert A.

    2016-07-01

    Pest resistance to pesticides is usually managed by switching between different types of pesticides. The optimal switching time, which depends on the dynamics of the pest population and on the evolution of the pesticide resistance, is critical. Here we address how the dynamic complexity of the pest population, the development of resistance and the spraying frequency of pulsed chemical control affect optimal switching strategies given different control aims. To do this, we developed novel discrete pest population growth models with both impulsive chemical control and the evolution of pesticide resistance. Strong and weak threshold conditions which guarantee the extinction of the pest population, based on the threshold values of the analytical formula for the optimal switching time, were derived. Further, we addressed switching strategies in the light of chosen economic injury levels. Moreover, the effects of the complex dynamical behaviour of the pest population on the pesticide switching times were also studied. The pesticide application period, the evolution of pesticide resistance and the dynamic complexity of the pest population may result in complex outbreak patterns, with consequent effects on the pesticide switching strategies.

  15. Insecticide resistance, control failure likelihood and the First Law of Geography.

    PubMed

    Guedes, Raul Narciso C

    2017-03-01

    Insecticide resistance is a broadly recognized ecological backlash resulting from insecticide use and is widely reported among arthropod pest species with well-recognized underlying mechanisms and consequences. Nonetheless, insecticide resistance is the subject of evolving conceptual views that introduces a different concept useful if recognized in its own right - the risk or likelihood of control failure. Here we suggest an experimental approach to assess the likelihood of control failure of an insecticide allowing for consistent decision-making regarding management of insecticide resistance. We also challenge the current emphasis on limited spatial sampling of arthropod populations for resistance diagnosis in favor of comprehensive spatial sampling. This necessarily requires larger population sampling - aiming to use spatial analysis in area-wide surveys - to recognize focal points of insecticide resistance and/or control failure that will better direct management efforts. The continuous geographical scale of such surveys will depend on the arthropod pest species, the pattern of insecticide use and many other potential factors. Regardless, distance dependence among sampling sites should still hold, following the maxim that the closer two things are, the more they resemble each other, which is the basis of Tobler's First Law of Geography. © 2016 Society of Chemical Industry.

  16. Genome-wide delineation of natural variation for pod shatter resistance in Brassica napus.

    PubMed

    Raman, Harsh; Raman, Rosy; Kilian, Andrzej; Detering, Frank; Carling, Jason; Coombes, Neil; Diffey, Simon; Kadkol, Gururaj; Edwards, David; McCully, Margaret; Ruperao, Pradeep; Parkin, Isobel A P; Batley, Jacqueline; Luckett, David J; Wratten, Neil

    2014-01-01

    Resistance to pod shattering (shatter resistance) is a target trait for global rapeseed (canola, Brassica napus L.), improvement programs to minimise grain loss in the mature standing crop, and during windrowing and mechanical harvest. We describe the genetic basis of natural variation for shatter resistance in B. napus and show that several quantitative trait loci (QTL) control this trait. To identify loci underlying shatter resistance, we used a novel genotyping-by-sequencing approach DArT-Seq. QTL analysis detected a total of 12 significant QTL on chromosomes A03, A07, A09, C03, C04, C06, and C08; which jointly account for approximately 57% of the genotypic variation in shatter resistance. Through Genome-Wide Association Studies, we show that a large number of loci, including those that are involved in shattering in Arabidopsis, account for variation in shatter resistance in diverse B. napus germplasm. Our results indicate that genetic diversity for shatter resistance genes in B. napus is limited; many of the genes that might control this trait were not included during the natural creation of this species, or were not retained during the domestication and selection process. We speculate that valuable diversity for this trait was lost during the natural creation of B. napus. To improve shatter resistance, breeders will need to target the introduction of useful alleles especially from genotypes of other related species of Brassica, such as those that we have identified.

  17. Controlling antimicrobial resistance in hospitals: infection control and use of antibiotics.

    PubMed Central

    Weinstein, R. A.

    2001-01-01

    Antimicrobial-drug resistance in hospitals is driven by failures of hospital hygiene, selective pressures created by overuse of antibiotics, and mobile genetic elements that can encode bacterial resistance mechanisms. Attention to hand hygiene is constrained by the time it takes to wash hands and by the adverse effects of repeated handwashing on the skin. Alcohol-based hand rubs can overcome the time problem and actually improve skin condition. Universal glove use could close gaps left by incomplete adherence to hand hygiene. Various interventions have been described to improve antibiotic use. The most effective have been programs restricting use of antibiotics and computer-based order forms for health providers. PMID:11294703

  18. Outbreak of resistant Acinetobacter baumannii- measures and proposal for prevention and control.

    PubMed

    Romanelli, Roberta Maia de Castro; Jesus, Lenize Adriana de; Clemente, Wanessa Trindade; Lima, Stella Sala Soares; Rezende, Edna Maria; Coutinho, Rosane Luiza; Moreira, Ricardo Luiz Fontes; Neves, Francelli Aparecida Cordeiro; Brás, Nelma de Jesus

    2009-10-01

    Acinetobacter baumannii colonization and infection, frequent in Intensive Care Unit (ICU) patients, is commonly associated with high morbimortality. Several outbreaks due to multidrug-resistant (MDR) A. baumanii have been reported but few of them in Brazil. This study aimed to identify risk factors associated with colonization and infection by MDR and carbapenem-resistant A. baumannii strains isolated from patients admitted to the adult ICU at HC/UFMG. A case-control study was performed from January 2007 to June 2008. Cases were defined as patients colonized or infected by MDR/carbapenem-resistant A. baumannii, and controls were patients without MDR/carbapenem-resistant A. baumannii isolation, in a 1:2 proportion. For statistical analysis, due to changes in infection control guidelines, infection criteria and the notification process, this study was divided into two periods. During the first period analyzed, from January to December 2007, colonization or infection by MDR/carbapenem-resistant A. baumannii was associated with prior infection, invasive device utilization, prior carbapenem use and clinical severity. In the multivariate analysis, prior infection and mechanical ventilation proved to be statistically significant risk factors. Carbapenem use showed a tendency towards a statistical association. During the second study period, from January to June 2008, variables with a significant association with MDR/carbapenem-resistant A. baumannii colonization/infection were catheter utilization, carbapenem and third-generation cephalosporin use, hepatic transplantation, and clinical severity. In the multivariate analysis, only CVC use showed a statistical difference. Carbapenem and third-generation cephalosporin use displayed a tendency to be risk factors. Risk factors must be focused on infection control and prevention measures considering A. baumanni dissemination.

  19. Effects of Dehydration on Cerebrovascular Control During Standing After Heavy Resistance Exercise

    DTIC Science & Technology

    2012-03-29

    flow; weight training ; cerebrovascular control PRESERVATION OF CEREBRAL PERFUSION is essential for maintaining consciousness. Heavy resistance exercise...cardiovascular and cerebrovascular regulatory mechanisms. Subjects also received famil- iarization training with the experimental protocol and procedures...increases in the power of MCAv LF oscillations was induced by breathing through an inspiratory threshold device and was associated with an improvement in

  20. Effects of Resistance Exercise Applied Early After Coronary Artery Bypass Grafting: a Randomized Controlled Trial

    PubMed Central

    Ximenes, Nayana Nazaré Pessoa Sousa; Borges, Daniel Lago; Lima, Reijane Oliveira; Silva, Mayara Gabrielle Barbosa e; da Silva, Luan Nascimento; Costa, Marina de Albuquerque Gonçalves; Baldez, Thiago Eduardo Pereira; Nina, Vinícius José da Silva

    2015-01-01

    OBJECTIVE To evaluate the effects of resistance exercise applied early after coronary artery bypass grafting. METHODS It is a randomized controlled trial with 34 patients undergoing coronary artery bypass grafting between August 2013 and May 2014. Patients were randomized into two groups by simple draw: a control group (n=17), who received conventional physical therapy and an intervention group (n=17), who received, additionally, resistance exercise. Pulmonary function and functional capacity were evaluated in preoperative period and hospital discharge by spirometry and the six-minute walk test. For statistical analysis, we used the following tests: Shapiro-Wilk, Mann-Whitney, Student's t and Fisher's exact. Variables with P<0.05 were considered significant. RESULTS Groups were homogeneous in terms of demographic, clinical and surgical variables. Resistance exercise exerted no effect on pulmonary function of intervention group compared to control group. However, intervention group maintained functional capacity at hospital discharge measured by percentage of predict distance in 6MWT (54.122.7% vs. 52.515.5%, P=0.42), while control group had a significant decrease (59.211.1% vs. 50.69.9%, P<0.016). CONCLUSION Our results indicate that resistance exercise, applied early, may promote maintenance of functional capacity on coronary artery bypass grafting patients, having no impact on pulmonary function when compared to conventional physical therapy. PMID:26934401

  1. Glyphosate-resistant horseweed (conyza canadensis) control with dicamba in Alabama

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Widespread horseweed resistance to glyphosate has resulted in the use of dicamba as an alternative treatment. Horseweed populations in Cherokee and DeKalb counties in northern Alabama were not well controlled following glyphosate and dicamba treatments. This research evaluates horseweed populations ...

  2. Do resisted temptations during smoking cessation deplete or augment self-control resources?

    PubMed

    O'Connell, Kathleen A; Schwartz, Joseph E; Shiffman, Saul

    2008-12-01

    A resource depletion model of self-control posits that for some period following performance of a task requiring self-control, self-control will be reduced and thus less available for use in a subsequent task. Using 2 substantial data sets collected in real time from individuals who were trying to quit smoking (1,660 and 9,516 temptation episodes collected from 61 and 248 individuals, respectively), we evaluated this model by testing the hypotheses that the number and length of resisted temptations and the intensity of the most recently reported urge during the prior 4 hr predict decreased self-control and increased likelihood of lapsing. Survival and multilevel regression modeling showed that contrary to the hypothesis, the number of recently resisted temptations predicted a lower risk of lapsing in both samples. Duration of resisted temptations had no significant effect in either sample. Intensity of most recently reported urge predicted lapsing in 1 data set but not in the other. Overall, there was little support for the resource depletion model. The protective effect of successfully resisting temptations was an unexpected but provocative finding.

  3. Genetic mapping and quantitative trait loci analysis for disease resistance using F2 and F5 generation-based genetic maps derived from 'Tifrunner' x'GT-C20' in peanut

    Technology Transfer Automated Retrieval System (TEKTRAN)

    One mapping population derived from Tifrunner × GT-C20 has shown great potential in developing a high dense genetic map and identification of QTLs for important disease resistance, Tomato spotted wilt virus (TSWV) and leaf spot (LS). Both F2 and F5 generation-based genetic maps were constructed prev...

  4. Individual and Combined Contributions of the Renbarb1, Renbarb2, and Renbarb3 Quantitative Trait Loci to Reniform Nematode (Rotylenchulus reniformis Linford & Oliveira) Resistance in Upland Cotton (Gossypium hirsutum L.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The infection of Upland cotton (Gossypium hirsutum L.) by the root parasite Rotylenchulus reniformis (Linford & Oliveira), the reniform nematode, results in massive annual yield losses throughout the southeastern United States and portions of Texas. Resistance to reniform nematode was identified in...

  5. A genotype-by-sequencing-single nucleotide polymorphism based linkage map and quantitative trait loci (QTL) associated with resistance to Fusarium oxysporum f. sp. niveum race 2 identified in Citrullus lanatus var. citroides

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fusarium wilt, a fungal disease caused by Fusarium oxysporum f. sp. niveum (Fon), devastates watermelon crop production worldwide. Several races, which are differentiated by host range, of the pathogen exist. Resistance to Fon race 2, a particularly virulent strain prevalent in the United States, do...

  6. Co-dominant SCAR Markers for Detection of the Ty-3 and Ty-3a Loci from Solanum chilense at 25 cM of Chromosome 6 of Tomato

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Breeding for resistance to begomoviruses in tomato can be greatly aided by the availability of PCR-based markers for the various resistance loci. Four begomovirus-resistance loci or regions have been mapped to chromosome 6 (Agrama and Scott, 2006; Chagué et al., 1997; Ji and Scott, 2006b; Ji et al....

  7. Riboswitch control of induction of aminoglycoside resistance acetyl and adenyl-transferases.

    PubMed

    He, Weizhi; Zhang, Xuhui; Zhang, Jun; Jia, Xu; Zhang, Jing; Sun, Wenxia; Jiang, Hengyi; Chen, Dongrong; Murchie, Alastair I H

    2013-08-01

    The acquisition of antibiotic resistance by human pathogens poses a significant threat to public health. The mechanisms that control the proliferation and expression of antibiotic resistance genes are not yet completely understood. The aminoglycosides are a historically important class of antibiotics that were introduced in the 1940s. Aminoglycoside resistance is conferred most commonly through enzymatic modification of the drug or enzymatic modification of the target rRNA through methylation or through the overexpression of efflux pumps. In our recent paper, we reported that expression of the aminoglycoside resistance genes encoding the aminoglycoside acetyl transferase (AAC) and aminoglycoside adenyl transferase (AAD) enzymes was controlled by an aminoglycoside-sensing riboswitch RNA. This riboswitch is embedded in the leader RNA of the aac/aad genes and is associated with the integron cassette system. The leader RNA can sense and bind specific aminoglycosides such that the binding causes a structural transition in the leader RNA, which leads to the induction of aminoglycoside antibiotic resistance. Specific aminoglycosides induce reporter gene expression mediated by the leader RNA. Aminoglycoside RNA binding was measured directly and, aminoglycoside-induced changes in RNA structure monitored by chemical probing. UV cross-linking and mutational analysis identified potential aminoglycoside binding sites on the RNA.

  8. Multicenter Quality Control of Hepatitis C Virus Protease Inhibitor Resistance Genotyping

    PubMed Central

    Larrat, Sylvie; Laperche, Syria; Le Guillou-Guillemette, Hélène; Legrand-Abravanel, Florence; Bouchardeau, Françoise; Pivert, Adeline; Henquell, Cécile; Mirand, Audrey; André-Garnier, Elisabeth; Giordanengo, Valérie; Lagathu, Gisèle; Thibault, Vincent; Scholtes, Caroline; Schvoerer, Evelyne; Gaudy-Graffin, Catherine; Maylin, Sarah; Trimoulet, Pascale; Brochot, Etienne; Hantz, Sébastien; Gozlan, Joël; Roque-Afonso, Anne-Marie; Soussan, Patrick; Plantier, Jean-Christophe; Charpentier, Charlotte; Chevaliez, Stéphane; Colson, Philippe; Mackiewicz, Vincent; Aguilera, Lina; Rosec, Sylvain; Gouriou, Stéphanie; Magnat, Nelly; Lunel-Fabiani, Françoise; Izopet, Jacques; Morand, Patrice; Payan, Christopher; Pawlotsky, Jean-Michel

    2013-01-01

    Hepatitis C virus (HCV) protease inhibitor resistance-associated substitutions are selected during triple-therapy breakthrough. This multicenter quality control study evaluated the expertise of 23 French laboratories in HCV protease inhibitor resistance genotyping. A panel of 12 well-defined blinded samples comprising two wild-type HCV strains, nine transcripts from synthetic NS3 mutant samples or from clinical strains, and one HCV RNA-negative sample was provided to the participating laboratories. The results showed that any laboratory with expertise in sequencing techniques should be able to provide reliable HCV protease inhibitor resistance genotyping. Only a 0.7% error rate was reported for the amino acid sites studied. The accuracy of substitution identification ranged from 75% to 100%, depending on the laboratory. Incorrect results were mainly related to the methodology used. The results could be improved by changing the primers and modifying the process in order to avoid cross-contamination. This study underlines the value of quality control programs for viral resistance genotyping, which is required prior to launching observational collaborative multicenter studies on HCV resistance to direct-acting antiviral agents. PMID:23426922

  9. Multicenter quality control of hepatitis C virus protease inhibitor resistance genotyping.

    PubMed

    Vallet, Sophie; Larrat, Sylvie; Laperche, Syria; Le Guillou-Guillemette, Hélène; Legrand-Abravanel, Florence; Bouchardeau, Françoise; Pivert, Adeline; Henquell, Cécile; Mirand, Audrey; André-Garnier, Elisabeth; Giordanengo, Valérie; Lagathu, Gisèle; Thibault, Vincent; Scholtes, Caroline; Schvoerer, Evelyne; Gaudy-Graffin, Catherine; Maylin, Sarah; Trimoulet, Pascale; Brochot, Etienne; Hantz, Sébastien; Gozlan, Joël; Roque-Afonso, Anne-Marie; Soussan, Patrick; Plantier, Jean-Christophe; Charpentier, Charlotte; Chevaliez, Stéphane; Colson, Philippe; Mackiewicz, Vincent; Aguilera, Lina; Rosec, Sylvain; Gouriou, Stéphanie; Magnat, Nelly; Lunel-Fabiani, Françoise; Izopet, Jacques; Morand, Patrice; Payan, Christopher; Pawlotsky, Jean-Michel

    2013-05-01

    Hepatitis C virus (HCV) protease inhibitor resistance-associated substitutions are selected during triple-therapy breakthrough. This multicenter quality control study evaluated the expertise of 23 French laboratories in HCV protease inhibitor resistance genotyping. A panel of 12 well-defined blinded samples comprising two wild-type HCV strains, nine transcripts from synthetic NS3 mutant samples or from clinical strains, and one HCV RNA-negative sample was provided to the participating laboratories. The results showed that any laboratory with expertise in sequencing techniques should be able to provide reliable HCV protease inhibitor resistance genotyping. Only a 0.7% error rate was reported for the amino acid sites studied. The accuracy of substitution identification ranged from 75% to 100%, depending on the laboratory. Incorrect results were mainly related to the methodology used. The results could be improved by changing the primers and modifying the process in order to avoid cross-contamination. This study underlines the value of quality control programs for viral resistance genotyping, which is required prior to launching observational collaborative multicenter studies on HCV resistance to direct-acting antiviral agents.

  10. Combining pest control and resistance management: synergy of engineered insects with Bt crops.

    PubMed

    Alphey, Nina; Bonsall, Michael B; Alphey, Luke

    2009-04-01

    Transgenic crops producing insecticidal toxins are widely used to control insect pests. Their benefits would be lost if resistance to the toxins became widespread in pest populations. The most widely used resistance management method is the high-dose/refuge strategy. This requires toxin-free host plants as refuges near insecticidal crops, and toxin doses intended to be sufficiently high to kill insects heterozygous for a resistant allele, thereby rendering resistance functionally recessive. We have previously shown by mathematical modeling that mass-release of harmless susceptible (toxin-sensitive) insects engineered with repressible female-specific lethality using release of insects carrying a dominant lethal ([RIDL] Oxitec Limited, United Kingdom) technology could substantially delay or reverse the spread of resistance and reduce refuge sizes. Here, we explore this proposal in depth, studying a wide range of scenarios, considering impacts on population dynamics as well as evolution of allele frequencies, comparing with releases of natural fertile susceptible insects, and examining the effect of seasonality. We investigate the outcome for pest control for which the plant-incorporated toxins are not necessarily at a high dose (i.e., they might not kill all homozygous susceptible and all heterozygous insects). We demonstrate that a RIDL-based approach could form an effective component of a resistance management strategy in a wide range of genetic and ecological circumstances. Because there are significant threshold effects for several variables, we expect that a margin of error would be advisable in setting release ratios and refuge sizes, especially as the frequency and properties of resistant alleles may be difficult to measure accurately in the field.

  11. Seven new loci associated with age-related macular degeneration.

    PubMed

    Fritsche, Lars G; Chen, Wei; Schu, Matthew; Yaspan, Brian L; Yu, Yi; Thorleifsson, Gudmar; Zack, Donald J; Arakawa, Satoshi; Cipriani, Valentina; Ripke, Stephan; Igo, Robert P; Buitendijk, Gabriëlle H S; Sim, Xueling; Weeks, Daniel E; Guymer, Robyn H; Merriam, Joanna E; Francis, Peter J; Hannum, Gregory; Agarwal, Anita; Armbrecht, Ana Maria; Audo, Isabelle; Aung, Tin; Barile, Gaetano R; Benchaboune, Mustapha; Bird, Alan C; Bishop, Paul N; Branham, Kari E; Brooks, Matthew; Brucker, Alexander J; Cade, William H; Cain, Melinda S; Campochiaro, Peter A; Chan, Chi-Chao; Cheng, Ching-Yu; Chew, Emily Y; Chin, Kimberly A; Chowers, Itay; Clayton, David G; Cojocaru, Radu; Conley, Yvette P; Cornes, Belinda K; Daly, Mark J; Dhillon, Baljean; Edwards, Albert O; Evangelou, Evangelos; Fagerness, Jesen; Ferreyra, Henry A; Friedman, James S; Geirsdottir, Asbjorg; George, Ronnie J; Gieger, Christian; Gupta, Neel; Hagstrom, Stephanie A; Harding, Simon P; Haritoglou, Christos; Heckenlively, John R; Holz, Frank G; Hughes, Guy; Ioannidis, John P A; Ishibashi, Tatsuro; Joseph, Peronne; Jun, Gyungah; Kamatani, Yoichiro; Katsanis, Nicholas; N Keilhauer, Claudia; Khan, Jane C; Kim, Ivana K; Kiyohara, Yutaka; Klein, Barbara E K; Klein, Ronald; Kovach, Jaclyn L; Kozak, Igor; Lee, Clara J; Lee, Kristine E; Lichtner, Peter; Lotery, Andrew J; Meitinger, Thomas; Mitchell, Paul; Mohand-Saïd, Saddek; Moore, Anthony T; Morgan, Denise J; Morrison, Margaux A; Myers, Chelsea E; Naj, Adam C; Nakamura, Yusuke; Okada, Yukinori; Orlin, Anton; Ortube, M Carolina; Othman, Mohammad I; Pappas, Chris; Park, Kyu Hyung; Pauer, Gayle J T; Peachey, Neal S; Poch, Olivier; Priya, Rinki Ratna; Reynolds, Robyn; Richardson, Andrea J; Ripp, Raymond; Rudolph, Guenther; Ryu, Euijung; Sahel, José-Alain; Schaumberg, Debra A; Scholl, Hendrik P N; Schwartz, Stephen G; Scott, William K; Shahid, Humma; Sigurdsson, Haraldur; Silvestri, Giuliana; Sivakumaran, Theru A; Smith, R Theodore; Sobrin, Lucia; Souied, Eric H; Stambolian, Dwight E; Stefansson, Hreinn; Sturgill-Short, Gwen M; Takahashi, Atsushi; Tosakulwong, Nirubol; Truitt, Barbara J; Tsironi, Evangelia E; Uitterlinden, André G; van Duijn, Cornelia M; Vijaya, Lingam; Vingerling, Johannes R; Vithana, Eranga N; Webster, Andrew R; Wichmann, H-Erich; Winkler, Thomas W; Wong, Tien Y; Wright, Alan F; Zelenika, Diana; Zhang, Ming; Zhao, Ling; Zhang, Kang; Klein, Michael L; Hageman, Gregory S; Lathrop, G Mark; Stefansson, Kari; Allikmets, Rando; Baird, Paul N; Gorin, Michael B; Wang, Jie Jin; Klaver, Caroline C W; Seddon, Johanna M; Pericak-Vance, Margaret A; Iyengar, Sudha K; Yates, John R W; Swaroop, Anand; Weber, Bernhard H F; Kubo, Michiaki; Deangelis, Margaret M; Léveillard, Thierry; Thorsteinsdottir, Unnur; Haines, Jonathan L; Farrer, Lindsay A; Heid, Iris M; Abecasis, Gonçalo R

    2013-04-01

    Age-related macular degeneration (AMD) is a common cause of blindness in older individuals. To accelerate the understanding of AMD biology and help design new therapies, we executed a collaborative genome-wide association study, including >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry. We identified 19 loci associated at P < 5 × 10(-8). These loci show enrichment for genes involved in the regulation of complement activity, lipid metabolism, extracellular matrix remodeling and angiogenesis. Our results include seven loci with associations reaching P < 5 × 10(-8) for the first time, near the genes COL8A1-FILIP1L, IER3-DDR1, SLC16A8, TGFBR1, RAD51B, ADAMTS9 and B3GALTL. A genetic risk score combining SNP genotypes from all loci showed similar ability to distinguish cases and controls in all samples examined. Our findings provide new directions for biological, genetic and therapeutic studies of AMD.

  12. Chlorfenapyr: a new insecticide with novel mode of action can control pyrethroid resistant malaria vectors

    PubMed Central

    2011-01-01

    Background Malaria vectors have acquired widespread resistance to many of the currently used insecticides, including synthetic pyrethroids. Hence, there is an urgent need to develop alternative insecticides for effective management of insecticide resistance in malaria vectors. In the present study, chlorfenapyr was evaluated against Anopheles culicifacies and Anopheles stephensi for its possible use in vector control. Methods Efficacy of chlorfenapyr against An. culicifacies and An. stephensi was assessed using adult bioassay tests. In the laboratory, determination of diagnostic dose, assessment of residual activity on different substrates, cross-resistance pattern with different insecticides and potentiation studies using piperonyl butoxide were undertaken by following standard procedures. Potential cross-resistance patterns were assessed on field populations of An. culicifacies. Results A dose of 5.0% chlorfenapyr was determined as the diagnostic concentration for assessing susceptibility applying the WHO tube test method in anopheline mosquitoes with 2 h exposure and 48 h holding period. The DDT-resistant/malathion-deltamethrin-susceptible strain of An. culicifacies species C showed higher LD50 and LD99 (0.67 and 2.39% respectively) values than the DDT-malathion-deltamethrin susceptible An. culicifacies species A (0.41 and 2.0% respectively) and An. stephensi strains (0.43 and 2.13% respectively) and there was no statistically significant difference in mortalities among the three mosquito species tested (p > 0.05). Residual activity of chlorfenapyr a.i. of 400 mg/m2 on five fabricated substrates, namely wood, mud, mud+lime, cement and cement + distemper was found to be effective up to 24 weeks against An. culicifacies and up to 34 weeks against An. stephensi. No cross-resistance to DDT, malathion, bendiocarb and deltamethrin was observed with chlorfenapyr in laboratory-reared strains of An. stephensi and field-caught An. culicifacies. Potentiation studies

  13. Strategic measures for the control of surging antimicrobial resistance in Hong Kong and mainland of China.

    PubMed

    Cheng, Vincent C C; Wong, Sally C Y; Ho, Pak-Leung; Yuen, Kwok-Yung

    2015-02-01

    Antimicrobial-resistant bacteria are either highly prevalent or increasing rapidly in Hong Kong and China. Treatment options for these bacteria are generally limited, less effective and more expensive. The emergence and dynamics of antimicrobial resistance genes in bacteria circulating between animals, the environment and humans are not entirely known. Nonetheless, selective pressure by antibiotics on the microbiomes of animal and human, and their associated environments (especially farms and healthcare institutions), sewage systems and soil are likely to confer survival advantages upon bacteria with antimicrobial-resistance genes, which may be further disseminated through plasmids or transposons with integrons. Therefore, antibiotic use must be tightly regulated to eliminate such selective pressure, including the illegalization of antibiotics as growth promoters in animal feed and regulation of antibiotic use in veterinary practice and human medicine. Heightened awareness of infection control measures to reduce the risk of acquiring resistant bacteria is essential, especially during antimicrobial use or institutionalization in healthcare facilities. The transmission cycle must be interrupted by proper hand hygiene, environmental cleaning, avoidance of undercooked or raw food and compliance with infection control measures by healthcare workers, visitors and patients, especially during treatment with antibiotics. In addition to these routine measures, proactive microbiological screening of hospitalized patients with risk factors for carrying resistant bacteria, including history of travel to endemic countries, transfer from other hospitals, and prolonged hospitalization; directly observed hand hygiene before oral intake of drugs, food and drinks; and targeted disinfection of high-touch or mutual-touch items, such as bed rails and bed curtains, are important. Transparency of surveillance data from each institute for public scrutiny provides an incentive for

  14. Strategic measures for the control of surging antimicrobial resistance in Hong Kong and mainland of China

    PubMed Central

    Cheng, Vincent CC; Wong, Sally CY; Ho, Pak-Leung; Yuen, Kwok-Yung

    2015-01-01

    Antimicrobial-resistant bacteria are either highly prevalent or increasing rapidly in Hong Kong and China. Treatment options for these bacteria are generally limited, less effective and more expensive. The emergence and dynamics of antimicrobial resistance genes in bacteria circulating between animals, the environment and humans are not entirely known. Nonetheless, selective pressure by antibiotics on the microbiomes of animal and human, and their associated environments (especially farms and healthcare institutions), sewage systems and soil are likely to confer survival advantages upon bacteria with antimicrobial-resistance genes, which may be further disseminated through plasmids or transposons with integrons. Therefore, antibiotic use must be tightly regulated to eliminate such selective pressure, including the illegalization of antibiotics as growth promoters in animal feed and regulation of antibiotic use in veterinary practice and human medicine. Heightened awareness of infection control measures to reduce the risk of acquiring resistant bacteria is essential, especially during antimicrobial use or institutionalization in healthcare facilities. The transmission cycle must be interrupted by proper hand hygiene, environmental cleaning, avoidance of undercooked or raw food and compliance with infection control measures by healthcare workers, visitors and patients, especially during treatment with antibiotics. In addition to these routine measures, proactive microbiological screening of hospitalized patients with risk factors for carrying resistant bacteria, including history of travel to endemic countries, transfer from other hospitals, and prolonged hospitalization; directly observed hand hygiene before oral intake of drugs, food and drinks; and targeted disinfection of high-touch or mutual-touch items, such as bed rails and bed curtains, are important. Transparency of surveillance data from each institute for public scrutiny provides an incentive for

  15. Resistive Wall Mode feedback on DIII-D using Linear Quadratic Gaussian control and a GPU powered control system

    NASA Astrophysics Data System (ADS)

    Clement, M. D.; Navratil, G. A.; Hanson, J. M.; Bialek, J.; Piglowski, D. A.; Penaflor, B. G.

    2015-11-01

    A Graphics Processing Unit (GPU) based control system has been installed on the DIII-D tokamak for Resistive Wall Mode (RWM) control similar to one implemented at the HBT-EP tokamak. DIII-D can excite RWMs, which are strong, locked or nearly locked kink modes whose rotation frequencies do not evolve quickly and are slow compared to their growth rates. Simulations have predicted that modern control techniques like Linear Quadratic Gaussian (LQG) control will perform better than classical control techniques when using control coils external to the vacuum vessel. An LQG control algorithm based on the VALEN model for the RWM has been developed and tested on this system. Early tests have shown the algorithm is able to track and suppress with external control coils the plasma response of an n=1 perturbation driven by internal control coils. An overview of the control hardware, VALEN model, control algorithm and initial results will be presented. Supported by the US DOE under DE-FG02-04ER54761 and DE-FC02-04ER54698.

  16. Haptic control of a pneumatic muscle actuator to provide resistance for simulated isokinetic exercise; part II: control development and testing.

