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Sample records for genetic background sensitizes

  1. GENETIC BACKGROUND BUT NOT METALLOTHIONEIN PHENOTYPE DICTATES SENSITIVITY TO CADMIUM-INDUCED TESTICULAR INJURY IN MICE

    Science.gov (United States)

    Genetic Background but not Metallothionein Phenotype Dictates Sensitivity to Cadmium-Induced Testicular Injury in MiceJie Liu1,2, Chris Corton3, David J. Dix4, Yaping Liu1, Michael P. Waalkes2 and Curtis D. Klaassen1 ABSTRACTParenteral administrati...

  2. Evolutionary concepts in ecotoxicology: tracing the genetic background of differential cadmium sensitivities in invertebrate lineages.

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    Dallinger, Reinhard; Höckner, Martina

    2013-07-01

    In many toxicological and ecotoxicological studies and experimental setups, the investigator is mainly interested in traditional parameters such as toxicity data and effects of toxicants on molecular, cellular or physiological functions of individuals, species or statistical populations. It is clear, however, that such approaches focus on the phenotype level of animal species, whilst the genetic and evolutionary background of reactions to environmental toxicants may remain untold. In ecotoxicological risk assessment, moreover, species sensitivities towards pollutants are often regarded as random variables in a statistical approach. Beyond statistics, however, toxicant sensitivity of every species assumes a biological significance, especially if we consider that sensitivity traits have developed in lineages of species with common evolutionary roots. In this article, the genetic and evolutionary background of differential Cd sensitivities among invertebrate populations and species and their potential of adaptation to environmental Cd exposure will be highlighted. Important evolutionary and population genetic concepts such as genome structure and their importance for evolutionary adaptation, population structure of affected individuals, as well as micro and macroevolutionary mechanisms of Cd resistance in invertebrate lineages will be stressed by discussing examples of work from our own laboratory along with a review of relevant literature data and a brief discussion of open questions along with some perspectives for further research. Both, differences and similarities in Cd sensitivity traits of related invertebrate species can only be understood if we consider the underlying evolutionary processes and genetic (or epigenetic) mechanisms. Keeping in mind this perception can help us to better understand and interpret more precisely why the sensitivity of some species or species groups towards a certain toxicant (or metal) may be ranked in the lower or higher range of

  3. Sensitivity of the distribution of mutational fitness effects to environment, genetic background, and adaptedness: a case study with Drosophila.

    Science.gov (United States)

    Wang, Alethea D; Sharp, Nathaniel P; Agrawal, Aneil F

    2014-03-01

    Heterogeneity in the fitness effects of individual mutations has been found across different environmental and genetic contexts. Going beyond effects on individual mutations, how is the distribution of selective effects, f(s), altered by changes in genetic and environmental context? In this study, we examined changes in the major features of f(s) by estimating viability selection on 36 individual mutations in Drosophila melanogaster across two different environments in two different genetic backgrounds that were either adapted or nonadapted to the two test environments. Both environment and genetic background affected selection on individual mutations. However, the overall distribution f(s) appeared robust to changes in genetic background but both the mean, E(s), and the variance, V(s) were dependent on the environment. Between these two properties, V(s) was more sensitive to environmental change. Contrary to predictions of fitness landscape theory, the match between genetic background and assay environment (i.e., adaptedness) had little effect on f(s).

  4. ALTERED SENSITIVITY OF THE MOUSE FETUS TO IMPAIRED PROSTATIC BUD FORMATION BY DIOXIN: INFLUENCE OF GENETIC BACKGROUND AND NULL EXPRESSION OF TGF-ALFA AND EGF

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    Altered sensitivity of the mouse fetus to impaired prostatic bud formation by dioxin: Influence of genetic background and null expression of TGF and EGF. Rasmussen, N.T., Lin T-M., Fenton, S.E., Abbott, B.D. and R.E. Peterson. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)...

  5. Analysis of DNA methylation variation in wheat genetic background after alien chromatin introduction based on methylation-sensitive amplification polymorphism

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    During the process of alien germplasm introduced into wheat genome by chromosome engineering,extensive genetic variations of genome structure and gene expression in recipient could be induced.In this study,we performed GISH(genome in situ hybridization)and AFLP(amplified fragment length polymorphism) on wheat-rye chromosome transIocation lines and their parents to detect the identity in genomic structure of different translocation lines.The results showed that the genome primary structure variations were not obviously detected in different translocation lines except the same 1RS chromosome translocation.Methylation sensitive amplification polymorphism(MSAP)analyses on genomic DNA showed that the ratios of fully-methylated sites were significantly increased in translocation lines(CN12,20.15%;CN17,20.91%;CN18,22.42%),but the ratios of hemimethylated sites were significantly lowered(CN12,21.41%;CN17,23.43%;CN18,22.42%),whereas 16.37%were fully-methylated and 25.44%were hemimethylated in case of their wheat parent.Twenty-nine classes of methylation patterns were identified in a comparative assay of cytosine methylation patterns between wheat-rye translocation lines and their wheat parent,including 13 hypermethylation patterns(33.74%),9 demethylation patterns(22.76%)and 7 uncertain patterns(4.07%).In further sequence analysis,the alterations of methylation pattern affected both repetitive DNA sequences,such as retrotransposons and tandem repetitive sequences,and low-copy DNA.

  6. Genetic background of phenotypic variation

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A noteworthy feature of the living world is its bewildering variability. A key issue in several biological disciplines is the achievement of an understanding of the hereditary basis of this variability. Two opposing, but not necessarily irreconcilable conceptions attempt to explain the underlying mechanism. The gene function paradigm postulates that phenotypic variance is generated by the polymorphism in the coding sequences of genes. However, comparisons of a great number of homologous gene and protein sequences have revealed that they predominantly remained functionally conserved even across distantly related phylogenic taxa. Alternatively, the gene regulation paradigm assumes that differences in the cis-regulatory region of genes do account for phenotype variation within species. An extension of this latter concept is that phenotypic variability is generated by the polyrnorphism in the overall gene expression profiles of gene networks.In other words, the activity of a particular gene is a system property determined both by the cis-regulatory sequences of the given genes and by the other genes of a gene network, whose expressions vary among individuals, too. Novel proponents of gene function paradigm claim that functional genetic variance within the coding sequences of regulatory genes is critical for the generation of morphological polymorphism. Note, however, that these developmental genes play direct regulatory roles in the control of gene expression.

  7. Missing Ancestry: Filling in a Genetic Background

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    ... A Missing Ancestry Follow us A Missing Ancestry Filling in a genetic background Many adopted children don’t know very much about their biological family. That was the case for David Hale. He didn’t know any of his biological family’s health. All Hale knew from his adoption papers was ...

  8. The genetic background of inflammatory bowel disease.

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    Yang, H; Rotter, J I

    2000-01-01

    Available evidence indicates that genetic factors are essential in providing the susceptibility to the majority of the various forms of inflammatory bowel disease occurring in man. It is also clear that the genetic susceptibility to these diseases is complex, and that more than one gene may predispose (the concept of multilocus/oligogenic inheritance), and likely in different etiologic combinations (the concept of genetic heterogeneity). Paradigms are now available that should lead to the identification of a number of these predisposing genes. These paradigms include the candidate gene approach, systematic genome wide scans, and mouse human synteny. While genome wide scans are currently limited to multiplex family linkage studies, both candidate genes and mouse human synteny can be approached in either linkage or association paradigms. Eventually whole genome association studies will be available as well. Identification of inflammatory bowel disease predisposing genes should lead to their incorporation in studies of natural history, investigation of environmental risk factors, and especially utilization of genetic markers in clinical trials. This will allow us to identify the best therapy available for the individual patient based on their unique genetic constitution. With advances in molecular technology, the search for genes influencing traits and diseases with a complex genetic background, such as the inflammatory bowel diseases, has become a realistic task. Although exogenous or infectious agents may contribute to the pathogenesis or may trigger the onset of disease, and the immune system almost certainly mediates the tissue damage, it is clear from available data that genetic factors determine the susceptibility of a given individual to inflammatory bowel disease (reviewed below). Thus, genetic studies are essential for the delineation of the basic etiologies of the various forms of inflammatory bowel disease and thus can aid in the development of radically

  9. Genetic background of Fuchs' heterochromic cyclitis.

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    Saari, M; Vuorre, I; Tiilikainen, A; Algvere, P

    1978-10-01

    We studied the genetic background of 24 patients with Fuchs' heterochromic cyclitis (FHC). Each was given a careful eye examination which included family history and serological determination of HLA antigens. Two families each had 2 cases of FHC in the same family; in addition an ancestor in the second family possibly had FHC; in both families one healthy member had simple heterochromia. One patient with FHC had congenital uveal coloboma, one pigmentary retinal dystrophy, and four had cysts of the ciliary body. The frequencies of all HLA antigens in patients with FHC compared well with the frequencies in the controls. In a family in which HLA haplotypes could be derived, the patients with FHC showed different HLA haplotypes. We conclude that FHC has a hereditary basis but its immunological component is not genetically associated with the HLA system.

  10. How Sensitive Is Genetic Data?

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    Sariyar, Murat; Suhr, Stephanie; Schlünder, Irene

    2017-09-07

    The rising demand to use genetic data for research goes hand in hand with an increased awareness of privacy issues related to its use. Using human genetic data in a legally compliant way requires an examination of the legal basis as well as an assessment of potential disclosure risks. Focusing on the relevant legal framework in the European Union, we discuss open questions and uncertainties around the handling of genetic data in research, which can result in the introduction of unnecessary hurdles for data sharing. First, we discuss defining features and relative disclosure risks of some DNA-related biomarkers, distinguishing between the risk for disclosure of (1) the identity of an individual, (2) information about an individual's health and behavior, including previously unknown phenotypes, and (3) information about an individual's blood relatives. Second, we discuss the European legal framework applicable to the use of DNA-related biomarkers in research, the implications of including both inherited and acquired traits in the legal definition, as well as the issue of "genetic exceptionalism"-the notion that genetic information has inherent characteristics that require different considerations than other health and medical information. Finally, by mapping the legal to specific technical definitions, we draw some initial conclusions concerning how sensitive different types of "genetic data" may actually be. We argue that whole genome sequences may justifiably be considered "exceptional" and require special protection, whereas other genetic data that do not fulfill the same criteria should be treated in a similar manner to other clinical data. This kind of differentiation should be reflected by the law and/or other governance frameworks as well as agreed Codes of Conduct when using the term "genetic data."

  11. Genetic backgrounds determine brown remodeling of white fat in rodents

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    Giulia Ferrannini

    2016-10-01

    Conclusion: Rodent genetic background determines the brown remodeling of different white fat depots. This study provides new insights into the role of genetic variation in fat remodeling in susceptibility to metabolic diseases.

  12. Longitudinal Genetic Analysis of Anxiety Sensitivity

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    Zavos, Helena M. S.; Gregory, Alice M.; Eley, Thalia C.

    2012-01-01

    Anxiety sensitivity is associated with both anxiety and depression and has been shown to be heritable. Little, however, is known about the role of genetic influence on continuity and change of symptoms over time. The authors' aim was to examine the stability of anxiety sensitivity during adolescence. By using a genetically sensitive design, the…

  13. Genetic testing in asymptomatic minors: background considerations towards ESHG Recommendations

    DEFF Research Database (Denmark)

    Borry, Pascal; Evers-Kiebooms, Gerry; Cornel, Martina C

    2009-01-01

    Although various guidelines and position papers have discussed, in the past, the ethical aspects of genetic testing in asymptomatic minors, the European Society of Human Genetics had not earlier endorsed any set of guidelines exclusively focused on this issue. This paper has served as a background...... document in preparation of the development of the policy recommendations of the Public and Professional Committee of the European Society of Human Genetics. This background paper first discusses some general considerations with regard to the provision of genetic tests to minors. It discusses the concept...... of best interests, participation of minors in health-care decisions, parents' responsibilities to share genetic information, the role of clinical genetics and the health-care system in communication within the family. Second, it discusses, respectively, the presymptomatic and predictive genetic testing...

  14. Distinguishing Hypertrophic Cardiomyopathy-Associated Mutations from Background Genetic Noise

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    Kapplinger, Jamie D.; Landstrom, Andrew P.; Bos, J. Martijn; Salisbury, Benjamin A.; Callis, Thomas E.; Ackerman, Michael J.

    2014-01-01

    Despite the significant progress that has been made in identifying disease-associated mutations, the utility of the Hypertrophic Cardiomyopathy (HCM) genetic test is limited by a lack of understanding of the background genetic variation inherent to these sarcomeric genes in seemingly healthy subjects. This study represents the first comprehensive analysis of genetic variation in 427 ostensibly healthy individuals for the HCM genetic test using the “Gold Standard” Sanger sequencing method validating the background rate identified in the publically available exomes. While mutations are clearly over-represented in disease, a background rate as high as ~5% among healthy individuals prevents diagnostic certainty. To this end, we have identified a number of estimated predictive value-based associations including gene-specific, topology, and conservation methods generating an algorithm aiding in the probabilistic interpretation of an HCM genetic test. PMID:24510615

  15. A Background-Free Direction-Sensitive Neutron Detector2 A Background-Free Direction-Sensitive Neutron Detector

    CERN Document Server

    Roccaro, Alvaro; Ahlen, S; Avery, D; Inglis, A; Battat, J; Dujmic, D; Fisher, P; Henderson, S; Kaboth, A; Kohse, G; Lanza, R; Monroe, J; Sciolla, G; Skvorodnev, N; Wellenstein, H; Yamamoto, R

    2009-01-01

    We show data from a new type of detector that can be used to determine neutron flux, energy distribution, and direction of neutron motion for both fast and thermal neutrons. Many neutron detectors are plagued by large backgrounds from x-rays and gamma rays, and most current neutron detectors lack single-event energy sensitivity or any information on neutron directionality. Even the best detectors are limited by cosmic ray neutron backgrounds. All applications (neutron scattering and radiography, measurements of solar and cosmic ray neutron flux, measurements of neutron interaction cross sections, monitoring of neutrons at nuclear facilities, oil exploration, and searches for fissile weapons of mass destruction) will benefit from the improved neutron detection sensitivity and improved measurements of neutron properties made possible by this detector. The detector is free of backgrounds from x-rays, gamma rays, beta particles, relativistic singely charged particles and cosmic ray neutrons. It is sensitive to th...

  16. Genetics Home Reference: warfarin sensitivity

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    ... SA, Patel M, Martis S, Lubitz SA, van der Zee S, Yoo C, Edelmann L, Halperin JL, Desnick RJ. ... or Free article on PubMed Central van der Zee SA, Halperin JL. Anticoagulant therapy: warfarin sensitivity genotyping ...

  17. PFAPA syndrome in siblings. Is there a genetic background?

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    Antón-Martín, Pilar; Ortiz Movilla, Roberto; Guillén Martín, Sara; Allende, Luis M; Cuesta Rubio, M Teresa; López González, M Fernanda; Ramos Amador, José Tomás

    2011-12-01

    "PFAPA syndrome" is an autoinflammatory entity composed of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis. There have been many reports of children with the disease, but only occasionally have been described in siblings, and no specific genetic mutation has been determined yet. Corticosteroids are the mainstay in the treatment of the acute attacks. The role of surgery in long-term follow-up (tonsillectomy with or without adenoidectomy) is controversial. We report two brothers affected with the syndrome, in whom corticosteroids as the only treatment led to an improvement. A genetic work-up was performed, making very unlikely other possible syndromes of recurrent fever. PFAPA syndrome is the most common recurrent periodic fever disorder described in childhood. Its genetic background has not been elucidated yet. Our contribution with two siblings affected with PFAPA syndrome further support the genetic basis for the entity.

  18. The quantitative genetics of disgust sensitivity.

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    Sherlock, James M; Zietsch, Brendan P; Tybur, Joshua M; Jern, Patrick

    2016-02-01

    [Correction Notice: An Erratum for this article was reported in Vol 16(1) of Emotion (see record 2015-57029-001). In the article, the name of author Joshua M. Tybur was misspelled as Joshua M. Tyber. All versions of this article have been corrected.] Response sensitivity to common disgust elicitors varies considerably among individuals. The sources of these individual differences are largely unknown. In the current study, we use a large sample of female identical and nonidentical twins (N = 1,041 individuals) and their siblings (N = 170) to estimate the proportion of variation due to genetic effects, the shared environment, and other (residual) sources across multiple domains of disgust sensitivity. We also investigate the genetic and environmental influences on the covariation between the different disgust domains. Twin modeling revealed that approximately half of the variation in pathogen, sexual, and moral disgust is due to genetic effects. An independent pathways twin model also revealed that sexual and pathogen disgust sensitivity were influenced by unique sources of genetic variation, while also being significantly affected by a general genetic factor underlying all 3 disgust domains. Moral disgust sensitivity, in contrast, did not exhibit domain-specific genetic variation. These findings are discussed in light of contemporary evolutionary approaches to disgust sensitivity.

  19. Impact of the mitochondrial genetic background in complex III deficiency.

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    Mari Carmen Gil Borlado

    Full Text Available BACKGROUND: In recent years clinical evidence has emphasized the importance of the mtDNA genetic background that hosts a primary pathogenic mutation in the clinical expression of mitochondrial disorders, but little experimental confirmation has been provided. We have analyzed the pathogenic role of a novel homoplasmic mutation (m.15533 A>G in the cytochrome b (MT-CYB gene in a patient presenting with lactic acidosis, seizures, mild mental delay, and behaviour abnormalities. METHODOLOGY: Spectrophotometric analyses of the respiratory chain enzyme activities were performed in different tissues, the whole muscle mitochondrial DNA of the patient was sequenced, and the novel mutation was confirmed by PCR-RFLP. Transmitochondrial cybrids were constructed to confirm the pathogenicity of the mutation, and assembly/stability studies were carried out in fibroblasts and cybrids by means of mitochondrial translation inhibition in combination with blue native gel electrophoresis. PRINCIPAL FINDINGS: Biochemical analyses revealed a decrease in respiratory chain complex III activity in patient's skeletal muscle, and a combined enzyme defect of complexes III and IV in fibroblasts. Mutant transmitochondrial cybrids restored normal enzyme activities and steady-state protein levels, the mutation was mildly conserved along evolution, and the proband's mother and maternal aunt, both clinically unaffected, also harboured the homoplasmic mutation. These data suggested a nuclear genetic origin of the disease. However, by forcing the de novo functioning of the OXPHOS system, a severe delay in the biogenesis of the respiratory chain complexes was observed in the mutants, which demonstrated a direct functional effect of the mitochondrial genetic background. CONCLUSIONS: Our results point to possible pitfalls in the detection of pathogenic mitochondrial mutations, and highlight the role of the genetic mtDNA background in the development of mitochondrial disorders.

  20. Vitamin D status in primary hyperparathyroidism: effect of genetic background.

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    Battista, Claudia; Guarnieri, Vito; Carnevale, Vincenzo; Baorda, Filomena; Pileri, Mauro; Garrubba, Maria; Salcuni, Antonio S; Chiodini, Iacopo; Minisola, Salvatore; Romagnoli, Elisabetta; Eller-Vainicher, Cristina; Santini, Stefano A; Parisi, Salvatore; Frusciante, Vincenzo; Fontana, Andrea; Copetti, Massimiliano; Hendy, Geoffrey N; Scillitani, Alfredo; Cole, David E C

    2017-01-01

    Primary hyperparathyroidism (PHPT) is associated with hypovitaminosis D as assessed by serum total 25-hydroxyvitamin D (TotalD) levels. The aim of this study is to evaluate whether this is also the case for the calculated bioavailable 25-hydroxyvitamin D (BioD) or free 25-hydroxyvitamin D (FreeD), and whether the vitamin D status is influenced by genetic background. We compared vitamin D status of 88 PHPT patients each with a matched healthy family member sharing genetic background, i.e., first-degree relative (FDR), or not, namely an in-law relative (ILR). We compared TotalD and vitamin D-binding protein (DBP), using the latter to calculate BioD and FreeD. We also genotyped two common DBP polymorphisms (rs7041 and rs4588) likely to affect the affinity for and levels of vitamin D metabolites. TotalD was lower (p < 0.001) in PHPT (12.3 ± 6.6 ng/mL) than either family member group (FDR: 19.4 ± 12.1 and ILR: 23.2 ± 14.1), whether adjusted for DBP or not. DBP levels were also significantly lower (p < 0.001) in PHPT (323 ± 73 mg/L) versus FDR (377 ± 98) or ILR (382 ± 101). The differences between PHPT and control groups for TotalD, BioD, and FreeD were maintained after adjustment for season, gender, and serum creatinine. 25-hydroxyvitamin D, evaluated as total, free, or bioavailable fractions, is decreased in PHPT. No difference was seen between first-degree relative and in-law controls, suggesting that neither genetic nor non-genetic background greatly influences the genesis of the hypovitaminosis D seen in PHPT.

  1. The W303 genetic background affects the isw2 delta mutant phenotype in Saccharomyces cerevisiae.

    Science.gov (United States)

    Trachtulcová, P; Frýdlová, I; Janatová, I; Dorosh, A; Hasek, J

    2003-01-01

    We performed detailed phenotypic analysis of the isw2 delta strains of the W303 genetic background and compared its results with those obtained previously in BY-derived genetic background. Shmoolike morphology was observed in the isw2 delta strain of alpha-mating type of the BY strains, but not in its W303-derived counterpart. On the other hand, derepression of a-specific genes in the isw2 delta (MAT alpha) strain was observed in both genetic backgrounds, although to a different extent. Unlike in BY-derived strain hyperactivation of the Ras2/cAMP pathway reduced invasiveness of the isw2 delta strain (MAT alpha) of the W303 background. Sensitivity to Calcofluor White indicating a cell wall-integrity defect was significantly increased in the isw2 delta strains of the W303 background in contrast to BY-derived strains. Our data indicate that the effects of the isw2 deletion strongly depend on the background in which the deletion, is made.

  2. Candidate genes detected in transcriptome studies are strongly dependent on genetic background.

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    Pernille Sarup

    Full Text Available Whole genome transcriptomic studies can point to potential candidate genes for organismal traits. However, the importance of potential candidates is rarely followed up through functional studies and/or by comparing results across independent studies. We have analysed the overlap of candidate genes identified from studies of gene expression in Drosophila melanogaster using similar technical platforms. We found little overlap across studies between putative candidate genes for the same traits in the same sex. Instead there was a high degree of overlap between different traits and sexes within the same genetic backgrounds. Putative candidates found using transcriptomics therefore appear very sensitive to genetic background and this can mask or override effects of treatments. The functional importance of putative candidate genes emerging from transcriptome studies needs to be validated through additional experiments and in future studies we suggest a focus on the genes, networks and pathways affecting traits in a consistent manner across backgrounds.

  3. Sensitivity of ENSO teleconnections to a warming background state.

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    Drouard, Marie; Cassou, Christophe

    2016-04-01

    The sensitivity of ENSO teleconnections to the background state is investigated using two ensembles of coupled model experiments, one representative of the pre-industrial climate and the other one expected of the end of the 21st century based on the high emission RCP85 scenario. A 30-year period of representative ENSO events bearing resemblance to observed ones is a priori selected from a 850-year pre-industrial simulation of the CNRM-CM5 model. Following the so-called pacemaker protocol, new coupled experiments are carried with the model SST being restored in the eastern tropical Pacific towards the selected anomalies, the rest of the globe being fully coupled. In the first set of experiments, the anomalous restoring is applied on top of pre-industrial mean ocean state and in the second, on top of RCP85 mean state. Two sets of 10-member of 30-year long integrations are then generated. By construction, they share the exact same ENSO and thus make it possible to strictly isolate the dependence of the ENSO teleconnections to a warmer background state. Results confirm the eastward shift of the ENSO-induced deepening Aleutian low as documented in the literature for the winter season. They also show changes in the wintertime teleconnection over the North Atlantic. Several diagnostic tools (such as E-vectors) are used to investigate the dynamics of the teleconnection between the tropical Pacific, the North Pacific and dowstream towards the North Atlantic along the jet wave guide. A more indirect route based on the change in the Walker cell and associated signals in the tropical Atlantic leading to the excitation of forced Rossby wave is also analysed.

  4. Genetic background determines response to hemostasis and thrombosis

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    Hill Annie E

    2006-10-01

    Full Text Available Abstract Background Thrombosis is the fatal and disabling consequence of cardiovascular diseases, the leading cause of mortality and morbidity in Western countries. Two inbred mouse strains, C57BL/6J and A/J, have marked differences in susceptibility to obesity, atherosclerosis, and vessel remodeling. However, it is unclear how these diverse genetic backgrounds influence pathways known to regulate thrombosis and hemostasis. The objective of this study was to evaluate thrombosis and hemostasis in these two inbred strains and determine the phenotypic response of A/J chromosomes in the C57BL/6J background. Methods A/J and C57Bl/6J mice were evaluated for differences in thrombosis and hemostasis. A thrombus was induced in the carotid artery by application of the exposed carotid to ferric chloride and blood flow measured until the vessel occluded. Bleeding and rebleeding times, as surrogate markers for thrombosis and hemostasis, were determined after clipping the tail and placing in warm saline. Twenty-one chromosome substitution strains, A/J chromosomes in a C57BL/6J background, were screened for response to the tail bleeding assay. Results Thrombus occlusion time was markedly decreased in the A/J mice compared to C57BL/6J mice. Tail bleeding time was similar in the two strains, but rebleeding time was markedly increased in the A/J mice compared to C57BL/6J mice. Coagulation times and tail morphology were similar, but tail collagen content was higher in A/J than C57BL/6J mice. Three chromosome substitution strains, B6-Chr5A/J, B6-Chr11A/J, and B6-Chr17A/J, were identified with increased rebleeding time, a phenotype similar to A/J mice. Mice heterosomic for chromosomes 5 or 17 had rebleeding times similar to C57BL/6J mice, but when these two chromosome substitution strains, B6-Chr5A/J and B6-Chr17A/J, were crossed, the A/J phenotype was restored in these doubly heterosomic progeny. Conclusion These results indicate that susceptibility to arterial

  5. Destabilizing protein polymorphisms in the genetic background direct phenotypic expression of mutant SOD1 toxicity.

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    Tali Gidalevitz

    2009-03-01

    Full Text Available Genetic background exerts a strong modulatory effect on the toxicity of aggregation-prone proteins in conformational diseases. In addition to influencing the misfolding and aggregation behavior of the mutant proteins, polymorphisms in putative modifier genes may affect the molecular processes leading to the disease phenotype. Mutations in SOD1 in a subset of familial amyotrophic lateral sclerosis (ALS cases confer dominant but clinically variable toxicity, thought to be mediated by misfolding and aggregation of mutant SOD1 protein. While the mechanism of toxicity remains unknown, both the nature of the SOD1 mutation and the genetic background in which it is expressed appear important. To address this, we established a Caenorhabditis elegans model to systematically examine the aggregation behavior and genetic interactions of mutant forms of SOD1. Expression of three structurally distinct SOD1 mutants in C. elegans muscle cells resulted in the appearance of heterogeneous populations of aggregates and was associated with only mild cellular dysfunction. However, introduction of destabilizing temperature-sensitive mutations into the genetic background strongly enhanced the toxicity of SOD1 mutants, resulting in exposure of several deleterious phenotypes at permissive conditions in a manner dependent on the specific SOD1 mutation. The nature of the observed phenotype was dependent on the temperature-sensitive mutation present, while its penetrance reflected the specific combination of temperature-sensitive and SOD1 mutations. Thus, the specific toxic phenotypes of conformational disease may not be simply due to misfolding/aggregation toxicity of the causative mutant proteins, but may be defined by their genetic interactions with cellular pathways harboring mildly destabilizing missense alleles.

  6. Genetic polymorphism as a background of animal behavior.

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    Inoue-Murayama, Miho

    2009-04-01

    Various studies have shown the associations between differences in human behavioral traits and genetic polymorphism of neurotransmitter-related proteins such as receptors, transporters and monoamine oxidase. To clarify the genetic background of animal behavior, corresponding regions in animals have been analyzed. The study has been especially focused on primates, as the evolutionally closest animal to humans, and on dogs, as the socially closest animal to humans. In primates, polymorphisms were discovered between or within species, and the functional effects on neural transmission were found to be different by alleles. Even in apes, the closest species to humans, function was different from that in humans. In dogs, allele distributions of several genes were different among breeds showing different behavioral traits, and genes associated with individual differences in aggressiveness and aptitude of working dogs were surveyed. The survey of behavior-related genes has also been carried out in other mammals such as horses and cetaceans. Genes controlling various behaviors in birds have also been reported. The marker genes for behavior will provide useful information for human evolution, welfare of zoo animals and effective selection of working dogs and industry animals.

  7. Empathy is moderated by genetic background in mice.

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    QiLiang Chen

    Full Text Available Empathy, as originally defined, refers to an emotional experience that is shared among individuals. When discomfort or alarm is detected in another, a variety of behavioral responses can follow, including greater levels of nurturing, consolation or increased vigilance towards a threat. Moreover, changes in systemic physiology often accompany the recognition of distressed states in others. Employing a mouse model of cue-conditioned fear, we asked whether exposure to conspecific distress influences how a mouse subsequently responds to environmental cues that predict this distress. We found that mice are responsive to environmental cues that predict social distress, that their heart rate changes when distress vocalizations are emitted from conspecifics, and that genetic background substantially influences the magnitude of these responses. Specifically, during a series of pre-exposure sessions, repeated experiences of object mice that were exposed to a tone-shock (CS-UCS contingency resulted in heart rate deceleration in subjects from the gregarious C57BL/6J (B6 strain, but not in subjects from the less social BALB/cJ (BALB strain. Following the pre-exposure sessions, subjects were individually presented with the CS-only for 5 consecutive trials followed by 5 consecutive pairings of the CS with the UCS. Pre-exposure to object distress increased the freezing responses of B6 mice, but not BALB mice, on both the CS-only and the CS-UCS trials. These physiological and behavioral responses of B6 mice to social distress parallel features of human empathy. Our paradigm thus has construct and face validity with contemporary views of empathy, and provides unequivocal evidence for a genetic contribution to the expression of empathic behavior.

  8. GABA(A)-benzodiazepine receptor complex sensitivity in 5-HT(1A) receptor knockout mice on a 129/Sv background.

    NARCIS (Netherlands)

    Pattij, T.; Groenink, L.; Oosting, R.S.; Gugten, J. van der; Maes, R.A.A.; Olivier, B.

    2002-01-01

    Previous studies in 5-HT(1A) receptor knockout (1AKO) mice on a mixed Swiss Websterx129/Sv (SWx129/Sv) and a pure 129/Sv genetic background suggest a differential gamma-aminobutyric acid (GABA(A))-benzodiazepine receptor complex sensitivity in both strains, independent from the anxious phenotype. To

  9. Estimation of genetic variance for macro- and micro-environmental sensitivity using double hierarchical generalized linear models

    NARCIS (Netherlands)

    Mulder, H.A.; Ronnegard, L.; Veerkamp, R.F.; Strandberg, E.

    2013-01-01

    Background Genetic variation for environmental sensitivity indicates that animals are genetically different in their response to environmental factors. Environmental factors are either identifiable (e.g. temperature) and called macro-environmental or unknown and called micro-environmental. The

  10. Phosphorylation networks regulating JNK activity in diverse genetic backgrounds

    DEFF Research Database (Denmark)

    Bakal, Chris; Linding, Rune; Llense, Flora;

    2008-01-01

    Cellular signaling networks have evolved to enable swift and accurate responses, even in the face of genetic or environmental perturbation. Thus, genetic screens may not identify all the genes that regulate different biological processes. Moreover, although classical screening approaches have suc...

  11. The genetic background of Southern Iranian couples before marriage

    Science.gov (United States)

    Nariman, A; Sobhan, MR; Savaei, M; Aref-Eshghi, E; Nourinejad, R; Manoochehri, M; Ghahremani, S; Daliri, F

    2016-01-01

    Abstract Genetic service for couples plays an increasingly important role in diagnosis and risk management. This study investigated the status of consanguinity and the medical genetic history (effectiveness and coverage of medical genetic services) in couples residing in a city in southern Iran. We questioned couples who were referred to Behbahan Marital Counseling Center, Behbahan, Iran, during the period from January to November 2014, to obtain information on consanguinity, disease history, and previous referral to a medical genetics center. For the collected data was obtained descriptive statistics with STATA 11.0 software. A total of 500 couples were questioned. Mean age was 24.8 ± 5.2 years. Almost one quarter (23.4%) of the couples were consanguineous. Consanguinity was almost twice as common in rural areas as in urban areas (33.9 vs. 19.2%, p = 0.001). Only a few couples (~3.0%) had ever been referred for genetic counseling. The main reason for previous genetic counseling was consanguinity (85.7%). The majority of the participants (96.3%) had never been tested for any genetic conditions. Our findings suggest that only a small proportion of couples in Khuzestan Province, Iran (Behbahan City) were receiving adequate genetics care. This may reflect the limited accessibility of such services, and inadequate awareness and education among the care providers. PMID:28289591

  12. Does your gene need a background check? How genetic background impacts the analysis of mutations, genes, and evolution.

    Science.gov (United States)

    Chandler, Christopher H; Chari, Sudarshan; Dworkin, Ian

    2013-06-01

    The premise of genetic analysis is that a causal link exists between phenotypic and allelic variation. However, it has long been documented that mutant phenotypes are not a simple result of a single DNA lesion, but are instead due to interactions of the focal allele with other genes and the environment. Although an experimentally rigorous approach focused on individual mutations and isogenic control strains has facilitated amazing progress within genetics and related fields, a glimpse back suggests that a vast complexity has been omitted from our current understanding of allelic effects. Armed with traditional genetic analyses and the foundational knowledge they have provided, we argue that the time and tools are ripe to return to the underexplored aspects of gene function and embrace the context-dependent nature of genetic effects. We assert that a broad understanding of genetic effects and the evolutionary dynamics of alleles requires identifying how mutational outcomes depend upon the 'wild type' genetic background. Furthermore, we discuss how best to exploit genetic background effects to broaden genetic research programs.

  13. The conditional nature of genetic interactions: the consequences of wild-type backgrounds on mutational interactions in a genome-wide modifier screen.

    Directory of Open Access Journals (Sweden)

    Sudarshan Chari

    Full Text Available The phenotypic outcome of a mutation cannot be simply mapped onto the underlying DNA variant. Instead, the phenotype is a function of the allele, the genetic background in which it occurs and the environment where the mutational effects are expressed. While the influence of genetic background on the expressivity of individual mutations is recognized, its consequences on the interactions between genes, or the genetic network they form, is largely unknown. The description of genetic networks is essential for much of biology; yet if, and how, the topologies of such networks are influenced by background is unknown. Furthermore, a comprehensive examination of the background dependent nature of genetic interactions may lead to identification of novel modifiers of biological processes. Previous work in Drosophila melanogaster demonstrated that wild-type genetic background influences the effects of an allele of scalloped (sd, with respect to both its principal consequence on wing development and its interactions with a mutation in optomotor blind. In this study we address whether the background dependence of mutational interactions is a general property of genetic systems by performing a genome wide dominant modifier screen of the sd(E3 allele in two wild-type genetic backgrounds using molecularly defined deletions. We demonstrate that ~74% of all modifiers of the sd(E3 phenotype are background-dependent due in part to differential sensitivity to genetic perturbation. These background dependent interactions include some with qualitative differences in the phenotypic outcome, as well as instances of sign epistasis. This suggests that genetic interactions are often contingent on genetic background, with flexibility in genetic networks due to segregating variation in populations. Such background dependent effects can substantially alter conclusions about how genes influence biological processes, the potential for genetic screens in alternative wild

  14. Background odour induces adaptation and sensitization of olfactory receptors in the antennae of houseflies

    NARCIS (Netherlands)

    Kelling, F.J; Ialenti, F.; den Otter, C.J

    2002-01-01

    The presence of background odour was found to have a small but significant effect on the sensitivity of the antennal olfactory system of houseflies, Musca domestica Linnaeus (Diptera: Muscidae), to new pulses of odour. We show that cross-adaptation and cross-sensitization between a background odour

  15. Associations between dietary intake and body fat independent of genetic and familial environmental background

    DEFF Research Database (Denmark)

    Hasselbalch, Ann Louise; Heitmann, B L; Kyvik, Kirsten Ohm;

    2010-01-01

    To determine whether habitual dietary intake was associated with body fat mass and body fat distribution, independently of possible confounding by the genetic and shared environmental background.......To determine whether habitual dietary intake was associated with body fat mass and body fat distribution, independently of possible confounding by the genetic and shared environmental background....

  16. Distinguishing Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia-Associated Mutations From Background Genetic Noise

    NARCIS (Netherlands)

    Kapplinger, Jamie D.; Landstrom, Andrew P.; Salisbury, Benjamin A.; Callis, Thomas E.; Pollevick, Guido D.; Tester, David J.; Cox, Moniek G. P. J.; Bhuiyan, Zahir; Bikker, Hennie; Wiesfeld, Ans C. P.; Hauer, Richard N. W.; van Tintelen, J. Peter; Jongbloed, Jan D. H.; Calkins, Hugh; Judge, Daniel P.; Wilde, Arthur A. M.; Ackerman, Michael J.

    2011-01-01

    Objectives The aims of this study were to determine the spectrum and prevalence of "background genetic noise" in the arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC) genetic test and to determine genetic associations that can guide the interpretation of a positive test result. Backgr

  17. Genetics of allergy and allergic sensitization

    DEFF Research Database (Denmark)

    Bønnelykke, Klaus; Sparks, Rachel; Waage, Johannes

    2015-01-01

    Our understanding of the specific genetic lesions in allergy has improved in recent years due to identification of common risk variants from genome-wide association studies (GWAS) and studies of rare, monogenic diseases. Large-scale GWAS have identified novel susceptibility loci and provided...... information about shared genetics between allergy, related phenotypes and autoimmunity. Studies of monogenic diseases have elucidated critical cellular pathways and protein functions responsible for allergy. These complementary approaches imply genetic mechanisms involved in Th2 immunity, T...

  18. [Genetic and molecular background in autoimmune diabetes mellitus].

    Science.gov (United States)

    Kantárová, D; Prídavková, D; Ságová, I; Vrlík, M; Mikler, J; Buc, M

    2015-09-01

    Type 1 diabetes mellitus (T1 DM) is caused by autoimmune-mediated and idiopathic beta-cell destruction of the pancreatic islets of Langerhans resulting in absolute insulin deficiency. Susceptibility to T1 DM is influenced by both genetic and environmental factors. It is generally believed that in genetically susceptible individuals, the disease is triggered by environmental agents, such as viral infections, dietary factors in early infancy, or climatic influences. Many candidate genes for diabetes have been reported; those within the Major Histocompatibility Complex being among the most important. The most common autoantigens are insulin, glutamic acid decarboxylase 65, insuloma-associated antigen 2, and zinc transporter ZnT8. The destruction of beta-cells is mediated mainly by cellular mechanisms; antibodies only seem to reflect the ongoing autoimmune processes and are not directly involved in the tissue damage. They, however, appear prior to the onset of insulin deficiency which makes them suitable for use in the prevention of the disease.

  19. GOODNESS-OF-FIT TEST WITH GENETIC BACKGROUND

    Institute of Scientific and Technical Information of China (English)

    WU Jihua; XIE Minyu; PENG Rong; SUN Zhihua

    2005-01-01

    The chi-square test is a well-known goodness-of-fit test. It is available for arbitrary alternative hypothesis, particularly for a very general alternative. However, when the alternative is a "one-sided" hypothesis, which usually appears in genetic linkage analysis, the chi-square test does not use the information offered by the one-sided hypothesis.Therefore, it is possible that an appropriate one-sided test, which uses the information,will be better than the chi-square test. This paper gives such an efficient one-sided test.Monte Carlo simulation results show that it is more powerful than the chi-square test, and its power has been in creased by 30 percent as compared with that of the chi-square test inmost situations.

  20. Premature birth and diseases in premature infants: common genetic background?

    Science.gov (United States)

    Hallman, Mikko

    2012-04-01

    It has been proposed that during human evolution, development of obligate bipedalism, narrow birth canal cross-sectional area and the large brain have forced an adjustment in duration of pregnancy (scaling of gestational age; Plunkett 2011). Children compared to other mammals are born with proportionally small brains (compared to adult brains), suggesting shortening of pregnancy duration during recent evolution. Prevalence of both obstructed delivery and premature birth is still exceptionally high. In near term infants, functional maturity and viability is high, and gene variants predisposing to respiratory distress syndrome (RDS) are rare. Advanced antenatal and neonatal treatment practices during the new era of medicine allowed survival of also very preterm infants (gestation premature birth. Specific genes associating with diseases in preterm infants may also contribute to the susceptibility to preterm birth. Understanding and applying the knowledge of genetic interactions in normal and abnormal perinatal-neonatal development requires large, well-structured population cohorts, studies involving the whole genome and international interdisciplinary collaboration.

  1. Genetic background affects human glial fibrillary acidic protein promoter activity.

    Directory of Open Access Journals (Sweden)

    Xianshu Bai

    Full Text Available The human glial fibrillary acidic protein (hGFAP promoter has been used to generate numerous transgenic mouse lines, which has facilitated the analysis of astrocyte function in health and disease. Here, we evaluated the expression levels of various hGFAP transgenes at different ages in the two most commonly used inbred mouse strains, FVB/N (FVB and C57BL/6N (B6N. In general, transgenic mice maintained on the B6N background displayed weaker transgene expression compared with transgenic FVB mice. Higher level of transgene expression in B6N mice could be regained by crossbreeding to FVB wild type mice. However, the endogenous murine GFAP expression was equivalent in both strains. In addition, we found that endogenous GFAP expression was increased in transgenic mice in comparison to wild type mice. The activities of the hGFAP transgenes were not age-dependently regulated. Our data highlight the importance of proper expression analysis when non-homologous recombination transgenesis is used.

  2. Differences in Genetic Background Between Active Smokers, Passive Smokers, and Non-Smokers With Crohn's Disease

    NARCIS (Netherlands)

    van der Heide, Frans; Nolte, Ilja M.; Kleibeuker, Jan H.; Wijmenga, Cisca; Dijkstra, Gerard; Weersma, Rinse K.

    OBJECTIVES: Smoking behavior and genetic variations are important factors for the development of Crohn's disease (CD), but studies investigating the interaction between smoking and genetic background are scarce. We studied allelic associations of 19 confirmed variants located in 14 CD-associated

  3. The genetic background of inflammatory bowel disease : from correlation to causality

    NARCIS (Netherlands)

    Uniken Venema, Werna Tc; Voskuil, Michiel D; Dijkstra, Gerard; Weersma, Rinse K; Festen, Eleonora Am

    2017-01-01

    Recent studies have greatly improved our insight into the genetic background of inflammatory bowel disease (IBD). New high-throughput technologies and large-scale international collaborations have contributed to the identification of 200 independent genetic risk loci for IBD. However, in most of the

  4. Mutagen sensitivity: a genetic predisposition factor for cancer.

    Science.gov (United States)

    Wu, Xifeng; Gu, Jian; Spitz, Margaret R

    2007-04-15

    Mutagen sensitivity, measured by quantifying the chromatid breaks induced by mutagens in short-term cultures of peripheral blood lymphocytes, has been used as an indirect measure of DNA repair capacity. Numerous epidemiologic studies have suggested that mutagen sensitivity is a cancer susceptibility factor for a variety of epithelial cancers. A recent classic twin study examined systematically the role of genetic and environmental factors on the mutagen sensitivity phenotype and provided compelling evidence that mutagen sensitivity is highly heritable. A new prospective analysis provides further support to the notion that mutagen sensitivity increases the risk of cancer. In this review, we briefly summarize nearly two decades of epidemiologic and genetic studies linking mutagen sensitivity and cancer risk. The evidence is becoming increasingly convincing that mutagen sensitivity is a risk factor for cancer development.

  5. Blood pressure, heart rate and tubuloglomerular feedback in A1AR-deficient mice with different genetic backgrounds.

    Science.gov (United States)

    Kim, S M; Mizel, D; Qin, Y; Huang, Y; Schnermann, J

    2015-01-01

    Differences in genetic background between control mice and mice with targeted gene mutations have been recognized as a potential cause for phenotypic differences. In this study, we have used A1AR-deficient mice in a C57Bl/6 and SWR/J congenic background to assess the influence of background on the effect of A1AR-deficiency on cardiovascular and renal functional parameters. In A1AR+/+ and A1AR-/- mice in C57Bl/6 and SWR/J congenic backgrounds, we assessed blood pressure and heart rate using radio-telemetry, plasma renin concentrations and tubuloglomerular feedback. We did not detect significant differences in arterial blood pressure (MAP) and heart rates (HR) between A1AR+/+ and A1AR-/- mice in either C57Bl/6, SWR/J or mixed backgrounds. MAP and HR were significantly higher in SWR/J than in C57Bl/6 mice. A high NaCl intake increased MAP in A1AR-/- mice on C57Bl/6 background while there was less or no salt sensitivity in the SWR/J background. No significant differences in plasma renin concentration were detected between A1AR-/- and A1AR+/+ mice in any of the strains. Tubuloglomerular feedback was found to be absent in A1AR-/- mice with SWR/J genetic background. While this study confirmed important differences between inbred mouse strains, we did not identify phenotypic modifications of A1AR-related effects on blood pressure, heart rate and plasma renin by differences in genetic background. © 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  6. Genetic background impacts soluble and cell wall-bound aromatics in brown midrib mutants of sorghum

    Science.gov (United States)

    To evaluate the effects that genetic background has on two sorghum brown midrib (bmr) mutants, plant phenolics, lignin biosynthetic enzymes and stem anatomy were evaluated in wild-type (WT), bmr-6, bmr-12 and double-mutants (bmr-6 and bmr-12) in near isogenic , RTx430 and Wheatland backgrounds. The...

  7. Sensitivity to a Frequency-Dependent Circular Polarization in an Isotropic Stochastic Gravitational Wave Background

    CERN Document Server

    Smith, Tristan L

    2016-01-01

    We calculate the sensitivity to a circular polarization of an isotropic stochastic gravitational wave background (ISGWB) as a function of frequency for ground- and space-based interferometers and observations of the cosmic microwave background. The origin of a circularly polarized ISGWB may be due to exotic primordial physics (i.e., parity violation in the early universe) and may be strongly frequency dependent. We present calculations within a coherent framework which clarifies the basic requirements for sensitivity to circular polarization, in distinction from previous work which focused on each of these techniques separately. We find that the addition of an interferometer with the sensitivity of the Einstein Telescope in the southern hemisphere improves the sensitivity of the ground-based network to circular polarization by about a factor of two. The sensitivity curves presented in this paper make clear that the wide range in frequencies of current and planned observations ($10^{-18}\\ {\\rm Hz} \\lesssim f \\...

  8. Testing an aging gene in long-lived Drosophila strains: increased longevity depends on sex and genetic background

    National Research Council Canada - National Science Library

    Spencer, Christine C; Howell, Christine E; Wright, Amber R; Promislow, Daniel E. L

    2003-01-01

    .... Typically, long-lived mutants are identified in relatively short-lived genetic backgrounds, and their effects are rarely tested in genetic backgrounds other than the one in which they were isolated or derived...

  9. No influence of Indy on lifespan in Drosophila after correction for genetic and cytoplasmic background effects.

    Directory of Open Access Journals (Sweden)

    Janne M Toivonen

    2007-06-01

    Full Text Available To investigate whether alterations in mitochondrial metabolism affect longevity in Drosophila melanogaster, we studied lifespan in various single gene mutants, using inbred and outbred genetic backgrounds. As positive controls we included the two most intensively studied mutants of Indy, which encodes a Drosophila Krebs cycle intermediate transporter. It has been reported that flies heterozygous for these Indy mutations, which lie outside the coding region, show almost a doubling of lifespan. We report that only one of the two mutants lowers mRNA levels, implying that the lifespan extension observed is not attributable to the Indy mutations themselves. Moreover, neither Indy mutation extended lifespan in female flies in any genetic background tested. In the original genetic background, only the Indy mutation associated with altered RNA expression extended lifespan in male flies. However, this effect was abolished by backcrossing into standard outbred genetic backgrounds, and was associated with an unidentified locus on the X chromosome. The original Indy line with long-lived males is infected by the cytoplasmic symbiont Wolbachia, and the longevity of Indy males disappeared after tetracycline clearance of this endosymbiont. These findings underscore the critical importance of standardisation of genetic background and of cytoplasm in genetic studies of lifespan, and show that the lifespan extension previously claimed for Indy mutants was entirely attributable to confounding variation from these two sources. In addition, we saw no effects on lifespan of expression knockdown of the Indy orthologues nac-2 and nac-3 in the nematode Caenorhabditis elegans.

  10. Detecting a stochastic background of gravitational radiation Signal processing strategies and sensitivities

    CERN Document Server

    Allen, B; Allen, Bruce; Romano, Joseph D.

    1999-01-01

    We analyze the signal processing required for the optimal detection of a stochastic background of gravitational radiation using laser interferometric detectors. Starting with basic assumptions about the statistical properties of a stochastic gravity-wave background, we derive expressions for the optimal filter function and signal-to-noise ratio for the cross-correlation of the outputs of two gravity-wave detectors. Sensitivity levels required for detection are then calculated. Issues related to: (i) calculating the signal-to-noise ratio for arbitrarily large stochastic backgrounds, (ii) performing the data analysis in the presence of nonstationary detector noise, (iii) combining data from multiple detector pairs to increase the sensitivity of a stochastic background search, (iv) correlating the outputs of 4 or more detectors, and (v) allowing for the possibility of correlated noise in the outputs of two detectors are discussed. We briefly describe a computer simulation which mimics the generation and detectio...

  11. Ogg1 genetic background determines the genotoxic potential of environmentally relevant arsenic exposures.

    Science.gov (United States)

    Bach, Jordi; Sampayo-Reyes, Adriana; Marcos, Ricard; Hernández, Alba

    2014-03-01

    Inorganic arsenic (i-As) is a well-established human carcinogen to which millions of people are exposed worldwide. It is generally accepted that the genotoxic effects of i-As after an acute exposure are partially linked to the i-As-induced production of reactive oxygen species, but it is necessary to better determine whether chronic sub-toxic i-As doses are able to induce biologically significant levels of oxidative DNA damage (ODD). To fill in this gap, we have tested the genotoxic and oxidative effects of environmentally relevant arsenic exposures using mouse embryonic fibroblast MEF mutant Ogg1 cells and their wild-type counterparts. Effects were examined by using the comet assay complemented with the use of FPG enzyme. Our findings indicate that MEF Ogg1-/- cells are more sensitive to arsenite-induced acute toxicity, genotoxicity and ODD. Long-term exposure to sub-toxic doses of arsenite generates a detectable increase in ODD and genotoxic DNA damage only in MEF Ogg1-deficient cells. Altogether, the data presented here point out the relevance of ODD and Ogg1 genetic background on the genotoxic risk of i-As at environmentally plausible doses. The persistent accumulation of DNA 8-OH-dG lesions in Ogg1-/- cells during the complete course of the exposure suggests a relevant role in arsenic-associated carcinogenic risk in turn.

  12. Intrauterine and genetic factors in early childhood sensitization

    DEFF Research Database (Denmark)

    Bønnelykke, Klaus

    2010-01-01

    The allergy-associated (atopic) diseases; asthma, eczema and rhinoconjunctivitis, are the most common chronic diseases in childhood. A large number of environmental and genetic risk factors have been suggested, but still our understanding of the underlying disease mechanisms and etiologies...... of opportunity” for prevention. The aim of this thesis was to increase the understanding of sensitization in early life. We studied indicators of sensitization in the newborn, and early development of sensitization and disease associated with a newly discovered genetic risk factor. Such insight may increase our...... and identifying the environmental risk factors interacting with this genetic susceptibility and the age at which intervention should be initiated. We found a FLG-associated pattern of atopic disease in early childhood characterized by early onset of eczema, early onset of asthma with severe exacerbations...

  13. Intrauterine and genetic factors in early childhood sensitization

    DEFF Research Database (Denmark)

    Bønnelykke, Klaus

    2010-01-01

    predictive value of elevated cord blood IgE found in recent studies. Future studies should control for materno-fetal transfer of IgE or preferably use other markers of atopy. Variation in the gene coding for the skin barrier protein filaggrin (FLG) is the strongest known genetic risk factor for eczema. FLG......The allergy-associated (atopic) diseases; asthma, eczema and rhinoconjunctivitis, are the most common chronic diseases in childhood. A large number of environmental and genetic risk factors have been suggested, but still our understanding of the underlying disease mechanisms and etiologies...... of opportunity” for prevention. The aim of this thesis was to increase the understanding of sensitization in early life. We studied indicators of sensitization in the newborn, and early development of sensitization and disease associated with a newly discovered genetic risk factor. Such insight may increase our...

  14. The Effect of Genetic Polymorphism upon Antineoplastic Sensitivity

    Institute of Scientific and Technical Information of China (English)

    Jun Liang

    2006-01-01

    In clinical practice, patients undergoing chemotherapy display prominent individual differences, adverse reactions and sensitivity to antineoplastic therapy. Those differences are caused by individual genetic polymorphism of related genes. Genetic variation can induce distinct alterations of drug-metabolizing enzymes, drug transporters, drug targets and DNA repair enzymes and thereby influence the ability of the drugs to reach their target sites. This article reviews in detail the potential interactions mentioned above.

  15. Identification of genetic variants associated with maize flowering time using an extremely large multi-genetic background population

    Science.gov (United States)

    Flowering time is one of the major adaptive traits in domestication of maize and an important selection criterion in breeding. To detect more maize flowering time variants we evaluated flowering time traits using an extremely large multi- genetic background population that contained more than 8000 l...

  16. Experimental study of variations in background radiation and the effect on Nuclear Car Wash sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Church, J; Slaughter, D; Norman, E; Asztalos, S; Biltoft, P

    2007-02-07

    Error rates in a cargo screening system such as the Nuclear Car Wash [1-7] depend on the standard deviation of the background radiation count rate. Because the Nuclear Car Wash is an active interrogation technique, the radiation signal for fissile material must be detected above a background count rate consisting of cosmic, ambient, and neutron-activated radiations. It was suggested previously [1,6] that the Corresponding negative repercussions for the sensitivity of the system were shown. Therefore, to assure the most accurate estimation of the variation, experiments have been performed to quantify components of the actual variance in the background count rate, including variations in generator power, irradiation time, and container contents. The background variance is determined by these experiments to be a factor of 2 smaller than values assumed in previous analyses, resulting in substantially improved projections of system performance for the Nuclear Car Wash.

  17. Nonverbal Sensitivity: Consequences for Learning and Satisfaction in Genetic Counseling

    Science.gov (United States)

    Roter, D. L.; Erby, L. H.; Hall, J. A.; Larson, S.; Ellington, L.; Dudley, W.

    2008-01-01

    Purpose: This study aims to explore the role of interactants' nonverbal sensitivity, anxiety and sociodemographic characteristics in learning and satisfaction within the genetic counseling context. Design/methodology/approach: This is a combined simulation and analogue study. Simulations were videotaped with 152 prenatal and cancer genetic…

  18. Understanding the Science-Learning Environment: A Genetically Sensitive Approach

    Science.gov (United States)

    Haworth, Claire M. A.; Davis, Oliver S. P.; Hanscombe, Ken B.; Kovas, Yulia; Dale, Philip S.; Plomin, Robert

    2013-01-01

    Previous studies have shown that environmental influences on school science performance increase in importance from primary to secondary school. Here we assess for the first time the relationship between the science-learning environment and science performance using a genetically sensitive approach to investigate the aetiology of this link. 3000…

  19. Genetic background may contribute to PAM50 gene expression breast cancer subtype assignments.

    Directory of Open Access Journals (Sweden)

    Ying Hu

    Full Text Available Recent advances in genome wide transcriptional analysis have provided greater insights into the etiology and heterogeneity of breast cancer. Molecular signatures have been developed that stratify the conventional estrogen receptor positive or negative categories into subtypes that are associated with differing clinical outcomes. It is thought that the expression patterns of the molecular subtypes primarily reflect cell-of-origin or tumor driver mutations. In this study however, using a genetically engineered mouse mammary tumor model we demonstrate that the PAM50 subtype signature of tumors driven by a common oncogenic event can be significantly influenced by the genetic background on which the tumor arises. These results have important implications for interpretation of "snapshot" expression profiles, as well as suggesting that incorporation of genetic background effects may allow investigation into phenotypes not initially anticipated in individual mouse models of cancer.

  20. [Recent progress in genetic background of chronic obstructive pulmonary disease (COPD)].

    Science.gov (United States)

    Teramoto, Shinji

    2016-05-01

    A genetic contribution to develop chronic obstructive pulmonary disease(COPD) is estimated. However, candidate gene studies on COPD and related phenotypes have not been well replicated. Research on the genetic pathologic background of COPD using genome-wide association studies (GWASs) has progressed in recent years. The novel candidate genes including CHRNA3/5 (cholinergic nicotine receptor alpha 3/5), IREB2 (iron regulatory binding protein 2), HHIP (hedgehog-interacting protein), and FAM13A (family with sequence similarity 13, member A) are identified in multiple populations. However, their pathological roles remain poorly understood. The nicotine dependency, pulmonary development, and pulmonary/systemic inflammatory diathesis may be involved in genetic background of COPD.

  1. Development of an underground low background instrument for high sensitivity measurements

    Science.gov (United States)

    Sala, E.; Hahn, I. S.; Kang, W. G.; Kim, G. W.; Kim, Y. D.; Lee, M. H.; Leonard, D. S.; Park, Su Yeon

    2016-05-01

    The Center for Underground Physics has developed in collaboration with CANBERRA a low background instrument composed of 14 HPGe detectors divided in two arrays facing each other. The performance and the background of a single detector of the array have been studied in order to improve the array final configuration. An accurate material selection, through the measurements of building material samples and Monte Carlo simulations based on Geant4, has been performed to reach the lowest possible intrinsic background. Alternative materials and configurations have been considered for the final design of the array simulating the expected intrinsic background of the instrument considering the needed changes. The expected sensitivity of the improved array configuration, concerning the low background material selection for rare events physics experiments, has been evaluated through Monte Carlo simulations considering 232Th concentration in a Copper sample. Since the array can also be used for rare decays searches, the expected sensitivity on the 156Dy resonant double electron capture has thus been calculated.

  2. Genetic background specific hypoxia resistance in rat is correlated with balanced activation of a cross-chromosomal genetic network centering on physiological homeostasis

    Directory of Open Access Journals (Sweden)

    Lei eMao

    2012-10-01

    Full Text Available Genetic background of an individual can drastically influence an organism’s response upon environmental stress and pathological stimulus. Previous studies in inbred rats showed that compared to Brown Norway (BN, Dahl salt-sensitive (SS rat exerts strong hypoxia susceptibility. However, despite extensive narrow-down approaches via the chromosome substitution methodology, this genome-based physiological predisposition could not be traced back to distinct quantitative trait loci. Upon the completion and public data availability of PhysGen SS-BN consomic rat platform, I employed systems biology approach attempting to further our understanding of the molecular basis of genetic background effect in light of hypoxia response. I analyzed the physiological screening data of 22 consomic rat strains under normoxia and two-weeks of hypoxia, and cross-compared them to the parental strains. The analyses showed that SS-9BN and SS-18BN represent the most hypoxia resistant CS strains with phenotype similar to BN, whereas SS-6BN and SS-YBN segregated to the direction of SS. A meta-analysis on the transcriptomic profiles of these consomic rat strains under hypoxia treatment showed that although polymorphisms on the substituted BN chromosomes could be directly involved in hypoxia resistance, this seems to be embedded in a more complex trans-chromosomal genetic regulatory network. Via information theory based modeling approach, this hypoxia-relevant core genetic network was reverse-engineered. Network analyses showed that the protective effects of BN chromosome 9 and 18 were reflected by a balanced activation of this core network centering on physiological homeostasis. Presumably, it is the system robustness constituted on such differential network activation that acts as hypoxia response modifier. Understanding of the intrinsic link between the individual genetic background and the network robustness will set a basis in the current scientific efforts toward

  3. Genetic Background Specific Hypoxia Resistance in Rat is Correlated with Balanced Activation of a Cross-Chromosomal Genetic Network Centering on Physiological Homeostasis.

    Science.gov (United States)

    Mao, Lei

    2012-01-01

    Genetic background of an individual can drastically influence an organism's response upon environmental stress and pathological stimulus. Previous studies in inbred rats showed that compared to Brown Norway (BN), Dahl salt-sensitive (SS) rat exerts strong hypoxia susceptibility. However, despite extensive narrow-down approaches via the chromosome substitution methodology, this genome-based physiological predisposition could not be traced back to distinct quantitative trait loci. Upon the completion and public data availability of PhysGen SS-BN consomic (CS) rat platform, I employed systems biology approach attempting to further our understanding of the molecular basis of genetic background effect in light of hypoxia response. I analyzed the physiological screening data of 22 CS rat strains under normoxia and 2-weeks of hypoxia, and cross-compared them to the parental strains. The analyses showed that SS-9(BN) and SS-18(BN) represent the most hypoxia-resistant CS strains with phenotype similar to BN, whereas SS-6(BN) and SS-Y(BN) segregated to the direction of SS. A meta-analysis on the transcriptomic profiles of these CS rat strains under hypoxia treatment showed that although polymorphisms on the substituted BN chromosomes could be directly involved in hypoxia resistance, this seems to be embedded in a more complex trans-chromosomal genetic regulatory network. Via information theory based modeling approach, this hypoxia relevant core genetic network was reverse engineered. Network analyses showed that the protective effects of BN chromosome 9 and 18 were reflected by a balanced activation of this core network centering on physiological homeostasis. Presumably, it is the system robustness constituted on such differential network activation that acts as hypoxia response modifier. Understanding of the intrinsic link between the individual genetic background and the network robustness will set a basis in the current scientific efforts toward personalized medicine.

  4. Neuro-genetic system for optimization of GMI samples sensitivity.

    Science.gov (United States)

    Pitta Botelho, A C O; Vellasco, M M B R; Hall Barbosa, C R; Costa Silva, E

    2016-03-01

    Magnetic sensors are largely used in several engineering areas. Among them, magnetic sensors based on the Giant Magnetoimpedance (GMI) effect are a new family of magnetic sensing devices that have a huge potential for applications involving measurements of ultra-weak magnetic fields. The sensitivity of magnetometers is directly associated with the sensitivity of their sensing elements. The GMI effect is characterized by a large variation of the impedance (magnitude and phase) of a ferromagnetic sample, when subjected to a magnetic field. Recent studies have shown that phase-based GMI magnetometers have the potential to increase the sensitivity by about 100 times. The sensitivity of GMI samples depends on several parameters, such as sample length, external magnetic field, DC level and frequency of the excitation current. However, this dependency is yet to be sufficiently well-modeled in quantitative terms. So, the search for the set of parameters that optimizes the samples sensitivity is usually empirical and very time consuming. This paper deals with this problem by proposing a new neuro-genetic system aimed at maximizing the impedance phase sensitivity of GMI samples. A Multi-Layer Perceptron (MLP) Neural Network is used to model the impedance phase and a Genetic Algorithm uses the information provided by the neural network to determine which set of parameters maximizes the impedance phase sensitivity. The results obtained with a data set composed of four different GMI sample lengths demonstrate that the neuro-genetic system is able to correctly and automatically determine the set of conditioning parameters responsible for maximizing their phase sensitivities.

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

    Science.gov (United States)

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

    2016-05-03

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

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

    Directory of Open Access Journals (Sweden)

    Chad M. Hunter

    2016-05-01

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

  7. Resistance to early-life stress in mice: effects of genetic background and stress duration

    Directory of Open Access Journals (Sweden)

    Helene M. Savignac

    2011-04-01

    Full Text Available Early-life stress can induce marked behavioural and physiological impairments in adulthood including cognitive deficits, depression, anxiety and gastrointestinal dysfunction. Although robust rat models of early-life stress exist there are few established effective paradigms in the mouse. Genetic background and protocol parameters used are two critical variables in such model development.Thus we investigated the impact of two different early-life stress protocols in two commonly used inbred mouse strains. C57BL/6 and innately anxious BALB/c male mice were maternally deprived 3 hrs daily, either from postnatal day 1 to 14 (Protocol 1 or 6 to 10 (Protocol 2. Animals were assessed in adulthood for cognitive performance (spontaneous alternation behaviour test, anxiety (open field, light/dark box and elevated plus maze tests and depression-related behaviours (forced swim test in addition to stress-sensitive physiological changes. Overall, the results showed that early-life stressed mice from both strains displayed good cognitive ability and no elevations in anxiety. However, paradoxical changes occurred in C57BL/6 mice as the longer protocol (protocol 1 decreased anxiety in the light-dark box and increased exploration in the elevated plus maze. In BALB/c mice there were also limited effects of maternal separation with both separation protocols inducing reductions in stress-induced defecation and protocol 1 reducing the colon length. These data suggest that, independent of stress duration, mice from both strains were on the whole resilient to the maladaptive effects of early-life stress. Thus maternal-separation models of brain-gut axis dysfunction should rely on either different stressor protocols or other strains of mice.

  8. The influence of genetic background versus commercial breeding programs on chicken immunocompetence.

    Science.gov (United States)

    Emam, Mehdi; Mehrabani-Yeganeh, Hassan; Barjesteh, Neda; Nikbakht, Gholamreza; Thompson-Crispi, Kathleen; Charkhkar, Saeid; Mallard, Bonnie

    2014-01-01

    Immunocompetence of livestock plays an important role in farm profitability because it directly affects health maintenance. Genetics significantly influences the immune system, and the genotypic structure of modern fast-growing chickens has been changed, particularly after decades of breeding for higher production. Therefore, this study was designed to help determine if intensive breeding programs have adversely affected immunocompetence or whether the immune response profiles are controlled to greater extent by genetic background. Thus, 3 indigenous chicken populations from different genetic backgrounds and 2 globally available modern broiler strains, Ross 308 and Cobb 500, were evaluated for various aspects of immune response. These included antibody responses against sheep red blood cells and Brucella abortus antigen, as well as some aspects of cell-mediated immunocompetence by toe web swelling test and in vitro blood mononuclear cell proliferation. Significant differences (P chickens is most likely due to differences in the genetic background between each strain of chicken rather than by commercial selection programs for high production.

  9. Sensitivity of soil moisture analyses to contrasting background and observation error scenarios

    Science.gov (United States)

    Munoz-Sabater, Joaquín; de Rosnay, Patricia; Albergel, Clément; Isaksen, Lars

    2017-04-01

    Soil moisture is a crucial variable for numerical weather prediction. Accurate, global initialization of soil moisture is obtained through data assimilation systems. However analyses depend largely on the way observations and background errors are defined. In this paper a wide range of short experiments with contrasted specification of the observation error and soil moisture background were conducted. As observations, screen-level variables and brightness temperatures from the Soil Moisture and Ocean Salinity (SMOS) mission were used. The region of interest was North America given the good availability of in-situ observations. The impact of these experiments on soil moisture and the atmospheric layer near the surface were evaluated. The results highlighted the importance of assimilating sensitive observations to soil moisture for air temperature and humidity forecasts. The benefits on the soil water content were more noticeable with increasing the SMOS observation error and with the introduction of soil texture dependency in the soil moisture background error.

  10. Enhanced biofilm formation and multi-host transmission evolve from divergent genetic backgrounds in Campylobacter jejuni.

    Science.gov (United States)

    Pascoe, Ben; Méric, Guillaume; Murray, Susan; Yahara, Koji; Mageiros, Leonardos; Bowen, Ryan; Jones, Nathan H; Jeeves, Rose E; Lappin-Scott, Hilary M; Asakura, Hiroshi; Sheppard, Samuel K

    2015-11-01

    Multicellular biofilms are an ancient bacterial adaptation that offers a protective environment for survival in hostile habitats. In microaerophilic organisms such as Campylobacter, biofilms play a key role in transmission to humans as the bacteria are exposed to atmospheric oxygen concentrations when leaving the reservoir host gut. Genetic determinants of biofilm formation differ between species, but little is known about how strains of the same species achieve the biofilm phenotype with different genetic backgrounds. Our approach combines genome-wide association studies with traditional microbiology techniques to investigate the genetic basis of biofilm formation in 102 Campylobacter jejuni isolates. We quantified biofilm formation among the isolates and identified hotspots of genetic variation in homologous sequences that correspond to variation in biofilm phenotypes. Thirteen genes demonstrated a statistically robust association including those involved in adhesion, motility, glycosylation, capsule production and oxidative stress. The genes associated with biofilm formation were different in the host generalist ST-21 and ST-45 clonal complexes, which are frequently isolated from multiple host species and clinical samples. This suggests the evolution of enhanced biofilm from different genetic backgrounds and a possible role in colonization of multiple hosts and transmission to humans.

  11. Laser-interferometric Detectors for Gravitational Wave Background at 100 MHz : Detector Design and Sensitivity

    CERN Document Server

    Nishizawa, Atsushi; Akutsu, Tomotada; Arai, Koji; Yamamoto, Kazuhiro; Tatsumi, Daisuke; Nishida, Erina; Sakagami, Masa-aki; Chiba, Takeshi; Takahashi, Ryuichi; Sugiyama, Naoshi

    2007-01-01

    Recently, observational searches for gravitational wave background (GWB) have developed and given direct and indirect constraints on the energy density of GWB in a broad range of frequencies. These constraints have already rejected some theoretical models of large GWB spectra. However, at 100 MHz, there is no strict upper limit from direct observation, though the indirect limit by He4 abundance due to big-bang nucleosynthesis exists. In this paper, we propose an experiment with laser interferometers searching GWB at 100 MHz. We considered three detector designs and evaluated the GW response functions of a single detector. As a result, we found that, at 100 MHz, the most sensitive detector is the design, a so-called synchronous recycling interferometer, which has better sensitivity than an ordinary Fabry-Perot Michelson interferometer by a factor of 3.3 at 100 MHz. We also give the best sensitivity achievable at 100 MHz with realistic experimental parameters.

  12. New application of intelligent agents in sporadic amyotrophic lateral sclerosis identifies unexpected specific genetic background

    Directory of Open Access Journals (Sweden)

    Marocchi Alessandro

    2008-05-01

    Full Text Available Abstract Background Few genetic factors predisposing to the sporadic form of amyotrophic lateral sclerosis (ALS have been identified, but the pathology itself seems to be a true multifactorial disease in which complex interactions between environmental and genetic susceptibility factors take place. The purpose of this study was to approach genetic data with an innovative statistical method such as artificial neural networks to identify a possible genetic background predisposing to the disease. A DNA multiarray panel was applied to genotype more than 60 polymorphisms within 35 genes selected from pathways of lipid and homocysteine metabolism, regulation of blood pressure, coagulation, inflammation, cellular adhesion and matrix integrity, in 54 sporadic ALS patients and 208 controls. Advanced intelligent systems based on novel coupling of artificial neural networks and evolutionary algorithms have been applied. The results obtained have been compared with those derived from the use of standard neural networks and classical statistical analysis Results Advanced intelligent systems based on novel coupling of artificial neural networks and evolutionary algorithms have been applied. The results obtained have been compared with those derived from the use of standard neural networks and classical statistical analysis. An unexpected discovery of a strong genetic background in sporadic ALS using a DNA multiarray panel and analytical processing of the data with advanced artificial neural networks was found. The predictive accuracy obtained with Linear Discriminant Analysis and Standard Artificial Neural Networks ranged from 70% to 79% (average 75.31% and from 69.1 to 86.2% (average 76.6% respectively. The corresponding value obtained with Advanced Intelligent Systems reached an average of 96.0% (range 94.4 to 97.6%. This latter approach allowed the identification of seven genetic variants essential to differentiate cases from controls: apolipoprotein E arg

  13. Cancer resistance of SR/CR mice in the genetic knockout backgrounds of leukocyte effector mechanisms: determinations for functional requirements

    Directory of Open Access Journals (Sweden)

    Sanders Anne M

    2010-03-01

    Full Text Available Abstract Background Spontaneous Regression/Complete Resistant (SR/CR mice are a colony of cancer-resistant mice that can detect and rapidly destroy malignant cells with innate cellular immunity, predominately mediated by granulocytes. Our previous studies suggest that several effector mechanisms, such as perforin, granzymes, or complements, may be involved in the killing of cancer cells. However, none of these effector mechanisms is known as critical for granulocytes. Additionally, it is unclear which effector mechanisms are required for the cancer killing activity of specific leukocyte populations and the survival of SR/CR mice against the challenges of lethal cancer cells. We hypothesized that if any of these effector mechanisms was required for the resistance to cancer cells, its functional knockout in SR/CR mice should render them sensitive to cancer challenges. This was tested by cross breeding SR/CR mice into the individual genetic knockout backgrounds of perforin (Prf-/-, superoxide (Cybb-/, or inducible nitric oxide (Nos2-/. Methods SR/CR mice were bred into individual Prf-/-, Cybb-/-, or Nos2-/- genetic backgrounds and then challenged with sarcoma 180 (S180. Their overall survival was compared to controls. The cancer killing efficiency of purified populations of macrophages and neutrophils from these immunodeficient mice was also examined. Results When these genetically engineered mice were challenged with cancer cells, the knockout backgrounds of Prf-/-, Cybb-/-, or Nos2-/- did not completely abolish the SR/CR cancer resistant phenotype. However, the Nos2-/- background did appear to weaken the resistance. Incidentally, it was also observed that the male mice in these immunocompromised backgrounds tended to be less cancer-resistant than SR/CR controls. Conclusion Despite the previously known roles of perforin, superoxide or nitric oxide in the effector mechanisms of innate immune responses, these effector mechanisms were not required

  14. Genetic Loci Associated with Allergic Sensitization in Lithuanians.

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    Ingrida Šaulienė

    Full Text Available Allergic rhinitis (AR is a common and complex disease. It is associated with environmental as well as genetic factors. Three recent genome-wide association studies (GWAS reported altogether 47 single nucleotide polymorphisms (SNPs associated with AR or allergic sensitization (AS in Europeans and North Americans. Two follow up studies in Swedish and Chinese replicated 15 associations. In these studies individuals were selected based on the self-reported AR, or AR/AS diagnosed using blood IgE test or skin prick test (SPT, which were performed often without restriction to specific allergens. Here we performed third replication study in Lithuanians. We used SPT and carefully selected set of allergens prevalent in Lithuania, as well as Illumina Core Exome chip for SNP detection. We genotyped 270 SPT-positive individuals (137 Betulaceae -, 174 Poaceae-, 199 Artemisia-, 70 Helianthus-, 22 Alternaria-, 22 Cladosporium-, 140 mites-, 95 cat- and 97 dog dander-sensitive cases and 162 SPT-negative controls. We found altogether 13 known SNPs associated with AS (p ≤0.05. Three SNPs were found in Lithuanians sensitive to several allergens, and 10 SNPs were found in Lithuanians sensitive to a certain allergen. For the first time, SNP rs7775228:C was associated with patient sensitivity to dog allergens (F_A=0,269, F_U=0.180, P=0.008. Thus, careful assessment of AS allowed us to detect known genetic variants associated with AS/AR in relatively small cohort of Lithuanians.

