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Sample records for dominant semi-dwarf phenotype

  1. A dominant semi dwarf mutant in rice

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    @@ In the winter of 1997, a semi dwarf mutant was found in the F6 population of M9056/ R8018 xuan in Hainan Province. In the spring of 1998, the seeds were sown in Hefei, Anhui Province and the plant height of the population was measured at maturity.

  2. Molecular characterization of barley 3H semi-dwarf genes.

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    Haobing Li

    Full Text Available The barley chromosome 3H accommodates many semi-dwarfing genes. To characterize these genes, the two-rowed semi-dwarf Chinese barley landrace 'TX9425' was crossed with the Australian barley variety 'Franklin' to generate a doubled haploid (DH population, and major QTLs controlling plant height have been identified in our previous study. The major QTL derived from 'TX9425' was targeted to investigate the allelism of the semi-dwarf gene uzu in barley. Twelve sets of near-isogenic lines and a large NILF2 fine mapping population segregating only for the dwarfing gene from 'TX9425' were developed. The semi-dwarfing gene in 'TX9425' was located within a 2.8 cM region close to the centromere on chromosome 3H by fine mapping. Molecular cloning and sequence analyses showed that the 'TX9425'-derived allele contained a single nucleotide substitution from A to G at position 2612 of the HvBRI1 gene. This was apparently the same mutation as that reported in six-rowed uzu barley. Markers co-segregating with the QTL were developed from the sequence of the HvBRI1 gene and were validated in the 'TX9425'/'Franklin' DH population. The other major dwarfing QTL derived from the Franklin variety was distally located on chromosome 3HL and co-segregated with the sdw1 diagnostic marker hv20ox2. A third dwarfing gene, expressed only in winter-sown trials, was identified and located on chromosome 3HS. The effects and interactions of these dwarfing genes under different growing conditions are discussed. These results improve our understanding of the genetic mechanisms controlling semi-dwarf stature in barley and provide diagnostic markers for the selection of semi-dwarfness in barley breeding programs.

  3. Function analysis of a semi-dwarf sdg in rice with near isogenic lines

    Institute of Scientific and Technical Information of China (English)

    LI Xiaobo; LIANG Guohua; LI Xiazhen; LI Hongchang; XU Jichen; ZHU Lihuang

    2004-01-01

    The physiological phenotype of the rice semi-dwarf mutant,sdg,was characterized in details using a pair of near isogenic .Neither gibberellin*deficient nor gibberellin-insensitive is characteristic of the sdgphenotype.Byanalyzing the secretion of aamylas and the promotion of stem growth caused by eogenous gibberellin(GA),the sdg plant was found to have decreased sensitivity to the GA at the seedling stage. The dwarfism stature of the sdg mutant can be attributed to the shortened internodes. Increase of the cell sults indicate the protein encded by the wild type gene of sdg may be a regulator for cell elogation.

  4. A new phenotype of autosomal dominant nemaline myopathy.

    NARCIS (Netherlands)

    Gommans, I.M.P.; Engelen, B.G.M. van; Laak, H.J. ter; Brunner, H.G.; Kremer, H.P.H.; Lammens, M.M.Y.; Vogels, O.J.M.

    2002-01-01

    We present a five-generation family with a novel phenotype of autosomal dominant nemaline myopathy not linked to the three genes known to be causative for nemaline myopathy (alpha-tropomyosin-3, nebulin, and alpha-actin). Although there was muscle weakness in the neck flexors and proximal muscles of

  5. Discriminating dominant computed tomography phenotypes in smokers without or with mild COPD

    NARCIS (Netherlands)

    Hoesein, Firdaus A. A. Mohamed; Schmidt, Michael; Mets, Onno M.; Gietema, Hester A.; Lammers, Jan-Willem J.; Zanen, Pieter; de Koning, Harry J.; van der Aalst, Carlijn; Oudkerk, Matthijs; Vliegenthart, Rozemarijn; Isgum, Ivana; Prokop, Mathias; van Ginneken, Bram; van Rikxoort, Eva M.; de Jong, Pim A.

    Background: Finding phenotypes within COPD patients may prove imperative for optimizing treatment and prognosis. We hypothesized that it would be possible to discriminate emphysematous, large airway wall thickening and small airways disease dominant phenotypes. Methods: Inspiratory and expiratory

  6. [CT imaging of COPD--importance of phenotyping (emphysema dominant and airway disorder dominant)].

    Science.gov (United States)

    Mishima, Michiaki

    2007-04-01

    We have been engaged in the analysis of the distribution of low attenuation area (LAA) representing emphysema, and the measurement of airway dimensions using CT images from the view point of phenotyping of COPD. (1) L AA% (area ratio of LAA to all lung area) did not correlate with reversibility to bronchodilators, whereas WA% (area ratio of bronchial wall to cross section of bronchus) positively correlated with reversibility. Thus, bronchodilators may be effective in proportional to the extent of airway disorders. (2) The incidence of Gc*1F(+) was significantly higher in patients with severe emphysema. These results indicate that the patients with Gc*1F(+) have rapid development of emphysema. (3) Polymorphism of MMP-9 (C -1562T) was associated with upper lung dominant emphysema in patients with COPD. (4) CT measurements of emphysema were greater in the patients with anorexia nervosa than in historical control subjects (p<0.001). Furthermore, there were significant correlations between the body mass index and the CT measures of emphysema. These data demonstrate that emphysema-like changes are present in the lungs of patients who are chronically malnourished.

  7. Autosomal dominant partial epilepsy with auditory features: Defining the phenotype

    Science.gov (United States)

    Winawer, Melodie R.; Hauser, W. Allen; Pedley, Timothy A.

    2009-01-01

    The authors previously reported linkage to chromosome 10q22-24 for autosomal dominant partial epilepsy with auditory features. This study describes seizure semiology in the original linkage family in further detail. Auditory hallucinations were most common, but other sensory symptoms (visual, olfactory, vertiginous, and cephalic) were also reported. Autonomic, psychic, and motor symptoms were less common. The clinical semiology points to a lateral temporal seizure origin. Auditory hallucinations, the most striking clinical feature, are useful for identifying new families with this synome. PMID:10851389

  8. Autosomal dominant cyclic hematopoiesis: Genetics, phenotype, and natural history

    Energy Technology Data Exchange (ETDEWEB)

    Palmer, S.E.; Stephens, K.; Dale, D.C. [Univ. of Washington, Seattle, WA (United States)

    1994-09-01

    Autosomal dominant cyclic hematopoiesis (ADCH; cyclic neutropenia) is a rare disorder manifested by transient neutropenia that recurs every three weeks. To facilitate mapping the ADCH gene by genetic linkage analysis, we studied 9 ADCH families with 42 affected individuals. Pedigrees revealed AD inheritance with no evidence for decreased penetrance. Similar intra- and interfamilial variable expression was observed, with no evidence to support heterogeneity. At least 3 families displayed apparent new mutations. Many adults developed chronic neutropenia, while offspring always cycled during childhood. Children displayed recurrent oral ulcers, gingivitis, lymphadenopathy, fever, and skin and other infections with additional symptoms. Interestingly, there were no cases of neonatal infection. Some children required multiple hospitalizations for treatment. Four males under age 18 died of Clostridium sepsis following necrotizing enterocolitis; all had affected mothers. No other deaths due to ADCH were found; most had improvement of symptoms and infections as adults. Adults experienced increased tooth loss prior to age 30 (16 out of 27 adults, with 9 edentulous). No increase in myelodysplasia, malignancy, or congenital anomalies was observed. Recombinant G-CSF treatment resulted in dramatic improvement of symptoms and infections. The results suggest that ADCH is not a benign disorder, especially in childhood, and abdominal pain requires immediate evaluation. Diagnosis of ADCH requires serial blood counts in the proband and at least one CBC in relatives to exclude similar disorders. Genetic counseling requires specific histories as well as CBCs of each family member at risk to determine status regardless of symptom history, especially to assess apparent new mutations.

  9. Molecular Basis for the Dominant White Phenotype in the Domestic Pig

    Science.gov (United States)

    Marklund, Stefan; Kijas, James; Rodriguez-Martinez, Heriberto; Rönnstrand, Lars; Funa, Keiko; Moller, Maria; Lange, Dirk; Edfors-Lilja, Inger; Andersson, Leif

    1998-01-01

    The change of phenotypic traits in domestic animals and crops as a response to selective breeding mimics the much slower evolutionary change in natural populations. Here, we describe that the dominant white phenotype in domestic pigs is caused by two mutations in the KIT gene encoding the mast/stem cell growth factor receptor (MGF), one gene duplication associated with a partially dominant phenotype and a splice mutation in one of the copies leading to the fully dominant allele. The splice mutation is a G to A substitution in the first nucleotide of intron 17 and leads to skipping of exon 17. The duplication is most likely a regulatory mutation affecting KIT expression, whereas the splice mutation is expected to cause a receptor with impaired or absent tyrosine kinase activity. Immunocytochemistry showed that this variant form is expressed in 17- to 19-day-old pig embryos. Hundreds of millions of white pigs around the world are assumed to be heterozygous or homozygous for the two mutations. [The EMBL accession numbers for porcine KIT1*0101, KIT1*0202, KIT2*0202, and KIT2*0101 are AJ223228–AJ223231, respectively.] PMID:9724328

  10. Identification and Studies of a Rice Mutant hya-1 with Semi-dwarf and Aneuploid Traits%一份水稻半矮秆非整倍突变体hya-1的鉴定与研究

    Institute of Scientific and Technical Information of China (English)

    郭涛; 刘永柱; 张建国; 陈志强; 王慧

    2012-01-01

    A semi-dwarfing rice mutant hya-1 , genetically unstable in plant height was obtained through space muta-genesis of Texianzhan 13. Compared to the wild type, hya-1 mutant was featured by semi-dwarfness, fewer tillers, slim culms, reduced grain number per panicle, low seed setting rate and low germination rate. Segregation of plant height in selfed progenies of the mutant was observed. Normal plants of selfed progenies, however, showed genetic stability. Plant height of F, hybrid and F2 progenies generated from the cross between hya-1 mutant and Texianzhan 13 did not follow Mendelian inheritance. Furthermore, selfed-progenies of the mutant had abnormal chromosome numbers (e.g. 2n = 22, 23, 25 and 36 instead of 2n- 24). In addition, there were some pollen mother cells of hya-1 with 11 bivalents at the diakinesis stage of meiosis. Real-time quantitative PCR analysis of normal and semi-dwarf plants from selfed progenies of the mutant along with Texianzhan 13 showed equal copy number of chromosome in normal and wild type plants while the copy number of chromosome 8 and 11 differed in hya-1 and semi-dwarf plants from the selfed progenies. It suggested that hya-1 mutant is a new aneuploid in which abnormal phenotype and genetic instability are caused by abnormal chromosome number and/or varying copy number of certain chromosomes.%通过空间诱变得到半矮秆突变体hya-1,该突变体半矮秆性状遗传稳定性丧失.与其野生型特籼占13相比,hya-1株高显著降低、分蘖少、茎秆细弱、每穗粒数减少、结实率降低、发芽率降低.单株收获半矮株hya-1自交种子,对半矮生性状进行连续选择,发现该性状无法纯合稳定,自交群体株高长期分离(半矮秆和野生型);分离群体中的野生型个体自交,其株高性状稳定.利用hya-1与特籼占13配制杂交组合,其F1及F2株高表型不符合孟德尔分离规律.hya-1自交收获种子根尖细胞染色体数目出现了 2n=22、23、24、25、36的变

  11. Mosaicism for dominant collagen 6 mutations as a cause for intrafamilial phenotypic variability.

    Science.gov (United States)

    Donkervoort, Sandra; Hu, Ying; Stojkovic, Tanya; Voermans, Nicol C; Foley, A Reghan; Leach, Meganne E; Dastgir, Jahannaz; Bolduc, Véronique; Cullup, Thomas; de Becdelièvre, Alix; Yang, Lin; Su, Hai; Meilleur, Katherine; Schindler, Alice B; Kamsteeg, Erik-Jan; Richard, Pascale; Butterfield, Russell J; Winder, Thomas L; Crawford, Thomas O; Weiss, Robert B; Muntoni, Francesco; Allamand, Valérie; Bönnemann, Carsten G

    2015-01-01

    Collagen 6-related dystrophies and myopathies (COL6-RD) are a group of disorders that form a wide phenotypic spectrum, ranging from severe Ullrich congenital muscular dystrophy, intermediate phenotypes, to the milder Bethlem myopathy. Both inter- and intrafamilial variable expressivity are commonly observed. We present clinical, immunohistochemical, and genetic data on four COL6-RD families with marked intergenerational phenotypic heterogeneity. This variable expression seemingly masquerades as anticipation is due to parental mosaicism for a dominant mutation, with subsequent full inheritance and penetrance of the mutation in the heterozygous offspring. We also present an additional fifth simplex patient identified as a mosaic carrier. Parental mosaicism was confirmed in the four families through quantitative analysis of the ratio of mutant versus wild-type allele (COL6A1, COL6A2, and COL6A3) in genomic DNA from various tissues, including blood, dermal fibroblasts, and saliva. Consistent with somatic mosaicism, parental samples had lower ratios of mutant versus wild-type allele compared with the fully heterozygote offspring. However, there was notable variability of the mutant allele levels between tissues tested, ranging from 16% (saliva) to 43% (fibroblasts) in one mosaic father. This is the first report demonstrating mosaicism as a cause of intrafamilial/intergenerational variability of COL6-RD, and suggests that sporadic and parental mosaicism may be more common than previously suspected.

  12. Phenotypic features in autistic individuals: the finger length ratio (2D:4D), hair whorl, and hand dominance

    National Research Council Canada - National Science Library

    Aksu, Funda; Baykara, Burak; Ergın, Canem; Arman, Candan

    2013-01-01

    The aim of this study was to compare the finger length ratio (2D:4D), hair whorl direction, and hand, foot, and eye dominance in autistic and healthy individuals, and to investigate the phenotypic characteristics of autism...

  13. Spectrum of mutations and phenotypic expression in patients with autosomal dominant hypercholesterolemia identified in Italy.

    Science.gov (United States)

    Bertolini, Stefano; Pisciotta, Livia; Rabacchi, Claudio; Cefalù, Angelo B; Noto, Davide; Fasano, Tommaso; Signori, Alessio; Fresa, Raffaele; Averna, Maurizio; Calandra, Sebastiano

    2013-04-01

    To determine the spectrum of gene mutations and the genotype-phenotype correlations in patients with Autosomal Dominant Hypercholesterolemia (ADH) identified in Italy. The resequencing of LDLR, PCSK9 genes and a selected region of APOB gene were conducted in 1018 index subjects clinically heterozygous ADH and in 52 patients clinically homozygous ADH. The analysis was also extended to 1008 family members of mutation positive subjects. Mutations were detected in 832 individuals: 97.4% with LDLR mutations, 2.2% with APOB mutations and 0.36% with PCSK9 mutations. Among the patients with homozygous ADH, 51 were carriers of LDLR mutations and one was an LDLR/PCSK9 double heterozygote. We identified 237 LDLR mutations (45 not previously reported), 4 APOB and 3 PCSK9 mutations. The phenotypic characterization of 1769 LDLR mutation carriers (ADH-1) revealed that in both sexes independent predictors of the presence of tendon xanthomas were age, the quintiles of LDL cholesterol, the presence of coronary heart disease (CHD) and of receptor negative mutations. Independent predictors of CHD were male gender, age, the presence of arterial hypertension, smoking, tendon xanthomas, the scalar increase of LDL cholesterol and the scalar decrease of HDL cholesterol. We identified 13 LDLR mutation clusters, which allowed us to compare the phenotypic impact of different mutations. The LDL cholesterol raising potential of these mutations was found to vary over a wide range. This study confirms the genetic and allelic heterogeneity of ADH and underscores that the variability in phenotypic expression of ADH-1 is greatly affected by the type of LDLR mutation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Hypo- and hypermorphic FOXC1 mutations in dominant glaucoma: transactivation and phenotypic variability.

