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Sample records for background modifies phenotypes

  1. Strain background modifies phenotypes in the ATP8B1-deficient mouse

    NARCIS (Netherlands)

    S. Shah; U.R. Sanford; J.C. Vargas; H. Xu; A. Groen; C.C. Paulusma; J.P. Grenert; L. Pawlikowska; S. Sen; R.P.J. Oude Elferink; L.N. Bull

    2010-01-01

    BACKGROUND: Mutations in ATP8B1 (FIC1) underlie cases of cholestatic disease, ranging from chronic and progressive (progressive familial intrahepatic cholestasis) to intermittent (benign recurrent intrahepatic cholestasis). The ATP8B1-deficient mouse serves as an animal model of human ATP8B1 deficie

  2. 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.

  3. 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.

  4. Phenotype of heterozygotes for low-density lipoprotein receptor mutations identified in different background populations

    DEFF Research Database (Denmark)

    Tybjaerg-Hansen, Anne; Jensen, Henrik Kjaerulf; Benn, Marianne;

    2005-01-01

    The effect of mutations on phenotype is often overestimated because of ascertainment bias. We determined the effect of background population on cholesterol phenotype associated with specific mutations in the low-density lipoprotein (LDL) receptor and the relative importance of background populati...

  5. Phenotype of heterozygotes for low-density lipoprotein receptor mutations identified in different background populations

    DEFF Research Database (Denmark)

    Tybjaerg-Hansen, Anne; Jensen, Henrik Kjaerulf; Benn, Marianne;

    2005-01-01

    The effect of mutations on phenotype is often overestimated because of ascertainment bias. We determined the effect of background population on cholesterol phenotype associated with specific mutations in the low-density lipoprotein (LDL) receptor and the relative importance of background population...

  6. Modifying factors and phenotypic diversity in Wilson's disease.

    Science.gov (United States)

    Lutsenko, Svetlana

    2014-05-01

    Wilson's disease (WD) is a human disorder of copper homeostasis caused by mutations in the copper-transporting ATPase ATP7B. WD is characterized by copper accumulation, predominantly in the liver and brain, hepatic pathology, and wide differences between patients in the age of onset and the spectrum of symptoms. Several factors contribute to the phenotypic variability of WD. The WD-causing mutations produce a wide range of changes in stability, activity, intracellular localization, and trafficking of ATP7B; the nonpathogenic genetic polymorphisms may contribute to the phenotype. In Atp7b(-/-) mice, a mouse model of WD, an abnormal intracellular distribution of copper in the liver triggers distinct changes in the transcriptome; these mRNA profiles might be used to more specifically define disease progression. The major effect of accumulating copper on lipid metabolism and especially cholesterol homeostasis in mice and humans suggests the importance of fat and cholesterol metabolism as modifying factors in WD.

  7. Constraining modified theories of gravity with gravitational wave stochastic background

    CERN Document Server

    Maselli, Andrea; Ferrari, Valeria; Kokkotas, Kostas; Schneider, Raffaella

    2016-01-01

    The direct discovery of gravitational waves has finally opened a new observational window on our Universe, suggesting that the population of coalescing binary black holes is larger than previously expected. These sources produce an unresolved background of gravitational waves, potentially observables by ground-based interferometers. In this paper we investigate how modified theories of gravity, modeled using the ppE formalism, affect the expected signal, and analyze the detectability of the resulting stochastic background by current and future ground-based interferometers. We find the constraints that AdLIGO would be able to set on modified theories, showing that they may significantly improve the current bounds obtained from astrophysical observations of binary pulsars.

  8. Can background cosmology hold the key for modified gravity tests?

    CERN Document Server

    Ceron-Hurtado, Juan J; Li, Baojiu

    2016-01-01

    Modified gravity theories are a popular alternative to dark energy as a possible explanation for the observed accelerating cosmic expansion, and their cosmological tests are currently an active research field. Studies in recent years have been increasingly focused on testing these theories in the nonlinear regime, which is computationally demanding. Here we show that, under certain circumstances, a whole class of theories can be ruled out by using background cosmology alone. This is possible because certain classes of models (i) are fundamentally incapable of producing specific background expansion histories, and (ii) said histories are incompatible with local gravity tests. As an example, we demonstrate that a popular class of models, $f(R)$ gravity, would not be viable if observations suggest even a slight deviation of the background expansion history from that of the $\\Lambda$CDM paradigm.

  9. Can background cosmology hold the key for modified gravity tests?

    Science.gov (United States)

    Ceron-Hurtado, Juan J.; He, Jian-hua; Li, Baojiu

    2016-09-01

    Modified gravity theories are a popular alternative to dark energy as a possible explanation for the observed accelerating cosmic expansion, and their cosmological tests are currently an active research field. Studies in recent years have been increasingly focused on testing these theories in the nonlinear regime, which is computationally demanding. Here we show that, under certain circumstances, a whole class of theories can be ruled out by using background cosmology alone. This is possible because certain classes of models (i) are fundamentally incapable of producing specific background expansion histories, and (ii) said histories are incompatible with local gravity tests. As an example, we demonstrate that a popular class of models, f (R ) gravity, would not be viable if observations suggest even a slight deviation of the background expansion history from that of the Λ CDM paradigm.

  10. Image Segmentation in Video Sequences Using Modified Background Subtraction

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    D. W. Chinchkhede

    2012-03-01

    Full Text Available In computer vision, "Background subtraction" is a technique for finding moving objects in a video sequences for example vehicle driving on a freeway. For to detect non stationary (dynamic objects, it is necessary to subtracting current image from a time-averaged background image. There are various background subtraction algorithms for detecting moving vehicles or any moving object(s like pedestrians in urban traffic video sequences. A crude approximation to the task of classifying each pixel on the frame of current image, locate slow-moving objects or in poor image qualities of videos and distinguish shadows from moving objects by using modified background subtraction method. While classifying each pixel on the frame of the current image, it is to be detect the moving object at foreground and background conditional environment that we can classify each pixel using a model of how that pixellooks when it is part of video frame classes. A mixture of Gaussians classification model for each pixel using an unsupervised technique is an efficient, incremental version of Expectation Maximization (EM is used for the purpose. Unlike standard image-averaging approach, this method automatically updates the mixture component for each video frame class according to likelihood of membership; hence slowmoving objects and poor image quality of videos are also being handled perfectly. Our approach identifies and eliminates shadows much more effectively than other techniques like thresholding.

  11. 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...

  12. Hand Gesture Recognition Using Modified 1$ and Background Subtraction Algorithms

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    Hazem Khaled

    2015-01-01

    Full Text Available Computers and computerized machines have tremendously penetrated all aspects of our lives. This raises the importance of Human-Computer Interface (HCI. The common HCI techniques still rely on simple devices such as keyboard, mice, and joysticks, which are not enough to convoy the latest technology. Hand gesture has become one of the most important attractive alternatives to existing traditional HCI techniques. This paper proposes a new hand gesture detection system for Human-Computer Interaction using real-time video streaming. This is achieved by removing the background using average background algorithm and the 1$ algorithm for hand’s template matching. Then every hand gesture is translated to commands that can be used to control robot movements. The simulation results show that the proposed algorithm can achieve high detection rate and small recognition time under different light changes, scales, rotation, and background.

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

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    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. The expression of HSP in human skeletal muscle. Effects of muscle fiber phenotype and training background

    DEFF Research Database (Denmark)

    Folkesson, Mattias; Mackey, Abigail L; Langberg, Henning;

    2013-01-01

    AIM: Exercise-induced adaptations of skeletal muscle are related to training mode and can be muscle fibre type specific. This study aimed to investigate heat shock protein expression in type I and type II muscle fibres in resting skeletal muscle of subjects with different training backgrounds...... HSPs in human skeletal muscle is influenced by muscle fibre phenotype. The fibre type specific expression of HSP70 is influenced by resistance and endurance training whereas those of αB-crystallin and HSP27 are influenced only by endurance training suggesting the existence of a training......-modality specific action on the adaptive processes including heat shock proteins in human skeletal muscle. This article is protected by copyright. All rights reserved....

  15. 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...... littermates. In conclusion, we have shown that the genetic background of P2X7(-/-) mice strongly influences the bone phenotype of the P2X7(-/-) mice and that P2X7 has a more significant regulatory role in bone remodeling than found in previous studies....

  16. MC1R Mutations Modify the Classic Phenotype of Oculocutaneous Albinism Type 2 (OCA2)

    OpenAIRE

    Richard A. King; Willaert, Rebecca K.; Schmidt, Ramona M.; Pietsch, Jacy; Savage, Sarah; Brott, Marcia J.; Fryer, James P.; Summers, C Gail; William S Oetting

    2003-01-01

    The heterogeneous group of disorders known as oculocutaneous albinism (OCA) shares cutaneous and ocular hypopigmentation associated with common developmental abnormalities of the eye. Mutations of at least 11 loci produce this phenotype. The majority of affected individuals develop some cutaneous melanin; this is predominantly seen as yellow/blond hair, whereas fewer have brown hair. The OCA phenotype is dependent on the constitutional pigmentation background of the family, with more OCA pigm...

  17. Age modifies the genotype-phenotype relationship for the bitter receptor TAS2R38

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    Duke Fujiko F

    2010-07-01

    Full Text Available Abstract Background The purpose of this study was to investigate the effect of TAS2R38 haplotypes and age on human bitter taste perception. Results Children (3 to 10 yrs, adolescents (11 to 19 yrs and adults (mostly mothers, 20 to 55 yrs (N = 980 were measured for bitter taste thresholds for 6-n-propylthiouracil (PROP and genotyped for three polymorphisms of the AS2R38 gene (A49P, V262A, I296V. Subjects were grouped by haplotype and age, as well as sex and race/ethnicity, and compared for PROP thresholds. Subjects with the same haplotype were similar in bitter threshold regardless of race/ethnicity (all ages or sex (children and adolescents; all p-values > 0.05 but age was a modifier of the genotype-phenotype relationship. Specifically, AVI/PAV heterozygous children could perceive a bitter taste at lower PROP concentrations than could heterozygous adults, with the thresholds of heterozygous adolescents being intermediate (p 0.05 perhaps because there is less variation in taste perception among these homozygotes. Conclusions These data imply that the change in PROP bitter sensitivity which occurs over the lifespan (from bitter sensitive to less so is more common in people with a particular haplotype combination, i.e., AVI/PAV heterozygotes.

  18. MutLα heterodimers modify the molecular phenotype of Friedreich ataxia.

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    Vahid Ezzatizadeh

    Full Text Available BACKGROUND: Friedreich ataxia (FRDA, the most common autosomal recessive ataxia disorder, is caused by a dynamic GAA repeat expansion mutation within intron 1 of FXN gene, resulting in down-regulation of frataxin expression. Studies of cell and mouse models have revealed a role for the mismatch repair (MMR MutS-heterodimer complexes and the PMS2 component of the MutLα complex in the dynamics of intergenerational and somatic GAA repeat expansions: MSH2, MSH3 and MSH6 promote GAA repeat expansions, while PMS2 inhibits GAA repeat expansions. METHODOLOGY/PRINCIPAL FINDINGS: To determine the potential role of the other component of the MutLα complex, MLH1, in GAA repeat instability in FRDA, we have analyzed intergenerational and somatic GAA repeat expansions from FXN transgenic mice that have been crossed with Mlh1 deficient mice. We find that loss of Mlh1 activity reduces both intergenerational and somatic GAA repeat expansions. However, we also find that loss of either Mlh1 or Pms2 reduces FXN transcription, suggesting different mechanisms of action for Mlh1 and Pms2 on GAA repeat expansion dynamics and regulation of FXN transcription. CONCLUSIONS/SIGNIFICANCE: Both MutLα components, PMS2 and MLH1, have now been shown to modify the molecular phenotype of FRDA. We propose that upregulation of MLH1 or PMS2 could be potential FRDA therapeutic approaches to increase FXN transcription.

  19. An interview study of phenotypic characterization of genetically-modified mice

    NARCIS (Netherlands)

    Thon, R.; Vondeling, H.; Lassen, J.; Hansen, A.K.; Ritskes-Hoitinga, M.

    2009-01-01

    An interview study was carried out with the aim of clarifying the reasons for the limited use of phenotypic characterization of genetically-modified mice (GMM) and identifying issues hindering its implementation. A total of 15 users of GMM participated in semi-structured face-to-face interviews, whi

  20. An interview study of phenotypic characterization of genetically-modified mice.

    NARCIS (Netherlands)

    Thon, R.; Vondeling, H.; Lassen, J.; Hansen, A.K.; Ritskes-Hoitinga, M.

    2009-01-01

    An interview study was carried out with the aim of clarifying the reasons for the limited use of phenotypic characterization of genetically-modified mice (GMM) and identifying issues hindering its implementation. A total of 15 users of GMM participated in semi-structured face-to-face interviews, whi

  1. Elevated oxidative membrane damage associated with genetic modifiers of Lyst-mutant phenotypes.

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    Colleen M Trantow

    2010-07-01

    Full Text Available LYST is a large cytosolic protein that influences the biogenesis of lysosome-related organelles, and mutation of the encoding gene, LYST, can cause Chediak-Higashi syndrome. Recently, Lyst-mutant mice were recognized to also exhibit an iris disease resembling exfoliation syndrome, a common cause of glaucoma in humans. Here, Lyst-mutant iris phenotypes were used in a search for genes that influence Lyst pathways. In a candidate gene-driven approach, albino Lyst-mutant mice homozygous for a mutation in Tyr, whose product is key to melanin synthesis within melanosomes, exhibited complete rescue of Lyst-mutant iris phenotypes. In a genetic background-driven approach using a DBA/2J strain of congenic mice, an interval containing Tyrp1 enhanced Lyst-dependent iris phenotypes. Thus, both experimental approaches implicated the melanosome, an organelle that is a potential source of oxidative stress, as contributing to the disease phenotype. Confirming an association with oxidative damage, Lyst mutation resulted in genetic context-sensitive changes in iris lipid hydroperoxide levels, being lowest in albino and highest in DBA/2J mice. Surprisingly, the DBA/2J genetic background also exposed a late-onset neurodegenerative phenotype involving cerebellar Purkinje-cell degeneration. These results identify an association between oxidative damage to lipid membranes and the severity of Lyst-mutant phenotypes, revealing a new mechanism that contributes to pathophysiology involving LYST.

  2. Phenotypic divergence in two lines of L-Fabp-/- mice reflects substrain differences and environmental modifiers.

    Science.gov (United States)

    Newberry, Elizabeth P; Kennedy, Susan; Xie, Yan; Luo, Jianyang; Jiang, Hui; Ory, Daniel S; Davidson, Nicholas O

    2015-10-15

    Phenotypic divergence in diet-induced obesity (DIO) and hepatic steatosis has been reported in two independently generated lines of L-Fabp(-/-) mice [New Jersey (NJ) L-Fabp(-/-) vs. Washington University (WU) L-Fabp(-/-) mice]. We performed side-by-side studies to examine differences between the lines and investigate the role of genetic background, intestinal microbiota, sex, and diet in the divergent phenotypes. Fasting-induced steatosis was attenuated in both L-Fabp(-/-) lines compared with C57BL/6J controls, with restoration of hepatic triglyceride levels following adenoviral L-Fabp rescue. Both lines were protected against DIO after high-saturated-fat diet feeding. Hepatic steatosis was attenuated in WU but not NJ L-Fabp(-/-) mice, although this difference between the lines disappeared upon antibiotic treatment and cohousing. In contrast, there was phenotypic divergence in L-Fabp(-/-) mice fed a high cocoa butter fat diet, with WU L-Fabp(-/-) mice, but not NJ L-Fabp(-/-) mice, showing protection against both DIO and hepatic steatosis, with some sex-dependent (female > male) differences. Dense mapping revealed no evidence of unintended targeting, duplications, or deletions surrounding the Fabp1 locus in either line and only minor differences in mRNA expression of genes located near the targeted allele. However, a C57BL/6 substrain screen showed that the NJ L-Fabp(-/-) line contains ∼40% C57BL/6N genomic DNA, despite reports that these mice were backcrossed six generations. Overall, these findings suggest that some of the phenotypic divergence between the two L-Fabp(-/-) lines may reflect unanticipated differences in genetic background, underscoring the importance of genetic background in phenotypic characterization. PMID:26251469

  3. Phenotypic divergence in two lines of L-Fabp-/- mice reflects substrain differences and environmental modifiers.

    Science.gov (United States)

    Newberry, Elizabeth P; Kennedy, Susan; Xie, Yan; Luo, Jianyang; Jiang, Hui; Ory, Daniel S; Davidson, Nicholas O

    2015-10-15

    Phenotypic divergence in diet-induced obesity (DIO) and hepatic steatosis has been reported in two independently generated lines of L-Fabp(-/-) mice [New Jersey (NJ) L-Fabp(-/-) vs. Washington University (WU) L-Fabp(-/-) mice]. We performed side-by-side studies to examine differences between the lines and investigate the role of genetic background, intestinal microbiota, sex, and diet in the divergent phenotypes. Fasting-induced steatosis was attenuated in both L-Fabp(-/-) lines compared with C57BL/6J controls, with restoration of hepatic triglyceride levels following adenoviral L-Fabp rescue. Both lines were protected against DIO after high-saturated-fat diet feeding. Hepatic steatosis was attenuated in WU but not NJ L-Fabp(-/-) mice, although this difference between the lines disappeared upon antibiotic treatment and cohousing. In contrast, there was phenotypic divergence in L-Fabp(-/-) mice fed a high cocoa butter fat diet, with WU L-Fabp(-/-) mice, but not NJ L-Fabp(-/-) mice, showing protection against both DIO and hepatic steatosis, with some sex-dependent (female > male) differences. Dense mapping revealed no evidence of unintended targeting, duplications, or deletions surrounding the Fabp1 locus in either line and only minor differences in mRNA expression of genes located near the targeted allele. However, a C57BL/6 substrain screen showed that the NJ L-Fabp(-/-) line contains ∼40% C57BL/6N genomic DNA, despite reports that these mice were backcrossed six generations. Overall, these findings suggest that some of the phenotypic divergence between the two L-Fabp(-/-) lines may reflect unanticipated differences in genetic background, underscoring the importance of genetic background in phenotypic characterization.

  4. Approaches for the identification of genetic modifiers of nutrient dependent phenotypes: Examples from folate

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    Amanda J. Macfarlane

    2014-07-01

    Full Text Available By combining the sciences of nutrition, bioinformatics, genomics, population genetics and epidemiology, nutrigenomics is improving our understanding of how diet and nutrient intake can interact with or modify gene expression and disease risk. In this review, we explore various approaches to examine gene-nutrient interactions and the modifying role of nutrient consumption, as they relate to nutrient status and disease risk in human populations. Two common approaches include the use of SNPs in candidate genes to identify their association with nutritional status or disease outcomes, or genome wide association studies to identify genetic polymorphisms associated with a given phenotype. Here, we examine the results of various gene-nutrient interaction studies, the association of genetic polymorphisms with disease expression and the identification of nutritional factors that modify gene-dependent disease phenotypes. We have focussed on specific examples from investigations of the interactions of folate and B-vitamin consumption and polymorphisms in the genes of B vitamin dependent enzymes and their association with disease risk, followed by an examination of the strengths and limitations of the methods employed. We also present suggestions for future studies, including an approach from an on-going large scale study, to examine the interaction of nutrient intake and genotypic variation and their impact on nutritional status.

  5. Constraining Modified Theories of Gravity with Gravitational-Wave Stochastic Backgrounds.

    Science.gov (United States)

    Maselli, Andrea; Marassi, Stefania; Ferrari, Valeria; Kokkotas, Kostas; Schneider, Raffaella

    2016-08-26

    The direct discovery of gravitational waves has finally opened a new observational window on our Universe, suggesting that the population of coalescing binary black holes is larger than previously expected. These sources produce an unresolved background of gravitational waves, potentially observable by ground-based interferometers. In this Letter we investigate how modified theories of gravity, modeled using the parametrized post-Einsteinian formalism, affect the expected signal, and analyze the detectability of the resulting stochastic background by current and future ground-based interferometers. We find the constraints that Advanced LIGO would be able to set on modified theories, showing that they may significantly improve the current bounds obtained from astrophysical observations of binary pulsars. PMID:27610838

  6. Constraining Modified Theories of Gravity with Gravitational-Wave Stochastic Backgrounds

    Science.gov (United States)

    Maselli, Andrea; Marassi, Stefania; Ferrari, Valeria; Kokkotas, Kostas; Schneider, Raffaella

    2016-08-01

    The direct discovery of gravitational waves has finally opened a new observational window on our Universe, suggesting that the population of coalescing binary black holes is larger than previously expected. These sources produce an unresolved background of gravitational waves, potentially observable by ground-based interferometers. In this Letter we investigate how modified theories of gravity, modeled using the parametrized post-Einsteinian formalism, affect the expected signal, and analyze the detectability of the resulting stochastic background by current and future ground-based interferometers. We find the constraints that Advanced LIGO would be able to set on modified theories, showing that they may significantly improve the current bounds obtained from astrophysical observations of binary pulsars.

  7. Hypomorphic phenotype of Foxn1 gene-modified rats by CRISPR/Cas9 system.

    Science.gov (United States)

    Goto, Teppei; Hara, Hiromasa; Nakauchi, Hiromitsu; Hochi, Shinichi; Hirabayashi, Masumi

    2016-08-01

    The Foxn1 gene is known as a critical factor for the differentiation of thymic and skin epithelial cells. This study was designed to examine the phenotype of Foxn1-modified rats generated by the CRISPR/Cas9 system. Guide-RNA designed for first exon of the Foxn1 and mRNA of Cas9 were co-injected into the pronucleus of Crlj:WI zygotes. Transfer of 158 injected zygotes resulted in the birth of 50 offspring (32 %), and PCR identified five (10 %) as Foxn1-edited. Genomic sequencing revealed the deletion of 44 or 60 bp from and/or insertion of 4 bp into the Foxn1 gene in a single allele. The number of T-cells in the peripheral blood lymphocytes of mutant rats decreased markedly. While homozygous deleted mutant rats had no thymus, the mutant rats were not completely hairless and showed normal performance in delivery and nursing. Splicing variants of the indel-mutation in the Foxn1 gene may cause hypomorphic allele, resulting in the phenotype of thymus deficiency and incomplete hairless. In conclusion, the mutant rats in Foxn1 gene edited by the CRISPR/Cas9 system showed the phenotype of thymus deficiency and incomplete hairless which was characterized by splicing variants. PMID:26931321

  8. Genetic background modifies neurodegeneration and neuroinflammation driven by misfolded human tau protein in rat model of tauopathy: implication for immunomodulatory approach to Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Kovacech Branislav

    2010-10-01

    Full Text Available Abstract Background Numerous epidemiological studies demonstrate that genetic background modifies the onset and the progression of Alzheimer's disease and related neurodegenerative disorders. The efficacious influence of genetic background on the disease pathway of amyloid beta has been meticulously described in rodent models. Since the impact of genetic modifiers on the neurodegenerative and neuroinflammatory cascade induced by misfolded tau protein is yet to be elucidated, we have addressed the issue by using transgenic lines expressing the same human truncated tau protein in either spontaneously hypertensive rat (SHR or Wistar-Kyoto (WKY genetic background. Methods Brains of WKY and SHR transgenic rats in the terminal stage of phenotype and their age-matched non-transgenic littermates were examined by means of immunohistochemistry and unbiased stereology. Basic measures of tau-induced neurodegeneration (load of neurofibrillary tangles and neuroinflammation (number of Iba1-positive microglia, their activated morphology, and numbers of microglia immunoreactive for MHCII and astrocytes immunoreactive for GFAP were quantified with an optical fractionator in brain areas affected by neurofibrillary pathology (pons, medulla oblongata. The stereological data were evaluated using two-way ANOVA and Student's t-test. Results Tau neurodegeneration (neurofibrillary tangles (NFTs, axonopathy and neuroinflammation (microgliosis, astrocytosis appeared in both WKY and SHR transgenic rats. Although identical levels of transgene expression in both lines were present, terminally-staged WKY transgenic rats displayed significantly lower final NFT loads than their SHR transgenic counterparts. Interestingly, microglial responses showed a striking difference between transgenic lines. Only 1.6% of microglia in SHR transgenic rats expressed MHCII in spite of having a robust phagocytic phenotype, whereas in WKY transgenic rats, 23.2% of microglia expressed MHCII despite

  9. Mapping gravitational-wave backgrounds in modified theories of gravity using pulsar timing arrays

    CERN Document Server

    Gair, Jonathan R; Taylor, Stephen R

    2015-01-01

    We extend our previous work on applying CMB techniques to the mapping of gravitational-wave backgrounds to backgrounds which have non-GR polarisations. Our analysis and results are presented in the context of pulsar-timing array observations, but the overarching methods are general, and can be easily applied to LIGO or eLISA observations using appropriately modified response functions. Analytic expressions for the pulsar-timing response to gravitational waves with non-GR polarisation are given for each mode of a spin-weighted spherical-harmonic decomposition of the background, which permit the signal to be mapped across the sky to any desired resolution. We also derive the pulsar-timing overlap reduction functions for the various non-GR polarisations, finding analytic forms for anisotropic backgrounds with scalar-transverse ("breathing") and vector-longitudinal polarisations, and a semi-analytic form for scalar-longitudinal backgrounds. Our results indicate that pulsar-timing observations will be completely i...

  10. Cosmic Microwave Background Radiation Constraints on a Modified Chaplygin Gas Model

    Institute of Scientific and Technical Information of China (English)

    LIU Dao-Jun; LI Xin-Zhou

    2005-01-01

    @@ A modified Chaplygin gas model of unifying dark energy and dark matter with the exotic equation of state p = Bρ- A/ρα , which can also explain the recent expansion of the universe, is investigated by means of constraining the location of the peak of the cosmic microwave background radiation spectrum. We find that the result of CMBR measurements does not exclude the nonzero value of parameter B, but allows it in the range -0.35 (<~) B (<~) 0.025.

  11. Arrhythmogenic Biophysical Phenotype for SCN5A Mutation S1787N Depends upon Splice Variant Background and Intracellular Acidosis.

    Directory of Open Access Journals (Sweden)

    Rou-Mu Hu

    Full Text Available SCN5A is a susceptibility gene for type 3 long QT syndrome, Brugada syndrome, and sudden infant death syndrome. INa dysfunction from mutated SCN5A can depend upon the splice variant background in which it is expressed and also upon environmental factors such as acidosis. S1787N was reported previously as a LQT3-associated mutation and has also been observed in 1 of 295 healthy white controls. Here, we determined the in vitro biophysical phenotype of SCN5A-S1787N in an effort to further assess its possible pathogenicity.We engineered S1787N in the two most common alternatively spliced SCN5A isoforms, the major isoform lacking a glutamine at position 1077 (Q1077del and the minor isoform containing Q1077, and expressed these two engineered constructs in HEK293 cells for electrophysiological study. Macroscopic voltage-gated INa was measured 24 hours after transfection with standard whole-cell patch clamp techniques. We applied intracellular solutions with pH7.4 or pH6.7. S1787N in the Q1077 background had WT-like INa including peak INa density, activation and inactivation parameters, and late INa amplitude in both pH 7.4 and pH 6.7. However, with S1787N in the Q1077del background, the percentages of INa late/peak were increased by 2.1 fold in pH 7.4 and by 2.9 fold in pH 6.7 when compared to WT.The LQT3-like biophysical phenotype for S1787N depends on both the SCN5A splice variant and on the intracellular pH. These findings provide further evidence that the splice variant and environmental factors affect the molecular phenotype of cardiac SCN5A-encoded sodium channel (Nav1.5, has implications for the clinical phenotype, and may provide insight into acidosis-induced arrhythmia mechanisms.

  12. 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.

  13. Identification of genetic modifiers of behavioral phenotypes in serotonin transporter knockout rats

    Directory of Open Access Journals (Sweden)

    Nijman Isaäc J

    2010-05-01

    Full Text Available Abstract Background Genetic variation in the regulatory region of the human serotonin transporter gene (SLC6A4 has been shown to affect brain functionality and personality. However, large heterogeneity in its biological effects is observed, which is at least partially due to genetic modifiers. To gain insight into serotonin transporter (SERT-specific genetic modifiers, we studied an intercross between the Wistar SERT-/- rat and the behaviorally and genetically divergent Brown Norway rat, and performed a QTL analysis. Results In a cohort of >150 intercross SERT-/- and control (SERT+/+ rats we characterized 12 traits that were previously associated with SERT deficiency, including activity, exploratory pattern, cocaine-induced locomotor activity, and abdominal and subcutaneous fat. Using 325 genetic markers, 10 SERT-/--specific quantitative trait loci (QTLs for parameters related to activity and exploratory pattern (Chr.1,9,11,14, and cocaine-induced anxiety and locomotor activity (Chr.5,8 were identified. No significant QTLs were found for fat parameters. Using in silico approaches we explored potential causal genes within modifier QTL regions and found interesting candidates, amongst others, the 5-HT1D receptor (Chr. 5, dopamine D2 receptor (Chr. 8, cannabinoid receptor 2 (Chr. 5, and genes involved in fetal development and plasticity (across chromosomes. Conclusions We anticipate that the SERT-/--specific QTLs may lead to the identification of new modulators of serotonergic signaling, which may be targets for pharmacogenetic and therapeutic approaches.

  14. Genetic heterogeneity, modifier genes, and quantitative phenotypes in psychiatric illness: searching for a framework.

    Science.gov (United States)

    Fanous, A H; Kendler, K S

    2005-01-01

    Schizophrenia has long been thought to be clinically heterogeneous. A range of studies suggests that this is due to genetic heterogeneity. Some clinical features, such as negative symptoms, are associated with a greater risk of illness in relatives. Affected sibling pairs are correlated for clinical and course features as well as subforms of illness, and twin studies suggest that this is due to genetic factors. This is further supported by findings that subjects from families linked to some chromosomal regions may differ clinically from those from unlinked families. Moreover, some genes may affect clinical features without altering susceptibility (ie are modifier genes). High-risk genotypes may have quantitative, rather than categorical effects, and may influence milder or subclinical phenotypes. Another recent finding is that nonpsychotic relatives may have personality features that resemble those of their affected relatives. These findings taken together suggest that there may be several classes of gene action in schizophrenia: some genes may influence susceptibility only, others may influence clinical features only, and still others may have a mixed effect. Furthermore, subsets of these classes may affect personality and other traits in nonpsychotic relatives. Understanding these classes of gene action may help guide the design of linkage and association studies that have increased power. We describe five classes of genes and their predictions of the outcomes of family, twin, and several types of linkage studies. We go on to explore how these predictions can in turn be used to aid in the design of linkage studies.

  15. ENU Mutagenesis Screen to Establish Motor Phenotypes in Wild-Type Mice and Modifiers of a Pre-Existing Motor Phenotype in Tau Mutant Mice

    Directory of Open Access Journals (Sweden)

    Xin Liu

    2011-01-01

    Full Text Available Modifier screening is a powerful genetic tool. While not widely used in the vertebrate system, we applied these tools to transgenic mouse strains that recapitulate key aspects of Alzheimer’s disease (AD, such as tau-expressing mice. These are characterized by a robust pathology including both motor and memory impairment. The phenotype can be modulated by ENU mutagenesis, which results in novel mutant mouse strains and allows identifying the underlying gene/mutation. Here we discuss this strategy in detail. We firstly obtained pedigrees that modify the tau-related motor phenotype, with mapping ongoing. We further obtained transgene-independent motor pedigrees: (i hyperactive, circling ENU 37 mice with a causal mutation in the Tbx1 gene—the complete knock-out of Tbx1 models DiGeorge Syndrome; (ii ENU12/301 mice that show sudden jerky movements and tremor constantly; they have a causal mutation in the Kcnq1 gene, modelling aspects of the Romano-Ward and Jervell and Lange-Nielsen syndromes; and (iii ENU16/069 mice with tremor and hypermetric gait that have a causal mutation in the Mpz (Myelin Protein Zero gene, modelling Charcot-Marie-Tooth disease type 1 (CMT1B. Together, we provide evidence for a real potential of an ENU mutagenesis to dissect motor functions in wild-type and tau mutant mice.

  16. 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.

  17. Detection of KPC Carbapenemase in Pseudomonas aeruginosa Isolated From Clinical Samples Using Modified Hodge Test and Boronic Acid Phenotypic Methods and Their Comparison With the Polymerase Chain Reaction

    Science.gov (United States)

    Falahat, Saeed; Shojapour, Mana; Sadeghi, Abdorrahim

    2016-01-01

    Background Bacterial resistance to antibiotics has become a major source of concern for public health. Pseudomonas aeruginosa strains are important opportunistic pathogens. These bacteria have a high resistance to a wide range of existing antimicrobials and antibiotics. Objectives The present study was performed to evaluate the frequency of KPC in P. aeruginosa isolated from clinical samples of educational hospitals of Arak University of Medical Sciences, using the mentioned phenotypic and genotypic methods. Materials and Methods One hundred and eight non-duplicate clinical isolates of P. aeruginosa were collected from hospitals of Arak University of Medical Sciences, Arak, Iran. Antibacterial susceptibility was determined by the disk diffusion method. KPC production was confirmed by the Modified Hodge Test (MHT), which is a phenotypic test, and combined-disk test with boronic acid and the Polymerase Chain Reaction (PCR). Results In the present study, 13 isolates (12%) of P. aeruginosa were positive for KPC, using PCR. Comparison of the two phenotypic methods used in this study showed that boronic acid is more sensitive than MHT in identification of KPC-producing strains (84.6% vs. 77%). Conclusions Utilization of reliable methods for identifying carbapenemase-producing strains and determining their antibiotic resistance pattern could have a very important role in treatment of infections caused by these strains. A substantial amount of P. aeruginosa isolated from clinical samples of hospitals in Arak (Iran) produce KPC carbapenemase. Due to their low specificity, MHT and boronic acid phenotypic methods could not completely identify KPC-producing P. aeruginosa. However, the sensitivity of boronic acid phenotypic method in detection of KPC was higher than MHT.

  18. Asthma phenotypes modify the impact of environmetnal factors on lung function

    Science.gov (United States)

    Previous studies have examined the role of childhood asthma phenotypes based on clinical history on asthma severity and symptom aggravation by environmental risk factors. The current study focuses on the associations between lung function in childhood and environmental factors an...

  19. Genetic modifiers of sickle cell anemia in the BABY HUG cohort: influence on laboratory and clinical phenotypes.

    Science.gov (United States)

    Sheehan, Vivien A; Luo, Zhaoyu; Flanagan, Jonathan M; Howard, Thad A; Thompson, Bruce W; Wang, Winfred C; Kutlar, Abdullah; Ware, Russell E

    2013-07-01

    The recently completed BABY HUG trial investigated the safety and efficacy of hydroxyurea in infants with sickle cell anemia (SCA). To investigate the effects of known genetic modifiers, genomic DNA on 190 randomized subjects were analyzed for alpha thalassemia, beta-globin haplotype, polymorphisms affecting endogenous fetal hemoglobin (HbF) levels (XmnI, BCL11A, and HBS1L-MYB), UGT1A1 promoter polymorphisms, and the common G6PD A(-) mutation. At study entry, infants with alpha thalassemia trait had significantly lower mean corpuscular volume, total bilirubin, and absolute reticulocyte count. Beta-globin haplotypes associated with milder disease had significantly higher hemoglobin and %HbF. BCL11A and XmnI polymorphisms had significant effects on baseline HbF, while UGT1A1 promoter polymorphisms significantly influenced baseline serum bilirubin. At study exit, subjects randomized to placebo still exhibited laboratory effects of alpha thalassemia and other modifiers, while those assigned hydroxyurea had treatment effects that exceeded most genetic influences. The pain phenotype was influenced by HbF modifiers in both treatment groups. These data document that genetic polymorphisms do modify laboratory and clinical phenotypes even in very young patients with SCA. The hydroxyurea effects are more potent, however, indicating that treatment criteria should not be limited to certain genetic subsets, and supporting the use of hydroxyurea for all young patients with SCA. PMID:23606168

  20. The effects of host age, host nuclear background and temperature on phenotypic effects of the virulent Wolbachia strain popcorn in Drosophila melanogaster.

    OpenAIRE

    Reynolds, K Tracy; Thomson, Linda J; Ary A Hoffmann

    2003-01-01

    Because of their obligate endosymbiotic nature, Wolbachia strains by necessity are defined by their phenotypic effects upon their host. Nevertheless, studies on the influence of host background and environmental conditions upon the manifestation of Wolbachia effects are relatively uncommon. Here we examine the behavior of the overreplicating Wolbachia strain popcorn in four different Drosophila melanogaster backgrounds at two temperatures. Unlike other strains of Wolbachia in Drosophila, popc...

  1. A modified protocol to maximize differentiation of human preadipocytes and improve metabolic phenotypes

    OpenAIRE

    Lee, Mi-Jeong; Wu, Yuanyuan; Fried, Susan K.

    2012-01-01

    Adipose stromal cells proliferate and differentiate into adipocytes, providing a valuable model system for studies of adipocyte biology. We compared differentiation protocols for human preadipocytes and report on their metabolic phenotypes. By simply prolonging the adipogenic induction period from the first 3 days to 7 days, the proportion of cells (passage 5–6) acquiring adipocyte morphology increased from 30–70% to over 80% in human subcutaneous preadipocytes. These morphological changes we...

  2. Detailed phenotypic and molecular analyses of genetically modified mice generated by CRISPR-Cas9-mediated editing.

    Directory of Open Access Journals (Sweden)

    Bijal A Parikh

    Full Text Available The bacterial CRISPR-Cas9 system has been adapted for use as a genome editing tool. While several recent reports have indicated that successful genome editing of mice can be achieved, detailed phenotypic and molecular analyses of the mutant animals are limited. Following pronuclear micro-injection of fertilized eggs with either wild-type Cas9 or the nickase mutant (D10A and single or paired guide RNA (sgRNA for targeting of the tyrosinase (Tyr gene, we assessed genome editing in mice using rapid phenotypic readouts (eye and coat color. Mutant mice with insertions or deletions (indels in Tyr were efficiently generated without detectable off-target cleavage events. Gene correction of a single nucleotide by homologous recombination (HR could only occur when the sgRNA recognition sites in the donor DNA were modified. Gene repair did not occur if the donor DNA was not modified because Cas9 catalytic activity was completely inhibited. Our results indicate that allelic mosaicism can occur following -Cas9-mediated editing in mice and appears to correlate with sgRNA cleavage efficiency at the single-cell stage. We also show that larger than expected deletions may be overlooked based on the screening strategy employed. An unbiased analysis of all the deleted nucleotides in our experiments revealed that the highest frequencies of nucleotide deletions were clustered around the predicted Cas9 cleavage sites, with slightly broader distributions than expected. Finally, additional analysis of founder mice and their offspring indicate that their general health, fertility, and the transmission of genetic changes were not compromised. These results provide the foundation to interpret and predict the diverse outcomes following CRISPR-Cas9-mediated genome editing experiments in mice.

  3. Staphylococcal phenotypes induced by naturally occurring and synthetic membrane-interactive polyphenolic β-lactam resistance modifiers.

    Directory of Open Access Journals (Sweden)

    Lucia Palacios

    Full Text Available Galloyl catechins, in particular (--epicatechin gallate (ECg, have the capacity to abrogate β-lactam resistance in methicillin-resistant strains of Staphylococcus aureus (MRSA; they also prevent biofilm formation, reduce the secretion of a large proportion of the exoproteome and induce profound changes to cell morphology. Current evidence suggests that these reversible phenotypic traits result from their intercalation into the bacterial cytoplasmic membrane. We have endeavoured to potentiate the capacity of ECg to modify the MRSA phenotype by stepwise removal of hydroxyl groups from the B-ring pharmacophore and the A:C fused ring system of the naturally occurring molecule. ECg binds rapidly to the membrane, inducing up-regulation of genes responsible for protection against cell wall stress and maintenance of membrane integrity and function. Studies with artificial membranes modelled on the lipid composition of the staphylococcal bilayer indicated that ECg adopts a position deep within the lipid palisade, eliciting major alterations in the thermotropic behaviour of the bilayer. The non-galloylated homolog (--epicatechin enhanced ECg-mediated effects by facilitating entry of ECg molecules into the membrane. ECg analogs with unnatural B-ring hydroxylation patterns induced higher levels of gene expression and more profound changes to MRSA membrane fluidity than ECg but adopted a more superficial location within the bilayer. ECg possessed a high affinity for the positively charged staphylococcal membrane and induced changes to the biophysical properties of the bilayer that are likely to account for its capacity to disperse the cell wall biosynthetic machinery responsible for β-lactam resistance. The ability to enhance these properties by chemical modification of ECg raises the possibility that more potent analogs could be developed for clinical evaluation.

  4. Can galaxy clusters, type Ia supernovae and cosmic microwave background ruled out a class of modified gravity theories?

    CERN Document Server

    Holanda, R F L

    2016-01-01

    In this paper we study cosmological signatures of modified gravity theories that can be written as a coupling between a extra scalar field and the electromagnetic part of the usual Lagrangian for the matter fields. In these frameworks all the electromagnetic sector of the theory is affected and variations of fundamental constants, of the cosmic distance duality relation and of the evolution law of the cosmic microwave background radiation (CMB) are expected and are related each other. In order to search these variations we perform jointly analyses with angular diameter distances of galaxy clusters, luminosity distances of type Ia supernovae and $T_{CMB}(z)$ measurements. We obtain tight constraints with no indication of violation of the standard framework.

  5. Production of a Marfan cellular phenotype by expressing a mutant human fibrillin allele on a normal human or murine genetic background

    Energy Technology Data Exchange (ETDEWEB)

    Eldadah, Z.A.; Dietz, H.C. [Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States); Brenn, T. [Stanford Univ. Medical Center, CA (United States)] [and others

    1994-09-01

    The Marfan Syndrome (MFS) is a heritable disorder of connective tissue caused by defects in fibrillin (FBN1), a 350 kD glycoprotein and principal component of the extracellular microfibril. Previous correlations of mutant transcript level and disease severity suggested a dominant negative model of MFS pathogenesis. To address this hypothesis we assembled an expression construct containing the mutant allele from a patient with severe MFS. This mutation causes skipping of FBN1 exon 2 and a frame shift, leading to a premature termination codon in exon 4. The predicted peptide would thus consist of 55 wild type and 45 missense amino acids. The construct was stably transfected into cultured human and mouse fibroblasts, and several clonal cell populations were established. Human and mouse cells expressing the truncated peptide exhibited markedly diminished fibrillin deposition and disorganized microfibrillar architecture by immunofluorescence. Pulse-chase analysis of these cells demonstrated normal levels of fibrillin synthesis but substantially decreased fibrillin deposition into the extracellular matrix. These data illustrate that expression of a mutant FBN1 allele, on a background of two normal alleles, is sufficient to disrupt normal fibrillin aggregation and reproduce the MFS cellular phenotype. This provides confirmation of a dominant negative model of MFS pathogenesis and may offer mutant allele knockout as a strategy for gene therapy. In addition, these data underscore the importance of the FBN1 amino-terminus in normal multimer formation and suggest that expression of the human extreme 5{prime} FBN1 coding sequence may be sufficient, in isolation, to produce an animal model of MFS. Indeed, transgenic mice harboring this mutant allele have been produced, and phenotype analysis is currently in progress.

  6. 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

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

    Directory of Open Access Journals (Sweden)

    Mojca Simčič

    Full Text Available 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

  8. Humans, Fish, and Whales: How Right Whales Modify Calling Behavior in Response to Shifting Background Noise Conditions.

    Science.gov (United States)

    Parks, Susan E; Groch, Karina; Flores, Paulo; Sousa-Lima, Renata; Urazghildiiev, Ildar R

    2016-01-01

    This study investigates the role of behavioral plasticity in the variation of sound production of southern right whales (Eubalaena australis) in response to changes in the ambient background noise conditions. Data were collected from southern right whales in Brazilian waters in October and November 2011. The goal of this study was to quantify differences in right whale vocalizations recorded in low background noise as a control, fish chorus noise, and vessel noise. Variation in call parameters were detected among the three background noise conditions and have implications for future studies of noise effects on whale sound production.

  9. Humans, Fish, and Whales: How Right Whales Modify Calling Behavior in Response to Shifting Background Noise Conditions.

    Science.gov (United States)

    Parks, Susan E; Groch, Karina; Flores, Paulo; Sousa-Lima, Renata; Urazghildiiev, Ildar R

    2016-01-01

    This study investigates the role of behavioral plasticity in the variation of sound production of southern right whales (Eubalaena australis) in response to changes in the ambient background noise conditions. Data were collected from southern right whales in Brazilian waters in October and November 2011. The goal of this study was to quantify differences in right whale vocalizations recorded in low background noise as a control, fish chorus noise, and vessel noise. Variation in call parameters were detected among the three background noise conditions and have implications for future studies of noise effects on whale sound production. PMID:26611036

  10. Genetic background modulates behavioral impairments in R6/2 mice and suggests a role for dominant genetic modifiers in Huntington’s disease pathogenesis

    OpenAIRE

    Cowin, Randi-Michelle; Bui, Nghiem; Graham, Deanna; Green, Jennie R.; Yuva-Paylor, Lisa A.; Weiss, Andreas; Paylor, Richard

    2012-01-01

    Variability and modification of the symptoms of Huntington’s disease (HD) are commonly observed in both patient populations and animal models of the disease. Utilizing a stable line of the R6/2 HD mouse model, the present study investigated the role of genetic background in the onset and severity of HD symptoms in a transgenic mouse. R6/2 congenic C57BL/6J and C57BL/6J × DBA/2J F1 (B6D2F1) mice were evaluated for survival and a number of behavioral phenotypes. This study reports that the pres...

  11. A Screen for Modifiers of Cilia Phenotypes Reveals Novel MKS Alleles and Uncovers a Specific Genetic Interaction between osm-3 and nphp-4.

    Science.gov (United States)

    Masyukova, Svetlana V; Landis, Dawn E; Henke, Scott J; Williams, Corey L; Pieczynski, Jay N; Roszczynialski, Kelly N; Covington, Jannese E; Malarkey, Erik B; Yoder, Bradley K

    2016-02-01

    Nephronophthisis (NPHP) is a ciliopathy in which genetic modifiers may underlie the variable penetrance of clinical features. To identify modifiers, a screen was conducted on C. elegans nphp-4(tm925) mutants. Mutations in ten loci exacerbating nphp-4(tm925) ciliary defects were obtained. Four loci have been identified, three of which are established ciliopathy genes mks-1, mks-2, and mks-5. The fourth allele (yhw66) is a missense mutation (S316F) in OSM-3, a kinesin required for cilia distal segment assembly. While osm-3(yhw66) mutants alone have no overt cilia phenotype, nphp-4(tm925);osm-3(yhw66) double mutants lack distal segments and are dye-filling (Dyf) and osmotic avoidance (Osm) defective, similar to osm-3(mn357) null mutants. In osm-3(yhw66) mutants anterograde intraflagellar transport (IFT) velocity is reduced. Furthermore, expression of OSM-3(S316F)::GFP reduced IFT velocities in nphp-4(tm925) mutants, but not in wild type animals. In silico analysis indicates the S316F mutation may affect a phosphorylation site. Putative phospho-null OSM-3(S316F) and phospho-mimetic OSM-3(S316D) proteins accumulate at the cilia base and tip respectively. FRAP analysis indicates that the cilia entry rate of OSM-3(S316F) is slower than OSM-3 and that in the presence of OSM-3(S316F), OSM-3 and OSM-3(S316D) rates decrease. In the presence OSM-3::GFP or OSM-3(S316D)::GFP, OSM-3(S316F)::tdTomato redistributes along the cilium and accumulates in the cilia tip. OSM-3(S316F) and OSM-3(S316D) are functional as they restore cilia distal segment formation in osm-3(mn357) null mutants; however, only OSM-3(S316F) rescues the osm-3(mn357) null Dyf phenotype. Despite rescue of cilia length in osm-3(mn357) null mutants, neither OSM-3(S316F) nor OSM-3(S316D) restores ciliary defects in nphp-4(tm925);osm-3(yhw66) double mutants. Thus, these OSM-3 mutations cause NPHP-4 dependent and independent phenotypes. These data indicate that in addition to regulating cilia protein entry or exit

  12. A Screen for Modifiers of Cilia Phenotypes Reveals Novel MKS Alleles and Uncovers a Specific Genetic Interaction between osm-3 and nphp-4.

    Directory of Open Access Journals (Sweden)

    Svetlana V Masyukova

    2016-02-01

    Full Text Available Nephronophthisis (NPHP is a ciliopathy in which genetic modifiers may underlie the variable penetrance of clinical features. To identify modifiers, a screen was conducted on C. elegans nphp-4(tm925 mutants. Mutations in ten loci exacerbating nphp-4(tm925 ciliary defects were obtained. Four loci have been identified, three of which are established ciliopathy genes mks-1, mks-2, and mks-5. The fourth allele (yhw66 is a missense mutation (S316F in OSM-3, a kinesin required for cilia distal segment assembly. While osm-3(yhw66 mutants alone have no overt cilia phenotype, nphp-4(tm925;osm-3(yhw66 double mutants lack distal segments and are dye-filling (Dyf and osmotic avoidance (Osm defective, similar to osm-3(mn357 null mutants. In osm-3(yhw66 mutants anterograde intraflagellar transport (IFT velocity is reduced. Furthermore, expression of OSM-3(S316F::GFP reduced IFT velocities in nphp-4(tm925 mutants, but not in wild type animals. In silico analysis indicates the S316F mutation may affect a phosphorylation site. Putative phospho-null OSM-3(S316F and phospho-mimetic OSM-3(S316D proteins accumulate at the cilia base and tip respectively. FRAP analysis indicates that the cilia entry rate of OSM-3(S316F is slower than OSM-3 and that in the presence of OSM-3(S316F, OSM-3 and OSM-3(S316D rates decrease. In the presence OSM-3::GFP or OSM-3(S316D::GFP, OSM-3(S316F::tdTomato redistributes along the cilium and accumulates in the cilia tip. OSM-3(S316F and OSM-3(S316D are functional as they restore cilia distal segment formation in osm-3(mn357 null mutants; however, only OSM-3(S316F rescues the osm-3(mn357 null Dyf phenotype. Despite rescue of cilia length in osm-3(mn357 null mutants, neither OSM-3(S316F nor OSM-3(S316D restores ciliary defects in nphp-4(tm925;osm-3(yhw66 double mutants. Thus, these OSM-3 mutations cause NPHP-4 dependent and independent phenotypes. These data indicate that in addition to regulating cilia protein entry or exit, NPHP-4

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Genetic background strongly modifies the severity of symptoms of Hirschsprung disease, but not hearing loss in rats carrying Ednrb(sl mutations.

    Directory of Open Access Journals (Sweden)

    Ruihua Dang

    Full Text Available Hirschsprung disease (HSCR is thought to result as a consequence of multiple gene interactions that modulate the ability of enteric neural crest cells to populate the developing gut. However, it remains unknown whether the single complete deletion of important HSCR-associated genes is sufficient to result in HSCR disease. In this study, we found that the null mutation of the Ednrb gene, thought indispensable for enteric neuron development, is insufficient to result in HSCR disease when bred onto a different genetic background in rats carrying Ednrb(sl mutations. Moreover, we found that this mutation results in serious congenital sensorineural deafness, and these strains may be used as ideal models of Waardenburg Syndrome Type 4 (WS4. Furthermore, we evaluated how the same changed genetic background modifies three features of WS4 syndrome, aganglionosis, hearing loss, and pigment disorder in these congenic strains. We found that the same genetic background markedly changed the aganglionosis, but resulted in only slight changes to hearing loss and pigment disorder. This provided the important evidence, in support of previous studies, that different lineages of neural crest-derived cells migrating along with various pathways are regulated by different signal molecules. This study will help us to better understand complicated diseases such as HSCR and WS4 syndrome.

  15. Levels of alpha-toxin correlate with distinct phenotypic response profiles of blood mononuclear cells and with agr background of community-associated Staphylococcus aureus isolates.

    Science.gov (United States)

    Mairpady Shambat, Srikanth; Haggar, Axana; Vandenesch, Francois; Lina, Gerard; van Wamel, Willem J B; Arakere, Gayathri; Svensson, Mattias; Norrby-Teglund, Anna

    2014-01-01

    Epidemiological studies of Staphylococcus aureus have shown a relation between certain clones and the presence of specific virulence genes, but how this translates into virulence-associated functional responses is not fully elucidated. Here we addressed this issue by analyses of community-acquired S. aureus strains characterized with respect to antibiotic resistance, ST types, agr types, and virulence gene profiles. Supernatants containing exotoxins were prepared from overnight bacterial cultures, and tested in proliferation assays using human peripheral blood mononuclear cells (PBMC). The strains displayed stable phenotypic response profiles, defined by either a proliferative or cytotoxic response. Although, virtually all strains elicited superantigen-mediated proliferative responses, the strains with a cytotoxic profile induced proliferation only in cultures with the most diluted supernatants. This indicated that the superantigen-response was masked by a cytotoxic effect which was also confirmed by flow cytometry analysis. The cytotoxic supernatants contained significantly higher levels of α-toxin than did the proliferative supernatants. Addition of α-toxin to supernatants characterized as proliferative switched the response into cytotoxic profiles. In contrast, no effect of Panton Valentine Leukocidin, δ-toxin or phenol soluble modulin α-3 was noted in the proliferative assay. Furthermore, a significant association between agr type and phenotypic profile was found, where agrII and agrIII strains had predominantly a proliferative profile whereas agrI and IV strains had a predominantly cytotoxic profile. The differential response profiles associated with specific S. aureus strains with varying toxin production could possibly have an impact on disease manifestations, and as such may reflect specific pathotypes.

  16. Randomly detected genetically modified (GM maize (Zea mays L. near a transport route revealed a fragile 45S rDNA phenotype.

    Directory of Open Access Journals (Sweden)

    Nomar Espinosa Waminal

    Full Text Available Monitoring of genetically modified (GM crops has been emphasized to prevent their potential effects on the environment and human health. Monitoring of the inadvertent dispersal of transgenic maize in several fields and transport routes in Korea was carried out by qualitative multiplex PCR, and molecular analyses were conducted to identify the events of the collected GM maize. Cytogenetic investigations through fluorescence in situ hybridization (FISH of the GM maize were performed to check for possible changes in the 45S rDNA cluster because this cluster was reported to be sensitive to replication and transcription stress. Three GM maize kernels were collected from a transport route near Incheon port, Korea, and each was found to contain NK603, stacked MON863 x NK603, and stacked NK603 x MON810 inserts, respectively. Cytogenetic analysis of the GM maize containing the stacked NK603 x MON810 insert revealed two normal compact 5S rDNA signals, but the 45S rDNA showed a fragile phenotype, demonstrating a "beads-on-a-string" fragmentation pattern, which seems to be a consequence of genetic modification. Implications of the 45S rDNA cluster fragility in GM maize are also discussed.

  17. 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.

  18. Histopathology reveals correlative and unique phenotypes in a high-throughput mouse phenotyping screen

    Directory of Open Access Journals (Sweden)

    Hibret A. Adissu

    2014-05-01

    Full Text Available The Mouse Genetics Project (MGP at the Wellcome Trust Sanger Institute aims to generate and phenotype over 800 genetically modified mouse lines over the next 5 years to gain a better understanding of mammalian gene function and provide an invaluable resource to the scientific community for follow-up studies. Phenotyping includes the generation of a standardized biobank of paraffin-embedded tissues for each mouse line, but histopathology is not routinely performed. In collaboration with the Pathology Core of the Centre for Modeling Human Disease (CMHD we report the utility of histopathology in a high-throughput primary phenotyping screen. Histopathology was assessed in an unbiased selection of 50 mouse lines with (n=30 or without (n=20 clinical phenotypes detected by the standard MGP primary phenotyping screen. Our findings revealed that histopathology added correlating morphological data in 19 of 30 lines (63.3% in which the primary screen detected a phenotype. In addition, seven of the 50 lines (14% presented significant histopathology findings that were not associated with or predicted by the standard primary screen. Three of these seven lines had no clinical phenotype detected by the standard primary screen. Incidental and strain-associated background lesions were present in all mutant lines with good concordance to wild-type controls. These findings demonstrate the complementary and unique contribution of histopathology to high-throughput primary phenotyping of mutant mice.

  19. Histopathology reveals correlative and unique phenotypes in a high-throughput mouse phenotyping screen.

    Science.gov (United States)

    Adissu, Hibret A; Estabel, Jeanne; Sunter, David; Tuck, Elizabeth; Hooks, Yvette; Carragher, Damian M; Clarke, Kay; Karp, Natasha A; Newbigging, Susan; Jones, Nora; Morikawa, Lily; White, Jacqueline K; McKerlie, Colin

    2014-05-01

    The Mouse Genetics Project (MGP) at the Wellcome Trust Sanger Institute aims to generate and phenotype over 800 genetically modified mouse lines over the next 5 years to gain a better understanding of mammalian gene function and provide an invaluable resource to the scientific community for follow-up studies. Phenotyping includes the generation of a standardized biobank of paraffin-embedded tissues for each mouse line, but histopathology is not routinely performed. In collaboration with the Pathology Core of the Centre for Modeling Human Disease (CMHD) we report the utility of histopathology in a high-throughput primary phenotyping screen. Histopathology was assessed in an unbiased selection of 50 mouse lines with (n=30) or without (n=20) clinical phenotypes detected by the standard MGP primary phenotyping screen. Our findings revealed that histopathology added correlating morphological data in 19 of 30 lines (63.3%) in which the primary screen detected a phenotype. In addition, seven of the 50 lines (14%) presented significant histopathology findings that were not associated with or predicted by the standard primary screen. Three of these seven lines had no clinical phenotype detected by the standard primary screen. Incidental and strain-associated background lesions were present in all mutant lines with good concordance to wild-type controls. These findings demonstrate the complementary and unique contribution of histopathology to high-throughput primary phenotyping of mutant mice.

  20. 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.

  1. Associations of allergic sensitization and clinical phenotypes with innate immune response genes polymorphisms are modified by house dust mite allergen exposure

    OpenAIRE

    Kurowski, Marcin; Majkowska-Wojciechowska, Barbara; Wardzyńska, Aleksandra; Kowalski, Marek L

    2011-01-01

    Introduction Polymorphisms within innate immunity genes are associated with allergic phenotypes but results are variable. These associations were not analyzed with respect to allergen exposure. We investigated associations of TLR and CD14 polymorphisms with allergy phenotypes in the context of house dust mite (HDM) exposure. Material and methods Children, aged 12-16 years (n=326), were recruited from downtown and rural locations and assessed by allergist. Skin prick tests, total and HDM-speci...

  2. Neonatal transplantation tolerance is associated with a systemic reduction in memory cells, altered chimeric cell phenotype, and modified eicosanoid and cytokine production.