  15. Genetic Loci Associated with Allergic Sensitization in Lithuanians.

    Science.gov (United States)

    Šaulienė, Ingrida; Greičiuvienė, Jūratė; Šukienė, Laura; Juškevičiūtė, Neringa; Benner, Christian; Zinkevičienė, Auksė; Ripatti, Samuli; Donner, Kati; Kainov, Denis

    2015-01-01

    Allergic rhinitis (AR) is a common and complex disease. It is associated with environmental as well as genetic factors. Three recent genome-wide association studies (GWAS) reported altogether 47 single nucleotide polymorphisms (SNPs) associated with AR or allergic sensitization (AS) in Europeans and North Americans. Two follow up studies in Swedish and Chinese replicated 15 associations. In these studies individuals were selected based on the self-reported AR, or AR/AS diagnosed using blood IgE test or skin prick test (SPT), which were performed often without restriction to specific allergens. Here we performed third replication study in Lithuanians. We used SPT and carefully selected set of allergens prevalent in Lithuania, as well as Illumina Core Exome chip for SNP detection. We genotyped 270 SPT-positive individuals (137 Betulaceae -, 174 Poaceae-, 199 Artemisia-, 70 Helianthus-, 22 Alternaria-, 22 Cladosporium-, 140 mites-, 95 cat- and 97 dog dander-sensitive cases) and 162 SPT-negative controls. We found altogether 13 known SNPs associated with AS (p ≤0.05). Three SNPs were found in Lithuanians sensitive to several allergens, and 10 SNPs were found in Lithuanians sensitive to a certain allergen. For the first time, SNP rs7775228:C was associated with patient sensitivity to dog allergens (F_A=0,269, F_U=0.180, P=0.008). Thus, careful assessment of AS allowed us to detect known genetic variants associated with AS/AR in relatively small cohort of Lithuanians.

  16. A new genomic library of melon introgression lines in a cantaloupe genetic background for dissecting desirable agronomical traits

    OpenAIRE

    2016-01-01

    Background Genomic libraries of introgression lines (ILs) consist of collections of homozygous lines with a single chromosomal introgression from a donor genotype in a common, usually elite, genetic background, representing the whole donor genome in the full collection. Currently, the only available melon IL collection was generated using Piel de sapo (var. inodorus) as the recurrent background. ILs are not available in genetic backgrounds representing other important market class cultivars, ...

  17. Genetic background and climatic droplet keratopathy incidence in a Mapuche population from Argentina.

    Science.gov (United States)

    Schurr, Theodore G; Dulik, Matthew C; Cafaro, Thamara A; Suarez, María F; Urrets-Zavalia, Julio A; Serra, Horacio M

    2013-01-01

    To determine whether the incidence of and susceptibility to climatic droplet keratopathy (CDK), an acquired, often bilateral degenerative corneal disease, is influenced by the genetic background of the individuals who exhibit the disorder. To determine whether the disease expression was influenced by the genetic ancestry of CDK cases in native Mapuche of the northwest area of Patagonia in Argentina, we examined mitochondrial DNA and Y-chromosome variation in 53 unrelated individuals. Twenty-nine of them were part of the CDK (patient) population, while 24 were part of the control group. The analysis revealed the maternal and paternal lineages that were present in the two study groups. This analysis demonstrated that nearly all persons had a Native American mtDNA background, whereas 50% of the CDK group and 37% of the control group had Native American paternal ancestry, respectively. There was no significant difference in the frequencies of mtDNA haplogroups between the CDK patient and control groups. Although the Y-chromosome data revealed differences in specific haplogroup frequencies between these two groups, there was no statistically significant relationship between individual paternal genetic backgrounds and the incidence or stage of disease. These results indicate a lack of correlation between genetic ancestry as represented by haploid genetic systems and the incidence of CDK in Mapuche populations. In addition, the mtDNA appears to play less of a role in CDK expression than for other complex diseases linked to bioenergetic processes. However, further analysis of the mtDNA genome sequence and other genes involved in corneal function may reveal the more precise role that mitochondria play in the expression of CDK.

  18. The joint effects of background selection and genetic recombination on local gene genealogies.

    Science.gov (United States)

    Zeng, Kai; Charlesworth, Brian

    2011-09-01

    Background selection, the effects of the continual removal of deleterious mutations by natural selection on variability at linked sites, is potentially a major determinant of DNA sequence variability. However, the joint effects of background selection and genetic recombination on the shape of the neutral gene genealogy have proved hard to study analytically. The only existing formula concerns the mean coalescent time for a pair of alleles, making it difficult to assess the importance of background selection from genome-wide data on sequence polymorphism. Here we develop a structured coalescent model of background selection with recombination and implement it in a computer program that efficiently generates neutral gene genealogies for an arbitrary sample size. We check the validity of the structured coalescent model against forward-in-time simulations and show that it accurately captures the effects of background selection. The model produces more accurate predictions of the mean coalescent time than the existing formula and supports the conclusion that the effect of background selection is greater in the interior of a deleterious region than at its boundaries. The level of linkage disequilibrium between sites is elevated by background selection, to an extent that is well summarized by a change in effective population size. The structured coalescent model is readily extendable to more realistic situations and should prove useful for analyzing genome-wide polymorphism data.

  19. A Polarization Sensitive Bolometric Detector for Observations of the Cosmic Microwave Background

    CERN Document Server

    Jones, W C; Bock, J J; Lange, A E

    2002-01-01

    We have developed a bolometric detector that is intrinsically sensitive to linear polarization which is optimized for making measurements of the polarization of the cosmic microwave background radiation. The receiver consists of a pair of co-located silicon nitride micromesh absorbers which couple anisotropically to linearly polarized radiation through a corrugated waveguide structure. This system allows simultaneous background limited measurements of the Stokes I and Q parameters over ~ 30% bandwidths at frequencies from ~ 60 to 600 GHz. Since both linear polarizations traverse identical optical paths from the sky to the point of detection, the susceptibility to systematic effects is minimized. The amount of uncorrelated noise between the two polarization senses is limited to the quantum limit of thermal and photon shot noise, while drifts in the relative responsivity to orthogonal polarizations are limited to the effect of non-uniformity in the thin film deposition of the leads and the intrinsic thermistor ...

  20. Confidence limits with multiple channels and arbitrary probability distributions for sensitivity and expected background

    CERN Document Server

    Perrotta, A

    2002-01-01

    A MC method is proposed to compute upper limits, in a pure Bayesian approach, when the errors associated with the experimental sensitivity and expected background content are not Gaussian distributed or not small enough to apply usual approximations. It is relatively easy to extend the procedure to the multichannel case (for instance when different decay branching, luminosities or experiments have to be combined). Some of the searches for supersymmetric particles performed in the DELPHI experiment at the LEP electron- positron collider use such a procedure to propagate systematics into the calculation of cross-section upper limits. One of these searches is described as an example. (6 refs).

  1. Multilocus spacer analysis revealed highly homogeneous genetic background of Asian type of Borrelia miyamotoi.

    Science.gov (United States)

    Mukhacheva, Tatyana A; Salikhova, Irina I; Kovalev, Sergey Y

    2015-04-01

    Borrelia miyamotoi, a member of the relapsing fever group borreliae, was first isolated in Japan and subsequently found in Ixodes ticks in North America, Europe and Russia. Currently, there are three types of B. miyamotoi: Asian or Siberian (transmitted mainly by Ixodes persulcatus), European (Ixodesricinus) and American (Ixodesscapularis and Ixodespacificus). Despite the great genetic distances between B. miyamotoi types, isolates within a type are characterised by an extremely low genetic variability. In particular, strains of B. miyamotoi of Asian type, isolated in Russia from the Baltic sea to the Far East, have been shown to be identical based on the analysis of several conventional genetic markers, such as 16S rRNA, flagellin, outer membrane protein p66 and glpQ genes. Thus, protein or rRNA - coding genes were shown not to be informative enough in studying genetic diversity of B. miyamotoi within a type. In the present paper, we have attempted to design a new multilocus technique based on eight non-coding intergenic spacers (3686bp in total) and have applied it to the analysis of intra-type genetic variability of В. miyamotoi detected in different regions of Russia and from two tick species, I. persulcatus and Ixodespavlovskyi. However, even though potentially the most variable loci were selected, no genetic variability between studied DNA samples was found, except for one nucleotide substitution in two of them. The sequences obtained were identical to those of the reference strain FR64b. Analysis of the data obtained with the GenBank sequences indicates a highly homogeneous genetic background of B. miyamotoi from the Baltic Sea to the Japanese Islands. In this paper, a hypothesis of clonal expansion of B. miyamotoi is discussed, as well as possible mechanisms for the rapid dissemination of one B. miyamotoi clone over large distances.

  2. Quantitative autistic trait measurements index background genetic risk for ASD in Hispanic families.

    Science.gov (United States)

    Page, Joshua; Constantino, John Nicholas; Zambrana, Katherine; Martin, Eden; Tunc, Ilker; Zhang, Yi; Abbacchi, Anna; Messinger, Daniel

    2016-01-01

    Recent studies have indicated that quantitative autistic traits (QATs) of parents reflect inherited liabilities that may index background genetic risk for clinical autism spectrum disorder (ASD) in their offspring. Moreover, preferential mating for QATs has been observed as a potential factor in concentrating autistic liabilities in some families across generations. Heretofore, intergenerational studies of QATs have focused almost exclusively on Caucasian populations-the present study explored these phenomena in a well-characterized Hispanic population. The present study examined QAT scores in siblings and parents of 83 Hispanic probands meeting research diagnostic criteria for ASD, and 64 non-ASD controls, using the Social Responsiveness Scale-2 (SRS-2). Ancestry of the probands was characterized by genotype, using information from 541,929 single nucleotide polymorphic markers. In families of Hispanic children with an ASD diagnosis, the pattern of quantitative trait correlations observed between ASD-affected children and their first-degree relatives (ICCs on the order of 0.20), between unaffected first-degree relatives in ASD-affected families (sibling/mother ICC = 0.36; sibling/father ICC = 0.53), and between spouses (mother/father ICC = 0.48) were in keeping with the influence of transmitted background genetic risk and strong preferential mating for variation in quantitative autistic trait burden. Results from analysis of ancestry-informative genetic markers among probands in this sample were consistent with that from other Hispanic populations. Quantitative autistic traits represent measurable indices of inherited liability to ASD in Hispanic families. The accumulation of autistic traits occurs within generations, between spouses, and across generations, among Hispanic families affected by ASD. The occurrence of preferential mating for QATs-the magnitude of which may vary across cultures-constitutes a mechanism by which background genetic liability

  3. Temporal Dependence of Chromosomal Aberration on Radiation Quality and Cellular Genetic Background

    Science.gov (United States)

    Lu, Tao; Zhang, Ye; Krieger, Stephanie; Yeshitla, Samrawit; Goss, Rosalin; Bowler, Deborah; Kadhim, Munira; Wilson, Bobby; Wu, Honglu

    2017-01-01

    Radiation induced cancer risks are driven by genetic instability. It is not well understood how different radiation sources induce genetic instability in cells with different genetic background. Here we report our studies on genetic instability, particularly chromosome instability using fluorescence in situ hybridization (FISH), in human primary lymphocytes, normal human fibroblasts, and transformed human mammary epithelial cells in a temporal manner after exposure to high energy protons and Fe ions. The chromosome spread was prepared 48 hours, 1 week, 2 week, and 1 month after radiation exposure. Chromosome aberrations were analyzed with whole chromosome specific probes (chr. 3 and chr. 6). After exposure to protons and Fe ions of similar cumulative energy (??), Fe ions induced more chromosomal aberrations at early time point (48 hours) in all three types of cells. Over time (after 1 month), more chromosome aberrations were observed in cells exposed to Fe ions than in the same type of cells exposed to protons. While the mammary epithelial cells have higher intrinsic genetic instability and higher rate of initial chromosome aberrations than the fibroblasts, the fibroblasts retained more chromosomal aberration after long term cell culture (1 month) in comparison to their initial frequency of chromosome aberration. In lymphocytes, the chromosome aberration frequency at 1 month after exposure to Fe ions was close to unexposed background, and the chromosome aberration frequency at 1 month after exposure to proton was much higher. In addition to human cells, mouse bone marrow cells isolated from strains CBA/CaH and C57BL/6 were irradiated with proton or Fe ions and were analyzed for chromosome aberration at different time points. Cells from CBA mice showed similar frequency of chromosome aberration at early and late time points, while cells from C57 mice showed very different chromosome aberration rate at early and late time points. Our results suggest that relative

  4. Genetic Variability in Susceptibility to Occupational Respiratory Sensitization

    Directory of Open Access Journals (Sweden)

    Berran Yucesoy

    2011-01-01

    Full Text Available Respiratory sensitization can be caused by a variety of substances at workplaces, and the health and economic burden linked to allergic respiratory diseases continues to increase. Although the main factors that affect the onset of the symptoms are the types and intensity of allergen exposure, there is a wide range of interindividual variation in susceptibility to occupational/environmental sensitizers. A number of gene variants have been reported to be associated with various occupational allergic respiratory diseases. Examples of genes include, but are not limited to, genes involved in immune/inflammatory regulation, antioxidant defenses, and fibrotic processes. Most of these variants act in combination with other genes and environmental factors to modify disease progression, severity, or resolution after exposure to allergens. Therefore, understanding the role of genetic variability and the interaction between genetic and environmental/occupational factors provides new insights into disease etiology and may lead to the development of novel preventive and therapeutic strategies. This paper will focus on the current state of knowledge regarding genetic influences on allergic respiratory diseases, with specific emphasis on diisocyanate-induced asthma and chronic beryllium disease.

  5. Developing culturally sensitive cancer genetics communication aids for African Americans.

    Science.gov (United States)

    Baty, Bonnie Jeanne; Kinney, Anita Yeomans; Ellis, Sara Marie

    2003-04-15

    The goal of this project was to develop educational materials to communicate genetic health information in a culturally sensitive manner. These materials were designed to communicate information about cancer risk, genetic testing options, and health management options in an African American kindred with a known BRCA1 mutation. Educational materials were pilot-tested in four African American focus groups varying in socioeconomic status and gender. The audiotaped focus groups consisted of presentation of the educational materials, followed by a feedback session led by an African American facilitator. Qualitative analysis of the focus group transcripts identified important themes and the educational materials were revised in response to the participants' suggestions. The products included a booklet and a flip chart for use in educational sessions. Focus group participants recommended a substantial reduction in technical detail, and recommended that information be personalized and made relevant to the lives of the target population. Other critical themes included the importance of building trust in the medical system and avoiding words and images that have strong negative associations in the African American community. Strategies that were successful included nontechnical images to explain genetic concepts, clip art images to energize and personalize word slides, vibrant color, identifiably African American figures, and the development of themes relevant to many African Americans. The use of these materials in an ongoing study offering BRCA1 counseling and testing to a large, rural Louisiana-based kindred will provide additional feedback about the effectiveness of the culturally tailored genetic education and counseling materials.

  6. Mutualism effectiveness and vertical transmission of symbiotic fungal endophytes in response to host genetic background.

    Science.gov (United States)

    Gundel, Pedro E; Martínez-Ghersa, María A; Omacini, Marina; Cuyeu, Romina; Pagano, Elba; Ríos, Raúl; Ghersa, Claudio M

    2012-12-01

    Certain species of the Pooideae subfamily develop stress tolerance and herbivory resistance through symbiosis with vertically transmitted, asexual fungi. This symbiosis is specific, and genetic factors modulate the compatibility between partners. Although gene flow is clearly a fitness trait in allogamous grasses, because it injects hybrid vigor and raw material for evolution, it could reduce compatibility and thus mutualism effectiveness. To explore the importance of host genetic background in modulating the performance of symbiosis, Lolium multiflorum plants, infected and noninfected with Neotyphodium occultans, were crossed with genetically distant plants of isolines (susceptible and resistant to diclofop-methyl herbicide) bred from two cultivars and exposed to stress. The endophyte improved seedling survival in genotypes susceptible to herbicide, while it had a negative effect on one of the genetically resistant crosses. Mutualism provided resistance to herbivory independently of the host genotype, but this effect vanished under stress. While no endophyte effect was observed on host reproductive success, it was increased by interpopulation plant crosses. Neither gene flow nor herbicide had an important impact on endophyte transmission. Host fitness improvements attributable to gene flow do not appear to result in direct conflict with mutualism while this seems to be an important mechanism for the ecological and contemporary evolution of the symbiotum.

  7. Extending the Spectrum of Radiological Findings in Patients With Severe Osteopetrosis and Different Genetic Backgrounds.

    Science.gov (United States)

    Simanovsky, Natalia; Rozovsky, Katya; Hiller, Nurith; Weintraub, Michael; Stepensky, Polina

    2016-07-01

    To evaluate radiological findings in a cohort of 22 patients with infantile malignant osteopetrosis in order to establish the correlation between radiological findings and different genetic backgrounds. Clinical files, genetic analysis results, and radiological examinations of children treated for osteopetrosis with bone marrow transplantation in a referral center in the last 5 years were retrospectively evaluated. The study received institutional review board (IRB) approval. Twenty-two patients were included in the study: 18 males, four females, ages 1 month-9 years 10 months, and the median age was 11 months (mean 23 months). There were 12 patients with different mutations in the TCIRG1 gene, five with mutations in the SNX10 gene, four children harbored RANK mutations, and one patient had a CLCN7 mutation. We noted more severe radiological findings in patients with TCIRG1 and RANK mutations, including fractures, osteopetrorickets, hydrocephalus, and hepatomegaly. Varus deformity of the femoral neck was seen exclusively in patients with a TCIRG1 mutation. The variable genetic spectrum of osteopetrosis is associated with a variable radiological presentation. These correlations may be helpful for priorities in genetic analysis. © 2016 Wiley Periodicals, Inc.

  8. Lung defenses against Pseudomonas aeruginosa in C5-deficient mice with different genetic backgrounds.

    Science.gov (United States)

    Cerquetti, M C; Sordelli, D O; Bellanti, J A; Hooke, A M

    1986-01-01

    Lung defenses against Pseudomonas aeruginosa were investigated in C5-deficient strains of mice with different genetic backgrounds. We studied pulmonary clearance and cell responses after aerosol exposure to P. aeruginosa in C5-deficient B10.D2/oSnJ and DBA/2J mice and their closest C5-sufficient counterparts, B10.D2/nSnJ and DBA/1J mice. Different patterns of lung clearance and pulmonary cell responses were found for the two C5-deficient strains. C5-deficient B10.D2/oSnJ mice showed defective lung clearance of P. aeruginosa 4 h after challenge compared with C5-sufficient B10.D2/nSnJ animals. This finding was associated with a decreased number of polymorphonuclear leukocytes recruited into the airways during the same time. Interestingly, C5-deficient DBA/2J mice recruited higher numbers of polymorphonuclear leukocytes than did C5-sufficient DBA/1J mice by 4 h after aerosolization. Nevertheless, lung clearance of P. aeruginosa in DBA/2J mice was not as effective as in C5-sufficient DBA/1J mice, suggesting that other functions of C5 besides chemotaxism could be involved. Lung clearance of P. aeruginosa was also investigated in C5-deficient and -sufficient hybrids sharing the same genetic background (DBA/2J X B10.D2). The results suggested that murine lung clearance of P. aeruginosa is markedly affected by lack of C5 in a specific genetic background (B10.D2). PMID:3086235

  9. Persistence of transmitted HIV-1 drug resistance mutations associated with fitness costs and viral genetic backgrounds.

    Directory of Open Access Journals (Sweden)

    Wan-Lin Yang

    2015-03-01

    Full Text Available Transmission of drug-resistant pathogens presents an almost-universal challenge for fighting infectious diseases. Transmitted drug resistance mutations (TDRM can persist in the absence of drugs for considerable time. It is generally believed that differential TDRM-persistence is caused, at least partially, by variations in TDRM-fitness-costs. However, in vivo epidemiological evidence for the impact of fitness costs on TDRM-persistence is rare. Here, we studied the persistence of TDRM in HIV-1 using longitudinally-sampled nucleotide sequences from the Swiss-HIV-Cohort-Study (SHCS. All treatment-naïve individuals with TDRM at baseline were included. Persistence of TDRM was quantified via reversion rates (RR determined with interval-censored survival models. Fitness costs of TDRM were estimated in the genetic background in which they occurred using a previously published and validated machine-learning algorithm (based on in vitro replicative capacities and were included in the survival models as explanatory variables. In 857 sequential samples from 168 treatment-naïve patients, 17 TDRM were analyzed. RR varied substantially and ranged from 174.0/100-person-years;CI=[51.4, 588.8] (for 184V to 2.7/100-person-years;[0.7, 10.9] (for 215D. RR increased significantly with fitness cost (increase by 1.6[1.3,2.0] per standard deviation of fitness costs. When subdividing fitness costs into the average fitness cost of a given mutation and the deviation from the average fitness cost of a mutation in a given genetic background, we found that both components were significantly associated with reversion-rates. Our results show that the substantial variations of TDRM persistence in the absence of drugs are associated with fitness-cost differences both among mutations and among different genetic backgrounds for the same mutation.

  10. The Flowering Repressor SVP Underlies a Novel Arabidopsis thaliana QTL Interacting with the Genetic Background

    Science.gov (United States)

    Méndez-Vigo, Belén; Martínez-Zapater, José M.; Alonso-Blanco, Carlos

    2013-01-01

    The timing of flowering initiation is a fundamental trait for the adaptation of annual plants to different environments. Large amounts of intraspecific quantitative variation have been described for it among natural accessions of many species, but the molecular and evolutionary mechanisms underlying this genetic variation are mainly being determined in the model plant Arabidopsis thaliana. To find novel A. thaliana flowering QTL, we developed introgression lines from the Japanese accession Fuk, which was selected based on the substantial transgression observed in an F2 population with the reference strain Ler. Analysis of an early flowering line carrying a single Fuk introgression identified Flowering Arabidopsis QTL1 (FAQ1). We fine-mapped FAQ1 in an 11 kb genomic region containing the MADS transcription factor gene SHORT VEGETATIVE PHASE (SVP). Complementation of the early flowering phenotype of FAQ1-Fuk with a SVP-Ler transgen demonstrated that FAQ1 is SVP. We further proved by directed mutagenesis and transgenesis that a single amino acid substitution in SVP causes the loss-of-function and early flowering of Fuk allele. Analysis of a worldwide collection of accessions detected FAQ1/SVP-Fuk allele only in Asia, with the highest frequency appearing in Japan, where we could also detect a potential ancestral genotype of FAQ1/SVP-Fuk. In addition, we evaluated allelic and epistatic interactions of SVP natural alleles by analysing more than one hundred transgenic lines carrying Ler or Fuk SVP alleles in five genetic backgrounds. Quantitative analyses of these lines showed that FAQ1/SVP effects vary from large to small depending on the genetic background. These results support that the flowering repressor SVP has been recently selected in A. thaliana as a target for early flowering, and evidence the relevance of genetic interactions for the intraspecific evolution of FAQ1/SVP and flowering time. PMID:23382706

  11. Ethnic background and genetic variation in the evaluation of cancer risk: a systematic review.

    Directory of Open Access Journals (Sweden)

    Lijun Jing

    Full Text Available The clinical use of genetic variation in the evaluation of cancer risk is expanding, and thus understanding how determinants of cancer susceptibility identified in one population can be applied to another is of growing importance. However there is considerable debate on the relevance of ethnic background in clinical genetics, reflecting both the significance and complexity of genetic heritage. We address this via a systematic review of reported associations with cancer risk for 82 markers in 68 studies across six different cancer types, comparing association results between ethnic groups and examining linkage disequilibrium between risk alleles and nearby genetic loci. We find that the relevance of ethnic background depends on the question. If asked whether the association of variants with disease risk is conserved across ethnic boundaries, we find that the answer is yes, the majority of markers show insignificant variability in association with cancer risk across ethnic groups. However if the question is whether a significant association between a variant and cancer risk is likely to reproduce, the answer is no, most markers do not validate in an ethnic group other than the discovery cohort's ancestry. This lack of reproducibility is not attributable to studies being inadequately populated due to low allele frequency in other ethnic groups. Instead, differences in local genomic structure between ethnic groups are associated with the strength of association with cancer risk and therefore confound interpretation of the implied physiologic association tracked by the disease allele. This suggest that a biological association for cancer risk alleles may be broadly consistent across ethnic boundaries, but reproduction of a clinical study in another ethnic group is uncommon, in part due to confounding genomic architecture. As clinical studies are increasingly performed globally this has important implications for how cancer risk stratifiers should be

  12. The flowering repressor SVP underlies a novel Arabidopsis thaliana QTL interacting with the genetic background.

    Directory of Open Access Journals (Sweden)

    Belén Méndez-Vigo

    Full Text Available The timing of flowering initiation is a fundamental trait for the adaptation of annual plants to different environments. Large amounts of intraspecific quantitative variation have been described for it among natural accessions of many species, but the molecular and evolutionary mechanisms underlying this genetic variation are mainly being determined in the model plant Arabidopsis thaliana. To find novel A. thaliana flowering QTL, we developed introgression lines from the Japanese accession Fuk, which was selected based on the substantial transgression observed in an F(2 population with the reference strain Ler. Analysis of an early flowering line carrying a single Fuk introgression identified Flowering Arabidopsis QTL1 (FAQ1. We fine-mapped FAQ1 in an 11 kb genomic region containing the MADS transcription factor gene SHORT VEGETATIVE PHASE (SVP. Complementation of the early flowering phenotype of FAQ1-Fuk with a SVP-Ler transgen demonstrated that FAQ1 is SVP. We further proved by directed mutagenesis and transgenesis that a single amino acid substitution in SVP causes the loss-of-function and early flowering of Fuk allele. Analysis of a worldwide collection of accessions detected FAQ1/SVP-Fuk allele only in Asia, with the highest frequency appearing in Japan, where we could also detect a potential ancestral genotype of FAQ1/SVP-Fuk. In addition, we evaluated allelic and epistatic interactions of SVP natural alleles by analysing more than one hundred transgenic lines carrying Ler or Fuk SVP alleles in five genetic backgrounds. Quantitative analyses of these lines showed that FAQ1/SVP effects vary from large to small depending on the genetic background. These results support that the flowering repressor SVP has been recently selected in A. thaliana as a target for early flowering, and evidence the relevance of genetic interactions for the intraspecific evolution of FAQ1/SVP and flowering time.

  13. Genetic background of nonmutant Piebald-Virol-Glaxo rats does not influence nephronophthisis phenotypes

    Directory of Open Access Journals (Sweden)

    Yengkopiong JP

    2013-02-01

    Full Text Available Jada Pasquale Yengkopiong, Joseph Daniel Wani LakoJohn Garang Memorial University of Science and Technology, Faculty of Science and Technology, Bor, Jonglei State, Republic of South SudanBackground: Nephronophthisis (NPHP, which affects multiple organs, is a hereditary cystic kidney disease (CKD, characterized by interstitial fibrosis and numerous fluid-filled cysts in the kidneys. It is caused by mutations in NPHP genes, which encode for ciliary proteins known as nephrocystins. The disorder affects many people across the world and leads to end-stage renal disease. The aim of this study was to determine if the genetic background of the nonmutant female Piebald-Virol-Glaxo (PVG/Seac-/- rat influences phenotypic inheritance of NPHP from mutant male Lewis polycystic kidney rats.Methods: Mating experiments were performed between mutant Lewis polycystic kidney male rats with CKD and nonmutant PVG and Wistar Kyoto female rats without cystic kidney disease to raise second filial and backcross 1 progeny, respectively. Rats that developed cystic kidneys were identified. Systolic blood pressure was determined in each rat at 12 weeks of age using the tail and cuff method. After euthanasia, blood samples were collected and chemistry was determined. Histological examination of the kidneys, pancreas, and liver of rats with and without cystic kidney disease was performed.Results: It was established that the genetic background of nonmutant female PVG rats did not influence the phenotypic inheritance of the CKD from mutant male Lewis polycystic kidney rats. The disease arose as a result of a recessive mutation in a single gene (second filial generation, CKD = 13, non-CKD = 39, Χ2 = 0.00, P ≥ 0.97; backcross 1 generation, CKD = 67, non-CKD = 72, Χ2 = 0.18, P > 0.05 and inherited as NPHP. The rats with CKD developed larger fluid-filled cystic kidneys, higher systolic blood pressure, and anemia, but there were no extrarenal cysts and disease did not lead to

  14. High Prevalence of Smoking in the Roma Population Seems to Have No Genetic Background.

    Science.gov (United States)

    Fiatal, Szilvia; Tóth, Réka; Moravcsik-Kornyicki, Ágota; Kósa, Zsigmond; Sándor, János; McKee, Martin; Ádány, Róza

    2016-12-01

    The prevalence of smoking in Romani of both genders is significantly higher than in the general population. Our aim was to determine whether a genetic susceptibility contributes to the high prevalence of smoking among Roma in a study based on data collected from cross-sectional surveys. Twenty single nucleotide polymorphisms known to be closely related to smoking behavior were investigated in DNA samples of Hungarian Roma (N = 1273) and general (N = 2388) populations. Differences in genotype and allele distribution were investigated. Genetic risk scores (GRSs) were generated to estimate the joint effect of single nucleotide polymorphisms in genes COMT, CHRNA3/4/5, CYP2A6, CTNNA3, DRD2, MAOA, KCNJ6, AGPHD1, ANKK1, TRPC7, GABRA4, and NRXN1. The distribution of scores in study populations was compared. Age, gender, and body mass index were considered as confounding factors. Difference in allele frequencies between the study populations remained significant for 16 polymorphisms after multiple test correction (p smoking behavior of the Roma population could not be accounted for by genetic susceptibility; therefore, interventions aimed at smoking prevention and cessation should focus on cultural and environmental factors. This is the first study designed to determine whether genetic background exists behind the harmful behavior of the smoking of the Roma population. Although the frequencies of susceptible and protective alleles strongly differ between the Hungarian Roma and general populations, it is shown that calculated GRSs being significantly higher in the general population, which do not support the hypothesis on the genetic susceptibility of the Roma population. Interventions aimed at smoking cessation in the Roma population should preferentially target cultural and environmental factors. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e

  15. Scalable background-limited polarization-sensitive detectors for mm-wave applications

    CERN Document Server

    Rostem, Karwan; Appel, John W; Bennett, Charles L; Chuss, David T; Colazo, Felipe A; Crowe, Erik; Denis, Kevin L; Essinger-Hileman, Tom; Marriage, Tobias A; Moseley, Samuel H; Stevenson, Thomas R; Towner, Deborah W; U-Yen, Kongpop; Wollack, Edward J

    2014-01-01

    We report on the status and development of polarization-sensitive detectors for millimeter-wave applications. The detectors are fabricated on single-crystal silicon, which functions as a low-loss dielectric substrate for the microwave circuitry as well as the supporting membrane for the Transition-Edge Sensor (TES) bolometers. The orthomode transducer (OMT) is realized as a symmetric structure and on-chip filters are employed to define the detection bandwidth. A hybridized integrated enclosure reduces the high-frequency THz mode set that can couple to the TES bolometers. An implementation of the detector architecture at Q-band achieves 90% efficiency in each polarization. The design is scalable in both frequency coverage, 30-300 GHz, and in number of detectors with uniform characteristics. Hence, the detectors are desirable for ground-based or space-borne instruments that require large arrays of efficient background-limited cryogenic detectors.

  16. Confidence Limits with Multiple Channels and Arbitrary Probability Distributions for Sensitivity and Expected Background

    Science.gov (United States)

    Perrotta, Andrea

    A MC method is proposed to compute upper limits, in a pure Bayesian approach, when the errors associated to the experimental sensitivity and to the expected background content are not Gaussian distributed or not small enough to apply the usual approximations. It is relatively easy to extend the procedure to the multichannel case (for instance when different decay branchings, or luminosities or experiments have to be combined). Some of the searches for supersymmetric particles performed in the DELPHI experiment at the LEP electron-positron collider use such a procedure to propagate the systematics into the calculation of the cross-section upper limits. One of these searches will be described as an example.

  17. Scalable Background-Limited Polarization-Sensitive Detectors for mm-wave Applications

    Science.gov (United States)

    Rostem, Karwan; Ali, Aamir; Appel, John W.; Bennett, Charles L.; Chuss, David T.; Colazo, Felipe A.; Crowe, Erik; Denis, Kevin L.; Essinger-Hileman, Tom; Marriage, Tobias A.; Moseley, Samuel H.; Stevenson, Thomas R.; Towner, Deborah W.; U-Yen, Kongpop; Wollack, Edward J.

    2014-01-01

    We report on the status and development of polarization-sensitive detectors for millimeter-wave applications. The detectors are fabricated on single-crystal silicon, which functions as a low-loss dielectric substrate for the microwave circuitry as well as the supporting membrane for the Transition-Edge Sensor (TES) bolometers. The orthomode transducer (OMT) is realized as a symmetric structure and on-chip filters are employed to define the detection bandwidth. A hybridized integrated enclosure reduces the high-frequency THz mode set that can couple to the TES bolometers. An implementation of the detector architecture at Q-band achieves 90% efficiency in each polarization. The design is scalable in both frequency coverage, 30-300 GHz, and in number of detectors with uniform characteristics. Hence, the detectors are desirable for ground-based or space-borne instruments that require large arrays of efficient background-limited cryogenic detectors.

  18. The particle background of the Rosat PSPC. [Position Sensitive Proportional Counter

    Science.gov (United States)

    Snowden, S. L.; Plucinsky, P. P.; Briel, U.; Hasinger, G.; Pfeffermann, E.

    1992-01-01

    In order to permit quantitative studies of the diffuse cosmic X-ray background and of extended X-ray sources, the particle induced background of the Roentgen Satellite, Rosat, Position Sensitive Proportional Counter (PSPC) is parameterized. Data collected during 210,000 s of PSPC operation have been analyzed and the temporal, spectral, and spatial distributions investigated. About 77 percent of the residual events originate within the detector while the remainder enter through the counter window. During typical conditions, the count rate of the residual events is well correlated with the Master Veto (MV) count rate. The spectrum of these events is well described by a flat component plus a soft power law and an Al K-alpha line at 1.5 keV. Also during typical conditions, the ratio between the power law and flat components remains constant to +/- 4 while the relative Al K-alpha contribution increases with increasing MV count rate. The distribution of the counts over the field of view is uniform except for a slight radial dependence and shadowing caused by blockage of the externally produced component by the window support structure.

  19. Reduction of Radioactive Backgrounds in Electroformed Copper for Ultra-Sensitive Radiation Detectors

    Energy Technology Data Exchange (ETDEWEB)

    Hoppe, Eric W. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Aalseth, Craig E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Farmer, Orville T. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hossbach, Todd W. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Liezers, Martin [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Miley, Harry S. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Overman, Nicole R. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Reeves, James H. [Reeves and Son LLC., Richland, WA (United States)

    2014-07-07

    Abstract Ultra-pure construction materials are required for the next generation of neutrino physics, dark matter and environmental science applications. These new efforts require materials with purity levels at or below 1 uBq/kg 232Th and 238U. Yet radiometric analysis lacks sensitivity below ~10 uBq/kg for the U and Th decay chains. This limits both the selection of clean materials and the validation of purification processes. Copper is an important high-purity material for low-background experiments due to the ease with which it can be purified by electrochemical methods. Electroplating for purification into near-final shapes, known as electroforming, is one such method. Continued refinement of the copper electroforming process is underway, for the first time guided by an ICP-MS based assay method that can measure 232Th and 238U near the desired purity levels. An assay of electroformed copper at 10 uBq/kg for 232Th has been achieved and is described. The implications of electroformed copper at or better than this purity on next-generation low-background experiments are discussed.

  20. Reduction of radioactive backgrounds in electroformed copper for ultra-sensitive radiation detectors

    Energy Technology Data Exchange (ETDEWEB)

    Hoppe, E.W., E-mail: eric.hoppe@pnnl.gov [Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Aalseth, C.E.; Farmer, O.T.; Hossbach, T.W.; Liezers, M.; Miley, H.S.; Overman, N.R. [Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Reeves, J.H. [Reeves and Son LLC, 10 Albert Ave., Richland, WA 99352 (United States)

    2014-11-11

    Ultra-pure construction materials are required for the next generation of neutrino physics, dark matter and environmental science applications. These materials are also important for use in high-purity germanium spectrometers used in screening materials for radiopurity. The next-generation science applications require materials with radiopurity levels at or below 1 μBq/kg {sup 232}Th and {sup 238}U. Yet radiometric analysis lacks sensitivity below ∼10 μBq/kg for the U and Th decay chains. This limits both the selection of clean materials and the validation of purification processes. Copper is an important high-purity material for low-background experiments due to the ease with which it can be purified by electrochemical methods. Electroplating for purification into near-final shapes, known as electroforming, is one such method. Continued refinement of the copper electroforming process is underway, for the first time guided by an ICP-MS based assay method that can measure {sup 232}Th and {sup 238}U near the desired purity levels. An assay of electroformed copper at a μBq/kg level has been achieved and is described. The implications of electroformed copper at or better than this purity on next-generation low-background experiments are discussed.

  1. Radiation-sensitive genetically susceptible pediatric sub-populations

    Energy Technology Data Exchange (ETDEWEB)

    Kleinerman, Ruth A. [National Cancer Institute, NIH, DHHS, Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, Rockville, MD (United States)

    2009-02-15

    Major advances in pediatric cancer treatment have resulted in substantial improvements in survival. However, concern has emerged about the late effects of cancer therapy, especially radiation-related second cancers. Studies of childhood cancer patients with inherited cancer syndromes can provide insights into the interaction between radiation and genetic susceptibility to multiple cancers. Children with retinoblastoma (Rb), neurofibromatosis type 1 (NF1), Li-Fraumeni syndrome (LFS), and nevoid basal cell carcinoma syndrome (NBCCS) are at substantial risk of developing radiation-related second and third cancers. A radiation dose-response for bone and soft-tissue sarcomas has been observed in hereditary Rb patients, with many of these cancers occurring in the radiation field. Studies of NF1 patients irradiated for optic pathway gliomas have reported increased risks of developing another cancer associated with radiotherapy. High relative risks for second and third cancers were observed for a cohort of 200 LFS family members, especially children, possibly related to radiotherapy. Children with NBCCS are very sensitive to radiation and develop multiple basal cell cancers in irradiated areas. Clinicians following these patients should be aware of their increased genetic susceptibility to multiple primary malignancies enhanced by sensitivity to ionizing radiation. (orig.)

  2. A Strong Impact of Genetic Background on Gut Microflora in Mice

    Directory of Open Access Journals (Sweden)

    R. Steven Esworthy

    2010-01-01

    Full Text Available Genetic background affects susceptibility to ileocolitis in mice deficient in two intracellular glutathione peroxidases, GPx1 and GPx2. The C57BL/6 (B6 GPx1/2 double-knockout (DKO mice have mild ileocolitis, and 129S1/Sv (129 DKO mice have severe inflammation. We used diet to modulate ileocolitis; a casein-based defined diet with AIN76A micronutrients (AIN attenuates inflammation compared to conventional LabDiets. Because luminal microbiota induce DKO ileocolitis, we assessed bacterial composition with automated ribosomal intergenic-spacer analysis (ARISA on cecal DNA. We found that mouse strain had the strongest impact on the composition of microbiota than diet and GPx genotypes. In comparing AIN and LabDiet, DKO mice were more resistant to change than the non-DKO or WT mice. However, supplementing yeast and inulin to AIN diet greatly altered microflora profiles in the DKO mice. From 129 DKO strictly, we found overgrowth of Escherichia coli. We conclude that genetic background predisposes mice to colonization of potentially pathogenic E. coli.

  3. Genetics of childhood steroid-sensitive nephrotic syndrome.

    Science.gov (United States)

    Karp, Alana M; Gbadegesin, Rasheed A

    2016-07-29

    The pathogenesis of childhood-onset nephrotic syndrome (NS), disparity in incidence of NS among races, and variable responses to therapies in children with NS have defied explanation to date. In the last 20 years over 50 genetic causes of steroid-resistant nephrotic syndrome (SRNS) have been identified, and at least two disease loci for two pathologic variants of SRNS (focal segmental glomerulosclerosis and membranous nephropathy) have been defined. However, the genetic causes and risk loci for steroid-sensitive nephrotic syndrome (SSNS) remain elusive, partly because SSNS is relatively rare and also because cases of SSNS vary widely in phenotypic expression over time. A recent study of a well-defined modest cohort of children with SSNS identified variants in HLA-DQA1 as a risk factor for SSNS. Here we review what is currently known about the genetics of SSNS and also discuss how recent careful phenotypic and genomic studies reinforce the role of adaptive immunity in the molecular mechanisms of SSNS.

  4. Individual Differences in Scotopic Visual Acuity and Contrast Sensitivity: Genetic and Non-Genetic Influences.

    Directory of Open Access Journals (Sweden)

    Alex J Bartholomew

    Full Text Available Despite the large amount of variation found in the night (scotopic vision capabilities of healthy volunteers, little effort has been made to characterize this variation and factors, genetic and non-genetic, that influence it. In the largest population of healthy observers measured for scotopic visual acuity (VA and contrast sensitivity (CS to date, we quantified the effect of a range of variables on visual performance. We found that young volunteers with excellent photopic vision exhibit great variation in their scotopic VA and CS, and this variation is reliable from one testing session to the next. We additionally identified that factors such as Circadian preference, iris color, astigmatism, depression, sex and education have no significant impact on scotopic visual function. We confirmed previous work showing that the amount of time spent on the vision test influences performance and that laser eye surgery results in worse scotopic vision. We also showed a significant effect of intelligence and photopic visual performance on scotopic VA and CS, but all of these variables collectively explain <30% of the variation in scotopic vision. The wide variation seen in young healthy volunteers with excellent photopic vision, the high test-retest agreement, and the vast majority of the variation in scotopic vision remaining unexplained by obvious non-genetic factors suggests a strong genetic component. Our preliminary genome-wide association study (GWAS of 106 participants ruled out any common genetic variants of very large effect and paves the way for future, larger genetic studies of scotopic vision.

  5. Background due to stored electrons following nuclear decays in the KATRIN spectrometers and its impact on the neutrino mass sensitivity

    CERN Document Server

    Mertens, S; Fraenkle, F M; Furse, D; Glueck, F; Goerhardt, S; Hoetzel, M; Kaefer, W; Leiber, B; Thuemmler, T; Wandkowsky, N; Wolf, J

    2012-01-01

    The KATRIN experiment is designed to measure the absolute neutrino mass scale with a sensitivity of 200 meV at 90% C.L. by high resolution tritium beta-spectroscopy. A low background level of 10 mHz at the beta-decay endpoint is required in order to achieve the design sensitivity. In this paper we discuss a novel background source arising from magnetically trapped keV electrons in electrostatic retarding spectrometers. The main sources of these electrons are alpha-decays of the radon isotopes (219,220)Rn as well as beta-decays of tritium in the volume of the spectrometers. We characterize the expected background signal by extensive MC simulations and investigate the impact on the KATRIN neutrino mass sensitivity. From these results we refine design parameters for the spectrometer vacuum system and propose active background reduction methods to meet the stringent design limits for the overall background rate.

  6. The Behavioral Consequence of Phenylketonuria in Mice Depends on the Genetic Background

    Science.gov (United States)

    Bruinenberg, Vibeke M.; van der Goot, Els; van Vliet, Danique; de Groot, Martijn J.; Mazzola, Priscila N.; Heiner-Fokkema, M. Rebecca; van Faassen, Martijn; van Spronsen, Francjan J.; van der Zee, Eddy A.

    2016-01-01

    To unravel the role of gene mutations in the healthy and the diseased state, countless studies have tried to link genotype with phenotype. However, over the years, it became clear that the strain of mice can influence these results. Nevertheless, identical gene mutations in different strains are often still considered equals. An example of this, is the research done in phenylketonuria (PKU), an inheritable metabolic disorder. In this field, a PKU mouse model (either on a BTBR or C57Bl/6 background) is often used to examine underlying mechanisms of the disease and/or new treatment strategies. Both strains have a point mutation in the gene coding for the enzyme phenylalanine hydroxylase which causes toxic concentrations of the amino acid phenylalanine in blood and brain, as found in PKU patients. Although the mutation is identical and therefore assumed to equally affect physiology and behavior in both strains, no studies directly compared the two genetic backgrounds to test this assumption. Therefore, this study compared the BTBR and C57Bl/6 wild-type and PKU mice on PKU-relevant amino acid- and neurotransmitter-levels and at a behavioral level. The behavioral paradigms were selected from previous literature on the PKU mouse model and address four domains, namely (1) activity levels, (2) motor performance, (3) anxiety and/or depression-like behavior, and (4) learning and memory. The results of this study showed comparable biochemical changes in phenylalanine and neurotransmitter concentrations. In contrast, clear differences in behavioral outcome between the strains in all four above-mentioned domains were found, most notably in the learning and memory domain. The outcome in this domain seem to be primarily due to factors inherent to the genetic background of the mouse and much less by differences in PKU-specific biochemical parameters in blood and brain. The difference in behavioral outcome between PKU of both strains emphasizes that the consequence of the PAH

  7. The Behavioral Consequence of Phenylketonuria in Mice Depends on the Genetic Background

    Directory of Open Access Journals (Sweden)

    Vibeke Marijn Bruinenberg

    2016-12-01

    Full Text Available To unravel the role of gene mutations in the healthy and the diseased state, countless studies have tried to link genotype with phenotype. However, over the years, it became clear that the strain of mice can influence these results. Nevertheless, identical gene mutations in different strains are often still considered equals. An example of this, is the research done in phenylketonuria (PKU, an inheritable metabolic disorder. In this field, a PKU mouse model (either on a BTBR or C57Bl/6 background is often used to examine underlying mechanisms of the disease and/or new treatment strategies. Both strains have a point mutation in the gene coding for the enzyme phenylalanine hydroxylase which causes toxic concentrations of the amino acid phenylalanine in blood and brain, as found in PKU patients. Although the mutation is identical and therefore assumed to equally affect physiology and behavior in both strains, no studies directly compared the two genetic backgrounds to test this assumption. Therefore, this study compared the BTBR and C57Bl/6 wild-type and PKU mice on PKU-relevant amino acid- and neurotransmitter levels and at a behavioral level. The behavioral paradigms were selected from previous literature on the PKU mouse model and address four domains, namely 1 activity levels, 2 motor performance, 3 anxiety and/or depression-like behavior, and 4 learning and memory. The results of this study showed comparable biochemical changes in phenylalanine and neurotransmitter concentrations. In contrast, clear differences in behavioral outcome between the strains in all four above-mentioned domains were found, most notably in the learning and memory domain. The outcome in this domain seem to be primarily due to factors inherent to the genetic background of the mouse and much less by differences in PKU-specific biochemical parameters in blood and brain. The difference in behavioral outcome between PKU of both strains emphasizes that the consequence of the

  8. Genetics, Synergists, and Age Affect Insecticide Sensitivity of the Honey Bee, Apis mellifera

    Science.gov (United States)

    Rinkevich, Frank D.; Margotta, Joseph W.; Pittman, Jean M.; Danka, Robert G.; Tarver, Matthew R.; Ottea, James A.; Healy, Kristen B.

    2015-01-01

    The number of honey bee colonies in the United States has declined to half of its peak level in the 1940s, and colonies lost over the winter have reached levels that are becoming economically unstable. While the causes of these losses are numerous and the interaction between them is very complex, the role of insecticides has garnered much attention. As a result, there is a need to better understand the risk of insecticides to bees, leading to more studies on both toxicity and exposure. While much research has been conducted on insecticides and bees, there have been very limited studies to elucidate the role that bee genotype and age has on the toxicity of these insecticides. The goal of this study was to determine if there are differences in insecticide sensitivity between honey bees of different genetic backgrounds (Carniolan, Italian, and Russian stocks) and assess if insecticide sensitivity varies with age. We found that Italian bees were the most sensitive of these stocks to insecticides, but variation was largely dependent on the class of insecticide tested. There were almost no differences in organophosphate bioassays between honey bee stocks (bees aged, the sensitivity to phenothrin significantly decreased, but the sensitivity to naled significantly increased. These results demonstrate the variation arising from the genetic background and physiological transitions in honey bees as they age. This information can be used to determine risk assessment, as well as establishing baseline data for future comparisons to explain the variation in toxicity differences for honey bees reported in the literature. PMID:26431171

  9. Early host gene expression responses to a Salmonella infection in the intestine of chickens with different genetic background

    NARCIS (Netherlands)

    Hemert, van S.; Hoekman, A.J.W.; Smith, M.A.; Rebel, J.M.J.

    2006-01-01

    So far the responses of chickens to Salmonella have not been studied in vivo on a whole genome-wide scale. Furthermore, the influence of the host genetic background on gene expression responses is unknown. In this study gene expression profiles in the chicken (Gallus gallus) intestine of two genetic

  10. Influence of background noise on the performance in the odor sensitivity task: effects of noise type and extraversion.

    Science.gov (United States)

    Seo, Han-Seok; Hähner, Antje; Gudziol, Volker; Scheibe, Mandy; Hummel, Thomas

    2012-10-01

    Recent research demonstrated that background noise relative to silence impaired subjects' performance in a cognitively driven odor discrimination test. The current study aimed to investigate whether the background noise can also modulate performance in an odor sensitivity task that is less cognitively loaded. Previous studies have shown that the effect of background noise on task performance can be different in relation to degree of extraversion and/or type of noise. Accordingly, we wanted to examine whether the influence of background noise on the odor sensitivity task can be altered as a function of the type of background noise (i.e., nonverbal vs. verbal noise) and the degree of extraversion (i.e., introvert vs. extrovert group). Subjects were asked to conduct an odor sensitivity task in the presence of either nonverbal noise (e.g., party sound) or verbal noise (e.g., audio book), or silence. Overall, the subjects' mean performance in the odor sensitivity task was not significantly different across three auditory conditions. However, with regard to the odor sensitivity task, a significant interaction emerged between the type of background noise and the degree of extraversion. Specifically, verbal noise relative to silence significantly impaired or improved the performance of the odor sensitivity task in the introvert or extrovert group, respectively; the differential effect of introversion/extraversion was not observed in the nonverbal noise-induced task performance. In conclusion, our findings provide new empirical evidence that type of background noise and degree of extraversion play an important role in modulating the effect of background noise on subjects' performance in an odor sensitivity task.

  11. Genetic basis for dosage sensitivity in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Isabelle M Henry

    2007-04-01

    Full Text Available Aneuploidy, the relative excess or deficiency of specific chromosome types, results in gene dosage imbalance. Plants can produce viable and fertile aneuploid individuals, while most animal aneuploids are inviable or developmentally abnormal. The swarms of aneuploid progeny produced by Arabidopsis triploids constitute an excellent model to investigate the mechanisms governing dosage sensitivity and aneuploid syndromes. Indeed, genotype alters the frequency of aneuploid types within these swarms. Recombinant inbred lines that were derived from a triploid hybrid segregated into diploid and tetraploid individuals. In these recombinant inbred lines, a single locus, which we call SENSITIVE TO DOSAGE IMBALANCE (SDI, exhibited segregation distortion in the tetraploid subpopulation only. Recent progress in quantitative genotyping now allows molecular karyotyping and genetic analysis of aneuploid populations. In this study, we investigated the causes of the ploidy-specific distortion at SDI. Allele frequency was distorted in the aneuploid swarms produced by the triploid hybrid. We developed a simple quantitative measure for aneuploidy lethality and using this measure demonstrated that distortion was greatest in the aneuploids facing the strongest viability selection. When triploids were crossed to euploids, the progeny, which lack severe aneuploids, exhibited no distortion at SDI. Genetic characterization of SDI in the aneuploid swarm identified a mechanism governing aneuploid survival, perhaps by buffering the effects of dosage imbalance. As such, SDI could increase the likelihood of retaining genomic rearrangements such as segmental duplications. Additionally, in species where triploids are fertile, aneuploid survival would facilitate gene flow between diploid and tetraploid populations via a triploid bridge and prevent polyploid speciation. Our results demonstrate that positional cloning of loci affecting traits in populations containing ploidy and

  12. Effect of mutation and genetic background on drug resistance in Mycobacterium tuberculosis.

    Science.gov (United States)

    Fenner, Lukas; Egger, Matthias; Bodmer, Thomas; Altpeter, Ekkehardt; Zwahlen, Marcel; Jaton, Katia; Pfyffer, Gaby E; Borrell, Sonia; Dubuis, Olivier; Bruderer, Thomas; Siegrist, Hans H; Furrer, Hansjakob; Calmy, Alexandra; Fehr, Jan; Stalder, Jesica Mazza; Ninet, Béatrice; Böttger, Erik C; Gagneux, Sebastien

    2012-06-01

    Bacterial factors may contribute to the global emergence and spread of drug-resistant tuberculosis (TB). Only a few studies have reported on the interactions between different bacterial factors. We studied drug-resistant Mycobacterium tuberculosis isolates from a nationwide study conducted from 2000 to 2008 in Switzerland. We determined quantitative drug resistance levels of first-line drugs by using Bactec MGIT-960 and drug resistance genotypes by sequencing the hot-spot regions of the relevant genes. We determined recent transmission by molecular methods and collected clinical data. Overall, we analyzed 158 isolates that were resistant to isoniazid, rifampin, or ethambutol, 48 (30.4%) of which were multidrug resistant. Among 154 isoniazid-resistant strains, katG mutations were associated with high-level and inhA promoter mutations with low-level drug resistance. Only katG(S315T) (65.6% of all isoniazid-resistant strains) and inhA promoter -15C/T (22.7%) were found in molecular clusters. M. tuberculosis lineage 2 (includes Beijing genotype) was associated with any drug resistance (adjusted odds ratio [OR], 3.0; 95% confidence interval [CI], 1.7 to 5.6; P mutations (OR, 6.4; 95% CI, 2.0 to 20.7; P = 0.002). We found that the genetic strain background influences the level of isoniazid resistance conveyed by particular mutations (interaction tests of drug resistance mutations across all lineages; P tuberculosis drug resistance mutations were associated with various levels of drug resistance and transmission, and M. tuberculosis lineages were associated with particular drug resistance-conferring mutations and phenotypic drug resistance. Our study also supports a role for epistatic interactions between different drug resistance mutations and strain genetic backgrounds in M. tuberculosis drug resistance.

  13. SAP modulates B cell functions in a genetic background-dependent manner.

    Science.gov (United States)

    Detre, Cynthia; Yigit, Burcu; Keszei, Marton; Castro, Wilson; Magelky, Erica M; Terhorst, Cox

    2013-06-01

    Mutations affecting the SLAM-associated protein (SAP) are responsible for the X-linked lympho-proliferative syndrome (XLP), a severe primary immunodeficiency syndrome with disease manifestations that include fatal mononucleosis, B cell lymphoma and dysgammaglobulinemia. It is well accepted that insufficient help by SAP-/- CD4+ T cells, in particular during the germinal center reaction, is a component of dysgammaglobulinemia in XLP patients and SAP-/- animals. It is however not well understood whether in XLP patients and SAP-/- mice B cell functions are affected, even though B cells themselves do not express SAP. Here we report that B cell intrinsic responses to haptenated protein antigens are impaired in SAP-/- mice and in Rag-/- mice into which B cells derived from SAP-/- mice together with wt CD4+ T cells had been transferred. This impaired B cells functions are in part depending on the genetic background of the SAP-/- mouse, which affects B cell homeostasis. Surprisingly, stimulation with an agonistic anti-CD40 causes strong in vivo and in vitro B cell responses in SAP-/- mice. Taken together, the data demonstrate that genetic factors play an important role in the SAP-related B cell functions. The finding that anti-CD40 can in part restore impaired B cell responses in SAP-/- mice, suggests potentially novel therapeutic interventions in subsets of XLP patients. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. A molecular pathway analysis informs the genetic background at risk for schizophrenia.

    Science.gov (United States)

    Crisafulli, Concetta; Drago, Antonio; Calabrò, Marco; Spina, Edoardo; Serretti, Alessandro

    2015-06-03

    Schizophrenia is a complex mental disorder marked by severely impaired thinking, delusional thoughts, hallucinations and poor emotional responsiveness. The biological mechanisms that lead to schizophrenia may be related to the genetic background of patients. Thus, a genetic perspective may help to unravel the molecular pathways disrupted in schizophrenia. In the present work, we used a molecular pathway analysis to identify the molecular pathways associated with schizophrenia. We collected data of genetic loci previously associated with schizophrenia, identified the genes located in those positions and created the metabolic pathways that are related to those genes' products. These pathways were tested for enrichment (a number of SNPs associated with the phenotype significantly higher than expected by chance) in a sample of schizophrenic patients and controls (4486 and 4477, respectively). The molecular pathway that resulted from the identification of all the genes located in the loci previously found to be associated with schizophrenia was found to be enriched, as expected (permutated p(10(6))=9.9999e-06).We found 60 SNPs amongst 30 different genes with a strong association with schizophrenia. The genes are related to the pathways related to neurodevelopment, apoptosis, vesicle traffic, immune response and MAPK cascade. The pathway related to the toll-like receptor family seemed to play a central role in the modulation/connection of various pathways whose disruption leads to schizophrenia. This pathway is related to the innate immune system, further stressing the role of immunological-related events in increasing the risk to schizophrenia. Copyright © 2014. Published by Elsevier Inc.

  15. Genetic background modifies nuclear mutant huntingtin accumulation and HD CAG repeat instability in Huntington's disease knock-in mice.

    Science.gov (United States)

    Lloret, Alejandro; Dragileva, Ella; Teed, Allison; Espinola, Janice; Fossale, Elisa; Gillis, Tammy; Lopez, Edith; Myers, Richard H; MacDonald, Marcy E; Wheeler, Vanessa C

    2006-06-15

    Genetically precise models of Huntington's disease (HD), Hdh CAG knock-in mice, are powerful systems in which phenotypes associated with expanded HD CAG repeats are studied. To dissect the genetic pathways that underlie such phenotypes, we have generated Hdh(Q111) knock-in mouse lines that are congenic for C57BL/6, FVB/N and 129Sv inbred genetic backgrounds and investigated four Hdh(Q111) phenotypes in these three genetic backgrounds: the intergenerational instability of the HD CAG repeat and the striatal-specific somatic HD CAG repeat expansion, nuclear mutant huntingtin accumulation and intranuclear inclusion formation. Our results reveal increased intergenerational and somatic instability of the HD CAG repeat in C57BL/6 and FVB/N backgrounds compared with the 129Sv background. The accumulation of nuclear mutant huntingtin and the formation of intranuclear inclusions were fastest in the C57BL/6 background, slowest in the 129Sv background and intermediate in the FVB/N background. Inbred strain-specific differences were independent of constitutive HD CAG repeat size and did not correlate with Hdh mRNA levels. These data provide evidence for genetic modifiers of both intergenerational HD CAG repeat instability and striatal-specific phenotypes. Different relative contributions of C57BL/6 and 129Sv genetic backgrounds to the onset of nuclear mutant huntingtin and somatic HD CAG repeat expansion predict that the initiation of each of these two phenotypes is modified by different genes. Our findings set the stage for defining disease-related genetic pathways that will ultimately provide insight into disease mechanism.

  16. Is there a genetic contribution to cultural differences? Collectivism, individualism and genetic markers of social sensitivity.

    Science.gov (United States)

    Way, Baldwin M; Lieberman, Matthew D

    2010-06-01

    Genes and culture are often thought of as opposite ends of the nature-nurture spectrum, but here we examine possible interactions. Genetic association studies suggest that variation within the genes of central neurotransmitter systems, particularly the serotonin (5-HTTLPR, MAOA-uVNTR) and opioid (OPRM1 A118G), are associated with individual differences in social sensitivity, which reflects the degree of emotional responsivity to social events and experiences. Here, we review recent work that has demonstrated a robust cross-national correlation between the relative frequency of variants in these genes and the relative degree of individualism-collectivism in each population, suggesting that collectivism may have developed and persisted in populations with a high proportion of putative social sensitivity alleles because it was more compatible with such groups. Consistent with this notion, there was a correlation between the relative proportion of these alleles and lifetime prevalence of major depression across nations. The relationship between allele frequency and depression was partially mediated by individualism-collectivism, suggesting that reduced levels of depression in populations with a high proportion of social sensitivity alleles is due to greater collectivism. These results indicate that genetic variation may interact with ecological and social factors to influence psychocultural differences.

  17. Antibiotic Resistance, Virulence, and Genetic Background of Community-Acquired Uropathogenic Escherichia coli from Algeria.

    Science.gov (United States)

    Yahiaoui, Merzouk; Robin, Frédéric; Bakour, Rabah; Hamidi, Moufida; Bonnet, Richard; Messai, Yamina

    2015-10-01

    The aim of the study was to investigate antibiotic resistance mechanisms, virulence traits, and genetic background of 150 nonrepetitive community-acquired uropathogenic Escherichia coli (CA-UPEC) from Algeria. A rate of 46.7% of isolates was multidrug resistant. bla genes detected were blaTEM (96.8% of amoxicillin-resistant isolates), blaCTX-M-15 (4%), overexpressed blaAmpC (4%), blaSHV-2a, blaTEM-4, blaTEM-31, and blaTEM-35 (0.7%). All tetracycline-resistant isolates (51.3%) had tetA and/or tetB genes. Sulfonamides and trimethoprim resistance genes were sul2 (60.8%), sul1 (45.9%), sul3 (6.7%), dfrA14 (25.4%), dfrA1 (18.2%), dfrA12 (16.3%), and dfrA25 (5.4%). High-level fluoroquinolone resistance (22.7%) was mediated by mutations in gyrA (S83L-D87N) and parC (S80I-E84G/V or S80I) genes. qnrB5, qnrS1, and aac(6')-Ib-cr were rare (5.3%). Class 1 and/or class 2 integrons were detected (40.7%). Isolates belonged to phylogroups B2+D (50%), A+B1 (36%), and F+C+Clade I (13%). Most of D (72.2%) and 38.6% of B2 isolates were multidrug resistant; they belong to 14 different sequence types, including international successful ST131, ST73, and ST69, reported for the first time in the community in Algeria and new ST4494 and ST4529 described in this study. Besides multidrug resistance, B2 and D isolates possessed virulence factors of colonization, invasion, and long-term persistence. The study highlighted multidrug-resistant CA-UPEC with high virulence traits and an epidemic genetic background.

  18. Eimeria Species and Genetic Background Influence the Serum Protein Profile of Broilers with Coccidiosis

    Science.gov (United States)

    Gilbert, Elizabeth R.; Cox, Chasity M.; Williams, Patricia M.; McElroy, Audrey P.; Dalloul, Rami A.; Ray, W. Keith; Barri, Adriana; Emmerson, Derek A.; Wong, Eric A.; Webb, Kenneth E.

    2011-01-01

    Background Coccidiosis is an intestinal disease caused by protozoal parasites of the genus Eimeria. Despite the advent of anti-coccidial drugs and vaccines, the disease continues to result in substantial annual economic losses to the poultry industry. There is still much unknown about the host response to infection and to date there are no reports of protein profiles in the blood of Eimeria-infected animals. The objective of this study was to evaluate the serum proteome of two genetic lines of broiler chickens after infection with one of three species of Eimeria. Methodology/Principal Findings Birds from lines A and B were either not infected or inoculated with sporulated oocysts from one of the three Eimeria strains at 15 d post-hatch. At 21 d (6 d post-infection), whole blood was collected and lesion scoring was performed. Serum was harvested and used for 2-dimensional gel electrophoresis. A total of 1,266 spots were quantitatively assessed by densitometry. Protein spots showing a significant effect of coccidia strain and/or broiler genetic line on density at P<0.05−0.01 (250 spots), P<0.01−0.001 (248 spots), and P<0.001 (314 spots) were excised and analyzed by matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry. Proteins were identified in 172 spots. A total of 46 different proteins were identified. Of the spots with a corresponding protein identification, 57 showed a main effect of coccidia infection and/or 2-way interaction of coccidia infection×broiler genetic line at P<0.001. Conclusions/Significance Several of the metabolic enzymes identified in this study are potential candidates for early diagnostic markers of E. acervulina infection including malate dehydrogenase 2, NADH dehydrogenase 1 alpha subcomplex 9, and an ATP synthase. These proteins were detected only in Line A birds that were inoculated with E. acervulina. Results from this study provide a basic framework for future research aimed at uncovering the complex

  19. Behavioral deficits in an Angelman syndrome model: effects of genetic background and age.

    Science.gov (United States)

    Huang, Hsien-Sung; Burns, Andrew J; Nonneman, Randal J; Baker, Lorinda K; Riddick, Natallia V; Nikolova, Viktoriya D; Riday, Thorfinn T; Yashiro, Koji; Philpot, Benjamin D; Moy, Sheryl S

    2013-04-15

    Angelman syndrome (AS) is a severe neurodevelopmental disorder associated with disruption of maternally inherited UBE3A (ubiquitin protein ligase E3A) expression. At the present time, there is no effective treatment for AS. Mouse lines with loss of maternal Ube3a (Ube3a(m-/p+)) recapitulate multiple aspects of the clinical AS profile, including impaired motor coordination, learning deficits, and seizures. Thus, these genetic mouse models could serve as behavioral screens for preclinical efficacy testing, a critical component of drug discovery for AS intervention. However, the severity and consistency of abnormal phenotypes reported in Ube3a(m-/p+) mice can vary, dependent upon age and background strain, which is problematic for the detection of beneficial drug effects. As part of an ongoing AS drug discovery initiative, we characterized Ube3a(m-/p+) mice on either a 129S7/SvEvBrd-Hprt(b-m2) (129) or C57BL/6J (B6) background across a range of functional domains and ages to identify reproducible and sufficiently large phenotypes suitable for screening therapeutic compounds. The results from the study showed that Ube3a(m-/p+) mice have significant deficits in acquisition and reversal learning in the Morris water maze. The findings also demonstrated that Ube3a(m-/p+) mice exhibit motor impairment in a rotarod task, hypoactivity, reduced rearing and marble-burying, and deficient fear conditioning. Overall, these profiles of abnormal phenotypes can provide behavioral targets for evaluating effects of novel therapeutic strategies relevant to AS. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Genetic determinants of sensitivity to beryllium in mice.

    Science.gov (United States)

    Tarantino-Hutchison, Lauren M; Sorrentino, Claudio; Nadas, Arthur; Zhu, Yiwen; Rubin, Edward M; Tinkle, Sally S; Weston, Ainsley; Gordon, Terry

    2009-06-01

    Chronic beryllium disease (CBD), an irreversible, debilitating granulomatous lung disease is caused by exposure to beryllium. This occupational hazard occurs in primary production and machining of Be-metal, BeO, beryllium - containing alloys, and other beryllium products. CBD begins as an MHC Class II-restricted, T(H)1 hypersensitivity, and the Human Leukocyte Antigen, HLA-DPB1E(69), is associated with risk of developing CBD. Because inbred strains of mice have not provided good models of CBD to date, three strains of HLA-DPB1 transgenic mice in an FVB/N background were developed; each contains a single allele of HLA-DPB1 that confers a different magnitude of risk for chronic beryllium disease: HLA-DPB1*0401 (OR approximately 0.2), HLA-DPB1*0201 (OR approximately 3), and HLA-DPB1*1701 (OR approximately 46). The mouse ear swelling test (MEST) was employed to determine if these different alleles would support a hypersensitivity response to beryllium. Mice were first sensitized on the back and subsequently challenged on the ear. In separate experiments, mice were placed into one of three groups (sensitization/challenge): C/C, C/Be, and Be/Be. In the HLA-DPB1*1701 mice, the strain with the highest risk transgene, the Be/Be group was the only group that displayed significant maximum increased ear thickness of 19.6% +/- 3.0% over the baseline measurement (p beryllium in seven inbred strains were investigated through use of the MEST, these included: FVB/N, AKR, Balb/c, C3H/HeJ, C57/BL6, DBA/2, and SJL/J. The FVB/N strain was least responsive, while the SJL/J and C57/BL6 strains were the highest responders. Our results suggest that the HLA-DPB1*1701 transgene product is an important risk factor for induction of the beryllium-sensitive phenotype. This model should be a useful tool for investigating beryllium sensitization.

  1. Genetic Modifiers Predisposing to Congenital Heart Disease in the Sensitized Down Syndrome Population

    Science.gov (United States)

    Li, Huiqing; Cherry, Sheila; Klinedinst, Donna; DeLeon, Valerie; Redig, Jennifer; Reshey, Benjamin; Chin, Michael T.; Sherman, Stephanie L.; Maslen, Cheryl L.; Reeves, Roger H.

    2012-01-01

    Background About half of people with Down syndrome (DS) exhibit some form of congenital heart disease (CHD). However, trisomy for human chromosome 21 (Hsa21) alone is insufficient to cause CHD as half of all people with DS have a normal heart, suggesting that genetic modifiers interact with dosage sensitive gene(s) on Hsa21 to result in CHD. We hypothesize that a threshold exists in both Down syndrome and euploid populations for the number of genetic perturbations that can be tolerated before CHD results. Methods and Results We ascertained a group of individuals with DS and complete atrioventricular septal defect (AVSD) and sequenced two candidate genes for CHD, CRELD1, which is associated with AVSD in people with or without DS, and HEY2, whose mouse ortholog produces septal defects when mutated. Several deleterious variants were identified but the frequency of these potential modifiers was low. We crossed mice with mutant forms of these potential modifiers to the Ts65Dn mouse model of Down syndrome. Crossing loss-of-function alleles of either Creld1 or Hey2 onto the trisomic background caused a significant increase in the frequency of CHD, demonstrating an interaction between the modifiers and trisomic genes. We showed further that although either of these mutant modifiers is benign by itself, they interact to affect heart development when inherited together. Conclusions Using mouse models of Down syndrome and of genes associated with congenital heart disease we demonstrate a biological basis for an interaction that supports a threshold hypothesis for additive effects of genetic modifiers in the sensitized trisomic population. PMID:22523272

  2. Fitness cost due to herbicide resistance may trigger genetic background evolution.

    Science.gov (United States)

    Darmency, Henri; Menchari, Yosra; Le Corre, Valérie; Délye, Christophe

    2015-01-01

    This article investigates the possible existence of mechanisms counterbalancing the negative pleiotropic effects on development and reproduction that are conferred by alleles responsible for herbicide resistance in the weed Alopecurus myosuroides. We considered three herbicide-resistant, mutant acetyl-coenzyme A carboxylase (ACCase) alleles, Leu1781, Asn2041, and Gly2078, found in eight resistant populations. Of these, Gly2078 is the only allele with a known fitness cost. We compared plants homozygous for wild-type ACCase alleles that were siblings of plants carrying a given mutant resistant ACCase allele with plants from three populations where resistance did not evolve. In each of two series of experiments, we measured germination dynamics, seedling vigor, plant height, vegetative biomass, and seed production. The wild-type siblings of plants carrying Gly2078 performed better in the field, on average, than wild-type plants that were sibling of plants carrying other mutant ACCase alleles, and particularly those carrying Leu1781. We propose that rapid evolution of the genetic background of plants from the populations where the Gly2078 allele originally arose could partially counterbalance Gly2078 fitness cost, enhancing the spread of the resistant genotypes.

  3. Genetic background of Escherichia coli isolates from peritoneal dialysis patients with peritonitis and uninfected control subjects.

    Science.gov (United States)

    Li, Y F; Su, N; Chen, S Y; Hu, W X; Li, F F; Jiang, Z P; Yu, X Q

    2016-03-28

    Escherichia coli is the most common cause of Gram-negative peritonitis resulting in peritoneal function deterioration as well as poor clinical outcome in continuous ambulatory peritoneal dialysis (PD) patients. In this study, we analyzed the phylogenetic background and genetic profile of the E. coli isolates and sought to determine the characteristics of specific bacteria associated with peritonitis. E. coli isolates from 56 episodes of peritonitis in 46 PD patient cases and rectal isolates from 57 matched PD control patient cases were compared for both phylogenetic groups and the presence of virulence factors (VFs). There were no significant differences in terms of demographic data between the peritonitis and control groups. Peritonitis isolates exhibited a significantly greater prevalence of 8 VFs. In multivariate logistic regression analysis, kpsMT II (group 2 capsule synthesis) was the strongest VF predictor of peritonitis (OR = 8.02; 95%CI = 3.18-20.25; P peritoneal isolates than rectal isolates (64.3 vs 31.6%, P = 0.001). Our results indicate that the E. coli peritonitis and rectal isolates are different in PD patients. The specific VFs associated with peritonitis isolates may directly contribute to the pathogenesis of peritonitis.

  4. Nucleotide Base Variation of Blast Disease Resistance Gene Pi33 in Rice Selected Broad Genetic Background

    Directory of Open Access Journals (Sweden)

    DWINITA WIKAN UTAMI

    2011-09-01

    Full Text Available Rice is one of the most important crops for human beings, thus increasing productivity are continually persecuted. Blast disease can reduce the rate of productivity of rice cultivation. Therefore, the program of blast disease-resistant varieties needs to do effectively. One of broad-spectrum blast disease-resistant gene is Pi33. This study was aimed to identify the variation in the sequence of nucleotide bases of Pi33 gene in five interspesific lines which derived from Bio46 (IR64/Oryza rufipogon and CT13432 crossing. DNA of five rice lines were amplified using the spesific primer for Pi33, G1010. Amplification results purified through Exonuclease 1 and Shrimp Alkaline Phosphatase protocols. Labelling using fluorescent dyes done before sequencing nucleotide base using CEQ8000 instrument. The results showed that lines number 28 showed introgesion of the three control parent genome (subspecies of Indica, subspecies of Japonica, and O. rufipogon while the Lines number 79, 136, and 143 were identical to Indica genome. Strain number 195 was identical to Japonica genome. These broad genetic background lines promise as durable performance to attack the expansion of the dynamic nature of the pathogen to blast. The result of ortholog sequence analysis found conserved nucleotide base sequence (CAGCAGCC which involved in heterotrimeric G-protein group. This protein has role as plant receptor for recognizing pathogen elicitor in interaction of rice and blast pathogen.

  5. Genetic Background is a Key Determinant of Glomerular Extracellular Matrix Composition and Organization.

    Science.gov (United States)

    Randles, Michael J; Woolf, Adrian S; Huang, Jennifer L; Byron, Adam; Humphries, Jonathan D; Price, Karen L; Kolatsi-Joannou, Maria; Collinson, Sophie; Denny, Thomas; Knight, David; Mironov, Aleksandr; Starborg, Toby; Korstanje, Ron; Humphries, Martin J; Long, David A; Lennon, Rachel

    2015-12-01

    Glomerular disease often features altered histologic patterns of extracellular matrix (ECM). Despite this, the potential complexities of the glomerular ECM in both health and disease are poorly understood. To explore whether genetic background and sex determine glomerular ECM composition, we investigated two mouse strains, FVB and B6, using RNA microarrays of isolated glomeruli combined with proteomic glomerular ECM analyses. These studies, undertaken in healthy young adult animals, revealed unique strain- and sex-dependent glomerular ECM signatures, which correlated with variations in levels of albuminuria and known predisposition to progressive nephropathy. Among the variation, we observed changes in netrin 4, fibroblast growth factor 2, tenascin C, collagen 1, meprin 1-α, and meprin 1-β. Differences in protein abundance were validated by quantitative immunohistochemistry and Western blot analysis, and the collective differences were not explained by mutations in known ECM or glomerular disease genes. Within the distinct signatures, we discovered a core set of structural ECM proteins that form multiple protein-protein interactions and are conserved from mouse to man. Furthermore, we found striking ultrastructural changes in glomerular basement membranes in FVB mice. Pathway analysis of merged transcriptomic and proteomic datasets identified potential ECM regulatory pathways involving inhibition of matrix metalloproteases, liver X receptor/retinoid X receptor, nuclear factor erythroid 2-related factor 2, notch, and cyclin-dependent kinase 5. These pathways may therefore alter ECM and confer susceptibility to disease.

  6. Genetic Background Strongly Influences the Bone Phenotype of P2X7 Receptor Knockout Mice

    DEFF Research Database (Denmark)

    Syberg, Susanne; Petersen, Solveig; Beck Jensen, Jens-Erik

    2012-01-01

    The purinergic P2X7 receptor is expressed by bone cells and has been shown to be important in both bone formation and bone resorption. In this study we investigated the importance of the genetic background of the mouse strains on which the P2X7 knock-out models were based by comparing bone status...... of a new BALB/cJ P2X7(-/-) strain with a previous one based on the C57BL/6 strain. Female four-month-old mice from both strains were DXA scanned on a PIXImus densitometer; femurs were collected for bone strength measurements and serum for bone marker analysis. Bone-related parameters that were altered only...... slightly in the B6 P2X7(-/-) became significantly altered in the BALB/cJ P2X7(-/-) when compared to their wild type littermates. The BALB/cJ P2X7(-/-) showed reduced levels of serum C-telopeptide fragment (s-CTX), higher bone mineral density, and increased bone strength compared to the wild type...