    Directory of Open Access Journals (Sweden)

    Cristina Medina-Trillo

    Full Text Available Dominant glaucoma, a heterogeneous, infrequent and irreversible optic neuropathy, is often associated with elevated intraocular pressure and early-onset. The role of FOXC1 in this type of glaucoma was investigated in twelve Spanish probands via nucleotide variation screening of its proximal promoter and unique exon. Functional evaluations of the identified variants included analyses of the transcriptional activity, protein stability, DNA binding ability and subcellular localization. Four different mutations that were identified in four probands (33.3% were associated with remarkable phenotypic variability and were functionally classified as either hypermorphic (p.Y47X, p.Q106X and p.G447_G448insDG or hypomorphic (p.I126S alleles. To the best of our knowledge, three of the variants are novel (p.Y47X, p.I126S and p.G447_G448insDG and, in addition, hypermorphic FOXC1 mutations are reported herein for the first time. The presence of an intact N-terminal activation domain in the truncated proteins p.Y47X and p.Q106X may underlie their associated transactivation hyperactivity by a gain-of-function mechanism involving dysregulated protein-protein interactions. Similarly, altered molecular interactions may also lead to increased p.G447_G448insDG activity. In contrast, the partial loss-of-function associated with p.I126S was due to impaired protein stability, DNA binding, protein phosphorylation and subcellular distribution. These results support that moderate and variable FOXC1 transactivation changes are associated with moderate goniodysgenesis, dominant glaucoma and remarkable phenotypic variability.

  15. The progeroid phenotype of Ku80 deficiency is dominant over DNA-PKCS deficiency.

    Directory of Open Access Journals (Sweden)

    Erwin Reiling

    Full Text Available Ku80 and DNA-PKCS are both involved in the repair of double strand DNA breaks via the nonhomologous end joining (NHEJ pathway. While ku80-/- mice exhibit a severely reduced lifespan and size, this phenotype is less pronounced in dna-pkcs-/- mice. However, these observations are based on independent studies with varying genetic backgrounds. Here, we generated ku80-/-, dna-pkcs-/- and double knock out mice in a C57Bl6/J*FVB F1 hybrid background and compared their lifespan, end of life pathology and mutation frequency in liver and spleen using a lacZ reporter. Our data confirm that inactivation of Ku80 and DNA-PKCS causes reduced lifespan and bodyweights, which is most severe in ku80-/- mice. All mutant mice exhibited a strong increase in lymphoma incidence as well as other aging-related pathology (skin epidermal and adnexal atrophy, trabacular bone reduction, kidney tubular anisokaryosis, and cortical and medullar atrophy and severe lymphoid depletion. LacZ mutation frequency analysis did not show strong differences in mutation frequencies between knock out and wild type mice. The ku80-/- mice had the most severe phenotype and the Ku80-mutation was dominant over the DNA-PKCS-mutation. Presumably, the more severe degenerative effect of Ku80 inactivation on lifespan compared to DNA-PKCS inactivation is caused by additional functions of Ku80 or activity of free Ku70 since both Ku80 and DNA-PKCS are essential for NHEJ.

  16. Testing Convergence Versus History: Convergence Dominates Phenotypic Evolution for over 150 Million Years in Frogs.

    Science.gov (United States)

    Moen, Daniel S; Morlon, Hélène; Wiens, John J

    2016-01-01

    Striking evolutionary convergence can lead to similar sets of species in different locations, such as in cichlid fishes and Anolis lizards, and suggests that evolution can be repeatable and predictable across clades. Yet, most examples of convergence involve relatively small temporal and/or spatial scales. Some authors have speculated that at larger scales (e.g., across continents), differing evolutionary histories will prevent convergence. However, few studies have compared the contrasting roles of convergence and history, and none have done so at large scales. Here we develop a two-part approach to test the scale over which convergence can occur, comparing the relative importance of convergence and history in macroevolution using phylogenetic models of adaptive evolution. We apply this approach to data from morphology, ecology, and phylogeny from 167 species of anuran amphibians (frogs) from 10 local sites across the world, spanning ~160 myr of evolution. Mapping ecology on the phylogeny revealed that similar microhabitat specialists (e.g., aquatic, arboreal) have evolved repeatedly across clades and regions, producing many evolutionary replicates for testing for morphological convergence. By comparing morphological optima for clades and microhabitat types (our first test), we find that convergence associated with microhabitat use dominates frog morphological evolution, producing recurrent ecomorphs that together encompass all sampled species in each community in each region. However, our second test, which examines whether and how much species differ from their inferred optima, shows that convergence is incomplete: that is, phenotypes of most species are still somewhat distant from the estimated optimum for each microhabitat, seemingly because of insufficient time for more complete adaptation (an effect of history). Yet, these effects of history are related to past ecologies, and not clade membership. Overall, our study elucidates the dominant drivers of

  17. Correlation between connexin 32 gene mutations and clinical phenotype in X-linked dominant Charcot-Marie-Tooth neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Ionasescu, V.; Ionasescu, R.; Searby, C. [Univ. of Iowa Hospitals and Clinics, Iowa City, IA (United States)

    1996-06-14

    We studied the relationship between the genotype and clinical phenotype in 27 families with dominant X-linked Charcot-Marie-Tooth (CMTX1) neuropathy. Twenty-two families showed mutations in the coding region of the connexin32 (cx32) gene. The mutations include four nonsense mutations, eight missense mutations, two medium size deletions, and one insertion. Most missense mutations showed a mild clinical phenotype (five out of eight), whereas all nonsense mutations, the larger of the two deletions, and the insertion that produced frameshifts showed severe phenotypes. Five CMTX1 families with mild clinical phenotype showed no point mutations of the cx32 gene coding region. Three of these families showed positive genetic linkage with the markers of the Xq13.1 region. The genetic linkage of the remaining two families could not be evaluated because of their small size. 25 refs., 1 fig., 1 tab.

  18. Comparison of phenotypes between different vangl2 mutants demonstrates dominant effects of the Looptail mutation during hair cell development.

    Directory of Open Access Journals (Sweden)

    Haifeng Yin

    Full Text Available Experiments utilizing the Looptail mutant mouse, which harbors a missense mutation in the vangl2 gene, have been essential for studies of planar polarity and linking the function of the core planar cell polarity proteins to other developmental signals. Originally described as having dominant phenotypic traits, the molecular interactions underlying the Looptail mutant phenotype are unclear because Vangl2 protein levels are significantly reduced or absent from mutant tissues. Here we introduce a vangl2 knockout mouse and directly compare the severity of the knockout and Looptail mutant phenotypes by intercrossing the two lines and assaying the planar polarity of inner ear hair cells. Overall the vangl2 knockout phenotype is milder than the phenotype of compound mutants carrying both the Looptail and vangl2 knockout alleles. In compound mutants a greater number of hair cells are affected and changes in the orientation of individual hair cells are greater when quantified. We further demonstrate in a heterologous cell system that the protein encoded by the Looptail mutation (Vangl2(S464N disrupts delivery of Vangl1 and Vangl2 proteins to the cell surface as a result of oligomer formation between Vangl1 and Vangl2(S464N, or Vangl2 and Vangl2(S464N, coupled to the intracellular retention of Vangl2(S464N. As a result, Vangl1 protein is missing from the apical cell surface of vestibular hair cells in Looptail mutants, but is retained at the apical cell surface of hair cells in vangl2 knockouts. Similarly the distribution of Prickle-like2, a putative Vangl2 interacting protein, is differentially affected in the two mutant lines. In summary, we provide evidence for a direct physical interaction between Vangl1 and Vangl2 through a combination of in vitro and in vivo approaches and propose that this interaction underlies the dominant phenotypic traits associated with the Looptail mutation.

  19. Complexity of the Class B Phenotype in Autosomal Dominant Retinitis Pigmentosa Due to Rhodopsin Mutations

    Science.gov (United States)

    Jacobson, Samuel G.; McGuigan, David B.; Sumaroka, Alexander; Roman, Alejandro J.; Gruzensky, Michaela L.; Sheplock, Rebecca; Palma, Judy; Schwartz, Sharon B.; Aleman, Tomas S.; Cideciyan, Artur V.

    2016-01-01

    Purpose Previously, patients with RHO mutations and a class A phenotype were found to have severe early-onset loss of rod function, whereas patients with a class B phenotype retained rod function at least in certain retinal regions. Here class B patients were studied at different disease stages to understand the topographic details of the phenotype in preparation for therapies of this regionalized retinopathy. Methods A cohort of patients with RHO mutations and class B phenotype (n = 28; ages 10–80 years) were studied with rod and cone perimetry and optical coherence tomography (OCT). Results At least three components of the phenotype were identified in these cross-sectional studies. Patients could have hemifield dysfunction, pericentral loss of function, or a diffuse rod sensitivity loss across the visual field. Combinations of these different patterns were also found. Colocalized photoreceptor layer thicknesses were in agreement with the psychophysical results. Conclusions These disorders with regional retinal variation of severity require pre-evaluations before enrollment into clinical trials to seek answers to questions about where in the retina would be appropriate to deliver focal treatments, and, for retina-wide treatment strategies, where in the retina should be monitored for therapeutic efficacy (or safety). PMID:27654411

  20. COMPLETENESS OF CATALOGS OF AUTOSOMAL DOMINANT, AUTOSOMAL RECESSIVE, AND X-LINKED PHENOTYPES

    NARCIS (Netherlands)

    TENKATE, LP

    1992-01-01

    The completeness of McKusick's catalogs of Mendelian Inheritance in Man (MIM) as to the number of phenotypes included was studied by estimating the degree of concordance with the Dutch Gene Catalog of the Department of Medical Genetics of the University of Groningen, The Netherlands. On a total of 3

  1. The progeroid phenotype of Ku80 deficiency is dominant over DNA-PKCS deficiency

    NARCIS (Netherlands)

    Reiling, Erwin; Dollé, Martijn E T; Youssef, Sameh A; Lee, Moonsook; Nagarajah, Bhawani; Roodbergen, Marianne; de With, Piet; de Bruin, Alain; Hoeijmakers, Jan H; Vijg, Jan; van Steeg, Harry; Hasty, Paul

    2014-01-01

    Ku80 and DNA-PKCS are both involved in the repair of double strand DNA breaks via the nonhomologous end joining (NHEJ) pathway. While ku80-/- mice exhibit a severely reduced lifespan and size, this phenotype is less pronounced in dna-pkcs-/- mice. However, these observations are based on independent

  2. The progeroid phenotype of Ku80 deficiency Is dominant over DNA-PK CS deficiency

    NARCIS (Netherlands)

    E. Reiling (Erwin); M.E.T. Dollé (Martijn); A.R. Youssef; M. Lee (Moonsook); B. Nagarajah (Bhawani); M. Roodbergen (Marianne); P. de With (Piet); A. de Bruin (Alain); J.H.J. Hoeijmakers (Jan); J. Vijg (Jan); H. van Steeg (Harry); P. Hasty (Paul)

    2014-01-01

    textabstractKu80 and DNA-PKCS are both involved in the repair of double strand DNA breaks via the nonhomologous end joining (NHEJ) pathway. While ku80-/- mice exhibit a severely reduced lifespan and size, this phenotype is less pronounced in dna-pkcs -/- mice. However, these observations are based

  3. A MITF mutation associated with a dominant white phenotype and bilateral deafness in German Fleckvieh cattle.

    Directory of Open Access Journals (Sweden)

    Ute Philipp

    Full Text Available A dominantly inherited syndrome associated with hypopigmentation, heterochromia irides, colobomatous eyes and bilateral hearing loss has been ascertained in Fleckvieh cattle (German White Fleckvieh syndrome. This syndrome has been mapped to bovine chromosome (BTA 22 using a genome-wide association study with the bovine high density single nucleotide polymorphism array. An R210I missense mutation has been identified within microphthalmia-associated transcription factor (MITF as responsible for this syndrome. The mutation is located in the highly conserved basic region of the protein and causes a negative-dominant effect. SOX10 and PAX3 promoter binding site mutations in MITF could be ruled out as causative for the German White Fleckvieh syndrome. Molecular characterization of this newly detected bovine syndrome means a large animal model is now available for the Tietz syndrome in humans.

  4. A MITF Mutation Associated with a Dominant White Phenotype and Bilateral Deafness in German Fleckvieh Cattle

    Science.gov (United States)

    Philipp, Ute; Lupp, Bettina; Mömke, Stefanie; Stein, Veronika; Tipold, Andrea; Eule, Johanna Corinna; Rehage, Jürgen; Distl, Ottmar

    2011-01-01

    A dominantly inherited syndrome associated with hypopigmentation, heterochromia irides, colobomatous eyes and bilateral hearing loss has been ascertained in Fleckvieh cattle (German White Fleckvieh syndrome). This syndrome has been mapped to bovine chromosome (BTA) 22 using a genome-wide association study with the bovine high density single nucleotide polymorphism array. An R210I missense mutation has been identified within microphthalmia-associated transcription factor (MITF) as responsible for this syndrome. The mutation is located in the highly conserved basic region of the protein and causes a negative-dominant effect. SOX10 and PAX3 promoter binding site mutations in MITF could be ruled out as causative for the German White Fleckvieh syndrome. Molecular characterization of this newly detected bovine syndrome means a large animal model is now available for the Tietz syndrome in humans. PMID:22174915

  5. [Phenotypic features in autistic individuals: the finger length ratio (2D:4D), hair whorl, and hand dominance].

    Science.gov (United States)

    Aksu, Funda; Baykara, Burak; Ergın, Canem; Arman, Candan

    2013-01-01

    The aim of this study was to compare the finger length ratio (2D:4D), hair whorl direction, and hand, foot, and eye dominance in autistic and healthy individuals, and to investigate the phenotypic characteristics of autism. The study included 37 males diagnosed with autistic disorder and 121 healthy males, all aged 4-18 years. The length of the index and ring fingers of both hands--from the proximal bend of the metacarpophalangeal joint to the fingertips--was measured with digital calipers and the index-ring finger (2D:4D) ratio was determined. The distance between hair whorls, their perpendicular distance from the mid-sagittal line, and their direction of rotation were calculated in the autism and control groups. Hand, foot, and eye dominance were determined in both groups. The findings were evaluated using SPSS v.15.0. The autism group had a greater number of hair whorls than the control group. The distance between hair whorls and the mid-sagittal line was longer in those with left hand and left eye dominance. A significant difference in the 2D:4D ratio of the right and left hands between the 2 groups was not observed. The autism group had more hair whorls than the control group and the hair whorls in the autistic individuals with left hand and left eye dominance were located further from the mid-saggital line. We think that these novel findings might contribute to the determination of the phenotypic features specific to autism.