    PubMed

    Hall, Kara L; Phillips, Chandler A; Reynolds, David B; Mohler, Stanley R; Rogers, Dana B; Neidhard-Doll, Amy T

    2015-01-01

    Pneumatic muscle actuators (PMAs) have a high power to weight ratio and possess unique characteristics which make them ideal actuators for applications involving human interaction. PMAs are difficult to control due to nonlinear dynamics, presenting challenges in system implementation. Despite these challenges, PMAs have great potential as a source of resistance for strength training and rehabilitation. The objective of this work was to control a PMA for use in isokinetic exercise, potentially benefiting anyone in need of optimal strength training through a joint's range of motion. The controller, based on an inverse three-element phenomenological model and adaptive nonlinear control, allows the system to operate as a type of haptic device. A human quadriceps dynamic simulator was developed (as described in Part I of this work) so that control effectiveness and accommodation could be tested prior to human implementation. Tracking error results indicate that the control system is effective at producing PMA displacement and resistance necessary for a scaled, simulated neuromuscular actuator to maintain low-velocity isokinetic movement during simulated concentric and eccentric knee extension.

  17. Computer-controlled system for measuring bulk resistivity of insulating solids as a function of temperature

    NASA Astrophysics Data System (ADS)

    Amin, Ahmed

    1986-07-01

    A computer-controlled system for measuring bulk resistivity of insulating solids as a function of temperature is described. The measuring circuit is a modification of that given in the ASTM standard D257-66, to allow for a number of operations during the data-acquisition cycle. The bulk resistivity of an acceptor-doped morphotropic lead zirconate-titanate piezoelectric composition has been measured over the temperature range +40 to +200 °C. The activation energy derived from the experimental data is compared to the published values of similar morphotropic compositions.

  18. Achievement of controlled resistive response of nanogapped palladium film to hydrogen

    SciTech Connect

    Zhao, M.; Wong, M. H.; Ong, C. W.

    2015-07-20

    Palladium (Pd) film containing nanogaps of well controlled dimension was fabricated on a Si wafer having a high-aspect-ratio micropillar. The Pd film was arranged to experience hydrogen (H{sub 2})-induced volume expansion. (i) If the nanogap is kept open, its width is narrowed down. A discharge current was generated to give a strong, fast, and repeatable on-off type resistive switching response. (ii) If the nanogap is closed, the cross section of the conduction path varies to give continuous H{sub 2}-concentration dependent resistive response. The influence of stresses and related physical mechanisms are discussed.

  19. Public health measures to control the spread of antimicrobial resistance in Neisseria gonorrhoeae in men who have sex with men.

    PubMed

    Xiridou, M; Soetens, L C; Koedijk, F D H; VAN DER Sande, M A B; Wallinga, J

    2015-06-01

    Gonorrhoea is one of the most common sexually transmitted infections. The control of gonorrhoea is extremely challenging because of the repeated development of resistance to the antibiotics used for its treatment. We explored different strategies to control the spread of antimicrobial resistance and prevent increases in gonorrhoea prevalence. We used a mathematical model that describes gonorrhoea transmission among men who have sex with men and distinguishes gonorrhoea strains sensitive or resistant to three antibiotics. We investigated the impact of combination therapy, switching first-line antibiotics according to resistance thresholds, and other control efforts (reduced sexual risk behaviour, increased treatment rate). Combination therapy can delay the spread of resistance better than using the 5% resistance threshold. Increased treatment rates, expected to enhance gonorrhoea control, may reduce gonorrhoea prevalence only in the short term, but could lead to more resistance and higher prevalence in the long term. Re-treatment of resistant cases with alternative antibiotics can substantially delay the spread of resistance. In conclusion, combination therapy and re-treatment of resistant cases with alternative antibiotics could be the most effective strategies to prevent increases in gonorrhoea prevalence due to antimicrobial resistance.

  20. The global regulator ArcA controls resistance to reactive nitrogen and oxygen intermediates in Salmonella enterica serovar Enteritidis.

    PubMed

    Lu, Sangwei; Killoran, Patrick B; Fang, Ferric C; Riley, Lee W

    2002-02-01

    Salmonella enterica serovar Enteritidis is a major cause of food-borne diseases associated with consumption of shell eggs. Clinical isolates of S. enterica serovar Enteritidis exhibit a wide spectrum of virulence in mice. A highly virulent isolate (SE2472) was previously shown to be more resistant in vitro than other clinical isolates to acidified sodium nitrite (ASN), a generator of reactive nitrogen and oxygen intermediates (RNI/ROI). SE2472 is also more resistant to S-nitrosoglutathione (GSNO) and hydrogen peroxide (H(2)O(2)) than an ASN-susceptible isolate of S. enterica serovar Enteritidis (SE8743). To investigate the molecular basis for the RNI/ROI resistance of S. enterica serovar Enteritidis, we transformed a genomic DNA library of SE2472 into SE8743. A plasmid clone conferred upon SE8743 enhanced resistance to ASN, GSNO, and H(2)O(2). The DNA insert in the clone encoded ArcA, a global regulator. An arcA mutant of SE2472 was constructed and was found to be more susceptible to GSNO and hydrogen peroxide but not more susceptible to ASN than wild-type SE2472. The susceptibility of the arcA mutant to GSNO and H(2)O(2) was complemented by a plasmid harboring arcA. The coding sequence of the arcA gene in SE2472 and the coding sequence of the arcA gene in SE8743 were identical, suggesting that the difference in resistance to RNI/ROI maybe due to the activity of genes regulated by ArcA. No significant difference in virulence between the wild type and the arcA mutant of SE2472 was observed in mice. These observations show that arcA is essential for resistance of S. enterica serovar Enteritidis to nitrosative and oxidative stress. However, additional genetic loci may contribute to the resistance to RNI/ROI and unusually high virulence for mice of SE2472.

  1. Uropathogenic Escherichia coli are less likely than paired fecal E. coli to have CRISPR loci.

    PubMed

    Dang, Trang Nguyen Doan; Zhang, Lixin; Zöllner, Sebastian; Srinivasan, Usha; Abbas, Khadija; Marrs, Carl F; Foxman, Betsy

    2013-10-01

    CRISPRs (Clustered Regularly Interspaced Short Palindromic Repeats) are short fragments of DNA that act as an adaptive immune system protecting bacteria against invasion by phages, plasmids or other forms of foreign DNA. Bacteria without a CRISPR locus may more readily adapt to environmental changes by acquiring foreign genetic material. Uropathogenic Escherichia coli (UPEC) live in a number of environments suggesting an ability to rapidly adapt to new environments. If UPEC are more adaptive than commensal E. coli we would expect that UPEC would have fewer CRISPR loci, and--if loci are present--that they would harbor fewer spacers than CRISPR loci in fecal E. coli. We tested this in vivo by comparing the number of CRISPR loci and spacers, and sensitivity to antibiotics (resistance is often obtained via plasmids) among 81 pairs of UPEC and fecal E. coli isolated from women with urinary tract infection. Each pair included one uropathogen and one commensal (fecal) sample from the same female patient. Fecal isolates had more repeats (p=0.009) and more unique spacers (p<0.0001) at four CRISPR loci than uropathogens. By contrast, uropathogens were more likely than fecal E. coli to be resistant to ampicillin, cefazolin and trimethoprim/sulfamethoxazole. However, no consistent association between CRISPRs and antibiotic resistance was identified. To our knowledge, this is the first study to compare fecal E. coli and pathogenic E. coli from the same individuals, and to test the association of CRISPR loci with antibiotic resistance. Our results suggest that the absence of CRISPR loci may make UPEC more susceptible to infection by phages or plasmids and allow them to adapt more quickly to various environments.

  2. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

    PubMed Central

    Dupuis, Josée; Langenberg, Claudia; Prokopenko, Inga; Saxena, Richa; Soranzo, Nicole; Jackson, Anne U; Wheeler, Eleanor; Glazer, Nicole L; Bouatia-Naji, Nabila; Gloyn, Anna L; Lindgren, Cecilia M; Mägi, Reedik; Morris, Andrew P; Randall, Joshua; Johnson, Toby; Elliott, Paul; Rybin, Denis; Thorleifsson, Gudmar; Steinthorsdottir, Valgerdur; Henneman, Peter; Grallert, Harald; Dehghan, Abbas; Hottenga, Jouke Jan; Franklin, Christopher S; Navarro, Pau; Song, Kijoung; Goel, Anuj; Perry, John R B; Egan, Josephine M; Lajunen, Taina; Grarup, Niels; Sparsø, Thomas; Doney, Alex; Voight, Benjamin F; Stringham, Heather M; Li, Man; Kanoni, Stavroula; Shrader, Peter; Cavalcanti-Proença, Christine; Kumari, Meena; Qi, Lu; Timpson, Nicholas J; Gieger, Christian; Zabena, Carina; Rocheleau, Ghislain; Ingelsson, Erik; An, Ping; O’Connell, Jeffrey; Luan, Jian'an; Elliott, Amanda; McCarroll, Steven A; Payne, Felicity; Roccasecca, Rosa Maria; Pattou, François; Sethupathy, Praveen; Ardlie, Kristin; Ariyurek, Yavuz; Balkau, Beverley; Barter, Philip; Beilby, John P; Ben-Shlomo, Yoav; Benediktsson, Rafn; Bennett, Amanda J; Bergmann, Sven; Bochud, Murielle; Boerwinkle, Eric; Bonnefond, Amélie; Bonnycastle, Lori L; Borch-Johnsen, Knut; Böttcher, Yvonne; Brunner, Eric; Bumpstead, Suzannah J; Charpentier, Guillaume; Chen, Yii-Der Ida; Chines, Peter; Clarke, Robert; Coin, Lachlan J M; Cooper, Matthew N; Cornelis, Marilyn; Crawford, Gabe; Crisponi, Laura; Day, Ian N M; de Geus, Eco; Delplanque, Jerome; Dina, Christian; Erdos, Michael R; Fedson, Annette C; Fischer-Rosinsky, Antje; Forouhi, Nita G; Fox, Caroline S; Frants, Rune; Franzosi, Maria Grazia; Galan, Pilar; Goodarzi, Mark O; Graessler, Jürgen; Groves, Christopher J; Grundy, Scott; Gwilliam, Rhian; Gyllensten, Ulf; Hadjadj, Samy; Hallmans, Göran; Hammond, Naomi; Han, Xijing; Hartikainen, Anna-Liisa; Hassanali, Neelam; Hayward, Caroline; Heath, Simon C; Hercberg, Serge; Herder, Christian; Hicks, Andrew A; Hillman, David R; Hingorani, Aroon D; Hofman, Albert; Hui, Jennie; Hung, Joe; Isomaa, Bo; Johnson, Paul R V; Jørgensen, Torben; Jula, Antti; Kaakinen, Marika; Kaprio, Jaakko; Kesaniemi, Y Antero; Kivimaki, Mika; Knight, Beatrice; Koskinen, Seppo; Kovacs, Peter; Kyvik, Kirsten Ohm; Lathrop, G Mark; Lawlor, Debbie A; Le Bacquer, Olivier; Lecoeur, Cécile; Li, Yun; Lyssenko, Valeriya; Mahley, Robert; Mangino, Massimo; Manning, Alisa K; Martínez-Larrad, María Teresa; McAteer, Jarred B; McCulloch, Laura J; McPherson, Ruth; Meisinger, Christa; Melzer, David; Meyre, David; Mitchell, Braxton D; Morken, Mario A; Mukherjee, Sutapa; Naitza, Silvia; Narisu, Narisu; Neville, Matthew J; Oostra, Ben A; Orrù, Marco; Pakyz, Ruth; Palmer, Colin N A; Paolisso, Giuseppe; Pattaro, Cristian; Pearson, Daniel; Peden, John F; Pedersen, Nancy L.; Perola, Markus; Pfeiffer, Andreas F H; Pichler, Irene; Polasek, Ozren; Posthuma, Danielle; Potter, Simon C; Pouta, Anneli; Province, Michael A; Psaty, Bruce M; Rathmann, Wolfgang; Rayner, Nigel W; Rice, Kenneth; Ripatti, Samuli; Rivadeneira, Fernando; Roden, Michael; Rolandsson, Olov; Sandbaek, Annelli; Sandhu, Manjinder; Sanna, Serena; Sayer, Avan Aihie; Scheet, Paul; Scott, Laura J; Seedorf, Udo; Sharp, Stephen J; Shields, Beverley; Sigurðsson, Gunnar; Sijbrands, Erik J G; Silveira, Angela; Simpson, Laila; Singleton, Andrew; Smith, Nicholas L; Sovio, Ulla; Swift, Amy; Syddall, Holly; Syvänen, Ann-Christine; Tanaka, Toshiko; Thorand, Barbara; Tichet, Jean; Tönjes, Anke; Tuomi, Tiinamaija; Uitterlinden, André G; van Dijk, Ko Willems; van Hoek, Mandy; Varma, Dhiraj; Visvikis-Siest, Sophie; Vitart, Veronique; Vogelzangs, Nicole; Waeber, Gérard; Wagner, Peter J; Walley, Andrew; Walters, G Bragi; Ward, Kim L; Watkins, Hugh; Weedon, Michael N; Wild, Sarah H; Willemsen, Gonneke; Witteman, Jaqueline C M; Yarnell, John W G; Zeggini, Eleftheria; Zelenika, Diana; Zethelius, Björn; Zhai, Guangju; Zhao, Jing Hua; Zillikens, M Carola; Borecki, Ingrid B; Loos, Ruth J F; Meneton, Pierre; Magnusson, Patrik K E; Nathan, David M; Williams, Gordon H; Hattersley, Andrew T; Silander, Kaisa; Salomaa, Veikko; Smith, George Davey; Bornstein, Stefan R; Schwarz, Peter; Spranger, Joachim; Karpe, Fredrik; Shuldiner, Alan R; Cooper, Cyrus; Dedoussis, George V; Serrano-Ríos, Manuel; Morris, Andrew D; Lind, Lars; Palmer, Lyle J; Hu, Frank B.; Franks, Paul W; Ebrahim, Shah; Marmot, Michael; Kao, W H Linda; Pankow, James S; Sampson, Michael J; Kuusisto, Johanna; Laakso, Markku; Hansen, Torben; Pedersen, Oluf; Pramstaller, Peter Paul; Wichmann, H Erich; Illig, Thomas; Rudan, Igor; Wright, Alan F; Stumvoll, Michael; Campbell, Harry; Wilson, James F; Hamsten, Anders; Bergman, Richard N; Buchanan, Thomas A; Collins, Francis S; Mohlke, Karen L; Tuomilehto, Jaakko; Valle, Timo T; Altshuler, David; Rotter, Jerome I; Siscovick, David S; Penninx, Brenda W J H; Boomsma, Dorret; Deloukas, Panos; Spector, Timothy D; Frayling, Timothy M; Ferrucci, Luigi; Kong, Augustine; Thorsteinsdottir, Unnur; Stefansson, Kari; van Duijn, Cornelia M; Aulchenko, Yurii S; Cao, Antonio; Scuteri, Angelo; Schlessinger, David; Uda, Manuela; Ruokonen, Aimo; Jarvelin, Marjo-Riitta; Waterworth, Dawn M; Vollenweider, Peter; Peltonen, Leena; Mooser, Vincent; Abecasis, Goncalo R; Wareham, Nicholas J; Sladek, Robert; Froguel, Philippe; Watanabe, Richard M; Meigs, James B; Groop, Leif; Boehnke, Michael; McCarthy, Mark I; Florez, Jose C; Barroso, Inês

    2010-01-01

    Circulating glucose levels are tightly regulated. To identify novel glycemic loci, we performed meta-analyses of 21 genome-wide associations studies informative for fasting glucose (FG), fasting insulin (FI) and indices of β-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 non-diabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with FG/HOMA-B and two associated with FI/HOMA-IR. These include nine new FG loci (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and FAM148B) and one influencing FI/HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB/TMEM195 with type 2 diabetes (T2D). Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify T2D risk loci, as well as loci that elevate FG modestly, but do not cause overt diabetes. PMID:20081858

  3. Rate-limiting hydrodynamic resistance for controlled reagent delivery for laboratory solution preparation.

    PubMed

    Oruganti, Prasad; Gratzl, Miklós

    2007-03-15

    The need for precise delivery of minute quantities of substances for solution preparation and other applications is well-known in research, clinical, industrial, and environmental settings. Currently available techniques for solution preparation in the laboratory include traditional transfer pipettes, micropipettes based on air displacement, and motorized devices using some form of a piston system. These techniques control the amount delivered by controlling the delivered volume. In this work we test the practicality of the concept of using a constant rate-limiting hydrodynamic resistance to achieve controlled reagent flow for solution preparation. The delivered amount is determined in this approach by time, pressure, flow resistance, or a combination of these. Good results are achieved comparable to conventional techniques without the use of fine mechanical instrumentation. This approach holds promise as an alternative to current methods of solution preparation and reagent delivery for routine laboratory use.

  4. Embedded resistance wire as a heating element for temperature control in microbioreactors

    NASA Astrophysics Data System (ADS)

    Nazrul Hisham Zainal Alam, Muhd; Schäpper, Daniel; Gernaey, Krist V.

    2010-05-01

    This paper presents the technical realization of a low-cost heating element consisting of a resistance wire in a microbioreactor, as well as the implementation and performance assessment of an on/off controller for temperature control of the microbioreactor content based on this heating element. The microbioreactor (working volume of 100 µL) is designed to work bubble-free, and is fabricated out of the polymers poly(methylmethacrylate) (PMMA) and poly(dimethylsiloxane) (PDMS). The temperature is measured with a Pt 100 sensor, and the resistance wires are embedded in the polymer such that they either surround the reactor chamber or are placed underneath it. The latter can achieve an even temperature distribution across the reactor chamber and direct heating of the reactor content. We show that an integrated resistance wire coupled to a simple on/off controller results in accurate temperature control of the reactor (±0.1 °C of the set point value) and provides a good disturbance rejection capability (corrective action for a sudden temperature drop of 2.5 °C at an operating temperature of 50 °C takes less than 30 s). Finally, we also demonstrate the workability of the established temperature control in a batch Saccharomyces cerevisiae cultivation in a microbioreactor.

  5. Transposon-induced mutations in two loci of Listeria monocytogenes serotype 1/2a result in phage resistance and lack of N-acetylglucosamine in the teichoic acid of the cell wall.

    PubMed

    Tran, H L; Fiedler, F; Hodgson, D A; Kathariou, S

    1999-11-01

    Teichoic acid-associated N-acetylglucosamine and rhamnose have been shown to serve as phage receptors in Listeria monocytogenes serotype 1/2a. We generated and characterized two single-copy Tn916DeltaE mutants which were resistant to phage A118 and several other serotype 1/2a-specific phages. In one mutant the insertion was immediately upstream of the recently identified ptsHI locus, which encodes two proteins of the phosphoenolpyruvate-dependent carbohydrate uptake system, whereas in the other the insertion was immediately upstream of an operon whose most distal gene was clpC, involved in stress responses and virulence. Transduction experiments confirmed the association of the phage-resistant phenotype of these mutants with the transposon insertion. Phage A118 resistance of the mutants could be attributed to inability of the phage to adsorb onto the mutant cells, and biochemical analysis of cell wall composition showed that the teichoic acids of both mutants were deficient in N-acetylglucosamine. Rhamnose and other teichoic acid and cell wall components were not affected.

  6. Undesirable Consequences of Insecticide Resistance following Aedes aegypti Control Activities Due to a Dengue Outbreak

    PubMed Central

    Maciel-de-Freitas, Rafael; Avendanho, Fernando Campos; Santos, Rosangela; Sylvestre, Gabriel; Araújo, Simone Costa; Lima, José Bento Pereira; Martins, Ademir Jesus; Coelho, Giovanini Evelim; Valle, Denise

    2014-01-01

    Background During a dengue outbreak with co-circulation of DENV-1 and -2 in the city of Boa Vista, one patient was diagnosed with DENV-4, a serotype supposed absent from Brazil for almost 30 years. The re-emergence of DENV-4 triggered the intensification of mechanical and chemical Aedes aegypti control activities in order to reduce vector density and avoid DENV-4 dissemination throughout the country. Methods/Principal Findings Vector control activities consisted of (a) source reduction, (b) application of diflubenzuron against larvae and (c) vehicle-mounted space spraying of 2% deltamethrin to eliminate adults. Control activity efficacy was monitored by comparing the infestation levels and the number of eggs collected in ovitraps before and after interventions, performed in 22 Boa Vista districts, covering an area of ∼80% of the city and encompassing 56,837 dwellings. A total of 94,325 containers were eliminated or treated with diflubenzuron. The most frequently positive containers were small miscellaneous receptacles, which corresponded to 59% of all positive breeding sites. Insecticide resistance to deltamethrin was assessed before, during and after interventions by dose-response bioassays adopting WHO-based protocols. The intense use of the pyrethroid increased fourfold the resistance ratio of the local Ae. aegypti population only six months after the beginning of vector control. Curiously, this trend was also observed in the districts in which no deltamethrin was applied by the public health services. On the other hand, changes in the resistance ratio to the organophosphate temephos seemed less influenced by insecticide in Boa Vista. Conclusions Despite the intense effort, mosquito infestation levels were only slightly reduced. Besides, the median number of eggs in ovitraps remained unaltered after control activity intensification. The great and rapid increase in pyrethroid resistance levels of natural Ae. aegypti populations is discussed in the context of

  7. Control of Dynamic Limb Motion Using Fatigue-Resistant Asynchronous Intrafascicular Multi-Electrode Stimulation

    PubMed Central

    Frankel, Mitchell A.; Mathews, V John; Clark, Gregory A.; Normann, Richard A.; Meek, Sanford G.

    2016-01-01

    Asynchronous intrafascicular multi-electrode stimulation (aIFMS) of small independent populations of peripheral nerve motor axons can evoke selective, fatigue-resistant muscle forces. We previously developed a real-time proportional closed-loop control method for aIFMS generation of isometric muscle force and the present work extends and adapts this closed-loop controller to the more demanding task of dynamically controlling joint position in the presence of opposing joint torque. A proportional-integral-velocity controller, with integrator anti-windup strategies, was experimentally validated as a means to evoke motion about the hind-limb ankle joint of an anesthetized feline via aIFMS stimulation of fast-twitch plantar-flexor muscles. The controller was successful in evoking steps in joint position with 2.4% overshoot, 2.3-s rise time, 4.5-s settling time, and near-zero steady-state error. Controlled step responses were consistent across changes in step size, stable against external disturbances, and reliable over time. The controller was able to evoke smooth eccentric motion at joint velocities up to 8 deg./s, as well as sinusoidal trajectories with frequencies up to 0.1 Hz, with time delays less than 1.5 s. These experiments provide important insights toward creating a robust closed-loop aIFMS controller that can evoke precise fatigue-resistant motion in paralyzed individuals, despite the complexities introduced by aIFMS. PMID:27679557

  8. Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine

    PubMed Central

    Gormley, Padhraig; Anttila, Verneri; Winsvold, Bendik S; Palta, Priit; Esko, Tonu; Pers, Tune H.; Farh, Kai-How; Cuenca-Leon, Ester; Muona, Mikko; Furlotte, Nicholas A; Kurth, Tobias; Ingason, Andres; McMahon, George; Ligthart, Lannie; Terwindt, Gisela M; Kallela, Mikko; Freilinger, Tobias M; Ran, Caroline; Gordon, Scott G; Stam, Anine H; Steinberg, Stacy; Borck, Guntram; Koiranen, Markku; Quaye, Lydia; Adams, Hieab HH; Lehtimäki, Terho; Sarin, Antti-Pekka; Wedenoja, Juho; Hinds, David A; Buring, Julie E; Schürks, Markus; Ridker, Paul M; Hrafnsdottir, Maria Gudlaug; Stefansson, Hreinn; Ring, Susan M; Hottenga, Jouke-Jan; Penninx, Brenda WJH; Färkkilä, Markus; Artto, Ville; Kaunisto, Mari; Vepsäläinen, Salli; Malik, Rainer; Heath, Andrew C; Madden, Pamela A F; Martin, Nicholas G; Montgomery, Grant W; Kurki, Mitja I; Kals, Mart; Mägi, Reedik; Pärn, Kalle; Hämäläinen, Eija; Huang, Hailiang; Byrnes, Andrea E; Franke, Lude; Huang, Jie; Stergiakouli, Evie; Lee, Phil H; Sandor, Cynthia; Webber, Caleb; Cader, Zameel; Muller-Myhsok, Bertram; Schreiber, Stefan; Meitinger, Thomas; Eriksson, Johan G; Salomaa, Veikko; Heikkilä, Kauko; Loehrer, Elizabeth; Uitterlinden, Andre G; Hofman, Albert; van Duijn, Cornelia M; Cherkas, Lynn; Pedersen, Linda M.; Stubhaug, Audun; Nielsen, Christopher S; Männikkä, Minna; Mihailov, Evelin; Milani, Lili; Göbel, Hartmut; Esserlind, Ann-Louise; Christensen, Anne Francke; Hansen, Thomas Folkmann; Werge, Thomas; Kaprio, Jaakko; Aromaa, Arpo J; Raitakari, Olli; Ikram, M Arfan; Spector, Tim; Järvelin, Marjo-Riitta; Metspalu, Andres; Kubisch, Christian; Strachan, David P; Ferrari, Michel D; Belin, Andrea C; Dichgans, Martin; Wessman, Maija; van den Maagdenberg, Arn MJM; Zwart, John-Anker; Boomsma, Dorret I; Smith, George Davey; Stefansson, Kari; Eriksson, Nicholas; Daly, Mark J; Neale, Benjamin M; Olesen, Jes; Chasman, Daniel I; Nyholt, Dale R; Palotie, Aarno

    2017-01-01

    Migraine is a debilitating neurological disorder affecting around 1 in 7 people worldwide, but its molecular mechanisms remain poorly understood. Some debate exists over whether migraine is a disease of vascular dysfunction or a result of neuronal dysfunction with secondary vascular changes. Genome-wide association (GWA) studies have thus far identified 13 independent loci associated with migraine. To identify new susceptibility loci, we performed the largest genetic study of migraine to date, comprising 59,674 cases and 316,078 controls from 22 GWA studies. We identified 44 independent single nucleotide polymorphisms (SNPs) significantly associated with migraine risk (P < 5 × 10−8) that map to 38 distinct genomic loci, including 28 loci not previously reported and the first locus identified on chromosome X. In subsequent computational analyses, the identified loci showed enrichment for genes expressed in vascular and smooth muscle tissues, consistent with a predominant theory of migraine that highlights vascular etiologies. PMID:27322543

  9. Controlling the Resistive Switching Behavior in Starch-Based Flexible Biomemristors.

    PubMed

    Raeis-Hosseini, Niloufar; Lee, Jang-Sik

    2016-03-23

    Implementation of biocompatible materials in resistive switching memory (ReRAM) devices provides opportunities to use them in biomedical applications. We demonstrate a robust, nonvolatile, flexible, and transparent ReRAM based on potato starch. We also introduce a biomolecular memory device that has a starch-chitosan composite layer. The ReRAM behavior can be controlled by mixing starch with chitosan in the resistive switching layer. Whereas starch-based biomemory devices which show abrupt changes in current level; the memory device with mixed biopolymers undergoes gradual changes. Both devices exhibit uniform and robust programmable memory properties for nonvolatile memory applications. The explicated source of the bipolar resistive switching behavior is assigned to formation and rupture of carbon-rich filaments. The gradual set/reset behavior in the memory device based on a starch-chitosan mixture makes it suitable for use in neuromorphic devices.

  10. Functional implications of disease-specific variants in loci jointly associated with coeliac disease and rheumatoid arthritis

    PubMed Central

    Gutierrez-Achury, Javier; Zorro, Maria Magdalena; Ricaño-Ponce, Isis; Zhernakova, Daria V.; Diogo, Dorothée; Raychaudhuri, Soumya; Franke, Lude; Trynka, Gosia; Wijmenga, Cisca; Zhernakova, Alexandra

    2016-01-01

    Hundreds of genomic loci have been associated with a significant number of immune-mediated diseases, and a large proportion of these associated loci are shared among traits. Both the molecular mechanisms by which these loci confer disease susceptibility and the extent to which shared loci are implicated in a common pathogenesis are unknown. We therefore sought to dissect the functional components at loci shared between two autoimmune diseases: coeliac disease (CeD) and rheumatoid arthritis (RA). We used a cohort of 12 381 CeD cases and 7827 controls, and another cohort of 13 819 RA cases and 12 897 controls, all genotyped with the Immunochip platform. In the joint analysis, we replicated 19 previously identified loci shared by CeD and RA and discovered five new non-HLA loci shared by CeD and RA. Our fine-mapping results indicate that in nine of 24 shared loci the associated variants are distinct in the two diseases. Using cell-type-specific histone markers, we observed that loci which pointed to the same variants in both diseases were enriched for marks of promoters active in CD14+ and CD34+ immune cells (P < 0.001), while loci pointing to distinct variants in one of the two diseases showed enrichment for marks of more specialized cell types, like CD4+ regulatory T cells in CeD (P < 0.0001) compared with Th17 and CD15+ in RA (P = 0.0029). PMID:26546613

  11. Control of Pyrethroid-Resistant Chagas Disease Vectors with Entomopathogenic Fungi

    PubMed Central

    Pedrini, Nicolás; Mijailovsky, Sergio J.; Girotti, Juan R.; Stariolo, Raúl; Cardozo, Rubén M.; Gentile, Alberto; Juárez, M. Patricia

    2009-01-01

    Background Triatoma infestans-mediated transmission of Tripanosoma cruzi, the causative agent of Chagas disease, remains as a major health issue in southern South America. Key factors of T. infestans prevalence in specific areas of the geographic Gran Chaco region—which extends through northern Argentina, Bolivia, and Paraguay—are both recurrent reinfestations after insecticide spraying and emerging pyrethroid-resistance over the past ten years. Among alternative control tools, the pathogenicity of entomopathogenic fungi against triatomines is already known; furthermore, these fungi have the ability to fully degrade hydrocarbons from T. infestans cuticle and to utilize them as fuel and for incorporation into cellular components. Methodology and Findings Here we provide evidence of resistance-related cuticle differences; capillary gas chromatography coupled to mass spectrometry analyses revealed that pyrethroid-resistant bugs have significantly larger amounts of surface hydrocarbons, peaking 56.2±6.4% higher than susceptible specimens. Also, a thicker cuticle was detected by scanning electron microscopy (32.1±5.9 µm and 17.8±5.4 µm for pyrethroid-resistant and pyrethroid-susceptible, respectively). In laboratory bioassays, we showed that the virulence of the entomopathogenic fungi Beauveria bassiana against T. infestans was significantly enhanced after fungal adaptation to grow on a medium containing insect-like hydrocarbons as the carbon source, regardless of bug susceptibility to pyrethroids. We designed an attraction-infection trap based on manipulating T. infestans behavior in order to facilitate close contact with B. bassiana. Field assays performed in rural village houses infested with pyrethroid-resistant insects showed 52.4% bug mortality. Using available mathematical models, we predicted that further fungal applications could eventually halt infection transmission. Conclusions This low cost, low tech, ecologically friendly methodology could help in

  12. Modeling and Simulation of Resistive Wall Mode Control In DIII-D

    NASA Astrophysics Data System (ADS)

    Walker, M. L.; Humphreys, D. A.; Jensen, T. H.; Leuer, J. A.; Nerem, A.; Strait, E. J.; Garofalo, A. M.