  7. Investigating the Reliability and Validity of Chen and Starosta’s Intercultural Sensitivity Scale (ISS) against Chinese Cultural Background

    Institute of Scientific and Technical Information of China (English)

    刘涵; Salasiah Che Lah

    2013-01-01

    Intercultural Communication Competence (ICC), as one of the research ifelds of intercultural communication, has been given much importance from scholars all around the world. Intercultural sensitivity is one of the three dimensions in Dr Chen’s ICC model. This research investigates the reliability and validity of Chen and Starosta’s Intercultural Sensitivity Scale (ISS) (2000) against Chinese cultural background by using Chinese university students majoring in English as respondents.

  8. Telomere length homeostasis and telomere position effect on a linear human artificial chromosome are dictated by the genetic background.

    Science.gov (United States)

    Weuts, An; Voet, Thierry; Verbeeck, Jelle; Lambrechts, Nathalie; Wirix, Evelyne; Schoonjans, Luc; Danloy, Sophie; Marynen, Peter; Froyen, Guy

    2012-12-01

    Telomere position effect (TPE) is the influence of telomeres on subtelomeric epigenetic marks and gene expression. Previous studies suggested that TPE depends on genetic background. As these analyses were performed on different chromosomes, cell types and species, it remains unclear whether TPE represents a chromosome-rather than genetic background-specific regulation. We describe the development of a Linear Human Artificial Chromosome (L-HAC) as a new tool for telomere studies. The L-HAC was generated through the Cre-loxP-mediated addition of telomere ends to an existing circular HAC (C-HAC). As it can be transferred to genetically distinct cell lines and animal models the L-HAC enables the study of TPE in an unprecedented manner. The HAC was relocated to four telomerase-positive cell lines via microcell-mediated chromosome transfer and subsequently to mice via blastocyst injection of L-HAC(+)-ES-cells. We could show consistent genetic background-dependent adaptation of telomere length and telomere-associated de novo subtelomeric DNA methylation in mouse ES-R1 cells as well as in mice. Expression of the subtelomeric neomycin gene was inversely correlated with telomere length and subtelomeric methylation. We thus provide a new tool for functional telomere studies and provide strong evidence that telomere length, subtelomeric chromatin marks and expression of subtelomeric genes are genetic background dependent.

  9. Teaching molecular genetics: Chapter 1--Background principles and methods of molecular biology.

    NARCIS (Netherlands)

    Knoers, N.V.A.M.; Monnens, L.A.H.

    2006-01-01

    In this first chapter of the series "Teaching molecular genetics," an introduction to molecular genetics is presented. We describe the structure of DNA and genes and explain in detail the central dogma of molecular biology, that is, the flow of genetic information from DNA via RNA to polypeptide (pr

  10. Genetic factors modulate the impact of pubertal androgen excess on insulin sensitivity and fertility.

    Directory of Open Access Journals (Sweden)

    Abigail R Dowling

    Full Text Available Polycystic ovary syndrome (PCOS is the most common endocrine disorder of reproductive age women. The syndrome is caused by a combination of environmental influences and genetic predisposition. Despite extensive efforts, the heritable factors contributing to PCOS development are not fully understood. The objective of this study was to test the hypothesis that genetic background contributes to the development of a PCOS-like reproductive and metabolic phenotype in mice exposed to excess DHEA during the pubertal transition. We tested whether the PCOS phenotype would be more pronounced on the diabetes-prone C57BL/6 background than the previously used strain, BALB/cByJ. In addition, we examined strain-dependent upregulation of the expression of ovarian and extra-ovarian candidate genes implicated in human PCOS, genes containing known strain variants, and genes involved with steroidogenesis or insulin sensitivity. These studies show that there are significant strain-related differences in metabolic response to excess androgen exposure during puberty. Additionally, our results suggest the C57BL/6J strain provides a more robust and uniform experimental platform for PCOS research than the BALB/cByJ strain.

  11. Study of the common genetic background for rheumatoid arthritis and systemic lupus erythematosus

    Science.gov (United States)

    Orozco, Gisela; Eyre, Steve; Hinks, Anne; Bowes, John; Morgan, Ann W; Wilson, Anthony G; Wordsworth, Paul; Steer, Sophia; Hocking, Lynne; Thomson, Wendy; Worthington, Jane; Barton, Anne

    2011-01-01

    Background Evidence is beginning to emerge that there may be susceptibility loci for rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) that are common to both diseases. Objective To investigate single nucleotide polymorphisms that have been reported to be associated with SLE in a UK cohort of patients with RA and controls. Methods 3962 patients with RA and 9275 controls were included in the study. Eleven SNPs mapping to confirmed SLE loci were investigated. These mapped to the TNFSF4, BANK1, TNIP1, PTTG1, UHRF1BP1, ATG5, JAZF1, BLK, KIAA1542, ITGAM and UBE2L3 loci. Genotype frequencies were compared between patients with RA and controls using the trend test. Results The SNPs mapping to the BLK and UBE2L3 loci showed significant evidence for association with RA. Two other SNPs, mapping to ATG5 and KIAA1542, showed nominal evidence for association with RA (p=0.02 and p=0.02, respectively) but these were not significant after applying a Bonferroni correction. Additionally, a significant global enrichment in carriage of SLE alleles in patients with RA compared with controls (p=9.1×10−7) was found. Meta-analysis of this and previous studies confirmed the association of the BLK and UBE2L3 gene with RA at genome-wide significance levels (p<5×10−8). Together, the authors estimate that the SLE and RA overlapping loci, excluding HLA-DRB1 alleles, identified so far explain ∼5.8% of the genetic susceptibility to RA as a whole. Conclusion The findings confirm the association of the BLK and UBE2L3 loci with RA, thus adding to the list of loci showing overlap between RA and SLE. PMID:21068098

  12. Genetic Background, Adipocytokines, and Metabolic Disorders in Postmenopausal Overweight and Obese Women.

    Science.gov (United States)

    Grygiel-Górniak, Bogna; Kaczmarek, Elżbieta; Mosor, Maria; Przysławski, Juliusz; Bogacz, Anna

    2016-10-01

    The relationship between the genetic background, adipocytokines, and metabolic state in postmenopausal women has not yet been fully described. The aim of this study was to determine the relationship between PPAR gamma-2 (Pro12Ala, C1431T) and ADRB3 (Trp64Arg) polymorphisms and serum adipocytokines (adiponectin, visfatin, and resistin) and metabolic disorders in 176 postmenopausal women with increased body mass (BMI ≥ 25 kg m(-2)). The distributions of selected alleles and genotype frequencies were determined with the PCR-RFLP method. The bioimpedance method was used to determine nutritional status, and enzyme-linked immunosorbent assays were applied to determine serum concentrations of adipocytokines. Viscerally obese postmenopausal women had higher body mass, body fat content, serum glucose, insulin, total cholesterol, LDL, triglycerides, uric acid, and HOMA-IR and a higher prevalence of the Ala12 allele. In models based on cytokine concentration, higher body mass and glucose concentration (visfatin model, p = 0.008) and higher insulin and triglyceride levels (resistin model, p = 0.002) were observed in visceral fat deposition and this was potentiated by the presence of the T1431 allele. In resistin models, co-existence of Ala12/X polymorphisms with the T1431 allele was associated with higher resistin and triglyceride concentrations (p = 0.045). In postmenopausal women, metabolic parameters are mainly determined by the distribution of body fat, but Ala12/X polymorphism may increase the metabolic disorders and this effect can be enhanced by the T1431 allele.

  13. Different thermotolerances in in vitro-produced embryos derived from different maternal and paternal genetic backgrounds.

    Science.gov (United States)

    Sakatani, Miki; Yamanaka, Kenichi; Balboula, Ahmed Zaky; Takahashi, Masashi

    2017-07-21

    The present study evaluated the effects of genetic backgrounds on the developmental competence and thermotolerance of bovine in vitro-produced (IVP) embryos. First, Holstein (Hol) and Japanese Black (JB) oocytes were fertilized with sperm from Hol, JB and a thermotolerant breed (Brahman), and in vitro development was evaluated when the embryos were exposed to heat shock on Day 2 (Day 0 = day of fertilization). Sperm genetic backgrounds affected the developmental competence in controls (P JB) and IVP embryos were evaluated. JB parthenotes showed developmental arrest after Day 4, and the rate of development to the blastocyst stage decreased by heat shock, but not in Hol parthenotes. Heat shock decreased developmental competence after cleavage of IVP embryos regardless of genetic background. The thermotolerance of IVP embryos would be controlled by both maternal and paternal factors but genetic involvement was still unclear. Further evaluation is needed to reveal the genetic contribution to thermotolerance. © 2017 Japanese Society of Animal Science.

  14. Teaching molecular genetics: Chapter 1--Background principles and methods of molecular biology.

    Science.gov (United States)

    Knoers, Nine V A M; Monnens, Leo A H

    2006-02-01

    In this first chapter of the series "Teaching molecular genetics," an introduction to molecular genetics is presented. We describe the structure of DNA and genes and explain in detail the central dogma of molecular biology, that is, the flow of genetic information from DNA via RNA to polypeptide (protein). In addition, several basic and frequently used general molecular tools, such as restriction enzymes, Southern blotting, DNA amplification and sequencing are discussed, in order to lay the foundations for the forthcoming chapters.

  15. Effect of dietary phosphorus and its interaction with genetic background on global gene expression in porcine muscle.

    Science.gov (United States)

    Qu, A; Rothschild, M F; Stahl, C H

    2007-08-01

    Environmental concerns and costs associated with dietary phosphorus (P) supplementation have lead to attempts to minimize the amount of P added to swine diets. In addition to its requirement for bone growth, dietary P is also necessary for muscular growth. To examine the effects of genetic background and dietary P on global gene expression in the muscle of young pigs, we utilized muscle tissue from 36 gilts sired from two different sire lines. These animals were fed either a P adequate, P deficient or P repletion diets for 14 days and showed differences in growth performance and bone integrity in response to the interaction of genetic background and dietary P. Total RNA from the loin muscle of these animals was obtained for microarray analysis. Significant differences (p<0.01) in gene expression were seen based on the effect of sire line (339 genes), dietary P (18 genes) and the interaction between sire line and dietary P (31 genes). The microarray data were validated by semi-quantitative real-time PCR. These results support our hypothesis that genetic background and dietary P treatment can affect the homeorhetic control of P metabolism in pigs. Genes identified as differentially expressed in this study may be excellent candidate genes for additional work to elucidate genotype specific P requirements as well as to identify a genetic background that can maintain superior growth in a more environmentally friendly manner.

  16. RAMBO-K: Rapid and Sensitive Removal of Background Sequences from Next Generation Sequencing Data.

    Directory of Open Access Journals (Sweden)

    Simon H Tausch

    Full Text Available The assembly of viral or endosymbiont genomes from Next Generation Sequencing (NGS data is often hampered by the predominant abundance of reads originating from the host organism. These reads increase the memory and CPU time usage of the assembler and can lead to misassemblies.We developed RAMBO-K (Read Assignment Method Based On K-mers, a tool which allows rapid and sensitive removal of unwanted host sequences from NGS datasets. Reaching a speed of 10 Megabases/s on 4 CPU cores and a standard hard drive, RAMBO-K is faster than any tool we tested, while showing a consistently high sensitivity and specificity across different datasets.RAMBO-K rapidly and reliably separates reads from different species without data preprocessing. It is suitable as a straightforward standard solution for workflows dealing with mixed datasets. Binaries and source code (java and python are available from http://sourceforge.net/projects/rambok/.

  17. Lay responses to health messages about the genetic risk factors for salt sensitivity: do mass media genetic health messages result in genetic determinism?

    Science.gov (United States)

    Smerecnik, Chris M R

    2010-08-01

    Media coverage of genetics may lead to overestimation of the impact of genetics on disease development. In this study, we presented one student sample and one general public sample from the Netherlands with a general or a genetic health message (HM) about salt sensitivity. After reading the genetic (but not the general) HM, participants reported higher perceived impact of genetic versus lifestyle factors and a higher attributable fraction of genetics on disease development. Nevertheless, participants were able to recognise the balance between lifestyle and genetic risk factors in disease development. They also contextualised and restricted the message's implications to the specific information provided, and did not extrapolate these implications to other diseases. These results illustrate the nuanced understanding the general public may have concerning genetic risk factors.

  18. Enhanced biofilm formation and multi‐host transmission evolve from divergent genetic backgrounds in C ampylobacter jejuni

    Science.gov (United States)

    Pascoe, Ben; Méric, Guillaume; Murray, Susan; Yahara, Koji; Mageiros, Leonardos; Bowen, Ryan; Jones, Nathan H.; Jeeves, Rose E.; Lappin‐Scott, Hilary M.; Asakura, Hiroshi

    2015-01-01

    Summary Multicellular biofilms are an ancient bacterial adaptation that offers a protective environment for survival in hostile habitats. In microaerophilic organisms such as C ampylobacter, biofilms play a key role in transmission to humans as the bacteria are exposed to atmospheric oxygen concentrations when leaving the reservoir host gut. Genetic determinants of biofilm formation differ between species, but little is known about how strains of the same species achieve the biofilm phenotype with different genetic backgrounds. Our approach combines genome‐wide association studies with traditional microbiology techniques to investigate the genetic basis of biofilm formation in 102 C ampylobacter jejuni isolates. We quantified biofilm formation among the isolates and identified hotspots of genetic variation in homologous sequences that correspond to variation in biofilm phenotypes. Thirteen genes demonstrated a statistically robust association including those involved in adhesion, motility, glycosylation, capsule production and oxidative stress. The genes associated with biofilm formation were different in the host generalist ST‐21 and ST‐45 clonal complexes, which are frequently isolated from multiple host species and clinical samples. This suggests the evolution of enhanced biofilm from different genetic backgrounds and a possible role in colonization of multiple hosts and transmission to humans. PMID:26373338

  19. The effects of the genetic background on herbicide resistance fitness cost and its associated dominance in Arabidopsis thaliana.

    Science.gov (United States)

    Paris, M; Roux, F; Bérard, A; Reboud, X

    2008-12-01

    The advantage of the resistance conferred by a mutation can sometimes be offset by a high fitness-cost penalty. This balance will affect possible fate of the resistance allele. Few studies have explored the impact of the genetic background on the expression of the resistance fitness cost and none has attempted to measure the variation in fitness-cost dominance. However, both the fitness penalty and its dominance may modify evolutionary trajectory and outcome. Here the impact of Arabidopsis thaliana intraspecific genetic diversity on fitness cost and its associated dominance was investigated by analysing 12 quantitative traits in crosses between a mutant conferring resistance to the herbicide 2,4-D and nine different natural genetic backgrounds. Fitness cost values were found to be more affected by intraspecific genetic diversity than fitness cost dominance, even though this effect depends on the quantitative trait measured. This observation has implications for the choice of the best strategy for preventing herbicide resistance development. In addition, our results pinpoint a potential compensatory improvement of the resistance fitness cost and its associated dominance by the genetic diversity locally present within a species.

  20. A trans-acting Variant within the Transcription Factor RIM101 Interacts with Genetic Background to Determine its Regulatory Capacity.

    Science.gov (United States)

    Read, Timothy; Richmond, Phillip A; Dowell, Robin D

    2016-01-01

    Most genetic variants associated with disease occur within regulatory regions of the genome, underscoring the importance of defining the mechanisms underlying differences in regulation of gene expression between individuals. We discovered a pair of co-regulated, divergently oriented transcripts, AQY2 and ncFRE6, that are expressed in one strain of Saccharomyces cerevisiae, ∑1278b, but not in another, S288c. By combining classical genetics techniques with high-throughput sequencing, we identified a trans-acting single nucleotide polymorphism within the transcription factor RIM101 that causes the background-dependent expression of both transcripts. Subsequent RNA-seq experiments revealed that RIM101 regulates many more targets in S288c than in ∑1278b and that deletion of RIM101 in both backgrounds abrogates the majority of differential expression between the strains. Strikingly, only three transcripts undergo a significant change in expression after swapping RIM101 alleles between backgrounds, implying that the differences in the RIM101 allele lead to a remarkably focused transcriptional response. However, hundreds of RIM101-dependent targets undergo a subtle but consistent shift in expression in the S288c RIM101-swapped strain, but not its ∑1278b counterpart. We conclude that ∑1278b may harbor a variant(s) that buffers against widespread transcriptional dysregulation upon introduction of a non-native RIM101 allele, emphasizing the importance of accounting for genetic background when assessing the impact of a regulatory variant.

  1. Extending the Sensitivity to the Detection of WIMP Dark Matter with an Improved Understanding of the Limiting Neutron Backgrounds

    Energy Technology Data Exchange (ETDEWEB)

    Kamat, Sharmila [Case Western Reserve Univ., Cleveland, OH (United States). Dept. of Physics

    2005-01-01

    The Cryogenic Dark Matter Search (CDMS) uses position-sensitive Germanium and Silicon crystals in the direct detection of Weakly Interacting Massive Particles (WIMPs) believed to constitute most of the dark matter in the Universe. WIMP interactions with matter being rare, identifying and eliminating known backgrounds is critical for detection. Event-by-event discrimination by the detectors rejects the predominant gamma and beta backgrounds while Monte Carlo simulations help estimate, and subtract, the contribution from the neutrons. This thesis describes the effort to understand neutron backgrounds as seen in the two stages of the CDMS search for WIMPs. The first stage of the experiment was at a shallow site at the Stanford Underground Facility where the limiting background came from high-energy neutrons produced by cosmic-ray muon interactions in the rock surrounding the cavern. Simulations of this background helped inform the analysis of data from an experimental run at this site and served as input for the background reduction techniques necessary to set new exclusion limits on the WIMP-nucleon cross-section, excluding new parameter space for WIMPs of masses 8-20 GeV/c2. This thesis considers the simulation methods used as well as how various event populations in the data served as checks on the simulations to allow them to be used in the interpretation of the WIMP-search data. The studies also confirmed the presence of a limiting neutron background at the shallow site, necessitating the move to the 713-meter deep Soudan Underground Facility. Similar computer-based studies helped quantify the neutron background seen at the deeper site and informed the analysis of the data emerging from the first physics run of the experiment at Soudan. In conjunction with the WIMP-search and calibration data, the simulations confirmed that increased depth considerably reduced the neutron backgrounds seen, greatly improving the sensitivity to WIMP detection. The data

  2. Emotional effects of startling background music during reading news reports: The moderating influence of dispositional BIS and BAS sensitivities.

    Science.gov (United States)

    Ravaja, Niklas; Kallinen, Kari

    2004-07-01

    We examined the moderating influence of dispositional behavioral inhibition system (BIS) and behavioral activation system (BAS) sensitivities on the relationship of startling background music with emotion-related subjective and physiological responses elicited during reading news reports, and with memory performance among 26 adult men and women. Physiological parameters measured were respiratory sinus arrhythmia (RSA), electrodermal activity (EDA), and facial electromyography (EMG). The results showed that, among high BAS individuals, news stories with startling background music were rated as more interesting and elicited higher zygomatic EMG activity and RSA than news stories with non-startling music. Among low BAS individuals, news stories with startling background music were rated as less pleasant and more arousing and prompted higher EDA. No BIS-related effects or effects on memory were found. Startling background music may have adverse (e.g., negative arousal) or beneficial effects (e.g., a positive emotional state and stronger positive engagement) depending on dispositional BAS sensitivity of an individual. Actual or potential applications of this research include the personalization of media presentations when using modern media and communications technologies.

  3. Confirming candidate genes for longevity in Drosophila melanogaster using two different genetic backgrounds and selection methods

    DEFF Research Database (Denmark)

    Wit, Janneke; Frydenberg, Jane; Sarup, Pernille Merete

    2013-01-01

    Elucidating genes that affect life span or that can be used as biomarkers for ageing has received attention in diverse studies in recent years. Using model organisms and various approaches several genes have been linked to the longevity phenotype. For Drosophila melanogaster those studies have...... usually focussed on one sex and on flies originating from one genetic background, and results from different studies often do not overlap. Using D. melanogaster selected for increased longevity we aimed to find robust longevity related genes by examining gene expression in both sexes of flies originating...... from different genetic backgrounds. Further, we compared expression changes across three ages, when flies were young, middle aged or old, to examine how candidate gene expression changes with the onset of ageing. We selected 10 genes based on their expression differences in prior microarray studies...

  4. Expression of Drosophila mushroom body mutations in alternative genetic backgrounds: a case study of the mushroom body miniature gene (mbm).

    Science.gov (United States)

    de Belle, J S; Heisenberg, M

    1996-01-01

    Mutations in 12 genes regulating Drosophila melanogaster mushroom body (MB) development were each studied in two genetic backgrounds. In all cases, brain structure was qualitatively or quantitatively different after replacement of the "original" genetic background with that of the Canton Special wild-type strain. The mushroom body miniature gene (mbm) was investigated in detail. mbm supports the maintenance of MB Kenyon cell fibers in third instar larvae and their regrowth during metamorphosis. Adult mbm1 mutant females are lacking many or most Kenyon cell fibers and are impaired in MB-mediated associative odor learning. We show here that structural defects in mbm1 are apparent only in combination with an X-linked, dosage-dependent modifier (or modifiers). In the Canton Special genetic background, the mbm1 anatomical phenotype is suppressed, and MBs develop to a normal size. However, the olfactory learning phenotype is not fully restored, suggesting that submicroscopic defects persist in the MBs. Mutant mbm1 flies with full-sized MBs have normal retention but show a specific acquisition deficit that cannot be attributed to reductions in odor avoidance, shock reactivity, or locomotor behavior. We propose that polymorphic gene interactions (in addition to ontogenetic factors) determine MB size and, concomitantly, the ability to recognize and learn odors. Images Fig. 1 Fig. 2 Fig. 3 PMID:8790424

  5. Expression of Drosophila mushroom body mutations in alternative genetic backgrounds: a case study of the mushroom body miniature gene (mbm).

    Science.gov (United States)

    de Belle, J S; Heisenberg, M

    1996-09-03

    Mutations in 12 genes regulating Drosophila melanogaster mushroom body (MB) development were each studied in two genetic backgrounds. In all cases, brain structure was qualitatively or quantitatively different after replacement of the "original" genetic background with that of the Canton Special wild-type strain. The mushroom body miniature gene (mbm) was investigated in detail. mbm supports the maintenance of MB Kenyon cell fibers in third instar larvae and their regrowth during metamorphosis. Adult mbm1 mutant females are lacking many or most Kenyon cell fibers and are impaired in MB-mediated associative odor learning. We show here that structural defects in mbm1 are apparent only in combination with an X-linked, dosage-dependent modifier (or modifiers). In the Canton Special genetic background, the mbm1 anatomical phenotype is suppressed, and MBs develop to a normal size. However, the olfactory learning phenotype is not fully restored, suggesting that submicroscopic defects persist in the MBs. Mutant mbm1 flies with full-sized MBs have normal retention but show a specific acquisition deficit that cannot be attributed to reductions in odor avoidance, shock reactivity, or locomotor behavior. We propose that polymorphic gene interactions (in addition to ontogenetic factors) determine MB size and, concomitantly, the ability to recognize and learn odors.

  6. Alcohol induces sensitization to gluten in genetically susceptible individuals: a case control study.

    Directory of Open Access Journals (Sweden)

    Stuart Currie

    Full Text Available BACKGROUND: The mechanisms of cerebellar degeneration attributed to prolonged and excessive alcohol intake remain unclear. Additional or even alternative causes of cerebellar degeneration are often overlooked in suspected cases of alcohol-related ataxia. The objectives of this study were two fold: (1 to investigate the prevalence of gluten-related serological markers in patients with alcohol-related ataxia and; (2 to compare the pattern of brain involvement on magnetic resonance imaging between patients with alcohol and gluten ataxias. MATERIALS & METHODS: Patients diagnosed with alcohol and gluten ataxias were identified from a retrospective review of patients attending a tertiary clinic. HLA genotype and serological markers of gluten-related disorders were recorded. Cerebellar volumetry, MR spectroscopy and voxel-based morphometric analyses were performed on patients and compared with matched control data. RESULTS: Of 904 registered patients, 104 had alcohol ataxia and 159 had gluten ataxia. 61% of the alcohol ataxia group and 70% of the gluten ataxia group had HLA DQ2/DQ8 genotype compared to 30% in healthy local blood donors. 44% of patients with alcohol ataxia had antigliadin antibodies compared to 12% in the healthy local population and 10% in patients with genetically confirmed ataxias. None of the patients with alcohol ataxia and antigliadin antibodies had celiac disease compared to 40% in patients with gluten ataxia. The pattern of structural brain abnormality in patients with alcohol ataxia who had antigliadin antibodies differed from gluten ataxia and was identical to that of alcohol ataxia. CONCLUSIONS: Alcohol related cerebellar degeneration may, in genetically susceptible individuals, induce sensitization to gluten. Such sensitization may result from a primary cerebellar insult, but a more systemic effect is also possible. The duration and amount of exposure to alcohol may not be the only factors responsible for the cerebellar

  7. Does the genetic and familial background of males undertaking ICSI affect the outcome?

    NARCIS (Netherlands)

    Maiburg, M.; Alizadeh, B.; Kastrop, P.; Lock, M.; Lans, S.; Giltay, J.

    2009-01-01

    Purpose: To investigate whether the success rate of ICSI is (1) related to the etiology of infertility or (2) adversely affected by a family history of potential genetic disorders. Methods: All men with an ICSI indication in our hospital between 1994 and 2005 were included in our cohort study. Data

  8. Influence of genetic background on anthocyanin and copigment composition and behavior during thermoalkaline processing of maize

    Science.gov (United States)

    Visual color is a primary factor for foods purchase; identifying factors that influence in-situ color quality of pigmented maize during processing is important. We used 24 genetically distinct pigmented maize hybrids (red/blue, blue, red, and purple) to investigate the effect of pigment and copigme...

  9. Common and different genetic background for rheumatoid arthritis and coeliac disease

    NARCIS (Netherlands)

    Coenen, Marieke J H; Trynka, Gosia; Heskamp, Sandra; Franke, Barbara; van Diemen, Cleo C; Smolonska, Joanna; van Leeuwen, Maria; Brouwer, Elisabeth; Boezen, Hendrika; Postma, Dirkje S; Platteel, Mathieu; Zanen, Pieter; Lammers, Jan-Willem W J; Groen, Hendricus; Mali, Willem P T M; Mulder, Chris J; Tack, Greetje J; Verbeek, Wieke H M; Wolters, Victorien M; Houwen, Roderick H J; Mearin, M Luisa; van Heel, David A; Radstake, Timothy R D J; van Riel, Piet L C M; Wijmenga, Cisca; Barrera, Pilar; Zhernakova, Alexandra

    2009-01-01

    Recent genome-wide association studies (GWAS) have revealed genetic risk factors in autoimmune and inflammatory disorders. Several of the associated genes and underlying pathways are shared by various autoimmune diseases. Rheumatoid arthritis (RA) and coeliac disease (CD) are two autoimmune

  10. Direct Detection of Nucleic Acid with Minimizing Background and Improving Sensitivity Based on a Conformation-Discriminating Indicator.

    Science.gov (United States)

    Zhu, Lixuan; Qing, Zhihe; Hou, Lina; Yang, Sheng; Zou, Zhen; Cao, Zhong; Yang, Ronghua

    2017-08-25

    As is well-known, the nucleic acid indicator-based strategy is one of the major approaches to monitor the nucleic acid hybridization-mediated recognition events in biochemical analysis, displaying obvious advantages including simplicity, low cost, convenience, and generality. However, conventional indicators either hold strong self-fluorescence or can be lighted by both ssDNA and dsDNA, lacking absolute selectivity for a certain conformation, always with high background interference and low sensitivity in sensing; and additional processing (e.g., nanomaterial-mediated background suppression, and enzyme-catalyzed signal amplification) is generally required to improve the detection performance. In this work, a carbazole derivative, EBCB, has been synthesized and screened as a dsDNA-specific fluorescent indicator. Compared with conventional indicators under the same conditions, EBCB displayed a much higher selective coefficient for dsDNA, with little self-fluorescence and negligible effect from ssDNA. Based on its superior capability in DNA conformation-discrimination, high sensitivity with minimizing background interference was demonstrated for direct detection of nucleic acid, and monitoring nucleic acid-based circuitry with good reversibity, resulting in low detection limit and high capability for discriminating base-mismatching. Thus, we expect that this highly specific DNA conformation-discriminating indicator will hold good potential for application in biochemical sensing and molecular logic switching.

  11. Effects of disclosing hypothetical genetic test results for salt sensitivity on salt restriction behavior

    Directory of Open Access Journals (Sweden)

    Takeshima T

    2013-05-01

    Full Text Available Taro Takeshima,1,2 Masanobu Okayama,1 Masanori Harada,3 Ryusuke Ae,4 Eiji Kajii1 1Division of Community and Family Medicine, Center for Community Medicine, Jichi Medical University, Tochigi, Japan; 2Department of Healthcare Epidemiology, Kyoto University Graduate School of Medicine and Public Health, Kyoto, Japan; 3Department for Support of Rural Medicine, Yamaguchi Grand Medical Center, Yamaguchi, Japan; 4Department of General Internal Medicine, Hamasaka Public Hospital, Mikata, Japan Background: A few studies have explored the effects of disclosure of genetic testing results on chronic disease predisposition. However, these effects remain unclear in cases of hypertension. Reducing salt intake is an important nonpharmacological intervention for hypertension. We investigated the effects of genetic testing for salt sensitivity on salt restriction behavior using hypothetical genetic testing results. Methods: We conducted a cross-sectional study using a self-completed questionnaire. We enrolled consecutive outpatients who visited primary care clinics and small hospitals between September and December 2009 in Japan. We recorded the patients’ baseline characteristics and data regarding their salt restriction behavior, defined as reducing salt intake before and after disclosure of hypothetical salt sensitivity genetic test results. Behavioral stage was assessed according to the five-stage transtheoretical model. After dividing subjects into salt restriction and no salt restriction groups, we compared their behavioral changes following positive and negative test results and analyzed the association between the respondents’ characteristics and their behavioral changes. Results: We analyzed 1562 participants with a mean age of 58 years. In the no salt restriction group, which included patients at the precontemplation, contemplation, and preparation stages, 58.7% stated that their behavioral stage progressed after a positive test result, although 29

  12. Refinement of the background genetic map of Xq26-q27 and gene localisation for Boerjeson-Forssman-Lehmann syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Gedeon, A.K.; Kozman, H.M.; Mulley, J.C. [Univ. of Adelaide (Australia)] [and others

    1996-07-12

    A detailed map of genetic markers was constructed around the gene for the X-linked mental retardation syndrome of Borjeson-Forssman-Lehmann (BFLS). A multipoint linkage map of framework markers across Xq26-27, based on CEPH families, was integrated with the physical map, based on a YAC contig, to confirm marker order. The remaining genetic markers, which could not be ordered by linkage, were added to create the comprehensive genetic background map, in the order determined by physical mapping, to determine genetic distances between adjacent markers. This background genetic map is applicable to the refinement of the regional localization for any disease gene mapping to this region. The BFLS gene was localized using this background map in an extended version of the family described by Turner et al. The regional localization for BFLS extends between recombination events at DXS425 and DXS105, an interval of 24.6 cM on the background genetic map. The phenotypic findings commonly seen in the feet of affected males and obligate carrier females may represent a useful clinical indicator of carrier status in potential female carriers in the family. Recombination between DXS425 and DXS105 in a female with such characteristic feet suggests that the distal limit of the regional localization for the BFLS gene might reasonably be reduced to DXS294 for the purpose of selecting candidate genes, reducing the interval for the BFLS gene to 15.5 cM. Positional candidate genes from the interval between DXS425 and DXS105 include the SOX3 gene, mapped between DXS51(52A) and DXS98(4D-8). SOX3 may have a role in regulating the development of the nervous system. The HMG-box region of this single exon gene was examined by PCR for a deletion and then sequenced. No deviation from normal was observed, excluding mutations in the conserved HMG-box region as the cause of BFLS in this family. 27 refs., 1 fig., 2 tabs.

  13. Exponential sensitivity of noise-driven switching in genetic networks

    Science.gov (United States)

    Mehta, Pankaj; Mukhopadhyay, Ranjan; Wingreen, Ned S.

    2008-06-01

    There is increasing experimental evidence that cells can utilize biochemical noise to switch probabilistically between distinct gene-expression states. In this paper, we demonstrate that such noise-driven switching is dominated by tails of probability distributions and is therefore exponentially sensitive to changes in physiological parameters such as transcription and translation rates. Exponential sensitivity limits the robustness of noise-driven switching, suggesting cells may use other mechanisms in order to switch reliably. We discuss our results in the context of competence in the bacterium Bacillus subtilis.

  14. Genetic background and phenotypic characterization over two farrowings of leg conformation defects in Landrace and Large White sows.

    Science.gov (United States)

    de Sevilla, X Fernàndez; Fàbrega, E; Tibau, J; Casellas, J

    2009-05-01

    A Bayesian threshold animal model was applied to evaluate the prevalence over 2 farrowings and genetic background of overall leg conformation score and the presence or absence of 6 specific leg defects (abnormal hoof growth, splay footed, plantigradism, straight pasterns, sickle-hocked legs, and the presence of swelling or injuries) in purebred Landrace and Large White sows. Data sets contained phenotypic records from 2,477 and 1,550 Landrace and Large White females, respectively, at the end of the growing period. Leg conformation data from first and second farrowings were available for 223 and 191 Landrace sows and 213 and 193 Large White sows, respectively. Overall leg conformation deteriorated with age, with statistically relevant differences between females at the end of the growing period, first farrowing (FF), and second farrowing (SF). In a similar way, the prevalence of the 6 specific leg defects increased between the end of the growing period and FF (with the exception of straight pasterns in the Landrace population). Differences between FF and second farrowing were statistically relevant for hoof growth (highest posterior density regions at 95% did not overlap), plantigradism, sickle-hocked legs, and overall leg conformation score in Landrace and for sickle-hocked leg and overall leg conformation score in Large White. The statistical relevance of the genetic background was tested through the Bayes factor (BF) between the model with the additive genetic component and the model with 0 heritability (nonheritable). Heritability (h(2)) was discarded (BF 100) of genetic background was obtained for overall leg conformation score in Landrace and Large White sows (h(2) = 0.27 and 0.38, respectively), hoof growth in both breeds (h(2) = 0.22 and 0.26, respectively), and plantigradism (h(2) = 0.34) and the presence of swelling or injuries in Landrace (h(2) = 0.27). Note that a BF > 100 implies that the model with infinitesimal genetic effects was more than 100 times

  15. The sensitivity of genetic connectivity measures to unsampled and under-sampled sites.

    Directory of Open Access Journals (Sweden)

    Erin L Koen

    Full Text Available Landscape genetic analyses assess the influence of landscape structure on genetic differentiation. It is rarely possible to collect genetic samples from all individuals on the landscape and thus it is important to assess the sensitivity of landscape genetic analyses to the effects of unsampled and under-sampled sites. Network-based measures of genetic distance, such as conditional genetic distance (cGD, might be particularly sensitive to sampling intensity because pairwise estimates are relative to the entire network. We addressed this question by subsampling microsatellite data from two empirical datasets. We found that pairwise estimates of cGD were sensitive to both unsampled and under-sampled sites, and F(ST, D(est, and d(eucl were more sensitive to under-sampled than unsampled sites. We found that the rank order of cGD was also sensitive to unsampled and under-sampled sites, but not enough to affect the outcome of Mantel tests for isolation by distance. We simulated isolation by resistance and found that although cGD estimates were sensitive to unsampled sites, by increasing the number of sites sampled the accuracy of conclusions drawn from landscape genetic analyses increased, a feature that is not possible with pairwise estimates of genetic differentiation such as F(ST, D(est, and d(eucl. We suggest that users of cGD assess the sensitivity of this measure by subsampling within their own network and use caution when making extrapolations beyond their sampled network.

  16. A common genetic background could explain early-onset Crohn's disease.

    Science.gov (United States)

    Bianco, Anna Monica; Zanin, Valentina; Girardelli, Martina; Magnolato, Andrea; Martelossi, Stefano; Martellossi, Stefano; Tommasini, Alberto; Marcuzzi, Annalisa; Crovella, Sergio

    2012-04-01

    Crohn's disease (CD) is a multifactorial disease, in which environmental, microbial and genetic factors play important roles. CD is characterized by a chronic granulomatous inflammation by necrotic scarring with aspects of full-thickness wall. In spite of affecting mainly young adults, sometimes, CD can be present in the first year of life (early onset Crohn disease, EOCD) showing an unpredictable course and being often more severe than at older ages. In this paper we propose the hypothesis that EOCD patients should be analyzed using a Mendelian approach with family studies aimed to identify new loci directly involved in the early onset Crohn's disease. So we will leave the classic association study approach used until now for the identification of genes responsible for susceptibility to CD and propose linkage family analysis as alternative and powerful tool for the identification of new genetic variants associated with familiar cases of EOCD.

  17. Sardinians genetic background explained by runs of homozygosity and genomic regions under positive selection.

    Directory of Open Access Journals (Sweden)

    Cornelia Di Gaetano

    Full Text Available The peculiar position of Sardinia in the Mediterranean sea has rendered its population an interesting biogeographical isolate. The aim of this study was to investigate the genetic population structure, as well as to estimate Runs of Homozygosity and regions under positive selection, using about 1.2 million single nucleotide polymorphisms genotyped in 1077 Sardinian individuals. Using four different methods--fixation index, inflation factor, principal component analysis and ancestry estimation--we were able to highlight, as expected for a genetic isolate, the high internal homogeneity of the island. Sardinians showed a higher percentage of genome covered by RoHs>0.5 Mb (F(RoH%0.5 when compared to peninsular Italians, with the only exception of the area surrounding Alghero. We furthermore identified 9 genomic regions showing signs of positive selection and, we re-captured many previously inferred signals. Other regions harbor novel candidate genes for positive selection, like TMEM252, or regions containing long non coding RNA. With the present study we confirmed the high genetic homogeneity of Sardinia that may be explained by the shared ancestry combined with the action of evolutionary forces.

  18. Ba2+- and bupivacaine-sensitive background K+ conductances mediate rapid EPSP attenuation in oligodendrocyte precursor cells.

    Science.gov (United States)

    Chan, Chu-Fang; Kuo, Tzu-Wei; Weng, Ju-Yun; Lin, Yen-Chu; Chen, Ting-Yu; Cheng, Jen-Kun; Lien, Cheng-Chang

    2013-10-01

    Glutamatergic transmission onto oligodendrocyte precursor cells (OPCs) may regulate OPC proliferation, migration and differentiation. Dendritic integration of excitatory postsynaptic potentials (EPSPs) is critical for neuronal functions, and mechanisms regulating dendritic propagation and summation of EPSPs are well understood. However, little is known about EPSP attenuation and integration in OPCs. We developed realistic OPC models for synaptic integration, based on passive membrane responses of OPCs obtained by simultaneous dual whole-cell patch-pipette recordings. Compared with neurons, OPCs have a very low value of membrane resistivity, which is largely mediated by Ba(2+)- and bupivacaine-sensitive background K(+) conductances. The very low membrane resistivity not only leads to rapid EPSP attenuation along OPC processes but also sharpens EPSPs and narrows the temporal window for EPSP summation. Thus, background K(+) conductances regulate synaptic responses and integration in OPCs, thereby affecting activity-dependent neuronal control of OPC development and function.

  19. Protective Effect of R Allele of PON1 Gene on the Coronary Artery Disease in the Presence of Specific Genetic Background

    Directory of Open Access Journals (Sweden)

    Anna Balcerzyk

    2008-01-01

    Full Text Available Background: Genetic susceptibility to CAD may be determined by polymorphic variants of genes encoding isoforms involved in the processes important in the pathogenesis of atherosclerosis, including lipids disorders. Participation of single polymorphic variants is relatively small, however its significance may increase in the presence of specific genetic or environmental background.

  20. A genetic variant near the PMAIP1/Noxa gene is associated with increased bleomycin sensitivity

    NARCIS (Netherlands)

    Gu, J.; Ye, Y.; Spitz, M.R.; Lin, J.; Kiemeney, L.A.L.M.; Xing, J.; Hildebrandt, M.A.T.; Ki Hong, W.; Amos, C.I.; Wu, X.

    2011-01-01

    Mutagen sensitivity, a measurement of chromatid breaks induced by various mutagens in short-term cultures of peripheral blood lymphocytes, is an established risk factor for a number of cancers and is highly heritable. The purpose of this study is to identify genetic predictors of mutagen sensitivity

  1. Genetic Background and Population Genetics of Hungarian Brown Trout Populations Using PCR-RFLP and Microsatellite Markers

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    Ágnes Ősz

    2015-12-01

    4 University of West Hungary, Mosonmagyaróvár Vár 2., 9200 Mosonmagyaróvár, Hungary Based on the analyses of the mitochondrial DNA of several European brown trout populations, five evolutionary lineages of brown trout were indentified (Atlantic, Danubian, Mediterranean, Adriatic, Marble. The species is bred primarily for stock enhancement of natural waters, however the most hatchery-maintained broodstocks originate from the Atlantic lineage. Due to the hydrogeography of Hungary our stocks should theoretically belong to the Danubian lineage; however, this has not been investigated earlier by genetic studies. For our genetic analysis, 702 fin clips were collected from two brown trout broodstocks (Lillafüred and Szilvásvárad as well as populations of natural streams (Bán, Jósva, Kemence, Apátkút, Bittva and Kölöntés in Hungary. Sequencing of the control region in mitochondrial DNA, three PCR-RFLP (mitochondrial DNA control region, lactate dehydrogenase and somatolactin genes and five microsatellite markers were used to distinguish between Danubian and Atlantic lineages of brown trout. The proportion of the mitochondrial haplotype of the Danubian lineage was low, with the exception of the Apátkúti, Kölöntés streams and Szilvásvárad broodstock. Analyses of nuclear PCR-RFLP and microsatellites markers showed various distributions of alleles characteristic of the Atlantic or Danubian lineages, although the Atlantic genotype has dominated in all population. In case of the analyses of microsatellites the polymorphism varied greatly at all locations. In addition we found several alleles that were not described earlier in other populations. Those alleles probably would be typical of Hungarian brown trout populations. Overall the populations were effectively in Hardy-Weinberg equilibrium for both PCR-RFLP and microsatellite markers. The remarkably high proportion of allochthonous Atlantic alleles in the analyzed sites is a clear indicator of the import

  2. Moroccan mitochondrial genetic background suggests prehistoric human migrations across the Gibraltar Strait.

    Science.gov (United States)

    Rhouda, Taha; Martínez-Redondo, Diana; Gómez-Durán, Aurora; Elmtili, Noureddine; Idaomar, Mouhamed; Díez-Sánchez, Carmen; Montoya, Julio; López-Pérez, Manuel José; Ruiz-Pesini, Eduardo

    2009-11-01

    Migrations into Africa from the Levant have greatly determined the mitochondrial genetic landscape of North Africa. After analyzing samples from North Morocco to Spain, we show that three fourths of the Moroccan individuals belong to Western Eurasian haplogroups and the frequencies of these are much more similar to those of the Iberian Peninsula than to those of the Middle East. This is particularly true for the mitochondrial haplogroups H1, H3 and V, which experienced a late-glacial expansion from this region, that repopulated much of Central and Northern Europe. Iberian Peninsula was also a source for prehistoric migrations to North Africa.

  3. Genetic background influences embryonic lethality and the occurrence of neural tube defects in Men1 null mice: relevance to genetic modifiers.

    Science.gov (United States)

    Lemos, Manuel C; Harding, Brian; Reed, Anita A C; Jeyabalan, Jeshmi; Walls, Gerard V; Bowl, Michael R; Sharpe, James; Wedden, Sarah; Moss, Julie E; Ross, Allyson; Davidson, Duncan; Thakker, Rajesh V

    2009-10-01

    Germline mutations of the multiple endocrine neoplasia type 1 (MEN1) gene cause parathyroid, pancreatic and pituitary tumours in man. MEN1 mutations also cause familial isolated primary hyperparathyroidism (FIHP) and the same MEN1 mutations, in different families, can cause either FIHP or MEN1. This suggests a role for genetic background and modifier genes in altering the expression of a mutation. We investigated the effects of genetic background on the phenotype of embryonic lethality that occurs in a mouse model for MEN1. Men1(+/-) mice were backcrossed to generate C57BL/6 and 129S6/SvEv incipient congenic strains, and used to obtain homozygous Men1(-/-) mice. No viable Men1(-/-) mice were obtained. The analysis of 411 live embryos obtained at 9.5-16.5 days post-coitum (dpc) revealed that significant deviations from the expected Mendelian 1:2:1 genotype ratio were first observed at 12.5 and 14.5 dpc in the 129S6/SvEv and C57BL/6 strains respectively (P<0.05). Moreover, live Men1(-/-) embryos were absent by 13.5 and 15.5 dpc in the 129S6/SvEv and C57BL/6 strains respectively thereby indicating an earlier lethality by 2 days in the 129S6/SvEv strain (P<0.01). Men1(-/-) embryos had macroscopic haemorrhages, and histology and optical projection tomography revealed them to have internal haemorrhages, myocardial hypotrophy, pericardial effusion, hepatic abnormalities and neural tube defects. The neural tube defects occurred exclusively in 129S6/SvEv embryos (21 vs 0%, P<0.01). Thus, our findings demonstrate the importance of genetic background in influencing the phenotypes of embryonic lethality and neural tube defects in Men1(-/-) mice, and implicate a role for genetic modifiers.

  4. Influence of Genetic Background on Anthocyanin and Copigment Composition and Behavior during Thermoalkaline Processing of Maize.

    Science.gov (United States)

    Collison, Amy; Yang, Liyi; Dykes, Linda; Murray, Seth; Awika, Joseph M

    2015-06-10

    Visual color is a primary quality factor for foods purchase; identifying factors that influence in situ color quality of pigmented maize during processing is important. Twenty-four genetically distinct pigmented maize hybrids (red/blue, blue, red, and purple) were used to investigate the effect of pigment and copigment composition on color stability during nixtamalization and tortilla chip processing. The red/blue and blue samples generally contained higher proportions of acylated anthocyanins (mainly cyanidin-3-(6″-malonylglucoside)) than the red and purple color classes. Phenolic amides were the major extractable copigments in all samples (450-764 μg/g), with red samples containing the most putrescines and blue samples containing the most spermidines. Even though samples with higher proportions of acylated anthocyanins retained more pigments during processing, this did not relate to final product color quality. In general, the red/blue samples retained their color quality the best and thus are good candidates for genetic improvement for direct processing into alkalized products.

  5. Recent perspectives on the genetic background of neural tube defects with special regard to iniencephaly.

    Science.gov (United States)

    Joó, József Gábor

    2009-04-01

    Iniencephaly is a rare and mostly lethal type of neural tube defect. The pattern of inheritance of this group of malformations is multifactorial, rendering the identification of the underlying causes. Numerous studies have been conducted to elucidate the genetic basis of human neurulation. Essential signaling pathways of the development of the CNS include the planar cell polarity pathway, which is important for the initiation of neural tube closure, as well as the sonic hedgehog pathway, which regulates the neural plate bending. Genes influencing the different stages of neurulation have been investigated for their eventual role in the development of these malformations. Among the environmental factors, folic acid seems to be the most important modifier of the risk of human neural tube defects. Genes of the folate metabolism pathways have also been investigated to identify mutations resulting in increased risk of neural tube defects. In this review we have attempted to summarize the knowledge on iniencephaly and neural tube defects, with special regard to genetic factors of the etiology.

  6. Primer on medical genomics part II: Background principles and methods in molecular genetics.

    Science.gov (United States)

    Tefferi, Ayalew; Wieben, Eric D; Dewald, Gordon W; Whiteman, David A H; Bernard, Matthew E; Spelsberg, Thomas C

    2002-08-01

    The nucleus of every human cell contains the full complement of the human genome, which consists of approximately 30,000 to 70,000 named and unnamed genes and many intergenic DNA sequences. The double-helical DNA molecule in a human cell, associated with special proteins, is highly compacted into 22 pairs of autosomal chromosomes and an additional pair of sex chromosomes. The entire cellular DNA consists of approximately 3 billion base pairs, of which only 1% is thought to encode a functional protein or a polypeptide. Genetic information is expressed and regulated through a complex system of DNA transcription, RNA processing, RNA translation, and posttranslational and cotranslational modification of proteins. Advances in molecular biology techniques have allowed accurate and rapid characterization of DNA sequences as well as identification and quantification of cellular RNA and protein. Global analytic methods and human genetic mapping are expected to accelerate the process of identification and localization of disease genes. In this second part of an educational series in medical genomics, selected principles and methods in molecular biology are recapped, with the intent to prepare the reader for forthcoming articles with a more direct focus on aspects of the subject matter.

  7. Cumulative BRCA mutation analysis in the Greek population confirms that homogenous ethnic background facilitates genetic testing.

    Science.gov (United States)

    Tsigginou, Alexandra; Vlachopoulos, Fotios; Arzimanoglou, Iordanis; Zagouri, Flora; Dimitrakakis, Constantine

    2015-01-01

    Screening for BRCA 1 and BRCA 2 mutations has long moved from the research lab to the clinic as a routine clinical genetic testing. BRCA molecular alteration pattern varies among ethnic groups which makes it already a less straightforward process to select the appropriate mutations for routine genetic testing on the basis of known clinical significance. The present report comprises an in depth literature review of the so far reported BRCA 1 and BRCA 2 molecular alterations in Greek families. Our analysis of Greek cumulative BRCA 1 and 2 molecular data, produced by several independent groups, confirmed that six recurrent deleterious mutations account for almost 60 % and 70 % of all BRCA 1 and 2 and BRCA 1 mutations, respectively. As a result, it makes more sense to perform BRCA mutation analysis in the clinic in two sequential steps, first conventional analysis for the six most prevalent pathogenic mutations and if none identified, a second step of New Generation Sequencing-based whole genome or whole exome sequencing would follow. Our suggested approach would enable more clinically meaningful, considerably easier and less expensive BRCA analysis in the Greek population which is considered homogenous.

  8. Electroretinogram analysis of relative spectral sensitivity in genetically identified dichromatic macaques.

    Science.gov (United States)

    Hanazawa, A; Mikami, A; Sulistyo Angelika, P; Takenaka, O; Goto, S; Onishi, A; Koike, S; Yamamori, T; Kato, K; Kondo, A; Suryobroto, B; Farajallah, A; Komatsu, H

    2001-07-03

    The retinas of macaque monkeys usually contain three types of photopigment, providing them with trichromatic color vision homologous to that of humans. However, we recently used molecular genetic analysis to identify several macaques with a dichromatic genotype. The affected X chromosome of these animals contains a hybrid gene of long-wavelength-sensitive (L) and middle-wavelength-sensitive (M) photopigments instead of separate genes encoding L and M photopigments. The product of the hybrid gene exhibits a spectral sensitivity close to that of M photopigment; consequently, male monkeys carrying the hybrid gene are genetic protanopes, effectively lacking L photopigment. In the present study, we assessed retinal expression of L photopigment in monkeys carrying the hybrid gene. The relative sensitivities to middle-wavelength (green) and long-wavelength (red) light were measured by electroretinogram flicker photometry. We found the sensitivity to red light to be extremely low in protanopic male monkeys compared with monkeys with the normal genotype. In female heterozygotes, sensitivity to red light was intermediate between the genetic protanopes and normal monkeys. Decreased sensitivity to long wavelengths was thus consistent with genetic loss of L photopigment.

  9. Genetic requirements for sensitivity of bacteriophage t7 to dideoxythymidine.

    Science.gov (United States)

    Tran, Ngoc Q; Tabor, Stanley; Richardson, Charles C

    2014-08-01

    We previously reported that the presence of dideoxythymidine (ddT) in the growth medium selectively inhibits the ability of bacteriophage T7 to infect Escherichia coli by inhibiting phage DNA synthese (N. Q. Tran, L. F. Rezende, U. Qimron, C. C. Richardson, and S. Tabor, Proc. Natl. Acad. Sci. U. S. A. 105:9373-9378, 2008, doi:10.1073/pnas.0804164105). In the presence of T7 gene 1.7 protein, ddT is taken up into the E. coli cell and converted to ddTTP. ddTTP is incorporated into DNA as ddTMP by the T7 DNA polymerase, resulting in chain termination. We have identified the pathway by which exogenous ddT is converted to ddTTP. The pathway consists of ddT transport by host nucleoside permeases and phosphorylation to ddTMP by the host thymidine kinase. T7 gene 1.7 protein phosphorylates ddTMP and ddTDP, resulting in ddTTP. A 74-residue peptide of the gene 1.7 protein confers ddT sensitivity to the same extent as the 196-residue wild-type gene 1.7 protein. We also show that cleavage of thymidine to thymine and deoxyribose-1-phosphate by the host thymidine phosphorylase greatly increases the sensitivity of phage T7 to ddT. Finally, a mutation in T7 DNA polymerase that leads to discrimination against the incorporation of ddTMP eliminates ddT sensitivity.

  10. Differential Cotton leaf crumple virus-VIGS-mediated gene silencing and viral genome localization in different Gossypium hirsutum genetic backgrounds

    KAUST Repository

    Idris, Ali

    2010-12-01

    A Cotton leaf crumple virus (CLCrV)-based gene silencing vector containing a fragment of the Gossypium hirsutum Magnesium chelatase subunit I was used to establish endogenous gene silencing in cotton of varied genetic backgrounds. Biolistic inoculation resulted in systemic and persistent photo-bleaching of the leaves and bolls of the seven cultivars tested, however, the intensity of silencing was variable. CLCrV-VIGS-mediated expression of green fluorescent protein was used to monitor the in planta distribution of the vector, indicating successful phloem invasion in all cultivars tested. Acala SJ-1, one of the cotton cultivars, was identified as a particularly optimal candidate for CLCrV-VIGS-based cotton reverse-genetics. © 2010 Elsevier Ltd.

  11. Virulence Genes, Genetic Diversity, Antimicrobial Susceptibility and Phylogenetic Background of Escherichia coli Isolates

    Directory of Open Access Journals (Sweden)

    Abdi

    2015-08-01

    Full Text Available Background The epidemiology of Uropathogenic Escherichia coli (UPEC in urban and rural communities in Iran was never investigated prior to this study. Objectives The aims of this study were to detect the frequency of virulence genes and determine the antimicrobial susceptibility and phylogenetic background of Escherichia coli isolates collected from urban and rural communities. Materials and Methods A total of 100 E. coli isolates were collected from urine samples of patients with urinary tract infections (UTIs residing in two different locations, and confirmed by current biochemical tests. The phylogenetic groups were determined by the triplex-polymerase chain reaction (PCR method, and multiplex PCRs were used to detect eight Vf genes (fimH, iucD, irp2, hlyA, ompT, iha, iroN, and cnf1. The susceptibility profile of E. coli isolates was determined by the disk diffusion method. Results Ninety-five percent of UPEC showed at least one of the virulence genes, the most prevalent being fimH (95%, followed by irp2 (89%, iucD (69%, ompT (67%, iroN (29%, and iha (29%. The various combinations of detected genes were designated as virulence patterns. Phylogenetic groups, B2 (55% and D (22%, comprised the majority of isolated strains. Phenotypic tests showed that 92%, 74% and 71% of the isolates were resistant to ampicillin, ceftizoxime and cefixime, respectively. Conclusions These findings indicate that the UPEC isolates had eight virulence factors with high frequencies. Moreover, these results suggest a direct connection between virulence factors, gene diversity, phylogenetic background, and antimicrobial resistance in UPEC isolates.

  12. [Permanent neonatal diabetes with known genetic background: oral drugs in treatment of childhood diabetes].

    Science.gov (United States)

    Gach, Agnieszka; Gadzicka, Anna; Młynarski, Wojciech

    2008-01-01

    Diabetes, which is diagnosed before 6 months of age, is patogenetically different than type 1 diabetes. This kind of diabetes also known as a neonatal diabetes is genetically determined with monogenic mode of inheritance. Most of these patients are carriers of heterozygous mutation in the KCNJ11 or ABCC8 gene. These mutations may activate the Kir6.2/SUR1 potassium channel in the beta cells and disturb insulin secretion, which in consequence leads to diabetes. This patological phenomenon is reversible if sulfonylureas are used as a first line therapy. In the current paper a systematic review of clinical aspects of sulfonylurea treatment in neonatal diabetes has been performed. This gives the further evidence that knowlegde of the patogenesis of neonatal diabetes may be easily transferred to bedside and clinical practice.

  13. [Clinical and genetic background of familial myelodysplasia and acute myeloid leukemia].

    Science.gov (United States)

    Király, Péter Attila; Kállay, Krisztián; Marosvári, Dóra; Benyó, Gábor; Szőke, Anita; Csomor, Judit; Bödör, Csaba

    2016-02-21

    Myelodysplastic syndrome and acute myeloid leukaemia are mainly sporadic diseases, however, rare familial cases exist. These disorders are considered rare, but are likely to be more common than currently appreciated, and are characterized by the autosomal dominant mutations of hematopoietic transcription factors. These syndromes have typical phenotypic features and are associated with an increased risk for developing overt malignancy. Currently, four recognized syndromes could be separated: familial acute myeloid leukemia with mutated CEBPA, familial myelodysplastic syndrome/acute myeloid leukemia with mutated GATA2, familial platelet disorder with propensity to myeloid malignancy with RUNX1 mutations, and telomere biology disorders due to mutations of TERC or TERT. Furthermore, there are new, emerging syndromes associated with germline mutations in novel genes including ANKRD26, ETV6, SRP72 or DDX41. This review will discuss the current understanding of the genetic basis and clinical presentation of familial leukemia and myelodysplasia.

  14. Response to dietary phosphorus deficiency is affected by genetic background in growing pigs.

    Science.gov (United States)

    Alexander, L S; Qu, A; Cutler, S A; Mahajan, A; Lonergan, S M; Rothschild, M F; Weber, T E; Kerr, B J; Stahl, C H

    2008-10-01

    Concern over the environmental effect of P excretion from pig production has led to reduced dietary P supplementation. To examine how genetics influence P utilization, 94 gilts sired by 2 genetic lines (PIC337 and PIC280) were housed individually and fed either a P-adequate diet (PA) or a 20% P-deficient diet (PD) for 14 wk. Initially and monthly, blood samples were collected and BW recorded after an overnight fast. Growth performance and plasma indicators of P status were determined monthly. At the end of the trial, carcass traits, meat quality, bone strength, and ash percentage were determined. Pigs fed the PD diet had decreased (P < 0.05) plasma P concentrations and poorer G:F (P < 0.05) over the length of the trial. After 4 wk on trial, pigs fed the PD diet had increased (P < 0.05) plasma 1,25(OH)(2)D(3) and decreased (P < 0.05) plasma parathyroid hormone compared with those fed the PA diet. At the end of the trial, pigs fed the PD diet had decreased (P < 0.05) BW, HCW, and percentage fat-free lean and tended to have decreased LM area (P = 0.06) and marbling (P = 0.09) and greater (P = 0.12) 10th-rib backfat than pigs fed the PA diet. Additionally, animals fed the PD diet had weaker bones and also decreased (P < 0.05) ash percentage and increased (P < 0.05) concentrations of 1alpha-hydroxylase and parathyroid hormone receptor mRNA in kidney tissue. Regardless of dietary treatment, PIC337-sired pigs consumed more feed and gained more BW than their PIC280-sired counterparts (P < 0.05) during the study. The PIC337-sired pigs also had greater (P < 0.05) HCW, larger (P < 0.01) LM area, and tended to have (P = 0.07) greater dressing percentage. Meat from the PIC337-sired pigs also tended to have greater (P = 0.12) concentrations of lactate but decreased (P = 0.07) concentrations of total glucose units 24 h postslaughter. Although plasma 1,25(OH)(2)D(3) concentrations were elevated (P < 0.05) in all the animals fed the PD diet, this elevation due to P deficiency

  15. Genetic Background Influences Adaptation To Cardiac Hypertrophy and Ca2+ Handling Gene Expression

    Directory of Open Access Journals (Sweden)

    Steve B Waters

    2013-03-01

    Full Text Available Genetic variability has a profound effect on the development of cardiac hypertrophy in response to stress. Consequently, using a variety of inbred mouse strains with known genetic profiles may be powerful models for studying the response to cardiovascular stress. To explore this approach we looked at male C57BL/6J and 129/SvJ mice. Hemodynamic analyses of left ventricular pressures indicated significant differences in 129/SvJ and C57BL/6J mice that implied altered Ca2+ handling. Specifically, 129/SvJ mice demonstrated reduced rates of relaxation and insensitivity to dobutamine(Db. We hypothesized that altered expression of genes controlling the influx and efflux of Ca2+ from the sarcoplasmic reticulum was responsible and investigated the expression of several genes involved in maintaining the intracellular and sarcoluminal Ca2+ concentration using quantitative real-time PCR analyses (qRT-PCR. We observed significant differences in baseline gene expression as well as different responses in expression to isoproterenol (ISO challenge. In untreated control animals, 129/SvJ mice expressed 1.68x more ryanodine recptor 2(Ryr2 mRNA than C57BL/6J mice but only 0.37x as much calsequestrin 2(Casq2. After treatment with ISO, sarco(endoplasmic reticulum Ca2+-ATPase(Serca2 expression was reduced nearly two-fold in 129/SvJ while expression in C57BL/6J was stable. Interestingly, β(1 adrenergic receptor(Adrb1 expression was lower in 129/SvJ compared to C57BL/6J at baseline and lower in both strains after treatment. Metabolically, the brain isoform of creatine kinase(Ckb was up-regulated in response to ISO in C57BL/6J but not in 129/SvJ. These data suggest that the two strains of mice regulate Ca2+ homeostasis via different mechanisms and may be useful in developing personalized therapies in human patients.

  16. Genetic background influences adaptation to cardiac hypertrophy and Ca(2+) handling gene expression.

    Science.gov (United States)

    Waters, Steve B; Diak, Douglass M; Zuckermann, Matthew; Goldspink, Paul H; Leoni, Lara; Roman, Brian B

    2013-01-01

    Genetic variability has a profound effect on the development of cardiac hypertrophy in response to stress. Consequently, using a variety of inbred mouse strains with known genetic profiles may be powerful models for studying the response to cardiovascular stress. To explore this approach we looked at male C57BL/6J and 129/SvJ mice. Hemodynamic analyses of left ventricular pressures (LVPs) indicated significant differences in 129/SvJ and C57BL/6J mice that implied altered Ca(2+) handling. Specifically, 129/SvJ mice demonstrated reduced rates of relaxation and insensitivity to dobutamine (Db). We hypothesized that altered expression of genes controlling the influx and efflux of Ca(2+) from the sarcoplasmic reticulum (SR) was responsible and investigated the expression of several genes involved in maintaining the intracellular and sarcoluminal Ca(2+) concentration using quantitative real-time PCR analyses (qRT-PCR). We observed significant differences in baseline gene expression as well as different responses in expression to isoproterenol (ISO) challenge. In untreated control animals, 129/SvJ mice expressed 1.68× more ryanodine receptor 2(Ryr2) mRNA than C57BL/6J mice but only 0.37× as much calsequestrin 2 (Casq2). After treatment with ISO, sarco(endo)plasmic reticulum Ca(2+)-ATPase(Serca2) expression was reduced nearly two-fold in 129/SvJ while expression in C57BL/6J was stable. Interestingly, β (1) adrenergic receptor(Adrb1) expression was lower in 129/SvJ compared to C57BL/6J at baseline and lower in both strains after treatment. Metabolically, the brain isoform of creatine kinase (Ckb) was up-regulated in response to ISO in C57BL/6J but not in 129/SvJ. These data suggest that the two strains of mice regulate Ca(2+) homeostasis via different mechanisms and may be useful in developing personalized therapies in human patients.

  17. On the contribution of Aitken mode particles to cloud droplet populations at continental background areas – a parametric sensitivity study

    Directory of Open Access Journals (Sweden)

    V.-M. Kerminen

    2007-05-01

    Full Text Available Aitken mode particles are potentially an important source of cloud droplets in continental background areas. In order to find out which physico-chemical properties of Aitken mode particles are most important regarding their cloud-nucleating ability, we applied a global sensitivity method to an adiabatic air parcel model simulating the number of cloud droplets formed on Aitken mode particles, CD2. The technique propagates uncertainties in the parameters describing the properties of Aitken mode to CD2. The results show that if the Aitken mode particles do not contain molecules that are able to reduce the particle surface tension more than 30% and/or decrease the mass accommodation coefficient of water, α, below 10−2, the chemical composition and modal properties may have roughly an equal importance at low updraft velocities characterized by maximum supersaturations <0.1%. For larger updraft velocities, however, the particle size distribution is clearly more important than the chemical composition. In general, CD2 exhibits largest sensitivity to the particle number concentration, followed by the particle size. Also the shape of the particle mode, characterized by the geometric standard deviation (GSD, can be as important as the mode mean size at low updraft velocities. Finally, the performed sensitivity analysis revealed also that the chemistry may dominate the total sensitivity of CD2 to the considered parameters if: 1 the value of α varies at least one order of magnitude more than what is expected for pure water surfaces (10−2–1, or 2 the particle surface tension varies more than roughly 30% under conditions close to reaching supersaturation.

  18. Influence of sex and genetic background on anxiety-related and stress-induced behaviour of prodynorphin-deficient mice.

    Science.gov (United States)

    Kastenberger, Iris; Lutsch, Christian; Herzog, Herbert; Schwarzer, Christoph

    2012-01-01

    The role of dynorphin/kappa opioid receptors in epilepsy and addiction are well accepted, but their function in emotional control is not yet fully understood. Data obtained from different strains of prodynorphin (Pdyn)- and kappa opioid receptor (KOP)-deficient mice do not provide a consistent picture of the functions of Dyn/KOP in anxiety, suggesting the influence of testing conditions and/or genetic background. Therefore, we investigated the behaviour and neurochemistry of male and female Pdyn KO mice on the balb/c and C57Bl/6N background. Consistent with our results obtained from male mice on the C57bl/6N background, we observed a less anxious phenotype in the elevated plus maze, open-field and light-dark test in male mice on the balb/c background. Female mice on the balb/c background also displayed less anxiety like behaviour; however these data reflect high trait anxiety and inter-individual differences. In contrast, female mice on the C57Bl/6N background displayed low trait anxiety and a paradigm-dependent reduction of anxiety. No differences were observed in the forced swim test, while balb/c Pdyn KO mice displayed prolonged immobility in the tail suspension test. In line with our previous results, we observed reduced CRH mRNA in the central amygdala in all groups of mice. In contrast, the recently observed CRH mRNA reduction in the hypothalamic paraventricular nucleus appears restricted to male, but not female mice. Our data support previous data suggesting a pronounced impact of endogenous prodynorphin-derived peptides on anxiety. Moreover, our data support the idea that the less anxious phenotype manifests only at elevated stress levels.

  19. Influence of sex and genetic background on anxiety-related and stress-induced behaviour of prodynorphin-deficient mice.

    Directory of Open Access Journals (Sweden)

    Iris Kastenberger

    Full Text Available The role of dynorphin/kappa opioid receptors in epilepsy and addiction are well accepted, but their function in emotional control is not yet fully understood. Data obtained from different strains of prodynorphin (Pdyn- and kappa opioid receptor (KOP-deficient mice do not provide a consistent picture of the functions of Dyn/KOP in anxiety, suggesting the influence of testing conditions and/or genetic background. Therefore, we investigated the behaviour and neurochemistry of male and female Pdyn KO mice on the balb/c and C57Bl/6N background. Consistent with our results obtained from male mice on the C57bl/6N background, we observed a less anxious phenotype in the elevated plus maze, open-field and light-dark test in male mice on the balb/c background. Female mice on the balb/c background also displayed less anxiety like behaviour; however these data reflect high trait anxiety and inter-individual differences. In contrast, female mice on the C57Bl/6N background displayed low trait anxiety and a paradigm-dependent reduction of anxiety. No differences were observed in the forced swim test, while balb/c Pdyn KO mice displayed prolonged immobility in the tail suspension test. In line with our previous results, we observed reduced CRH mRNA in the central amygdala in all groups of mice. In contrast, the recently observed CRH mRNA reduction in the hypothalamic paraventricular nucleus appears restricted to male, but not female mice. Our data support previous data suggesting a pronounced impact of endogenous prodynorphin-derived peptides on anxiety. Moreover, our data support the idea that the less anxious phenotype manifests only at elevated stress levels.

  20. Measuring and modeling for the assessment of the genetic background behind cognitive processes in donkeys.

    Science.gov (United States)

    Navas, Francisco Javier; Jordana, Jordi; León, José Manuel; Arando, Ander; Pizarro, Gabriela; McLean, Amy Katherine; Delgado, Juan Vicente

    2017-09-14

    New productive niches can offer new commercial perspectives linked to donkeys' products and human therapeutic or leisure applications. However, no assessment for selection criteria has been carried out yet. First, we assessed the animal inherent features and environmental factors that may potentially influence several cognitive processes in donkeys. Then, we aimed at describing a practical methodology to quantify such cognitive processes, seeking their inclusion in breeding and conservation programmes, through a multifactorial linear model. Sixteen cognitive process-related traits were scored on a problem-solving test in a sample of 300 Andalusian donkeys for three consecutive years from 2013 to 2015. The linear model assessed the influence and interactions of four environmental factors, sex as an animal-inherent factor, age as a covariable, and the interactions between these factors. Analyses of variance were performed with GLM procedure of SPSS Statistics for Windows, Version 24.0 software to assess the relative importance of each factor. All traits were significantly (Pprocesses, and stimulus which was not significant (Pprocesses. The development of complex multifactorial models to study cognitive processes may counteract the inherent variability in behavior genetics and the estimation and prediction of related breeding parameters, key for the implementation of successful conservation programmes in apparently functionally misplaced endangered breeds. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. An Enterobacter plasmid as a new genetic background for the transposon Tn1331

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    Alavi MR

    2011-11-01

    Full Text Available Mohammad R Alavi1,2, Vlado Antonic2, Adrien Ravizee1, Peter J Weina3, Mina Izadjoo1,2, Alexander Stojadinovic21Division of Wound Biology and Translational Research, Armed Forces Institute of Pathology and American Registry of Pathology, Washington DC, 2Combat Wound Initiative Program, Walter Reed Army Medical Center, Washington DC, 3The Walter Reed Army Institute of Research, Silver Spring, MD, USABackground: Genus Enterobacter includes important opportunistic nosocomial pathogens that could infect complex wounds. The presence of antibiotic resistance genes in these microorganisms represents a challenging clinical problem in the treatment of these wounds. In the authors’ screening of antibiotic-resistant bacteria from complex wounds, an Enterobacter species was isolated that harbors antibiotic-resistant plasmids conferring resistance to Escherichia coli. The aim of this study was to identify the resistance genes carried by one of these plasmids.Methods: The plasmids from the Enterobacter isolate were propagated in E. coli and one of the plasmids, designated as pR23, was sequenced by the Sanger method using fluorescent dye-terminator chemistry on a genetic analyzer. The assembled sequence was annotated by search of the GenBank database.Results: Plasmid pR23 is composed of the transposon Tn1331 and a backbone plasmid that is identical to the plasmid pPIGDM1 from Enterobacter agglomerans. The multidrug-resistance transposon Tn1331, which confers resistance to aminoglycoside and beta lactam antibiotics, has been previously isolated only from Klebsiella. The Enterobacter plasmid pPIGDM1, which carries a ColE1-like origin of replication and has no apparent selective marker, appears to provide a backbone for propagation of Tn1331 in Enterobacter. The recognition sequence of Tn1331 transposase for insertion into pPIGDM1 is the pentanucleotide TATTA, which occurs only once throughout the length of this plasmid.Conclusion: Transposition of Tn1331 into

  2. Genetic control of lithium sensitivity and regulation of inositol biosynthetic genes.

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    Jason King

    Full Text Available Lithium (Li(+ is a common treatment for bipolar mood disorder, a major psychiatric illness with a lifetime prevalence of more than 1%. Risk of bipolar disorder is heavily influenced by genetic predisposition, but is a complex genetic trait and, to date, genetic studies have provided little insight into its molecular origins. An alternative approach is to investigate the genetics of Li(+ sensitivity. Using the social amoeba Dictyostelium, we previously identified prolyl oligopeptidase (PO as a modulator of Li(+ sensitivity. In a link to the clinic, PO enzyme activity is altered in bipolar disorder patients. Further studies demonstrated that PO is a negative regulator of inositol(1,4,5trisphosphate (IP(3 synthesis, a Li(+ sensitive intracellular signal. However, it was unclear how PO could influence either Li(+ sensitivity or risk of bipolar disorder. Here we show that in both Dictyostelium and cultured human cells PO acts via Multiple Inositol Polyphosphate Phosphatase (Mipp1 to control gene expression. This reveals a novel, gene regulatory network that modulates inositol metabolism and Li(+ sensitivity. Among its targets is the inositol monophosphatase gene IMPA2, which has also been associated with risk of bipolar disorder in some family studies, and our observations offer a cellular signalling pathway in which PO activity and IMPA2 gene expression converge.

  3. Japanese quail's genetic background modulates effects of chronic stress on emotional reactivity but not spatial learning.

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    Agathe Laurence

    Full Text Available Chronic stress is known to enhance mammals' emotional reactivity and alters several of their cognitive functions, especially spatial learning. Few studies have investigated such effects in birds. We investigated the impact of a two-week stress on Japanese quail's emotional reactivity and spatial learning. Quail is an avian model widely used in laboratory studies and for extrapolation of data to other poultry species. As sensitivity to chronic stress can be modulated by intrinsic factors, we tested juvenile female Japanese quail from three lines, two of them divergently selected on tonic immobility duration, an indicator of general fearfulness. The different emotional reactivity levels of quail belonging to these lines can be revealed by a large variety of tests. Half of the birds were submitted to repeated unpredictable aversive events for two weeks, whereas the other half were left undisturbed. After this procedure, two tests (open field and emergence tests evaluated the emotional reactivity of treated and control quails. They were then trained in a T-maze for seven days and their spatial learning was tested. The chronic stress protocol had an impact on resting, preening and foraging in the home cage. As predicted, the emotional reactivity of treated quails, especially those selected for long tonic immobility duration, was higher. Our spatial learning data showed that the treatment enhanced acquisition but not memorization. However, intrinsic fearfulness did not seem to interact with the treatment in this test. According to an inverted U-shaped relationship between stress and cognition, chronic stress can improve the adaptability of birds to a stressful environment. We discussed the mechanisms possibly implied in the increase of emotional reactivity and spatial abilities.

  4. Marker-assisted introgression of five QTLs controlling fruit quality traits into three tomato lines revealed interactions between QTLs and genetic backgrounds.