  6. Genetic linkage studies in autosomal dominant ataxia families with an MJD phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Silveira, I.; Lopes-Cendes, I.; Paciel, P. [McGill Univ., Montreal (Canada)] [and others

    1994-09-01

    Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar degeneration which was originally described in patients originating from the Portuguese islands of the Azores. The first non-Portuguese kindred was described in 1979 and was an American black family originating from North Carolina. Since then the number of pedigrees of non-Azorean, non-Portuguese origin has increased with families being reported from other European countries, as well as Brazil, Japan, India, The United States and Australia. The autosomal dominant ataxias are a clinically and genetically heterogeneous group of disorders. To date, genetic analysis of families with autosomal dominant ataxias has permitted the identification of four loci, the SCA1 (spinocerebellar ataxia type 1) locus on chromosome 6p, the SCA2 locus on chromosome 12q, a third locus on chromosome 14q, the MJD/SCA3 and, more recently, the DRPLA (Dentatorubral-pallidoluysian atrophy) locus on chromosome 12p. We ascertained a total of 181 individuals with 60 affected from eight Indian, two Brazilian and one Sicilian-American family; all of them have received the clinical diagnosis of MJD. Recently, we have begun molecular genetic studies in these families in order to test these four candidate regions. The SCA1 mutation and the DRPLA mutation has been found to be an expansion of a CAG repeat. Direct analysis of the SCA1 and DRPLA expansion has been performed in all families and no expansion was found in the affected individuals. We are now running flanking markers for the SCA2 and MJD/SCA3 loci. These results will also be presented.

  7. Non dominant-negative KCNJ2 gene mutations leading to Andersen-Tawil syndrome with an isolated cardiac phenotype.

    Science.gov (United States)

    Limberg, Maren M; Zumhagen, Sven; Netter, Michael F; Coffey, Alison J; Grace, Andrew; Rogers, Jane; Böckelmann, Doris; Rinné, Susanne; Stallmeyer, Birgit; Decher, Niels; Schulze-Bahr, Eric

    2013-05-01

    Andersen-Tawil syndrome (ATS) is characterized by dysmorphic features, periodic paralyses and abnormal ventricular repolarization. After genotyping a large set of patients with congenital long-QT syndrome, we identified two novel, heterozygous KCNJ2 mutations (p.N318S, p.W322C) located in the C-terminus of the Kir2.1 subunit. These mutations have a different localization than classical ATS mutations which are mostly located at a potential interaction face with the slide helix or at the interface between the C-termini. Mutation carriers were without the key features of ATS, causing an isolated cardiac phenotype. While the N318S mutants regularly reached the plasma membrane, W322C mutants primarily resided in late endosomes. Co-expression of N318S or W322C with wild-type Kir2.1 reduced current amplitudes only by 20-25 %. This mild loss-of-function for the heteromeric channels resulted from defective channel trafficking (W322C) or gating (N318S). Strikingly, and in contrast to the majority of ATS mutations, neither mutant caused a dominant-negative suppression of wild-type Kir2.1, Kir2.2 and Kir2.3 currents. Thus, a mild reduction of native Kir2.x currents by non dominant-negative mutants may cause ATS with an isolated cardiac phenotype.

  8. Autosomal dominant cerebellar ataxia type I: A review of the phenotypic and genotypic characteristics

    Science.gov (United States)

    2011-01-01

    Type I autosomal dominant cerebellar ataxia (ADCA) is a type of spinocerebellar ataxia (SCA) characterized by ataxia with other neurological signs, including oculomotor disturbances, cognitive deficits, pyramidal and extrapyramidal dysfunction, bulbar, spinal and peripheral nervous system involvement. The global prevalence of this disease is not known. The most common type I ADCA is SCA3 followed by SCA2, SCA1, and SCA8, in descending order. Founder effects no doubt contribute to the variable prevalence between populations. Onset is usually in adulthood but cases of presentation in childhood have been reported. Clinical features vary depending on the SCA subtype but by definition include ataxia associated with other neurological manifestations. The clinical spectrum ranges from pure cerebellar signs to constellations including spinal cord and peripheral nerve disease, cognitive impairment, cerebellar or supranuclear ophthalmologic signs, psychiatric problems, and seizures. Cerebellar ataxia can affect virtually any body part causing movement abnormalities. Gait, truncal, and limb ataxia are often the most obvious cerebellar findings though nystagmus, saccadic abnormalities, and dysarthria are usually associated. To date, 21 subtypes have been identified: SCA1-SCA4, SCA8, SCA10, SCA12-SCA14, SCA15/16, SCA17-SCA23, SCA25, SCA27, SCA28 and dentatorubral pallidoluysian atrophy (DRPLA). Type I ADCA can be further divided based on the proposed pathogenetic mechanism into 3 subclasses: subclass 1 includes type I ADCA caused by CAG repeat expansions such as SCA1-SCA3, SCA17, and DRPLA, subclass 2 includes trinucleotide repeat expansions that fall outside of the protein-coding regions of the disease gene including SCA8, SCA10 and SCA12. Subclass 3 contains disorders caused by specific gene deletions, missense mutation, and nonsense mutation and includes SCA13, SCA14, SCA15/16, SCA27 and SCA28. Diagnosis is based on clinical history, physical examination, genetic molecular

  9. Autosomal dominant cerebellar ataxia type I: A review of the phenotypic and genotypic characteristics

    Directory of Open Access Journals (Sweden)

    Fujioka Shinsuke

    2011-05-01

    Full Text Available Abstract Type I autosomal dominant cerebellar ataxia (ADCA is a type of spinocerebellar ataxia (SCA characterized by ataxia with other neurological signs, including oculomotor disturbances, cognitive deficits, pyramidal and extrapyramidal dysfunction, bulbar, spinal and peripheral nervous system involvement. The global prevalence of this disease is not known. The most common type I ADCA is SCA3 followed by SCA2, SCA1, and SCA8, in descending order. Founder effects no doubt contribute to the variable prevalence between populations. Onset is usually in adulthood but cases of presentation in childhood have been reported. Clinical features vary depending on the SCA subtype but by definition include ataxia associated with other neurological manifestations. The clinical spectrum ranges from pure cerebellar signs to constellations including spinal cord and peripheral nerve disease, cognitive impairment, cerebellar or supranuclear ophthalmologic signs, psychiatric problems, and seizures. Cerebellar ataxia can affect virtually any body part causing movement abnormalities. Gait, truncal, and limb ataxia are often the most obvious cerebellar findings though nystagmus, saccadic abnormalities, and dysarthria are usually associated. To date, 21 subtypes have been identified: SCA1-SCA4, SCA8, SCA10, SCA12-SCA14, SCA15/16, SCA17-SCA23, SCA25, SCA27, SCA28 and dentatorubral pallidoluysian atrophy (DRPLA. Type I ADCA can be further divided based on the proposed pathogenetic mechanism into 3 subclasses: subclass 1 includes type I ADCA caused by CAG repeat expansions such as SCA1-SCA3, SCA17, and DRPLA, subclass 2 includes trinucleotide repeat expansions that fall outside of the protein-coding regions of the disease gene including SCA8, SCA10 and SCA12. Subclass 3 contains disorders caused by specific gene deletions, missense mutation, and nonsense mutation and includes SCA13, SCA14, SCA15/16, SCA27 and SCA28. Diagnosis is based on clinical history, physical

  10. An allele of sequoia dominantly enhances a trio mutant phenotype to influence Drosophila larval behavior.

    Directory of Open Access Journals (Sweden)

    Kathryn E Dean

    Full Text Available The transition of Drosophila third instar larvae from feeding, photo-phobic foragers to non-feeding, photo-neutral wanderers is a classic behavioral switch that precedes pupariation. The neuronal network responsible for this behavior has recently begun to be defined. Previous genetic analyses have identified signaling components for food and light sensory inputs and neuropeptide hormonal outputs as being critical for the forager to wanderer transition. Trio is a Rho-Guanine Nucleotide Exchange Factor integrated into a variety of signaling networks including those governing axon pathfinding in early development. Sequoia is a pan-neuronally expressed zinc-finger transcription factor that governs dendrite and axon outgrowth. Using pre-pupal lethality as an endpoint, we have screened for dominant second-site enhancers of a weakly lethal trio mutant background. In these screens, an allele of sequoia has been identified. While these mutants have no obvious disruption of embryonic central nervous system architecture and survive to third instar larvae similar to controls, they retain forager behavior and thus fail to pupariate at high frequency.

  11. Autosomal dominant cerebellar ataxia type III: a review of the phenotypic and genotypic characteristics

    Science.gov (United States)

    2013-01-01

    Autosomal Dominant Cerebellar Ataxia (ADCA) Type III is a type of spinocerebellar ataxia (SCA) classically characterized by pure cerebellar ataxia and occasionally by non-cerebellar signs such as pyramidal signs, ophthalmoplegia, and tremor. The onset of symptoms typically occurs in adulthood; however, a minority of patients develop clinical features in adolescence. The incidence of ADCA Type III is unknown. ADCA Type III consists of six subtypes, SCA5, SCA6, SCA11, SCA26, SCA30, and SCA31. The subtype SCA6 is the most common. These subtypes are associated with four causative genes and two loci. The severity of symptoms and age of onset can vary between each SCA subtype and even between families with the same subtype. SCA5 and SCA11 are caused by specific gene mutations such as missense, inframe deletions, and frameshift insertions or deletions. SCA6 is caused by trinucleotide CAG repeat expansions encoding large uninterrupted glutamine tracts. SCA31 is caused by repeat expansions that fall outside of the protein-coding region of the disease gene. Currently, there are no specific gene mutations associated with SCA26 or SCA30, though there is a confirmed locus for each subtype. This disease is mainly diagnosed via genetic testing; however, differential diagnoses include pure cerebellar ataxia and non-cerebellar features in addition to ataxia. Although not fatal, ADCA Type III may cause dysphagia and falls, which reduce the quality of life of the patients and may in turn shorten the lifespan. The therapy for ADCA Type III is supportive and includes occupational and speech modalities. There is no cure for ADCA Type III, but a number of recent studies have highlighted novel therapies, which bring hope for future curative treatments. PMID:23331413

  12. Expression of a dominant negative PKA mutation in the kidney elicits a diabetes insipidus phenotype.

    Science.gov (United States)

    Gilbert, Merle L; Yang, Linghai; Su, Thomas; McKnight, G Stanley

    2015-03-15

    PKA plays a critical role in water excretion through regulation of the production and action of the antidiuretic hormone arginine vasopressin (AVP). The AVP prohormone is produced in the hypothalamus, where its transcription is regulated by cAMP. Once released into the circulation, AVP stimulates antidiuresis through activation of vasopressin 2 receptors in renal principal cells. Vasopressin 2 receptor activation increases cAMP and activates PKA, which, in turn, phosphorylates aquaporin (AQP)2, triggering apical membrane accumulation, increased collecting duct permeability, and water reabsorption. We used single-minded homolog 1 (Sim1)-Cre recombinase-mediated expression of a dominant negative PKA regulatory subunit (RIαB) to disrupt kinase activity in vivo and assess the role of PKA in fluid homeostasis. RIαB expression gave rise to marked polydipsia and polyuria; however, neither hypothalamic Avp mRNA expression nor urinary AVP levels were attenuated, indicating a primary physiological effect on the kidney. RIαB mice displayed a marked deficit in urinary concentrating ability and greatly reduced levels of AQP2 and phospho-AQP2. Dehydration induced Aqp2 mRNA in the kidney of both control and RIαB-expressing mice, but AQP2 protein levels were still reduced in RIαB-expressing mutants, and mice were unable to fully concentrate their urine and conserve water. We conclude that partial PKA inhibition in the kidney leads to posttranslational effects that reduce AQP2 protein levels and interfere with apical membrane localization. These findings demonstrate a distinct physiological role for PKA signaling in both short- and long-term regulation of AQP2 and characterize a novel mouse model of diabetes insipidus.

  13. Phenotypic distribution models corroborate species distribution models: A shift in the role and prevalence of a dominant prairie grass in response to climate change.

    Science.gov (United States)

    Smith, Adam B; Alsdurf, Jacob; Knapp, Mary; Baer, Sara G; Johnson, Loretta C

    2017-10-01

    Phenotypic distribution within species can vary widely across environmental gradients but forecasts of species' responses to environmental change often assume species respond homogenously across their ranges. We compared predictions from species and phenotype distribution models under future climate scenarios for Andropogon gerardii, a widely distributed, dominant grass found throughout the central United States. Phenotype data on aboveground biomass, height, leaf width, and chlorophyll content were obtained from 33 populations spanning a ~1000 km gradient that encompassed the majority of the species' environmental range. Species and phenotype distribution models were trained using current climate conditions and projected to future climate scenarios. We used permutation procedures to infer the most important variable for each model. The species-level response to climate was most sensitive to maximum temperature of the hottest month, but phenotypic variables were most sensitive to mean annual precipitation. The phenotype distribution models predict that A. gerardii could be largely functionally eliminated from where this species currently dominates, with biomass and height declining by up to ~60% and leaf width by ~20%. By the 2070s, the core area of highest suitability for A. gerardii is projected to shift up to ~700 km northeastward. Further, short-statured phenotypes found in the present-day short grass prairies on the western periphery of the species' range will become favored in the current core ~800 km eastward of their current location. Combined, species and phenotype models predict this currently dominant prairie grass will decline in prevalence and stature. Thus, sourcing plant material for grassland restoration and forage should consider changes in the phenotype that will be favored under future climate conditions. Phenotype distribution models account for the role of intraspecific variation in determining responses to anticipated climate change and

  14. A de novo dominant mutation in ACTA1 causing congenital nemaline myopathy associated with a milder phenotype: expanding the spectrum of dominant ACTA1 mutations.

    Science.gov (United States)

    Levesque, L; Del Bigio, M R; Krawitz, S; Mhanni, A A

    2013-03-01

    We describe the presentation and six-year follow up of a child with nemaline myopathy due to a de novo mutation in the skeletal muscle α-actin gene (ACTA1) characterized by dramatic improvement during the early childhood years. The presentation in this female patient was infantile-onset weakness in the facial, bulbar, respiratory and neck flexor muscles. A six-year follow-up revealed continued progressive improvement in her muscle strength. Based upon the histopathologic and ultrastructural features of nemaline rod disease, ACTA1 was sequenced. This revealed a mutation in exon 4 of ACTA1 (c.557A>G). Our report further expands the phenotypic spectrum associated with ACTA1 mutations. Although it is difficult to infer any genotype-phenotype correlation, this report stimulates the discussion regarding the pathophysiologic mechanism of the clinical improvement seen in some patients with ACTA1 mutations. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Two variants in the KIT gene as candidate causative mutations for a dominant white and a white spotting phenotype in the donkey.