    Science.gov (United States)

    Ruiz, P; Nassiri, M; Gregorian, S; Viciana, A L; Streilein, J W

    1996-04-27

    Certain B10 background mice are resistant to tolerance induction following a neonatal inoculation of semiallogeneic class I/II MHC-disparate cells despite early thymic clonal deletion of alloreactive cells. The emergence of memory T cells and persistence of particular chimeric cells in the thymus has an association with this resistance. In these studies, we utilized a hemisplenectomy technique to examine systemic cell populations of adult Bl0.S (H2s, H2E-) mice that received (Bl0.S x B10.A)F1 cells at birth and before and following application (and rejection or acceptance) of Bl0.A (H2k/d, H2E+) skin grafts. Prior to skin graft challenge, tolerant mice had reduced splenic levels of memory (CD45hi, PgP-1hi, Mel-14neg) T cells as compared with the rejecting recipients and following B10.A graft challenge, the nontolerant mice showed a further increase in these cells. Elevated pretransplant levels of donor H2Kk+ cells coexpressing B220, CD11b, or CD3 were seen in the tolerant mice. Following skin grafting, splenic chimerism was reduced with differing chimeric cell phenotypes between the tolerant and nontolerant mice. In vitro production of PGE2 in a MLC was delayed in the tolerant mice with minimal production of IL-2 and IL-4. Nontolerant mice made high levels of TxB2 and heightened, early production of IL-2 and IL-4 during the MLC. Thus, tolerance induction is associated with increased numbers of particular chimeric cells, fewer peripheral lymphoid immunocompetant memory T cells, impaired eicosanoid secretion, and reduced alloreactivity and alloantigen-driven IL-2/IL-4 production. It appears that alloreactive cells necessary to break tolerance are generated when fewer class II+ (e.g., B220+, CD11b+) chimeric cells are present and that there is a coexistence of effector and regulatory T cell subpopulations in the nontolerant mice. By comparison, tolerance acquisition does not appear associated with the presence or generation of a predominant subtype of T cell but

  3. Comparison of palladium chemical modifiers for the determination of selenium in plasma by Zeeman-effect background corrected electrothermal atomic absorption spectrometry

    DEFF Research Database (Denmark)

    Gammelgaard, Bente; Jons, O.

    1997-01-01

    , It was not possible to stabilize trimethylselenonium to the same extent with this modifier, Peak shapes and appearance times of the atomization signals were equal for the four selenium species with this modifier, The addition of 20 mu g of palladium was used for the analysis of the serum reference material Seronorm...

  4. Real-time detection of cofactor availability in genetically modified living Saccharomyces cerevisiae cells - Simultaneous probing of different geno- and phenotypes

    DEFF Research Database (Denmark)

    Kostesha, Natalie; Heiskanen, Arto; Spegel, C.;

    2009-01-01

    This work describes a mediated amperometric method for simultaneous real-time probing of the NAD(P)H availability in two different phenotypes, fermentative and respiratory, of the phosphoglucose isomerase deletion mutant strain of S. cerevisiae. EBY44 [ENY.WA-1A pgi1-1D::URA3], and its parental s...

  5. Human TRMU encoding the mitochondrial 5-methylaminomethyl-2-thiouridylate-methyltransferase is a putative nuclear modifier gene for the phenotypic expression of the deafness-associated 12S rRNA mutations

    International Nuclear Information System (INIS)

    Nuclear modifier genes have been proposed to modulate the phenotypic manifestation of human mitochondrial 12S rRNA A1491G mutation associated with deafness in many families world-wide. Here we identified and characterized the putative nuclear modifier gene TRMU encoding a highly conserved mitochondrial protein related to tRNA modification. A 1937 bp TRMU cDNA has been isolated and the genomic organization of TRMU has been elucidated. The human TRMU gene containing 11 exons encodes a 421 residue protein with a strong homology to the TRMU-like proteins of bacteria and other homologs. TRMU is ubiquitously expressed in various tissues, but abundantly in tissues with high metabolic rates including heart, liver, kidney, and brain. Immunofluorescence analysis of human 143B cells expressing TRMU-GFP fusion protein demonstrated that the human Trmu localizes and functions in mitochondrion. Furthermore, we show that in families with the deafness-associated 12S rRNA A1491G mutation there is highly suggestive linkage and linkage disequilibrium between microsatellite markers adjacent to TRMU and the presence of deafness. These observations suggest that human TRMU may modulate the phenotypic manifestation of the deafness-associated mitochondrial 12S rRNA mutations

  6. A Screen for Modifiers of Cilia Phenotypes Reveals Novel MKS Alleles and Uncovers a Specific Genetic Interaction between osm-3 and nphp-4

    OpenAIRE

    Masyukova, Svetlana V.; Dawn E Landis; Henke, Scott J.; Williams, Corey L.; Pieczynski, Jay N.; Roszczynialski, Kelly N.; Jannese E Covington; Malarkey, Erik B.; Yoder, Bradley K.

    2016-01-01

    Nephronophthisis (NPHP) is a ciliopathy in which genetic modifiers may underlie the variable penetrance of clinical features. To identify modifiers, a screen was conducted on C. elegans nphp-4(tm925) mutants. Mutations in ten loci exacerbating nphp-4(tm925) ciliary defects were obtained. Four loci have been identified, three of which are established ciliopathy genes mks-1, mks-2, and mks-5. The fourth allele (yhw66) is a missense mutation (S316F) in OSM-3, a kinesin required for cilia distal ...

  7. Elevated paternal glucocorticoid exposure alters the small noncoding RNA profile in sperm and modifies anxiety and depressive phenotypes in the offspring.

    Science.gov (United States)

    Short, A K; Fennell, K A; Perreau, V M; Fox, A; O'Bryan, M K; Kim, J H; Bredy, T W; Pang, T Y; Hannan, A J

    2016-01-01

    Recent studies have suggested that physiological and behavioral traits may be transgenerationally inherited through the paternal lineage, possibly via non-genomic signals derived from the sperm. To investigate how paternal stress might influence offspring behavioral phenotypes, a model of hypothalamic-pituitary-adrenal (HPA) axis dysregulation was used. Male breeders were administered water supplemented with corticosterone (CORT) for 4 weeks before mating with untreated female mice. Female, but not male, F1 offspring of CORT-treated fathers displayed altered fear extinction at 2 weeks of age. Only male F1 offspring exhibited altered patterns of ultrasonic vocalization at postnatal day 3 and, as adults, showed decreased time in open on the elevated-plus maze and time in light on the light-dark apparatus, suggesting a hyperanxiety-like behavioral phenotype due to paternal CORT treatment. Interestingly, expression of the paternally imprinted gene Igf2 was increased in the hippocampus of F1 male offspring but downregulated in female offspring. Male and female F2 offspring displayed increased time spent in the open arm of the elevated-plus maze, suggesting lower levels of anxiety compared with control animals. Only male F2 offspring showed increased immobility time on the forced-swim test and increased latency to feed on the novelty-supressed feeding test, suggesting a depression-like phenotype in these animals. Collectively, these data provide evidence that paternal CORT treatment alters anxiety and depression-related behaviors across multiple generations. Analysis of the small RNA profile in sperm from CORT-treated males revealed marked effects on the expression of small noncoding RNAs. Sperm from CORT-treated males contained elevated levels of three microRNAs, miR-98, miR-144 and miR-190b, which are predicted to interact with multiple growth factors, including Igf2 and Bdnf. Sustained elevation of glucocorticoids is therefore involved in the transmission of paternal

  8. The exome sequencing identified the mutation in YARS2 encoding the mitochondrial tyrosyl-tRNA synthetase as a nuclear modifier for the phenotypic manifestation of Leber's hereditary optic neuropathy-associated mitochondrial DNA mutation.

    Science.gov (United States)

    Jiang, Pingping; Jin, Xiaofen; Peng, Yanyan; Wang, Meng; Liu, Hao; Liu, Xiaoling; Zhang, Zengjun; Ji, Yanchun; Zhang, Juanjuan; Liang, Min; Zhao, Fuxin; Sun, Yan-Hong; Zhang, Minglian; Zhou, Xiangtian; Chen, Ye; Mo, Jun Qin; Huang, Taosheng; Qu, Jia; Guan, Min-Xin

    2016-02-01

    Leber's hereditary optic neuropathy (LHON) is the most common mitochondrial disorder. Nuclear modifier genes are proposed to modify the phenotypic expression of LHON-associated mitochondrial DNA (mtDNA) mutations. By using an exome sequencing approach, we identified a LHON susceptibility allele (c.572G>T, p.191Gly>Val) in YARS2 gene encoding mitochondrial tyrosyl-tRNA synthetase, which interacts with m.11778G>A mutation to cause visual failure. We performed functional assays by using lymphoblastoid cell lines derived from members of Chinese families (asymptomatic individuals carrying m.11778G>A mutation, or both m.11778G>A and heterozygous p.191Gly>Val mutations and symptomatic subjects harboring m.11778G>A and homozygous p.191Gly>Val mutations) and controls lacking these mutations. The 191Gly>Val mutation reduced the YARS2 protein level in the mutant cells. The aminoacylated efficiency and steady-state level of tRNA(Tyr) were markedly decreased in the cell lines derived from patients both carrying homozygous YARS2 p.191Gly>Val and m.11778G>A mutations. The failure in tRNA(Tyr) metabolism impaired mitochondrial translation, especially for polypeptides with high content of tyrosine codon such as ND4, ND5, ND6 and COX2 in cells lines carrying homozygous YARS2 p.191Gly>Val and m.11778G>A mutations. The YARS2 p.191Gly>Val mutation worsened the respiratory phenotypes associated with m.11778G>A mutation, especially reducing activities of complexes I and IV. The respiratory deficiency altered the efficiency of mitochondrial ATP synthesis and increased the production of reactive oxygen species. Thus, mutated YARS2 aggravates mitochondrial dysfunctions associated with the m.11778G>A mutation, exceeding the threshold for the expression of blindness phenotype. Our findings provided new insights into the pathophysiology of LHON that were manifested by interaction between mtDNA mutation and mutated nuclear-modifier YARS2. PMID:26647310

  9. The exome sequencing identified the mutation in YARS2 encoding the mitochondrial tyrosyl-tRNA synthetase as a nuclear modifier for the phenotypic manifestation of Leber's hereditary optic neuropathy-associated mitochondrial DNA mutation.

    Science.gov (United States)

    Jiang, Pingping; Jin, Xiaofen; Peng, Yanyan; Wang, Meng; Liu, Hao; Liu, Xiaoling; Zhang, Zengjun; Ji, Yanchun; Zhang, Juanjuan; Liang, Min; Zhao, Fuxin; Sun, Yan-Hong; Zhang, Minglian; Zhou, Xiangtian; Chen, Ye; Mo, Jun Qin; Huang, Taosheng; Qu, Jia; Guan, Min-Xin

    2016-02-01

    Leber's hereditary optic neuropathy (LHON) is the most common mitochondrial disorder. Nuclear modifier genes are proposed to modify the phenotypic expression of LHON-associated mitochondrial DNA (mtDNA) mutations. By using an exome sequencing approach, we identified a LHON susceptibility allele (c.572G>T, p.191Gly>Val) in YARS2 gene encoding mitochondrial tyrosyl-tRNA synthetase, which interacts with m.11778G>A mutation to cause visual failure. We performed functional assays by using lymphoblastoid cell lines derived from members of Chinese families (asymptomatic individuals carrying m.11778G>A mutation, or both m.11778G>A and heterozygous p.191Gly>Val mutations and symptomatic subjects harboring m.11778G>A and homozygous p.191Gly>Val mutations) and controls lacking these mutations. The 191Gly>Val mutation reduced the YARS2 protein level in the mutant cells. The aminoacylated efficiency and steady-state level of tRNA(Tyr) were markedly decreased in the cell lines derived from patients both carrying homozygous YARS2 p.191Gly>Val and m.11778G>A mutations. The failure in tRNA(Tyr) metabolism impaired mitochondrial translation, especially for polypeptides with high content of tyrosine codon such as ND4, ND5, ND6 and COX2 in cells lines carrying homozygous YARS2 p.191Gly>Val and m.11778G>A mutations. The YARS2 p.191Gly>Val mutation worsened the respiratory phenotypes associated with m.11778G>A mutation, especially reducing activities of complexes I and IV. The respiratory deficiency altered the efficiency of mitochondrial ATP synthesis and increased the production of reactive oxygen species. Thus, mutated YARS2 aggravates mitochondrial dysfunctions associated with the m.11778G>A mutation, exceeding the threshold for the expression of blindness phenotype. Our findings provided new insights into the pathophysiology of LHON that were manifested by interaction between mtDNA mutation and mutated nuclear-modifier YARS2.

  10. A sensitized mutagenesis screen identifies Gli3 as a modifier of Sox10 neurocristopathy

    OpenAIRE

    Matera, Ivana; Watkins-Chow, Dawn E.; Loftus, Stacie K.; Hou, Ling; Incao, Arturo; Silver, Debra L.; Rivas, Cecelia; Elliott, Eugene C.; Baxter, Laura L.; Pavan, William J.

    2008-01-01

    Haploinsufficiency for the transcription factor SOX10 is associated with the pigmentary deficiencies of Waardenburg syndrome (WS) and is modeled in Sox10 haploinsufficient mice (Sox10LacZ/+). As genetic background affects WS severity in both humans and mice, we established an N-ethyl-N-nitrosourea (ENU) mutagenesis screen to identify modifiers that increase the phenotypic severity of Sox10LacZ/+ mice. Analysis of 230 pedigrees identified three modifiers, named modifier of Sox10 neurocristopat...

  11. Hereditary hemochromatosis type 1 phenotype modifiers in Italian patients. The controversial role of variants in HAMP, BMP2, FTL and SLC40A1 genes.

    Science.gov (United States)

    Radio, Francesca Clementina; Majore, Silvia; Aurizi, Caterina; Sorge, Fiammetta; Biolcati, Gianfranco; Bernabini, Sara; Giotti, Irene; Torricelli, Francesca; Giannarelli, Diana; De Bernardo, Carmelilia; Grammatico, Paola

    2015-06-01

    Hereditary hemochromatosis (HH) is a heterogeneous disorder of iron metabolism. The most common form of the disease is Classic or type 1 HH, mainly caused by a biallelic missense p.Cys282Tyr (c.845G>A) mutation in the HFE gene. However, the penetrance of p.Cys282Tyr/p.Cys282Tyr genotype is incomplete in terms of both biochemical and clinical expressivity. Lack of penetrance is thought to be caused by several genetic and environmental factors. Recently, a lot of evidences on HH genetic modifiers were produced, often without conclusive results. We investigated 6 polymorphisms (rs10421768 in HAMP gene, rs235756 in BMP2 gene, rs2230267 in FTL gene, rs1439816 in SLC40A1 gene, rs41295942 in TFR2 gene and rs2111833 in TMPRSS6 gene) with uncertain function in order to further evaluate their role in an independent cohort of 109 HH type 1 patients. Our results make it likely the role of rs10421768, rs235756, rs2230267 and rs1439816 polymorphisms, respectively in HAMP, BMP2, FTL and SLC40A1 genes in HH expressivity. In addition, previous and our findings support a hypothetical multifactorial model of HH, characterized by a principal gene (HFE in HH type 1) and minor genetic and environmental factors that still have to be fully elucidated.

  12. 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....

  13. Modifier factors influencing the phenotypic manifestation of the deafness-associated mitochondrial DNA mutations%修饰因子对线粒体DNA突变致聋的影响

    Institute of Scientific and Technical Information of China (English)

    杨爱芬; 郑静; 吕建新; 管敏鑫

    2011-01-01

    Mutations in the mitochondrial DNA have been found to be one of the most important causes of sensorineural hearing loss. In particular, these mutations often occur in the mitochondrial 12S rRNA and tRNA genes. Of these, the homoplasmic A1555G and C1494T mutations in the 12S rRNA have been associated with both aminoglycoside induced and nonsyndromic hearing impairment in many families worldwide. Children carrying the A1555G or C1494T mutation are susceptible to the exposure of ototoxic drugs, thereby inducing or worsening hearing loss. Individuals harboring A1555G or C1494T mutation can also develop hearing loss even in the absence of aminoglycoside exposure. However, matrilineal relatives of intra-families or inter-families carrying the A1555G or C1494T mutation exhibit a wide range of severity,age-at-onset, and audiometric configuration of hearing impairment. These indicate that the A1555G or C1494T mutation is a primary factor underlying the development of deafness but insufficient to produce the clinical phenotype. Thus, other modifier factors, such as aminoglycoside (s), mitochondrial DNA haplotype(s) or nuclear modifier gene(s), play a role in the phenotypic expression of the deafness-associated mitochondrial 12S rRNA A1555G or C1494T mutation. In this review, we summarize the modifier factors for the phenotypic expression of deafness-associated 12S rRNA A1555G and C1494T mutations and propose the molecular pathogenetic mechanism of maternally inherited deafness.%线粒体DNA突变是引起感音神经性耳聋的重要原因之一,这些突变主要位于线粒体12SrRNA和tRNA基因上.其中12S rRNA基因上的同质性A1555G和C1494T突变与氨基糖甙类抗生素造成的耳聋相关.携带这两个突变的个体对耳毒性药物高度敏感,导致临床上常见的"一针致聋"现象.但携带A1555G或C1494T突变的个体在没用药的情况下也能产生非综合征型耳聋,而且同一家系内和不同家系间的母系成员在听力损失

  14. Genetic modification of glaucoma associated phenotypes between AKXD-28/Ty and DBA/2J mice

    Directory of Open Access Journals (Sweden)

    Zabaleta Adriana

    2001-01-01

    Full Text Available Abstract Background Glaucoma is a common disease but its molecular etiology is poorly understood. It involves retinal ganglion cell death and optic nerve damage that is often associated with elevated intraocular pressure. Identifying genes that modify glaucoma associated phenotypes is likely to provide insights to mechanisms of glaucoma. We previously reported glaucoma in DBA/2J mice caused by recessive alleles at two loci, isa and ipd, that cause iris stromal atrophy and iris pigment dispersion, respectively. A approach for identifying modifier genes is to study the effects of specific mutations in different mouse strains. When the phenotypic effect of a mutation is modified upon its introduction into a new strain, crosses between the parental strains can be used to identify modifier genes. The purpose of this study was to determine if the effects of the DBA/2J derived isa and ipd loci are modified in strain AKXD-28/Ty. Results AKXD-28/Ty mice develop glaucoma characterized by intraocular pressure elevation, retinal ganglion loss, and optic nerve excavation. In AKXD-28/Ty, isa causes an iris stromal atrophy phenotype as in DBA/2J. However, the iris pigment dispersion phenotype associated with ipd in DBA/2J does not occur in AKXD-28/Ty. Additionally, a greater severity and speed of retinal and optic nerve damage following intraocular pressure elevation in AKXD-28/Ty compared to DBA/2J mice suggests that AKXD-28/Ty is more susceptible to pressure-induced cell death. Conclusions The consequences of the ipd and isa mutations are modified in the AKXD-28/Ty background. These strains provide a resource for the identification of modifier genes that modulate pigment dispersion and susceptibility to pressure-induced cell death.

  15. Human CD4-major histocompatibility complex class II (DQw6) transgenic mice in an endogenous CD4/CD8-deficient background: reconstitution of phenotype and human-restricted function

    OpenAIRE

    1994-01-01

    To reconstitute the human immune system in mice, transgenic mice expressing human CD4 and human major histocompatibility complex (MHC) class II (DQw6) molecules in an endogenous CD4- and CD8-deficient background (mCD4/8-/-), after homologous recombination, have been generated. We report that expression of human CD4 molecule in mCD4/8-/- mice rescues thymocyte development and completely restores the T cell compartment in peripheral lymphoid organs. Upon vesicular stomatitis virus (VSV) challen...

  16. Chromosomal phenotypes and submicroscopic abnormalities

    Directory of Open Access Journals (Sweden)

    Devriendt Koen

    2004-01-01

    Full Text Available Abstract The finding, during the last decade, that several common, clinically delineated syndromes are caused by submicroscopic deletions or, more rarely, by duplications, has provided a powerful tool in the annotation of the human genome. Since most microdeletion/microduplication syndromes are defined by a common deleted/duplicated region, abnormal dosage of genes located within these regions can explain the phenotypic similarities among individuals with a specific syndrome. As such, they provide a unique resource towards the genetic dissection of complex phenotypes such as congenital heart defects, mental and growth retardation and abnormal behaviour. In addition, the study of phenotypic differences in individuals with the same microdeletion syndrome may also become a treasury for the identification of modifying factors for complex phenotypes. The molecular analysis of these chromosomal anomalies has led to a growing understanding of their mechanisms of origin. Novel tools to uncover additional submicroscopic chromosomal anomalies at a higher resolution and higher speed, as well as the novel tools at hand for deciphering the modifying factors and epistatic interactors, are 'on the doorstep' and will, besides their obvious diagnostic role, play a pivotal role in the genetic dissection of complex phenotypes.

  17. Superoxide dismutase phenotypes in duodenal ulcers: A genetic marker?

    Directory of Open Access Journals (Sweden)

    Sulekha S

    2006-01-01

    Full Text Available Background:Cu-Zn superoxide dismutases are antioxidative defensive enzymes that catalyze the reduction of superoxide anions to hydrogen peroxide. Aim:The study focuses on the association of electromorph of superoxide dismutase with duodenal ulcers, which result due to an imbalance between aggressive and defensive factors. Materials and Methods:Endoscopically confirmed 210 duodenal ulcer patients and 185 healthy individuals for comparative analysis were considered for the present study. Phenotyping of superoxide dismutase was carried out by subjecting the RBC membranes to polyacrylamide gel electrophoresis, using appropriate staining protocols. Results:Statistical analysis of SOD phenotypes revealed a significant increase of SOD AFNx012 allele and Superoxide dismutases (SOD 2-2 phenotype in duodenal ulcer group. Among these individuals, a predominance of Helicobacter pylori infection was observed. The increased preponderance of homozygotes can be explained on the basis of reduced and altered enzyme activity, which may lead to disturbance in homeostasis of antioxidant/oxidant culminating in high lipid peroxidative gastric mucosal tissue damage and ulceration. No variation in the distribution of SOD phenotypes with respect to Helicobacter pylori indicates the role of Mn-SOD rather than Cu-Zn SOD in the Helicobacter pylori infected cases as reported earlier. Conclusions:Superoxide dismutase as a genetic marker / gene modifier, encoding for an antioxidant enzyme in maintaining tissue homeostasis of the gastric mucosa is discussed.

  18. Latent phenotypes pervade gene regulatory circuits.

    OpenAIRE

    Payne, Joshua L.; Wagner, Andreas

    2014-01-01

    BACKGROUND Latent phenotypes are non-adaptive byproducts of adaptive phenotypes. They exist in biological systems as different as promiscuous enzymes and genome-scale metabolic reaction networks, and can give rise to evolutionary adaptations and innovations. We know little about their prevalence in the gene expression phenotypes of regulatory circuits, important sources of evolutionary innovations. RESULTS Here, we study a space of more than sixteen million three-gene model regulatory circ...

  19. Latent phenotypes pervade gene regulatory circuits

    OpenAIRE

    Payne, Joshua L.; Wagner, Andreas

    2014-01-01

    Background Latent phenotypes are non-adaptive byproducts of adaptive phenotypes. They exist in biological systems as different as promiscuous enzymes and genome-scale metabolic reaction networks, and can give rise to evolutionary adaptations and innovations. We know little about their prevalence in the gene expression phenotypes of regulatory circuits, important sources of evolutionary innovations. Results Here, we study a space of more than sixteen million three-gene model regulatory circuit...

  20. Phenotypic plasticity can facilitate adaptive evolution in gene regulatory circuits

    OpenAIRE

    Martin Olivier C; Espinosa-Soto Carlos; Wagner Andreas

    2011-01-01

    Abstract Background Many important evolutionary adaptations originate in the modification of gene regulatory circuits to produce new gene activity phenotypes. How do evolving populations sift through an astronomical number of circuits to find circuits with new adaptive phenotypes? The answer may often involve phenotypic plasticity. Phenotypic plasticity allows a genotype to produce different - alternative - phenotypes after non-genetic perturbations that include gene expression noise, environ...

  1. Phenotypic plasticity can facilitate adaptive evolution in gene regulatory circuits

    OpenAIRE

    Espinosa-Soto, C.; Martin, O. C.; Wagner, A

    2011-01-01

    BACKGROUND: Many important evolutionary adaptations originate in the modification of gene regulatory circuits to produce new gene activity phenotypes. How do evolving populations sift through an astronomical number of circuits to find circuits with new adaptive phenotypes? The answer may often involve phenotypic plasticity. Phenotypic plasticity allows a genotype to produce different - alternative - phenotypes after non-genetic perturbations that include gene expression noise, environment...

  2. Myelin alters the inflammatory phenotype of macrophages by activating PPARs

    OpenAIRE

    Bogie, Jeroen; Jorissen, Winde; Mailleux, Jo; Vanmierlo, Tim; van Horssen, Jack; Hellings, Niels; Stinissen, Piet; Hendriks, J. J. A.; Nijland, Philip G.; Zelcer, Noam

    2013-01-01

    Background Foamy macrophages, containing myelin degradation products, are abundantly found in active multiple sclerosis (MS) lesions. Recent studies have described an altered phenotype of macrophages after myelin internalization. However, mechanisms by which myelin affects the phenotype of macrophages and how this phenotype influences lesion progression remain unclear. Results We demonstrate that myelin as well as phosphatidylserine (PS), a phospholipid found in myelin, reduce nitri...

  3. Phenotypic plasticity in the range-margin population of the lycaenid butterfly Zizeeria maha

    Directory of Open Access Journals (Sweden)

    Otaki Joji M

    2010-08-01

    Full Text Available Abstract Background Many butterfly species have been experiencing the northward range expansion and physiological adaptation, probably due to climate warming. Here, we document an extraordinary field case of a species of lycaenid butterfly, Zizeeria maha, for which plastic phenotypes of wing color-patterns were revealed at the population level in the course of range expansion. Furthermore, we examined whether this outbreak of phenotypic changes was able to be reproduced in a laboratory. Results In the recently expanded northern range margins of this species, more than 10% of the Z. maha population exhibited characteristic color-pattern modifications on the ventral wings for three years. We physiologically reproduced similar phenotypes by an artificial cold-shock treatment of a normal southern population, and furthermore, we genetically reproduced a similar phenotype after selective breeding of a normal population for ten generations, demonstrating that the cold-shock-induced phenotype was heritable and partially assimilated genetically in the breeding line. Similar genetic process might have occurred in the previous and recent range-margin populations as well. Relatively minor modifications expressed in the tenth generation of the breeding line together with other data suggest a role of founder effect in this field case. Conclusions Our results support the notion that the outbreak of the modified phenotypes in the recent range-margin population was primed by the revelation of plastic phenotypes in response to temperature stress and by the subsequent genetic process in the previous range-margin population, followed by migration and temporal establishment of genetically unstable founders in the recent range margins. This case presents not only an evolutionary role of phenotypic plasticity in the field but also a novel evolutionary aspect of range expansion at the species level.

  4. Microglia phenotype diversity

    NARCIS (Netherlands)

    Olah, M.; Biber, K.; Vinet, J.; Boddeke, H. W. G. M.

    2011-01-01

    Microglia, the tissue macrophages of the brain, have under healthy conditions a resting phenotype that is characterized by a ramified morphology. With their fine processes microglia are continuously scanning their environment. Upon any homeostatic disturbance microglia rapidly change their phenotype

  5. Fine Mapping of an Epilepsy Modifier Gene on Mouse Chromosome 19

    OpenAIRE

    Bergren, Sarah K.; Rutter, Elizabeth D.; Kearney, Jennifer A.

    2009-01-01

    Mutations in voltage-gated sodium channels are associated with several types of human epilepsy. Variable expressivity and penetrance are common features of inherited epilepsy caused by sodium channel mutations, suggesting that genetic modifiers may influence clinical severity. The mouse model Scn2aQ54 has an epilepsy phenotype due to a mutation in Scn2a that results in elevated persistent sodium current. Phenotype severity in Scn2aQ54 mice is dependent on the genetic background. Congenic C57B...

  6. Genetic background determines response to hemostasis and thrombosis

    Directory of Open Access Journals (Sweden)

    Hill Annie E

    2006-10-01

    thrombosis and haemostasis is remarkably different in C57BL/and A/J mice. Three A/J chromosome substitution strains were identified that expressed a phenotype similar to A/J for rebleeding, the C57Bl/6J background could modify the A/J phenotype, and the combination of two A/J QTL could restore the phenotype. The diverse genetic backgrounds and differences in response to vascular injury induced thrombosis and the tail bleeding assay, suggest the potential for identifying novel genetic determinants of thrombotic risk.

  7. Metabolomic phenotyping of af cloned pig model

    DEFF Research Database (Denmark)

    Clausen, Morten Rahr; Christensen, Kirstine Lykke; Hedemann, Mette Skou;

    2011-01-01

    Background Pigs are widely used as models for human physiological changes in intervention studies, because of the close resemblance between human and porcine physiology and the high degree of experimental control when using an animal model. Cloned animals have, in principle, identical genotypes...... and possibly also phenotypes and this offer an extra level of experimental control which could possibly make them a desirable tool for intervention studies. Therefore, in the present study, we address how phenotype and phenotypic variation is affected by cloning, through comparison of cloned pigs and normal...... outbred pigs. Results The metabolic phenotype of cloned pigs (n = 5) was for the first time elucidated by nuclear magnetic resonance (NMR)-based metabolomic analysis of multiple bio-fluids including plasma, bile and urine. The metabolic phenotype of the cloned pigs was compared with normal outbred pigs (n...

  8. A Regulatory RNA Inducing Transgenerationally Inherited Phenotypes

    DEFF Research Database (Denmark)

    Jensen, Lea Møller

    . The variation in Arabidopsis enables different regulatory networks and mechanisms to shape the phenotypic characteristics. The thesis describes the identification of regulatory RNA encoded by an enzyme encoding gene. The RNA regulates by inducing transgenerationally inherited phenotypes. The function of the RNA...... is dependent on the genetic background illustrating that polymorphisms are found in either interactors or target genes of the RNA. Furthermore, the RNA provides a mechanistic link between accumulation of glucosinolate and onset of flowering....

  9. Color change, phenotypic plasticity, and camouflage

    Directory of Open Access Journals (Sweden)

    Martin eStevens

    2016-05-01

    Full Text Available The ability to change appearance over a range of timescales is widespread in nature, existing in many invertebrate and vertebrate groups. This can include color change occurring in seconds, minutes, and hours, to longer term changes associated with phenotypic plasticity and development. A major function is for camouflage against predators because color change and plasticity enables animals to match their surroundings and potentially reduce the risk of predation. Recently, we published findings (Stevens et al. 2014a showing how shore crabs can change their appearance and better match the background to predator vision in the short term. This, coupled with a number of past studies, emphasizes the potential that animals have to modify their appearance for camouflage. However, the majority of studies on camouflage and color plasticity have focused on a small number of species capable of unusually rapid changes. There are many broad questions that remain about the nature, mechanisms, evolution, and adaptive value of color change and plasticity for concealment. Here, I discuss past work and outline six questions relating to color change and plasticity, as well as major avenues for future work.

  10. Large phenotype jumps in biomolecular evolution

    CERN Document Server

    Bardou, F

    2003-01-01

    By defining the phenotype of a biopolymer by its active three-dimensional shape, and its genotype by its primary sequence, we propose a model that predicts and characterizes the statistical distribution of a population of biopolymers with a specific phenotype, that originated from a given genotypic sequence by a single mutational event. Depending on the ratio g0 that characterizes the spread of potential energies of the mutated population with respect to temperature, three different statistical regimes have been identified. We suggest that biopolymers found in nature are in a critical regime with g0 in the range 1-6, corresponding to a broad, but not too broad, phenotypic distribution resembling a truncated Levy flight. Thus the biopolymer phenotype can be considerably modified in just a few mutations.

  11. Hanford Site background: Part 3, Groundwater background

    International Nuclear Information System (INIS)

    This report presents and interprets groundwater background data collected from the unconfined aquifer beneath the Hanford Site, a U.S. Department of Energy complex located near Richland, Washington. Characterization of background composition is an important component of environmental characterization activities and serves as a basis for distinguishing the presence and significance of contamination. Background data can also be used to assess the levels of baseline risk to which humans or other receptors are typically exposed and to establish remediation goals. Evaluating background on a sitewide basis provides a consistent, technically defensible definition of background as opposed to determining area-specific background compositions for each waste management unit being considered for remediation across the Hanford Site

  12. Determining Which Phenotypes Underlie a Pleiotropic Signal.

    Science.gov (United States)

    Majumdar, Arunabha; Haldar, Tanushree; Witte, John S

    2016-07-01

    Discovering pleiotropic loci is important to understand the biological basis of seemingly distinct phenotypes. Most methods for assessing pleiotropy only test for the overall association between genetic variants and multiple phenotypes. To determine which specific traits are pleiotropic, we evaluate via simulation and application three different strategies. The first is model selection techniques based on the inverse regression of genotype on phenotypes. The second is a subset-based meta analysis ASSET [Bhattacharjee et al., ], which provides an optimal subset of nonnull traits. And the third is a modified Benjamini-Hochberg (B-H) procedure of controlling the expected false discovery rate [Benjamini and Hochberg, ] in the framework of phenome-wide association study. From our simulations we see that an inverse regression-based approach MultiPhen [O'Reilly et al., ] is more powerful than ASSET for detecting overall pleiotropic association, except for when all the phenotypes are associated and have genetic effects in the same direction. For determining which specific traits are pleiotropic, the modified B-H procedure performs consistently better than the other two methods. The inverse regression-based selection methods perform competitively with the modified B-H procedure only when the phenotypes are weakly correlated. The efficiency of ASSET is observed to lie below and in between the efficiency of the other two methods when the traits are weakly and strongly correlated, respectively. In our application to a large GWAS, we find that the modified B-H procedure also performs well, indicating that this may be an optimal approach for determining the traits underlying a pleiotropic signal. PMID:27238845

  13. Phenotype definition in epilepsy.

    Science.gov (United States)

    Winawer, Melodie R

    2006-05-01

    Phenotype definition consists of the use of epidemiologic, biological, molecular, or computational methods to systematically select features of a disorder that might result from distinct genetic influences. By carefully defining the target phenotype, or dividing the sample by phenotypic characteristics, we can hope to narrow the range of genes that influence risk for the trait in the study population, thereby increasing the likelihood of finding them. In this article, fundamental issues that arise in phenotyping in epilepsy and other disorders are reviewed, and factors complicating genotype-phenotype correlation are discussed. Methods of data collection, analysis, and interpretation are addressed, focusing on epidemiologic studies. With this foundation in place, the epilepsy subtypes and clinical features that appear to have a genetic basis are described, and the epidemiologic studies that have provided evidence for the heritability of these phenotypic characteristics, supporting their use in future genetic investigations, are reviewed. Finally, several molecular approaches to phenotype definition are discussed, in which the molecular defect, rather than the clinical phenotype, is used as a starting point.

  14. Metabolomic phenotyping of a cloned pig model

    DEFF Research Database (Denmark)

    Clausen, Morten Rahr; Christensen, Kirstine Lykke; Hedemann, Mette Skou;

    2011-01-01

    Background Pigs are widely used as models for human physiological changes in intervention studies, because of the close resemblance between human and porcine physiology and the high degree of experimental control when using an animal model. Cloned animals have, in principle, identical genotypes and...... established. Conclusions From the present study we conclude that cloned and normal outbred pigs are phenotypically different. However, it cannot be concluded that the use of cloned animals will reduce the inter-individual variation in intervention studies, though this is based on a limited number of animals....... possibly also phenotypes and this offer an extra level of experimental control which could possibly make them a desirable tool for intervention studies. Therefore, in the present study, we address how phenotype and phenotypic variation is affected by cloning, through comparison of cloned pigs and normal...

  15. Metabolomic phenotyping of a cloned pig model

    Directory of Open Access Journals (Sweden)

    Callesen Henrik

    2011-08-01

    Full Text Available Abstract Background Pigs are widely used as models for human physiological changes in intervention studies, because of the close resemblance between human and porcine physiology and the high degree of experimental control when using an animal model. Cloned animals have, in principle, identical genotypes and possibly also phenotypes and this offer an extra level of experimental control which could possibly make them a desirable tool for intervention studies. Therefore, in the present study, we address how phenotype and phenotypic variation is affected by cloning, through comparison of cloned pigs and normal outbred pigs. Results The metabolic phenotype of cloned pigs (n = 5 was for the first time elucidated by nuclear magnetic resonance (NMR-based metabolomic analysis of multiple bio-fluids including plasma, bile and urine. The metabolic phenotype of the cloned pigs was compared with normal outbred pigs (n = 6 by multivariate data analysis, which revealed differences in the metabolic phenotypes. Plasma lactate was higher for cloned vs control pigs, while multiple metabolites were altered in the bile. However a lower inter-individual variability for cloned pigs compared with control pigs could not be established. Conclusions From the present study we conclude that cloned and normal outbred pigs are phenotypically different. However, it cannot be concluded that the use of cloned animals will reduce the inter-individual variation in intervention studies, though this is based on a limited number of animals.

  16. Para Bombay phenotype--a case report.

    Science.gov (United States)

    Mathai, J; Sulochana, P V; Sathyabhama, S

    1997-10-01

    Bombay phenotype is peculiar in that red cells are not agglutinated by antisera A, B or H; while serum contains anti A, B and H. Existence of modifying genes at independent loci with variable expression of ABO genes is postulated. We report here a case of partial suppression where antigens could be detected by elution tests and unlike classical Bombay type, normal amount of appropriate blood group substances were present in saliva. This case of para Bombay phenotype was detected as a result of discrepancy in cell and serum group ng. This highlights the importance of both forward and reverse grouping in ABO testing.

  17. Mitochondrial haplogroup M9a specific variant ND1 T3394C may have a modifying role in the phenotypic expression of the LHON-associated ND4 G11778A mutation.

    Science.gov (United States)

    Zhang, Minglian; Zhou, Xiangtian; Li, Chengwu; Zhao, Fuxin; Zhang, Juanjuan; Yuan, Meixia; Sun, Yan-Hong; Wang, Jingzheng; Tong, Yi; Liang, Min; Yang, Li; Cai, Wanshi; Wang, Lifei; Qu, Jia; Guan, Min-Xin

    2010-01-01

    We report here the clinical, genetic and molecular characterization of four Han Chinese families with Leber's hereditary optic neuropathy (LHON). The penetrances of optic neuropathy in these Chinese pedigrees were 38%, 38%, 44% and 56%. This observation is in contrast with the previously identified 14 Chinese families with very low penetrance of LHON. The age-at-onset for visual impairment in matrilineal relatives in these Chinese families varied from 18 to 30years. Furthermore, the ratios between affected male and female matrilineal relatives in these families were 3:0, 3:0, 3:1 and 2:3, respectively. Molecular analysis of mitochondrial genomes identified the known ND4 G11778A mutation and distinct sets of variants belonging to the Asian haplogroups M9a. Of these, the ND1 T3394C mutation caused the substitution of a highly conserved histidine for tyrosine (Y30H) at amino acid position 30. This mutation was associated with LHON in other families with low penetrance of optic neuropathy and other clinical abnormalities. The presence of both G11778A and T3394C mutations appears to contribute to higher penetrance of optic neuropathy in these four Chinese families than other Chinese families carrying only the G11778A mutation. Therefore, the mitochondrial haplogroup M9a specific variant T3394C may modulate the phenotypic manifestation of LHON-associated G11778A mutation in these Chinese pedigrees.

  18. The Behavioural Phenotype of Angelman Syndrome

    Science.gov (United States)

    Horsler, K.; Oliver, C.

    2006-01-01

    Background: The purpose of this review is to examine the notion of a behavioural phenotype for Angelman syndrome and identify methodological and conceptual influences on the accepted presentation. Methods: Studies examining the behavioural characteristics associated with Angelman syndrome are reviewed and methodology is described. Results:…

  19. Modified binary particle swam optimization

    Institute of Scientific and Technical Information of China (English)

    Sangwook Lee; Sangmoon Soak; Sanghoun Oh; Witold Pedrycz; Moongu Jeon

    2008-01-01

    This paper presents a modified binary particle swarm optimization(BPSO)which adopts concepts of the genotype-phenotype rep-resentation and the mutation operator of genetic algorithms.Its main feature is that the BPSO can be treated as a continuous PSO.The proposed BPSO algorithm is tested on various benchmark functions,and its performance is compared with that of the original BPSO.Experimental results show that the modified BPSO outperforms the original BPSO algorithm.

  20. Background independence in a background dependent renormalization group

    Science.gov (United States)

    Labus, Peter; Morris, Tim R.; Slade, Zöe H.

    2016-07-01

    Within the derivative expansion of conformally reduced gravity, the modified split Ward identities are shown to be compatible with the flow equations if and only if either the anomalous dimension vanishes or the cutoff profile is chosen to have a power-law form. No solutions exist if the Ward identities are incompatible. In the compatible case, a clear reason is found for why Ward identities can still forbid the existence of fixed points; however, for any cutoff profile, a background independent (and parametrization independent) flow equation is uncovered. Finally, expanding in vertices, the combined equations are shown generically to become either overconstrained or highly redundant beyond the six-point level.

  1. Describing the phenotype in Rett syndrome using a population database

    OpenAIRE

    Colvin, L; Fyfe, S.; Leonard, S.; Schiavello, T; ELLAWAY, C; N de Klerk; Christodoulou, J.; Msall, M; Leonard, H

    2003-01-01

    Background: Mutations in the MECP2 gene have been recently identified as the cause of Rett syndrome, prompting research into genotype-phenotype relations. However, despite these genetic advances there has been little descriptive epidemiology of the full range of phenotypes.

  2. Phenotypic evolution from genetic polymorphisms in a radial network architecture

    Directory of Open Access Journals (Sweden)

    Siegel Paul B

    2007-11-01

    Full Text Available Abstract Background The genetic architecture of a quantitative trait influences the phenotypic response to natural or artificial selection. One of the main objectives of genetic mapping studies is to identify the genetic factors underlying complex traits and understand how they contribute to phenotypic expression. Presently, we are good at identifying and locating individual loci with large effects, but there is a void in describing more complex genetic architectures. Although large networks of connected genes have been reported, there is an almost complete lack of information on how polymorphisms in these networks contribute to phenotypic variation and change. To date, most of our understanding comes from theoretical, model-based studies, and it remains difficult to assess how realistic their conclusions are as they lack empirical support. Results A previous study provided evidence that nearly half of the difference in eight-week body weight between two divergently selected lines of chickens was a result of four loci organized in a 'radial' network (one central locus interacting with three 'radial' loci that, in turn, only interacted with the central locus. Here, we study the relationship between phenotypic change and genetic polymorphism in this empirically detected network. We use a model-free approach to study, through individual-based simulations, the dynamic properties of this polymorphic and epistatic genetic architecture. The study provides new insights to how epistasis can modify the selection response, buffer and reveal effects of major loci leading to a progressive release of genetic variation. We also illustrate the difficulty of predicting genetic architecture from observed selection response, and discuss mechanisms that might lead to misleading conclusions on underlying genetic architectures from quantitative trait locus (QTL experiments in selected populations. Conclusion Considering both molecular (QTL and phenotypic (selection

  3. Phenotypic Approaches to Drought in Cassava: Review

    Directory of Open Access Journals (Sweden)

    Emmanuel eOkogbenin

    2013-05-01

    Full Text Available Cassava is an important crop in Africa, Asia, Latin America and the Caribbean. Cassava can be produced adequately in drought conditions making it the ideal food security crop in marginal environments. Although cassava can tolerate drought stress, it can be genetically improved to enhance productivity in such environments. Drought adaptation studies in over three decades in cassava have identified relevant mechanisms which have been explored in conventional breeding. Drought is a quantitative trait and its multigenic nature makes it very challenging to effectively manipulate and combine genes in breeding for rapid genetic gain and selection process. Cassava has a long growth cycle of 12 - 18 months which invariably contributes to a long breeding scheme for the crop. Modern breeding using advances in genomics and improved genotyping, is facilitating the dissection and genetic analysis of complex traits including drought tolerance, thus helping to better elucidate and understand the genetic basis of such traits. A beneficial goal of new innovative breeding strategies is to shorten the breeding cycle using minimized, efficient or fast phenotyping protocols. While high throughput genotyping have been achieved, this is rarely the case for phenotyping for drought adaptation. Some of the storage root phenotyping in cassava are often done very late in the evaluation cycle making selection process very slow. This paper highlights some modified traits suitable for early-growth phase phenotyping that may be used to reduce drought phenotyping cycle in cassava. Such modified traits can significantly complement the high throughput genotyping procedures to fast track breeding of improved drought tolerant varieties. The need for metabolite profiling, improved phenomics to take advantage of next generation sequencing technologies and high throughput phenotyping are basic steps for future direction to improve genetic gain and maximize speed for drought tolerance

  4. Phenotypic approaches to drought in cassava: review.

    Science.gov (United States)

    Okogbenin, Emmanuel; Setter, Tim L; Ferguson, Morag; Mutegi, Rose; Ceballos, Hernan; Olasanmi, Bunmi; Fregene, Martin

    2013-01-01

    Cassava is an important crop in Africa, Asia, Latin America, and the Caribbean. Cassava can be produced adequately in drought conditions making it the ideal food security crop in marginal environments. Although cassava can tolerate drought stress, it can be genetically improved to enhance productivity in such environments. Drought adaptation studies in over three decades in cassava have identified relevant mechanisms which have been explored in conventional breeding. Drought is a quantitative trait and its multigenic nature makes it very challenging to effectively manipulate and combine genes in breeding for rapid genetic gain and selection process. Cassava has a long growth cycle of 12-18 months which invariably contributes to a long breeding scheme for the crop. Modern breeding using advances in genomics and improved genotyping, is facilitating the dissection and genetic analysis of complex traits including drought tolerance, thus helping to better elucidate and understand the genetic basis of such traits. A beneficial goal of new innovative breeding strategies is to shorten the breeding cycle using minimized, efficient or fast phenotyping protocols. While high throughput genotyping have been achieved, this is rarely the case for phenotyping for drought adaptation. Some of the storage root phenotyping in cassava are often done very late in the evaluation cycle making selection process very slow. This paper highlights some modified traits suitable for early-growth phase phenotyping that may be used to reduce drought phenotyping cycle in cassava. Such modified traits can significantly complement the high throughput genotyping procedures to fast track breeding of improved drought tolerant varieties. The need for metabolite profiling, improved phenomics to take advantage of next generation sequencing technologies and high throughput phenotyping are basic steps for future direction to improve genetic gain and maximize speed for drought tolerance breeding. PMID

  5. Modified cyanobacteria

    Science.gov (United States)

    Vermaas, Willem F J.

    2014-06-17

    Disclosed is a modified photoautotrophic bacterium comprising genes of interest that are modified in terms of their expression and/or coding region sequence, wherein modification of the genes of interest increases production of a desired product in the bacterium relative to the amount of the desired product production in a photoautotrophic bacterium that is not modified with respect to the genes of interest.

  6. The Diffuse Supernova Neutrino Background

    CERN Document Server

    Beacom, John F

    2010-01-01

    The Diffuse Supernova Neutrino Background (DSNB) is the weak glow of MeV neutrinos and antineutrinos from distant core-collapse supernovae. The DSNB has not been detected yet, but the Super-Kamiokande (SK) 2003 upper limit on the electron antineutrino flux is close to predictions, now quite precise, based on astrophysical data. If SK is modified with dissolved gadolinium to reduce detector backgrounds and increase the energy range for analysis, then it should detect the DSNB at a rate of a few events per year, providing a new probe of supernova neutrino emission and the cosmic core-collapse rate. If the DSNB is not detected, then new physics will be required. Neutrino astronomy, while uniquely powerful, has proven extremely difficult -- only the Sun and the nearby Supernova 1987A have been detected to date -- so the promise of detecting new sources soon is exciting indeed.

  7. 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.

  8. Social-Cognition and the Broad Autism Phenotype: Identifying Genetically Meaningful Phenotypes

    Science.gov (United States)

    Losh, Molly; Piven, Joseph

    2007-01-01

    Background: Strong evidence from twin and family studies suggests that the genetic liability to autism may be expressed through personality and language characteristics qualitatively similar, but more subtly expressed than those defining the full syndrome. This study examined behavioral features of this "broad autism phenotype" (BAP) in relation…

  9. 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

  10. The Cosmic Microwave Background

    OpenAIRE

    Silk, Joseph

    2001-01-01

    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.

  11. Genetic basis of hidden phenotypic variation revealed by increased translational readthrough in yeast.

    Directory of Open Access Journals (Sweden)

    Noorossadat Torabi

    Full Text Available Eukaryotic release factors 1 and 3, encoded by SUP45 and SUP35, respectively, in Saccharomyces cerevisiae, are required for translation termination. Recent studies have shown that, besides these two key factors, several genetic and epigenetic mechanisms modulate the efficiency of translation termination. These mechanisms, through modifying translation termination fidelity, were shown to affect various cellular processes, such as mRNA degradation, and in some cases could confer a beneficial phenotype to the cell. The most studied example of such a mechanism is [PSI+], the prion conformation of Sup35p, which can have pleiotropic effects on growth that vary among different yeast strains. However, genetic loci underlying such readthrough-dependent, background-specific phenotypes have yet to be identified. Here, we used sup35(C653R, a partial loss-of-function allele of the SUP35 previously shown to increase readthrough of stop codons and recapitulate some [PSI+]-dependent phenotypes, to study the genetic basis of phenotypes revealed by increased translational readthrough in two divergent yeast strains: BY4724 (a laboratory strain and RM11_1a (a wine strain. We first identified growth conditions in which increased readthrough of stop codons by sup35(C653R resulted in different growth responses between these two strains. We then used a recently developed linkage mapping technique, extreme QTL mapping (X-QTL, to identify readthrough-dependent loci for the observed growth differences. We further showed that variation in SKY1, an SR protein kinase, underlies a readthrough-dependent locus observed for growth on diamide and hydrogen peroxide. We found that the allelic state of SKY1 interacts with readthrough level and the genetic background to determine growth rate in these two conditions.

  12. Behavioral phenotyping enhanced--beyond (environmental) standardization.

    Science.gov (United States)

    Würbel, H

    2002-01-01

    It is basic biology that the phenotype of an animal is the product of a complex and dynamic interplay between nature (genotype) and nurture (environment). It is far less clear, however, how this might translate into experimental design and the interpretation of animal experiments. Animal experiments are a compromise between modelling real world phenomena with maximal validity (complexity) and designing practicable research projects (abstraction). Textbooks on laboratory animal science generally favour abstraction over complexity. Depending on the area of research, however, abstraction can seriously compromise information gain, with respect to the real world phenomena an experiment is designed to model. Behavioral phenotyping of mouse mutants often deals with particularly complex manifestations of life, such as learning, memory or anxiety, that are strongly modulated by environmental factors. A growing body of evidence indicates that current approaches to behavioral phenotyping might often produce results that are idiosyncratic to the study in which they were obtained, because the interactive nature of genotype-environment relationships underlying behavioral phenotypes was not taken into account. This paper argues that systematic variation of genetic and environmental backgrounds, instead of excessive standardization, is needed to control the robustness of the results and to detect biologically relevant interactions between the mutation and the genetic and environmental background of the animals. PMID:12886944

  13. COPD: Definition and Phenotypes

    DEFF Research Database (Denmark)

    Vestbo, J.

    2014-01-01

    particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients. The evolution of this definition and the diagnostic criteria currently in use are discussed. COPD is increasingly divided in subgroups or phenotypes based on specific features and association...

  14. Mixed phenotype acute leukemia

    Institute of Scientific and Technical Information of China (English)

    Ye Zixing; Wang Shujie

    2014-01-01

    Objective To highlight the current understanding of mixed phenotype acute leukemia (MPAL).Data sources We collected the relevant articles in PubMed (from 1985 to present),using the terms "mixed phenotype acute leukemia","hybrid acute leukemia","biphenotypic acute leukemia",and "mixed lineage leukemia".We also collected the relevant studies in WanFang Data base (from 2000 to present),using the terms "mixed phenotype acute leukemia" and "hybrid acute leukemia".Study selection We included all relevant studies concerning mixed phenotype acute leukemia in English and Chinese version,with no limitation of research design.The duplicated articles are excluded.Results MPAL is a rare subgroup of acute leukemia which expresses the myeloid and lymphoid markers simultaneously.The clinical manifestations of MPAL are similar to other acute leukemias.The World Health Organization classification and the European Group for Immunological classification of Leukaemias 1998 cdteria are most widely used.MPAL does not have a standard therapy regimen.Its treatment depends mostly on the patient's unique immunophenotypic and cytogenetic features,and also the experience of individual physician.The lack of effective treatment contributes to an undesirable prognosis.Conclusion Our understanding about MPAL is still limited.The diagnostic criteria have not been unified.The treatment of MPAL remains to be investigated.The prognostic factor is largely unclear yet.A better diagnostic cdteria and targeted therapeutics will improve the therapy effect and a subsequently better prognosis.

  15. Maxwell-Chern-Simons theory for curved spacetime backgrounds

    International Nuclear Information System (INIS)

    We consider a modified version of four-dimensional electrodynamics, which has a photonic Chern-Simons-like term with spacelike background vector in the action. Light propagation in curved spacetime backgrounds is discussed using the geometrical-optics approximation. The corresponding light path is modified, which allows for new effects. In a Schwarzschild background, for example, there now exist stable bounded orbits of light rays and the two polarization modes of light rays in unbounded orbits can have different gravitational redshifts

  16. Phenotypic variation in Blastocystis sp. ST3

    OpenAIRE

    Ragavan, Nanthiney Devi; Govind, Suresh Kumar; Chye, Tan Tian; Mahadeva, Sanjiv

    2014-01-01

    Background Blastocystis, is one of the most common human intestinal protozoan, which has many conflicting reports on its pathogenic role. Gut conditions which obviously varies in asymptomatic individuals, symptomatic and irritable bowel syndrome (IBS) patients in terms of gut flora, pH, osmotic pressure and water potentials could play an important role in its pathogenicity. The present study is the first study to investigate phenotypic characteristics of Blastocystis sp. ST3 isolated from asy...

  17. 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{\

  18. 背景音乐联合改良式拉玛择呼吸法对初产妇活跃期的影响%Effects of background music combined with modified Ramaze breathing onprimiparas during the active period of delivery

    Institute of Scientific and Technical Information of China (English)

    余小慧; 王步军; 曲双双; 陈小雷

    2014-01-01

    Objective To understand the effects of background music combined with modified Ramaze breathing on primiparas during the active period of delivery .Method From December,2012 to December, 2013, 100 primiparas were chosen as an experimental group and another 100 primiparas were chosen as a control group for the study .Theprimiparas of the experimental group were attended with modified Ramaze breathing of during the active period after they entered the labor ward, while the control group were attended with routine care .Pain intensity, blood pressure, heart rate and the length of the active period of the two groups were observed and recorded .Findings In the study group, the pain was found to be significantly reduced .Pressure difference and difference of heart rate were significantly lower than that in the control group . The time of the active period was shortened considerably .The difference has statistical significance .Conclusion The application of background music combined with modified Ramaze breathing has significant analgesic effect onprimiparas during the active period of delivery .It can stabilize blood pressure and heart rate and can also shorten the active period of delivery .%目的:观察100例初产妇第一产程活跃期应用背景音乐联合改良式拉玛择呼吸法的效果。方法2012年12月至2013年12月间临产的初产妇200例,随机分为研究组和常规组各100例。研究组活跃期进入待产室开始使用改良式拉玛择呼吸法,常规组活跃期进入待产室常规观察照护。观察两组疼痛强度、血压差、心率差及活跃期所需时间。结果研究组疼痛程度明显减轻,血压差和心率差显著低于常规组( P<0.05),活跃期所需时间明显缩短,差异有统计学意义(P<0.05)。结论背景音乐联合改良式拉玛择呼吸法在初产妇活跃期的应用中镇痛效果显著,可以稳定血压、心率,缩短活跃期。

  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. On Background Independence

    OpenAIRE

    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 cons...

  1. MeCP2 Related Studies Benefit from the Use of CD1 as Genetic Background.

    Science.gov (United States)

    Cobolli Gigli, Clementina; Scaramuzza, Linda; Gandaglia, Anna; Bellini, Elisa; Gabaglio, Marina; Parolaro, Daniela; Kilstrup-Nielsen, Charlotte; Landsberger, Nicoletta; Bedogni, Francesco

    2016-01-01

    MECP2 mutations cause a number of neurological disorders of which Rett syndrome (RTT) represents the most thoroughly analysed condition. Many Mecp2 mouse models have been generated through the years; their validity is demonstrated by the presence of a broad spectrum of phenotypes largely mimicking those manifested by RTT patients. These mouse models, between which the C57BL/6 Mecp2tm1.1Bird strain probably represents the most used, enabled to disclose much of the roles of Mecp2. However, small litters with little viability and poor maternal care hamper the maintenance of the colony, thus limiting research on such animals. For this reason, past studies often used Mecp2 mouse models on mixed genetic backgrounds, thus opening questions on whether modifier genes could be responsible for at least part of the described effects. To verify this possibility, and facilitate the maintenance of the Mecp2 colony, we transferred the Mecp2tm1.1Bird allele on the stronger CD1 background. The CD1 strain is easier to maintain and largely recapitulates the phenotypes already described in Mecp2-null mice. We believe that this mouse model will foster the research on RTT. PMID:27097329

  2. Covert genetic selections to optimize phenotypes.

    Directory of Open Access Journals (Sweden)

    Di Wu

    Full Text Available In many high complexity systems (cells, organisms, institutions, societies, economies, etc., it is unclear which components should be regulated to affect overall performance. To identify and prioritize molecular targets which impact cellular phenotypes, we have developed a selection procedure ("SPI"-single promoting/inhibiting target identification which monitors the abundance of ectopic cDNAs. We have used this approach to identify growth regulators. For this purpose, complex pools of S. cerevisiae cDNA transformants were established and we quantitated the evolution of the spectrum of cDNAs which was initially present. These data emphasized the importance of translation initiation and ER-Golgi traffic for growth. SPI provides functional insight into the stability of cellular phenotypes under circumstances in which established genetic approaches cannot be implemented. It provides a functional "synthetic genetic signature" for each state of the cell (i.e. genotype and environment by surveying complex genetic libraries, and does not require specialized arrays of cDNAs/shRNAs, deletion strains, direct assessment of clonal growth or even a conditional phenotype. Moreover, it establishes a hierarchy of importance of those targets which can contribute, either positively or negatively, to modify the prevailing phenotype. Extensions of these proof-of-principle experiments to other cell types should provide a novel and powerful approach to analyze multiple aspects of the basic biology of yeast and animal cells as well as clinically-relevant issues.

  3. Neutrino refraction by the cosmic neutrino background

    CERN Document Server

    Diaz, J S

    2015-01-01

    We have determined the dispersion relation of a neutrino test particle propagating in the cosmic neutrino background. Describing the relic neutrinos and antineutrinos from the hot big bang as a dense medium, a matter potential or refractive index is obtained. The vacuum neutrino mixing angles are unchanged, but the energy of each mass state is modified. Using a matrix in the space of neutrino species, the induced potential is decomposed into a part which produces signatures in beta-decay experiments and another part which modifies neutrino oscillations. The low temperature of the relic neutrinos makes a direct detection extremely challenging. From a different point of view, the identified refractive effects of the cosmic neutrino background constitute an ultralow background for future experimental studies of nonvanishing Lorentz violation in the neutrino sector.

  4. Neutrino refraction by the cosmic neutrino background

    Science.gov (United States)

    Díaz, J. S.; Klinkhamer, F. R.