    Science.gov (United States)

    Lecomte, L; Duffé, P; Buret, M; Servin, B; Hospital, F; Causse, M

    2004-08-01

    The evaluation of organoleptic quality of tomato fruit requires physical, chemical and sensory analyses, which are expensive and difficult to assess. Therefore, their practical use in phenotypic selection is difficult. In a previous study, the genetic control of several traits related to organoleptic quality of fresh-market tomato fruit was investigated. Five chromosome regions strongly involved in organoleptic quality attributes were then chosen to be introgressed into three different recipient lines through marker-assisted selection. A marker-assisted backcross (MABC) strategy was performed, as all the favorable alleles for quality traits were provided by the same parental tomato line, whose fruit weight (FW) and firmness were much lower than those of the lines commonly used to develop fresh market varieties. Three improved lines were obtained after three backcrossing and two selfing generations. The implementation of the MABC scheme is described. The three improved lines were crossed together and with the recipient lines in a half-diallel mating scheme, and the simultaneous effect of the five quantitative trait locus (QTL) regions was compared in different genetic backgrounds. Significant effects of the introgressed regions and of the genetic backgrounds were shown. Additive effects were detected for soluble solid and reducing sugar content in two genetic backgrounds. A partially dominant effect on titratable acidity was detected in only one genetic background. In contrast, additive to dominant unfavorable effects of the donor alleles were detected for FW and locule number in the three genetic backgrounds. Recessive QTL effects on firmness were only detected in the two firmest genetic backgrounds. Comparison of the hybrids in the half-diallel gave complementary information on the effects of: (1) the alleles at the selected regions, (2) the genetic backgrounds and (3) their interaction. Breeding efficiency strongly varied according to the recipient parent, and

  5. Neuropeptide Y-Y2 receptor knockout mice: influence of genetic background on anxiety-related behaviors.

    Science.gov (United States)

    Zambello, E; Zanetti, L; Hédou, G F; Angelici, O; Arban, R; Tasan, R O; Sperk, G; Caberlotto, L

    2011-03-10

    Neuropeptide Y (NPY) has been extensively studied in relation to anxiety and depression but of the seven NPY receptors known to date, it is not yet clear which one is mainly involved in mediating its effects in emotional behavior. Mice lacking the NPY-Y2 receptors were previously shown to be less anxious due to their improved ability to cope with stressful situations. In the present study, the behavioral phenotype including the response to challenges was analyzed in NPY-Y2 knockout (KO) mice backcrossed in to congenic C57BL/6 background. In the elevated plus-maze (EPM) and the forced swim test (FST), the anxiolytic-like or antidepressant-like phenotype of the NPY-Y2 KO mice could not be confirmed, although this study differs from the previous one only with regard to the genetic background of the mice. In addition, no differences in response to acute stress or to the antidepressant desipramine in the FST were detected between wild type (WT) and NPY-Y2 KO animals. These results suggest that the genetic background of the animals appears to have a strong influence on the behavioral phenotype of NPY-Y2 KO mice. Additionally, to further characterize the animals by their biochemical response to a challenge, the neurochemical changes induced by the anxiogenic compound yohimbine were measured in the medial prefrontal cortex (mPFC) of NPY-Y2 KO and compared to WT mice. Dopamine (DA) levels were significantly increased by yohimbine in the WT but unaffected in the KO mice, suggesting that NPY-Y2 receptor exerts a direct control over both the tonic and phasic release of DA and that, although the anxiety-like behavior of these NPY-Y2 KO mice is unaltered, there are clear modifications of DA dynamics. However, yohimbine led to a significant increase in noradrenaline (NA) concentration and a slight reduction in serotonin concentration that were identical for both phenotypes.

  6. DBA/2J genetic background exacerbates spontaneous lethal seizures but lessens amyloid deposition in a mouse model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Harriet M Jackson

    Full Text Available Alzheimer's disease (AD is a leading cause of dementia in the elderly and is characterized by amyloid plaques, neurofibrillary tangles (NFTs and neuronal dysfunction. Early onset AD (EOAD is commonly caused by mutations in amyloid precursor protein (APP or genes involved in the processing of APP including the presenilins (e.g. PSEN1 or PSEN2. In general, mouse models relevant to EOAD recapitulate amyloidosis, show only limited amounts of NFTs and neuronal cell dysfunction and low but significant levels of seizure susceptibility. To investigate the effect of genetic background on these phenotypes, we generated APPswe and PSEN1de9 transgenic mice on the seizure prone inbred strain background, DBA/2J. Previous studies show that the DBA/2J genetic background modifies plaque deposition in the presence of mutant APP but the impact of PSEN1de9 has not been tested. Our study shows that DBA/2J.APPswePSEN1de9 mice are significantly more prone to premature lethality, likely to due to lethal seizures, compared to B6.APPswePSEN1de9 mice-70% of DBA/2J.APPswePSEN1de9 mice die between 2-3 months of age. Of the DBA/2J.APPswePSEN1de9 mice that survived to 6 months of age, plaque deposition was greatly reduced compared to age-matched B6.APPswePSEN1de9 mice. The reduction in plaque deposition appears to be independent of microglia numbers, reactive astrocytosis and complement C5 activity.

  7. Effect of the genetic background on recombination frequency in the cn-vg region of the second chromosome of natural populations of Drosophila melanogaster.

    Science.gov (United States)

    Hofmanová, J

    1975-01-01

    Newly established test stocks made it possible to follow the effect of three different defined genetic backgrounds (first and third chromosomes) on recombination frequency in the cn-vg region of the second chromosomes isolated from four natural populations of Drosophila melanogaster. One background was composed of the chromosomes with inversions obtained from the stock (see article) and another two backgrounds were of the standard type consisting one-half of the original chromosomes from the natural population and one-half of the chromosomes of the stocks Oregon R or Samarkand. Using the analysis of variance significant differences in RF values were found between and within populations and especially between the different backgrounds. Some simple and double interactions between the above factors played a role. The highest RF values were obtained on the background [corrected] with inversions. The effect of the different genetic backgrounds [corrected] by the action of the genetic modifiers of RF. The different genetic backgrounds affected the variations in RF values in individual populations and the different populations reacted differentially to the changed genetic background. The design of the experiment permitted an estimation of the causal compoenents of variance and heritability of RF from the sib analysis. The additive component of variance was present in only two of the populations under test; the respective estimates of heritability were very low.

  8. Effect of test duration and feeding on relative sensitivity of genetically distinct clades of Hyalella azteca.

    Science.gov (United States)

    Soucek, David J; Dickinson, Amy; Major, Kaley M; McEwen, Abigail R

    2013-11-01

    The amphipod Hyalella azteca is widely used in ecotoxicology laboratories for the assessment of chemical risks to aquatic environments, and it is a cryptic species complex with a number of genetically distinct strains found in wild populations. While it would be valuable to note differences in contaminant sensitivity among different strains collected from various field sites, those findings would be influenced by acclimation of the populations to local conditions. In addition, potential differences in metabolism or lipid storage among different strains may confound assessment of sensitivity in unfed acute toxicity tests. In the present study, our aim was to assess whether there are genetic differences in contaminant sensitivity among three cryptic provisional species of H. azteca. Therefore, we used organisms cultured under the same conditions, assessed their ability to survive for extended periods without food, and conducted fed and unfed acute toxicity tests with two anions (nitrate and chloride) whose toxicities are not expected to be altered by the addition of food. We found that the three genetically distinct clades of H. azteca had substantially different responses to starvation, and the presence/absence of food during acute toxicity tests had a strong role in determining the relative sensitivity of the three clades. In fed tests, where starvation was no longer a potential stressor, significant differences in sensitivity were still observed among the three clades. In light of these differences in sensitivity, we suggest that ecotoxicology laboratories consider using a provisional species in toxicity tests that is a regionally appropriate surrogate.

  9. Sensitivity Analyses for Robust Causal Inference from Mendelian Randomization Analyses with Multiple Genetic Variants

    Science.gov (United States)

    Bowden, Jack; Fall, Tove; Ingelsson, Erik; Thompson, Simon G.

    2017-01-01

    Mendelian randomization investigations are becoming more powerful and simpler to perform, due to the increasing size and coverage of genome-wide association studies and the increasing availability of summarized data on genetic associations with risk factors and disease outcomes. However, when using multiple genetic variants from different gene regions in a Mendelian randomization analysis, it is highly implausible that all the genetic variants satisfy the instrumental variable assumptions. This means that a simple instrumental variable analysis alone should not be relied on to give a causal conclusion. In this article, we discuss a range of sensitivity analyses that will either support or question the validity of causal inference from a Mendelian randomization analysis with multiple genetic variants. We focus on sensitivity analyses of greatest practical relevance for ensuring robust causal inferences, and those that can be undertaken using summarized data. Aside from cases in which the justification of the instrumental variable assumptions is supported by strong biological understanding, a Mendelian randomization analysis in which no assessment of the robustness of the findings to violations of the instrumental variable assumptions has been made should be viewed as speculative and incomplete. In particular, Mendelian randomization investigations with large numbers of genetic variants without such sensitivity analyses should be treated with skepticism. PMID:27749700

  10. Aggressive Behavior between Siblings and the Development of Externalizing Problems: Evidence from a Genetically Sensitive Study

    Science.gov (United States)

    Natsuaki, Misaki N.; Ge, Xiaojia; Reiss, David; Neiderhiser, Jenae M.

    2009-01-01

    This study investigated the prospective links between sibling aggression and the development of externalizing problems using a multilevel modeling approach with a genetically sensitive design. The sample consisted of 780 adolescents (390 sibling pairs) who participated in 2 waves of the Nonshared Environment in Adolescent Development project.…

  11. Genetic variants associated with thermal pain sensitivity in a paediatric population

    NARCIS (Netherlands)

    Matic, M.; Bosch, G.E. van den; Wildt, S.N. de; Tibboel, D.; Schaik, R.H. van

    2016-01-01

    Pain sensitivity is an inherited factor that varies strongly between individuals. We investigated whether genetic polymorphisms in the candidate genes COMT, OPRM1, OPRD1, TAOK3, TRPA1, TRPV1, and SCN9A are contributing to experimental pain variability between children. Our study included 136

  12. Genetic variance in micro-environmental sensitivity for milk and milk quality in Walloon Holstein cattle

    NARCIS (Netherlands)

    Vandenplas, J.; Bastin, C.; Gengler, N.; Mulder, H.A.

    2013-01-01

    Animals that are robust to environmental changes are desirable in the current dairy industry. Genetic differences in micro-environmental sensitivity can be studied through heterogeneity of residual variance between animals. However, residual variance between animals is usually assumed to be homogene

  13. Differential Insulin Secretion of High-Fat Diet-Fed C57BL/6NN and C57BL/6NJ Mice: Implications of Mixed Genetic Background in Metabolic Studies.

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    Camille Attané

    Full Text Available Many metabolic studies employ tissue-specific gene knockout mice, which requires breeding of floxed gene mice, available mostly on C57BL/6N (NN genetic background, with cre or Flp recombinase-expressing mice, available on C57BL/6J (JJ background, resulting in the generation of mixed C57BL/6NJ (NJ genetic background mice. Recent awareness of many genetic differences between NN and JJ strains including the deletion of nicotinamide nucleotide transhydrogenase (nnt, necessitates examination of the consequence of mixed NJ background on glucose tolerance, beta cell function and other metabolic parameters. Male mice with NN and NJ genetic background were fed with normal or high fat diets (HFD for 12 weeks and glucose and insulin homeostasis were studied. Genotype had no effect on body weight and food intake in mice fed normal or high fat diets. Insulinemia in the fed and fasted states and after a glucose challenge was lower in HFD-fed NJ mice, even though their glycemia and insulin sensitivity were similar to NN mice. NJ mice showed mild glucose intolerance. Moreover, glucose- but not KCl-stimulated insulin secretion in isolated islets was decreased in HFD-fed NJ vs NN mice without changes in insulin content and beta cell mass. Under normal diet, besides reduced fed insulinemia, NN and NJ mice presented similar metabolic parameters. However, HFD-fed NJ mice displayed lower fed and fasted insulinemia and glucose-induced insulin secretion in vivo and ex vivo, as compared to NN mice. These results strongly caution against using unmatched mixed genetic background C57BL/6 mice for comparisons, particularly under HFD conditions.

  14. The background of mitochondrial DNA haplogroup J increases the sensitivity of Leber's hereditary optic neuropathy cells to 2,5-hexanedione toxicity.

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    Anna Ghelli

    Full Text Available Leber's hereditary optic neuropathy (LHON is a maternally inherited blinding disease due to mitochondrial DNA (mtDNA point mutations in complex I subunit genes, whose incomplete penetrance has been attributed to both genetic and environmental factors. Indeed, the mtDNA background defined as haplogroup J is known to increase the penetrance of the 11778/ND4 and 14484/ND6 mutations. Recently it was also documented that the professional exposure to n-hexane might act as an exogenous trigger for LHON. Therefore, we here investigate the effect of the n-hexane neurotoxic metabolite 2,5-hexanedione (2,5-HD on cell viability and mitochondrial function of different cell models (cybrids and fibroblasts carrying the LHON mutations on different mtDNA haplogroups. The viability of control and LHON cybrids and fibroblasts, whose mtDNAs were completely sequenced, was assessed using the MTT assay. Mitochondrial ATP synthesis rate driven by complex I substrates was determined with the luciferine/luciferase method. Incubation with 2,5-HD caused the maximal loss of viability in control and LHON cells. The toxic effect of this compound was similar in control cells irrespective of the mtDNA background. On the contrary, sensitivity to 2,5-HD induced cell death was greatly increased in LHON cells carrying the 11778/ND4 or the 14484/ND6 mutation on haplogroup J, whereas the 11778/ND4 mutation in association with haplogroups U and H significantly improved cell survival. The 11778/ND4 mutation on haplogroup U was also more resistant to inhibition of complex I dependent ATP synthesis by 2,5-HD. In conclusion, this study shows that mtDNA haplogroups modulate the response of LHON cells to 2,5-HD. In particular, haplogroup J makes cells more sensitive to its toxic effect. This is the first evidence that an mtDNA background plays a role by interacting with an environmental factor and that 2,5-HD may be a risk element for visual loss in LHON. This proof of principle has broad

  15. Evidence That Transition from Health to Psychotic Disorder Can Be Traced to Semi-Ubiquitous Environmental Effects Operating against Background Genetic Risk

    NARCIS (Netherlands)

    van Nierop, Martine; Janssens, Mayke; Bruggeman, Richard; Cahn, Wiepke; de Haan, Lieuwe; Kahn, Rene S.; Meijer, Carin J.; Myin-Germeys, Inez; van Os, Jim; Wiersma, Durk

    2013-01-01

    Background: In order to assess the importance of environmental and genetic risk on transition from health to psychotic disorder, a prospective study of individuals at average (n=462) and high genetic risk (n=810) was conducted. Method: A three-year cohort study examined the rate of transition to psy

  16. MOESHA: A genetic algorithm for automatic calibration and estimation of parameter uncertainty and sensitivity of hydrologic models

    Science.gov (United States)

    Characterization of uncertainty and sensitivity of model parameters is an essential and often overlooked facet of hydrological modeling. This paper introduces an algorithm called MOESHA that combines input parameter sensitivity analyses with a genetic algorithm calibration routin...

  17. Ultrasonic and sensory characterization of dry-cured ham fat from Iberian pigs with different genetics and feeding backgrounds.

    Science.gov (United States)

    Niñoles, L; Sanjuan, N; Ventanas, S; Benedito, J

    2008-11-01

    The textural and ultrasonic properties of the subcutaneous fat from five batches of dry-cured hams from animals with different genetics (Iberian, Iberian×Duroc) and type of feeding ("montanera", concentrate feeds with different oleic acid content) were studied and related to the sensory traits (oiliness and brightness) of their biceps femoris muscle. The different genetics and feeding backgrounds found in the batches brought about differences in their ultrasonic velocities (average velocity from 4 to 20°C ranged from 1608 to 1650m/s) and textural parameters (maximum force at 8°C ranged from 11 to 21N). On average, batches with lower textural parameters had lower velocities and higher sensory scores. Ultrasonic measurements were used to carry out a discriminant analysis which allowed 78.3% of the samples to be correctly classified in the batches considered. Therefore, ultrasonic and sensory techniques could be useful in the characterization and differentiation of dry-cured hams from Iberian pigs.

  18. [Genetic background in common forms of obesity - from studies on identical twins to candidate genes of obesity].

    Science.gov (United States)

    Bendlová, Běla; Lukášová, Petra; Vaňková, Markéta; Vejražková, Daniela; Bradnová, Olga; Včelák, Josef; Stanická, Soňa; Zamrazilová, Hana; Aldhoon-Hainerová, Irena; Dušátková, Lenka; Kunešová, Marie; Hainer, Vojtěch

    2014-01-01

    Common obesity is a result of interaction between genes and environmental/lifestyle factors, with heritability estimates 40-70%. Not only the susceptibility to obesity but also the success of weight management depends on the genetic background of each individual. This paper summarizes the up-to-date knowledge on genetic causes of common obesities. Introduction of genome-wide association studies (GWAS) led to an identification of a total of 32 variants associated with obesity/BMI and 14 with body fat distribution. Further, a great progress in revealing the mechanisms regulating the energy balance was also noted. However, the proportion of explained variance for BMI is still low, suggesting other mechanisms such as gene-gene and gene-environment interactions, rare gene variants, copy number variants polymorphisms, or epigenetic modifications and microRNAs regulating gene transcription. In summary, we present results of our studies on obesity risk variants in Czech adults, children and adolescents including those evaluating the influence of selected gene variants on the outcomes of weight management.

  19. Genes and personality characteristics: Possible association of the genetic background with intelligence and decision making in 830 Caucasian Greek subjects.

    Science.gov (United States)

    Marinos, Georgios; Naziris, Nikolaos; Limnaios, Stefanos A; Drakoulis, Nikolaos

    2014-12-01

    It is well known that intelligence consists of a variety of interactional and cognitive skills and abilities (e.g. tradecraft; critical and divergent thinking; perception of foreign information). Decision making is defined as the conscious choice between given options, relating to a problem. Both genetic background and environment comprise key elements for personality characteristics of the human being. The aim of this study is to determine the frequency distribution of rs324420, rs1800497, rs363050, rs6265, rs1328674 polymorphisms known to be involved in individual personality characteristics, in 830 Greek Subjects. The study is independent from direct clinical measurements (e.g. IQ measurements; physiological tests). The population of the volunteers is described, based on genotype, sex, with the respective gene frequencies, including the Minor Allele Frequency (MAF). A potential influence of the volunteer gender with the above characteristics (based on genotypes and alleles) is examined and finally, volunteers are classified as follows: A volunteer receives + 1, for each genotype/allele, which enhances his intelligence or his decision-making. In contrast, he receives - 1, for each genotype/allele, which relegates the individual characteristic. No statistically significant gender-characteristics correlation is observed. According to their genetic profile, a rate of 92.5%, of the volunteers may be characterized by prudence and temperance of thought, with only a small proportion of them (7.5%) may be classified as genetically spontaneous and adventurous. Regarding intelligence, the study population may lay around average and a little above it, at a rate of 96.3%, while the edges of the scale suggest only a 0.5% of the volunteers, who, although the "smartest", somehow seem to lack prudence. In conclusion, individuals with low cognitive ability may be more prudent than others and vice versa, while the "smartest" ones tend to be more risky, in decision

  20. Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons

    DEFF Research Database (Denmark)

    Rotger, Margalida; Glass, Tracy R; Junier, Thomas

    2013-01-01

    BACKGROUND: Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the set...

  1. Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons

    NARCIS (Netherlands)

    Rotger, Margalida; Glass, Tracy R; Junier, Thomas; Lundgren, Jens; Neaton, James D; Poloni, Estella S; van 't Wout, Angélique B; Lubomirov, Rubin; Colombo, Sara; Martinez, Raquel; Rauch, Andri; Günthard, Huldrych F; Neuhaus, Jacqueline; Wentworth, Deborah; van Manen, Danielle; Gras, Luuk A; Schuitemaker, Hanneke; Albini, Laura; Torti, Carlo; Jacobson, Lisa P; Li, Xiuhong; Kingsley, Lawrence A; Carli, Federica; Guaraldi, Giovanni; Ford, Emily S; Sereti, Irini; Hadigan, Colleen; Martinez, Esteban; Arnedo, Mireia; Egaña-Gorroño, Lander; Gatell, Jose M; Law, Matthew; Bendall, Courtney; Petoumenos, Kathy; Rockstroh, Jürgen; Wasmuth, Jan-Christian; Kabamba, Kabeya; Delforge, Marc; De Wit, Stephane; Berger, Florian; Mauss, Stefan; de Paz Sierra, Mariana; Losso, Marcelo; Belloso, Waldo H; Leyes, Maria; Campins, Antoni; Mondi, Annalisa; De Luca, Andrea; Bernardino, Ignacio; Barriuso-Iglesias, Mónica; Torrecilla-Rodriguez, Ana; Gonzalez-Garcia, Juan; Arribas, José R; Fanti, Iuri; Gel, Silvia; Puig, Jordi; Negredo, Eugenia; Gutierrez, Mar; Domingo, Pere; Fischer, Julia; Fätkenheuer, Gerd; Alonso-Villaverde, Carlos; Macken, Alan; Woo, James; McGinty, Tara; Mallon, Patrick; Mangili, Alexandra; Skinner, Sally; Wanke, Christine A; Reiss, Peter; Weber, Rainer; Bucher, Heiner C; Fellay, Jacques; Telenti, Amalio; Tarr, Philip E; Schölvinck, Elisabeth H.

    2013-01-01

    BACKGROUND: Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the settin

  2. Progression of Left Ventricular Dysfunction and Remodelling under Optimal Medical Therapy in CHF Patients: Role of Individual Genetic Background

    Directory of Open Access Journals (Sweden)

    Marzia Rigolli

    2011-01-01

    Full Text Available Background. Neurohormonal systems play an important role in chronic heart failure (CHF. Due to interindividual heterogeneity in the benefits of therapy, it may be hypothesized that polymorphisms of neurohormonal systems may affect left ventricular (LV remodelling and systolic function. We aimed to assess whether genetic background of maximally treated CHF patients predicts variations in LV systolic function and volumes. Methods and Results. We prospectively studied 131 CHF outpatients on optimal treatment for at least six months. Echocardiographic evaluations were performed at baseline and after 12 months. Genotype analysis for ACE I/D, β1adrenergic receptor (AR Arg389Gly, β2AR Arg16Gly, and β2AR Gln27Glu polymorphisms was performed. No differences in baseline characteristics were detected among subgroups. ACE II was a significant predictor of improvement of LV end-diastolic and end-systolic volume (=.003 and =.002, respectively but not of LV ejection fraction (LVEF; β1AR389 GlyGly was related to improvement of LVEF (=.02 and LV end-systolic volume (=.01. The predictive value of polymorphisms remained after adjustment for other clinically significant predictors (<.05 for all. Conclusions. ACE I/D and β1AR Arg389Gly polymorphisms are independent predictors of reverse remodeling and systolic function recovery in CHF patients under optimal treatment.

  3. Shared genetic background for regulation of mood and sleep: association of GRIA3 with sleep duration in healthy Finnish women.

    Science.gov (United States)

    Utge, Siddheshwar; Kronholm, Erkki; Partonen, Timo; Soronen, Pia; Ollila, Hanna M; Loukola, Anu; Perola, Markus; Salomaa, Veikko; Porkka-Heiskanen, Tarja; Paunio, Tiina

    2011-10-01

    Sleeping 7 to 8 hours per night appears to be optimal, since both shorter and longer sleep times are related to increased morbidity and mortality. Depressive disorder is almost invariably accompanied by disturbed sleep, leading to decreased sleep duration, and disturbed sleep may be a precipitating factor in the initiation of depressive illness. Here, we examined whether, in healthy individuals, sleep duration is associated with genes that we earlier found to be associated with depressive disorder. Population-based molecular genetic study. Regression analysis of 23 risk variants for depressive disorder from 12 genes to sleep duration in healthy individuals. Three thousand, one hundred, forty-seven individuals (25-75 y) from population-based Health 2000 and FINRISK 2007 samples. We found a significant association of rs687577 from GRIA3 on the X-chromosome with sleep duration in women (permutation-based corrected empirical P=0.00001, β=0.27; Bonferroni corrected P=0.0052; f=0.11). The frequency of C/C genotype previously found to increase risk for depression in women was highest among those who slept for 8 hours or less in all age groups younger than 70 years. Its frequency decreased with the lengthening of sleep duration, and those who slept for 9 to 10 hours showed a higher frequency of C/A or A/A genotypes, when compared with the midrange sleepers (7-8 hours) (permutation-based corrected empirical P=0.0003, OR=1.81). The GRIA3 polymorphism that was previously found to be associated with depressive disorder in women showed an association with sleep duration in healthy women. Mood disorders and short sleep may share a common genetic background and biologic mechanisms that involve glutamatergic neurotransmission.

  4. Insulin-like signaling (IIS) responses to temperature, genetic background, and growth variation in garter snakes with divergent life histories.

    Science.gov (United States)

    Reding, Dawn M; Addis, Elizabeth A; Palacios, Maria G; Schwartz, Tonia S; Bronikowski, Anne M

    2016-07-01

    The insulin/insulin-like signaling pathway (IIS) has been shown to mediate life history trade-offs in mammalian model organisms, but the function of this pathway in wild and non-mammalian organisms is understudied. Populations of western terrestrial garter snakes (Thamnophis elegans) around Eagle Lake, California, have evolved variation in growth and maturation rates, mortality senescence rates, and annual reproductive output that partition into two ecotypes: "fast-living" and "slow-living". Thus, genes associated with the IIS network are good candidates for investigating the mechanisms underlying ecological divergence in this system. We reared neonates from each ecotype for 1.5years under two thermal treatments. We then used qPCR to compare mRNA expression levels in three tissue types (brain, liver, skeletal muscle) for four genes (igf1, igf2, igf1r, igf2r), and we used radioimmunoassay to measure plasma IGF-1 and IGF-2 protein levels. Our results show that, in contrast to most mammalian model systems, igf2 mRNA and protein levels exceed those of igf1 and suggest an important role for igf2 in postnatal growth in reptiles. Thermal rearing treatment and recent growth had greater impacts on IGF levels than genetic background (i.e., ecotype), and the two ecotypes responded similarly. This suggests that observed ecotypic differences in field measures of IGFs may more strongly reflect plastic responses in different environments than evolutionary divergence. Future analyses of additional components of the IIS pathway and sequence divergence between the ecotypes will further illuminate how environmental and genetic factors influence the endocrine system and its role in mediating life history trade-offs.

  5. Genes and personality characteristics: Possible association of the genetic background with intelligence and decision making in 830 Caucasian Greek subjects

    Directory of Open Access Journals (Sweden)

    Georgios Marinos

    2014-12-01

    Full Text Available It is well known that intelligence consists of a variety of interactional and cognitive skills and abilities (e.g. tradecraft; critical and divergent thinking; perception of foreign information. Decision making is defined as the conscious choice between given options, relating to a problem. Both genetic background and environment comprise key elements for personality characteristics of the human being. The aim of this study is to determine the frequency distribution of rs324420, rs1800497, rs363050, rs6265, rs1328674 polymorphisms known to be involved in individual personality characteristics, in 830 Greek Subjects. The study is independent from direct clinical measurements (e.g. IQ measurements; physiological tests. The population of the volunteers is described, based on genotype, sex, with the respective gene frequencies, including the Minor Allele Frequency (MAF. A potential influence of the volunteer gender with the above characteristics (based on genotypes and alleles is examined and finally, volunteers are classified as follows: A volunteer receives +1, for each genotype/allele, which enhances his intelligence or his decision-making. In contrast, he receives −1, for each genotype/allele, which relegates the individual characteristic. No statistically significant gender-characteristics correlation is observed. According to their genetic profile, a rate of 92.5%, of the volunteers may be characterized by prudence and temperance of thought, with only a small proportion of them (7.5% may be classified as genetically spontaneous and adventurous. Regarding intelligence, the study population may lay around average and a little above it, at a rate of 96.3%, while the edges of the scale suggest only a 0.5% of the volunteers, who, although the “smartest”, somehow seem to lack prudence. In conclusion, individuals with low cognitive ability may be more prudent than others and vice versa, while the “smartest” ones tend to be more risky, in

  6. Genetic Variants Associated With Glycine Metabolism and Their Role in Insulin Sensitivity and Type 2 Diabetes

    DEFF Research Database (Denmark)

    Xie, W. J.; Wood, A. R.; Lyssenko, V.;

    2013-01-01

    . The top-ranking metabolites were in the glutathione and glycine biosynthesis pathways. We aimed to identify common genetic variants associated with metabolites in these pathways and test their role in insulin sensitivity and type 2 diabetes. With 1,004 nondiabetic individuals from the RISC study, we...... performed a genome-wide association study (GWAS) of 14 insulin sensitivity-related metabolites and one metabolite ratio. We replicated our results in the Botnia study (n = 342). We assessed the association of these variants with diabetes-related traits in GWAS meta-analyses (GENESIS [including RISC, EUGENE2...... for association between these variants and insulin resistance or diabetes. Genetic variants associated with genes in the glycine biosynthesis pathways do not provide consistent evidence for a role of glycine in diabetes-related traits....

  7. Strain Dependent Genetic Networks for Antibiotic-Sensitivity in a Bacterial Pathogen with a Large Pan-Genome.

    Directory of Open Access Journals (Sweden)

    Tim van Opijnen

    2016-09-01

    Full Text Available The interaction between an antibiotic and bacterium is not merely restricted to the drug and its direct target, rather antibiotic induced stress seems to resonate through the bacterium, creating selective pressures that drive the emergence of adaptive mutations not only in the direct target, but in genes involved in many different fundamental processes as well. Surprisingly, it has been shown that adaptive mutations do not necessarily have the same effect in all species, indicating that the genetic background influences how phenotypes are manifested. However, to what extent the genetic background affects the manner in which a bacterium experiences antibiotic stress, and how this stress is processed is unclear. Here we employ the genome-wide tool Tn-Seq to construct daptomycin-sensitivity profiles for two strains of the bacterial pathogen Streptococcus pneumoniae. Remarkably, over half of the genes that are important for dealing with antibiotic-induced stress in one strain are dispensable in another. By confirming over 100 genotype-phenotype relationships, probing potassium-loss, employing genetic interaction mapping as well as temporal gene-expression experiments we reveal genome-wide conditionally important/essential genes, we discover roles for genes with unknown function, and uncover parts of the antibiotic's mode-of-action. Moreover, by mapping the underlying genomic network for two query genes we encounter little conservation in network connectivity between strains as well as profound differences in regulatory relationships. Our approach uniquely enables genome-wide fitness comparisons across strains, facilitating the discovery that antibiotic responses are complex events that can vary widely between strains, which suggests that in some cases the emergence of resistance could be strain specific and at least for species with a large pan-genome less predictable.

  8. Strain Dependent Genetic Networks for Antibiotic-Sensitivity in a Bacterial Pathogen with a Large Pan-Genome.

    Science.gov (United States)

    van Opijnen, Tim; Dedrick, Sandra; Bento, José

    2016-09-01

    The interaction between an antibiotic and bacterium is not merely restricted to the drug and its direct target, rather antibiotic induced stress seems to resonate through the bacterium, creating selective pressures that drive the emergence of adaptive mutations not only in the direct target, but in genes involved in many different fundamental processes as well. Surprisingly, it has been shown that adaptive mutations do not necessarily have the same effect in all species, indicating that the genetic background influences how phenotypes are manifested. However, to what extent the genetic background affects the manner in which a bacterium experiences antibiotic stress, and how this stress is processed is unclear. Here we employ the genome-wide tool Tn-Seq to construct daptomycin-sensitivity profiles for two strains of the bacterial pathogen Streptococcus pneumoniae. Remarkably, over half of the genes that are important for dealing with antibiotic-induced stress in one strain are dispensable in another. By confirming over 100 genotype-phenotype relationships, probing potassium-loss, employing genetic interaction mapping as well as temporal gene-expression experiments we reveal genome-wide conditionally important/essential genes, we discover roles for genes with unknown function, and uncover parts of the antibiotic's mode-of-action. Moreover, by mapping the underlying genomic network for two query genes we encounter little conservation in network connectivity between strains as well as profound differences in regulatory relationships. Our approach uniquely enables genome-wide fitness comparisons across strains, facilitating the discovery that antibiotic responses are complex events that can vary widely between strains, which suggests that in some cases the emergence of resistance could be strain specific and at least for species with a large pan-genome less predictable.

  9. Lactic Acid Bacteria Protects Caenorhabditis elegans from Toxicity of Graphene Oxide by Maintaining Normal Intestinal Permeability under different Genetic Backgrounds

    Science.gov (United States)

    Zhao, Yunli; Yu, Xiaoming; Jia, Ruhan; Yang, Ruilong; Rui, Qi; Wang, Dayong

    2015-11-01

    Lactic acid bacteria (LAB) is safe and useful for food and feed fermentation. We employed Caenorhabditis elegans to investigate the possible beneficial effect of LAB (Lactobacillus bulgaricus) pretreatment against toxicity of graphene oxide (GO) and the underlying mechanisms. LAB prevented GO toxicity on the functions of both primary and secondary targeted organs in wild-type nematodes. LAB blocked translocation of GO into secondary targeted organs through intestinal barrier by maintaining normal intestinal permeability in wild-type nematodes. Moreover, LAB prevented GO damage on the functions of both primary and secondary targeted organs in exposed nematodes with mutations of susceptible genes (sod-2, sod-3, gas-1, and aak-2) to GO toxicity by sustaining normal intestinal permeability. LAB also sustained the normal defecation behavior in both wild-type nematodes and nematodes with mutations of susceptible genes. Therefore, the beneficial role of LAB against GO toxicity under different genetic backgrounds may be due to the combinational effects on intestinal permeability and defecation behavior. Moreover, the beneficial effects of LAB against GO toxicity was dependent on the function of ACS-22, homologous to mammalian FATP4 to mammalian FATP4. Our study provides highlight on establishment of pharmacological strategy to protect intestinal barrier from toxicity of GO.

  10. A specific superoxide dismutase mutation is on the same genetic background in sporadic and familial cases of amyotrophic lateral sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Hayward, C.; Brock, D.J.H. [Univ. of Edinburgh (United Kingdom); Swingler, R.J. [Dundee Royal Infirmary (United Kingdom)] [and others

    1996-11-01

    Amyotrophic lateral sclerosis (ALS) is a degenerative disease of motor neurons, causing progressive muscular atrophy, weakness, and death from respiratory failure, often within 2-3 years. Although most cases are sporadic, some 5%-10% are inherited as autosomal dominants with age-dependent penetrance. An ALS locus has been mapped to chromosome 21q, and causative mutations identified in the Cu/Zn superoxide dismutase (SOD1) gene. A majority of SOD1 mutations have been found in cases with a clear family history of ALS. However, we and others have also described SOD1 mutations in patients where the disease appears to be sporadic. This is especially true for the missense mutation in codon 113 of the SOD1 gene, which substitutes threonine for isoleucine (I113T). One explanation for this finding is that this codon is a mutational hot spot with sporadic cases representing new mutations. Another is that the inherited nature of the cases is disguised by the reduced penetrance of this specific mutation. We have now shown that each of six unrelated cases of I113T mutation that we have collected in the Scottish population occurs on the same genetic background. Association analysis of multiple flanking loci on chromosome 21q supports the conclusion of a founder effect, with the original mutational event occurring {ge}10 generations ago. 12 refs., 1 fig., 1 tab.

  11. Phenolic Contents and Compositions in Skins of Red Wine Grape Cultivars among Various Genetic Backgrounds and Originations

    Directory of Open Access Journals (Sweden)

    Lei Zhu

    2012-03-01

    Full Text Available In order to analyze and compare the phenolic characteristics of red wine grapes with diverse genetic backgrounds, skin phenolics among 21 different cultivars belonging to Vitis vinifera L., East Asian and North American Vitis species and hybrids, as well as 2 varieties of muscadine grapes were estimated by HPLC-MS/MS. There were 45 anthocyanins, 28 flavonols, 8 flavan-3-ols, 9 cinnamic acids, 5 benzoic acids, 5 ellagic acids and 2 stilbenes detected in all the samples. Total contents of each phenolic type varied significantly among the different grape cultivars investigated. There was also a large variability in the phenolic compositions of different grape groups. The differences in anthocyanin composition were obvious between V. vinifera and non-V. vinifera grapes and also between the grapes originating from Eurasia and North America. Quercetin-3-glucuronide and quercetin-3-glucoside were marker flavonol compounds for Euvitis grape skins. Flavan-3-ol monomers were dominant in the skins of muscadine and non-V. amurensis East Asian grapes, whereas polymers were more common in V. vinifera and North American grapes. The muscadine grapes were very rich in flavonols, flavan-3-ols and ellagic acids. Via principal component analysis, these grape cultivars were clustered into three groups according to their characteristic phenolic content and composition.

  12. A new era of semiconductor genetics using ion-sensitive field-effect transistors: the gene-sensitive integrated cell.

    Science.gov (United States)

    Toumazou, Christofer; Thay, Tan Sri Lim Kok; Georgiou, Pantelis

    2014-03-28

    Semiconductor genetics is now disrupting the field of healthcare owing to the rapid parallelization and scaling of DNA sensing using ion-sensitive field-effect transistors (ISFETs) fabricated using commercial complementary metal -oxide semiconductor technology. The enabling concept of DNA reaction monitoring introduced by Toumazou has made this a reality and we are now seeing relentless scaling with Moore's law ultimately achieving the $100 genome. In this paper, we present the next evolution of this technology through the creation of the gene-sensitive integrated cell (GSIC) for label-free real-time analysis based on ISFETs. This device is derived from the traditional metal-oxide semiconductor field-effect transistor (MOSFET) and has electrical performance identical to that of a MOSFET in a standard semiconductor process, yet is capable of incorporating DNA reaction chemistries for applications in single nucleotide polymorphism microarrays and DNA sequencing. Just as application-specific integrated circuits, which are developed in much the same way, have shaped our consumer electronics industry and modern communications and memory technology, so, too, do GSICs based on a single underlying technology principle have the capacity to transform the life science and healthcare industries.

  13. Genetic variance in micro-environmental sensitivity for milk and milk quality in Walloon Holstein cattle.

    Science.gov (United States)

    Vandenplas, J; Bastin, C; Gengler, N; Mulder, H A

    2013-09-01

    Animals that are robust to environmental changes are desirable in the current dairy industry. Genetic differences in micro-environmental sensitivity can be studied through heterogeneity of residual variance between animals. However, residual variance between animals is usually assumed to be homogeneous in traditional genetic evaluations. The aim of this study was to investigate genetic heterogeneity of residual variance by estimating variance components in residual variance for milk yield, somatic cell score, contents in milk (g/dL) of 2 groups of milk fatty acids (i.e., saturated and unsaturated fatty acids), and the content in milk of one individual fatty acid (i.e., oleic acid, C18:1 cis-9), for first-parity Holstein cows in the Walloon Region of Belgium. A total of 146,027 test-day records from 26,887 cows in 747 herds were available. All cows had at least 3 records and a known sire. These sires had at least 10 cows with records and each herd × test-day had at least 5 cows. The 5 traits were analyzed separately based on fixed lactation curve and random regression test-day models for the mean. Estimation of variance components was performed by running iteratively expectation maximization-REML algorithm by the implementation of double hierarchical generalized linear models. Based on fixed lactation curve test-day mean models, heritability for residual variances ranged between 1.01×10(-3) and 4.17×10(-3) for all traits. The genetic standard deviation in residual variance (i.e., approximately the genetic coefficient of variation of residual variance) ranged between 0.12 and 0.17. Therefore, some genetic variance in micro-environmental sensitivity existed in the Walloon Holstein dairy cattle for the 5 studied traits. The standard deviations due to herd × test-day and permanent environment in residual variance ranged between 0.36 and 0.45 for herd × test-day effect and between 0.55 and 0.97 for permanent environmental effect. Therefore, nongenetic effects also

  14. Sensitivity of blackbody effective emissivity to wavelength and temperature: By genetic algorithm

    Science.gov (United States)

    Ejigu, E. K.; Liedberg, H. G.

    2013-09-01

    A variable-temperature blackbody (VTBB) is used to calibrate an infrared radiation thermometer (pyrometer). The effective emissivity (ɛeff) of a VTBB is dependent on temperature and wavelength other than the geometry of the VTBB. In the calibration process the effective emissivity is often assumed to be constant within the wavelength and temperature range. There are practical situations where the sensitivity of the effective emissivity needs to be known and correction has to be applied. We present a method using a genetic algorithm to investigate the sensitivity of the effective emissivity to wavelength and temperature variation. Two matlab® programs are generated: the first to model the radiance temperature calculation and the second to connect the model to the genetic algorithm optimization toolbox. The effective emissivity parameter is taken as a chromosome and optimized at each wavelength and temperature point. The difference between the contact temperature (reading from a platinum resistance thermometer or liquid in glass thermometer) and radiance temperature (calculated from the ɛeff values) is used as an objective function where merit values are calculated and best fit ɛeff values selected. The best fit ɛeff values obtained as a solution show how sensitive they are to temperature and wavelength parameter variation. Uncertainty components that arise from wavelength and temperature variation are determined based on the sensitivity analysis. Numerical examples are considered for illustration.

  15. Genetic loci for ventricular dilatation in the LEW/Jms rat with fetal-onset hydrocephalus are influenced by gender and genetic background

    Directory of Open Access Journals (Sweden)

    Mayorga David A

    2005-06-01

    Full Text Available Abstract Background The LEW/Jms rat strain has inherited hydrocephalus, with more males affected than females and an overall expression rate of 28%. This study aimed to determine chromosomal positions for genetic loci causing the hydrocephalus. Methods An F1 backcross was made to the parental LEW/Jms strain from a cross with non-hydrocephalic Fischer 344 rats. BC1 rats were generated for two specific crosses: the first with a male LEW/Jms rat as parent and grandparent, [(F × L × L], designated B group, and the second with a female LEW/Jms rat as the parent and grandparent [L × (L × F], designated C group. All hydrocephalic and a similar number of non-hydrocephalic rats from these two groups were genotyped with microsatellite markers and the data was analyzed separately for each sex by MAPMAKER. Results The frequency of hydrocephalus was not significantly different between the two groups (18.2 and 19.9 %, but there was a significant excess of males in the B group. The mean severity of hydrocephalus, measured as the ventricle-to-brain width ratio, was ranked as B group Conclusion Phenotypic expression of hydrocephalus in Lew/Jms, although not X-linked, has a strong male bias. One, and possibly two chromosomal regions are associated with the hydrocephalus.

  16. Impact of the genetic background on the composition of the chicken plasma MiRNome in response to a stress.

    Directory of Open Access Journals (Sweden)

    Marie-Laure Endale Ahanda

    Full Text Available Circulating extra-cellular microRNAs (miRNAs have emerged as promising minimally invasive markers in human medicine. We evaluated miRNAs isolated from total plasma as biomarker candidates of a response to an abiotic stress (feed deprivation in a livestock species. Two chicken lines selected for high (R+ and low (R- residual feed intake were chosen as an experimental model because of their extreme divergence in feed intake and energy metabolism. Adult R+ and R- cocks were sampled after 16 hours of feed deprivation and again four hours after re-feeding. More than 292 million sequence reads were generated by small RNA-seq of total plasma RNA. A total of 649 mature miRNAs were identified; after quality filtering, 148 miRNAs were retained for further analyses. We identified 23 and 19 differentially abundant miRNAs between feeding conditions and between lines respectively, with only two miRNAs identified in both comparisons. We validated a panel of six differentially abundant miRNAs by RT-qPCR on a larger number of plasma samples and checked their response to feed deprivation in liver. Finally, we evaluated the conservation and tissue distribution of differentially abundant miRNAs in plasma across a variety of red jungle fowl tissues. We show that the chicken plasma miRNome reacts promptly to the alteration of the animal physiological condition driven by a feed deprivation stress. The plasma content of stress-responsive miRNAs is strongly influenced by the genetic background, with differences reflecting the phenotypic divergence acquired through long-term selection, as evidenced by the profiles of conserved miRNAs with a regulatory role in energy metabolism (gga-miR-204, gga-miR-let-7f-5p and gga-miR-122-5p. These results reinforce the emerging view in human medicine that even small genetic differences can have a considerable impact on the resolution of biomarker studies, and provide support for the emerging interest in miRNAs as potential novel and

  17. A contrast-sensitive channelized-Hotelling observer to predict human performance in a detection task using lumpy backgrounds and Gaussian signals

    Science.gov (United States)

    Park, Subok; Badano, Aldo; Gallas, Brandon D.; Myers, Kyle J.

    2007-03-01

    Previously, a non-prewhitening matched filter (NPWMF) incorporating a model for the contrast sensitivity of the human visual system was introduced for modeling human performance in detection tasks with different viewing angles and white-noise backgrounds by Badano et al. But NPWMF observers do not perform well detection tasks involving complex backgrounds since they do not account for random backgrounds. A channelized-Hotelling observer (CHO) using difference-of-Gaussians (DOG) channels has been shown to track human performance well in detection tasks using lumpy backgrounds. In this work, a CHO with DOG channels, incorporating the model of the human contrast sensitivity, was developed similarly. We call this new observer a contrast-sensitive CHO (CS-CHO). The Barten model was the basis of our human contrast sensitivity model. A scalar was multiplied to the Barten model and varied to control the thresholding effect of the contrast sensitivity on luminance-valued images and hence the performance-prediction ability of the CS-CHO. The performance of the CS-CHO was compared to the average human performance from the psychophysical study by Park et al., where the task was to detect a known Gaussian signal in non-Gaussian distributed lumpy backgrounds. Six different signal-intensity values were used in this study. We chose the free parameter of our model to match the mean human performance in the detection experiment at the strongest signal intensity. Then we compared the model to the human at five different signal-intensity values in order to see if the performance of the CS-CHO matched human performance. Our results indicate that the CS-CHO with the chosen scalar for the contrast sensitivity predicts human performance closely as a function of signal intensity.

  18. Role of oxygen tension and genetic background during the epigenetic conversion of mouse fibroblasts into insulin secreting cells

    Directory of Open Access Journals (Sweden)

    Alessandro Zenobi

    2015-07-01

    Full Text Available Epigenetic cell conversion overcomes the stability of a mature cell phenotype transforming a somatic cell in an unlimited source of autologous cells of a different type. It is based on the exposure to a demethylating agent followed by an induction protocol. In our work we exposed mouse dermal fibroblasts to the demethylating agent 5-azacytidine. Cell differentiation was directed toward the endocrine pancreatic lineage with a sequential combination of Activin A, Retinoic Acid, B27 supplement, ITS and bFGF. The overall duration of the process was 10 days. Aim of this work was to evaluate the role of oxygen during differentiation of dermal fibroblasts derived from two different mouse strains, NOD and C57 BL/6J. During differentiation, both cell lines were cultured either in the standard in vitro culture 20% oxygen concentration or in the lower and more physiological 5% of oxygen. Our results show that C57 BL/6J cells are able to differentiate into insulin secreting cells in both oxygen tensions with a higher amount of insulin release in low oxygen conditions. On the other hand, cells of NOD mice, which are physiologically predisposed to the onset of diabetes, differentiate in 20% of oxygen but not in low oxygen and they died after three days of culture. However, if these cells are moved to 5% of oxygen after their differentiation in high oxygen they remain viable for up to four days. Furthermore, their capacity to release insulin remains unchanged for 24 hours. Results suggest that genetic background has a profound effect on the role of oxygen during the in vitro differentiation process, possibly reflecting the different susceptibility to the disease of the strains used in the experiment.Supported by EFSD and Carraresi Foundation

  19. Monitoring perinatal gut microbiota in mouse models by mass spectrometry approaches: parental genetic background and breastfeeding effects

    Directory of Open Access Journals (Sweden)

    Stefano Levi Mortera

    2016-09-01

    Full Text Available At birth, contact with external stimuli, such as nutrients derived from food, is necessary to modulate the symbiotic balance between commensal and pathogenic bacteria, protect against bacterial dysbiosis, and initiate the development of the mucosal immune response. Among a variety of different feeding patterns, breastfeeding represents the best modality. In fact, the capacity of breast milk to modulate the composition of infants’ gut microbiota leads to beneficial effects on their health. In this study, we used newborn mice as a model to evaluate the effect of parental genetic background (i.e., IgA-producing mice and IgA-deficient mice and feeding modulation (i.e., maternal feeding and cross-feeding on the onset and shaping of gut microbiota after birth. To investigate these topics, we used either a culturomic approach that employed Matrix Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry (MS, or bottom-up Liquid Chromatography, with subsequent MSMS shotgun metaproteomic analysis that compared and assembled results of the two techniques. We found that the microbial community was enriched by lactic acid bacteria when pups were breastfed by wild-type (WT mothers, while IgA-deficient milk led to an increase in the opportunistic bacterial pathogen (OBP population. Cross-feeding results suggested that IgA supplementation promoted the exclusion of some OBPs and the temporary appearance of beneficial species in pups fed by WT foster mothers. Our results show that both techniques yield a picture of microbiota from different angles and with varying depths. In particular, our metaproteomic pipeline was found to be a reliable tool in the description of microbiota. Data from these studies are available via ProteomeXchange, with identifier PXD004033.

  20. Monitoring Perinatal Gut Microbiota in Mouse Models by Mass Spectrometry Approaches: Parental Genetic Background and Breastfeeding Effects

    Science.gov (United States)

    Levi Mortera, Stefano; Del Chierico, Federica; Vernocchi, Pamela; Rosado, Maria M.; Cavola, Agnese; Chierici, Marco; Pieroni, Luisa; Urbani, Andrea; Carsetti, Rita; Lante, Isabella; Dallapiccola, Bruno; Putignani, Lorenza

    2016-01-01

    At birth, contact with external stimuli, such as nutrients derived from food, is necessary to modulate the symbiotic balance between commensal and pathogenic bacteria, protect against bacterial dysbiosis, and initiate the development of the mucosal immune response. Among a variety of different feeding patterns, breastfeeding represents the best modality. In fact, the capacity of breast milk to modulate the composition of infants’ gut microbiota leads to beneficial effects on their health. In this study, we used newborn mice as a model to evaluate the effect of parental genetic background (i.e., IgA-producing mice and IgA-deficient mice) and feeding modulation (i.e., maternal feeding and cross-feeding) on the onset and shaping of gut microbiota after birth. To investigate these topics, we used either a culturomic approach that employed Matrix Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry (MS), or bottom–up Liquid Chromatography, with subsequent MSMS shotgun metaproteomic analysis that compared and assembled results of the two techniques. We found that the microbial community was enriched by lactic acid bacteria when pups were breastfed by wild-type (WT) mothers, while IgA-deficient milk led to an increase in the opportunistic bacterial pathogen (OBP) population. Cross-feeding results suggested that IgA supplementation promoted the exclusion of some OBPs and the temporary appearance of beneficial species in pups fed by WT foster mothers. Our results show that both techniques yield a picture of microbiota from different angles and with varying depths. In particular, our metaproteomic pipeline was found to be a reliable tool in the description of microbiota. Data from these studies are available via ProteomeXchange, with identifier PXD004033. PMID:27725814

  1. Genetic variation and combining ability analysis of bruising sensitivity in Agaricus bisporus.

    Directory of Open Access Journals (Sweden)

    Wei Gao

    Full Text Available Advanced button mushroom cultivars that are less sensitive to mechanical bruising are required by the mushroom industry, where automated harvesting still cannot be used for the fresh mushroom market. The genetic variation in bruising sensitivity (BS of Agaricus bisporus was studied through an incomplete set of diallel crosses to get insight in the heritability of BS and the combining ability of the parental lines used and, in this way, to estimate their breeding value. To this end nineteen homokaryotic lines recovered from wild strains and cultivars were inter-crossed in a diallel scheme. Fifty-one successful hybrids were grown under controlled conditions, and the BS of these hybrids was assessed. BS was shown to be a trait with a very high heritability. The results also showed that brown hybrids were generally less sensitive to bruising than white hybrids. The diallel scheme allowed to estimate the general combining ability (GCA for each homokaryotic parental line and to estimate the specific combining ability (SCA of each hybrid. The line with the lowest GCA is seen as the most attractive donor for improving resistance to bruising. The line gave rise to hybrids sensitive to bruising having the highest GCA value. The highest negative SCA possibly indicates heterosis effects for resistance to bruising. This study provides a foundation for estimating breeding value of parental lines to further study the genetic factors underlying bruising sensitivity and other quality-related traits, and to select potential parental lines for further heterosis breeding. The approach of studying combining ability in a diallel scheme was used for the first time in button mushroom breeding.

  2. Genetic Analysis and Molecular Mapping of Light-Sensitive Red-Root Mutant in Rice

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jun-zhi; LIU Xiao; LI Chao; XIAO Ke; DONG Yan-jun

    2009-01-01

    The light-sensitive red-root mutant, designated as HG1, was newly observed from an indica rice variety, Nankinkodo, when seedlings were grown with roots exposed to natural light. The root color of the mutant began to turn slight-red when the roots were exposed to the light at the intensity of 29 μmol/(m2·s), then turned dark-red at the light intensity of 180 μmol/(m2·s), suggesting that the root color of the mutant was evidently sensitive to light. Furthermore, genetic analysis showed that the character of light-sensitive red-root of the HG1 mutant was controlled by a single dominant gene, tentatively designated as Lsr. With simple sequence repeat markers, Lsr gene was located between the markers RM252 and RM303 on chromosome 4 with the genetic distances of 9.8 cM and 6.4 cM, respectively. These results could be useful for fine mapping and cloning of Lsr gene in rice.

  3. Analysis of Fungicide Sensitivity and Genetic Diversity among Colletotrichum Species in Sweet Persimmon.

    Science.gov (United States)

    Gang, Geun-Hye; Cho, Hyun Ji; Kim, Hye Sun; Kwack, Yong-Bum; Kwak, Youn-Sig

    2015-06-01

    Anthracnose, caused by Colletotrichum gloeosporioides (C. gloeosporioides; Teleomorph: Glomerella cingulata), is the most destructive disease that affects sweet persimmon production worldwide. However, the biology, ecology, and genetic variations of C. gloeosporioides remain largely unknown. Therefore, in this study, the development of fungicide resistance and genetic diversity among an anthracnose pathogen population with different geographical origins and the exposure of this population to different cultivation strategies were investigated. A total of 150 pathogen isolates were tested in fungicide sensitivity assays. Five of the tested fungicides suppressed mycelial pathogen growth effectively. However, there were significant differences in the sensitivities exhibited by the pathogen isolates examined. Interestingly, the isolates obtained from practical management orchards versus organic cultivation orchards showed no differences in sensitivity to the same fungicide. PCR-restriction fragment length polymorphism (RFLP) analyses were performed to detect internal transcribed spacer regions and the β-tubulin and glutamine synthetase genes of the pathogens examined. Both the glutamine synthetase and β-tubulin genes contained a complex set of polymorphisms. Based on these results, the pathogens isolated from organic cultivation orchards were found to have more diversity than the isolates obtained from the practical management orchards.

  4. Analysis of Fungicide Sensitivity and Genetic Diversity among Colletotrichum Species in Sweet Persimmon

    Directory of Open Access Journals (Sweden)

    Geun-Hye Gang

    2015-06-01

    Full Text Available Anthracnose, caused by Colletotrichum gloeosporioides (C. gloeosporioides; Teleomorph: Glomerella cingulata, is the most destructive disease that affects sweet persimmon production worldwide. However, the biology, ecology, and genetic variations of C. gloeosporioides remain largely unknown. Therefore, in this study, the development of fungicide resistance and genetic diversity among an anthracnose pathogen population with different geographical origins and the exposure of this population to different cultivation strategies were investigated. A total of 150 pathogen isolates were tested in fungicide sensitivity assays. Five of the tested fungicides suppressed mycelial pathogen growth effectively. However, there were significant differences in the sensitivities exhibited by the pathogen isolates examined. Interestingly, the isolates obtained from practical management orchards versus organic cultivation orchards showed no differences in sensitivity to the same fungicide. PCR-restriction fragment length polymorphism (RFLP analyses were performed to detect internal transcribed spacer regions and the β-tubulin and glutamine synthetase genes of the pathogens examined. Both the glutamine synthetase and β-tubulin genes contained a complex set of polymorphisms. Based on these results, the pathogens isolated from organic cultivation orchards were found to have more diversity than the isolates obtained from the practical management orchards.

  5. Common genetic variation in the human CTF1 locus, encoding cardiotrophin-1, determines insulin sensitivity.

    Directory of Open Access Journals (Sweden)

    Stefan Z Lutz

    Full Text Available AIMS/HYPOTHESIS: Recently, cardiotrophin-1, a member of the interleukin-6 family of cytokines was described to protect beta-cells from apoptosis, to improve glucose-stimulated insulin secretion and insulin resistance, and to prevent streptozotocin-induced diabetes in mice. Here, we studied whether common single nucleotide polymorphisms (SNPs in the CTF1 locus, encoding cardiotrophin-1, influence insulin secretion and insulin sensitivity in humans. METHODS: We genotyped 1,771 German subjects for three CTF1 tagging SNPs (rs1046276, rs1458201, and rs8046707. The subjects were metabolically characterized by an oral glucose tolerance test. Subgroups underwent magnetic resonance (MR imaging/spectroscopy and hyperinsulinaemic-euglycaemic clamps. RESULTS: After appropriate adjustment, the minor allele of CTF1 SNP rs8046707 was significantly associated with decreased in vivo measures of insulin sensitivity. The other tested SNPs were not associated with OGTT-derived sensitivity parameters, nor did the three tested SNPs show any association with OGTT-derived parameters of insulin release. In the MR subgroup, SNP rs8046707 was nominally associated with lower visceral adipose tissue. Furthermore, the SNP rs1458201 showed a nominal association with increased VLDL levels. CONCLUSIONS: In conclusion, this study, even though preliminary and awaiting further confirmation by independent replication, provides first evidence that common genetic variation in CTF1 could contribute to insulin sensitivity in humans. Our SNP data indicate an insulin-desensitizing effect of cardiotrophin-1 and underline that cardiotrophin-1 represents an interesting target to influence insulin sensitivity.

  6. Cost-sensitive case-based reasoning using a genetic algorithm: application to medical diagnosis.

    Science.gov (United States)

    Park, Yoon-Joo; Chun, Se-Hak; Kim, Byung-Chun

    2011-02-01

    The paper studies the new learning technique called cost-sensitive case-based reasoning (CSCBR) incorporating unequal misclassification cost into CBR model. Conventional CBR is now considered as a suitable technique for diagnosis, prognosis and prescription in medicine. However it lacks the ability to reflect asymmetric misclassification and often assumes that the cost of a positive diagnosis (an illness) as a negative one (no illness) is the same with that of the opposite situation. Thus, the objective of this research is to overcome the limitation of conventional CBR and encourage applying CBR to many real world medical cases associated with costs of asymmetric misclassification errors. The main idea involves adjusting the optimal cut-off classification point for classifying the absence or presence of diseases and the cut-off distance point for selecting optimal neighbors within search spaces based on similarity distribution. These steps are dynamically adapted to new target cases using a genetic algorithm. We apply this proposed method to five real medical datasets and compare the results with two other cost-sensitive learning methods-C5.0 and CART. Our finding shows that the total misclassification cost of CSCBR is lower than other cost-sensitive methods in many cases. Even though the genetic algorithm has limitations in terms of unstable results and over-fitting training data, CSCBR results with GA are better overall than those of other methods. Also the paired t-test results indicate that the total misclassification cost of CSCBR is significantly less than C5.0 and CART for several datasets. We have proposed a new CBR method called cost-sensitive case-based reasoning (CSCBR) that can incorporate unequal misclassification costs into CBR and optimize the number of neighbors dynamically using a genetic algorithm. It is meaningful not only for introducing the concept of cost-sensitive learning to CBR, but also for encouraging the use of CBR in the medical area

  7. Genetic backgrounds and modifier genes of NTD mouse models: An opportunity for greater understanding of the multifactorial etiology of neural tube defects.

    Science.gov (United States)

    Leduc, Renee Y M; Singh, Parmveer; McDermid, Heather E

    2016-10-21

    Neurulation, the early embryonic process of forming the presumptive brain and spinal cord, is highly complex and involves hundreds of genes in multiple genetic pathways. Mice have long served as a genetic model for studying human neurulation, and the resulting neural tube defects (NTDs) that arise when neurulation is disrupted. Because mice appear to show mostly single gene inheritance for NTDs and humans show multifactorial inheritance, mice sometimes have been characterized as a simpler model for the identification and study of NTD genes. But are they a simple model? When viewed on different genetic backgrounds, many genes show significant variation in the penetrance and expressivity of NTD phenotypes, suggesting the presence of modifier loci that interact with the target gene to affect the phenotypic expression. Looking at mutations on different genetic backgrounds provides us with an opportunity to explore these complex genetic interactions, which are likely to better emulate similar processes in human neurulation. Here, we review NTD genes known to show strain-specific phenotypic variation. We focus particularly on the gene Cecr2, which is studied using both a hypomorphic and a presumptive null mutation on two different backgrounds: one susceptible (BALB/c) and one resistant (FVB/N) to NTDs. This strain difference has led to a search for genetic modifiers within a region on murine chromosome 19. Understanding how genetic variants alter the phenotypic outcome in NTD mouse models will help to direct future studies in humans, particularly now that more genome wide sequencing approaches are being used. Birth Defects Research (Part A), 2016. © 2016 Wiley Periodicals, Inc.

  8. Contribution of Genetic Background, Traditional Risk Factors, and HIV-Related Factors to Coronary Artery Disease Events in HIV-Positive Persons

    Science.gov (United States)

    Rotger, Margalida; Glass, Tracy R.; Junier, Thomas; Lundgren, Jens; Neaton, James D.; Poloni, Estella S.; van 't Wout, Angélique B.; Lubomirov, Rubin; Colombo, Sara; Martinez, Raquel; Rauch, Andri; Günthard, Huldrych F.; Neuhaus, Jacqueline; Wentworth, Deborah; van Manen, Danielle; Gras, Luuk A.; Schuitemaker, Hanneke; Albini, Laura; Torti, Carlo; Jacobson, Lisa P.; Li, Xiuhong; Kingsley, Lawrence A.; Carli, Federica; Guaraldi, Giovanni; Ford, Emily S.; Sereti, Irini; Hadigan, Colleen; Martinez, Esteban; Arnedo, Mireia; Egaña-Gorroño, Lander; Gatell, Jose M.; Law, Matthew; Bendall, Courtney; Petoumenos, Kathy; Rockstroh, Jürgen; Wasmuth, Jan-Christian; Kabamba, Kabeya; Delforge, Marc; De Wit, Stephane; Berger, Florian; Mauss, Stefan; de Paz Sierra, Mariana; Losso, Marcelo; Belloso, Waldo H.; Leyes, Maria; Campins, Antoni; Mondi, Annalisa; De Luca, Andrea; Bernardino, Ignacio; Barriuso-Iglesias, Mónica; Torrecilla-Rodriguez, Ana; Gonzalez-Garcia, Juan; Arribas, José R.; Fanti, Iuri; Gel, Silvia; Puig, Jordi; Negredo, Eugenia; Gutierrez, Mar; Domingo, Pere; Fischer, Julia; Fätkenheuer, Gerd; Alonso-Villaverde, Carlos; Macken, Alan; Woo, James; McGinty, Tara; Mallon, Patrick; Mangili, Alexandra; Skinner, Sally; Wanke, Christine A.; Reiss, Peter; Weber, Rainer; Bucher, Heiner C.; Fellay, Jacques; Telenti, Amalio; Tarr, Philip E.

    2013-01-01

    Background Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection. Methods In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort. Results A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9×10−4). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05–2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06–1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16–1.96), diabetes (OR = 1.66; 95% CI, 1.10–2.49), ≥1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06–1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17–2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD. Conclusions In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD. PMID:23532479

  9. Optimization of biotinyl-tyramide-based in situ hybridization for sensitive background-free applications on formalin-fixed, paraffin-embedded tissue specimens

    Directory of Open Access Journals (Sweden)

    Aliesky Holly A

    2003-06-01

    Full Text Available Abstract Background Over the past five years in situ hybridization techniques employing tyramide amplification reagents have been developed and promise the potential detection of low/single-copy nucleic acid sequences. However the increased sensitivity that tyramide amplification brings about may also lead to problems of background staining that confound data interpretation. Methods In this study those factors enabling background-free biotinyl-tyramide based in situ hybridization assay of formalin-fixed paraffin-embedded tissues have been examined. SiHa, HeLa and CaSki cell lines known to contain HPV integrated into the cell genome, and archival cervical pre-invasive lesions and carcinomas have been successfully assessed using biotinylated HPV and centromeric probes. Results The single most important factor both for sensitivity and clean background was a tissue unmasking regimen that included treatment with 10 mM sodium citrate pH 6.0 at 95°C followed by digestion with pepsin/0.2 M HCl. Concentrations both of probe and primary streptavidin-peroxidase conjugate and pH of hybridization mix and stringency washes were also critical for sensitivity. Certain probes were more associated with background staining than others. This problem was not related to probe purity or size. In these instances composition of hybridization mix solution was especially critical to avoid background. 3-amino-9-ethylcarbazole was preferred over 3,3'-diaminobenzidene as a chromogen because background was cleaner and the 1–2 copies of HPV16 integrated in SiHa cells were readily demonstrable. HPV detection on metaphase spreads prepared from SiHa cells was only successful when a fluorescent detection method was combined with tyramide reagent. 'Punctate' and 'diffuse' signal patterns were identified amongst tissues consistent with the former representing integration and 'diffuse' representing episomal HPV. Only punctate signals were detected amongst the cell lines and were

  10. Introgression of Brown Norway CYP4A genes on to the Dahl salt-sensitive background restores vascular function in SS-5(BN) consomic rats.

    Science.gov (United States)

    Lukaszewicz, Kathleen M; Falck, John R; Manthati, Vijaya L; Lombard, Julian H

    2013-03-01

    The present study tested the hypothesis that the Dahl SS (salt-sensitive) rat has vascular dysfunction due, in part, to the up-regulation of the CYP4A/20-HETE (cytochrome P450 ω-hydroxylase 4A)/20-hydroxyeicosatetraenoic acid) system. To assess the role of vascular 20-HETE, SS rats were compared with SS-5(BN) consomic rats, carrying CYP4A alleles on chromosome 5 from the normotensive BN (Brown Norway) introgressed on to the SS genetic background. Cerebral arteries from SS-5(BN) rats had less CYP4A protein than arteries from SS rats fed either NS (normal-salt, 0.4% NaCl) or HS (high-salt, 4.0% NaCl) diet. ACh (acetylcholine)-induced dilation of MCAs (middle cerebral arteries) from SS and SS-5(BN) rats was present in SS-5(BN) rats fed on either an NS or HS diet, but absent in SS rats. In SS rats fed on either diet, ACh-induced dilation was restored by acute treatment with the CYP4A inhibitor DDMS (N-methyl-sulfonyl-12,12-dibromododec-11-enamide) or the 20-HETE antagonist 20-HEDE [20-hydroxyeicosa-6(Z),15(Z)-dienoic acid]. The restored response to ACh in DDMS-treated SS rats was inhibited by L-NAME (N(G)nitro-L-arginine methyl ester) and unaffected by indomethacin or MS-PPOH [N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide]. Vascular relaxation responses to the NO donor C(5)FeN(6)Na(2)O were intact in both SS and SS-5(BN) rats and unaffected by the acute addition of DDMS, indicating that the vascular dysfunction of the SS rat is due to a reduced bioavailability of NO instead of failure of the VSMCs (vascular smooth muscle cells) to respond to the vasodilator. Superoxide levels in cerebral arteries of SS-5(BN) rats [evaluated semi-quantitatively by DHE (dihydroethidium) fluorescence] were lower than those in the arteries of SS rats. These findings indicate that SS rats have an up-regulation of the CYP4A/20-HETE pathway resulting in elevated ROS (reactive oxygen species) and reduced NO bioavailability causing vascular dysfunction.

  11. Improving Sensitivity and Specificity when Measuring Environmental Exposure to Engineered Nanoparticle Releases with the use of Low-Background Techniques

    OpenAIRE

    Papinchak, Heather Laine

    2013-01-01

    As applications of nanotechnology expand, there is an increasing need to develop inexpensive, sensitive, and specific procedures to measure occupational exposures to engineered nanoparticles (ENPs). The use of hand-held direct reading instruments to screen for airborne ENPs is attractive due to the relatively low cost of such commercially available instruments and the immediate feedback provided. However, because ambient air typically contains thousands of non-engineered nanoparticles per cu...

  12. Genetic contribution to variation in DNA methylation at maternal smoking-sensitive loci in exposed neonates.

    Science.gov (United States)

    Gonseth, Semira; de Smith, Adam J; Roy, Ritu; Zhou, Mi; Lee, Seung-Tae; Shao, Xiaorong; Ohja, Juhi; Wrensch, Margaret R; Walsh, Kyle M; Metayer, Catherine; Wiemels, Joseph L

    2016-09-01

    Epigenome-wide DNA methylation association studies have identified highly replicable genomic loci sensitive to maternal smoking during gestation. The role of inter-individual genetic variation in influencing DNA methylation, leading to the possibility of confounding or bias of such associations, has not been assessed. We investigated whether the DNA methylation levels at the top 10 CpG sites previously associated with exposure to maternal smoking during gestation were associated with individual genetic variation at the genome-wide level. Genome-wide association tests between DNA methylation at the top 10 candidate CpG and genome-wide SNPs were performed in 736 case and control participants of the California Childhood Leukemia Study. Three of the strongest maternal-smoking sensitive CpG sites in newborns were significantly associated with SNPs located proximal to each gene: cg18146737 in the GFI1 gene with rs141819830 (P = 8.2×10(-44)), cg05575921 in the AHRR gene with rs148405299 (P = 5.3×10(-10)), and cg12803068 in the MYO1G gene with rs61087368 (P = 1.3×10(-18)). For the GFI1 CpG cg18146737, the underlying genetic variation at rs141819830 confounded the association between maternal smoking and DNA methylation in our data (the regression coefficient changed from -0.02 [P = 0.139] to -0.03 [P = 0.015] after including the genotype). Our results suggest that further studies using DNA methylation at cg18146737, cg05575921, or cg12803068 that aim to assess exposure to maternal smoking during gestation should include genotype at the corresponding SNP. New methods are required for adequate and routine inclusion of genotypic influence on DNA methylation in epigenome-wide association studies to control for potential confounding.

  13. Genetic background influences age-related decline in visual and nonvisual retinal responses, circadian rhythms, and sleep.

    OpenAIRE

    Banks, G; Heise, I; Starbuck, B; Osborne, T.; Wisby, L; De Potter, P; Jackson, IJ; Foster, RG; Peirson, SN; Nolan, PM

    2015-01-01

    The circadian system is entrained to the environmental light/dark cycle via retinal photoreceptors and regulates numerous aspects of physiology and behavior, including sleep. These processes are all key factors in healthy aging showing a gradual decline with age. Despite their importance, the exact mechanisms underlying this decline are yet to be fully understood. One of the most effective tools we have to understand the genetic factors underlying these processes are genetically inbred mouse ...

  14. Recovery of native genetic background in admixed populations using haplotypes, phenotypes, and pedigree information--using Cika cattle as a case breed.

    Science.gov (United States)

    Simčič, Mojca; Smetko, Anamarija; Sölkner, Johann; Seichter, Doris; Gorjanc, Gregor; Kompan, Dragomir; Medugorac, Ivica

    2015-01-01

    The aim of this study was to obtain unbiased estimates of the diversity parameters, the population history, and the degree of admixture in Cika cattle which represents the local admixed breeds at risk of extinction undergoing challenging conservation programs. Genetic analyses were performed on the genome-wide Single Nucleotide Polymorphism (SNP) Illumina Bovine SNP50 array data of 76 Cika animals and 531 animals from 14 reference populations. To obtain unbiased estimates we used short haplotypes spanning four markers instead of single SNPs to avoid an ascertainment bias of the BovineSNP50 array. Genome-wide haplotypes combined with partial pedigree and type trait classification show the potential to improve identification of purebred animals with a low degree of admixture. Phylogenetic analyses demonstrated unique genetic identity of Cika animals. Genetic distance matrix presented by rooted Neighbour-Net suggested long and broad phylogenetic connection between Cika and Pinzgauer. Unsupervised clustering performed by the admixture analysis and two-dimensional presentation of the genetic distances between individuals also suggest Cika is a distinct breed despite being similar in appearance to Pinzgauer. Animals identified as the most purebred could be used as a nucleus for a recovery of the native genetic background in the current admixed population. The results show that local well-adapted strains, which have never been intensively managed and differentiated into specific breeds, exhibit large haplotype diversity. They suggest a conservation and recovery approach that does not rely exclusively on the search for the original native genetic background but rather on the identification and removal of common introgressed haplotypes would be more powerful. Successful implementation of such an approach should be based on combining phenotype, pedigree, and genome-wide haplotype data of the breed of interest and a spectrum of reference breeds which potentially have had

  15. Finding the most appropriate mouse model of juvenile CLN3 (Batten disease for therapeutic studies: the importance of genetic background and gender

    Directory of Open Access Journals (Sweden)

    Attila D. Kovács

    2015-04-01

    Full Text Available Mutations in the CLN3 gene cause a fatal neurodegenerative disorder: juvenile CLN3 disease, also known as juvenile Batten disease. The two most commonly utilized mouse models of juvenile CLN3 disease are Cln3-knockout (Cln3−/− and Cln3Δex7/8-knock-in mice, the latter mimicking the most frequent disease-causing human mutation. To determine which mouse model has the most pronounced neurological phenotypes that can be used as outcome measures for therapeutic studies, we compared the exploratory activity, motor function and depressive-like behavior of 1-, 3- and 6-month-old Cln3−/− and Cln3Δex7/8-knock-in mice on two different genetic backgrounds (129S6/SvEv and C57BL/6J. Although, in many cases, the behavior of Cln3−/− and Cln3Δex7/8 mice was similar, we found genetic-background-, gender- and age-dependent differences between the two mouse models. We also observed large differences in the behavior of the 129S6/SvEv and C57BL/6J wild-type strains, which highlights the strong influence that genetic background can have on phenotype. Based on our results, Cln3−/− male mice on the 129S6/SvEv genetic background are the most appropriate candidates for therapeutic studies. They exhibit motor deficits at 1 and 6 months of age in the vertical pole test, and they were the only mice to show impaired motor coordination in the rotarod test at both 3 and 6 months. Cln3−/− males on the C57BL/6J background and Cln3Δex7/8 males on the 129S6/SvEv background also provide good outcome measures for therapeutic interventions. Cln3−/− (C57BL/6J males had serious difficulties in climbing down (at 1 and 6 months and turning downward on (at 1, 3 and 6 months the vertical pole, whereas Cln3Δex7/8 (129S6/SvEv males climbed down the vertical pole drastically slower than wild-type males at 3 and 6 months of age. Our study demonstrates the importance of testing mouse models on different genetic backgrounds and comparing males and females in order to

  16. Genetic Algorithm Used for Load Shedding Based on Sensitivity to Enhance Voltage Stability

    Science.gov (United States)

    Titare, L. S.; Singh, P.; Arya, L. D.

    2014-12-01

    This paper presents an algorithm to calculate optimum load shedding with voltage stability consideration based on sensitivity of proximity indicator using genetic algorithm (GA). Schur's inequality based proximity indicator of load flow Jacobian has been selected, which indicates system state. Load flow Jacobian of the system is obtained using Continuation power flow method. If reactive power and active rescheduling are exhausted, load shedding is the last line of defense to maintain the operational security of the system. Load buses for load shedding have been selected on the basis of sensitivity of proximity indicator. The load bus having large sensitivity is selected for load shedding. Proposed algorithm predicts load bus rank and optimum load to be shed on load buses. The algorithm accounts inequality constraints not only in present operating conditions, but also for predicted next interval load (with load shedding). Developed algorithm has been implemented on IEEE 6-bus system. Results have been compared with those obtained using Teaching-Learning-Based Optimization (TLBO), particle swarm optimization (PSO) and its variant.

  17. The effect of wheat-rye translocation 1BL.1RS in a different quality genetic background on biological traits in wheat

    Directory of Open Access Journals (Sweden)

    Dimitrijević Miodrag

    2008-01-01

    Full Text Available A sample of 139 varieties of common wheat (Triticum aestivum L., predominantly Serbian winter wheat varieties originated in the Institute of Field and Vegetable Crops in Novi Sad, has been examined for presence of 1BL/1RS wheat-rye translocation. Two genotype groups consisted of varieties possessing and lacking the translocation have been compared. Stem rust, leaf rust, powdery mildew as well as, winter hardiness were studied. The influence of 1BL/1RS translocation was also studied in a light of wheat seed storage protein (glutenin and gliadin genetic background composition. Genotypes having the translocation appeared to be more tolerant to stem rust, and leaf rust, but more susceptible to powdery mildew. These effects were slightly modified depending on the examined genetic background, but the effect of the rye 1RS translocated chromosome arm was the main cause for the observed differences.