    Science.gov (United States)

    Haase, B; Rieder, S; Leeb, T

    2015-06-01

    White spotting phenotypes have been intensively studied in horses, and although similar phenotypes occur in the donkey, little is known about the molecular genetics underlying these patterns in donkeys. White spotting in donkeys can range from only a few white areas to almost complete depigmentation and is characterised by a loss of pigmentation usually progressing from a white spot in the hip area. Completely white-born donkeys are rare, and the phenotype is characterised by the complete absence of pigment resulting in pink skin and a white coat. A dominant mode of inheritance has been demonstrated for spotting in donkeys. Although the mode of inheritance for the completely white phenotype in donkeys is not clear, the phenotype shows similarities to dominant white in horses. As variants in the KIT gene are known to cause a range of white phenotypes in the horse, we investigated the KIT gene as a potential candidate gene for two phenotypes in the donkey, white spotting and white. A mutation analysis of all 21 KIT exons identified a missense variant in exon 4 (c.662A>C; p.Tyr221Ser) present only in a white-born donkey. A second variant affecting a splice donor site (c.1978+2T>A) was found exclusively in donkeys with white spotting. Both variants were absent in 24 solid-coloured controls. To the authors' knowledge, this is the first study investigating genetic mechanisms underlying white phenotypes in donkeys. Our results suggest that two independent KIT alleles are probably responsible for white spotting and white in donkeys.

  16. Mutation spectrum in the large GTPase dynamin 2, and genotype-phenotype correlation in autosomal dominant centronuclear myopathy

    DEFF Research Database (Denmark)

    Böhm, Johann; Biancalana, Valérie; Dechene, Elizabeth T

    2012-01-01

    Centronuclear myopathy (CNM) is a genetically heterogeneous disorder associated with general skeletal muscle weakness, type I fiber predominance and atrophy, and abnormally centralized nuclei. Autosomal dominant CNM is due to mutations in the large GTPase dynamin 2 (DNM2), a mechanochemical enzym...

  17. Relative Contribution of Mutations in Genes for Autosomal Dominant Distal Hereditary Motor Neuropathies: A Genotype-Phenotype Correlation Study

    Science.gov (United States)

    Dierick, Ines; Baets, Jonathan; Irobi, Joy; Jacobs, An; De Vriendt, Els; Deconinck, Tine; Merlini, Luciano; Van den Bergh, Peter; Rasic, Vedrana Milic; Robberecht, Wim; Fischer, Dirk; Morales, Raul Juntas; Mitrovic, Zoran; Seeman, Pavel; Mazanec, Radim; Kochanski, Andrzej; Jordanova, Albena; Auer-Grumbach, Michaela; Helderman-van den Enden, A. T. J. M.; Wokke, John H. J.; Nelis, Eva; De Jonghe, Peter; Timmerman, Vincent

    2008-01-01

    Distal hereditary motor neuropathy (HMN) is a clinically and genetically heterogeneous group of disorders affecting spinal alpha-motor neurons. Since 2001, mutations in six different genes have been identified for autosomal dominant distal HMN; "glycyl-tRNA synthetase (GARS)," "dynactin 1 (DCTN1)," "small heat shock 27 kDa…

  18. Relative Contribution of Mutations in Genes for Autosomal Dominant Distal Hereditary Motor Neuropathies: A Genotype-Phenotype Correlation Study

    Science.gov (United States)

    Dierick, Ines; Baets, Jonathan; Irobi, Joy; Jacobs, An; De Vriendt, Els; Deconinck, Tine; Merlini, Luciano; Van den Bergh, Peter; Rasic, Vedrana Milic; Robberecht, Wim; Fischer, Dirk; Morales, Raul Juntas; Mitrovic, Zoran; Seeman, Pavel; Mazanec, Radim; Kochanski, Andrzej; Jordanova, Albena; Auer-Grumbach, Michaela; Helderman-van den Enden, A. T. J. M.; Wokke, John H. J.; Nelis, Eva; De Jonghe, Peter; Timmerman, Vincent

    2008-01-01

    Distal hereditary motor neuropathy (HMN) is a clinically and genetically heterogeneous group of disorders affecting spinal alpha-motor neurons. Since 2001, mutations in six different genes have been identified for autosomal dominant distal HMN; "glycyl-tRNA synthetase (GARS)," "dynactin 1 (DCTN1)," "small heat shock 27 kDa protein 1 (HSPB1),"…

  19. Autosomal dominant precocious osteoarthropathy due to a mutation of the cartilage oligomeric matrix protein (COMP) gene: further expansion of the phenotypic variations of COMP defects

    Energy Technology Data Exchange (ETDEWEB)

    Kawaji, Hiroyuki [Department of Orthopaedic Surgery, Sanyudo Hospital, 6-1-219 Chuou, Yonezawa, Yamagata 992-0045 (Japan); Nishimura, Gen [Department of Radiology, Nasu Chuou Hospital, Tochigi (Japan); Watanabe, Sobei; Sasaki, Akira; Sano, Tokuhisa [Department of Orthopaedic Surgery, Tohoku Kohsei-Nenkin Hospital, Miyagi (Japan); Mabuchi, Akihiko; Ikeda, Toshiyuki; Ikegawa, Shiro [Laboratory for Bone and Joint Diseases, SNP Research Center, Tokyo (Japan); Ohashi, Hirofumi [Division of Medical Genetics, Saitama Children' s Medical Center, Saitama (Japan)

    2002-12-01

    We report on a Japanese family of four generations with an autosomal dominant precocious osteoarthropathy. The cardinal clinical manifestations of affected individuals were painful weight-bearing large joints, which started in late childhood or adolescence. The radiological hallmarks included coxa plana, mild epiphyseal dysplasia of the knee, and round talar domes with tibiotalar slant in childhood, which evolved into degenerative joint diseases in adulthood. The disease phenotype was cosegregated with a mutation of the cartilage oligomeric matrix protein (COMP) gene in the family members, who underwent molecular evaluation. COMP mutations have been reported in a mild form of multiple epiphyseal dysplasia (MED), Ribbing type, as well as allied disorders with more severe manifestations, such as MED Fairbank type and pseudoachondroplasia. Unlike previously reported cases with the Ribbing type, the present patients did not have short stature or brachydactyly. This report expands further the phenotypic variations of COMP defects. (orig.)

  20. Whole exome analysis identifies dominant COL4A1 mutations in patients with complex ocular phenotypes involving microphthalmia.

    Science.gov (United States)

    Deml, B; Reis, L M; Maheshwari, M; Griffis, C; Bick, D; Semina, E V

    2014-11-01

    Anophthalmia/microphthalmia (A/M) is a developmental ocular malformation defined as complete absence or reduction in size of the eye. A/M is a heterogenous disorder with numerous causative genes identified; however, about half the cases lack a molecular diagnosis. We undertook whole exome sequencing in an A/M family with two affected siblings, two unaffected siblings, and unaffected parents; the ocular phenotype was isolated with only mild developmental delay/learning difficulties reported and a normal brain magnetic resonance imaging (MRI) in the proband at 16 months. No pathogenic mutations were identified in 71 known A/M genes. Further analysis identified a shared heterozygous mutation in COL4A1, c.2317G>A, p.(Gly773Arg) that was not seen in the unaffected parents and siblings. Analysis of 24 unrelated A/M exomes identified a novel c.2122G>A, p.(Gly708Arg) mutation in an additional patient with unilateral microphthalmia, bilateral microcornea and Peters anomaly; the mutation was absent in the unaffected mother and the unaffected father was not available. Mutations in COL4A1 have been linked to a spectrum of human disorders; the most consistent feature is cerebrovascular disease with variable ocular anomalies, kidney and muscle defects. This study expands the spectrum of COL4A1 phenotypes and indicates screening in patients with A/M regardless of MRI findings or presumed inheritance pattern.

  1. Mutation Spectrum in the Large GTPase Dynamin 2, and Genotype–Phenotype Correlation in Autosomal Dominant Centronuclear Myopathy

    OpenAIRE

    Böhm, Johann; Biancalana, Valérie; DeChene, Elizabeth T; Bitoun, Marc; Pierson, Christopher R.; Schaefer, Elise; Karasoy, Hatice; Dempsey, Melissa A.; Klein, Fabrice; Dondaine, Nicolas; Kretz, Christine; Haumesser, Nicolas; Poirson, Claire; Toussaint, Anne; Greenleaf, Rebecca S.

    2012-01-01

    Centronuclear myopathy (CNM) is a genetically heterogeneous disorder associated with general skeletal muscle weakness, type I fiber predominance and atrophy, and abnormally centralized nuclei. Autosomal dominant CNM is due to mutations in the large GTPase dynamin 2 (DNM2), a mechanochemical enzyme regulating cytoskeleton and membrane trafficking in cells. To date, 40 families with CNM-related DNM2 mutations have been described, and here we report 60 additional families encompassing a broad ge...

  2. Local amino acid sequence patterns dominate the heterogeneous phenotype for the collagen connective tissue disease Osteogenesis Imperfecta resulting from Gly mutations.

    Science.gov (United States)

    Xiao, Jianxi; Yang, Zhangfu; Sun, Xiuxia; Addabbo, Rayna; Baum, Jean

    2015-10-01

    Osteogenesis Imperfecta (OI), a hereditary connective tissue disease in collagen that arises from a single Gly → X mutation in the collagen chain, varies widely in phenotype from perinatal lethal to mild. It is unclear why there is such a large variation in the severity of the disease considering the repeating (Gly-X-Y)n sequence and the uniform rod-like structure of collagen. We systematically evaluate the effect of local (Gly-X-Y)n sequence around the mutation site on OI phenotype using integrated bio-statistical approaches, including odds ratio analysis and decision tree modeling. We show that different Gly → X mutations have different local sequence patterns that are correlated with lethal and nonlethal phenotypes providing a mechanism for understanding the sensitivity of local context in defining lethal and non-lethal OI. A number of important trends about which factors are related to OI phenotypes are revealed by the bio-statistical analyses; most striking is the complementary relationship between the placement of Pro residues and small residues and their correlation to OI phenotype. When Pro is present or small flexible residues are absent nearby a mutation site, the OI case tends to be lethal; when Pro is present or small flexible residues are absent further away from the mutation site, the OI case tends to be nonlethal. The analysis also reveals the dominant role of local sequence around mutation sites in the Major Ligand Binding Regions that are primarily responsible for collagen binding to its receptors and shows that non-lethal mutations are highly predicted by local sequence considerations alone whereas lethal mutations are not as easily predicted and may be a result of more complex interactions. Understanding the sequence determinants of OI mutations will enhance genetic counseling and help establish which steps in the collagen hierarchy to target for drug therapy.

  3. Genotype-phenotype heterogeneity of ganglion cell and inner plexiform layer deficit in autosomal-dominant optic atrophy

    DEFF Research Database (Denmark)

    Rönnbäck, Cecilia; Nissen, Claus; Almind, Gitte J;

    2015-01-01

    PURPOSE: To describe the thickness of the combined ganglion cell and inner plexiform layers (GC-IPL) and the peripapillary retinal nerve fibre layer (RNFL) in patients with OPA1 c.983A>G or c.2708_2711delTTAG autosomal-dominant optic atrophy (ADOA). METHODS: The study included 20 individuals with c...... measurement and high-definition optical coherence tomography. RESULTS: There was overlap in GC-IPL thickness in subjects younger than 20-30 years between the two new groups of ADOA patients and controls. Numerical decreases in GC-IPL thickness with age did not reach statistical significance in individuals...

  4. NEFL N98S mutation: another cause of dominant intermediate Charcot-Marie-Tooth disease with heterogeneous early-onset phenotype.

    Science.gov (United States)

    Berciano, José; Peeters, Kristien; García, Antonio; López-Alburquerque, Tomás; Gallardo, Elena; Hernández-Fabián, Arantxa; Pelayo-Negro, Ana L; De Vriendt, Els; Infante, Jon; Jordanova, Albena

    2016-02-01

    The purpose of this study was to describe a pedigree with NEFL N98S mutation associated with a dominant intermediate Charcot-Marie-Tooth disease (DI-CMT) and heterogeneous early-onset phenotype. The pedigree comprised two patients, the proband and her son, aged 38 and 5 years. The proband, evaluated at age 31, showed delayed motor milestones that, as of the second decade, evolved into severe phenotype consisting of sensorimotor neuropathy, pes cavus, clawing hands, gait and kinetic cerebellar ataxia, nystagmus and dysarthria, she being wheelchair bound. By then, a working diagnosis of sporadic early onset cerebellar ataxia with peripheral neuropathy was established. Screening of mutations associated with SCA and autosomal recessive cerebellar ataxias was negative. Her son showed a mild phenotype characterized by delayed motor milestones, and lower-limb hypotonia and areflexia. Electrophysiology in both patients showed nerve conduction slowing in the intermediate range, both in proximal and distal nerve segments, but where compound muscle action potentials exhibited severe attenuation there was conduction slowing down to the demyelinating range. In the proband, cranial magnetic resonance imaging (MRI) showed cerebellar atrophy, electromyography disclosed active denervation in tibialis anterior, and MRI of lower-limb musculature demonstrated widespread and distally accentuated muscle fatty atrophy; furthermore, on water sensitive MRI sequences there was edema of calf muscles. We conclude that the NEFL N98S mutation is associated with a DI-CMT phenotype characterized by early-onset sensorimotor neuropathy delaying motor milestones, which may evolve into a severe and complex clinical picture including cerebellar ataxia.

  5. Dominant negative phenotype of Bacillus thuringiensis Cry1Ab, Cry11Aa and Cry4Ba mutants suggest hetero-oligomer formation among different Cry toxins.

    Directory of Open Access Journals (Sweden)

    Daniela Carmona

    Full Text Available BACKGROUND: Bacillus thuringiensis Cry toxins are used worldwide in the control of different insect pests important in agriculture or in human health. The Cry proteins are pore-forming toxins that affect the midgut cell of target insects. It was shown that non-toxic Cry1Ab helix α-4 mutants had a dominant negative (DN phenotype inhibiting the toxicity of wildtype Cry1Ab when used in equimolar or sub-stoichiometric ratios (1∶1, 0.5∶1, mutant∶wt indicating that oligomer formation is a key step in toxicity of Cry toxins. METHODOLOGY/PRINCIPAL FINDINGS: The DN Cry1Ab-D136N/T143D mutant that is able to block toxicity of Cry1Ab toxin, was used to analyze its capacity to block the activity against Manduca sexta larvae of other Cry1 toxins, such as Cry1Aa, Cry1Ac, Cry1Ca, Cry1Da, Cry1Ea and Cry1Fa. Cry1Ab-DN mutant inhibited toxicity of Cry1Aa, Cry1Ac and Cry1Fa. In addition, we isolated mutants in helix α-4 of Cry4Ba and Cry11Aa, and demonstrate that Cry4Ba-E159K and Cry11Aa-V142D are inactive and completely block the toxicity against Aedes aegypti of both wildtype toxins, when used at sub-stoichiometric ratios, confirming a DN phenotype. As controls we analyzed Cry1Ab-R99A or Cry11Aa-E97A mutants that are located in helix α-3 and are affected in toxin oligomerization. These mutants do not show a DN phenotype but were able to block toxicity when used in 10∶1 or 100∶1 ratios (mutant∶wt probably by competition of binding with toxin receptors. CONCLUSIONS/SIGNIFICANCE: We show that DN phenotype can be observed among different Cry toxins suggesting that may interact in vivo forming hetero-oligomers. The DN phenotype cannot be observed in mutants affected in oligomerization, suggesting that this step is important to inhibit toxicity of other toxins.