    2016-03-01

    We have determined the dispersion relation of a neutrino test particle propagating in the cosmic neutrino background. Describing the relic neutrinos and antineutrinos from the hot big bang as a dense medium, a matter potential or refractive index is obtained. The vacuum neutrino mixing angles are unchanged, but the energy of each mass state is modified. Using a matrix in the space of neutrino species, the induced potential is decomposed into a part which produces signatures in beta-decay experiments and another part which modifies neutrino oscillations. The low temperature of the relic neutrinos makes a direct detection extremely challenging. From a different point of view, the identified refractive effects of the cosmic neutrino background constitute an ultralow background for future experimental studies of nonvanishing Lorentz violation in the neutrino sector.

  5. Early and sustained treatment modifies the phenotype of birdshot retinochoroiditis.

    Science.gov (United States)

    Knecht, Pascal B; Papadia, Marina; Herbort, Carl P

    2014-06-01

    In this single-centre retrospective case review, we investigate the long-term follow-up of birdshot retinochoroiditis (BRC) patients, analysing the impact of early, vigorous, and prolonged treatment on the evolution of indocyanine green angiography (ICGA) signs and fundus appearance. Treatment delay was calculated for each BRC patient, and patients were classified into two groups--treatment delay of 10 months (delayed-treatment group). Fundus photographs and ICGA frames from the initial visit and from the last follow-up visit were assessed. Fundus photographs were evaluated for the presence of at least three circumpapillary, typical, rice-shaped birdshot lesions in one eye, inferior or nasal to the optic disc. ICGA pictures were evaluated for the presence of lesions (hypofluorescent dark dots, fuzziness). Differences were compared between the two groups and between the first visit and the last follow-up visit. In the early-treatment group, 5/6 patients had no characteristic BRC fundus lesions, but 7/7 patients in the delayed-treatment group displayed typical lesions. At last follow-up, 5/6 early-treatment patients showed no fundus lesions, and 6/7 delayed-treatment patients retained their fundus lesions. At presentation, all 13 patients exhibited lesions on ICGA. At last follow-up, ICGA lesions had completely disappeared in 4/6 early-treatment patients and 3/7 delayed-treatment patients. Thus, early and sufficiently dosed inflammation-suppressive treatment can prevent the appearance of typical BRC fundus lesions. It is therefore crucial to perform ICGA to detect otherwise occult stromal choroiditis in suspected BRC cases and to initiate adequate therapy immediately. PMID:24081916

  6. Reciprocal Effects on Neurocognitive and Metabolic Phenotypes in Mouse Models of 16p11.2 Deletion and Duplication Syndromes

    Science.gov (United States)

    Arbogast, Thomas; Ouagazzal, Abdel-Mouttalib; Chevalier, Claire; Kopanitsa, Maksym; Afinowi, Nurudeen; Migliavacca, Eugenia; Cowling, Belinda S.; Birling, Marie-Christine; Champy, Marie-France; Reymond, Alexandre; Herault, Yann

    2016-01-01

    The 16p11.2 600 kb BP4-BP5 deletion and duplication syndromes have been associated with developmental delay; autism spectrum disorders; and reciprocal effects on the body mass index, head circumference and brain volumes. Here, we explored these relationships using novel engineered mouse models carrying a deletion (Del/+) or a duplication (Dup/+) of the Sult1a1-Spn region homologous to the human 16p11.2 BP4-BP5 locus. On a C57BL/6N inbred genetic background, Del/+ mice exhibited reduced weight and impaired adipogenesis, hyperactivity, repetitive behaviors, and recognition memory deficits. In contrast, Dup/+ mice showed largely opposite phenotypes. On a F1 C57BL/6N × C3B hybrid genetic background, we also observed alterations in social interaction in the Del/+ and the Dup/+ animals, with other robust phenotypes affecting recognition memory and weight. To explore the dosage effect of the 16p11.2 genes on metabolism, Del/+ and Dup/+ models were challenged with high fat and high sugar diet, which revealed opposite energy imbalance. Transcriptomic analysis revealed that the majority of the genes located in the Sult1a1-Spn region were sensitive to dosage with a major effect on several pathways associated with neurocognitive and metabolic phenotypes. Whereas the behavioral consequence of the 16p11 region genetic dosage was similar in mice and humans with activity and memory alterations, the metabolic defects were opposite: adult Del/+ mice are lean in comparison to the human obese phenotype and the Dup/+ mice are overweight in comparison to the human underweight phenotype. Together, these data indicate that the dosage imbalance at the 16p11.2 locus perturbs the expression of modifiers outside the CNV that can modulate the penetrance, expressivity and direction of effects in both humans and mice. PMID:26872257

  7. Reciprocal Effects on Neurocognitive and Metabolic Phenotypes in Mouse Models of 16p11.2 Deletion and Duplication Syndromes.

    Directory of Open Access Journals (Sweden)

    Thomas Arbogast

    2016-02-01

    Full Text Available The 16p11.2 600 kb BP4-BP5 deletion and duplication syndromes have been associated with developmental delay; autism spectrum disorders; and reciprocal effects on the body mass index, head circumference and brain volumes. Here, we explored these relationships using novel engineered mouse models carrying a deletion (Del/+ or a duplication (Dup/+ of the Sult1a1-Spn region homologous to the human 16p11.2 BP4-BP5 locus. On a C57BL/6N inbred genetic background, Del/+ mice exhibited reduced weight and impaired adipogenesis, hyperactivity, repetitive behaviors, and recognition memory deficits. In contrast, Dup/+ mice showed largely opposite phenotypes. On a F1 C57BL/6N × C3B hybrid genetic background, we also observed alterations in social interaction in the Del/+ and the Dup/+ animals, with other robust phenotypes affecting recognition memory and weight. To explore the dosage effect of the 16p11.2 genes on metabolism, Del/+ and Dup/+ models were challenged with high fat and high sugar diet, which revealed opposite energy imbalance. Transcriptomic analysis revealed that the majority of the genes located in the Sult1a1-Spn region were sensitive to dosage with a major effect on several pathways associated with neurocognitive and metabolic phenotypes. Whereas the behavioral consequence of the 16p11 region genetic dosage was similar in mice and humans with activity and memory alterations, the metabolic defects were opposite: adult Del/+ mice are lean in comparison to the human obese phenotype and the Dup/+ mice are overweight in comparison to the human underweight phenotype. Together, these data indicate that the dosage imbalance at the 16p11.2 locus perturbs the expression of modifiers outside the CNV that can modulate the penetrance, expressivity and direction of effects in both humans and mice.

  8. CGRP修饰的间充质干细胞及其CGRP受体对血管平滑肌细胞增殖及表型转化的影响%Effects of CGRP and CGRP receptor modified mesenchymal stem cells on proliferation and phenotypic transformation of vascular smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    石蓓; 崔璨; 龙仙萍; 陈文明; 赵然尊; 刘志江; 敖竹君

    2013-01-01

    Objective To explore the effects and mechanism of secretory calcitonin gene-related peptide (CGRP) and CGRP receptor modified mesenchymal stem cells on proliferation and phenotypic transformation of vascular smooth muscle cell.Methods Firstly (Lenti-GFP-CGRP,referred to CGRP +/+)MSCs were transfected with high expression lentivirus vector of CGRP (MSCsCGRP+/+).Protein secretion in the above-mentioned MSCsCGRP+/+ supernatant was detected with enzyme-linked immunosorbent assay (ELISA).And then MSCsCGRP+/+ was co-cultured with VSMCsRAMP1 +/+ and VSMCsRAMP1-/-respectively.Experimental groups were as follows:MSCs + VSMCs MSCsCGRP+/+ + VSMCs,MSCsCGRP+/+ + VSMCsRAMP1 +/+ and MSCsCGRP+/+ + VSMCs RAMP1-/-Flow cytometry was applied to detect the cycle variation of smooth muscle cells,thiazolyl blue tetrazolium bromide method for detecting the proliferation of smooth muscle cells and Western blot for examining the expression changes of spectrin α-SM-actin and synthetic protein OPN in each group respectively.Results After the transfection of CGRP+/+,MSCsCGRP+/+ secreted and expressed CGRP protein,the secretory volume of CGRP protein in MSCsCGRP+/+ increased significantly compared with the control group(19.530 ± 0.498 vs 3.133 ± 0.160 and 3.120 ± 0.001,P <0.05).After a 72 h co-culturing with VSMCs,the proliferation of VSMCs in MSCsCGRP+/+ + VSMCsRAMP1 +/+ group declined significantly (0.270 ± 0.263 vs 0.413 ± 0.070,P < 0.05) and the number of cells staying in G0 phase significantly increased(93.51% ±0.38% vs 84.48% ±0.31%,P <0.05),the expression of contractile phenotype protein α-SM-actin increased and intermediate phenotype OPN declined significantly as compared with MSCsCGRP+/+ + VSMCs group { (α-SM-actin 102 946 ± 3847 vs 51 759 ±635,P < 0.05),OPN (26 026 ± 2595 vs 44 201 ± 2811,P < 0.05) } ; but compared with MSCsCGRP +/+ +VSMCsRAMP1+/+ group,the proliferation of VSMCs in MSCsCGRP+/+ + VSMCsRAMP1-/-group significantly increased(0.601 ± 0

  9. Unitarity and singular backgrounds

    CERN Document Server

    Brouzakis, Nikos

    2013-01-01

    We compute the graviton Kaluza-Klein spectrum on a gravity-dilaton background with a naked singularity for all possible boundary conditions at the singularity which are consistent with unitary evolution. We apply methods from non-relativistic quantum mechanics with singular Schr\\"{o}dinger potentials. In general the spectrum contains a tachyon, a sign of instability. Only for a particular boundary condition at the singularity the spectrum is free of tachyons. In this case the lowest-lying graviton mode is massless. We argue that this result will also hold for other backgrounds with similar geometry near the curvature singularity. We complete our study with a brief discussion on radion perturbations and Higgs mechanism on this singular background.

  10. 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.

  11. Berkeley Low Background Facility

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, K. J.; Norman, E. B. [Department of Nuclear Engineering, University of California-Berkeley, CA 94720 (United States); Nuclear Science Division, Lawrence Berkeley National Laboratory, CA 94720 (United States); Smith, A. R.; Poon, A. W. P.; Chan, Y. D. [Nuclear Science Division, Lawrence Berkeley National Laboratory, CA 94720 (United States); Lesko, K. T. [Physics Division, Lawrence Berkeley National Laboratory, CA 94720 (United States)

    2015-08-17

    The Berkeley Low Background Facility (BLBF) at Lawrence Berkeley National Laboratory (LBNL) in Berkeley, California provides low background gamma spectroscopy services to a wide array of experiments and projects. The analysis of samples takes place within two unique facilities; locally within a carefully-constructed, low background laboratory on the surface at LBNL and at the Sanford Underground Research Facility (SURF) in Lead, SD. These facilities provide a variety of gamma spectroscopy services to low background experiments primarily in the form of passive material screening for primordial radioisotopes (U, Th, K) or common cosmogenic/anthropogenic products; active screening via neutron activation analysis for U,Th, and K as well as a variety of stable isotopes; and neutron flux/beam characterization measurements through the use of monitors. A general overview of the facilities, services, and sensitivities will be presented. Recent activities and upgrades will also be described including an overview of the recently installed counting system at SURF (recently relocated from Oroville, CA in 2014), the installation of a second underground counting station at SURF in 2015, and future plans. The BLBF is open to any users for counting services or collaboration on a wide variety of experiments and projects.

  12. Backgrounded but not peripheral

    DEFF Research Database (Denmark)

    Hovmark, Henrik

    2013-01-01

    -cultural construction of identity, and, as a matter of fact, that their role might be quite important. I argue that the DDAs are backgrounded but not peripheral, i.e. marginal or insignificant. And I introduce the notion of “contextualization cue” in this argument (Levinson, 2003a, Gumperz, 1992)....

  13. Berkeley Low Background Facility

    International Nuclear Information System (INIS)

    The Berkeley Low Background Facility (BLBF) at Lawrence Berkeley National Laboratory (LBNL) in Berkeley, California provides low background gamma spectroscopy services to a wide array of experiments and projects. The analysis of samples takes place within two unique facilities; locally within a carefully-constructed, low background laboratory on the surface at LBNL and at the Sanford Underground Research Facility (SURF) in Lead, SD. These facilities provide a variety of gamma spectroscopy services to low background experiments primarily in the form of passive material screening for primordial radioisotopes (U, Th, K) or common cosmogenic/anthropogenic products; active screening via neutron activation analysis for U,Th, and K as well as a variety of stable isotopes; and neutron flux/beam characterization measurements through the use of monitors. A general overview of the facilities, services, and sensitivities will be presented. Recent activities and upgrades will also be described including an overview of the recently installed counting system at SURF (recently relocated from Oroville, CA in 2014), the installation of a second underground counting station at SURF in 2015, and future plans. The BLBF is open to any users for counting services or collaboration on a wide variety of experiments and projects

  14. 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…

  15. Local microwave background radiation

    OpenAIRE

    Soares, Domingos

    2006-01-01

    An inquiry on a possible local origin for the Microwave Background Radiation is made. Thermal MBR photons are contained in a system called {\\it magnetic bottle} which is due to Earth magnetic field and solar wind particles, mostly electrons. Observational tests are anticipated.

  16. Invasion strategies in clonal aquatic plants: Are phenotypic differences caused by phenotypic plasticity or local adaptation?

    DEFF Research Database (Denmark)

    Riis, Tenna; Lambertini, Carla; Olesen, Birgit;

    2010-01-01

    Background and Aims: The successful spread of invasive plants in new environments is often linked to multiple introductions and a diverse gene pool that facilitates local adaptation to variable environmental conditions. For clonal plants, however, phenotypic plasticity may be equally important...... conditions and plant morphological characteristics. Conclusions: The results indicate that at the current stage of spread into New Zealand, the primary adaptive strategy of these three invasive macrophytes is phenotypic plasticity. However, while limited, the possibility that genetic diversity between...... populations may facilitate ecotypic differentiation in the future cannot be excluded. These results thus indicate that invasive clonal aquatic plants adapt to new introduced areas by phenotypic plasticity. Inorganic carbon, nitrogen and phosphorous were important in controlling plant size of E. canadensis...

  17. 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.

  18. Sri Lanka; Background Papers

    OpenAIRE

    International Monetary Fund

    1995-01-01

    This Background Paper on Sri Lanka provides information on the economic developments during 1992–95. Developments in the domestic and external sectors are discussed. The deficiencies of the official consumer price index that resulted in a substantial understatement of inflation performance in 1994 and alternative estimates of underlying inflation are described. The structural rigidities in the labor market that perpetuate high unemployment and limit job growth are also described. The paper ...

  19. Background, phenomenology, and motivation

    International Nuclear Information System (INIS)

    The authors discuss the background to the kinetics of adsorption and desorption after an elementary introduction to the problem of chemisorption in two limiting cases. Other topics discussed include the thermodynamics of adsorption, reaction mechanisms outside surfaces, and a case history of catalytic hydrogenation of carbon monoxide. Figures show the potential energy barrier as a function of an appropriate reaction coordinate, and bonding of carbon monoxide to platinum metal

  20. Australia; Background Material

    OpenAIRE

    International Monetary Fund

    1995-01-01

    This paper describes the developments in the Australian labor market during the 1990s. In 1994, a number of new labor market programs were launched, directed especially at the long-term unemployed, and a further step was taken in the evolutionary reform of the industrial relations system. The paper reviews developments in employment, wages, and productivity in Australia that formed the background to these policy initiatives. It also examines the conduct of fiscal policy at the Commonwealth an...

  1. Some background about satellites

    Science.gov (United States)

    Burns, Joseph A.

    1986-01-01

    Four tables of planetary and satellite data are presented which list satellite discoveries, planetary parameters, satellite orbits, and satellite physical properties respectively. A scheme for classifying the satellites is provided and it is noted that most known moons fall into three general classes: regular satellites, collisional shards, and irregular satellites. Satellite processes are outlined with attention given to origins, dynamical and thermal evolution, surface processes, and composition and cratering. Background material is provided for each family of satellites.

  2. Histomorphological Phenotyping of the Adult Mouse Brain.

    Science.gov (United States)

    Mikhaleva, Anna; Kannan, Meghna; Wagner, Christel; Yalcin, Binnaz

    2016-01-01

    This article describes a series of standard operating procedures for morphological phenotyping of the mouse brain using basic histology. Many histological studies of the mouse brain use qualitative approaches based on what the human eye can detect. Consequently, some phenotypic information may be missed. Here we describe a quantitative approach for the assessment of brain morphology that is simple and robust. A total of 78 measurements are made throughout the brain at specific and well-defined regions, including the cortex, the hippocampus, and the cerebellum. Experimental design and timeline considerations, including strain background effects, the importance of sectioning quality, measurement variability, and efforts to correct human errors are discussed. © 2016 by John Wiley & Sons, Inc. PMID:27584555

  3. Background and introduction

    DEFF Research Database (Denmark)

    Jensen, Per Anker; van der Voordt, Theo; Coenen, Christian

    2012-01-01

    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...... in scope between FM and CREM is that CREM has its focus on real estate as physical and economical assets utilized by an organisation, while FM has a wider service focus. The difference in scope between FM and CREM on one side and B2B marketing on the other is that FM and CREM are related to organisations...

  4. 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...... effects as determinants of entrepreneurship. We start by estimating sibling correlations in entrepreneurship. We find that between 20 and 50 percent of the variance in different entrepreneurial outcomes is explained by factors that siblings share. The average is 28 percent. Allowing for differential...... entrepreneurship does play a large role, as do shared genes....

  5. 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...

  6. The Backgrounds Data Center

    Science.gov (United States)

    Snyder, W. A.; Gursky, H.; Heckathorn, H. M.; Lucke, R. L.; Berg, S. L.; Dombrowski, E. G.; Kessel, R. A.

    1993-01-01

    The Strategic Defense Initiative Organization has created data centers for midcourse, plumes, and backgrounds phenomenologies. The Backgrounds Data Center (BDC) has been designated as the prime archive for data collected by SDIO programs. The BDC maintains a Summary Catalog that contains 'metadata,' that is, information about data, such as when the data were obtained, what the spectral range of the data is, and what region of the Earth or sky was observed. Queries to this catalog result in a listing of all data sets (from all experiments in the Summary Catalog) that satisfy the specified criteria. Thus, the user can identify different experiments that made similar observations and order them from the BDC for analysis. On-site users can use the Science Analysis Facility (SAFE for this purpose. For some programs, the BDC maintains a Program Catalog, which can classify data in as many ways as desired (rather than just by position, time, and spectral range as in the Summary Catalog). For example, data sets could be tagged with such diverse parameters as solar illumination angle, signal level, or the value of a particular spectral ratio, as long as these quantities can be read from the digital record or calculated from it by the ingest program. All unclassified catalogs and unclassified data will be remotely accessible.

  7. Strain background influences neurotoxicity and behavioral abnormalities in mice expressing the tetracycline transactivator.

    Science.gov (United States)

    Han, Harry J; Allen, Carolyn C; Buchovecky, Christie M; Yetman, Michael J; Born, Heather A; Marin, Miguel A; Rodgers, Shaefali P; Song, Bryan J; Lu, Hui-Chen; Justice, Monica J; Probst, Frank J; Jankowsky, Joanna L

    2012-08-01

    The tet-off system has been widely used to create transgenic models of neurological disorders including Alzheimer's, Parkinson's, Huntington's, and prion disease. The utility of this system lies in the assumption that the tetracycline transactivator (TTA) acts as an inert control element and does not contribute to phenotypes under study. Here we report that neuronal expression of TTA can affect hippocampal cytoarchitecture and behavior in a strain-dependent manner. While studying neurodegeneration in two tet-off Alzheimer's disease models, we unexpectedly discovered neuronal loss within the dentate gyrus of single transgenic TTA controls. Granule neurons appeared most sensitive to TTA exposure during postnatal development, and doxycycline treatment during this period was neuroprotective. TTA-induced degeneration could be rescued by moving the transgene onto a congenic C57BL/6J background and recurred on reintroduction of either CBA or C3H/He backgrounds. Quantitative trait analysis of B6C3 F2 TTA mice identified a region on Chromosome 14 that contains a major modifier of the neurodegenerative phenotype. Although B6 mice were resistant to degeneration, they were not ideal for cognitive testing. F1 offspring of TTA C57BL/6J and 129X1/SvJ, FVB/NJ, or DBA/1J showed improved spatial learning, but TTA expression caused subtle differences in contextual fear conditioning on two of these backgrounds, indicating that strain and genotype can interact independently under different behavioral settings. All model systems have limitations that should be recognized and mitigated where possible; our findings stress the importance of mapping the effects caused by TTA alone when working with tet-off models.

  8. Modified Ureterosigmoidostomy

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To introduce an operation procedure and evaluate the coutinence diversion results of the modified ureterosigmoidostomy after radical cystectomy. Methods Fourteen cases of bladder cancer or prostate carcinoma were operated on with modified Sigma pouch from Feb, 1998 to Dec, 1999. A longitudinal incision about 25 cm on the sigmoid uall was done to form a low pressure pouch. The vertex of the new pouch was fixed to sacrum. Both ends of ureters were anastomosed side to side and to form a big nipple and inserted into the top of pouch for 2 to 3 centimeters. Results It took about sixty five minutes to create a new low pressure pouch after radical cystectomy. Early complication of was found in two cases postoperatively, and cured with temporary colonostomy. Hydronephrosis and hypokalemia in one patient were cured by percutaneous anterograde ureter dilatation with balloon and oral replacement of potassium salt. All patients displayed urinary continence. No symptomatic renal infection or hypercholoraemic acidosis occurred. Conclusion Modified ureterosigmoidostomy is a safe procedure of urinary diversion and provides a big volume, low intravesical pressure pouch. The patients are free from the troublesome urine-bag, intermittert catheterization , and upper urinary tracts are protected effectively. The quality of life is satisfied.

  9. Modified Ureterosigmoidostomy

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To introduce an operation procedure and evaluate the coutinence diversion results of the modified ureterosigmoidostomy after radical cystectomy. Methods Fourteen cases of bladder cancer or prostate carcinoma were operated on with modified Sigma pouch from Feb, 1998 to Dec, 1999. A longitudinal incision about 25 cm on the sigmoid uall was done to form a low pressure pouch. The vertex of the new pouch was fixed to sacrum. Both ends of ureters were anastomosed side to side and to form a big nipple and inserted into the top of pouch for 2 to 3 centimeters. Results It took about sixty five minutes to create a new low pressure pouch after radical cystectomy. Early complication of was found in two cases postoperatively, and cured with temporary colonostomy. Hydronephrosis and hypokalemia in one patient were cured by percutaneous anterograde ureter dilatation with balloon and oral replacement of potassium salt. A~ patients displayed urinary continence. No symptomatic renal infection or hypercholoraemic acidosis occurred. Conclusion Modified ureterosigmoidostomy is a safe procedure of urinary diversion and provides a big volume, low intravesical pressure pouch. The patients are free from the troublesome urine-bag, intermittert catheterization , and upper urinary tracts are protected effectively. The quality of life is satisfied.

  10. Ultraviolet Background Radiation

    Science.gov (United States)

    Henry, R. C.; Murthy, J.

    1993-12-01

    The UVX experiment was carried on the Space Shuttle Columbia between 1986 January 12 and 19 (STS-61C). Several ultraviolet spectrometers were used to obtain measurements of the diffuse ultraviolet background at 8 locations in the sky. We have reanalysed the UVX measurements of the surface brightness of the diffuse ultraviolet background above b = 40 using the dust-scattering model of Onaka & Kodaira (1991), which explicitly takes into account the variation of the source function with galactic longitude. The range of allowed values of interstellar grain albedoJa, and scattering asymmetry parameter g, is considerably expanded over those of a previous analysis. The new chi square probability contours come close to, but do not include, the values of a and g found for the interstellar grains by Witt et al. (1992) using the Ultraviolet Imaging Telescope (UIT) on the Astro mission. If we hypothesize in additon to the dust-scattered light an extragalactic component, of 300 1 100 photons cm-2 s-1 sr-1 A-1, attenuated by a cosecant b law, the new reduction of the UVX data gives complete consistency with the Witt et al. determination of the optical parameters of the grains in the ultraviolet. This work was supported by United States Air Force Contract F19628-93-K-0004, and by National Aeronautics and Space Administration grant NASA NAG5-619. We are grateful for the encouragement of Dr. Stephan Price, and we thank Dr. L. Danly for information. Onaka, T., & Kodaira, K. 1991, ApJ, 379, 532 Witt, A. N., Petersohn, J. K., Bohlin, R. C., O'Connell, R. W., Roberts, M. S., Smith, A. M., & Stecher, T. P. 1992, ApJ, 395, L5

  11. Cosmic microwave background theory.

    Science.gov (United States)

    Bond, J R

    1998-01-01

    A long-standing goal of theorists has been to constrain cosmological parameters that define the structure formation theory from cosmic microwave background (CMB) anisotropy experiments and large-scale structure (LSS) observations. The status and future promise of this enterprise is described. Current band-powers in -space are consistent with a DeltaT flat in frequency and broadly follow inflation-based expectations. That the levels are approximately (10(-5))2 provides strong support for the gravitational instability theory, while the Far Infrared Absolute Spectrophotometer (FIRAS) constraints on energy injection rule out cosmic explosions as a dominant source of LSS. Band-powers at 100 suggest that the universe could not have re-ionized too early. To get the LSS of Cosmic Background Explorer (COBE)-normalized fluctuations right provides encouraging support that the initial fluctuation spectrum was not far off the scale invariant form that inflation models prefer: e.g., for tilted Lambda cold dark matter sequences of fixed 13-Gyr age (with the Hubble constant H0 marginalized), ns = 1.17 +/- 0.3 for Differential Microwave Radiometer (DMR) only; 1.15 +/- 0.08 for DMR plus the SK95 experiment; 1.00 +/- 0.04 for DMR plus all smaller angle experiments; 1.00 +/- 0.05 when LSS constraints are included as well. The CMB alone currently gives weak constraints on Lambda and moderate constraints on Omegatot, but theoretical forecasts of future long duration balloon and satellite experiments are shown which predict percent-level accuracy among a large fraction of the 10+ parameters characterizing the cosmic structure formation theory, at least if it is an inflation variant.

  12. A multifaceted analysis of HIV-1 protease multidrug resistance phenotypes

    Directory of Open Access Journals (Sweden)

    Doherty Kathleen M

    2011-12-01

    Full Text Available Abstract Background Great strides have been made in the effective treatment of HIV-1 with the development of second-generation protease inhibitors (PIs that are effective against historically multi-PI-resistant HIV-1 variants. Nevertheless, mutation patterns that confer decreasing susceptibility to available PIs continue to arise within the population. Understanding the phenotypic and genotypic patterns responsible for multi-PI resistance is necessary for developing PIs that are active against clinically-relevant PI-resistant HIV-1 variants. Results In this work, we use globally optimal integer programming-based clustering techniques to elucidate multi-PI phenotypic resistance patterns using a data set of 398 HIV-1 protease sequences that have each been phenotyped for susceptibility toward the nine clinically-approved HIV-1 PIs. We validate the information content of the clusters by evaluating their ability to predict the level of decreased susceptibility to each of the available PIs using a cross validation procedure. We demonstrate the finding that as a result of phenotypic cross resistance, the considered clinical HIV-1 protease isolates are confined to ~6% or less of the clinically-relevant phenotypic space. Clustering and feature selection methods are used to find representative sequences and mutations for major resistance phenotypes to elucidate their genotypic signatures. We show that phenotypic similarity does not imply genotypic similarity, that different PI-resistance mutation patterns can give rise to HIV-1 isolates with similar phenotypic profiles. Conclusion Rather than characterizing HIV-1 susceptibility toward each PI individually, our study offers a unique perspective on the phenomenon of PI class resistance by uncovering major multidrug-resistant phenotypic patterns and their often diverse genotypic determinants, providing a methodology that can be applied to understand clinically-relevant phenotypic patterns to aid in the

  13. PRTFDC1 is a genetic modifier of HPRT-deficiency in the mouse.

    Directory of Open Access Journals (Sweden)

    Alaine C Keebaugh

    Full Text Available Lesch-Nyhan disease (LND is a severe X-linked neurological disorder caused by a deficiency of hypoxanthine phosphoribosyltransferase (HPRT. In contrast, HPRT-deficiency in the mouse does not result in the profound phenotypes such as self-injurious behavior observed in humans, and the genetic basis for this phenotypic disparity between HPRT-deficient humans and mice is unknown. To test the hypothesis that HPRT deficiency is modified by the presence/absence of phosphoribosyltransferase domain containing 1 (PRTFDC1, a paralog of HPRT that is a functional gene in humans but an inactivated pseudogene in mice, we created transgenic mice that express human PRTFDC1 in wild-type and HPRT-deficient backgrounds. Male mice expressing PRTFDC1 on either genetic background were viable and fertile. However, the presence of PRTFDC1 in the HPRT-deficient, but not wild-type mice, increased aggression as well as sensitivity to a specific amphetamine-induced stereotypy, both of which are reminiscent of the increased aggressive and self-injurious behavior exhibited by patients with LND. These results demonstrate that PRTFDC1 is a genetic modifier of HPRT-deficiency in the mouse and could therefore have important implications for unraveling the molecular etiology of LND.

  14. Invasion strategies in clonal aquatic plants: are phenotypic differences caused by phenotypic plasticity or local adaptation?

    Science.gov (United States)

    Riis, Tenna; Lambertini, Carla; Olesen, Birgit; Clayton, John S.; Brix, Hans; Sorrell, Brian K.

    2010-01-01

    Background and Aims The successful spread of invasive plants in new environments is often linked to multiple introductions and a diverse gene pool that facilitates local adaptation to variable environmental conditions. For clonal plants, however, phenotypic plasticity may be equally important. Here the primary adaptive strategy in three non-native, clonally reproducing macrophytes (Egeria densa, Elodea canadensis and Lagarosiphon major) in New Zealand freshwaters were examined and an attempt was made to link observed differences in plant morphology to local variation in habitat conditions. Methods Field populations with a large phenotypic variety were sampled in a range of lakes and streams with different chemical and physical properties. The phenotypic plasticity of the species before and after cultivation was studied in a common garden growth experiment, and the genetic diversity of these same populations was also quantified. Key Results For all three species, greater variation in plant characteristics was found before they were grown in standardized conditions. Moreover, field populations displayed remarkably little genetic variation and there was little interaction between habitat conditions and plant morphological characteristics. Conclusions The results indicate that at the current stage of spread into New Zealand, the primary adaptive strategy of these three invasive macrophytes is phenotypic plasticity. However, while limited, the possibility that genetic diversity between populations may facilitate ecotypic differentiation in the future cannot be excluded. These results thus indicate that invasive clonal aquatic plants adapt to new introduced areas by phenotypic plasticity. Inorganic carbon, nitrogen and phosphorous were important in controlling plant size of E. canadensis and L. major, but no other relationships between plant characteristics and habitat conditions were apparent. This implies that within-species differences in plant size can be explained

  15. Low background infrared (LBIR) facility

    Data.gov (United States)

    Federal Laboratory Consortium — The Low background infrared (LBIR) facility was originally designed to calibrate user supplied blackbody sources and to characterize low-background IR detectors and...

  16. Hanford Site background: Part 1, Soil background for nonradioactive analytes

    International Nuclear Information System (INIS)

    Volume two contains the following appendices: Description of soil sampling sites; sampling narrative; raw data soil background; background data analysis; sitewide background soil sampling plan; and use of soil background data for the detection of contamination at waste management unit on the Hanford Site

  17. Sex hormone binding globulin phenotypes

    DEFF Research Database (Denmark)

    Cornelisse, M M; Bennett, Patrick; Christiansen, M;

    1994-01-01

    Human sex hormone binding globulin (SHBG) is encoded by a normal and a variant allele. The resulting SHBG phenotypes (the homozygous normal SHBG, the heterozygous SHBG and the homozygous variant SHBG phenotype) can be distinguished by their electrophoretic patterns. We developed a novel detection...

  18. The Broad Autism Phenotype Questionnaire

    Science.gov (United States)

    Hurley, Robert S. E.; Losh, Molly; Parlier, Morgan; Reznick, J. Steven; Piven, Joseph

    2007-01-01

    The broad autism phenotype (BAP) is a set of personality and language characteristics that reflect the phenotypic expression of the genetic liability to autism, in non-autistic relatives of autistic individuals. These characteristics are milder but qualitatively similar to the defining features of autism. A new instrument designed to measure the…

  19. Plant Phenotype Characterization System

    Energy Technology Data Exchange (ETDEWEB)

    Daniel W McDonald; Ronald B Michaels

    2005-09-09

    This report is the final scientific report for the DOE Inventions and Innovations Project: Plant Phenotype Characterization System, DE-FG36-04GO14334. The period of performance was September 30, 2004 through July 15, 2005. The project objective is to demonstrate the viability of a new scientific instrument concept for the study of plant root systems. The root systems of plants are thought to be important in plant yield and thus important to DOE goals in renewable energy sources. The scientific study and understanding of plant root systems is hampered by the difficulty in observing root activity and the inadequacy of existing root study instrumentation options. We have demonstrated a high throughput, non-invasive, high resolution technique for visualizing plant root systems in-situ. Our approach is based upon low-energy x-ray radiography and the use of containers and substrates (artificial soil) which are virtually transparent to x-rays. The system allows us to germinate and grow plant specimens in our containers and substrates and to generate x-ray images of the developing root system over time. The same plant can be imaged at different times in its development. The system can be used for root studies in plant physiology, plant morphology, plant breeding, plant functional genomics and plant genotype screening.

  20. Integration of curated databases to identify genotype-phenotype associations

    Directory of Open Access Journals (Sweden)

    Li Jianrong

    2006-10-01

    Full Text Available Abstract Background The ability to rapidly characterize an unknown microorganism is critical in both responding to infectious disease and biodefense. To do this, we need some way of anticipating an organism's phenotype based on the molecules encoded by its genome. However, the link between molecular composition (i.e. genotype and phenotype for microbes is not obvious. While there have been several studies that address this challenge, none have yet proposed a large-scale method integrating curated biological information. Here we utilize a systematic approach to discover genotype-phenotype associations that combines phenotypic information from a biomedical informatics database, GIDEON, with the molecular information contained in National Center for Biotechnology Information's Clusters of Orthologous Groups database (NCBI COGs. Results Integrating the information in the two databases, we are able to correlate the presence or absence of a given protein in a microbe with its phenotype as measured by certain morphological characteristics or survival in a particular growth media. With a 0.8 correlation score threshold, 66% of the associations found were confirmed by the literature and at a 0.9 correlation threshold, 86% were positively verified. Conclusion Our results suggest possible phenotypic manifestations for proteins biochemically associated with sugar metabolism and electron transport. Moreover, we believe our approach can be extended to linking pathogenic phenotypes with functionally related proteins.

  1. MPHASYS: a mouse phenotype analysis system

    Directory of Open Access Journals (Sweden)

    Mian I

    2007-06-01

    Full Text Available Abstract Background Systematic, high-throughput studies of mouse phenotypes have been hampered by the inability to analyze individual animal data from a multitude of sources in an integrated manner. Studies generally make comparisons at the level of genotype or treatment thereby excluding associations that may be subtle or involve compound phenotypes. Additionally, the lack of integrated, standardized ontologies and methodologies for data exchange has inhibited scientific collaboration and discovery. Results Here we introduce a Mouse Phenotype Analysis System (MPHASYS, a platform for integrating data generated by studies of mouse models of human biology and disease such as aging and cancer. This computational platform is designed to provide a standardized methodology for working with animal data; a framework for data entry, analysis and sharing; and ontologies and methodologies for ensuring accurate data capture. We describe the tools that currently comprise MPHASYS, primarily ones related to mouse pathology, and outline its use in a study of individual animal-specific patterns of multiple pathology in mice harboring a specific germline mutation in the DNA repair and transcription-specific gene Xpd. Conclusion MPHASYS is a system for analyzing multiple data types from individual animals. It provides a framework for developing data analysis applications, and tools for collecting and distributing high-quality data. The software is platform independent and freely available under an open-source license 1.

  2. Genetical background of intelligence.

    Science.gov (United States)

    Junkiert-Czarnecka, Anna; Haus, Olga

    2016-01-01

    Intelligence as an ability to reason, think abstractly and adapt effectively to the environment is a subject of research in the field of psychology, neurobiology, and in the last twenty years genetics as well. Genetical testing of twins carried out from XX century indicated heritebility of intelligence, therefore confirmed an influence of genetic factor on cognitive processes. Studies on genetic background of intelligence focus on dopaminergic (DRD2, DRD4, COMT, SLC6A3, DAT1, CCKAR) and adrenergic system (ADRB2, CHRM2) genes as well as, neutrofins (BDNF) and oxidative stress genes (LTF, PRNP). Positive effect of investigated gene polymorphism was indicated by variation c.957C>T DRD2 gene (if in polymorphic site is thymine), polymorphism c.472G>A COMT gene (presence of adenine) and also gene ADRB2 c.46A->G (guanine), CHRM2 (thymine in place c.1890A>T) and BDNF (guanine in place c.472G>A) Obtained results indicate that intelligence is a feature dependent not only on genetic but also an environmental factor. PMID:27333929

  3. Biological aerosol background characterization

    Science.gov (United States)

    Blatny, Janet; Fountain, Augustus W., III

    2011-05-01

    To provide useful information during military operations, or as part of other security situations, a biological aerosol detector has to respond within seconds or minutes to an attack by virulent biological agents, and with low false alarms. Within this time frame, measuring virulence of a known microorganism is extremely difficult, especially if the microorganism is of unknown antigenic or nucleic acid properties. Measuring "live" characteristics of an organism directly is not generally an option, yet only viable organisms are potentially infectious. Fluorescence based instruments have been designed to optically determine if aerosol particles have viability characteristics. Still, such commercially available biological aerosol detection equipment needs to be improved for their use in military and civil applications. Air has an endogenous population of microorganisms that may interfere with alarm software technologies. To design robust algorithms, a comprehensive knowledge of the airborne biological background content is essential. For this reason, there is a need to study ambient live bacterial populations in as many locations as possible. Doing so will permit collection of data to define diverse biological characteristics that in turn can be used to fine tune alarm algorithms. To avoid false alarms, improving software technologies for biological detectors is a crucial feature requiring considerations of various parameters that can be applied to suppress alarm triggers. This NATO Task Group will aim for developing reference methods for monitoring biological aerosol characteristics to improve alarm algorithms for biological detection. Additionally, they will focus on developing reference standard methodology for monitoring biological aerosol characteristics to reduce false alarm rates.

  4. Emerging molecular phenotypes of asthma.

    Science.gov (United States)

    Ray, Anuradha; Oriss, Timothy B; Wenzel, Sally E

    2015-01-15

    Although asthma has long been considered a heterogeneous disease, attempts to define subgroups of asthma have been limited. In recent years, both clinical and statistical approaches have been utilized to better merge clinical characteristics, biology, and genetics. These combined characteristics have been used to define phenotypes of asthma, the observable characteristics of a patient determined by the interaction of genes and environment. Identification of consistent clinical phenotypes has now been reported across studies. Now the addition of various 'omics and identification of specific molecular pathways have moved the concept of clinical phenotypes toward the concept of molecular phenotypes. The importance of these molecular phenotypes is being confirmed through the integration of molecularly targeted biological therapies. Thus the global term asthma is poised to become obsolete, being replaced by terms that more specifically identify the pathology associated with the disease. PMID:25326577

  5. Matrix and cell phenotype differences in Dupuytren's disease

    NARCIS (Netherlands)

    van Beuge, Marike M; Ten Dam, Evert-Jan P M; Werker, Paul M N; Bank, Ruud A

    2016-01-01

    BACKGROUND: Dupuytren's disease is a fibroproliferative disease of the hand and fingers, which usually manifests as two different phenotypes within the same patient. The disease first causes a nodule in the palm of the hand, while later, a cord develops, causing contracture of the fingers. RESULTS:

  6. Using iterative cluster merging with improved gap statistics to perform online phenotype discovery in the context of high-throughput RNAi screens

    Directory of Open Access Journals (Sweden)

    Sun Youxian

    2008-06-01

    Full Text Available Abstract Background The recent emergence of high-throughput automated image acquisition technologies has forever changed how cell biologists collect and analyze data. Historically, the interpretation of cellular phenotypes in different experimental conditions has been dependent upon the expert opinions of well-trained biologists. Such qualitative analysis is particularly effective in detecting subtle, but important, deviations in phenotypes. However, while the rapid and continuing development of automated microscope-based technologies now facilitates the acquisition of trillions of cells in thousands of diverse experimental conditions, such as in the context of RNA interference (RNAi or small-molecule screens, the massive size of these datasets precludes human analysis. Thus, the development of automated methods which aim to identify novel and biological relevant phenotypes online is one of the major challenges in high-throughput image-based screening. Ideally, phenotype discovery methods should be designed to utilize prior/existing information and tackle three challenging tasks, i.e. restoring pre-defined biological meaningful phenotypes, differentiating novel phenotypes from known ones and clarifying novel phenotypes from each other. Arbitrarily extracted information causes biased analysis, while combining the complete existing datasets with each new image is intractable in high-throughput screens. Results Here we present the design and implementation of a novel and robust online phenotype discovery method with broad applicability that can be used in diverse experimental contexts, especially high-throughput RNAi screens. This method features phenotype modelling and iterative cluster merging using improved gap statistics. A Gaussian Mixture Model (GMM is employed to estimate the distribution of each existing phenotype, and then used as reference distribution in gap statistics. This method is broadly applicable to a number of different types of

  7. Molecular complementarity between simple, universal molecules and ions limited phenotype space in the precursors of cells

    OpenAIRE

    Norris, Vic; Reusch, Rosetta N.; IGARASHI, KAZUEI; Root-Bernstein, Robert

    2014-01-01

    Background Fundamental problems faced by the protocells and their modern descendants include how to go from one phenotypic state to another; escape from a basin of attraction in the space of phenotypes; reconcile conflicting growth and survival strategies (and thereby live on ‘the scales of equilibria’); and create a coherent, reproducible phenotype from a multitude of constituents. Presentation of the hypothesis The solutions to these problems are likely to be found with the organic and inor...

  8. Phenotypic integration of brain size and head morphology in Lake Tanganyika Cichlids

    OpenAIRE

    Tsuboi, Masahito; González-Voyer, Alejandro; Kolm, N.

    2014-01-01

    Abstract Background Phenotypic integration among different anatomical parts of the head is a common phenomenon across vertebrates. Interestingly, despite centuries of research into the factors that contribute to the existing variation in brain size among vertebrates, little is known about the role of phenotypic integration in brain size diversification. Here we used geometric morphometrics on the morphologically diverse Tanganyikan cichlids to investigate phenotypic integration across key mor...

  9. Computable visually observed phenotype ontological framework for plants

    Directory of Open Access Journals (Sweden)

    Schaeffer Mary

    2011-06-01

    Full Text Available Abstract Background The ability to search for and precisely compare similar phenotypic appearances within and across species has vast potential in plant science and genetic research. The difficulty in doing so lies in the fact that many visual phenotypic data, especially visually observed phenotypes that often times cannot be directly measured quantitatively, are in the form of text annotations, and these descriptions are plagued by semantic ambiguity, heterogeneity, and low granularity. Though several bio-ontologies have been developed to standardize phenotypic (and genotypic information and permit comparisons across species, these semantic issues persist and prevent precise analysis and retrieval of information. A framework suitable for the modeling and analysis of precise computable representations of such phenotypic appearances is needed. Results We have developed a new framework called the Computable Visually Observed Phenotype Ontological Framework for plants. This work provides a novel quantitative view of descriptions of plant phenotypes that leverages existing bio-ontologies and utilizes a computational approach to capture and represent domain knowledge in a machine-interpretable form. This is accomplished by means of a robust and accurate semantic mapping module that automatically maps high-level semantics to low-level measurements computed from phenotype imagery. The framework was applied to two different plant species with semantic rules mined and an ontology constructed. Rule quality was evaluated and showed high quality rules for most semantics. This framework also facilitates automatic annotation of phenotype images and can be adopted by different plant communities to aid in their research. Conclusions The Computable Visually Observed Phenotype Ontological Framework for plants has been developed for more efficient and accurate management of visually observed phenotypes, which play a significant role in plant genomics research. The

  10. Multidimensionality of behavioural phenotypes in Atlantic cod, Gadus morhua.

    Science.gov (United States)

    Meager, Justin J; Fernö, Anders; Skjæraasen, Jon Egil; Järvi, Torbjörn; Rodewald, Petra; Sverdrup, Gisle; Winberg, Svante; Mayer, Ian

    2012-06-25

    Much of the inter-individual variation observed in animal behaviour is now attributed to the existence of behavioural phenotypes or animal personalities. Such phenotypes may be fundamental to fisheries and aquaculture, yet there have been few detailed studies of this phenomenon in exploited marine animals. We investigated the behavioural and neuroendocrine responses of Atlantic cod (Gadus morhua L.), to situations reflecting critical ecological challenges: predator attacks and territorial challenges. Both hatchery-reared and wild fish were tested and behavioural profiles were compared with baseline conditions. We then used an objective, multivariate approach, rather than assigning individuals along one-dimensional behavioural axes, to examine whether distinct behavioural phenotypes were present. Our results indicate that two distinct behavioural phenotypes were evident in fish from each background. In hatchery-reared fish, phenotypes displayed divergent locomotor activity, sheltering, brain monoamine concentrations and responses to competitive challenges. In wild fish, phenotypes were distinguished primarily by locomotor activity, sheltering and responsiveness to predator stimuli. Hatcheries presumably represent a more stressful social environment, and social behaviour and neuroendocrine responses were important in discerning behavioural phenotypes in hatchery fish, whereas antipredator responses were important in discerning phenotypes in wild fish that have previously encountered predators. In both fish types, behavioural and physiological traits that classified individuals into phenotypes were not the same as those that were correlated across situations. These results highlight the multidimensionality of animal personalities, and that the processes that regulate one suite of behavioural traits may be very different to the processes that regulate other behaviours. PMID:22465310

  11. Phenotype and genotype in 101 males with X-linked creatine transporter deficiency

    NARCIS (Netherlands)

    Kamp, J.M. van de; Betsalel, O.T.; Mercimek-Mahmutoglu, S.; Abulhoul, L.; Grunewald, S.; Anselm, I.; Azzouz, H.; Bratkovic, D.; Brouwer, A.; Hamel, B.C.J.; Kleefstra, T.; Yntema, H.G.; Campistol, J.; Vilaseca, M.A.; Cheillan, D.; D'Hooghe, M.; Diogo, L.; Garcia, P.; Valongo, C.; Fonseca, M.; Frints, S.; Wilcken, B.; Haar, S. van der; Meijers-Heijboer, H.E.; Hofstede, F.; Johnson, D.; Kant, S.G.; Lion-Francois, L.; Pitelet, G.; Longo, N.; Maat-Kievit, J.A.; Monteiro, J.P.; Munnich, A.; Muntau, A.C.; Nassogne, M.C.; Osaka, H.; Ounap, K.; Pinard, J.M.; Quijano-Roy, S.; Poggenburg, I.; Poplawski, N.; Abdul-Rahman, O.; Ribes, A.; Arias Vasquez, A.; Yaplito-Lee, J.; Schulze, A.; Schwartz, C.E.; Schwenger, S.; Soares, G.; Sznajer, Y.; Valayannopoulos, V.; Esch, H. van; Waltz, S.; Wamelink, M.M.; Pouwels, P.J.; Errami, A.; Knaap, M.S. van der; Jakobs, C.; Mancini, G.M.; Salomons, G.S.

    2013-01-01

    BACKGROUND: Creatine transporter deficiency is a monogenic cause of X-linked intellectual disability. Since its first description in 2001 several case reports have been published but an overview of phenotype, genotype and phenotype-genotype correlation has been lacking. METHODS: We performed a retro

  12. Genotype-phenotype matching analysis of 38 Lactococcus lactis strains using random forest methods

    NARCIS (Netherlands)

    Bayjanov, J.; Starrenburg, M.J.; Sijde, M.R. van der; Siezen, R.J.; Hijum, S.A.F.T. van

    2013-01-01

    BACKGROUND: Lactococcus lactis is used in dairy food fermentation and for the efficient production of industrially relevant enzymes. The genome content and different phenotypes have been determined for multiple L. lactis strains in order to understand intra-species genotype and phenotype diversity a

  13. Perinatal risk factors for wheezing phenotypes in the first 8 years of life

    NARCIS (Netherlands)

    Caudri, D.; Savenije, O. E. M.; Smit, H. A.; Postma, D. S.; Koppelman, G. H.; Wijga, A. H.; Kerkhof, M.; Gehring, U.; Hoekstra, M. O.; Brunekreef, B.; de Jongste, J. C.

    2013-01-01

    Background A novel data-driven approach was used to identify wheezing phenotypes in pre-schoolchildren aged 0-8 years, in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort. Five phenotypes were identified: never/infrequent wheeze, transient early wheeze, intermediate onset

  14. Primary sclerosing cholangitis is associated with a distinct phenotype of inflammatory bowel disease

    NARCIS (Netherlands)

    Boonstra, K.; Erpecum, K.J. van; Nieuwkerk, K.M. van; Drenth, J.P.H.; Poen, A.C.; Witteman, B.J.; Tuynman, H.A.; Beuers, U.; Ponsioen, C.Y.

    2012-01-01

    BACKGROUND: Primary sclerosing cholangitis (PSC) is strongly associated with inflammatory bowel disease (IBD). The aim of this study was to assess the IBD phenotype associated with PSC in a large well-phenotyped population-based PSC cohort using endoscopic and histopathologic criteria. METHODS: PSC

  15. Root Traits and Phenotyping Strategies for Plant Improvement

    Directory of Open Access Journals (Sweden)

    Ana Paez-Garcia

    2015-06-01

    Full Text Available Roots are crucial for nutrient and water acquisition and can be targeted to enhance plant productivity under a broad range of growing conditions. A current challenge for plant breeding is the limited ability to phenotype and select for desirable root characteristics due to their underground location. Plant breeding efforts aimed at modifying root traits can result in novel, more stress-tolerant crops and increased yield by enhancing the capacity of the plant for soil exploration and, thus, water and nutrient acquisition. Available approaches for root phenotyping in laboratory, greenhouse and field encompass simple agar plates to labor-intensive root digging (i.e., shovelomics and soil boring methods, the construction of underground root observation stations and sophisticated computer-assisted root imaging. Here, we summarize root architectural traits relevant to crop productivity, survey root phenotyping strategies and describe their advantages, limitations and practical value for crop and forage breeding programs.

  16. Next-generation phenotypic screening.

    Science.gov (United States)

    Warchal, Scott J; Unciti-Broceta, Asier; Carragher, Neil O

    2016-07-01

    Phenotypic drug discovery (PDD) strategies are defined by screening and selection of hit or lead compounds based on quantifiable phenotypic endpoints without prior knowledge of the drug target. We outline the challenges associated with traditional phenotypic screening strategies and propose solutions and new opportunities to be gained by adopting modern PDD technologies. We highlight both historical and recent examples of approved drugs and new drug candidates discovered by modern phenotypic screening. Finally, we offer a prospective view of a new era of PDD underpinned by a wealth of technology advances in the areas of in vitro model development, high-content imaging and image informatics, mechanism-of-action profiling and target deconvolution. PMID:27357617

  17. Epigenetics in heart failure phenotypes.

    Science.gov (United States)

    Berezin, Alexander

    2016-12-01

    Chronic heart failure (HF) is a leading clinical and public problem posing a higher risk of morbidity and mortality in different populations. HF appears to be in both phenotypic forms: HF with reduced left ventricular ejection fraction (HFrEF) and HF with preserved left ventricular ejection fraction (HFpEF). Although both HF phenotypes can be distinguished through clinical features, co-morbidity status, prediction score, and treatment, the clinical outcomes in patients with HFrEF and HFpEF are similar. In this context, investigation of various molecular and cellular mechanisms leading to the development and progression of both HF phenotypes is very important. There is emerging evidence that epigenetic regulation may have a clue in the pathogenesis of HF. This review represents current available evidence regarding the implication of epigenetic modifications in the development of different HF phenotypes and perspectives of epigenetic-based therapies of HF. PMID:27335803

  18. Capturing phenotypes for precision medicine.

    Science.gov (United States)

    Robinson, Peter N; Mungall, Christopher J; Haendel, Melissa

    2015-10-01

    Deep phenotyping followed by integrated computational analysis of genotype and phenotype is becoming ever more important for many areas of genomic diagnostics and translational research. The overwhelming majority of clinical descriptions in the medical literature are available only as natural language text, meaning that searching, analysis, and integration of medically relevant information in databases such as PubMed is challenging. The new journal Cold Spring Harbor Molecular Case Studies will require authors to select Human Phenotype Ontology terms for research papers that will be displayed alongside the manuscript, thereby providing a foundation for ontology-based indexing and searching of articles that contain descriptions of phenotypic abnormalities-an important step toward improving the ability of researchers and clinicians to get biomedical information that is critical for clinical care or translational research. PMID:27148566

  19. Finding our way through phenotypes.

    Directory of Open Access Journals (Sweden)

    Andrew R Deans

    2015-01-01

    Full Text Available Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility.

  20. An audit of thiopurine methyltransferase genotyping and phenotyping before intended azathioprine treatment for dermatological conditions

    DEFF Research Database (Denmark)

    Vestergaard, T; Bygum, A

    2009-01-01

    Summary Background. Determining thiopurine methyltransferase (TPMT) genotype and phenotype before azathioprine treatment predicts which patients are most likely to develop myelosuppression. Aim. To evaluate the course of azathioprine treatment in people with TPMT heterozygosity and whether this d...

  1. Genetic background of hyperphenylalaninemia in Nagasaki, Japan.

    Science.gov (United States)

    Dateki, Sumito; Watanabe, Satoshi; Nakatomi, Akiko; Kinoshita, Eiichi; Matsumoto, Tadashi; Yoshiura, Koh-Ichiro; Moriuchi, Hiroyuki

    2016-05-01

    Phenylketonuria (PKU) and related hyperphenylalaninemia (HPA) are caused by a deficiency in hepatic phenylalanine hydroxylase (PAH). The incidence of PKU in Nagasaki prefecture is higher than that in all parts of Japan (1/15 894 vs 1/120 000). To investigate the genetic background of patients with HPA in Nagasaki prefecture, mutation analysis was done in 14 patients with PKU or mild HPA. Homozygous or compound heterozygous PAH mutations were identified in all the patients. The spectrum of PAH mutations in the cohort was broad and similar to those in all parts of Japan and East Asian countries. R53H is the most common mutation in patients with mild HPA. The present results provide further support for genotype-phenotype correlations in patients with HPA. The high incidence of PKU in Nagasaki, the westernmost part of Japan, might be due to migration of people with PAH mutations from China and Korea, and geographic factors. PMID:27173423

  2. Coulomb field in a constant electromagnetic background

    CERN Document Server

    Adorno, T C; Shabad, A E

    2016-01-01

    Nonlinear Maxwell equations are written up to the third-power deviations from a constant-field background, valid within any local nonlinear electrodynamics including QED with Euler-Heisenberg effective Lagrangian. Linear electric response to imposed static finite-sized charge is found in the vacuum filled by an arbitrary combination of constant and homogeneous electric and magnetic fields. The modified Coulomb field, corrections to the total charge and to the charge density are given in terms of derivatives of the effective Lagrangian with respect to the field invariants.

  3. Primordial perturbation with a modified dispersion relation

    CERN Document Server

    Cai, Yi-Fu

    2009-01-01

    In this paper we study the generation of primordial perturbation with a modified dispersion relation in various cosmological evolutions. We stress that the formation of the power spectrum is strongly dependent on the background. Working in a bounce model with a matter-like contracting phase, we obtain a red tilt spectrum due to the modified dispersion relation.

  4. JEM-X background models

    DEFF Research Database (Denmark)

    Huovelin, J.; Maisala, S.; Schultz, J.;

    2003-01-01

    revolution 41 of INTEGRAL. Total observing time used for the analysis was 216 502 s, with the average of 25 cps of background for each of the two JEM-X telescopes. JEM-X1 showed slightly higher average background intensity than JEM-X2. The detectors were stable during the long exposures, and weak orbital...... phase dependence in the background outside radiation belts was observed. The analysis yielded an average of 5 cps for the diffuse background, and 20 cps for the instrument background. The instrument background was found highly dependent on position, both for spectral shape and intensity. Diff use...... background was enhanced in the central area of a detector, and it decreased radially towards the edge, with a clear vignetting effect for both JEM-X units. The instrument background was weakest in the central area of a detector and showed a steep increase at the very edges of both JEM-X detectors, with...

  5. Spice: discovery of phenotype-determining component interplays

    Directory of Open Access Journals (Sweden)

    Chen Zhengzhang

    2012-05-01

    Full Text Available Abstract Background A latent behavior of a biological cell is complex. Deriving the underlying simplicity, or the fundamental rules governing this behavior has been the Holy Grail of systems biology. Data-driven prediction of the system components and their component interplays that are responsible for the target system’s phenotype is a key and challenging step in this endeavor. Results The proposed approach, which we call System Phenotype-related Interplaying Components Enumerator (Spice, iteratively enumerates statistically significant system components that are hypothesized (1 to play an important role in defining the specificity of the target system’s phenotype(s; (2 to exhibit a functionally coherent behavior, namely, act in a coordinated manner to perform the phenotype-specific function; and (3 to improve the predictive skill of the system’s phenotype(s when used collectively in the ensemble of predictive models. Spice can be applied to both instance-based data and network-based data. When validated, Spice effectively identified system components related to three target phenotypes: biohydrogen production, motility, and cancer. Manual results curation agreed with the known phenotype-related system components reported in literature. Additionally, using the identified system components as discriminatory features improved the prediction accuracy by 10% on the phenotype-classification task when compared to a number of state-of-the-art methods applied to eight benchmark microarray data sets. Conclusion We formulate a problem—enumeration of phenotype-determining system component interplays—and propose an effective methodology (Spice to address this problem. Spice improved identification of cancer-related groups of genes from various microarray data sets and detected groups of genes associated with microbial biohydrogen production and motility, many of which were reported in literature. Spice also improved the predictive skill of the

  6. Latent cluster analysis of ALS phenotypes identifies prognostically differing groups.

    Directory of Open Access Journals (Sweden)

    Jeban Ganesalingam

    Full Text Available BACKGROUND: Amyotrophic lateral sclerosis (ALS is a degenerative disease predominantly affecting motor neurons and manifesting as several different phenotypes. Whether these phenotypes correspond to different underlying disease processes is unknown. We used latent cluster analysis to identify groupings of clinical variables in an objective and unbiased way to improve phenotyping for clinical and research purposes. METHODS: Latent class cluster analysis was applied to a large database consisting of 1467 records of people with ALS, using discrete variables which can be readily determined at the first clinic appointment. The model was tested for clinical relevance by survival analysis of the phenotypic groupings using the Kaplan-Meier method. RESULTS: The best model generated five distinct phenotypic classes that strongly predicted survival (p<0.0001. Eight variables were used for the latent class analysis, but a good estimate of the classification could be obtained using just two variables: site of first symptoms (bulbar or limb and time from symptom onset to diagnosis (p<0.00001. CONCLUSION: The five phenotypic classes identified using latent cluster analysis can predict prognosis. They could be used to stratify patients recruited into clinical trials and generating more homogeneous disease groups for genetic, proteomic and risk factor research.