    2001-10-01

    Detailed dynamic response models have been developed for all relevant subsystems comprising the DIII-D resistive wall mode (RWM) closed loop control system. These include the switching power amplifiers (SPA), digital plasma control system (PCS), acquisition and control circuitry, and a fully toroidal model of plasma/vessel dynamics based on specification of the marginal wall position from stability codes such as GATO and DCON. These models have been validated with experimental data, including open-loop excitation of the SPA, PCS, and vacuum vessel dynamic responses, and measurement of the growth rate and mode structure of the unstable plasma. These models are incorporated into a closed-loop control simulation to investigate the control limitations which are due to realistic power supply responses. Consequences of and approaches to the intrinsically multivariable RWM control problem are also investigated.

  13. Passive microfluidic control of two merging streams by capillarity and relative flow resistance.

    PubMed

    Kim, Sung-Jin; Lim, Yong Taik; Yang, Haesik; Shin, Yong Beom; Kim, Kyuwon; Lee, Dae-Sik; Park, Se Ho; Kim, Youn Tae

    2005-10-01

    In the progress of microfluidic devices, a simple and precise control of multiple streams has been essential for complex microfluidic networks. Consequently, microfluidic devices, which have a simple structure, typically use external energy sources to control the multiple streams. Here, we propose a pure passive scheme that uses capillarity without using external force or external regulation to control the merging of two streams and even to regulate their volumetric flow rate (VFR). We accomplish this process by controlling the geometry of two inlets and a junction, and by regulating the hydrophilicity of a substrate. Additionally, we use the relative flow resistance to control the VFR ratio of the merged two streams. Our results will significantly simplify the control of multiple streams without sacrificing precision.

  14. Resistance Training and Executive Functions: A 12-Month Randomised Controlled Trial

    PubMed Central

    Liu-Ambrose, Teresa; Nagamatsu, Lindsay S; Graf, Peter; Beattie, B Lynn; Ashe, Maureen C; Handy, Todd C

    2012-01-01

    BACKGROUND Cognitive decline among seniors is a pressing health care issue. Specific exercise training may combat cognitive decline. We compared the effect of once-weekly and twice-weekly resistance training with twice-weekly balance and tone exercise training on the performance of executive cognitive functions in senior women. METHODS In this single-blinded randomised trial, 155 community-dwelling women aged 65 to 75 years old living in Vancouver, Canada were randomly allocated to once-weekly resistance training (n=54), twice-weekly resistance training (n=52), or to twice-weekly balance and tone training (i.e., control group) (n=49). Primary outcome measure was performance on the Stroop Test, an executive cognitive test of selective attention and conflict resolution. Secondary outcomes of executive cognitive functions included set shifting as measured by the Trail Making Tests (Part A & B) and working memory as assessed by verbal digits forward and backward tests. Gait speed, muscular function, and whole brain volume were also secondary outcome measures. RESULTS Both resistance training groups significantly improved their performance on the Stroop Test compared with those in the balance and tone group (p≤0.03). Specifically, task performance improved by 12.6% and 10.9% in the once-weekly and twice-weekly resistance training groups respectively; it deteriorated by 0.5% in the balance and tone group. Enhanced selective attention and conflict resolution was significantly associated with increased gait speed. Also, both resistance training groups demonstrated reductions in whole brain volume compared with the balance and tone group at the end of the study (p≤0.03). CONCLUSIONS Twelve months of once-weekly or twice-weekly resistance training benefited the executive cognitive function of selective attention and conflict resolution among senior women. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT00426881 PMID:20101012

  15. Superior Inhibitory Control and Resistance to Mental Fatigue in Professional Road Cyclists

    PubMed Central

    Menaspà, Paolo; Hennessey, Tom; Marcora, Samuele; Keegan, Richard; Thompson, Kevin G.; Martin, David; Halson, Shona; Rattray, Ben

    2016-01-01

    Purpose Given the important role of the brain in regulating endurance performance, this comparative study sought to determine whether professional road cyclists have superior inhibitory control and resistance to mental fatigue compared to recreational road cyclists. Methods After preliminary testing and familiarization, eleven professional and nine recreational road cyclists visited the lab on two occasions to complete a modified incongruent colour-word Stroop task (a cognitive task requiring inhibitory control) for 30 min (mental exertion condition), or an easy cognitive task for 10 min (control condition) in a randomized, counterbalanced cross-over order. After each cognitive task, participants completed a 20-min time trial on a cycle ergometer. During the time trial, heart rate, blood lactate concentration, and rating of perceived exertion (RPE) were recorded. Results The professional cyclists completed more correct responses during the Stroop task than the recreational cyclists (705±68 vs 576±74, p = 0.001). During the time trial, the recreational cyclists produced a lower mean power output in the mental exertion condition compared to the control condition (216±33 vs 226±25 W, p = 0.014). There was no difference between conditions for the professional cyclists (323±42 vs 326±35 W, p = 0.502). Heart rate, blood lactate concentration, and RPE were not significantly different between the mental exertion and control conditions in both groups. Conclusion The professional cyclists exhibited superior performance during the Stroop task which is indicative of stronger inhibitory control than the recreational cyclists. The professional cyclists also displayed a greater resistance to the negative effects of mental fatigue as demonstrated by no significant differences in perception of effort and time trial performance between the mental exertion and control conditions. These findings suggest that inhibitory control and resistance to mental fatigue may contribute to

  16. Data quality control methodologies for large, non-conventional DC resistivity datasets

    NASA Astrophysics Data System (ADS)

    Mitchell, Michael A.; Oldenburg, Douglas W.

    2016-12-01

    With developments in instrumentation and computational resources, the collection of large, non-conventional DC resistivity datasets has become commonplace. While the increased data content of these large datasets can significantly improve the resolution of inverse models, these datasets also present challenges for standard data quality control (QC) methodologies. Standard QC methodologies for DC resistivity datasets typically rely on our ability to decompose the dataset into 2D lines and/or reciprocal measurements. Non-conventional electrode geometries and the cost of collecting a large number of reciprocal measurements can severely limit the applicability of standard DC resistivity QC methodologies. To address these limitations, we developed a more generalized data QC methodology which utilizes statistical analysis and classification tools. The merit of this methodology is illustrated using a field dataset collected in an underground potash mine and several synthetic examples. Results from these applications show that the methodology has the ability to identify and characterize highly noise-contaminated data from a number of different sources. The flexibility of the 4-stage methodology allows it be tailored to accommodate data from any type of DC resistivity survey and the use of statistical analysis and classification tools decreases the subjectivity of the process. Although this study focuses on the applicability of this methodology for DC resistivity data, it is potentially applicable to a variety of geophysical surveys.

  17. Major QTLs Control Resistance to Rice Hoja Blanca Virus and Its Vector Tagosodes orizicolus

    PubMed Central

    Romero, Luz E.; Lozano, Ivan; Garavito, Andrea; Carabali, Silvio J.; Triana, Monica; Villareal, Natalia; Reyes, Luis; Duque, Myriam C.; Martinez, César P.; Calvert, Lee; Lorieux, Mathias

    2013-01-01

    Rice hoja blanca (white leaf) disease can cause severe yield losses in rice in the Americas. The disease is caused by the rice hoja blanca virus (RHBV), which is transmitted by the planthopper vector Tagosodes orizicolus. Because classical breeding schemes for this disease rely on expensive, time-consuming screenings, there is a need for alternatives such as marker-aided selection. The varieties Fedearroz 2000 and Fedearroz 50, which are resistant to RHBV and to the feeding damage caused by T. orizicolus, were crossed with the susceptible line WC366 to produce segregating F2:3 populations. The F3 families were scored for their resistance level to RHBV and T. orizicolus. The F2:3 lines of both crosses were genotyped using microsatellite markers. One major QTL on the short arm of chromosome 4 was identified for resistance to RHBV in the two populations. Two major QTL on chromosomes 5 and 7 were identified for resistance to T. orizicolus in the Fd2000 × WC366 and Fd50 × WC366 crosses, respectively. This comparative study using two distinct rice populations allowed for a better understanding of how the resistance to RHBV and its vector are controlled genetically. Simple marker-aided breeding schemes based on QTL information can be designed to improve rice germplasm to reduce losses caused by this important disease. PMID:24240781

  18. Major QTLs control resistance to rice hoja blanca virus and its vector Tagosodes orizicolus.

    PubMed

    Romero, Luz E; Lozano, Ivan; Garavito, Andrea; Carabali, Silvio J; Triana, Monica; Villareal, Natalia; Reyes, Luis; Duque, Myriam C; Martinez, César P; Calvert, Lee; Lorieux, Mathias

    2014-01-10

    Rice hoja blanca (white leaf) disease can cause severe yield losses in rice in the Americas. The disease is caused by the rice hoja blanca virus (RHBV), which is transmitted by the planthopper vector Tagosodes orizicolus. Because classical breeding schemes for this disease rely on expensive, time-consuming screenings, there is a need for alternatives such as marker-aided selection. The varieties Fedearroz 2000 and Fedearroz 50, which are resistant to RHBV and to the feeding damage caused by T. orizicolus, were crossed with the susceptible line WC366 to produce segregating F2:3 populations. The F3 families were scored for their resistance level to RHBV and T. orizicolus. The F2:3 lines of both crosses were genotyped using microsatellite markers. One major QTL on the short arm of chromosome 4 was identified for resistance to RHBV in the two populations. Two major QTL on chromosomes 5 and 7 were identified for resistance to T. orizicolus in the Fd2000 × WC366 and Fd50 × WC366 crosses, respectively. This comparative study using two distinct rice populations allowed for a better understanding of how the resistance to RHBV and its vector are controlled genetically. Simple marker-aided breeding schemes based on QTL information can be designed to improve rice germplasm to reduce losses caused by this important disease.

  19. Joint QTL analyses for partial resistance to Phytophthora sojae using six nested inbred populations with heterogeneous conditions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Partial resistance to Phytophthora sojae in soybean is controlled by multiple quantitative trait loci (QTL). With traditional QTL mapping approaches, power to detect these QTL, frequently of small effect, can be limited by population size. Joint linkage QTL analysis of nested recombinant inbred li...

  20. Tuning resistance states by thickness control in an electroforming-free nanometallic complementary resistance random access memory

    SciTech Connect

    Yang, Xiang; Lu, Yang; Lee, Jongho; Chen, I-Wei

    2016-01-04

    Tuning low resistance state is crucial for resistance random access memory (RRAM) that aims to achieve optimal read margin and design flexibility. By back-to-back stacking two nanometallic bipolar RRAMs with different thickness into a complementary structure, we have found that its low resistance can be reliably tuned over several orders of magnitude. Such high tunability originates from the exponential thickness dependence of the high resistance state of nanometallic RRAM, in which electron wave localization in a random network gives rise to the unique scaling behavior. The complementary nanometallic RRAM provides electroforming-free, multi-resistance-state, sub-100 ns switching capability with advantageous characteristics for memory arrays.

  1. Sunflower Resistance to Broomrape (Orobanche cumana) Is Controlled by Specific QTLs for Different Parasitism Stages.

    PubMed

    Louarn, Johann; Boniface, Marie-Claude; Pouilly, Nicolas; Velasco, Leonardo; Pérez-Vich, Begoña; Vincourt, Patrick; Muños, Stéphane

    2016-01-01

    Orobanche cumana (sunflower broomrape) is an obligatory and non-photosynthetic root parasitic plant that specifically infects the sunflower. It is located in Europe and in Asia, where it can cause yield losses of over 80%. More aggressive races have evolved, mainly around the Black Sea, and broomrape can rapidly spread to new areas. Breeding for resistance seems to be the most efficient and sustainable approach to control broomrape infestation. In our study, we used a population of 101 recombinant inbred lines (RILs), derived from a cross between the two lines HA89 and LR1 (a line derived from an interspecific cross with Helianthus debilis). Rhizotrons, pots and field experiments were used to characterize all RILs for their resistance to O. cumana race F parasitism at three post vascular connection life stages: (i) early attachment of the parasite to the sunflower roots, (ii) young tubercle and (iii) shoot emergence. In addition, RIL resistance to race G at young tubercle development stage was evaluated in pots. The entire population was genotyped, and QTLs were mapped. Different QTLs were identified for each race (F from Spain and G from Turkey) and for the three stages of broomrape development. The results indicate that there are several quantitative resistance mechanisms controlling the infection by O. cumana that can be used in sunflower breeding.

  2. Alkali- and Sulfur-Resistant Tungsten-Based Catalysts for NOx Emissions Control.

    PubMed

    Huang, Zhiwei; Li, Hao; Gao, Jiayi; Gu, Xiao; Zheng, Li; Hu, Pingping; Xin, Ying; Chen, Junxiao; Chen, Yaxin; Zhang, Zhaoliang; Chen, Jianmin; Tang, Xingfu

    2015-12-15

    The development of catalysts with simultaneous resistance to alkalis and sulfur poisoning is of great importance for efficiently controlling NOx emissions using the selective catalytic reduction of NOx with NH3 (SCR), because the conventional V2O5/WO3-TiO2 catalysts often suffer severe deactivation by alkalis. Here, we support V2O5 on a hexagonal WO3 (HWO) to develop a V2O5/HWO catalyst, which has exceptional resistance to alkali and sulfur poisoning in the SCR reactions. A 350 μmol g(-1) K(+) loading and the presence of 1,300 mg m(-3) SO2 do not almost influence the SCR activity of the V2O5/HWO catalyst, and under the same conditions, the conventional V2O5/WO3-TiO2 catalysts completely lost the SCR activity within 4 h. The strong resistance to alkali and sulfur poisoning of the V2O5/HWO catalysts mainly originates from the hexagonal structure of the HWO. The HWO allows the V2O5 to be highly dispersed on the external surfaces for catalyzing the SCR reactions and has the relatively smooth surfaces and the size-suitable tunnels specifically for alkalis' diffusion and trapping. This work provides a useful strategy to develop SCR catalysts with exceptional resistance to alkali and sulfur poisoning for controlling NOx emissions from the stationary source and the mobile source.

  3. Sunflower Resistance to Broomrape (Orobanche cumana) Is Controlled by Specific QTLs for Different Parasitism Stages

    PubMed Central

    Louarn, Johann; Boniface, Marie-Claude; Pouilly, Nicolas; Velasco, Leonardo; Pérez-Vich, Begoña; Vincourt, Patrick; Muños, Stéphane

    2016-01-01

    Orobanche cumana (sunflower broomrape) is an obligatory and non-photosynthetic root parasitic plant that specifically infects the sunflower. It is located in Europe and in Asia, where it can cause yield losses of over 80%. More aggressive races have evolved, mainly around the Black Sea, and broomrape can rapidly spread to new areas. Breeding for resistance seems to be the most efficient and sustainable approach to control broomrape infestation. In our study, we used a population of 101 recombinant inbred lines (RILs), derived from a cross between the two lines HA89 and LR1 (a line derived from an interspecific cross with Helianthus debilis). Rhizotrons, pots and field experiments were used to characterize all RILs for their resistance to O. cumana race F parasitism at three post vascular connection life stages: (i) early attachment of the parasite to the sunflower roots, (ii) young tubercle and (iii) shoot emergence. In addition, RIL resistance to race G at young tubercle development stage was evaluated in pots. The entire population was genotyped, and QTLs were mapped. Different QTLs were identified for each race (F from Spain and G from Turkey) and for the three stages of broomrape development. The results indicate that there are several quantitative resistance mechanisms controlling the infection by O. cumana that can be used in sunflower breeding. PMID:27242810

  4. Reduced efficacy of pyrethroid space sprays for dengue control in an area of Martinique with pyrethroid resistance.

    PubMed

    Marcombe, Sébastien; Carron, Alexandre; Darriet, Frédéric; Etienne, Manuel; Agnew, Philip; Tolosa, Michel; Yp-Tcha, Marie Michèle; Lagneau, Christophe; Yébakima, André; Corbel, Vincent

    2009-05-01

    In the Caribbean, insecticide resistance is widely developed in Aedes aegypti and represents a serious obstacle for dengue vector control. The efficacy of pyrethroid and organophosphate ultra-low volume space sprays was investigated in Martinique where Ae. aegypti has been shown to be resistant to conventional insecticides. In the laboratory, a wild-field caught population showed high levels of resistance to deltamethrin, organophosphate (naled), and pyrethrum. Simulated-field trials showed that this resistance can strongly reduce the knock-down effect and mortality of deltamethrin and synergized pyrethrins when applied by thermal-fogging. Conversely, the efficacy of naled was high against insecticide-resistant mosquitoes. Chemical analyses of nettings exposed to the treatments showed a decrease in residues over distance from release for the pyrethroids, and naled was not detected. This finding has important implications for dengue vector control and emphasizes the need to develop innovative strategies to maintain effective control of resistant Ae. aegypti populations.

  5. Analysis of the features of 45 identified CRISPR loci in 32 Staphylococcus aureus.

    PubMed

    Yang, Siyu; Liu, Jing; Shao, Fuye; Wang, Pengfei; Duan, Guangcai; Yang, Haiyan

    2015-08-28

    Staphylococcus aureus (S. aureus) is a common pathogen that can cause serious infections, even death. Because of the horizontal gene transfer (HGT) of antibiotic resistance genes, the drug resistant condition is becoming increasingly prevalent. Recently, an adaptive immunity system, named clustered regularly interspaced short palindromic repeats (CRISPR), was discovered and demonstrated to confer a defense against foreign invading elements that may carry the antibiotic resistance genes. In this study, we reveal the features of 45 identified CRISPR loci and the CRISPR associated gene (Cas) in 32 S. aureus strains from CRISPR database. Five spacers of S. aureus 08BA02176 and MSHR1132 were homologous with foreign genetic sequences from phages or plasmids, even containing a spacer sequence identical to part of some phages' genomes containing lukPV gene that encodes the PVL toxin. Many S. aureus strains with the same CRISPR type shared the same MLST type. CRISPR loci that had 3 or more similar protein loci mostly belonged to the same CRISPR type. We came to the conclusion that the CRISPR/Cas of strains 08BA02176 and MSHR1132 were inherited from a common ancestor or recombined from Staphylococcus lugdunensis. CRISPR loci can be mobilized and can transfer among different but closely related species, and the same types of MLST strains exhibit a higher affinity to the same types of CRISPR loci. Bacteriophages may be the predominant challenge facing S. aureus. The CRISPR/Cas structure may limit the transmission of bacterial virulence among S. aureus.

  6. Impaired baroreflex control of vascular resistance and heart rate in acute myocardial infarction.

    PubMed Central

    Imaizumi, T; Takeshita, A; Makino, N; Ashihara, T; Yamamoto, K; Nakamura, M

    1984-01-01

    The baroreflex control of vascular resistance and heart rate was studied in 11 patients to determine whether it is impaired in patients with acute myocardial infarction. Reflex forearm vasoconstriction in response to lower body negative pressure at 40 mm Hg was less in the early convalescent phase (mean seven days) than in the late convalescent phase (mean 41 days). Pressor as well as vasoconstricting responses to the cold pressor test did not differ between the early and late convalescent phases. The slope of the regression line relating systolic blood pressure and the RR interval during a transient rise in blood pressure produced by intravenous phenylephrine was appreciably reduced in the early convalescent phase of myocardial infarction. These results suggest that baroreflex control of vascular resistance and heart rate is impaired in patients with acute myocardial infarction. PMID:6477780

  7. Flow resistance dynamics in step-pool stream channels: 1. Large woody debris and controls on total resistance

    USGS Publications Warehouse

    Wilcox, A.C.; Wohl, E.E.

    2006-01-01

    Flow resistance dynamics in step-pool channels were investigated through physical modeling using a laboratory flume. Variables contributing to flow resistance in step-pool channels were manipulated in order to measure the effects of various large woody debris (LWD) configurations, steps, grains, discharge, and slope on total flow resistance. This entailed nearly 400 flume runs, organized into a series of factorial experiments. Factorial analyses of variance indicated significant two-way and three-way interaction effects between steps, grains, and LWD, illustrating the complexity of flow resistance in these channels. Interactions between steps and LWD resulted in substantially greater flow resistance for steps with LWD than for steps lacking LWD. LWD position contributed to these interactions, whereby LWD pieces located near the lip of steps, analogous to step-forming debris in natural channels, increased the effective height of steps and created substantially higher flow resistance than pieces located farther upstream on step treads. Step geometry and LWD density and orientation also had highly significant effects on flow resistance. Flow resistance dynamics and the resistance effect of bed roughness configurations were strongly discharge-dependent; discharge had both highly significant main effects on resistance and highly significant interactions with all other variables. Copyright 2006 by the American Geophysical Union.

  8. Preschoolers' motor and verbal self-control strategies during a resistance-to-temptation task.

    PubMed

    Manfra, Louis; Davis, Kelly D; Ducenne, Lesley; Winsler, Adam

    2014-01-01

    Although prior research has shown that young children exhibit enhanced self-control when they use verbal strategies provided through adult instructions, little work has examined the role of children's spontaneous verbalizations or motor behavior as strategies for enhancing self-control. The present study examined the usefulness of spontaneous verbal and motor strategies for 39 3- and 4-year-old children's ability to exercise self-control during a resistance-to-temptation task. After a 2-min play period, participants were asked by an experimenter not to touch an attractive train set while he was out of the room. Children were videotaped during the 3-min waiting period and videos were coded for frequency and duration of touches, motor movements, and verbalizations. Results indicated that self-control was improved by using both motor and verbal strategies. Children who were unable to resist touching the forbidden toy used limited motor or verbal strategies. These findings add to the growing literature demonstrating the positive role of verbalizations on cognitive control and draw attention to motor behaviors as additional strategies used by young children to exercise self-control.

  9. A shorter set reduces the loss of cardiac autonomic and baroreflex control after resistance exercise.

    PubMed

    Mayo, Xián; Iglesias-Soler, Eliseo; Carballeira-Fernández, Eduardo; Fernández-Del-Olmo, Miguel

    2016-11-01

    Set configuration may affect the recovery pattern of cardiac vagal autonomic and reflex modulation after a resistance exercise, since it is closely associated with intensity and volume and determines the metabolic involvement of the session. We tested the hypothesis that longer set configurations have a higher impact on cardiac autonomic control and baroreflex sensitivity compared with shorter set configurations. We studied the effects of three set configurations with the same components of work on the cardiac autonomic control and baroreflex sensitivity. Seventeen subjects performed one control session and three experimental sessions of a leg-press exercise with the same volume (40 repetitions), resting time (720 s) and intensity (10RM load): (a) 5 sets of 8 repetitions with 3 min of rest between sets (8S), (b) 10 sets of 4 repetitions with 80 s of rest between sets (4S) and (c) 40 sets of 1 repetition with 18.5 s of rest between each repetition (1S). Longer set configurations (8S and 4S) induced greater reductions of the vagal cardiac autonomic control and baroreflex sensitivity (p ≤ .001) compared with a shorter set configuration (1S). Also, 1S had non-significant reductions versus the control session (p > .05). These findings suggest that a shorter set configuration can reduce the impact of resistance exercise on the post-exercise cardiac vagal autonomic control and baroreflex sensitivity.

  10. Control of foliar pathogens of spring barley using a combination of resistance elicitors

    PubMed Central

    Walters, Dale R.; Havis, Neil D.; Paterson, Linda; Taylor, Jeanette; Walsh, David J.; Sablou, Cecile

    2014-01-01

    The ability of the resistance elicitors acibenzolar-S-methyl (ASM), β-aminobutyric acid (BABA), cis-jasmone (CJ), and a combination of the three products, to control infection of spring barley by Rhynchosporium commune was examined under glasshouse conditions. Significant control of R. commune was provided by ASM and CJ, but the largest reduction in infection was obtained with the combination of the three elicitors. This elicitor combination was found to up-regulate the expression of PR-1b, which is used as a molecular marker for systemic acquired resistance (SAR). However, the elicitor combination also down-regulated the expression of LOX2, a gene involved in the biosynthesis of jasmonic acid (JA). In field experiments over 3 consecutive years, the effects of the elicitor combination were influenced greatly by crop variety and by year. For example, the elicitor combination applied on its own provided significant control of powdery mildew (Blumeria graminis f.sp. hordei) and R. commune in 2009, whereas no control on either variety was observed in 2007. In contrast, treatments involving both the elicitor combination and fungicides provided disease control and yield increases which were equal to, and in some cases better than that provided by the best fungicide-only treatment. The prospects for the use of elicitor plus fungicide treatments to control foliar pathogens of spring barley in practice are discussed. PMID:24904629

  11. High-density genotyping of immune-related loci identifies new SLE risk variants in individuals with Asian ancestry.

    PubMed

    Sun, Celi; Molineros, Julio E; Looger, Loren L; Zhou, Xu-Jie; Kim, Kwangwoo; Okada, Yukinori; Ma, Jianyang; Qi, Yuan-Yuan; Kim-Howard, Xana; Motghare, Prasenjeet; Bhattarai, Krishna; Adler, Adam; Bang, So-Young; Lee, Hye-Soon; Kim, Tae-Hwan; Kang, Young Mo; Suh, Chang-Hee; Chung, Won Tae; Park, Yong-Beom; Choe, Jung-Yoon; Shim, Seung Cheol; Kochi, Yuta; Suzuki, Akari; Kubo, Michiaki; Sumida, Takayuki; Yamamoto, Kazuhiko; Lee, Shin-Seok; Kim, Young Jin; Han, Bok-Ghee; Dozmorov, Mikhail; Kaufman, Kenneth M; Wren, Jonathan D; Harley, John B; Shen, Nan; Chua, Kek Heng; Zhang, Hong; Bae, Sang-Cheol; Nath, Swapan K

    2016-03-01

    Systemic lupus erythematosus (SLE) has a strong but incompletely understood genetic architecture. We conducted an association study with replication in 4,478 SLE cases and 12,656 controls from six East Asian cohorts to identify new SLE susceptibility loci and better localize known loci. We identified ten new loci and confirmed 20 known loci with genome-wide significance. Among the new loci, the most significant locus was GTF2IRD1-GTF2I at 7q11.23 (rs73366469, Pmeta = 3.75 × 10(-117), odds ratio (OR) = 2.38), followed by DEF6, IL12B, TCF7, TERT, CD226, PCNXL3, RASGRP1, SYNGR1 and SIGLEC6. We identified the most likely functional variants at each locus by analyzing epigenetic marks and gene expression data. Ten candidate variants are known to alter gene expression in cis or in trans. Enrichment analysis highlights the importance of these loci in B cell and T cell biology. The new loci, together with previously known loci, increase the explained heritability of SLE to 24%. The new loci share functional and ontological characteristics with previously reported loci and are possible drug targets for SLE therapeutics.

  12. Antibiotic Resistance Surveillance and Control in the Mediterranean region: report of the ARMed Consensus Conference.

    PubMed

    Borg, Michael A; Cookson, Barry D; Zarb, Peter; Scicluna, Elizabeth A

    2009-10-22

    Antimicrobial resistance has become a global threat to effective health care delivery. This is particularly the case within the Mediterranean region, where data from recent studies suggests the situation to be particularly acute. A better knowledge base, as well as a collaborative effort, is therefore required to address this ever increasing challenge to effective patient care. Over its four-year period, the Antibiotic Resistance Surveillance and Control in the Mediterranean Region (ARMed) project investigated the epidemiology of antimicrobial resistance, as well as its contributory factors, in a number of countries in the southern and eastern Mediterranean region through the collection of comparable and validated data. The project culminated in a consensus conference held in Malta in November 2006. The conference provided a forum for expert delegates to agree on a number of priority strategic recommendations that would be relevant to resistance containment efforts in the region. There was general agreement on the need for surveillance and audit to underpin any intervention to tackle antimicrobial resistance, both to monitor changing epidemiological trends in critical pathogens as well as to identify antibiotic consumption practices and effectiveness of prevention and control of health care associated infections. In addition, the importance to convey these data to key users was also stressed in all workshops, as was better education and training of health care workers. The recommendations also made it clear that ownership of the problem needs to be improved throughout the region and that resources, both financial as well as human, must be allocated by the respective policy makers in order to combat it.

  13. Seven newly identified loci for autoimmune thyroid disease.

    PubMed

    Cooper, Jason D; Simmonds, Matthew J; Walker, Neil M; Burren, Oliver; Brand, Oliver J; Guo, Hui; Wallace, Chris; Stevens, Helen; Coleman, Gillian; Franklyn, Jayne A; Todd, John A; Gough, Stephen C L

    2012-12-01

    Autoimmune thyroid disease (AITD), including Graves' disease (GD) and Hashimoto's thyroiditis (HT), is one of the most common of the immune-mediated diseases. To further investigate the genetic determinants of AITD, we conducted an association study using a custom-made single-nucleotide polymorphism (SNP) array, the ImmunoChip. The SNP array contains all known and genotype-able SNPs across 186 distinct susceptibility loci associated with one or more immune-mediated diseases. After stringent quality control, we analysed 103 875 common SNPs (minor allele frequency >0.05) in 2285 GD and 462 HT patients and 9364 controls. We found evidence for seven new AITD risk loci (P < 1.12 × 10(-6); a permutation test derived significance threshold), five at locations previously associated and two at locations awaiting confirmation, with other immune-mediated diseases.

  14. High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis.

    PubMed

    Eyre, Steve; Bowes, John; Diogo, Dorothée; Lee, Annette; Barton, Anne; Martin, Paul; Zhernakova, Alexandra; Stahl, Eli; Viatte, Sebastien; McAllister, Kate; Amos, Christopher I; Padyukov, Leonid; Toes, Rene E M; Huizinga, Tom W J; Wijmenga, Cisca; Trynka, Gosia; Franke, Lude; Westra, Harm-Jan; Alfredsson, Lars; Hu, Xinli; Sandor, Cynthia; de Bakker, Paul I W; Davila, Sonia; Khor, Chiea Chuen; Heng, Khai Koon; Andrews, Robert; Edkins, Sarah; Hunt, Sarah E; Langford, Cordelia; Symmons, Deborah; Concannon, Pat; Onengut-Gumuscu, Suna; Rich, Stephen S; Deloukas, Panos; Gonzalez-Gay, Miguel A; Rodriguez-Rodriguez, Luis; Ärlsetig, Lisbeth; Martin, Javier; Rantapää-Dahlqvist, Solbritt; Plenge, Robert M; Raychaudhuri, Soumya; Klareskog, Lars; Gregersen, Peter K; Worthington, Jane

    2012-12-01

    Using the Immunochip custom SNP array, which was designed for dense genotyping of 186 loci identified through genome-wide association studies (GWAS), we analyzed 11,475 individuals with rheumatoid arthritis (cases) of European ancestry and 15,870 controls for 129,464 markers. We combined these data in a meta-analysis with GWAS data from additional independent cases (n = 2,363) and controls (n = 17,872). We identified 14 new susceptibility loci, 9 of which were associated with rheumatoid arthritis overall and five of which were specifically associated with disease that was positive for anticitrullinated peptide antibodies, bringing the number of confirmed rheumatoid arthritis risk loci in individuals of European ancestry to 46. We refined the peak of association to a single gene for 19 loci, identified secondary independent effects at 6 loci and identified association to low-frequency variants at 4 loci. Bioinformatic analyses generated strong hypotheses for the causal SNP at seven loci. This study illustrates the advantages of dense SNP mapping analysis to inform subsequent functional investigations.