  6. Phenotypic and genotypic characterization of lactic acid bacteria isolated from raw goat milk and effect of farming practices on the dominant species of lactic acid bacteria.

    Science.gov (United States)

    Tormo, Hélène; Ali Haimoud Lekhal, Djamila; Roques, C

    2015-10-01

    Lactic acid bacteria, in particular Lactococcus lactis, play a decisive role in the cheese making process and more particularly in lactic cheeses which are primarily produced on goat dairy farms. The objective of this study was therefore to identify the main lactic acid bacteria found in raw goats' milk from three different regions in France and evaluate if certain farming practices have an effect on the distribution of species of lactic acid bacteria in the various milk samples. Identification at genus or species level was carried out using phenotypic tests and genotypic methods including repetitive element REP-PCR, species-specific PCR and 16S rRNA gene sequencing. The distribution of the main bacterial species in the milk samples varied depending on farms and their characteristics. Out of the 146 strains identified, L. lactis was the dominant species (60% of strains), followed by Enterococcus (38%) of which Enterococcus faecalis and Enterococcus faecium. Within the species L. lactis, L. lactis subsp lactis was detected more frequently than L. lactis subsp cremoris (74% vs. 26%). The predominance of L. lactis subsp cremoris was linked to geographical area studied. It appears that the animals' environment plays a role in the balance between the dominance of L. lactis and enterococci in raw goats' milk. The separation between the milking parlor and the goat shed (vs no separation) and only straw in the bedding (vs straw and hay) seems to promote L. lactis in the milk (vs enterococci).

  7. Melhoramento do cafeeiro XXXVI: produtividade do café de porte pequeno com poda dos ramos inferiores Coffee breeding XXXVI: yielding capacity of semi-dwarf coffee trees before and after prunning of lower lateral branches

    Directory of Open Access Journals (Sweden)

    A. Carvalho

    1976-07-01

    Full Text Available Cafeeiros portadores dos fatores caturra (Ct, san ramon (Sr, laurina (Ir, dos cultivares pacas e villa sarchi e híbridos diversos foram estudados em Campinas, visando à seleção de cafeeiros de porte pequeno e de alta produtividade. Estudou-se também o efeito da poda de ramos inferiores sobre a produtividade e desenvolvimento das plantas. Utilizaram-se delineamento látice retangular triplo 5x6, 30 tratamentos, nove repetições, sendo as parcelas constituídas por duas covas, com uma planta por cova. As progênies derivadas do catuaí amarelo H 2077-2-12 e H 2077-2-5, que vêm sendo extensivamente cultivadas, apresentaram, em quatro anos, produções médias de 41,2, e 41,6 kg de café cereja, respectivamente. Os dados também mostraram que o caturra amarelo tem produção semelhante à dos cultivares pacas e villa sarchi. Entre as demais progênies analisadas, as de prefixo LCH 2077-2-5, H 2077-2-12-158, H 2077-2-5-47 e H 2077-2-12-283 salientaram-se quanto à produção no período de quatro anos. De modo geral, as progênies mais produtivas aos quatro anos foram aquelas que se destacaram por suas produções acumuladas aos seis anos. O mesmo ocorreu com as progênies menos produtivas. Após o quarto ano de colheita retiraram-se, ao acaso, em uma das plantas de cada parcela, todos os ramos inferiores até a altura de 60 cm, enquanto a outra planta permaneceu intacta. A média de produção de café cereja das plantas podadas foi de 7,1 kg e a das não podadas de 7,2 kg, no período de dois anos. A prática de retirada dos ramos laterais inferiores até 60 cm não contribuiu para alterar a produtividade e o desenvolvimento das plantas. Também não se verificou interação entre as produções das plantas podadas e não podadas, em relação aos tratamentos.Thirty coffee progenies homozygous or heterozygous for the genes caturra (Ct, San Ramon (Sr or laurina (lr were studied in Campinas to evaluate the yielding capacity of these semi-dwarf

  8. Morbidly obese human subjects have increased peripheral blood CD4+ T cells with skewing toward a Treg- and Th2-dominated phenotype.

    Science.gov (United States)

    van der Weerd, Kim; Dik, Willem A; Schrijver, Benjamin; Schweitzer, Dave H; Langerak, Anton W; Drexhage, Hemmo A; Kiewiet, Rosalie M; van Aken, Maarten O; van Huisstede, Astrid; van Dongen, Jacques J M; van der Lelij, Aart-Jan; Staal, Frank J T; van Hagen, P Martin

    2012-02-01

    Obesity is associated with local T-cell abnormalities in adipose tissue. Systemic obesity-related abnormalities in the peripheral blood T-cell compartment are not well defined. In this study, we investigated the peripheral blood T-cell compartment of morbidly obese and lean subjects. We determined all major T-cell subpopulations via six-color flow cytometry, including CD8+ and CD4+ T cells, CD4+ T-helper (Th) subpopulations, and natural CD4+CD25+FoxP3+ T-regulatory (Treg) cells. Moreover, molecular analyses to assess thymic output, T-cell proliferation (T-cell receptor excision circle analysis), and T-cell receptor-β (TCRB) repertoire (GeneScan analysis) were performed. In addition, we determined plasma levels of proinflammatory cytokines and cytokines associated with Th subpopulations and T-cell proliferation. Morbidly obese subjects had a selective increase in peripheral blood CD4+ naive, memory, natural CD4+CD25+FoxP3+ Treg, and Th2 T cells, whereas CD8+ T cells were normal. CD4+ and CD8+ T-cell proliferation was increased, whereas the TCRB repertoire was not significantly altered. Plasma levels of cytokines CCL5 and IL-7 were elevated. CD4+ T-cell numbers correlated positively with fasting insulin levels. The peripheral blood T-cell compartment of morbidly obese subjects is characterized by increased homeostatic T-cell proliferation to which cytokines IL-7 and CCL5, among others, might contribute. This is associated with increased CD4+ T cells, with skewing toward a Treg- and Th2-dominated phenotype, suggesting a more anti-inflammatory set point.

  9. Comprehensive genetic screening of KCNQ4 in a large autosomal dominant nonsyndromic hearing loss cohort: genotype-phenotype correlations and a founder mutation.

    Directory of Open Access Journals (Sweden)

    Takehiko Naito

    Full Text Available The present study of KCNQ4 mutations was carried out to 1 determine the prevalence by unbiased population-based genetic screening, 2 clarify the mutation spectrum and genotype/phenotype correlations, and 3 summarize clinical characteristics. In addition, a review of the reported mutations was performed for better understanding of this deafness gene. The screening using 287 probands from unbiased Japanese autosomal dominant nonsyndromic hearing loss (ADNSHL families identified 19 families with 7 different disease causing mutations, indicating that the frequency is 6.62% (19/287. While the majority were private mutations, one particular recurrent mutation, c.211delC, was observed in 13 unrelated families. Haplotype analysis in the vicinity of c.211delC suggests existence of a common ancestor. The majority of the patients showed all frequency, but high-frequency predominant, sensorineural hearing loss. The present study adds a new typical audiogram configuration characterized by mid-frequency predominant hearing loss caused by the p.V230E mutation. A variant at the N-terminal site (c. 211delC showed typical ski-slope type audiogram configuration. Concerning clinical features, onset age was from 3 to 40 years old, and mostly in the teens, and hearing loss was gradually progressive. Progressive nature is a common feature of patients with KCNQ4 mutations regardless of the mutation type. In conclusion, KCNQ4 mutations are frequent among ADNSHL patients, and therefore screening of the gene and molecular confirmation of these mutations have become important in the diagnosis of these conditions.

  10. Combining high-throughput phenotyping and genome-wide association studies to reveal natural genetic variation in rice.

    Science.gov (United States)

    Yang, Wanneng; Guo, Zilong; Huang, Chenglong; Duan, Lingfeng; Chen, Guoxing; Jiang, Ni; Fang, Wei; Feng, Hui; Xie, Weibo; Lian, Xingming; Wang, Gongwei; Luo, Qingming; Zhang, Qifa; Liu, Qian; Xiong, Lizhong

    2014-10-08

    Even as the study of plant genomics rapidly develops through the use of high-throughput sequencing techniques, traditional plant phenotyping lags far behind. Here we develop a high-throughput rice phenotyping facility (HRPF) to monitor 13 traditional agronomic traits and 2 newly defined traits during the rice growth period. Using genome-wide association studies (GWAS) of the 15 traits, we identify 141 associated loci, 25 of which contain known genes such as the Green Revolution semi-dwarf gene, SD1. Based on a performance evaluation of the HRPF and GWAS results, we demonstrate that high-throughput phenotyping has the potential to replace traditional phenotyping techniques and can provide valuable gene identification information. The combination of the multifunctional phenotyping tools HRPF and GWAS provides deep insights into the genetic architecture of important traits.

  11. 一个新的水稻半矮化小穗突变体的遗传分析与基因定位%Genetic Analysis and Gene Mapping of a New Semi-Dwarf and Small Panicle Mutant in Rice

    Institute of Scientific and Technical Information of China (English)

    汪庆; 汪得凯; 陶跃之

    2011-01-01

    A semi-dwarf and small panicle mutant was obtained from a japonica rice variety Zhonghua 11 through T-DNA transformation. The mutant, characterized by semi-dwarf plant, abnormal small and semi-enclosed panicle* and poor growth potential was designated as sd-sp2(semi-dwarf and small panicle 2). Genetic analysis indicated that the mutant was controlled by a single recessive gene. A genetic linkage map was constructed using an Fz mapping population derived from a cross between the sd-sp2 mutant and an indica variety Longtefu B on chromosome 6. The gene was finally located on a 116-kb region between the STS markers RH6-32 and RH6-40.where 14 ORFs were predicted based on Rice Genome Annotation.%从粳稻中花11转基因后代中发现了一个半矮化小穗突变体,表现为植株半矮化、生长势弱、半包茎穗、穗型变小等特点,将其命名为sd-sp2(semi-dwarf and small panicle 2).遗传分析显示,该突变体表型受1对隐性核基因控制.以sd-sp2突变体为母本与龙特甫B杂交构建F2分离群体,将该基因定位在水稻第6染色体的RH6-32和RH6-40之间的116 kb的物理距离内.通过水稻基因组注释系统在此区域预测到14个开放阅读框,未发现与已报道穗型发育相关基因的同源基因.

  12. Multidose Streptozotocin Induction of Diabetes in BALB/c Mice Induces a Dominant Oxidative Macrophage and a Conversion of TH1 to TH2 Phenotypes During Disease Progression

    Directory of Open Access Journals (Sweden)

    Naxin Sun

    2005-01-01

    Full Text Available Macrophages (Mp are implicated in both early and late phases in type 1 diabetes development. Recent study has suggested that a balance between reductive Mp (RMp and oxidative Mp (OMp is possible to regulate TH1/TH2 balance. The aim of this study is to investigate the redox status of peritoneal Mp and its cytokine profile during the development of autoimmune diabetes induced by multiple low-dose streptozotocin in BALB/c mice. Meanwhile, the polarization of TH1/TH2 of splenocytes or thymocytes was also examined. We found that peritoneal Mp appeared as an “incomplete” OMp phenotype with decreased icGSH along with disease progression. The OMp showed reduced TNF-α, IL-12, and NO production as well as defective phagocytosis activity compared to nondiabetic controls; however, there was no significant difference with IL-6 production. On the other hand, the levels of IFN-γ or IL-4 of splenocytes in diabetic mice were significantly higher compared to the control mice. The ratio of IFN-γ to IL-4 was also higher at the early stage of diabetes and then declined several weeks later after the occurrence of diabetes, suggesting a pathogenetic TH1 phenotype from the beginning gradually to a tendency of TH2 during the development of diabetes. Our results implied that likely OMp may be relevant in the development of type 1 diabetes; however, it is not likely the only factor regulating the TH1H/TH2 balance in MLD-STZ-induced diabetic mice.

  13. Genotype-phenotype correlation for DFNA22: characterization of non-syndromic, autosomal dominant, progressive sensorineural hearing loss due to MYO6 mutations

    DEFF Research Database (Denmark)

    Tranebjærg, Lisbeth; Rendtorff, Nanna D; Topsakal, Vedat;

    2010-01-01

    Clinical and audiological examination was done in 2 Belgian families with autosomal dominant sensorineural hearing loss (SNHL) linked to DFNA22. Nineteen subjects in family 1 had mild to moderate SNHL starting in the third decade. The hearing loss was characterized by a flat audiogram affecting all...... tested frequencies with statistically significant progression. In family 2 eleven subjects were affected with mild to moderate SNHL starting in the second decade. Most of them showed a flat audiogram, but some had mid-frequency hearing loss. Significant progression of thresholds was present at 4 and 8 k...

  14. CD8+ regulatory T cells, and not CD4+ T cells, dominate suppressive phenotype and function after in vitro live Mycobacterium bovis-BCG activation of human cells.

    Science.gov (United States)

    Boer, Mardi C; van Meijgaarden, Krista E; Joosten, Simone A; Ottenhoff, Tom H M

    2014-01-01

    Mycobacterium bovis bacillus Calmette-Guérin (M. bovis BCG), the only currently available vaccine against tuberculosis, has been reported to induce regulatory T cells in humans. The activity of regulatory T cells may not only dampen immunogenicity and protective efficacy of tuberculosis-vaccines, but also hamper diagnosis of infection of tuberculosis, when using immune (e.g. IFNγ-release) assays. Still, in settings of infectious diseases and vaccination, most studies have focused on CD4+ regulatory T cells, and not CD8+ regulatory T-cells. Here, we present a comparative analysis of the suppressive phenotype and function of CD4+ versus CD8+ T cells after in vitro live BCG activation of human cells. Moreover, as BCG is administered as a (partly) live vaccine, we also compared the ability of live versus heatkilled BCG in activating CD4+ and CD8+ regulatory T cell responses. BCG-activated CD8+ T cells consistently expressed higher levels of regulatory T cell markers, and after live BCG activation, density and (co-)expression of markers were significantly higher, compared to CD4+ T cells. Furthermore, selection on CD25-expression after live BCG activation enriched for CD8+ T cells, and selection on co-expression of markers further increased CD8+ enrichment. Ultimately, only T cells activated by live BCG were functionally suppressive and this suppressive activity resided predominantly in the CD8+ T cell compartment. These data highlight the important contribution of live BCG-activated CD8+ Treg cells to immune regulation and emphasize their possible negative impact on immunity and protection against tuberculosis, following BCG vaccination.

  15. Phenotypic variability in a seven-generation Swedish family segregating autosomal dominant hearing impairment due to a novel EYA4 frameshift mutation.