  7. Distribution profile of paraoxonase phenotypes among the Gujaratis

    Directory of Open Access Journals (Sweden)

    Patel A

    2007-01-01

    Full Text Available Background: Paraoxonase (PON1 can hydrolyze organophosphate pesticides (OP and has a key role in the susceptibility of human in OP toxicity. The human-enzyme shows polymorphism and variations in the distribution profile of its phenotypes among different ethnic groups have been observed. Aims: To see the distribution pattern of total PON1 activity in 45 healthy attendants of poisoning cases; 121 healthy unrelated farm-labours and 59 normal subjects of trauma. Materials and Methods: The PON1 activities from serum/plasma samples of these healthy normal individuals were estimated with/without addition of 1M NaCl in order to determine salt-stimulated and basal activity. The PON 1 phenotypes were determined on the basis of percent activation of enzyme activity. Results: Tri-modal distribution of basal PON1 activity was observed among all these individuals. 52.0% of the individuals belonged to Phenotype A, 46.6% to phenotype AB while 1.4% to Phenotype B with gene frequency of allele-A and allele-B being 0.753 and 0.247 respectively in excellent agreement with Hardy-Weinberg equilibrium. Conclusion: Maximum number of individuals belonged to phenotype-A (low PON1 activity showing potential vulnerability towards Op-poisoning.

  8. Evaluating diabetes and hypertension disease causality using mouse phenotypes

    Directory of Open Access Journals (Sweden)

    Han Jing-Dong J

    2010-07-01

    Full Text Available Abstract Background Genome-wide association studies (GWAS have found hundreds of single nucleotide polymorphisms (SNPs associated with common diseases. However, it is largely unknown what genes linked with the SNPs actually implicate disease causality. A definitive proof for disease causality can be demonstration of disease-like phenotypes through genetic perturbation of the genes or alleles, which is obviously a daunting task for complex diseases where only mammalian models can be used. Results Here we tapped the rich resource of mouse phenotype data and developed a method to quantify the probability that a gene perturbation causes the phenotypes of a disease. Using type II diabetes (T2D and hypertension (HT as study cases, we found that the genes, when perturbed, having high probability to cause T2D and HT phenotypes tend to be hubs in the interactome networks and are enriched for signaling pathways regulating metabolism but not metabolic pathways, even though the genes in these metabolic pathways are often the most significantly changed in expression levels in these diseases. Conclusions Compared to human genetic disease-based predictions, our mouse phenotype based predictors greatly increased the coverage while keeping a similarly high specificity. The disease phenotype probabilities given by our approach can be used to evaluate the likelihood of disease causality of disease-associated genes and genes surrounding disease-associated SNPs.

  9. Supergravity backgrounds and symmetry superalgebras

    CERN Document Server

    Ertem, Ümit

    2016-01-01

    We consider the bosonic sectors of supergravity theories in ten and eleven dimensions which correspond to the low energy limits of string theories and M-theory. The solutions of supergravity field equations are known as supergravity backgrounds and the number of preserved supersymmetries in those backgrounds are determined by Killing spinors. We provide some examples of supergravity backgrounds which preserve different fractions of supersymmetry. An important invariant for the characterization of supergravity backgrounds is their Killing superalgebras which are constructed out of Killing vectors and Killing spinors of the background. After constructing Killing superalgebras of some special supergravity backgrounds, we discuss about the possibilities of the extensions of these superalgebras to include the higher degree hidden symmetries of the background.

  10. Epigenetic reversion of breast carcinoma phenotype is accompaniedby DNA sequestration

    Energy Technology Data Exchange (ETDEWEB)

    Sandal, Tone; Valyi-Nagy, Klara; Spencer, Virginia A.; Folberg,Robert; Bissell, Mina J.; Maniotis, Andrew J.

    2006-07-19

    The importance of microenvironment and context in regulation of tissue-specific genes is finally well established. DNA exposure to, or sequestration from, nucleases can be used to detect differences in higher order chromatin structure in intact cells without disturbing cellular or tissue architecture. To investigate the relationship between chromatin organization and tumor phenotype, we utilized an established 3-D assay where normal and malignant human breast cells can be easily distinguished by the morphology of the structures they make (acinus-like vs tumor-like, respectively). We show that these phenotypes can be distinguished also by sensitivity to AluI digestion where the malignant cells are resistant to digestion relative to non-malignant cells. Reversion of the T4-2 breast cancer cells by either cAMP analogs, or a phospatidylinositol 3-kinase (P13K) inhibitor not only reverted the phenotype, but also the chromatin sensitivity to AluI. By using different cAMP-analogs, we show that the cAMP-induced phenotypic reversion, polarization, and shift in DNA organization act through a cAMP-dependent-protein-kinase A-coupled signaling pathway. Importantly, inhibitory antibody to fibronectin also reverted the malignant phenotype, polarized the acini, and changed chromatin sequestration. These experiments show not only that modifying the tumor microenvironment can alter the organization of tumor cells but also that architecture of the tissues and the global chromatin organization are coupled and yet highly plastic.

  11. Snowshoe hares display limited phenotypic plasticity to mismatch in seasonal camouflage

    Science.gov (United States)

    Zimova, Marketa; Mills, L. Scott; Lukacs, Paul M.; Mitchell, Michael S.

    2014-01-01

    As duration of snow cover decreases owing to climate change, species undergoing seasonal colour moults can become colour mismatched with their background. The immediate adaptive solution to this mismatch is phenotypic plasticity, either in phenology of seasonal colour moults or in behaviours that reduce mismatch or its consequences. We observed nearly 200 snowshoe hares across a wide range of snow conditions and two study sites in Montana, USA, and found minimal plasticity in response to mismatch between coat colour and background. We found that moult phenology varied between study sites, likely due to differences in photoperiod and climate, but was largely fixed within study sites with only minimal plasticity to snow conditions during the spring white-to-brown moult. We also found no evidence that hares modify their behaviour in response to colour mismatch. Hiding and fleeing behaviours and resting spot preference of hares were more affected by variables related to season, site and concealment by vegetation, than by colour mismatch. We conclude that plasticity in moult phenology and behaviours in snowshoe hares is insufficient for adaptation to camouflage mismatch, suggesting that any future adaptation to climate change will require natural selection on moult phenology or behaviour.

  12. Double Layered-Background Removal Filter for Detecting Small Infrared Targets in Heterogenous Backgrounds

    Science.gov (United States)

    Kim, Sungho

    2011-01-01

    Detecting small targets is essential for mitigating the sea-based Infrared search and track (IRST) problem. It is easy to detect small targets in homogeneous backgrounds such as the sky. When targets are on the border line of heterogeneous backgrounds such as the horizon in the sky and sea surface, solving the problem of detection becomes difficult. This paper presents a novel spatial filtering method, called Double Layered-Background Removal Filter (DL-BRF), for achieving high detection rates and low false alarm rates. DL-BRF consists of a Modified-Mean Subtraction Filter (M-MSF) and a consecutive Local-Directional Background Removal Filter (L-DBRF). M-MSF enhances the target signal and reduces background noise. L-DBRF removes horizontal structures, which upgrade the signal-to-clutter ratio and background suppression factor. L-DBRF used after M-MSF enhances the synergistic performance of horizontal target detection. Additionally, the adaptive Hysteresis threshold-based scheme is a suitable detection method. We validate the superior performance of the proposed method via three types of evaluation tests, including a real test scenario.

  13. The case for background independence

    CERN Document Server

    Smolin, L

    2005-01-01

    The aim of this paper is to explain carefully the arguments behind the assertion that the correct quantum theory of gravity must be background independent. We begin by recounting how the debate over whether quantum gravity must be background independent is a continuation of a long-standing argument in the history of physics and philosophy over whether space and time are relational or absolute. This leads to a careful statement of what physicists mean when we speak of background independence. Given this we can characterize the precise sense in which general relativity is a background independent theory. The leading background independent approaches to quantum gravity are then discussed, including causal set models, loop quantum gravity and dynamical triangulations and their main achievements are summarized along with the problems that remain open. Some first attempts to cast string/M theory into a background independent formulation are also mentioned. The relational/absolute debate has implications also for ot...

  14. Background subtraction theory and practice

    CERN Document Server

    Elgammal, Ahmed

    2014-01-01

    Background subtraction is a widely used concept for detection of moving objects in videos. In the last two decades there has been a lot of development in designing algorithms for background subtraction, as well as wide use of these algorithms in various important applications, such as visual surveillance, sports video analysis, motion capture, etc. Various statistical approaches have been proposed to model scene backgrounds. The concept of background subtraction also has been extended to detect objects from videos captured from moving cameras. This book reviews the concept and practice of back

  15. Different human copper-zinc superoxide dismutase mutants, SOD1G93A and SOD1H46R, exert distinct harmful effects on gross phenotype in mice.

    Directory of Open Access Journals (Sweden)

    Lei Pan

    Full Text Available Amyotrophic lateral sclerosis (ALS is a heterogeneous group of fatal neurodegenerative diseases characterized by a selective loss of motor neurons in the brain and spinal cord. Creation of transgenic mice expressing mutant Cu/Zn superoxide dismutase (SOD1, as ALS models, has made an enormous impact on progress of the ALS studies. Recently, it has been recognized that genetic background and gender affect many physiological and pathological phenotypes. However, no systematic studies focusing on such effects using ALS models other than SOD1(G93A mice have been conducted. To clarify the effects of genetic background and gender on gross phenotypes among different ALS models, we here conducted a comparative analysis of growth curves and lifespans using congenic lines of SOD1(G93A and SOD1(H46R mice on two different genetic backgrounds; C57BL/6N (B6 and FVB/N (FVB. Copy number of the transgene and their expression between SOD1(G93A and SOD1(H46R lines were comparable. B6 congenic mutant SOD1 transgenic lines irrespective of their mutation and gender differences lived longer than corresponding FVB lines. Notably, the G93A mutation caused severer disease phenotypes than did the H46R mutation, where SOD1(G93A mice, particularly on a FVB background, showed more extensive body weight loss and earlier death. Gender effect on survival also solely emerged in FVB congenic SOD1(G93A mice. Conversely, consistent with our previous study using B6 lines, lack of Als2, a murine homolog for the recessive juvenile ALS causative gene, in FVB congenic SOD1(H46R, but not SOD1(G93A, mice resulted in an earlier death, implying a genetic background-independent but mutation-dependent phenotypic modification. These results indicate that SOD1(G93A- and SOD1(H46R-mediated toxicity and their associated pathogenic pathways are not identical. Further, distinctive injurious effects resulted from different SOD1 mutations, which are associated with genetic background and/or gender

  16. Hanford Site background: Part 1, Soil background for nonradioactive analytes

    International Nuclear Information System (INIS)

    The determination of soil background is one of the most important activities supporting environmental restoration and waste management on the Hanford Site. Background compositions serve as the basis for identifying soil contamination, and also as a baseline in risk assessment processes used to determine soil cleanup and treatment levels. These uses of soil background require an understanding of the extent to which analytes of concern occur naturally in the soils. This report documents the results of sampling and analysis activities designed to characterize the composition of soil background at the Hanford Site, and to evaluate the feasibility for use as Sitewide background. The compositions of naturally occurring soils in the vadose Zone have been-determined for-nonradioactive inorganic and organic analytes and related physical properties. These results confirm that a Sitewide approach to the characterization of soil background is technically sound and is a viable alternative to the determination and use of numerous local or area backgrounds that yield inconsistent definitions of contamination. Sitewide soil background consists of several types of data and is appropriate for use in identifying contamination in all soils in the vadose zone on the Hanford Site. The natural concentrations of nearly every inorganic analyte extend to levels that exceed calculated health-based cleanup limits. The levels of most inorganic analytes, however, are well below these health-based limits. The highest measured background concentrations occur in three volumetrically minor soil types, the most important of which are topsoils adjacent to the Columbia River that are rich in organic carbon. No organic analyte levels above detection were found in any of the soil samples

  17. Similarity-based search of model organism, disease and drug effect phenotypes

    KAUST Repository

    Hoehndorf, Robert

    2015-02-19

    Background: Semantic similarity measures over phenotype ontologies have been demonstrated to provide a powerful approach for the analysis of model organism phenotypes, the discovery of animal models of human disease, novel pathways, gene functions, druggable therapeutic targets, and determination of pathogenicity. Results: We have developed PhenomeNET 2, a system that enables similarity-based searches over a large repository of phenotypes in real-time. It can be used to identify strains of model organisms that are phenotypically similar to human patients, diseases that are phenotypically similar to model organism phenotypes, or drug effect profiles that are similar to the phenotypes observed in a patient or model organism. PhenomeNET 2 is available at http://aber-owl.net/phenomenet. Conclusions: Phenotype-similarity searches can provide a powerful tool for the discovery and investigation of molecular mechanisms underlying an observed phenotypic manifestation. PhenomeNET 2 facilitates user-defined similarity searches and allows researchers to analyze their data within a large repository of human, mouse and rat phenotypes.

  18. Phenotypic features and phylogenetic background of extraintestinal hemolytic Escherichia coli responsible of mortality in puppies.

    Science.gov (United States)

    Turchetto, Sara; Ustulin, Martina; Citterio, Carlo Vittorio; Zanardello, Claudia; Vascellari, Marta; Vio, Denis; Conedera, Gabriella; Milone, Nicola Maria Ferro; Cocchi, Monia

    2015-08-31

    A 10-day-old litter of five puppies of Bracco Italiano dog breed showed weakness and diarrhea and, 2 days later, four of them died. At the same time, the bitch showed high hyperthermia (40 °C) and endometritis. The necropsy of a puppy revealed a severe lobar pneumonia accompanied with a bilateral nephrosis. No gross lesions were detected in other organs. Histopathology of the lung revealed severe multifocal fibrino-suppurative necrotizing bronchiolar-alveolitis associated with rod-shaped bacterial aggregates and diffuse interstitial lymphocytic infiltration. The kidney showed severe multifocal necrosis of the tubular epithelium and diffuse severe congestion of the parenchyma. A pure culture of hemolytic Escherichia coli carrying the Cnf-1 gene was identified, from both the puppy organs and bitch's milk. Moreover, phylo-typing assigned them to the phylogroup B2. Two weeks later, fecal samples from the bitch and the survived puppy were collected for a second microbiological analysis, identifying two hemolytic E. coli strains, Cnf positive and Cdt negative and Cnf and Cdt negative, respectively. Some E. coli pathogenic strains may cause enteric or extraintestinal disease. In dogs and cats, strains of extraintestinal pathogenic E. coli (ExPEC) produce specific virulent factors such as hemolysis and cytotoxin necrotizing factors (Cnf). In this episode, we hypothesize that the bitch's milk could be the main source of ExPEC infection causing high puppies mortality. The role of the bitch as a carrier could not be excluded: stressful conditions, such as pregnancy and delivery, would change the host-pathogen dynamics possibly increasing the release of the infectious burden.

  19. The thrifty phenotype hypothesis revisited

    DEFF Research Database (Denmark)

    Vaag, A A; Grunnet, L G; Arora, G P;

    2012-01-01

    Twenty years ago, Hales and Barker along with their co-workers published some of their pioneering papers proposing the 'thrifty phenotype hypothesis' in Diabetologia (4;35:595-601 and 3;36:62-67). Their postulate that fetal programming could represent an important player in the origin of type 2...

  20. Leaf segmentation in plant phenotyping

    NARCIS (Netherlands)

    Scharr, Hanno; Minervini, Massimo; French, Andrew P.; Klukas, Christian; Kramer, David M.; Liu, Xiaoming; Luengo, Imanol; Pape, Jean Michel; Polder, Gerrit; Vukadinovic, Danijela; Yin, Xi; Tsaftaris, Sotirios A.

    2016-01-01

    Image-based plant phenotyping is a growing application area of computer vision in agriculture. A key task is the segmentation of all individual leaves in images. Here we focus on the most common rosette model plants, Arabidopsis and young tobacco. Although leaves do share appearance and shape cha

  1. Phenotypic spectrum of GABRA1

    DEFF Research Database (Denmark)

    Johannesen, Katrine; Marini, Carla; Pfeffer, Siona;

    2016-01-01

    OBJECTIVE: To delineate phenotypic heterogeneity, we describe the clinical features of a cohort of patients with GABRA1 gene mutations. METHODS: Patients with GABRA1 mutations were ascertained through an international collaboration. Clinical, EEG, and genetic data were collected. Functional analy...

  2. Evaluation of Phenotypic Methods for Detection of Klebsiella Pneumoniae Carbapenemase-Producing K. Pneumoniae in Tehran

    Directory of Open Access Journals (Sweden)

    Leila Azimi

    2015-10-01

    Full Text Available Background: One of the main mechanisms of resistance to carbapenems is potential of Klebsiella pneumoniae to produce K. pneumoniae Carbapenemase (KPC. KPC is an important type of carbapenemase, which can hydrolyze carbapenems and other beta-lactam antibiotics. Modified Hodge Test (MHT and  use  of  boronic  acid  as  a  KPC  inhibitor  are  two  types  of  phenotypic methods, which are used for detection of carbanemase-producing bacteria. Specificity of these two phenotypic tests for identification of KPC was assessed in this study.Methods:   Forty-four   K.   pneumoniae   strains   were   isolated   from  woundinfections   of   burn   patients.   All   isolates   were   identified   with   specific biochemical tests. Carbapenem-resistant K. pneumoniae isolates were identified by disc diffusion method and analyzed with cut off-points of CLSI 2011 guideline.   For   detection   of   KPC-producing   strains,   carbapenem-resistant isolates were examined with two different phenotypic (i.e. MHT and Boronic acid methods. Subsequently, strains with positive phenotypic methods were examined by PCR as a molecular method.Results: Twenty-eight (64% out of 44 isolates were resistant to carbapenem according  to  CLSI  breakpoints  and  16  (36%  were  susceptible.  MHT  was positive in all of carbapenem-resistant isolates but none of them have had the synergism effect between meropenem and boronic acid. Also, all isolates were negative for presence of KPC genes on gel electrophoresis. According to resultsMHT has not enough specificity for detection of KPC. 

  3. Natural variation of model mutant phenotypes in Ciona intestinalis.

    Directory of Open Access Journals (Sweden)

    Paolo Sordino

    Full Text Available BACKGROUND: The study of ascidians (Chordata, Tunicata has made a considerable contribution to our understanding of the origin and evolution of basal chordates. To provide further information to support forward genetics in Ciona intestinalis, we used a combination of natural variation and neutral population genetics as an approach for the systematic identification of new mutations. In addition to the significance of developmental variation for phenotype-driven studies, this approach can encompass important implications in evolutionary and population biology. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report a preliminary survey for naturally occurring mutations in three geographically interconnected populations of C. intestinalis. The influence of historical, geographical and environmental factors on the distribution of abnormal phenotypes was assessed by means of 12 microsatellites. We identified 37 possible mutant loci with stereotyped defects in embryonic development that segregate in a way typical of recessive alleles. Local populations were found to differ in genetic organization and frequency distribution of phenotypic classes. CONCLUSIONS/SIGNIFICANCE: Natural genetic polymorphism of C. intestinalis constitutes a valuable source of phenotypes for studying embryonic development in ascidians. Correlating genetic structure and the occurrence of abnormal phenotypes is a crucial focus for understanding the selective forces that shape natural finite populations, and may provide insights of great importance into the evolutionary mechanisms that generate animal diversity.

  4. Hypertriglyceridemic Waist Phenotype in Adolescents Aged 15 to 18 Years

    Directory of Open Access Journals (Sweden)

    Caridad Hernández Gutiérrez

    2015-09-01

    Full Text Available Background: presence of the hypertriglyceridemic waist phenotype is a predictor of cardiometabolic deterioration, increased type 2 diabetes mellitus and coronary heart disease. Objective: to determine the hypertriglyceridemic waist phenotype in adolescents aged 15 to 18 years from the Area III of Cienfuegos. Method: a case series study was conducted in a universe of 198 adolescents aged 15 to 18 years who attended a consultation created for this study at the Octavio de la Concepción y de la Pedraja University Polyclinic in Cienfuegos municipality from March to December 2013. Each patient completed a questionnaire including the following variables: age, sex, personal medical history, family medical history, weight, height, body mass index, presence of acanthosis nigricans, triglycerides and perimeter. Results: frequency of the phenotype was determined in 15.1 % of the participants with a slight predominance of the 18 age group (16.3 % and female sex (8.6 %. Twenty-one point six percent of the adolescents with a family history of obesity and 21.7 % of those with first-degree diabetic relatives presented the phenotype, being hypertriglyceridemia the most significant condition. Conclusions: a relationship between a family history of diabetes mellitus, obesity, body mass index above the 90th percentile value and presence of the phenotype was established.

  5. Individual odortypes: Interaction of MHC and background genes

    Energy Technology Data Exchange (ETDEWEB)

    Willse, Alan R.; Kwak, Jae; Yamazaki, Kunio; Preti, George; Wahl, Jon H.; Beauchamp, Gary

    2006-12-01

    Genes of the major histocompatibility complex (MHC) influence the urinary odors of mice. Behavioral studies have shown (1) that mice differing only at MHC have distinct urinary odors, suggesting an MHC odor phenotype or odortype; (2) that the MHC odortype can be recognized across different (potentially interfering) background strains; and (3) that the MHC odortype is not an additive trait. Very little is known about the odorants underlying this behavioral phenotype. We compared urinary volatile metabolite profiles of two MHC haplotypes (H-2b and H-2k) and their heterozygous cross (H-2b ? H-2k) for two different background strains using SPME headspace analysis followed by gas chromatography/mass spectrometry. For a surprisingly large number of compounds an MHC association was found to be moderated by background genotype (i.e., there is a significant MHC ? background interaction effect in the statistical model relating genotype to relative compound concentration). A few compounds have an MHC association that is independent of background strain, consistent with MHC discriminations across background strains observed in behavioral experiments. Perhaps more relevant to the role of MHC in social settings where odors are perceived combinatorially, numerous relative ratios between pairs of compounds were found to discriminate MHC types invariant of background type. In addition, a heterozygous effect ? where the metabolite expression (concentration) for the heterozygote is more extreme than the expression for either homozygote ? was observed for many compounds. The large number of compounds involved as well as the strong background and heterozygous influence suggest a complex (but unknown) mechanism of MHC-related odor expression.

  6. Boc modifies the holoprosencephaly spectrum of Cdo mutant mice

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2011-05-01

    Holoprosencephaly (HPE is caused by a failure to form the midline of the forebrain and/or midface. It is one of the most common human birth defects, but clinical expression is extremely variable. HPE is associated with mutations in the sonic hedgehog (SHH pathway. Mice lacking the Shh pathway regulator Cdo (also called Cdon display HPE with strain-dependent penetrance and expressivity, implicating silent modifier genes as one cause of the variability. However, the identities of potential HPE modifiers of this type are unknown. We report here that whereas mice lacking the Cdo paralog Boc do not have HPE, Cdo;Boc double mutants on a largely Cdo-resistant genetic background have lobar HPE with strong craniofacial anomalies and defects in Shh target gene expression in the developing forebrain. Boc is therefore a silent HPE modifier gene in mice. Furthermore, Cdo and Boc have specific, selective roles in Shh signaling in mammals, because Cdo;Boc double-mutant mice do not display the most severe HPE phenotype seen in Shh-null mice, nor do they have major defects in digit patterning or development of vertebrae, which are also Shh-dependent processes. This is in contrast to reported observations in Drosophila, where genetic removal of the Cdo and Boc orthologs Ihog and Boi results in a complete loss of response to the hedgehog ligand. Therefore, there is evolutionary divergence between mammals and insects in the requirement of the hedgehog pathway for Cdo/Ihog family members, with mammalian development involving additional factors and/or distinct mechanisms at this level of pathway regulation.

  7. Genetic association analysis of complex diseases incorporating intermediate phenotype information.

    Directory of Open Access Journals (Sweden)

    Yafang Li

    Full Text Available Genetic researchers often collect disease related quantitative traits in addition to disease status because they are interested in understanding the pathophysiology of disease processes. In genome-wide association (GWA studies, these quantitative phenotypes may be relevant to disease development and serve as intermediate phenotypes or they could be behavioral or other risk factors that predict disease risk. Statistical tests combining both disease status and quantitative risk factors should be more powerful than case-control studies, as the former incorporates more information about the disease. In this paper, we proposed a modified inverse-variance weighted meta-analysis method to combine disease status and quantitative intermediate phenotype information. The simulation results showed that when an intermediate phenotype was available, the inverse-variance weighted method had more power than did a case-control study of complex diseases, especially in identifying susceptibility loci having minor effects. We further applied this modified meta-analysis to a study of imputed lung cancer genotypes with smoking data in 1154 cases and 1137 matched controls. The most significant SNPs came from the CHRNA3-CHRNA5-CHRNB4 region on chromosome 15q24-25.1, which has been replicated in many other studies. Our results confirm that this CHRNA region is associated with both lung cancer development and smoking behavior. We also detected three significant SNPs--rs1800469, rs1982072, and rs2241714--in the promoter region of the TGFB1 gene on chromosome 19 (p = 1.46×10(-5, 1.18×10(-5, and 6.57×10(-6, respectively. The SNP rs1800469 is reported to be associated with chronic obstructive pulmonary disease and lung cancer in cigarette smokers. The present study is the first GWA study to replicate this result. Signals in the 3q26 region were also identified in the meta-analysis. We demonstrate the intermediate phenotype can potentially enhance the power of complex

  8. Facial Identity Recognition in the Broader Autism Phenotype

    OpenAIRE

    C Ellie Wilson; Phillipa Freeman; Jon Brock; A Mike Burton; Romina Palermo

    2010-01-01

    BACKGROUND: The 'broader autism phenotype' (BAP) refers to the mild expression of autistic-like traits in the relatives of individuals with autism spectrum disorder (ASD). Establishing the presence of ASD traits provides insight into which traits are heritable in ASD. Here, the ability to recognise facial identity was tested in 33 parents of ASD children. METHODOLOGY AND RESULTS: In experiment 1, parents of ASD children completed the Cambridge Face Memory Test (CFMT), and a questionnaire asse...

  9. Computational investigation of epithelial cell dynamic phenotype in vitro

    OpenAIRE

    Debnath Jayanta; Mostov Keith; Park Sunwoo; Kim Sean HJ; Hunt C Anthony

    2009-01-01

    Abstract Background When grown in three-dimensional (3D) cultures, epithelial cells typically form cystic organoids that recapitulate cardinal features of in vivo epithelial structures. Characterizing essential cell actions and their roles, which constitute the system's dynamic phenotype, is critical to gaining deeper insight into the cystogenesis phenomena. Methods Starting with an earlier in silico epithelial analogue (ISEA1) that validated for several Madin-Darby canine kidney (MDCK) epith...

  10. Genetic interactions and modifier genes in Hirschsprung's disease

    Institute of Scientific and Technical Information of China (English)

    Adam S Wallace; Richard B Anderson

    2011-01-01

    Hirschsprung's disease is a congenital disorder that occurs in 1:5000 live births. It is characterised by an absence of enteric neurons along a variable region of the gastrointestinal tract. Hirschsprung's disease is classified as a multigenic disorder, because the same phenotype is associated with mutations in multiple distinct genes. Furthermore, the genetics of Hirschsprung's disease are highly complex and not strictly Mendelian. The phenotypic variability and incomplete penetrance observed in Hirschsprung's disease also suggests the involvement of modifier genes. Here, we summarise the current knowledge of the genetics underlying Hirschsprung's disease based on human and animal studies, focusing on the principal causative genes, their interactions, and the role of modifier genes.

  11. Generalized Background-Field Method

    CERN Document Server

    Feng, Y J

    1997-01-01

    The graphical method discussed previously can be used to create new gauges not reachable by the path-integral formalism. By this means a new gauge is designed for more efficient two-loop QCD calculations. It is related to but simpler than the ordinary background-field gauge, in that even the triple-gluon vertices for internal lines contain only four terms, not the usual six. This reduction simplifies the calculation inspite of the necessity to include other vertices for compensation. Like the ordinary background-field gauge, this generalized background-field gauge also preserves gauge invariance of the external particles. As a check of the result and an illustration for the reduction in labour, an explicit calculation of the two-loop QCD 45% of computation compared to the ordinary background-field gauge.

  12. Geometrodynamics on a background spacetime

    CERN Document Server

    Papadopoulos, P P; Papadopoulos, Philippos; Sopuerta, Carlos F.

    2001-01-01

    The formulation of the initial value problem for the Einstein equations is at the heart of obtaining interesting new solutions using numerical relativity and still very much under theoretical and applied scrutiny. We develop a specialised background geometry approach, for systems where there is non-trivial a priori knowledge about the spacetime under study. The background three-geometry and associated connection are used to express the ADM evolution equations in terms of physical non-linear deviations from that background. Expressing the equations in first order form leads naturally to a system closely linked to the Einstein-Christoffel system, introduced by Anderson and York, and sharing its hyperbolicity properties. The background metric approach can drastically alter the source structure of the equations, and we present an argument as to why this is likely to be numerically advantageous.

  13. Backgrounds in AFP Detector Estimation

    CERN Document Server

    Huang, Yicong

    2016-01-01

    The ATLAS Forward Proton (AFP) detectors aim to measure protons that are scattered in the ATLAS interaction point under very small angles ($90-160 \\mu rad$). The diffractive protons detected by the AFP may be accompanied by beam halo. This report presents an estimation of the beam halo backgrounds in the AFP using low pile-up data, and position distributions of the backgrounds in the AFP.

  14. Background independent quantization and wave propagation

    International Nuclear Information System (INIS)

    We apply a type of background independent 'polymer' quantization to a free scalar field in a flat spacetime. Using semiclassical states, we find an effective wave equation that is both nonlinear and Lorentz invariance violating. We solve this equation perturbatively for several cases of physical interest, and show that polymer corrections to solutions of the Klein-Gordon equation depend on the amplitude of the field. This leads to an effective dispersion relation that depends on the amplitude, frequency, and shape of the wave packet, and is hence distinct from other modified dispersion relations found in the literature. We also demonstrate that polymer effects tend to accumulate with time for plane-symmetric waveforms. We conclude by discussing the possibility of measuring deviations from the Klein-Gordon equation in particle accelerators or astrophysical observations.

  15. Deciphering the Galaxy Guppy phenotype

    Directory of Open Access Journals (Sweden)

    Philip Shaddock

    2011-01-01

    Full Text Available Animal breeding hobbyists have been useful to science because they identify and isolate colorcoat mutations that geneticists can in turn use in their studies of the development and differentiation ofcolor cells. This paper discusses a very interesting color mutant, the Japanese Galaxy, tracing its creationfrom back to a self-educated genetics hobbyist, Hoskiki Tsutsui. The paper discusses a constituent genepreviously studied by Dr. Violet Phang, the snakeskin gene (the linked body and fin genes Ssb and Sst.And it discusses a gene previously unknown to science, the Schimmelpfennig Platinum gene (Sc.Through crossing experiments, the author determines that the combination of these two genes producesan intermediate phenotype, the Medusa. Incorporating the Grass (Gr, another gene unknown to sciencegene into the Medusa through a crossover produces the Galaxy phenotype. Microscope studies of thesnakeskin pattern in Galaxies and snakeskins reveals some parallels with similar studies made of theZebrafish Danio.

  16. Phenotypic expression in mucopolysaccharidosis VII.

    OpenAIRE

    Bernsen, P L; Wevers, R. A.; Gabreëls, F J; Lamers, K J; Sonnen, A E; Stekhoven, J H

    1987-01-01

    beta-glucuronidase deficiency is an extremely rare disorder which is known to have a considerable phenotypic variation. A survey of the clinical findings in 19 previously reported patients with mucopolysaccharidosis VII is presented together with the results of clinical and biochemical studies in two further patients. Because a similar clinical picture is present in a heterozygotic sister it is doubted whether all signs and symptoms can be attributed to the beta-glucuronidase deficiency. The ...

  17. Statistical models for trisomic phenotypes

    Energy Technology Data Exchange (ETDEWEB)

    Lamb, N.E.; Sherman, S.L.; Feingold, E. [Emory Univ., Atlanta, GA (United States)

    1996-01-01

    Certain genetic disorders are rare in the general population but more common in individuals with specific trisomies, which suggests that the genes involved in the etiology of these disorders may be located on the trisomic chromosome. As with all aneuploid syndromes, however, a considerable degree of variation exists within each phenotype so that any given trait is present only among a subset of the trisomic population. We have previously presented a simple gene-dosage model to explain this phenotypic variation and developed a strategy to map genes for such traits. The mapping strategy does not depend on the simple model but works in theory under any model that predicts that affected individuals have an increased likelihood of disomic homozygosity at the trait locus. This paper explores the robustness of our mapping method by investigating what kinds of models give an expected increase in disomic homozygosity. We describe a number of basic statistical models for trisomic phenotypes. Some of these are logical extensions of standard models for disomic phenotypes, and some are more specific to trisomy. Where possible, we discuss genetic mechanisms applicable to each model. We investigate which models and which parameter values give an expected increase in disomic homozygosity in individuals with the trait. Finally, we determine the sample sizes required to identify the increased disomic homozygosity under each model. Most of the models we explore yield detectable increases in disomic homozygosity for some reasonable range of parameter values, usually corresponding to smaller trait frequencies. It therefore appears that our mapping method should be effective for a wide variety of moderately infrequent traits, even though the exact mode of inheritance is unlikely to be known. 21 refs., 8 figs., 1 tab.

  18. Wine Expertise Predicts Taste Phenotype.

    Science.gov (United States)

    Hayes, John E; Pickering, Gary J

    2012-03-01

    Taste phenotypes have long been studied in relation to alcohol intake, dependence, and family history, with contradictory findings. However, on balance - with appropriate caveats about populations tested, outcomes measured and psychophysical methods used - an association between variation in taste responsiveness and some alcohol behaviors is supported. Recent work suggests super-tasting (operationalized via propylthiouracil (PROP) bitterness) not only associates with heightened response but also with more acute discrimination between stimuli. Here, we explore relationships between food and beverage adventurousness and taste phenotype. A convenience sample of wine drinkers (n=330) were recruited in Ontario and phenotyped for PROP bitterness via filter paper disk. They also filled out a short questionnaire regarding willingness to try new foods, alcoholic beverages and wines as well as level of wine involvement, which was used to classify them as a wine expert (n=110) or wine consumer (n=220). In univariate logisitic models, food adventurousness predicted trying new wines and beverages but not expertise. Likewise, wine expertise predicted willingness to try new wines and beverages but not foods. In separate multivariate logistic models, willingness to try new wines and beverages was predicted by expertise and food adventurousness but not PROP. However, mean PROP bitterness was higher among wine experts than wine consumers, and the conditional distribution functions differed between experts and consumers. In contrast, PROP means and distributions did not differ with food adventurousness. These data suggest individuals may self-select for specific professions based on sensory ability (i.e., an active gene-environment correlation) but phenotype does not explain willingness to try new stimuli.

  19. [Plasticity of the cellular phenotype].

    Science.gov (United States)

    Chneiweiss, Hervé

    2011-01-01

    The tragical consequences of the Hiroshima and Nagasaki atomic bombs in 1945 were to lead to the discovery of hematopoietic stem cells and their phenotypic plasticity, in response to environmental factors. These concepts were much later extended to the founding cells of other tissues. In the following collection of articles, the mechanisms underlying this plasticity, at the frontiers of developmental biology and oncology, are illustrated in the case of various cell types of neural origin and of some tumours. PMID:21501574

  20. Adaptive evolution of molecular phenotypes

    Science.gov (United States)

    Held, Torsten; Nourmohammad, Armita; Lässig, Michael

    2014-09-01

    Molecular phenotypes link genomic information with organismic functions, fitness, and evolution. Quantitative traits are complex phenotypes that depend on multiple genomic loci. In this paper, we study the adaptive evolution of a quantitative trait under time-dependent selection, which arises from environmental changes or through fitness interactions with other co-evolving phenotypes. We analyze a model of trait evolution under mutations and genetic drift in a single-peak fitness seascape. The fitness peak performs a constrained random walk in the trait amplitude, which determines the time-dependent trait optimum in a given population. We derive analytical expressions for the distribution of the time-dependent trait divergence between populations and of the trait diversity within populations. Based on this solution, we develop a method to infer adaptive evolution of quantitative traits. Specifically, we show that the ratio of the average trait divergence and the diversity is a universal function of evolutionary time, which predicts the stabilizing strength and the driving rate of the fitness seascape. From an information-theoretic point of view, this function measures the macro-evolutionary entropy in a population ensemble, which determines the predictability of the evolutionary process. Our solution also quantifies two key characteristics of adapting populations: the cumulative fitness flux, which measures the total amount of adaptation, and the adaptive load, which is the fitness cost due to a population's lag behind the fitness peak.

  1. Atypical disease phenotypes in pediatric ulcerative colitis

    DEFF Research Database (Denmark)

    Levine, Arie; de Bie, Charlotte I; Turner, Dan;

    2013-01-01

    Definitive diagnosis of pediatric ulcerative colitis (UC) may be particularly challenging since isolated colitis with overlapping features is common in pediatric Crohn's disease (CD), while atypical phenotypes of UC are not uncommon. The Paris classification allows more accurate phenotyping...

  2. Integrating binary traits with quantitative phenotypes for association mapping of multivariate phenotypes.

    Science.gov (United States)

    Mukhopadhyay, Indranil; Saha, Sujayam; Ghosh, Saurabh

    2011-01-01

    Clinical binary end-point traits are often governed by quantitative precursors. Hence it may be a prudent strategy to analyze a clinical end-point trait by considering a multivariate phenotype vector, possibly including both quantitative and qualitative phenotypes. A major statistical challenge lies in integrating the constituent phenotypes into a reduced univariate phenotype for association analyses. We assess the performances of certain reduced phenotypes using analysis of variance and a model-free quantile-based approach. We find that analysis of variance is more powerful than the quantile-based approach in detecting association, particularly for rare variants. We also find that using a principal component of the quantitative phenotypes and the residual of a logistic regression of the binary phenotype on the quantitative phenotypes may be an optimal method for integrating a binary phenotype with quantitative phenotypes to define a reduced univariate phenotype. PMID:22373144

  3. Phenotype prediction in regulated metabolic networks

    Directory of Open Access Journals (Sweden)

    Centler Florian

    2008-04-01

    Full Text Available Abstract Background Due to the growing amount of biological knowledge that is incorporated into metabolic network models, their analysis has become more and more challenging. Here, we examine the capabilities of the recently introduced chemical organization theory (OT to ease this task. Considering only network stoichiometry, the theory allows the prediction of all potentially persistent species sets and therewith rigorously relates the structure of a network to its potential dynamics. By this, the phenotypes implied by a metabolic network can be predicted without the need for explicit knowledge of the detailed reaction kinetics. Results We propose an approach to deal with regulation – and especially inhibitory interactions – in chemical organization theory. One advantage of this approach is that the metabolic network and its regulation are represented in an integrated way as one reaction network. To demonstrate the feasibility of this approach we examine a model by Covert and Palsson (J Biol Chem, 277(31, 2002 of the central metabolism of E. coli that incorporates the regulation of all involved genes. Our method correctly predicts the known growth phenotypes on 16 different substrates. Without specific assumptions, organization theory correctly predicts the lethality of knockout experiments in 101 out of 116 cases. Taking into account the same model specific assumptions as in the regulatory flux balance analysis (rFBA by Covert and Palsson, the same performance is achieved (106 correctly predicted cases. Two model specific assumptions had to be considered: first, we have to assume that secreted molecules do not influence the regulatory system, and second, that metabolites with increasing concentrations indicate a lethal state. Conclusion The introduced approach to model a metabolic network and its regulation in an integrated way as one reaction network makes organization analysis a universal technique to study the potential behavior of

  4. Multivariate Analysis of Genotype-Phenotype Association.

    Science.gov (United States)

    Mitteroecker, Philipp; Cheverud, James M; Pavlicev, Mihaela

    2016-04-01

    With the advent of modern imaging and measurement technology, complex phenotypes are increasingly represented by large numbers of measurements, which may not bear biological meaning one by one. For such multivariate phenotypes, studying the pairwise associations between all measurements and all alleles is highly inefficient and prevents insight into the genetic pattern underlying the observed phenotypes. We present a new method for identifying patterns of allelic variation (genetic latent variables) that are maximally associated-in terms of effect size-with patterns of phenotypic variation (phenotypic latent variables). This multivariate genotype-phenotype mapping (MGP) separates phenotypic features under strong genetic control from less genetically determined features and thus permits an analysis of the multivariate structure of genotype-phenotype association, including its dimensionality and the clustering of genetic and phenotypic variables within this association. Different variants of MGP maximize different measures of genotype-phenotype association: genetic effect, genetic variance, or heritability. In an application to a mouse sample, scored for 353 SNPs and 11 phenotypic traits, the first dimension of genetic and phenotypic latent variables accounted for >70% of genetic variation present in all 11 measurements; 43% of variation in this phenotypic pattern was explained by the corresponding genetic latent variable. The first three dimensions together sufficed to account for almost 90% of genetic variation in the measurements and for all the interpretable genotype-phenotype association. Each dimension can be tested as a whole against the hypothesis of no association, thereby reducing the number of statistical tests from 7766 to 3-the maximal number of meaningful independent tests. Important alleles can be selected based on their effect size (additive or nonadditive effect on the phenotypic latent variable). This low dimensionality of the genotype-phenotype map

  5. Low Background Micromegas in CAST

    Science.gov (United States)

    Garza, J. G.; Aune, S.; 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.

    2015-11-01

    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/cm2/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/cm2/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 the strategies to further reduce the background level. Finally, we will describe the R&D paths to achieve sub-keV energy thresholds, which could broaden the physics case of axion helioscopes.

  6. Background Independent String Field Theory

    CERN Document Server

    Bars, Itzhak

    2014-01-01

    We develop a new background independent Moyal star formalism in bosonic open string field theory. The new star product is formulated in a half-phase-space, and because phase space is independent of any background fields, the interactions are background independent. In this basis there is a large amount of symmetry, including a supersymmetry OSp(d|2) that acts on matter and ghost degrees of freedom, and simplifies computations. The BRST operator that defines the quadratic kinetic term of string field theory may be regarded as the solution of the equation of motion A*A=0 of a purely cubic background independent string field theory. We find an infinite number of non-perturbative solutions to this equation, and are able to associate them to the BRST operator of conformal field theories on the worldsheet. Thus, the background emerges from a spontaneous-type breaking of a purely cubic highly symmetric theory. The form of the BRST field breaks the symmetry in a tractable way such that the symmetry continues to be us...

  7. Transgene x environment interactions in genetically modified wheat.

    Directory of Open Access Journals (Sweden)

    Simon L Zeller

    Full Text Available BACKGROUND: The introduction of transgenes into plants may cause unintended phenotypic effects which could have an impact on the plant itself and the environment. Little is published in the scientific literature about the interrelation of environmental factors and possible unintended effects in genetically modified (GM plants. METHODS AND FINDINGS: We studied transgenic bread wheat Triticum aestivum lines expressing the wheat Pm3b gene against the fungus powdery mildew Blumeria graminis f.sp. tritici. Four independent offspring pairs, each consisting of a GM line and its corresponding non-GM control line, were grown under different soil nutrient conditions and with and without fungicide treatment in the glasshouse. Furthermore, we performed a field experiment with a similar design to validate our glasshouse results. The transgene increased the resistance to powdery mildew in all environments. However, GM plants reacted sensitive to fungicide spraying in the glasshouse. Without fungicide treatment, in the glasshouse GM lines had increased vegetative biomass and seed number and a twofold yield compared with control lines. In the field these results were reversed. Fertilization generally increased GM/control differences in the glasshouse but not in the field. Two of four GM lines showed up to 56% yield reduction and a 40-fold increase of infection with ergot disease Claviceps purpurea compared with their control lines in the field experiment; one GM line was very similar to its control. CONCLUSIONS: Our results demonstrate that, depending on the insertion event, a particular transgene can have large effects on the entire phenotype of a plant and that these effects can sometimes be reversed when plants are moved from the glasshouse to the field. However, it remains unclear which mechanisms underlie these effects and how they may affect concepts in molecular plant breeding and plant evolutionary ecology.

  8. Genome-wide screen for modifiers of Parkinson's disease genes in Drosophila

    Directory of Open Access Journals (Sweden)

    Fernandes Caroline

    2011-04-01

    Full Text Available Abstract Background Mutations in parkin and PTEN-induced kinase 1 (Pink1 lead to autosomal recessive forms of Parkinson's disease (PD. parkin and Pink1 encode a ubiquitin-protein ligase and a mitochondrially localized serine/threonine kinase, respectively. Recent studies have implicated Parkin and Pink1 in a common and evolutionarily conserved pathway for protecting mitochondrial integrity. Results To systematically identify novel components of the PD pathways, we generated a genetic background that allowed us to perform a genome-wide F1 screen for modifiers of Drosophila parkin (park and Pink1 mutant phenotype. From screening ~80% of the fly genome, we identified a number of cytological regions that interact with park and/or Pink1. Among them, four cytological regions were selected for identifying corresponding PD-interacting genes. By analyzing smaller deficiency chromosomes, available transgenic RNAi lines, and P-element insertions, we identified five PD-interacting genes. Among them, opa1 and drp1 have been previously implicated in the PD pathways, whereas debra (dbr, Pi3K21B and β4GalNAcTA are novel PD-interacting genes. Conclusions We took an unbiased genetic approach to systematically isolate modifiers of PD genes in Drosophila. Further study of novel PD-interacting genes will shed new light on the function of PD genes and help in the development of new therapeutic strategies for treating Parkinson's disease.

  9. Genotype-phenotype correlation in 21 patients with Wolf-Hirschhorn syndrome using high resolution array comparative genome hybridisation (CGH)

    NARCIS (Netherlands)

    Maas, N. M. C.; Van Buggenhout, G.; Hannes, F.; Thienpont, B.; Sanlaville, D.; Kok, K.; Midro, A.; Andrieux, J.; Anderlid, B-M; Schoumans, J.; Hordijk, R.; Devriendt, K.; Fryns, J-P; Vermeesch, J. R.

    2008-01-01

    Background: The Wolf-Hirschhorn syndrome (WHS) is usually caused by terminal deletions of the short arm of chromosome 4 and is phenotypically defined by growth and mental retardation, seizures, and specific craniofacial manifestations. Large variation is observed in phenotypic expression of these fe

  10. Gene-environment and protein degradation signatures characterize genomic and phenotypic diversity in wild Caenorhabditis elegans populations

    NARCIS (Netherlands)

    Volkers, J.M.; Snoek, L.B.; Hellenberg Hubar, van C.J.; Coopman, R.; Chen, W.; Yang, Wentao; Sterken, M.G.; Schulenburg, H.; Braeckman, B.; Kammenga, J.E.

    2013-01-01

    Background: Analyzing and understanding the relationship between genotypes and phenotypes is at the heart of genetics. Research on the nematode Caenorhabditis elegans has been instrumental for unraveling genotype-phenotype relations, and has important implications for understanding the biology of ma

  11. Chinese newspaper coverage of genetically modified organisms

    OpenAIRE

    Du Li; Rachul Christen

    2012-01-01

    Abstract Background Debates persist around the world over the development and use of genetically modified organisms (GMO). News media has been shown to both reflect and influence public perceptions of health and science related debates, as well as policy development. To better understand the news coverage of GMOs in China, we analyzed the content of articles in two Chinese newspapers that relate to the development and promotion of genetically modified technologies and GMOs. Methods Searching ...

  12. A definition of background independence

    International Nuclear Information System (INIS)

    We propose a definition for background (in)/dependence in dynamical theories of the evolution of configurations that have a continuous symmetry and test this definition on particle models and on gravity. Our definition draws from Barbour's best matching framework developed for the purpose of implementing spatial and temporal relationalism. Among other interesting theories, general relativity can be derived within this framework in novel ways. We study the detailed canonical structure of a wide range of best matching theories and show that their actions must have a local gauge symmetry. When gauge theory is derived in this way, we obtain at the same time a conceptual framework for distinguishing between background-dependent and -independent theories. Gauge invariant observables satisfying Kuchar's criterion are identified and, in simple cases, explicitly computed. We propose a procedure for inserting a global background time into temporally relational theories. Interestingly, using this procedure in general relativity leads to unimodular gravity.

  13. The isotropic radio background revisited

    CERN Document Server

    Fornengo, Nicolao; Regis, Marco; Taoso, Marco

    2014-01-01

    We present an extensive analysis on the determination of the isotropic radio background. We consider six different radio maps, ranging from 22 MHz to 2.3 GHz and covering a large fraction of the sky. The large scale emission is modeled as a linear combination of an isotropic component plus the Galactic synchrotron radiation and thermal bremsstrahlung. Point-like and extended sources are either masked or accounted for by means of a template. We find a robust estimate of the isotropic radio background, with limited scatter among different Galactic models. The level of the isotropic background lies significantly above the contribution obtained by integrating the number counts of observed extragalactic sources. Since the isotropic component dominates at high latitudes, thus making the profile of the total emission flat, a Galactic origin for such excess appears unlikely. We conclude that, unless a systematic offset is present in the maps, and provided that our current understanding of the Galactic synchrotron emi...

  14. Neutron background estimates in GESA

    Directory of Open Access Journals (Sweden)

    Fernandes A.C.

    2014-01-01

    Full Text Available The SIMPLE project looks for nuclear recoil events generated by rare dark matter scattering interactions. Nuclear recoils are also produced by more prevalent cosmogenic neutron interactions. While the rock overburden shields against (μ,n neutrons to below 10−8 cm−2 s−1, it itself contributes via radio-impurities. Additional shielding of these is similar, both suppressing and contributing neutrons. We report on the Monte Carlo (MCNP estimation of the on-detector neutron backgrounds for the SIMPLE experiment located in the GESA facility of the Laboratoire Souterrain à Bas Bruit, and its use in defining additional shielding for measurements which have led to a reduction in the extrinsic neutron background to ∼ 5 × 10−3 evts/kgd. The calculated event rate induced by the neutron background is ∼ 0,3 evts/kgd, with a dominant contribution from the detector container.

  15. JK null alleles identified from Japanese individuals with Jk(a−b−) phenotype.

    Science.gov (United States)

    Onodera, T; Sasaki, K; Tsuneyama, H; Isa, K; Ogasawara, K; Satake, M; Tadokoro, K; Uchikawa, M

    2014-05-01

    The Kidd blood group system consists of three common phenotypes: Jk(a+b−), Jk(a−b+) and Jk(a+b+), and one rare phenotype, Jk(a−b−). Jka/Jkb polymorphism is associated with c.838G>A (p.Asp280Asn) in exon 9 of the JK (SLC14A1) gene, and the corresponding alleles are named JK*01 and JK*02. The rare phenotype Jk(a−b−) was first found in a Filipina of Spanish and Chinese ancestry, and to date, several JK null alleles responsible for the Jk(a−b−) phenotype have been reported. We report seven novel JK null alleles, 4 with a JK*01 background and 3 with a JK*02 background, identified from Jk(a−b−) Japanese. PMID:24877238

  16. Annexin A6 modifies muscular dystrophy by mediating sarcolemmal repair

    OpenAIRE

    Swaggart, KA; Demonbreun, AR; Vo, AH; Swanson, KE; Kim, EY; Fahrenbach, JP; Holley-Cuthrell, J; Eskin, A; Z. Chen; Squire, K; Heydemann, A; Palmer, AA; Nelson, SF; McNally, EM

    2014-01-01

    Many monogenic disorders, including the muscular dystrophies, display phenotypic variability despite the same disease-causing mutation. To identify genetic modifiers of muscular dystrophy and its associated cardiomyopathy, we used quantitative trait locus mapping and whole genome sequencing in a mouse model. This approach uncovered a modifier locus on chromosome 11 associated with sarcolemmal membrane damage and heart mass. Whole genome and RNA sequencing identified Anxa6, encoding annexin A6...

  17. Distinct genetic regions modify specific muscle groups in muscular dystrophy

    OpenAIRE

    Swaggart, Kayleigh A.; Heydemann, Ahlke; Palmer, Abraham A.; McNally, Elizabeth M.

    2010-01-01

    Phenotypic expression in the muscular dystrophies is variable, even with the identical mutation, providing strong evidence that genetic modifiers influence outcome. To identify genetic modifier loci, we used quantitative trait locus mapping in two differentially affected mouse strains with muscular dystrophy. Using the Sgcg model of limb girdle muscular dystrophy that lacks the dystrophin-associated protein γ-sarcoglycan, we evaluated chromosomal regions that segregated with two distinct quan...

  18. Latent TGF-β–binding protein 4 modifies muscular dystrophy in mice

    OpenAIRE

    Heydemann, Ahlke; Ceco, Ermelinda; Lim, Jackie E.; Hadhazy, Michele; Ryder, Pearl; Moran, Jennifer L; Beier, David R.; Palmer, Abraham A.; McNally, Elizabeth M.

    2009-01-01

    Most single-gene diseases, including muscular dystrophy, display a nonuniform phenotype. Phenotypic variability arises, in part, due to the presence of genetic modifiers that enhance or suppress the disease process. We employed an unbiased mapping approach to search for genes that modify muscular dystrophy in mice. In a genome-wide scan, we identified a single strong locus on chromosome 7 that influenced two pathological features of muscular dystrophy, muscle membrane permeability and muscle ...

  19. Detector Background at Muon Colliders

    Energy Technology Data Exchange (ETDEWEB)

    Mokhov, N.V.; Striganov, S.I.; /Fermilab

    2011-09-01

    Physics goals of a Muon Collider (MC) can only be reached with appropriate design of the ring, interaction region (IR), high-field superconducting magnets, machine-detector interface (MDI) and detector. Results of the most recent realistic simulation studies are presented for a 1.5-TeV MC. It is shown that appropriately designed IR and MDI with sophisticated shielding in the detector have a potential to substantially suppress the background rates in the MC detector. The main characteristics of backgrounds are studied.

  20. Children of ethnic minority backgrounds

    DEFF Research Database (Denmark)

    Johansen, Stine Liv

    2010-01-01

    media products and toys just as they will have knowledge of different media texts, play genres, rhymes etc. This has consequences for their ability to access social settings, for instance in play. New research in this field will focus on how children themselves make sense of this balancing of cultures......Children of ethnic minority background balance their everyday life between a cultural background rooted in their ethnic origin and a daily life in day care, schools and with peers that is founded in a majority culture. This means, among other things, that they often will have access to different...

  1. Background music and cognitive performance.

    Science.gov (United States)

    Angel, Leslie A; Polzella, Donald J; Elvers, Greg C

    2010-06-01

    The present experiment employed standardized test batteries to assess the effects of fast-tempo music on cognitive performance among 56 male and female university students. A linguistic processing task and a spatial processing task were selected from the Criterion Task Set developed to assess verbal and nonverbal performance. Ten excerpts from Mozart's music matched for tempo were selected. Background music increased the speed of spatial processing and the accuracy of linguistic processing. The findings suggest that background music can have predictable effects on cognitive performance. PMID:20865993

  2. Generative electronic background music system

    International Nuclear Information System (INIS)

    In this short paper-extended abstract the new approach to generation of electronic background music has been presented. The Generative Electronic Background Music System (GEBMS) has been located between other related approaches within the musical algorithm positioning framework proposed by Woller et al. The music composition process is performed by a number of mini-models parameterized by further described properties. The mini-models generate fragments of musical patterns used in output composition. Musical pattern and output generation are controlled by container for the mini-models - a host-model. General mechanism has been presented including the example of the synthesized output compositions

  3. Generative electronic background music system

    Energy Technology Data Exchange (ETDEWEB)

    Mazurowski, Lukasz [Faculty of Computer Science, West Pomeranian University of Technology in Szczecin, Zolnierska Street 49, Szczecin, PL (Poland)

    2015-03-10

    In this short paper-extended abstract the new approach to generation of electronic background music has been presented. The Generative Electronic Background Music System (GEBMS) has been located between other related approaches within the musical algorithm positioning framework proposed by Woller et al. The music composition process is performed by a number of mini-models parameterized by further described properties. The mini-models generate fragments of musical patterns used in output composition. Musical pattern and output generation are controlled by container for the mini-models - a host-model. General mechanism has been presented including the example of the synthesized output compositions.

  4. Exotic branes and nongeometric backgrounds.

    Science.gov (United States)

    de Boer, Jan; Shigemori, Masaki

    2010-06-25

    When string or M theory is compactified to lower dimensions, the U-duality symmetry predicts so-called exotic branes whose higher-dimensional origin cannot be explained by the standard string or M-theory branes. We argue that exotic branes can be understood in higher dimensions as nongeometric backgrounds or U folds, and that they are important for the physics of systems which originally contain no exotic charges, since the supertube effect generically produces such exotic charges. We discuss the implications of exotic backgrounds for black hole microstate (non-)geometries. PMID:20867363

  5. Schizophrenia patients with a history of childhood trauma have a pro-inflammatory phenotype

    OpenAIRE

    Dennison, Una; McKernan, Declan P.; Cryan, John F; Dinan, Timothy G.

    2012-01-01

    Background. Increasing evidence indicates that childhood trauma is a risk factor for schizophrenia and patients with this syndrome have a pro-inflammatory phenotype. We tested the hypothesis that the pro-inflammatory phenotype in schizophrenia is associated with childhood trauma and that patients without a history of such trauma have a similar immune profile to healthy controls. Method. We recruited 40 schizophrenia patients and 40 controls, all of whom completed the Childhood Trauma ...

  6. Microenvironment-dependent phenotypic changes in a SCID mouse model for malignant mesothelioma

    OpenAIRE

    Eva eDarai-Ramqvist; Gustav eNilsonne; Carmen eFlores-Staino; Anders eHjerpe; Katalin eDobra

    2013-01-01

    Background and Aims: Malignant mesothelioma is an aggressive, therapy-resistant tumor. Mesothelioma cells may assume an epithelioid or a sarcomatoid phenotype, and presence of sarcomatoid cells predicts poor prognosis. In this study, we investigated differentiation of mesothelioma cells in a xenograft model, where mesothelioma cells of both phenotypes were induced to form tumors in SCID mice. Methods: Xenografts were established and thoroughly characterized using a comprehensive immunohistoch...

  7. The broad autism phenotype predicts child functioning in autism spectrum disorders

    OpenAIRE

    Maxwell, Christina R.; Parish-Morris, Julia; Hsin, Olivia; Bush, Jennifer C; Schultz, Robert T.

    2013-01-01

    Background Broad autism phenotype (BAP) is a milder expression of the social and communication impairments seen in autism spectrum disorders (ASD). While prior studies characterized the BAP in unaffected family members of probands with ASD, the relationship between parental BAP traits and proband symptomatology remains poorly understood. This study utilizes the Broad Autism Phenotype Questionnaire (BAPQ) in parents and the Social Responsiveness Scale (SRS) in children to examine this connecti...

  8. Phenotypic, genetic, and genome-wide structure in the metabolic syndrome

    OpenAIRE

    Comuzzie Anthony G; Blangero John; Dyer Tom; North Kari E; Martin Lisa J; Williams Jeff

    2003-01-01

    Abstract Background Insulin resistance, obesity, dyslipidemia, and high blood pressure characterize the metabolic syndrome. In an effort to explore the utility of different multivariate methods of data reduction to better understand the genetic influences on the aggregation of metabolic syndrome phenotypes, we calculated phenotypic, genetic, and genome-wide LOD score correlation matrices using five traits (total cholesterol, high density lipoprotein cholesterol, triglycerides, systolic blood ...