  15. Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

    PubMed Central

    Couch, Fergus J.; Kuchenbaecker, Karoline B.; Michailidou, Kyriaki; Mendoza-Fandino, Gustavo A.; Nord, Silje; Lilyquist, Janna; Olswold, Curtis; Hallberg, Emily; Agata, Simona; Ahsan, Habibul; Aittomäki, Kristiina; Ambrosone, Christine; Andrulis, Irene L.; Anton-Culver, Hoda; Arndt, Volker; Arun, Banu K.; Arver, Brita; Barile, Monica; Barkardottir, Rosa B.; Barrowdale, Daniel; Beckmann, Lars; Beckmann, Matthias W.; Benitez, Javier; Blank, Stephanie V.; Blomqvist, Carl; Bogdanova, Natalia V.; Bojesen, Stig E.; Bolla, Manjeet K.; Bonanni, Bernardo; Brauch, Hiltrud; Brenner, Hermann; Burwinkel, Barbara; Buys, Saundra S.; Caldes, Trinidad; Caligo, Maria A.; Canzian, Federico; Carpenter, Jane; Chang-Claude, Jenny; Chanock, Stephen J.; Chung, Wendy K.; Claes, Kathleen B. M.; Cox, Angela; Cross, Simon S.; Cunningham, Julie M.; Czene, Kamila; Daly, Mary B.; Damiola, Francesca; Darabi, Hatef; de la Hoya, Miguel; Devilee, Peter; Diez, Orland; Ding, Yuan C.; Dolcetti, Riccardo; Domchek, Susan M.; Dorfling, Cecilia M.; dos-Santos-Silva, Isabel; Dumont, Martine; Dunning, Alison M.; Eccles, Diana M.; Ehrencrona, Hans; Ekici, Arif B.; Eliassen, Heather; Ellis, Steve; Fasching, Peter A.; Figueroa, Jonine; Flesch-Janys, Dieter; Försti, Asta; Fostira, Florentia; Foulkes, William D.; Friebel, Tara; Friedman, Eitan; Frost, Debra; Gabrielson, Marike; Gammon, Marilie D.; Ganz, Patricia A.; Gapstur, Susan M.; Garber, Judy; Gaudet, Mia M.; Gayther, Simon A.; Gerdes, Anne-Marie; Ghoussaini, Maya; Giles, Graham G.; Glendon, Gord; Godwin, Andrew K.; Goldberg, Mark S.; Goldgar, David E.; González-Neira, Anna; Greene, Mark H.; Gronwald, Jacek; Guénel, Pascal; Gunter, Marc; Haeberle, Lothar; Haiman, Christopher A.; Hamann, Ute; Hansen, Thomas V. O.; Hart, Steven; Healey, Sue; Heikkinen, Tuomas; Henderson, Brian E.; Herzog, Josef; Hogervorst, Frans B. L.; Hollestelle, Antoinette; Hooning, Maartje J.; Hoover, Robert N.; Hopper, John L.; Humphreys, Keith; Hunter, David J.; Huzarski, Tomasz; Imyanitov, Evgeny N.; Isaacs, Claudine; Jakubowska, Anna; James, Paul; Janavicius, Ramunas; Jensen, Uffe Birk; John, Esther M.; Jones, Michael; Kabisch, Maria; Kar, Siddhartha; Karlan, Beth Y.; Khan, Sofia; Khaw, Kay-Tee; Kibriya, Muhammad G.; Knight, Julia A.; Ko, Yon-Dschun; Konstantopoulou, Irene; Kosma, Veli-Matti; Kristensen, Vessela; Kwong, Ava; Laitman, Yael; Lambrechts, Diether; Lazaro, Conxi; Lee, Eunjung; Le Marchand, Loic; Lester, Jenny; Lindblom, Annika; Lindor, Noralane; Lindstrom, Sara; Liu, Jianjun; Long, Jirong; Lubinski, Jan; Mai, Phuong L.; Makalic, Enes; Malone, Kathleen E.; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Marme, Frederik; Martens, John W. M.; McGuffog, Lesley; Meindl, Alfons; Miller, Austin; Milne, Roger L.; Miron, Penelope; Montagna, Marco; Mazoyer, Sylvie; Mulligan, Anna M.; Muranen, Taru A.; Nathanson, Katherine L.; Neuhausen, Susan L.; Nevanlinna, Heli; Nordestgaard, Børge G.; Nussbaum, Robert L.; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I.; Olson, Janet E.; Osorio, Ana; Park, Sue K.; Peeters, Petra H.; Peissel, Bernard; Peterlongo, Paolo; Peto, Julian; Phelan, Catherine M.; Pilarski, Robert; Poppe, Bruce; Pylkäs, Katri; Radice, Paolo; Rahman, Nazneen; Rantala, Johanna; Rappaport, Christine; Rennert, Gad; Richardson, Andrea; Robson, Mark; Romieu, Isabelle; Rudolph, Anja; Rutgers, Emiel J.; Sanchez, Maria-Jose; Santella, Regina M.; Sawyer, Elinor J.; Schmidt, Daniel F.; Schmidt, Marjanka K.; Schmutzler, Rita K.; Schumacher, Fredrick; Scott, Rodney; Senter, Leigha; Sharma, Priyanka; Simard, Jacques; Singer, Christian F.; Sinilnikova, Olga M.; Soucy, Penny; Southey, Melissa; Steinemann, Doris; Stenmark-Askmalm, Marie; Stoppa-Lyonnet, Dominique; Swerdlow, Anthony; Szabo, Csilla I.; Tamimi, Rulla; Tapper, William; Teixeira, Manuel R.; Teo, Soo-Hwang; Terry, Mary B.; Thomassen, Mads; Thompson, Deborah; Tihomirova, Laima; Toland, Amanda E.; Tollenaar, Robert A. E. M.; Tomlinson, Ian; Truong, Thérèse; Tsimiklis, Helen; Teulé, Alex; Tumino, Rosario; Tung, Nadine; Turnbull, Clare; Ursin, Giski; van Deurzen, Carolien H. M.; van Rensburg, Elizabeth J.; Varon-Mateeva, Raymonda; Wang, Zhaoming; Wang-Gohrke, Shan; Weiderpass, Elisabete; Weitzel, Jeffrey N.; Whittemore, Alice; Wildiers, Hans; Winqvist, Robert; Yang, Xiaohong R.; Yannoukakos, Drakoulis; Yao, Song; Zamora, M Pilar; Zheng, Wei; Hall, Per; Kraft, Peter; Vachon, Celine; Slager, Susan; Chenevix-Trench, Georgia; Pharoah, Paul D. P.; Monteiro, Alvaro A. N.; García-Closas, Montserrat; Easton, Douglas F.

    2016-01-01

    Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10−8) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for ∼11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction. PMID:27117709

  16. Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer.

    PubMed

    Couch, Fergus J; Kuchenbaecker, Karoline B; Michailidou, Kyriaki; Mendoza-Fandino, Gustavo A; Nord, Silje; Lilyquist, Janna; Olswold, Curtis; Hallberg, Emily; Agata, Simona; Ahsan, Habibul; Aittomäki, Kristiina; Ambrosone, Christine; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Arun, Banu K; Arver, Brita; Barile, Monica; Barkardottir, Rosa B; Barrowdale, Daniel; Beckmann, Lars; Beckmann, Matthias W; Benitez, Javier; Blank, Stephanie V; Blomqvist, Carl; Bogdanova, Natalia V; Bojesen, Stig E; Bolla, Manjeet K; Bonanni, Bernardo; Brauch, Hiltrud; Brenner, Hermann; Burwinkel, Barbara; Buys, Saundra S; Caldes, Trinidad; Caligo, Maria A; Canzian, Federico; Carpenter, Jane; Chang-Claude, Jenny; Chanock, Stephen J; Chung, Wendy K; Claes, Kathleen B M; Cox, Angela; Cross, Simon S; Cunningham, Julie M; Czene, Kamila; Daly, Mary B; Damiola, Francesca; Darabi, Hatef; de la Hoya, Miguel; Devilee, Peter; Diez, Orland; Ding, Yuan C; Dolcetti, Riccardo; Domchek, Susan M; Dorfling, Cecilia M; Dos-Santos-Silva, Isabel; Dumont, Martine; Dunning, Alison M; Eccles, Diana M; Ehrencrona, Hans; Ekici, Arif B; Eliassen, Heather; Ellis, Steve; Fasching, Peter A; Figueroa, Jonine; Flesch-Janys, Dieter; Försti, Asta; Fostira, Florentia; Foulkes, William D; Friebel, Tara; Friedman, Eitan; Frost, Debra; Gabrielson, Marike; Gammon, Marilie D; Ganz, Patricia A; Gapstur, Susan M; Garber, Judy; Gaudet, Mia M; Gayther, Simon A; Gerdes, Anne-Marie; Ghoussaini, Maya; Giles, Graham G; Glendon, Gord; Godwin, Andrew K; Goldberg, Mark S; Goldgar, David E; González-Neira, Anna; Greene, Mark H; Gronwald, Jacek; Guénel, Pascal; Gunter, Marc; Haeberle, Lothar; Haiman, Christopher A; Hamann, Ute; Hansen, Thomas V O; Hart, Steven; Healey, Sue; Heikkinen, Tuomas; Henderson, Brian E; Herzog, Josef; Hogervorst, Frans B L; Hollestelle, Antoinette; Hooning, Maartje J; Hoover, Robert N; Hopper, John L; Humphreys, Keith; Hunter, David J; Huzarski, Tomasz; Imyanitov, Evgeny N; Isaacs, Claudine; Jakubowska, Anna; James, Paul; Janavicius, Ramunas; Jensen, Uffe Birk; John, Esther M; Jones, Michael; Kabisch, Maria; Kar, Siddhartha; Karlan, Beth Y; Khan, Sofia; Khaw, Kay-Tee; Kibriya, Muhammad G; Knight, Julia A; Ko, Yon-Dschun; Konstantopoulou, Irene; Kosma, Veli-Matti; Kristensen, Vessela; Kwong, Ava; Laitman, Yael; Lambrechts, Diether; Lazaro, Conxi; Lee, Eunjung; Le Marchand, Loic; Lester, Jenny; Lindblom, Annika; Lindor, Noralane; Lindstrom, Sara; Liu, Jianjun; Long, Jirong; Lubinski, Jan; Mai, Phuong L; Makalic, Enes; Malone, Kathleen E; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Marme, Frederik; Martens, John W M; McGuffog, Lesley; Meindl, Alfons; Miller, Austin; Milne, Roger L; Miron, Penelope; Montagna, Marco; Mazoyer, Sylvie; Mulligan, Anna M; Muranen, Taru A; Nathanson, Katherine L; Neuhausen, Susan L; Nevanlinna, Heli; Nordestgaard, Børge G; Nussbaum, Robert L; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I; Olson, Janet E; Osorio, Ana; Park, Sue K; Peeters, Petra H; Peissel, Bernard; Peterlongo, Paolo; Peto, Julian; Phelan, Catherine M; Pilarski, Robert; Poppe, Bruce; Pylkäs, Katri; Radice, Paolo; Rahman, Nazneen; Rantala, Johanna; Rappaport, Christine; Rennert, Gad; Richardson, Andrea; Robson, Mark; Romieu, Isabelle; Rudolph, Anja; Rutgers, Emiel J; Sanchez, Maria-Jose; Santella, Regina M; Sawyer, Elinor J; Schmidt, Daniel F; Schmidt, Marjanka K; Schmutzler, Rita K; Schumacher, Fredrick; Scott, Rodney; Senter, Leigha; Sharma, Priyanka; Simard, Jacques; Singer, Christian F; Sinilnikova, Olga M; Soucy, Penny; Southey, Melissa; Steinemann, Doris; Stenmark-Askmalm, Marie; Stoppa-Lyonnet, Dominique; Swerdlow, Anthony; Szabo, Csilla I; Tamimi, Rulla; Tapper, William; Teixeira, Manuel R; Teo, Soo-Hwang; Terry, Mary B; Thomassen, Mads; Thompson, Deborah; Tihomirova, Laima; Toland, Amanda E; Tollenaar, Robert A E M; Tomlinson, Ian; Truong, Thérèse; Tsimiklis, Helen; Teulé, Alex; Tumino, Rosario; Tung, Nadine; Turnbull, Clare; Ursin, Giski; van Deurzen, Carolien H M; van Rensburg, Elizabeth J; Varon-Mateeva, Raymonda; Wang, Zhaoming; Wang-Gohrke, Shan; Weiderpass, Elisabete; Weitzel, Jeffrey N; Whittemore, Alice; Wildiers, Hans; Winqvist, Robert; Yang, Xiaohong R; Yannoukakos, Drakoulis; Yao, Song; Zamora, M Pilar; Zheng, Wei; Hall, Per; Kraft, Peter; Vachon, Celine; Slager, Susan; Chenevix-Trench, Georgia; Pharoah, Paul D P; Monteiro, Alvaro A N; García-Closas, Montserrat; Easton, Douglas F; Antoniou, Antonis C

    2016-04-27

    Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for ∼11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.

  17. Design III with Marker Loci

    PubMed Central

    Cockerham, C. C.; Zeng, Z. B.

    1996-01-01

    Design III is an experimental design originally proposed by R. E. COMSTOCK and H. F. ROBINSON for estimating genetic variances and the average degree of dominance for quantitative trait loci (QTL) and has recently been extended for mapping QTL. In this paper, we first extend COMSTOCK and ROBINSON's analysis of variance to include linkage, two-locus epistasis and the use of F(3) parents. Then we develop the theory and statistical analysis of orthogonal contrasts and contrast X environment interaction for a single marker locus to characterize the effects of QTL. The methods are applied to the maize data of C. W. STUBER. The analyses strongly suggest that there are multiple linked QTL in many chromosomes for several traits examined. QTL effects are largely environment-independent for grain yield, ear height, plant height and ear leaf area and largely environment dependent for days to tassel, grain moisture and ear number. There is significant QTL epistasis. The results are generally in favor of the hypothesis of dominance of favorable genes to explain the observed heterosis in grain yield and other traits, although epistasis could also play an important role and overdominance at individual QTL level can not be ruled out. PMID:8807314

  18. Multidrug-resistant organisms in refugees: prevalences and impact on infection control in hospitals

    PubMed Central

    Heudorf, Ursel; Albert-Braun, Sabine; Hunfeld, Klaus-Peter; Birne, Franz-Ulrich; Schulze, Jörg; Strobel, Klaus; Petscheleit, Knut; Kempf, Volkhard A. J.; Brandt, Christian

    2016-01-01

    Introduction: The refugee crisis is a great challenge to the social and healthcare system in European countries, especially in Germany. An abundance of data has been published on the refugees’ health problems (infections as well as physical diseases and psychiatric problems) and their prevention (i.e., sanitary and vaccination programs). However, data on prevalences of multidrug-resistant organisms (MDRO) in refugees are scarce, although it is known that most refugees are from or travelled through countries with high prevalences of MDRO. This paper presents current data on MDRO colonization of refugees admitted to hospitals, and the impact of screening upon admission and infection control in hospitals is discussed. Methods: Anonymous data obtained by screening upon hospital admission were reported by hospitals in the Rhine-Main region of Germany to the local public health department. Screening and microbiological analyses were performed from December 2015 to March 2016 according to standardized and validated methods. Results: 9.8% of the refugees screened (32/325) exhibited colonization with methicillin-resistant Staphylococcus aureus (MRSA), and 23.3% of the refugees (67/290) were colonized with Gram-negative bacteria with extended spectrum beta-lactamases, and/or enterobacteria with resistance against 3 or 4 groups of antibacterials, so-called 3MRGN (multidrug-resistant Gram-negative bacteria with resistance against penicillins, cephalosporins and quinolones) and 4MRGN (with additional resistance against carbapenems). Carbapenem-resistant Gram-negative bacteria (CRGN) were detected in 2.1% (6/290) of the refugees. Conclusion: The data confirms the studies published between 2014 and 2016, encompassing refugees tested in Germany, the Netherlands and Israel, with prevalences of MRSA and CRGN up to 13.5% and 5.6%. The MDRO prevalences are higher than those of “risk groups” for MRSA, such as hemodialysis patients and patients depending on outpatient home

  19. Transgenic resistance confers effective field level control of bacterial spot disease in tomato.

    PubMed

    Horvath, Diana M; Stall, Robert E; Jones, Jeffrey B; Pauly, Michael H; Vallad, Gary E; Dahlbeck, Doug; Staskawicz, Brian J; Scott, John W

    2012-01-01

    We investigated whether lines of transgenic tomato (Solanum lycopersicum) expressing the Bs2 resistance gene from pepper, a close relative of tomato, demonstrate improved resistance to bacterial spot disease caused by Xanthomonas species in replicated multi-year field trials under commercial type growing conditions. We report that the presence of the Bs2 gene in the highly susceptible VF 36 background reduced disease to extremely low levels, and VF 36-Bs2 plants displayed the lowest disease severity amongst all tomato varieties tested, including commercial and breeding lines with host resistance. Yields of marketable fruit from transgenic lines were typically 2.5 times that of the non-transformed parent line, but varied between 1.5 and 11.5 fold depending on weather conditions and disease pressure. Trials were conducted without application of any copper-based bactericides, presently in wide use despite negative impacts on the environment. This is the first demonstration of effective field resistance in a transgenic genotype based on a plant R gene and provides an opportunity for control of a devastating pathogen while eliminating ineffective copper pesticides.

  20. Transgenic Resistance Confers Effective Field Level Control of Bacterial Spot Disease in Tomato

    PubMed Central

    Horvath, Diana M.; Stall, Robert E.; Jones, Jeffrey B.; Pauly, Michael H.; Vallad, Gary E.; Dahlbeck, Doug; Staskawicz, Brian J.; Scott, John W.

    2012-01-01

    We investigated whether lines of transgenic tomato (Solanum lycopersicum) expressing the Bs2 resistance gene from pepper, a close relative of tomato, demonstrate improved resistance to bacterial spot disease caused by Xanthomonas species in replicated multi-year field trials under commercial type growing conditions. We report that the presence of the Bs2 gene in the highly susceptible VF 36 background reduced disease to extremely low levels, and VF 36-Bs2 plants displayed the lowest disease severity amongst all tomato varieties tested, including commercial and breeding lines with host resistance. Yields of marketable fruit from transgenic lines were typically 2.5 times that of the non-transformed parent line, but varied between 1.5 and 11.5 fold depending on weather conditions and disease pressure. Trials were conducted without application of any copper-based bactericides, presently in wide use despite negative impacts on the environment. This is the first demonstration of effective field resistance in a transgenic genotype based on a plant R gene and provides an opportunity for control of a devastating pathogen while eliminating ineffective copper pesticides. PMID:22870280

  1. Resistant dextrin, as a prebiotic, improves insulin resistance and inflammation in women with type 2 diabetes: a randomised controlled clinical trial.

    PubMed

    Aliasgharzadeh, Akbar; Dehghan, Parvin; Gargari, Bahram Pourghassem; Asghari-Jafarabadi, Mohammad

    2015-01-28

    Improvement of insulin resistance and inflammation is a basic strategy in the management of type 2 diabetes. There is limited evidence that prebiotics improve insulin resistance and inflammation. However, the ameliorating effect of resistant dextrin, as a prebiotic, on insulin resistance and inflammation in patients with type 2 diabetes has not been investigated so far. Therefore, the present study aimed to examine the effects of resistant dextrin on insulin resistance and inflammation in type 2 diabetic patients. In a randomised controlled clinical trial, fifty-five women with type 2 diabetes were assigned to two groups: the intervention group (n 30) and the control group (n 25). The intervention group received a daily supplement of 10 g resistant dextrin and the control group received a similar amount of maltodextrin as placebo for 8 weeks. Fasting plasma glucose (FPG), HbA1c, insulin, high-sensitivity C-reactive protein (hs-CRP), IL-6, TNF-α, malondialdehyde (MDA) and serum endotoxin concentrations were measured before and after the intervention. Data were analysed using SPSS (version 13). Paired and unpaired t tests and ANCOVA were used to compare quantitative variables after the intervention. Patients supplemented with resistant dextrin exhibited a significant decrease in fasting insulin (20.1 pmol/l, 22.8%), homeostasis model assessment of insulin resistance (1.3, 24.9%), quantitative insulin sensitivity check index (0.2, 7.2%), IL-6 (1.4 pg/ml, 28.4 %), TNF-α (5.4 pg/ml, 18.8 %), MDA (1.2 nmol/ml, 25.6 %) and endotoxin (6.2 endotoxin units/ml, 17.8%) concentrations than those supplemented with maltodextrin (P< 0.05). Decreases in FPG (0.05 mmol/l, 0.6%), HbA1c (0.5%, 9.6%) and hs-CRP (2.7 ng/ml, 35.1%) concentrations in the resistant dextrin group were not significant when compared with the maltodextrin group. In conclusion, resistant dextrin supplementation can modulate inflammation and improve insulin resistance in women with type 2 diabetes.

  2. Genetic architecture of resistance in Daphnia hosts against two species of host-specific parasites

    PubMed Central

    Routtu, J; Ebert, D

    2015-01-01

    Understanding the genetic architecture of host resistance is key for understanding the evolution of host–parasite interactions. Evolutionary models often assume simple genetics based on few loci and strong epistasis. It is unknown, however, whether these assumptions apply to natural populations. Using a quantitative trait loci (QTL) approach, we explore the genetic architecture of resistance in the crustacean Daphnia magna to two of its natural parasites: the horizontally transmitted bacterium Pasteuria ramosa and the horizontally and vertically transmitted microsporidium Hamiltosporidium tvaerminnensis. These two systems have become models for studies on the evolution of host–parasite interactions. In the QTL panel used here, Daphnia's resistance to P. ramosa is controlled by a single major QTL (which explains 50% of the observed variation). Resistance to H. tvaerminnensis horizontal infections shows a signature of a quantitative trait based in multiple loci with weak epistatic interactions (together explaining 38% variation). Resistance to H. tvaerminnensis vertical infections, however, shows only one QTL (explaining 13.5% variance) that colocalizes with one of the QTLs for horizontal infections. QTLs for resistance to Pasteuria and Hamiltosporidium do not colocalize. We conclude that the genetics of resistance in D. magna are drastically different for these two parasites. Furthermore, we infer that based on these and earlier results, the mechanisms of coevolution differ strongly for the two host–parasite systems. Only the Pasteuria–Daphnia system is expected to follow the negative frequency-dependent selection (Red Queen) model. How coevolution works in the Hamiltosporidium–Daphnia system remains unclear. PMID:25335558

  3. Relative resistance of HIV-1 founder viruses to control by interferon-alpha

    PubMed Central

    2013-01-01

    Background Following mucosal human immunodeficiency virus type 1 (HIV-1) transmission, type 1 interferons (IFNs) are rapidly induced at sites of initial virus replication in the mucosa and draining lymph nodes. However, the role played by IFN-stimulated antiviral activity in restricting HIV-1 replication during the initial stages of infection is not clear. We hypothesized that if type 1 IFNs exert selective pressure on HIV-1 replication in the earliest stages of infection, the founder viruses that succeed in establishing systemic infection would be more IFN-resistant than viruses replicating during chronic infection, when type 1 IFNs are produced at much lower levels. To address this hypothesis, the relative resistance of virus isolates derived from HIV-1-infected individuals during acute and chronic infection to control by type 1 IFNs was analysed. Results The replication of plasma virus isolates generated from subjects acutely infected with HIV-1 and molecularly cloned founder HIV-1 strains could be reduced but not fully suppressed by type 1 IFNs in vitro. The mean IC50 value for IFNα2 (22 U/ml) was lower than that for IFNβ (346 U/ml), although at maximally-inhibitory concentrations both IFN subtypes inhibited virus replication to similar extents. Individual virus isolates exhibited differential susceptibility to inhibition by IFNα2 and IFNβ, likely reflecting variation in resistance to differentially up-regulated IFN-stimulated genes. Virus isolates from subjects acutely infected with HIV-1 were significantly more resistant to in vitro control by IFNα than virus isolates generated from the same individuals during chronic, asymptomatic infection. Viral IFN resistance declined rapidly after the acute phase of infection: in five subjects, viruses derived from six-month consensus molecular clones were significantly more sensitive to the antiviral effects of IFNs than the corresponding founder viruses. Conclusions The establishment of systemic HIV-1 infection by

  4. Multiple loci on 8q24 associated with prostate cancer susceptibility.

    PubMed

    Al Olama, Ali Amin; Kote-Jarai, Zsofia; Giles, Graham G; Guy, Michelle; Morrison, Jonathan; Severi, Gianluca; Leongamornlert, Daniel A; Tymrakiewicz, Malgorzata; Jhavar, Sameer; Saunders, Ed; Hopper, John L; Southey, Melissa C; Muir, Kenneth R; English, Dallas R; Dearnaley, David P; Ardern-Jones, Audrey T; Hall, Amanda L; O'Brien, Lynne T; Wilkinson, Rosemary A; Sawyer, Emma; Lophatananon, Artitaya; Horwich, Alan; Huddart, Robert A; Khoo, Vincent S; Parker, Christopher C; Woodhouse, Christopher J; Thompson, Alan; Christmas, Tim; Ogden, Chris; Cooper, Colin; Donovan, Jenny L; Hamdy, Freddie C; Neal, David E; Eeles, Rosalind A; Easton, Douglas F

    2009-10-01

    Previous studies have identified multiple loci on 8q24 associated with prostate cancer risk. We performed a comprehensive analysis of SNP associations across 8q24 by genotyping tag SNPs in 5,504 prostate cancer cases and 5,834 controls. We confirmed associations at three previously reported loci and identified additional loci in two other linkage disequilibrium blocks (rs1006908: per-allele OR = 0.87, P = 7.9 x 10(-8); rs620861: OR = 0.90, P = 4.8 x 10(-8)). Eight SNPs in five linkage disequilibrium blocks were independently associated with prostate cancer susceptibility.

  5. Immunochip analysis identifies multiple susceptibility loci for systemic sclerosis.

    PubMed

    Mayes, Maureen D; Bossini-Castillo, Lara; Gorlova, Olga; Martin, José Ezequiel; Zhou, Xiaodong; Chen, Wei V; Assassi, Shervin; Ying, Jun; Tan, Filemon K; Arnett, Frank C; Reveille, John D; Guerra, Sandra; Teruel, María; Carmona, Francisco David; Gregersen, Peter K; Lee, Annette T; López-Isac, Elena; Ochoa, Eguzkine; Carreira, Patricia; Simeón, Carmen Pilar; Castellví, Iván; González-Gay, Miguel Ángel; Zhernakova, Alexandra; Padyukov, Leonid; Alarcón-Riquelme, Marta; Wijmenga, Cisca; Brown, Matthew; Beretta, Lorenzo; Riemekasten, Gabriela; Witte, Torsten; Hunzelmann, Nicolas; Kreuter, Alexander; Distler, Jörg H W; Voskuyl, Alexandre E; Schuerwegh, Annemie J; Hesselstrand, Roger; Nordin, Annika; Airó, Paolo; Lunardi, Claudio; Shiels, Paul; van Laar, Jacob M; Herrick, Ariane; Worthington, Jane; Denton, Christopher; Wigley, Fredrick M; Hummers, Laura K; Varga, John; Hinchcliff, Monique E; Baron, Murray; Hudson, Marie; Pope, Janet E; Furst, Daniel E; Khanna, Dinesh; Phillips, Kristin; Schiopu, Elena; Segal, Barbara M; Molitor, Jerry A; Silver, Richard M; Steen, Virginia D; Simms, Robert W; Lafyatis, Robert A; Fessler, Barri J; Frech, Tracy M; Alkassab, Firas; Docherty, Peter; Kaminska, Elzbieta; Khalidi, Nader; Jones, Henry Niall; Markland, Janet; Robinson, David; Broen, Jasper; Radstake, Timothy R D J; Fonseca, Carmen; Koeleman, Bobby P; Martin, Javier

    2014-01-02

    In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci.

  6. Immunochip Analysis Identifies Multiple Susceptibility Loci for Systemic Sclerosis

    PubMed Central

    Mayes, Maureen D.; Bossini-Castillo, Lara; Gorlova, Olga; Martin, José Ezequiel; Zhou, Xiaodong; Chen, Wei V.; Assassi, Shervin; Ying, Jun; Tan, Filemon K.; Arnett, Frank C.; Reveille, John D.; Guerra, Sandra; Teruel, María; Carmona, Francisco David; Gregersen, Peter K.; Lee, Annette T.; López-Isac, Elena; Ochoa, Eguzkine; Carreira, Patricia; Simeón, Carmen Pilar; Castellví, Iván; González-Gay, Miguel Ángel; Ortego-Centeno, Norberto; Ríos, Raquel; Callejas, José Luis; Navarrete, Nuria; García Portales, Rosa; Camps, María Teresa; Fernández-Nebro, Antonio; González-Escribano, María F.; Sánchez-Román, Julio; García-Hernández, Francisco José; Castillo, María Jesús; Aguirre, María Ángeles; Gómez-Gracia, Inmaculada; Fernández-Gutiérrez, Benjamín; Rodríguez-Rodríguez, Luis; Vicente, Esther; Andreu, José Luis; Fernández de Castro, Mónica; García de la Peña, Paloma; López-Longo, Francisco Javier; Martínez, Lina; Fonollosa, Vicente; Espinosa, Gerard; Tolosa, Carlos; Pros, Anna; Rodríguez Carballeira, Mónica; Narváez, Francisco Javier; Rubio Rivas, Manel; Ortiz Santamaría, Vera; Díaz, Bernardino; Trapiella, Luis; Freire, María del Carmen; Sousa, Adrián; Egurbide, María Victoria; Fanlo Mateo, Patricia; Sáez-Comet, Luis; Díaz, Federico; Hernández, Vanesa; Beltrán, Emma; Román-Ivorra, José Andrés; Grau, Elena; Alegre Sancho, Juan José; Blanco García, Francisco J.; Oreiro, Natividad; Fernández Sueiro, Luis; Zhernakova, Alexandra; Padyukov, Leonid; Alarcón-Riquelme, Marta; Wijmenga, Cisca; Brown, Matthew; Beretta, Lorenzo; Riemekasten, Gabriela; Witte, Torsten; Hunzelmann, Nicolas; Kreuter, Alexander; Distler, Jörg H.W.; Voskuyl, Alexandre E.; Schuerwegh, Annemie J.; Hesselstrand, Roger; Nordin, Annika; Airó, Paolo; Lunardi, Claudio; Shiels, Paul; van Laar, Jacob M.; Herrick, Ariane; Worthington, Jane; Denton, Christopher; Wigley, Fredrick M.; Hummers, Laura K.; Varga, John; Hinchcliff, Monique E.; Baron, Murray; Hudson, Marie; Pope, Janet E.; Furst, Daniel E.; Khanna, Dinesh; Phillips, Kristin; Schiopu, Elena; Segal, Barbara M.; Molitor, Jerry A.; Silver, Richard M.; Steen, Virginia D.; Simms, Robert W.; Lafyatis, Robert A.; Fessler, Barri J.; Frech, Tracy M.; AlKassab, Firas; Docherty, Peter; Kaminska, Elzbieta; Khalidi, Nader; Jones, Henry Niall; Markland, Janet; Robinson, David; Broen, Jasper; Radstake, Timothy R.D.J.; Fonseca, Carmen; Koeleman, Bobby P.; Martin, Javier

    2014-01-01

    In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci. PMID:24387989

  7. Nonrigid, Resistive Linear Plasma Response Models Based on Perturbed Equilibria for Axisymmetric Tokamak Control Design

    NASA Astrophysics Data System (ADS)

    Humphreys, D. A.; Ferron, J. R.; Leuer, J. A.; Walker, M. L.; Welander, A. S.