  18. Silicon-Based Antenna-Coupled Polarization-Sensitive Millimeter-Wave Bolometer Arrays for Cosmic Microwave Background Instruments

    CERN Document Server

    Rostem, Karwan; Appel, John W; Bennett, Charles L; Brown, Ari; Chang, Meng-Ping; Chuss, David T; Colazo, Felipe A; Costen, Nick; Denis, Kevin L; Essinger-Hileman, Tom; Hu, Ron; Marriage, Tobias A; Moseley, Samuel H; Stevenson, Thomas R; U-Yen, Kongpop; Wollack, Edward J; Xu, Zhilei

    2016-01-01

    We describe feedhorn-coupled polarization-sensitive detector arrays that utilize monocrystalline silicon as the dielectric substrate material. Monocrystalline silicon has a low-loss tangent and repeatable dielectric constant, characteristics that are critical for realizing efficient and uniform superconducting microwave circuits. An additional advantage of this material is its low specific heat. In a detector pixel, two Transition-Edge Sensor (TES) bolometers are antenna-coupled to in-band radiation via a symmetric planar orthomode transducer (OMT). Each orthogonal linear polarization is coupled to a separate superconducting microstrip transmission line circuit. On-chip filtering is employed to both reject out-of-band radiation from the upper band edge to the gap frequency of the niobium superconductor, and to flexibly define the bandwidth for each TES to meet the requirements of the application. The microwave circuit is compatible with multi-chroic operation. Metalized silicon platelets are used to define th...

  19. Effect of genetic background and diet on plasma fibrinogen in mice. Possible relation with susceptibility to atherosclerosis

    NARCIS (Netherlands)

    Rezaee, F.; Maas, A.; Maat, M.P.M.de; Verheijen, J.H.; Koopman, J.

    2002-01-01

    Many epidemiological studies suggest that elevated plasma fibrinogen concentrations form one of the most important independent risk factors in blood for cardiovascular disease and particularly atherosclerosis in humans. To clarify the effect of genetic factors, diets and their interactions on plasma

  20. Temperature-sensitive mutants of fowl plague virus: isolation and genetic characterization. [UV radiation

    Energy Technology Data Exchange (ETDEWEB)

    Almond, J.W.; McGeoch, D.; Barry, R.D.

    1979-01-30

    Forty-nine temperature-sensitive mutants of fowl plague virus (FPV) strain Rostock and four ts mutants of FPV-strain Dobson were isolated by utilizing two methods of plaque screening, after either spontaneous or chemically induced mutagenesis. Twenty-nine of the FPV-Rostock mutants were further characterized by genetic recombination studies and were found to fall into six high frequency recombination groups. The genome segment carrying the ts mutation in each group was identified by analyzing the gene composition of ts/sup +/ recombinants generated from crosses between representatives of each group and ts mutants of FPV-Dobson. It was concluded that the six groups correspond to mutations in six different genome segments, namely, those coding for the P/sub 1/, P/sub 2/, P/sub 3/, HA, NP, and NS proteins.

  1. Sensitive dependencies and separation distances for genetically modified herbicide-tolerant crops.

    Science.gov (United States)

    Perry, Joe N

    2002-06-07

    The amount of land available for the coexistent growing of both organic and genetically modified herbicide-tolerant (GMHT) crops depends on the separation distance between the two types of crop. The form of the decline in the proportion of land available for growing one of these crop types due to increasing separation distance is linear on a suitable scale, but with a slope and intercept that are sensitively dependent on the proportion of the other crop already present. Spatially explicit simulations from realistic scenarios indicate that a major increase in separation distances, currently under review by the UK government, may have serious implications for the future coexistence of organic and GMHT crops in the UK.

  2. Efficacy of EGFR inhibition is modulated by model, sex, genetic background and diet: implications for preclinical cancer prevention and therapy trials.

    Directory of Open Access Journals (Sweden)

    Erica S Rinella

    Full Text Available Molecule-targeted therapies are being widely developed and deployed, but they are frequently less effective in clinical trials than predicted based upon preclinical studies. Frequently, only a single model or genetic background is utilized using diets that are not relevant to that consumed by most cancer patients, which may contribute to the lack of predictability of many preclinical therapeutic studies. Inhibition of epidermal growth factor receptor (EGFR in colorectal cancer was used to investigate potential causes for low predictive values of many preclinical studies. The efficacy of the small molecule EGFR inhibitor AG1478 was evaluated using two mouse models, Apc(Min/+ and azoxymethane (AOM, both sexes on three genetic backgrounds, C57BL/6J (B6 and A/J (A inbred strains and AB6F1 hybrids, and two diets, standard chow (STD or Western-style diet (WD. AG1478 has significant anti-tumor activity in the B6-Apc(Min/+ model with STD but only moderately on the WD and in the AOM model on an A background with a WD but not STD. On the F1 hybrid background AG1478 is effective in the Apc(Min/+ model with either STD or WD, but has only moderate efficacy in the AOM model with either diet. Sex differences were also observed. Unexpectedly, the level of liver EGFR phosphorylation inhibition by AG1478 was not positively correlated with inhibition of tumor growth in the AOM model. Model-dependent interactions between genetic background and diet can dramatically impact preclinical results, and indicate that low predictive values of preclinical studies can be attributed to study designs that do not account for the heterogeneous patient population or the diets they consume. Better-designed preclinical studies should lead to more accurate predictions of therapeutic response in the clinic.

  3. Genetic background impacts developmental potential of enteric neural crest-derived progenitors in the Sox10Dom model of Hirschsprung disease.

    Science.gov (United States)

    Walters, Lauren C; Cantrell, V Ashley; Weller, Kevin P; Mosher, Jack T; Southard-Smith, E Michelle

    2010-11-15

    Abnormalities in the development of enteric neural crest-derived progenitors (ENPs) that generate the enteric nervous system (ENS) can lead to aganglionosis in a variable portion of the distal gastrointestinal tract. Cumulative evidence suggests that variation of aganglionosis is due to gene interactions that modulate the ability of ENPs to populate the intestine; however, the developmental processes underlying this effect are unknown. We hypothesized that differences in enteric ganglion deficits could be attributable to the effects of genetic background on early developmental processes, including migration, proliferation, or lineage divergence. Developmental processes were investigated in congenic Sox10(Dom) mice, an established Hirschsprung disease (HSCR) model, on distinct inbred backgrounds, C57BL/6J (B6) and C3HeB/FeJ (C3Fe). Immuno-staining on whole-mount fetal gut tissue and dissociated cell suspensions was used to assess migration and proliferation. Flow cytometry utilizing the cell surface markers p75 and HNK-1 was used to isolate live ENPs for analysis of developmental potential. Frequency of ENPs was reduced in Sox10(Dom) embryos relative to wild-type embryos, but was unaffected by genetic background. Both migration and developmental potential of ENPs in Sox10(Dom) embryos were altered by inbred strain background with the most highly significant differences seen for developmental potential between strains and genotypes. In vivo imaging of fetal ENPs and postnatal ganglia demonstrates that altered lineage divergence impacts ganglia in the proximal intestine. Our analysis demonstrates that genetic background alters early ENS development and suggests that abnormalities in lineage diversification can shift the proportions of ENP populations and thus may contribute to ENS deficiencies in vivo.

  4. Impact of Assimilation on Heavy Rainfall Simulations Using WRF Model: Sensitivity of Assimilation Results to Background Error Statistics

    Science.gov (United States)

    Rakesh, V.; Kantharao, B.

    2017-03-01

    Data assimilation is considered as one of the effective tools for improving forecast skill of mesoscale models. However, for optimum utilization and effective assimilation of observations, many factors need to be taken into account while designing data assimilation methodology. One of the critical components that determines the amount and propagation observation information into the analysis, is model background error statistics (BES). The objective of this study is to quantify how BES in data assimilation impacts on simulation of heavy rainfall events over a southern state in India, Karnataka. Simulations of 40 heavy rainfall events were carried out using Weather Research and Forecasting Model with and without data assimilation. The assimilation experiments were conducted using global and regional BES while the experiment with no assimilation was used as the baseline for assessing the impact of data assimilation. The simulated rainfall is verified against high-resolution rain-gage observations over Karnataka. Statistical evaluation using several accuracy and skill measures shows that data assimilation has improved the heavy rainfall simulation. Our results showed that the experiment using regional BES outperformed the one which used global BES. Critical thermo-dynamic variables conducive for heavy rainfall like convective available potential energy simulated using regional BES is more realistic compared to global BES. It is pointed out that these results have important practical implications in design of forecast platforms while decision-making during extreme weather events

  5. Genetic Determinism of Sensitivity to Corynespora cassiicola Exudates in Rubber Tree (Hevea brasiliensis).

    Science.gov (United States)

    Tran, Dinh Minh; Clément-Demange, André; Déon, Marine; Garcia, Dominique; Le Guen, Vincent; Clément-Vidal, Anne; Soumahoro, Mouman; Masson, Aurélien; Label, Philippe; Le, Mau Tuy; Pujade-Renaud, Valérie

    2016-01-01

    An indirect phenotyping method was developed in order to estimate the susceptibility of rubber tree clonal varieties to Corynespora Leaf Fall (CLF) disease caused by the ascomycete Corynespora cassiicola. This method consists in quantifying the impact of fungal exudates on detached leaves by measuring the induced electrolyte leakage (EL%). The tested exudates were either crude culture filtrates from diverse C. cassiicola isolates or the purified cassiicolin (Cas1), a small secreted effector protein produced by the aggressive isolate CCP. The test was found to be quantitative, with the EL% response proportional to toxin concentration. For eight clones tested with two aggressive isolates, the EL% response to the filtrates positively correlated to the response induced by conidial inoculation. The toxicity test applied to 18 clones using 13 toxinic treatments evidenced an important variability among clones and treatments, with a significant additional clone x treatment interaction effect. A genetic linkage map was built using 306 microsatellite markers, from the F1 population of the PB260 x RRIM600 family. Phenotyping of the population for sensitivity to the purified Cas1 effector and to culture filtrates from seven C. cassiicola isolates revealed a polygenic determinism, with six QTL detected on five chromosomes and percentages of explained phenotypic variance varying from 11 to 17%. Two common QTL were identified for the CCP filtrate and the purified cassiicolin, suggesting that Cas1 may be the main effector of CCP filtrate toxicity. The CCP filtrate clearly contrasted with all other filtrates. The toxicity test based on Electrolyte Leakage Measurement offers the opportunity to assess the sensitivity of rubber genotypes to C. cassiicola exudates or purified effectors for genetic investigations and early selection, without risk of spreading the fungus in plantations. However, the power of this test for predicting field susceptibility of rubber clones to CLF will have

  6. Genetic Determinism of Sensitivity to Corynespora cassiicola Exudates in Rubber Tree (Hevea brasiliensis)

    Science.gov (United States)

    Tran, Dinh Minh; Clément-Demange, André; Déon, Marine; Garcia, Dominique; Le Guen, Vincent; Clément-Vidal, Anne; Soumahoro, Mouman; Masson, Aurélien; Label, Philippe; Le, Mau Tuy; Pujade-Renaud, Valérie

    2016-01-01

    An indirect phenotyping method was developed in order to estimate the susceptibility of rubber tree clonal varieties to Corynespora Leaf Fall (CLF) disease caused by the ascomycete Corynespora cassiicola. This method consists in quantifying the impact of fungal exudates on detached leaves by measuring the induced electrolyte leakage (EL%). The tested exudates were either crude culture filtrates from diverse C. cassiicola isolates or the purified cassiicolin (Cas1), a small secreted effector protein produced by the aggressive isolate CCP. The test was found to be quantitative, with the EL% response proportional to toxin concentration. For eight clones tested with two aggressive isolates, the EL% response to the filtrates positively correlated to the response induced by conidial inoculation. The toxicity test applied to 18 clones using 13 toxinic treatments evidenced an important variability among clones and treatments, with a significant additional clone x treatment interaction effect. A genetic linkage map was built using 306 microsatellite markers, from the F1 population of the PB260 x RRIM600 family. Phenotyping of the population for sensitivity to the purified Cas1 effector and to culture filtrates from seven C. cassiicola isolates revealed a polygenic determinism, with six QTL detected on five chromosomes and percentages of explained phenotypic variance varying from 11 to 17%. Two common QTL were identified for the CCP filtrate and the purified cassiicolin, suggesting that Cas1 may be the main effector of CCP filtrate toxicity. The CCP filtrate clearly contrasted with all other filtrates. The toxicity test based on Electrolyte Leakage Measurement offers the opportunity to assess the sensitivity of rubber genotypes to C. cassiicola exudates or purified effectors for genetic investigations and early selection, without risk of spreading the fungus in plantations. However, the power of this test for predicting field susceptibility of rubber clones to CLF will have

  7. Context-sensitive network-based disease genetics prediction and its implications in drug discovery.

    Science.gov (United States)

    Chen, Yang; Xu, Rong

    2017-04-01

    Disease phenotype networks play an important role in computational approaches to identifying new disease-gene associations. Current disease phenotype networks often model disease relationships based on pairwise similarities, therefore ignore the specific context on how two diseases are connected. In this study, we propose a new strategy to model disease associations using context-sensitive networks (CSNs). We developed a CSN-based phenome-driven approach for disease genetics prediction, and investigated the translational potential of the predicted genes in drug discovery. We constructed CSNs by directly connecting diseases with associated phenotypes. Here, we constructed two CSNs using different data sources; the two networks contain 26 790 and 13 822 nodes respectively. We integrated the CSNs with a genetic functional relationship network and predicted disease genes using a network-based ranking algorithm. For comparison, we built Similarity-Based disease Networks (SBN) using the same disease phenotype data. In a de novo cross validation for 3324 diseases, the CSN-based approach significantly increased the average rank from top 12.6 to top 8.8% for all tested genes comparing with the SBN-based approach ( pdisease using CSNs, and demonstrated that the top-ranked genes are highly relevant to PD pathologenesis. We pin-pointed a top-ranked drug target gene for PD, and found its association with neurodegeneration supported by literature. In summary, CSNs lead to significantly improve the disease genetics prediction comparing with SBNs and provide leads for potential drug targets. nlp.case.edu/public/data/. rxx@case.edu.

  8. Genetic Sensitivity to Phenylthiocarbamide – Effect on Body Mass Indices and DNA damage

    Directory of Open Access Journals (Sweden)

    Gursatej Gandhi

    2012-06-01

    Full Text Available As sensitivity to bitter taste (phenylthiocarbamide [PTC] perception has been maintained at high frequency worldwide, its use as a potential genetic marker for food preferences and dietary choices and its influence on body weight/adiposity which in turn maybe a contributor to various co-morbidities including malignancy needs to be explored in the Punjabi context where there is higher per capita income, an adapted ‘western’ dietary pattern with traditional culinary habits and reduced physical activity. Since studies linking PTC tasting status, indices of obesity and DNA damage have not come to attention, the present study, using the alkaline Single Cell Gel Electrophoresis assay was carried out to assess genomic damage in peripheral blood leukocytes (PBL of 144 individuals, both obese (n=96, as determined by body mass index [BMI] and waist-hip ratio [WHR] and normal weight healthy (n=46 subjects. Their PTC status revealed 73 tasters and 69 non-tasters. The odds ratio revealed a 2.51 times increased risk in non-tasters (OR=2.51; 95%CI 1.20-5.25 for having BMI≥ 25.0 kg/m2 in comparison to risk in tasters while the risk ratio revealed a 1.32 times increased probability of non-tasters for having BMI≥ 25.0 kg/m2 in comparison to tasters (RR=1.32; 95%CI 1.05-1.66. The genetic damage in the obese group (characterized on the bases of their gender and PTC tasting ability was very highly significant (p<0.001 compared to the values in the matched control group (healthy, normal weight subjects. In both the taster and non-taster groups, BMI and WC (waist circumference significantly correlated to genetic damage indices though PTC tasting ability did not appear to influence BMI, WHR and WC.

  9. The Genetic Structure, Virulence, and Fungicide Sensitivity of Fusarium fujikuroi in Taiwan.

    Science.gov (United States)

    Chen, Yu-Chia; Lai, Ming-Hsin; Wu, Chia-Yi; Lin, Tsung-Chun; Cheng, An-Hsiu; Yang, Chin-Cheng; Wu, Hsin-Yuh; Chu, Sheng-Chi; Kuo, Chien-Chih; Wu, Yea-Fang; Lin, Guo-Cih; Tseng, Min-Nan; Tsai, Yi-Chen; Lin, Chun-Chi; Chen, Chi-Yu; Huang, Jenn-Wen; Lin, Heng-An; Chung, Chia-Lin

    2016-06-01

    The rice disease bakanae, caused by Fusarium fujikuroi Nirenberg, has been present in Taiwan for over a century. To better understand the genetic diversity and structure of F. fujikuroi, a set of 16 polymorphic simple sequence repeat (SSR) markers were newly developed and used to analyze 637 F. fujikuroi isolates collected in 14 cities or counties around Taiwan from 1996 to 2013. On the basis of Bayesian clustering, the isolates were classified into four highly differentiated clusters: cluster B likely derived from the more widespread and genetically diversified clusters A or C, and cluster D was restricted to four cities or counties and may have been introduced from unknown sources genetically distinct from clusters A, B, and C. The coexistence of both mating types (MAT1-1:MAT1-2 = 1:1.88) and the highly diversified vegetative compatibility groups (VCG) (16 VCG among the 21 assessed isolates) suggest the likelihood of sexual reproduction in the field. However, the biased mating type ratios and linkage disequilibrium in the population suggest nonrandom mating between individuals. A significant pattern of isolation by distance was also detected, which implies a geographical restricted gene flow and low dissemination ability of F. fujikuroi. Evaluation of 24 representative isolates on eight rice varieties revealed differential levels of virulence, however no clear pattern of specific variety x isolate interaction was observed. Investigations of the differences in virulence and fungicide sensitivity between 8 early isolates (1998 and 2002) and 52 recent isolates (2012) indicate the evolution of increased resistance to the fungicide prochloraz in F. fujikuroi in Taiwan.

  10. Abrupt millennial variability and interdecadal-interstadial oscillations in a global coupled model: sensitivity to the background climate state

    Energy Technology Data Exchange (ETDEWEB)

    Arzel, Olivier [The University of New South Wales, Climate Change Research Centre (CCRC), Sydney (Australia); Universite de Bretagne Occidentale, Laboratoire de Physique des Oceans (LPO), Brest (France); England, Matthew H. [The University of New South Wales, Climate Change Research Centre (CCRC), Sydney (Australia); Verdiere, Alain Colin de; Huck, Thierry [Universite de Bretagne Occidentale, Laboratoire de Physique des Oceans (LPO), Brest (France)

    2012-07-15

    The origin and bifurcation structure of abrupt millennial-scale climate transitions under steady external solar forcing and in the absence of atmospheric synoptic variability is studied by means of a global coupled model of intermediate complexity. We show that the origin of Dansgaard-Oeschger type oscillations in the model is caused by the weaker northward oceanic heat transport in the Atlantic basin. This is in agreement with previous studies realized with much simpler models, based on highly idealized geometries and simplified physics. The existence of abrupt millennial-scale climate transitions during glacial times can therefore be interpreted as a consequence of the weakening of the negative temperature-advection feedback. This is confirmed through a series of numerical experiments designed to explore the sensitivity of the bifurcation structure of the Atlantic meridional overturning circulation to increased atmospheric CO{sub 2} levels under glacial boundary conditions. Contrasting with the cold, stadial, phases of millennial oscillations, we also show the emergence of strong interdecadal variability in the North Atlantic sector during warm interstadials. The instability driving these interdecadal-interstadial oscillations is shown to be identical to that found in ocean-only models forced by fixed surface buoyancy fluxes, that is, a large-scale baroclinic instability developing in the vicinity of the western boundary current in the North Atlantic. Comparisons with modern observations further suggest a physical mechanism similar to that driving the 30-40 years time scale associated with the Atlantic multidecadal oscillation. (orig.)

  11. Silicon-based antenna-coupled polarization-sensitive millimeter-wave bolometer arrays for cosmic microwave background instruments

    Science.gov (United States)

    Rostem, Karwan; Ali, Aamir; Appel, John W.; Bennett, Charles L.; Brown, Ari; Chang, Meng-Ping; Chuss, David T.; Colazo, Felipe A.; Costen, Nick; Denis, Kevin L.; Essinger-Hileman, Tom; Hu, Ron; Marriage, Tobias A.; Moseley, Samuel H.; Stevenson, Thomas R.; U-Yen, Kongpop; Wollack, Edward J.; Xu, Zhilei

    2016-07-01

    We describe feedhorn-coupled polarization-sensitive detector arrays that utilize monocrystalline silicon as the dielectric substrate material. Monocrystalline silicon has a low-loss tangent and repeatable dielectric constant, characteristics that are critical for realizing efficient and uniform superconducting microwave circuits. An additional advantage of this material is its low specific heat. In a detector pixel, two Transition-Edge Sensor (TES) bolometers are antenna-coupled to in-band radiation via a symmetric planar orthomode transducer (OMT). Each orthogonal linear polarization is coupled to a separate superconducting microstrip transmission line circuit. On-chip filtering is employed to both reject out-of-band radiation from the upper band edge to the gap frequency of the niobium superconductor, and to flexibly define the bandwidth for each TES to meet the requirements of the application. The microwave circuit is compatible with multi-chroic operation. Metalized silicon platelets are used to define the backshort for the waveguide probes. This micro-machined structure is also used to mitigate the coupling of out-of-band radiation to the microwave circuit. At 40 GHz, the detectors have a measured efficiency of ˜90%. In this paper, we describe the development of the 90 GHz detector arrays that will be demonstrated using the Cosmology Large Angular Scale Surveyor (CLASS) ground-based telescope.

  12. Punishment sensitivity and tension reduction: Exploring the potential influence of genetics on South Korean alcohol consumption

    Directory of Open Access Journals (Sweden)

    Benjamin J. Mahoney

    2016-12-01

    Full Text Available Aldehyde dehydrogenase 2*2 (ALDH2*2 is a genetically mutated enzyme that affects the liver’s ability to break down acetaldehyde, resulting in immediate negative physical effects following alcohol consumption. This usually leads to reduced lifetime alcohol dependence rates among those with ALDH2*2. Paradoxically, while around 30% of South Koreans have ALDH2*2, they still maintain both high levels of alcohol consumption and dependence. Therefore, how the negative reactions to alcohol experienced by those with ALDH2*2 interact with the expected effects of alcohol and sensitivity to punishment is of interest. Four hundred and sixty South Korean university students were tested for the ALDH2 gene type and completed alcohol expectancy and sensitivity to reward/punishment measures. The results indicated that there are different predictors of alcohol consumption depending on gene type, with ALDH2*2 heavy drinkers exhibiting lower levels of SP and higher levels of tension reduction expectancy. These findings suggest that ALDH2*2 plays a central role in differences in motivation for alcohol consumption among South Koreans.

  13. An Efficient Cost-Sensitive Feature Selection Using Chaos Genetic Algorithm for Class Imbalance Problem

    Directory of Open Access Journals (Sweden)

    Jing Bian

    2016-01-01

    Full Text Available In the era of big data, feature selection is an essential process in machine learning. Although the class imbalance problem has recently attracted a great deal of attention, little effort has been undertaken to develop feature selection techniques. In addition, most applications involving feature selection focus on classification accuracy but not cost, although costs are important. To cope with imbalance problems, we developed a cost-sensitive feature selection algorithm that adds the cost-based evaluation function of a filter feature selection using a chaos genetic algorithm, referred to as CSFSG. The evaluation function considers both feature-acquiring costs (test costs and misclassification costs in the field of network security, thereby weakening the influence of many instances from the majority of classes in large-scale datasets. The CSFSG algorithm reduces the total cost of feature selection and trades off both factors. The behavior of the CSFSG algorithm is tested on a large-scale dataset of network security, using two kinds of classifiers: C4.5 and k-nearest neighbor (KNN. The results of the experimental research show that the approach is efficient and able to effectively improve classification accuracy and to decrease classification time. In addition, the results of our method are more promising than the results of other cost-sensitive feature selection algorithms.

  14. Enhanced biofilm formation and multi‐host transmission evolve from divergent genetic backgrounds in C ampylobacter jejuni

    OpenAIRE

    Pascoe, Ben; Méric, Guillaume; Murray, Susan; Yahara, Koji; Mageiros, Leonardos; Bowen, Ryan; Jones, Nathan H.; Jeeves, Rose E.; Lappin‐Scott, Hilary M.; Asakura, Hiroshi; Sheppard, Samuel K.

    2015-01-01

    Summary Multicellular biofilms are an ancient bacterial adaptation that offers a protective environment for survival in hostile habitats. In microaerophilic organisms such as C ampylobacter, biofilms play a key role in transmission to humans as the bacteria are exposed to atmospheric oxygen concentrations when leaving the reservoir host gut. Genetic determinants of biofilm formation differ between species, but little is known about how strains of the same species achieve the biofilm phenotype...

  15. Genetic knockout of the α7 nicotinic acetylcholine receptor gene alters hippocampal long-term potentiation in a background strain-dependent manner.

    Science.gov (United States)

    Freund, Ronald K; Graw, Sharon; Choo, Kevin S; Stevens, Karen E; Leonard, Sherry; Dell'Acqua, Mark L

    2016-08-01

    Reduced α7 nicotinic acetylcholine receptor (nAChR) function is linked to impaired hippocampal-dependent sensory processing and learning and memory in schizophrenia. While knockout of the Chrna7 gene encoding the α7nAChR on a C57/Bl6 background results in changes in cognitive measures, prior studies found little impact on hippocampal synaptic plasticity in these mice. However, schizophrenia is a multi-genic disorder where complex interactions between specific genetic mutations and overall genetic background may play a prominent role in determining phenotypic penetrance. Thus, we compared the consequences of knocking out the α7nAChR on synaptic plasticity in C57/Bl6 and C3H mice, which differ in their basal α7nAChR expression levels. Homozygous α7 deletion in C3H mice, which normally express higher α7nAChR levels, resulted in impaired long-term potentiation (LTP) at hippocampal CA1 synapses, while C3H α7 heterozygous mice maintained robust LTP. In contrast, homozygous α7 deletion in C57 mice, which normally express lower α7nAChR levels, did not alter LTP, as had been previously reported for this strain. Thus, the threshold of Chrna7 expression required for LTP may be different in the two strains. Measurements of auditory gating, a hippocampal-dependent behavioral paradigm used to identify schizophrenia-associated sensory processing deficits, was abnormal in C3H α7 knockout mice confirming that auditory gating also requires α7nAChR expression. Our studies highlight the importance of genetic background on the regulation of synaptic plasticity and could be relevant for understanding genetic and cognitive heterogeneity in human studies of α7nAChR dysfunction in mental disorders.

  16. On the (In)Efficiency of the Cross-Correlation Statistic for Gravitational Wave Stochastic Background Signals with Non-Gaussian Noise and Heterogeneous Detector Sensitivities

    CERN Document Server

    Lionel, Martellini

    2015-01-01

    Under standard assumptions including stationary and serially uncorrelated Gaussian gravitational wave stochastic background signal and noise distributions, as well as homogenous detector sensitivities, the standard cross-correlation detection statistic is known to be optimal in the sense of minimizing the probability of a false dismissal at a fixed value of the probability of a false alarm. The focus of this paper is to analyze the comparative efficiency of this statistic, versus a simple alternative statistic obtained by cross-correlating the \\textit{squared} measurements, in situations that deviate from such standard assumptions. We find that differences in detector sensitivities have a large impact on the comparative efficiency of the cross-correlation detection statistic, which is dominated by the alternative statistic when these differences reach one order of magnitude. This effect holds even when both the signal and noise distributions are Gaussian. While the presence of non-Gaussian signals has no mate...

  17. Influence of the Earth on the background and the sensitivity of the GRM and ECLAIRs instruments aboard the Chinese-French mission SVOM

    CERN Document Server

    Zhao, Donghua; Sizun, Patrick; Wu, Bobing; Dong, Yongwei; Schanne, Stéphane; Song, Liming; Liu, Jiangtao

    2012-01-01

    SVOM (Space-based multi-band astronomical Variable Object Monitor) is a future Chinese-French satellite mission which is dedicated to Gamma-Ray Burst (GRB) studies. Its anti-solar pointing strategy makes the Earth cross the field of view of its payload every orbit. In this paper, we present the variations of the gamma-ray background of the two high energy instruments aboard SVOM, the Gamma-Ray Monitor (GRM) and ECLAIRs, as a function of the Earth position. We conclude with an estimate of the Earth influence on their sensitivity and their GRB detection capability.

  18. Allergic sensitization: screening methods

    DEFF Research Database (Denmark)

    Ladics, Gregory S.; Fry, Jeremy; Goodman, Richard

    2014-01-01

    Experimental in silico, in vitro, and rodent models for screening and predicting protein sensitizing potential are discussed, including whether there is evidence of new sensitizations and allergies since the introduction of genetically modified crops in 1996, the importance of linear versus...... of infection; (f) role of the gut microbiota; (g) influence of the structure and physicochemical properties of the protein; and (h) the genetic background and physiology of consumers. The consensus view is that sensitization screening models are not yet validated to definitively predict the de novo sensitizing...

  19. Effectiveness of vaccination with recombinant HpaA from Helicobacter pylori is influenced by host genetic background.

    Science.gov (United States)

    Sutton, Philip; Doidge, Christopher; Pinczower, Gideon; Wilson, John; Harbour, Stacey; Swierczak, Agnieszka; Lee, Adrian

    2007-07-01

    Several studies have explored the production and immunogenicity of HpaA as a potential protective antigen against Helicobacter pylori but little is known regarding its protective capabilities. We therefore evaluated the protective efficacy of recombinant HpaA (rHpaA) as a candidate vaccine antigen against H. pylori. To explore the impact of genetic diversity, inbred and outbred mice were prophylactically and therapeutically immunized with rHpaA adjuvanted with cholera toxin (CT). Prophylactic immunization induced a reduction in bacterial colonization in BALB/c and QS mice, but was ineffective in C57BL/6 mice, despite induction of antigen-specific antibodies. By contrast, therapeutic immunization was effective in all three strains of mice. Prophylactic immunization with CT-adjuvanted rHpaA was more effective when delivered via the nasal route than following intragastric delivery in BALB/c mice. However, HpaA-mediated protection was inferior to that induced by bacterial lysate. Hence, protective efficacy is inducible with vaccines containing HpaA, most relevantly shown in an outbred population of mice. The effectiveness of protection induced by HpaA antigen was influenced by host genetics and was less effective than lysate. HpaA therefore has potential for the development of effective immunization against H. pylori but this would probably entail the antigen to be one component of a multiantigenic vaccine.

  20. [Recent perspectives on the development of the central nervous system and the genetic background of neural tube defects].

    Science.gov (United States)

    Joó, József Gábor

    2009-05-10

    Neural tube defects are rare and mostly lethal malformations. The pattern of inheritance of these malformations is multifactorial, rendering the identification of the underlying causes. Numerous studies have been conducted to elucidate the genetic basis of the development of the central nervous system. Essential signaling pathways of the development of the central nervous system include the planar cell polarity pathway, which is important for the initiation of neural tube closure as well as sonic hedgehog pathway, which regulates the neural plate bending. Genes and their mutations influencing the different stages of neurulation have been investigated for their eventual role in the development of these malformations. Among the environmental factors, folic acid seems to be the most important modifier of the risk of human neural tube defects. Genes of the folate metabolism pathways have also been investigated to identify mutations resulting in increased risk of NTDs. In this review the author has attempted to summarize the knowledge on neural tube defects, with special regard to genetic factors of the etiology.

  1. The Protective Effect of Minocycline in a Paraquat-Induced Parkinson's Disease Model in Drosophila is Modified in Altered Genetic Backgrounds

    Directory of Open Access Journals (Sweden)

    Arati A. Inamdar

    2012-01-01

    Full Text Available Epidemiological studies link the herbicide paraquat to increased incidence of Parkinson's disease (PD. We previously reported that Drosophila exposed to paraquat recapitulate PD symptoms, including region-specific degeneration of dopaminergic neurons. Minocycline, a tetracycline derivative, exerts ameliorative effects in neurodegenerative disease models, including Drosophila. We investigated whether our environmental toxin-based PD model could contribute to an understanding of cellular and genetic mechanisms of minocycline action and whether we could assess potential interference with these drug effects in altered genetic backgrounds. Cofeeding of minocycline with paraquat prolonged survival, rescued mobility defects, blocked generation of reactive oxygen species, and extended dopaminergic neuron survival, as has been reported previously for a genetic model of PD in Drosophila. We then extended this study to identify potential interactions of minocycline with genes regulating dopamine homeostasis that might modify protection against paraquat and found that deficits in GTP cyclohydrolase adversely affect minocycline rescue. We further performed genetic studies to identify signaling pathways that are necessary for minocycline protection against paraquat toxicity and found that mutations in the Drosophila genes that encode c-Jun N-terminal kinase (JNK and Akt/Protein kinase B block minocycline rescue.

  2. Skewed Helper T-Cell Responses to IL-12 Family Cytokines Produced by Antigen-Presenting Cells and the Genetic Background in Behcet’s Disease

    Directory of Open Access Journals (Sweden)

    Jun Shimizu

    2013-01-01

    Full Text Available Behcet’s disease (BD is a multisystemic inflammatory disease and is characterized by recurrent attacks on eyes, brain, skin, and gut. There is evidence that skewed T-cell responses contributed to its pathophysiology in patients with BD. Recently, we found that Th17 cells, a new helper T (Th cell subset, were increased in patients with BD, and both Th type 1 (Th1 and Th17 cell differentiation signaling pathways were overactivated. Several researches revealed that genetic polymorphisms in Th1/Th17 cell differentiation signaling pathways were associated with the onset of BD. Here, we summarize current findings on the Th cell subsets, their contribution to the pathogenesis of BD and the genetic backgrounds, especially in view of IL-12 family cytokine production and pattern recognition receptors of macrophages/monocytes.

  3. The physiological effects of deleting the mouse SLC30A8 gene encoding zinc transporter-8 are influenced by gender and genetic background.

    Directory of Open Access Journals (Sweden)

    Lynley D Pound

    Full Text Available The SLC30A8 gene encodes the islet-specific transporter ZnT-8, which is hypothesized to provide zinc for insulin-crystal formation. A polymorphic variant in SLC30A8 is associated with altered susceptibility to type 2 diabetes. Several groups have examined the effect of global Slc30a8 gene deletion but the results have been highly variable, perhaps due to the mixed 129SvEv/C57BL/6J genetic background of the mice studied. We therefore sought to remove the conflicting effect of 129SvEv-specific modifier genes.The impact of Slc30a8 deletion was examined in the context of the pure C57BL/6J genetic background.Male C57BL/6J Slc30a8 knockout (KO mice had normal fasting insulin levels and no change in glucose-stimulated insulin secretion (GSIS from isolated islets in marked contrast to the ∼50% and ∼35% decrease, respectively, in both parameters observed in male mixed genetic background Slc30a8 KO mice. This observation suggests that 129SvEv-specific modifier genes modulate the impact of Slc30a8 deletion. In contrast, female C57BL/6J Slc30a8 KO mice had reduced (∼20% fasting insulin levels, though this was not associated with a change in fasting blood glucose (FBG, or GSIS from isolated islets. This observation indicates that gender also modulates the impact of Slc30a8 deletion, though the physiological explanation as to why impaired insulin secretion is not accompanied by elevated FBG is unclear. Neither male nor female C57BL/6J Slc30a8 KO mice showed impaired glucose tolerance.Our data suggest that, despite a marked reduction in islet zinc content, the absence of ZnT-8 does not have a substantial impact on mouse physiology.

  4. 达乌尔黄鼠对溴敌隆敏感性的测定%The determination on sensitive background of S. dauricus to Bromadiolone

    Institute of Scientific and Technical Information of China (English)

    陈显赫; 孙启廷; 张雁冰; 段天一

    2012-01-01

    Objective To establish sensitive background of S. dauricus to Bromadiolone and to provide scientific theoretical basis for checking resistance of S. dauricus to Bromadiolone. Methods With alternative feeding test and methods of WHO, upper limit of 95% effective dose were established as the most suitable dose for eliminating mice; With the methods of Litchfield, the sensitive background of S. dauricus to the second generation anticoagulant poison were calculated by eating poison period with death rate. Results The most dose was 4. 87mg/kg which sensitive background of Bromadiolone was determined on S. dauricus and eating poison period was twenty days. The rush hour of animal death arised in the third and fourth days and animals died overall in the seventh after feeding poisons. Conclusions Investigating resistance of S. dauricus to Bromadiolone has practical meaning with 0. 01% baits for sensitive determination and eating poison period 20 days as standard.%目的 确立达乌尔黄鼠对溴敌隆的敏感本底(即食毒期),为检测达乌尔黄鼠对溴敌隆抗药性提供科学的理论依据.方法 通过摄食试验,以世界卫生组织(WHO)提供的方法,ED95置信上限确立最适宜的灭鼠剂量;通过食毒期与其对应的死亡率,用Litchfield方法计算出达乌尔黄鼠对第2代抗凝血灭鼠剂的敏感本底.结果 达乌尔黄鼠对溴敌隆敏感本底测定最适宜的剂量为4.87 mg/kg,食毒期为20 d.测定中动物死亡高峰出现在饲毒后第3~4d,第10 d全部死亡.结论 以0.01%浓度配制毒饵进行敏感性测定,以20d为食毒期作为标准进行达乌尔黄鼠对溴敌隆的抗药性调查具有实际意义.

  5. A new measurement for the revised reinforcement sensitivity theory: psychometric criteria and genetic validation

    Directory of Open Access Journals (Sweden)

    Martin eReuter

    2015-03-01

    Full Text Available Jeffrey Gray’s Reinforcement Sensitivity Theory (RST represents one of the most influential biologically-based personality theories describing individual differences in approach and avoidance tendencies. The most prominent self-report inventory to measure individual differences in approach and avoidance behavior to date is the BIS/BAS scale by Carver & White (1994. As Gray & McNaughton (2000 revised the RST after its initial formulation in the 1970/80s, and given the Carver & White measure is based on the initial conceptualization of RST, there is a growing need for self-report inventories measuring individual differences in the revised behavioral inhibition system (BIS, behavioral activation system (BAS and the fight, flight, freezing system (FFFS. Therefore, in this paper we present a new questionnaire measuring individual differences in the revised constructs of the BIS, BAS and FFFS in N = 1814 participants (German sample. An English translated version of the new measure is also presented and tested in N = 299 English language participants. A large number of German participants (N = 1090 also filled in the BIS/BAS scales by Carver & White (1994 and the correlations between these measures are presented. Finally, this same subgroup of participants provided buccal swaps for the investigation of the arginine vasopressin receptor 1a (AVPR1a gene. Here, a functional genetic polymorphism (rs11174811 on the AVPR1a gene was shown to be associated with individual differences in both the revised BIS and classic BIS dimensions.

  6. Mass Rearing of Temperature Sensitive Genetic Sexing Strains in the Mediterranean Fruit Fly (Ceratitis Capitata)

    Energy Technology Data Exchange (ETDEWEB)

    Caceres, C. [FAO/IAEA Agriculture and Biotechnology Laboratory, Entomology Unit, A-2444 Seibersdorf (Austria)]. E-mail: c.caceres@iaea.org

    2002-09-15

    Genetic sexing strains (GSS) based on the temperature sensitive lethal(tsl) mutation are being used to produce sterile male medflies for large scale sterile insect technique (SIT) programmes for this pest. The use of male-only strains increases the overall efficiency of the technique. Currently more than 1.4 billion sterile male-only pupae are produced per week in different facilities around the world. Due to the mutations used to construct these strains, that is, translocations and selectable markers, they require different and more careful mass rearing procedures than do bisexual strains (BSS). The basic rearing technology has been developed and can be used to produce only males on a predictable basis to a level of 99.9% accuracy. If specific rearing procedures are followed, then tsl-based GSS has a rearing efficiency that is equal to that of a BSS and it is already know that males produced by the tsl-based GSS are of equal quality to males produced by BSS. Based on current rearing technology the cost of production of male pupae is about the same for both types of strain. This is due to the large colony that is required for the tsl-based GSS. This paper discusses the considerations that need to be taken into account during mass rearing of GSS and identifies the most efficient production processes that are currently available. (author)

  7. A new measure for the revised reinforcement sensitivity theory: psychometric criteria and genetic validation.

    Science.gov (United States)

    Reuter, Martin; Cooper, Andrew J; Smillie, Luke D; Markett, Sebastian; Montag, Christian

    2015-01-01

    Jeffrey Gray's Reinforcement Sensitivity Theory (RST) represents one of the most influential biologically-based personality theories describing individual differences in approach and avoidance tendencies. The most prominent self-report inventory to measure individual differences in approach and avoidance behavior to date is the BIS/BAS scale by Carver and White (1994). As Gray and McNaughton (2000) revised the RST after its initial formulation in the 1970/80s, and given the Carver and White measure is based on the initial conceptualization of RST, there is a growing need for self-report inventories measuring individual differences in the revised behavioral inhibition system (BIS), behavioral activation system (BAS) and the fight, flight, freezing system (FFFS). Therefore, in this paper we present a new questionnaire measuring individual differences in the revised constructs of the BIS, BAS and FFFS in N = 1814 participants (German sample). An English translated version of the new measure is also presented and tested in N = 299 English language participants. A large number of German participants (N = 1090) also filled in the BIS/BAS scales by Carver and White (1994) and the correlations between these measures are presented. Finally, this same subgroup of participants provided buccal swaps for the investigation of the arginine vasopressin receptor 1a (AVPR1a) gene. Here, a functional genetic polymorphism (rs11174811) on the AVPR1a gene was shown to be associated with individual differences in both the revised BIS and classic BIS dimensions.

  8. The genetics of multiple sclerosis: principles, background and updated results of the United Kingdom systematic genome screen.

    Science.gov (United States)

    Chataway, J; Feakes, R; Coraddu, F; Gray, J; Deans, J; Fraser, M; Robertson, N; Broadley, S; Jones, H; Clayton, D; Goodfellow, P; Sawcer, S; Compston, A

    1998-10-01

    Genetic susceptibility to multiple sclerosis is implicated on the basis of classical family studies and phenotype analyses. The only reproducible legacy from the candidate gene approach has been the discovery of population associations with alleles of the major histocompatibility complex. Systematic genome scanning has since been applied using a panel of anonymous markers to identify areas of linkage in co-affected siblings. Here, we describe the principles of genome screening and update the UK survey of multiple sclerosis. This identified 20 regions of potential interest, but in none was there unequivocal linkage. In theory, attempting to replicate these findings in a second set of sibling pair families is the most appropriate way to distinguish true from false positives, but unfortunately the number of families required to do this reliably is prohibitively large. We used three approaches to increase the definition achieved by the screen: (i) the number of sibling pairs typed in an identified region of potential linkage was extended; (ii) the information extraction was increased in an identified region; and (iii) a search was made for missed regions of potential linkage. Each of these approaches has considerable limitations. A chromosome-by-chromosome account is given to direct future searches. Although an additional marker placed distal to the 'hit' on chromosome 14q increased linkage in this area, and typing extra sibling pairs increased linkage on chromosomes 6p and 17q, evidence for linkage was more commonly reduced and no additional regions of interest were found. A further refinement of the genome screen was undertaken by conditioning for the presence of HLA-DR15. This produced a surprising degree of segregation among the regions of interest, which divided into two distinct groups depending on DR15 sharing: the DR15-sharing cohort comprised loci on chromosomal areas 1p, 17q and X; and the DR15-non-sharing cohort was made up of loci on 1cen, 3p, 7p, 14q and

  9. Cis-effects on meiotic recombination across distinct a1-sh2 intervals in a common Zea genetic background.

    Science.gov (United States)

    Yao, Hong; Schnable, Patrick S

    2005-08-01

    Genetic distances across the a1-sh2 interval varied threefold in three near-isogenic stocks that carry structurally distinct teosinte A1 Sh2 haplotypes (from Z. mays spp. mexicana Chalco, Z. mays spp. parviglumis, and Z. luxurians) and a common maize a1::rdt sh2 haplotype. In each haplotype >85% of recombination events resolved in the proximal 10% of the approximately 130-kb a1-sh2 interval. Even so, significant differences in the distributions of recombination breakpoints were observed across subintervals among haplotypes. Each of the three previously detected recombination hot spots was detected in at least one of the three teosinte haplotypes and two of these hot spots were not detected in at least one teosinte haplotype. Moreover, novel hot spots were detected in two teosinte haplotypes. Due to the near-isogenic nature of the three stocks, the observed variation in the distribution of recombination events is the consequence of cis-modifications. Although generally negatively correlated with rates of recombination per megabase, levels of sequence polymorphisms do not fully account for the nonrandom distribution of recombination breakpoints. This study also suggests that estimates of linkage disequilibrium must be interpreted with caution when considering whether a gene has been under selection.

  10. Interaction of environment conditions and genotypes on expression of genetic background in micro-phenophases of strawberry mixed flower bud

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    Selamovska Ana

    2013-01-01

    Full Text Available The aim of this research is differentiation or micro-phenophases of reproductive organs on two junebearing strawberry (Fragaria x anannassa varieties senga sengana and pocahontas, depending on climate conditions, rosettes ordering and cultivate manner (orchard mulched on black foil and orchard on bare soil. The beginning of differentiation of flower buds is genetic characteristic depending on climate conditions (insulations, day length, higher midday and night air temperatures from 1.05 till the beginning of differentiation, the sum of rainfalls from the beginning of May until the end of July, order of rosettes and cultivate manner The sum of effective temperatures over 10ºC from 1st of May till the beginning of differentiation has no influence on beginning of flower buds differentiation. First morphological changes of the apical meristem were started in the first decade of August that has coincided with the day length of 14 hours and day insulations of 9.3 hours. Micro-phenophases were undergoing almost at the same time in both varieties, only the beginning at pocahontas was 2-3 days earlier. Primary rosettes differ 10-15 days earlier than the secondary rosettes. Plants that grown on black foil had 7-10 days earlier flower bud differentiation compared to those grown on bare soil.

  11. Genetic recombination variation in wild Robertsonian mice: on the role of chromosomal fusions and Prdm9 allelic background

    Science.gov (United States)

    Capilla, Laia; Medarde, Nuria; Alemany-Schmidt, Alexandra; Oliver-Bonet, Maria; Ventura, Jacint; Ruiz-Herrera, Aurora

    2014-01-01

    Despite the existence of formal models to explain how chromosomal rearrangements can be fixed in a population in the presence of gene flow, few empirical data are available regarding the mechanisms by which genome shuffling contributes to speciation, especially in mammals. In order to shed light on this intriguing evolutionary process, here we present a detailed empirical study that shows how Robertsonian (Rb) fusions alter the chromosomal distribution of recombination events during the formation of the germline in a Rb system of the western house mouse (Mus musculus domesticus). Our results indicate that both the total number of meiotic crossovers and the chromosomal distribution of recombination events are reduced in mice with Rb fusions and that this can be related to alterations in epigenetic signatures for heterochromatinization. Furthermore, we detected novel house mouse Prdm9 allelic variants in the Rb system. Remarkably, mean recombination rates were positively correlated with a decrease in the number of ZnF domains in the Prdm9 gene. The suggestion that recombination can be modulated by both chromosomal reorganizations and genetic determinants that control the formation of double-stranded breaks during meiosis opens new avenues for understanding the role of recombination in chromosomal speciation. PMID:24850922

  12. Genome survey sequencing and genetic background characterization of Gracilariopsis lemaneiformis (Rhodophyta based on next-generation sequencing.

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    Wei Zhou

    Full Text Available Gracilariopsis lemaneiformis has a high economic value and is one of the most important aquaculture species in China. Despite it is economic importance, it has remained largely unstudied at the genomic level. In this study, we conducted a genome survey of Gp. lemaneiformis using next-generation sequencing (NGS technologies. In total, 18.70 Gb of high-quality sequence data with an estimated genome size of 97 Mb were obtained by HiSeq 2000 sequencing for Gp. lemaneiformis. These reads were assembled into 160,390 contigs with a N50 length of 3.64 kb, which were further assembled into 125,685 scaffolds with a total length of 81.17 Mb. Genome analysis predicted 3490 genes and a GC% content of 48%. The identified genes have an average transcript length of 1,429 bp, an average coding sequence size of 1,369 bp, 1.36 exons per gene, exon length of 1,008 bp, and intron length of 191 bp. From the initial assembled scaffold, transposable elements constituted 54.64% (44.35 Mb of the genome, and 7737 simple sequence repeats (SSRs were identified. Among these SSRs, the trinucleotide repeat type was the most abundant (up to 73.20% of total SSRs, followed by the di- (17.41%, tetra- (5.49%, hexa- (2.90%, and penta- (1.00% nucleotide repeat type. These characteristics suggest that Gp. lemaneiformis is a model organism for genetic study. This is the first report of genome-wide characterization within this taxon.

  13. Gene expression profiling in C57BL/6J and A/J mouse inbred strains reveals gene networks specific for brain regions independent of genetic background

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    Horvath Steve

    2010-01-01

    Full Text Available Abstract Background We performed gene expression profiling of the amygdala and hippocampus taken from inbred mouse strains C57BL/6J and A/J. The selected brain areas are implicated in neurobehavioral traits while these mouse strains are known to differ widely in behavior. Consequently, we hypothesized that comparing gene expression profiles for specific brain regions in these strains might provide insight into the molecular mechanisms of human neuropsychiatric traits. We performed a whole-genome gene expression experiment and applied a systems biology approach using weighted gene co-expression network analysis. Results We were able to identify modules of co-expressed genes that distinguish a strain or brain region. Analysis of the networks that are most informative for hippocampus and amygdala revealed enrichment in neurologically, genetically and psychologically related pathways. Close examination of the strain-specific gene expression profiles, however, revealed no functional relevance but a significant enrichment of single nucleotide polymorphisms in the probe sequences used for array hybridization. This artifact was not observed for the modules of co-expressed genes that distinguish amygdala and hippocampus. Conclusions The brain-region specific modules were found to be independent of genetic background and are therefore likely to represent biologically relevant molecular networks that can be studied to complement our knowledge about pathways in neuropsychiatric disease.

  14. Quantitative trait locus mapping with background control in genetic populations of clonal F1 and double cross.

    Science.gov (United States)

    Zhang, Luyan; Li, Huihui; Ding, Junqiang; Wu, Jianyu; Wang, Jiankang

    2015-12-01

    In this study, we considered five categories of molecular markers in clonal F1 and double cross populations, based on the number of distinguishable alleles and the number of distinguishable genotypes at the marker locus. Using the completed linkage maps, incomplete and missing markers were imputed as fully informative markers in order to simplify the linkage mapping approaches of quantitative trait genes. Under the condition of fully informative markers, we demonstrated that dominance effect between the female and male parents in clonal F1 and double cross populations can cause the interactions between markers. We then developed an inclusive linear model that includes marker variables and marker interactions so as to completely control additive effects of the female and male parents, as well as the dominance effect between the female and male parents. The linear model was finally used for background control in inclusive composite interval mapping (ICIM) of quantitative trait locus (QTL). The efficiency of ICIM was demonstrated by extensive simulations and by comparisons with simple interval mapping, multiple-QTL models and composite interval mapping. Finally, ICIM was applied in one actual double cross population to identify QTL on days to silking in maize.

  15. Oppositional defiant- and conduct disorder-like problems: neurodevelopmental predictors and genetic background in boys and girls, in a nationwide twin study

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    Nóra Kerekes

    2014-04-01

    Full Text Available Background. Previous research has supported gender-specific aetiological factors in oppositional defiant disorder (ODD and conduct disorder (CD. The aims of this study were to identify gender-specific associations between the behavioural problems–ODD/CD-like problems–and the neurodevelopmental disorders–attention deficit hyperactivity disorder (ADHD, autism spectrum disorder (ASD–and to investigate underlying genetic effects.Methods. 17,220 twins aged 9 or 12 were screened using the Autism–Tics, AD/HD and other Comorbidities inventory. The main covariates of ODD- and CD-like problems were investigated, and the relative importance of unique versus shared hereditary and environmental effects was estimated using twin model fitting.Results. Social interaction problems (one of the ASD subdomains was the strongest neurodevelopmental covariate of the behavioural problems in both genders, while ADHD-related hyperactivity/impulsiveness in boys and inattention in girls stood out as important covariates of CD-like problems. Genetic effects accounted for 50%–62% of the variance in behavioural problems, except in CD-like problems in girls (26%. Genetic and environmental effects linked to ADHD and ASD also influenced ODD-like problems in both genders and, to a lesser extent, CD-like problems in boys, but not in girls.Conclusions. The gender-specific patterns should be considered in the assessment and treatment, especially of CD.

  16. A possible correlation between the host genetic background in the epidemiology of Hepatitis B virus in the Amazon region of Brazil

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    A. K. C. R. Santos

    1995-08-01

    Full Text Available The Amazon region of Brazil is an area of great interest because of the large distribution of hepatitis B virus in specific Western areas. Seven urban communities and 24 Indian groups were visited in a total of 4,244 persons. Each individual was interviewed in order to obtain demographic and familial information. Whole blood was collected for serology and genetic determinations. Eleven genetic markers and three HBV markers were tested. Among the most relevant results it was possible to show that (i there was a large variation of previous exposure to HBV in both urban and non-urban groups ranging from 0 to 59.2%; (ii there was a different pattern of epidemiological distribution of HBV that was present even among a same linguistic Indian group, with mixed patterns of correlation between HBsAg and anti-HBs and (iii the prevalence of HBV markers (HBsAg and anti-HBs were significantly higher (P=0.0001 among the Indian population (18.8% than the urban groups (12.5%. Its possible that the host genetic background could influence and modulate the replication of the virus in order to generate HB carrier state.

  17. The mecA homolog mecC confers resistance against β-lactams in Staphylococcus aureus irrespective of the genetic strain background.

    Science.gov (United States)

    Ballhausen, Britta; Kriegeskorte, André; Schleimer, Nina; Peters, Georg; Becker, Karsten

    2014-07-01

    In staphylococci, methicillin resistance is mediated by mecA-encoded penicillin-binding protein 2a (PBP2a), which has a low affinity for beta-lactams. Recently, a novel PBP2a homolog was described as being encoded by mecC, which shares only 70% similarity to mecA. To prove that mecC is the genetic determinant that confers methicillin resistance in Staphylococcus aureus, a mecC knockout strain was generated. The S. aureus ΔmecC strain showed considerably reduced oxacillin and cefoxitin MICs (0.25 and 4 μg/ml, respectively) compared to those of the corresponding wild-type methicillin-resistant S. aureus (MRSA) strain (8 and 16 μg/ml, respectively). Complementing the mutant in trans with wild-type mecC restored the resistance to oxacillin and cefoxitin. By expressing mecC and mecA in different S. aureus clonal lineages, we found that mecC mediates resistance irrespective of the genetic strain background, yielding oxacillin and cefoxitin MIC values comparable to those with mecA. In addition, we showed that mecC expression is inducible by oxacillin, which supports the assumption that a functional beta-lactam-dependent regulatory system is active in MRSA strains possessing staphylococcal cassette chromosome mec (SCCmec) type XI. In summary, we showed that mecC is inducible by oxacillin and mediates beta-lactam resistance in SCCmec type XI-carrying strains as well as in different S. aureus genetic backgrounds. Furthermore, our results could explain the comparatively low MICs for clinical mecC-harboring S. aureus isolates. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  18. Genetic background contributes to the co-morbidity of anxiety and depression with audiogenic seizure propensity and responses to fluoxetine treatment.

    Science.gov (United States)

    Sarkisova, Karine Yu; Fedotova, Irina B; Surina, Natalia M; Nikolaev, Georgy M; Perepelkina, Olga V; Kostina, Zoya A; Poletaeva, Inga I

    2017-03-01

    Anxiety and depression are the most frequent comorbidities of different types of convulsive and non-convulsive epilepsies. Increased anxiety and depression-like phenotype have been described in the genetic absence epilepsy models as well as in models of limbic epilepsy and acquired seizure models, suggesting a neurobiological connection. However, whether anxiety and/or depression are comorbid to audiogenic epilepsy remains unclear. The aim of this study was to investigate whether anxiety or depression-like behavior can be found in rat strains with different susceptibility to audiogenic seizures (AS) and whether chronic fluoxetine treatment affects this co-morbidity. Behavior in the elevated plus-maze and the forced swimming test was studied in four strains: Wistar rats non-susceptible to AS; Krushinsky-Molodkina (KM) strain, selectively bred for AS propensity from outbred Wistar rats; and a selection lines bred for maximal AS expression (strain "4") and for a lack of AS (strain "0") from KM×Wistar F2 hybrids. Effects of chronic antidepressant treatment on AS and behavior were also evaluated. Anxiety and depression levels were higher in KM rats (with AS) compared with Wistar rats (without AS), indicating the comorbidity with AS. However, in strains "4" and "0" with contrasting AS expression, but with a genetic background close to KM rats, anxiety and depression were not as divergent as in KMs versus Wistars. Fluoxetine treatment exerted an antidepressant effect in all rat strains irrespective of its effect on AS. Genetic background contributes substantively to the co-morbidity of anxiety and depression with AS propensity. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Prevalence and diversity of enterotoxin genes with genetic background of Staphylococcus aureus isolates from different origins in China.

    Science.gov (United States)

    Chao, Guoxiang; Bao, Guangyu; Cao, Yongzhong; Yan, Wenguang; Wang, Yan; Zhang, Xiaorong; Zhou, Liping; Wu, Yantao

    2015-10-15

    Staphylococcal enterotoxins (SE) induce toxin-mediated diseases, such as food poisoning. In the present study, 568 isolates from different sources were tested for the prevalence of 18 SE genes and performed spa typing. In addition, we characterized the relationships between the distribution of SE genes and molecular clones based on multilocus sequence typing (MLST), spa and staphylococcal cassette chromosome mec (SCCmec) typing in selected 250 isolates. Approximately 54.40% of the isolates from different sources harbored one or more SE genes forming 120 distinct gene profiles. Seven genes, sea, seb, seg, seo, sem, seq, and sel were more frequently detected. The distributions of the SE genes among the isolates from human, animals, and foodborne origins were highly different with isolates from environments (P0.05). We identified two important gene clusters, sea-sek-seq, which is closely related to hospital-acquired (HA) methicillin-resistant Staphylococcus aureus (MRSA)-III, and the egc cluster, which accounts for nearly half of all genes. Approximately 71% isolates could be typed by spa, yielding 103 spa types, of which 18 spa types were primary types. In clonal complex (CC) 239, an important Asian HA-MRSA-III clone from humans, nearly all isolates harbored complete or partial sea-sek-seq cluster; the main spa types were t030 and t037. In CC630, an important new community-associated (CA) MRSA-V CC in China, only sporadic SE genes, three main spa types, t4549, t2196, and t377 were observed. The egc cluster coexisting with other genes was present in isolates of CC5, CC9, CC1281, CC1301, CC30 and sequence type (ST) 25, but completely absent in isolates of CC239, CC59, CC7, and CC88. The results illustrate the genetic clonal diversity and the identity of S. aureus isolates from different sources with respect to SE genes and highlight a correlation between SE genes or gene clusters and CCs, spa, and MRSA clones. The foodborne and human origin isolates were the main

  20. Mitochondrial genetic background modifies the relationship between traffic-related air pollution exposure and systemic biomarkers of inflammation.

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    Sharine Wittkopp

    Full Text Available BACKGROUND: Mitochondria are the main source of reactive oxygen species (ROS. Human mitochondrial haplogroups are linked to differences in ROS production and oxidative-stress induced inflammation that may influence disease pathogenesis, including coronary artery disease (CAD. We previously showed that traffic-related air pollutants were associated with biomarkers of systemic inflammation in a cohort panel of subjects with CAD in the Los Angeles air basin. OBJECTIVE: We tested whether air pollutant exposure-associated inflammation was stronger in mitochondrial haplogroup H than U (high versus low ROS production in this panel (38 subjects and 417 observations. METHODS: Inflammation biomarkers were measured weekly in each subject (≤ 12 weeks, including interleukin-6 (IL-6, tumor necrosis factor-α (TNF-α, C-reactive protein, interleukin-6 soluble receptor and tumor necrosis factor-soluble receptor II. We determined haplogroup by restriction fragment length polymorphism analysis. Air pollutants included nitrogen oxides (NOx, carbon monoxide (CO, organic carbon, elemental and black carbon (EC, BC; and particulate matter mass, three size fractions (<0.25 µm, 0.25-2.5 µm, and 2.5-10 µm in aerodynamic diameter. Particulate matter extracts were analyzed for organic compounds, including polycyclic aromatic hydrocarbons (PAH, and in vitro oxidative potential of aqueous extracts. Associations between exposures and biomarkers, stratified by haplogroup, were analyzed by mixed-effects models. RESULTS: IL-6 and TNF-α were associated with traffic-related air pollutants (BC, CO, NOx and PAH, and with mass and oxidative potential of quasi-ultrafine particles <0.25 µm. These associations were stronger for haplogroup H than haplogroup U. CONCLUSIONS: Results suggest that mitochondrial haplogroup U is a novel protective factor for air pollution-related systemic inflammation in this small group of subjects.

  1. Subtle genetic changes enhance virulence of methicillin resistant and sensitive Staphylococcus aureus

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    Hawes Alicia C

    2007-11-01

    Full Text Available Abstract Background Community acquired (CA methicillin-resistant Staphylococcus aureus (MRSA increasingly causes disease worldwide. USA300 has emerged as the predominant clone causing superficial and invasive infections in children and adults in the USA. Epidemiological studies suggest that USA300 is more virulent than other CA-MRSA. The genetic determinants that render virulence and dominance to USA300 remain unclear. Results We sequenced the genomes of two pediatric USA300 isolates: one CA-MRSA and one CA-methicillin susceptible (MSSA, isolated at Texas Children's Hospital in Houston. DNA sequencing was performed by Sanger dideoxy whole genome shotgun (WGS and 454 Life Sciences pyrosequencing strategies. The sequence of the USA300 MRSA strain was rigorously annotated. In USA300-MRSA 2658 chromosomal open reading frames were predicted and 3.1 and 27 kilobase (kb plasmids were identified. USA300-MSSA contained a 20 kb plasmid with some homology to the 27 kb plasmid found in USA300-MRSA. Two regions found in US300-MRSA were absent in USA300-MSSA. One of these carried the arginine deiminase operon that appears to have been acquired from S. epidermidis. The USA300 sequence was aligned with other sequenced S. aureus genomes and regions unique to USA300 MRSA were identified. Conclusion USA300-MRSA is highly similar to other MRSA strains based on whole genome alignments and gene content, indicating that the differences in pathogenesis are due to subtle changes rather than to large-scale acquisition of virulence factor genes. The USA300 Houston isolate differs from another sequenced USA300 strain isolate, derived from a patient in San Francisco, in plasmid content and a number of sequence polymorphisms. Such differences will provide new insights into the evolution of pathogens.

  2. Use of a Combined Duplex PCR/Dot Blot Assay for more sensitive genetic characterization

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    Erin Curry

    2008-01-01

    Full Text Available A reliable and sensitive method of genetic analysis is necessary to detect multiple specific nucleic acid sequences from samples containing limited template. The most widely utilized method of specific gene detection, polymerase chain reaction (PCR, imparts inconsistent results when assessing samples with restricted template, especially in a multiplex reaction when copies of target genes are unequal. This study aimed to compare two methods of PCR product analysis, fluorescent detection following agarose gel electrophoresis or dot blot hybridization with chemiluminescent evaluation, in the detection of a single copy gene (SRY and a multicopy gene (β-actin. Bovine embryo sex determination was employed to exploit the limited DNA template available and the target genes of unequal copies. Primers were used either independently or together in a duplex reaction with purified bovine genomic DNA or DNA isolated from embryos. When used independently, SRY and β-actin products were detected on a gel at the equivalent of 4-cell or 1-cell of DNA, respectively; however, the duplex reaction produced visible SRY bands at the 256 cell DNA equivalent and β-actin products at the 64 cell DNA equivalent. Upon blotting and hybridization of the duplex PCR reaction, product was visible at the 1–4 cell DNA equivalent. Duplex PCR was also conducted on 186 bovine embryos and product was subjected to gel electrophoresis or dot-blot hybridization in duplicate. Using PCR alone, sex determination was not possible for 22.6% of the samples. Using PCR combined with dot blot hybridization, 100.0% of the samples exhibited either both the male specific and β-actin products or the β-actin signal alone, indicating that the reaction worked in all samples. This study demonstrated that PCR amplification followed by dot blot hybridization provided more conclusive results in the evaluation of samples with low DNA concentrations and target genes of unequal copies.

  3. Genetic background can result in a marked or minimal effect of gene knockout (GPR55 and CB2 receptor in experimental autoimmune encephalomyelitis models of multiple sclerosis.

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    Sofia Sisay

    Full Text Available Endocannabinoids and some phytocannabinoids bind to CB1 and CB2 cannabinoid receptors, transient receptor potential vanilloid one (TRPV1 receptor and the orphan G protein receptor fifty-five (GPR55. Studies using C57BL/10 and C57BL/6 (Cnr2 (tm1Zim CB2 cannabinoid receptor knockout mice have demonstrated an immune-augmenting effect in experimental autoimmune encephalomyelitis (EAE models of multiple sclerosis. However, other EAE studies in Biozzi ABH mice often failed to show any treatment effect of either CB2 receptor agonism or antagonism on inhibition of T cell autoimmunity. The influence of genetic background on the induction of EAE in endocannabinoid system-related gene knockout mice was examined. It was found that C57BL/6.GPR55 knockout mice developed less severe disease, notably in female mice, following active induction with myelin oligodendrocyte glycoprotein 35-55 peptide. In contrast C57BL/6.CB2 (Cnr2 (Dgen receptor knockout mice developed augmented severity of disease consistent with the genetically and pharmacologically-distinct, Cnr2 (tm1Zim mice. However, when the knockout gene was bred into the ABH mouse background and EAE induced with spinal cord autoantigens the immune-enhancing effect of CB2 receptor deletion was lost. Likewise CB1 receptor and transient receptor potential vanilloid one knockout mice on the ABH background demonstrated no alteration in immune-susceptibility, in terms of disease incidence and severity of EAE, in contrast to that reported in some C57BL/6 mouse studies. Furthermore the immune-modulating influence of GPR55 was marginal on the ABH mouse background. Whilst sedative doses of tetrahydrocannabinol could induce immunosuppression, this was associated with a CB1 receptor rather than a CB2 receptor-mediated effect. These data support the fact that non-psychoactive doses of medicinal cannabis have a marginal influence on the immune response in MS. Importantly, it adds a note of caution for the translational

  4. Genetics

    Science.gov (United States)

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

  5. A resposta oxidativa em corações de camundongos é modulada por background genético The oxidative response of mouse hearts is modulated by genetic background

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    Marco Aurélio Santos-Silva

    2013-02-01

    observed in the Swiss strain mice (p < 0.05, while a decrease was observed in the C3H (p < 0.05 and BALB/c (p < 0.001 strain mice as compared with their respective control groups. The reduced glutathione/reduced glutathione ratio showed a reduction in the Swiss and C57BL/6 (p < 0.05 strain mice as compared with their respective control groups. CONCLUSIONS: The genetic background of mice can influence the antioxidant response after exposure to cigarette smoke and seems to be a determinant factor for redox imbalance in Swiss and C57BL/6 strain mice. Understanding antioxidant responses and genetic background of C3H and BALB/c strain mice might provide important information regarding cardiac resistance to cigarette smoke.

  6. Genome-wide association mapping and biochemical markers reveal that seed ageing and longevity are intricately affected by genetic background and developmental and environmental conditions in barley.

    Science.gov (United States)

    Nagel, Manuela; Kranner, Ilse; Neumann, Kerstin; Rolletschek, Hardy; Seal, Charlotte E; Colville, Louise; Fernández-Marín, Beatriz; Börner, Andreas

    2015-06-01

    Globally, over 7.4 million accessions of crop seeds are stored in gene banks, and conservation of genotypic variation is pivotal for breeding. We combined genetic and biochemical approaches to obtain a broad overview of factors that influence seed storability and ageing in barley (Hordeum vulgare). Seeds from a germplasm collection of 175 genotypes from four continents grown in field plots with different nutrient supply were subjected to two artificial ageing regimes. Genome-wide association mapping revealed 107 marker trait associations, and hence, genotypic effects on seed ageing. Abiotic and biotic stresses were found to affect seed longevity. To address aspects of abiotic, including oxidative, stress, two major antioxidant groups were analysed. No correlation was found between seed deterioration and the lipid-soluble tocochromanols, nor with oil, starch and protein contents. Conversely, the water-soluble glutathione and related thiols were converted to disulphides, indicating a strong shift towards more oxidizing intracellular conditions, in seeds subjected to long-term dry storage at two temperatures or to two artificial ageing treatments. The data suggest that intracellular pH and (bio)chemical processes leading to seed deterioration were influenced by the type of ageing or storage. Moreover, seed response to ageing or storage treatment appears to be significantly influenced by both maternal environment and genetic background. © 2014 John Wiley & Sons Ltd.

  7. Characterization of near-isogenic lines carrying QTL for high spikelet number with the genetic background of an indica rice variety IR64 (Oryza sativa L.).

    Science.gov (United States)

    Fujita, Daisuke; Tagle, Analiza G; Ebron, Leodegario A; Fukuta, Yoshimichi; Kobayashi, Nobuya

    2012-03-01

    Total spikelet number per panicle (TSN) is one of the most important traits associated with rice yield potential. This trait was assessed in a set of 334 chromosomal segment introgression lines (ILs: BC(3)-derived lines), developed from new plant type (NPT) varieties as donor parents and having the genetic background of an indica-type rice variety IR64. Among the 334 ILs, five lines which had different donor parents and showed significantly higher TSN than IR64 were used for genetic analysis. Quantitative trait locus (QTL) analysis was conducted using F(2) populations derived from crosses between IR64 and these ILs. As a result, a QTL for high TSN (one from each NPT donor variety) was detected on common region of the long arm of chromosome 4. The effect of the QTL was confirmed by an increase in TSN of five near-isogenic lines (NILs) developed in the present study. The variation in TSN was found among these NILs, attributing to the panicle architecture in the numbers of primary, secondary and tertiary branches. The NILs for TSN and the SSR markers linked to the TSN QTLs are expected to be useful materials for research and breeding to enhance the yield potential of rice varieties.

  8. Evaluation of a Method Using Three Genomic Guided Escherichia coli Markers for Phylogenetic Typing of E. coli Isolates of Various Genetic Backgrounds.

    Science.gov (United States)

    Hamamoto, Kouta; Ueda, Shuhei; Yamamoto, Yoshimasa; Hirai, Itaru

    2015-06-01

    Genotyping and characterization of bacterial isolates are essential steps in the identification and control of antibiotic-resistant bacterial infections. Recently, one novel genotyping method using three genomic guided Escherichia coli markers (GIG-EM), dinG, tonB, and dipeptide permease (DPP), was reported. Because GIG-EM has not been fully evaluated using clinical isolates, we assessed this typing method with 72 E. coli collection of reference (ECOR) environmental E. coli reference strains and 63 E. coli isolates of various genetic backgrounds. In this study, we designated 768 bp of dinG, 745 bp of tonB, and 655 bp of DPP target sequences for use in the typing method. Concatenations of the processed marker sequences were used to draw GIG-EM phylogenetic trees. E. coli isolates with identical sequence types as identified by the conventional multilocus sequence typing (MLST) method were localized to the same branch of the GIG-EM phylogenetic tree. Sixteen clinical E. coli isolates were utilized as test isolates without prior characterization by conventional MLST and phylogenetic grouping before GIG-EM typing. Of these, 14 clinical isolates were assigned to a branch including only isolates of a pandemic clone, E. coli B2-ST131-O25b, and these results were confirmed by conventional typing methods. Our results suggested that the GIG-EM typing method and its application to phylogenetic trees might be useful tools for the molecular characterization and determination of the genetic relationships among E. coli isolates.

  9. Plant Genetic Background Increasing the Efficiency and Durability of Major Resistance Genes to Root-knot Nematodes Can Be Resolved into a Few Resistance QTLs

    Science.gov (United States)

    Barbary, Arnaud; Djian-Caporalino, Caroline; Marteu, Nathalie; Fazari, Ariane; Caromel, Bernard; Castagnone-Sereno, Philippe; Palloix, Alain

    2016-01-01

    With the banning of most chemical nematicides, the control of root-knot nematodes (RKNs) in vegetable crops is now based essentially on the deployment of single, major resistance genes (R-genes). However, these genes are rare and their efficacy is threatened by the capacity of RKNs to adapt. In pepper, several dominant R-genes are effective against RKNs, and their efficacy and durability have been shown to be greater in a partially resistant genetic background. However, the genetic determinants of this partial resistance were unknown. Here, a quantitative trait loci (QTL) analysis was performed on the F2:3 population from the cross between Yolo Wonder, an accession considered partially resistant or resistant, depending on the RKN species, and Doux Long des Landes, a susceptible cultivar. A genetic linkage map was constructed from 130 F2 individuals, and the 130 F3 families were tested for resistance to the three main RKN species, Meloidogyne incognita, M. arenaria, and M. javanica. For the first time in the pepper-RKN pathosystem, four major QTLs were identified and mapped to two clusters. The cluster on chromosome P1 includes three tightly linked QTLs with specific effects against individual RKN species. The fourth QTL, providing specific resistance to M. javanica, mapped to pepper chromosome P9, which is known to carry multiple NBS–LRR repeats, together with major R-genes for resistance to nematodes and other pathogens. The newly discovered cluster on chromosome P1 has a broad spectrum of action with major additive effects on resistance. These data highlight the role of host QTLs involved in plant-RKN interactions and provide innovative potential for the breeding of new pepper cultivars or rootstocks combining quantitative resistance and major R-genes, to increase both the efficacy and durability of RKN control by resistance genes. PMID:27242835

  10. Plant genetic background increasing the efficiency and durability of major resistance genes to root-knot nematodes can be resolved into a few resistance QTLs

    Directory of Open Access Journals (Sweden)

    Arnaud eBarbary

    2016-05-01

    Full Text Available With the banning of most chemical nematicides, the control of root-knot nematodes (RKNs in vegetable crops is now based essentially on the deployment of single, major resistance genes (R-genes. However, these genes are rare and their efficacy is threatened by the capacity of RKNs to adapt. In pepper, several dominant R-genes are effective against RKNs, and their efficacy and durability have been shown to be greater in a partially resistant genetic background. However, the genetic determinants of this partial resistance were unknown. Here, a QTL analysis was performed on the F2:3 population from the cross between Yolo Wonder, an accession considered partially resistant or resistant, depending on the RKN species, and Doux Long des Landes, a susceptible cultivar. A genetic linkage map was constructed from 130 F2 individuals, and the 130 F3 families were tested for resistance to the three main RKN species, M. incognita, M. arenaria and M. javanica. For the first time in the pepper-RKN pathosystem, four major QTLs were identified and mapped to two clusters. The cluster on chromosome P1 includes three tightly linked QTLs with specific effects against individual RKN species. The fourth QTL, providing specific resistance to M. javanica, mapped to pepper chromosome P9, which is known to carry multiple NBS-LRR repeats, together with major R-genes for resistance to nematodes and other pathogens. The newly discovered cluster on chromosome P1 has a broad spectrum of action with major additive effects on resistance. These data highlight the role of host QTLs involved in plant-RKN interactions and provide innovative potential for the breeding of new pepper cultivars or rootstocks combining quantitative resistance and major R-genes, to increase both the efficacy and durability of RKN control by resistance genes.