  9. Knowledge-based analysis of phenotypes

    KAUST Repository

    Hoendorf, Robert

    2016-01-27

    Phenotypes are the observable characteristics of an organism, and they are widely recorded in biology and medicine. To facilitate data integration, ontologies that formally describe phenotypes are being developed in several domains. I will describe a formal framework to describe phenotypes. A formalized theory of phenotypes is not only useful for domain analysis, but can also be applied to assist in the diagnosis of rare genetic diseases, and I will show how our results on the ontology of phenotypes is now applied in biomedical research.

  10. Acetylation phenotype variation in pediatric patients with atopic dermatitis

    Directory of Open Access Journals (Sweden)

    Rafi A Majeed Al-Razzuqi

    2011-01-01

    Full Text Available Background: Few studies have been done on the relation between acetylator status and allergic diseases. Aim: To determine any possible association between acetylating phenotype in pediatric patients with atopic dermatitis (AD and the disease prognosis. Patients and Methods: Thirty-six pediatric patients and forty two healthy children as a control group were participated in the study. All participants received a single oral dose of dapsone of 1.54 mg/kg body weight, after an overnight fast. Using high performance liquid chromatography (HPLC, plasma concentrations of dapsone and its metabolite (monoacetyldapsone were estimated to phenotype the participants as slow and rapid acetylators according to their acetylation ratio (ratio of monoacetyldapsone to dapsone. Results: 72.2% of pediatric patients with AD showed slow acetylating status as compared to 69.4% of control individuals. Also, 73% of AD patients with slow acetylating phenotype had familial history of allergy. The severity of AD occurred only in slow acetylator patients. The eczematous lesions in slow acetylators presented mainly in the limbs, while in rapid acetylators, they were found mostly in face and neck. Conclusion: This study shows an association between the N-acetylation phenotype variation and clinical aspects of AD.

  11. Educational Choice. A Background Paper.

    Science.gov (United States)

    Quality Education for Minorities Network, Washington, DC.

    This paper addresses school choice, one proposal to address parental involvement concerns, focusing on historical background, definitions, rationale for advocating choice, implementation strategies, and implications for minorities and low-income families. In the past, transfer payment programs such as tuition tax credits and vouchers were…

  12. Low Background Micromegas in CAST

    DEFF Research Database (Denmark)

    Garza, J G; Aune, S.; Aznar, F.;

    2014-01-01

    to background levels below 10−6 counts/keV/cm2/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/cm2/s, showing good prospects for the application of this technology in IAXO...

  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. Analysis of Pena Shokeir phenotype.

    Science.gov (United States)

    Hall, J G

    1986-09-01

    At this point in time, we recognize that "Pena Shokeir" is not a diagnosis or a specific syndrome but rather a description of a phenotype produced by fetal akinesia or decreased in utero movement. In its "full blown" form, it is characterized by polyhydramnios, intrauterine growth retardation, pulmonary hypoplasia, craniofacial and limb anomalies, congenital contractures, short umbilical cord, and lethality. From the cases thus far reported, we would anticipate that the phenotype is present in a very heterogeneous group of disorders--heterogeneous both with regard to the specific anomalies present and with regard to the causes (which must include many environmental agents and multiple genetic forms). One challenge for the future is to better describe and delineate specific entities. In the meantime, we would do well to use the terms "Pena Shokeir phenotype" or "fetal akinesia/hypokinesia sequence," which do not imply a single entity. There are many practical aspects of recognizing this phenotype. The presence of any one of the cardinal signs of the fetal akinesia/hypokinesia sequence should alert the physician to look for the other associated anomalies, since specific treatment may be indicated, and catch-up or compensatory growth may occur, if given a chance. The ability to provide prenatal diagnosis and perhaps prenatal treatment in the future may allow us to alter dramatically the natural history of some cases. In others, we need to establish when treatment is possible and when it gives no benefit. Perhaps the most important insight gained from the study of the fetal akinesia sequence is the reaffirmation of the concept that function is an integral part of normal development. Specific structures do not develop in isolation but are part of a carefully timed and integrated system. The "use" of a structure in utero is necessary for its continuing and normal development. The old adage "use it or lose it" seems to apply just as appropriately to prenatal normal

  15. Hemogoblin phenotypes in Murgese horse

    OpenAIRE

    Carmela Bottiglieri; Rosario Rullo; Aldo Di Luccia; Elisa Pieragostini

    2010-01-01

    In this note we describe two new equine hemoglobin phenotypes found during a survey of the Murgese horse, a rare  Apulian native breed, among whose ancestors the Arabian surely plays an important role. To date we have analysed about  300 individual hemolysates by different chromatographic analyses (PAGIF, IPG, CMC). The results pointed out two unusu-  al patterns where the ratio of the α24Phe60Gln band to the α24Phe60Lys band was 93:7 and 70:30 rather than 60:40&nbs...

  16. Locating a modifier gene of Ovum mutant through crosses between DDK and C57BL/6J inbred strains in mice

    Indian Academy of Sciences (India)

    JING TAN; GEN DI SONG; JIA SHENG SONG; SHI HAO REN; CHUN LI LI; ZHEN YU ZHENG; WEI DONG ZHAO

    2016-06-01

    A striking infertile phenotype has been discovered in the DDK strain of mouse. The DDK females are usually infertile when crossed with males of other inbred strains, whereas DDK males exhibit normal fertility in reciprocal crosses. This phenomenon is caused by mutation in the ovum (Om) locus on chromosome 11 and known as the DDK syndrome. Previously, some research groups reported that the embryonic mortality deviated from the semilethal rate in backcrosses between heterozygous (Om/+) females and males of other strains. This embryonic mortality exhibited an aggravated trend with increasing background genes of other strains. These results indicated that some modifier genes of Om were present in other strains. In the present study, a population of N 2(Om/+) females from the backcrosses between C57BL/6J (B6) and F1(B6♀×DDK♂) was used to map potential modifier genes of Om. Quantitative trait locus showed that a major locus, namely Amom1 (aggravate modifier gene of Om 1), was located at the middle part of chromosome 9 in mice. The Amom1 could increase the expressivity of Om gene, thereby aggravating embryonic lethality when heterozygous (Om/+)females mated with males of B6 strain. Further, the 1.5 LOD-drop analysis indicated that the confidence interval was between 37.54 and 44.46 cM,∼6.92 cM. Amom1 is the first modifier gene of Om in the B6 background.

  17. Modelling neuroinflammatory phenotypes in vivo

    Directory of Open Access Journals (Sweden)

    Wyss-Coray Tony

    2004-07-01

    Full Text Available Abstract Inflammation of the central nervous system is an important but poorly understood part of neurological disease. After acute brain injury or infection there is a complex inflammatory response that involves activation of microglia and astrocytes and increased production of cytokines, chemokines, acute phase proteins, and complement factors. Antibodies and T lymphocytes may be involved in the response as well. In neurodegenerative disease, where injury is more subtle but consistent, the inflammatory response is continuous. The purpose of this prolonged response is unclear, but it is likely that some of its components are beneficial and others are harmful. Animal models of neurological disease can be used to dissect the specific role of individual mediators of the inflammatory response and assess their potential benefit. To illustrate this approach, we discuss how mutant mice expressing different levels of the cytokine transforming growth factor β-1 (TGF-β1, a major modulator of inflammation, produce important neuroinflammatory phenotypes. We then demonstrate how crosses of TGF-β1 mutant mice with mouse models of Alzheimer's disease (AD produced important new information on the role of inflammation in AD and on the expression of different neuropathological phenotypes that characterize this disease.

  18. Phenotypic plasticity in bacterial plasmids.

    Science.gov (United States)

    Turner, Paul E

    2004-01-01

    Plasmid pB15 was previously shown to evolve increased horizontal (infectious) transfer at the expense of reduced vertical (intergenerational) transfer and vice versa, a key trade-off assumed in theories of parasite virulence. Whereas the models predict that susceptible host abundance should determine which mode of transfer is selectively favored, host density failed to mediate the trade-off in pB15. One possibility is that the plasmid's transfer deviates from the assumption that horizontal spread (conjugation) occurs in direct proportion to cell density. I tested this hypothesis using Escherichia coli/pB15 associations in laboratory serial culture. Contrary to most models of plasmid transfer kinetics, my data show that pB15 invades static (nonshaking) bacterial cultures only at intermediate densities. The results can be explained by phenotypic plasticity in traits governing plasmid transfer. As cells become more numerous, the plasmid's conjugative transfer unexpectedly declines, while the trade-off between transmission routes causes vertical transfer to increase. Thus, at intermediate densities the plasmid's horizontal transfer can offset selection against plasmid-bearing cells, but at high densities pB15 conjugates so poorly that it cannot invade. I discuss adaptive vs. nonadaptive causes for the phenotypic plasticity, as well as potential mechanisms that may lead to complex transfer dynamics of plasmids in liquid environments. PMID:15166133

  19. Robust suppression of background reflections in PIV images

    International Nuclear Information System (INIS)

    Strong background reflections in PIV images are known to bias velocity estimates and their concomitant statistical ensembles. Many methods have been developed to eliminate background reflections, with the common premise of generating a reference background intensity map that is then subtracted from each individual PIV image prior to interrogation. This reference background intensity map can be generated in several ways, including acquiring a background image without particles, calculating the average or minimum intensity map based on an ensemble of PIV images, generating a reference intensity map for each individual PIV realization by means of various local sliding filters or considering the second frame of any PIV realization as its reference intensity map. Motivated by the need to suppress background reflections in a PIV study of flow over highly irregular surface roughness that generated significant diffuse background reflections from the complex topography, the efficacy of these methods was studied. It was found that all failed to adequately suppress such reflections, rendering the resulting velocity fields biased. A local-median normalization algorithm was developed to further suppress background reflections and this note reports the performance of this modified algorithm compared to those previously reported in the literature. (technical design note)

  20. Stealths on Anisotropic Holographic Backgrounds

    CERN Document Server

    Ayón-Beato, Eloy; Juárez-Aubry, María Montserrat

    2015-01-01

    In this paper, we are interested in exploring the existence of stealth configurations on anisotropic backgrounds playing a prominent role in the non-relativistic version of the gauge/gravity correspondence. By stealth configuration, we mean a nontrivial scalar field nonminimally coupled to gravity whose energy-momentum tensor evaluated on the anisotropic background vanishes identically. In the case of a Lifshitz spacetime with a nontrivial dynamical exponent z, we spotlight the role played by the anisotropy to establish the holographic character of the stealth configurations, i.e. the scalar field is shown to only depend on the radial holographic direction. This configuration which turns out to be massless and without integration constants is possible for a unique value of the nonminimal coupling parameter. Then, using a simple conformal argument, we map this configuration into a stealth solution defined on the so-called hyperscaling violation metric which is conformally related to the Lifshitz spacetime. Thi...

  1. Simulation of PEP-II Accelerator Backgrounds Using TURTLE

    CERN Document Server

    Barlow, Roger J; Kozanecki, Witold; Majewski, Stephanie; Roudeau, Patrick; Stocchi, Achille

    2005-01-01

    We present studies of accelerator-induced backgrounds in the BaBar detector at the SLAC B-Factory, carried out using a modified version ofthe DECAY TURTLE simulation package. Lost-particle backgrounds in PEP-II are dominated by a combination of beam-gas bremstrahlung, beam-gas Coulomb scattering, radiative-Bhabha events and beam-beam blow-up. The radiation damage and detector occupancy caused by the associated electromagnetic shower debris can limit the usable luminosity. In order to understand and mitigate such backgrounds, we have performed a full programme of beam-gas and luminosity-background simulations, that include the effects of the detector solenoidal field, detailed modelling of limiting apertures in both collider rings, and optimization of the betatron collimation scheme in the presence of large transverse tails.

  2. Background paper on aquaculture research

    OpenAIRE

    Wenblad, Axel; Jokumsen, Alfred; Eskelinen, Unto; Torrissen, Ole

    2013-01-01

    The Board of MISTRA established in 2012 a Working Group (WG) on Aquaculture to provide the Board with background information for its upcoming decision on whether the foundation should invest in aquaculture research. The WG included Senior Advisor Axel Wenblad, Sweden (Chairman), Professor Ole Torrissen, Norway, Senior Advisory Scientist Unto Eskelinen, Finland and Senior Advisory Scientist Alfred Jokumsen, Denmark. The WG performed an investigation of the Swedish aquaculture sector including ...

  3. Stochastic background of gravitational waves

    CERN Document Server

    D'Araújo, J C N; Aguiar, O D

    2000-01-01

    A continuous stochastic background of gravitational waves (GWs) for burst sources is produced if the mean time interval between the occurrence of bursts is smaller than the average time duration of a single burst at the emission, i.e., the so called duty cycle must be greater than one. To evaluate the background of GWs produced by an ensemble of sources, during their formation, for example, one needs to know the average energy flux emitted during the formation of a single object and the formation rate of such objects as well. In many cases the energy flux emitted during an event of production of GWs is not known in detail, only characteristic values for the dimensionless amplitude and frequencies are known. Here we present a shortcut to calculate stochastic backgrounds of GWs produced from cosmological sources. For this approach it is not necessary to know in detail the energy flux emitted at each frequency. Knowing the characteristic values for the ``lumped'' dimensionless amplitude and frequency we show tha...

  4. Cystatin C is Associated With Plaque Phenotype and Plaque Burden

    Directory of Open Access Journals (Sweden)

    Yufeng Wen

    2016-03-01

    Full Text Available Background/Aims: The relationship between carotid artery plaque burden, phenotype and serum cystatin C at normal and impaired renal function is still unclear. Methods: Demographic characteristics, carotid ultrasonography and other relevant information of 1,477 patients were collected. The association of carotid artery plaque burden, plaque phenotype with serum cystatin C was evaluated by strategy analysis based on renal function. Results: Serum cystatin C (OR=2.05, 95% CI: 1.83-2.29, POR=1.60, 95%CI: 1.43-1.78, POR=1.21, 95%CI: 1.10-1.32, P Conclusion: In normal renal function, serum cystatin C may confer stability of plaques. In mildly impaired renal function, serum cystatin C is a risk predictor of plaques. In normal renal function circumstances, serum cystatin C may benefit to the stability of plaques. In mild impaired renal function circumstances, serum cystatin C are a risk predictors of plaques.

  5. Alanine aminotransferase variants conferring diverse NUE phenotypes in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Chandra H McAllister

    Full Text Available Alanine aminotransferase (AlaAT, E.C. 2.6.1.2, is a pyridoxal-5'-phosphate-dependent (PLP enzyme that catalyzes the reversible transfer of an amino group from alanine to 2-oxoglutarate to produce glutamate and pyruvate, or vice versa. It has been well documented in both greenhouse and field studies that tissue-specific over-expression of AlaAT from barley (Hordeum vulgare, HvAlaAT results in a significant increase in plant NUE in both canola and rice. While the physical phenotypes associated with over-expression of HvAlaAT have been well characterized, the role this enzyme plays in vivo to create a more N efficient plant remains unknown. Furthermore, the importance of HvAlaAT, in contrast to other AlaAT enzyme homologues in creating this phenotype has not yet been explored. To address the role of AlaAT in NUE, AlaAT variants from diverse sources and different subcellular locations, were expressed in the wild-type Arabidopsis thaliana Col-0 background and alaat1;2 (alaat1-1;alaat2-1 knockout background in various N environments. The analysis and comparison of both the physical and physiological properties of AlaAT over-expressing transgenic plants demonstrated significant differences between plants expressing the different AlaAT enzymes under different external conditions. This analysis indicates that the over-expression of AlaAT variants other than HvAlaAT in crop plants could further increase the NUE phenotype(s previously observed.

  6. Phenotype microarray profiling of the antibacterial activity of red cabbage

    Directory of Open Access Journals (Sweden)

    Hafidh RR

    2012-06-01

    Full Text Available Background: Functional food can be a potent source of wide array of biocomonents with antimicrobial activity. We investigated the antibacterial activity of red cabbage (RC extract on Gram negative and positive ATCC strains. Most intersting, we, for the first time, explored and analysed the complete phenotypic profile of RC-treated bacteria using Omnilog Phenotype Microarray. Results: This study revealed that the phenotype microarray (PM screen was a valuable tool in the search for compounds and their antibacterial mechanisms that can inhibit bacterial growth by affecting certain metabolic pathways. It was shown that RC exerted remarkable antibacterial effect on S. aureus and E. coli bacteria, and PM showed a wide range phenotypic profile of the exerted RC antibacterial activity. RC targeted the peptide, carbon, nutriontional assembly, and sulfur metbolic pathways altogether. The peptidoglycan synthesis pathway was inferred to be targeted by RC extract at a metabolic point different from other available cell wall-targeting drugs; these could be hot targets for the discovery of new therapy for many problematic microbes.Conclusions: Taken together, the phenotype microarray for functional food and medicinal plants can be a very useful tool for profiling their antimicrobial activity. Moreover, extracts of functional food can exert antibacterial activity by hitting a wide range of metabolic pathways, at the same time leading to very difficult condition for bacteria to rapidly develop resistance. Therefore, using functional foods or medicinal plants as such, or as extracts, can be superior on mono-targeting antibiotics if the optimal concentrations and conditions of these functional foods were sought.

  7. Neutrinos and electrons in background matter: a new approach

    CERN Document Server

    Studenikin, A

    2006-01-01

    We present a rather powerful method in investigations of different phenomena that can appear when neutrinos and electrons are moving in the background matter. This method is based on the use of the modified Dirac equations for the particles wave functions, in which the correspondent effective potentials that account for the matter influence on particles are included. The developed approach establishes a basis for investigation of different phenomena which can arise when neutrinos and electrons move in dense media, including those peculiar for astrophysical and cosmological environments. The approach developed is similar to the Furry representation of quantum electrodynamics, widely used for description of particles interactions in the presence of external electromagnetic fields, and it works when a macroscopic amount of the background particles are confined within the scale of a neutrino or electron de Broglie wave lengths. We consider the modified Dirac equations for neutrinos (of both Dirac and Majorana typ...

  8. Hemogoblin phenotypes in Murgese horse

    Directory of Open Access Journals (Sweden)

    Carmela Bottiglieri

    2010-01-01

    Full Text Available In this note we describe two new equine hemoglobin phenotypes found during a survey of the Murgese horse, a rare  Apulian native breed, among whose ancestors the Arabian surely plays an important role. To date we have analysed about  300 individual hemolysates by different chromatographic analyses (PAGIF, IPG, CMC. The results pointed out two unusu-  al patterns where the ratio of the α24Phe60Gln band to the α24Phe60Lys band was 93:7 and 70:30 rather than 60:40  which would have been expected of BII homozygote. Given that the three horses exhibiting the unusual patterns shared  a common ancestor and that none of the possible combinations of the known haplotypes can account for 7-8%  α24Phe60Lys, reasonably a triplicated arrangement has to be postulated. 

  9. [Toothache with a neuropathic background].

    Science.gov (United States)

    Khatchaturian, V; de Wijer, A; Kalaykova, S I; Steenks, M H

    2015-03-01

    A 48-year old woman in good general health was referred to the orofacial pain clinic in a centre for special dentistry with a toothache in the premolar region of the left maxillary quadrant. The complaints had existed for 15 years and various dental treatments, including endodontic treatments, apical surgery, extraction and splint therapy, had not helped to alleviate the complaints. As a result of the fact that anti-epileptic drugs were able to reduce the pain it was concluded that this 'toothache' satisfied the criteria of an atypical odontalgia: 'toothache' with a neuropathic background. PMID:26181392

  10. Breast cancer - background and overview

    International Nuclear Information System (INIS)

    This summary is to provide the reader with a brief overview of the key concepts relating to epidemiology and etiology; clinical presentation and patterns of spread; Canadian guidelines for management; prognosis; and current Canadian screening recommendations in the diagnosis and treatment of breast cancer. This information will enable the reader to have the appropriate background knowledge before delving into the subsequent articles in this special CJMRT breast cancer edition. A variety of references have been provided for readers who are interested in more than a skeleton version of the current literature. (author)

  11. Equilibrium thermodynamics in modified gravitational theories

    CERN Document Server

    Bamba, Kazuharu; Tsujikawa, Shinji

    2009-01-01

    We show that it is possible to obtain a picture of equilibrium thermodynamics on the apparent horizon in the expanding cosmological background for a wide class of modified gravity theories with the Lagrangian density $f(R, \\phi, X)$, where $R$ is the Ricci scalar and $X=-(\

  12. Asthma trajectories in early childhood: identifying modifiable factors.

    Directory of Open Access Journals (Sweden)

    Lidia Panico

    Full Text Available BACKGROUND: There are conflicting views as to whether childhood wheezing represents several discreet entities or a single but variable disease. Classification has centered on phenotypes often derived using subjective criteria, small samples, and/or with little data for young children. This is particularly problematic as asthmatic features appear to be entrenched by age 6/7. In this paper we aim to: identify longitudinal trajectories of wheeze and other atopic symptoms in early childhood; characterize the resulting trajectories by the socio-economic background of children; and identify potentially modifiable processes in infancy correlated with these trajectories. DATA AND METHODS: The Millennium Cohort Study is a large, representative birth cohort of British children born in 2000-2002. Our analytical sample includes 11,632 children with data on key variables (wheeze in the last year; ever hay-fever and/or eczema reported by the main carers at age 3, 5 and 7 using a validated tool, the International Study of Asthma and Allergies in Childhood module. We employ longitudinal Latent Class Analysis, a clustering methodology which identifies classes underlying the observed population heterogeneity. RESULTS: Our model distinguished four latent trajectories: a trajectory with both low levels of wheeze and other atopic symptoms (54% of the sample; a trajectory with low levels of wheeze but high prevalence of other atopic symptoms (29%; a trajectory with high prevalence of both wheeze and other atopic symptoms (9%; and a trajectory with high levels of wheeze but low levels of other atopic symptoms (8%. These groups differed in terms of socio-economic markers and potential intervenable factors, including household damp and breastfeeding initiation. CONCLUSION: Using data-driven techniques, we derived four trajectories of asthmatic symptoms in early childhood in a large, population based sample. These groups differ in terms of their socio-economic profiles

  13. Clinical Asthma Phenotypes and Therapeutic Responses

    OpenAIRE

    Zedan, M.; Attia, G.; Zedan, M. M.; Osman, A; Abo-Elkheir, N.; Maysara, N.; Barakat, T.; Gamil, N.

    2013-01-01

    Asthma is a heterogeneous disease that means not all asthmatics respond to the same treatment. We hypothesize an approach to characterize asthma phenotypes based on symptomatology (shortness of breath (SOB), cough, and wheezy phenotypes) in correlation with airway inflammatory biomarkers and FEV1. We aimed to detect whether those clinical phenotypes have an impact on the response to asthma medications. Two hundred three asthmatic children were allocated randomly to receive either montelukast ...

  14. Phenotypes and Survival of Hatchling Lizards

    OpenAIRE

    Warner, Daniel Augustus

    2001-01-01

    The phenotypes of hatchling reptiles are influenced by the environmental conditions that embryos experience during incubation, by yolk invested into the egg, and by the genetic contributions of the parents. Phenotypic traits are influenced by these factors in ways that potentially affect the fitness of hatchlings. The physical conditions that embryos experience within the nest affects development, hatching success, and hatchling phenotypes. Thus, the nest site that a female selects can inf...

  15. Marital assortment and phenotypic convergence: longitudinal evidence.

    Science.gov (United States)

    Caspi, A; Herbener, E S

    1993-01-01

    This study provides a direct test of whether the observed similarity of spouses is due to initial assortment rather than to convergence of phenotypes. With data from three well-known longitudinal studies, phenotypic convergence is examined using both variable- and person-centered analyses. The longitudinal evidence does not support the hypothesis that couples increasingly resemble each other with time. Spouse correlations most likely reflect initial assortment at marriage and not the convergence of phenotypes.

  16. [Cosmic Microwave Background (CMB) Anisotropies

    Science.gov (United States)

    Silk, Joseph

    1998-01-01

    One of the main areas of research is the theory of cosmic microwave background (CMB) anisotropies and analysis of CMB data. Using the four year COBE data we were able to improve existing constraints on global shear and vorticity. We found that, in the flat case (which allows for greatest anisotropy), (omega/H)0 less than 10-7, where omega is the vorticity and H is the Hubble constant. This is two orders of magnitude lower than the tightest, previous constraint. We have defined a new set of statistics which quantify the amount of non-Gaussianity in small field cosmic microwave background maps. By looking at the distribution of power around rings in Fourier space, and at the correlations between adjacent rings, one can identify non-Gaussian features which are masked by large scale Gaussian fluctuations. This may be particularly useful for identifying unresolved localized sources and line-like discontinuities. Levin and collaborators devised a method to determine the global geometry of the universe through observations of patterns in the hot and cold spots of the CMB. We have derived properties of the peaks (maxima) of the CMB anisotropies expected in flat and open CDM models. We represent results for angular resolutions ranging from 5 arcmin to 20 arcmin (antenna FWHM), scales that are relevant for the MAP and COBRA/SAMBA space missions and the ground-based interferometer. Results related to galaxy formation and evolution are also discussed.

  17. Diagnosis, assessment, and phenotyping of COPD

    DEFF Research Database (Denmark)

    Lange, Peter; Halpin, David M; O'Donnell, Denis E;

    2016-01-01

    biomarkers to confirm and further assess the diagnosis of COPD. However, it is possible to identify patients who display different phenotypic characteristics of COPD that relate to clinically relevant outcomes. Currently, validated phenotypes of COPD include alpha-1 antitrypsin deficiency, and "frequent...... exacerbators". Recently, a definition and assessment of a new phenotype comprising patients with overlapping features of asthma and COPD has been suggested and is known as "asthma COPD overlap syndrome". Several other phenotypes have been proposed, but require validation against clinical outcomes. Defining...

  18. Immunogenetic phenotypes in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Marla C Dubinsky; Kent Taylor; Stephan R Targan; Jerome I Rotter

    2006-01-01

    The currently accepted etiopathogenic hypothesis suggests that the chronic intestinal inflammation and related systemic manifestations characteristic of inflammatory bowel disease (IBD) are due to an overly aggressive or pathologic immune response to resident luminal bacterial constituents. Predisposing factors are genetic dysregulation of mucosal immune responses and/or barrier function, with onset triggered by environmental stimuli. These factors and their interactions may also be important determinants of disease phenotype and disease progression. The emergence of immunogenetic phenotypes lends support to the proposed hypothesis that susceptibility genes regulate distinct immune processes, driven by luminal antigens, expressed as specific immune phenotypes which in turn influence clinical phenotypes in IBD patient

  19. Phenotypic plasticity's impacts on diversification and speciation.

    Science.gov (United States)

    Pfennig, David W; Wund, Matthew A; Snell-Rood, Emilie C; Cruickshank, Tami; Schlichting, Carl D; Moczek, Armin P

    2010-08-01

    Phenotypic plasticity (the ability of a single genotype to produce multiple phenotypes in response to variation in the environment) is commonplace. Yet its evolutionary significance remains controversial, especially in regard to whether and how it impacts diversification and speciation. Here, we review recent theory on how plasticity promotes: (i) the origin of novel phenotypes, (ii) divergence among populations and species, (iii) the formation of new species and (iv) adaptive radiation. We also discuss the latest empirical support for each of these evolutionary pathways to diversification and identify potentially profitable areas for future research. Generally, phenotypic plasticity can play a largely underappreciated role in driving diversification and speciation.

  20. Colour and pattern change against visually heterogeneous backgrounds in the tree frog Hyla japonica

    OpenAIRE

    Changku Kang; Ye Eun Kim; Yikweon Jang

    2016-01-01

    Colour change in animals can be adaptive phenotypic plasticity in heterogeneous environments. Camouflage through background colour matching has been considered a primary force that drives the evolution of colour changing ability. However, the mechanism to which animals change their colour and patterns under visually heterogeneous backgrounds (i.e. consisting of more than one colour) has only been identified in limited taxa. Here, we investigated the colour change process of the Japanese tree ...

  1. String Thermodynamics in D-Brane Backgrounds

    CERN Document Server

    Abel, S A; Kogan, I I; Rabinovici, Eliezer

    1999-01-01

    We discuss the thermal properties of string gases propagating in various D-brane backgrounds in the weak-coupling limit, and at temperatures close to the Hagedorn temperature. We determine, in the canonical ensemble, whether the Hagedorn temperature is limiting or non-limiting. This depends on the dimensionality of the D-brane, and the size of the compact dimensions. We find that in many cases the non-limiting behaviour manifest in the canonical ensemble is modified to a limiting behaviour in the microcanonical ensemble and show that, when there are different systems in thermal contact, the energy flows into open strings on the `limiting' D-branes of largest dimensionality. Such energy densities may eventually exceed the D-brane intrinsic tension. We discuss possible implications of this for the survival of Dp-branes with large values of p in an early cosmological Hagedorn regime. We also discuss the general phase diagram of the interacting theory, as implied by the holographic and black-hole/string correspon...

  2. The superhealing MRL background improves muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Heydemann Ahlke

    2012-12-01

    Full Text Available Abstract Background Mice from the MRL or “superhealing” strain have enhanced repair after acute injury to the skin, cornea, and heart. We now tested an admixture of the MRL genome and found that it altered the course of muscle pathology and cardiac function in a chronic disease model of skeletal and cardiac muscle. Mice lacking γ-sarcoglycan (Sgcg, a dystrophin-associated protein, develop muscular dystrophy and cardiomyopathy similar to their human counterparts with limb girdle muscular dystrophy. With disruption of the dystrophin complex, the muscle plasma membrane becomes leaky and muscles develop increased fibrosis. Methods MRL/MpJ mice were bred with Sgcg mice, and cardiac function was measured. Muscles were assessed for fibrosis and membrane leak using measurements of hydroxyproline and Evans blue dye. Quantitative trait locus mapping was conducted using single nucleotide polymorphisms distinct between the two parental strains. Results Introduction of the MRL genome reduced fibrosis but did not alter membrane leak in skeletal muscle of the Sgcg model. The MRL genome was also associated with improved cardiac function with reversal of depressed fractional shortening and the left ventricular ejection fraction. We conducted a genome-wide analysis of genetic modifiers and found that a region on chromosome 2 was associated with cardiac, diaphragm muscle and abdominal muscle fibrosis. Conclusions These data are consistent with a model where the MRL genome acts in a dominant manner to suppress fibrosis in this chronic disease setting of heart and muscle disease.

  3. A Turner syndrome neurocognitive phenotype maps to Xp22.3

    Directory of Open Access Journals (Sweden)

    Elder Frederick F

    2007-05-01

    Full Text Available Abstract Background Turner syndrome (TS is associated with a neurocognitive phenotype that includes selective nonverbal deficits, e.g., impaired visual-spatial abilities. We previously reported evidence that this phenotype results from haploinsufficiency of one or more genes on distal Xp. This inference was based on genotype/phenotype comparisons of individual girls and women with partial Xp deletions, with the neurocognitive phenotype considered a dichotomous trait. We sought to confirm our findings in a large cohort (n = 47 of adult women with partial deletions of Xp or Xq, enriched for subjects with distal Xp deletions. Methods Subjects were recruited from North American genetics and endocrinology clinics. Phenotype assessment included measures of stature, ovarian function, and detailed neurocognitive testing. The neurocognitive phenotype was measured as a quantitative trait, the Turner Syndrome Cognitive Summary (TSCS score, derived from discriminant function analysis. Genetic analysis included karyotyping, X inactivation studies, fluorescent in situ hybridization, microsatellite marker genotyping, and array comparative genomic hybridization. Results We report statistical evidence that deletion of Xp22.3, an interval containing 31 annotated genes, is sufficient to cause the neurocognitive phenotype described by the TSCS score. Two other cardinal TS features, ovarian failure and short stature, as well as X chromosome inactivation pattern and subject's age, were unrelated to the TSCS score. Conclusion Detailed mapping suggests that haploinsufficiency of one or more genes in Xp22.3, the distal 8.3 megabases (Mb of the X chromosome, is responsible for a TS neurocognitive phenotype. This interval includes the 2.6 Mb Xp-Yp pseudoautosomal region (PAR1. Haploinsufficiency of the short stature gene SHOX in PAR1 probably does not cause this TS neurocognitive phenotype. Two genes proximal to PAR1 within the 8.3 Mb critical region, STS and NLGN4X, are

  4. Phenotypic resistance of resistant strains of HIV type-1 subtype B in China

    Institute of Scientific and Technical Information of China (English)

    LI Jue; WANG Zhe; WU Hao; LI Jing-yun; LU Jun-feng; DONG Hua-huang; BAO Zuo-yi; LIU Si-yang; LI Han-ping; ZHUANG Dao-min; LIU Yong-jian; LI Hong

    2006-01-01

    Background This study was aim to explore the characteristics of phenotypic resistance of resistant strains of HIV type-1 (HIV-1) subtype B and to compare the concordance between the phenotypic resistance and genotypic resistance. Methods The genotypic resistance assay for the HIV-1 clinical isolates was performed. One isolate without resistance mutation was chosen as a drug-sensitive reference strain and seven subtype B isolates with resistance mutations were phenotypically tested. Fifty percent inhibitory concentrations (IC50) between resistant and sensitive viruses were compared. The resistance extent was determined by the folds of the increased IC50. The concordance between the phenotypic resistance and genotypic resistance was also analyzed.Results IC50 of resistant isolates were 0.0006-0.1300 μmol/L for zidovudine (AZT), 0.0016-0.0390 μmol/L for lamivudine (3TC), 0.0104-0.4234 μmol/L for nevirapine (NVP), and 0.0163-0.1142 μmol/L for indinavir (IDV), respectively. Genotypic and phenotypic resistance assays indicated that the resistant strains were intermediately and highly resistant to nucleotide analog reverse transcriptase inhibitors and non-nucleotide analog reverse transcriptase inhibitors. The phenotypic assay was consistent with the genotypic assay. For measuring the potential resistance, the genotypic assay was more sensitive than the phenotypic. In evaluating the resistance to protease inhibitors, these two assays were discrepant.Conclusions Both the phenotypic and genotypic assays indicate that the resistant viruses exist in HIV-infected patients in China who have received treatment. Phenotypic and genotypic assays have high concordance, and the genotypic assay could replace the phenotypic assay to predict the HIV-1 resistance.

  5. Low background aspects of GERDA

    International Nuclear Information System (INIS)

    The GERDA experiment operates bare Germanium diodes enriched in 76Ge in an environment of pure liquid argon to search for neutrinoless double beta decay. A very low radioactive background is essential for the success of the experiment. We present here the research done in order to remove radio-impurities coming from the liquid argon, the stainless steel cryostat and the front-end electronics. We found that liquid argon can be purified efficiently from 222Rn. The main source of 222Rn in GERDA is the cryostat which emanates about 55 mBq. A thin copper shroud in the center of the cryostat was implemented to prevent radon from approaching the diodes. Gamma ray screening of radio-pure components for front-end electronics resulted in the development of a pre-amplifier with a total activity of less than 1 mBq 228Th.

  6. Polarization of Cosmic Microwave Background

    CERN Document Server

    Buzzelli, Alessandro; de Gasperis, Giancarlo; Vittorio, Nicola

    2016-01-01

    In this work we present an extension of the ROMA map-making code for data analysis of Cosmic Microwave Background polarization, with particular attention given to the inflationary polarization B-modes. The new algorithm takes into account a possible cross-correlated noise component among the different detectors of a CMB experiment. We tested the code on the observational data of the BOOMERanG (2003) experiment and we show that we are provided with a better estimate of the power spectra, in particular the error bars of the BB spectrum are smaller up to 20% for low multipoles. We point out the general validity of the new method. A possible future application is the LSPE balloon experiment, devoted to the observation of polarization at large angular scales.

  7. The Cosmic Background Imager 2

    CERN Document Server

    Taylor, Angela C; Allison, James R; Angelakis, Emmanouil; Bond, J Richard; Bronfman, Leonardo; Bustos, Ricardo; Davis, Richard J; Dickinson, Clive; Leech, Jamie; Mason, Brian S; Myers, Steven T; Pearson, Timothy J; Readhead, Anthony C S; Reeves, Rodrigo; Shepherd, Martin C; Sievers, Jonathan L

    2011-01-01

    We describe an upgrade to the Cosmic Background Imager instrument to increase its surface brightness sensitivity at small angular scales. The upgrade consisted of replacing the thirteen 0.9-m antennas with 1.4-m antennas incorporating a novel combination of design features, which provided excellent sidelobe and spillover performance for low manufacturing cost. Off-the-shelf spun primaries were used, and the secondary mirrors were oversized and shaped relative to a standard Cassegrain in order to provide an optimum compromise between aperture efficiency and low spillover lobes. Low-order distortions in the primary mirrors were compensated for by custom machining of the secondary mirrors. The secondaries were supported on a transparent dielectric foam cone to minimize scattering. The antennas were tested in the complete instrument, and the beam shape and spillover noise contributions were as expected. We demonstrate the performance of the telescope and the inter-calibration with the previous system using observ...

  8. Recognizing foreground-background interaction

    Science.gov (United States)

    Jenkins, Jeffrey; Szu, Harold

    2010-04-01

    Can the background affect a foreground target in distant, low-quality imagery? If it does, it might occur in our mind, or perhaps it may represent a snapshot of our early vision. An affirmative answer, one way or another, may affect our current understanding of this phenomena and potentially for related applications. How can we be sure about this in the psycho-physical sense? We begin with the physiology of our brain's homeostasis, of which an isothermal equilibrium is characterized by the minimum of Helmholtz isothermal Free Energy: A = U - T0S >= 0, where T0 = 37°C, the Boltzmann Entropy S = KB1n(W), and U is the unknown internal energy to be computed.

  9. Gauging the cosmic microwave background

    International Nuclear Information System (INIS)

    We provide a new derivation of the anisotropies of the cosmic microwave background (CMB), and find an exact expression that can be readily expanded perturbatively. Close attention is paid to gauge issues, with the motivation to examine the effect of super-Hubble modes on the CMB. We calculate a transfer function that encodes the behavior of the dipole, and examine its long-wavelength behavior. We show that contributions to the dipole from adiabatic super-Hubble modes are strongly suppressed, even in the presence of a cosmological constant, contrary to claims in the literature. We also introduce a naturally defined CMB monopole, which exhibits closely analogous long-wavelength behavior. We discuss the geometrical origin of this super-Hubble suppression, pointing out that it is a simple reflection of adiabaticity, and hence argue that it will occur regardless of the matter content.

  10. Phenotypic robustness can increase phenotypic variability after non-genetic perturbations in gene regulatory circuits

    OpenAIRE

    Espinosa-Soto, C.; Martin, O. C.; Wagner, A

    2010-01-01

    Non-genetic perturbations, such as environmental change or developmental noise, can induce novel phenotypes. If an induced phenotype confers a fitness advantage, selection may promote its genetic stabilization. Non-genetic perturbations can thus initiate evolutionary innovation. Genetic variation that is not usually phenotypically visible may play an important role in this process. Populations under stabilizing selection on a phenotype that is robust to mutations can accumulate such variation...

  11. On Modified Bar recursion

    DEFF Research Database (Denmark)

    Oliva, Paulo Borges

    2002-01-01

    Modified bar recursion is a variant of Spector's bar recursion which can be used to give a realizability interpretation of the classical axiom of dependent choice. This realizability allows for the extraction of witnesses from proofs of forall-exists-formulas in classical analysis. In this talk I...... shall report on results regarding the relationship between modified and Spector's bar recursion. I shall also show that a seemingly weak form of modified bar recursion is as strong as "full" modified bar recursion in higher types....

  12. POLYCAPROLACTAM MODIFIED BY POLYPHENYLQUINOXALINE

    Institute of Scientific and Technical Information of China (English)

    YANG Guisheng; LU Fengcai

    1990-01-01

    Three polycaprolactam samples modified by 0.05- 0.50% polyphenylquinoxaline (PPQ) by weight were prepared. Their structure and mechanical properties were characterized by FT-IR, SEM, density, tensile,impact,DTA and visco-elastic method. PPQ induced the formation of "crystal grains" distributed evenly over nylon spherulites in modified samples, which were observed for the first time, and strengthened modified samples. Modified nylons had higher crystallinities, higher Tg ,more nearly perfect spherulites than MC nylon itself, and showed typical reinforcing effect on mechanical properties.

  13. 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.

  14. The Human Phenotype Ontology project: linking molecular biology and disease through phenotype data

    NARCIS (Netherlands)

    Kohler, S.; Doelken, S.C.; Mungall, C.J.; Bauer, S.; Firth, H.V.; Bailleul-Forestier, I.; Black, G.C.M.; Brown, D.L.; Brudno, M.; Campbell, J.; FitzPatrick, D.R.; Eppig, J.T.; Jackson, A.P.; Freson, K.; Girdea, M.; Helbig, I.; Hurst, J.A.; Jahn, J.; Jackson, L.G.; Kelly, A.M.; Ledbetter, D.H.; Mansour, S.; Martin, C.L.; Moss, C.; Mumford, A.; Ouwehand, W.H.; Park, S.M.; Riggs, E.R.; Scott, R.H.; Sisodiya, S.; Vooren, S. van der; Wapner, R.J.; Wilkie, A.O.; Wright, C.F.; Silfhout, A.T. van; Leeuw, N. de; Vries, B. de; Washingthon, N.L.; Smith, C.L.; Westerfield, M.; Schofield, P.; Ruef, B.J.; Gkoutos, G.V.; Haendel, M.; Smedley, D.; Lewis, S.E.; Robinson, P.N.

    2014-01-01

    The Human Phenotype Ontology (HPO) project, available at http://www.human-phenotype-ontology.org, provides a structured, comprehensive and well-defined set of 10,088 classes (terms) describing human phenotypic abnormalities and 13,326 subclass relations between the HPO classes. In addition we have d

  15. The Cognitive Phenotype of Spina Bifida Meningomyelocele

    Science.gov (United States)

    Dennis, Maureen; Barnes, Marcia A.

    2010-01-01

    A cognitive phenotype is a product of both assets and deficits that specifies what individuals with spina bifida meningomyelocele (SBM) can and cannot do and why they can or cannot do it. In this article, we review the cognitive phenotype of SBM and describe the processing assets and deficits that cut within and across content domains, sensory…

  16. Adjusting phenotypes by noise control.

    Directory of Open Access Journals (Sweden)

    Kyung H Kim

    2012-01-01

    Full Text Available Genetically identical cells can show phenotypic variability. This is often caused by stochastic events that originate from randomness in biochemical processes involving in gene expression and other extrinsic cellular processes. From an engineering perspective, there have been efforts focused on theory and experiments to control noise levels by perturbing and replacing gene network components. However, systematic methods for noise control are lacking mainly due to the intractable mathematical structure of noise propagation through reaction networks. Here, we provide a numerical analysis method by quantifying the parametric sensitivity of noise characteristics at the level of the linear noise approximation. Our analysis is readily applicable to various types of noise control and to different types of system; for example, we can orthogonally control the mean and noise levels and can control system dynamics such as noisy oscillations. As an illustration we applied our method to HIV and yeast gene expression systems and metabolic networks. The oscillatory signal control was applied to p53 oscillations from DNA damage. Furthermore, we showed that the efficiency of orthogonal control can be enhanced by applying extrinsic noise and feedback. Our noise control analysis can be applied to any stochastic model belonging to continuous time Markovian systems such as biological and chemical reaction systems, and even computer and social networks. We anticipate the proposed analysis to be a useful tool for designing and controlling synthetic gene networks.

  17. The autonomic phenotype of rumination.

    Science.gov (United States)

    Ottaviani, Cristina; Shapiro, David; Davydov, Dmitry M; Goldstein, Iris B; Mills, Paul J

    2009-06-01

    Recent studies suggest that ruminative thoughts may be mediators of the prolonged physiological effects of stress. We hypothesized that autonomic dysregulation plays a role in the relation between rumination and health. Rumination was induced by an anger-recall task in 45 healthy subjects. Heart rate variability (HRV), baroreflex sensitivity (BRS), and baroreflex effectiveness index (BEI) change scores were evaluated to obtain the autonomic phenotype of rumination. Personality traits and endothelial activation were examined for their relation to autonomic responses during rumination. Degree of endothelial activation was assessed by circulating soluble intercellular adhesion molecule-1 (sICAM-1). Vagal withdrawal during rumination was greater for women than men. Larger decreases in the high frequency component of HRV were associated with higher levels of anger-in, depression, and sICAM-1 levels. BRS reactivity was negatively related to trait anxiety. BEI reactivity was positively related to anger-in, hostility, anxiety, and depression. Lower BEI and BRS recovery were associated with lower social desirability and higher anger-out, anxiety, and depression. Findings suggest that the autonomic dysregulation that characterizes rumination plays a role in the relationships between personality and cardiovascular health. PMID:19272312

  18. Phenotypic and genotypic data integration and exploration through a web-service architecture

    Science.gov (United States)

    Nuzzo, Angelo; Riva, Alberto; Bellazzi, Riccardo

    2009-01-01

    Background Linking genotypic and phenotypic information is one of the greatest challenges of current genetics research. The definition of an Information Technology infrastructure to support this kind of studies, and in particular studies aimed at the analysis of complex traits, which require the definition of multifaceted phenotypes and the integration genotypic information to discover the most prevalent diseases, is a paradigmatic goal of Biomedical Informatics. This paper describes the use of Information Technology methods and tools to develop a system for the management, inspection and integration of phenotypic and genotypic data. Results We present the design and architecture of the Phenotype Miner, a software system able to flexibly manage phenotypic information, and its extended functionalities to retrieve genotype information from external repositories and to relate it to phenotypic data. For this purpose we developed a module to allow customized data upload by the user and a SOAP-based communications layer to retrieve data from existing biomedical knowledge management tools. In this paper we also demonstrate the system functionality by an example application of the system in which we analyze two related genomic datasets. Conclusion In this paper we show how a comprehensive, integrated and automated workbench for genotype and phenotype integration can facilitate and improve the hypothesis generation process underlying modern genetic studies. PMID:19828081

  19. Computer-Assisted Transgenesis of Caenorhabditis elegans for Deep Phenotyping.

    Science.gov (United States)

    Gilleland, Cody L; Falls, Adam T; Noraky, James; Heiman, Maxwell G; Yanik, Mehmet F

    2015-09-01

    A major goal in the study of human diseases is to assign functions to genes or genetic variants. The model organism Caenorhabditis elegans provides a powerful tool because homologs of many human genes are identifiable, and large collections of genetic vectors and mutant strains are available. However, the delivery of such vector libraries into mutant strains remains a long-standing experimental bottleneck for phenotypic analysis. Here, we present a computer-assisted microinjection platform to streamline the production of transgenic C. elegans with multiple vectors for deep phenotyping. Briefly, animals are immobilized in a temperature-sensitive hydrogel using a standard multiwell platform. Microinjections are then performed under control of an automated microscope using precision robotics driven by customized computer vision algorithms. We demonstrate utility by phenotyping the morphology of 12 neuronal classes in six mutant backgrounds using combinations of neuron-type-specific fluorescent reporters. This technology can industrialize the assignment of in vivo gene function by enabling large-scale transgenic engineering.

  20. HDACs and the senescent phenotype of WI-38 cells

    Directory of Open Access Journals (Sweden)

    Noonan Emily J

    2005-10-01

    Full Text Available Abstract Background Normal cells possess a limited proliferative life span after which they enter a state of irreversible growth arrest. This process, known as replicative senescence, is accompanied by changes in gene expression that give rise to a variety of senescence-associated phenotypes. It has been suggested that these gene expression changes result in part from alterations in the histone acetylation machinery. Here we examine the influence of HDAC inhibitors on the expression of senescent markers in pre- and post-senescent WI-38 cells. Results Pre- and post-senescent WI-38 cells were treated with the HDAC inhibitors butyrate or trichostatin A (TSA. Following HDAC inhibitor treatment, pre-senescent cells increased p21WAF1 and β-galactosidase expression, assumed a flattened senescence-associated morphology, and maintained a lower level of proteasome activity. These alterations also occurred during normal replicative senescence of WI-38 cells, but were not accentuated further by HDAC inhibitors. We also found that HDAC1 levels decline during normal replicative senescence. Conclusion Our findings indicate that HDACs impact numerous phenotypic changes associated with cellular senescence. Reduced HDAC1 expression levels in senescent cells may be an important event in mediating the transition to a senescent phenotype.

  1. Gaussianity of LISA's confusion backgrounds

    International Nuclear Information System (INIS)

    different time scales, so no single background source closely resembles any search template. We also briefly discuss other types of LISA searches where the non-Gaussianity of LISA's confusion backgrounds could perhaps have a much greater impact on search reliability and efficacy

  2. Constraints on the evolution of phenotypic plasticity

    DEFF Research Database (Denmark)

    Murren, Courtney J; Auld, Josh R.; Callahan, Hilary S;

    2015-01-01

    costly. In addition, we examine opportunities to offset costs of phenotypes through ontogeny, amelioration of phenotypic costs across environments, and the condition-dependent hypothesis. We propose avenues of further inquiry in the limits of plasticity using new and classic methods of ecological......Phenotypic plasticity is ubiquitous and generally regarded as a key mechanism for enabling organisms to survive in the face of environmental change. Because no organism is infinitely or ideally plastic, theory suggests that there must be limits (for example, the lack of ability to produce...... an optimal trait) to the evolution of phenotypic plasticity, or that plasticity may have inherent significant costs. Yet numerous experimental studies have not detected widespread costs. Explicitly differentiating plasticity costs from phenotype costs, we re-evaluate fundamental questions of the limits...

  3. Phenotypic character gradient variation of Melia azedarach

    Institute of Scientific and Technical Information of China (English)

    CHENG Shiming; GU Wanchun

    2007-01-01

    Canonical Correlation Analysis (CCA) was applied on the research data of five geographical-climatic factors and 18 phenotypic characters of 729 trees of 24 populations of Melia azedarach distributed in China.The eigenvalue of the first canonical variable is 0.997 9 (significant at 0.01 level),accounting for 78% of all eigenvalues.A study on the principal component analysis (PCA) was done,taking the first canonical variable coordinate values as the phenotypic character gradient axes (PCGA).The isogram of the PCGA was drawn out with 0.2 contours,which showed a geographical model with a northeast-southwest variation trend of the phenotypic characters of M.azedarach.Meanwhile,the path analysis results show the direct and indirect effects of phenotypic characters with phenotypic character gradient values,which prove that the propagative organs,are steadily changing.

  4. Modulation of Lupus Phenotype by Adiponectin Deficiency in Autoimmune Mouse Models

    OpenAIRE

    Parker, Jennifer; Menn-Josephy, Hanni; Laskow, Bari; Takemura, Yukihiro; Aprahamian, Tamar

    2010-01-01

    Adiponectin is an adipocyte-derived cytokine with anti-inflammatory properties. Paradoxically, circulating adiponectin levels are increased in a number of inflammatory diseases. Thus, we sought to define the role of adiponectin deficiency in mouse models of autoimmunity. Adiponectin-deficient mice on a C57BL/6 background do not develop an autoimmune phenotype. Autoimmunity was also not observed in adiponectin-deficient mice generated on the permissive MRL background. However, adiponectin defi...

  5. Fried frailty phenotype assessment components as applied to geriatric inpatients

    Directory of Open Access Journals (Sweden)

    Bieniek J

    2016-04-01

    Full Text Available Joanna Bieniek, Krzysztof Wilczynski, Jan Szewieczek Department of Geriatrics, School of Health Sciences in Katowice, Medical University of Silesia, Katowice, Poland Background: Management of geriatric patients would be simplified if a universally accepted definition of frailty for clinical use was defined. Among definitions of frailty, Fried frailty phenotype criteria constitute a common reference frame for many geriatric studies. However, this reference frame has been tested primarily in elderly patients presenting with relatively good health status. Objective: The aim of this article was to assess the usefulness and limitations of Fried frailty phenotype criteria in geriatric inpatients, characterized by comorbidity and functional impairments, and to estimate the frailty phenotype prevalence in this group. Patients and methods: Five hundred consecutive patients of the university hospital subacute geriatric ward, aged 79.0±8.4 years (67% women and 33% men, participated in this cross-sectional study. Comprehensive geriatric assessment and Fried frailty phenotype component evaluation were performed in all patients. Results: Multimorbidity (6.0±2.8 diseases characterized our study group, with a wide range of clinical conditions and functional states (Barthel Index of Activities of Daily Living 72.2±28.2 and Mini-Mental State Examination 23.6±7.1 scores. All five Fried frailty components were assessed in 65% of patients (95% confidence interval [CI] =60.8–69.2 (diagnostic group. One or more components were not feasible to be assessed in 35% of the remaining patients (nondiagnostic group because of lack of past patient’s body mass control and/or cognitive or physical impairment. Patients from the nondiagnostic group, as compared to patients from the diagnostic group, presented with more advanced age, higher prevalence of dementia, lower prevalence of hypertension, lower systolic and diastolic blood pressure, body mass index, Mini

  6. The other side of phenotypic plasticity: a developmental system that generates an invariant phenotype despite environmental variation.

    Science.gov (United States)

    Braendle, Christian; Felix, Marie-Anne

    2009-10-01

    Understanding how the environment impacts development is of central interest in developmental and evolutionary biology. On the one hand, we would like to understand how the environment induces phenotypic changes (the study of phenotypic plasticity). On the other hand, we may ask how a development system maintains a stable and precise phenotypic output despite the presence of environmental variation. We study such developmental robustness to environmental variation using vulval cell fate patterning in the nematode Caenorhabditis elegans as a study system. Here we review both mechanistic and evolutionary aspects of these studies, focusing on recently obtained experimental results. First, we present evidence indicating that vulval formation is under stabilizing selection. Second, we discuss quantitative data on the precision and variability in the output of the vulval developmental system in different environments and different genetic backgrounds. Third, we illustrate how environmental and genetic variation modulate the cellular and molecular processes underlying the formation of the vulva. Fourth, we discuss the evolutionary significance of environmental sensitivity of this developmental system.

  7. The other side of phenotypic plasticity: a developmental system that generates an invariant phenotype despite environmental variation

    Indian Academy of Sciences (India)

    Christian Braendle; Marie-Anne Félix

    2009-10-01

    Understanding how the environment impacts development is of central interest in developmental and evolutionary biology. On the one hand, we would like to understand how the environment induces phenotypic changes (the study of phenotypic plasticity). On the other hand, we may ask how a development system maintains a stable and precise phenotypic output despite the presence of environmental variation. We study such developmental robustness to environmental variation using vulval cell fate patterning in the nematode Caenorhabditis elegans as a study system. Here we review both mechanistic and evolutionary aspects of these studies, focusing on recently obtained experimental results. First, we present evidence indicating that vulval formation is under stabilizing selection. Second, we discusss quantitative data on the precision and variability in the output of the vulval developmental system in different environments and different genetic backgrounds. Third, we illustrate how environmental and genetic variation modulate the cellular and molecular processes underlying the formation of the vulva. Fourth, we discuss the evolutionary significance of environmental sensitivity of this developmental system.

  8. Nonderivative Modified Gravity: a Classification

    CERN Document Server

    Comelli, Denis; Pilo, Luigi

    2014-01-01

    We analyze the theories of gravity modified by a generic nonderivative potential built from the metric, under the minimal requirement of unbroken spatial rotations. Using the canonical analysis, we classify the potentials $V$ according to the number of degrees of freedom (DoF) that propagate at the nonperturbative level. We then compare the nonperturbative results with the perturbative DoF propagating around Minkowski and FRW backgrounds. A generic $V$ implies 6 propagating DoF at the non-perturbative level, with a ghost on Minkowski background. There exist potentials which propagate 5 DoF, as already studied in previous works. Here, no $V$ with unbroken rotational invariance admitting 4 DoF is found. Theories with 3 DoF turn out to be strongly coupled on Minkowski background. Finally, potentials with only the 2 DoF of a massive graviton exist. Their effect on cosmology is simply equivalent to a cosmological constant. Potentials with 2 or 5 DoF and explicit time dependence appear to be a further viable possib...

  9. The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 2

    DEFF Research Database (Denmark)

    Kölker, Stefan; Valayannopoulos, Vassili; Burlina, Alberto B;

    2015-01-01

    BACKGROUND: The disease course and long-term outcome of patients with organic acidurias (OAD) and urea cycle disorders (UCD) are incompletely understood. AIMS: To evaluate the complex clinical phenotype of OAD and UCD patients at different ages. RESULTS: Acquired microcephaly and movement disorde...

  10. Early phenotypic differences between Parkinson's disease patients with and without freezing of gait

    NARCIS (Netherlands)

    Hall, J. M.; Shine, J. M.; Walton, C. C.; Gilat, M.; Kamsma, Y. P. T.; Naismith, S. L.; Lewis, S. J. G.

    2014-01-01

    Background: Previous studies have associated freezing of gait in Parkinson's disease with the presence of specific phenotypic features such as mood disturbances, REM sleep behavior disorder and selective cognitive impairments. However, it is not clear whether these features are present in the earlie

  11. Measurement Equivalence of the Autism Symptom Phenotype in Children and Youth

    Science.gov (United States)

    Duku, Eric; Szatmari, Peter; Vaillancourt, Tracy; Georgiades, Stelios; Thompson, Ann; Liu, Xiao-Qing; Paterson, Andrew D.; Bennett, Terry

    2013-01-01

    Background: The Autism Diagnostic Interview-Revised (ADI-R) is a gold standard assessment of Autism Spectrum Disorder (ASD) symptoms and behaviours. A key underlying assumption of studies using the ADI-R is that it measures the same phenotypic constructs across different populations (i.e. males/females, younger/older, verbal/nonverbal). The…

  12. A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study

    Science.gov (United States)

    Abstract Background: Blood lipid levels including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) are highly heritable. Genome-wide association is a promising approach to map genetic loci related to these heritable phenotypes. Metho...

  13. The Behavioural Phenotype of Smith-Magenis Syndrome: Evidence for a Gene-Environment Interaction

    Science.gov (United States)

    Taylor, L.; Oliver, C.

    2008-01-01

    Background: Behaviour problems and a preference for adult contact are reported to be prominent in the phenotype of Smith-Magenis syndrome. In this study we examined the relationship between social interactions and self-injurious and aggressive/disruptive behaviour in Smith-Magenis syndrome to explore potential operant reinforcement of problem…

  14. Genotypes and phenotypes for apolipoprotein E and Alzheimer disease in the Honolulu-Asia aging study

    NARCIS (Netherlands)

    J.W.P.F. Kardaun (Jan); L. White (Lon); H.E. Resnick; H. Petrovitch; S.M. Marcovina; A.M. Saunders (Ann); D.J. Foley (Dan); R.J. Havlik

    2000-01-01

    textabstractBACKGROUND: The utility of apolipoprotein E (ApoE) type as an indicator of genetic susceptibility to Alzheimer disease (AD) depends on the reliability of typing. Although ApoE protein isoform phenotyping is generally assumed equivalent to genotyping from DNA

  15. HDL does not influence the polarization of human monocytes toward an alternative phenotype

    NARCIS (Netherlands)

    Colin, Sophie; Fanchon, Melanie; Belloy, Loic; Bochem, Andrea E.; Copin, Corinne; Derudas, Bruno; Stroes, Erik S. G.; Hovingh, G. Kees; Kuivenhoven, Jan A.; Dallinga-Thie, Geesje M.; Staels, Bart; Chinetti-Gbaguidi, Giulia

    2014-01-01

    BACKGROUND: Macrophages are crucial cells in the pathogenesis of atherosclerosis. Macrophages are plastic cells which can switch from a classical pro-inflammatory M1 to an alternative anti-inflammatory M2 macrophage phenotype, depending on the environmental stimuli. Because high-density lipoprotein

  16. Multivariate genetic analysis of atopy phenotypes in a selected sample of twins

    DEFF Research Database (Denmark)

    Thomsen, SF; Ulrik, Charlotte Suppli; Kyvik, KO;

    2006-01-01

    , to a large extent, a common genetic background. In particular, upper and lower respiratory symptoms seem to be different phenotypic expressions of a common set of genes. These results add new insight into the origins of clinical heterogeneity within atopy and should stimulate the search for pleiotropic genes...