    Science.gov (United States)

    Frykholm, Carina; Klar, Joakim; Arnesson, Hanna; Rehnman, Anna-Carin; Lodahl, Marianne; Wedén, Ulla; Dahl, Niklas; Tranebjærg, Lisbeth; Rendtorff, Nanna D

    2015-05-25

    Linkage to an interval overlapping the DFNA10 locus on chromosome 6q22-23 was found through genome wide linkage analysis in a seven-generation Swedish family segregating postlingual, autosomal dominant nonsyndromic sensorineural hearing impairment. A novel heterozygous frame-shift mutation (c.579_580insTACC, p.(Asp194Tyrfs*52)) in EYA4 was identified that truncates the so-called variable region of the protein. The mutation is predicted to result in haploinsufficiency of the EYA4 product. No evidence for dilated cardiomyopathy was found in the family, contrasting to a previous family with a deletion resulting in a similar truncation in the variable region. A highly variable age of onset was seen in the mutation carriers. For assessment of the aetiology of this variability, clinical and audiometric data analyses were performed. The affected family members all had similar cross-sectional and longitudinal deterioration of pure tone average (PTA) once the process of hearing deterioration had started, and no gender, parent-of-origin or family branch differences on PTA could be found. Age at onset varied between the family branches. In summary, this is the ninth published genetically verified DFNA10 family. The results imply that unidentified factors, genetic or environmental, other than the EYA4 mutation, are of importance for the age at onset of DFNA10, and that mutation early in the variable region of the EYA4 protein can occur in the absence of dilated cardiomyopathy.

  16. Phenotypic and genotypic characterization of Brucella strains isolated from autochthonous livestock reveals the dominance of B. abortus biovar 3a in Nigeria.

    Science.gov (United States)

    Bertu, Wilson J; Ducrotoy, Marie J; Muñoz, Pilar M; Mick, Virginie; Zúñiga-Ripa, Amaia; Bryssinckx, Ward; Kwaga, Jacob K P; Kabir, Junaid; Welburn, Susan C; Moriyón, Ignacio; Ocholi, Reuben A

    2015-10-22

    Brucellosis is a worldwide widespread zoonosis caused by bacteria of the genus Brucella. Control of this disease in a given area requires an understanding of the Brucella species circulating in livestock and humans. However, because of the difficulties intrinsic to Brucella isolation and typing, such data are scarce for resource-poor areas. The paucity of bacteriological data and the consequent imperfect epidemiological picture are particularly critical for Sahelian and Sub-Sahara African countries. Here, we report on the characterization of 34 isolates collected between 1976 and 2012 from cattle, sheep and horses in Nigeria. All isolates were identified as Brucella abortus by Bruce-ladder PCR and assigned to biovar 3 by conventional typing. Further analysis by enhanced AMOS-ERY PCR showed that all of them belonged to the 3a sub-biovar, and MLVA analysis grouped them in a cluster clearly distinct from that formed by European B. abortus biovar 3b strains. Nevertheless, MLVA detected heterogeneity within the Nigerian biovar 3a strains. The close genetic profiles of the isolates from cattle, sheep and horses, suggest that, at least in some parts of Nigeria, biovar 3a circulates among animal species that are not the preferential hosts of B. abortus. Consistent with previous genetic analyses of 7 strains from Ivory Cost, Gambia and Togo, the analysis of these 34 Nigerian strains supports the hypothesis that the B. abortus biovar 3a lineage is dominant in West African countries.

  17. Autosomal dominant osteopetrosis revisited

    DEFF Research Database (Denmark)

    Bollerslev, Jens; Henriksen, Kim; Nielsen, Morten Frost Munk

    2013-01-01

    Systematic studies of autosomal dominant osteopetrosis (ADO) were followed by the identification of underlying mutations giving unique possibilities to perform translational studies. What was previously designated ADO1 turned out to be a high bone mass phenotype caused by a missense mutation...

  18. Dominantly-inherited lop ears.

    Science.gov (United States)

    Leung, Alexander K C; Kong, Albert Y F; Robson, W Lane M; McLeod, D Ross

    2007-10-01

    We describe a four-generation Chinese family that included five members who had an isolated bilateral lop ear anomaly. The presentation suggested a dominant mode of inheritance. The absence of male-to-male transmission does not exclude an X-linked dominant mode of inheritance. Since the phenotypic anomaly of the male proband was no more severe than the affected female members, an autosomal dominant mode of inheritance is most likely. 2007 Wiley-Liss, Inc

  19. Additivity dominance

    Directory of Open Access Journals (Sweden)

    Paul Rozin

    2009-10-01

    Full Text Available Judgments of naturalness of foods tend to be more influenced by the process history of a food, rather than its actual constituents. Two types of processing of a ``natural'' food are to add something or to remove something. We report in this study, based on a large random sample of individuals from six countries (France, Germany, Italy, Switzerland, UK and USA that additives are considered defining features of what makes a food not natural, whereas ``subtractives'' are almost never mentioned. In support of this, skim milk (with major subtraction of fat is rated as more natural than whole milk with a small amount of natural vitamin D added. It is also noted that ``additives'' is a common word, with a synonym reported by a native speaker in 17 of 18 languages, whereas ``subtractive'' is lexicalized in only 1 of the 18 languages. We consider reasons for additivity dominance, relating it to omission bias, feature positive bias, and notions of purity.

  20. Domination, Eternal Domination, and Clique Covering

    Directory of Open Access Journals (Sweden)

    Klostermeyer William F.

    2015-05-01

    Full Text Available Eternal and m-eternal domination are concerned with using mobile guards to protect a graph against infinite sequences of attacks at vertices. Eternal domination allows one guard to move per attack, whereas more than one guard may move per attack in the m-eternal domination model. Inequality chains consisting of the domination, eternal domination, m-eternal domination, independence, and clique covering numbers of graph are explored in this paper.

  1. Sex-linked dominant

    Science.gov (United States)

    Inheritance - sex-linked dominant; Genetics - sex-linked dominant; X-linked dominant; Y-linked dominant ... can be either an autosomal chromosome or a sex chromosome. It also depends on whether the trait ...

  2. Mouse phenotyping.

    Science.gov (United States)

    Fuchs, Helmut; Gailus-Durner, Valérie; Adler, Thure; Aguilar-Pimentel, Juan Antonio; Becker, Lore; Calzada-Wack, Julia; Da Silva-Buttkus, Patricia; Neff, Frauke; Götz, Alexander; Hans, Wolfgang; Hölter, Sabine M; Horsch, Marion; Kastenmüller, Gabi; Kemter, Elisabeth; Lengger, Christoph; Maier, Holger; Matloka, Mikolaj; Möller, Gabriele; Naton, Beatrix; Prehn, Cornelia; Puk, Oliver; Rácz, Ildikó; Rathkolb, Birgit; Römisch-Margl, Werner; Rozman, Jan; Wang-Sattler, Rui; Schrewe, Anja; Stöger, Claudia; Tost, Monica; Adamski, Jerzy; Aigner, Bernhard; Beckers, Johannes; Behrendt, Heidrun; Busch, Dirk H; Esposito, Irene; Graw, Jochen; Illig, Thomas; Ivandic, Boris; Klingenspor, Martin; Klopstock, Thomas; Kremmer, Elisabeth; Mempel, Martin; Neschen, Susanne; Ollert, Markus; Schulz, Holger; Suhre, Karsten; Wolf, Eckhard; Wurst, Wolfgang; Zimmer, Andreas; Hrabě de Angelis, Martin

    2011-02-01

    Model organisms like the mouse are important tools to learn more about gene function in man. Within the last 20 years many mutant mouse lines have been generated by different methods such as ENU mutagenesis, constitutive and conditional knock-out approaches, knock-down, introduction of human genes, and knock-in techniques, thus creating models which mimic human conditions. Due to pleiotropic effects, one gene may have different functions in different organ systems or time points during development. Therefore mutant mouse lines have to be phenotyped comprehensively in a highly standardized manner to enable the detection of phenotypes which might otherwise remain hidden. The German Mouse Clinic (GMC) has been established at the Helmholtz Zentrum München as a phenotyping platform with open access to the scientific community (www.mousclinic.de; [1]). The GMC is a member of the EUMODIC consortium which created the European standard workflow EMPReSSslim for the systemic phenotyping of mouse models (http://www.eumodic.org/[2]). Copyright © 2010 Elsevier Inc. All rights reserved.

  3. Phenotype Diversity and Dominant Species of Yeasts during Spontaneous Fermentation Process of Musalais from Xinjiang%新疆慕萨莱思自然发酵过程中酵母菌表型多样性及优势菌分析

    Institute of Scientific and Technical Information of China (English)

    朱丽霞; 李红梅; 郭东起; 侯旭杰; 龚明福

    2012-01-01

    Objective: To investigate the phenotype diversity and dominant species of yeasts during spontaneous fermentation process of Musalais from Xinjiang, and explore the effect of traditional technology on yeast community. Methods: A total of 19 samples were collected from the traditional spontaneous fermentation process of Musalals (including grapes, grape juice, boiled juice and fermentation broth) to analyze yeast phenotype diversity and corresponding dominant species. The isolated strains from these samples were typed and representative strains were selected for colony characteristic analysis on Wallerstein laboratory nutrient agar (WL nutrient agar) and grouped by unweighted pair group method with arithmetic mean (UPGMA) method and primarily identified according to their morphological and physiological characteristics. Results: Totally 217 isolates, 13 types based on WL agar culture, and 8 phenotype groups from 13 representative strains were harvested. Meanwhile, 7 generaand 13 species were primarily identified. The diversity of yeasts was associated with spontaneous fermentation of Musalais. Hanseniaspora spp. was the dominant strain in grape skin, grape juice and boiled grape juice. Saccharomyces cerevisiae is a starter and the only dominant strain during spontaneous fermentation of Musalais; however, other yeast species were also occasionally observed in fermentation broth. Conclusion: Almost all yeasts from grapes are killed by boiling during the production of Musalais. S. cerevisiae may come from brewing utensils and locations, and has high adaptability to spontaneous fermentation of Musalais.%目的:研究新疆慕萨莱思自然发酵过程中酵母菌种群表型多样性与其优势菌,探讨慕萨莱思传统工艺对其主要菌群结构的影响。方法:来自于新疆阿瓦提一古作坊的慕萨莱思酿制原料、原料处理液及发酵液(自然发酵过程中)共19份样品被用于酵母菌分离,分离株利

  4. Topics on domination

    CERN Document Server

    Hedetniemi, ST

    1991-01-01

    The contributions in this volume are divided into three sections: theoretical, new models and algorithmic. The first section focuses on properties of the standard domination number &ggr;(G), the second section is concerned with new variations on the domination theme, and the third is primarily concerned with finding classes of graphs for which the domination number (and several other domination-related parameters) can be computed in polynomial time.

  5. Dominance in domestic dogs

    NARCIS (Netherlands)

    Borg, Van Der J.A.M.; Schilder, M.B.H.; Vinke, C.M.; Vries, De Han; Petit, Odile

    2015-01-01

    A dominance hierarchy is an important feature of the social organisation of group living animals. Although formal and/or agonistic dominance has been found in captive wolves and free-ranging dogs, applicability of the dominance concept in domestic dogs is highly debated, and quantitative data are

  6. Total well dominated trees

    DEFF Research Database (Denmark)

    Finbow, Arthur; Frendrup, Allan; Vestergaard, Preben D.

    cardinality then G is a total well dominated graph. In this paper we study composition and decomposition of total well dominated trees. By a reversible process we prove that any total well dominated tree can both be reduced to and constructed from a family of three small trees....

  7. Dominance in domestic dogs

    NARCIS (Netherlands)

    Borg, Van Der J.A.M.; Schilder, M.B.H.; Vinke, C.M.; Vries, De Han; Petit, Odile

    2015-01-01

    A dominance hierarchy is an important feature of the social organisation of group living animals. Although formal and/or agonistic dominance has been found in captive wolves and free-ranging dogs, applicability of the dominance concept in domestic dogs is highly debated, and quantitative data are

  8. Dominating Sets and Domination Polynomials of Paths

    Directory of Open Access Journals (Sweden)

    Saeid Alikhani

    2009-01-01

    Full Text Available Let G=(V,E be a simple graph. A set S⊆V is a dominating set of G, if every vertex in V\\S is adjacent to at least one vertex in S. Let 𝒫ni be the family of all dominating sets of a path Pn with cardinality i, and let d(Pn,j=|𝒫nj|. In this paper, we construct 𝒫ni, and obtain a recursive formula for d(Pn,i. Using this recursive formula, we consider the polynomial D(Pn,x=∑i=⌈n/3⌉nd(Pn,ixi, which we call domination polynomial of paths and obtain some properties of this polynomial.

  9. 先天性非进展性常染色体显性遗传非综合症型耳聋家系临床表型特征分析%Phenotype characteristics of a Chinese family with congenital, stable, autosomal dominant non-syndromic sensorineural hearing loss

    Institute of Scientific and Technical Information of China (English)

    郭亿莲; 赖海彪; 袁慧军; 李征玥; 何琦; 孙一帆; 徐庆文; 周小军; 张丽娟; 王明松; 孔祥廉

    2011-01-01

    目的 一个连续三代的常染色体显性遗传先天性非进展性非综合症型耳聋家系的临床听力学特征及遗传规律.方法 对耳聋家系成员进行病史采集、体格检查、纯音测听、声导抗、听性脑干反应检测,其中一名患者进行颞骨CT扫描检查.绘制遗传图谱并进行遗传学特征分析.结果 该家系成员共计18人,耳聋患者11人,其中一例为氨基糖苷类药物致聋患者.该耳聋家系每代及男女均有发病,非药物致聋患者均表现为语前聋、平稳型、全频中度听力下降,听力曲线呈平坦型.结论 该家系遗传方式符合常染色体显性遗传规律,表现为全频中度感音神经性耳聋.该研究为下一步的致聋基因的定位与鉴定奠定了良好的工作基础.%Objective To study the phenotypes and genetic characteristics of a three-generation Chinese family with autosomal dominant inherited progressive nonsyndromic hearing loss. Methods Pedigree was drawn after the investigation. Eighteen family members were examined including detailed audiology tesing (pure tone assay, acoustic immittance testing and auditory brainstem response audiometry). One patient received temporal bone CT. Results This family was comprised of 18 members, of whom 11 were affected. One patient had a history of using aminoglycosides. The pattern of inheritance of this family was autosomal dominant based on the investigation information. The affected members showed pre-lingual, stable, bilateral moderate sensorineural hearing impairment involving all frequencies. The audiograms showed generally flat hearing loss. Conclusion Pedigree analysis suggests an autosomal dominant hereditary pattern in this family. The information from this study will facilitate linkage analysis and positional cloning for identifying the causative gene in this family.

  10. Autosomal dominant lamellar ichthyosis.

    Science.gov (United States)

    Toribio, J; Fernández Redondo, V; Peteiro, C; Zulaica, A; Fabeiro, J M

    1986-08-01

    Five members of two generations of one family were affected with lamellar ichthyosis, suggesting autosomal dominant transmission. The clinical and histopathological characteristics of the cases described here are similar to those reported by Traupe et al. (1984) as autosomal dominant lamellar ichthyosis and thus confirm the existence of this new form of ichthyosis.

  11. Clinical neurogenetics: autosomal dominant spinocerebellar ataxia.

    Science.gov (United States)

    Shakkottai, Vikram G; Fogel, Brent L

    2013-11-01

    The autosomal dominant spinocerebellar ataxias are a diverse and clinically heterogeneous group of disorders characterized by degeneration and dysfunction of the cerebellum and its associated pathways. Clinical and diagnostic evaluation can be challenging because of phenotypic overlap among causes, and a stratified and systematic approach is essential. Recent advances include the identification of additional genes causing dominant genetic ataxia, a better understanding of cellular pathogenesis in several disorders, the generation of new disease models that may stimulate development of new therapies, and the use of new DNA sequencing technologies, including whole-exome sequencing, to improve diagnosis.