    2003-10-01

    Linear, perturbed equilibrium plasma response models can accurately represent the experimental response of tokamak plasmas to applied fields [A. Coutlis, et al., Nucl. Fusion 39, 663 (1999)]. However, agreement between experiment and model is much better when average flux over the plasma, rather than at each fluid element, is conserved [P. Vyas, et al., Nucl. Fusion 38, 1043 (1998)]. The close experimental agreement of average flux-conserving models is consistent with approximating field penetration effects produced by finite plasma resistivity, particularly in the edge region. We report on the development of nonrigid linear plasma response models which include finite local plasma resistivity in order to more accurately represent the dynamic response due to this field penetration. Such response models are expected to be important for designing profile control algorithms in advanced tokamaks. Accounting for finite plasma resistivity is also important in designing multivariable integrated controllers which must simultaneously regulate plasma shape and plasma current. Consequences of including resisitivity will be illustrated and comparisons with DIII-D experimental plasma responses will be made.

  8. [Grupo Colaborativo de Resistencia Bacteriana, Chile: recommendations 2014 towards the control of bacteria resistance].

    PubMed

    Cifuentes, Marcela; Silva, Francisco; Arancibia, J Miguel; Rosales, Ruth; Ajenjo, M Cristina; Riedel, Gisela; Camponovo, Rossana; Labarca, Jaime

    2015-06-01

    Five issues were reviewed in depth at the 2014 annual meeting of Colaborative Group Against Bacterial Resistance and the antecedents and conclusions are detailed in this document. I.- News in CLSI 2014: the difficulties and implications on its implementation at the local level were reviewed and recommendations were set. II.- Criteria for determining the incidence of multi-resistant microorganism in critical care units where indicators and monitoring methodology for better quantification of microorganisms were defined. III.- Quality requirements were established to be considered by the professionals involved in the selection of antimicrobials in the hospital. IV.- Transfer policies, screening and contact precautions for the control of transmission of multiresistant bacteria. V.- Recommendations for health facilities when a carbapenemase producing enterobacteriacea is detected, in a checklist format for rapid deployment in hospitals without endemia of these agents. These are suggestions that arise from the joint work of specialists from many hospitals that do not represent consensus or recommendation, but may help to control the resistance level of each health facility in the country.

  9. Development of myoelectric control type speaking valve with low flow resistance

    NASA Astrophysics Data System (ADS)

    Ooe, Katsutoshi; Sakurai, Kohei; Mimaki, Shinya

    2015-12-01

    We aimed to develop welfare devices for patients with phonation disorder. One of these devices is the electrical controltype speaking valve system. The conventional speaking valves have one-way valve architecture, they open when the user breathes in, and they close when user breathes out and produce voices. This type is very simple and tough, but some users feel closeness in case of exhalation without phonation. This problem is caused by its mechanism what can not be controlled by user's will. Therefore, we proposed an electrical control-type speaking valve system to resolve this problem. This valve is controlled by neck myoelectric signal of sternohyoid muscle. From our previous report, it was clarified that this valve had better performance about easy-to-breath. Furthermore, we proposed the compact myoelectric control-type speaking valve system. The new-type speaking valve was enough small to attach the human body, and its opening area is larger than that of conventional one. Additionally, we described the improvement of flow channel shape by using of FEM analysis. According to the result of the analysis, it was clarified that the shape-improved speaking valve gets the low flow resistance channel in case of inspiration. In this report, we tried to make the flow resistance lower by the shape of current plates, in case of both inspiration and exhalation. From the result of FEM analysis, our speaking valve could get better flow channel than older one.

  10. Significant variance in genetic diversity among populations of Schistosoma haematobium detected using microsatellite DNA loci from a genome-wide database

    PubMed Central

    2013-01-01

    Background Urogenital schistosomiasis caused by Schistosoma haematobium is widely distributed across Africa and is increasingly being targeted for control. Genome sequences and population genetic parameters can give insight into the potential for population- or species-level drug resistance. Microsatellite DNA loci are genetic markers in wide use by Schistosoma researchers, but there are few primers available for S. haematobium. Methods We sequenced 1,058,114 random DNA fragments from clonal cercariae collected from a snail infected with a single Schistosoma haematobium miracidium. We assembled and aligned the S. haematobium sequences to the genomes of S. mansoni and S. japonicum, identifying microsatellite DNA loci across all three species and designing primers to amplify the loci in S. haematobium. To validate our primers, we screened 32 randomly selected primer pairs with population samples of S. haematobium. Results We designed >13,790 primer pairs to amplify unique microsatellite loci in S. haematobium, (available at http://www.cebio.org/projetos/schistosoma-haematobium-genome). The three Schistosoma genomes contained similar overall frequencies of microsatellites, but the frequency and length distributions of specific motifs differed among species. We identified 15 primer pairs that amplified consistently and were easily scored. We genotyped these 15 loci in S. haematobium individuals from six locations: Zanzibar had the highest levels of diversity; Malawi, Mauritius, Nigeria, and Senegal were nearly as diverse; but the sample from South Africa was much less diverse. Conclusions About half of the primers in the database of Schistosoma haematobium microsatellite DNA loci should yield amplifiable and easily scored polymorphic markers, thus providing thousands of potential markers. Sequence conservation among S. haematobium, S. japonicum, and S. mansoni is relatively high, thus it should now be possible to identify markers that are universal among Schistosoma

  11. Control of volume resistivity in inorganic-organic separators. [for alkaline batteries

    NASA Technical Reports Server (NTRS)

    Sheibley, D. W.; Manzo, M. A.

    1980-01-01

    Control of resistivity in NASA inorganic-organic separators is achieved by incorporating small percentages of high surface area, fine-particle silica with other ingredients in the separator coating. The volume resistivity appears to be predictable from coating composition, that is, from the surface area of filler particles in the coating. The approach has been applied to two polymer-'plasticizer'-filler coating systems, where the filler content of each is below the generally acknowledged critical pigment volume concentration of the coating. Application of these coating systems to 0.0254 cm thick (10 mil) fuel-cell grade asbestos sheet produces inexpensive, flexible, microporous separators that perform at least as well as the original inorganic-organic concept, the Astropower separator.

  12. The Importance of Movement Velocity as a Measure to Control Resistance Training Intensity

    PubMed Central

    González-Badillo, Juan J.; Marques, Mário C.; Sánchez-Medina, Luis

    2011-01-01

    Configuration of the exercise stimulus in resitance training has been traditionally associated with a combination of the so-called ‘acute resistance exercise variables’ (exercise type and order, loading, number of repetitions and sets, rests duration and movement velocity). During typical resistance exercise in isoinertial conditions, and assuming every repetition is performed with maximal voluntary effort, velocity unintentionally declines as fatigue develops. However, few studies analyzing the response to different resitance training schemes have described changes in repetition velocity or power. It thus seems necessary to conduct more research using models of fatigue that analyze the reduction in mechanical variables such as force, velocity and power output over repeated dynamic contractions in actual training or competition settings. Thus, the aim of this paper was to discuss the importance of movement velocity concerning control training intensity. PMID:23487504

  13. Linezolid-resistant staphylococcal bacteraemia: A multicentre case-case-control study in Italy.

    PubMed

    Russo, Alessandro; Campanile, Floriana; Falcone, Marco; Tascini, Carlo; Bassetti, Matteo; Goldoni, Paola; Trancassini, Maria; Della Siega, Paola; Menichetti, Francesco; Stefani, Stefania; Venditti, Mario

    2015-03-01

    The aim of this multicentre study was to analyse the characteristics of patients with bloodstream infections due to staphylococcal strains resistant to linezolid. This was a retrospective case-case-control study of patients hospitalised in three large teaching hospitals in Italy. A linezolid-resistant (LIN-R) Staphylococcus spp. group and a linezolid-susceptible (LIN-S) Staphylococcus spp. group were compared with control patients to determine the clinical features and factors associated with isolation of LIN-R strains. All LIN-R Staphylococcus spp. strains underwent molecular typing. Compared with the LIN-S group, central venous catheters were the main source of infection in the LIN-R group. The LIN-R and LIN-S groups showed a similar incidence of severe sepsis or septic shock, and both showed a higher incidence of these compared with the control group. Overall, patients in the LIN-R group had a higher 30-day mortality rate. Multivariate analysis found previous linezolid therapy, linezolid therapy >14 days, antibiotic therapy in the previous 30 days, antibiotic therapy >14 days, previous use of at least two antibiotics and hospitalisation in the previous 90 days as independent risk factors associated with isolation of a LIN-R strain. The G2576T mutation in domain V of 23S rRNA was the principal mechanism of resistance; only one strain of Staphylococcus epidermidis carried the cfr methylase gene (A2503), together with L4 insertion (71GGR72) and L3 substitution (H146Q). LIN-R strains are associated with severe impairment of clinical conditions and unfavourable patient outcomes. Reinforcement of infection control measures may have an important role in preventing these infections.

  14. Control of Alopecurus myosuroides (black-grass) resistant to mesosulfuron+iodosulfuron.

    PubMed

    Moss, S R; Hull, R; Marshall, R

    2009-01-01

    Resistance to the ALS inhibitor mesosulfuron+iodosulfuron ('Atlantis') had been identified in 293 populations of A. myosuroides in the UK by 2008. Two field trials were conducted in winter wheat crops where ALS target site resistance (Pro197Thr) occurred. Mesosulfuron+iodosulfuron (12+2.4 g a.i. ha(-1)) gave 73% - 79% reductions in head numbers in Town Mead field, but only -7% - 5% reductions in Long Covert. Mixtures and sequences improved overall control. Pre-emergence flufenacet+pendimethalin (240+1200 g a.i. ha(-1)) followed by mesosulfuron+ iodosulfuron plus pendimethalin (1320 g a.i. ha(-1)) or clodinafop+trifluralin (30+960 g a.i. ha(-1)) gave 93 - 98% reductions in Town Mead but only 60 - 73% reductions in Long Covert. A non-ALS treatment of pre-emergence flufenacet+pendimethalin followed by isoproturon+pendimethalin (1500+1320 g a.i. ha(-1)) in late October and clodinafop+trifluralin in November or February achieved 97% and 93% reductions in the two trials. Seed samples collected from surviving plants were evaluated in glasshouse assays to quantify any changes in the incidence of resistance. There was an increase in the proportion of plants resistant to mesosulfuron+iodosulfuron regardless of whether it was used alone, in mixture or sequence. No such changes occured with non-ALS treatments. The trials highlight the difficulty of achieving adequate control with alternative herbicides, especially as isoproturon and trifluralin will not be available for use in the UK after 2009.

  15. Genetic Diversity in Cytokines Associated with Immune Variation and Resistance to Multiple Pathogens in a Natural Rodent Population

    PubMed Central

    Turner, Andrew K.; Begon, Mike; Jackson, Joseph A.; Bradley, Janette E.; Paterson, Steve

    2011-01-01

    Pathogens are believed to drive genetic diversity at host loci involved in immunity to infectious disease. To date, studies exploring the genetic basis of pathogen resistance in the wild have focussed almost exclusively on genes of the Major Histocompatibility Complex (MHC); the role of genetic variation elsewhere in the genome as a basis for variation in pathogen resistance has rarely been explored in natural populations. Cytokines are signalling molecules with a role in many immunological and physiological processes. Here we use a natural population of field voles (Microtus agrestis) to examine how genetic diversity at a suite of cytokine and other immune loci impacts the immune response phenotype and resistance to several endemic pathogen species. By using linear models to first control for a range of non-genetic factors, we demonstrate strong effects of genetic variation at cytokine loci both on host immunological parameters and on resistance to multiple pathogens. These effects were primarily localized to three cytokine genes (Interleukin 1 beta (Il1b), Il2, and Il12b), rather than to other cytokines tested, or to membrane-bound, non-cytokine immune loci. The observed genetic effects were as great as for other intrinsic factors such as sex and body weight. Our results demonstrate that genetic diversity at cytokine loci is a novel and important source of individual variation in immune function and pathogen resistance in natural populations. The products of these loci are therefore likely to affect interactions between pathogens and help determine survival and reproductive success in natural populations. Our study also highlights the utility of wild rodents as a model of ecological immunology, to better understand the causes and consequences of variation in immune function in natural populations including humans. PMID:22039363

  16. Simple evaporation controller for thin-film deposition from a resistively heated boat

    NASA Technical Reports Server (NTRS)

    Scofield, John H.; Bajuk, Lou; Mohler, William

    1990-01-01

    A simple, inexpensive circuit is described for switching the current through a resistively heated evaporation boat during thin-film deposition. The circuit uses a silicon-controlled rectifier (SCR) to switch the 0-15-A current in the primary of a 2-kV A step-down transformer that supplies the 0-200-A current to an evaporation boat. The circuit is controlled by a 0-10 V-dc signal similar to that furnished by an Inficon XTC deposition-rate controller. This circuit may be assembled from a handful of parts for a cost of about $400, nearly one-tenth the cost of similar commercial units. Minimum construction is required, since the circuit is built around an off-the-shelf, self-contained SCR unit.

  17. Decision making, impulse control and loss of willpower to resist drugs: a neurocognitive perspective.

    PubMed

    Bechara, Antoine

    2005-11-01

    Here I argue that addicted people become unable to make drug-use choices on the basis of long-term outcome, and I propose a neural framework that explains this myopia for future consequences. I suggest that addiction is the product of an imbalance between two separate, but interacting, neural systems that control decision making: an impulsive, amygdala system for signaling pain or pleasure of immediate prospects, and a reflective, prefrontal cortex system for signaling pain or pleasure of future prospects. After an individual learns social rules, the reflective system controls the impulsive system via several mechanisms. However, this control is not absolute; hyperactivity within the impulsive system can override the reflective system. I propose that drugs can trigger bottom-up, involuntary signals originating from the amygdala that modulate, bias or even hijack the goal-driven cognitive resources that are needed for the normal operation of the reflective system and for exercising the willpower to resist drugs.

  18. Implementation of model predictive control for resistive wall mode stabilization on EXTRAP T2R

    NASA Astrophysics Data System (ADS)

    Setiadi, A. C.; Brunsell, P. R.; Frassinetti, L.

    2015-10-01

    A model predictive control (MPC) method for stabilization of the resistive wall mode (RWM) in the EXTRAP T2R reversed-field pinch is presented. The system identification technique is used to obtain a linearized empirical model of EXTRAP T2R. MPC employs the model for prediction and computes optimal control inputs that satisfy performance criterion. The use of a linearized form of the model allows for compact formulation of MPC, implemented on a millisecond timescale, that can be used for real-time control. The design allows the user to arbitrarily suppress any selected Fourier mode. The experimental results from EXTRAP T2R show that the designed and implemented MPC successfully stabilizes the RWM.

  19. Optimization of Feedback Control Coils for Resistive Wall Mode Stabilization in DIII-D

    NASA Astrophysics Data System (ADS)

    Bialek, J.; Boozer, A. H.; Garofalo, A. M.; Mauel, M. E.; Navratil, G. A.; Turnbull, A. D.

    1999-11-01

    Recent experiments in DIII--D on Resistive Wall Mode (RWM) stabilization with active feedback have been very promising. We investigated extensions to the sensor and control coil set that would further improve RWM stabilization. The VALEN computer code models the RWM as an equivalent current distribution on the unperturbed plasma boundary which duplicates the plasma external magnetic field of the mode, as calculated by GATO. This surface current determines the plasma interaction with all conducting structures. In three dimensions the VALEN code models the unstable plasma, passive structure, proposed sensors, and proposed control coils together with the control logic. The problem may be examined as a transient simulation, or for a linear power supply model, as an eigenvalue calculation. A summary of the configurations examined and their predicted effectiveness will be presented.

  20. Loci-STREAM Version 0.9

    NASA Technical Reports Server (NTRS)

    Wright, Jeffrey; Thakur, Siddharth

    2006-01-01

    Loci-STREAM is an evolving computational fluid dynamics (CFD) software tool for simulating possibly chemically reacting, possibly unsteady flows in diverse settings, including rocket engines, turbomachines, oil refineries, etc. Loci-STREAM implements a pressure- based flow-solving algorithm that utilizes unstructured grids. (The benefit of low memory usage by pressure-based algorithms is well recognized by experts in the field.) The algorithm is robust for flows at all speeds from zero to hypersonic. The flexibility of arbitrary polyhedral grids enables accurate, efficient simulation of flows in complex geometries, including those of plume-impingement problems. The present version - Loci-STREAM version 0.9 - includes an interface with the Portable, Extensible Toolkit for Scientific Computation (PETSc) library for access to enhanced linear-equation-solving programs therein that accelerate convergence toward a solution. The name "Loci" reflects the creation of this software within the Loci computational framework, which was developed at Mississippi State University for the primary purpose of simplifying the writing of complex multidisciplinary application programs to run in distributed-memory computing environments including clusters of personal computers. Loci has been designed to relieve application programmers of the details of programming for distributed-memory computers.

  1. Seven New Loci Associated with Age-Related Macular Degeneration

    PubMed Central

    2013-01-01

    Age-related macular degeneration (AMD) is a common cause of blindness in older individuals. To accelerate understanding of AMD biology and help design new therapies, we executed a collaborative genomewide association study, examining >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry. We identified 19 genomic loci associated with AMD with p<5×10−8 and enriched for genes involved in regulation of complement activity, lipid metabolism, extracellular matrix remodeling and angiogenesis. Our results include 7 loci reaching p<5×10−8 for the first time, near the genes COL8A1/FILIP1L, IER3/DDR1, SLC16A8, TGFBR1, RAD51B, ADAMTS9/MIR548A2, and B3GALTL. A genetic risk score combining SNPs from all loci displayed similar good ability to distinguish cases and controls in all samples examined. Our findings provide new directions for biological, genetic and therapeutic studies of AMD. PMID:23455636

  2. Optimized feedback control system modeling of resistive wall modes for burning plasmas experiments

    NASA Astrophysics Data System (ADS)

    Katsuro-Hopkins, Oksana Nikolaevna

    A numerical study of active feedback control system performance and optimization for tokamak Resistive Wall Modes (RWM) is the subject of this thesis. The ability to accurately model and predict the performance of an active MHD control systems is critical to present and future advanced confinement scenarios and fusion reactor design studies. The computer code VALEN has been designed to calculate the performance of a MHD feedback control system in an arbitrary geometry. The simulation of realistic effects in feedback systems, such as noise, time delays and filters is of particular importance. In this work realistic measurement noise analysis was added to VALEN and used to design the RWM feedback control amplifier power level for the DIII-D experiment. Modern control theory based on a state-space formulation obtained from VALEN was applied to design an Optimal Controller and Observer based on a reduced VALEN model. A quantitative low order model of the VALEN state space was derived from the high dimensional intrinsic state space structure of the VALEN using methods of a balanced realization and matched DC gain truncation. These techniques for the design of an optimal controller and optimal observer were applied to models of the DIII-D and ITER experiments and showed an order of magnitude reduction of the required control coil current and voltage in the presence of white noise as compared to a traditional, classical PID controller. This optimal controller for the ITER burning plasma experiment was robust from the no-wall pressure limit to a pressure value well above those achieved with a classical PID controller and could approach the ideal wall limit.

  3. New basal cell carcinoma susceptibility loci

    PubMed Central

    Stacey, Simon N.; Helgason, Hannes; Gudjonsson, Sigurjon A.; Thorleifsson, Gudmar; Zink, Florian; Sigurdsson, Asgeir; Kehr, Birte; Gudmundsson, Julius; Sulem, Patrick; Sigurgeirsson, Bardur; Benediktsdottir, Kristrun R.; Thorisdottir, Kristin; Ragnarsson, Rafn; Fuentelsaz, Victoria; Corredera, Cristina; Gilaberte, Yolanda; Grasa, Matilde; Planelles, Dolores; Sanmartin, Onofre; Rudnai, Peter; Gurzau, Eugene; Koppova, Kvetoslava; Nexø, Bjørn A.; Tjønneland, Anne; Overvad, Kim; Jonasson, Jon G.; Tryggvadottir, Laufey; Johannsdottir, Hrefna; Kristinsdottir, Anna M.; Stefansson, Hreinn; Masson, Gisli; Magnusson, Olafur T.; Halldorsson, Bjarni V.; Kong, Augustine; Rafnar, Thorunn; Thorsteinsdottir, Unnur; Vogel, Ulla; Kumar, Rajiv; Nagore, Eduardo; Mayordomo, José I.; Gudbjartsson, Daniel F.; Olafsson, Jon H.; Stefansson, Kari

    2015-01-01

    In an ongoing screen for DNA sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conduct a genome-wide association study (GWAS) of 24,988,228 SNPs and small indels detected through whole-genome sequencing of 2,636 Icelanders and imputed into 4,572 BCC patients and 266,358 controls. Here we show the discovery of four new BCC susceptibility loci: 2p24 MYCN (rs57244888[C], OR=0.76, P=4.7 × 10−12), 2q33 CASP8-ALS2CR12 (rs13014235[C], OR=1.15, P=1.5 × 10−9), 8q21 ZFHX4 (rs28727938[G], OR=0.70, P=3.5 × 10−12) and 10p14 GATA3 (rs73635312[A], OR=0.74, P=2.4 × 10−16). Fine mapping reveals that two variants correlated with rs73635312[A] occur in conserved binding sites for the GATA3 transcription factor. In addition, expression microarrays and RNA-seq show that rs13014235[C] and a related SNP rs700635[C] are associated with expression of CASP8 splice variants in which sequences from intron 8 are retained. PMID:25855136

  4. New basal cell carcinoma susceptibility loci.

    PubMed

    Stacey, Simon N; Helgason, Hannes; Gudjonsson, Sigurjon A; Thorleifsson, Gudmar; Zink, Florian; Sigurdsson, Asgeir; Kehr, Birte; Gudmundsson, Julius; Sulem, Patrick; Sigurgeirsson, Bardur; Benediktsdottir, Kristrun R; Thorisdottir, Kristin; Ragnarsson, Rafn; Fuentelsaz, Victoria; Corredera, Cristina; Gilaberte, Yolanda; Grasa, Matilde; Planelles, Dolores; Sanmartin, Onofre; Rudnai, Peter; Gurzau, Eugene; Koppova, Kvetoslava; Nexø, Bjørn A; Tjønneland, Anne; Overvad, Kim; Jonasson, Jon G; Tryggvadottir, Laufey; Johannsdottir, Hrefna; Kristinsdottir, Anna M; Stefansson, Hreinn; Masson, Gisli; Magnusson, Olafur T; Halldorsson, Bjarni V; Kong, Augustine; Rafnar, Thorunn; Thorsteinsdottir, Unnur; Vogel, Ulla; Kumar, Rajiv; Nagore, Eduardo; Mayordomo, José I; Gudbjartsson, Daniel F; Olafsson, Jon H; Stefansson, Kari

    2015-04-09

    In an ongoing screen for DNA sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conduct a genome-wide association study (GWAS) of 24,988,228 SNPs and small indels detected through whole-genome sequencing of 2,636 Icelanders and imputed into 4,572 BCC patients and 266,358 controls. Here we show the discovery of four new BCC susceptibility loci: 2p24 MYCN (rs57244888[C], OR=0.76, P=4.7 × 10(-12)), 2q33 CASP8-ALS2CR12 (rs13014235[C], OR=1.15, P=1.5 × 10(-9)), 8q21 ZFHX4 (rs28727938[G], OR=0.70, P=3.5 × 10(-12)) and 10p14 GATA3 (rs73635312[A], OR=0.74, P=2.4 × 10(-16)). Fine mapping reveals that two variants correlated with rs73635312[A] occur in conserved binding sites for the GATA3 transcription factor. In addition, expression microarrays and RNA-seq show that rs13014235[C] and a related SNP rs700635[C] are associated with expression of CASP8 splice variants in which sequences from intron 8 are retained.

  5. Genetic analysis and molecular mapping of QTLs for resistance to rice black-streaked dwarf disease in rice.

    PubMed

    Zhou, Tong; Du, Linlin; Wang, Lijiao; Wang, Ying; Gao, Cunyi; Lan, Ying; Sun, Feng; Fan, Yongjian; Wang, Guoliang; Zhou, Yijun

    2015-07-22

    Rice black-streaked dwarf disease, caused by rice black-streaked dwarf virus (RBSDV), is transmitted by small brown planthoppers (Laodelphax striatellus Fallén, SBPH) and causes severe yield loss in epidemic years in China and other East Asian countries. Breeding for resistance to RBSDV is a promising strategy to control the disease. We identified Tetep that showed resistance to RBSDV using a field test and artificial inoculation test. An evaluation of the resistance mechanism revealed that Tetep was resistant to RBSDV but not to SBPH. Genetic analysis showed that the resistance of Tetep to RBSDV was controlled by quantitative trait loci (QTLs). Three new QTLs for RBSDV resistance were identified in this study, i.e., qRBSDV-3, qRBSDV-10 and qRBSDV-11. The LOD scores of qRBSDV-3, qRBSDV-10 and qRBSDV-11 were 4.07, 2.24 and 2.21, accounting for 17.5%, 0.3% and 12.4% of the total phenotypic variation, respectively. All the resistance loci identified in this study were associated with virus resistance genes. The alleles for enhancing resistance on chromosomes 3 and 11 originated from Tetep, whereas the other allele on chromosome 10 originated from a susceptible parent. The identified new resistance QTLs in this study are useful resources for efficiently breeding resistant rice cultivars to RBSDV.

  6. Bacterial quorum sensing inhibitors: attractive alternatives for control of infectious pathogens showing multiple drug resistance.

    PubMed

    Bhardwaj, Ashima K; Vinothkumar, Kittappa; Rajpara, Neha

    2013-04-01

    Quorum sensing (QS) is a bacterial communication process that depends on the bacterial population density. It involves small diffusible signaling molecules which activate the expression of myriad genes that control diverse array of functions like bioluminescence, virulence, biofilm formation, sporulation, to name a few. Since QS is responsible for virulence in the clinically relevant bacteria, inhibition of QS appears to be a promising strategy to control these pathogenic bacteria. With indiscriminate use of antibiotics, there has been an alarming increase in the number of antibiotic resistant pathogens. Antibiotics are no longer the magic bullets they were once thought to be and therefore there is a need for development of new antibiotics and/or other novel strategies to combat the infections caused by multidrug resistant organisms. Quorum sensing inhibition or quorum quenching has been pursued as one of such novel strategies. While antibiotics kill or slow down the growth of bacteria, quorum sensing inhibitors (QSIs) or quorum quenchers (QQs) attenuate bacterial virulence. A large body of work on QS has been carried out in deadly pathogens like Pseudomonas aeruginosa, Staphylococcus aureus, Vibrio fischeri, V. harveyi, Escherichia coli and V. cholerae etc to unravel the mechanisms of QS as well as identify and study QSIs. This review describes various aspects of QS, QSI, different model systems to study these phenomena and recent patents on various QSIs. It suggests QSIs as attractive alternatives for controlling human, animal and plant pathogens and their utility in agriculture and other industries.

  7. Control of the pollution of antibiotic resistance genes in soils by quorum sensing inhibition.

    PubMed

    Lai, Bai-Min; Zhang, Kun; Shen, Dong-Sheng; Wang, Mei-Zhen; Shentu, Jia-Li; Li, Na

    2017-02-01

    To investigate whether pollution from antibiotic resistance genes (ARGs) could be affected by bacterial quorum sensing, the oxytetracycline (OTC)-containing manure was fertilized to establish the ARG-polluted soil environment. Under long-term OTC stress, substantial ARGs in the range from 10(-4) to 10(-3) RG/16S rRNA (resistance genes/16S rRNA) were detected in the antibiotics control (AC) group, in which OTC-containing manure was fertilized. Meanwhile, 10(-6) RG/16S rRNA was detected in biological control (BC) group, in which non-OTC-containing manure was fertilized. Subsequently, two typical quorum sensing inhibitors, 4-nitropyridine N-oxide (4-NPO) and 3,4-dibromo-2H-furan-5-one (DBF), were used to treat the ARG-polluted soils. These two groups called 4-NPO treatments (NT) and DBF treatments (FT), respectively. There were no significant differences in bacterial growth and OTC degradation in NT and FT groups, compared to AC group. However, acyl-homoserine lactones such as C4-HSL, C6-HSL, and C8-HSL decreased significantly in both NT and FT groups, compared to AC group. Meanwhile, the abundance of most ARGs decreased dramatically. In FT group, the concentrations of tet(L) and tet(Q) were below the detection limits. It was demonstrated that quorum sensing inhibition could be an effective way to prevent and control the pollution of ARGs in soil.

  8. Identifying modifier loci in existing genome scan data.

    PubMed

    Daw, E W; Lu, Y; Marian, A J; Shete, S

    2008-09-01

    In many genetic disorders in which a primary disease-causing locus has been identified, evidence exists for additional trait variation due to genetic factors. These findings have led to studies seeking secondary 'modifier' loci. Identification of modifier loci provides insight into disease mechanisms and may provide additional screening and treatment targets. We believe that modifier loci can be identified by re-analysis of genome screen data while controlling for primary locus effects. To test this hypothesis, we simulated multiple replicates of typical genome screening data on to two real family structures from a study of hypertrophic cardiomyopathy. With this marker data, we simulated two trait models with characteristics similar to one measure of hypertrophic cardiomyopathy. Both trait models included 3 genes. In the first, the trait was influenced by a primary gene, a secondary 'modifier' gene, and a third very small effect gene. In the second, we modeled an interaction between the first two genes. We examined power and false positive rates to map the secondary locus while controlling for the effect of the primary locus with two types of analyses. First, we examined Monte Carlo Markov chain (MCMC) simultaneous segregation and linkage analysis as implemented in Loki, for which we calculated two scoring statistics. Second, we calculated LOD scores using an individual-specific liability class based on the quantitative trait value. We found that both methods produced scores that are significant on a genome-wide level in some replicates. We conclude that mapping of modifier loci in existing samples is possible with these methods.

  9. Resistance of vectors of disease to pesticides. Fifth report of the WHO Expert Committee in Vector Biology and Control.

    PubMed

    1980-01-01

    The resistance of vectors (the term includes primary and intermediate vertebrate and invertebrate hosts and animal reservoirs of human and animal diseases) of disease to pesticides is a major problem faced by WHO member states in the control of vectorborne diseases. Since the meeting of the WHO Expert Committee on Insecticides in 1975, resistance has continued to increase and to affect disease control programs in many countries. The appearance of multiresistance in several important vectors has been the most significant development since the 1975 meeting. The sandfly Phlebotomus papatasi in Bihar, India has been found to be resistant to DDT, leaving the tsetse fly the only important vector species in which resistance has not been reported. This book discusses 1) pesticide resistance in arthropod vectors, malaria vectors, vectors of other diseases and disease reservoirs (rodents); 2) present status of research on resistance of vectors to pesticides, including the biochemistry and genetics of resistance; 3) measures to counteract resistance; 4) detection and monitoring of vector resistance to pesticides; 5) disseminatin of information and training; and 6) recommendations for future research and courses of action.

  10. Unstable pyrethroid resistance in sheep body lice Bovicola ovis (Schrank), (Phthiraptera: Trichodectidae) and its implications for lice control on sheep.