  17. Phenotype-genotype discordance in congenital malformations with communication disorders resembling trisomy 18 (Edwards syndrome)

    OpenAIRE

    Pruszewicz, Antoni; Wiskirska-Woźnica, Bożena; Wojnowski, Waldemar; Czerniejewska, Hanna; Jackowska, Joanna; Jarmuż, Małgorzata; Szyfter, Krzysztof; Leszczyńska, Małgorzata

    2014-01-01

    Patient: Female, 6 Final Diagnosis: Phenotype-genotype discordance in congenital malformations with communication disorders resembling trisomy 18 (Edwards syndrome) Symptoms: — Medication: — Clinical Procedure: — Specialty: Otolaryngology Objective: Congenital defects Background: Communication process disorders are very frequent in rare cases of chromosomal aberrations (deletions, insertions, and trisomies) such as Down syndrome (trisomy 21), Turner syndrome, Edwards syndrome (trisomy 18), or...

  18. Investigating Phenotypic Heterogeneity in Children with Autism Spectrum Disorder: A Factor Mixture Modeling Approach

    Science.gov (United States)

    Georgiades, Stelios; Szatmari, Peter; Boyle, Michael; Hanna, Steven; Duku, Eric; Zwaigenbaum, Lonnie; Bryson, Susan; Fombonne, Eric; Volden, Joanne; Mirenda, Pat; Smith, Isabel; Roberts, Wendy; Vaillancourt, Tracy; Waddell, Charlotte; Bennett, Teresa; Thompson, Ann

    2013-01-01

    Background: Autism spectrum disorder (ASD) is characterized by notable phenotypic heterogeneity, which is often viewed as an obstacle to the study of its etiology, diagnosis, treatment, and prognosis. On the basis of empirical evidence, instead of three binary categories, the upcoming edition of the DSM 5 will use two dimensions--social…

  19. Multi-dimensional discovery of biomarker and phenotype complexes

    Directory of Open Access Journals (Sweden)

    Huang Kun

    2010-10-01

    Full Text Available Abstract Background Given the rapid growth of translational research and personalized healthcare paradigms, the ability to relate and reason upon networks of bio-molecular and phenotypic variables at various levels of granularity in order to diagnose, stage and plan treatments for disease states is highly desirable. Numerous techniques exist that can be used to develop networks of co-expressed or otherwise related genes and clinical features. Such techniques can also be used to create formalized knowledge collections based upon the information incumbent to ontologies and domain literature. However, reports of integrative approaches that bridge such networks to create systems-level models of disease or wellness are notably lacking in the contemporary literature. Results In response to the preceding gap in knowledge and practice, we report upon a prototypical series of experiments that utilize multi-modal approaches to network induction. These experiments are intended to elicit meaningful and significant biomarker-phenotype complexes spanning multiple levels of granularity. This work has been performed in the experimental context of a large-scale clinical and basic science data repository maintained by the National Cancer Institute (NCI funded Chronic Lymphocytic Leukemia Research Consortium. Conclusions Our results indicate that it is computationally tractable to link orthogonal networks of genes, clinical features, and conceptual knowledge to create multi-dimensional models of interrelated biomarkers and phenotypes. Further, our results indicate that such systems-level models contain interrelated bio-molecular and clinical markers capable of supporting hypothesis discovery and testing. Based on such findings, we propose a conceptual model intended to inform the cross-linkage of the results of such methods. This model has as its aim the identification of novel and knowledge-anchored biomarker-phenotype complexes.

  20. PHENOTYPIC TRAITS IN ZAGORJE TURKEY

    Directory of Open Access Journals (Sweden)

    Z. Janječić

    2007-06-01

    Full Text Available Production of turkeys in the region of Hrvatsko zagorje began in second half of 16th century, when there was a little influence of other turkey breeds from other region. Recently, interest for protection and preservation of autochthonous poultry breeds in Croatia is growing and in that sense this investigation was set to determine the phenotypic traits of Zagorje turkey. One hundred 10-month old turkeys (5 males and 20 females of four strains (bronze, black, grey and pale were measured, while egg production data were collected by a poll among the breeders. Average body weight of bronze, black, grey and pale strain males were 7.08, 6.88, 6.10 and 6.09 kg, respectively, while in females the average values were 4.02, 4.07, 3.63, and 3.68 kg. Generally, according to body measures of male birds, other than body weight, of all of the strains of Zagorje turkey, the black one is the biggest, as it had the highest values for body length, length of sternum, length of drumstick, length of shank, depth of chest and head measures. At the same time, the bronze strain had the highest value for carcass width. Body measures mentioned previously were not so different in females. Number of reared chicks was lowest in the pale strain. From the body measures assessed it is possible to conclude that Zagorje turkeys are rather uniform within the strain but differences in most of the breed traits are present between the strains, especially in males of bronze and black strain, when compared to gray and pale strain.

  1. Scientific background of the project

    International Nuclear Information System (INIS)

    The main objective of the proposed project is the development of radioimmunometric assay(s) for the determination of free and total PSA in serum samples from normal and pathological individuals (BPH, PCa). This will be achieved by: A. Selection of appropriate antibody pairs (capture and labelled antibody) for determination of total PSA (free and complex) and for determination of free PSA. From bibliography we have already spotted some antibody pairs. B. Radiolabelling of antibodies. Several labelling and purification procedures will be followed in order to obtain the required analytical sensitivity and dynamic range of the assays. Special attention will be given to the affinity constant as well as to the stability of the radiolabelled molecules. C. Development of protocols for immobilisation of capture antibodies. We will use several solid support formats (plastic tubes, beads and magnetizable particles). Direct adsorption or covalent binding will be used. Immunoadsorption through immobilised second antibody will be also tested in order to decrease the preparation cost of the solid phase reagents. D. Preparation of standards of suitable purity levels. We will test different PSA-free matrices (Bovine serum, buffer solutions etc.) in order to select the most appropriate among them in terms of low background determination and low reagents cost. E. Optimisation of the immunoassays conditions for the free PSA and total PSA (e.g. assay buffers, incubation time, temperature, one or two step procedure, washings). F. Optimisation and standardisation of assay protocols for kit production. G. Production of kits for distribution in clinical laboratories in Greece for comparison with commercial kits. H. Evaluation of the developed assays in real clinical conditions using well characterised human serum samples. This will be performed in co-operation with the Hellenic Society for Tumor Markers, and other anticancer institutions and hospital clinicians of long standing relation

  2. Cosmic Microwave Background Data Analysis

    Science.gov (United States)

    Paykari, Paniez; Starck, Jean-Luc Starck

    2012-03-01

    About 400,000 years after the Big Bang the temperature of the Universe fell to about a few thousand degrees. As a result, the previously free electrons and protons combined and the Universe became neutral. This released a radiation which we now observe as the cosmic microwave background (CMB). The tiny fluctuations* in the temperature and polarization of the CMB carry a wealth of cosmological information. These so-called temperature anisotropies were predicted as the imprints of the initial density perturbations which gave rise to the present large-scale structures such as galaxies and clusters of galaxies. This relation between the present-day Universe and its initial conditions has made the CMB radiation one of the most preferred tools to understand the history of the Universe. The CMB radiation was discovered by radio astronomers Arno Penzias and Robert Wilson in 1965 [72] and earned them the 1978 Nobel Prize. This discovery was in support of the Big Bang theory and ruled out the only other available theory at that time - the steady-state theory. The crucial observations of the CMB radiation were made by the Far-Infrared Absolute Spectrophotometer (FIRAS) instrument on the Cosmic Background Explorer (COBE) satellite [86]- orbited in 1989-1996. COBE made the most accurate measurements of the CMB frequency spectrum and confirmed it as being a black-body to within experimental limits. This made the CMB spectrum the most precisely measured black-body spectrum in nature. The CMB has a thermal black-body spectrum at a temperature of 2.725 K: the spectrum peaks in the microwave range frequency of 160.2 GHz, corresponding to a 1.9mmwavelength. The results of COBE inspired a series of ground- and balloon-based experiments, which measured CMB anisotropies on smaller scales over the next decade. During the 1990s, the first acoustic peak of the CMB power spectrum (see Figure 5.1) was measured with increasing sensitivity and by 2000 the BOOMERanG experiment [26] reported

  3. Phenotyping: targeting genotype's rich cousin for diagnosis.

    Science.gov (United States)

    Baynam, Gareth; Walters, Mark; Claes, Peter; Kung, Stefanie; LeSouef, Peter; Dawkins, Hugh; Bellgard, Matthew; Girdea, Marta; Brudno, Michael; Robinson, Peter; Zankl, Andreas; Groza, Tudor; Gillett, David; Goldblatt, Jack

    2015-04-01

    There are many current and evolving tools to assist clinicians in their daily work of phenotyping. In medicine, the term 'phenotype' is usually taken to mean some deviation from normal morphology, physiology and behaviour. It is ascertained via history, examination and investigations, and a primary aim is diagnosis. Therefore, doctors are, by necessity, expert 'phenotypers'. There is an inherent and partially realised power in phenotypic information that when harnessed can improve patient care. Furthermore, phenotyping developments are increasingly important in an era of rapid advances in genomic technology. Fortunately, there is an expanding network of phenotyping tools that are poised for clinical translation. These tools will preferentially be implemented to mirror clinical workflows and to integrate with advances in genomic and information-sharing technologies. This will synergise with and augment the clinical acumen of medical practitioners. We outline key enablers of the ascertainment, integration and interrogation of clinical phenotype by using genetic diseases, particularly rare ones, as a theme. Successes from the test bed or rare diseases will support approaches to common disease.

  4. Evolution of molecular phenotypes under stabilizing selection

    Science.gov (United States)

    Nourmohammad, Armita; Schiffels, Stephan; Lässig, Michael

    2013-01-01

    Molecular phenotypes are important links between genomic information and organismic functions, fitness, and evolution. Complex phenotypes, which are also called quantitative traits, often depend on multiple genomic loci. Their evolution builds on genome evolution in a complicated way, which involves selection, genetic drift, mutations and recombination. Here we develop a coarse-grained evolutionary statistics for phenotypes, which decouples from details of the underlying genotypes. We derive approximate evolution equations for the distribution of phenotype values within and across populations. This dynamics covers evolutionary processes at high and low recombination rates, that is, it applies to sexual and asexual populations. In a fitness landscape with a single optimal phenotype value, the phenotypic diversity within populations and the divergence between populations reach evolutionary equilibria, which describe stabilizing selection. We compute the equilibrium distributions of both quantities analytically and we show that the ratio of mean divergence and diversity depends on the strength of selection in a universal way: it is largely independent of the phenotype’s genomic encoding and of the recombination rate. This establishes a new method for the inference of selection on molecular phenotypes beyond the genome level. We discuss the implications of our findings for the predictability of evolutionary processes.

  5. Efficient α, β-motif finder for identification of phenotype-related functional modules

    Directory of Open Access Journals (Sweden)

    Schmidt Matthew C

    2011-11-01

    Full Text Available Abstract Background Microbial communities in their natural environments exhibit phenotypes that can directly cause particular diseases, convert biomass or wastewater to energy, or degrade various environmental contaminants. Understanding how these communities realize specific phenotypic traits (e.g., carbon fixation, hydrogen production is critical for addressing health, bioremediation, or bioenergy problems. Results In this paper, we describe a graph-theoretical method for in silico prediction of the cellular subsystems that are related to the expression of a target phenotype. The proposed (α, β-motif finder approach allows for identification of these phenotype-related subsystems that, in addition to metabolic subsystems, could include their regulators, sensors, transporters, and even uncharacterized proteins. By comparing dozens of genome-scale networks of functionally associated proteins, our method efficiently identifies those statistically significant functional modules that are in at least α networks of phenotype-expressing organisms but appear in no more than β networks of organisms that do not exhibit the target phenotype. It has been shown via various experiments that the enumerated modules are indeed related to phenotype-expression when tested with different target phenotypes like hydrogen production, motility, aerobic respiration, and acid-tolerance. Conclusion Thus, we have proposed a methodology that can identify potential statistically significant phenotype-related functional modules. The functional module is modeled as an (α, β-clique, where α and β are two criteria introduced in this work. We also propose a novel network model, called the two-typed, divided network. The new network model and the criteria make the problem tractable even while very large networks are being compared. The code can be downloaded from http://www.freescience.org/cs/ABClique/

  6. Genetics of human sleep behavioral phenotypes.

    Science.gov (United States)

    Hsu, Pei-Ken; Ptáček, Louis J; Fu, Ying-Hui

    2015-01-01

    Quality sleep is critical for daily functions of human beings and thus the timing and duration of sleep are tightly controlled. However, rare genetic variants affecting sleep regulatory mechanisms can result in sleep phenotypes of extremely deviated sleep/wake onset time or duration. Using genetic analyses in families with multiple members expressing particular sleep phenotypes, these sleep-associated genetic variants can be identified. Deciphering the nature of these genetic variants using animal models or biochemical methods helps further our understanding of sleep processes. In this chapter, we describe the methods for studying genetics of human sleep behavioral phenotypes.

  7. Metabolic phenotype of bladder cancer.

    Science.gov (United States)

    Massari, Francesco; Ciccarese, Chiara; Santoni, Matteo; Iacovelli, Roberto; Mazzucchelli, Roberta; Piva, Francesco; Scarpelli, Marina; Berardi, Rossana; Tortora, Giampaolo; Lopez-Beltran, Antonio; Cheng, Liang; Montironi, Rodolfo

    2016-04-01

    serine hydroxymethyltransferase-2 (SHMT2), resulting in an increased glycine and purine ring of nucleotides synthesis, thus supporting cells proliferation. A deep understanding of the metabolic phenotype of bladder cancer will provide novel opportunities for targeted therapeutic strategies.

  8. Holographic modified gravity

    CERN Document Server

    Setare, M R

    2009-01-01

    In this paper we study cosmological application of holographic dark energy density in the modified gravity framework. We employ the holographic model of dark energy to obtain the equation of state for the holographic energy density in spatially flat universe. Our calculation show, taking $\\Omega_{\\Lambda}=0.73$ for the present time, it is possible to have $w_{\\rm \\Lambda}$ crossing -1. This implies that one can generate phantom-like equation of state from a holographic dark energy model in flat universe in the modified gravity cosmology framework. Also we develop a reconstruction scheme for the modified gravity with $f(R)$ action.

  9. Annual research review: Reaction time variability in ADHD and autism spectrum disorders: measurement and mechanisms of a proposed trans-diagnostic phenotype

    NARCIS (Netherlands)

    S.L. Karalunas; H.M. Geurts; K. Konrad; S. Bender; J.T. Nigg

    2014-01-01

    Background: Intraindividual variability in reaction time (RT) has received extensive discussion as an indicator of cognitive performance, a putative intermediate phenotype of many clinical disorders, and a possible trans-diagnostic phenotype that may elucidate shared risk factors for mechanisms of p

  10. Thermodynamics in Modified Gravity Theories

    CERN Document Server

    Bamba, Kazuharu; Tsujikawa, Shinji

    2011-01-01

    We demonstrate that there does exist an equilibrium description of thermodynamics on the apparent horizon in the expanding cosmological background for a wide class of modified gravity theories with the Lagrangian density $f(R, \\phi, X)$, where $R$ is the Ricci scalar and $X$ is the kinetic energy of a scalar field $\\phi$. This comes from a suitable definition of an energy momentum tensor of the "dark" component obeying the local energy conservation law in the Jordan frame. It is shown that the equilibrium description in terms of the horizon entropy $S$ is convenient because it takes into account the contribution of the horizon entropy $\\hat{S}$ in non-equilibrium thermodynamics as well as an entropy production term.

  11. Minimal parameterizations for modified gravity

    CERN Document Server

    Scott, Ali Narimani Douglas

    2013-01-01

    The increasing precision of cosmological data provides us with an opportunity to test general relativity (GR) on the largest accessible scales. Parameterizing modified gravity models facilitates the systematic testing of the predictions of GR, and gives a framework for detecting possible deviations from it. Several different parameterizations have already been suggested, some linked to classifications of theories, and others more empirically motivated. Here we describe a particular new approach which casts modifications to gravity through two free functions of time and scale, which are directly linked to the field equations, but also easy to confront with observational data. We compare our approach with other existing methods of parameterizing modied gravity, specifically the parameterized post-Friedmann approach and the older method using the parameter set $\\{\\mu,\\gamma\\}$. We explain the connection between our parameters and the physics that is most important for generating cosmic microwave background aniso...

  12. Modified gravity without dark matter

    CERN Document Server

    Sanders, R H

    2006-01-01

    On an empirical level, the most successful alternative to dark matter in bound gravitational systems is the modified Newtonian dynamics, or MOND, proposed by Milgrom. Here I discuss the attempts to formulate MOND as a modification of General Relativity. I begin with a summary of the phenomenological successes of MOND and then discuss the various covariant theories that have been proposed as a basis for the idea. I show why these proposals have led inevitably to a multi-field theory. I describe in some detail TeVeS, the tensor-vector-scalar theory proposed by Bekenstein, and discuss its successes and shortcomings. This lecture is primarily pedagogical and directed to those with some, but not a deep, background in General Relativity

  13. Phenotypic plasticity as an adaptive response to predictable and unpredictable environmental changes

    DEFF Research Database (Denmark)

    Manenti, Tommaso

    Phenotypic plasticity is the ability of a genotype to modify its phenotype in response to environmental changes as a consequence of an interaction between genes and environment (Bradshaw, 1965). Plasticity contributes to the vast phenotypic variation observed in natural populations. Many examples...... of a plastic response are expected to depend on the environmental conditions experienced by organisms. Thus, in populations exposed to a non-changing environment, the plastic machinery might be a waste of resources. Contrary, in populations experiencing varying environmental conditions, plasticity is expected...... for many generations in three thermal regimes, specifically designed to affect the levels of plasticity. The three environments were found to induce high levels of plasticity and to affect stress resistance and life history traits differently. However, flies selected in different thermal regimes maintained...

  14. PhenoBlocks: Phenotype Comparison Visualizations.

    Science.gov (United States)

    Glueck, Michael; Hamilton, Peter; Chevalier, Fanny; Breslav, Simon; Khan, Azam; Wigdor, Daniel; Brudno, Michael

    2016-01-01

    The differential diagnosis of hereditary disorders is a challenging task for clinicians due to the heterogeneity of phenotypes that can be observed in patients. Existing clinical tools are often text-based and do not emphasize consistency, completeness, or granularity of phenotype reporting. This can impede clinical diagnosis and limit their utility to genetics researchers. Herein, we present PhenoBlocks, a novel visual analytics tool that supports the comparison of phenotypes between patients, or between a patient and the hallmark features of a disorder. An informal evaluation of PhenoBlocks with expert clinicians suggested that the visualization effectively guides the process of differential diagnosis and could reinforce the importance of complete, granular phenotypic reporting.

  15. Mining skeletal phenotype descriptions from scientific literature.

    Directory of Open Access Journals (Sweden)

    Tudor Groza

    Full Text Available Phenotype descriptions are important for our understanding of genetics, as they enable the computation and analysis of a varied range of issues related to the genetic and developmental bases of correlated characters. The literature contains a wealth of such phenotype descriptions, usually reported as free-text entries, similar to typical clinical summaries. In this paper, we focus on creating and making available an annotated corpus of skeletal phenotype descriptions. In addition, we present and evaluate a hybrid Machine Learning approach for mining phenotype descriptions from free text. Our hybrid approach uses an ensemble of four classifiers and experiments with several aggregation techniques. The best scoring technique achieves an F-1 score of 71.52%, which is close to the state-of-the-art in other domains, where training data exists in abundance. Finally, we discuss the influence of the features chosen for the model on the overall performance of the method.

  16. Phenotypic profiles of Armenian grape cultivars

    Directory of Open Access Journals (Sweden)

    Aroutiounian Rouben

    2015-01-01

    Full Text Available The conservation and sustainable use of grapevine biodiversity in Armenia is particularly important due to the large number of traditional local varieties. Being partially different from European grapevine gene pool, the material of Armenian local cultivars significantly contributes to the understanding of the genetic variation and is valuable source for target selection. During last years many Armenian grapevine cultivars have been already described and their genotypes determined, but some local varieties and wild accessions remain unidentified and their phenotypic characteristics overlooked. The comprehensive analysis of phenotypes is essential for research, including genetic association studies, cultivar evaluation and selection. The goal of our research was the phenotyping on the base of reproductive, carpological and analytical characteristics of 80 Armenian aboriginal and new grape cultivars. Description of phenotypic profiles is important step towards identification and conservation of genetic resources of Armenian grapes. In future, these data can be applied for breeding of improved grape varieties targeted to fresh consumption and wine production.

  17. Modified Desert Cooler (MDC

    Directory of Open Access Journals (Sweden)

    CHANDRAKANT B. KOTHARE,

    2011-04-01

    Full Text Available “Modified Desert Cooler (MDC” as the name suggest that it is the modification of the conventional cooler. It is the Air Conditioner cum refrigerator for people who cannot afford costly equipments like air conditioner, refrigerator and other such appliances. It cools the air more than the conventional Desert cooler. The modified desert cooler is developed for providing better cooling effect than conventional desert cooler. It also provides cold-pure water for drinking purpose comparatively at low cost than Refrigerator with the help of modifies Matka attached with it. It also decreased moisture content of the air coming through desert cooler upto someextent. The MDC consists of a desert cooler with storage box, two concentric simple small size earthen pot known as modify Matka, a purifier, humidity controller and connecting tubes or pipes. Storage box provided in the desert cooler can be used to store regular food items, vegetables, fruits etc.

  18. Next Generation Sequencing Demands Next Generation Phenotyping

    OpenAIRE

    Hennekam, Raoul CM; Biesecker, Leslie G

    2012-01-01

    Next-Generation Sequencing (NGS) is the most powerful diagnostic tool since the roentgenogram. NGS will facilitate diagnosis on a massive scale –allowing interrogation of all genes in a single assay. It has been suggested that NGS will decrease the need for phenotyping in general, and medical geneticists in particular. We argue that NGS will shift focus and approach of phenotyping. We predict that NGS performed for diagnostic purposes will yield variants in several genes, and consequences of ...

  19. Phenotyping of robustness and milk quality

    OpenAIRE

    Berry, D. P.; Mcparland, S.; Bastin, Catherine; Wall, E.; Gengler, Nicolas; Soyeurt, Hélène

    2013-01-01

    A phenotype describes the outcome of the interacting development between the genotype of an individual and its specific environment throughout life. Animal breeding currently exploits large data sets of phenotypic and pedigree information to estimate the genetic merit of animals. Here we describe rapid, low-cost phenomic tools for dairy cattle. We give particular emphasis to infrared spectroscopy of milk because the necessary spectral data are already routinely available on milk samples from ...

  20. Recurrent duplications of 17q12 associated with variable phenotypes.

    Science.gov (United States)

    Mitchell, Elyse; Douglas, Andrew; Kjaegaard, Susanne; Callewaert, Bert; Vanlander, Arnaud; Janssens, Sandra; Yuen, Amy Lawson; Skinner, Cindy; Failla, Pinella; Alberti, Antonino; Avola, Emanuela; Fichera, Marco; Kibaek, Maria; Digilio, Maria C; Hannibal, Mark C; den Hollander, Nicolette S; Bizzarri, Veronica; Renieri, Alessandra; Mencarelli, Maria Antonietta; Fitzgerald, Tomas; Piazzolla, Serena; van Oudenhove, Elke; Romano, Corrado; Schwartz, Charles; Eichler, Evan E; Slavotinek, Anne; Escobar, Luis; Rajan, Diana; Crolla, John; Carter, Nigel; Hodge, Jennelle C; Mefford, Heather C

    2015-12-01

    The ability to identify the clinical nature of the recurrent duplication of chromosome 17q12 has been limited by its rarity and the diverse range of phenotypes associated with this genomic change. In order to further define the clinical features of affected patients, detailed clinical information was collected in the largest series to date (30 patients and 2 of their siblings) through a multi-institutional collaborative effort. The majority of patients presented with developmental delays varying from mild to severe. Though dysmorphic features were commonly reported, patients do not have consistent and recognizable features. Cardiac, ophthalmologic, growth, behavioral, and other abnormalities were each present in a subset of patients. The newly associated features potentially resulting from 17q12 duplication include height and weight above the 95th percentile, cataracts, microphthalmia, coloboma, astigmatism, tracheomalacia, cutaneous mosaicism, pectus excavatum, scoliosis, hypermobility, hypospadias, diverticulum of Kommerell, pyloric stenosis, and pseudohypoparathryoidism. The majority of duplications were inherited with some carrier parents reporting learning disabilities or microcephaly. We identified additional, potentially contributory copy number changes in a subset of patients, including one patient each with 16p11.2 deletion and 15q13.3 deletion. Our data further define and expand the clinical spectrum associated with duplications of 17q12 and provide support for the role of genomic modifiers contributing to phenotypic variability. PMID:26420380

  1. Genetically Modified Organisms

    OpenAIRE

    Claro Llaguno

    2001-01-01

    Recent reports have brought to public attention concerns about Bt corn and genetically modified organisms (GMO) in general. The timing, it seems, is most appropriate considering two related developments early this year: the final approval of the Cartagena Protocol on Biosafety in Montreal on January 29, 2001, and the OECD Edinburgh Conference on GM food safety last February 28- March 1, 2001. The protocol makes clear that GMOs include all living modified organisms (LMO) defined as "any living...

  2. POLYCAPROLACTAM MODIFIED BY POLYBENZIMIDAZOLE

    Institute of Scientific and Technical Information of China (English)

    YANG Guisheng; LU Fengcai

    1990-01-01

    Three polycaprolactam samples modified by 0.05 - 0.50% polybenzimidazole (PBI) by weight were prepared. Their structure and mechanical properties were characterized by means of FT- IR, SEM, DTA,density tensile,impact and viscoelastic method. PBI delayed the superimposed polymerization-crystallization process of the activated anionic polymerization of caprolactam. The monomer casting (MC) nylons modified by PBI had lower crystallinities,lower Tg and more nearly perfect spherulites than MCnylon itself, and showed a typical toughening effect.

  3. Biological response modifiers

    Energy Technology Data Exchange (ETDEWEB)

    Weller, R.E.

    1991-10-01

    Much of what used to be called immunotherapy is now included in the term biological response modifiers. Biological response modifiers (BRMs) are defined as those agents or approaches that modify the relationship between the tumor and host by modifying the host's biological response to tumor cells with resultant therapeutic effects.'' Most of the early work with BRMs centered around observations of spontaneous tumor regression and the association of tumor regression with concurrent bacterial infections. The BRM can modify the host response in the following ways: Increase the host's antitumor responses through augmentation and/or restoration of effector mechanisms or mediators of the host's defense or decrease the deleterious component by the host's reaction; Increase the host's defenses by the administration of natural biologics (or the synthetic derivatives thereof) as effectors or mediators of an antitumor response; Augment the host's response to modified tumor cells or vaccines, which might stimulate a greater response by the host or increase tumor-cell sensitivity to an existing response; Decrease the transformation and/or increase differentiation (maturation) of tumor cells; or Increase the ability of the host to tolerate damage by cytotoxic modalities of cancer treatment.

  4. The proton pump inhibitor lansoprazole improves the skeletal phenotype in dystrophin deficient mdx mice.

    Directory of Open Access Journals (Sweden)

    Arpana Sali

    Full Text Available BACKGROUND: In Duchenne muscular dystrophy (DMD, loss of the membrane stabilizing protein dystrophin results in myofiber damage. Microinjury to dystrophic myofibers also causes secondary imbalances in sarcolemmic ion permeability and resting membrane potential, which modifies excitation-contraction coupling and increases proinflammatory/apoptotic signaling cascades. Although glucocorticoids remain the standard of care for the treatment of DMD, there is a need to investigate the efficacy of other pharmacological agents targeting the involvement of imbalances in ion flux on dystrophic pathology. METHODOLOGY/PRINCIPAL FINDINGS: We designed a preclinical trial to investigate the effects of lansoprazole (LANZO administration, a proton pump inhibitor, on the dystrophic muscle phenotype in dystrophin deficient (mdx mice. Eight to ten week-old female mice were assigned to one of four treatment groups (n = 12 per group: (1 vehicle control; (2 5 mg/kg/day LANZO; (3 5 mg/kg/day prednisolone; and (4 combined treatment of 5 mg/kg/day prednisolone (PRED and 5 mg/kg/day LANZO. Treatment was administered orally 5 d/wk for 3 months. At the end of the study, behavioral (Digiscan and functional outcomes (grip strength and Rotarod were assessed prior to sacrifice. After sacrifice, body, tissue and organ masses, muscle histology, in vitro muscle force, and creatine kinase levels were measured. Mice in the combined treatment groups displayed significant reductions in the number of degenerating muscle fibers and number of inflammatory foci per muscle field relative to vehicle control. Additionally, mice in the combined treatment group displayed less of a decline in normalized forelimb and hindlimb grip strength and declines in in vitro EDL force after repeated eccentric contractions. CONCLUSIONS/SIGNIFICANCE: Together our findings suggest that combined treatment of LANZO and prednisolone attenuates some components of dystrophic pathology in mdx mice. Our findings

  5. The multi-systemic nature of diabetes mellitus: Genotype or phenotype?

    Directory of Open Access Journals (Sweden)

    Graham Wilfred Ewing

    2010-10-01

    Full Text Available Background: This article discusses factors which materially influence the diagnosis, prevention and treatment of diabetes mellitus but which may be overlooked by the prevailing biomedical paradigm. That cognition can be mathematically linked to the function of the autonomic nervous system and physiological systems casts new light upon the mechanisms responsible for homeostasis and origins of disease. In particular, it highlights the limitations of the reductionist biomedical approach which considers mainly the biochemistry of single pathologies rather than considering the neural mechanisms which regulate the function of physiological systems, and inherent visceral organs; and which are subsequently manifest as biochemistries of varying degrees of complexity and severity. As a consequence, histopathological tests are fraught with inherent limitations and many categories of drugs are significantly ineffective. Aims: Such limitations may be explained if disease (in particular diabetes mellitus has multiple origins, is multi-systemic in nature and, depending upon the characteristics of each pathology, is influenced by genotype and/or phenotype. Results: This article highlights the influence of factors which are not yet considered re. the aetiology of diabetes mellitus e.g. the influence of light and sensory input upon the stability of the autonomic nervous system; the influence of raised plasma viscosity upon rates of reaction; the influence of viruses and/or of modified live viruses given in vaccinations; systemic instability, in particular the adverse influence of drinks and lack of exercise upon the body’s prevailing pH and its subsequent influence upon levels of magnesium and other essential trace elements. Conclusions: This application of the top-down systems biology approach may provide a plausible and inclusive explanation for the nature and occurrence of diabetes mellitus.

  6. The multi-systemic nature of diabetes mellitus: Genotype or phenotype?

    Directory of Open Access Journals (Sweden)

    Graham Wilfred Ewing

    2010-01-01

    Full Text Available Background: This article discusses factors which materially influence the diagnosis, prevention and treatment of diabetes mellitus but which may be overlooked by the prevailing biomedical paradigm. That cognition can be mathematically linked to the function of the autonomic nervous system and physiological systems casts new light upon the mechanisms responsible for homeostasis and origins of disease. In particular, it highlights the limitations of the reductionist biomedical approach which considers mainly the biochemistry of single pathologies rather than considering the neural mechanisms which regulate the function of physiological systems, and inherent visceral organs; and which are subsequently manifest as biochemistries of varying degrees of complexity and severity. As a consequence, histopathological tests are fraught with inherent limitations and many categories of drugs are significantly ineffective. Aims: Such limitations may be explained if disease (in particular diabetes mellitus has multiple origins, is multi-systemic in nature and, depending upon the characteristics of each pathology, is influenced by genotype and/or phenotype. Results:This article highlights the influence of factors which are not yet considered re. the aetiology of diabetes mellitus e.g. the influence of light and sensory input upon the stability of the autonomic nervous system; the influence of raised plasma viscosity upon rates of reaction; the influence of viruses and/or of modified live viruses given in vaccinations; systemic instability, in particular the adverse influence of drinks and lack of exercise upon the body′s prevailing pH and its subsequent influence upon levels of magnesium and other essential trace elements. Conclusions: This application of the top-down systems biology approach may provide a plausible and inclusive explanation for the nature and occurrence of diabetes mellitus.

  7. iTAP: integrated transcriptomics and phenotype database for stress response of Escherichia coli and Saccharomyces cerevisiae

    OpenAIRE

    Sundararaman, Niveda; Ash, Christine; Guo, Weihua; Button, Rebecca; Singh, Jugroop; Feng, Xueyang

    2015-01-01

    Abstract Background Organisms are subject to various stress conditions, which affect both the organism’s gene expression and phenotype. It is critical to understand microbial responses to stress conditions and uncover the underlying molecular mechanisms. To this end, it is necessary to build a database that collects transcriptomics and phenotypic data of microbes growing under various stress factors for in-depth systems biology analysis....

  8. The prevalence of metabolic disorders in various phenotypes of polycystic ovary syndrome: a community based study in Southwest of Iran

    OpenAIRE

    Ramezani Tehrani, Fahimeh; Rashidi, Homeira; Bahri Khomami, Mahnaz; Tohidi, Maryam; Azizi, Fereidoun

    2014-01-01

    Background Polycystic ovary syndrome (PCOS) is a common endocrinopathy, associated with metabolic abnormalities. Metabolic features of various phenotypes of this syndrome are still debatable. The aim of present study hence was to evaluate the metabolic and hormonal features of PCOS phenotypes in comparison to a group of healthy control. Methods A total of 646 reproductive-aged women were randomly selected using the stratified, multistage probability cluster sampling method. The subjects were ...

  9. In vitro analysis of the invasive phenotype of SUM 149, an inflammatory breast cancer cell line

    OpenAIRE

    Dharmawardhane Suranganie F; Wall Kristin M; Hoffmeyer Michaela R

    2005-01-01

    Abstract Background Inflammatory breast cancer (IBC) is the most lethal form of locally invasive breast cancer known. However, very little information is available on the cellular mechanisms responsible for manifestation of the IBC phenotype. To understand the unique phenotype of IBC, we compared the motile and adhesive interactions of an IBC cell line, SUM 149, to the non-IBC cell line SUM 102. Results Our results demonstrate that both IBC and non-IBC cell lines exhibit similar adhesive prop...

  10. Type I collagen inhibits differentiation and promotes a stem cell-like phenotype in human colorectal carcinoma cells

    OpenAIRE

    Kirkland, S. C.

    2009-01-01

    Background: Human colorectal cancer is caused by mutations and is thought to be maintained by a population of cancer stem cells. Further phenotypic changes occurring at the invasive edge suggest that colon cancer cells are also regulated by their microenvironment. Type I collagen, a promoter of the malignant phenotype in pancreatic carcinoma cells, is highly expressed at the invasive front of human colorectal cancer. Methods: This study investigates the role of type I collagen in specifying t...

  11. A Dysmorphometric Analysis to Investigate Facial Phenotypic Signatures as a Foundation for Non-invasive Monitoring of Lysosomal Storage Disorders

    OpenAIRE

    Kung, Stefanie; Walters, Mark; Claes, Peter; Goldblatt, Jack; Le Souef, Peter; Baynam, Gareth

    2012-01-01

    Background: Some lysosomal storage disorders (LSDs), including Muccopolysaccharidosis type 1 (MPSI), are associated with characteristic facies. Methods such as three-dimensional (3D) facial scanning and geometric morphometric techniques can potentially generate detailed objective descriptions of these facial phenotypes. This approach can facilitate discriminating the inherent overlap in facial phenotypes within these disease spectra, and the non-invasive monitoring of disease progression and ...

  12. Phenotypic plasticity in the range-margin population of the lycaenid butterfly Zizeeria maha

    OpenAIRE

    Otaki Joji M; Hiyama Atsuki; Iwata Masaki; Kudo Tadashi

    2010-01-01

    Abstract Background Many butterfly species have been experiencing the northward range expansion and physiological adaptation, probably due to climate warming. Here, we document an extraordinary field case of a species of lycaenid butterfly, Zizeeria maha, for which plastic phenotypes of wing color-patterns were revealed at the population level in the course of range expansion. Furthermore, we examined whether this outbreak of phenotypic changes was able to be reproduced in a laboratory. Resul...

  13. Disease profile and differential diagnosis of hereditary transthyretin-related amyloidosis with exclusively cardiac phenotype: An Italian perspective

    OpenAIRE

    Rapezzi, Claudio; Quarta, Candida Cristina; Obici, Laura; Perfetto, Federico; Longhi, Simone; Salvi, Fabrizio; Biagini, Elena; Lorenzini, Massimiliano; Grigioni, Francesco; Leone, Ornella; Cappelli, Francesco; Palladini, Giovanni; Rimessi, Paola; Ferlini, Alessandra; Arpesella, Giorgio

    2013-01-01

    AIMS: Hereditary transthyretin (TTR)-related amyloidosis (ATTR) is mainly considered a neurologic disease. We assessed the phenotypic and genotypic spectra of ATTR in a Caucasian area and evaluated the prevalence, genetic background, and disease profile of cases with an exclusively cardiac phenotype, highlighting possible hints for the differential diagnosis with hypertrophic cardiomyopathy (HCM) and senile systemic amyloidosis (SSA). METHODS AND RESULTS: In this Italian multicentr...

  14. Genetic variations strongly influence phenotypic outcome in the mouse retina.

    Directory of Open Access Journals (Sweden)

    Austin S Jelcick

    Full Text Available Variation in genetic background can significantly influence the phenotypic outcome of both disease and non-disease associated traits. Additionally, differences in temporal and strain specific gene expression can also contribute to phenotypes in the mammalian retina. This is the first report of microarray based cross-strain analysis of gene expression in the retina investigating genetic background effects. Microarray analyses were performed on retinas from the following mouse strains: C57BL6/J, AKR/J, CAST/EiJ, and NOD.NON-H2(-nb1 at embryonic day 18.5 (E18.5 and postnatal day 30.5 (P30.5. Over 3000 differentially expressed genes were identified between strains and developmental stages. Differential gene expression was confirmed by qRT-PCR, Western blot, and immunohistochemistry. Three major gene networks were identified that function to regulate retinal or photoreceptor development, visual perception, cellular transport, and signal transduction. Many of the genes in these networks are implicated in retinal diseases such as bradyopsia, night-blindness, and cone-rod dystrophy. Our analysis revealed strain specific variations in cone photoreceptor cell patterning and retinal function. This study highlights the substantial impact of genetic background on both development and function of the retina and the level of gene expression differences tolerated for normal retinal function. These strain specific genetic variations may also be present in other tissues. In addition, this study will provide valuable insight for the development of more accurate models for human retinal diseases.

  15. Cluster analysis in severe emphysema subjects using phenotype and genotype data: an exploratory investigation

    Directory of Open Access Journals (Sweden)

    Martinez Fernando J

    2010-03-01

    Full Text Available Abstract Background Numerous studies have demonstrated associations between genetic markers and COPD, but results have been inconsistent. One reason may be heterogeneity in disease definition. Unsupervised learning approaches may assist in understanding disease heterogeneity. Methods We selected 31 phenotypic variables and 12 SNPs from five candidate genes in 308 subjects in the National Emphysema Treatment Trial (NETT Genetics Ancillary Study cohort. We used factor analysis to select a subset of phenotypic variables, and then used cluster analysis to identify subtypes of severe emphysema. We examined the phenotypic and genotypic characteristics of each cluster. Results We identified six factors accounting for 75% of the shared variability among our initial phenotypic variables. We selected four phenotypic variables from these factors for cluster analysis: 1 post-bronchodilator FEV1 percent predicted, 2 percent bronchodilator responsiveness, and quantitative CT measurements of 3 apical emphysema and 4 airway wall thickness. K-means cluster analysis revealed four clusters, though separation between clusters was modest: 1 emphysema predominant, 2 bronchodilator responsive, with higher FEV1; 3 discordant, with a lower FEV1 despite less severe emphysema and lower airway wall thickness, and 4 airway predominant. Of the genotypes examined, membership in cluster 1 (emphysema-predominant was associated with TGFB1 SNP rs1800470. Conclusions Cluster analysis may identify meaningful disease subtypes and/or groups of related phenotypic variables even in a highly selected group of severe emphysema subjects, and may be useful for genetic association studies.

  16. Computer aided data acquisition tool for high-throughput phenotyping of plant populations

    Directory of Open Access Journals (Sweden)

    Basha Pinjari

    2009-12-01

    Full Text Available Abstract Background The data generated during a course of a biological experiment/study can be sometimes be massive and its management becomes quite critical for the success of the investigation undertaken. The accumulation and analysis of such large datasets often becomes tedious for biologists and lab technicians. Most of the current phenotype data acquisition management systems do not cater to the specialized needs of large-scale data analysis. The successful application of genomic tools/strategies to introduce desired traits in plants requires extensive and precise phenotyping of plant populations or gene bank material, thus necessitating an efficient data acquisition system. Results Here we describe newly developed software "PHENOME" for high-throughput phenotyping, which allows researchers to accumulate, categorize, and manage large volume of phenotypic data. In this study, a large number of individual tomato plants were phenotyped with the "PHENOME" application using a Personal Digital Assistant (PDA with built-in barcode scanner in concert with customized database specific for handling large populations. Conclusion The phenotyping of large population of plants both in the laboratory and in the field is very efficiently managed using PDA. The data is transferred to a specialized database(s where it can be further analyzed and catalogued. The "PHENOME" aids collection and analysis of data obtained in large-scale mutagenesis, assessing quantitative trait loci (QTLs, raising mapping population, sampling of several individuals in one or more ecological niches etc.

  17. Morphogenesis of an extended phenotype: four-dimensional ant nest architecture

    OpenAIRE

    Minter, Nicholas J.; Franks, Nigel R.; Robson Brown, Katharine A.

    2011-01-01

    Animals produce a variety of structures to modify their environments adaptively. Such structures represent extended phenotypes whose development is rarely studied. To begin to rectify this, we used micro-computed tomography (CT) scanning and time-series experiments to obtain the first high-resolution dataset on the four-dimensional growth of ant nests. We show that extrinsic features within the environment, such as the presence of planes between layers of sediment, influence the architecture ...

  18. Increased entropy of signal transduction in the cancer metastasis phenotype

    Directory of Open Access Journals (Sweden)

    Teschendorff Andrew E

    2010-07-01

    Full Text Available Abstract Background The statistical study of biological networks has led to important novel biological insights, such as the presence of hubs and hierarchical modularity. There is also a growing interest in studying the statistical properties of networks in the context of cancer genomics. However, relatively little is known as to what network features differ between the cancer and normal cell physiologies, or between different cancer cell phenotypes. Results Based on the observation that frequent genomic alterations underlie a more aggressive cancer phenotype, we asked if such an effect could be detectable as an increase in the randomness of local gene expression patterns. Using a breast cancer gene expression data set and a model network of protein interactions we derive constrained weighted networks defined by a stochastic information flux matrix reflecting expression correlations between interacting proteins. Based on this stochastic matrix we propose and compute an entropy measure that quantifies the degree of randomness in the local pattern of information flux around single genes. By comparing the local entropies in the non-metastatic versus metastatic breast cancer networks, we here show that breast cancers that metastasize are characterised by a small yet significant increase in the degree of randomness of local expression patterns. We validate this result in three additional breast cancer expression data sets and demonstrate that local entropy better characterises the metastatic phenotype than other non-entropy based measures. We show that increases in entropy can be used to identify genes and signalling pathways implicated in breast cancer metastasis and provide examples of de-novo discoveries of gene modules with known roles in apoptosis, immune-mediated tumour suppression, cell-cycle and tumour invasion. Importantly, we also identify a novel gene module within the insulin growth factor signalling pathway, alteration of which may

  19. The International Mouse Phenotyping Consortium: past and future perspectives on mouse phenotyping

    OpenAIRE

    Steve D M Brown; Moore, Mark W.

    2012-01-01

    Determining the function of all mammalian genes remains a major challenge for the biomedical science community in the 21st century. The goal of the International Mouse Phenotyping Consortium (IMPC) over the next 10 years is to undertake broad-based phenotyping of 20,000 mouse genes, providing an unprecedented insight into mammalian gene function. This short article explores the drivers for large-scale mouse phenotyping and provides an overview of the aims and processes involved in IMPC mouse ...

  20. Kinetics of spontaneous baryogenesis in non-stationary background

    CERN Document Server

    Arbuzova, Elena; Novikov, Victor

    2016-01-01

    Generation of the cosmological baryon asymmetry in frameworks of spontaneous baryogenesis is studied in detail. It is shown that the relation between baryonic chemical potential and the time derivative of the (pseudo)Goldstone field essentially depends upon the representation chosen for the fermionic fields with non-zero baryonic number (quarks). Kinetic equation is modified and numerically solved in equilibrium for the case of time dependent external background or finite integration time to be applicable to the case when energy conservation law is formally violated.

  1. Kinetics of spontaneous baryogenesis in non-stationary background

    Directory of Open Access Journals (Sweden)

    Arbuzova Elena

    2016-01-01

    Full Text Available Generation of the cosmological baryon asymmetry in frameworks of spontaneous baryogenesis is studied in detail. It is shown that the relation between baryonic chemical potential and the time derivative of the (pseudoGoldstone field essentially depends upon the representation chosen for the fermionic fields with non-zero baryonic number (quarks. Kinetic equation is modified and numerically solved in equilibrium for the case of time dependent external background or finite integration time to be applicable to the case when energy conservation law is formally violated.

  2. Deriving modified rankin scores from medical records

    OpenAIRE

    Quinn, T J; Ray, G.; Atula, S.; Walters, M.R.; Dawson, J.; Lees, K R

    2008-01-01

    Background and Purpose: Modified Rankin score (mRS) is traditionally graded using a face-to-face or telephone interview. Certain stroke assessment scales can be derived from a review of a patient’s case-record alone. We hypothesized that mRS could be successfully derived from the narrative within patient case-records. Methods: Sequential patients attending our cerebrovascular outpatient clinic were included. Two independent, blinded clinicians, trained in mRS, assessed case-records to der...

  3. Multipurpose background for standardization in medical photography.

    Science.gov (United States)

    Hallock, G G

    1985-08-01

    A dual photography background system consisting of a quadrilled format on one side and a plain background on the other is described. It is mobile and efficient as a space- and time-saving device for medical photography.

  4. Background subtraction using probabilistic event weights

    OpenAIRE

    Wang, Yadi; Liu, Beijiang; Shen, Xiaoyan; Zhang, Ziping

    2014-01-01

    Background treatment is crucial to extract physics from precision experiments. In this paper, we introduce a novel method to assign each event a signal probability. This could then be used to weight the event's contribution to the likelihood during fitting. To illustrate the effect of this method, we test it with MC samples. The consistence between the constructed background and the background from MC truth shows that the background subtraction method with probabilistic event weights is feasi...

  5. Characterization of Rett Syndrome-like phenotypes in Mecp2-knockout rats

    OpenAIRE

    Wu, Yang; Zhong, Weiwei; Cui, Ningren; Johnson, Christopher M.; Xing, Hao; Zhang, Shuang; Jiang, Chun

    2016-01-01

    Background Rett Syndrome (RTT) is a neurodevelopmental disease caused by the disruption of the MECP2 gene. Several mouse models of RTT have been developed with Mecp2 disruptions. Although the mouse models are widely used in RTT research, results obtained need to be validated in other species. Therefore, we performed these studies to characterize phenotypes of a novel Mecp2 −/Y rat model and compared them with the Mecp2 tm1.1Bird mouse model of RTT. Methods RTT-like phenotypes were systematica...

  6. Differences in phenotype and disease course in adult and paediatric inflammatory bowel disease

    DEFF Research Database (Denmark)

    Jakobsen, Christian; Bartek, Jiri; Wewer, Anne Vibeke;

    2011-01-01

    Background Few studies have compared phenotype and disease course in children and adults with inflammatory bowel disease (IBD). Aim To compare phenotype, treatment and disease course in children (IBD. Methods Two population-based cohorts comprising paediatric...... or disease course. Cumulative 5-year surgery rates for paediatric and adult patients were 5% and 9% for UC (N.S.) and 18% and 21% for CD (N.S.), respectively. Conclusions Paediatric UC patients had more extensive disease, were more often treated with systemic steroids and AZA, had a higher frequency...

  7. Modifying Factors of Cystic Fibrosis Disease: Residual Chloride Secrefion, Genefic Background and Epigenetics

    NARCIS (Netherlands)

    I. Bronsveld (Inez)

    2000-01-01

    textabstractCystic fibrosis (CF) is an autosomal recessive disease caused by genetic lesions in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This CFTR gene was cloned in 1989,1-3 and located to the long arm of chromosome 7 (7q3L2). lt encodes the CFTR protein that functions a

  8. Beam-Generated Detector Backgrounds at CESR

    OpenAIRE

    Henderson, Stuart; Cinabro, David

    2000-01-01

    The CESR/CLEO Phase II interaction region is described. The operational experience with beam-generated detector backgrounds is reviewed. The status of our understanding of beam-generated detector backgrounds at CESR is described and comparisons of background measurements with simulation predictions are presented.

  9. Recursive least squares background prediction of univariate syndromic surveillance data

    Directory of Open Access Journals (Sweden)

    Burkom Howard

    2009-01-01

    Full Text Available Abstract Background Surveillance of univariate syndromic data as a means of potential indicator of developing public health conditions has been used extensively. This paper aims to improve the performance of detecting outbreaks by using a background forecasting algorithm based on the adaptive recursive least squares method combined with a novel treatment of the Day of the Week effect. Methods Previous work by the first author has suggested that univariate recursive least squares analysis of syndromic data can be used to characterize the background upon which a prediction and detection component of a biosurvellance system may be built. An adaptive implementation is used to deal with data non-stationarity. In this paper we develop and implement the RLS method for background estimation of univariate data. The distinctly dissimilar distribution of data for different days of the week, however, can affect filter implementations adversely, and so a novel procedure based on linear transformations of the sorted values of the daily counts is introduced. Seven-days ahead daily predicted counts are used as background estimates. A signal injection procedure is used to examine the integrated algorithm's ability to detect synthetic anomalies in real syndromic time series. We compare the method to a baseline CDC forecasting algorithm known as the W2 method. Results We present detection results in the form of Receiver Operating Characteristic curve values for four different injected signal to noise ratios using 16 sets of syndromic data. We find improvements in the false alarm probabilities when compared to the baseline W2 background forecasts. Conclusion The current paper introduces a prediction approach for city-level biosurveillance data streams such as time series of outpatient clinic visits and sales of over-the-counter remedies. This approach uses RLS filters modified by a correction for the weekly patterns often seen in these data series, and a threshold

  10. Genotypic and Phenotypic Analysis of Fasciola Isolates

    Directory of Open Access Journals (Sweden)

    SN Mosavinasab

    2009-07-01

    Full Text Available "nBackground: To identify the fasciolid species by morphometric and molecular methods in Zanjan, north­west of Iran. "nMethods: Adult Fasciola worms (n=584 were obtained from cattle and sheep in Zanjan slaughterhouse in 2007. Living flukes were washed, then worms' images were taken by 3CCD camera and finally apical zone of each worm was obtained. Morphometric values such as body length, body width, body area, body pe­rimeter and the distance between ventral sucker and posterior end of body were obtained using Auto­CAD image analysis software. Total gDNA was extracted from individual flukes by modified phenol-chloroform method. PCR amplification of ITS2 fragment was performed the isolated DNA samples and the amplicons were consequently subjected to RFLP assay and nucleotide sequencing to distinguish be­tween fasciolid species. "nResults: Mean of morphometric values in flukes from sheep was greater than those of cattle. Accordingly, the identified species included 31% F. hepatica-like, 7% F. gigantica-like and 62% intermediate forms. How­ever, ITS2 fragment of 535 amplified specimens, showed no variation at the species-specific nucleo­tide sites 230, 340 and 341. The amplified fragment composed of partial 5.8S sequence (62bp, the com­plete ITS2 sequence (361bp and partial 28S sequence (34bp. The nucleotide contents of ITS2 region were 69 A, 116 T, 81 C and 95 G and the average G+C content was approximately 49%. Comparing of ITS2 sequences with the BLAST GenBank database, also confirmed that all specimens were F. hepatica. "nConclusion: A simple and rapid PCR-RFLP assay can be used for distinguishing between these species.

  11. Meta-analysis of melanin-concentrating hormone signaling-deficient mice on behavioral and metabolic phenotypes.

    Directory of Open Access Journals (Sweden)

    Kenkichi Takase

    Full Text Available The demand for meta-analyses in basic biomedical research has been increasing because the phenotyping of genetically modified mice does not always produce consistent results. Melanin-concentrating hormone (MCH has been reported to be involved in a variety of behaviors that include feeding, body-weight regulation, anxiety, sleep, and reward behavior. However, the reported behavioral and metabolic characteristics of MCH signaling-deficient mice, such as MCH-deficient mice and MCH receptor 1 (MCHR1-deficient mice, are not consistent with each other. In the present study, we performed a meta-analysis of the published data related to MCH-deficient and MCHR1-deficient mice to obtain robust conclusions about the role of MCH signaling. Overall, the meta-analysis revealed that the deletion of MCH signaling enhanced wakefulness, locomotor activity, aggression, and male sexual behavior and that MCH signaling deficiency suppressed non-REM sleep, anxiety, responses to novelty, startle responses, and conditioned place preferences. In contrast to the acute orexigenic effect of MCH, MCH signaling deficiency significantly increased food intake. Overall, the meta-analysis also revealed that the deletion of MCH signaling suppressed the body weight, fat mass, and plasma leptin, while MCH signaling deficiency increased the body temperature, oxygen consumption, heart rate, and mean arterial pressure. The lean phenotype of the MCH signaling-deficient mice was also confirmed in separate meta-analyses that were specific to sex and background strain (i.e., C57BL/6 and 129Sv. MCH signaling deficiency caused a weak anxiolytic effect as assessed with the elevated plus maze and the open field test but also caused a weak anxiogenic effect as assessed with the emergence test. MCH signaling-deficient mice also exhibited increased plasma corticosterone under non-stressed conditions, which suggests enhanced activity of the hypothalamic-pituitary-adrenal axis. To the best of our

  12. Volatile organic compounds as non-invasive markers for plant phenotyping.

    Science.gov (United States)

    Niederbacher, B; Winkler, J B; Schnitzler, J P

    2015-09-01

    Plants emit a great variety of volatile organic compounds (VOCs) that can actively participate in plant growth and protection against biotic and abiotic stresses. VOC emissions are strongly dependent on environmental conditions; the greatest ambiguity is whether or not the predicted change in climate will influence and modify plant-pest interactions that are mediated by VOCs. The constitutive and induced emission patterns between plant genotypes, species, and taxa are highly variable and can be used as pheno(chemo)typic markers to distinguish between different origins and provenances. In recent years significant progress has been made in molecular and genetic plant breeding. However, there is actually a lack of knowledge in functionally linking genotypes and phenotypes, particularly in analyses of plant-environment interactions. Plant phenotyping, the assessment of complex plant traits such as growth, development, tolerance, resistance, etc., has become a major bottleneck, and quantitative information on genotype-environment relationships is the key to addressing major future challenges. With increasing demand to support and accelerate progress in breeding for novel traits, the plant research community faces the need to measure accurately increasingly large numbers of plants and plant traits. In this review article, we focus on the promising outlook of VOC phenotyping as a fast and non-invasive measure of phenotypic dynamics. The basic principle is to define plant phenotypes according to their disease resistance and stress tolerance, which in turn will help in improving the performance and yield of economically relevant plants. PMID:25969554

  13. The evolution of phenotypic plasticity: genealogy of a debate in genetics.

    Science.gov (United States)

    Nicoglou, Antonine

    2015-04-01

    The paper describes the context and the origin of a particular debate that concerns the evolution of phenotypic plasticity. In 1965, British biologist A. D. Bradshaw proposed a widely cited model intended to explain the evolution of norms of reaction, based on his studies of plant populations. Bradshaw's model went beyond the notion of the "adaptive norm of reaction" discussed before him by Dobzhansky and Schmalhausen by suggesting that "plasticity"--the ability of a phenotype to be modified by the environment--should be genetically determined. To prove Bradshaw's hypothesis, it became necessary for some authors to identify the pressures exerted by natural selection on phenotypic plasticity in particular traits, and thus to model its evolution. In this paper, I contrast two different views, based on quantitative genetic models, proposed in the mid-1980s: Russell Lande and Sara Via's conception of phenotypic plasticity, which assumes that the evolution of plasticity is linked to the evolution of the plastic trait itself, and Samuel Scheiner and Richard Lyman's view, which assumes that the evolution of plasticity is independent from the evolution of the trait. I show how the origin of this specific debate, and different assumptions about the evolution of phenotypic plasticity, depended on Bradshaw's definition of plasticity and the context of quantitative genetics.

  14. iBeetle-Base: a database for RNAi phenotypes in the red flour beetle Tribolium castaneum.

    Science.gov (United States)

    Dönitz, Jürgen; Schmitt-Engel, Christian; Grossmann, Daniela; Gerischer, Lizzy; Tech, Maike; Schoppmeier, Michael; Klingler, Martin; Bucher, Gregor

    2015-01-01

    The iBeetle-Base (http://ibeetle-base.uni-goettingen.de) makes available annotations of RNAi phenotypes, which were gathered in a large scale RNAi screen in the red flour beetle Tribolium castaneum (iBeetle screen). In addition, it provides access to sequence information and links for all Tribolium castaneum genes. The iBeetle-Base contains the annotations of phenotypes of several thousands of genes knocked down during embryonic and metamorphic epidermis and muscle development in addition to phenotypes linked to oogenesis and stink gland biology. The phenotypes are described according to the EQM (entity, quality, modifier) system using controlled vocabularies and the Tribolium morphological ontology (TrOn). Furthermore, images linked to the respective annotations are provided. The data are searchable either for specific phenotypes using a complex 'search for morphological defects' or a 'quick search' for gene names and IDs. The red flour beetle Tribolium castaneum has become an important model system for insect functional genetics and is a representative of the most species rich taxon, the Coleoptera, which comprise several devastating pests. It is used for studying insect typical development, the evolution of development and for research on metabolism and pest control. Besides Drosophila, Tribolium is the first insect model organism where large scale unbiased screens have been performed.

  15. Comparison of TaqMan® Array Card and MYCOTB™ with conventional phenotypic susceptibility testing in MDR-TB

    Science.gov (United States)

    Foongladda, S.; Banu, S.; Pholwat, S.; Gratz, J.; O-Thong, S.; Nakkerd, N.; Chinli, R.; Ferdous, S. S.; Rahman, S. M. M.; Rahman, A.; Ahmed, S.; Heysell, S.; Sariko, M.; Kibiki, G.