  12. Downhill Domination in Graphs

    OpenAIRE

    Haynes Teresa W.; Hedetniemi Stephen T.; Jamieson Jessie D.; Jamieson William B.

    2014-01-01

    A path π = (v1, v2, . . . , vk+1) in a graph G = (V,E) is a downhill path if for every i, 1 ≤ i ≤ k, deg(vi) ≥ deg(vi+1), where deg(vi) denotes the degree of vertex vi ∈ V. The downhill domination number equals the minimum cardinality of a set S ⊆ V having the property that every vertex v ∈ V lies on a downhill path originating from some vertex in S. We investigate downhill domination numbers of graphs and give upper bounds. In particular, we show that the downhill domination number of a grap...

  13. Downhill Domination in Graphs

    Directory of Open Access Journals (Sweden)

    Haynes Teresa W.

    2014-08-01

    Full Text Available A path π = (v1, v2, . . . , vk+1 in a graph G = (V,E is a downhill path if for every i, 1 ≤ i ≤ k, deg(vi ≥ deg(vi+1, where deg(vi denotes the degree of vertex vi ∈ V. The downhill domination number equals the minimum cardinality of a set S ⊆ V having the property that every vertex v ∈ V lies on a downhill path originating from some vertex in S. We investigate downhill domination numbers of graphs and give upper bounds. In particular, we show that the downhill domination number of a graph is at most half its order, and that the downhill domination number of a tree is at most one third its order. We characterize the graphs obtaining each of these bounds

  14. Dominantly Inherited Nemaline Myopathy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2003-08-01

    Full Text Available A locus on chromosome 15q21-23 for a dominantly inherited nemaline myopathy with core-like lesions is reported in two unrelated families evaluated at University Medical Center, Nijmegen, The Netherlands.

  15. Dominant Voice in Hamlet

    Institute of Scientific and Technical Information of China (English)

    李丹

    2015-01-01

    <正>The Tragedy of Hamlet dramatizes the revenge Prince Hamlet exacts on his uncle Claudius for murdering King Hamlet,Claudius’s brother and Prince Hamlet’s father,and then succeeding to the throne and taking as his wife Gertrude,the old king’s widow and Prince Hamlet’s mother.This paper will discuss something about dominant voice in the play.Dominant voice is the major voice in the country,the society,or the whole world.Those people who have the power or

  16. Dominant cystoid macular dystrophy

    NARCIS (Netherlands)

    Saksens, N.T.M.; Huet, R.A.C. van; Lith-Verhoeven, J.J. van; Hollander, A.I. den; Hoyng, C.B.; Boon, C.J.

    2015-01-01

    OBJECTIVE: To describe the clinical characteristics and long-term follow-up in patients with autosomal dominant cystoid macular dystrophy (DCMD). DESIGN: Retrospective case series. PARTICIPANTS: Ninety-seven patients with DCMD. METHODS: Extensive ophthalmic examination, including visual acuity (VA),

  17. Iron dominated magnets

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, G.E.

    1985-07-01

    These two lectures on iron dominated magnets are meant for the student of accelerator science and contain general treatments of the subjects design and construction. The material is arranged in the categories: General Concepts and Cost Considerations, Profile Configuration and Harmonics, Magnetic Measurements, a few examples of ''special magnets'' and Materials and Practices. Extensive literature is provided.

  18. discourse of domination

    African Journals Online (AJOL)

    suffering justifies the position and work of The Bank and other social forces with similar ... include accounts of the growing and increasingly interwoven resistance in .... tural domination or as parasites able to feed off a social body weakened by the ... through objective analysis of poor people's descriptions of their realities'.

  19. Searching for world domination

    CERN Multimedia

    Quillen, E

    2004-01-01

    "Optimists might believe Microsoft suffered a setback last week that will impede its progress toward world domination, but I suspect the company has already found a way to prevail. At issue before the European Union was Microsoft's bundling of its Windows Media Player with its operating system" (1 page)

  20. Dominant optic atrophy

    DEFF Research Database (Denmark)

    Lenaers, Guy; Hamel, Christian; Delettre, Cécile

    2012-01-01

    DEFINITION OF THE DISEASE: Dominant Optic Atrophy (DOA) is a neuro-ophthalmic condition characterized by a bilateral degeneration of the optic nerves, causing insidious visual loss, typically starting during the first decade of life. The disease affects primary the retinal ganglion cells (RGC...

  1. Dominantly inherited isolated hyperparathyroidism: a syndromic association?

    Energy Technology Data Exchange (ETDEWEB)

    Kozlowski, K. [Department of Radiology, Royal Alexandra Hospital for Children, Sydney (Australia)]|[Department of Radiology, New Children`s Hospital, PO Box 3515, Parramatta, NSW 2124 (Australia); Czerminska-Kowalska, A. [Department of Radiology, Children`s Memorial Health Institute, Warsaw (Poland); Kulczycka, H.; Rowinska, E.; Pronicka, E. [Department of Metabolism, Children`s Memorial Health Institute, Warsaw (Poland)

    1999-01-01

    Dominantly inherited isolated hyperparathyroidism (DIIH) is rare in childhood. It may be the first biochemical abnormality in the multiple endocrine neoplasia type I (MEN I) and type II (MEN II) syndromes. Its clinical course is usually asymptomatic or of low morbidity. Radiographic examination is most often normal. We describe six members of a family with distinctive phenotype and DIIH. Limited systemic symptoms and severe radiographic osteitis fibrosa cystica were further unusual features in this family. The diagnosis of DIIH was made only after a 9-year-old girl developed hypercalcaemic crisis after a pathological femoral fracture. Distinctive phenotype, unusual clinical course and unparalleled radiographic changes suggest a not yet described syndromic association. (orig.) With 7 figs., 3 tabs., 23 refs.

  2. Dominance Genetic Variance for Traits Under Directional Selection in Drosophila serrata

    Science.gov (United States)

    Sztepanacz, Jacqueline L.; Blows, Mark W.

    2015-01-01

    In contrast to our growing understanding of patterns of additive genetic variance in single- and multi-trait combinations, the relative contribution of nonadditive genetic variance, particularly dominance variance, to multivariate phenotypes is largely unknown. While mechanisms for the evolution of dominance genetic variance have been, and to some degree remain, subject to debate, the pervasiveness of dominance is widely recognized and may play a key role in several evolutionary processes. Theoretical and empirical evidence suggests that the contribution of dominance variance to phenotypic variance may increase with the correlation between a trait and fitness; however, direct tests of this hypothesis are few. Using a multigenerational breeding design in an unmanipulated population of Drosophila serrata, we estimated additive and dominance genetic covariance matrices for multivariate wing-shape phenotypes, together with a comprehensive measure of fitness, to determine whether there is an association between directional selection and dominance variance. Fitness, a trait unequivocally under directional selection, had no detectable additive genetic variance, but significant dominance genetic variance contributing 32% of the phenotypic variance. For single and multivariate morphological traits, however, no relationship was observed between trait–fitness correlations and dominance variance. A similar proportion of additive and dominance variance was found to contribute to phenotypic variance for single traits, and double the amount of additive compared to dominance variance was found for the multivariate trait combination under directional selection. These data suggest that for many fitness components a positive association between directional selection and dominance genetic variance may not be expected. PMID:25783700

  3. Dominating biological networks.

    Directory of Open Access Journals (Sweden)

    Tijana Milenković

    Full Text Available Proteins are essential macromolecules of life that carry out most cellular processes. Since proteins aggregate to perform function, and since protein-protein interaction (PPI networks model these aggregations, one would expect to uncover new biology from PPI network topology. Hence, using PPI networks to predict protein function and role of protein pathways in disease has received attention. A debate remains open about whether network properties of "biologically central (BC" genes (i.e., their protein products, such as those involved in aging, cancer, infectious diseases, or signaling and drug-targeted pathways, exhibit some topological centrality compared to the rest of the proteins in the human PPI network.To help resolve this debate, we design new network-based approaches and apply them to get new insight into biological function and disease. We hypothesize that BC genes have a topologically central (TC role in the human PPI network. We propose two different concepts of topological centrality. We design a new centrality measure to capture complex wirings of proteins in the network that identifies as TC those proteins that reside in dense extended network neighborhoods. Also, we use the notion of domination and find dominating sets (DSs in the PPI network, i.e., sets of proteins such that every protein is either in the DS or is a neighbor of the DS. Clearly, a DS has a TC role, as it enables efficient communication between different network parts. We find statistically significant enrichment in BC genes of TC nodes and outperform the existing methods indicating that genes involved in key biological processes occupy topologically complex and dense regions of the network and correspond to its "spine" that connects all other network parts and can thus pass cellular signals efficiently throughout the network. To our knowledge, this is the first study that explores domination in the context of PPI networks.

  4. Challenging Credit Dominance

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    @@ Europe's widening sovereign debt crisis has brought independent credit ratings to the forefront of the EU's agenda.To directly address the mat ter,the EU announced plans to set up a European creditrating authority for sovereign debt ratings on April 30.This marked a milestone in the international credit history,and the beginning of changes to U.S.-dominated international credit ratings and the pattern of international politics and economics,said Sun Zhe,Director of the Center for U.S.

  5. 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

  6. 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

  7. Microglia phenotype diversity

    NARCIS (Netherlands)

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

    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

  8. Rings dominate western Gulf

    Science.gov (United States)

    Vidal L., Francisco V.; Vidal L., Victor M. V.; Molero, José María Pérez

    Surface and deep circulation of the central and western Gulf of Mexico is controlled by interactions of rings of water pinched from the gulf's Loop Current. The discovery was made by Mexican oceanographers who are preparing a full-color, 8-volume oceanographic atlas of the gulf.Anticyclonic warm-core rings pinch off the Loop Current at a rate of about one to two per year, the scientists of the Grupo de Estudios Oceanográficos of the Instituto de Investigaciones Eléctricas (GEO-IIE) found. The rings migrate west until they collide with the continental shelf break of the western gulf, almost always between 22° and 23°N latitude. On their westward travel they transfer angular momentum and vorticity to the surrounding water, generating cyclonic circulations and vortex pairs that completely dominate the entire surface and deep circulation of the central and western gulf.

  9. Dominant modal decomposition method

    Science.gov (United States)

    Dombovari, Zoltan

    2017-03-01

    The paper deals with the automatic decomposition of experimental frequency response functions (FRF's) of mechanical structures. The decomposition of FRF's is based on the Green function representation of free vibratory systems. After the determination of the impulse dynamic subspace, the system matrix is formulated and the poles are calculated directly. By means of the corresponding eigenvectors, the contribution of each element of the impulse dynamic subspace is determined and the sufficient decomposition of the corresponding FRF is carried out. With the presented dominant modal decomposition (DMD) method, the mode shapes, the modal participation vectors and the modal scaling factors are identified using the decomposed FRF's. Analytical example is presented along with experimental case studies taken from machine tool industry.

  10. 一个迟发性非综合征型常染色体显性遗传性聋家系表型特征及致病基因初步探讨%A Preliminary Study of Phenotypic Characteristics and Causative Genes in a Family with Late-onset Nonsyndromic Autosomal Dominant Hereditary Hearing Loss

    Institute of Scientific and Technical Information of China (English)

    王鸿涵; 刘亚兰; 卢焰梅; 贺楚峰; 冯永; 王行炜; 梅凌云; 陈红胜; 蒋璐; 门美超; 张华; 李海波

    2012-01-01

    Objective To analyze the clinical phenotype of a pedigree with late - onset hereditary hearing loss, and investigate the disease- causing genes of this family. Methods The detailed medical history information of the participants in a large Hunan Province family with hereditary hearing loss were collected. Physical and augdio logical examination were administered.Two individuals were carried out Computed tomography (CT) scan of the temporal bone, The participants' inrormation was sorted, out and the geoalogica tree map was charted. Alter revie wiog the literature, we speculated oo geoes that could lead to desfness sccordiog to pheootype of this family. Some candidate geoes codiog regioo were amplified by polymerase chain reaction (PCR) using geocmic DNA which was extracted from the proband's peripheral blood. PCR products were purified by exopeptidase. Ao ABI 3730XL geoetic soslyzer was used for direct sequeociog, and data was analyzed usiog DNASTAR-Lasergeoe SeqMan Pro software. Results The family tree showed that this was 30 autosomal domioant non-syodromic deafoess pedigree. Clioical fea tures were remarkably similar amoog subjects. All of them were operated oo for "buzz-like" tinnitus between 9 and 25 years old, and then for bilateral hearing loss. Pure tone audiometry examination showed the hearing loss be gan at the higher frequencies,then the lower frequencies with the aggravation of hearing loss. Conclusion Pedigree analysis suggested this family conformed to the characteristics of autosomal dominant hereditary pattern. The causa tive gene of this family needs more exploration.%目的 分析一个迟发性遗传性聋大家系的临床表型,探讨该家系耳聋患者的致病基因.方法 对一个湖南籍耳聋大家系成员进行详细的病史资料采集、体格检查、听力学检查,其中两名患者做了颞骨CT检查.绘制家系图.以先证者外周血基因组DNA为模板对候选致病基因进行涵盖全部编码序列聚

  11. Spotted phenotypes in horses lost attractiveness in the Middle Ages

    DEFF Research Database (Denmark)

    Wutke, Saskia; Benecke, Norbert; Sandoval-Castellanos, Edson

    2016-01-01

    were influenced by humans. Our results from genotype analyses show a significant increase in spotted coats in early domestic horses (Copper Age to Iron Age). In contrast, medieval horses carried significantly fewer alleles for these phenotypes, whereas solid phenotypes (i.e., chestnut) became dominant...

  12. Onset dominance in lateralization.

    Science.gov (United States)

    Freyman, R L; Zurek, P M; Balakrishnan, U; Chiang, Y C

    1997-03-01

    Saberi and Perrott [Acustica 81, 272-275 (1995)] found that the in-head lateralization of a relatively long-duration pulse train could be controlled by the interaural delay of the single pulse pair that occurs at onset. The present study examined this further, using an acoustic pointer measure of lateralization, with stimulus manipulations designed to determine conditions under which lateralization was consistent with the interaural onset delay. The present stimuli were wideband pulse trains, noise-burst trains, and inharmonic complexes, 250 ms in duration, chosen for the ease with which interaural delays and correlations of select temporal segments of the stimulus could be manipulated. The stimulus factors studied were the periodicity of the ongoing part of the signal as well as the multiplicity and ambiguity of interaural delays. The results, in general, showed that the interaural onset delay controlled lateralization when the steady state binaural cues were relatively weak, either because the spectral components were only sparsely distributed across frequency or because the interaural time delays were ambiguous. Onset dominance can be disrupted by sudden stimulus changes within the train, and several examples of such changes are described. Individual subjects showed strong left-right asymmetries in onset effectiveness. The results have implications for understanding how onset and ongoing interaural delay cues contribute to the location estimates formed by the binaural auditory system.