    PubMed

    Levot, Garry

    2012-04-30

    A retrospective study in which the 18 years treatment history of a mob of sheep hosting a pyrethroid resistant strain of sheep body lice was compared with the coincidental changes in that strain's response to cypermethrin, provided a unique opportunity to investigate the stability of pyrethroid resistance in this species. Resistance levels remained very high (resistance factors (RF)=75-145) for at least five years following the cessation of pyrethroid treatments but within ten years had dropped to only 5, a level similar to many normal field strains and certainly not indicative of high-level resistance. Resumption of pyrethroid treatment of sheep infested with these lice caused a coincidental increase in resistance to an extreme level (RF=321) within two years. Wool producers considering a return to pyrethroid use to control louse infestations should be aware that such a strategy may not be sustainable in the long term and that in Australia effective registered alternative treatments are available.

  11. Gastrointestinal nematodes of dairy goats, anthelmintic resistance and practices of parasite control in Northern Italy

    PubMed Central

    2014-01-01

    Background Gastrointestinal nematodes (GINs) are one of the main constraints to ruminant production worldwide. Anthelmintic resistance (AR) has been reported in goats throughout Europe, yet little is known about the AR status in Italy. The aims of the study were: i) determine the frequency of AR in GINs in goat flocks in Northern Italy, Italy, ii) survey goat farmers on the current practices of parasite control, iii) update the species composition of the gastrointestinal helminthofauna. Thirty three flocks were enrolled and 1288 individual fecal samples were collected. Based on the egg per gram (EPG), 15 flocks were selected to evaluate the presence of AR in GINs with the Fecal Egg Count Reduction Test (FECRT). A questionnaire surveyed 110 dairy goat farmers to acquire information about farm management and drenching practices against GINs. Further, the gastrointestinal tracts of 42 goats were analyzed. Results The FECRs indicated that five of the 15 flocks had problems of AR, which was identified in all two of the anthelmintic classes tested. Resistance and suspected resistance was found in 40% of the flocks selected for AR testing that were treated with benzimidazoles while 20% of the flocks treated with eprinomectin had resistant GINs. Teladorsagia/Trichostrongylus L3 were isolated from the post-treatment coprocultures of all flocks with resistance but not from the flock with suspected oxfendazole resistance. Treatments against helminths were performed once annually in 73.63% of the flocks, but 20.00% of farmers declared not regularly treating their goats every year. Annual treatments usually occurred in autumn or winter at dose rate for sheep. Te. circumcincta, H. contortus, Tr. colubriformis, Skrjabinema caprae and Oesophagostomum venulosum were the most abundant and prevalent species of the gastrointestinal tract. Conclusions Strategies to prevent the development of AR should be widely adopted in Northern Italy. Further, farmers and practitioners should be

  12. Hybridization of an invasive shrub affects tolerance and resistance to defoliation by a biological control agent

    USGS Publications Warehouse

    Williams, Wyatt I.; Friedman, Jonathan M.; Gaskin, John F.; Norton, Andrew P.

    2014-01-01

    Evolution has contributed to the successful invasion of exotic plant species in their introduced ranges, but how evolution affects particular control strategies is still under evaluation. For instance, classical biological control, a common strategy involving the utilization of highly specific natural enemies to control exotic pests, may be negatively affected by host hybridization because of shifts in plant traits, such as root allocation or chemical constituents. We investigated introgression between two parent species of the invasive shrub tamarisk (Tamarix spp.) in the western United States, and how differences in plant traits affect interactions with a biological control agent. Introgression varied strongly with latitude of origin and was highly correlated with plant performance. Increased levels of T. ramosissima introgression resulted in both higher investment in roots and tolerance to defoliation and less resistance to insect attack. Because tamarisk hybridization occurs predictably on the western U.S. landscape, managers may be able to exploit this information to maximize control efforts. Genetic differentiation in plant traits in this system underpins the importance of plant hybridization and may explain why some biological control releases are more successful than others.

  13. White-light-controlled resistive switching chearacteristics of TiO2/Cu2O composite nanorods array

    NASA Astrophysics Data System (ADS)

    Sun, Bai; Liu, Yonghong; Lou, Fangming; Chen, Peng

    2015-08-01

    TiO2/Cu2O composite nanorods array were grown on fluorine-doped tin oxide (FTO) substrate by hydrothermal process, and white-light-controlled resistive switching characteristics of Ag/[TiO2/Cu2O]/FTO structure were further investigated. The current-voltage characteristics of the composite nanorods array represent a good rectifying property and bipolar resistive switching behavior. Specially, the resistive switching behavior can be regulated by white-light illuminating at room temperature. This study is helpful for exploring the memory materials and their applications in nonvolatile light-controlled memory devices.

  14. Selection for increased desiccation resistance in Drosophila melanogaster: Additive genetic control and correlated responses for other stresses

    SciTech Connect

    Hoffmann, A.A.; Parsons, P.A. )

    1989-08-01

    Previously we found that Drosophila melanogaster lines selected for increased desiccation resistance have lowered metabolic rate and behavioral activity levels, and show correlated responses for resistance to starvation and a toxic ethanol level. These results were consistent with a prediction that increased resistance to many environmental stresses may be genetically correlated because of a reduction in metabolic energy expenditure. Here we present experiments on the genetic basis of the selection response and extend the study of correlated responses to other stresses. The response to selection was not sex-specific and involved X-linked and autosomal genes acting additively. Activity differences contributed little to differences in desiccation resistance between selected and control lines. Selected lines had lower metabolic rates than controls in darkness when activity was inhibited. Adults from selected lines showed increased resistance to a heat shock, {sup 60}Co-gamma-radiation, and acute ethanol and acetic acid stress. The desiccation, ethanol and starvation resistance of isofemale lines set up from the F2s of a cross between one of the selected and one of the control lines were correlated. Selected and control lines did not differ in ether-extractable lipid content or in resistance to acetone, ether or a cold shock.

  15. The study of develop optimization to control various resist defect in Photomask fabrication

    NASA Astrophysics Data System (ADS)

    Lim, JongHoon; Kim, ByungJu; Son, JaeSik; Park, EuiSang; Kim, SangPyo; Yim, DongGyu

    2015-07-01

    To reduce the pattern size in photomask is an inevitable trend because of the minimization of chip size. So it makes a big challenge to control defects in photomask industry. Defects below a certain size that had not been any problem in previous technology node are becoming an issue as the patterns are smaller. Therefore, the acceptable tolerance levels for current defect size and quantity are dramatically reduced. Because these defects on photomask can be the sources of the repeating defects on wafer, small size defects smaller than 200nm should not be ignored any more. Generally, almost defects are generated during develop process and etch process. Especially it is difficult to find the root cause of defects formed during the develop process because of their various types and very small size. In this paper, we studied how these small defects can be eliminated by analyzing the defects and tuning the develop process. There are 3 types of resist defects which are named as follows. The first type is `Popcorn' defect which is mainly occurred in negative resist and exists on the dark features. The second type is `Frog eggs' defect which is occurred in 2nd process of HTPSM and exists on the wide space area. The last type is `Spot' defect which also exists on the wide space area. These defects are generally appeared on the entire area of a plate and the number of these defects is about several hundred. It is thought that the original source is the surface's hydrophilic state before develop process or the incongruity between resist and developer. This study shows that the optimizing the develop process can be a good solution for some resist defects.

  16. Resist profile and CD control improvement by using optimized resist thickness and substrate film stack ratio for 0.35-um logic process

    NASA Astrophysics Data System (ADS)

    Fan, Ming H.; Yu, Raymond; Chu, Ronfu; Lim, Chet Ping

    1997-08-01

    LOCOS is the most widely used method for 0.35 micrometers process isolation. 2000 angstrom silicon nitride on 200 angstrom padoxide was selected as oxidation barrier before process optimization for the need of control the bird's beak and stress which affects the subsequent gate oxide quality. However, resist profile is prone to footing at this film stack. Severe footing could make minimum space CD too small, even not opened, to cause isolation failure. Experiment data shows that if nitride thickness varies from 1.9 K to 2.1 K, line CD variation can be up to 0.08 micrometers for a 0.6 micrometers line, which is about 80 percent of CD variation budget. Based on simulation results, 8 different nitride thickness in the range of 1750 angstrom to 2100 angstrom with step of 50 angstrom were deposited on 200 angstrom padoxide. Swing curve, CD versus nitride thickness for resist Emax and Emin, CD versus different exposure dose charts were obtained. Resist profile cross-sectional SEM pictures were also done to confirm simulation and in-line CD SEM measurement. An optimum combination of substrate film stack and resist thickness was selected. After implementation of this optimization, the sensitivity of CD to the nitride thickness was greatly reduced. Better resist profile and CD control were obtained. This was well confirmed by in-line monitoring data.

  17. Dental care resistance prevention and antibiotic prescribing modification—the cluster-randomised controlled DREAM trial

    PubMed Central

    2014-01-01

    Background Bacterial resistance development is one of the most urgent problems in healthcare worldwide. In Europe, dentistry accounts for a comparatively high amount of antibiotic prescriptions. In light of increasing levels of bacterial resistance, this development is alarming. So far, very few interventional studies have been performed, and further research is urgently needed. By means of a complex educational intervention, the DREAM trial aims at optimising antibiotic prescribing behaviour of general dentists in Germany. Method This is a cluster-randomised controlled trial, where each cluster consists of one dental practice and all of its patients in a defined period. Participants are general dentists practicing in the German region of Mecklenburg-Western Pomerania. Randomisation takes place after baseline data collection (6 months) and will be stratified by the antibiotic prescribing rates of the participating dental practices. Dentists randomised into the intervention group will participate in a complex small group educational seminar that aims at: increasing knowledge on bacterial resistance, pharmacology, and prophylaxis of infectious endocarditis; increasing awareness of dentist-patient communication using video-taped vignettes of dentist-patient communication on antibiotic treatment; improving collaboration between general dentists, general practitioners, and practice-based cardiologists on the necessity of antibiotic prophylaxis; enhancing awareness of the dentists’ own prescribing habits by providing antibiotic prescribing feedback; and increasing patient knowledge on antibiotic treatment by providing patient-centred information material on antibiotic prophylaxis of endocarditis. The dentists randomised into the control group will not receive any educational programme and provide care as usual. Primary outcome is the overall antibiotic prescribing rate measured at T1 (period of six months after intervention). In a subgroup of adult patients affected

  18. Combined aerobic and resistance training in breast cancer survivors: A randomized, controlled pilot trial.

    PubMed

    Herrero, F; San Juan, A F; Fleck, S J; Balmer, J; Pérez, M; Cañete, S; Earnest, C P; Foster, C; Lucía, A

    2006-07-01

    The purpose of this pilot study was to examine the effects of a combined cardiorespiratory and resistance exercise training program of short duration on the cardiorespiratory fitness, strength endurance, task specific functional muscle capacity, body composition and quality of life (QOL) in women breast cancer survivors. Sixteen subjects were randomly assigned to either a training (n = 8; age: 50 +/- 5 yrs) or control non-exercising group (n = 8; age: 51 +/- 10 yrs). The training group followed an 8-week exercise program consisting of 3 weekly sessions of 90-min duration, supervised by an experienced investigator and divided into resistance exercises and aerobic training. Before and after the intervention period, all of the subjects performed a cardiorespiratory test to measure peak oxygen uptake (VO2peak), a dynamic strength endurance test (maximum number of repetitions for chest and leg press exercise at 30 - 35 % and 100 - 110 % of body mass, respectively) and a sit-stand test. Quality of life was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 (EORTC-C30) questionnaire. In response to training, QOL, VO2peak (mean 3.9 ml/kg/min; 95 % CI, 0.93, 6.90) performance in leg press (17.9 kg; 95 % CI, 12.8, 22.4) and sit-stand test (- 0.67 s; 95 % CI, - 0.52, - 1.2) improved (p < or = 0.05). We observed no significant changes in the control group. Combined cardiorespiratory and resistance training, even of very brief duration, improves the QOL and the overall physical fitness of women breast cancer survivors.

  19. Genome-wide meta-analysis identifies new susceptibility loci for migraine.

    PubMed

    Anttila, Verneri; Winsvold, Bendik S; Gormley, Padhraig; Kurth, Tobias; Bettella, Francesco; McMahon, George; Kallela, Mikko; Malik, Rainer; de Vries, Boukje; Terwindt, Gisela; Medland, Sarah E; Todt, Unda; McArdle, Wendy L; Quaye, Lydia; Koiranen, Markku; Ikram, M Arfan; Lehtimäki, Terho; Stam, Anine H; Ligthart, Lannie; Wedenoja, Juho; Dunham, Ian; Neale, Benjamin M; Palta, Priit; Hamalainen, Eija; Schürks, Markus; Rose, Lynda M; Buring, Julie E; Ridker, Paul M; Steinberg, Stacy; Stefansson, Hreinn; Jakobsson, Finnbogi; Lawlor, Debbie A; Evans, David M; Ring, Susan M; Färkkilä, Markus; Artto, Ville; Kaunisto, Mari A; Freilinger, Tobias; Schoenen, Jean; Frants, Rune R; Pelzer, Nadine; Weller, Claudia M; Zielman, Ronald; Heath, Andrew C; Madden, Pamela A F; Montgomery, Grant W; Martin, Nicholas G; Borck, Guntram; Göbel, Hartmut; Heinze, Axel; Heinze-Kuhn, Katja; Williams, Frances M K; Hartikainen, Anna-Liisa; Pouta, Anneli; van den Ende, Joyce; Uitterlinden, Andre G; Hofman, Albert; Amin, Najaf; Hottenga, Jouke-Jan; Vink, Jacqueline M; Heikkilä, Kauko; Alexander, Michael; Muller-Myhsok, Bertram; Schreiber, Stefan; Meitinger, Thomas; Wichmann, Heinz Erich; Aromaa, Arpo; Eriksson, Johan G; Traynor, Bryan J; Trabzuni, Daniah; Rossin, Elizabeth; Lage, Kasper; Jacobs, Suzanne B R; Gibbs, J Raphael; Birney, Ewan; Kaprio, Jaakko; Penninx, Brenda W; Boomsma, Dorret I; van Duijn, Cornelia; Raitakari, Olli; Jarvelin, Marjo-Riitta; Zwart, John-Anker; Cherkas, Lynn; Strachan, David P; Kubisch, Christian; Ferrari, Michel D; van den Maagdenberg, Arn M J M; Dichgans, Martin; Wessman, Maija; Smith, George Davey; Stefansson, Kari; Daly, Mark J; Nyholt, Dale R; Chasman, Daniel I; Palotie, Aarno

    2013-08-01

    Migraine is the most common brain disorder, affecting approximately 14% of the adult population, but its molecular mechanisms are poorly understood. We report the results of a meta-analysis across 29 genome-wide association studies, including a total of 23,285 individuals with migraine (cases) and 95,425 population-matched controls. We identified 12 loci associated with migraine susceptibility (P<5×10(-8)). Five loci are new: near AJAP1 at 1p36, near TSPAN2 at 1p13, within FHL5 at 6q16, within C7orf10 at 7p14 and near MMP16 at 8q21. Three of these loci were identified in disease subgroup analyses. Brain tissue expression quantitative trait locus analysis suggests potential functional candidate genes at four loci: APOA1BP, TBC1D7, FUT9, STAT6 and ATP5B.

  20. Genome-wide meta-analysis identifies five new susceptibility loci for cutaneous malignant melanoma.

    PubMed

    Law, Matthew H; Bishop, D Timothy; Lee, Jeffrey E; Brossard, Myriam; Martin, Nicholas G; Moses, Eric K; Song, Fengju; Barrett, Jennifer H; Kumar, Rajiv; Easton, Douglas F; Pharoah, Paul D P; Swerdlow, Anthony J; Kypreou, Katerina P; Taylor, John C; Harland, Mark; Randerson-Moor, Juliette; Akslen, Lars A; Andresen, Per A; Avril, Marie-Françoise; Azizi, Esther; Scarrà, Giovanna Bianchi; Brown, Kevin M; Dȩbniak, Tadeusz; Duffy, David L; Elder, David E; Fang, Shenying; Friedman, Eitan; Galan, Pilar; Ghiorzo, Paola; Gillanders, Elizabeth M; Goldstein, Alisa M; Gruis, Nelleke A; Hansson, Johan; Helsing, Per; Hočevar, Marko; Höiom, Veronica; Ingvar, Christian; Kanetsky, Peter A; Chen, Wei V; Landi, Maria Teresa; Lang, Julie; Lathrop, G Mark; Lubiński, Jan; Mackie, Rona M; Mann, Graham J; Molven, Anders; Montgomery, Grant W; Novaković, Srdjan; Olsson, Håkan; Puig, Susana; Puig-Butille, Joan Anton; Qureshi, Abrar A; Radford-Smith, Graham L; van der Stoep, Nienke; van Doorn, Remco; Whiteman, David C; Craig, Jamie E; Schadendorf, Dirk; Simms, Lisa A; Burdon, Kathryn P; Nyholt, Dale R; Pooley, Karen A; Orr, Nick; Stratigos, Alexander J; Cust, Anne E; Ward, Sarah V; Hayward, Nicholas K; Han, Jiali; Schulze, Hans-Joachim; Dunning, Alison M; Bishop, Julia A Newton; Demenais, Florence; Amos, Christopher I; MacGregor, Stuart; Iles, Mark M

    2015-09-01

    Thirteen common susceptibility loci have been reproducibly associated with cutaneous malignant melanoma (CMM). We report the results of an international 2-stage meta-analysis of CMM genome-wide association studies (GWAS). This meta-analysis combines 11 GWAS (5 previously unpublished) and a further three stage 2 data sets, totaling 15,990 CMM cases and 26,409 controls. Five loci not previously associated with CMM risk reached genome-wide significance (P < 5 × 10(-8)), as did 2 previously reported but unreplicated loci and all 13 established loci. Newly associated SNPs fall within putative melanocyte regulatory elements, and bioinformatic and expression quantitative trait locus (eQTL) data highlight candidate genes in the associated regions, including one involved in telomere biology.

  1. Genome-wide meta-analysis identifies five new susceptibility loci for cutaneous malignant melanoma

    PubMed Central

    Law, Matthew H.; Bishop, D. Timothy; Martin, Nicholas G.; Moses, Eric K.; Song, Fengju; Barrett, Jennifer H.; Kumar, Rajiv; Easton, Douglas F.; Pharoah, Paul D. P.; Swerdlow, Anthony J.; Kypreou, Katerina P.; Taylor, John C.; Harland, Mark; Randerson-Moor, Juliette; Akslen, Lars A.; Andresen, Per A.; Avril, Marie-Françoise; Azizi, Esther; Scarrà, Giovanna Bianchi; Brown, Kevin M.; Dębniak, Tadeusz; Duffy, David L.; Elder, David E.; Fang, Shenying; Friedman, Eitan; Galan, Pilar; Ghiorzo, Paola; Gillanders, Elizabeth M.; Goldstein, Alisa M.; Gruis, Nelleke A.; Hansson, Johan; Helsing, Per; Hočevar, Marko; Höiom, Veronica; Ingvar, Christian; Kanetsky, Peter A.; Chen, Wei V.; Landi, Maria Teresa; Lang, Julie; Lathrop, G. Mark; Lubiński, Jan; Mackie, Rona M.; Mann, Graham J.; Molven, Anders; Montgomery, Grant W.; Novaković, Srdjan; Olsson, Håkan; Puig, Susana; Puig-Butille, Joan Anton; Qureshi, Abrar A.; Radford-Smith, Graham L.; van der Stoep, Nienke; van Doorn, Remco; Whiteman, David C.; Craig, Jamie E.; Schadendorf, Dirk; Simms, Lisa A.; Burdon, Kathryn P.; Nyholt, Dale R.; Pooley, Karen A.; Orr, Nick; Stratigos, Alexander J.; Cust, Anne E.; Ward, Sarah V.; Hayward, Nicholas K.; Han, Jiali; Schulze, Hans-Joachim; Dunning, Alison M.; Bishop, Julia A. Newton; MacGregor, Stuart; Iles, Mark M.

    2015-01-01

    Thirteen common susceptibility loci have been reproducibly associated with cutaneous malignant melanoma (CMM). We report the results of an international 2-stage meta-analysis of CMM genome-wide association studies (GWAS). This meta-analysis combines 11 GWAS (5 previously unpublished) and a further three stage 2 data sets, totaling 15,990 CMM cases and 26,409 controls. Five loci not previously associated with CMM risk reached genome-wide significance (P < 5×10–8), as did two previously-reported but un-replicated loci and all thirteen established loci. Novel SNPs fall within putative melanocyte regulatory elements, and bioinformatic and expression quantitative trait locus (eQTL) data highlight candidate genes including one involved in telomere biology. PMID:26237428

  2. Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci.

    PubMed

    Cortes, Adrian; Hadler, Johanna; Pointon, Jenny P; Robinson, Philip C; Karaderi, Tugce; Leo, Paul; Cremin, Katie; Pryce, Karena; Harris, Jessica; Lee, Seunghun; Joo, Kyung Bin; Shim, Seung-Cheol; Weisman, Michael; Ward, Michael; Zhou, Xiaodong; Garchon, Henri-Jean; Chiocchia, Gilles; Nossent, Johannes; Lie, Benedicte A; Førre, Øystein; Tuomilehto, Jaakko; Laiho, Kari; Jiang, Lei; Liu, Yu; Wu, Xin; Bradbury, Linda A; Elewaut, Dirk; Burgos-Vargas, Ruben; Stebbings, Simon; Appleton, Louise; Farrah, Claire; Lau, Jonathan; Kenna, Tony J; Haroon, Nigil; Ferreira, Manuel A; Yang, Jian; Mulero, Juan; Fernandez-Sueiro, Jose Luis; Gonzalez-Gay, Miguel A; Lopez-Larrea, Carlos; Deloukas, Panos; Donnelly, Peter; Bowness, Paul; Gafney, Karl; Gaston, Hill; Gladman, Dafna D; Rahman, Proton; Maksymowych, Walter P; Xu, Huji; Crusius, J Bart A; van der Horst-Bruinsma, Irene E; Chou, Chung-Tei; Valle-Oñate, Raphael; Romero-Sánchez, Consuelo; Hansen, Inger Myrnes; Pimentel-Santos, Fernando M; Inman, Robert D; Videm, Vibeke; Martin, Javier; Breban, Maxime; Reveille, John D; Evans, David M; Kim, Tae-Hwan; Wordsworth, Bryan Paul; Brown, Matthew A

    2013-07-01

    Ankylosing spondylitis is a common, highly heritable inflammatory arthritis affecting primarily the spine and pelvis. In addition to HLA-B*27 alleles, 12 loci have previously been identified that are associated with ankylosing spondylitis in populations of European ancestry, and 2 associated loci have been identified in Asians. In this study, we used the Illumina Immunochip microarray to perform a case-control association study involving 10,619 individuals with ankylosing spondylitis (cases) and 15,145 controls. We identified 13 new risk loci and 12 additional ankylosing spondylitis-associated haplotypes at 11 loci. Two ankylosing spondylitis-associated regions have now been identified encoding four aminopeptidases that are involved in peptide processing before major histocompatibility complex (MHC) class I presentation. Protective variants at two of these loci are associated both with reduced aminopeptidase function and with MHC class I cell surface expression.

  3. Self-assembled oxide films with tailored nanoscale ionic and electronic channels for controlled resistive switching

    NASA Astrophysics Data System (ADS)

    Cho, Seungho; Yun, Chao; Tappertzhofen, Stefan; Kursumovic, Ahmed; Lee, Shinbuhm; Lu, Ping; Jia, Quanxi; Fan, Meng; Jian, Jie; Wang, Haiyan; Hofmann, Stephan; MacManus-Driscoll, Judith L.

    2016-08-01

    Resistive switches are non-volatile memory cells based on nano-ionic redox processes that offer energy efficient device architectures and open pathways to neuromorphics and cognitive computing. However, channel formation typically requires an irreversible, not well controlled electroforming process, giving difficulty to independently control ionic and electronic properties. The device performance is also limited by the incomplete understanding of the underlying mechanisms. Here, we report a novel memristive model material system based on self-assembled Sm-doped CeO2 and SrTiO3 films that allow the separate tailoring of nanoscale ionic and electronic channels at high density (~1012 inch-2). We systematically show that these devices allow precise engineering of the resistance states, thus enabling large on-off ratios and high reproducibility. The tunable structure presents an ideal platform to explore ionic and electronic mechanisms and we expect a wide potential impact also on other nascent technologies, ranging from ionic gating to micro-solid oxide fuel cells and neuromorphics.

  4. Identification and control of a gentamicin resistant, meticillin susceptible Staphylococcus aureus outbreak on a neonatal unit

    PubMed Central

    Davies, Bethany; Menson, Esse; Klein, John L; Watts, Timothy L; Kearns, Angela M; Pichon, Bruno; Edgeworth, Jonathan D; French, Gary L

    2014-01-01

    We describe the identification and control of an outbreak of gentamicin resistant, meticillin susceptible Staphylococcus aureus (GR-MSSA) on a 36-bed neonatal unit (NNU) in London. Control measures included admission and weekly screening for GR-MSSA, cohorting affected babies, environmental and staff screening, hydrogen peroxide vapour (HPV) for terminal disinfection of cohort rooms, and reinforcement of hand hygiene. Seventeen babies were affected by the outbreak strain over ten months; seven were infected and ten were asymptomatic carriers. The outbreak strain was gentamicin resistant and all isolates were indistinguishable by pulsed-field gel electrophoresis. The outbreak strains spread rapidly and were associated with a high rate of bacteraemia (35% of 17 affected patients had bacteraemia vs. 10% of 284 patients with MSSA prior to the outbreak, p=0.007). None of 113 staff members tested were colonised with GR-MSSA. GR-MSSA was recovered from 11.5% of 87 environmental surfaces in cohort rooms, 7.1% of 28 communal surfaces and 4.1% of 74 surfaces after conventional terminal disinfection. None of 64 surfaces sampled after HPV decontamination yielded GR-MSSA. Recovery of GR-MSSA from two high level sites suggested that the organism could have been transmitted via air. Occasional breakdown in hand hygiene compliance and contaminated environmental surfaces probably contributed to transmission.

  5. By passing microbial resistance: xylitol controls microorganisms growth by means of its anti-adherence property.

    PubMed

    Ferreira, Aline S; Silva-Paes-Leme, Annelisa F; Raposo, Nádia R B; da Silva, Sílvio S

    2015-01-01

    Xylitol is an important polyalcohol suitable for use in odontological, medical and pharmaceutical products and as an additive in food. The first studies on the efficacy of xylitol in the control and treatment of infections started in the late 1970s and it is still applied for this purpose, with safety and very little contribution to resistance. Xylitol seems to act against microorganisms exerting an anti-adherence effect. Some research studies have demonstrated its action against Gram-positive and Gram-negative bacteria and yeasts. However, a clear explanation of how xylitol is effective has not been completely established yet. Some evidence shows that xylitol acts on gene expression, down-regulating the ones which are involved in the microorganisms' virulence, such as capsule formation. Another possible clarification is that xylitol blocks lectin-like receptors. The most important aspect is that, over time, xylitol bypasses microbial resistance and succeeds in controlling infection, either alone or combined with another compound. In this review, the effect of xylitol in inhibiting the growth of a different microorganism is described, focusing on studies in which such an anti-adherent property was highlighted. This is the first mini-review to describe xylitol as an anti-adherent compound and take into consideration how it exerts such action.

  6. Self-assembled oxide films with tailored nanoscale ionic and electronic channels for controlled resistive switching

    PubMed Central

    Cho, Seungho; Yun, Chao; Tappertzhofen, Stefan; Kursumovic, Ahmed; Lee, Shinbuhm; Lu, Ping; Jia, Quanxi; Fan, Meng; Jian, Jie; Wang, Haiyan; Hofmann, Stephan; MacManus-Driscoll, Judith L.

    2016-01-01

    Resistive switches are non-volatile memory cells based on nano-ionic redox processes that offer energy efficient device architectures and open pathways to neuromorphics and cognitive computing. However, channel formation typically requires an irreversible, not well controlled electroforming process, giving difficulty to independently control ionic and electronic properties. The device performance is also limited by the incomplete understanding of the underlying mechanisms. Here, we report a novel memristive model material system based on self-assembled Sm-doped CeO2 and SrTiO3 films that allow the separate tailoring of nanoscale ionic and electronic channels at high density (∼1012 inch−2). We systematically show that these devices allow precise engineering of the resistance states, thus enabling large on–off ratios and high reproducibility. The tunable structure presents an ideal platform to explore ionic and electronic mechanisms and we expect a wide potential impact also on other nascent technologies, ranging from ionic gating to micro-solid oxide fuel cells and neuromorphics. PMID:27491392

  7. Self-assembled oxide films with tailored nanoscale ionic and electronic channels for controlled resistive switching

    DOE PAGES

    Cho, Seungho; Yun, Chao; Tappertzhofen, Stefan; ...

    2016-08-05

    Resistive switches are non-volatile memory cells based on nano-ionic redox processes that offer energy efficient device architectures and open pathways to neuromorphics and cognitive computing. However, channel formation typically requires an irreversible, not well controlled electroforming process, giving difficulty to independently control ionic and electronic properties. The device performance is also limited by the incomplete understanding of the underlying mechanisms. Here, we report a novel memristive model material system based on self-assembled Sm-doped CeO2 and SrTiO3 films that allow the separate tailoring of nanoscale ionic and electronic channels at high density (~1012 inch–2). Here, we systematically show that these devicesmore » allow precise engineering of the resistance states, thus enabling large on–off ratios and high reproducibility. The tunable structure presents an ideal platform to explore ionic and electronic mechanisms and we expect a wide potential impact also on other nascent technologies, ranging from ionic gating to micro-solid oxide fuel cells and neuromorphics.« less

  8. Self-assembled oxide films with tailored nanoscale ionic and electronic channels for controlled resistive switching

    SciTech Connect

    Cho, Seungho; Yun, Chao; Tappertzhofen, Stefan; Kursumovic, Ahmed; Lee, Shinbuhm; Lu, Ping; Jia, Quanxi; Fan, Meng; Jian, Jie; Wang, Haiyan; Hofmann, Stephan; MacManus-Driscoll, Judith L.

    2016-08-05

    Resistive switches are non-volatile memory cells based on nano-ionic redox processes that offer energy efficient device architectures and open pathways to neuromorphics and cognitive computing. However, channel formation typically requires an irreversible, not well controlled electroforming process, giving difficulty to independently control ionic and electronic properties. The device performance is also limited by the incomplete understanding of the underlying mechanisms. Here, we report a novel memristive model material system based on self-assembled Sm-doped CeO2 and SrTiO3 films that allow the separate tailoring of nanoscale ionic and electronic channels at high density (~1012 inch–2). Here, we systematically show that these devices allow precise engineering of the resistance states, thus enabling large on–off ratios and high reproducibility. The tunable structure presents an ideal platform to explore ionic and electronic mechanisms and we expect a wide potential impact also on other nascent technologies, ranging from ionic gating to micro-solid oxide fuel cells and neuromorphics.

  9. [Importance of quality control for the detection of β-lactam antibiotic resistance in Enterobacteriaceae].