  11. The Genetic Architecture of Flowering Time and Photoperiod Sensitivity in Maize as Revealed by QTL Review and Meta Analysis

    Institute of Scientific and Technical Information of China (English)

    Jie Xu; Tingzhao Rong; Yaxi Liu; Jian Liu; Moju Cao; Jing Wang; Hai Lan; Yunbi Xu; Yanli Lu; Guangtang Pan

    2012-01-01

    The control of flowering is not only important for reproduction,but also plays a key role in the processes of domestication and adaptation.To reveal the genetic architecture for flowering time and photoperiod sensitivity,a comprehensive evaluation of the relevant literature was performed and followed by meta analysis.A total of 25 synthetic consensus quantitative trait loci (QTL) and four hot-spot genomic regions were identified for photoperiod sensitivity including 11 genes related to photoperiod response or flower morphogenesis and development.Besides,a comparative analysis of the QTL for flowering time and photoperiod sensitivity highlighted the regions containing shared and unique QTL for the two traits.Candidate genes associated with maize flowering were identified through integrated analysis of the homologous genes for flowering time in plants and the consensus QTL regions for photoperiod sensitivity in maize (Zea mays L.).Our results suggest that the combination of literature review,meta-analysis and homologous blast is an efficient approach to identify new candidate genes and create a global view of the genetic architecture for maize photoperiodic flowering.Sequences of candidate genes can be used to develop molecular markers for various models of marker-assisted selection,such as marker-assisted recurrent selection and genomic selection that can contribute significantly to crop environmental adaptation.

  12. Chemogenomic landscape of RUNX1-mutated AML reveals importance of RUNX1 allele dosage in genetics and glucocorticoid sensitivity.

    Science.gov (United States)

    Simon, Laura; Lavallée, Vincent-Philippe; Bordeleau, Marie-Eve; Krosl, Jana; Baccelli, Irene; Boucher, Geneviève; Lehnertz, Bernhard; Chagraoui, Jalila; MacRae, Tara; Ruel, Réjean; Chantigny, Yves A; Lemieux, Sébastien; Marinier, Anne; Hébert, Josée; Sauvageau, Guy

    2017-08-30

    RUNX1-mutated (RUNX1mut) Acute Myeloid Leukemia (AML) is associated with adverse outcome, highlighting the urgent need for a better genetic characterization of this AML subgroup and for the design of efficient therapeutic strategies for this disease. Towards this goal, we further dissected the mutational spectrum and gene expression profile of RUNX1mut AML and correlated these results to drug sensitivity to identify novel compounds targeting this AML subgroup. RNA-sequencing of 47 RUNX1mut primary AML specimens was performed and sequencing results were compared to those of RUNX1 wild-type samples. Chemical screens were also conducted using RUNX1mut specimens to identify compounds selectively affecting the viability of RUNX1mut AML. We show that samples with no remaining RUNX1 wild-type allele are clinically and genetically distinct and display a more homogeneous gene expression profile. Chemical screening revealed that most RUNX1mut specimens are sensitive to glucocorticoids (GCs) and we confirmed that GCs inhibit AML cell proliferation through their interaction with the Glucocorticoid Receptor (GR). We observed that specimens harboring RUNX1 mutations expected to result in low residual RUNX1 activity are most sensitive to GCs, and that co-associating mutations as well as that GR levels contribute to GC sensitivity. Accordingly, acquired glucocorticoid sensitivity was achieved by negatively regulating RUNX1 expression in human AML cells. Our findings show the profound impact of RUNX1 allele dosage on gene expression profile and glucocorticoid sensitivity in AML, thereby opening opportunities for preclinical testing which may lead to drug repurposing and improved disease characterization. Copyright ©2017, American Association for Cancer Research.

  13. High-sensitive spectrometer of fast neutrons and the results of fast neutron background flux measurements at the Gallium-Germanium Solar Neutrino Experiment

    CERN Document Server

    Abdurashitov, J N; Kalikhov, A V; Matushko, V L; Shikhin, A A; Yants, V E; Zaborskaia, O S

    2002-01-01

    The principle of operation, design, registration system and main characteristics of a fast neutron spectrometer are described. The spectrometer is intended for direct measurements of ultra low fluxes of fast neutrons. It is sensitive to neutron fluxes of 10 sup - sup 7 cm sup - sup 2 s sup - sup 1 and lower. The detection efficiency of fast neutrons with simultaneous energy measurement was determined from Monte-Carlo simulation to be equal to 0.11+-0.01. The background counting rate in the detector corresponds to a neutron flux of (6.5+-2.1)x10 sup - sup 7 cm sup - sup 2 s sup - sup 1 in the range 1.0-11.0 MeV. The natural neutron flux from the surrounding mine rock at the depth of 4600 m of water equivalent was measured to be (7.3+-2.4)x10 sup - sup 7 cm sup - sup 2 s sup - sup 1 in the range 1.0-11.0 MeV. The flux of fast neutrons in the SAGE main room was measured to be <2.3x10 sup - sup 7 cm sup - sup 2 s sup - sup 1 in 1.0-11.0 MeV energy range.

  14. The NuSTAR extragalactic survey: a first sensitive look at the high-energy cosmic x-ray background population

    DEFF Research Database (Denmark)

    Alexander, D. M.; Stern, D.; Del Moro, A.;

    2013-01-01

    of broad-band ≈ 0.5-32 keV spectroscopy, optical spectroscopy, and broad-band ultraviolet-to-mid-infrared spectral energy distribution analyses. We find that the dominant source population is quasars with L10-40 keV > 1044 erg s-1, of which ≈ 50% are obscured with NH ≳ 1022 cm-2. However, none of the 10 NuSTAR......We report on the first 10 identifications of sources serendipitously detected by the Nuclear Spectroscopic Telescope Array ( NuSTAR ) to provide the first sensitive census of the cosmic X-ray background source population at ≳ 10 keV. We find that these NuSTAR -detected sources are ≈ 100 times...... times higher than the median stellar mass of nearby high-energy selected AGNs, which may be at least partially driven by the order of magnitude higher X-ray luminosities of the NuSTAR sources. Within the low source-statistic limitations of our study, our results suggest that the overall properties...

  15. Genetic Analysis and Primary Mapping of pms4,a Photoperiod-Sensitive Genic Male Sterility Gene in Rice (Oryza sativa)

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    To understand the genetic characteristics of a new photoperiod-sensitive genic male sterile line Mian 9S,some reciprocal crosses were made between Mian 9S and six indica rice materials,Yangdao 6,Luhui 602,Shuihui 527,Mianhui 725,Fuhui 838 and Yixiang 1B.Genetic analysis results suggested that the photoperiod-sensitive genic male sterility (PGMS) of Mian 9S was controlled by a single recessive nuclear gene.Thus,the F2 population derived from the cross of Yangdao 6/Mian 9S was used to map the PGMS gene in Mian 9S.By using SSR markers,the PGMS gene of Mian 9S was mapped on one side of the markers,RM6659 and RM1305,on rice chromosome 4,with the genetic distances of 3.0 cM and 3.5 cM,respectively.The gene was a novel PGMS gene and designated tentatively as pros4.In addition,the application of the pros4 gene was discussed.

  16. X-ray sensitivity of fifty-three human diploid fibroblast cell strains from patients with characterized genetic disorders

    Energy Technology Data Exchange (ETDEWEB)

    Weichselbaum, R.R.; Nove, J.; Little, J.B.

    1980-03-01

    The in vitro response of 53 human diploid fibroblast strains to x-irradiation was studied using a clonogenic survival assay. The strains, derived from patients with a variety of characterized clinical conditions, most with a genetic component, ranged in Do (a measure of the slope of the survival curve) from 43 to 168 rads. The mean Do's of six strains from normal individuals was 140 to 152 rads, with an overall range, based on the extremes of their standard errors, of 128 to 164 rads. Three-quarters of the strains studied fell within this range. Strains identified as sensitive came from patients with ataxia telangiectasia, progeria, the two genetic forms of retinoblastoma, and partial trisomy of chromosome 13. No marked radiosensitivity was found among strains derived from patients with a number of other conditions associated with a predisposition to malignancy.

  17. Rapid sensitive analysis of IDH1 mutation in lower-grade gliomas by automated genetic typing involving a quenching probe.

    Science.gov (United States)

    Kurimoto, Michihiro; Suzuki, Hiromichi; Aoki, Kosuke; Ohka, Fumiharu; Kondo, Goro; Motomura, Kazuya; Iijima, Kentaro; Yamamichi, Akane; Ranjit, Melissa; Wakabayashi, Toshihiko; Kimura, Shinya; Natsume, Atsushi

    2016-01-01

    The authors recently found that 80% of lower-grade gliomas (LGGs) harbored a mutation in IDH1. Intraoperative detection of the mutated IDH1 helps not only differentiate LGGs from other type of brain tumors, but determine the resection border. In the current study, the authors have applied an automated genetic typing involving a quenching probe to detect the mutated IDH1. If tumor cells with the mutated IDH1 contained 10% or more in the mixture of normal and tumor cells, the device could detect it sensitively. The intraoperative assessment of IDH1 mutation is useful in brain tumor surgeries.

  18. A common genetic determinism for sensitivities to soil water deficit and evaporative demand: meta-analysis of quantitative trait Loci and introgression lines of maize.

    Science.gov (United States)

    Welcker, Claude; Sadok, Walid; Dignat, Grégoire; Renault, Morgan; Salvi, Silvio; Charcosset, Alain; Tardieu, François

    2011-10-01

    Evaporative demand and soil water deficit equally contribute to water stress and to its effect on plant growth. We have compared the genetic architectures of the sensitivities of maize (Zea mays) leaf elongation rate with evaporative demand and soil water deficit. The former was measured via the response to leaf-to-air vapor pressure deficit in well-watered plants, the latter via the response to soil water potential in the absence of evaporative demand. Genetic analyses of each sensitivity were performed over 21 independent experiments with (1) three mapping populations, with temperate or tropical materials, (2) one population resulting from the introgression of a tropical drought-tolerant line in a temperate line, and (3) two introgression libraries genetically independent from mapping populations. A very large genetic variability was observed for both sensitivities. Some lines maintained leaf elongation at very high evaporative demand or water deficit, while others stopped elongation in mild conditions. A complex architecture arose from analyses of mapping populations, with 19 major meta-quantitative trait loci involving strong effects and/or more than one mapping population. A total of 68% of those quantitative trait loci affected sensitivities to both evaporative demand and soil water deficit. In introgressed lines, 73% of the tested genomic regions affected both sensitivities. To our knowledge, this study is the first genetic demonstration that hydraulic processes, which drive the response to evaporative demand, also have a large contribution to the genetic variability of plant growth under water deficit in a large range of genetic material.

  19. The genetic background affects composition, oxidative stability and quality traits of Iberian dry-cured hams: purebred Iberian versus reciprocal Iberian × Duroc crossbred pigs.

    Science.gov (United States)

    Fuentes, Verónica; Ventanas, Sonia; Ventanas, Jesús; Estévez, Mario

    2014-02-01

    This study examined the physico-chemical characteristics, oxidative stability and sensory properties of Iberian cry-cured hams as affected by the genetic background of the pigs: purebred Iberian (PBI) pigs vs reciprocal cross-bred Iberian × Duroc pigs (IB × D pigs: Iberian dams × Duroc sires; D × IB pigs: Duroc dams × Iberian sires). Samples from PBI pigs contained significantly higher amounts of IMF, monounsaturated fatty acids, heme pigments and iron than those from crossbred pigs. The extent of lipid and protein oxidation was significantly larger in dry-cured hams of crossbred pigs than in those from PBI pigs. Dry-cured hams from PBI pigs were defined by positive sensory properties (i.e. redness, brightness and juiciness) while hams from crossbred pigs were ascribed to negative ones (i.e. hardness, bitterness and sourness). Hams from PBI pigs displayed a superior quality than those from crossbred pigs. The position of the dam or the sire in reciprocal Iberian × Duroc crosses had no effect on the quality of Iberian hams.

  20. An orthogonal comparison of the proteome of human embryonic stem cells with that of human induced pluripotent stem cells of different genetic background.

    Science.gov (United States)

    Faradonbeh, Mojtaba Zamani; Gharechahi, Javad; Mollamohammadi, Sepideh; Pakzad, Mohammad; Taei, Adeleh; Rassouli, Hassan; Baharvand, Hossein; Salekdeh, Ghasem Hosseini

    2012-06-01

    Induced pluripotent stem cells (iPSCs) provide an invaluable resource for drug or toxicology screening, medical research and patient-specific cell therapy. However, the potential applications of iPSCs are largely dependent on the degree of similarity between iPSCs and embryonic stem cells (ESCs). In the present study, we analyzed the proteome of human ESCs and hiPSCs with different genetic background. We carried out an orthogonal contrast analysis of the proteome pattern of two human ESC lines (Royan H5 and Royan H6) and two hiPSC lines from a normal individual, three hiPSC lines from a normal individual with Bombay blood group phenotype, and two hiPSC lines from a patient with tyrosinemia. Forty-nine protein spots showed statistically significant differences between two human ESC lines and seven human iPSCs. Mass spectrometry analysis resulted in the identification of 48 proteins belonging to different biological processes, including cytoskeleton organization, energy and metabolic processes, protein synthesis and processing, signal transduction, cell growth and proliferation, cellular trafficking, transcription, calcium binding and immune response. Our results showed that hESCs and hiPSCs had subtle differences at the proteome level thus warranting more detailed and systematic examinations of these cells.

  1. A new mouse model for marfan syndrome presents phenotypic variability associated with the genetic background and overall levels of Fbn1 expression.

    Directory of Open Access Journals (Sweden)

    Bruno L Lima

    Full Text Available Marfan syndrome is an autosomal dominant disease of connective tissue caused by mutations in the fibrillin-1 encoding gene FBN1. Patients present cardiovascular, ocular and skeletal manifestations, and although being fully penetrant, MFS is characterized by a wide clinical variability both within and between families. Here we describe a new mouse model of MFS that recapitulates the clinical heterogeneity of the syndrome in humans. Heterozygotes for the mutant Fbn1 allele mgΔloxPneo, carrying the same internal deletion of exons 19-24 as the mgΔ mouse model, present defective microfibrillar deposition, emphysema, deterioration of aortic wall and kyphosis. However, the onset of a clinical phenotypes is earlier in the 129/Sv than in C57BL/6 background, indicating the existence of genetic modifiers of MFS between these two mouse strains. In addition, we characterized a wide clinical variability within the 129/Sv congenic heterozygotes, suggesting involvement of epigenetic factors in disease severity. Finally, we show a strong negative correlation between overall levels of Fbn1 expression and the severity of the phenotypes, corroborating the suggested protective role of normal fibrillin-1 in MFS pathogenesis, and supporting the development of therapies based on increasing Fbn1 expression.

  2. Genetic background alters the severity and onset of neuromuscular disease caused by the loss of ubiquitin-specific protease 14 (usp14.

    Directory of Open Access Journals (Sweden)

    Andrea G Marshall

    Full Text Available In this study, we identified and characterized an N-ethyl-N-nitrosourea (ENU induced mutation in Usp14 (nmf375 that leads to adult-onset neurological disease. The nmf375 mutation causes aberrant splicing of Usp14 mRNA, resulting in a 95% reduction in USP14. We previously showed that loss of USP14 in ataxia (ax (J mice results in reduced ubiquitin levels, motor endplate disease, Purkinje cell axonal dystrophy and decreased hippocampal paired pulse facilitation (PPF during the first 4-6 weeks of life, and early postnatal lethality by two months of age. Although the loss of USP14 is comparable between the nmf375 and ax (J mice, the nmf375 mice did not exhibit these ax (J developmental abnormalities. However, by 12 weeks of age the nmf375 mutants present with ubiquitin depletion and motor endplate disease, indicating a continual role for USP14-mediated regulation of ubiquitin pools and neuromuscular junction (NMJ structure in adult mice. The observation that motor endplate disease was only seen after ubiquitin depletion suggests that the preservation of NMJ structure requires the stable maintenance of synaptic ubiquitin pools. Differences in genetic background were shown to affect ubiquitin expression and dramatically alter the phenotypes caused by USP14 deficiency.

  3. New progress in genetic background of vitiligo immunology%白癜风免疫学遗传背景新进展

    Institute of Scientific and Technical Information of China (English)

    王倩倩; 项蕾红

    2014-01-01

    近来白癜风致病基因被证实可以调控与白癜风相关自身免疫性疾病的发病,这说明白癜风与其他自身免疫性疾病发病密切关联,它们有共同的致病因素,受共同易感基因调控。因此探讨白癜风免疫学遗传背景可以为白癜风的治疗提供良好的科研基础。%Recently, vitiligo pathogenic genes were confirmed to regulate the incidence of vitiligo associated autoimmune diseases, which indicated that vitiligo and some other autoimmune diseases may be closely related. Common pathogenetic factors and predisposing genes regulation may affect both vitiligo and vitiligo associated autoimmune diseases. Therefore, the investigation of the genetic background of vitiligo immunology will provide good scientific research basement for the vitiligo treatment.

  4. Control of the sensitivity of CRLH interdigital microstrip balanced structures using a co-design genetic algorithm approach

    Science.gov (United States)

    Siragusa, R.; Perret, E.; Nguyen, H. V.; Lemaître-Auger, P.; Tedjini, S.; Caloz, C.

    2011-06-01

    A fully automated tool for designing CRLH interdigital microstrip structures using a co-design synthesis computational approach is proposed and demonstrated experimentally. This approach uses an electromagnetic simulator in conjunction with a genetic algorithm to synthesize and optimize a balanced CRLH interdigital microstrip transmission line. The high sensitivity of a long balanced transmission line to fabrication tolerances is controlled by the use of a high precision 3D simulator. The 2.5D simulator used was found insufficient for a large number of unit cells. A 13 UC CRLH transmission line is designed with the proposed approach. The response sensitivity of the balanced transmission lines to the over/under-etching factor is highlighted by comparing the measurements of four lines with different factors. The effect of over/under-etching is significant for values larger than 10 μm.

  5. Illumination of the Spatial Order of Intracellular pH by Genetically Encoded pH-Sensitive Sensors

    Directory of Open Access Journals (Sweden)

    Mojca Benčina

    2013-12-01

    Full Text Available Fluorescent proteins have been extensively used for engineering genetically encoded sensors that can monitor levels of ions, enzyme activities, redox potential, and metabolites. Certain fluorescent proteins possess specific pH-dependent spectroscopic features, and thus can be used as indicators of intracellular pH. Moreover, concatenated pH-sensitive proteins with target proteins pin the pH sensors to a definite location within the cell, compartment, or tissue. This study provides an overview of the continually expanding family of pH-sensitive fluorescent proteins that have become essential tools for studies of pH homeostasis and cell physiology. We describe and discuss the design of intensity-based and ratiometric pH sensors, their spectral properties and pH-dependency, as well as their performance. Finally, we illustrate some examples of the applications of pH sensors targeted at different subcellular compartments.

  6. Genetic variation during persistent reovirus infection: isolation of cold-sensitive and temperature-sensitive mutants from persistently infected L cells.

    Science.gov (United States)

    Ahmed, R; Kauffman, R S; Fields, B N

    1983-11-01

    We have examined the evolution of reovirus in two independently established persistently infected (p.i.) cell lines. We found that reovirus undergoes extensive mutation during persistent infection in L cells. However, there was no consistent pattern of virus evolution; in one p.i. cell line temperature-sensitive (ts) mutants were selected, whereas cold-sensitive (cs) mutants were isolated from the second p.i. culture. Neither the cs nor the ts mutants isolated from the carrier cultures expressed their defect at 37 degrees, the temperature at which the p.i. cells were maintained, indicating that the cs and ts phenotypes were nonselected markers. These results emphasize the point that emergence of the ts or cs mutants during persistent infection only signifies that the virus has changed; it does not necessarily imply that the particular mutant is essential for the maintenance of the persistent infection. Given the high mutation rate of viruses, and the wide spectrum of viral mutants present in carrier cultures, it is essential to distinguish the relevant changes from those which may simply represent an epiphenomenon. In the accompanying paper (R. S. Kauffman, R. Ahmed, and B. N. Fields Virology, 130, 79-87, 1983), we show that by using a genetic approach, it is possible to identify the viral gene(s) which are critical for the maintenance of persistent reovirus infection.

  7. Genetic and Environmental Risk Factors for Childhood Eczema Development and Allergic Sensitization in the CCAAPS Cohort

    OpenAIRE

    Myers, Jocelyn M. Biagini; Wang, Ning; LeMasters, Grace; Bernstein, David I; Epstein, Tolly; Lindsey, Mark; Ericksen, Mark; Chakraborty, Ranajit; Ryan, Patrick; Villareal, Manuel; Burkle, Jeff; Lockey, James; Reponen, Tiina; Hershey, Gurjit K Khurana

    2009-01-01

    Eczema is very common and increasing in prevalence. Prospective studies investigating environmental and genetic risk factors for eczema in a birth cohort are lacking. We evaluated risk factors that may promote development of childhood eczema in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) birth cohort (n = 762) of infants with at least one atopic parent. Objective environmental exposure data were available for each participant. At annual physical examinations, children un...

  8. Ultraviolet sensitivity of the addition, deletion and replacement of long nonhomologous DNA segments by genetic transformation of Haemophilus influenzae

    Energy Technology Data Exchange (ETDEWEB)

    Walter, R.B.; Stuy, J.H. (Florida State Univ., Tallahassee (USA). Dept. of Biological Science)

    1982-03-01

    The construction and some properties of Haemophilus influenzae Rd strains with long and different R plasmid-derived DNA segments (nonhomologous inserts) at the same site in the HP1 prophage have previously been described. These inserts can be added to a recipient's genome by genetic transformation, they can be deleted from the recipient genome, or they can be replaced by another insert. It is reported that the UV inactivation of all three phenomena followed single hit kinetics. Deletion was roughly 10 times more resistant; its UV-sensitivity equalled that of a high-efficiency point mutation. There was an inverse correlation between UV-sensitivity and additive transformation efficiency of the various inserts; sensitivity may thus be a measure of insert size. This correlation was not seen for deletion. All three phenomena were more sensitive when they were measured on excision repair-deficient uvr/sup -/ recipients. The dose-reduction factor for addition was about 1.5 while it was about 2.6 for deletion.

  9. Evaluating the effects of genetic variants of DNA repair genes using cytogenetic mutagen sensitivity approaches.

    Science.gov (United States)

    Abdel-Rahman, Sherif Z; El-Zein, Randa A

    2011-08-01

    Mutagen sensitivity, measured in short-term cultures of peripheral blood lymphocytes by cytogenetic endpoints, is an indirect measure for DNA repair capacity and has been used for many years as a biomarker for intrinsic susceptibility for cancer. In this article, we briefly give an overview of the different cytogenetic mutagen sensitivity approaches that have been used successfully to evaluate the biological effects of polymorphisms in DNA repair genes based on a current review of the literature and based on the need for biomarkers that would allow the characterization of the biological and functional significance of such polymorphisms. We also address some of the future challenges facing this emerging area of research.

  10. Reduced Cortical Thickness as an Outcome of Differential Sensitivity to Environmental Risks in Schizophrenia

    NARCIS (Netherlands)

    Habets, Petra; Marcelis, Machteld; Gronenschild, Ed; Drukker, Marian; van Os, Jim

    2011-01-01

    Background: The etiology of schizophrenia is thought to involve differential likely genetically mediated sensitivity to environmental exposures. However, examination of differential sensitivity in models of psychopathologic constructs is subject to bias because psychopathology itself may distort exp

  11. Genetic Sensitivity to Peer Behaviors: "5HTTLPR", Smoking, and Alcohol Consumption

    Science.gov (United States)

    Daw, Jonathan; Shanahan, Michael; Harris, Kathleen Mullan; Smolen, Andrew; Haberstick, Brett; Boardman, Jason D.

    2013-01-01

    We investigate whether the serotonin transporter-linked polymorphic region ("5HTTLPR"), a gene associated with environmental sensitivity, moderates the association between smoking and drinking patterns at adolescents' schools and their corresponding risk for smoking and drinking themselves. Drawing on the school-based design of the National…

  12. Genetic Sensitivity to Peer Behaviors: "5HTTLPR", Smoking, and Alcohol Consumption

    Science.gov (United States)

    Daw, Jonathan; Shanahan, Michael; Harris, Kathleen Mullan; Smolen, Andrew; Haberstick, Brett; Boardman, Jason D.

    2013-01-01

    We investigate whether the serotonin transporter-linked polymorphic region ("5HTTLPR"), a gene associated with environmental sensitivity, moderates the association between smoking and drinking patterns at adolescents' schools and their corresponding risk for smoking and drinking themselves. Drawing on the school-based design of the National…

  13. Chemical Genetics Approach to Engineer Kinesins with Sensitivity towards a Small-Molecule Inhibitor of Eg5.

    Science.gov (United States)

    Möckel, Martin M; Hund, Corinna; Mayer, Thomas U

    2016-11-03

    Due to their fast and often reversible mode of action, small molecules are ideally suited to dissect biological processes. Yet, the validity of small-molecule studies is intimately tied to the specificity of the applied compounds, thus imposing a great challenge to screens for novel inhibitors. Here, we applied a chemical-genetics approach to render kinesin motor proteins sensitive to inhibition by the well-characterized small molecule S-Trityl-l-cysteine (STLC). STLC specifically inhibits the kinesin Eg5 through binding to a known allosteric site within the motor domain. Transfer of this allosteric binding site into the motor domain of the human kinesins Kif3A and Kif4A sensitizes them towards STLC. Single-molecule microscopy analyses confirmed that STLC inhibits the movement of chimeric but not wild-type Kif4A along microtubules. Thus, our proof-of-concept study revealed that this chemical-genetic approach provides a powerful strategy to specifically inhibit kinesins in vitro for which small-molecule inhibitors are not yet available. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Plasma Taurine, Diabetes Genetic Predisposition, and Changes of Insulin Sensitivity in Response to Weight-Loss Diets.

    Science.gov (United States)

    Zheng, Yan; Ceglarek, Uta; Huang, Tao; Wang, Tiange; Heianza, Yoriko; Ma, Wenjie; Bray, George A; Thiery, Joachim; Sacks, Frank M; Qi, Lu

    2016-10-01

    Taurine metabolism disturbance is closely linked to obesity, insulin resistance, and diabetes. Previous evidence suggested that the preventative effects of taurine on diabetes might be through regulating the expression levels of diabetes-related genes. We estimated whether blood taurine levels modified the overall genetic susceptibility to diabetes on improvement of insulin sensitivity in a randomized dietary trial. We genotyped 31 diabetes-associated variants to calculate a genetic risk score (GRS) and measured plasma taurine levels and glycemic traits among participants from the Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) trial. Seven-hundred eleven overweight or obese participants (age 30-70 y; 60% females) had genetic variants genotyped and blood taurine levels measured. Participants went on 2-year weight-loss diets, which were different in macronutrient composition. Improvements in glycemic traits were measured. We found that baseline taurine levels significantly modified the effects of diabetes GRS on changes in fasting glucose, insulin, and homeostatic model assessment of insulin resistance (HOMA-IR) during the 2-year diet intervention (P-interaction = .04, .01, .002, respectively), regardless of weight loss. High baseline taurine levels were associated with a less reduction in both glucose and HOMA-IR among the participants with the lowest tertile of diabetes GRS (both P = .02), and with a greater reduction in both insulin and HOMA-IR among those with the highest tertile of diabetes GRS (both P = .04). Our data suggest that blood taurine levels might differentially modulate the effects of diabetes-related genes on improvement of insulin sensitivity among overweight/obese patients on weight-loss diets.

  15. Label-free and high-sensitive detection for genetic point mutation based on hyperspectral interferometry

    Science.gov (United States)

    Fu, Rongxin; Li, Qi; Zhang, Junqi; Wang, Ruliang; Lin, Xue; Xue, Ning; Su, Ya; Jiang, Kai; Huang, Guoliang

    2016-10-01

    Label free point mutation detection is particularly momentous in the area of biomedical research and clinical diagnosis since gene mutations naturally occur and bring about highly fatal diseases. In this paper, a label free and high sensitive approach is proposed for point mutation detection based on hyperspectral interferometry. A hybridization strategy is designed to discriminate a single-base substitution with sequence-specific DNA ligase. Double-strand structures will take place only if added oligonucleotides are perfectly paired to the probe sequence. The proposed approach takes full use of the inherent conformation of double-strand DNA molecules on the substrate and a spectrum analysis method is established to point out the sub-nanoscale thickness variation, which benefits to high sensitive mutation detection. The limit of detection reach 4pg/mm2 according to the experimental result. A lung cancer gene point mutation was demonstrated, proving the high selectivity and multiplex analysis capability of the proposed biosensor.

  16. STUDY OF SENSITIVITY OF THE PARAMETERS OF A GENETIC ALGORITHM FOR DESIGN OF WATER DISTRIBUTION NETWORKS

    Directory of Open Access Journals (Sweden)

    Pedro L. Iglesias

    2007-01-01

    Full Text Available The Genetic Algorithms (GAs are a technique of optimization used for water distribution networks design. This work has been made with a modified pseudo genetic algorithm (PGA, whose main variation with a classical GA is a change in the codification of the chromosomes, which is made of numerical form instead of the binary codification. This variation entails a series of special characteristics in the codification and in the definition of the operations of mutation and crossover. Initially, the work displays the results of the PGA on a water network studied in the literature. The results show the kindness of the method. Also is made a statistical analysis of the obtained solutions. This analysis allows verifying the values of mutation and crossing probability more suitable for the proposed method. Finally, in the study of the analyzed water supply networks the concept of reliability in introduced. This concept is essential to understand the validity of the obtained results. The second part, starting with values optimized for the probability of crossing and mutation, the influence of the population size is analyzed in the final solutions on the network of Hanoi, widely studied in the bibliography. The aim is to find the most suitable configuration of the problem, so that good solutions are obtained in the less time.

  17. STUDY OF SENSITIVITY OF THE PARAMETERS OF A GENETIC ALGORITHM FOR DESIGN OF WATER DISTRIBUTION NETWORKS

    Directory of Open Access Journals (Sweden)

    Pedro L. Iglesias

    2007-12-01

    Full Text Available The Genetic Algorithms (GAs are a technique of optimization used for water distribution networks design. This work has been made with a modified pseudo genetic algorithm (PGA, whose main variation with a classical GA is a change in the codification of the chromosomes, which is made of numerical form instead of the binary codification. This variation entails a series of special characteristics in the codification and in the definition of the operations of mutation and crossover. Initially, the work displays the results of the PGA on a water network studied in the literature. The results show the kindness of the method. Also is made a statistical analysis of the obtained solutions. This analysis allows verifying the values of mutation and crossing probability more suitable for the proposed method. Finally, in the study of the analyzed water supply networks the concept of reliability in introduced. This concept is essential to understand the validity of the obtained results. The second part, starting with values optimized for the probability of crossing and mutation, the influence of the population size is analyzed in the final solutions on the network of Hanoi, widely studied in the bibliography. The aim is to find the most suitable configuration of the problem, so that good solutions are obtained in the less time.

  18. Efficiently Hiding Sensitive Itemsets with Transaction Deletion Based on Genetic Algorithms

    Directory of Open Access Journals (Sweden)

    Chun-Wei Lin

    2014-01-01

    Full Text Available Data mining is used to mine meaningful and useful information or knowledge from a very large database. Some secure or private information can be discovered by data mining techniques, thus resulting in an inherent risk of threats to privacy. Privacy-preserving data mining (PPDM has thus arisen in recent years to sanitize the original database for hiding sensitive information, which can be concerned as an NP-hard problem in sanitization process. In this paper, a compact prelarge GA-based (cpGA2DT algorithm to delete transactions for hiding sensitive itemsets is thus proposed. It solves the limitations of the evolutionary process by adopting both the compact GA-based (cGA mechanism and the prelarge concept. A flexible fitness function with three adjustable weights is thus designed to find the appropriate transactions to be deleted in order to hide sensitive itemsets with minimal side effects of hiding failure, missing cost, and artificial cost. Experiments are conducted to show the performance of the proposed cpGA2DT algorithm compared to the simple GA-based (sGA2DT algorithm and the greedy approach in terms of execution time and three side effects.

  19. 黑龙江省主栽糯稻遗传背景研究%Research on Genetic Background of Main Cultivated Glutinous Rice in Heilongjiang Province

    Institute of Scientific and Technical Information of China (English)

    刘宇强; 刘晴; 高世伟; 聂守军; 谢树鹏; 魏中华; 王翠玲; 刘立超

    2016-01-01

    选取黑龙江省近年审定的糯稻品种,对其遗传背景进行分析,试图挖掘其系谱中的骨干亲本,为糯稻品种的选育和改良提供理论依据。结果表明,大部分通过审定的糯稻品种都含有日本水稻的血缘;一些骨干亲本能够直接育成或衍生出糯稻品种,为优秀的糯稻品种选育奠定了基础。今后,应加强骨干亲本的筛选和利用,以为糯稻品种的选育和改良提供帮助。%The genetic backgrounds of main glutinous rice were analyzed in this study, which were approved in recent years in Hei-longjiang Province. The author tries to find out the mainstay parents in pedigree, provides theoretical basis for glutinous rice variety breeding and improvement. The results showed that most of the glutinous rice approved contain the consanguinity of Japanese rice, some mainstay parents can directly breed or derived glutinous rice varieties and lay the foundations for the breeding of glutinous rice. The authors suggested that future breeding program, emphysives on the selection and utilization of mainstay parents.

  20. Effects of feeding deoxynivalenol (DON)-contaminated wheat to laying hens and roosters of different genetic background on the reproductive performance and health of the newly hatched chicks.

    Science.gov (United States)

    Ebrahem, Mohammad; Kersten, Susanne; Valenta, Hana; Breves, Gerhard; Beineke, Andreas; Hermeyer, Kathrin; Dänicke, Sven

    2014-08-01

    A total of 216 23-week-old laying hens from two different genetic backgrounds (half of the birds were Lohmann brown [LB] and [LSL] hens, respectively) and 24 adult roosters were assigned to a feeding trial to study the effect of increasing concentrations of deoxynivalenol (DON) in the diet (0, 5, 10 mg/kg) on the reproductive performance of hens and roosters, and the health of the newly hatched chicks. Hatchability was adversely affected by the presence of DON in LB hens' diet, while the hatchability of the LSL chicks was significantly higher than LB chicks. An interaction effect between DON in the hens' diet and the breed was noticed on fertility, as the fertility was decreased in the eggs of LB hens receiving 10 mg/kg DON in their diet and increased in the eggs of LSL hens fed 10 mg/kg DON. Moreover, spleen relative weight was significantly decreased in the chicks hatched from eggs of hens fed contaminated diets, while gizzard relative weight was significantly decreased in LB chicks with 10 mg/kg DON in their diet compared with the control group. On the other hand, the chicks' haematology and organ histopathology were not affected by the dietary treatment. Additionally, the presence of DON in the roosters' diet had no effect on fertility (the percentage of fertile eggs of all laid eggs). Consequently, the current results indicate a negative impact of DON in LB hens' diet on fertility and hatchability, indicating that the breed of the hens seems to be an additional factor influencing the effect of DON on reproductive performance of the laying hens.

  1. [Justifying genetic and immune markers of efficiency and sensitivity under combined exposure to risk factors in mining industry workers].

    Science.gov (United States)

    Dolgikh, O V; Zaitseva, N V; Krivtsov, A V; Gorshkova, K G; Lanin, D V; Bubnova, O A; Dianova, D G; Lykhina, T S; Vdovina, N A

    2014-01-01

    The authors evaluated and justified immunologic and genetic markers under combined exposure to risk factors in mining industry workers. Analysis covered polymorphism features of 29 genes with variant alleles possibly participating in occupationally conditioned diseases formation and serving as sensitivity markers of these diseases risk. The genes association selected demonstrates reliably changed polymorphism vs. the reference group (SOD2 superoxidedismutase gene, ANKK1 dophamine receptor gene, SULT1A1 sulphtransaminase gene, MTHFR methylene tetrahydrofolate reductase gene, VEGF endothelial growth factor gene, TNF-alpha tumor necrosis factor gene). Under combined exposure to occupational hazards (sylvinite dust, noise) in mining industry, this association can serve as adequate marking complex of sensitivity to development of occupationally conditioned diseases. Increased-production of immune cytokine regulation markers: tumor necrosis factor and vascular endothelial growth factor. Genes SOD2, ANKK1, SULT1A1, VEGF, TNFalpha are recommended as sensitivity markers, and the coded cytokines (tumor necrosis factor and endothelial growth factor) are proposed as effect markers in evaluation of health risk for workers in mining industry.

  2. The Intolerance of Regulatory Sequence to Genetic Variation Predicts Gene Dosage Sensitivity.

    Directory of Open Access Journals (Sweden)

    Slavé Petrovski

    2015-09-01

    Full Text Available Noncoding sequence contains pathogenic mutations. Yet, compared with mutations in protein-coding sequence, pathogenic regulatory mutations are notoriously difficult to recognize. Most fundamentally, we are not yet adept at recognizing the sequence stretches in the human genome that are most important in regulating the expression of genes. For this reason, it is difficult to apply to the regulatory regions the same kinds of analytical paradigms that are being successfully applied to identify mutations among protein-coding regions that influence risk. To determine whether dosage sensitive genes have distinct patterns among their noncoding sequence, we present two primary approaches that focus solely on a gene's proximal noncoding regulatory sequence. The first approach is a regulatory sequence analogue of the recently introduced residual variation intolerance score (RVIS, termed noncoding RVIS, or ncRVIS. The ncRVIS compares observed and predicted levels of standing variation in the regulatory sequence of human genes. The second approach, termed ncGERP, reflects the phylogenetic conservation of a gene's regulatory sequence using GERP++. We assess how well these two approaches correlate with four gene lists that use different ways to identify genes known or likely to cause disease through changes in expression: 1 genes that are known to cause disease through haploinsufficiency, 2 genes curated as dosage sensitive in ClinGen's Genome Dosage Map, 3 genes judged likely to be under purifying selection for mutations that change expression levels because they are statistically depleted of loss-of-function variants in the general population, and 4 genes judged unlikely to cause disease based on the presence of copy number variants in the general population. We find that both noncoding scores are highly predictive of dosage sensitivity using any of these criteria. In a similar way to ncGERP, we assess two ensemble-based predictors of regional noncoding

  3. The Intolerance of Regulatory Sequence to Genetic Variation Predicts Gene Dosage Sensitivity.

    Science.gov (United States)

    Petrovski, Slavé; Gussow, Ayal B; Wang, Quanli; Halvorsen, Matt; Han, Yujun; Weir, William H; Allen, Andrew S; Goldstein, David B

    2015-09-01

    Noncoding sequence contains pathogenic mutations. Yet, compared with mutations in protein-coding sequence, pathogenic regulatory mutations are notoriously difficult to recognize. Most fundamentally, we are not yet adept at recognizing the sequence stretches in the human genome that are most important in regulating the expression of genes. For this reason, it is difficult to apply to the regulatory regions the same kinds of analytical paradigms that are being successfully applied to identify mutations among protein-coding regions that influence risk. To determine whether dosage sensitive genes have distinct patterns among their noncoding sequence, we present two primary approaches that focus solely on a gene's proximal noncoding regulatory sequence. The first approach is a regulatory sequence analogue of the recently introduced residual variation intolerance score (RVIS), termed noncoding RVIS, or ncRVIS. The ncRVIS compares observed and predicted levels of standing variation in the regulatory sequence of human genes. The second approach, termed ncGERP, reflects the phylogenetic conservation of a gene's regulatory sequence using GERP++. We assess how well these two approaches correlate with four gene lists that use different ways to identify genes known or likely to cause disease through changes in expression: 1) genes that are known to cause disease through haploinsufficiency, 2) genes curated as dosage sensitive in ClinGen's Genome Dosage Map, 3) genes judged likely to be under purifying selection for mutations that change expression levels because they are statistically depleted of loss-of-function variants in the general population, and 4) genes judged unlikely to cause disease based on the presence of copy number variants in the general population. We find that both noncoding scores are highly predictive of dosage sensitivity using any of these criteria. In a similar way to ncGERP, we assess two ensemble-based predictors of regional noncoding importance, nc

  4. The NuSTAR Extragalactic Survey: A First Sensitive Look at the High-Energy Cosmic X-Ray Background Population

    Science.gov (United States)

    Alexander, D. M.; Stern, D.; DelMoro, A.; Lansbury, G. B.; Assef, R. J.; Aird, J.; Ajello, M.; Ballantyne, D. R.; Bauer, F. E.; Boggs, S. E.; hide

    2013-01-01

    We report on the first 10 identifications of sources serendipitously detected by the Nuclear Spectroscopic Telescope Array (NuSTAR) to provide the first sensitive census of the cosmic X-ray background source population at approximately greater than 10 keV. We find that these NuSTAR-detected sources are approximately 100 times fainter than those previously detected at approximately greater than 10 keV and have a broad range in redshift and luminosity (z = 0.020-2.923 and L(sub 10-40 keV) approximately equals 4 × 10(exp 41) - 5 × 10(exp 45) erg per second; the median redshift and luminosity are z approximately equal to 0.7 and L(sub 10-40 keV) approximately equal to 3 × 10(exp 44) erg per second, respectively. We characterize these sources on the basis of broad-band approximately equal to 0.5 - 32 keV spectroscopy, optical spectroscopy, and broad-band ultraviolet-to-mid-infrared spectral energy distribution analyses. We find that the dominant source population is quasars with L(sub 10-40 keV) greater than 10(exp 44) erg per second, of which approximately 50% are obscured with N(sub H) approximately greater than 10(exp 22) per square centimeters. However, none of the 10 NuSTAR sources are Compton thick (N(sub H) approximately greater than 10(exp 24) per square centimeters) and we place a 90% confidence upper limit on the fraction of Compton-thick quasars (L(sub 10-40 keV) greater than 10(exp 44) erg per second) selected at approximately greater than 10 keV of approximately less than 33% over the redshift range z = 0.5 - 1.1. We jointly fitted the rest-frame approximately equal to 10-40 keV data for all of the non-beamed sources with L(sub 10-40 keV) greater than 10(exp 43) erg per second to constrain the average strength of reflection; we find R less than 1.4 for gamma = 1.8, broadly consistent with that found for local active galactic nuclei (AGNs) observed at approximately greater than 10 keV. We also constrain the host-galaxy masses and find a median stellar

  5. Mutantes rin, norA, og c e hp em diferentes backgrounds genotípicos de tomateiro Rin, norA, og c and hp mutants in tomatos with different genetic backgrounds

    Directory of Open Access Journals (Sweden)

    Marcos Ventura Faria

    2006-05-01

    Full Text Available O objetivo deste trabalho foi avaliar a viabilidade do emprego isolado e simultâneo dos mutantes rin, norA, og c e hp em heterozigose, em genótipos de tomateiro, visando à melhoria da qualidade pós-colheita dos frutos. Foram avaliados 18 genótipos que diferem quanto às combinações entre estes locos em dois diferentes backgrounds (FloraDade e background experimental. Contrastes não ortogonais foram estabelecidos para quantificar os efeitos dos alelos mutantes, isoladamente ou combinados em um mesmo genótipo, em dois backgrounds, sobre a produção total e produção precoce de frutos, massa média, firmeza, coloração externa, teores de licopeno e betacaroteno dos frutos. Os alelos norA e rin em heterozigose, no background FloraDade, desaceleraram a taxa de perda de firmeza e reduziram os teores de licopeno e betacaroteno nos frutos maduros. As combinações heterozigotas entre o mutante rin e os mutantes norA, og c e hp aumentaram a firmeza dos frutos. O efeito do genótipo rin+/rin nor+/norA sobre a firmeza dos frutos foi o somatório dos efeitos individuais dos locos. O alelo rin mostrou-se, individualmente, mais eficiente do que norA, em prolongar a firmeza dos frutos. Os genótipos og c+/og c e hp+/hp, juntos ou isolados, aumentaram a coloração dos frutos rin+/rin. Recomenda-se a utilização dos genótipos rin+/rin nor+/norA no desenvolvimento de híbridos longa vida, buscando-se, contudo, backgrounds que sofram prejuízo menor sobre a coloração dos frutos e adicionando-se mutantes og c+/og c e hp+/hp.The objective of this work was to assess the viability of single and simultaneous use of rin, norA, og c and hp as heterozygotes in tomato genotypes in order to improve post-harvest fruit quality. Eighteen genotypes differing in combinations among these loci in two backgrounds (Floradade and experimental background were evaluated. Contrasts were used to quantify the effects of single and simultaneous application of mutant loci

  6. Syndromes of reduced sensitivity to thyroid hormone: genetic defects in hormone receptors, cell transporters and deiodination.

    Science.gov (United States)

    Refetoff, Samuel; Dumitrescu, Alexandra M

    2007-06-01

    At least six major steps are required for secreted thyroid hormone (TH) to exert its action on target tissues. Mutations interfering with three of these steps have been so far identified. The first recognized defect, which causes resistance to TH, involves the TH receptor beta gene and has been given the acronym RTH. Occurring in approximately 1 per 40,000 newborns, more than 1000 affected subjects, from 339 families, have been identified. The gene defect remains unknown in 15% of subjects with RTH. Two novel syndromes causing reduced sensitivity to TH were recently identified. One, producing severe psychomotor defects in > 100 males from 26 families, is caused by mutations in the cell-membrane transporter of TH, MCT8; the second, affecting the intracellular metabolism of TH in four individuals from two families, is caused by mutations in the SECISBP2 gene, which is required for the synthesis of selenoproteins, including TH deiodinases.

  7. Sharing privacy-sensitive access to neuroimaging and genetics data: a review and preliminary validation

    Science.gov (United States)

    Sarwate, Anand D.; Plis, Sergey M.; Turner, Jessica A.; Arbabshirani, Mohammad R.; Calhoun, Vince D.

    2014-01-01

    The growth of data sharing initiatives for neuroimaging and genomics represents an exciting opportunity to confront the “small N” problem that plagues contemporary neuroimaging studies while further understanding the role genetic markers play in the function of the brain. When it is possible, open data sharing provides the most benefits. However, some data cannot be shared at all due to privacy concerns and/or risk of re-identification. Sharing other data sets is hampered by the proliferation of complex data use agreements (DUAs) which preclude truly automated data mining. These DUAs arise because of concerns about the privacy and confidentiality for subjects; though many do permit direct access to data, they often require a cumbersome approval process that can take months. An alternative approach is to only share data derivatives such as statistical summaries—the challenges here are to reformulate computational methods to quantify the privacy risks associated with sharing the results of those computations. For example, a derived map of gray matter is often as identifiable as a fingerprint. Thus alternative approaches to accessing data are needed. This paper reviews the relevant literature on differential privacy, a framework for measuring and tracking privacy loss in these settings, and demonstrates the feasibility of using this framework to calculate statistics on data distributed at many sites while still providing privacy. PMID:24778614

  8. A drug-sensitive genetic network masks fungi from the immune system.

    Directory of Open Access Journals (Sweden)

    Robert T Wheeler

    2006-04-01

    Full Text Available Fungal pathogens can be recognized by the immune system via their beta-glucan, a potent proinflammatory molecule that is present at high levels but is predominantly buried beneath a mannoprotein coat and invisible to the host. To investigate the nature and significance of "masking" this molecule, we characterized the mechanism of masking and consequences of unmasking for immune recognition. We found that the underlying beta-glucan in the cell wall of Candida albicans is unmasked by subinhibitory doses of the antifungal drug caspofungin, causing the exposed fungi to elicit a stronger immune response. Using a library of bakers' yeast (Saccharomyces cerevisiae mutants, we uncovered a conserved genetic network that is required for concealing beta-glucan from the immune system and limiting the host response. Perturbation of parts of this network in the pathogen C. albicans caused unmasking of its beta-glucan, leading to increased beta-glucan receptor-dependent elicitation of key proinflammatory cytokines from primary mouse macrophages. By creating an anti-inflammatory barrier to mask beta-glucan, opportunistic fungi may promote commensal colonization and have an increased propensity for causing disease. Targeting the widely conserved gene network required for creating and maintaining this barrier may lead to novel broad-spectrum antimycotics.

  9. Genetic disruption of oncogenic Kras sensitizes lung cancer cells to Fas receptor-mediated apoptosis.

    Science.gov (United States)

    Mou, Haiwei; Moore, Jill; Malonia, Sunil K; Li, Yingxiang; Ozata, Deniz M; Hough, Soren; Song, Chun-Qing; Smith, Jordan L; Fischer, Andrew; Weng, Zhiping; Green, Michael R; Xue, Wen

    2017-04-04

    Genetic lesions that activate KRAS account for ∼30% of the 1.6 million annual cases of lung cancer. Despite clinical need, KRAS is still undruggable using traditional small-molecule drugs/inhibitors. When oncogenic Kras is suppressed by RNA interference, tumors initially regress but eventually recur and proliferate despite suppression of Kras Here, we show that tumor cells can survive knockout of oncogenic Kras, indicating the existence of Kras-independent survival pathways. Thus, even if clinical KRAS inhibitors were available, resistance would remain an obstacle to treatment. Kras-independent cancer cells exhibit decreased colony formation in vitro but retain the ability to form tumors in mice. Comparing the transcriptomes of oncogenic Kras cells and Kras knockout cells, we identified 603 genes that were specifically up-regulated in Kras knockout cells, including the Fas gene, which encodes a cell surface death receptor involved in physiological regulation of apoptosis. Antibodies recognizing Fas receptor efficiently induced apoptosis of Kras knockout cells but not oncogenic Kras-expressing cells. Increased Fas expression in Kras knockout cells was attributed to decreased association of repressive epigenetic marks at the Fas promoter. Concordant with this observation, treating oncogenic Kras cells with histone deacetylase inhibitor and Fas-activating antibody efficiently induced apoptosis, thus bypassing the need to inhibit Kras. Our results suggest that activation of Fas could be exploited as an Achilles' heel in tumors initiated by oncogenic Kras.

  10. Capillary electrophoresis with electrochemiluminescent detection for highly sensitive assay of genetically modified organisms.

    Science.gov (United States)

    Guo, Longhua; Yang, Huanghao; Qiu, Bin; Xiao, Xueyang; Xue, Linlin; Kim, Donghwan; Chen, Guonan

    2009-12-01

    A capillary electrophoresis coupled with electrochemiluminescent detection system (CE-ECL) was developed for the detection of polymerase chain reaction (PCR) amplicons. The ECL luminophore, tris(1,10-phenanthroline) ruthenium(II) (Ru(phen)(3)(2+)), was labeled to the PCR primers before amplification. Ru(phen)(3)(2+) was then introduced to PCR amplicons by PCR amplification. Eventually, the PCR amplicons were separated and detected by the homemade CE-ECL system. The detection of a typical genetically modified organism (GMO), Roundup Ready Soy (RRS), was shown as an example to demonstrate the reliability of the proposed approach. Four pairs of primers were amplified by multiple PCR (MPCR) simultaneously, three of which were targeted on the specific sequence of exogenous genes of RRS, and another was targeted on the endogenous reference gene of soybean. Both the conditions for PCR amplification and CE-ECL separation and detection were investigated in detail. Results showed that, under the optimal conditions, the proposed method can accurately identifying RRS. The corresponding limit of detection (LOD) was below 0.01% with 35 PCR cycles.

  11. Integrative approach to pain genetics identifies pain sensitivity loci across diseases.

    Science.gov (United States)

    Ruau, David; Dudley, Joel T; Chen, Rong; Phillips, Nicholas G; Swan, Gary E; Lazzeroni, Laura C; Clark, J David; Butte, Atul J; Angst, Martin S

    2012-01-01

    Identifying human genes relevant for the processing of pain requires difficult-to-conduct and expensive large-scale clinical trials. Here, we examine a novel integrative paradigm for data-driven discovery of pain gene candidates, taking advantage of the vast amount of existing disease-related clinical literature and gene expression microarray data stored in large international repositories. First, thousands of diseases were ranked according to a disease-specific pain index (DSPI), derived from Medical Subject Heading (MESH) annotations in MEDLINE. Second, gene expression profiles of 121 of these human diseases were obtained from public sources. Third, genes with expression variation significantly correlated with DSPI across diseases were selected as candidate pain genes. Finally, selected candidate pain genes were genotyped in an independent human cohort and prospectively evaluated for significant association between variants and measures of pain sensitivity. The strongest signal was with rs4512126 (5q32, ABLIM3, P = 1.3×10⁻¹⁰) for the sensitivity to cold pressor pain in males, but not in females. Significant associations were also observed with rs12548828, rs7826700 and rs1075791 on 8q22.2 within NCALD (P = 1.7×10⁻⁴, 1.8×10⁻⁴, and 2.2×10⁻⁴ respectively). Our results demonstrate the utility of a novel paradigm that integrates publicly available disease-specific gene expression data with clinical data curated from MEDLINE to facilitate the discovery of pain-relevant genes. This data-derived list of pain gene candidates enables additional focused and efficient biological studies validating additional candidates.

  12. Integrative approach to pain genetics identifies pain sensitivity loci across diseases.

    Directory of Open Access Journals (Sweden)

    David Ruau

    Full Text Available Identifying human genes relevant for the processing of pain requires difficult-to-conduct and expensive large-scale clinical trials. Here, we examine a novel integrative paradigm for data-driven discovery of pain gene candidates, taking advantage of the vast amount of existing disease-related clinical literature and gene expression microarray data stored in large international repositories. First, thousands of diseases were ranked according to a disease-specific pain index (DSPI, derived from Medical Subject Heading (MESH annotations in MEDLINE. Second, gene expression profiles of 121 of these human diseases were obtained from public sources. Third, genes with expression variation significantly correlated with DSPI across diseases were selected as candidate pain genes. Finally, selected candidate pain genes were genotyped in an independent human cohort and prospectively evaluated for significant association between variants and measures of pain sensitivity. The strongest signal was with rs4512126 (5q32, ABLIM3, P = 1.3×10⁻¹⁰ for the sensitivity to cold pressor pain in males, but not in females. Significant associations were also observed with rs12548828, rs7826700 and rs1075791 on 8q22.2 within NCALD (P = 1.7×10⁻⁴, 1.8×10⁻⁴, and 2.2×10⁻⁴ respectively. Our results demonstrate the utility of a novel paradigm that integrates publicly available disease-specific gene expression data with clinical data curated from MEDLINE to facilitate the discovery of pain-relevant genes. This data-derived list of pain gene candidates enables additional focused and efficient biological studies validating additional candidates.

  13. Background Material

    DEFF Research Database (Denmark)

    Zandersen, Marianne; Hyytiäinen, Kari; Saraiva, Sofia

    2016-01-01

    This document serves as a background material to the BONUS Pilot Scenario Workshop, which aims to develop harmonised regional storylines of socio-ecological futures in the Baltic Sea region in a collaborative effort together with other BONUS projects and stakeholders.......This document serves as a background material to the BONUS Pilot Scenario Workshop, which aims to develop harmonised regional storylines of socio-ecological futures in the Baltic Sea region in a collaborative effort together with other BONUS projects and stakeholders....

  14. Construction and Genetic Analysis of Murine Hepatitis Virus Strain A59 Nsp16 Temperature Sensitive Mutant and the Revertant Virus

    Institute of Scientific and Technical Information of China (English)

    Guo-hui Chang; Bao-jun Luo; Pin Lu; Lei Lin; Xiao-yan Wu; Jing Li; Yi Hu; Qing-yu Zhu

    2011-01-01

    Coronaviruses (CoVs) are generally associated with respiratory and enteric infections and have long been recognized as important pathogens of livestock and companion animals. Mouse hepatitis virus (MHV) is a widely studied model system for Coronavirus replication and pathogenesis. In this study, we created a MHV-A59 temperature sensitive (ts) mutant Wu"-ts18(cd) using the recombinant vaccinia reverse genetics system. Virus replication assay in 17C1-1 cells showed the plaque phenotype and replication characterization of constructed Wu"-ts18(cd) were indistinguishable from the reported ts mutant Wu"-ts 18. Then we cultured the ts mutant Wu"-ts 18(cd) at non-permissive temperature 39.5℃, which "forced" the ts recombinant virus to use second-site mutation to revert from a ts to a non-ts phenotype. Sequence analysis showed most of the revertants had the same single amino acid mutation at Nsp16 position 43. The single amino acid mutation at Nsp16 position 76 or position 130 could also revert the ts mutant Wu"-ts 18 (cd) to non-ts phenotype, an additional independent mutation in Nsp13 position 115 played an important role on plaque size. The results provided us with genetic information on the functional determinants of Nsp16. This allowed us to build up a more reasonable model of CoVs replication-transcription complex.

  15. Genetic and environmental risk factors for childhood eczema development and allergic sensitization in the CCAAPS cohort.

    Science.gov (United States)

    Biagini Myers, Jocelyn M; Wang, Ning; LeMasters, Grace K; Bernstein, David I; Epstein, Tolly G; Lindsey, Mark A; Ericksen, Mark B; Chakraborty, Ranajit; Ryan, Patrick H; Villareal, Manuel S; Burkle, Jeff W; Lockey, James E; Reponen, Tiina; Khurana Hershey, Gurjit K

    2010-02-01

    Eczema is very common and increasing in prevalence. Prospective studies investigating environmental and genetic risk factors for eczema in a birth cohort are lacking. We evaluated risk factors that may promote development of childhood eczema in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) birth cohort (n=762) of infants with at least one atopic parent. Objective environmental exposure data were available for each participant. At annual physical examinations, children underwent skin prick tests (SPTs), eczema was diagnosed by a clinician, and DNA was collected. Among Caucasian children, 39% developed eczema by age 3. Children with a pet dog were significantly less likely to have eczema at age one (odds ratio (OR)=0.62, 95% confidence interval (CI): 0.40-0.97) or at both ages 2 and 3 (OR=0.54, 95% CI: 0.30-0.97). This finding was most significant among children carrying the CD14-159C/T CC genotype. Carriers of the CD14-159C/T and IL4Ralpha I75V single-nucleotide polymorphisms (SNPs) had an increased risk of eczema at both ages 2 and 3 (OR=3.44, 95% CI: 1.56-7.57), especially among children who were SPT+. These results provide new insights into the pathogenesis of eczema in high-risk children and support a protective role for early exposure to dog, especially among those carrying the CD14-159C/T SNP. The results also demonstrate a susceptibility effect of the combination of CD14 and IL4Ralpha SNPs with eczema.

  16. Childhood Trauma and Children’s Emerging Psychotic Symptoms: A Genetically Sensitive Longitudinal Cohort Study

    Science.gov (United States)

    Arseneault, Louise; Cannon, Mary; Fisher, Helen L.; Polanczyk, Guilherme; Moffitt, Terrie E.; Caspi, Avshalom

    2012-01-01

    Objective Using longitudinal and prospective measures of trauma during childhood, the authors assessed the risk of developing psychotic symptoms associated with maltreatment, bullying, and accidents in a nationally representative U.K. cohort of young twins. Method Data were from the Environmental Risk Longitudinal Twin Study, which follows 2,232 twin children and their families. Mothers were interviewed during home visits when children were ages 5, 7, 10, and 12 on whether the children had experienced maltreatment by an adult, bullying by peers, or involvement in an accident. At age 12, children were asked about bullying experiences and psychotic symptoms. Children’s reports of psychotic symptoms were verified by clinicians. Results Children who experienced maltreatment by an adult (relative risk=3.16, 95% CI=1.92–5.19) or bullying by peers (relative risk=2.47, 95% CI=1.74–3.52) were more likely to report psychotic symptoms at age 12 than were children who did not experience such traumatic events. The higher risk for psychotic symptoms was observed whether these events occurred early in life or later in childhood. The risk associated with childhood trauma remained significant in analyses controlling for children’s gender, socioeconomic deprivation, and IQ; for children’s early symptoms of internalizing or externalizing problems; and for children’s genetic liability to developing psychosis. In contrast, the risk associated with accidents was small (relative risk=1.47, 95% CI=1.02–2.13) and inconsistent across ages. Conclusions Trauma characterized by intention to harm is associated with children’s reports of psychotic symptoms. Clinicians working with children who report early symptoms of psychosis should inquire about traumatic events such as maltreatment and bullying. PMID:20952460

  17. G-quadruplex DNA biosensor for sensitive visible detection of genetically modified food.

    Science.gov (United States)

    Jiang, Xiaohua; Zhang, Huimin; Wu, Jun; Yang, Xiang; Shao, Jingwei; Lu, Yujing; Qiu, Bin; Lin, Zhenyu; Chen, Guonan

    2014-10-01

    In this paper, a novel label-free G-quadruplex DNAzyme sensor has been proposed for colorimetric identification of GMO using CaMV 35S promoter sequence as the target. The binary probes can fold into G-quadruplex structure in the presence of DNA-T (Target DNA) and then combine with hemin to form a DNAzyme resembling horseradish peroxidase. The detection system consists of two G-rich probes with 2:2 split mode by using the absorbance and color of ABTS(2-) as signal reporter. Upon the addition of a target sequence, two probes both hybridize with target and then their G-rich sequences combine to form a G-quadruplex DNAzyme, and the DNAzyme can catalyze the reaction of ABTS(2-) with H2O2. Then the linear range is from 0.05 to 0.5 μM while detection limit is 5nM. These results demonstrate that the proposed G-quadruplex DNAzyme method could be used as a simple, sensitive and cost-effective approach for assays of GMO.

  18. A highly sensitive and specific method for the screening detection of genetically modified organisms based on digital PCR without pretreatment.

    Science.gov (United States)

    Fu, Wei; Zhu, Pengyu; Wang, Chenguang; Huang, Kunlun; Du, Zhixin; Tian, Wenying; Wang, Qin; Wang, Huiyu; Xu, Wentao; Zhu, Shuifang

    2015-08-04

    Digital PCR has developed rapidly since it was first reported in the 1990 s. It was recently reported that an improved method facilitated the detection of genetically modified organisms (GMOs). However, to use this improved method, the samples must be pretreated, which could introduce inaccuracy into the results. In our study, we explored a pretreatment-free digital PCR detection method for the screening for GMOs. We chose the CaMV35s promoter and the NOS terminator as the templates in our assay. To determine the specificity of our method, 9 events of GMOs were collected, including MON810, MON863, TC1507, MIR604, MIR162, GA21, T25, NK603 and Bt176. Moreover, the sensitivity, intra-laboratory and inter-laboratory reproducibility of our detection method were assessed. The results showed that the limit of detection of our method was 0.1%, which was lower than the labeling threshold level of the EU. The specificity and stability among the 9 events were consistent, respectively. The intra-laboratory and inter-laboratory reproducibility were both good. Finally, the perfect fitness for the detection of eight double-blind samples indicated the good practicability of our method. In conclusion, the method in our study would allow more sensitive, specific and stable screening detection of the GMO content of international trading products.

  19. Genetics

    DEFF Research Database (Denmark)

    Christensen, Kaare; McGue, Matt

    2016-01-01

    The sequenced genomes of individuals aged ≥80 years, who were highly educated, self-referred volunteers and with no self-reported chronic diseases were compared to young controls. In these data, healthy ageing is a distinct phenotype from exceptional longevity and genetic factors that protect...

  20. The effect of background hydrometeorological conditions on the sensitivity of evapotranspiration to model parameters: analysis with measurements from an Italian alpine catchment

    Directory of Open Access Journals (Sweden)

    N. Montaldo

    2003-01-01

    Full Text Available Recent developments have made land-surface models (LSMs more complex through the inclusion of more processes and controlling variables, increasing numbers of parameters and uncertainty in their estimates. To overcome these uncertainties, prior to applying a distributed LSM over the whole Toce basin (Italian Alps, a field campaign was carried out at an experimental plot within the basin before exploring the skill and parameter importance (sensitivity using the TOPLATS model, an existing LSM. In the summer and autumn of 1999, which included both wet (atmosphere controlled and dry (soil controlled periods, actual evapotranspiration estimates were performed using Bowen ratio and, for a short period, eddy correlation methods. Measurements performed with the two methods are in good agreement. The calibrated LSM predicts actual evapotranspiration quite well over the whole observation period. A sensitivity analysis of the evapotranspiration to model parameters was performed through the global multivariate technique during both wet and dry periods of the campaign. This approach studies the influence of each parameter without conditioning on certain values of the other variables. Hence, all parameters are varied simultaneously using, for instance, a uniform sampling strategy through a Monte Carlo simulation framework. The evapotranspiration is highly sensitive to the soil parameters, especially during wet periods. However, the evapotranspiration is also sensitive to some vegetation parameters and, during dry periods, wilting point is the most critical for evapotranspiration predictions. This result confirms the importance of correct representation of vegetation properties which, in water-limited conditions, control evapotranspiration. Keywords: evapotranspiration, sensitivity analysis, land surface model, eddy correlation, Alpine basin

  1. Interparental conflict, parent psychopathology, hostile parenting, and child antisocial behavior: examining the role of maternal versus paternal influences using a novel genetically sensitive research design.

    Science.gov (United States)

    Harold, Gordon T; Elam, Kit K; Lewis, Gemma; Rice, Frances; Thapar, Anita

    2012-11-01

    Past research has linked interparental conflict, parent psychopathology, hostile parenting, and externalizing behavior problems in childhood. However, few studies have examined these relationships while simultaneously allowing the contribution of common genetic factors underlying associations between family- and parent-level variables on child psychopathology to be controlled. Using the attributes of a genetically sensitive in vitro fertilization research design, the present study examined associations among interparental conflict, parents' antisocial behavior problems, parents' anxiety symptoms, and hostile parenting on children's antisocial behavior problems among genetically related and genetically unrelated mother-child and father-child groupings. Path analyses revealed that for genetically related mothers, interparental conflict and maternal antisocial behavior indirectly influenced child antisocial behavior through mother-to-child hostility. For genetically unrelated mothers, effects were apparent only for maternal antisocial behavior on child antisocial behavior through mother-to-child hostility. For both genetically related and genetically unrelated fathers and children, interparental conflict and paternal antisocial behavior influenced child antisocial behavior through father-to-child hostility. Effects of parental anxiety symptoms on child antisocial behavior were apparent only for genetically related mothers and children. Results are discussed with respect to the relative role of passive genotype-environment correlation as a possible confounding factor underlying family process influences on childhood psychopathology.

  2. Phenotypic and Genetic Analyses of the Varroa Sensitive Hygienic Trait in Russian Honey Bee (Hymenoptera: Apidae) Colonies

    Science.gov (United States)

    Kirrane, Maria J.; de Guzman, Lilia I.; Holloway, Beth; Frake, Amanda M.; Rinderer, Thomas E.; Whelan, Pádraig M.

    2015-01-01

    Varroa destructor continues to threaten colonies of European honey bees. General hygiene, and more specific Varroa Sensitive Hygiene (VSH), provide resistance towards the Varroa mite in a number of stocks. In this study, 32 Russian (RHB) and 14 Italian honey bee colonies were assessed for the VSH trait using two different assays. Firstly, colonies were assessed using the standard VSH behavioural assay of the change in infestation of a highly infested donor comb after a one-week exposure. Secondly, the same colonies were assessed using an “actual brood removal assay” that measured the removal of brood in a section created within the donor combs as a potential alternative measure of hygiene towards Varroa-infested brood. All colonies were then analysed for the recently discovered VSH quantitative trait locus (QTL) to determine whether the genetic mechanisms were similar across different stocks. Based on the two assays, RHB colonies were consistently more hygienic toward Varroa-infested brood than Italian honey bee colonies. The actual number of brood cells removed in the defined section was negatively correlated with the Varroa infestations of the colonies (r2 = 0.25). Only two (percentages of brood removed and reproductive foundress Varroa) out of nine phenotypic parameters showed significant associations with genotype distributions. However, the allele associated with each parameter was the opposite of that determined by VSH mapping. In this study, RHB colonies showed high levels of hygienic behaviour towards Varroa -infested brood. The genetic mechanisms are similar to those of the VSH stock, though the opposite allele associates in RHB, indicating a stable recombination event before the selection of the VSH stock. The measurement of brood removal is a simple, reliable alternative method of measuring hygienic behaviour towards Varroa mites, at least in RHB stock. PMID:25909856

  3. Phenotypic and genetic analyses of the varroa sensitive hygienic trait in Russian honey bee (hymenoptera: apidae colonies.

    Directory of Open Access Journals (Sweden)

    Maria J Kirrane

    Full Text Available Varroa destructor continues to threaten colonies of European honey bees. General hygiene, and more specific Varroa Sensitive Hygiene (VSH, provide resistance towards the Varroa mite in a number of stocks. In this study, 32 Russian (RHB and 14 Italian honey bee colonies were assessed for the VSH trait using two different assays. Firstly, colonies were assessed using the standard VSH behavioural assay of the change in infestation of a highly infested donor comb after a one-week exposure. Secondly, the same colonies were assessed using an "actual brood removal assay" that measured the removal of brood in a section created within the donor combs as a potential alternative measure of hygiene towards Varroa-infested brood. All colonies were then analysed for the recently discovered VSH quantitative trait locus (QTL to determine whether the genetic mechanisms were similar across different stocks. Based on the two assays, RHB colonies were consistently more hygienic toward Varroa-infested brood than Italian honey bee colonies. The actual number of brood cells removed in the defined section was negatively correlated with the Varroa infestations of the colonies (r2 = 0.25. Only two (percentages of brood removed and reproductive foundress Varroa out of nine phenotypic parameters showed significant associations with genotype distributions. However, the allele associated with each parameter was the opposite of that determined by VSH mapping. In this study, RHB colonies showed high levels of hygienic behaviour towards Varroa -infested brood. The genetic mechanisms are similar to those of the VSH stock, though the opposite allele associates in RHB, indicating a stable recombination event before the selection of the VSH stock. The measurement of brood removal is a simple, reliable alternative method of measuring hygienic behaviour towards Varroa mites, at least in RHB stock.

  4. Sensitivity to Antibiotics of Bacteria Exposed to Gamma Radiation Emitted from Hot Soils of the High Background Radiation Areas of Ramsar, Northern Iran.

    Science.gov (United States)

    Mortazavi, Seyed Mohammad Javad; Zarei, Samira; Taheri, Mohammad; Tajbakhsh, Saeed; Mortazavi, Seyed Alireza; Ranjbar, Sahar; Momeni, Fatemeh; Masoomi, Samaneh; Ansari, Leila; Movahedi, Mohammad Mehdi; Taeb, Shahram; Zarei, Sina; Haghani, Masood

    2017-04-01

    Over the past several years our laboratories have investigated different aspects of the challenging issue of the alterations in bacterial susceptibility to antibiotics induced by physical stresses. To explore the bacterial susceptibility to antibiotics in samples of Salmonella enterica subsp. enterica serovar Typhimurium (S. typhimurium), Staphylococcus aureus, and Klebsiella pneumoniae after exposure to gamma radiation emitted from the soil samples taken from the high background radiation areas of Ramsar, northern Iran. Standard Kirby-Bauer test, which evaluates the size of the zone of inhibition as an indicator of the susceptibility of different bacteria to antibiotics, was used in this study. The maximum alteration of the diameter of inhibition zone was found for K. pneumoniae when tested for ciprofloxacin. In this case, the mean diameter of no growth zone in non-irradiated control samples of K. pneumoniae was 20.3 (SD 0.6) mm; it was 14.7 (SD 0.6) mm in irradiated samples. On the other hand, the minimum changes in the diameter of inhibition zone were found for S. typhimurium and S. aureus when these bacteria were tested for nitrofurantoin and cephalexin, respectively. Gamma rays were capable of making significant alterations in bacterial susceptibility to antibiotics. It can be hypothesized that high levels of natural background radiation can induce adaptive phenomena that help microorganisms better cope with lethal effects of antibiotics.

  5. Somatic point mutations in mtDNA control region are influenced by genetic background and associated with healthy aging: a GEHA study

    DEFF Research Database (Denmark)

    Rose, Giuseppina; Romeo, Giuseppe; Dato, Serena

    2010-01-01

    Tissue specific somatic mutations occurring in the mtDNA control region have been proposed to provide a survival advantage. Data on twins and on relatives of long-lived subjects suggested that the occurrence/accumulation of these mutations may be genetically influenced. To further investigate con...

  6. Genetic Effects and Heterosis of Yield and Yield Component Traits Based on Gossypium Barbadense Chromosome Segment Substitution Lines in Two Gossypium Hirsutum Backgrounds.

    Directory of Open Access Journals (Sweden)

    Botao Li

    Full Text Available We hybridized 10 chromosome segment substitution lines (CSSLs each from two CSSL populations and produced 50 F1 hybrids according to North Carolina Design II. We analyzed the genetic effects and heterosis of yield and yield components in the F1 hybrids and parents in four environments via the additive-dominance genetic model. Yield and yield components of the CSSLs were controlled by combined additive and dominance effects, and lint percentage was mainly controlled by additive effects, but boll weight, boll number, seedcotton yield and lint yield were mainly controlled by dominance effects. We detected significant interaction effects between genetics and the environment for all yields traits. Similar interactions were detected between two CSSL populations (Pop CCRI 36 and Pop CCRI 45. Significant positive mid-parent heterosis was detected for all yield traits in both populations, and significant positive better-parent heterosis was also detected for all yield traits except lint percentage. The differences among parents were relatively small, but significant heterosis was detected for yield and yield components. Therefore, the relationship between heterosis and genetic distance for yield traits is complicated and requires further study. These CSSLs represent useful tools for improving yield and yield components in cotton.

  7. Measurement of natural background neutron

    CERN Document Server

    Li Jain, Ping; Tang Jin Hua; Tang, E S; Xie Yan Fong

    1982-01-01

    A high sensitive neutron monitor is described. It has an approximate counting rate of 20 cpm for natural background neutrons. The pulse amplitude resolution, sensitivity and direction dependence of the monitor were determined. This monitor has been used for natural background measurement in Beijing area. The yearly average dose is given and compared with the results of KEK and CERN.

  8. Highly Sensitive Detection of Organophosphate Insecticides Using Biosensors Based on Genetically Engineered Acetylcholinesterase and Poly(3,4-Ethylenedioxythiophene

    Directory of Open Access Journals (Sweden)

    Tomasz Sikora

    2011-01-01

    Full Text Available A poly(3,4-ethylenedioxythiophene (PEDOT conducting ink is presented as a new electroactive material to be incorporated in acetylcholinesterase-(AChE- based screen printed biosensors, acting not only as a conducting template but also as an electrochemical mediator for thiocholine oxidation. Two different strategies have been studied for the chemical synthesis of PEDOT: (a a classical oxidative polymerisation and (b a more innovative enzymatic polymerisation, giving a water-soluble PEDOT. The use of this water-soluble conducting polymer as mediator in screen-printed biosensors enables its deposition by printing like the rest of the layers. Highly sensitive acetylcholinesterase-(AChE- based screen-printed biosensors have been constructed using both classical and enzymatic PEDOT, in combination with genetically modified AChE. These electrodes allow the measurement of thiocholine oxidation at potentials of 100 mV versus Ag/AgCl reference electrode through the mediation of PEDOT. Inhibition of thiocholine production in presence of CPO allow for detection of this pesticide in concentrations as low as 1·10−10 M.

  9. Evaluation of a reverse-hybridization StripAssay for the detection of genetic polymorphisms leading to acenocoumarol sensitivity.

    Science.gov (United States)

    Gialeraki, Argyri; Markatos, Christos; Grouzi, Elisabeth; Merkouri, Efrosyni; Travlou, Anthi; Politou, Marianna

    2010-04-01

    Acenocoumarol is mainly catabolized by CYP2C9 isoform of cytochrome P450 (CYP) liver complex and exerts its anticoagulant effect through the inhibition of Vitamin K Epoxide Reductase (VKOR). The most important genetic polymorphisms which lead to an impaired enzymatic activity and therefore predispose to acenocoumarol sensitivity, are considered to be CYP2C9*2 (Arg144Cys), CYP2C9*3 (Ile359Leu) and VKORC1-1639G>A, respectively. In this study we compared the results of the PGXThrombo StripAssay kit (ViennaLab Diagnostics,Vienna, Austria) with direct DNA sequencing and in house Restriction Fragment Length Polymorphisms (RFLP) for the detection of the aforementioned Single Nucleotide Polymorphisms (SNPs). The reverse hybridization StripAssay was found to be equally effective with RFLP and direct DNA sequencing for the detection of CYP2C9*2 and CYP2C9*3 polymorphisms, respectively. The comparison of the RFLP reference method with the reverse hybridization StripAssay for the detection of VKORC1-1639 G>A polymorphism showed that the reverse hybridization StripAsssay might misclassify some A/A homozygotes as heterozygotes. Optimization of the hybridization procedures may eliminate the extra low signal band observed in some samples at the reverse hybridization StripAssay and improve its diagnostic value.