    2016-01-01

    SUMMARY BACKGROUND: Although phenotypic drug susceptibility testing (DST) is endorsed as the standard for second-line drug testing of Mycobacterium tuberculosis, it is slow and laborious. METHODS: We evaluated the accuracy of two faster, easier methodologies that provide results for multiple drugs: a genotypic TaqMan® Array Card (TAC) and the Sensititre® MYCOTB™ plate. Both methods were tested at three central laboratories in Bangladesh, Tanzania, and Thailand with 212 multidrug-resistant tuberculosis (MDR-TB) isolates and compared with the laboratories' phenotypic method in use. RESULTS: The overall accuracy for ethambutol, streptomycin, amikacin, kanamycin, ofloxacin, and moxifloxacin vs. the phenotypic standard was 87% for TAC (range 70–99) and 88% for the MYCOTB plate (range 76–98). To adjudicate discordances, we re-defined the standard as the consensus of the three methods, against which the TAC and MYCOTB plate yielded 94–95% accuracy, while the phenotypic result yielded 93%. Some isolates with genotypic mutations and high minimum inhibitory concentration (MIC) were phenotypically susceptible, and some isolates without mutations and low MIC were phenotypically resistant, questioning the phenotypic standard. CONCLUSIONS: In our view, the TAC, the MYCOTB plate, and the conventional phenotypic method have similar performance for second-line drugs; however, the former methods offer speed, throughput, and quantitative DST information. PMID:27393547

  16. Stain Detection in Video with Background Restructured

    Directory of Open Access Journals (Sweden)

    Jia Wang

    2014-07-01

    Full Text Available Nowadays, multimedia, especially video, is used widely in many domains. But camera lens are easily stained because they are always outside, such as in traffic and monitoring. Admittedly, the video from these cameras is out of action because it cannot provide clear frames. In this paper, we provide a detecting method from video with background restructure. This method is presented to detect stains in video. Firstly, the first video frame is used as a pseudo-background because original cameras are clear with no stains. Then, background is constructed by the pseudo-background and the continuous frames which are from the video. Moreover, with training in the frames, we restructure background by dropped moving objects in it. Finally, after background restructured, we detect stains in camera lenses by the restructured background, and provide positions of stained area. Experimental results show its robustness and practicability

  17. A New Method to Infer Causal Phenotype Networks Using QTL and Phenotypic Information

    NARCIS (Netherlands)

    Wang, H.; Eeuwijk, van F.

    2014-01-01

    In the context of genetics and breeding research on multiple phenotypic traits, reconstructing the directional or causal structure between phenotypic traits is a prerequisite for quantifying the effects of genetic interventions on the traits. Current approaches mainly exploit the genetic effects at

  18. Phenotypic and genotypic variations within a single bacteriophage species

    Directory of Open Access Journals (Sweden)

    Kulakov Leonid

    2011-03-01

    Full Text Available Abstract Background Although horizontal gene transfer plays a pivotal role in bacteriophage evolution, many lytic phage genomes are clearly shaped by vertical evolution. We investigated the influence of minor genomic deletions and insertions on various phage-related phenotypic and serological properties. Findings We collected ten different isolates of Pseudomonas aeruginosa bacteriophage ϕKMV. All sequenced genomes (42-43 kb, long direct terminal repeats are nearly identical, which intuitively implied strongly similar infections cycles. However, their latent periods vary between 21 and 28 minutes and they are able to lyse between 5 and 58% of a collection of 107 clinical P. aeruginosa strains. We also noted that phages with identical tail structures displayed profound differences in host spectra. Moreover, point mutations in tail and spike proteins were sufficient to evade neutralization by two phage-specific antisera, isolated from rabbits. Conclusion Although all analyzed phages are 83-97% identical at the genome level, they display a surprisingly large variation in various phenotypic properties. The small overlap in host spectrum and their ability to readily escape immune defences against a nearly identical phage are promising elements for the application of these phages in phage therapy.

  19. Detection of fruit by the Cerrado's marmoset (Callithrix penicillata): modeling color signals for different background scenarios and ambient light intensities.

    Science.gov (United States)

    Perini, Eduardo Sosti; Pessoa, Valdir Filgueiras; Pessoa, Daniel Marques de Almeida

    2009-04-01

    Among placental mammals, only primates have trichromatic color vision, however this is not a uniform condition. Under different genetic status, Old World monkeys have routine trichromacy, while New World monkeys show a visual polymorphism, characterized by obligatory male dichromacy. The ecological role of this genetic difference still remains unclear, but some studies show that dichromats and trichromats appear to have different abilities in detecting colored targets against a background of leaves. The Cerrado's marmoset (Callithrix penicillata) is known to forage in brightly illuminated (savanna-like vegetation) and dimly illuminated (forests) environments, exploiting a high amount of dark fruits. Hence, it seems to be a good model for studying the differential advantages enjoyed by each color vision phenotype under natural conditions. Our aim was to verify how the different phenotypes of Cerrado's marmoset detect components of their diet, evaluating the existence of differential phenotype advantages. Under two different light conditions, visual signals of naturally consumed fruits were modeled against different backgrounds scenarios. Even though dichromats and trichromats appear to be equally suited for tasks involving fruit detection, phenotype differential advantages are observed in this marmoset. In many conditions trichromats are predicted to perform better than dichromats, but under low ambient light dichromats manage to outperform trichromats in some scenarios. Phenotypes that carry widely spaced and longer M/L pigments enjoy the most advantage. These differential performances of trichromatic phenotypes, together with overdominance selection, seem to explain the maintenance of the tri-allelic system found in callitrichids.

  20. Detection of fruit by the Cerrado's marmoset (Callithrix penicillata): modeling color signals for different background scenarios and ambient light intensities.

    Science.gov (United States)

    Perini, Eduardo Sosti; Pessoa, Valdir Filgueiras; Pessoa, Daniel Marques de Almeida

    2009-04-01

    Among placental mammals, only primates have trichromatic color vision, however this is not a uniform condition. Under different genetic status, Old World monkeys have routine trichromacy, while New World monkeys show a visual polymorphism, characterized by obligatory male dichromacy. The ecological role of this genetic difference still remains unclear, but some studies show that dichromats and trichromats appear to have different abilities in detecting colored targets against a background of leaves. The Cerrado's marmoset (Callithrix penicillata) is known to forage in brightly illuminated (savanna-like vegetation) and dimly illuminated (forests) environments, exploiting a high amount of dark fruits. Hence, it seems to be a good model for studying the differential advantages enjoyed by each color vision phenotype under natural conditions. Our aim was to verify how the different phenotypes of Cerrado's marmoset detect components of their diet, evaluating the existence of differential phenotype advantages. Under two different light conditions, visual signals of naturally consumed fruits were modeled against different backgrounds scenarios. Even though dichromats and trichromats appear to be equally suited for tasks involving fruit detection, phenotype differential advantages are observed in this marmoset. In many conditions trichromats are predicted to perform better than dichromats, but under low ambient light dichromats manage to outperform trichromats in some scenarios. Phenotypes that carry widely spaced and longer M/L pigments enjoy the most advantage. These differential performances of trichromatic phenotypes, together with overdominance selection, seem to explain the maintenance of the tri-allelic system found in callitrichids. PMID:19296489

  1. Phenotypic and genetic consequences of protein damage.

    Directory of Open Access Journals (Sweden)

    Anita Krisko

    Full Text Available Although the genome contains all the information necessary for maintenance and perpetuation of life, it is the proteome that repairs, duplicates and expresses the genome and actually performs most cellular functions. Here we reveal strong phenotypes of physiological oxidative proteome damage at the functional and genomic levels. Genome-wide mutations rates and biosynthetic capacity were monitored in real time, in single Escherichia coli cells with identical levels of reactive oxygen species and oxidative DNA damage, but with different levels of irreversible oxidative proteome damage (carbonylation. Increased protein carbonylation correlates with a mutator phenotype, whereas reducing it below wild type level produces an anti-mutator phenotype identifying proteome damage as the leading cause of spontaneous mutations. Proteome oxidation elevates also UV-light induced mutagenesis and impairs cellular biosynthesis. In conclusion, protein damage reduces the efficacy and precision of vital cellular processes resulting in high mutation rates and functional degeneracy akin to cellular aging.

  2. Intra familial phenotypical variations in adrenoleukodystrophy

    Directory of Open Access Journals (Sweden)

    Gosalakkal Jayaprakash

    2010-01-01

    Full Text Available Adrenoleukodystrophy (ALD is an X-linked recessively inherited peroxisomal disorder, characterized by progressive white-matter demyelination of the central nervous system and adrenocortical insufficiency. It has a wide phenotypical variability ranging from symptomatic childhood cerebral form to the asymptomatic with biochemical defects only; sometimes within the same family. We report a family of three siblings diagnosed with ALD confirmed with the mutations in ABCD1 gene having phenotypical variability ranging from pure adrenal insufficiency to progressive neurodegeneration in the same family. The mother was identified as the carrier and maternal uncle was diagnosed with Adrenomyeloneuropathy. We discuss the variable presentation in our family and the possible causes of phenotypical variability.

  3. Navigating the Phenotype Frontier: The Monarch Initiative.

    Science.gov (United States)

    McMurry, Julie A; Köhler, Sebastian; Washington, Nicole L; Balhoff, James P; Borromeo, Charles; Brush, Matthew; Carbon, Seth; Conlin, Tom; Dunn, Nathan; Engelstad, Mark; Foster, Erin; Gourdine, Jean-Philippe; Jacobsen, Julius O B; Keith, Daniel; Laraway, Bryan; Xuan, Jeremy Nguyen; Shefchek, Kent; Vasilevsky, Nicole A; Yuan, Zhou; Lewis, Suzanna E; Hochheiser, Harry; Groza, Tudor; Smedley, Damian; Robinson, Peter N; Mungall, Christopher J; Haendel, Melissa A

    2016-08-01

    The principles of genetics apply across the entire tree of life. At the cellular level we share biological mechanisms with species from which we diverged millions, even billions of years ago. We can exploit this common ancestry to learn about health and disease, by analyzing DNA and protein sequences, but also through the observable outcomes of genetic differences, i.e. phenotypes. To solve challenging disease problems we need to unify the heterogeneous data that relates genomics to disease traits. Without a big-picture view of phenotypic data, many questions in genetics are difficult or impossible to answer. The Monarch Initiative (https://monarchinitiative.org) provides tools for genotype-phenotype analysis, genomic diagnostics, and precision medicine across broad areas of disease. PMID:27516611

  4. Gene therapy for muscular dystrophy using secondary modifiers of the dystrophic phenotype

    OpenAIRE

    Abmayr, Simone

    2005-01-01

    The absence of dystrophin in Duchenne muscular dystrophy causes sarcolemmal instability and renders muscle fibers susceptible to contraction-induced injury. Muscle repair mechanisms cannot compensate for progressive muscle degeneration, leading to a gradual replacement of muscle with adipose and connective tissue. Viral vectors have been successfully used to deliver dystrophin cDNA to dystrophin-deficient mdx mice, leading to a partial functional and morphological recovery of dystrophic mus...

  5. Infant rat infection modifies phenotypic properties of an invasive nontypeable Haemophilus influenzae

    OpenAIRE

    Tsao, David; Nelson, Kevin L.; Kim, Daniel; Smith, Arnold L.

    2011-01-01

    Enhancing the virulence trait of a specific bacterium in an animal model is often performed prior to the use of the strain for ex vivo human studies, such as reactivity with complement and antibody, or with phagocytic cells. For example, in S. penumoniae mouse passage is used to enhance capsule production. While investigating an unusual serum-resistant unencapsulated H. influenzae (R2866), we found that animal passage yielded an isolate (R3392) which had decreased resistance to human serum, b...

  6. Global changes in gene expression associated with phenotypic switching of wild yeast

    DEFF Research Database (Denmark)

    Stovicek, Vratislav; Váchová, Libuše; Begany, Markéta;

    2014-01-01

    Background : Saccharomyces cerevisiae strains isolated from natural settings form structured biofilm colonies that are equipped with intricate protective mechanisms. These wild strains are able to reprogram themselves with a certain frequency during cultivation in plentiful laboratory conditions....... The resulting domesticated strains switch off certain protective mechanisms and form smooth colonies that resemble those of common laboratory strains.  Results : Here, we show that domestication can be reversed when a domesticated strain is challenged by various adverse conditions; the resulting feral strain...... restores its ability to form structured biofilm colonies. Phenotypic, microscopic and transcriptomic analyses show that phenotypic transition is a complex process that affects various aspects of feral strain physiology; it leads to a phenotype that resembles the original wild strain in some aspects...

  7. Familial adenomatous polyposis patients without an identified APC germline mutation have a severe phenotype

    DEFF Research Database (Denmark)

    Bisgaard, M L; Ripa, R; Knudsen, Anne Louise;

    2004-01-01

    BACKGROUND: Development of more than 100 colorectal adenomas is diagnostic of the dominantly inherited autosomal disease familial adenomatous polyposis (FAP). Germline mutations can be identified in the adenomatous polyposis coli (APC) gene in approximately 80% of patients. The APC protein...... comprises several regions and domains for interaction with other proteins, and specific clinical manifestations are associated with the mutation assignment to one of these regions or domains. AIMS: The phenotype in patients without an identified causative APC mutation was compared with the phenotype...... in patients with a known APC mutation and with the phenotypes characteristic of patients with mutations in specific APC regions and domains. PATIENTS: Data on 121 FAP probands and 149 call up patients from 70 different families were extracted from the Danish Polyposis register. METHODS: Differences in 16...

  8. Computational genes: a tool for molecular diagnosis and therapy of aberrant mutational phenotype

    Directory of Open Access Journals (Sweden)

    Ignatova Zoya

    2007-09-01

    Full Text Available Abstract Background A finite state machine manipulating information-carrying DNA strands can be used to perform autonomous molecular-scale computations at the cellular level. Results We propose a new finite state machine able to detect and correct aberrant molecular phenotype given by mutated genetic transcripts. The aberrant mutations trigger a cascade reaction: specific molecular markers as input are released and induce a spontaneous self-assembly of a wild type protein or peptide, while the mutational disease phenotype is silenced. We experimentally demostrated in in vitro translation system that a viable protein can be autonomously assembled. Conclusion Our work demostrates the basic principles of computational genes and particularly, their potential to detect mutations, and as a response thereafter administer an output that suppresses the aberrant disease phenotype and/or restores the lost physiological function.

  9. Bone phenotypes of P2 receptor knockout mice

    DEFF Research Database (Denmark)

    Orriss, Isabel; Syberg, Susanne; Wang, Ning;

    2011-01-01

    The action of extracellular nucleotides is mediated by ionotropic P2X receptors and G-protein coupled P2Y receptors. The human genome contains 7 P2X and 8 P2Y receptor genes. Knockout mice strains are available for most of them. As their phenotypic analysis is progressing, bone abnormalities have...... been observed in an impressive number of these mice: distinct abnormalities in P2X7-/- mice, depending on the gene targeting construct and the genetic background, decreased bone mass in P2Y1-/- mice, increased bone mass in P2Y2-/- mice, decreased bone resorption in P2Y6-/- mice, decreased bone...... formation and bone resorption in P2Y13-/- mice. These findings demonstrate the unexpected importance of extracellular nucleotide signalling in the regulation of bone metabolism via multiple P2 receptors and distinct mechanisms involving both osteoblasts and osteoclasts....

  10. Pharmacogenetics of antipsychotic-induced movement disorders as a resource for better understanding Parkinson's disease modifier genes

    Directory of Open Access Journals (Sweden)

    Lior eGreenbaum

    2015-02-01

    Full Text Available Antipsychotic-induced movement disorders are major side effects of antipsychotic drugs among schizophrenia patients, and include antipsychotic-induced parkinsonism (AIP and tardive dyskinesia (TD. Substantial pharmacogenetic work has been done in this field, and several susceptibility variants have been suggested. In this paper, the genetics of antipsychotic-induced movement disorders is considered in a broader context. We hypothesize that genetic variants that are risk factors for AIP and TD may provide insights into the pathophysiology of Parkinson's disease (PD. Since loss of dopaminergic stimulation (albeit pharmacological in AIP and degenerative in PD is shared by the two clinical entities, genes associated with susceptibility to AIP may be modifier genes that influence clinical expression of PD sub-phenotypes, such as age at onset, disease severity or rate of progression. This is due to their possible functional influence on compensatory mechanisms for striatal dopamine loss. Better compensatory potential might be beneficial at the early and later stages of the PD course. AIP vulnerability variants may also be related to latent impairment in the nigrostriatal pathway, affecting its functionality, and leading to subclinical dopaminergic deficits in the striatum. Susceptibility of PD patients to early development of L-dopa induced dyskinesia (LID, is an additional relevant sub-phenotype. LID may share a common genetic background with TD, with which it shares clinical features. Genetic risk variants may predispose to both phenotypes, exerting a pleiotropic effect. According to this hypothesis, elucidating the genetics of antipsychotic-induced movement disorders may advance our understanding of multiple aspects of PD and it clinical course, rendering this a potentially rewarding field of study.

  11. The Phenotype of Spontaneous Preterm Birth: Application of a Clinical Phenotyping Tool

    Science.gov (United States)

    Manuck, Tracy A.; Esplin, M. Sean; Biggio, Joseph; Bukowski, Radek; Parry, Samuel; Zhang, Heping; Varner, Michael W.; Andrews, William; Saade, George; Sadovsky, Yoel; Reddy, Uma M.; Ilekis, John

    2015-01-01

    Objective Spontaneous preterm birth (SPTB) is a complex condition that is likely a final common pathway with multiple possible etiologies. We hypothesized that a comprehensive classification system could appropriately group women with similar STPB etiologies, and provide an explanation, at least in part, for the disparities in SPTB associated with race and gestational age at delivery. Study Design Planned analysis of a multicenter, prospective study of singleton SPTB. Women with SPTB < 34 weeks were included. We defined 9 potential SPTB phenotypes based on clinical data, including infection/inflammation, maternal stress, decidual hemorrhage, uterine distention, cervical insufficiency, placental dysfunction, premature rupture of the membranes, maternal comorbidities, and familial factors. Each woman was evaluated for each phenotype. Delivery gestational age was compared between those with and without each phenotype. Phenotype profiles were also compared between women with very early (20.0–27.9 weeks) SPTB vs. those with early SPTB (28.0–34.0 weeks), and between African-American and Caucasian women. Statistical analysis was by t-test and chi-square as appropriate. Results The phenotyping tool was applied to 1025 women with SPTB who delivered at a mean 30.0 (+/− 3.2) weeks gestation. Of these, 800 (78%) had ≥2 phenotypes. Only 43 (4.2%) had no phenotypes. The 281 women with early SPTB were more likely to have infection/inflammation, decidual hemorrhage, and cervical insufficiency phenotypes (all p≤0.001). African-American women had more maternal stress and cervical insufficiency but less decidual hemorrhage and placental dysfunction compared to Caucasian women (all p<0.05). Gestational age at delivery decreased as the number of phenotypes present increased. Conclusions Precise SPTB phenotyping classifies women with SPTB and identifies specific differences between very early and early SPTB and between African-Americans and Caucasians. PMID:25687564

  12. Tip-modified Propellers

    DEFF Research Database (Denmark)

    Andersen, Poul

    1999-01-01

    The paper deals with tip-modified propellers and the methods which, over a period of two decades, have been applied to develop such propellers. The development is driven by the urge to increase the efficiency of propellers and can be seen as analogous to fitting end plates and winglets to aircraft...

  13. Extragalactic Background Light: Measurements and Applications

    CERN Document Server

    Cooray, Asantha

    2016-01-01

    This review covers the measurements related to the extragalactic background light (EBL) intensity from gamma-rays to radio in the electromagnetic spectrum over 20 decades in the wavelength. The cosmic microwave background (CMB) remains the best measured spectrum with an accuracy better than 1%. The measurements related to the cosmic optical background (COB), centered at 1 microns, are impacted by the large zodiacal light associated with interplanetary dust in the inner Solar system. The best measurements of COB come from an indirect technique involving Gamma-ray spectra of bright blazars with an absorption feature resulting from pair-production off of COB photons. The cosmic infrared background (CIB) peaking at around 100 microns established an energetically important background with an intensity comparable to the optical background. This discovery paved the path for large aperture far-infrared and sub-millimeter observations resulting in the discovery of dusty, starbursting galaxies. Their role in galaxy for...

  14. CMB with the background primordial magnetic field

    CERN Document Server

    Yamazaki, Dai G

    2014-01-01

    We investigate the effects of the background primordial magnetic field (PMF) on the cosmic microwave background (CMB). The sound speed of the tightly coupled photon-baryon fluid is increased by the background PMF. The increased sound speed causes the odd peaks of the CMB temperature fluctuations to be suppressed and the CMB peak positions to be shifted to a larger scale. The background PMF causes a stronger decaying potential and increases the amplitude of the CMB. These two effects of the background PMF on a smaller scale cancel out, and the overall effects of the background PMF are the suppression of the CMB around the first peak and the shifting of peaks to a large scale. We also discuss obtaining information about the PMF generation mechanisms, and we examine the nonlinear evolution of the PMF by the constraint on the maximum scale for the PMF distributions. Finally, we discuss degeneracies between the PMF parameters and the standard cosmological parameters.

  15. Perturbative Double Field Theory on General Backgrounds

    CERN Document Server

    Hohm, Olaf

    2015-01-01

    We develop the perturbation theory of double field theory around arbitrary solutions of its field equations. The exact gauge transformations are written in a manifestly background covariant way and contain at most quadratic terms in the field fluctuations. We expand the generalized curvature scalar to cubic order in fluctuations and thereby determine the cubic action in a manifestly background covariant form. As a first application we specialize this theory to group manifold backgrounds, such as $SU(2) \\simeq S^3$ with $H$-flux. In the full string theory this corresponds to a WZW background CFT. Starting from closed string field theory, the cubic action around such backgrounds has been computed before by Blumenhagen, Hassler and L\\"ust. We establish precise agreement with the cubic action derived from double field theory. This result confirms that double field theory is applicable to arbitrary curved background solutions, disproving assertions in the literature to the contrary.

  16. Compressive Background Modeling for Foreground Extraction

    Directory of Open Access Journals (Sweden)

    Yong Wang

    2015-01-01

    Full Text Available Robust and efficient foreground extraction is a crucial topic in many computer vision applications. In this paper, we propose an accurate and computationally efficient background subtraction method. The key idea is to reduce the data dimensionality of image frame based on compressive sensing and in the meanwhile apply sparse representation to build the current background by a set of preceding background images. According to greedy iterative optimization, the background image and background subtracted image can be recovered by using a few compressive measurements. The proposed method is validated through multiple challenging video sequences. Experimental results demonstrate the fact that the performance of our approach is comparable to those of existing classical background subtraction techniques.

  17. On Cultural Background Knowledge in English Reading

    Institute of Scientific and Technical Information of China (English)

    苏琴; 郭成

    2009-01-01

    Reading comprehension is undoubtedly one of the most important abilities for English learners. This paper firstly makes a brief introduction to the reading theory and cultural background knowledge. Then using schema theory and typical examples, the paper demons~ates the role of cultural background knowledge in reading comprehension. The application of cultural background knowledge inreading practice is proposed as the keys to the improvement of reading comprehension ability.

  18. Frequentist Hypothesis Testing with Background Uncertainty

    OpenAIRE

    Cranmer, Kyle S.

    2003-01-01

    We consider the standard Neyman-Pearson hypothesis test of a signal-plus-background hypothesis and background-only hypothesis in the presence of uncertainty on the background-only prediction. Surprisingly, this problem has not been addressed in the recent conferences on statistical techniques in high-energy physics -- although the its confidence-interval equivalent has been. We discuss the issues of power, similar tests, coverage, and ordering rules. The method presented is compared to the Co...

  19. Gauge theories with non-trivial backgrounds

    CERN Document Server

    Binosi, Daniele

    2014-01-01

    We review our most recent results in formulating gauge theories in the presence of a background field on the basis of symmetry arguments only. In particular we show how one can gain full control over the dependence on the background field of the effective action, and how the so-called background field method emerges naturally from the requirement of invariance under the BRST and antiBRST symmetries.

  20. Thermal inflation and the gravitational wave background

    International Nuclear Information System (INIS)

    We consider the impact of thermal inflation—a short, secondary period of inflation that can arise in supersymmetric scenarios—on the stochastic gravitational wave background. We show that while the primordial inflationary gravitational wave background is essentially unchanged at cosmic microwave background scales, it is massively diluted at solar system scales and would be unobservable by a Big Bang Observer (BBO) style experiment. Conversely, bubble collisions at the end of thermal inflation can generate a new stochastic background. We calculate the likely properties of the bubbles created during this phase transition, and show that the expected amplitude and frequency of this signal would fall within the BBO range

  1. Significance of Lewis Phenotyping Using Saliva and Gastric Tissue: Comparison with the Lewis Phenotype Inferred from Lewis and Secretor Genotypes

    Directory of Open Access Journals (Sweden)

    Yun Ji Hong

    2014-01-01

    , and le59 alleles was 74.6%, 21.3%, 3.1%, and 1.0%, respectively, among 418 alleles. The saliva Lewis phenotype was completely consistent with the Lewis phenotype inferred from Lewis and Secretor genotypes, but that of gastric mucosa could not be predicted from genotypes. Lewis phenotyping using erythrocytes is only adequate for transfusion needs. Saliva testing for the Lewis phenotype is a more reliable method for determining the peripheral Lewis phenotype of an individual and the gastric Lewis phenotype must be used for the study on the association between Helicobacter pylori and the Lewis phenotype.

  2. Are cuckoos maximizing egg mimicry by selecting host individuals with better matching egg phenotypes?

    Directory of Open Access Journals (Sweden)

    Anton Antonov

    Full Text Available BACKGROUND: Avian brood parasites and their hosts are involved in complex offence-defense coevolutionary arms races. The most common pair of reciprocal adaptations in these systems is egg discrimination by hosts and egg mimicry by parasites. As mimicry improves, more advanced host adaptations evolve such as decreased intra- and increased interclutch variation in egg appearance to facilitate detection of parasitic eggs. As interclutch variation increases, parasites able to choose hosts matching best their own egg phenotype should be selected, but this requires that parasites know their own egg phenotype and select host nests correspondingly. METHODOLOGY/PRINCIPAL FINDINGS: We compared egg mimicry of common cuckoo Cuculus canorus eggs in naturally parasitized marsh warbler Acrocephalus palustris nests and their nearest unparasitized conspecific neighbors having similar laying dates and nest-site characteristics. Modeling of avian vision and image analyses revealed no evidence that cuckoos parasitize nests where their eggs better match the host eggs. Cuckoo eggs were as good mimics, in terms of background and spot color, background luminance, spotting pattern and egg size, of host eggs in the nests actually exploited as those in the neighboring unparasitized nests. CONCLUSIONS/SIGNIFICANCE: We reviewed the evidence for brood parasites selecting better-matching host egg phenotypes from several relevant studies and argue that such selection probably cannot exist in host-parasite systems where host interclutch variation is continuous and overall low or moderate. To date there is also no evidence that parasites prefer certain egg phenotypes in systems where it should be most advantageous, i.e., when both hosts and parasites lay polymorphic eggs. Hence, the existence of an ability to select host nests to maximize mimicry by brood parasites appears unlikely, but this possibility should be further explored in cuckoo-host systems where the host has evolved

  3. Modeling Lost-Particle Accelerator Backgrounds in PEP-II Using LPTURTLE

    CERN Document Server

    Fieguth, Theodore; Kozanecki, Witold

    2005-01-01

    Background studies during the design, construction, commissioning, operation and improvement of BaBar and PEP-II have been greatly influenced by results from a program referred to as LPTURTLE (Lost Particle TURTLE a modified version of Decay TURTLE) which was originally conceived for the purpose of studying gas background for SLC. This venerable program is still in use today. We describe its use, capabilities and improvements and refer to current results now being applied to BaBar.

  4. Lubiprostone ameliorates the cystic fibrosis mouse intestinal phenotype

    Directory of Open Access Journals (Sweden)

    De Lisle Robert C

    2010-09-01

    Full Text Available Abstract Background Cystic fibrosis (CF is caused by mutations in the CFTR gene that impair the function of CFTR, a cAMP-regulated anion channel. In the small intestine loss of CFTR function creates a dehydrated, acidic luminal environment which is believed to cause an accumulation of mucus, a phenotype characteristic of CF. CF mice have small intestinal bacterial overgrowth, an altered innate immune response, and impaired intestinal transit. We investigated whether lubiprostone, which can activate the CLC2 Cl- channel, would improve the intestinal phenotype in CF mice. Methods Cftrtm1UNC (CF and wildtype (WT littermate mice on the C57BL/6J background were used. Lubiprostone (10 μg/kg-day was administered by gavage for two weeks. Mucus accumulation was estimated from crypt lumen widths in periodic acid-Schiff base, Alcian blue stained sections. Luminal bacterial load was measured by qPCR for the bacterial 16S gene. Gastric emptying and small intestinal transit in fasted mice were assessed using gavaged rhodamine dextran. Gene expression was evaluated by Affymetrix Mouse430 2.0 microarray and qRT-PCR. Results Crypt width in control CF mice was 700% that of WT mice (P P = 0.001. Lubiprostone increased bacterial load in WT mice to 490% of WT control levels (P = 0.008. Conversely, lubiprostone decreased bacterial overgrowth in CF mice by 60% (P = 0.005. Lubiprostone increased gastric emptying at 20 min postgavage in both WT (P P P = 0.024 but not in CF mice (P = 0.377. Among other innate immune markers, expression of mast cell genes was elevated 4-to 40-fold in the CF intestine as compared to WT, and lubiprostone treatment of CF mice decreased expression to WT control levels. Conclusions These results indicate that lubiprostone has some benefits for the CF intestinal phenotype, especially on bacterial overgrowth and the innate immune response. The unexpected observation of increased mucus accumulation in the crypts of lubiprostone-treated CF mice

  5. A new method to infer causal phenotype networks using QTL and phenotypic information.

    Directory of Open Access Journals (Sweden)

    Huange Wang

    Full Text Available In the context of genetics and breeding research on multiple phenotypic traits, reconstructing the directional or causal structure between phenotypic traits is a prerequisite for quantifying the effects of genetic interventions on the traits. Current approaches mainly exploit the genetic effects at quantitative trait loci (QTLs to learn about causal relationships among phenotypic traits. A requirement for using these approaches is that at least one unique QTL has been identified for each trait studied. However, in practice, especially for molecular phenotypes such as metabolites, this prerequisite is often not met due to limited sample sizes, high noise levels and small QTL effects. Here, we present a novel heuristic search algorithm called the QTL+phenotype supervised orientation (QPSO algorithm to infer causal directions for edges in undirected phenotype networks. The two main advantages of this algorithm are: first, it does not require QTLs for each and every trait; second, it takes into account associated phenotypic interactions in addition to detected QTLs when orienting undirected edges between traits. We evaluate and compare the performance of QPSO with another state-of-the-art approach, the QTL-directed dependency graph (QDG algorithm. Simulation results show that our method has broader applicability and leads to more accurate overall orientations. We also illustrate our method with a real-life example involving 24 metabolites and a few major QTLs measured on an association panel of 93 tomato cultivars. Matlab source code implementing the proposed algorithm is freely available upon request.

  6. X-ray Rietveld analysis with a physically based background

    International Nuclear Information System (INIS)

    On the basis of known equations for calculating X-ray diffraction intensities from a given number of unit cells of a crystal phase in polycrystalline material, as due to: (i) Bragg reflections; (ii) average diffuse scattering caused by thermal plus first-kind disorder; and (iii) incoherent scattering, a relationship has been found that ties, in the Rietveld analysis, the Bragg scale factor to a scale factor for 'disorder' as well as incoherent scattering. Instead of fitting the background with a polynomial function, it becomes possible to describe the background by physically based equations. Air scattering is included in the background simulation. By this means, the refinement can be carried out with fewer parameters (six fewer than when a fifth-order polynomial is used). The DBWS-9006PC computer program written by Sakthivel and Young [(1990), Georgia Institute of Technology, Atlanta, GA, USA] has been modified to follow this approach and it has been used to refine the crystal structures of the cubic form of Y2O3 and of α-Al2O3. Peak asymmetry has been described by a function based on an exponential approximation. The results from refinements using polynomial physically based background function are, in terms of final structural parameters and reliability indices, very close to each other and in agreement with results reported in the literature. The reconstruction and optimization of the background scattering by means of physically based equations helps the implementation in the Rietveld code of other possible specific diffuse scattering contributions, such as that due to an amorphous phase. (orig.)

  7. Hanford Site background: Part 1, Soil background for nonradioactive analytes. Revision 1, Volume 2

    Energy Technology Data Exchange (ETDEWEB)

    1993-04-01

    Volume two contains the following appendices: Description of soil sampling sites; sampling narrative; raw data soil background; background data analysis; sitewide background soil sampling plan; and use of soil background data for the detection of contamination at waste management unit on the Hanford Site.

  8. Mapping Phenotypic Information in Heterogeneous Textual Sources to a Domain-Specific Terminological Resource.

    Science.gov (United States)

    Alnazzawi, Noha; Thompson, Paul; Ananiadou, Sophia

    2016-01-01

    Biomedical literature articles and narrative content from Electronic Health Records (EHRs) both constitute rich sources of disease-phenotype information. Phenotype concepts may be mentioned in text in multiple ways, using phrases with a variety of structures. This variability stems partly from the different backgrounds of the authors, but also from the different writing styles typically used in each text type. Since EHR narrative reports and literature articles contain different but complementary types of valuable information, combining details from each text type can help to uncover new disease-phenotype associations. However, the alternative ways in which the same concept may be mentioned in each source constitutes a barrier to the automatic integration of information. Accordingly, identification of the unique concepts represented by phrases in text can help to bridge the gap between text types. We describe our development of a novel method, PhenoNorm, which integrates a number of different similarity measures to allow automatic linking of phenotype concept mentions to known concepts in the UMLS Metathesaurus, a biomedical terminological resource. PhenoNorm was developed using the PhenoCHF corpus-a collection of literature articles and narratives in EHRs, annotated for phenotypic information relating to congestive heart failure (CHF). We evaluate the performance of PhenoNorm in linking CHF-related phenotype mentions to Metathesaurus concepts, using a newly enriched version of PhenoCHF, in which each phenotype mention has an expert-verified link to a concept in the UMLS Metathesaurus. We show that PhenoNorm outperforms a number of alternative methods applied to the same task. Furthermore, we demonstrate PhenoNorm's wider utility, by evaluating its ability to link mentions of various other types of medically-related information, occurring in texts covering wider subject areas, to concepts in different terminological resources. We show that PhenoNorm can maintain

  9. Mapping Phenotypic Information in Heterogeneous Textual Sources to a Domain-Specific Terminological Resource.

    Science.gov (United States)

    Alnazzawi, Noha; Thompson, Paul; Ananiadou, Sophia

    2016-01-01

    Biomedical literature articles and narrative content from Electronic Health Records (EHRs) both constitute rich sources of disease-phenotype information. Phenotype concepts may be mentioned in text in multiple ways, using phrases with a variety of structures. This variability stems partly from the different backgrounds of the authors, but also from the different writing styles typically used in each text type. Since EHR narrative reports and literature articles contain different but complementary types of valuable information, combining details from each text type can help to uncover new disease-phenotype associations. However, the alternative ways in which the same concept may be mentioned in each source constitutes a barrier to the automatic integration of information. Accordingly, identification of the unique concepts represented by phrases in text can help to bridge the gap between text types. We describe our development of a novel method, PhenoNorm, which integrates a number of different similarity measures to allow automatic linking of phenotype concept mentions to known concepts in the UMLS Metathesaurus, a biomedical terminological resource. PhenoNorm was developed using the PhenoCHF corpus-a collection of literature articles and narratives in EHRs, annotated for phenotypic information relating to congestive heart failure (CHF). We evaluate the performance of PhenoNorm in linking CHF-related phenotype mentions to Metathesaurus concepts, using a newly enriched version of PhenoCHF, in which each phenotype mention has an expert-verified link to a concept in the UMLS Metathesaurus. We show that PhenoNorm outperforms a number of alternative methods applied to the same task. Furthermore, we demonstrate PhenoNorm's wider utility, by evaluating its ability to link mentions of various other types of medically-related information, occurring in texts covering wider subject areas, to concepts in different terminological resources. We show that PhenoNorm can maintain

  10. Phenotyping for Abiotic Stress Tolerance in Maize

    Institute of Scientific and Technical Information of China (English)

    Benhilda Masuka; Jose Luis Araus; Biswanath Das; Kai Sonder; Jill E. Cairns

    2012-01-01

    The ability to quickly develop germplasm having tolerance to several complex polygenic inherited abiotic and biotic stresses combined is critical to the resilience of cropping systems in the face of climate change.Molecular breeding offers the tools to accelerate cereal breeding; however,suitable phenotyping protocols are essential to ensure that the much-anticipated benefits of molecular breeding can be realized.To facilitate the full potential of molecular tools,greater emphasis needs to be given to reducing the within-experimental site variability,application of stress and characterization of the environment and appropriate phenotyping tools.Yield is a function of many processes throughout the plant cycle,and thus integrative traits that encompass crop performance over time or organization level (i.e.canopy level) will provide a better alternative to instantaneous measurements which provide only a snapshot of a given plant process.Many new phenotyping tools based on remote sensing are now available including non-destructive measurements of growth-related parameters based on spectral reflectance and infrared thermometry to estimate plant water status.Here we describe key field phenotyping protocols for maize with emphasis on tolerance to drought and low nitrogen.

  11. Phenotype Presentation of Hypophosphatemic Rickets in Adults

    DEFF Research Database (Denmark)

    Beck-Nielsen, Signe S; Brusgaard, Klaus; Rasmussen, Lars M;

    2010-01-01

    Hypophosphatemic rickets (HR) is a group of rare disorders caused by excessive renal phosphate wasting. The purpose of this cross-sectional study of 38 HR patients was to characterize the phenotype of adult HR patients. Moreover, skeletal and endodontic severity scores were defined to assess...

  12. Behavioural Phenotypes in Disability Research: Historical Perspectives

    Science.gov (United States)

    Goodey, C. F.

    2006-01-01

    Western medicine has a long history of accounting for behaviour by reducing the body to ultimate explanatory entities. In pre-modern medicine these were invisible "animal spirits" circulating the body. In modern medicine, they are "genes". Both raise questions. The psychological phenotype is defined by human consensus, varying according to time…

  13. Radiofrequency treatment alters cancer cell phenotype

    Science.gov (United States)

    Ware, Matthew J.; Tinger, Sophia; Colbert, Kevin L.; Corr, Stuart J.; Rees, Paul; Koshkina, Nadezhda; Curley, Steven; Summers, H. D.; Godin, Biana

    2015-07-01

    The importance of evaluating physical cues in cancer research is gradually being realized. Assessment of cancer cell physical appearance, or phenotype, may provide information on changes in cellular behavior, including migratory or communicative changes. These characteristics are intrinsically different between malignant and non-malignant cells and change in response to therapy or in the progression of the disease. Here, we report that pancreatic cancer cell phenotype was altered in response to a physical method for cancer therapy, a non-invasive radiofrequency (RF) treatment, which is currently being developed for human trials. We provide a battery of tests to explore these phenotype characteristics. Our data show that cell topography, morphology, motility, adhesion and division change as a result of the treatment. These may have consequences for tissue architecture, for diffusion of anti-cancer therapeutics and cancer cell susceptibility within the tumor. Clear phenotypical differences were observed between cancerous and normal cells in both their untreated states and in their response to RF therapy. We also report, for the first time, a transfer of microsized particles through tunneling nanotubes, which were produced by cancer cells in response to RF therapy. Additionally, we provide evidence that various sub-populations of cancer cells heterogeneously respond to RF treatment.

  14. Phenotype as Agent for Epigenetic Inheritance

    Directory of Open Access Journals (Sweden)

    John S. Torday

    2016-07-01

    Full Text Available The conventional understanding of phenotype is as a derivative of descent with modification through Darwinian random mutation and natural selection. Recent research has revealed Lamarckian inheritance as a major transgenerational mechanism for environmental action on genomes whose extent is determined, in significant part, by germ line cells during meiosis and subsequent stages of embryological development. In consequence, the role of phenotype can productively be reconsidered. The possibility that phenotype is directed towards the effective acquisition of epigenetic marks in consistent reciprocation with the environment during the life cycle of an organism is explored. It is proposed that phenotype is an active agent in niche construction for the active acquisition of epigenetic marks as a dominant evolutionary mechanism rather than a consequence of Darwinian selection towards reproductive success. The reproductive phase of the life cycle can then be appraised as a robust framework in which epigenetic inheritance is entrained to affect growth and development in continued reciprocal responsiveness to environmental stresses. Furthermore, as first principles of physiology determine the limits of epigenetic inheritance, a coherent justification can thereby be provided for the obligate return of all multicellular eukaryotes to the unicellular state.

  15. Phenotypic impact of genomic structural variation

    DEFF Research Database (Denmark)

    Weischenfeldt, Joachim; Symmons, Orsolya; Spitz, François;

    2013-01-01

    Genomic structural variants have long been implicated in phenotypic diversity and human disease, but dissecting the mechanisms by which they exert their functional impact has proven elusive. Recently however, developments in high-throughput DNA sequencing and chromosomal engineering technology have...

  16. Biodiversity of spoilage lactobacilli: phenotypic characterisation

    NARCIS (Netherlands)

    Sanders, J.W.; Oomes, S.J.; Membre, J.M.; Wegkamp, A.; Wels, M.W.

    2015-01-01

    Preventing food spoilage is a challenge for the food industry, especially when applying mild preservation methods and when avoiding the use of preservatives. Therefore, it is essential to explore the boundaries of preservation by better understanding the causative microbes, their phenotypic behaviou

  17. Genetical metabolomics: closing in on phenotypes

    NARCIS (Netherlands)

    Keurentjes, J.J.B.

    2009-01-01

    One of the long-standing goals in plant biology has been to link genotypic variation to natural variation in plant development and adaptive traits. From recent studies it has become clear that a complex interacting network is underlying phenotypic diversity. A major role in this regulatory mechanism

  18. Colorectal Cancer "Methylator Phenotype": Fact or Artifact?

    Directory of Open Access Journals (Sweden)

    Charles Anacleto

    2005-04-01

    Full Text Available It has been proposed that human colorectal tumors can be classified into two groups: one in which methylation is rare, and another with methylation of several loci associated with a "CpG island methylated phenotype (CIMP," characterized by preferential proximal location in the colon, but otherwise poorly defined. There is considerable overlap between this putative methylator phenotype and the well-known mutator phenotype associated with microsatellite instability (MSI. We have examined hypermethylation of the promoter region of five genes (DAPK, MGMT, hMLH1, p16INK4a, and p14ARF in 106 primary colorectal cancers. A graph depicting the frequency of methylated loci in the series of tumors showed a continuous, monotonically decreasing distribution quite different from the previously claimed discontinuity. We observed a significant association between the presence of three or more methylated loci and the proximal location of the tumors. However, if we remove from analysis the tumors with hMLH1 methylation or those with MSI, the significance vanishes, suggesting that the association between multiple methylations and proximal location was indirect due to the correlation with MSI. Thus, our data do not support the independent existence of the so-called methylator phenotype and suggest that it rather may represent a statistical artifact caused by confounding of associations.

  19. Delineating the GRIN1 phenotypic spectrum

    DEFF Research Database (Denmark)

    Lemke, Johannes R; Geider, Kirsten; Helbig, Katherine L;

    2016-01-01

    impairment as well as oculomotor and movement disorders being discriminating phenotypic features. Loss of NMDA receptor function appears to be the underlying disease mechanism. The identification of both heterozygous and homozygous mutations blurs the borders of dominant and recessive inheritance of GRIN1...

  20. Phenotype Information Retrieval for Existing GWAS Studies.

    Science.gov (United States)

    Alipanah, Neda; Lin, Ko-Wei; Venkatesh, Vinay; Farzaneh, Seena; Kim, Hyeon-Eui

    2013-01-01

    The database of Genotypes and Phenotypes (dbGaP) is archiving the results of different Genome Wide Association Studies (GWAS). dbGaP has a multitude of phenotype variables, but they are not harmonized across studies. We proposed a method to standardize phenotype variables by classifying similar variables based on semantic distances. We first extracted variables description, enriched them using domain knowledge, and computed the distances among them. We used clustering techniques to classify the most similar variables. We used domain experts to audit clusters, annotated the clusters with appropriate labels, and used re-clustering to build a semantically-driven Genotypes and Phenotypes (sdGaP) ontology using the UMLS semantic network and metathesaurus. The sdGaP ontology allowed us to expand user queries and retrieve information using a semantic metric called density measure (DM). We illustrated the potential improvement of information retrieval using the sdGaP ontology in one search scenario using the variables from the Cleveland Family Study.

  1. Cognitive Phenotype of Velocardiofacial Syndrome: A Review

    Science.gov (United States)

    Furniss, Frederick; Biswas, Asit B.; Gumber, Rohit; Singh, Niraj

    2011-01-01

    The behavioural phenotype of velocardiofacial syndrome (VCFS), one of the most common human multiple anomaly syndromes, includes developmental disabilities, frequently including intellectual disability (ID) and high risk of diagnosis of psychotic disorders including schizophrenia. VCFS may offer a model of the relationship between ID and risk of…

  2. Phenotype as Agent for Epigenetic Inheritance.

    Science.gov (United States)

    Torday, John S; Miller, William B

    2016-01-01

    The conventional understanding of phenotype is as a derivative of descent with modification through Darwinian random mutation and natural selection. Recent research has revealed Lamarckian inheritance as a major transgenerational mechanism for environmental action on genomes whose extent is determined, in significant part, by germ line cells during meiosis and subsequent stages of embryological development. In consequence, the role of phenotype can productively be reconsidered. The possibility that phenotype is directed towards the effective acquisition of epigenetic marks in consistent reciprocation with the environment during the life cycle of an organism is explored. It is proposed that phenotype is an active agent in niche construction for the active acquisition of epigenetic marks as a dominant evolutionary mechanism rather than a consequence of Darwinian selection towards reproductive success. The reproductive phase of the life cycle can then be appraised as a robust framework in which epigenetic inheritance is entrained to affect growth and development in continued reciprocal responsiveness to environmental stresses. Furthermore, as first principles of physiology determine the limits of epigenetic inheritance, a coherent justification can thereby be provided for the obligate return of all multicellular eukaryotes to the unicellular state. PMID:27399791

  3. Venom Evolution: Gene Loss Shapes Phenotypic Adaptation.

    Science.gov (United States)

    Casewell, Nicholas R

    2016-09-26

    Snake venoms are variable protein mixtures with a multitude of bioactivities. New work shows, surprisingly, that it is the loss of toxin-encoding genes that strongly influences venom function in rattlesnakes, highlighting how gene loss can underpin adaptive phenotypic change. PMID:27676304

  4. Parasitism and phenotypic change in colonial hosts.

    Science.gov (United States)

    Hartikainen, Hanna; Fontes, Inês; Okamura, Beth

    2013-09-01

    Changes in host phenotype are often attributed to manipulation that enables parasites to complete trophic transmission cycles. We characterized changes in host phenotype in a colonial host–endoparasite system that lacks trophic transmission (the freshwater bryozoan Fredericella sultana and myxozoan parasite Tetracapsuloides bryosalmonae). We show that parasitism exerts opposing phenotypic effects at the colony and module levels. Thus, overt infection (the development of infectious spores in the host body cavity) was linked to a reduction in colony size and growth rate, while colony modules exhibited a form of gigantism. Larger modules may support larger parasite sacs and increase metabolite availability to the parasite. Host metabolic rates were lower in overtly infected relative to uninfected hosts that were not investing in propagule production. This suggests a role for direct resource competition and active parasite manipulation (castration) in driving the expression of the infected phenotype. The malformed offspring (statoblasts) of infected colonies had greatly reduced hatching success. Coupled with the severe reduction in statoblast production this suggests that vertical transmission is rare in overtly infected modules. We show that although the parasite can occasionally infect statoblasts during overt infections, no infections were detected in the surviving mature offspring, suggesting that during overt infections, horizontal transmission incurs a trade-off with vertical transmission. PMID:23965820

  5. Phenotype as Agent for Epigenetic Inheritance

    Science.gov (United States)

    Torday, John S.; Miller, William B.

    2016-01-01

    The conventional understanding of phenotype is as a derivative of descent with modification through Darwinian random mutation and natural selection. Recent research has revealed Lamarckian inheritance as a major transgenerational mechanism for environmental action on genomes whose extent is determined, in significant part, by germ line cells during meiosis and subsequent stages of embryological development. In consequence, the role of phenotype can productively be reconsidered. The possibility that phenotype is directed towards the effective acquisition of epigenetic marks in consistent reciprocation with the environment during the life cycle of an organism is explored. It is proposed that phenotype is an active agent in niche construction for the active acquisition of epigenetic marks as a dominant evolutionary mechanism rather than a consequence of Darwinian selection towards reproductive success. The reproductive phase of the life cycle can then be appraised as a robust framework in which epigenetic inheritance is entrained to affect growth and development in continued reciprocal responsiveness to environmental stresses. Furthermore, as first principles of physiology determine the limits of epigenetic inheritance, a coherent justification can thereby be provided for the obligate return of all multicellular eukaryotes to the unicellular state. PMID:27399791

  6. An expanded model of HIV cell entry phenotype based on multi-parameter single-cell data

    Directory of Open Access Journals (Sweden)

    Bozek Katarzyna

    2012-07-01

    Full Text Available Abstract Background Entry of human immunodeficiency virus type 1 (HIV-1 into the host cell involves interactions between the viral envelope glycoproteins (Env and the cellular receptor CD4 as well as a coreceptor molecule (most importantly CCR5 or CXCR4. Viral preference for a specific coreceptor (tropism is in particular determined by the third variable loop (V3 of the Env glycoprotein gp120. The approval and use of a coreceptor antagonist for antiretroviral therapy make detailed understanding of tropism and its accurate prediction from patient derived virus isolates essential. The aim of the present study is the development of an extended description of the HIV entry phenotype reflecting its co-dependence on several key determinants as the basis for a more accurate prediction of HIV-1 entry phenotype from genotypic data. Results Here, we established a new protocol of quantitation and computational analysis of the dependence of HIV entry efficiency on receptor and coreceptor cell surface levels as well as viral V3 loop sequence and the presence of two prototypic coreceptor antagonists in varying concentrations. Based on data collected at the single-cell level, we constructed regression models of the HIV-1 entry phenotype integrating the measured determinants. We developed a multivariate phenotype descriptor, termed phenotype vector, which facilitates a more detailed characterization of HIV entry phenotypes than currently used binary tropism classifications. For some of the tested virus variants, the multivariant phenotype vector revealed substantial divergences from existing tropism predictions. We also developed methods for computational prediction of the entry phenotypes based on the V3 sequence and performed an extrapolating calculation of the effectiveness of this computational procedure. Conclusions Our study of the HIV cell entry phenotype and the novel multivariate representation developed here contributes to a more detailed

  7. The expanding phenotypic spectra of kidney diseases: insights from genetic studies.

    Science.gov (United States)

    Stokman, Marijn F; Renkema, Kirsten Y; Giles, Rachel H; Schaefer, Franz; Knoers, Nine V A M; van Eerde, Albertien M

    2016-08-01

    Next-generation sequencing (NGS) has led to the identification of previously unrecognized phenotypes associated with classic kidney disease genes. In addition to improving diagnostics for genetically heterogeneous diseases and enabling a faster rate of gene discovery, NGS has enabled an expansion and redefinition of nephrogenetic disease categories. Findings from these studies raise the question of whether disease diagnoses should be made on clinical grounds, on genetic evidence or a combination thereof. Here, we discuss the major kidney disease-associated genes and gene categories for which NGS has expanded the phenotypic spectrum. For example, COL4A3-5 genes, which are classically associated with Alport syndrome, are now understood to also be involved in the aetiology of focal segmental glomerulosclerosis. DGKE, which is associated with nephrotic syndrome, is also mutated in patients with atypical haemolytic uraemic syndrome. We examine how a shared genetic background between diverse clinical phenotypes can provide insight into the function of genes and novel links with essential pathophysiological mechanisms. In addition, we consider genetic and epigenetic factors that contribute to the observed phenotypic heterogeneity of kidney diseases and discuss the challenges in the interpretation of genetic data. Finally, we discuss the implications of the expanding phenotypic spectra associated with kidney disease genes for clinical practice, genetic counselling and personalized care, and present our recommendations for the use of NGS-based tests in routine nephrology practice. PMID:27374918

  8. Multivariate models of mixed assortment: phenotypic assortment and social homogamy for education and fluid ability.

    Science.gov (United States)

    Reynolds, C A; Baker, L A; Pedersen, N L

    2000-11-01

    Phenotypic assortment is assumed to be the principal mechanism of spouse similarity in most biometrical studies. Other assortment mechanisms, such as social homogamy, may be plausible. Two models are presented that consider phenotypic assortment and social homogamy simultaneously (i.e., mixed assortment), where selective associations between social background factors (Model I) versus selective associations between total environments (Model II) distinguish the models. A series of illustrative analyses was undertaken for education and fluid ability available on a sample of 116 Swedish twin pairs and their spouses. On the basis of several fit criteria Model I was preferred over Model II. Both social homogamy and phenotypic assortment may contribute to spouse similarity for educational attainment and fluid ability. Furthermore, spouse similarity for fluid ability may arise indirectly from social homogamy and phenotypic assortment for educational attainment. Power analyses indicated greater observed power for Model I than Model II. Additional power analyses indicated that considerably more twin-spouse sets would be needed for Model II than Model I, to resolve social homogamy and phenotypic assortment. Effects of misspecification of mechanisms of spouse similarity are also briefly discussed.

  9. Supermembrane actions for Gaiotto-Maldacena backgrounds

    OpenAIRE

    Stefanski, B.

    2013-01-01

    We write down the supermembrane actions for M-theory backgrounds dual to general N=2 four-dimensional superconformal field theories. The actions are given to all orders in fermions and are in a particular κ -gauge. When an extra U(1) isometry is present, our actions reduce to κ -gauge fixed Green–Schwarz actions for the corresponding Type IIA backgrounds.

  10. 45 CFR 650.16 - Background rights.

    Science.gov (United States)

    2010-10-01

    ... of the Bayh-Dole Act (35 U.S.C. 202(f)) as implemented by 37 CFR 401.12). ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Background rights. 650.16 Section 650.16 Public... Background rights. The Foundation will acquire rights to a research performer's pre-existing technology...

  11. Genetically modified bacteriophages.

    Science.gov (United States)

    Sagona, Antonia P; Grigonyte, Aurelija M; MacDonald, Paul R; Jaramillo, Alfonso

    2016-04-18

    Phages or bacteriophages, viruses that infect and replicate inside bacteria, are the most abundant microorganisms on earth. The realization that antibiotic resistance poses a substantial risk to the world's health and global economy is revitalizing phage therapy as a potential solution. The increasing ease by which phage genomes can be modified, owing to the influx of new technologies, has led to an expansion of their natural capabilities, and a reduced dependence on phage isolation from environmental sources. This review will discuss the way synthetic biology has accelerated the construction of genetically modified phages and will describe the wide range of their applications. It will further provide insight into the societal and economic benefits that derive from the use of recombinant phages in various sectors, from health to biodetection, biocontrol and the food industry.

  12. Genetically modified bacteriophages.

    Science.gov (United States)

    Sagona, Antonia P; Grigonyte, Aurelija M; MacDonald, Paul R; Jaramillo, Alfonso

    2016-04-18

    Phages or bacteriophages, viruses that infect and replicate inside bacteria, are the most abundant microorganisms on earth. The realization that antibiotic resistance poses a substantial risk to the world's health and global economy is revitalizing phage therapy as a potential solution. The increasing ease by which phage genomes can be modified, owing to the influx of new technologies, has led to an expansion of their natural capabilities, and a reduced dependence on phage isolation from environmental sources. This review will discuss the way synthetic biology has accelerated the construction of genetically modified phages and will describe the wide range of their applications. It will further provide insight into the societal and economic benefits that derive from the use of recombinant phages in various sectors, from health to biodetection, biocontrol and the food industry. PMID:26906932

  13. Gravitational wave background from binary systems

    CERN Document Server

    Rosado, Pablo A

    2011-01-01

    Basic aspects of the background of gravitational waves and its mathematical characterization are reviewed. The spectral energy density parameter $\\Omega(f)$, commonly used as a quantifier of the background, is derived for an ensemble of many identical sources emitting at different times and locations. For such an ensemble, $\\Omega(f)$ is generalized to account for the duration of the signals and of the observation, so that one can distinguish the resolvable and unresolvable parts of the background. The unresolvable part, often called confusion noise or stochastic background, is made by signals that cannot be either individually identified or subtracted out of the data. To account for the resolvability of the background, the overlap function is introduced. This function is a generalization of the duty cycle, which has been commonly used in the literature, in some cases leading to incorrect results. The spectra produced by binary systems (stellar binaries and massive black hole binaries) are presented over the ...

  14. RNA-modifying enzymes.

    Science.gov (United States)

    Ferré-D'Amaré, Adrian R

    2003-02-01

    A bewildering number of post-transcriptional modifications are introduced into cellular RNAs by enzymes that are often conserved among archaea, bacteria and eukaryotes. The modifications range from those with well-understood functions, such as tRNA aminoacylation, to widespread but more mysterious ones, such as pseudouridylation. Recent structure determinations have included two types of RNA nucleobase modifying enzyme: pseudouridine synthases and tRNA guanine transglycosylases.

  15. Metabolomics to unveil and understand phenotypic diversity between pathogen populations.

    Directory of Open Access Journals (Sweden)

    Ruben t'Kindt

    Full Text Available Leishmaniasis is a debilitating disease caused by the parasite Leishmania. There is extensive clinical polymorphism, including variable responsiveness to treatment. We study Leishmania donovani parasites isolated from visceral leishmaniasis patients in Nepal that responded differently to antimonial treatment due to differing intrinsic drug sensitivity of the parasites. Here, we present a proof-of-principle study in which we applied a metabolomics pipeline specifically developed for L. donovani to characterize the global metabolic differences between antimonial-sensitive and antimonial-resistant L. donovani isolates. Clones of drug-sensitive and drug-resistant parasite isolates from clinical samples were cultured in vitro and harvested for metabolomics analysis. The relative abundance of 340 metabolites was determined by ZIC-HILIC chromatography coupled to LTQ-Orbitrap mass spectrometry. Our measurements cover approximately 20% of the predicted core metabolome of Leishmania and additionally detected a large number of lipids. Drug-sensitive and drug-resistant parasites showed distinct metabolic profiles, and unsupervised clustering and principal component analysis clearly distinguished the two phenotypes. For 100 metabolites, the detected intensity differed more than three-fold between the 2 phenotypes. Many of these were in specific areas of lipid metabolism, suggesting that the membrane composition of the drug-resistant parasites is extensively modified. Untargeted metabolomics has been applied on clinical Leishmania isolates to uncover major metabolic differences between drug-sensitive and drug-resistant isolates. The identified major differences provide novel insights into the mechanisms involved in resistance to antimonial drugs, and facilitate investigations using targeted approaches to unravel the key changes mediating drug resistance.