    PubMed

    Rivera, Alba; Larrosa, Nieves; Mirelis, Beatriz; Navarro, Ferran

    2014-02-01

    β-lactam antimicrobial agents are frequently used to treat infections caused by Enterobacteriaceae. The main mechanism of resistance to these antibiotics is the production of certain enzymes, collectively named β-lactamases. Due to their substrate profile and their epidemiological implications, the most clinically important β-lactamases are extended-spectrum β-lactamases, class C β-lactamases and carbapenemases. Phenotypic detection of these enzymes may be complicated and is based on the use of specific inhibitors of each β-lactamase and on the loss of activity on some β-lactam indicators. Various international committees postulate that it is no longer necessary to interpret the susceptibility results or determine the mechanism of resistance. Several critics disagree, however, and consider that susceptibility results should be interpreted until more data are available on the clinical efficacy of treatment with β-lactams. Given these methodological difficulties and constant changes in the interpretation criteria, we consider that training and external quality controls are essential to keep updated in this field. For learning purposes, these external quality controls should always be accompanied by a review of the results and methodology used, and the analysis of errors. In this paper we review and contextualize all the aspects related to the detection and interpretation of these β-lactamases.

  10. Self-assembled oxide films with tailored nanoscale ionic and electronic channels for controlled resistive switching.

    PubMed

    Cho, Seungho; Yun, Chao; Tappertzhofen, Stefan; Kursumovic, Ahmed; Lee, Shinbuhm; Lu, Ping; Jia, Quanxi; Fan, Meng; Jian, Jie; Wang, Haiyan; Hofmann, Stephan; MacManus-Driscoll, Judith L

    2016-08-05

    Resistive switches are non-volatile memory cells based on nano-ionic redox processes that offer energy efficient device architectures and open pathways to neuromorphics and cognitive computing. However, channel formation typically requires an irreversible, not well controlled electroforming process, giving difficulty to independently control ionic and electronic properties. The device performance is also limited by the incomplete understanding of the underlying mechanisms. Here, we report a novel memristive model material system based on self-assembled Sm-doped CeO2 and SrTiO3 films that allow the separate tailoring of nanoscale ionic and electronic channels at high density (∼10(12) inch(-2)). We systematically show that these devices allow precise engineering of the resistance states, thus enabling large on-off ratios and high reproducibility. The tunable structure presents an ideal platform to explore ionic and electronic mechanisms and we expect a wide potential impact also on other nascent technologies, ranging from ionic gating to micro-solid oxide fuel cells and neuromorphics.

  11. Genome-wide association study identifies five new schizophrenia loci

    PubMed Central

    2012-01-01

    We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 × 10−11) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10−9), ANK3 (rs10994359, P = 2.5 × 10−8) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10−9). PMID:21926974

  12. Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation

    PubMed Central

    Andlauer, Till F. M.; Buck, Dorothea; Antony, Gisela; Bayas, Antonios; Bechmann, Lukas; Berthele, Achim; Chan, Andrew; Gasperi, Christiane; Gold, Ralf; Graetz, Christiane; Haas, Jürgen; Hecker, Michael; Infante-Duarte, Carmen; Knop, Matthias; Kümpfel, Tania; Limmroth, Volker; Linker, Ralf A.; Loleit, Verena; Luessi, Felix; Meuth, Sven G.; Mühlau, Mark; Nischwitz, Sandra; Paul, Friedemann; Pütz, Michael; Ruck, Tobias; Salmen, Anke; Stangel, Martin; Stellmann, Jan-Patrick; Stürner, Klarissa H.; Tackenberg, Björn; Then Bergh, Florian; Tumani, Hayrettin; Warnke, Clemens; Weber, Frank; Wiendl, Heinz; Wildemann, Brigitte; Zettl, Uwe K.; Ziemann, Ulf; Zipp, Frauke; Arloth, Janine; Weber, Peter; Radivojkov-Blagojevic, Milena; Scheinhardt, Markus O.; Dankowski, Theresa; Bettecken, Thomas; Lichtner, Peter; Czamara, Darina; Carrillo-Roa, Tania; Binder, Elisabeth B.; Berger, Klaus; Bertram, Lars; Franke, Andre; Gieger, Christian; Herms, Stefan; Homuth, Georg; Ising, Marcus; Jöckel, Karl-Heinz; Kacprowski, Tim; Kloiber, Stefan; Laudes, Matthias; Lieb, Wolfgang; Lill, Christina M.; Lucae, Susanne; Meitinger, Thomas; Moebus, Susanne; Müller-Nurasyid, Martina; Nöthen, Markus M.; Petersmann, Astrid; Rawal, Rajesh; Schminke, Ulf; Strauch, Konstantin; Völzke, Henry; Waldenberger, Melanie; Wellmann, Jürgen; Porcu, Eleonora; Mulas, Antonella; Pitzalis, Maristella; Sidore, Carlo; Zara, Ilenia; Cucca, Francesco; Zoledziewska, Magdalena; Ziegler, Andreas; Hemmer, Bernhard; Müller-Myhsok, Bertram

    2016-01-01

    We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis. PMID:27386562

  13. Flux control-based design of furfural-resistance strains of Saccharomyces cerevisiae for lignocellulosic biorefinery.

    PubMed

    Unrean, Pornkamol

    2016-12-26

    We have previously developed a dynamic flux balance analysis of Saccharomyces cerevisiae for elucidation of genome-wide flux response to furfural perturbation (Unrean and Franzen, Biotechnol J 10(8):1248-1258, 2015). Herein, the dynamic flux distributions were analyzed by flux control analysis to identify target overexpressed genes for improved yeast robustness against furfural. The flux control coefficient (FCC) identified overexpressing isocitrate dehydrogenase (IDH1), a rate-controlling flux for ethanol fermentation, and dicarboxylate carrier (DIC1), a limiting flux for cell growth, as keys of furfural-resistance phenotype. Consistent with the model prediction, strain characterization showed 1.2- and 2.0-fold improvement in ethanol synthesis and furfural detoxification rates, respectively, by IDH1 overexpressed mutant compared to the control. DIC1 overexpressed mutant grew at 1.3-fold faster and reduced furfural at 1.4-fold faster than the control under the furfural challenge. This study hence demonstrated the FCC-based approach as an effective tool for guiding the design of robust yeast strains.

  14. The effect of chest expansion resistance exercise in chronic stroke patients: a randomized controlled trial

    PubMed Central

    Kim, Chang-Beom; Shin, Jun-Ho; Choi, Jong-Duk

    2015-01-01

    [Purpose] The aim of this study was to examine the initial effects of chest expansion resistance exercise (CERE) applied to chronic stroke patients on their pulmonary functions, chest expansion, and functional gait ability. [Subjects] Forty chronic stroke patients without any respiration-related rehabilitation program experience (21 men and 19 women; times elapsed since occurrence of stroke: 21.8 ± 5.3 months) were randomly and equally allocated to a CERE group (experimental group) and a control group. [Methods] An ordinary stroke rehabilitation program was performed on the subjects. While the experimental group received a CERE intervention, the control group performed passive range of motion exercise with automatic instruments. [Results] The CERE group’s chest expansion significantly increased after the intervention, whereas the control group did not see any significant difference. As regards VC (vital capacity), FVC (forced vital capacity), and FEV1 (forced expiratory volume in one second), there were no significant changes in either the CERE or control group. In the 10MTWT (10-meter timed walking test), there were no significant changes in either group, but in the 6MWT (6-minute walk test), while there were no significant differences in the control group, the CERE group saw significant changes. [Conclusion] The results of application of CERE to chronic stroke patients demonstrated the importance of respiratory exercise in an approach to stroke rehabilitation treatment intervention and the need to add respiratory exercise to a rehabilitation intervention program. PMID:25729188

  15. Parasite control in the age of drug resistance and changing agricultural practices.

    PubMed

    Molento, Marcelo Beltrão

    2009-08-07

    The benefits of using antiparasitic drugs in farm animals are unquestionable. However, despite anthelmintic use as the predominant control strategy, extreme parasite infection cases are appearing in sheep and goat production; these impact productivity and have show mortality rates reaching pre-drug use levels. This was a predictable situation resulting from the loss of efficacy by all available products, particularly when some products were used as the sole intervention. The concepts of agroecology and holistic agriculture, which advocate the use of integrated management strategies, such as target selected treatment, herbal medicine, and the application of other parasite control alternatives, are not completely new, but are undergoing a resurgence because of their more sustainable appeal. The objective of this review article is to examine the problem of parasite control in the face of parasite drug resistance and to outline some strategies that may be used in parasite control programmes. Before they are accepted and recommended by the WAAVP, agroecological methods such as those listed above and described in detail herein should be validated based on scientific evidence of their efficacy for parasite control and should be tested for both host and environmental safety.

  16. Surveillance, insecticide resistance and control of an invasive Aedes aegypti (Diptera: Culicidae) population in California

    PubMed Central

    Cornel, Anthony J.; Holeman, Jodi; Nieman, Catelyn C.; Lee, Yoosook; Smith, Charles; Amorino, Mark; Brisco, Katherine K.; Barrera, Roberto; Lanzaro, Gregory C.; Mulligan III, F. Stephen

    2016-01-01

    The invasion and subsequent establishment in California of Aedes aegypti in 2013 has created new challenges for local mosquito abatement and vector control districts. Studies were undertaken to identify effective and economical strategies to monitor the abundance and spread of this mosquito species as well as for its control. Overall, BG Sentinel (BGS) traps were found to be the most sensitive trap type to measure abundance and spread into new locations. Autocidal-Gravid-Ovitraps (AGO-B), when placed at a site for a week, performed equally to BGS in detecting the presence of female Ae. aegypti. Considering operational cost and our findings, we recommend use of BGS traps for surveillance in response to service requests especially in locations outside the known infestation area. We recommend AGO-Bs be placed at fixed sites, cleared and processed once a week to monitor mosquito abundance within a known infestation area. Long-term high density placements of AGO-Bs were found to show promise as an environmentally friendly trap-kill control strategy. California Ae. aegypti were found to be homozygous for the V1016I mutation in the voltage gated sodium channel gene, which is implicated to be involved in insecticide resistance. This strain originating from Clovis, California was resistant to some pyrethroids but not to deltamethrin in bottle bio-assays. Sentinel cage ultra-low-volume (ULV) trials using a new formulation of deltamethrin (DeltaGard®) demonstrated that it provided some control (average of 56% death in sentinel cages in a 91.4 m spray swath) after a single truck mounted aerial ULV application in residential areas. PMID:27158450

  17. Risk factors for multidrug-resistant tuberculosis among tuberculosis patients: a case-control study

    PubMed Central

    Workicho, Abdulhalik; Kassahun, Wondwosen; Alemseged, Fessahaye

    2017-01-01

    Background Multidrug-resistant tuberculosis (MDR-TB) did not receive major attention until recently in sub-Saharan Africa where the tuberculosis incidence and risk factors are highest. Factors leading to development of drug resistance need to be understood to develop appropriate control strategies for national programs. The objective of this study was to identify the risk factors for MDR-TB among tuberculosis patients. Methods A case-control study was conducted to assess sociodemographic, behavioral and clinical risk factors using a structured questionnaire and clinical record reviewing. The data were entered and analyzed using SPSS windows version 16. Descriptive analysis was done to generate summary values for the variables and those significant variables in the bivariate analysis at p-value less than 0.25 were entered to multivariable logistic regression to identify independent determinants. Statistical significance was declared at p-value less than or equal to 0.05. Results A total of 90 cases and 90 controls were included in the study. Age of respondents (adjusted odds ratio [AOR] =7; 95% confidence interval [CI]: 2.6–24.5), living in a household with only one room (AOR=5; 95%CI: 1.68–15.38), history of previous treatment (AOR=21; 95% CI: 17.8–28) and being HIV infected (AOR=3.1; 95%CI: 1.02–9.4) were found to be independent predictors of MDR-TB. Conclusion In light of these findings, the strategies in controlling MDR-TB should emphasize on patients with HIV coinfection, young patients, those who have a history of previous treatment, and those living in crowded places. PMID:28331350

  18. Surveillance, insecticide resistance and control of an invasive Aedes aegypti (Diptera: Culicidae) population in California.

    PubMed

    Cornel, Anthony J; Holeman, Jodi; Nieman, Catelyn C; Lee, Yoosook; Smith, Charles; Amorino, Mark; Brisco, Katherine K; Barrera, Roberto; Lanzaro, Gregory C; Mulligan Iii, F Stephen

    2016-01-01

    The invasion and subsequent establishment in California of Aedes aegypti in 2013 has created new challenges for local mosquito abatement and vector control districts. Studies were undertaken to identify effective and economical strategies to monitor the abundance and spread of this mosquito species as well as for its control. Overall, BG Sentinel (BGS) traps were found to be the most sensitive trap type to measure abundance and spread into new locations. Autocidal-Gravid-Ovitraps (AGO-B), when placed at a site for a week, performed equally to BGS in detecting the presence of female Ae. aegypti. Considering operational cost and our findings, we recommend use of BGS traps for surveillance in response to service requests especially in locations outside the known infestation area. We recommend AGO-Bs be placed at fixed sites, cleared and processed once a week to monitor mosquito abundance within a known infestation area. Long-term high density placements of AGO-Bs were found to show promise as an environmentally friendly trap-kill control strategy. California Ae. aegypti were found to be homozygous for the V1016I mutation in the voltage gated sodium channel gene, which is implicated to be involved in insecticide resistance. This strain originating from Clovis, California was resistant to some pyrethroids but not to deltamethrin in bottle bio-assays. Sentinel cage ultra-low-volume (ULV) trials using a new formulation of deltamethrin (DeltaGard®) demonstrated that it provided some control (average of 56% death in sentinel cages in a 91.4 m spray swath) after a single truck mounted aerial ULV application in residential areas.

  19. Controlling multidrug-resistant tuberculosis and access to expensive drugs: a rational framework.

    PubMed Central

    Pablos-Mendez, Ariel; Gowda, Deepthiman K.; Frieden, Thomas R.

    2002-01-01

    The emergence and spread of multidrug-resistant tuberculosis (MDR-TB), i.e. involving resistance to at least isoniazid and rifampicin, could threaten the control of TB globally. Controversy has emerged about the best way of confronting MDR-TB in settings with very limited resources. In 1999, the World Health Organization (WHO) created a working group on DOTS-Plus, an initiative exploring the programmatic feasibility and cost-effectiveness of treating MDR-TB in low-income and middle-income countries, in order to consider the management of MDR-TB under programme conditions. The challenges of implementation have proved more daunting than those of access to second-line drugs, the prices of which are dropping. Using data from the WHO/International Union Against Tuberculosis and Lung Disease surveillance project, we have grouped countries according to the proportion of TB patients completing treatment successfully and the level of MDR-TB among previously untreated patients. The resulting matrix provides a reasonable framework for deciding whether to use second-line drugs in a national programme. Countries in which the treatment success rate, i.e. the proportion of new patients who complete the scheduled treatment, irrespective of whether bacteriological cure is documented, is below 70% should give the highest priority to introducing or improving DOTS, the five-point TB control strategy recommended by WHO and the International Union Against Tuberculosis and Lung Disease. A poorly functioning programme can create MDR-TB much faster than it can be treated, even if unlimited resources are available. There is no single prescription for controlling MDR-TB but the various tools available should be applied wisely. Firstly, good DOTS and infection control; then appropriate use of second-line drug treatment. The interval between the two depends on the local context and resources. As funds are allocated to treat MDR-TB, human and financial resources should be increased to expand

  20. Ground reaction force comparison of controlled resistance methods to isoinertial loading of the squat exercise - biomed 2010.

    PubMed

    Paulus, David C; Reynolds, Michael C; Schilling, Brian K

    2010-01-01

    The ground reaction force during the concentric (raising) portion of the squat exercise was compared to that of isoinertial loading (free weights) for three pneumatically controlled resistance methods: constant resistance, cam force profile, and proportional force control based on velocity. Constant force control showed lower ground reaction forces than isoinertial loading throughout the range of motion (ROM). The cam force profile exhibited slightly greater ground reaction forces than isoinertial loading at 10 and 40% ROM with fifty-percent greater loading at 70% ROM. The proportional force control consistently elicited greater ground reaction force than isoinertial loading, which progressively ranged from twenty to forty percent increase over isoinertial loading except for being approximately equal at 85% ROM. Based on these preliminary results, the proportional control shows the most promise for providing loading that is comparable in magnitude to isoinertial loading. This technology could optimize resistance exercise for sport-specific training or as a countermeasure to atrophy during spaceflight.

  1. Natural genetic and induced plant resistance, as a control strategy to plant-parasitic nematodes alternative to pesticides.

    PubMed

    Molinari, Sergio

    2011-03-01

    Plant-parasitic nematodes are pests of a wide range of economically important crops, causing severe losses to agriculture. Natural genetic resistance of plants is expected to be a valid solution of the many problems nematodes cause all over the world. Progress in resistance applications is particularly important for the less-developed countries of tropical and subtropical regions, since use of resistant cultivars may be the only possible and economically feasible control strategy in those farming systems. Resistance is being considered of particular importance also in modern high-input production systems of developed countries, as the customary reliance on chemical nematicides has been restricted or has come to an end. This review briefly describes the genetic bases of resistance to nematodes in plants and focuses on the chances and problems of its exploitation as a key element in an integrated management program. Much space is dedicated to the major problem of resistance durability, in that the intensive use of resistant cultivars is likely to increasingly induce the selection of virulent populations able to "break" the resistance. Protocols of pest-host suitability are described, as bioassays are being used to evaluate local nematode populations in their potential to be selected on resistant germplasm and endanger resistant crops. The recent progress in using robust and durable resistances against nematodes as an efficient method for growers in vegetable cropping systems is reported, as well as the possible use of chemicals that do not show any unfavorable impact on environment, to induce in plants resistance against plant-parasitic nematodes.

  2. Comparison of deep and superficial abdominal muscle activity between experienced Pilates and resistance exercise instructors and controls during stabilization exercise

    PubMed Central

    Moon, Ji-Hyun; Hong, Sang-Min; Kim, Chang-Won; Shin, Yun-A

    2015-01-01

    Pilates and resistance exercises are used for lumbar stabilization training. However, it is unclear which exercise is more effective for lumbar stabilization. In our study, we aimed to compare surface muscle activity and deep muscle thickness during relaxation and spinal stabilization exercise in experienced Pilates and resistance exercise instructors. This study is a retrospective case control study set in the Exercise Prescription Laboratory and Sports Medicine Center. The participants included Pilates instructors (mean years of experience, 3.20±1.76; n=10), resistance exercise instructors (mean years of experience, 2.53±0.63; n=10), and controls (n=10). The participants performed 4 different stabilization exercises: abdominal drawing-in maneuver, bridging, roll-up, and one-leg raise. During the stabilization exercises, surface muscle activity was measured with electromyography, whereas deep muscle thickness was measured by ultrasound imaging. During the 4 stabilization exercises, the thickness of the transverse abdominis (TrA) was significantly greater in the Pilates-trained group than the other 2 other groups. The internal oblique (IO) thickness was significantly greater in the Pilates- and resistance-trained group than the control group, during the 4 exercises. However, the surface muscle activities were similar between the groups. Both Pilates and resistance exercise instructors had greater activation of deep muscles, such as the TrA and IO, than the control subjects. Pilates and resistance exercise are both effective for increasing abdominal deep muscle thickness. PMID:26171383

  3. Comparison of deep and superficial abdominal muscle activity between experienced Pilates and resistance exercise instructors and controls during stabilization exercise.

    PubMed

    Moon, Ji-Hyun; Hong, Sang-Min; Kim, Chang-Won; Shin, Yun-A

    2015-06-01

    Pilates and resistance exercises are used for lumbar stabilization training. However, it is unclear which exercise is more effective for lumbar stabilization. In our study, we aimed to compare surface muscle activity and deep muscle thickness during relaxation and spinal stabilization exercise in experienced Pilates and resistance exercise instructors. This study is a retrospective case control study set in the Exercise Prescription Laboratory and Sports Medicine Center. The participants included Pilates instructors (mean years of experience, 3.20±1.76; n=10), resistance exercise instructors (mean years of experience, 2.53±0.63; n=10), and controls (n=10). The participants performed 4 different stabilization exercises: abdominal drawing-in maneuver, bridging, roll-up, and one-leg raise. During the stabilization exercises, surface muscle activity was measured with electromyography, whereas deep muscle thickness was measured by ultrasound imaging. During the 4 stabilization exercises, the thickness of the transverse abdominis (TrA) was significantly greater in the Pilates-trained group than the other 2 other groups. The internal oblique (IO) thickness was significantly greater in the Pilates- and resistance-trained group than the control group, during the 4 exercises. However, the surface muscle activities were similar between the groups. Both Pilates and resistance exercise instructors had greater activation of deep muscles, such as the TrA and IO, than the control subjects. Pilates and resistance exercise are both effective for increasing abdominal deep muscle thickness.

  4. GWAS identifies four novel eosinophilic esophagitis loci

    PubMed Central

    Sleiman, Patrick MA; Wang, Mei-Lun; Cianferoni, Antonella; Aceves, Seema; Gonsalves, Nirmala; Nadeau, Kari; Bredenoord, Albert J.; Furuta, Glenn T.; Spergel, Jonathan M.; Hakonarson, Hakon

    2014-01-01

    Eosinophilic esophagitis (EoE) is an allergic disorder characterized by infiltration of the esophagus with eosinophils. We had previously reported association of the TSLP/WDR36 locus with EoE. Here we report genome-wide significant associations at four additional loci; c11orf30 and STAT6, which have been previously associated with both atopic and autoimmune disease, and two EoE-specific loci, ANKRD27 that regulates the trafficking of melanogenic enzymes to epidermal melanocytes and CAPN14, that encodes a calpain whose expression is highly enriched in the esophagus. The identification of five EoE loci, not only expands our etiological understanding of the disease but may also represent new therapeutic targets to treat the most debilitating aspect of EoE, esophageal inflammation and remodeling. PMID:25407941

  5. Identification of a locus in arabidopsis controlling both the expression of rhizobacteria-mediated induced systemic resistance (ISR) and basal resistance against Pseudomonas syringae pv. tomato.

    PubMed

    Ton, J; Pieterse, C M; Van Loon, L C

    1999-10-01

    Selected nonpathogenic rhizobacteria with biological disease control activity are able to elicit an induced systemic resistance (ISR) response that is phenotypically similar to pathogen-induced systemic acquired resistance (SAR). Ten ecotypes of Arabidopsis thaliana were screened for their potential to express rhizobacteria-mediated ISR and pathogen-induced SAR against the leaf pathogen Pseudomonas syringae pv. tomato DC3000 (Pst). All ecotypes expressed SAR. However, of the 10 ecotypes tested, ecotypes RLD and Wassilewskija (Ws) did not develop ISR after treatment of the roots with nonpathogenic Pseudomonas fluorescens WCS417r bacteria. This nonresponsive phenotype was associated with relatively high susceptibility to Pst infection. The F1 progeny of crosses between the non-responsive ecotypes RLD and Ws on the one hand, and the responsive ecotypes Columbia (Col) and Landsberg erecta (Ler) on the other hand, were fully capable of expressing ISR and exhibited a relatively high level of basal resistance, similar to that of their WCS417r-responsive parent. This indicates that the potential to express ISR and the relatively high level of basal resistance against Pst are both inherited as dominant traits. Analysis of the F2 and F3 progeny of a Col x RLD cross revealed that inducibility of ISR and relatively high basal resistance against Pst cosegregate in a 3:1 fashion, suggesting that both resistance mechanisms are monogenically determined and genetically linked. Neither the responsiveness to WCS417r nor the relatively high level of basal resistance against Pst were complemented in the F1 progeny of crosses between RLD and Ws, indicating that RLD and Ws are both affected in the same locus, necessary for the expression of ISR and basal resistance against Pst. The corresponding locus, designated ISR1, was mapped between markers B4 and GL1 on chromosome 3. The observed association between ISR and basal resistance against Pst suggests that rhizobacteria-mediated ISR

  6. Control of antibiotic resistance in China must not be delayed: The current state of resistance and policy suggestions for the government, medical facilities, and patients.

    PubMed

    Tang, Qi; Song, Peipei; Li, Jiajia; Kong, Fanlei; Sun, Long; Xu, Lingzhong

    2016-02-01

    Antibiotics are medicines used to prevent and treat bacterial infections. Antibiotic resistance occurs when bacteria change in response to the use of these medicines. Antibiotic resistance is rising to dangerously high levels in all parts of the world, leading to higher medical costs, prolonged hospital stays, and increased mortality. In the European Union alone, drug-resistant bacteria are estimated to cause 25,000 deaths and cost more than US$1.5 billion every year in healthcare expenses and productivity losses. The problems of antibiotic misuse and antibiotic resistance are quite serious in China. In 2015, results of a study by the State Key Laboratory of Organic Geochemistry, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences indicated that the total antibiotic usage in China in 2013 was approximately 162,000 tons, including human use (48%) and use in animals (52%). This amount accounted for about half of the antibiotic usage worldwide. The per-capita use of antibiotics in China is more than 5 times that in Europe and the United States. These data mean that China is one of the world's leading countries with serious problems in terms of antibiotic misuse and antibiotic resistance. The current article analyzes the current state and harms of antibiotic misuse and causes of antibiotic resistance in China. The Government needs to pay close attention to the issue of antibiotic resistance in China and formulate a strategy at the national level. Thus, the following suggestions are offered: i) The Chinese Government should implement policies that promote antibiotic research and development; ii) Medical facilities in China should create multidisciplinary teams (MDTs) and encourage early action by MDTs to control the spread of multi-drug-resistant bacteria (MDRB); iii) An intervention in the form of health education should target patients and accompanying family members (AFM) in China. In other words, antibiotic resistance is not a personal problem but an

  7. Technological approaches to optimize colonial resistance control for humans in artificial environment

    NASA Astrophysics Data System (ADS)

    Viacheslav, Ilyin; Skedina, Marina; Muokhamedieva, Lana; Gegenava, Anna; Mardanov, Robert

    Infectious safety of humans in confined habitat is one of the most important problems of contem-porary space medicine. It is known that together with increasing of space station exploration increases the risc of nosocomial-like strains formation. Investigations analyzing spaceflights on spaceships Spollo, Soyuz, Saljut, Mir revealed shifts in content of human microflora, decreas-ing of protective microflora and immunity, translocation of conventional pathogens, mainly, spaphylococci, to different biotopes. At present time, control on microbial state of cosmo-nauts is performed on Earth before and after the flight, and once in flight 5 days prior to landing. This seems to me not enough. Together with increasing of spaceflight duration it starts to be mostly actual to develop contemporary technological approaches to perform op-erative control on colonial resistance of cosmonauts. It is preferable that these means and measures should be simple and biologically safe, i.e. non-cultivating. One of such technologies is express-diagnostics of human disbiotic shifts with the aid of automatised method of digital treatment of microscopy microbial images. At present the standardized swab and automatised recognizing of microbial cells with calculation of quantitative rate of different microbial groups in tested materials and it's transformation via telecommunication channels. Knowing content and quantity of microbes in tested biotope, one can forecast risk of infection development and give countermeasures recommendation. Other prospective technology -gaseous chromatomass spectrometry which basing on analysis of different microbial volatile lipid acids can determine quantity and content of microbes. These markers are unique for different microbial specia and allow to isolate them from plenty of bioobjects. This technology was also successfully tested for space crewmembers in groundbase studies and in spaceflight. The data revealed increasing of pathogenicity potential on

  8. Quantitative trait loci for resistance to Maize rayado fino virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maize rayado fino virus (MRFV) causes one of the most important virus diseases of maize in regions of Mexico, Central and South America, where it causes moderate to severe yield losses. The virus is found from the southern United States. to northern Argentina where its vector, the maize leafhopper D...

  9. Snail controls the mesenchymal phenotype and drives erlotinib resistance in Oral epithelial and HNSCC cells

    PubMed Central

    Dennis, Miranda; Wang, Guanyu; Luo, Jie; Lin, Yuan; Dohadwala, Mariam; Sidell, Douglas; DeConde, Adam; Abemayor, Elliot; Elashoff, David A.; Sharma, Sherven; Dubinett, Steven M.; St John, Maie A.

    2014-01-01

    PURPOSE The presence of regional metastases in HNSCC patients is a common and adverse event associated with poor prognosis. Understanding the molecular mechanisms that mediate HNSCC metastasis may enable identification of novel therapeutic targets. Our recent work on human HNSCC tissues underlies Snail’s role as a molecular prognostic marker for HNSCC. Snail positivity is significantly predictive of poorly differentiated, lymphovascular invasive, as well as regionally metastatic tumors. We recently reported the role of Snail in the inflammation-induced promotion of EMT in HNSCC. However, other important Snail-dependent malignant phenotypes have not been fully explored. Here, we investigate the capacity of Snail to drive EMT in human oral epithelial cell lines, and its ability to confer drug resistance. EXPERIMENTAL DESIGN Snail was overexpressed HNSCC and oral epithelial cell lines. AIG assays, wound healing assays, invasion & migration assays, spheroid modeling, and cell survival assays were performed. RESULTS The overexpression of Snail in human HNSCC and oral epithelial cell lines drives EMT. The sole transfection of Snail confers the expression of a mesenchymal molecular signature including down-regulation of the epithelial adherens, such as E-cadherin and β-catenin, and induction of mesenchymal markers, Snail overexpressing cell lines demonstrate rapid growth in Anchorage-independent growth assays; a decreased capacity to form tight spheroids; increased resistance to erlotinib; and have an increased capacity for invasion. CONCLUSION Snail controls the mesenchymal phenotype and drives erlotinib resistance in HNSCC cells. Snail may prove to be a useful marker in predicting EGFR inhibitor responsiveness. PMID:22568942

  10. Integrated management of fusarium wilt of chickpea with sowing date, host resistance, and biological control.

    PubMed

    Landa, Blanca B; Navas-Cortés, Juan A; Jiménez-Díaz, Rafael M

    2004-09-01

    ABSTRACT A 3-year experiment was conducted in field microplots infested with Fusarium oxysporum f. sp. ciceris race 5 at Córdoba, Spain, in order to assess efficacy of an integrated management strategy for Fusarium wilt of chickpea that combined the choice of sowing date, use of partially resistant chickpea genotypes, and seed and soil treatments with biocontrol agents Bacillus megaterium RGAF 51, B. subtilis GB03, nonpathogenic F. oxysporum Fo 90105, and Pseudomonas fluorescens RG 26. Advancing the sowing date from early spring to winter significantly delayed disease onset, reduced the final disease intensity (amount of disease in a microplot that combines disease incidence and severity, expressed as a percentage of the maximum possible amount of disease in that microplot), and increased chickpea seed yield. A significant linear relationship was found between disease development over time and weather variables at the experimental site, with epidemics developing earlier and faster as mean temperature increased and accumulated rainfall decreased. Under conditions highly conducive for Fusarium wilt development, the degree of disease control depended primarily on choice of sowing date, and to a lesser extent on level of resistance of chickpea genotypes to F. oxysporum f. sp. ciceris race 5, and the biocontrol treatments. The main effects of sowing date, partially resistant genotypes, and biocontrol agents were a reduction in the rate of epidemic development over time, a reduction of disease intensity, and an increase in chickpea seedling emergence, respectively. Chickpea seed yield was influenced by all three factors in the study. The increase in chickpea seed yield was the most consistent effect of the biocontrol agents. However, that effect was primarily influenced by sowing date, which also determined disease development. Effectiveness of biocontrol treatments in disease management was lowest in January sowings, which were least favorable for Fusarium wilt. Sowing

  11. Insecticide resistance in Culex quinquefasciatus from Zanzibar: implications for vector control programmes

    PubMed Central

    2012-01-01

    Background Zanzibar has a long history of lymphatic filariasis (LF) caused by the filarial parasite Wuchereria bancrofti, and transmitted by the mosquito Culex quinquefasciatus Say. The LF Programme in Zanzibar has successfully implemented mass drug administration (MDA) to interrupt transmission, and is now in the elimination phase. Monitoring infections in mosquitoes, and assessing the potential role of interventions such as vector control, is important in case the disease re-emerges as a public health problem. Here, we examine Culex mosquito species from the two main islands to detect W. bancrofti infection and to determine levels of susceptibility to the insecticides used for vector control. Methods Culex mosquitoes collected during routine catches in Vitongoji, Pemba Island, and Makadara, Unguja Island were tested for W. bancrofti infection using PCR. Insecticide bioassays on Culex mosquitoes were performed to determine susceptibility to permethrin, deltamethrin, lambda-cyhalothrin, DDT and bendiocarb. Additional synergism assays with piperonyl butoxide (PBO) were used for lambda-cyhalothrin. Pyrosequencing was used to determine the kdr genotype and sequencing of the mitochondrial cytochrome oxidase I (mtCOI) subunit performed to identify ambiguous Culex species. Results None of the wild-caught Culex mosquitoes analysed were found to be positive for W. bancrofti. High frequencies of resistance to all insecticides were found in Wete, Pemba Island, whereas Culex from the nearby site of Tibirinzi (Pemba) and in Kilimani, Unguja Island remained relatively susceptible. Species identification confirmed that mosquitoes from Wete were Culex quinquefasciatus. The majority of the Culex collected from Tibirinzi and all from Kilimani could not be identified to species by molecular assays. Two alternative kdr alleles, both resulting in a L1014F substitution were detected in Cx. quinquefasciatus from Wete with no homozygote susceptible detected. Metabolic resistance to

  12. Field Efficacy of New Larvicide Products for Control of Multi-Resistant Aedes aegypti Populations in Martinique (French West Indies)

    PubMed Central

    Marcombe, Sébastien; Darriet, Frédéric; Agnew, Philip; Etienne, Manuel; Yp-Tcha, Marie-Michelle; Yébakima, André; Corbel, Vincent

    2011-01-01

    World-wide dengue vector control is hampered by the spread of insecticide resistance in Aedes aegypti. We report the resistance status of a wild Ae. aegypti population from Martinique (Vauclin) to conventional larvicides (Bacillus thuringiensis var israeliensis [Bti] and temephos) and potential alternatives (spinosad, diflubenzuron, and pyriproxyfen). The efficacy and residual activity of these insecticides were evaluated under simulated and field conditions. The Vauclin strain exhibited a high level of resistance to temephos, a tolerance to insect growth regulators, and full susceptibility to spinosad and Bti. In simulated trials, pyriproxyfen and Bti showed long residual activities in permanent breeding containers (28 and 37 weeks), whereas under field conditions they failed to curtail Ae. aegypti populations after four weeks. Conversely, diflubenzuron and spinosad showed a residual efficacy of 16 weeks, suggesting that these chemicals may be promising alternatives to Bti and temephos for controlling insecticide-resistant Ae. aegypti populations. PMID:21212213

  13. Field efficacy of new larvicide products for control of multi-resistant Aedes aegypti populations in Martinique (French West Indies).