  10. A sensitive method to extract DNA from biological traces present on ammunition for the purpose of genetic profiling.

    Science.gov (United States)

    Dieltjes, Patrick; Mieremet, René; Zuniga, Sofia; Kraaijenbrink, Thirsa; Pijpe, Jeroen; de Knijff, Peter

    2011-07-01

    Exploring technological limits is a common practice in forensic DNA research. Reliable genetic profiling based on only a few cells isolated from trace material retrieved from a crime scene is nowadays more and more the rule rather than the exception. On many crime scenes, cartridges, bullets, and casings (jointly abbreviated as CBCs) are regularly found, and even after firing, these potentially carry trace amounts of biological material. Since 2003, the Forensic Laboratory for DNA Research is routinely involved in the forensic investigation of CBCs in the Netherlands. Reliable DNA profiles were frequently obtained from CBCs and used to match suspects, victims, or other crime scene-related DNA traces. In this paper, we describe the sensitive method developed by us to extract DNA from CBCs. Using PCR-based genotyping of autosomal short tandem repeats, we were able to obtain reliable and reproducible DNA profiles in 163 out of 616 criminal cases (26.5%) and in 283 out of 4,085 individual CBC items (6.9%) during the period January 2003-December 2009. We discuss practical aspects of the method and the sometimes unexpected effects of using cell lysis buffer on the subsequent investigation of striation patterns on CBCs.

  11. Genetic background for development of resistance mutations within the HCV NS3 protease-helicase in direct acting antiviral naive patients.

    Science.gov (United States)

    Grammatikos, Georgios; Jabara, Cassandra B; Ahmad, Monazza Q; Herrmann, Eva; Zeuzem, Stefan; Welsch, Christoph

    2014-01-01

    Subtype-specific response to ketoamide NS3 protease inhibitors is observed in patients with genotype 1 HCV infection. Whether the genetic diversity in the molecular target site of ketoamide compounds prior to treatment plays a role for resistance development and lower treatment response in subtype 1a is poorly understood. Using a public database, we retrieved worldwide NS3-sequence information of 581 dominant HCV variants from patients chronically infected with genotype 1 that were naive to direct-acting antivirals. We applied measures from phylogeny to study the pretreatment genetic diversity and complexity in NS3 full-length as well as the protease-helicase interface for subtype 1a and 1b, respectively. We found polymorphic sites more frequently in variants of subtype 1b than subtype 1a. Moreover, a significantly higher number of synonymous and non-synonymous substitutions were found in subtype 1b (P<0.001). Transitions were more frequent than transversions, most notably in subtype 1a, whereas the higher average number of nucleotide differences per site was found in subtype 1b. A comparison of NS3 full-length versus domain interface residues for both subtypes revealed a significant difference only for synonymous substitutions (P<0.001). Our study suggests that the nature of a mismatch nucleotide exchange in NS3 may constitute an important viral genetic factor for response to ketoamide protease inhibitors. Our analysis further suggests that the subtype-specific pace of resistance development seen in clinical trials is not primarily related to differences in genetic diversity in the direct acting antiviral naive population, but rather appears to correlate with the natural frequency of transition mutations characteristic of each subtype.

  12. Arthroscopic removal of palmar/plantar osteochondral fragments (POF) in the metacarpo- and metatarso-phalangeal joints of standardbred trotters--outcome and possible genetic background to POF.

    Science.gov (United States)

    Roneus, B; Arnason, T; Collinder, E; Rasmussen, M

    1998-01-01

    A clinical material of 133 Standardbred horses with palmar/plantar osteochondral fragments (POF) in the metacarpo- and metatarsophalangeal joints were studied. All horses had their fragments removed with arthroscopic surgery. 102 of the horses were 3 years old or younger when surgery was performed. Anatomical localisations of the fragments were in agreement with earlier reports. There was no statistical significant difference in month of birth in the POF--group compared to the total population. Eighty % of the horses that had raced before surgery came back to racing. The racing performance relative to their contemporaries remained the same after the POF operation. 65% of the horses that had not raced before surgery raced after the operation. The breeding index BLUP (Best Linear Unbiased Prediction) was used to evaluate if the POF-horses differed genetically in racing ability from the total population. The average BLUP value of the POF group was 103.4 (+/- 0.65), while the mean BLUP value of the total population was 98.9. This difference was highly significant and indicated that these POF horses belonged to a selected group. A homogeneity test of allele frequencies in blood type systems was performed to evaluate if any genetic difference was persistent between POF horses compared to the total population. The statistical analysis of gene frequencies for alleles in blood type systems indicated a genetic discrimination in blood type systems D and Tf.

  13. Gene expression profiling in C57BL/6J and A/J mouse inbred strains reveals gene networks specific for brain regions independent of genetic background

    NARCIS (Netherlands)

    de Jong, Simone; Fuller, Tova F; Janson, Esther; Strengman, Eric; Horvath, Steve; Kas, Martien J H; Ophoff, Roel A

    2010-01-01

    BACKGROUND: We performed gene expression profiling of the amygdala and hippocampus taken from inbred mouse strains C57BL/6J and A/J. The selected brain areas are implicated in neurobehavioral traits while these mouse strains are known to differ widely in behavior. Consequently, we hypothesized that

  14. Generation of human iPSC line GRX-MCiPS4F-A2 from adult peripheral blood mononuclear cells (PBMCs with Spanish genetic background

    Directory of Open Access Journals (Sweden)

    Sonia Cabrera

    2015-09-01

    Full Text Available We have generated iPSCs from peripheral blood mononuclear cells (PBMCs of a healthy man using heat sensitive and non-integrative Sendai virus containing Sox2, Oct3/4, c-Myc and Klf4. Human GRX-MCiPS4F-A2 cell line was established and characterized through this study.

  15. Cosmogenic Backgrounds to 0{\

    CERN Document Server

    :,; Auty, D J; Barbeau, P S; Beck, D; Belov, V; Breidenbach, M; Brunner, T; Burenkov, A; Cao, G F; Chambers, C; Cleveland, B; Coon, M; Craycraft, A; Daniels, T; Danilov, M; Daugherty, S J; Davis, J; Delaquis, S; Der Mesrobian-Kabakian, A; DeVoe, R; Didberidze, T; Dilling, J; Dolgolenko, A; Dolinski, M J; Dunford, M; Fairbank, W; Farine, J; Feldmeier, W; Feyzbakhsh, S; Fierlinger, P; Fudenberg, D; Gornea, R; Graham, K; Gratta, G; Hall, C; Herrin, S; Hughes, M; Jewell, M J; Johnson, A; Johnson, T N; Johnston, S; Karelin, A; Kaufman, L J; Killick, R; Koffas, T; Kravitz, S; Krücken, R; Kuchenkov, A; Kumar, K S; Leonard, D S; Licciardi, C; Lin, Y H; Ling, J; MacLellan, R; Marino, M G; Mong, B; Moore, D; Njoya, O; Nelson, R; Odian, A; Ostrovskiy, I; Piepke, A; Pocar, A; Prescott, C Y; Retière, F; Rowson, P C; Russell, J J; Schubert, A; Sinclair, D; Smith, E; Stekhanov, V; Tarka, M; Tolba, T; Tsang, R; Twelker, K; Vuilleumier, J -L; Waite, A; Walton, J; Walton, T; Weber, M; Wen, L J; Wichoski, U; Wood, J; Yang, L; Yen, Y -R; Zeldovich, O Ya

    2015-01-01

    As neutrinoless double-beta decay experiments become more sensitive and intrinsic radioactivity in detector materials is reduced, previously minor contributions to the background must be understood and eliminated. With this in mind, cosmogenic backgrounds have been studied with the EXO-200 experiment. Using the EXO-200 TPC, the muon flux (through a flat horizontal surface) underground at the Waste Isolation Pilot Plant (WIPP) has been measured to be {\\Phi} = 4.07 $\\pm$ 0.14 (sys) $\\pm$ 0.03 (stat) $\\times$ $10^{-7}$cm$^{-2}$ s$^{-1}$, with a vertical intensity of $I_{v}$ = 2.97$^{+0.14}_{-0.13}$ (sys) $\\pm$ 0.02 (stat) $\\times$ $10^{-7}$cm$^{-2}$ s$^{-1}$ sr$^{-1}$. Simulations of muon-induced backgrounds identified several potential cosmogenic radionuclides, though only 137Xe is a significant background for the 136Xe 0{\

  16. Targeting helicase-dependent amplification products with an electrochemical genosensor for reliable and sensitive screening of genetically modified organisms.

    Science.gov (United States)

    Moura-Melo, Suely; Miranda-Castro, Rebeca; de-Los-Santos-Álvarez, Noemí; Miranda-Ordieres, Arturo J; Dos Santos Junior, J Ribeiro; da Silva Fonseca, Rosana A; Lobo-Castañón, Maria Jesús

    2015-08-18

    Cultivation of genetically modified organisms (GMOs) and their use in food and feed is constantly expanding; thus, the question of informing consumers about their presence in food has proven of significant interest. The development of sensitive, rapid, robust, and reliable methods for the detection of GMOs is crucial for proper food labeling. In response, we have experimentally characterized the helicase-dependent isothermal amplification (HDA) and sequence-specific detection of a transgene from the Cauliflower Mosaic Virus 35S Promoter (CaMV35S), inserted into most transgenic plants. HDA is one of the simplest approaches for DNA amplification, emulating the bacterial replication machinery, and resembling PCR but under isothermal conditions. However, it usually suffers from a lack of selectivity, which is due to the accumulation of spurious amplification products. To improve the selectivity of HDA, which makes the detection of amplification products more reliable, we have developed an electrochemical platform targeting the central sequence of HDA copies of the transgene. A binary monolayer architecture is built onto a thin gold film where, upon the formation of perfect nucleic acid duplexes with the amplification products, these are enzyme-labeled and electrochemically transduced. The resulting combined system increases genosensor detectability up to 10(6)-fold, allowing Yes/No detection of GMOs with a limit of detection of ∼30 copies of the CaMV35S genomic DNA. A set of general utility rules in the design of genosensors for detection of HDA amplicons, which may assist in the development of point-of-care tests, is also included. The method provides a versatile tool for detecting nucleic acids with extremely low abundance not only for food safety control but also in the diagnostics and environmental control areas.

  17. Development and Genetic Characterization of Advanced Backcross Materials and An Introgression Line Population of Solanum incanum in a S. melongena Background.

    Science.gov (United States)

    Gramazio, Pietro; Prohens, Jaime; Plazas, Mariola; Mangino, Giulio; Herraiz, Francisco J; Vilanova, Santiago

    2017-01-01

    Advanced backcrosses (ABs) and introgression lines (ILs) of eggplant (Solanum melongena) can speed up genetics and genomics studies and breeding in this crop. We have developed the first full set of ABs and ILs in eggplant using Solanum incanum, a wild eggplant that has a relatively high tolerance to drought, as a donor parent. The development of these ABs and IL eggplant populations had a low efficiency in the early stages, because of the lack of molecular markers and genomic tools. However, this dramatically improved after performing genotyping-by-sequencing in the first round of selfing, followed by high-resolution-melting single nucleotide polymorphism genotyping in subsequent selection steps. A set of 73 selected ABs covered 99% of the S. incanum genome, while 25 fixed immortal ILs, each carrying a single introgressed fragment in homozygosis, altogether spanned 61.7% of the S. incanum genome. The introgressed size fragment in the ILs contained between 0.1 and 10.9% of the S. incanum genome, with a mean value of 4.3%. Sixty-eight candidate genes involved in drought tolerance were identified in the set of ILs. This first set of ABs and ILs of eggplant will be extremely useful for the genetic dissection of traits of interest for eggplant, and represents an elite material for introduction into the breeding pipelines for developing new eggplant cultivars adapted to the challenges posed by the climate-change scenario.

  18. Either the dorsal hippocampus or the dorsolateral striatum is selectively involved in consolidation of forced swim-induced immobility depending on genetic background.

    Science.gov (United States)

    Colelli, V; Campus, P; Conversi, D; Orsini, C; Cabib, S

    2014-05-01

    Healthy subjects differ in the memory system they engage to learn dual-solution tasks. Both genotype and stress experience could contribute to this phenotypic variability. The present experiments tested whether the hippocampus and the dorsal striatum, the core nodes of two different memory systems, are differently involved in 24 h retention of a stress-associated memory in two genetically unrelated inbred strains of mice. Mice from both the C57BL/6J and the DBA/2J inbred strains showed progressive increase of immobility during 10 min exposure to forced swim (FS) and retrieved the acquired levels of immobility when tested 24h later. The pattern of c-fos immunostaining promoted by FS revealed activation of a large number of brain areas in both strains, including CA1 and CA3 fields of the hippocampus. However, only DBA/2J mice showed activation of the dorsolateral striatum (DLS). In addition, FS induced a positive correlation between c-fos expression in the amygdala and CA1 and CA3 in C57BL/6J mice whereas it induced a positive correlation between c-fos expression in the amygdala and DLS in DBA/2J mice. Finally, temporary post-training inactivation of the dorsal hippocampus, by local infusion of lidocaine, prevented 24h retention of immobility in C57BL/6J mice only, whereas inactivation of the DLS prevented retention in DBA/2J mice only. These findings support the view that genetic factors can determine whether the dorsal hippocampus or the DLS are selectively engaged to consolidate stress-related memory.

  19. Genetic sensitivity to bitter taste of 6-n Propylthiouracil: A useful diagnostic aid to detect early childhood caries in pre-school children

    Directory of Open Access Journals (Sweden)

    Raghavendra Pidamale

    2012-01-01

    Full Text Available Purpose: Genetic factor to bitter taste perception appears to be largely mediated by the TAS2R38 gene. The insensitivity to bitter compounds like 6-n-propylthiouracil (PROP is mediated by this gene. PROP, a pharmacological drug used in treatment of Graves′ disease, proved to be useful tool in determining the genetic sensitivity levels to bitter and sweet taste. The purpose of this study is to show much simpler PROP sensitivity technique for the clinical examiner and its application as a diagnostic aid in Early Childhood Caries (ECC detection among preschool children. Materials and Methods: A total of 119 children belonging to the age group of 36 to 71 months of both sexes, were recruited from A. J. Institute of Dental Sciences, Mangalore (Karnataka. PROP sensitivity test was carried out to determine the inherent genetic ability to taste a bitter or sweet substance. This study used simpler scaling method to find out genetic sensitivity to bitter taste; one who tasted bitter as taster and one who was not able to differentiate/tasted like paper as non-taster. A questionnaire was provided to evaluate their dietary habits and caries experience was recorded. Collected data were tabulated and subjected to statistical analysis. Results: In the total of 119 children the mean dmfs was definitely higher in non-taster children compared to tasters. The tasters had a mean dmfs value of 9.5120 (S.D. 7.0543 and non-tasters had a value of 7.7250 (S.D. 8.33147, which was statistically significant. The results suggested that there was increase in caries experience among the group of non-tasters as compared to tasters. Tasters tended to be sweet dislikers and non-tasters tended to be sweet likers. On the whole, tasters had a bad dentition as compared to non tasters. Conclusion: The PROP sensitivity test (filter paper test proved to be a useful diagnostic tool in determining the genetic sensitivity levels of bitter taste. The knowledge of a child′s taste

  20. Effect of Genetic Information Regarding Salt-Sensitive Hypertension on the Intent to Maintain a Reduced Salt Diet: Implications for Health Communication in Japan.

    Science.gov (United States)

    Miyamoto, Keiko; Iwakuma, Miho; Nakayama, Takeo

    2017-03-01

    The authors investigated the relationship between the awareness of dietary salt and genetics and the intent to maintain a low-salt diet. In particular, they assessed whether hypothetical genetic information regarding salt-sensitive hypertension motivates the intent to reduce dietary salt for communicating the health benefits of lower salt consumption to citizens. A self-administered questionnaire survey was conducted with 2500 randomly sampled residents aged 30 to 69 years living in Nagahama, Japan. Genetic information regarding higher salt sensitivity increased motivation to reduce salt intake for both those who agreed that genes cause hypertension and those who did not. Less than 50% of those who agreed that genes cause hypertension lost their intention to lower their salt consumption when they found they did not possess the susceptibility gene. Communicating genetic information positively affected motivation to reduce salt intake. The present study clarifies the difficulty in changing the behavioral intent of those who have significantly less incentive to reduce salt intake. Therefore, a multidimensional approach is crucial to reduce salt consumption. ©2016 Wiley Periodicals, Inc.

  1. Sensitive and background-free determination of thiols from wastewater samples by MOF-5 extraction coupled with high-performance liquid chromatography with fluorescence detection using a novel fluorescence probe of carbazole-9-ethyl-2-maleimide.

    Science.gov (United States)

    Lv, Zhengxian; Sun, Zhiwei; Song, Cuihua; Lu, Shuaimin; Chen, Guang; You, Jinmao

    2016-12-01

    A sensitive and background-free pre-column derivatization method for the determination of thiol compounds using metal-organic framework material (MOF-5) as dispersive solid-phase extraction (DSPE) adsorbent followed by high-performance liquid chromatography fluorescence detection (HPLC-FLD) has been developed. In this paper, a novel labeling reagent, carbazole-9-ethyl-2-maleimide(CAEM), was synthesized and reacted with thiols at 40°C for 10min in the presence of PBS buffer (0.02mol/L, pH 7.5). Interestingly, CAEM itself had no fluorescence, while its derivatives exhibited intense fluorescence with an excitation maximum at λex 274nm and an emission maximum at λem 363nm, which greatly reduced the background interference and improved the sensitivity of the method. Furthermore, the MOF-5 was prepared and used as DSPE adsorbent for the selective adsorption of thiols from wastewater sample. Under the optimized experimental conditions, an excellent linearity for all analytes over their concentration ranges of 0.01-1.0μmol/L (R(2)>0.9986)were obtained with the limit of detection (LOD) ranging from 8 to 17.1pmol/L for nine tested thiols. The feasibility of this method for the determination of thiols in wastewater samples had been evaluated and satisfactory average recoveries (n=3) were achieved with the range of 86.6-98.5%.

  2. Genetic Sensitivity to the Environment: The Case of the Serotonin Transporter Gene and Its Implications for Studying Complex Diseases and Traits

    Science.gov (United States)

    Caspi, Avshalom; Hariri, Ahmad R.; Holmes, Andrew; Uher, Rudolf; Moffitt, Terrie E.

    2010-01-01

    Evidence of marked variability in response among people exposed to the same environmental risk implies that individual differences in genetic susceptibility might be at work. The study of such Gene-by-Environment (G×E) interactions has gained momentum. In this article, the authors review research about one of the most extensive areas of inquiry: variation in the promoter region of the serotonin transporter gene (SLC6A4; also known as 5-HTT) and its contribution to stress sensitivity. Research in this area has both advanced basic science and generated broader lessons for studying complex diseases and traits. The authors evaluate four lines of evidence about the 5-HTT stress-sensitivity hypothesis: 1) observational studies about the serotonin transporter linked polymorphic region (5-HTTLPR), stress sensitivity, and depression in humans; 2) experimental neuroscience studies about the 5-HTTLPR and biological phenotypes relevant to the human stress response; 3) studies of 5-HTT variation and stress sensitivity in nonhuman primates; and 4) studies of stress sensitivity and genetically engineered 5-HTT mutations in rodents. The authors then dispel some misconceptions and offer recommendations for G×E research. The authors discuss how G×E interaction hypotheses can be tested with large and small samples, how G×E research can be carried out before as well as after replicated gene discovery, the uses of G×E research as a tool for gene discovery, the importance of construct validation in evaluating G×E research, and the contribution of G×E research to the public understanding of genetic science. PMID:20231323

  3. Influence of family history on the willingness of outpatients to undergo genetic testing for salt-sensitive hypertension: a cross-sectional study.

    Science.gov (United States)

    Takeshima, Taro; Okayama, Masanobu; Ae, Ryusuke; Harada, Masanori; Kajii, Eiji

    2017-07-17

    It is unclear whether family medical history influences the willingness to undergo genetic testing. This study aimed to determine how family history affected the willingness to undergo genetic testing for salt-sensitive hypertension in patients with and without hypertension. Cross-sectional study using a self-administered questionnaire. Six primary care clinics and hospitals in Japan. Consecutive 1705 outpatients aged >20 years, 578 of whom had hypertension. The primary outcome variable was the willingness to undergo genetic testing to determine the risk of salt-sensitive hypertension, and the secondary variables were age, sex, education level, family history and concerns about hypertension. Factors associated with a willingness to undergo genetic testing were evaluated in patients with and without hypertension using a logistic regression model. In the hypertension and non-hypertension groups, 323 (55.9%) and 509 patients (45.2%), respectively, were willing to undergo genetic testing. This willingness was related with a high level of education (adjusted OR (ad-OR): 1.81, 95% CI 1.12 to 2.93), family history of stroke (1.55, 1.04 to 2.31) and concerns about hypertension (2.04, 1.27 to 3.28) in the hypertension group, whereas in the non-hypertension group, it was influenced by education level (ad-OR: 1.45, 95% CI 1.13 to 1.86), family history of hypertension (1.52, 1.17 to 1.98) and concerns about hypertension (2.03, 1.53 to 2.68). The influence of family history on the willingness to undergo genetic testing for risk of salt-sensitivity hypertension differed between participants with and without hypertension. In particular, participants without hypertension wished to know their likelihood of developing hypertension, whereas those with hypertension were interested to know the risk of stroke (a complication of hypertension). Family history could help better counsel patients about genetic testing on the basis of their medical history. © Article author(s) (or their

  4. Berkeley Low Background Counting Facility

    Data.gov (United States)

    Federal Laboratory Consortium — Sensitive low background assay detectors and sample analysis are available for non-destructive direct gamma-ray assay of samples. Neutron activation analysis is also...

  5. Identification and mapping stripe rust resistance gene YrLM168a using extreme individuals and recessive phenotype class in a complicate genetic background.

    Science.gov (United States)

    Feng, Junyan; Chen, Guoyue; Wei, Yuming; Liu, Yaxi; Jiang, Qiantao; Li, Wei; Pu, Zhien; Lan, Xiujin; Dai, Shoufen; Zhang, Min; Zheng, Youliang

    2015-12-01

    The identification and characterization of resistance genes effective against stripe rust of wheat is beneficial for modern wheat breeding programs. Molecular markers to such genes facilitate their deployment. The variety Milan has resistance that is effective against the predominant stripe rust races in the Sichuan region. Two resistant and two susceptible F8 lines from a cross between Milan and the susceptible variety Chuannong 16 were used to investigate inheritance of the Milan resistance. Three F2 populations were developed from crosses between the resistant lines and their susceptible sibling lines (LM168a × LM168c, LM168c × LM168a, LM168b × LM168d) and used for genetic analysis and molecular mapping of the genes for resistance. The stripe rust resistance in LM168a and LM168b was conferred by a single dominant gene, temporarily designated as YrLM168a. Forty-five extreme susceptible plants from the F2 families of LM168d × LM168b were genotyped with 836 simple sequence repeat (SSR) markers to map YrLM168a. YrLM168a was mapped in chromosome 6BL. The nearest flanking markers Xwmc756 and Xbarc146 were 4.6 and 4.6 cM away from the gene at both sides, respectively. The amplification results of twenty extreme resistant (IT 0) and susceptible (IT 4) F2 plants of LM168c × LM168a and LM168a × LM168c with marker Xwmc756 further validated the mapping results. The study suggested that extreme individuals and recessive phenotype class can be successfully used for mapping genes, which should be efficient and reliable. In addition, the flanking markers near YrLM168a should be helpful in marker-assisted breeding.

  6. Genetic adaptation of Pseudomonas aeruginosa during chronic lung infection of patients with cystic fibrosis: strong and weak mutators with heterogeneous genetic backgrounds emerge in mucA and/or lasR mutants

    DEFF Research Database (Denmark)

    Ciofu, Oana; Mandsberg, Lotte F.; Bjarnsholt, Thomas

    2010-01-01

    During the chronic lung infection of patients with cystic fibrosis (CF), Pseudomonas aeruginosa can survive for long periods due to adaptive evolution mediated by genetic variation. Hypermutability is considered to play an important role in this adaptive evolution and it has been demonstrated tha...... evolutionary pathways concordant with adaptive radiation were observed in different clonal lineages of P. aeruginosa from CF patients.......During the chronic lung infection of patients with cystic fibrosis (CF), Pseudomonas aeruginosa can survive for long periods due to adaptive evolution mediated by genetic variation. Hypermutability is considered to play an important role in this adaptive evolution and it has been demonstrated...... that mutator populations are amplified in the CF lung by hitchhiking with adaptive mutations. Two of the genes that are frequently mutated in isolates from chronic infection are mucA and lasR. Loss-of-function mutations in these genes determine the phenotypic switch to mucoidy and loss of quorum sensing, which...

  7. Combination of Human Leukocyte Antigen and Killer Cell Immunoglobulin-Like Receptor Genetic Background Influences the Onset Age of Hepatocellular Carcinoma in Male Patients with Hepatitis B Virus Infection

    Directory of Open Access Journals (Sweden)

    Ning Pan

    2013-01-01

    Full Text Available To investigate whether killer cell immunoglobulin-like receptor (KIR and human leukocyte antigen (HLA genetic background could influence the onset age of hepatocellular carcinoma (HCC in patients with hepatitis B virus (HBV infection, one hundred and seventy-one males with HBV-related HCC were enrolled. The presence of 12 loci of KIR was detected individually. HLA-A, -B, and -C loci were genotyped with high resolution by a routine sequence-based typing method. The effect of each KIR locus, HLA ligand, and HLA-KIR combination was examined individually by Kaplan-Meier (KM analysis. Multivariate Cox hazard regression model was also applied. We identified C1C1-KIR2DS2/2DL2 as an independent risk factor for earlier onset age of HCC (median onset age was 44 for C1C1-KIR2DS2/2DL2 positive patients compared to 50 for negative patients, P=0.04 for KM analysis; HR = 1.70, P=0.004 for multivariate Cox model. We conclude that KIR and HLA genetic background can influence the onset age of HCC in male patients with HBV infection. This study may be useful to improve the current HCC surveillance program in HBV-infected patients. Our findings also suggest an important role of natural killer cells (or other KIR-expressing cells in the progress of HBV-related HCC development.

  8. Molecular and Functional Characterization of GR2-R1 Event Based Backcross Derived Lines of Golden Rice in the Genetic Background of a Mega Rice Variety Swarna

    Science.gov (United States)

    Bollinedi, Haritha; S., Gopala Krishnan; Prabhu, Kumble Vinod; Singh, Nagendra Kumar; Mishra, Sushma; Khurana, Jitendra P.; Singh, Ashok Kumar

    2017-01-01

    Homozygous Golden Rice lines developed in the background of Swarna through marker assisted backcross breeding (MABB) using transgenic GR2-R1 event as a donor for the provitamin A trait have high levels of provitamin A (up to 20 ppm) but are dwarf with pale green leaves and drastically reduced panicle size, grain number and yield as compared to the recurrent parent, Swarna. In this study, we carried out detailed morphological, biochemical and molecular characterization of these lines in a quest to identify the probable reasons for their abnormal phenotype. Nucleotide blast analysis with the primer sequences used to amplify the transgene revealed that the integration of transgene disrupted the native OsAux1 gene, which codes for an auxin transmembrane transporter protein. Real time expression analysis of the transgenes (ZmPsy and CrtI) driven by endosperm-specific promoter revealed the leaky expression of the transgene in the vegetative tissues. We propose that the disruption of OsAux1 disturbed the fine balance of plant growth regulators viz., auxins, gibberellic acid and abscisic acid, leading to the abnormalities in the growth and development of the lines homozygous for the transgene. The study demonstrates the conserved roles of OsAux1 gene in rice and Arabidopsis. PMID:28068433

  9. Molecular and Functional Characterization of GR2-R1 Event Based Backcross Derived Lines of Golden Rice in the Genetic Background of a Mega Rice Variety Swarna.

    Science.gov (United States)

    Bollinedi, Haritha; S, Gopala Krishnan; Prabhu, Kumble Vinod; Singh, Nagendra Kumar; Mishra, Sushma; Khurana, Jitendra P; Singh, Ashok Kumar

    2017-01-01

    Homozygous Golden Rice lines developed in the background of Swarna through marker assisted backcross breeding (MABB) using transgenic GR2-R1 event as a donor for the provitamin A trait have high levels of provitamin A (up to 20 ppm) but are dwarf with pale green leaves and drastically reduced panicle size, grain number and yield as compared to the recurrent parent, Swarna. In this study, we carried out detailed morphological, biochemical and molecular characterization of these lines in a quest to identify the probable reasons for their abnormal phenotype. Nucleotide blast analysis with the primer sequences used to amplify the transgene revealed that the integration of transgene disrupted the native OsAux1 gene, which codes for an auxin transmembrane transporter protein. Real time expression analysis of the transgenes (ZmPsy and CrtI) driven by endosperm-specific promoter revealed the leaky expression of the transgene in the vegetative tissues. We propose that the disruption of OsAux1 disturbed the fine balance of plant growth regulators viz., auxins, gibberellic acid and abscisic acid, leading to the abnormalities in the growth and development of the lines homozygous for the transgene. The study demonstrates the conserved roles of OsAux1 gene in rice and Arabidopsis.

  10. Mathematics is differentially related to reading comprehension and word decoding: Evidence from a genetically-sensitive design

    Science.gov (United States)

    Harlaar, Nicole; Kovas, Yulia; Dale, Philip S.; Petrill, Stephen A.; Plomin, Robert

    2013-01-01

    Although evidence suggests that individual differences in reading and mathematics skills are correlated, this relationship has typically only been studied in relation to word decoding or global measures of reading. It is unclear whether mathematics is differentially related to word decoding and reading comprehension. The current study examined these relationships at both a phenotypic and etiological level in a population-based cohort of 5162 twin pairs at age 12. Multivariate genetic analyses of latent phenotypic factors of mathematics, word decoding and reading comprehension revealed substantial genetic and shared environmental correlations among all three domains. However, the phenotypic and genetic correlations between mathematics and reading comprehension were significantly greater than between mathematics and word decoding. Independent of mathematics, there was also evidence for genetic and nonshared environmental links between word decoding and reading comprehension. These findings indicate that word decoding and reading comprehension have partly distinct relationships with mathematics in the middle school years. PMID:24319294

  11. Genetic Sensitivity to the Bitter Taste of 6-n-Propylthiouracil (PROP and Its Association with Physiological Mechanisms Controlling Body Mass Index (BMI

    Directory of Open Access Journals (Sweden)

    Beverly J. Tepper

    2014-08-01

    Full Text Available Taste sensitivity to the bitter compound 6-n-propylthiouracil (PROP is considered a marker for individual differences in taste perception that may influence food preferences and eating behavior, and thereby energy metabolism. This review describes genetic factors that may contribute to PROP sensitivity including: (1 the variants of the TAS2R38 bitter receptor with their different affinities for the stimulus; (2 the gene that controls the gustin protein that acts as a salivary trophic factor for fungiform taste papillae; and (3 other specific salivary proteins that could be involved in facilitating the binding of the PROP molecule with its receptor. In addition, we speculate on the influence of taste sensitivity on energy metabolism, possibly via modulation of the endocannabinoid system, and its possible role in regulating body composition homeostasis.

  12. Metabolic and clinical response to Escherichia coli lipopolysaccharide in layer pullets of different genetic backgrounds supplied with graded dietary L-arginine.

    Science.gov (United States)

    Lieboldt, M A; Frahm, J; Halle, I; Görs, S; Schrader, L; Weigend, S; Preisinger, R; Metges, C C; Breves, G; Dänicke, S

    2016-03-01

    L-arginine (Arg) is an essential amino acid in birds that plays a decisive role in avian protein synthesis and immune response. Effects of graded dietary Arg supply on metabolic and clinical response to Escherichia coli lipopolysaccharide (LPS) were studied over 48 hours after a single intramuscular LPS injection in 18-week-old genetically diverse purebred pullets. LPS induced a genotype-specific fever response within 4 hours post injectionem. Whereas brown genotypes showed an initial hypothermia followed by longer-lasting moderate hyperthermia, white genotypes exhibited a biphasic hyperthermia without initial hypothermia. Furthermore, within 2 hours after LPS injection, sickness behavior characterized by lethargy, anorexia, intensified respiration, and ruffled feathers appeared, persisted for 3 to 5 hours and recovered 12 hours post injectionem. The varying grades of Arg did not alter the examined traits named above, whereas insufficient Arg reduced body growth and increased relative weights of liver and pancreas significantly. At 48 hours post injectionem, increased relative weights of liver and spleen were also found in LPS treated pullets, whereas LPS decreased those of pancreas, bursa, thymus, and cecal tonsils. Moreover, LPS lowered the sum of plasma amino acids and decreased plasma concentrations of Arg, citrulline, glutamate, methionine, ornithine, phenylalanine, proline, tryptophan, and tyrosine, and increased those of aspartate, glutamine, lysine, 1- and 3-methyl-histidine. Elevating concentrations of dietary Arg led to increasing plasma concentrations of Arg, citrulline, ornithine, and 3-methyl-histidine subsequently. As quantitative expression of LPS-induced anorexia, proteolysis, and the following changes in plasma amino acids, pullets showed a significant decrease of feed and nitrogen intake and catabolic metabolism characterized by negative nitrogen balance and body weight loss in the first 24 hours post injectionem. Pullets recovered from the

  13. Temporal and anatomical host resistance to chronic Salmonella infection is quantitatively dictated by Nramp1 and influenced by host genetic background.

    Directory of Open Access Journals (Sweden)

    Wendy P Loomis

    Full Text Available The lysosomal membrane transporter, Nramp1, plays a key role in innate immunity and resistance to infection with intracellular pathogens such as non-typhoidal Salmonella (NTS. NTS-susceptible C57BL/6 (B6 mice, which express the mutant Nramp1D169 allele, are unable to control acute infection with Salmonella enterica serovar Typhimurium following intraperitoneal or oral inoculation. Introducing functional Nramp1G169 into the B6 host background, either by constructing a congenic strain carrying Nramp1G169 from resistant A/J mice (Nramp-Cg or overexpressing Nramp1G169 from a transgene (Nramp-Tg, conferred equivalent protection against acute Salmonella infection. In contrast, the contributions of Nramp1 for controlling chronic infection are more complex, involving temporal and anatomical differences in Nramp1-dependent host responses. Nramp-Cg, Nramp-Tg and NTS-resistant 129×1/SvJ mice survived oral Salmonella infection equally well for the first 2-3 weeks, providing evidence that Nramp1 contributes to the initial control of NTS bacteremia preceding establishment of chronic Salmonella infection. By day 30, increased host Nramp1 expression (Tg>Cg provided greater protection as indicated by decreased splenic bacterial colonization (Tg

  14. Temporal and anatomical host resistance to chronic Salmonella infection is quantitatively dictated by Nramp1 and influenced by host genetic background.

    Science.gov (United States)

    Loomis, Wendy P; Johnson, Matthew L; Brasfield, Alicia; Blanc, Marie-Pierre; Yi, Jaehun; Miller, Samuel I; Cookson, Brad T; Hajjar, Adeline M

    2014-01-01

    The lysosomal membrane transporter, Nramp1, plays a key role in innate immunity and resistance to infection with intracellular pathogens such as non-typhoidal Salmonella (NTS). NTS-susceptible C57BL/6 (B6) mice, which express the mutant Nramp1D169 allele, are unable to control acute infection with Salmonella enterica serovar Typhimurium following intraperitoneal or oral inoculation. Introducing functional Nramp1G169 into the B6 host background, either by constructing a congenic strain carrying Nramp1G169 from resistant A/J mice (Nramp-Cg) or overexpressing Nramp1G169 from a transgene (Nramp-Tg), conferred equivalent protection against acute Salmonella infection. In contrast, the contributions of Nramp1 for controlling chronic infection are more complex, involving temporal and anatomical differences in Nramp1-dependent host responses. Nramp-Cg, Nramp-Tg and NTS-resistant 129×1/SvJ mice survived oral Salmonella infection equally well for the first 2-3 weeks, providing evidence that Nramp1 contributes to the initial control of NTS bacteremia preceding establishment of chronic Salmonella infection. By day 30, increased host Nramp1 expression (Tg>Cg) provided greater protection as indicated by decreased splenic bacterial colonization (Tg

  15. Lifestyle and Metformin Ameliorate Insulin Sensitivity Independently of the Genetic Burden of Established Insulin Resistance Variants in Diabetes Prevention Program Participants.

    Science.gov (United States)

    Hivert, Marie-France; Christophi, Costas A; Franks, Paul W; Jablonski, Kathleen A; Ehrmann, David A; Kahn, Steven E; Horton, Edward S; Pollin, Toni I; Mather, Kieren J; Perreault, Leigh; Barrett-Connor, Elizabeth; Knowler, William C; Florez, Jose C

    2016-02-01

    Large genome-wide association studies of glycemic traits have identified genetics variants that are associated with insulin resistance (IR) in the general population. It is unknown whether people with genetic enrichment for these IR variants respond differently to interventions that aim to improve insulin sensitivity. We built a genetic risk score (GRS) based on 17 established IR variants and effect sizes (weighted IR-GRS) in 2,713 participants of the Diabetes Prevention Program (DPP) with genetic consent. We tested associations between the weighted IR-GRS and insulin sensitivity index (ISI) at baseline in all participants, and with change in ISI over 1 year of follow-up in the DPP intervention (metformin and lifestyle) and control (placebo) arms. All models were adjusted for age, sex, ethnicity, and waist circumference at baseline (plus baseline ISI for 1-year ISI change models). A higher IR-GRS was associated with lower baseline ISI (β = -0.754 [SE = 0.229] log-ISI per unit, P = 0.001 in fully adjusted models). There was no differential effect of treatment for the association between the IR-GRS on the change in ISI; higher IR-GRS was associated with an attenuation in ISI improvement over 1 year (β = -0.520 [SE = 0.233], P = 0.03 in fully adjusted models; all treatment arms). Lifestyle intervention and metformin treatment improved the ISI, regardless of the genetic burden of IR variants. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  16. Background reduction in cryogenic detectors

    Energy Technology Data Exchange (ETDEWEB)

    Bauer, Daniel A.; /Fermilab

    2005-04-01

    This paper discusses the background reduction and rejection strategy of the Cryogenic Dark Matter Search (CDMS) experiment. Recent measurements of background levels from CDMS II at Soudan are presented, along with estimates for future improvements in sensitivity expected for a proposed SuperCDMS experiment at SNOLAB.

  17. X-ray survival characteristics and genetic analysis for nine saccharomyces deletion mutants that show altered radiation sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Game, John C.; Williamson, Marsha S.; Baccari, Clelia

    2004-01-07

    The availability of a genome-wide set of Saccharomyces deletion mutants provides a chance to identify all the yeast genes involved in DNA repair. Using X-rays, we are screening these mutants to identify additional genes that show increased sensitivity to the lethal effects of ionizing radiation. For each mutant identified as sensitive, we are confirming that the sensitivity phenotype co-segregates with the deletion allele and are obtaining multipoint survival-versus-dose assays in at least two haploid and one homozygous diploid strains. We present data for deletion mutants involving the genes DOT1, MDM20, NAT3, SPT7, SPT20, GCN5, HFI1, DCC1 and VID21/EAF1, and discuss their potential roles in repair. Eight of these genes have a clear radiation-sensitive phenotype when deleted, but the ninth, GCN5, has at most a borderline phenotype. None of the deletions confer substantial sensitivity to ultra-violet radiation, although one or two may confer marginal sensitivity. The DOT1 gene is of interest because its only known function is to methylate one lysine residue in the core of the histone H3 protein. We find that histone H3 mutants (supplied by K. Struhl) in which this residue is replaced by other amino-acids are also X-ray sensitive, seeming to confirm that methylation of the lysine-79 residue is required for effective repair of radiation damage.

  18. Genetic and environmental causes of individual differences in daily life positive affect and reward experience and its overlap with stress-sensitivity.

    Science.gov (United States)

    Menne-Lothmann, Claudia; Jacobs, Nele; Derom, Catherine; Thiery, Evert; van Os, Jim; Wichers, Marieke

    2012-09-01

    Momentary positive affect (PA) and reward experience may underlie subjective wellbeing, and index mental health resilience. This study examines their underlying sources of variation and the covariation with stress-sensitivity. The experience sampling method was used to collect multiple appraisals of mood and daily life events in 520 female twins. Structural equation model fitting was employed to determine sources of variation of PA, reward experience, and the association between reward experience and stress-sensitivity. PA was best explained by shared and non-shared environmental factors, and reward experience by non-shared environmental factors only, although the evidence was also suggestive of a small genetic contribution. Reward experience and stress-sensitivity showed no association. PA was not heritable. Most-if not all-variance of reward experience was explained by environmental influences. Stress-sensitivity, indexing depression vulnerability, and reward experience were non-overlapping, suggesting that resilience traits are independent from stress-sensitivity levels in a general population sample.

  19. Prediction of alcohol drinking in adolescents: Personality-traits, behavior, brain responses, and genetic variations in the context of reward sensitivity.

    Science.gov (United States)

    Heinrich, Angela; Müller, Kathrin U; Banaschewski, Tobias; Barker, Gareth J; Bokde, Arun L W; Bromberg, Uli; Büchel, Christian; Conrod, Patricia; Fauth-Bühler, Mira; Papadopoulos, Dimitri; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Ittermann, Bernd; Mann, Karl; Martinot, Jean-Luc; Paus, Tomáš; Pausova, Zdenka; Smolka, Michael; Ströhle, Andreas; Rietschel, Marcella; Flor, Herta; Schumann, Gunter; Nees, Frauke

    2016-07-01

    Adolescence is a time that can set the course of alcohol abuse later in life. Sensitivity to reward on multiple levels is a major factor in this development. We examined 736 adolescents from the IMAGEN longitudinal study for alcohol drinking during early (mean age=14.37) and again later (mean age=16.45) adolescence. Conducting structural equation modeling we evaluated the contribution of reward-related personality traits, behavior, brain responses and candidate genes. Personality seems to be most important in explaining alcohol drinking in early adolescence. However, genetic variations in ANKK1 (rs1800497) and HOMER1 (rs7713917) play an equal role in predicting alcohol drinking two years later and are most important in predicting the increase in alcohol consumption. We hypothesize that the initiation of alcohol use may be driven more strongly by personality while the transition to increased alcohol use is more genetically influenced.

  20. Chemical-genetic inhibition of a sensitized mutant myosin Vb demonstrates a role in peripheral-pericentriolar membrane traffic

    OpenAIRE

    Provance, D. William; Gourley, Christopher R.; Silan, Colleen M.; Cameron, L. C.; Kevan M Shokat; Goldenring, James R.; Shah, Kavita; Gillespie, Peter G.; John A. Mercer

    2004-01-01

    Selective, in situ inhibition of individual unconventional myosins is a powerful approach to determine their specific physiological functions. Here, we report the engineering of a myosin Vb mutant that still hydrolyzes ATP, yet is selectively sensitized to an N6-substituted ADP analog that inhibits its activity, causing it to remain tightly bound to actin. Inhibition of the sensitized mutant causes inhibition of accumulation of transferrin in the cytoplasm and increases levels of plasma-membr...

  1. On the optimization of fiber Bragg grating optical sensor using genetic algorithm to monitor the strain of civil structure with high sensitivity

    Science.gov (United States)

    Kaur, Gurpreet; Kaler, Rajinder Singh; Kwatra, Naveen

    2016-08-01

    The effect of strain on civil structures is experimentally studied using fiber Bragg grating (FBG). The genetic algorithm is implemented to optimize the multiple parameters (Poisson's ratio, photoelastic coefficient P11, and photoelastic coefficient P12) of the proposed sensor. The optimized results helped in increasing the sensitivity in terms of wavelength shift. It is observed that the proposed FBG provides maximum wavelength shift of 38.16 nm with Poisson's ratio of 1.94, photoelastic coefficient P11 of 1.994, and photoelastic coefficient P12 of 1.8103.

  2. Does a medical history of hypertension influence disclosing genetic testing results of the risk for salt-sensitive hypertension, in primary care?

    Directory of Open Access Journals (Sweden)

    Okayama M

    2016-07-01

    Full Text Available Masanobu Okayama,1,2 Taro Takeshima,2 Masanori Harada,3 Ryusuke Ae,4 Eiji Kajii2 1Division of Community Medicine and Medical Education, Kobe University Graduate School of Medicine, Kobe, Hyogo, 2Division of Community and Family Medicine, Center for Community Medicine, Jichi Medical University, Shimotsuke, Tochigi, 3Department of Support of Rural Medicine, Yamaguchi Grand Medical Center, Hofu, Yamaguchi, 4Division of Public Health, Center for Community Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan Objective: Disclosing genetic testing results may contribute to the prevention and management of many common diseases. However, whether the presence of a disease influences these effects is unclear. This study aimed to clarify the difference in the effects of disclosing genetic testing results of the risk for developing salt-sensitive hypertension on the behavioral modifications with respect to salt intake in hypertensive and nonhypertensive patients.Methods: A cross-sectional study using a self-administered questionnaire was conducted for outpatients aged >20 years (N=2,237 at six primary care clinics and hospitals in Japan. The main factors assessed were medical histories of hypertension, salt preferences, reduced salt intakes, and behavior modifications for reducing salt intake. Behavioral modifications of participants were assessed using their behavior stages before and after disclosure of the hypothetical genetic testing results. Results: Of the 2,237 participants, 1,644 (73.5% responded to the survey. Of these respondents, 558 (33.9% patients were hypertensive and 1,086 (66.1% were nonhypertensive. After being notified of the result “If with genetic risk”, the nonhypertensive participants were more likely to make positive behavioral modifications compared to the hypertensive patients among all participants and in those aged <65 years (adjusted relative ratio [ad-RR], 1.76; 95% confidence interval, 1.12−2.76 and ad-RR, 1

  3. Chemical-genetic inhibition of a sensitized mutant myosin Vb demonstrates a role in peripheral-pericentriolar membrane traffic.

    Science.gov (United States)

    Provance, D William; Gourley, Christopher R; Silan, Colleen M; Cameron, L C; Shokat, Kevan M; Goldenring, James R; Shah, Kavita; Gillespie, Peter G; Mercer, John A

    2004-02-17

    Selective, in situ inhibition of individual unconventional myosins is a powerful approach to determine their specific physiological functions. Here, we report the engineering of a myosin Vb mutant that still hydrolyzes ATP, yet is selectively sensitized to an N(6)-substituted ADP analog that inhibits its activity, causing it to remain tightly bound to actin. Inhibition of the sensitized mutant causes inhibition of accumulation of transferrin in the cytoplasm and increases levels of plasma-membrane transferrin receptor, suggesting that myosin Vb functions in traffic between peripheral and pericentrosomal compartments.

  4. Neuropeptide s alters anxiety but not depression-like behaviors in the flinders sensitive line rats, a genetic animal model

    DEFF Research Database (Denmark)

    Mathe, A.; Wegener, Gregers; Finger, B.

    2010-01-01

    Background: Neuropeptide S (NPS) and its receptor (NPSR) have been implicated in the mediation of anxiolytic-like behavior in rodents. However, little knowledge is available to what extent the NPS system is involved in depression-related behaviors. The aim of the present work was to characterize ...

  5. Genetic background of extreme violent behavior.

    Science.gov (United States)

    Tiihonen, J; Rautiainen, M-R; Ollila, H M; Repo-Tiihonen, E; Virkkunen, M; Palotie, A; Pietiläinen, O; Kristiansson, K; Joukamaa, M; Lauerma, H; Saarela, J; Tyni, S; Vartiainen, H; Paananen, J; Goldman, D; Paunio, T

    2015-06-01

    In developed countries, the majority of all violent crime is committed by a small group of antisocial recidivistic offenders, but no genes have been shown to contribute to recidivistic violent offending or severe violent behavior, such as homicide. Our results, from two independent cohorts of Finnish prisoners, revealed that a monoamine oxidase A (MAOA) low-activity genotype (contributing to low dopamine turnover rate) as well as the CDH13 gene (coding for neuronal membrane adhesion protein) are associated with extremely violent behavior (at least 10 committed homicides, attempted homicides or batteries). No substantial signal was observed for either MAOA or CDH13 among non-violent offenders, indicating that findings were specific for violent offending, and not largely attributable to substance abuse or antisocial personality disorder. These results indicate both low monoamine metabolism and neuronal membrane dysfunction as plausible factors in the etiology of extreme criminal violent behavior, and imply that at least about 5-10% of all severe violent crime in Finland is attributable to the aforementioned MAOA and CDH13 genotypes.

  6. Phenotypic and genetic analyses of the Varroa Sensitive Hygienic trait in Russian Honey Bee (Hymenoptera: Apidae) colonies

    Science.gov (United States)

    Varroa destructor continues to threaten colonies of European honey bees. General hygiene and more specific VarroaVarroa Sensitive Hygiene (VSH) provide resistance toward the Varroa mite in a number of stocks. In this study, Russian (RHB) and Italian honey bees were assessed for the VSH trait. Two...

  7. X-ray survival characteristics and genetic analysis for nineSaccharomyces deletion mutants that affect radiation sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Game, John C.; Williamson, Marsha S.; Baccari, Clelia

    2006-07-21

    We examine ionizing radiation (IR) sensitivity and epistasisrelationships of several Saccharomyces mutants affectingpost-translational modifications of histones H2B and H3. Mutantsbre1delta, lge1delta, and rtf1delta, defective in histone H2B lysine 123ubiquitination, show IR sensitivity equivalent to that of the dot1deltamutant that we reported on earlier, consistent with published findingsthat Dot1p requires H2B K123 ubiquitination to fully methylate histone H3K79. This implicates progressive K79 methylation rather thanmono-methylation in IR resistance. The set2delta mutant, defective in H3K36 methylation, shows mild IR sensitivity whereas mutants that abolishH3 K4 methylation resemble wild type. The dot1delta, bre1delta, andlge1delta mutants show epistasis for IR sensitivity. The paf1deltamutant, also reportedly defective in H2B K123 ubiquitination, confers nosensitivity. The rad6delta, rad51null, rad50delta, and rad9deltamutations are epistatic to bre1? and dot1delta, but rad18delta andrad5delta show additivity with bre1delta, dot1delta, and each other. Thebre1delta rad18delta double mutant resembles rad6delta in sensitivity;thus the role of Rad6p in ubiquitinating H2B accounts for its extrasensitivity compared to rad18delta. We conclude that IR resistanceconferred by BRE1 and DOT1 is mediated through homologous recombinationalrepair, not postreplication repair, and confirm findings of a G1checkpoint role for the RAD6/BRE1/DOT1 pathway.

  8. Elevation of naloxone-sensitive /sup 3/H-dihydromorphine binding in hippocampal formation of genetically epilepsy-prone rats

    Energy Technology Data Exchange (ETDEWEB)

    Savage, D.D.; Mills, S.A.; Jobe, P.C.; Reigel, C.E.

    1988-01-01

    /sup 3/H-Dihydromorphine (DHM) binding sites were measured in the brain of non-epileptic control and GEPR rats using in vitro autoradiographic techniques. The number of naloxone-sensitive /sup 3/H-DHM binding sites was increased 38-57% in the pyramidal cell layer of ventral hippocampal CA/sub 3/ and CA/sub 1/ of GEPR-3 and GEPR-9 rats compared to non-epileptic controls. No significant differences in /sup 3/H-DHM binding were observed in dorsal hippocampal formation, lateral entorhinal cortex, lateral geniculate or cerebellum. The results suggest that an increase in the number of opioid receptors in ventral hippocampus of GEPR rats may be one factor contributing to the enhanced sensitivity of GEPR-9 rats to the proconvulsant effects of morphine.

  9. Relationship between interferon regulatory factor 4 genetic polymorphisms, measures of sun sensitivity and risk for non-Hodgkin lymphoma.

    Science.gov (United States)

    Gathany, Allison H; Hartge, Patricia; Davis, Scott; Cerhan, James R; Severson, Richard K; Cozen, Wendy; Rothman, Nathaniel; Chanock, Stephen J; Wang, Sophia S

    2009-10-01

    Sun exposure and sensitivity, including pigmentation, are associated with risk for non-Hodgkin lymphoma (NHL). One variant in the immune regulatory factor 4 (IRF4) gene (rs12203592) is associated with pigmentation, and a different IRF4 variant (rs12211228) is associated with NHL risk. We evaluated the independent roles of these IRF4 polymorphisms and sun sensitivity in mediating NHL risk and explored whether they are confounded or modified by each other. Genotyping of tag single nucleotide polymorphisms (SNPs) in the IRF4 gene was conducted in 990 NHL cases and 828 controls from a multi-center US study. Measures of sun sensitivity and exposure were ascertained from computer-assisted personal interviews. We used logistic regression to compute odds ratios (OR) and 95% confidence intervals (CI) for NHL in relation to sun exposures, sun exposures in relation to IRF4 genotypes, and NHL in relation to sun exposures. We further assessed the effects of sun exposures in relation to IRF4 genotypes. As previously reported, we found significant associations between IRF4 rs12211228 and NHL and between hair and eye color and NHL. The IRF4 rs12203592 polymorphism (CT/TT genotype) was statistically significantly associated with eye color and particularly with hair color (OR(Light Blonde) = 0.24, 95% CI = 0.11-0.50, overall Chi square p = 0.0002). Analysis of joint effects between eye and hair color with the IRF4 rs12203592 SNP did not reveal statistically significant p-interactions although NHL risk did decline with lighter hair color and presence of the variant IRF4 rs12203592 allele, compared to those without a variant allele and with black/brown hair color. Our data do not statistically support a joint effect between IRF4 and sun sensitivity in mediating risk for NHL. Further evaluation of joint effects in other and larger populations is warranted.

  10. Assessing the Risk for Resistance and Elucidating the Genetics of Colletotrichum truncatum That Is Only Sensitive to Some DMI Fungicides

    Directory of Open Access Journals (Sweden)

    Can Zhang

    2017-09-01

    Full Text Available The genus Colletotrichum contains a wide variety of important plant pathogens, and Colletotrichum truncatum is one of the most prevalent species of Colletotrichum on chili in China. Demethylation-inhibitor fungicides (DMIs are currently registered chemical agents for the management of the anthracnose disease caused by Colletotrichum spp. To assess the risk for DMI resistance development, 112 C. truncatum isolates were collected from infected pepper in 13 regions of China. The sensitivity of C. truncatum isolates to five DMI fungicides was determined based on mycelial growth inhibition assay. C. truncatum was sensitive to prochloraz, epoxiconazole, and difenoconazole, but not to tebuconazole or myclobutanil. Baseline sensitivity using the 112 C. truncatum isolates was established for the first three effective DMIs. Prochloraz, epoxiconazole, and difenoconazole EC50 values were 0.053 ± 0.023, 1.956 ± 0.815, and 1.027 ± 0.644 μg/ml, respectively. Eleven stable DMI-resistant mutants all exhibited lower fitness levels than their wild-type parents, suggesting a low risk of DMI resistance in C. truncatum. By inducing gene expression, CtCYP51 expression increased slightly in the resistant mutants as compared to wild-types when exposed to DMI fungicides and thus contributed at least partially to resistance. Molecular docking with CYP51 structure models was used to explain differential sensitivity of the DMI fungicides in C. truncatum. Our results suggest that the M376L/H373N mutations in CYP51 changed the conformation of DMIs in the binding pocket. These changes prevented the formation of the Fe – N coordinate bond between the heme iron active site and tebuconazole or myclobutanil, and apparently contributed to tebuconazole and myclobutanil insensitivity of C. truncatum.

  11. Genetic Relationships, Carbendazim Sensitivity and Mycotoxin Production of the Fusarium Graminearum Populations from Maize, Wheat and Rice in Eastern China

    Directory of Open Access Journals (Sweden)

    Jianbo Qiu

    2014-08-01

    Full Text Available Members of the Fusarium graminearum species complex (FGSC are important pathogens on wheat, maize, barley, and rice in China. Harvested grains are often contaminated by mycotoxins, such as the trichothecene nivalenol (NIV and deoxynivalenol (DON and the estrogenic mycotoxin zearalenone (ZEN, which is a big threat to humans and animals. In this study, 97 isolates were collected from maize, wheat, and rice in Jiangsu and Anhui provinces in 2013 and characterized by species- and chemotype-specific PCR. F. graminearum sensu stricto (s. str. was predominant on maize, while most of the isolates collected from rice and wheat were identified as F. asiaticum. Fusarium isolates from three hosts varied in trichothecene chemotypes. The 3-acetyldeoxynivalenol (3ADON chemotype predominated on wheat and rice population, while 15ADON was prevailing in the remaining isolates. Sequence analysis of the translation elongation factor 1α and trichodiene synthase indicated the accuracy of the above conclusion. Additionally, phylogenetic analysis suggested four groups with strong correlation with species, chemotype, and host. These isolates were also evaluated for their sensitivity to carbendazim and mycotoxins production. The maize population was less sensitive than the other two. The DON levels were similar in three populations, while those isolates on maize produced more ZEN. More DON was produced in carbendazim resistant strains than sensitive ones, but it seemed that carbendazim resistance had no effect on ZEN production in wheat culture.

  12. Genetic Relationships, Carbendazim Sensitivity and Mycotoxin Production of the Fusarium Graminearum Populations from Maize, Wheat and Rice in Eastern China

    Science.gov (United States)

    Qiu, Jianbo; Shi, Jianrong

    2014-01-01

    Members of the Fusarium graminearum species complex (FGSC) are important pathogens on wheat, maize, barley, and rice in China. Harvested grains are often contaminated by mycotoxins, such as the trichothecene nivalenol (NIV) and deoxynivalenol (DON) and the estrogenic mycotoxin zearalenone (ZEN), which is a big threat to humans and animals. In this study, 97 isolates were collected from maize, wheat, and rice in Jiangsu and Anhui provinces in 2013 and characterized by species- and chemotype-specific PCR. F. graminearum sensu stricto (s. str.) was predominant on maize, while most of the isolates collected from rice and wheat were identified as F. asiaticum. Fusarium isolates from three hosts varied in trichothecene chemotypes. The 3-acetyldeoxynivalenol (3ADON) chemotype predominated on wheat and rice population, while 15ADON was prevailing in the remaining isolates. Sequence analysis of the translation elongation factor 1α and trichodiene synthase indicated the accuracy of the above conclusion. Additionally, phylogenetic analysis suggested four groups with strong correlation with species, chemotype, and host. These isolates were also evaluated for their sensitivity to carbendazim and mycotoxins production. The maize population was less sensitive than the other two. The DON levels were similar in three populations, while those isolates on maize produced more ZEN. More DON was produced in carbendazim resistant strains than sensitive ones, but it seemed that carbendazim resistance had no effect on ZEN production in wheat culture. PMID:25093387

  13. Genetic background of novel sequence types of CTX-M-8- and CTX-M-15-producing Escherichia coli and Klebsiella pneumoniae from public wastewater treatment plants in São Paulo, Brazil.

    Science.gov (United States)

    Dropa, Milena; Lincopan, Nilton; Balsalobre, Livia C; Oliveira, Danielle E; Moura, Rodrigo A; Fernandes, Miriam Rodriguez; da Silva, Quézia Moura; Matté, Glavur R; Sato, Maria I Z; Matté, Maria H

    2016-03-01

    The release of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae to the environment is a public health issue worldwide. The aim of this study was to investigate the genetic background of genes encoding ESBLs in wastewater treatment plants (WWTPs) in São Paulo, southeastern Brazil. In 2009, during a local surveillance study, seven ESBL-producing Enterobacteriaceae strains were recovered from five WWTPs and screened for ESBL genes and mobile genetic elements. Multilocus sequence typing (MLST) was carried out, and wild plasmids were transformed into electrocompetent Escherichia coli. S1-PFGE technique was used to verify the presence of high molecular weight plasmids in wild-type strains and in bla ESBL-containing E. coli transformants. Strains harbored bla CTX-M-8, bla CTX-M-15, and/or bla SHV-28. Sequencing results showed that bla CTX-M-8 and bla CTX-M-15 genes were associated with IS26. MLST revealed new sequence types for E. coli (ST4401, ST4402, ST4403, and ST4445) and Klebsiella pneumoniae (ST1574), except for one K. pneumoniae from ST307 and Enterobacter cloacae from ST131. PCR and S1-PFGE results showed CTX-M-producing E. coli transformants carried heavy plasmids sizing 48.5-209 kb, which belonged to IncI1, IncF, and IncM1 incompatibility groups. This is the first report of CTX-M-8 and SHV-28 enzymes in environmental samples, and the present results demonstrate the plasmid-mediated spread of CTX-M-encoding genes through five WWTPs in São Paulo, Brazil, suggesting WWTPs are hotspots for the transfer of ESBL genes and confirming the urgent need to improve the management of sewage in order to minimize the dissemination of resistance genes to the environment.

  14. Subjects heterozygous for genetic loss of function of the thiazide-sensitive cotransporter have reduced blood pressure.

    Science.gov (United States)

    Fava, C; Montagnana, M; Rosberg, L; Burri, P; Almgren, P; Jönsson, A; Wanby, P; Lippi, G; Minuz, P; Hulthèn, L U; Aurell, M; Melander, O

    2008-02-01

    Gitelmańs syndrome (GS) is an inherited recessive disorder caused by homozygous or compound heterozygous loss of function mutations of the NaCl cotransporter (NCCT) gene encoding the kidney-expressed NCCT, the pharmacological target of thiazide diuretics. An observational study estimated the prevalence of GS to 19/1,000,000, in Sweden, suggesting that approximately 1% of the population carries one mutant NCCT allele. As the phenotype of GS patients, who always carry two mutant alleles, is indistinguishable from that seen in patients treated with high-dose thiazide diuretics, we aimed at investigating whether subjects carrying one mutated NCCT allele have a phenotype resembling that of treatment with low-dose thiazide diuretics. We screened first-degree relatives of 18 of our patients with an established clinical end genetic diagnosis of GS for NCCT loss of function mutations and identified 35 healthy subjects carrying one mutant allele (GS-heterozygotes). Each GS-heterozygote was assigned a healthy control subject matched for age, BMI and sex. GS-heterozygotes had markedly lower blood pressure (systolic 103.3 +/- 16.4 versus 123.2 +/- 19.4 mmHg; diastolic 62.5 +/- 10.5 versus 73.1 +/- 9.4 mmHg; P pressure and slightly higher fasting plasma glucose compared with control subjects. Our findings suggest that GS-heterozygotes, the prevalence of which can be estimated to 1%, are partially protected from hypertension through partial genetic loss of function of the NCCT. However, as our study had a case-control design, it is important to underline that any potential effects on population blood pressure and risk of future cardiovascular disease need to be examined in prospective and population-based studies.

  15. Developing a set of ancestry-sensitive DNA markers reflecting continental origins of humans

    NARCIS (Netherlands)

    P. Kersbergen (Paula); K. van Duijn (Kate); A. Kloosterman (Ate); J.T. den Dunnen (Johan); M.H. Kayser (Manfred); P. de Knijff (Peter)

    2009-01-01

    textabstractBackground: The identification and use of Ancestry-Sensitive Markers (ASMs), i.e. genetic polymorphisms facilitating the genetic reconstruction of geographical origins of individuals, is far from straightforward. Results: Here we describe the ascertainment and application of five

  16. Developing a set of ancestry-sensitive DNA markers reflecting continental origins of humans

    NARCIS (Netherlands)

    P. Kersbergen (Paula); K. van Duijn (Kate); A. Kloosterman (Ate); J.T. den Dunnen (Johan); M.H. Kayser (Manfred); P. de Knijff (Peter)

    2009-01-01

    textabstractBackground: The identification and use of Ancestry-Sensitive Markers (ASMs), i.e. genetic polymorphisms facilitating the genetic reconstruction of geographical origins of individuals, is far from straightforward. Results: Here we describe the ascertainment and application of five differe

  17. Genetic variants in cytosolic 5'-nucleotidase II are associated with its expression and cytarabine sensitivity in HapMap cell lines and in patients with acute myeloid leukemia.

    Science.gov (United States)

    Mitra, Amit K; Crews, Kristine R; Pounds, Stanley; Cao, Xueyuan; Feldberg, Tanya; Ghodke, Yogita; Gandhi, Varsha; Plunkett, William; Dolan, M Eileen; Hartford, Christine; Raimondi, Susana; Campana, Dario; Downing, James; Rubnitz, Jeffrey E; Ribeiro, Raul C; Lamba, Jatinder K

    2011-10-01

    Cytosolic 5'-nucleotidase II (NT5C2) is involved in the development of 1-β-d-arabinofuranosylcytosine (ara-C) resistance and has been associated with clinical outcome in patients receiving ara-C-based chemotherapy. NT5C2 inactivates ara-C by dephosphorylating ara-C monophosphate to ara-C. In this study, we sequenced NT5C2 in genomic DNA samples from International HapMap project panels with European [Centre d'Etude du Polymorphisme Humain (CEU); n = 90] or African [Yoruba people in Ibadan, Nigeria (YRI); n = 90] ancestry. We identified 41 genetic variants [one insertion-deletion and 40 single nucleotide polymorphisms (SNPs)], including three nonsynonymous SNPs (Y3A, K47R, and Q136R). Twenty-five SNPs were novel and 16 overlapped with the HapMap data. Subjects with African ancestry had NT5C2 mRNA expression levels that was significantly higher than those with European ancestry (p = 0.005). Furthermore, there was a correlation between NT5C2 mRNA expression and ara-C sensitivity in CEU but not in YRI cell lines. None of the nonsynonymous SNPs demonstrated any effect on NT5C2 activity. The genotypes of several SNPs were significantly associated with NT5C2 mRNA expression and/or ara-C sensitivity in CEU cell lines, but very few were significant in YRI cell lines. Of most interest, SNPs (linkage disequilibrium group CEU.12) in the 5'-untranslated region were associated with NT5C2 expression and ara-C sensitivity in HapMap cell lines and with NT5C2 mRNA expression and ara-C sensitivity in diagnostic leukemic blasts from pediatric patients with acute myeloid leukemia. Functional genomics analysis demonstrated that the promoter SNP rs11191612 was associated with altered luciferase activation in reporter assays and altered DNA-protein binding in gel shift assays. These results suggest that genetic variations in NT5C2 influence its expression and, potentially, cellular responses to nucleoside analogs.

  18. Pathogenicity of Genetically Similar, H5N1 Highly Pathogenic Avian Influenza Virus Strains in Chicken and the Differences in Sensitivity among Different Chicken Breeds.

    Science.gov (United States)

    Matsuu, Aya; Kobayashi, Tomoko; Patchimasiri, Tuangthong; Shiina, Takashi; Suzuki, Shingo; Chaichoune, Kridsada; Ratanakorn, Parntep; Hiromoto, Yasuaki; Abe, Haruka; Parchariyanon, Sujira; Saito, Takehiko

    2016-01-01

    Differences in the pathogenicity of genetically closely related H5N1 highly pathogenic avian influenza viruses (HPAIVs) were evaluated in White Leghorn chickens. These viruses varied in the clinical symptoms they induced, including lethality, virus shedding, and replication in host tissues. A comparison of the host responses in the lung, brain, and spleen suggested that the differences in viral replication efficiency were related to the host cytokine response at the early phase of infection, especially variations in the proinflammatory cytokine IL-6. Based on these findings, we inoculated the virus that showed the mildest pathogenicity among the five tested, A/pigeon/Thailand/VSMU-7-NPT/2004, into four breeds of Thai indigenous chicken, Phadu-Hung-Dang (PHD), Chee, Dang, and Luang-Hung-Khao (LHK), to explore effects of genetic background on host response. Among these breeds, Chee, Dang, and LHK showed significantly longer survival times than White Leghorns. Virus shedding from dead Thai indigenous chickens was significantly lower than that from White Leghorns. Although polymorphisms were observed in the Mx and MHC class I genes, there was no significant association between the polymorphisms in these loci and resistance to HPAIV.

  19. Neuropeptide s alters anxiety but not depression-like behaviors in the flinders sensitive line rats, a genetic animal model

    DEFF Research Database (Denmark)

    Mathe, A.; Wegener, Gregers; Finger, B.

    2010-01-01

    of cannula, 0.25 or 1.0 nmol NPS, or vehicle/5 ml were infused into the lateral ventricle. 45 min after NPS infusion animals were tested on elevated plus maze (EPM). Five days later the animals were subjected to the two-day forced swim test (FST); NPS or vehicle were injected 45 min before the second day FST...... the effects of centrally administered NPS on depression- and anxiety-related behaviors, using a well validated animal model of depression, the Flinders Sensitive Line (FSL) rats and their controls the Flinders Resistant Line (FRL). Methods: Male and female were tested. Seven days following insertion...... while no difference in the anxiety-like behavior was observed. These findings confirm the utility of the FSL as a model of depression useful in exploration of neurobiological correlates both of depression and those discriminating between depression and anxiety endophenotypes. NPS had marked anxiolytic...

  20. Ultra-sensitive biosensor based on genetically engineered acetylcholinesterase immobilized in poly (vinyl alcohol)/Fe-Ni alloy nanocomposite for phosmet detection in olive oil.

    Science.gov (United States)

    El-Moghazy, A Y; Soliman, E A; Ibrahim, H Z; Noguer, T; Marty, J-L; Istamboulie, G

    2016-07-15

    An ultra-sensitive screen-printed biosensor was successfully developed for phosmet detection in olive oil, based on a genetically-engineered acetylcholinesterase (AChE) immobilized in a azide-unit water-pendant polyvinyl alcohol (PVA-AWP)/Fe-Ni alloy nanocomposite. Fe-Ni not only allowed amplifying the response current but also lowering the applied potential from 80 mV to 30 mV vs Ag/AgCl. The biosensor showed a very good analytical performance for phosmet detection, with a detection limit of 0.1 nM. This detection limit is lower than the allowable concentrations set by international regulations. In addition to the good reproducibility, operational and storage stability, the developed biosensor was successfully used for the determination of phosmet in olive oil samples without any laborious pre-treatment. The phosmet recovery rate was about 96% after a simple liquid-liquid extraction.

  1. Contrasting effects of chloride on growth, reproduction, and toxicant sensitivity in two genetically distinct strains of Hyalella azteca.

    Science.gov (United States)

    Soucek, David J; Mount, David R; Dickinson, Amy; Hockett, J Russell; McEwen, Abigail R

    2015-10-01

    The strain of Hyalella azteca (Saussure: Amphipoda) commonly used for aquatic toxicity testing in the United States has been shown to perform poorly in some standardized reconstituted waters frequently used for other test species. In 10-d and 42-d experiments, the growth and reproduction of the US laboratory strain of H. azteca was shown to vary strongly with chloride concentration in the test water, with declining performance observed below 15 mg/L to 20 mg/L. In contrast to the chloride-dependent performance of the US laboratory strain of H. azteca, growth of a genetically distinct strain of H. azteca obtained from an Environment Canada laboratory in Burlington, Ontario, Canada, was not influenced by chloride concentration. In acute toxicity tests with the US laboratory strain of H. azteca, the acute toxicity of sodium nitrate increased with decreasing chloride in a pattern similar not only to that observed for control growth, but also to previous acute toxicity testing with sodium sulfate. Subsequent testing with the Burlington strain showed no significant relationship between chloride concentration and the acute toxicity of sodium nitrate or sodium sulfate. These findings suggest that the chloride-dependent toxicity shown for the US laboratory strain may be an unusual feature of that strain and perhaps not broadly representative of aquatic organisms as a whole.

  2. Evidence for genetic regulation of mRNA expression of the dosage-sensitive gene retinoic acid induced-1 (RAI1) in human brain

    Science.gov (United States)

    Chen, Li; Tao, Yu; Song, Fan; Yuan, Xi; Wang, Jian; Saffen, David

    2016-01-01

    RAI1 (retinoic acid induced-1) is a dosage-sensitive gene that causes Smith-Magenis syndrome (SMS) when mutated or deleted and Potocki-Lupski Syndrome (PTLS) when duplicated, with psychiatric features commonly observed in both syndromes. How common genetic variants regulate this gene, however, is unknown. In this study, we found that RAI1 mRNA expression in Chinese prefrontal and temporal cortex correlate with genotypes of common single nucleotide polymorphisms (SNPs) located in the RAI1 5′-upstream region. Using genotype imputation, “R2-Δ2” analysis, and data from the RegulomeDB database, we identified SNPs rs4925102 and rs9907986 as possible regulatory variants, accounting for approximately 30–40% of the variance in RAI1 mRNA expression in both brain regions. Specifically, rs4925102 and rs9907986 are predicted to disrupt the binding of retinoic acid RXR-RAR receptors and the transcription factor DEAF1 (Deformed epidermal autoregulatory factor-1), respectively. Consistent with these predictions, we observed binding of RXRα and RARα to the predicted RAI1 target in chromatin immunoprecipitation assays. Retinoic acid is crucial for early development of the central neural system, and DEAF1 is associated with intellectual disability. The observation that a significant portion of RAI1 mRNA expression is genetically controlled raises the possibility that common RAI1 5′-region regulatory variants contribute more generally to psychiatric disorders. PMID:26743651

  3. Low Background Micromegas in CAST

    DEFF Research Database (Denmark)

    Garza, J G; Aune, S.; Aznar, F.

    2014-01-01

    Solar axions could be converted into x-rays inside the strong magnetic field of an axion helioscope, triggering the detection of this elusive particle. Low background x-ray detectors are an essential component for the sensitivity of these searches. We report on the latest developments of the Micr...

  4. Genetic Basis of Spectral Tuning in the Violet-Sensitive Visual Pigment of African Clawed Frog, Xenopus laevis

    Science.gov (United States)

    Takahashi, Yusuke; Yokoyama, Shozo

    2005-01-01

    Ultraviolet (UV) and violet vision in vertebrates is mediated by UV and violet visual pigments that absorb light maximally (λmax) at ∼360 and 390–440 nm, respectively. So far, a total of 11 amino acid sites only in transmembrane (TM) helices I–III are known to be involved in the functional differentiation of these short wavelength-sensitive type 1 (SWS1) pigments. Here, we have constructed chimeric pigments between the violet pigment of African clawed frog (Xenopus laevis) and its ancestral UV pigment. The results show that not only are the absorption spectra of these pigments modulated strongly by amino acids in TM I–VII, but also, for unknown reasons, the overall effect of amino acid changes in TM IV–VII on the λmax-shift is abolished. The spectral tuning of the contemporary frog pigment is explained by amino acid replacements F86M, V91I, T93P, V109A, E113D, L116V, and S118T, in which V91I and V109A are previously unknown, increasing the total number of critical amino acid sites that are involved in the spectral tuning of SWS1 pigments in vertebrates to 13. PMID:16079229

  5. Sensitivity Analysis and Calibration of a Rainfall-runoff Model with the Combined Use of EPA-SWMM and Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Del Giudice Giuseppe

    2016-10-01

    Full Text Available An integrated Visual Basic Application interface is described that allows for sensitivity analysis, calibration and routing of hydraulichydrological models. The routine consists in the combination of three freeware tools performing hydrological modelling, hydraulic modelling and calibration. With such an approach, calibration is made possible even if information about sewers geometrical features is incomplete. Model parameters involve storage coefficient, time of concentration, runoff coefficient, initial abstraction and Manning coefficient; literature formulas are considered and manipulated to obtain novel expressions and variation ranges. A sensitivity analysis with a local method is performed to obtain information about collinearity among parameters and a ranking of influence. The least important parameters are given a fixed value, and for the remaining ones calibration is performed by means of a genetic algorithm implemented in GANetXL. Single-event calibration is performed with a selection of six rainfall events, which are chosen so to avoid non-uniform rainfall distribution; results are then successfully validated with a sequence of four events.