  16. Alcohol consumption, Lewis phenotypes, and risk of ischemic heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Hein, H.O.; Suadicani, P.; Gyntelberg, F. (Rigshospitalet State Univ. Hospital, Copenhagen (Denmark). Epidemiological Research Unit); Sorenson, H. (Rigshospitalet State Univ. Hospital, Copenhagen (Denmark). Dept. of Chemical Immunology); Hein, H.O. (Univ. of Copenhagen (Denmark). Dept. of Internal Medicine)

    1993-02-13

    The authors have previously found an increased risk of ischemic heart disease (IHD) in men with the Lewis phenotype Le(a[minus]b[minus]) and suggested that the Lewis blood group has a close genetic relation with insulin resistance. The authors have investigated whether any conventional risk factors explain the increased risk in Le(a[minus]b[minus]) men. 3,383 men aged 53-75 years were examined in 1985-86, and morbidity and mortality during the next 4 years were recorded. At baseline, the authors excluded 343 men with a history of myocardial infarction, angina pectoris, intermittent claudication, or stroke. The potential risk factors examined were alcohol consumption, physical activity, tobacco smoking, serum cotinine, serum lipids, body-mass index, blood pressure, prevalence of hypertension and non-insulin-dependent diabetes mellitus, and social class. In 280 (9.6%) men with Le(a[minus]b[minus]), alcohol was the only risk factor significantly associated with risk of IHD. There was a significant inverse dose-effect relation between alcohol consumption and risk; trend tests, with adjustment for age, were significant for fatal IHD (p=0.02), all IHD (p=0.03), and all causes of death (p=0.02). In 2649 (90.4%) men with other phenotypes, there was a limited negative association with alcohol consumption. In Le(a[minus]b[minus]) men, a group genetically at high risk of IHD, alcohol consumption seems to be especially protective. The authors suggest that alcohol consumption may modify insulin resistance in Le(a[minus]b[minus]) men.

  17. Background sounds contribute to spectrotemporal plasticity in primary auditory cortex.

    Science.gov (United States)

    Moucha, Raluca; Pandya, Pritesh K; Engineer, Navzer D; Rathbun, Daniel L; Kilgard, Michael P

    2005-05-01

    The mammalian auditory system evolved to extract meaningful information from complex acoustic environments. Spectrotemporal selectivity of auditory neurons provides a potential mechanism to represent natural sounds. Experience-dependent plasticity mechanisms can remodel the spectrotemporal selectivity of neurons in primary auditory cortex (A1). Electrical stimulation of the cholinergic nucleus basalis (NB) enables plasticity in A1 that parallels natural learning and is specific to acoustic features associated with NB activity. In this study, we used NB stimulation to explore how cortical networks reorganize after experience with frequency-modulated (FM) sweeps, and how background stimuli contribute to spectrotemporal plasticity in rat auditory cortex. Pairing an 8-4 kHz FM sweep with NB stimulation 300 times per day for 20 days decreased tone thresholds, frequency selectivity, and response latency of A1 neurons in the region of the tonotopic map activated by the sound. In an attempt to modify neuronal response properties across all of A1 the same NB activation was paired in a second group of rats with five downward FM sweeps, each spanning a different octave. No changes in FM selectivity or receptive field (RF) structure were observed when the neural activation was distributed across the cortical surface. However, the addition of unpaired background sweeps of different rates or direction was sufficient to alter RF characteristics across the tonotopic map in a third group of rats. These results extend earlier observations that cortical neurons can develop stimulus specific plasticity and indicate that background conditions can strongly influence cortical plasticity.

  18. PENGARUH BACKGROUND MAHASISWA TERHADAP KINERJA AKADEMIK

    Directory of Open Access Journals (Sweden)

    Trianasari Angkawijaya

    2014-09-01

    Full Text Available Abstract: The Effect of Students’ Background on Academic Performance. This study examines the effect of background variables on the academic performance of accounting students in a private university in Surabaya. The background variables under study included previous academic performance, prior knowledge on accounting, sex, motivation, preparedness, and expectations. The results show that previous academic performance, motivation, and expectations have positive and significant effects on the students’ overall academic performance in accounting, while preparedness affects only the students’ performance in management accounting. In contrast, prior knowledge on accounting and sex do not give significant impacts to the students’ overall academic performance.These findings indicate the importance of previous aca­demic performance as well as motivation and expectations as background variables in current academic performance. Keywords: students’ background, academic performance, accounting Abstrak: Pengaruh Background Mahasiswa terhadap Kinerja Akademik. Penelitian ini mengkaji pengaruh variabel background terhadap kinerja akademik mahasiswa akuntansi di Universitas Surabaya. Lima variabel background utama dipergunakan, yaitu kinerja akademik sebelumnya, pengetahuan akun­tansi sebelumnya, jenis kelamin, motivasi, kesiapan, dan ekspektasi. Hipotesis diuji menggunakan model regresi linier berganda OLS dan Robust Standar Error. Hasil penelitian memerlihatkan bahwa kinerja akademik sebelumnya, motivasi, dan ekspektasi memiliki pengaruh positif signifikan terhadap kinerja akademik keseluruhan, sementara kesiapan memberikan pengaruh positif hanya pada kinerja akademik akuntansi manajemen. Sebaliknya, pengetahuan akuntansi sebelumnya dan jenis kelamin tidak memberi­kan pengaruh signifikan terhadap kinerja akademik keseluruhan. Temuan ini mengindikasikan bahwa kinerja akademik sebelumnya beserta motivasi dan ekspektasi adalah variabel background

  19. Genetically Modified Organisms

    Directory of Open Access Journals (Sweden)

    Claro Llaguno

    2001-06-01

    Full Text Available Recent reports have brought to public attention concerns about Bt corn and genetically modified organisms (GMO in general. The timing, it seems, is most appropriate considering two related developments early this year: the final approval of the Cartagena Protocol on Biosafety in Montreal on January 29, 2001, and the OECD Edinburgh Conference on GM food safety last February 28- March 1, 2001. The protocol makes clear that GMOs include all living modified organisms (LMO defined as "any living organism that possesses a novel combination of genetic material obtained through the use of modern biotechnology". This includes seeds, live fish, and other organisms intentionally obtained for release to the environment. It would seem that the common understanding about GMOs as referring to farm-to-table products is perforce expanded to embrace genetically modified farm animals and aquatic resources. Being a trade agreement, the Montreal accord primarily deals with the safety issues related to the transboundary movement of LMOs around the globe. The OECD conference on the other hand, called for an international body "to address all sides of the GM debate" in response to the public outcry, particularly in Western Europe, regarding the risks the new products pose to human health and the environment. Some points of contention, which remain unresolved, include issues such as whether countries should be allowed to develop their own GM food based on their needs, and whether a global moratorium on GMOs and mandatory labeling should be enforced worldwide.

  20. Modified Supersymmetric Dark Sectors

    CERN Document Server

    Redino, Christopher

    2015-01-01

    SUSY models with a modified dark sector require constraints to be reinterpreted, which may allow for scenarios with low tuning. A modified dark sector can also change the phenomenology greatly. The addition of the QCD axion to the Minimal Supersymmetric Standard Model (MSSM) solves the strong CP problem and also modifies the dark sector with new dark matter candidates. While SUSY axion phenomenology is usually restricted to searches for the axion itself or searches for the ordinary SUSY particles, this work focuses on scenarios where the axion's superpartner, the axino may be detectable at the Large Hadron Collider (LHC) in the decays of neutralinos displaced from the primary vertex. In particular this work focuses on the KSVZ axino. The decay length of neutralinos in this scenario easily fits the ATLAS detector for SUSY spectra expected to be testable at the 14 TeV LHC. This signature of displaced decays to axinos is compared to other well motivated scenarios containing a long lived neutralino which decays i...

  1. Phenotypic plasticity changes correlations of traits following experimental introductions of Trinidadian guppies (Poecilia reticulata).

    Science.gov (United States)

    Handelsman, Corey A; Ruell, Emily W; Torres-Dowdall, Julián; Ghalambor, Cameron K

    2014-11-01

    Colonization of novel environments can alter selective pressures and act as a catalyst for rapid evolution in nature. Theory and empirical studies suggest that the ability of a population to exhibit an adaptive evolutionary response to novel selection pressures should reflect the presence of sufficient additive genetic variance and covariance for individual and correlated traits. As correlated traits should not respond to selection independently, the structure of correlations of traits can bias or constrain adaptive evolution. Models of how multiple correlated traits respond to selection often assume spatial and temporal stability of trait-correlations within populations. Yet, trait-correlations can also be plastic in response to environmental variation. Phenotypic plasticity, the ability of a single genotype to produce different phenotypes across environments, is of particular interest because it can induce population-wide changes in the combination of traits exposed to selection and change the trajectory of evolutionary divergence. We tested the ability of phenotypic plasticity to modify trait-correlations by comparing phenotypic variance and covariance in the body-shapes of four experimental populations of Trinidadian guppies (Poecilia reticulata) to their ancestral population. We found that phenotypic plasticity produced both adaptive and novel aspects of body-shape, which was repeated in all four experimental populations. Further, phenotypic plasticity changed patterns of covariance among morphological characters. These findings suggest our ability to make inferences about patterns of divergence based on correlations of traits in extant populations may be limited if novel environments not only induce plasticity in multiple traits, but also change the correlations among the traits.

  2. Mucopolysaccharidosis type VI phenotypes-genotypes and antibody response to galsulfase

    OpenAIRE

    Brands, Marion M; Hoogeveen-Westerveld, Marianne; Kroos, Marian A.; Nobel, Willemieke; Ruijter, George J.; Özkan, Lale; Plug, Iris; Grinberg, Daniel; Vilageliu, Lluïsa; Halley, Dicky J; van der Ploeg, Ans T.; Reuser, Arnold J.

    2013-01-01

    textabstractBackground: Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome; MPS VI) is an autosomal recessive lysosomal storage disorder in which deficiency of N-acetylgalactosamine 4-sulfatase (arylsulfatase B; ARSB) leads to the storage of glycosaminoglycans (GAGs) in connective tissue. The genotype-phenotype correlation has been addressed in several publications but the picture is not complete. Since 2007, enzyme-replacement therapy (ERT) has been available for patients with MPS VI in ...

  3. Novel Meta-Analysis-Derived Type 2 Diabetes Risk Loci Do Not Determine Prediabetic Phenotypes

    OpenAIRE

    Staiger, Harald; Machicao, Fausto; Kantartzis, Konstantinos; Schäfer, Silke A.; Kirchhoff, Kerstin; Guthoff, Martina; Silbernagel, Günther; Stefan, Norbert; Fritsche, Andreas; Häring, Hans-Ulrich

    2008-01-01

    Background Genome-wide association (GWA) studies identified a series of novel type 2 diabetes risk loci. Most of them were subsequently demonstrated to affect insulin secretion of pancreatic β-cells. Very recently, a meta-analysis of GWA data revealed nine additional risk loci with still undefined roles in the pathogenesis of type 2 diabetes. Using our thoroughly phenotyped cohort of subjects at an increased risk for type 2 diabetes, we assessed the association of the nine latest genetic vari...

  4. Phenotypic and Molecular Characterization of Extended-Spectrum Beta-Lactamase-Producing Escherichia coli in Bangladesh

    OpenAIRE

    Lina, Taslima T.; Khajanchi, Bijay K.; Azmi, Ishrat J.; Mohammad Aminul Islam; Belal Mahmood; Mahmuda Akter; Atanu Banik; Rumana Alim; Armando Navarro; Gabriel Perez; Alejandro Cravioto; Talukder, Kaisar A

    2014-01-01

    BACKGROUND: Resistance to cephalosporins in Enterobacteriaceae is mainly due to the production of extended-spectrum beta-lactamase (ESBL). Little is known about ESBL-producing bacteria in Bangladesh. Therefore, the study presents results of phenotypic and molecular characterization of ESBL-producing Escherichia coli from hospitals in Bangladesh. METHODS: A total of 339 E. coli isolated from patients with urinary tract and wound infections attending three different medical hospitals in urban a...

  5. SparSNP: Fast and memory-efficient analysis of all SNPs for phenotype prediction

    OpenAIRE

    Abraham Gad; Kowalczyk Adam; Zobel Justin; Inouye Michael

    2012-01-01

    Abstract Background A central goal of genomics is to predict phenotypic variation from genetic variation. Fitting predictive models to genome-wide and whole genome single nucleotide polymorphism (SNP) profiles allows us to estimate the predictive power of the SNPs and potentially develop diagnostic models for disease. However, many current datasets cannot be analysed with standard tools due to their large size. Results We introduce SparSNP, a tool for fitting lasso linear models for massive S...

  6. Gelam honey potentiates ex vivo corneal keratocytes proliferation with desirable phenotype expression

    OpenAIRE

    Yusof, Alia Md; Abd Ghafar, Norzana; Kamarudin, Taty Anna; Hui, Chua Kien; Yusof, Yasmin Anum Mohd

    2016-01-01

    Background This study aimed to evaluate the effects of Gelam honey on corneal keratocytes proliferative capacity and phenotypic characterization via MTT assay, gene expression and immunocytochemistry. Methods Corneal keratocytes from New Zealand white rabbits were cultured in basal medium (BM) and serum enriched medium (BMS). Serial dilutions of Gelam honey (GH) were added to both media and cells were cultured until passage 1. MTT assay was performed on corneal keratocytes in both media to as...

  7. Mitochondria Biogenesis and Bioenergetics Gene Profiles in Isogenic Prostate Cells with Different Malignant Phenotypes

    OpenAIRE

    Tanya C. Burch; Rhim, Johng S.; Julius O Nyalwidhe

    2016-01-01

    Background. The most significant hallmarks of cancer are directly or indirectly linked to deregulated mitochondria. In this study, we sought to profile mitochondria associated genes in isogenic prostate cell lines with different tumorigenic phenotypes from the same patient. Results. Two isogenic human prostate cell lines RC77N/E (nonmalignant cells) and RC77T/E (malignant cells) were profiled for expression of mitochondrial biogenesis and energy metabolism genes by qRT-PCR using the Human Mit...

  8. Phenotypes of severe asthma among children and adolescents in Brazil: a prospective study

    OpenAIRE

    Andrade, Wenderson Clay Correia de; Lasmar, Laura Maria de Lima Belizário Facury; Ricci, Cristiane de Abreu Tonelli; Camargos, Paulo Augusto Moreira; Álvaro A Cruz

    2015-01-01

    Background The morbidity associated with severe uncontrolled asthma is disproportionately higher in low- and middle-income countries than in high-income countries. The aim of this study was to describe the phenotypic characteristics of difficult-to-treat severe asthma and treatment-resistant severe asthma in a sample of children and adolescents in Brazil. Methods This was a prospective study, conducted between 2010 and 2014, following 61 patients (6–18 years of age) who had been diagnosed wit...

  9. Dysfunctional breathing phenotype in adults with asthma - incidence and risk factors

    OpenAIRE

    Agache, Ioana; Ciobanu, Cristina; Paul, Gabriela; ROGOZEA, LILIANA

    2012-01-01

    Background Abnormal breathing patterns may cause characteristic symptoms and impair quality of life. In a cross-sectional survey 29% of adults treated for asthma in primary care had symptoms suggestive of dysfunctional breathing (DB), more likely to be female and younger, with no differences for severity of asthma. No clear risk factors were demonstrated for DB in asthma, nor the impact of asthma medication was evaluated. The objective of this study was to describe the DB phenotype in adults ...

  10. Dysfunctional breathing phenotype in adults with asthma - incidence and risk factors

    OpenAIRE

    Agache Ioana; Ciobanu Cristina; Paul Gabriela; Rogozea Liliana

    2012-01-01

    Abstract Background Abnormal breathing patterns may cause characteristic symptoms and impair quality of life. In a cross-sectional survey 29% of adults treated for asthma in primary care had symptoms suggestive of dysfunctional breathing (DB), more likely to be female and younger, with no differences for severity of asthma. No clear risk factors were demonstrated for DB in asthma, nor the impact of asthma medication was evaluated. The objective of this study was to describe the DB phenotype i...

  11. Hair Analysis for Determination of Isoniazid Concentrations and Acetylator Phenotype during Antituberculous Treatment

    OpenAIRE

    Michael Eisenhut; Detlef Thieme; Dagmar Schmid; Sybille Fieseler; Hans Sachs

    2012-01-01

    Background. Analysis of isoniazid (INH) uptake has been based on measurement of plasma concentrations providing a short-term and potentially biased view. Objectives. To establish hair analysis as a tool to measure long-term uptake of INH and to assess whether acetylator phenotype in hair reflects N-acetyltransferase-2 (NAT2) genotype. Design and Methods. INH and acetyl-INH concentrations in hair were determined in patients on INH treatment for M. tuberculosis infection using high pressure liq...

  12. Magnifying Endoscopy with Narrow Band Imaging of Early Gastric Cancer: Correlation with Histopathology and Mucin Phenotype

    OpenAIRE

    Ok, Kyung-Sun; Kim, Gwang Ha; Park, Do Youn; Lee, Hyun Jeong; Jeon, Hye Kyung; Baek, Dong Hoon; Lee, Bong Eun; Song, Geun Am

    2016-01-01

    Background/Aims Magnifying endoscopy with narrow band imaging (ME-NBI) is a useful modality for the detailed visualization of microsurface (MS) and microvascular (MV) structures in the gastrointestinal tract. This study aimed to determine whether the MS and MV patterns in ME-NBI differ according to the histologic type, invasion depth, and mucin phenotype of early gastric cancers (EGCs). Methods The MS and MV patterns of 160 lesions in 160 patients with EGC who underwent ME-NBI before endoscop...

  13. Bridging the gap between gene expression and metabolic phenotype via kinetic models

    OpenAIRE

    Vital-Lopez, Francisco G; Wallqvist, Anders; Reifman, Jaques

    2013-01-01

    Background Despite the close association between gene expression and metabolism, experimental evidence shows that gene expression levels alone cannot predict metabolic phenotypes, indicating a knowledge gap in our understanding of how these processes are connected. Here, we present a method that integrates transcriptome, fluxome, and metabolome data using kinetic models to create a mechanistic link between gene expression and metabolism. Results We developed a modeling framework to construct ...

  14. Candidate gene resequencing to identify rare, pedigree-specific variants influencing healthy aging phenotypes in the long life family study

    DEFF Research Database (Denmark)

    Druley, Todd E; Wang, Lihua; Lin, Shiow J;

    2016-01-01

    BACKGROUND: The Long Life Family Study (LLFS) is an international study to identify the genetic components of various healthy aging phenotypes. We hypothesized that pedigree-specific rare variants at longevity-associated genes could have a similar functional impact on healthy phenotypes. METHODS......: We performed custom hybridization capture sequencing to identify the functional variants in 464 candidate genes for longevity or the major diseases of aging in 615 pedigrees (4,953 individuals) from the LLFS, using a multiplexed, custom hybridization capture. Variants were analyzed individually...... that was significantly associated with three phenotypes (GSK3B with the Healthy Aging Index, NOTCH1 with diastolic blood pressure and TP53 with serum HDL). CONCLUSIONS: Sequencing analysis of family-based associations for age-related phenotypes can identify rare or novel variants....

  15. A single point-mutation within the melanophilin gene causes the lavender plumage colour dilution phenotype in the chicken

    Directory of Open Access Journals (Sweden)

    Tixier-Boichard Michèle

    2008-01-01

    Full Text Available Abstract Background The lavender phenotype in the chicken causes the dilution of both black (eumelanin and red/brown (phaeomelanin pigments. Defects in three genes involved in intracellular melanosomal transport, previously described in mammals, give rise to similar diluted pigmentation phenotypes as those seen in lavender chickens. Results We have used a candidate-gene approach based on an expectation of homology with mammals to isolate a gene involved in pigmentation in chicken. Comparative sequence analysis of candidate genes in the chicken identified a strong association between a mutation in the MLPH gene and the diluted pigmentation phenotype. This mutation results in the amino acid change R35W, at a site also associated with similar phenotypes in mice, humans and cats. Conclusion This is the first time that an avian species with a mutation in the MLPH gene has been reported.

  16. The efficiency of reading around learned backgrounds

    Science.gov (United States)

    Eckstein, Miguel P.; Pham, Binh T.; Abbey, Craig K.; Zhang, Yani

    2006-03-01

    Most metrics of medical image quality typically treat all variability components of the background as a Gaussian noise process. This includes task based model observers (non-prewhitening matched filter without and with an eye filter, NPW and NPWE; Hotelling and Channelized Hotelling) as well as Fourier metrics of medical image quality based on the noise power spectra. However, many investigators have observed that unlike many of the models/metrics, physicians often can discount signal-looking structures that are part of the normal anatomic background. This process has been referred to as reading around the background or noise. The purpose of this paper is to develop an experimental framework to systematically study the ability of human observers to read around learned backgrounds and compare their ability to that of an optimal ideal observer which has knowledge of the background. We measured human localization performance of one of twelve targets in the presence of a fixed background consisting of randomly placed Gaussians with random contrasts and sizes, and white noise. Performance was compared to a condition in which the test images contained only white noise but with higher contrast. Human performance was compared to standard model observers that treat the background as a Gaussian noise process (NPW, NPWE and Hotelling), a Fourier-based prewhitening matched filter, and an ideal observer. The Hotelling, NPW, NPWE models as well as the Fourier-based prewhitening matched filter predicted higher performance for the white noise test images than the background plus white noise. In contrast, ideal and human performance was higher for the background plus white noise condition. Furthermore, human performance exceeded that of the NPW, NPWE and Hotelling models and reached an efficiency of 19% relative to the ideal observer. Our results demonstrate that for some types of images human signal localization performance is consistent with use of knowledge about the high order

  17. Endemic species have highly integrated phenotypes, environmental distributions and phenotype-environment relationships

    NARCIS (Netherlands)

    Hermant, M.; Prinzing, A.; Vernon, P.; Convey, P.; Hennion, F.

    2013-01-01

    Keywords: Abiotic environmental gradients; endemism level; functional biogeography; island biogeography; Kerguelen Islands; life-history traits; multi-species comparison; phenotypic integration; range size; sub-Antarctic Abstract Aim: Why are some species geographically restricted? Ecological explan

  18. String pair production in non homogeneous backgrounds

    Science.gov (United States)

    Bolognesi, S.; Rabinovici, E.; Tallarita, G.

    2016-04-01

    We consider string pair production in non homogeneous electric backgrounds. We study several particular configurations which can be addressed with the Euclidean world-sheet instanton technique, the analogue of the world-line instanton for particles. In the first case the string is suspended between two D-branes in flat space-time, in the second case the string lives in AdS and terminates on one D-brane (this realizes the holographic Schwinger effect). In some regions of parameter space the result is well approximated by the known analytical formulas, either the particle pair production in non-homogeneous background or the string pair production in homogeneous background. In other cases we see effects which are intrinsically stringy and related to the non-homogeneity of the background. The pair production is enhanced already for particles in time dependent electric field backgrounds. The string nature enhances this even further. For spacial varying electrical background fields the string pair production is less suppressed than the rate of particle pair production. We discuss in some detail how the critical field is affected by the non-homogeneity, for both time and space dependent electric field backgrouds. We also comment on what could be an interesting new prediction for the small field limit. The third case we consider is pair production in holographic confining backgrounds with homogeneous and non-homogeneous fields.

  19. Lorentz-invariant ensembles of vector backgrounds

    International Nuclear Information System (INIS)

    We consider gauge field theories in the presence of ensembles of vector backgrounds. While Lorentz invariance is explicitly broken in the presence of any single background, here, the Lorentz invariance of the theory is restored by averaging over a Lorentz-invariant ensemble of backgrounds, i.e., a set of background vectors that is mapped onto itself under Lorentz transformations. This framework is used to study the effects of a non-trivial but Lorentz-invariant vacuum structure or mass dimension two vector condensates by identifying the background with a shift of the gauge field. Up to now, the ensembles used in the literature comprise configurations corresponding to non-zero field tensors together with such with vanishing field strength. We find that even when constraining the ensembles to pure gauge configurations, the usual high-energy degrees of freedom are removed from the spectrum of asymptotic states in the presence of said backgrounds in Euclidean and in Minkowski space. We establish this result not only for the propagators to all orders in the background and otherwise at tree level but for the full propagator

  20. Sources of the Radio Background Considered

    Energy Technology Data Exchange (ETDEWEB)

    Singal, J.; /KIPAC, Menlo Park /Stanford U.; Stawarz, L.; /KIPAC, Menlo Park /Stanford U. /Jagiellonian U., Astron. Observ.; Lawrence, A.; /Edinburgh U., Inst. Astron. /KIPAC, Menlo Park /Stanford U.; Petrosian, V.; /KIPAC, Menlo Park /Stanford U., Phys. Dept. /Stanford U., Appl. Phys. Dept.

    2011-08-22

    We investigate possible origins of the extragalactic radio background reported by the ARCADE 2 collaboration. The surface brightness of the background is several times higher than that which would result from currently observed radio sources. We consider contributions to the background from diffuse synchrotron emission from clusters and the intergalactic medium, previously unrecognized flux from low surface brightness regions of radio sources, and faint point sources below the flux limit of existing surveys. By examining radio source counts available in the literature, we conclude that most of the radio background is produced by radio point sources that dominate at sub {mu}Jy fluxes. We show that a truly diffuse background produced by elections far from galaxies is ruled out because such energetic electrons would overproduce the observed X-ray/{gamma}-ray background through inverse Compton scattering of the other photon fields. Unrecognized flux from low surface brightness regions of extended radio sources, or moderate flux sources missed entirely by radio source count surveys, cannot explain the bulk of the observed background, but may contribute as much as 10%. We consider both radio supernovae and radio quiet quasars as candidate sources for the background, and show that both fail to produce it at the observed level because of insufficient number of objects and total flux, although radio quiet quasars contribute at the level of at least a few percent. We conclude that the most important population for production of the background is likely ordinary starforming galaxies above redshift 1 characterized by an evolving radio far-infrared correlation, which increases toward the radio loud with redshift.

  1. Sources of the Radio Background Considered

    International Nuclear Information System (INIS)

    We investigate possible origins of the extragalactic radio background reported by the ARCADE 2 collaboration. The surface brightness of the background is several times higher than that which would result from currently observed radio sources. We consider contributions to the background from diffuse synchrotron emission from clusters and the intergalactic medium, previously unrecognized flux from low surface brightness regions of radio sources, and faint point sources below the flux limit of existing surveys. By examining radio source counts available in the literature, we conclude that most of the radio background is produced by radio point sources that dominate at sub μJy fluxes. We show that a truly diffuse background produced by elections far from galaxies is ruled out because such energetic electrons would overproduce the observed X-ray/γ-ray background through inverse Compton scattering of the other photon fields. Unrecognized flux from low surface brightness regions of extended radio sources, or moderate flux sources missed entirely by radio source count surveys, cannot explain the bulk of the observed background, but may contribute as much as 10%. We consider both radio supernovae and radio quiet quasars as candidate sources for the background, and show that both fail to produce it at the observed level because of insufficient number of objects and total flux, although radio quiet quasars contribute at the level of at least a few percent. We conclude that the most important population for production of the background is likely ordinary starforming galaxies above redshift 1 characterized by an evolving radio far-infrared correlation, which increases toward the radio loud with redshift.

  2. NIC: a robust background extraction algorithm for foreground detection in dynamic scenes

    NARCIS (Netherlands)

    Huynh-The, Thien; Banos, Oresti; Lee, Sungyoung; Kang, Byeong Ho; Kim, Eun-Soo; Le-Tien, Thuong

    2016-01-01

    This paper presents a robust foreground detection method capable of adapting to different motion speeds in scenes. A key contribution of this paper is the background estimation using a proposed novel algorithm, neighbor-based intensity correction (NIC), that identifies and modifies the motion pixels

  3. Belief propagation in genotype-phenotype networks.

    Science.gov (United States)

    Moharil, Janhavi; May, Paul; Gaile, Daniel P; Blair, Rachael Hageman

    2016-03-01

    Graphical models have proven to be a valuable tool for connecting genotypes and phenotypes. Structural learning of phenotype-genotype networks has received considerable attention in the post-genome era. In recent years, a dozen different methods have emerged for network inference, which leverage natural variation that arises in certain genetic populations. The structure of the network itself can be used to form hypotheses based on the inferred direct and indirect network relationships, but represents a premature endpoint to the graphical analyses. In this work, we extend this endpoint. We examine the unexplored problem of perturbing a given network structure, and quantifying the system-wide effects on the network in a node-wise manner. The perturbation is achieved through the setting of values of phenotype node(s), which may reflect an inhibition or activation, and propagating this information through the entire network. We leverage belief propagation methods in Conditional Gaussian Bayesian Networks (CG-BNs), in order to absorb and propagate phenotypic evidence through the network. We show that the modeling assumptions adopted for genotype-phenotype networks represent an important sub-class of CG-BNs, which possess properties that ensure exact inference in the propagation scheme. The system-wide effects of the perturbation are quantified in a node-wise manner through the comparison of perturbed and unperturbed marginal distributions using a symmetric Kullback-Leibler divergence. Applications to kidney and skin cancer expression quantitative trait loci (eQTL) data from different mus musculus populations are presented. System-wide effects in the network were predicted and visualized across a spectrum of evidence. Sub-pathways and regions of the network responded in concert, suggesting co-regulation and coordination throughout the network in response to phenotypic changes. We demonstrate how these predicted system-wide effects can be examined in connection with

  4. Radiation background of Black Sea coastal environment

    International Nuclear Information System (INIS)

    The main objective of the project is to establish the level of radiation background and its sources in the Black Sea coastal environment. Marine samples will be collected in the Black Sea Coast area. The content of different radionuclides will be analyzed and the results will be used in a GIS application. The gamma emitting radionuclides will be measured in ultralow radiation background in the Romanian underground laboratory in salt mine in Slanic-Prahova. The main expected results is an up to date quantification of the radiation sources of the background of the Black Sea coastal environment. (authors)

  5. LAr instrumentation studies for low background experiments

    Energy Technology Data Exchange (ETDEWEB)

    Janicsko Csathy, Jozsef [Technische Universitaet Muenchen (Germany); Collaboration: GERDA-Collaboration

    2013-07-01

    We investigated different options to instrument a large volume of liquid Argon in a low background experiment like GERDA with special regard to alternatives to PMTs. The difficulty consists in producing all the components with a radiopurity that is compatible with the background goal of the experiment. WLS fibers read out with SiPMs seem to offer the best compromise between veto efficiency and induced background. We present optimization studies for about one ton instrumented LAr volume and preliminary results from our test stand at TUM.

  6. The astrophysical gravitational wave stochastic background

    Institute of Scientific and Technical Information of China (English)

    Tania Regimbau

    2011-01-01

    A stochastic background of gravitational waves with astrophysical origins may have resulted from the superposition of a large number of unresolved sources since the beginning of stellar activity.Its detection would put very strong constraints on the physical properties of compact objects, the initial mass function and star formarion history.On the other hand, it could be a ‘noise' that would mask the stochastic background of its cosmological origin.We review the main astrophysical processes which are able to produce a stochastic background and discuss how they may differ from the primordial contribution in terms of statistical properties.Current detection methods are also presented.

  7. Frequentist Hypothesis Testing with Background Uncertainty

    CERN Document Server

    Cranmer, K

    2003-01-01

    We consider the standard Neyman-Pearson hypothesis test of a signal-plus-background hypothesis and background-only hypothesis in the presence of uncertainty on the background-only prediction. Surprisingly, this problem has not been addressed in the recent conferences on statistical techniques in high-energy physics -- although the its confidence-interval equivalent has been. We discuss the issues of power, similar tests, coverage, and ordering rules. The method presented is compared to the Cousins-Highland technique, the ratio of Poisson means, and ``profile'' method.

  8. Do instantons like a colorful background?

    Energy Technology Data Exchange (ETDEWEB)

    Gies, H.; Pawlowski, J.M.; Wetterich, C. [Heidelberg Univ. (Germany). Inst. fuer Theoretische Physik; Jaeckel, J. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2006-08-15

    We investigate chiral symmetry breaking and color symmetry breaking in QCD. The effective potential of the corresponding scalar condensates is discussed in the presence of non-perturbative contributions from the semiclassical one-instanton sector. We concentrate on a color singlet scalar background which can describe chiral condensation, as well as a color cotet scalar background which can generate mass for the gluons. Whereas a non-vanishing singlet chiral field is favored by the instantons, we have found no indication for a preference of color octet backgrounds. (orig.)

  9. The Human Phenotype Ontology project: linking molecular biology and disease through phenotype data

    Science.gov (United States)

    Köhler, Sebastian; Doelken, Sandra C.; Mungall, Christopher J.; Bauer, Sebastian; Firth, Helen V.; Bailleul-Forestier, Isabelle; Black, Graeme C. M.; Brown, Danielle L.; Brudno, Michael; Campbell, Jennifer; FitzPatrick, David R.; Eppig, Janan T.; Jackson, Andrew P.; Freson, Kathleen; Girdea, Marta; Helbig, Ingo; Hurst, Jane A.; Jähn, Johanna; Jackson, Laird G.; Kelly, Anne M.; Ledbetter, David H.; Mansour, Sahar; Martin, Christa L.; Moss, Celia; Mumford, Andrew; Ouwehand, Willem H.; Park, Soo-Mi; Riggs, Erin Rooney; Scott, Richard H.; Sisodiya, Sanjay; Vooren, Steven Van; Wapner, Ronald J.; Wilkie, Andrew O. M.; Wright, Caroline F.; Vulto-van Silfhout, Anneke T.; de Leeuw, Nicole; de Vries, Bert B. A.; Washingthon, Nicole L.; Smith, Cynthia L.; Westerfield, Monte; Schofield, Paul; Ruef, Barbara J.; Gkoutos, Georgios V.; Haendel, Melissa; Smedley, Damian; Lewis, Suzanna E.; Robinson, Peter N.

    2014-01-01

    The Human Phenotype Ontology (HPO) project, available at http://www.human-phenotype-ontology.org, provides a structured, comprehensive and well-defined set of 10,088 classes (terms) describing human phenotypic abnormalities and 13,326 subclass relations between the HPO classes. In addition we have developed logical definitions for 46% of all HPO classes using terms from ontologies for anatomy, cell types, function, embryology, pathology and other domains. This allows interoperability with several resources, especially those containing phenotype information on model organisms such as mouse and zebrafish. Here we describe the updated HPO database, which provides annotations of 7,278 human hereditary syndromes listed in OMIM, Orphanet and DECIPHER to classes of the HPO. Various meta-attributes such as frequency, references and negations are associated with each annotation. Several large-scale projects worldwide utilize the HPO for describing phenotype information in their datasets. We have therefore generated equivalence mappings to other phenotype vocabularies such as LDDB, Orphanet, MedDRA, UMLS and phenoDB, allowing integration of existing datasets and interoperability with multiple biomedical resources. We have created various ways to access the HPO database content using flat files, a MySQL database, and Web-based tools. All data and documentation on the HPO project can be found online. PMID:24217912

  10. Phenotypical Expression of Maize Seedlings from Lines with the “Tallos Gemelos” Trait

    Directory of Open Access Journals (Sweden)

    Ma. Lorena Meraz-Fonseca

    2015-01-01

    Full Text Available In the Colegio de Postgraduados in Mexico, we have generated lines of maize (Zea mays L. with the particularity that from a seed two or more stalks emerge and develop normally, calling that character “tallos gemelos.” This trait possibly modifies the proportions of the constituent tissues of the seed and could increase the nutritional and nutraceutical quality of the grain. The aim of this study was to evaluate the germination percentage and quantify and describe the types of phenotypic expression of seedling with twin stalks in the lines. 100 seeds of each of the 26 S5 lines tested were used. At 15 days after planting in a greenhouse, the seedlings were classified based on their morphology. The results showed that, on average, the lines had 81.3% of emergence and 51% of twin stalks. Eight types of phenotypic expression in seedlings were identified and described with the character “tallos gemelos”; Type II showed the highest proportion (59.5%. The phenotypical expressions identified in seedlings with the “tallos gemelos” trait are evidence of epigenetic mechanisms, since they present one of the features of epimutants, which is that they are reversible, that is; they can return to the original phenotype, in the present circumstance to normal plants (single stalk.

  11. Phenotyping structural abnormalities in mouse embryos using high-resolution episcopic microscopy

    Directory of Open Access Journals (Sweden)

    Wolfgang J. Weninger

    2014-10-01

    Full Text Available The arrival of simple and reliable methods for 3D imaging of mouse embryos has opened the possibility of analysing normal and abnormal development in a far more systematic and comprehensive manner than has hitherto been possible. This will not only help to extend our understanding of normal tissue and organ development but, by applying the same approach to embryos from genetically modified mouse lines, such imaging studies could also transform our knowledge of gene function in embryogenesis and the aetiology of developmental disorders. The International Mouse Phenotyping Consortium is coordinating efforts to phenotype single gene knockouts covering the entire mouse genome, including characterising developmental defects for those knockout lines that prove to be embryonic lethal. Here, we present a pilot study of 34 such lines, utilising high-resolution episcopic microscopy (HREM for comprehensive 2D and 3D imaging of homozygous null embryos and their wild-type littermates. We present a simple phenotyping protocol that has been developed to take advantage of the high-resolution images obtained by HREM and that can be used to score tissue and organ abnormalities in a reliable manner. Using this approach with embryos at embryonic day 14.5, we show the wide range of structural abnormalities that are likely to be detected in such studies and the variability in phenotypes between sibling homozygous null embryos.

  12. A simple and cost-saving phenotypic drug susceptibility testing of HIV-1

    Science.gov (United States)

    Weng, Yunceng; Zhang, Ling; Huang, Jianfeng; Zhao, Jin; Luo, Peifang; Bi, Siyuan; Yang, Zhengrong; Zhu, Hai; Allain, Jean-Pierre; Li, Chengyao

    2016-01-01

    It is essential to monitor the occurrence of drug-resistant strains and to provide guidance for clinically adapted antiviral treatment of HIV/AIDS. In this study, an individual patient’s HIV-1 pol gene encoding the full length of protease and part of the reverse transcriptase was packaged into a modified lentivirus carrying dual-reporters ZsGreen and luciferase. The optimal coefficient of correlation between drug concentration and luciferase activity was optimized. A clear-cut dose-dependent relationship between lentivirus production and luciferase activity was found in the phenotypic testing system. Fold changes (FC) to a wild-type control HIV-1 strain ratios were determined reflecting the phenotypic susceptibility of treatment-exposed patient’s HIV-1 strains to 12 HIV-1 inhibitors including 6 nucleoside reverse-transcriptase inhibitors (NRTIs), 4 non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 2 protease inhibitors (PIs). Phenotypic susceptibility calls from 8 HIV-1 infected patients were consistent with 80–90% genotypic evaluations, while phenotypic assessments rectified 10–20% genotypic resistance calls. By a half of replacement with ZsGreen reporter, the consumption of high cost Bright-Glo Luciferase Assay is reduced, making this assay cheaper when a large number of HIV-1 infected individuals are tested. The study provides a useful tool for interpreting meaningful genotypic mutations and guiding tailored antiviral treatment of HIV/AIDS in clinical practice. PMID:27640883

  13. Not in their genes: Phenotypic flexibility, behavioural traditions and cultural evolution in wild bonnet macaques

    Indian Academy of Sciences (India)

    Anindya Sinha

    2005-02-01

    Phenotypic flexibility, or the within-genotype, context-dependent, variation in behaviour expressed by single reproductively mature individuals during their lifetimes, often impart a selective advantage to organisms and profoundly influence their survival and reproduction. Another phenomenon apparently not under direct genetic control is behavioural inheritance whereby higher animals are able to acquire information from the behaviour of others by social learning, and, through their own modified behaviour, transmit such information between individuals and across generations. Behavioural information transfer of this nature thus represents another form of inheritance that operates in many animals in tandem with the more basic genetic system. This paper examines the impact that phenotypic flexibility, behavioural inheritance and socially transmitted cultural traditions may have in shaping the structure and dynamics of a primate society – that of the bonnet macaque (Macaca radiata), a primate species endemic to peninsular India. Three principal issues are considered: the role of phenotypic flexibility in shaping social behaviour, the occurrence of individual behavioural traits leading to the establishment of social traditions, and the appearance of cultural evolution amidst such social traditions. Although more prolonged observations are required, these initial findings suggest that phenotypic plasticity, behavioural inheritance and cultural traditions may be much more widespread among primates than have previously been assumed but may have escaped attention due to a preoccupation with genetic inheritance in zoological thinking.

  14. PIAS1 Regulates Mutant Huntingtin Accumulation and Huntington's Disease-Associated Phenotypes In Vivo.

    Science.gov (United States)

    Ochaba, Joseph; Monteys, Alex Mas; O'Rourke, Jacqueline G; Reidling, Jack C; Steffan, Joan S; Davidson, Beverly L; Thompson, Leslie M

    2016-05-01

    The disruption of protein quality control networks is central to pathology in Huntington's disease (HD) and other neurodegenerative disorders. The aberrant accumulation of insoluble high-molecular-weight protein complexes containing the Huntingtin (HTT) protein and SUMOylated protein corresponds to disease manifestation. We previously identified an HTT-selective E3 SUMO ligase, PIAS1, that regulates HTT accumulation and SUMO modification in cells. Here we investigated whether PIAS1 modulation in neurons alters HD-associated phenotypes in vivo. Instrastriatal injection of a PIAS1-directed miRNA significantly improved behavioral phenotypes in rapidly progressing mutant HTT (mHTT) fragment R6/2 mice. PIAS1 reduction prevented the accumulation of mHTT and SUMO- and ubiquitin-modified proteins, increased synaptophysin levels, and normalized key inflammatory markers. In contrast, PIAS1 overexpression exacerbated mHTT-associated phenotypes and aberrant protein accumulation. These results confirm the association between aberrant accumulation of expanded polyglutamine-dependent insoluble protein species and pathogenesis, and they link phenotypic benefit to reduction of these species through PIAS1 modulation. PMID:27146268

  15. The impact of CYP2D6-predicted phenotype on tamoxifen treatment outcome in patients with metastatic breast cancer

    NARCIS (Netherlands)

    L.A. Lammers (Laureen); R.H.J. Matthijsen (Ron); T. van Gelder (Teun); M.J. Bijl (Monique); A.J.M. de Graan (Anne-Joy); C.M. Seynaeve (Caroline); M.A. van Fessem (Marianne); P.M.J.J. Berns (Els); A.G. Vulto (Arnold); R.H.N. van Schaik (Ron)

    2010-01-01

    textabstractAbstract BACKGROUND: Cytochrome P450 2D6 (CYP2D6) has a crucial role in the metabolic conversion of tamoxifen into the active metabolite endoxifen. In this cohort study, the effect of CYP2D6-predicted phenotype, defined as the combined effect of CYP2D6 genetic variation and concomitant

  16. Body size, physical activity and risk of colorectal cancer with or without the CpG island methylator phenotype (CIMP)

    NARCIS (Netherlands)

    Hughes, L.A.E.; Simons, C.C.J.M.; Brandt, P.A. van den; Goldbohm, R.A.; Goeij, A.F. de; Bruïne, A.P. de; Engeland, M. van; Weijenberg, M.P.

    2011-01-01

    Background: We investigated how body size and physical activity influence the risk of the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC). Methods: In the Netherlands Cohort Study (n = 120,852), risk factors were self-reported at baseline in 1986. After 7.3 years of follow-up, 603

  17. Non-CLL-like monoclonal B-Cell lymphocytosis in the general population: Prevalence and phenotypic/genetic characteristics

    NARCIS (Netherlands)

    W.G. Nieto (Wendy); C. Teodosio (Cristina); A. López (Antonio); A. Rodríguez-Caballero (Arancha); A. Romero (Alfonso); P. Bárcena (Paloma); M.L. Gutierrez; A.W. Langerak (Ton); P. Fernandez-Navarro (Paulino); A. Orfao; J. Almeida (Julia); A.O.M.C.C.S. Santa Marta de Tormes; B.H.P.C.S. Garrido Sur; C.L.M.T.C.S. Ledesma; C.R.J.M.C.S. Alba de Tormes; C.L.R.C.S.F. Villalobos; D.V.P.J.C.S. Peñaranda; F.E.E.C.S. Pizarrales-Vidal; G.R.B.L.C.S. La Alberca; G.S.F.C.S. Periurbana Norte; G.M.J.C.S. Guijuelo; G.M.J.M.C.S. Vitigudino; J.R.M.J.C.S. Garrido Norte; J.C.T.B.C.S. Elena Ginel Diez; M.P.M.C.S. Fuentes de Oñoro; M.L.J.C.S. San Juan; M.D.M.P.C.S. Miguel Armijo; S.A.B.C.S. Aldeadavila de La Ribera; S.P.R.C.S. San Jose

    2010-01-01

    textabstractBackground: Monoclonal B-cell lymphocytosis (MBL) indicates <5 × 109peripheral blood (PB) clonal B-cells/L in healthy individuals. In most cases, MBL cells show similar phenotypic/genetic features to chronic lymphocytic leukemia cells - CLL-like MBL - but little is known about non-CLL-li

  18. The Spin-2 Equation on Minkowski Background

    CERN Document Server

    Beyer, Florian; Frauendiener, Jörg; Whale, Ben

    2014-01-01

    The linearised general conformal field equations in their first and second order form are used to study the behaviour of the spin-2 zero-rest-mass equation on Minkowski background in the vicinity of space-like infinity.

  19. Background by neutron activation in GERDA

    International Nuclear Information System (INIS)

    The observation of the neutrinoless double beta decay is a proof of the Majorana nature of the neutrino. The long half-life of this decay requires experiments of very low background rates in the region of interest at Qββ. Prompt γ-rays after neutron capture on germanium and the β-decay of 77Ge contribute to the background in experiments using 76Ge for the search of the neutrinoless double beta decay. The poorly known prompt γ-ray spectra and the neutron capture cross sections for the (n,γ) reactions of 74Ge and 76Ge were measured at the research reactor FRM II (Munich). The obtained data are needed in MC simulations for qualitative and quantitative background prediction in the Gerda experiment. The data and their implication on the background in Gerda are presented.

  20. Background field method and nonrelativistic QED matching

    CERN Document Server

    Lee, Jong-Wan

    2014-01-01

    We discuss the resolution of inconsistency between lattice background field methods and nonrelativistic QED matching conditions. In particular, we show that lack of on-shell conditions in lattice QCD with time-dependent background fields generally requires that certain operators related by equations of motion should be retained in an effective field theory to correctly describe the behavior of Green's functions. The coefficients of such operators in a nonrelativistic hadronic theory are determined by performing a robust nonrelativistic expansion of QED for relativistic scalar and spin-half hadrons including nonminimal electromagnetic couplings. Provided that nonrelativistic QED is augmented with equation-of-motion operators, we find that the background field method can be reconciled with the nonrelativistic QED matching conditions without any inconsistency. We further investigate whether nonrelativistic QED can be employed in the analysis of lattice QCD correlation function in background fields, but we are co...

  1. Background by neutron activation in GERDA

    Energy Technology Data Exchange (ETDEWEB)

    Meierhofer, Georg; Dietrich, Dennis; Freund, Kai; Grabmayr, Peter; Hegai, Alexander; Jochum, Josef; Knapp, Markus; Ritter, Florian [Kepler Center for Astro and Particle Physics, Universitaet Tuebingen (Germany); Canella, Lea [Institut fuer Radiochemie, Technische Universitaet Muenchen (Germany); Jolie, Jan [Institut fuer Kernphysik, Universitaet zu Koeln (Germany); Kudejova, Petra [FRM II, Technische Universitaet Muenchen (Germany)

    2010-07-01

    The observation of the neutrinoless double beta decay is a proof of the Majorana nature of the neutrino. The long half-life of this decay requires experiments of very low background rates in the region of interest at Q{sub {beta}}{sub {beta}}. Prompt {gamma}-rays after neutron capture on germanium and the {beta}-decay of {sup 77}Ge contribute to the background in experiments using {sup 76}Ge for the search of the neutrinoless double beta decay. The poorly known prompt {gamma}-ray spectra and the neutron capture cross sections for the (n,{gamma}) reactions of {sup 74}Ge and {sup 76}Ge were measured at the research reactor FRM II (Munich). The obtained data are needed in MC simulations for qualitative and quantitative background prediction in the Gerda experiment. The data and their implication on the background in Gerda are presented.

  2. Background-cross-section-dependent subgroup parameters

    International Nuclear Information System (INIS)

    A new set of subgroup parameters was derived that can reproduce the self-shielded cross section against a wide range of background cross sections. The subgroup parameters are expressed with a rational equation which numerator and denominator are expressed as the expansion series of background cross section, so that the background cross section dependence is exactly taken into account in the parameters. The advantage of the new subgroup parameters is that they can reproduce the self-shielded effect not only by group basis but also by subgroup basis. Then an adaptive method is also proposed which uses fitting procedure to evaluate the background-cross-section-dependence of the parameters. One of the simple fitting formula was able to reproduce the self-shielded subgroup cross section by less than 1% error from the precise evaluation. (author)

  3. Evolution of environmental cues for phenotypic plasticity.

    Science.gov (United States)

    Chevin, Luis-Miguel; Lande, Russell

    2015-10-01

    Phenotypically plastic characters may respond to multiple variables in their environment, but the evolutionary consequences of this phenomenon have rarely been addressed theoretically. We model the evolution of linear reaction norms in response to several correlated environmental variables, in a population undergoing stationary environmental fluctuations. At evolutionary equilibrium, the linear combination of environmental variables that acts as a developmental cue for the plastic trait is the multivariate best linear predictor of changes in the optimum. However, the reaction norm with respect to any single environmental variable may exhibit nonintuitive patterns. Apparently maladaptive, or hyperadaptive plasticity can evolve with respect to single environmental variables, and costs of plasticity may increase, rather than reduce, plasticity in response to some variables. We also find conditions for the evolution of an indirect environmental indicator that affects expression of a plastic phenotype, despite not influencing natural selection on it. PMID:26292649

  4. Mathematical Background of Public Key Cryptography

    DEFF Research Database (Denmark)

    Frey, Gerhard; Lange, Tanja

    2005-01-01

    The two main systems used for public key cryptography are RSA and protocols based on the discrete logarithm problem in some cyclic group. We focus on the latter problem and state cryptographic protocols and mathematical background material.......The two main systems used for public key cryptography are RSA and protocols based on the discrete logarithm problem in some cyclic group. We focus on the latter problem and state cryptographic protocols and mathematical background material....

  5. Supermembrane actions for Gaiotto–Maldacena backgrounds

    International Nuclear Information System (INIS)

    We write down the supermembrane actions for M-theory backgrounds dual to general N=2 four-dimensional superconformal field theories. The actions are given to all orders in fermions and are in a particular κ-gauge. When an extra U(1) isometry is present, our actions reduce to κ-gauge fixed Green–Schwarz actions for the corresponding Type IIA backgrounds

  6. Supermembrane actions for Gaiotto–Maldacena backgrounds

    Energy Technology Data Exchange (ETDEWEB)

    Stefański, Bogdan, E-mail: Bogdan.Stefanski.1@city.ac.uk

    2014-06-15

    We write down the supermembrane actions for M-theory backgrounds dual to general N=2 four-dimensional superconformal field theories. The actions are given to all orders in fermions and are in a particular κ-gauge. When an extra U(1) isometry is present, our actions reduce to κ-gauge fixed Green–Schwarz actions for the corresponding Type IIA backgrounds.

  7. Supermembrane actions for Gaiotto-Maldacena backgrounds

    Science.gov (United States)

    Stefański, Bogdan

    2014-06-01

    We write down the supermembrane actions for M-theory backgrounds dual to general N=2 four-dimensional superconformal field theories. The actions are given to all orders in fermions and are in a particular κ-gauge. When an extra U(1) isometry is present, our actions reduce to κ-gauge fixed Green-Schwarz actions for the corresponding Type IIA backgrounds.

  8. Standard Model Background of the Cosmological Collider

    CERN Document Server

    Chen, Xingang; Xianyu, Zhong-Zhi

    2016-01-01

    The inflationary universe can be viewed as a "Cosmological Collider" with energy of Hubble scale, producing very massive particles and recording their characteristic signals in primordial non-Gaussianities. To utilize this collider to explore any new physics at very high scales, it is a prerequisite to understand the background signals from the particle physics Standard Model. In this paper we describe the Standard Model background of the Cosmological Collider.

  9. Cosmic Coincidences: Investigations for Neutron Background Suppression

    OpenAIRE

    Heimbach, Craig R.

    2007-01-01

    Two experimental investigations were made in order to reduce background counts in neutron detectors. Each investigation relied upon the fact that neutron background is largely due to cosmic ray interactions with the air and ground. The first attempt was to look at neutron arrival times. Neutron events close in time were taken to have been of a common origin due to cosmic rays. The second investigation was similar, but based on coincident neutron/muon events. The investigations showed only a s...

  10. Cross correlations of the cosmic infrared background

    OpenAIRE

    Zhang, Pengjie

    2003-01-01

    The cosmic infrared background (CIB) is a sensitive measure of the star formation history. But this background is overwhelmed by foregrounds, which bias the CIB mean flux and auto correlation measurement severely. Since dominant foregrounds do not correlate with the large scale structure, the cross correlation of CIB with galaxies is free of such foregrounds and presents as an unbiased measure of the star formation history. This also allows the measurement of CIB based on integrated intensity...

  11. Interferometric Observation of Cosmic Microwave Background Anisotropies

    CERN Document Server

    White, M; Dragovan, M; White, Martin; Carlstrom, John E.; Dragovan, Mark

    1999-01-01

    We present a formalism for analyzing interferometric observations of Cosmic Microwave Background (CMB) anisotropy and polarization data. The formalism is based upon the ell-space expansion of the angular power spectrum favoured in recent years. Explicit discussions of maximum likelihood analysis, power spectrum reconstruction, parameter estimation, imaging and polarization are given. As an example, several calculations for the Degree Angular Scale Interferometer (DASI) and Cosmic Background Interferometer (CBI) experiments are presented.

  12. Blank Background Image Lossless Compression Technique

    OpenAIRE

    Samer Sawalha; Arafat Awajan

    2014-01-01

    This paper presents a new technique able to provide a very good compression ratio in preserving the quality of the important components of the image called main objects. It focuses on applications where the image is of large size and consists of an object or a set of objects on background such as identity photos. In these applications, the background of the objects is in general uniform and represents insignificant information for the application. The results of this new techniques show that ...

  13. Gravitational wave background from binary systems

    International Nuclear Information System (INIS)

    Basic aspects of the background of gravitational waves and its mathematical characterization are reviewed. The spectral energy density parameter Ω(f), commonly used as a quantifier of the background, is derived for an ensemble of many identical sources emitting at different times and locations. For such an ensemble, Ω(f) is generalized to account for the duration of the signals and of the observation, so that one can distinguish the resolvable and unresolvable parts of the background. The unresolvable part, often called confusion noise or stochastic background, is made by signals that cannot be either individually identified or subtracted out of the data. To account for the resolvability of the background, the overlap function is introduced. This function is a generalization of the duty cycle, which has been commonly used in the literature, in some cases leading to incorrect results. The spectra produced by binary systems (stellar binaries and massive black hole binaries) are presented over the frequencies of all existing and planned detectors. A semi-analytical formula for Ω(f) is derived in the case of stellar binaries (containing white dwarfs, neutron stars or stellar-mass black holes). Besides a realistic expectation of the level of background, upper and lower limits are given, to account for the uncertainties in some astrophysical parameters such as binary coalescence rates. One interesting result concerns all current and planned ground-based detectors (including the Einstein Telescope). In their frequency range, the background of binaries is resolvable and only sporadically present. In other words, there is no stochastic background of binaries for ground-based detectors.

  14. Moving object detection using background subtraction

    CERN Document Server

    Shaikh, Soharab Hossain; Chaki, Nabendu

    2014-01-01

    This Springer Brief presents a comprehensive survey of the existing methodologies of background subtraction methods. It presents a framework for quantitative performance evaluation of different approaches and summarizes the public databases available for research purposes. This well-known methodology has applications in moving object detection from video captured with a stationery camera, separating foreground and background objects and object classification and recognition. The authors identify common challenges faced by researchers including gradual or sudden illumination change, dynamic bac

  15. The Modified Magnetohydrodynamical Equations

    Institute of Scientific and Technical Information of China (English)

    EvangelosChaliasos

    2003-01-01

    After finding the really self-consistent electromagnetic equations for a plasma, we proceed in a similar fashion to find how the magnetohydrodynamical equations have to be modified accordingly. Substantially this is done by replacing the "Lorentz" force equation by the correct (in our case) force equation. Formally we have to use the vector potential instead of the magnetic field intensity. The appearance of the formulae presented is the one of classical vector analysis. We thus find a set of eight equations in eight unknowns, as previously known concerning the traditional MHD equations.

  16. The Modified Magnetohydrodynamical Equations

    Institute of Scientific and Technical Information of China (English)

    Evangelos Chaliasos

    2003-01-01

    After finding the really self-consistent electromagnetic equations for a plasma, we proceed in a similarfashion to find how the magnetohydrodynamical equations have to be modified accordingly. Substantially this is doneby replacing the "Lorentz" force equation by the correct (in our case) force equation. Formally we have to use the vectorpotential instead of the magnetic field intensity. The appearance of the formulae presented is the one of classical vectoranalysis. We thus find a set of eight equations in eight unknowns, as previously known concerning the traditional MHDequations.

  17. Surface modified aerogel monoliths

    Science.gov (United States)

    Leventis, Nicholas (Inventor); Johnston, James C. (Inventor); Kuczmarski, Maria A. (Inventor); Meador, Mary Ann B. (Inventor)

    2013-01-01

    This invention comprises reinforced aerogel monoliths such as silica aerogels having a polymer coating on its outer geometric surface boundary, and to the method of preparing said aerogel monoliths. The polymer coatings on the aerogel monoliths are derived from polymer precursors selected from the group consisting of isocyanates as a precursor, precursors of epoxies, and precursors of polyimides. The coated aerogel monoliths can be modified further by encapsulating the aerogel with the polymer precursor reinforced with fibers such as carbon or glass fibers to obtain mechanically reinforced composite encapsulated aerogel monoliths.

  18. Sleep Duration and Breast Cancer Phenotype

    OpenAIRE

    Ali Khawaja; Santosh Rao; Li Li; Thompson, Cheryl L.

    2013-01-01

    Emerging evidence suggests that short sleep is associated with an increased risk of cancer; however, little has been done to study the role of sleep on tumor characteristics. In this study, we evaluated the relationship between sleep duration and tumor phenotype in 972 breast cancer patients. Sleep duration was inversely associated with tumor grade (univariate P = 0.032), particularly in postmenopausal women (univariate P = 0.018). This association did not reach statistical significance after...

  19. Color change, phenotypic plasticity, and camouflage

    OpenAIRE

    Martin eStevens

    2016-01-01

    The ability to change appearance over a range of timescales is widespread in nature, existing in many invertebrate and vertebrate groups. This can include color change occurring in seconds, minutes, and hours, to longer term changes associated with phenotypic plasticity and development. A major function is for camouflage against predators because color change and plasticity enables animals to match their surroundings and potentially reduce the risk of predation. Recently, we published finding...

  20. Prions, protein homeostasis, and phenotypic diversity

    OpenAIRE

    Halfmann, Randal; Alberti, Simon; Lindquist, Susan

    2010-01-01

    Prions are fascinating but often misunderstood protein aggregation phenomena. The traditional association of the mammalian prion protein with disease has overshadowed a potentially more interesting attribute of prions: their ability to create protein-based molecular memories. In fungi, prions alter the relationship between genotype and phenotype in a heritable way that diversifies clonal populations. Recent findings in yeast indicate that prions might be much more common than previously real...