    PubMed

    Marcombe, Sébastien; Darriet, Frédéric; Agnew, Philip; Etienne, Manuel; Yp-Tcha, Marie-Michelle; Yébakima, André; Corbel, Vincent

    2011-01-01

    World-wide dengue vector control is hampered by the spread of insecticide resistance in Aedes aegypti. We report the resistance status of a wild Ae. aegypti population from Martinique (Vauclin) to conventional larvicides (Bacillus thuringiensis var israeliensis [Bti] and temephos) and potential alternatives (spinosad, diflubenzuron, and pyriproxyfen). The efficacy and residual activity of these insecticides were evaluated under simulated and field conditions. The Vauclin strain exhibited a high level of resistance to temephos, a tolerance to insect growth regulators, and full susceptibility to spinosad and Bti. In simulated trials, pyriproxyfen and Bti showed long residual activities in permanent breeding containers (28 and 37 weeks), whereas under field conditions they failed to curtail Ae. aegypti populations after four weeks. Conversely, diflubenzuron and spinosad showed a residual efficacy of 16 weeks, suggesting that these chemicals may be promising alternatives to Bti and temephos for controlling insecticide-resistant Ae. aegypti populations.

  14. Quickest detection of drug-resistant seizures: An optimal control approach

    PubMed Central

    Santaniello, Sabato; Burns, Samuel P.; Golby, Alexandra J.; Singer, Jedediah M.; Anderson, William S.; Sarma, Sridevi V.

    2011-01-01

    Epilepsy affects 50 million people worldwide, and seizures in 30% of the cases remain drug resistant. This has increased interest in responsive neurostimulation, which is most effective when administered during seizure onset. We propose a novel framework for seizure onset detection that involves (i) constructing statistics from multichannel intracranial EEG (iEEG) to distinguish nonictal versus ictal states; (ii) modeling the dynamics of these statistics in each state and the state transitions; you can remove this word if there is no room. (iii) developing an optimal control-based “quickest detection” (QD) strategy to estimate the transition times from nonictal to ictal states from sequential iEEG measurements. The QD strategy minimizes a cost function of detection delay and false positive probability. The solution is a threshold that non-monotonically decreases over time and avoids responding to rare events that normally trigger false positives. We applied QD to four drug resistant epileptic patients (168 hour continuous recordings, 26–44 electrodes, 33 seizures) and achieved 100% sensitivity with low false positive rates (0.16 false positive/hour). This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction. PMID:22078519

  15. Control of diabetic hyperglycaemia and insulin resistance through TSC22D4

    PubMed Central

    Ekim Üstünel, Bilgen; Friedrich, Kilian; Maida, Adriano; Wang, Xiaoyue; Krones-Herzig, Anja; Seibert, Oksana; Sommerfeld, Anke; Jones, Allan; Sijmonsma, Tjeerd P.; Sticht, Carsten; Gretz, Norbert; Fleming, Thomas; Nawroth, Peter P.; Stremmel, Wolfgang; Rose, Adam J.; Berriel-Diaz, Mauricio; Blüher, Matthias; Herzig, Stephan

    2016-01-01

    Obesity-related insulin resistance represents the core component of the metabolic syndrome, promoting glucose intolerance, pancreatic beta cell failure and type 2 diabetes. Efficient and safe insulin sensitization and glucose control remain critical therapeutic aims to prevent diabetic late complications Here, we identify transforming growth factor beta-like stimulated clone (TSC) 22 D4 as a molecular determinant of insulin signalling and glucose handling. Hepatic TSC22D4 inhibition both prevents and reverses hyperglycaemia, glucose intolerance and insulin resistance in diabetes mouse models. TSC22D4 exerts its effects on systemic glucose homeostasis—at least in part—through the direct transcriptional regulation of the small secretory protein lipocalin 13 (LCN13). Human diabetic patients display elevated hepatic TSC22D4 expression, which correlates with decreased insulin sensitivity, hyperglycaemia and LCN13 serum levels. Our results establish TSC22D4 as a checkpoint in systemic glucose metabolism in both mice and humans, and propose TSC22D4 inhibition as an insulin sensitizing option in diabetes therapy. PMID:27827363

  16. GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer

    PubMed Central

    Pharoah, Paul D. P.; Tsai, Ya-Yu; Ramus, Susan J.; Phelan, Catherine M.; Goode, Ellen L.; Lawrenson, Kate; Price, Melissa; Fridley, Brooke L.; Tyrer, Jonathan P.; Shen, Howard; Weber, Rachel; Karevan, Rod; Larson, Melissa C.; Song, Honglin; Tessier, Daniel C.; Bacot, François; Vincent, Daniel; Cunningham, Julie M.; Dennis, Joe; Dicks, Ed; Aben, Katja K.; Anton-Culver, Hoda; Antonenkova, Natalia; Armasu, Sebastian M.; Baglietto, Laura; Bandera, Elisa V.; Beckmann, Matthias W.; Birrer, Michael J.; Bloom, Greg; Bogdanova, Natalia; Brenton, James D.; Brinton, Louise A.; Brooks-Wilson, Angela; Brown, Robert; Butzow, Ralf; Campbell, Ian; Carney, Michael E; Carvalho, Renato S.; Chang-Claude, Jenny; Chen, Y. Anne; Chen, Zhihua; Chow, Wong-Ho; Cicek, Mine S.; Coetzee, Gerhard; Cook, Linda S.; Cramer, Daniel W.; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Despierre, Evelyn; Doherty, Jennifer A; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Eccles, Diana; Edwards, Robert; Ekici, Arif B.; Fasching, Peter A.; Fenstermacher, David; Flanagan, James; Gao, Yu-Tang; Garcia-Closas, Montserrat; Gentry-Maharaj, Aleksandra; Giles, Graham; Gjyshi, Anxhela; Gore, Martin; Gronwald, Jacek; Guo, Qi; Halle, Mari K; Harter, Philipp; Hein, Alexander; Heitz, Florian; Hillemanns, Peter; Hoatlin, Maureen; Høgdall, Estrid; Høgdall, Claus K.; Hosono, Satoyo; Jakubowska, Anna; Jensen, Allan; Kalli, Kimberly R.; Karlan, Beth Y.; Kelemen, Linda E.; Kiemeney, Lambertus A.; Kjaer, Susanne Krüger; Konecny, Gottfried E.; Krakstad, Camilla; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Nathan; Lee, Janet; Leminen, Arto; Lim, Boon Kiong; Lissowska, Jolanta; Lubiński, Jan; Lundvall, Lene; Lurie, Galina; Massuger, Leon F.A.G.; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; Menon, Usha; Modugno, Francesmary; Moysich, Kirsten B.; Nakanishi, Toru; Narod, Steven A.; Ness, Roberta B.; Nevanlinna, Heli; Nickels, Stefan; Noushmehr, Houtan; Odunsi, Kunle; Olson, Sara; Orlow, Irene; Paul, James; Pejovic, Tanja; Pelttari, Liisa M; Permuth-Wey, Jenny; Pike, Malcolm C; Poole, Elizabeth M; Qu, Xiaotao; Risch, Harvey A.; Rodriguez-Rodriguez, Lorna; Rossing, Mary Anne; Rudolph, Anja; Runnebaum, Ingo; Rzepecka, Iwona K; Salvesen, Helga B.; Schwaab, Ira; Severi, Gianluca; Shen, Hui; Shridhar, Vijayalakshmi; Shu, Xiao-Ou; Sieh, Weiva; Southey, Melissa C.; Spellman, Paul; Tajima, Kazuo; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J; Timorek, Agnieszka; Tworoger, Shelley S.; van Altena, Anne M.; Berg, David Van Den; Vergote, Ignace; Vierkant, Robert A.; Vitonis, Allison F.; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S.; Wik, Elisabeth; Winterhoff, Boris; Woo, Yin Ling; Wu, Anna H; Yang, Hannah P.; Zheng, Wei; Ziogas, Argyrios; Zulkifli, Famida; Goodman, Marc T.; Hall, Per; Easton, Douglas F; Pearce, Celeste L; Berchuck, Andrew; Chenevix-Trench, Georgia; Iversen, Edwin; Monteiro, Alvaro N.A.; Gayther, Simon A.; Schildkraut, Joellen M.; Sellers, Thomas A.

    2013-01-01

    Genome wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC) with another two loci being close to genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the United Kingdom. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. Follow-up genotyping was carried out in 18,174 cases and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 previously near genome-wide significance and identified three novel loci associated with risk; two loci associated with all EOC subtypes, at 8q21 (rs11782652, P=5.5×10-9) and 10p12 (rs1243180; P=1.8×10-8), and another locus specific to the serous subtype at 17q12 (rs757210; P=8.1×10-10). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility that implicates CHMP4C in the pathogenesis of ovarian cancer. PMID:23535730

  17. Evaluation of Genome Wide Association Study Associated Type 2 Diabetes Susceptibility Loci in Sub Saharan Africans

    PubMed Central

    Adeyemo, Adebowale A.; Tekola-Ayele, Fasil; Doumatey, Ayo P.; Bentley, Amy R.; Chen, Guanjie; Huang, Hanxia; Zhou, Jie; Shriner, Daniel; Fasanmade, Olufemi; Okafor, Godfrey; Eghan, Benjamin; Agyenim-Boateng, Kofi; Adeleye, Jokotade; Balogun, Williams; Elkahloun, Abdel; Chandrasekharappa, Settara; Owusu, Samuel; Amoah, Albert; Acheampong, Joseph; Johnson, Thomas; Oli, Johnnie; Adebamowo, Clement; Collins, Francis; Dunston, Georgia; Rotimi, Charles N.

    2015-01-01

    Genome wide association studies (GWAS) for type 2 diabetes (T2D) undertaken in European and Asian ancestry populations have yielded dozens of robustly associated loci. However, the genomics of T2D remains largely understudied in sub-Saharan Africa (SSA), where rates of T2D are increasing dramatically and where the environmental background is quite different than in these previous studies. Here, we evaluate 106 reported T2D GWAS loci in continental Africans. We tested each of these SNPs, and SNPs in linkage disequilibrium (LD) with these index SNPs, for an association with T2D in order to assess transferability and to fine map the loci leveraging the generally reduced LD of African genomes. The study included 1775 unrelated Africans (1035 T2D cases, 740 controls; mean age 54 years; 59% female) enrolled in Nigeria, Ghana, and Kenya as part of the Africa America Diabetes Mellitus (AADM) study. All samples were genotyped on the Affymetrix Axiom PanAFR SNP array. Forty-one of the tested loci showed transferability to this African sample (p < 0.05, same direction of effect), 11 at the exact reported SNP and 30 others at SNPs in LD with the reported SNP (after adjustment for the number of tested SNPs). TCF7L2 SNP rs7903146 was the most significant locus in this study (p = 1.61 × 10−8). Most of the loci that showed transferability were successfully fine-mapped, i.e., localized to smaller haplotypes than in the original reports. The findings indicate that the genetic architecture of T2D in SSA is characterized by several risk loci shared with non-African ancestral populations and that data from African populations may facilitate fine mapping of risk loci. The study provides an important resource for meta-analysis of African ancestry populations and transferability of novel loci. PMID:26635871

  18. Sexual assault resistance education for university women: study protocol for a randomized controlled trial (SARE trial)

    PubMed Central

    2013-01-01

    Background More than one in six women will be sexually assaulted in their lifetimes, most by men they know. The situation on university campuses is even more startling, with as many as 1 in 4 female students being victims of rape or attempted rape. The associated physical and mental health effects are extensive and the social and economic costs are staggering. The aim of this randomized controlled trial is to determine whether a novel, small-group sexual assault resistance education program can reduce the incidence of sexual assault among university-attending women, when compared to current university practice of providing informational brochures. Methods/Design The trial will evaluate a theoretically and empirically sound four-unit, 12-hour education program that has been demonstrated in pilot studies to have short-term efficacy. Three of the four units provide information, skills, and practice aimed at decreasing the time needed for women to assess situations with elevated risk of acquaintance sexual assault as dangerous and to take action, reducing emotional obstacles to taking action, and increasing the use of the most effective methods of verbal and physical self-defense. The fourth unit focuses on facilitating a stronger positive sexuality from which women may resist sexual coercion by male intimates more successfully. The trial will extend the pilot evaluations by expanding the participant pool and examining the long term efficacy of the program. A total of 1716 first-year female students (age 17 to 24 years) from three Canadian universities will be enrolled. The primary outcome is completed sexual assault, measured by The Sexual Experiences Survey - Short Form Victimization instrument. Secondary outcomes include changes in knowledge, attitudes, and skills related to the process of sexual assault resistance. Outcomes will be measured at baseline, 1 week, 6, 12, 18, and 24 months. Discussion The results of the trial will be used to produce a maximally

  19. Control of wire heating with resistively guided fast electrons through an inverse conical taper

    SciTech Connect

    Robinson, A. P. L. Schmitz, H.; Green, J. S.; Booth, N.; Ridgers, C. P.; Pasley, J.

    2015-04-15

    The heating of a solid wire embedded in a solid substrate (of lower Z material) with relativistic electrons generated by ultra-intense laser irradiation is considered. Previously, it has been noted that the initial angular distribution of the fast electrons is a highly important factor in the efficacy of the heating [Robinson et al., Phys. Plasmas 20, 122701 (2013)]. We show that, using 3D numerical simulations, the addition of an inverse conical taper at the front of wire can considerably improve the heating of the wire due to the reduction of angular spread of the fast electrons which is caused by transport through the inverse conical taper [Robinson et al., “Guiding of laser-generated fast electrons by exploiting the resistivity-gradients around a conical guide element,” Plasma Phys. Controlled Fusion (to be published)].

  20. On the designing of a tamper resistant prescription RFID access control system.

    PubMed

    Safkhani, Masoumeh; Bagheri, Nasour; Naderi, Majid

    2012-12-01

    Recently, Chen et al. have proposed a novel tamper resistant prescription RFID access control system, published in the Journal of Medical Systems. In this paper we consider the security of the proposed protocol and identify some existing weaknesses. The main attack is a reader impersonation attack which allows an active adversary to impersonate a legitimate doctor, e.g. the patient's doctor, to access the patient's tag and change the patient prescription. The presented attack is quite efficient. To impersonate a doctor, the adversary should eavesdrop one session between the doctor and the patient's tag and then she can impersonate the doctor with the success probability of '1'. In addition, we present efficient reader-tag to back-end database impersonation, de-synchronization and traceability attacks against the protocol. Finally, we propose an improved version of protocol which is more efficient compared to the original protocol while provides the desired security against the presented attacks.

  1. The novel ABC transporter ABCH1 is a potential target for RNAi-based insect pest control and resistance management.

    PubMed

    Guo, Zhaojiang; Kang, Shi; Zhu, Xun; Xia, Jixing; Wu, Qingjun; Wang, Shaoli; Xie, Wen; Zhang, Youjun

    2015-09-03

    Insect pests cause serious crop damage and develop high-level resistance to chemical insecticides and Bacillus thuringiensis (Bt) insecticidal Cry toxins. A new promising approach for controlling them and overcoming this resistance is RNA interference (RNAi). The RNAi-based insect control strategy depends on the selection of suitable target genes. In this study, we cloned and characterized a novel ABC transporter gene PxABCH1 in diamondback moth, Plutella xylostella (L.). Phylogenetic analysis showed that PxABCH1 is closely related to ABCA and ABCG subfamily members. Spatial-temporal expression detection revealed that PxABCH1 was expressed in all tissues and developmental stages, and highest expressed in head and male adult. Midgut sequence variation and expression analyses of PxABCH1 in all the susceptible and Bt-resistant P. xylostella strains and the functional analysis by sublethal RNAi demonstrated that Cry1Ac resistance was independent of this gene. Silencing of PxABCH1 by a relatively high dose of dsRNA dramatically reduced its expression and resulted in larval and pupal lethal phenotypes in both susceptible and Cry1Ac-resistant P. xylostella strains. To our knowledge, this study provides the first insight into ABCH1 in lepidopterans and reveals it as an excellent target for RNAi-based insect pest control and resistance management.

  2. Effects of chest resistance exercise and chest expansion exercise on stroke patients’ respiratory function and trunk control ability

    PubMed Central

    Song, Gui bin; Park, Eun cho

    2015-01-01

    [Purpose] The purpose of this study was to examine the efficiency of chest resistance and chest expansion exercises for improving respiratory function and trunk control ability in patients with stroke. [Subjects] Forty patients with stroke were randomly allocated into a chest resistance exercise group (CREG, n = 20) and a chest expansion exercise group (CEEG, n = 20). [Methods] CREG patients underwent chest resistance exercises, and diaphragmatic resistance exercises by way of the proprioceptive neuromuscular facilitation. CEEG patients underwent respiratory exercises with chest expansion in various positions. Both groups received 30 minutes of training per day, five times per week, for eight weeks. [Results] Both the CERG and CEEG groups showed significant changes in FVC, FEV1, and TIS after the intervention. TIS was significantly increased in the CREG compared to the CEEG after the intervention. [Conclusion] Both chest resistance and chest expansion exercises were effective for improving respiratory function and trunk control ability in stroke patients; however, chest resistance exercise is more efficient for increasing trunk control ability. PMID:26180292

  3. The novel ABC transporter ABCH1 is a potential target for RNAi-based insect pest control and resistance management

    PubMed Central

    Guo, Zhaojiang; Kang, Shi; Zhu, Xun; Xia, Jixing; Wu, Qingjun; Wang, Shaoli; Xie, Wen; Zhang, Youjun

    2015-01-01

    Insect pests cause serious crop damage and develop high-level resistance to chemical insecticides and Bacillus thuringiensis (Bt) insecticidal Cry toxins. A new promising approach for controlling them and overcoming this resistance is RNA interference (RNAi). The RNAi-based insect control strategy depends on the selection of suitable target genes. In this study, we cloned and characterized a novel ABC transporter gene PxABCH1 in diamondback moth, Plutella xylostella (L.). Phylogenetic analysis showed that PxABCH1 is closely related to ABCA and ABCG subfamily members. Spatial-temporal expression detection revealed that PxABCH1 was expressed in all tissues and developmental stages, and highest expressed in head and male adult. Midgut sequence variation and expression analyses of PxABCH1 in all the susceptible and Bt-resistant P. xylostella strains and the functional analysis by sublethal RNAi demonstrated that Cry1Ac resistance was independent of this gene. Silencing of PxABCH1 by a relatively high dose of dsRNA dramatically reduced its expression and resulted in larval and pupal lethal phenotypes in both susceptible and Cry1Ac-resistant P. xylostella strains. To our knowledge, this study provides the first insight into ABCH1 in lepidopterans and reveals it as an excellent target for RNAi-based insect pest control and resistance management. PMID:26333918

  4. [Control locus, stress resistance and personal growth of the participants in experiment Mars-500].

    PubMed

    Solcova, I; Vinokhodova, A G

    2013-01-01

    The article deals with positive personal transformations in a simulated space mission. The investigation was focused on the aspects of control locus, stamina, proactive behavior to overcome challenges, and stress-related personal growth. Besides, ingenious psychophysiological techniques designed to select Russian cosmonauts were used for assessing stress-resistance and ability to control own emotions voluntarily. Experiment Mars-500 simulated the basic features of a mission to Mars. The crew consisted of 6 males 27 to 38 years of age who volunteered to spend 520 days in isolation and confinement in the IBMP experimental facility (Moscow). To detect personality changes, the volunteers were tested before the experiment and after its completion. According to the test results, the participants commonly demonstrated the ability to see the bright side of the Mars-500 adversities, which most often was caused by their social growth. Positive changes were particularly pronounced in the crewmembers who possessed a better ability to control own emotions. The simulated challenges were also beneficial for personal growth of the volunteers.

  5. Octopamine controls starvation resistance, life span and metabolic traits in Drosophila

    PubMed Central

    Li, Yong; Hoffmann, Julia; Li, Yang; Stephano, Flora; Bruchhaus, Iris; Fink, Christine; Roeder, Thomas

    2016-01-01

    The monoamines octopamine (OA) and tyramine (TA) modulate numerous behaviours and physiological processes in invertebrates. Nevertheless, it is not clear whether these invertebrate counterparts of norepinephrine are important regulators of metabolic and life history traits. We show that flies (Drosophila melanogaster) lacking OA are more resistant to starvation, while their overall life span is substantially reduced compared with control flies. In addition, these animals have increased body fat deposits, reduced physical activity and a reduced metabolic resting rate. Increasing the release of OA from internal stores induced the opposite effects. Flies devoid of both OA and TA had normal body fat and metabolic rates, suggesting that OA and TA act antagonistically. Moreover, OA-deficient flies show increased insulin release rates. We inferred that the OA-mediated control of insulin release accounts for a substantial proportion of the alterations observed in these flies. Apparently, OA levels control the balance between thrifty and expenditure metabolic modes. Thus, changes in OA levels in response to external and internal signals orchestrate behaviour and metabolic processes to meet physiological needs. Moreover, chronic deregulation of the corresponding signalling systems in humans may be associated with metabolic disorders, such as obesity or diabetes. PMID:27759117

  6. Management and control of multidrug-resistant tuberculosis (MDR-TB): Addressing policy needs for India.

    PubMed

    Atre, Sachin R; Murray, Megan B

    2016-05-06

    Multidrug-resistant tuberculosis (MDR-TB) challenges TB control efforts because of delays in diagnosis plus its long-term treatment which has toxic effects. Of TB high-incidence countries, India carries the highest burden of MDR-TB cases. We describe policy issues in India concerning MDR-TB diagnosis and management in a careful review of the literature including a systematic review of studies on the prevalence of MDR-TB. Of 995 articles published during 2001-2016 and retrieved from the PubMed, only 20 provided data on the population prevalence of MDR-TB. We further reviewed and describe diagnostic criteria and treatment algorithms in use and endorsed by the Revised National TB Control Program of India. We discuss problems encountered in treating MDR-TB patients with standardized regimens. Finally, we provide realistic suggestions for policymakers and program planners to improve the management and control of MDR-TB in India.Journal of Public Health Policy advance online publication, 6 May 2016; doi:10.1057/jphp.2016.14.

  7. "I'm not dog, no!": cries of resistance against cholera control campaigns.

    PubMed

    Nations, M K; Monte, C M

    1996-09-01

    Popular reactions toward government efforts to control the recent cholera epidemic in Northeast Brazil are evaluated. Intensive ethnographic interviews and participant-observation in two urban slums (favelas), reveal a high level of resistance on the part of impoverished residents towards official cholera control interventions and mass media campaigns. "Non-compliance" with recommended regimens is described more as a revolt against accusatory attitudes and actions of the elite than as an outright rejection of care by the poor. "Hidden transcripts" about "The Dog's Disease," as cholera is popularly called, voices a history of social and economic inequity and domination in Northeast Brazil. Here, cholera is encumbered by the trappings of metaphor. Two lurid cultural stereotypes, pessoa imunda (filthy, dirty person) and vira lata (stray mutt dog) are used, it is believed, to equate the poor with cholera. The morally disgracing and disempowering imagery of cholera is used to blame and punish the poor and to collectively taint and separate their communities from wealthy neighborhoods. The authors argue that metaphoric trappings have tragic consequences: they deform the experience of having cholera and inhibit the sick and dying from seeking treatment early enough. Controlling cholera requires eliminating "blaming the victim" rhetoric while attacking the social roots of cholera: poverty, low earning power, female illiteracy, sexism, lack of basic sanitation and clean water supplies, medical hegemony, etc. For health interventions to be effective, it is necessary to take into account people's "hidden transcripts" when designing action programs.

  8. Smart earthquake-resistant materials: using time-released adhesives for damping, stiffening, and deflection control

    NASA Astrophysics Data System (ADS)

    Dry, Carolyn M.

    1996-04-01

    Preventing buildings and bridges from damage from severe dynamic loading events is a primary goal of civil infrastructure. Present designs attempt to control structural response by making the structures more massive, by increasing lateral stiffness through bracing, and by damping technology such as mass damping and base-isolation. These attempts affect portions of the governing equation: for an idealized building frame or bridge, the free vibrational behavior is described by Mu + cu + ku equals -mug(t) where m equals mass, c equals damping coefficient, k equals lateral stiffness, u equals deflection, and ug(t) equals ground acceleration. The use of adhesive released internally in a material based way of addressing the problem. The time release of low modulus adhesive chemicals would assist the damping characteristics of the structure, use of a stiffer adhesive would allow the damaged structure to regain some lateral stiffness (k) and adjustment of the set times of the adhesives would act to control the deflection. These can be thought of as potential new method of controlling vibration of behavior in case of a dynamic loading event. In past experiments, self-healing concrete matrices were shown to increase post-yield deflection and load carrying capability by the release and setting of adhesives. The results were promising in resisting damage of dynamic loads applied to frames. This indicates that self-healing concrete would be extremely valuable in civil engineering structures that were subjected to failure-inducing loads such as earthquakes.

  9. Strengthened tuberculosis control programme and trend of multidrug resistant tuberculosis rate in Osaka City, Japan

    PubMed Central

    Ohkado, Akihiro; Matsumoto, Kenji; Komukai, Jun; Yoshida, Hideki; Ishikawa, Nobukatsu

    2013-01-01

    Osaka City has the highest tuberculosis (TB) notification rates in Japan. In the period 1999–2003, the TB control programme was strengthened, and the Stop TB Strategy was implemented to reduce the number of notified cases. The objective of this study was to assess the effect of these control activities in Osaka City, including the implementation of directly observed treatment (DOT), by analysing TB surveillance and routinely collected data. We reviewed the surveillance data of all sputum smear-positive pulmonary tuberculosis (PTB) cases registered in the Osaka City Public Health Office from 2001 to 2008 and data collected from the routine TB programme. The DOT implementation rate increased from 0% in 2001 to 68% in 2008 for smear-positive PTB cases of the general public and to 61% for all PTB cases of the homeless. The proportion of smear-positive PTB cases that had treatment failure and default combined, declined from 8.0% (52 of 650) in 2001 to 3.6% (20 of 548) in 2006. The proportion of cases among the homeless with previous treatment declined from 28% in 2001 to 15% in 2008. The proportion of cases with multidrug resistant-TB (MDR-TB) among those without previous treatment declined from 1.7% in 2001 to 0.9% in 2008. It is logical that reduction in the failure and default rate would lead to the reduction of cases with previous treatment and TB transmission, including resistant TB, therefore to the reduction of MDR-TB rates. PMID:23908949

  10. 3D resistivity inversion using an improved Genetic Algorithm based on control method of mutation direction

    NASA Astrophysics Data System (ADS)

    Liu, B.; Li, S. C.; Nie, L. C.; Wang, J.; L, X.; Zhang, Q. S.

    2012-12-01

    Traditional inversion method is the most commonly used procedure for three-dimensional (3D) resistivity inversion, which usually takes the linearization of the problem and accomplish it by iterations. However, its accuracy is often dependent on the initial model, which can make the inversion trapped in local optima, even cause a bad result. Non-linear method is a feasible way to eliminate the dependence on the initial model. However, for large problems such as 3D resistivity inversion with inversion parameters exceeding a thousand, main challenges of non-linear method are premature and quite low search efficiency. To deal with these problems, we present an improved Genetic Algorithm (GA) method. In the improved GA method, smooth constraint and inequality constraint are both applied on the object function, by which the degree of non-uniqueness and ill-conditioning is decreased. Some measures are adopted from others by reference to maintain the diversity and stability of GA, e.g. real-coded method, and the adaptive adjustment of crossover and mutation probabilities. Then a generation method of approximately uniform initial population is proposed in this paper, with which uniformly distributed initial generation can be produced and the dependence on initial model can be eliminated. Further, a mutation direction control method is presented based on the joint algorithm, in which the linearization method is embedded in GA. The update vector produced by linearization method is used as mutation increment to maintain a better search direction compared with the traditional GA with non-controlled mutation operation. By this method, the mutation direction is optimized and the search efficiency is improved greatly. The performance of improved GA is evaluated by comparing with traditional inversion results in synthetic example or with drilling columnar sections in practical example. The synthetic and practical examples illustrate that with the improved GA method we can eliminate

  11. Resistance training reduces s