  6. Sensitivity Analysis and Calibration of a Rainfall-Runoff Model with the Combined Use of EPA-SWMM and Genetic Algorithm

    Science.gov (United States)

    Del Giudice, Giuseppe; Padulano, Roberta

    2016-10-01

    An integrated Visual Basic Application interface is described that allows for sensitivity analysis, calibration and routing of hydraulichydrological models. The routine consists in the combination of three freeware tools performing hydrological modelling, hydraulic modelling and calibration. With such an approach, calibration is made possible even if information about sewers geometrical features is incomplete. Model parameters involve storage coefficient, time of concentration, runoff coefficient, initial abstraction and Manning coefficient; literature formulas are considered and manipulated to obtain novel expressions and variation ranges. A sensitivity analysis with a local method is performed to obtain information about collinearity among parameters and a ranking of influence. The least important parameters are given a fixed value, and for the remaining ones calibration is performed by means of a genetic algorithm implemented in GANetXL. Single-event calibration is performed with a selection of six rainfall events, which are chosen so to avoid non-uniform rainfall distribution; results are then successfully validated with a sequence of four events.

  7. Genetic algorithm-assisted optimization of nanoporous TiO₂ for low-temperature processable photoanodes of dye-sensitized solar cells.

    Science.gov (United States)

    Kim, Soyoung; Sohn, Kee-Sun; Pyo, Myoungho

    2011-03-14

    Genetic algorithm (GA), a promising optimization process in Heuristics, has proven to be a powerful tool in controlling the nanostructure of low-temperature processable photoanodes in dye-sensitized solar cells (DSSC). For photoanodes that are composed of various sizes of TiO₂ nanoparticles and multiwalled carbon nanotubes in a double-layer configuration, the best composition was determined based on the objective functions of cell efficiency (η) and its variance. The latter function was chosen since TiO₂ dispersions with no organic binders often aggravated the efficiency of reproducibility. From a total of 64,536 cases, 24 different cases (6 samples prepared for each composition) per generation were selected, and their objective functions were compared. GA was effective in the optimization of photoanodes, and resulted in a cell efficiency of 7.3 ± 0.2% with a short circuit current of 13.8 ± 0.4 mA cm(-2), an open circuit voltage of 0.737 ± 0.006 V, and a fill factor of 71.8 ± 0.6% after 3 generations. The η of 7.3 ± 0.2% is the highest value for low-temperature processable dye-sensitized solar cells prepared without further treatment of TiO₂ films to enhance interparticle connections.

  8. Bitter taste study in a sardinian genetic isolate supports the association of phenylthiocarbamide sensitivity to the TAS2R38 bitter receptor gene.

    Science.gov (United States)

    Prodi, D A; Drayna, D; Forabosco, P; Palmas, M A; Maestrale, G B; Piras, D; Pirastu, M; Angius, A

    2004-10-01

    Recently, a major locus on chromosome 7q was found in association with the taste sensitivity to phenylthiocarbamide (PTC) in humans. This region contains the TAS2R38 gene that encodes a member of the TAS2R bitter taste receptor family. Three SNPs within this gene demonstrated a strong association with taster status in Utah families and in an additional sample of 85 unrelated individuals. We studied a small isolated village in eastern Sardinia and carried out a genome-wide scan to map the genetic basis of PTC perception in this population. We performed both qualitative and quantitative PTC-taste linkage analysis. Qualitative analysis was carried out by defining a cut-off from the bimodal distribution of the trait and classifying subjects as tasters and non-tasters (75 and 25%, respectively). Linkage analysis on 131 subjects belonging to a unique large multi-generation pedigree comprising 239 subjects confirmed significant evidence for linkage at 7q35 also in our population. Haplotype analyses of the three SNPs inside the PTC gene allowed us to identify only two haplotypes that were associated with the non-taster phenotype (80% AVI homozygous) and to taster phenotype (40% PAV homozygous and 56% PAV/AVI heterozygous). Sex, age and haplotype effect explained 77.2 % of the total variance in PTC sensitivity.

  9. Genetic reconstitution of the human Adenovirus type 2 temperature-sensitive 1 mutant defective in endosomal escape

    Directory of Open Access Journals (Sweden)

    Gastaldelli Michele

    2009-10-01

    genetic analyses of distinct host requirements for Ad endocytosis and escape from endosomes.

  10. Quantifying single nucleotide variant detection sensitivity in exome sequencing

    OpenAIRE

    Meynert, Alison; Bicknell, Louise; Jackson, Andrew; Taylor, Martin S.

    2013-01-01

    BACKGROUND: The targeted capture and sequencing of genomic regions has rapidlydemonstrated its utility in genetic studies. Inherent in this technology isconsiderable heterogeneity of target coverage and this is expected tosystematically impact our sensitivity to detect genuine polymorphisms. To fullyinterpret the polymorphisms identified in a genetic study it is often essentialto both detect polymorphisms and to understand where and with what probabilityreal polymorphisms may have been missed...

  11. Genetic background (DDD/Sgn versus C57BL/6J) strongly influences postnatal growth of male mice carrying the Ay allele at the agouti locus: identification of quantitative trait loci associated with diabetes and body weight loss

    Science.gov (United States)

    2013-01-01

    Background Mice carrying the Ay allele at the agouti locus become obese and are heavier than their non-Ay littermates. However, this does not hold true for the genetic background of the DDD mouse strain. At 22 weeks of age, DDD.Cg-Ay females are heavier than DDD females, whereas DDD.Cg-Ay males are lighter than DDD males. This study aimed to determine the possible cause and identify the genes responsible for the lower body weight of DDD.Cg-Ay males. Results Growth curves of DDD.Cg-Ay mice were analyzed and compared with those of B6.Cg-Ay mice from 5 to 25 weeks. In DDD.Cg-Ay males, body weight gain stopped between 16 and 17 weeks and the body weight gradually decreased; thus, the lower body weight was a consequence of body weight loss. Quantitative trait locus (QTL) mapping was performed in backcrossed (BC) males of DDD × (B6 × DDD.Cg-Ay) F1-Ay mice. For the body weight at 25 weeks, significant QTLs were identified on chromosomes 1 and 4. The DDD allele was associated with a lower body weight at both loci. In particular, the QTL on chromosome 4 interacted with the Ay allele. Furthermore, suggestive QTLs for plasma glucose and high molecular weight adiponectin levels were coincidentally mapped to chromosome 4. The DDD allele was associated with increased glucose and decreased adiponectin levels. When the body weight at 25 weeks and plasma glucose levels were considered as dependent and independent variables, respectively, BC Ay males were classified into two groups according to statistical analysis using the partition method. Mice of one group had significantly higher glucose and lower adiponectin levels than those of the other group and exhibited body weight loss as observed with DDD-Ay males. Conclusions The lower body weight of DDD.Cg-Ay male mice was a consequence of body weight loss. Diabetes mellitus has been suggested to be a possible contributory factor causing body weight loss. The QTL on distal chromosome 4 contained the major responsible genes

  12. Aminoglycoside resistance pattern and genetic background in multi-drug resistant acinetobacter baumannii%多药耐药鲍氏不动杆菌氨基糖苷类药物耐药遗传学背景研究

    Institute of Scientific and Technical Information of China (English)

    陈月馨; 周惠芬; 钟育红; 吴润香; 黄烈; 陈智睿

    2011-01-01

    OBJECTIVE To investigate the background of the Aminoglycoside resistance pattern and genetic type in multidrug-resistant Acinetobacter baumannii (MDR-ABA). METHODS From Apr 2009 to Aug 2009, twenty MDRABA strains were isolated from The Third Affiliated Hospital of Sun Yat-sen University. Drug susceptibility test to 10 kinds of antimicrobial agents was detected by K-B disk diffusion tests. Then, resistant genes and genetic markers were analyzed by PCR and verified by DNA sequencing, including 8 kinds of aminoglycoside modifying enzyme genes(aac(3)- Ⅰ ,aac(3)- Ⅱ ,aac(6′)- Ⅰ ad,aac(6′)- Ⅰ b,aac(6′)- Ⅱ ,ant(3″)- Ⅰ ,ant(2″)- Ⅰ , aph(3′)- Ⅰ ),and 6 kinds of 16S rRNA methylase genes (rmtA, rmtB, rmtC, rmtD, armA, npmA). RESULTS A total of 4 kinds of aminoglycoside modifying enzyme genes of MDR-ABA were detected, including aac(3)-Ⅰ , aac(6′)-Ⅰ b, ant (3″)- Ⅰ , aph(3′)- Ⅰ , and 6 kinds of 16S rRNA methylase genes in twenty MDR-ABA strains were not detected.CONCLUSIONS There is a very high positive rate of aminoglycoside modifying enzyme genes in MDR-ABA isolated from inpatients; The aminoglycosides-resistant MDR-ABA is mainly related to aminoglycoside modifying enzyme genes; The mobile genetic element is the main factor for MDR-ABA to acquire aminoglycoside modifying enzyme genes.%目的 了解临床分离的多药耐药鲍氏不动杆菌(MDR-ABA)氨基糖苷类药物耐药遗传学背景.方法 从2009年4-8月中山大学附属第三医院住院患者中分离20株MDR-ABA,用K-B法测定鲍氏不动杆菌对10种抗菌药物的敏感性,采用PCR及序列分析的方法分析氨基糖苷类修饰酶基因.结果 20株MDR-ABA检出aac(3)-Ⅰ、aac(6′)-Ⅰb、ant(3′)-Ⅰ、aph(3′)-Ⅰ4种基因阳性,6种16S rRNA甲基化酶基因未检出.结论 临床分离的MDR-ABA中氨基糖苷类修饰酶基因阳性率较高,MDR-ABA氨基糖苷类抗菌药物耐药主要与氨基糖苷类修饰酶基因有关;通过可移动遗传元

  13. Genes involved in sex pheromone discrimination in Drosophila melanogaster and their background-dependent effect.

    Directory of Open Access Journals (Sweden)

    Benjamin Houot

    Full Text Available Mate choice is based on the comparison of the sensory quality of potential mating partners, and sex pheromones play an important role in this process. In Drosophila melanogaster, contact pheromones differ between male and female in their content and in their effects on male courtship, both inhibitory and stimulatory. To investigate the genetic basis of sex pheromone discrimination, we experimentally selected males showing either a higher or lower ability to discriminate sex pheromones over 20 generations. This experimental selection was carried out in parallel on two different genetic backgrounds: wild-type and desat1 mutant, in which parental males showed high and low sex pheromone discrimination ability respectively. Male perception of male and female pheromones was separately affected during the process of selection. A comparison of transcriptomic activity between high and low discrimination lines revealed genes not only that varied according to the starting genetic background, but varied reciprocally. Mutants in two of these genes, Shaker and quick-to-court, were capable of producing similar effects on discrimination on their own, in some instances mimicking the selected lines, in others not. This suggests that discrimination of sex pheromones depends on genes whose activity is sensitive to genetic context and provides a rare, genetically defined example of the phenomenon known as "allele flips," in which interactions have reciprocal effects on different genetic backgrounds.

  14. Isolation of a hop-sensitive variant of Lactobacillus lindneri and identification of genetic markers for beer spoilage ability of lactic acid bacteria.

    Science.gov (United States)

    Suzuki, Koji; Iijima, Kazumaru; Ozaki, Kazutaka; Yamashita, Hiroshi

    2005-09-01

    We have isolated a hop-sensitive variant of the beer spoilage bacterium Lactobacillus lindneri DSM 20692. The variant lost a plasmid carrying two contiguous open reading frames (ORF s) designated horB(L) and horC(L) that encode a putative regulator and multidrug transporter presumably belonging to the resistance-nodulation-cell division superfamily. The loss of hop resistance ability occurred with the loss of resistance to other drugs, including ethidium bromide, novobiocin, and cetyltrimethylammonium bromide. PCR and Southern blot analysis using 51 beer spoilage strains of various species of lactic acid bacteria (LAB) revealed that 49 strains possessed homologs of horB and horC. No false-positive results have been observed for nonspoilage LAB or frequently encountered brewery isolates. These features are superior to those of horA and ORF 5, previously reported genetic markers for determining the beer spoilage ability of LAB. It was further shown that the combined use of horB/horC and horA is able to detect all 51 beer spoilage strains examined in this study. Furthermore sequence comparison of horB and horC homologs identified in four different beer spoilage species indicates these homologs are 96.6 to 99.5% identical, which is not typical of distinct species. The wide and exclusive distribution of horB and horC homologs among beer spoilage LAB and their sequence identities suggest that the hop resistance ability of beer spoilage LAB has been acquired through horizontal gene transfer. These insights provide a foundation for applying trans-species genetic markers to differentiating beer spoilage LAB including previously unencountered species.

  15. Sensitivity Analysis of the MGMT-STP27 Model and Impact of Genetic and Epigenetic Context to Predict the MGMT Methylation Status in Gliomas and Other Tumors.

    Science.gov (United States)

    Bady, Pierre; Delorenzi, Mauro; Hegi, Monika E

    2016-05-01

    The methylation status of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene is an important predictive biomarker for benefit from alkylating agent therapy in glioblastoma. Our model MGMT-STP27 allows prediction of the methylation status of the MGMT promoter using data from the Illumina's Human Methylation BeadChips (HM-27K and HM-450K) that is publically available for many cancer data sets. Here, we investigate the impact of the context of genetic and epigenetic alterations and tumor type on the classification and report on technical aspects, such as robustness of cutoff definition and preprocessing of the data. The association between gene copy number variation, predicted MGMT methylation, and MGMT expression revealed a gene dosage effect on MGMT expression in lower grade glioma (World Health Organization grade II/III) that in contrast to glioblastoma usually carry two copies of chromosome 10 on which MGMT resides (10q26.3). This implies some MGMT expression, potentially conferring residual repair function blunting the therapeutic effect of alkylating agents. A sensitivity analyses corroborated the performance of the original cutoff for various optimization criteria and for most data preprocessing methods. Finally, we propose an R package mgmtstp27 that allows prediction of the methylation status of the MGMT promoter and calculation of appropriate confidence and/or prediction intervals. Overall, MGMT-STP27 is a robust model for MGMT classification that is independent of tumor type and is adapted for single sample prediction.

  16. Individual radiation sensitivity (gender, age, genetic disposition). Consequences for radiation protection; Individuelle Strahlenempfindlichkeit (Geschlecht-Alter-genetische Disposition). Konsequenzen fuer den Strahlenschutz?

    Energy Technology Data Exchange (ETDEWEB)

    Streffer, C. [Universitaetsklinikum Essen (Germany)

    2013-07-01

    The effects of ionising radiation on human health is influenced by a number of physiological and molecular biological factors. This is also valid for the causation of stochastic radiation effects especially the causation of cancer. Several epidemiological studies have resulted with respect to the total rate of solid cancers that women are more sensitive than men by a factor of 1.6 to 2.0. For leukaemia this is not the case. The largest studies come from the investigations on the survivors of the atomic bombs in Hiroshima and Nagasaki. But also studies on the population of the Techa River (Southeast Urals) yield such data. The analyses of single cancer localizations come to different results with respect to the dependence on the sex. Secondary cancers after radiotherapy for cancer treatment show also higher rates in women than in men. A similar situation is observed with respect to the dependence of cancer rate on age. The total rate of solid cancers is highest with children and decreases with increasing age. The effects are very different again with single cancer localizations. An especially strong age dependence was observed for thyroid cancer. Increasingly individuals have been found who are especially radiosensitive on the basis of their genetic disposition also with respect to the causation of cancer. Mechanisms and possibilities to trace these individuals are discussed. It is also discussed whether and to which extent these data should have consequences for the practical radiological protection. (orig.)

  17. Molecular cytogenetic characterization of canine histiocytic sarcoma: A spontaneous model for human histiocytic cancer identifies deletion of tumor suppressor genes and highlights influence of genetic background on tumor behavior

    Directory of Open Access Journals (Sweden)

    Abadie Jerome

    2011-05-01

    Full Text Available Abstract Background Histiocytic malignancies in both humans and dogs are rare and poorly understood. While canine histiocytic sarcoma (HS is uncommon in the general domestic dog population, there is a strikingly high incidence in a subset of breeds, suggesting heritable predisposition. Molecular cytogenetic profiling of canine HS in these breeds would serve to reveal recurrent DNA copy number aberrations (CNAs that are breed and/or tumor associated, as well as defining those shared with human HS. This process would identify evolutionarily conserved cytogenetic changes to highlight regions of particular importance to HS biology. Methods Using genome wide array comparative genomic hybridization we assessed CNAs in 104 spontaneously occurring HS from two breeds of dog exhibiting a particularly elevated incidence of this tumor, the Bernese Mountain Dog and Flat-Coated Retriever. Recurrent CNAs were evaluated further by multicolor fluorescence in situ hybridization and loss of heterozygosity analyses. Statistical analyses were performed to identify CNAs associated with tumor location and breed. Results Almost all recurrent CNAs identified in this study were shared between the two breeds, suggesting that they are associated more with the cancer phenotype than with breed. A subset of recurrent genomic imbalances suggested involvement of known cancer associated genes in HS pathogenesis, including deletions of the tumor suppressor genes CDKN2A/B, RB1 and PTEN. A small number of aberrations were unique to each breed, implying that they may contribute to the major differences in tumor location evident in these two breeds. The most highly recurrent canine CNAs revealed in this study are evolutionarily conserved with those reported in human histiocytic proliferations, suggesting that human and dog HS share a conserved pathogenesis. Conclusions The breed associated clinical features and DNA copy number aberrations exhibited by canine HS offer a valuable model

  18. Genetic background (DDD/Sgn versus C57BL/6J) strongly influences postnatal growth of male mice carrying the A(y) allele at the agouti locus: identification of quantitative trait loci associated with diabetes and body weight loss.

    Science.gov (United States)

    Suto, Jun-ichi; Satou, Kunio

    2013-05-04

    Mice carrying the A(y) allele at the agouti locus become obese and are heavier than their non-A(y) littermates. However, this does not hold true for the genetic background of the DDD mouse strain. At 22 weeks of age, DDD.Cg-A(y) females are heavier than DDD females, whereas DDD.Cg-A(y) males are lighter than DDD males. This study aimed to determine the possible cause and identify the genes responsible for the lower body weight of DDD.Cg-A(y) males. Growth curves of DDD.Cg-A(y) mice were analyzed and compared with those of B6.Cg-A(y) mice from 5 to 25 weeks. In DDD.Cg-A(y) males, body weight gain stopped between 16 and 17 weeks and the body weight gradually decreased; thus, the lower body weight was a consequence of body weight loss. Quantitative trait locus (QTL) mapping was performed in backcrossed (BC) males of DDD × (B6 × DDD.Cg-A(y)) F(1)-A(y) mice. For the body weight at 25 weeks, significant QTLs were identified on chromosomes 1 and 4. The DDD allele was associated with a lower body weight at both loci. In particular, the QTL on chromosome 4 interacted with the A(y) allele. Furthermore, suggestive QTLs for plasma glucose and high molecular weight adiponectin levels were coincidentally mapped to chromosome 4. The DDD allele was associated with increased glucose and decreased adiponectin levels. When the body weight at 25 weeks and plasma glucose levels were considered as dependent and independent variables, respectively, BC A(y) males were classified into two groups according to statistical analysis using the partition method. Mice of one group had significantly higher glucose and lower adiponectin levels than those of the other group and exhibited body weight loss as observed with DDD-A(y) males. The lower body weight of DDD.Cg-A(y) male mice was a consequence of body weight loss. Diabetes mellitus has been suggested to be a possible contributory factor causing body weight loss. The QTL on distal chromosome 4 contained the major responsible genes. This QTL

  19. Cigarettes, genetic background, and menopausal timing: the presence of single nucleotide polymorphisms in cytochrome P450 genes is associated with increased risk of natural menopause in European-American smokers.

    Science.gov (United States)

    Butts, Samantha F; Sammel, Mary D; Greer, Christine; Rebbeck, Timothy R; Boorman, David W; Freeman, Ellen W

    2014-07-01

    This study aims to evaluate associations between variations in genes involved in the metabolism of environmental chemicals and steroid hormones and risk of menopause in smokers. Survival analysis was performed on 410 eligible participants from the Penn Ovarian Aging study (ongoing for 14 years), a cohort study of late-reproductive-age women. Single nucleotide polymorphisms at the following loci were studied: COMT Val158Met, CYP1B1*4 Asn452Ser, CYP1B1*3 Leu432Val, and CYP3A4*1B. Significant interactions between smoking and single nucleotide polymorphisms were observed in European-American carriers of CYP3A4*1B and CYP1B1*3, supporting a greater risk of menopause entry compared with those not carrying these alleles. Among CYP1B1*3 carriers, smokers had a greater risk of menopause entry than nonsmokers (adjusted hazard ratio [HR], 2.26; 95% CI, 1.4-3.67; median time to menopause, 10.42 and 11.07 y, respectively). No association between smoking and menopause was identified in CYP1B1 wild types. Among CYP3A4*1B carriers, smokers were at greater risk for menopause entry than nonsmokers (adjusted HR, 15.1; 95% CI, 3.31-69.2; median time to menopause, 11.36 and 13.91 y, respectively). Risk of menopause entry in CYP3A4 wild types who smoked was far lower (adjusted HR, 1.59; 95% CI, 1.03-2.44). Heavily smoking CYP1B1*3 carriers (adjusted HR, 3.0; 95% CI, 1.54-5.84; median time to menopause, 10.41 y) and heavily smoking CYP3A4*1B carriers (adjusted HR, 17.79; 95% CI, 3.21-98.65; median time to menopause, 5.09 y) had the greatest risk of menopause entry. Our finding that the risk of menopause entry in European-American smokers varies depending on genetic background represents a novel gene-environment interaction in reproductive aging.

  20. Background simulations and shielding calculations

    Science.gov (United States)

    Kudryavtsev, Vitaly A.

    2011-04-01

    Key improvements in the sensitivity of the underground particle astrophysics experiments can only be achieved if the radiation causing background events in detectors is well understood and proper measures are taken to suppress it. The background radiation arising from radioactivity and cosmic-ray muons is discussed here together with the methods of its suppression. Different shielding designs are considered to attenuate gamma-rays and neutrons coming from radioactivity in rock and lab walls. Purity of materials used in detector construction is analysed and the background event rates due to the presence of radioactive isotopes in detector components are discussed. Event rates in detectors caused by muon-induced neutrons with and without active veto systems are presented leading to the requirements for the depth of an underground laboratory and the efficiency of the veto system.

  1. Background sources at PEP

    Energy Technology Data Exchange (ETDEWEB)

    Lynch, H.; Schwitters, R.F.; Toner, W.T.

    1988-01-01

    Important sources of background for PEP experiments are studied. Background particles originate from high-energy electrons and positrons which have been lost from stable orbits, ..gamma..-rays emitted by the primary beams through bremsstrahlung in the residual gas, and synchrotron radiation x-rays. The effect of these processes on the beam lifetime are calculated and estimates of background rates at the interaction region are given. Recommendations for the PEP design, aimed at minimizing background are presented. 7 figs., 4 tabs.

  2. Building Background Knowledge

    Science.gov (United States)

    Neuman, Susan B.; Kaefer, Tanya; Pinkham, Ashley

    2014-01-01

    This article make a case for the importance of background knowledge in children's comprehension. It suggests that differences in background knowledge may account for differences in understanding text for low- and middle-income children. It then describes strategies for building background knowledge in the age of common core standards.

  3. Genetic Polymorphisms and Phenotypic Profiles of Sulfadiazine-Resistant and Sensitive Toxoplasma gondii Isolates Obtained from Newborns with Congenital Toxoplasmosis in Minas Gerais, Brazil

    Science.gov (United States)

    Silva, Letícia Azevedo; Reis-Cunha, João Luís; Bartholomeu, Daniella Castanheira; Vítor, Ricardo Wagner Almeida

    2017-01-01

    Background Previous Toxoplasma gondii studies revealed that mutations in the dhps (dihydropteroate synthase) gene are associated with resistance to sulfonamides. Although Brazilian strains are genotypically different, very limited data are available regarding the susceptibility of strains obtained from human to sulfonamides. The aim of this study was to evaluate the efficacy of sulfadiazine (SDZ) against Brazilian isolates of T. gondii and verify whether isolates present polymorphisms in the dhps gene. We also investigated whether the virulence-phenotype and/or genotype were associated with the profile of susceptibility to SDZ. Methods Five T. gondii isolates obtained from newborns with congenital toxoplasmosis were used to verify susceptibility. Mice were infected with 104 tachyzoites and orally treated with different doses of SDZ. The mortality curve was evaluated by the Log-rank test. The presence of polymorphisms in the dhps gene was verified using sequencing. A descriptive analysis for 11 Brazilian isolates was used to assess the association between susceptibility, genotype, and virulence-phenotype. Results Statistical analysis showed that TgCTBr03, 07, 08, and 16 isolates were susceptible to SDZ, whereas TgCTBr11 isolate presented a profile of resistance to SDZ. Nineteen polymorphisms were identified in dhps exons. Seven polymorphisms corresponded to non-synonymous mutations, with four being new mutations, described for the first time in this study. No association was found between the profile of susceptibility and the virulence-phenotype or genotype of the parasite. Conclusions There is a high variability in the susceptibilities of Brazilian T. gondii strains to SDZ, with evidence of drug resistance. Despite the large number of polymorphisms identified, the profile of susceptibility to SDZ was not associated with any of the dhps variants identified in this study. Other genetic factors, not yet determined, may be associated with the resistance to SDZ; thus

  4. The Cosmic Infrared Background Experiment

    CERN Document Server

    Bock, J; Cooray, A R; Kawada, M; Keating, B; Lange, A; Lee, D H; Matsumoto, T; Matsuura, S; Pak, S; Renbarger, T; Sullivan, I; Tsumura, K; Wada, T; Watabe, T; Bock, James; Battle, John; Cooray, Asantha; Kawada, Mitsunobu; Keating, Brian; Lange, Andrew; Lee, Dae-Hea; Matsumoto, Toshio; Matsuura, Shuji; Pak, Soojong; Renbarger, Tom; Sullivan, Ian; Tsumura, Kohji; Wada, Takehiko; Watabe, Toyoki

    2006-01-01

    We are developing a rocket-borne instrument (the Cosmic Infrared Background ExpeRiment, or CIBER) to search for signatures of primordial galaxy formation in the cosmic near-infrared extra-galactic background. CIBER consists of a wide-field two-color camera, a low-resolution absolute spectrometer, and a high-resolution narrow-band imaging spectrometer. The cameras will search for spatial fluctuations in the background on angular scales from 7 arcseconds to 2 degrees over a range of angular scales poorly covered by previous experiments. CIBER will determine if the fluctuations reported by the IRTS arise from first-light galaxies or have a local origin. In a short rocket flight CIBER has sensitivity to probe fluctuations 100 times fainter than IRTS/DIRBE. By jointly observing regions of the sky studied by Spitzer and ASTRO-F, CIBER will build a multi-color view of the near-infrared background, accurately assessing the contribution of local (z = 1-3) galaxies to the observed background fluctuations, allowing a de...

  5. Neuropeptide S alters anxiety, but not depression-like behaviour in Flinders Sensitive Line rats: a genetic animal model of depression.

    Science.gov (United States)

    Wegener, Gregers; Finger, Beate C; Elfving, Betina; Keller, Kirsten; Liebenberg, Nico; Fischer, Christina W; Singewald, Nicolas; Slattery, David A; Neumann, Inga D; Mathé, Aleksander A

    2012-04-01

    Neuropeptide S (NPS) and its receptor (NPSR) have been implicated in the mediation of anxiolytic-like behaviour in rodents. However, little knowledge is available regarding the NPS system in depression-related behaviours, and whether NPS also exerts anxiolytic effects in an animal model of psychopathology. Therefore, the aim of this work was to characterize the effects of NPS on depression- and anxiety-related parameters, using male and female rats in a well-validated animal model of depression: the Flinders Sensitive Line (FSL), their controls, the Flinders Resistant Line (FRL), and Sprague-Dawley (SD) rats. We found that FSL showed greater immobility in the forced swim test (FST) than FRL, confirming their phenotype. However, NPS did not affect depression-related behaviour in any rat line. No significant differences in baseline anxiety levels between the FSL and FRL strains were observed, but FSL and FRL rats displayed less anxiety-like behaviour compared to SD rats. NPS decreased anxiety-like behaviour on the elevated plus-maze in all strains. The expression of the NPSR in the amygdala, periventricular hypothalamic nucleus, and hippocampus was equal in all male strains, although a trend towards reduced expression within the amygdala was observed in FSL rats compared to SD rats. In conclusion, NPS had a marked anxiolytic effect in FSL, FRL and SD rats, but did not modify the depression-related behaviour in any strain, in spite of the significant differences in innate level between the strains. These findings suggest that NPS specifically modifies anxiety behaviour but cannot overcome/reverse a genetically mediated depression phenotype.

  6. Cultivation of Intercultural Competence under Background of Sensitivity and Communication Educational Internationalization%教育国际化背景下文化敏感性和文化能力的培养

    Institute of Scientific and Technical Information of China (English)

    王焱

    2011-01-01

    On the basis of the explanation of intercultural sensitivity and the content of cultural competence, the introduction of cultural knowledge teaching to combine language knowledge with pragmatic competence is discussed, so as to overcome cultural conflicts in cultural communication, and the cultivation strategies of intercultural sensitivity and intercultural communication competence are raised.%在阐述文化敏感性和文化能力内涵的基础上,探讨文化教育的引入,在语言学习的过程中,实现语言知识与语用能力的有机结合,克服跨文化交际中的文化缺失与摩擦,研究培养文化敏感性和文化能力的策略。

  7. Neurobiological background of negative symptoms.

    Science.gov (United States)

    Galderisi, Silvana; Merlotti, Eleonora; Mucci, Armida

    2015-10-01

    Studies investigating neurobiological bases of negative symptoms of schizophrenia failed to provide consistent findings, possibly due to the heterogeneity of this psychopathological construct. We tried to review the findings published to date investigating neurobiological abnormalities after reducing the heterogeneity of the negative symptoms construct. The literature in electronic databases as well as citations and major articles are reviewed with respect to the phenomenology, pathology, genetics and neurobiology of schizophrenia. We searched PubMed with the keywords "negative symptoms," "deficit schizophrenia," "persistent negative symptoms," "neurotransmissions," "neuroimaging" and "genetic." Additional articles were identified by manually checking the reference lists of the relevant publications. Publications in English were considered, and unpublished studies, conference abstracts and poster presentations were not included. Structural and functional imaging studies addressed the issue of neurobiological background of negative symptoms from several perspectives (considering them as a unitary construct, focusing on primary and/or persistent negative symptoms and, more recently, clustering them into factors), but produced discrepant findings. The examined studies provided evidence suggesting that even primary and persistent negative symptoms include different psychopathological constructs, probably reflecting the dysfunction of different neurobiological substrates. Furthermore, they suggest that complex alterations in multiple neurotransmitter systems and genetic variants might influence the expression of negative symptoms in schizophrenia. On the whole, the reviewed findings, representing the distillation of a large body of disparate data, suggest that further deconstruction of negative symptomatology into more elementary components is needed to gain insight into underlying neurobiological mechanisms.

  8. Genetic Studies on Photo- and Thermo-Sensitive Genic Male Sterility of Indica Rice%籼型光温敏核不育水稻雄性不育性遗传研究

    Institute of Scientific and Technical Information of China (English)

    邓启云; 盛孝邦; 段美娟; 李新奇

    2001-01-01

    以安农S-1等籼型光温敏核不育系和二九青等不同生态型常规籼稻品种为材料,在长日高温条件下考察分离群体单株的套袋自交结实率,应用极大似然法系统研究了籼型光温敏核雄性不育性的遗传规律,结果表明:a)安农S-1、测64S、衡农S-1和W6154S等不育系的不育性遗传受1对隐性主基因控制,而W7415S的不育性受至少2对隐性主基因控制;b)光温敏不育主基因的表达受微效多基因的修饰,不同不育系的微基因效应有明显差异;c)不同生态型常规籼稻品种中均具有主效恢复基因,同时也存在相应的影响不育性表达效果的遗传背景(其实质就是微效多基因群),而且品种间有较大差异。对光温敏不育系不育起点温度“漂移”机制以及在育种实践中如何选育不育起点温度“缓漂移”的实用光温敏新不育系等问题进行了讨论。%The inheritance of photo- and thermo-sensitive genic male sterility (PTGMS) in rice was studied on the basis of the bagged seed setting rate of segregating populations from the crosses of five indica PTGMS lines and three conventional indica varieties of different ecotypes under long daylength conditions by the Maximum Likelihood method. The results showed that: a) The sterility of Annong S-1, Ce-64S, Hengnong S-1 and W6154S was controlled by one pair of recessive major genes, while that of W7415S was controlled by more than one pair of recessive major genes; b) The expression of sterile major genes was modified by minor genes and the effect of minor genes was varied with PTGMS lines; c)The conventional indica varieties of different ecotypes possessed both the corresponding dominant major gene(s) and the genetic background affecting the expression of male sterility. The genetic background, in fact, was a group of minor genes and there existed a great difference among varieties. Furthermore, the mechanism of drift in critical sterility

  9. The Cosmic Microwave Background

    OpenAIRE

    Silk, Joseph

    2002-01-01

    This set of lectures provides an overview of the basic theory and phenomenology of the cosmic microwave background. Topics include a brief historical review; the physics of temperature and polarization fluctuations; acoustic oscillations of the primordial plasma; the space of inflationary cosmological models; current and potential constraints on these models from the microwave background; and constraints on inflation.

  10. Supersymmetric heterotic string backgrounds

    NARCIS (Netherlands)

    Gran, U.; Papadopoulos, G.; Roest, D.; Cvetič, M.

    2007-01-01

    We present the main features of the solution of the gravitino and dilatino Killing spinor equations derived in hep-th/0510176 and hep-th/0703143 which have led to the classification of geometric types of all type I backgrounds. We then apply these results to the supersymmetric backgrounds of the het

  11. The Athena Background

    Science.gov (United States)

    Piro, Luigi; Lotti, Simone; Macculi, Claudio; Molendi, Silvano; Eraerds, Tanja; Laurent, Philippe

    2015-09-01

    Estimating, reducing and controlling the residual particle background is fundamental for achieving the objectives of several science topics of Athena, in particular those connected with background dominated observations of faint and/or diffuse sources. This requires assessing the particle environment in L2, propagating the various particle components throughout the mirror, spacecraft, and instruments via proper modelling and simulations of various physical processes, implementing design and h/w measures at instrument and mission level to reduce the un-rejected background and identifying proper calibration methods to control the background variations. Likewise, an adequate knowledge of the XRB, made of components that may vary spatially or temporally, is required as well. Here we will review the present status of the background knowledge, and summarize the activities on-going within Athena at various levels.

  12. Nationwide survey of the development of drug resistance in the pediatric field in 2000-2001, 2004, 2007, 2010, and 2012: evaluation of the changes in drug sensitivity of Haemophilus influenzae and patients' background factors.

    Science.gov (United States)

    Shiro, Hiroyuki; Sato, Yoshitake; Toyonaga, Yoshikiyo; Hanaki, Hideaki; Sunakawa, Keisuke

    2015-04-01

    The Drug-Resistant Pathogen Surveillance Group in Pediatric Infectious Disease has conducted surveillance of pediatric patients with respiratory tract infections, meningitis, and sepsis five times (in 2000-2001 [period 1], 2004 [period 2], 2007 [period 3], 2010 [period 4], and 2012 [period 5]). With respect to the clinically isolated Haemophilus influenzae, the drug susceptibility, the frequency of drug-resistant strains, and patients' background factors in each period have already been reported. Here we evaluate trends in the development of drug resistance in H. influenzae, and the relationship between the development of drug resistance and patients' background factors in the aforementioned five periods. H. influenzae derived from pediatric patients with respiratory tract infections that had been previously collected (period 1, 448 isolates; period 2, 376 isolates; period 3, 386 isolates; period 4, 484 isolates; and period 5, 411 isolates) were analyzed. The proportions of ß-lactamase-nonproducing ampicillin (ABPC)-intermediate resistant (BLNAI) strains + β-lactamase-nonproducing ABPC-resistant (BLNAR) strains were 28.8% in period 1, 59.3% in period 2, 61.1% in period 3, 58.1% in period 4, and 63.5% in period 5, showing a rapid increase from period 1 to period 2 followed by an almost constant rate of approximately 60%. The proportion of ß-lactamase-producing ABPC-resistant (BLPAR) strains + ß-lactamase-producing clavulanic acid/amoxicillin-resistant (BLPACR) strains was 4.4% in period 3, which was somewhat low; however, there were no significant changes in the proportions of these strains, which ranged between 6.4% and 8.7% throughout the surveillance period except for period 3. The drugs whose MIC90 values against BLNAR strains were low throughout the surveillance included piperacillin (0.25 μg/mL) and tazobactam/piperacillin (0.125-0.25 μg/mL) in the penicillins; cefditoren and ceftriaxone (0.25-0.5 μg/mL for both) in the cephems; meropenem (0.5-1

  13. Low Background Micromegas in CAST

    CERN Document Server

    Garza, J G; Aznar, F.; Calvet, D.; Castel, J.F.; Christensen, F.E.; Dafni, T.; Davenport, M.; Decker, T.; Ferrer-Ribas, E.; Galán, J.; García, J.A.; Giomataris, I.; Hill, R.M.; Iguaz, F.J.; Irastorza, I.G.; Jakobsen, A.C.; Jourde, D.; Mirallas, H.; Ortega, I.; Papaevangelou, T.; Pivovaroff, M.J.; Ruz, J.; Tomás, A.; Vafeiadis, T.; Vogel, J.K.

    2015-01-01

    Solar axions could be converted into x-rays inside the strong magnetic field of an axion helioscope, triggering the detection of this elusive particle. Low background x-ray detectors are an essential component for the sensitivity of these searches. We report on the latest developments of the Micromegas detectors for the CERN Axion Solar Telescope (CAST), including technological pathfinder activities for the future International Axion Observatory (IAXO). The use of low background techniques and the application of discrimination algorithms based on the high granularity of the readout have led to background levels below 10$^{-6}$ counts/keV/cm$^2$/s, more than a factor 100 lower than the first generation of Micromegas detectors. The best levels achieved at the Canfranc Underground Laboratory (LSC) are as low as 10$^{-7}$ counts/keV/cm$^2$/s, showing good prospects for the application of this technology in IAXO. The current background model, based on underground and surface measurements, is presented, as well as ...

  14. Background illumination and automated perimetry.

    Science.gov (United States)

    Klewin, K M; Radius, R L

    1986-03-01

    Visual field function in the right and left eyes of 31 normal volunteers was evaluated with an automated projection perimeter (OCTOPUS). Serial visual field evaluations were repeated in these same eyes with neutral filters of increasing optical density. We compared the results of threshold determinations with the different neutral filters in place before the examined eye. Significant reduction in threshold sensitivity at several test spots throughout the central 30 degrees visual field was seen with neutral density filters of 0.5 log units or greater. The low level of background illumination of the OCTOPUS perimeter (4.0 apostilbs) may allow relatively minor reduction in light transmission by the ocular media to produce significant changes in the recorded level of threshold sensitivity during visual field evaluation.

  15. The Cosmic Background Explorer Satellite

    Science.gov (United States)

    Mather, J.; Kelsall, T.

    1980-01-01

    The Cosmic Background Explorer (COBE) satellite, planned for launch in 1985, will measure the diffuse infrared and microwave radiation of the universe over the entire wavelength range from a few microns to 1.3 cm. It will include three instruments: a set of microwave isotropy radiometers at 23, 31, 53, and 90 GHz, an interferometer spectrometer from 1 to 100/cm, and a filter photometer from 1 to 300 microns. The COBE satellite is designed to reach the sensitivity limits set by foreground sources such as the interstellar and interplanetary dust, starlight, and galactic synchrotron radiation, so that a diffuse residual radiation may be interpreted unambiguously as extragalactic

  16. Genetic Variation for Thermotolerance in Lettuce Seed Germination Is Associated with Temperature-Sensitive Regulation of ETHYLENE RESPONSE FACTOR1 (ERF1)1[OPEN

    Science.gov (United States)

    O’Brien, Laurel K.; Truco, Maria Jose; Huo, Heqiang; Sideman, Rebecca; Hayes, Ryan; Michelmore, Richard W.

    2016-01-01

    Seeds of most lettuce (Lactuca sativa) cultivars are susceptible to thermoinhibition, or failure to germinate at temperatures above approximately 28°C, creating problems for crop establishment in the field. Identifying genes controlling thermoinhibition would enable the development of cultivars lacking this trait and, therefore, being less sensitive to high temperatures during planting. Seeds of a primitive accession (PI251246) of lettuce exhibited high-temperature germination capacity up to 33°C. Screening a recombinant inbred line population developed from PI215246 and cv Salinas identified a major quantitative trait locus (Htg9.1) from PI251246 associated with the high-temperature germination phenotype. Further genetic analyses discovered a tight linkage of the Htg9.1 phenotype with a specific DNA marker (NM4182) located on a single genomic sequence scaffold. Expression analyses of the 44 genes encoded in this genomic region revealed that only a homolog of Arabidopsis (Arabidopsis thaliana) ETHYLENE RESPONSE FACTOR1 (termed LsERF1) was differentially expressed between PI251246 and cv Salinas seeds imbibed at high temperature (30°C). LsERF1 belongs to a large family of transcription factors associated with the ethylene-signaling pathway. Physiological assays of ethylene synthesis, response, and action in parental and near-isogenic Htg9.1 genotypes strongly implicate LsERF1 as the gene responsible for the Htg9.1 phenotype, consistent with the established role for ethylene in germination thermotolerance of Compositae seeds. Expression analyses of genes associated with the abscisic acid and gibberellin biosynthetic pathways and results of biosynthetic inhibitor and hormone response experiments also support the hypothesis that differential regulation of LsERF1 expression in PI251246 seeds elevates their upper temperature limit for germination through interactions among pathways regulated by these hormones. Our results support a model in which LsERF1 acts through

  17. Genetic Variation for Thermotolerance in Lettuce Seed Germination Is Associated with Temperature-Sensitive Regulation of ETHYLENE RESPONSE FACTOR1 (ERF1).

    Science.gov (United States)

    Yoong, Fei-Yian; O'Brien, Laurel K; Truco, Maria Jose; Huo, Heqiang; Sideman, Rebecca; Hayes, Ryan; Michelmore, Richard W; Bradford, Kent J

    2016-01-01

    Seeds of most lettuce (Lactuca sativa) cultivars are susceptible to thermoinhibition, or failure to germinate at temperatures above approximately 28°C, creating problems for crop establishment in the field. Identifying genes controlling thermoinhibition would enable the development of cultivars lacking this trait and, therefore, being less sensitive to high temperatures during planting. Seeds of a primitive accession (PI251246) of lettuce exhibited high-temperature germination capacity up to 33°C. Screening a recombinant inbred line population developed from PI215246 and cv Salinas identified a major quantitative trait locus (Htg9.1) from PI251246 associated with the high-temperature germination phenotype. Further genetic analyses discovered a tight linkage of the Htg9.1 phenotype with a specific DNA marker (NM4182) located on a single genomic sequence scaffold. Expression analyses of the 44 genes encoded in this genomic region revealed that only a homolog of Arabidopsis (Arabidopsis thaliana) ETHYLENE RESPONSE FACTOR1 (termed LsERF1) was differentially expressed between PI251246 and cv Salinas seeds imbibed at high temperature (30°C). LsERF1 belongs to a large family of transcription factors associated with the ethylene-signaling pathway. Physiological assays of ethylene synthesis, response, and action in parental and near-isogenic Htg9.1 genotypes strongly implicate LsERF1 as the gene responsible for the Htg9.1 phenotype, consistent with the established role for ethylene in germination thermotolerance of Compositae seeds. Expression analyses of genes associated with the abscisic acid and gibberellin biosynthetic pathways and results of biosynthetic inhibitor and hormone response experiments also support the hypothesis that differential regulation of LsERF1 expression in PI251246 seeds elevates their upper temperature limit for germination through interactions among pathways regulated by these hormones. Our results support a model in which LsERF1 acts through

  18. On Background Independence

    CERN Document Server

    Anderson, Edward

    2013-01-01

    This paper concerns what Background Independence itself is (as opposed to some particular physical theory that is background independent). The notions presented mostly arose from a layer-by-layer analysis of the facets of the Problem of Time in Quantum Gravity. Part of this coincides with two relational postulates which are thus identified as classical precursors of two of the facets of the Problem of Time. These are furthemore tied to the forms of each of the GR Hamiltonian and momentum constraints. Other aspects of Background Independence include the algebraic closure of these constraints, expressing physics in terms of beables, foliation independence as implemented by refoliation invariance, the reconstruction of spacetime from space. The final picture is that Background Independence - a philosophically desirable and physically implementable feature for a theory to have - has the facets of the Problem of Time among its consequences. Thus these arise naturally and are problems to be resolved, as opposed to ...

  19. Zambia Country Background Report

    DEFF Research Database (Denmark)

    Hampwaye, Godfrey; Jeppesen, Søren; Kragelund, Peter

    This paper provides background data and general information for the Zambia studies focusing on local food processing sub­‐sector; and the local suppliers to the mines as part of the SAFIC project (Successful African Firms and Institutional Change).......This paper provides background data and general information for the Zambia studies focusing on local food processing sub­‐sector; and the local suppliers to the mines as part of the SAFIC project (Successful African Firms and Institutional Change)....

  20. Riboswitch-based sensor in low optical background

    Science.gov (United States)

    Harbaugh, Svetlana V.; Davidson, Molly E.; Chushak, Yaroslav G.; Kelley-Loughnane, Nancy; Stone, Morley O.

    2008-08-01

    Riboswitches are a type of natural genetic control element that use untranslated sequence in the RNA to recognize and bind to small molecules that regulate expression of that gene. Creation of synthetic riboswitches to novel ligands depends on the ability to screen for analyte binding sensitivity and specificity. In our work, we have coupled a synthetic riboswitch to an optical reporter assay based on fluorescence resonance energy transfer (FRET) between two genetically-coded fluorescent proteins. Specifically, a theophylline-sensitive riboswitch was placed upstream of the Tobacco Etch Virus (TEV) protease coding sequence, and a FRET-based construct, BFP-eGFP or eGFP-REACh, was linked by a peptide encoding the recognition sequence for TEV protease. Cells expressing the riboswitch showed a marked optical difference in fluorescence emission in the presence of theophylline. However, the BFP-eGFP FRET pair posses significant optical background that reduces the sensitivity of a FRET-based assay. To improve the optical assay, we designed a nonfluorescent yellow fluorescent protein (YFP) mutant called REACh (for Resonance Energy-Accepting Chromoprotein) as the FRET acceptor for eGFP. The advantage of using an eGFP-REACh pair is the elimination of acceptor fluorescence which leads to an improved detection of FRET via better signal-to-noise ratio. The EGFP-REACh fusion protein was constructed with the TEV protease cleavage site; thus upon TEV translation, cleavage occurs diminishing REACh quenching and increasing eGFP emission resulting in a 4.5-fold improvement in assay sensitivity.

  1. The Cosmic Infrared Background Experiment

    Science.gov (United States)

    Bock, James; Battle, J.; Cooray, A.; Hristov, V.; Kawada, M.; Keating, B.; Lee, D.; Matsumoto, T.; Matsuura, S.; Nam, U.; Renbarger, T.; Sullivan, I.; Tsumura, K.; Wada, T.; Zemcov, M.

    2009-01-01

    We are developing the Cosmic Infrared Background ExpeRiment (CIBER) to search for signatures of first-light galaxy emission in the extragalactic background. The first generation of stars produce characteristic signatures in the near-infrared extragalactic background, including a redshifted Ly-cutoff feature and a characteristic fluctuation power spectrum, that may be detectable with a specialized instrument. CIBER consists of two wide-field cameras to measure the fluctuation power spectrum, and a low-resolution and a narrow-band spectrometer to measure the absolute background. The cameras will search for fluctuations on angular scales from 7 arcseconds to 2 degrees, where the first-light galaxy spatial power spectrum peaks. The cameras have the necessary combination of sensitivity, wide field of view, spatial resolution, and multiple bands to make a definitive measurement. CIBER will determine if the fluctuations reported by Spitzer arise from first-light galaxies. The cameras observe in a single wide field of view, eliminating systematic errors associated with mosaicing. Two bands are chosen to maximize the first-light signal contrast, at 1.6 um near the expected spectral maximum, and at 1.0 um; the combination is a powerful discriminant against fluctuations arising from local sources. We will observe regions of the sky surveyed by Spitzer and Akari. The low-resolution spectrometer will search for the redshifted Lyman cutoff feature in the 0.7 - 1.8 um spectral region. The narrow-band spectrometer will measure the absolute Zodiacal brightness using the scattered 854.2 nm Ca II Fraunhofer line. The spectrometers will test if reports of a diffuse extragalactic background in the 1 - 2 um band continues into the optical, or is caused by an under estimation of the Zodiacal foreground. We report performance of the assembled and tested instrument as we prepare for a first sounding rocket flight in early 2009. CIBER is funded by the NASA/APRA sub-orbital program.

  2. Exploring String Theory Backgrounds

    CERN Document Server

    Williams, B P

    2004-01-01

    This thesis examines phenomenological and theoretical questions by exploring string theoretic backgrounds. Part I focuses on cosmology. First we propose that the induced metric along a brane moving through a curved bulk may be interpreted as the cosmology of the brane universe, providing a resolution to the apparent cosmological singularity on the brane. We then look at various decay channels of the certain meta-stable de Sitter vacua and show that there exist NS5-brane meditated decays which are much faster than decays to decompactification. Part II discusses a new class of nongeometric vacua in string theory. These backgrounds may be described locally as T2 fibrations. By enlarging the monodromy group of the fiber to include perturbative stringy duality symmetries we are able to explicitly construct nongeometric backgrounds.

  3. Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity.

    Directory of Open Access Journals (Sweden)

    Stephen R Doyle

    2017-07-01

    Full Text Available Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana-exposed to more than a decade of regular ivermectin treatment-have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread.Pooled next generation sequencing (Pool-seq was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR and sub-optimal responder (SOR parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs, with little overlap in putative QTL position and gene content between the two countries. Published candidate ivermectin SOR genes were largely absent in these regions; QTLs differentiating GR and SOR worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. Finally, single worm genotyping demonstrated that geographic isolation and genetic change over time (in the presence of drug exposure had a significantly greater role in shaping genetic diversity than the evolution of SOR.This study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT whereby identical or related molecular pathways but not necessarily individual genes are likely to determine the extent of ivermectin response in different parasite populations. Furthermore, we propose that genetic

  4. Cosmic Tachyon Background Radiation

    CERN Document Server

    Tomaschitz, R

    1999-01-01

    The equilibrium statistical mechanics of a background radiation of superluminal particles is investigated, based on a vectorial wave equation for tachyons of the Proca type. The partition function, the spectral energy density, and the various thermodynamic variables of an ideal Bose gas of tachyons in an open Robertson-Walker cosmology are derived. The negative mass square in the wave equation changes the frequency scaling in the Rayleigh-Jeans law, and there are also significant changes in the low temperature regime as compared to the microwave background, in particular in the caloric and thermal equations of state.

  5. China: Background Notes Series.

    Science.gov (United States)

    Reams, Joanne Reppert

    Concise background information on the People's Republic of China is provided. The publication begins with a profile of the country, outlining the people, geography, economy, and membership in international organizations. The bulk of the document then discusses in more detail China's people, geography, history, government, education, economy, and…

  6. Combination of genetics and spatial modelling highlights the sensitivity of cod (Gadus morhua) population diversity in the North Sea to distributions of fishing

    DEFF Research Database (Denmark)

    Heath, Michael R.; Culling, Mark A.; Crozier, Walter W.

    2014-01-01

    Conserving genetic diversity in animal populations is important for sustaining their ability to respond to environmental change. However, the “between-population” component of genetic diversity (biocomplexity) is threatened in many exploited populations, particularly marine fish, where harvest...... North Sea (Viking) unit by the more widespread (Dogger) unit, and its premature extinction under some spatial patterns of fishing. Fishery catch limits for cod are set at the scale of the whole North Sea without regard to such subpopulation dynamics. Our model offers a method to quantify adjustments...

  7. Basic genetics for dermatologists

    Directory of Open Access Journals (Sweden)

    Muthu Sendhil Kumaran

    2013-01-01

    Full Text Available During the past few decades, advances in the field of molecular genetics have enriched us in understanding the pathogenesis of diseases, their identification, and appropriate therapeutic interventions. In the last 20 years, genetic basis of more than 350 monogenic skin diseases have been elucidated and is counting. The widespread use of molecular genetics as a tool in diagnosis is not practiced routinely due to genetic heterogenicity, limited access and low sensitivity. In this review, we have presented the very basics of genetics so as to enable dermatologists to have working understanding of medical genetics.

  8. Genetic aspects of female reproduction

    NARCIS (Netherlands)

    Collins, J.; Diedrich, K.; Franks, S.; Geraedts, J. P. M.; Jacobs, P. A.; Karges, B.; Kennedy, S.; Marozzi, A.; Regan, L.; Baird, D. T.; Crosignani, P. G.; Devroey, P.; Diczfalusy, E.; Evers, J. L. H.; Fauser, B. C. J. M.; Fraser, L.; Gianaroli, L.; Glasier, A.; Liebaers, I.; Ragni, G.; Sunde, A.; Tarlatzis, B.; Van Steirteghem, A.

    2008-01-01

    BACKGROUND: Sexual reproduction provides the means for preserving genetic identity and in turn, genetic variability may affect the ability to reproduce. This review aims to summarize current research on genetic diagnosis and genetic causes of reproductive disorders.METHODS: Searches were done by sub

  9. The fibroblast growth factor receptor genetic status as a potential predictor of the sensitivity to CH5183284/Debio 1347, a novel selective FGFR inhibitor.

    Science.gov (United States)

    Nakanishi, Yoshito; Akiyama, Nukinori; Tsukaguchi, Toshiyuki; Fujii, Toshihiko; Sakata, Kiyoaki; Sase, Hitoshi; Isobe, Takehito; Morikami, Kenji; Shindoh, Hidetoshi; Mio, Toshiyuki; Ebiike, Hirosato; Taka, Naoki; Aoki, Yuko; Ishii, Nobuya

    2014-11-01

    The FGF receptors (FGFR) are tyrosine kinases that are constitutively activated in a subset of tumors by genetic alterations such as gene amplifications, point mutations, or chromosomal translocations/rearrangements. Recently, small-molecule inhibitors that can inhibit the FGFR family as well as the VEGF receptor (VEGFR) or platelet-derived growth factor receptor (PDGFR) family displayed clinical benefits in cohorts of patients with FGFR genetic alterations. However, to achieve more potent and prolonged activity in such populations, a selective FGFR inhibitor is still needed. Here, we report the identification of CH5183284/Debio 1347, a selective and orally available FGFR1, FGFR2, and FGFR3 inhibitor that has a unique chemical scaffold. By interacting with unique residues in the ATP-binding site of FGFR1, FGFR2, or FGFR3, CH5183284/Debio 1347 selectively inhibits FGFR1, FGFR2, and FGFR3 but does not inhibit kinase insert domain receptor (KDR) or other kinases. Consistent with its high selectivity for FGFR enzymes, CH5183284/Debio 1347 displayed preferential antitumor activity against cancer cells with various FGFR genetic alterations in a panel of 327 cancer cell lines and in xenograft models. Because of its unique binding mode, CH5183284/Debio 1347 can inhibit FGFR2 harboring one type of the gatekeeper mutation that causes resistance to other FGFR inhibitors and block FGFR2 V564F-driven tumor growth. CH5183284/Debio 1347 is under clinical investigation for the treatment of patients harboring FGFR genetic alterations.

  10. The extragalactic IR background

    CERN Document Server

    De Zotti, G; Mazzei, P; Toffolatti, L; Danese, L; De Zotti, G; Franceschini, A; Mazzei, P; Toffolatti, L; Danese, L

    1994-01-01

    Current limits on the intensity of the extragalactic infrared background are consistent with the expected contribution from evolving galaxies. Depending on the behaviour of the star formation rate and of the initial mass function, we can expect that dust extinction during early evolutionary phases ranges from moderate to strong. An example of the latter case may be the ultraluminous galaxy IRAS F10214 + 4724. The remarkable lack of high redshift galaxies in faint optically selected samples may be indirect evidence that strong extinction is common during early phases. Testable implications of different scenarios are discussed; ISO can play a key role in this context. Estimates of possible contributions of galaxies to the background under different assumptions are presented. The COBE/FIRAS limits on deviations from a blackbody spectrum at sub-mm wavelengths already set important constraints on the evolution of the far-IR emission of galaxies and on the density of obscured (``Type 2'') AGNs. A major progress in ...

  11. Background and introduction

    DEFF Research Database (Denmark)

    2012-01-01

    background information to understand the following chapters in this book. Research limitations: The chapter is mainly based on the experience and knowledge of the editors. It does not include original research but provides an introductory overview of the book. Originality/value: This chapter takes a look......Purpose: To explain the purpose and background of this book and introduce the three basic perspectives behind the research presented as well as the structure and editing process of the book. Methodology: The editors shared and discussed individual contributions to this chapter, based on their own...... expertise, the involvement in the process leading to this the book including a number of workshops, and a literature review of the development of their disciplinary fields: Facilities Management (FM), Corporate Real Estate Management (CREM) and Business to Business (B2B) Marketing. Findings: The difference...

  12. The Cosmic Microwave Background

    Directory of Open Access Journals (Sweden)

    Jones Aled

    1998-01-01

    Full Text Available We present a brief review of current theory and observations of the cosmic microwave background (CMB. New predictions for cosmological defect theories and an overview of the inflationary theory are discussed. Recent results from various observations of the anisotropies of the microwave background are described and a summary of the proposed experiments is presented. A new analysis technique based on Bayesian statistics that can be used to reconstruct the underlying sky fluctuations is summarised. Current CMB data is used to set some preliminary constraints on the values of fundamental cosmological parameters $Omega$ and $H_circ$ using the maximum likelihood technique. In addition, secondary anisotropies due to the Sunyaev-Zel'dovich effect are described.

  13. Selected Readings in Genetic Engineering

    Science.gov (United States)

    Mertens, Thomas R.; Robinson, Sandra K.

    1973-01-01

    Describes different sources of readings for understanding issues and concepts of genetic engineering. Broad categories of reading materials are: concerns about genetic engineering; its background; procedures; and social, ethical and legal issues. References are listed. (PS)

  14. Differences in salivary α-amylase levels among women with different taste sensitivities

    OpenAIRE

    Sequeira, Márcia; Rodrigues, Lénia; Costa, Ana R; Pinheiro, C.; Antunes, Célia M.; Lamy, Elsa

    2013-01-01

    Saliva is the main component of taste receptor cells external environment, and consequently it may have a decisive role in taste perception. Taste sensitivity varies among different individuals. Sensitivity to the compound n-6-propylthiouracil (PROP) has been considerably studied and besides the known influence of genetic background, the contribution of perireceptor environment is not completely clear yet. Salivary α-amylase (one of the main proteins of saliva) is involved in carbohydrate dig...

  15. Differences in salivary α-amylase levels among women ith different taste sensitivities.

    OpenAIRE

    Sequeira, Márcia; Rodrigues, Lénia; R Costa, Ana; Antunes, Célia; Pinheiro, Cristina; Lamy, Elsa

    2012-01-01

    Saliva is the main component of taste receptor cells external environment, and consequently it may have a decisive role in taste perception. Taste sensitivity varies among different individuals. Sensitivity to the compound n-6-propylthiouracil (PROP) has been considerably studied and besides the known influence of genetic background, the contribution of perireceptor environment is not completely clear yet. Salivary α-amylase (one of the main proteins of saliva) is involved in carbohydrate dig...

  16. Genetic progression of malignant melanoma.

    Science.gov (United States)

    Tímár, J; Vizkeleti, L; Doma, V; Barbai, T; Rásó, E

    2016-03-01

    Malignant melanoma of the skin is the most aggressive human cancer given that a primary tumor a few millimeters in diameter frequently has full metastatic competence. In view of that, revealing the genetic background of this potential may also help to better understand tumor dissemination in general. Genomic analyses have established the molecular classification of melanoma based on the most frequent driver oncogenic mutations (BRAF, NRAS, KIT) and have also revealed a long list of rare events, including mutations and amplifications as well as genetic microheterogeneity. At the moment, it is unclear whether any of these rare events have role in the metastasis initiation process since the major drivers do not have such a role. During lymphatic and hematogenous dissemination, the clonal selection process is evidently reflected by differences in oncogenic drivers in the metastases versus the primary tumor. Clonal selection is also evident during lymphatic progression, though the genetic background of this immunoselection is less clear. Genomic analyses of metastases identified further genetic alterations, some of which may correspond to metastasis maintenance genes. The natural genetic progression of melanoma can be modified by targeted (BRAF or MEK inhibitor) or immunotherapies. Some of the rare events in primary tumors may result in primary resistance, while further new genetic lesions develop during the acquired resistance to both targeted and immunotherapies. Only a few genetic lesions of the primary tumor are constant during natural or therapy-modulated progression. EGFR4 and NMDAR2 mutations, MITF and MET amplifications and PTEN loss can be considered as metastasis drivers. Furthermore, BRAF and MITF amplifications as well as PTEN loss are also responsible for resistance to targeted therapies, whereas NRAS mutation is the only founder genetic lesion showing any association with sensitivity to immunotherapies. Unfortunately, there are hardly any data on the

  17. Human longevity: Genetics or Lifestyle? It takes two to tango.

    Science.gov (United States)

    Passarino, Giuseppe; De Rango, Francesco; Montesanto, Alberto

    2016-01-01

    Healthy aging and longevity in humans are modulated by a lucky combination of genetic and non-genetic factors. Family studies demonstrated that about 25 % of the variation in human longevity is due to genetic factors. The search for genetic and molecular basis of aging has led to the identification of genes correlated with the maintenance of the cell and of its basic metabolism as the main genetic factors affecting the individual variation of the aging phenotype. In addition, studies on calorie restriction and on the variability of genes associated with nutrient-sensing signaling, have shown that ipocaloric diet and/or a genetically efficient metabolism of nutrients, can modulate lifespan by promoting an efficient maintenance of the cell and of the organism. Recently, epigenetic studies have shown that epigenetic modifications, modulated by both genetic background and lifestyle, are very sensitive to the aging process and can either be a biomarker of the quality of aging or influence the rate and the quality of aging. On the whole, current studies are showing that interventions modulating the interaction between genetic background and environment is essential to determine the individual chance to attain longevity.

  18. Malaysia; Background Paper

    OpenAIRE

    International Monetary Fund

    1996-01-01

    This Background Paper on Malaysia examines developments and trends in the labor market since the mid-1980s. The paper describes the changes in the employment structure and the labor force. It reviews wages and productivity trends and their effects on unit labor cost. The paper highlights that Malaysia’s rapid growth, sustained since 1987, has had a major impact on the labor market. The paper outlines the major policy measures to address the labor constraints. It also analyzes Malaysia’s r...

  19. Family Background and Entrepreneurship

    DEFF Research Database (Denmark)

    Lindquist, Matthew J.; Sol, Joeri; Van Praag, Mirjam

    Vast amounts of money are currently being spent on policies aimed at promoting entrepreneurship. The success of such policies, however, rests in part on the assumption that individuals are not ‘born entrepreneurs’. In this paper, we assess the importance of family background and neighborhood...... treatment within families by gender and birth order does little to further increase our estimates of the importance of family-wide factors. We then go on to show that neighborhood effects, sibling peer effects, and parental income and education explain very little of these correlations. Parental...

  20. Ultraviolet Background Radiation (Preprint)

    Science.gov (United States)

    1991-03-01

    importance is that the sky may be truly outstandingly black in the far ultraviolet, offering a "dark site " that is unprecedented in astronomy...Estimated spectral energy distribution of the night-sky background near the zenith at an excellent ground-based site on a moonless night and in a...1977. Ap. J. Suppl. 33:451 31. Henry, R. C. 1981. Ap. J. Lett. 244: L69 32. Henry, R. C. 1981. 16th Rencontre de Moriond, ed. J. Tran Thanh Van, p

  1. Family Background and Entrepreneurship

    DEFF Research Database (Denmark)

    Lindquist, Matthew J.; Sol, Joeri; Van Praag, Mirjam

    Vast amounts of money are currently being spent on policies aimed at promoting entrepreneurship. The success of such policies, however, rests in part on the assumption that individuals are not ‘born entrepreneurs’. In this paper, we assess the importance of family background and neighborhood...... treatment within families by gender and birth order does little to further increase our estimates of the importance of family-wide factors. We then go on to show that neighborhood effects, sibling peer effects, and parental income and education explain very little of these correlations. Parental...

  2. Salt sensitivity correlates positively with insulin sensitivity in healthy volunteers

    NARCIS (Netherlands)

    ter Maaten, JC; Voordouw, JJ; Bakker, SJL; Gans, ROB

    1999-01-01

    Background The aim of the study was to assess the relationship between insulin sensitivity and salt sensitivity in healthy subjects who display a wide range of insulin sensitivity. As a secondary objective, we assessed the relationship between salt sensitivity and the other characteristics of the in

  3. Time course of cytokine upregulation in the lacrimal gland and presence of autoantibodies in a predisposed mouse model of Sjögren's Syndrome: the influence of sex hormones and genetic background.

    Science.gov (United States)

    Czerwinski, Stefanie; Mostafa, Safinaz; Rowan, Vanessa Seamon; Azzarolo, Ana Maria

    2014-11-01

    Sjögren's Syndrome (SS) is a chronic, inflammatory autoimmune disease characterized by lacrimal gland lymphocytic infiltration and epithelial cell death, as well as by the presence of serum autoantibodies. Although the symptoms of this syndrome are well characterized, patients are not diagnosed until 5-10 years into disease progression; furthermore, the early series of events leading to the initiation of SS are not well understood. In order to better understand the early events of the disease, we have been using ovariectomized (OVX) NOD.B10.H2(b) mice as a genetically predisposed model of SS. Previously, we have shown that removal of ovarian hormones through ovariectomy accelerated the symptoms of this disease, and in early events of SS in the lacrimal glands, lymphocytic infiltration preceded acinar cell apoptosis. To further elucidate the earlier events of this disease in the SS animal model, we investigated the expression and concentration of pro-inflammatory cytokines in the lacrimal glands as well as the presence of autoantibodies in both lacrimal glands and serum. Six weeks old NOD.B10.H2(b) and C57BL/10 control mice were either sham-operated, OVX, OVX and treated with 17β-estradiol (E2), or OVX and treated with dihydrotestosterone (DHT). Lacrimal glands were collected at 3, 7, 21, and 30 days after surgery and analyzed for cytokines IL-1β, TNF-α, IFN-γ, IL-10, and IL-4 gene expression by using quantitative RT-PCR and for cytokine levels using ELISA. Furthermore, anti-Ro/SSA and anti-La/SSB autoantibodies were measured in the serum and lacrimal glands supernatants using ELISA. The results of this study showed that OVX caused a significant increase in the expression and levels of the cytokines IL-1β, TNF-α, and IL-4 in the lacrimal glands of the NOD.B10.H2(b) mice starting at 3 days after OVX, while a significant increase of IL-10 gene expression and levels was observed only at later experimental time points. A small but significant increase in the

  4. 青少年抑郁情绪的行为遗传学研究%The Genetic and Environmental Influence on Adolescent Depressive Symptoms:A Genetic Sensitive Study

    Institute of Scientific and Technical Information of China (English)

    侯金芹; 陈祉妍; 李新影; 杨小冬; 张建新

    2012-01-01

    Epidemiological and developmental studies showed that one of the obvious phenomena during adolescence is a marked increase in depressive symptoms. Behavioral genetic studies found that shared environmental influences account for the majority of the variance for children's symptoms while genetic factors are substantial for adolescent depressive symptoms. However, whether the results of behavioral genetic studies from Westerncountries can be generalized to adolescents in China with a collectivism culture remains unexplored. First, prevalence of depression varies dramatically across cultures with a lower rate in China than in other countries. Second, factors that are associated with depressive symptoms and the extent to which these factors are consequential for adolescents' mood are also different across cultures. Existing evidences showed that the quality of family relationships and grades in school had significantly stronger associations with depressive symptoms among Chinese youths than among U.S. youths. Third, genes that contribute to depressive symptoms have different frequencies in different races. Moreover, culture may moderate the expression of genes. Therefore, the first objective of the study was to examine the heritability of adolescent depressive symptoms for boys and girls in China, respectively.Results from the family study, the adoption study and the twin study suggest that adolescent depressive symptoms are heritable (range 15-80%). Moreover, empirical work showed that the relative contributions of genetic and environmental influences to depressive symptoms vary as a function of age. The second objective of the study was to extend previous ones by examining whether the heritability of depressive symptoms in early-adolescence was different from that in mid-adolescence. We hypothesized that the heritability of depressive symptoms in early adolescence was higher than that in middle adolescence according to the theory and empirical work. Depressive

  5. The Relationship between Cultural Background and Organizational Commitment: Consistency Meaning and Different Sensitivity of Formation Paths%文化背景与组织承诺的关系:内涵一致性与形成路径敏感性的差异化

    Institute of Scientific and Technical Information of China (English)

    张旭; 樊耘; 颜静

    2013-01-01

    In this paper,the formation process model of commitment integrated with basic psychological needs satisfaction is used to analyze the influence of Chinese and western cultural background on sensitivity of formation paths of organizational commitment.Based on the comparison of volition,responsibility,and dedication in philosophy and ethics,this study proposes that the sensitive formation paths of organizational commitment are from "salience,control" and "autonomy need and competence need satisfaction" to "organizational commitment in western cultural background",and from "affect,trust" and "relatedness need satisfaction" to "organizational commitment" in Chinese cultural background.%以整合基本心理需求满意度的承诺形成过程模型作为分析中西文化背景对组织承诺形成路径敏感性影响的平台,通过在哲学和伦理学等方面对自主性、责任感和奉献的理论溯源与比较,研究得出在西方文化背景下,组织承诺的敏感性形成路径:显著性、控制→自主需求和胜任需求满意度→组织承诺;在中国文化背景下,组织承诺的敏感性形成路径:情感、信任→关系需求满意度→组织承诺.

  6. Genetic Background Screen of Inter-specific Hybrids between SSR Marker Assisted Chinese Kale and Rapeseed%SSR标记辅助芥蓝×甘蓝型油菜种间杂交后代的遗传背景筛选

    Institute of Scientific and Technical Information of China (English)

    于海龙; 方智远; 杨丽梅; 刘玉梅; 庄木; 李占省; 吕红豪; 张扬勇

    2015-01-01

    To screen the genetic background and increase the back-cross breeding efficiency of the interspecific hybrids and their back-cross offsprings between Chinese kale(Brassica oleracea var.alboglabra, CC,2n=2x=18) and rapeseed(Brassica napus,AACC),the F1 inter-specific hybrids and their BC1 backcross offsprings between Ogu-CMS Chinese kale and rapaseed were obtained through hand pollination combined with embryo rescue technology. A total of 220 SSR primers were used to detect polymorphisms between the parents, in which 51 pairs of SSR primers showed polymorphism. 33 pairs of primers were selected to analyze the genetic background of 3 F1 plants and 35 BC1 plants,with even distribution on 9 chromosomes and stable amplifications. The results of analysis by software NTSYSpc2.11a showed that the similarity coefficients between F1 plants and rapeseed was 0.74,which indicated that the genetic background of F1 plants was closer to rapeseed than to Chinese kale,while the similarity coefficients between BC1 plants and Chinese kale varied from 0.26-0.65,with big genetic background differences among BC1 plants.In all 35 BC1 plants,the genetic background of individual 14Y1 was the closest to Chinese kale,which was further confirmed by morphological observation.Thus,the individual 14Y1 could be used as donor plant for further backcross.%为筛选芥蓝×甘蓝型油菜种间杂交后代的遗传背景,加速回交转育进程,采用蕾期授粉结合胚挽救手段进行远缘杂交,获得芥蓝和甘蓝型油菜的种间杂种F1和BC1群体。利用已有的220对SSR引物对双亲进行多态性筛选,获得多态性引物51对。挑选均匀分布在甘蓝9条染色体上、扩增稳定、条带清晰的33对多态性SSR引物,对3株F1单株和35株BC1单株进行遗传背景筛选。NTSYSpc2.11a分析结果表明:F1植株的遗传背景与亲本甘蓝型油菜更为接近,遗传相似系数为0.74;而BC1植株的遗传背景差异较大,与亲本

  7. Face Detection under Complex Background and Illumination

    Institute of Scientific and Technical Information of China (English)

    Shao-Dong Lv; Yong-Duan Song; Mei Xu; Cong-Ying Huang

    2015-01-01

    Abstract⎯For face detection under complex background and illumination, a detection method that combines the skin color segmentation and cost-sensitive Adaboost algorithm is proposed in this paper. First, by using the characteristic of human skin color clustering in the color space, the skin color area inYCbCr color space is extracted and a large number of irrelevant backgrounds are excluded; then for remedyingthe deficiencies of Adaboost algorithm, the cost-sensitive function is introduced into the Adaboost algorithm; finally the skin color segmentation and cost-sensitive Adaboost algorithm are combined for the face detection. Experimental results show that the proposed detection method has a higher detection rate and detection speed, which can more adapt to the actual field environment.

  8. Background and introduction

    DEFF Research Database (Denmark)

    2012-01-01

    by their particular theories and conceptual analyses, data, tools, and best practices, with a focus on respectively costs and benefits of facilities and services, alignment of corporate and public real estate to organizational objectives and organisational performance, and relationship management in market...... background information to understand the following chapters in this book. Research limitations: The chapter is mainly based on the experience and knowledge of the editors. It does not include original research but provides an introductory overview of the book. Originality/value: This chapter takes a look...... behind the scenes of the making of this book and connects contributions from three different fields - FM, CREM, and B2B marketing - to shed more light on the concept of added value of FM. It serves as an introduction to the research presented in the other chapters in this book....

  9. Backgrounded but not peripheral

    DEFF Research Database (Denmark)

    Hovmark, Henrik

    2013-01-01

    In this paper I pay a closer look at the use of the CENTRE-PERIPHERY schema in context. I address two specific issues: first, I show how the CENTRE-PERIPHERY schema, encoded in the DDAs, enters into discourses that conceptualize and characterize a local community as both CENTRE and PERIPHERY, i...... in question contribute to the socio-cultural construction of identity, i.e. that they play a rather specific role in discursive communication and socio-cultural meaning construction. On the other hand it is clear that the semantics of the DDAs in question, seen in isolation, is very abstract or general......; furthermore, the DDAs are backgrounded in discourse. Is it reasonable to claim, rather boldly, that “the informants express their identity in the use of the directional adverb ud ‘out’ etc.”? In the course of this article, however, I suggest that the DDAs in question do contribute to the socio...

  10. A Glycine max homolog of NON-RACE SPECIFIC DISEASE RESISTANCE 1 (NDR1) alters defense gene expression while functioning during a resistance response to different root pathogens in different genetic backgrounds.

    Science.gov (United States)

    McNeece, Brant T; Pant, Shankar R; Sharma, Keshav; Niruala, Prakash; Lawrence, Gary W; Klink, Vincent P

    2017-05-01

    A Glycine max homolog of the Arabidopsis thaliana NON-RACE SPECIFIC DISEASE RESISTANCE 1 (NDR1) coiled-coil nucleotide binding leucine rich repeat (CC-NB-LRR) defense signaling gene (Gm-NDR1-1) is expressed in root cells undergoing a defense response to the root pathogenic nematode, Heterodera glycines. Gm-NDR1-1 overexpression in the H. glycines-susceptible genotype G. max[Williams 82/PI 518671] impairs parasitism. In contrast, Gm-NDR1-1 RNA interference (RNAi) in the H. glycines-resistant genotype G. max[Peking/PI 548402] facilitates parasitism. The broad effectiveness of Gm-NDR1-1 in impairing parasitism has then been examined by engineering its heterologous expression