  13. [Autosomal dominant cerebellar ataxias in the Netherlands: a national inventory

    NARCIS (Netherlands)

    Warrenburg, B.P.C. van de

    2001-01-01

    OBJECTIVE: To provide a comprehensive estimate of the number of Dutch autosomal dominant cerebellar ataxias (ADCA) families and patients and thus estimate the minimal prevalence of ADCA in the Netherlands. Furthermore, to observe the relative frequency of SCA mutations and to study genotype-phenotyp

  14. The dominance of norm

    Directory of Open Access Journals (Sweden)

    Edward L. Rubin

    2017-06-01

    Full Text Available Objective to revisit the debate about rational choice theory from the legal cultural and historical perspectives. Methods dialectic approach to the cognition of social phenomena allowing to analyze them in their historical development and functioning in the context of the integrity of subjective and objective factors this determines the choice of the research methods systemicstructural formallegal and comparative. Results The first part of this chapter will explain the way in which people in societies different from our own were subject to other motivations in situations where selfinterest would tend to dominate in our society. The reasoning is based on three examples one drawn from the history of Ancient Rome one from the High Middle Ages of the European society and one from a contemporary nonWestern culture. The second part of the chapter analyzes the reason why material selfinterest maximizing became a dominant motivation in the modern Western society. The works on historical sociology attribute this development to Calvinism but this hypothesis suffers from some serious defects. In the article we prove that the modern sensibility resulted from much longeracting trends specifically secularization urbanization and commercialization. The final section of the chapter explores the relationship between the Westrsquos prevailing norm of selfinterest maximization and the particular norms that have been discussed in microeconomic theory. It argues that some of these norms are internal to the prevailing one and are thus explicable in terms of material selfinterest but that others reflect additional norms in the general society that exist alongside and sometimes in competition with the prevailing norm of selfinterest maximization. The historicallybased view that selfinterest maximizing is a prevailing norm rather than a human universal allows these other norms to be acknowledged in a plausible and realistic manner rather than being explained away by a

  15. Delineating the GRIN1 phenotypic spectrum

    Science.gov (United States)

    Geider, Kirsten; Helbig, Katherine L.; Heyne, Henrike O.; Schütz, Hannah; Hentschel, Julia; Courage, Carolina; Depienne, Christel; Nava, Caroline; Heron, Delphine; Møller, Rikke S.; Hjalgrim, Helle; Lal, Dennis; Neubauer, Bernd A.; Nürnberg, Peter; Thiele, Holger; Kurlemann, Gerhard; Arnold, Georgianne L.; Bhambhani, Vikas; Bartholdi, Deborah; Pedurupillay, Christeen Ramane J.; Misceo, Doriana; Frengen, Eirik; Strømme, Petter; Dlugos, Dennis J.; Doherty, Emily S.; Bijlsma, Emilia K.; Ruivenkamp, Claudia A.; Hoffer, Mariette J.V.; Goldstein, Amy; Rajan, Deepa S.; Narayanan, Vinodh; Ramsey, Keri; Belnap, Newell; Schrauwen, Isabelle; Richholt, Ryan; Koeleman, Bobby P.C.; Sá, Joaquim; Mendonça, Carla; de Kovel, Carolien G.F.; Weckhuysen, Sarah; Hardies, Katia; De Jonghe, Peter; De Meirleir, Linda; Milh, Mathieu; Badens, Catherine; Lebrun, Marine; Busa, Tiffany; Francannet, Christine; Piton, Amélie; Riesch, Erik; Biskup, Saskia; Vogt, Heinrich; Dorn, Thomas; Helbig, Ingo; Michaud, Jacques L.; Laube, Bodo; Syrbe, Steffen

    2016-01-01

    Objective: To determine the phenotypic spectrum caused by mutations in GRIN1 encoding the NMDA receptor subunit GluN1 and to investigate their underlying functional pathophysiology. Methods: We collected molecular and clinical data from several diagnostic and research cohorts. Functional consequences of GRIN1 mutations were investigated in Xenopus laevis oocytes. Results: We identified heterozygous de novo GRIN1 mutations in 14 individuals and reviewed the phenotypes of all 9 previously reported patients. These 23 individuals presented with a distinct phenotype of profound developmental delay, severe intellectual disability with absent speech, muscular hypotonia, hyperkinetic movement disorder, oculogyric crises, cortical blindness, generalized cerebral atrophy, and epilepsy. Mutations cluster within transmembrane segments and result in loss of channel function of varying severity with a dominant-negative effect. In addition, we describe 2 homozygous GRIN1 mutations (1 missense, 1 truncation), each segregating with severe neurodevelopmental phenotypes in consanguineous families. Conclusions: De novo GRIN1 mutations are associated with severe intellectual disability with cortical visual 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-associated disorders. PMID:27164704

  16. On Dominator Colorings in Graphs

    Indian Academy of Sciences (India)

    S Arumugam; Jay Bagga; K Raja Chandrasekar

    2012-11-01

    A dominator coloring of a graph is a proper coloring of in which every vertex dominates every vertex of at least one color class. The minimum number of colors required for a dominator coloring of is called the dominator chromatic number of and is denoted by $ d(G)$. In this paper we present several results on graphs with $ d(G)=(G)$ and $ d(G)=(G)$ where $(G)$ and $(G)$ denote respectively the chromatic number and the domination number of a graph . We also prove that if $(G)$ is the Mycielskian of , then $ d(G)+1≤ d((G))≤ d(G)+2$.

  17. Single cell dynamic phenotyping

    OpenAIRE

    Katherin Patsch; Chi-Li Chiu; Mark Engeln; Agus, David B.; Parag Mallick; Shannon M. Mumenthaler; Daniel Ruderman

    2016-01-01

    Live cell imaging has improved our ability to measure phenotypic heterogeneity. However, bottlenecks in imaging and image processing often make it difficult to differentiate interesting biological behavior from technical artifact. Thus there is a need for new methods that improve data quality without sacrificing throughput. Here we present a 3-step workflow to improve dynamic phenotype measurements of heterogeneous cell populations. We provide guidelines for image acquisition, phenotype track...

  18. Dominant optic atrophy

    Directory of Open Access Journals (Sweden)

    Lenaers Guy

    2012-07-01

    Full Text Available Abstract Definition of the disease Dominant Optic Atrophy (DOA is a neuro-ophthalmic condition characterized by a bilateral degeneration of the optic nerves, causing insidious visual loss, typically starting during the first decade of life. The disease affects primary the retinal ganglion cells (RGC and their axons forming the optic nerve, which transfer the visual information from the photoreceptors to the lateral geniculus in the brain. Epidemiology The prevalence of the disease varies from 1/10000 in Denmark due to a founder effect, to 1/30000 in the rest of the world. Clinical description DOA patients usually suffer of moderate visual loss, associated with central or paracentral visual field deficits and color vision defects. The severity of the disease is highly variable, the visual acuity ranging from normal to legal blindness. The ophthalmic examination discloses on fundoscopy isolated optic disc pallor or atrophy, related to the RGC death. About 20% of DOA patients harbour extraocular multi-systemic features, including neurosensory hearing loss, or less commonly chronic progressive external ophthalmoplegia, myopathy, peripheral neuropathy, multiple sclerosis-like illness, spastic paraplegia or cataracts. Aetiology Two genes (OPA1, OPA3 encoding inner mitochondrial membrane proteins and three loci (OPA4, OPA5, OPA8 are currently known for DOA. Additional loci and genes (OPA2, OPA6 and OPA7 are responsible for X-linked or recessive optic atrophy. All OPA genes yet identified encode mitochondrial proteins embedded in the inner membrane and ubiquitously expressed, as are the proteins mutated in the Leber Hereditary Optic Neuropathy. OPA1 mutations affect mitochondrial fusion, energy metabolism, control of apoptosis, calcium clearance and maintenance of mitochondrial genome integrity. OPA3 mutations only affect the energy metabolism and the control of apoptosis. Diagnosis Patients are usually diagnosed during their early childhood, because of

  19. Boy with autosomal recessive polycystic kidney and autosomal dominant polycystic liver disease.

    NARCIS (Netherlands)

    Zingg-Schenk, A.; Caduff, J.; Azzarello-Burri, S.; Bergmann, C.; Drenth, J.P.H.; Neuhaus, T.J.

    2012-01-01

    BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) shows a great phenotypic variability between patients, ranging from perinatal demise to mildly affected adults. Autosomal dominant polycystic liver disease (PCLD) does not manifest in childhood. CASE-DIAGNOSIS/TREATMENT: A boy was

  20. Imaging of the Macula Indicates Early Completion of Structural Deficit in Autosomal-Dominant Optic Atrophy

    DEFF Research Database (Denmark)

    Rönnbäck, Cecilia; Milea, Dan; Larsen, Michael

    2013-01-01

    Optical coherence tomography (OCT) enables 3-dimensional imaging of the retina, including the layer of ganglion cells that supplies the optic nerve with its axons. We tested OCT as means of diagnosing and phenotyping autosomal-dominant optic atrophy (ADOA).......Optical coherence tomography (OCT) enables 3-dimensional imaging of the retina, including the layer of ganglion cells that supplies the optic nerve with its axons. We tested OCT as means of diagnosing and phenotyping autosomal-dominant optic atrophy (ADOA)....

  1. 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.

  2. Huntington's Disease: Relationship Between Phenotype and Genotype.

    Science.gov (United States)

    Sun, Yi-Min; Zhang, Yan-Bin; Wu, Zhi-Ying

    2017-01-01

    Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disease with the typical manifestations of involuntary movements, psychiatric and behavior disorders, and cognitive impairment. It is caused by the dynamic mutation in CAG triplet repeat number in exon 1 of huntingtin (HTT) gene. The symptoms of HD especially the age at onset are related to the genetic characteristics, both the CAG triplet repeat and the modified factors. Here, we reviewed the recent advancement on the genotype-phenotype relationship of HD, mainly focus on the characteristics of different expanded CAG repeat number, genetic modifiers, and CCG repeat number in the 3' end of CAG triplet repeat and their effects on the phenotype. We also reviewed the special forms of HD (juvenile HD, atypical onset HD, and homozygous HD) and their phenotype-genotype correlations. The review will aid clinicians to predict the onset age and disease course of HD, give the genetic counseling, and accelerate research into the HD mechanism.

  3. Brain Dominance & Self-Actualization.

    Science.gov (United States)

    Bernhoft, Franklin O.

    Numerous areas associated with brain dominance have been researched since Bogen and Sperry's work with split-brain patients in the 1960s, but only slight attention has been given to the connection between brain dominance and personality. No study appears in the literature seeking to understand optimal mental health as defined by Maslow's…

  4. Distributional dominance with dirty data

    OpenAIRE

    2001-01-01

    Distributional dominance criteria are commonly applied to draw welfare in- ferences about comparisons, but conclusions drawn from empirical imple- mentations of dominance criteria may be inßuenced by data contamination. We examine a non-parametric approach to reÞning Lorenz-type comparisons and apply the technique to two important examples from the LIS data-base.

  5. Dominant Leadership Style in Schools

    Science.gov (United States)

    Rajbhandari, Mani Man Singh

    2006-01-01

    The dominant leadership style is defined by the situation and the kind of organizational environment and climate. This, however, does not sufficiently define the leadership qualities in school organizations. There are other factors which also determine the dominant leadership style, which are the traits and style, teachers commitments, pass out…

  6. Eternal Domination: Criticality and Reachability

    Directory of Open Access Journals (Sweden)

    Klostermeyer William F.

    2017-02-01

    Full Text Available We show that for every minimum eternal dominating set, D, of a graph G and every vertex v ∈ D, there is a sequence of attacks at the vertices of G which can be defended in such a way that an eternal dominating set not containing v is reached. The study of the stronger assertion that such a set can be reached after a single attack is defended leads to the study of graphs which are critical in the sense that deleting any vertex reduces the eternal domination number. Examples of these graphs and tight bounds on connectivity, edge-connectivity and diameter are given. It is also shown that there exist graphs in which deletion of any edge increases the eternal domination number, and graphs in which addition of any edge decreases the eternal domination number.

  7. Chorioretinal dysplasia-microcephaly-mental retardation syndrome : Another family with autosomal dominant inheritance

    NARCIS (Netherlands)

    Hordijk, R; VandeLogt, F; Houtman, WA; VanEssen, AJ

    1996-01-01

    We describe a boy and his father with the chorioretinal dysplasia-microcephaly-mental retardation syndrome (CDMMS). Our report extends the phenotypic spectrum of autosomal dominant CDMMS by describing microphthalmia for the first time in an autosomal dominant family. The boy was also severely

  8. Chorioretinal dysplasia-microcephaly-mental retardation syndrome : Another family with autosomal dominant inheritance

    NARCIS (Netherlands)

    Hordijk, R; VandeLogt, F; Houtman, WA; VanEssen, AJ

    1996-01-01

    We describe a boy and his father with the chorioretinal dysplasia-microcephaly-mental retardation syndrome (CDMMS). Our report extends the phenotypic spectrum of autosomal dominant CDMMS by describing microphthalmia for the first time in an autosomal dominant family. The boy was also severely mental

  9. A severe autosomal-dominant periodic inflammatory disorder with renal AA amyloidosis and colchicine resistance associated to the MEFV H478Y variant in a Spanish kindred: an unusual familial Mediterranean fever phenotype or another MEFV-associated periodic inflammatory disorder?

    Science.gov (United States)

    Aldea, Anna; Campistol, Josep M; Arostegui, Juan I; Rius, Josefa; Maso, Montserrat; Vives, Jordi; Yagüe, Jordi

    2004-01-01

    Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurring short attacks of fever and serositis. Secondary AA amyloidosis is the worst complication of the disease and often determines the prognosis. The MEFV gene, on chromosome 16p13.3, is responsible for the disease and around 30 mutations have been reported to date. Colchicine is the standard FMF treatment today, and prevents both attacks and amyloid deposition in 95% of patients. Here we describe a three-generation Spanish kindred with five family members affected by a severe periodic inflammatory disorder associated with renal AA amyloidosis and colchicine unresponsiveness. Clinical diagnosis of definite FMF disease was made based on the Tel-Hashomer criteria set. Genetic analyses revealed that all subjects were heterozygous for the new H478Y MEFV variant, segregating with the disease. In addition, mutations in the TNFRSF1A and CIAS1/PYPAF1/NALP3 genes, related to the dominantly inherited autoinflammatory periodic syndromes, were ruled out. However, the dominant inheritance of the disease, the long fever episodes with a predominant joint involvement, and the resistance to colchicine in these patients raise the question of whether the periodic syndrome seen in this kindred is a true FMF disease with unusual manifestations or rather another MEFV-associated periodic syndrome. We conclude that the new H478Y MEFV mutation is the dominant pathological variant causing the inflammatory periodic syndrome in this kindred and that full-length analyses of the MEFV gene are needed to obtain an adequate diagnosis of patients with clinical suspicion of a hereditary periodic fever syndrome, especially those from non-ancestral populations.

  10. Generalized connected domination in graphs

    Directory of Open Access Journals (Sweden)

    M. Kouider

    2006-01-01

    Full Text Available As a generalization of connected domination in a graph G we consider domination by sets having at most k components. The order γ c k (G of such a smallest set we relate to γ c (G, the order of a smallest connected dominating set. For a tree T we give bounds on γ c k (T in terms of minimum valency and diameter. For trees the inequality γ c k (T≤ n-k-1 is known to hold, we determine the class of trees, for which equality holds.

  11. Dominant investors and strategic transparency

    NARCIS (Netherlands)

    E.C. Perotti; E.-L. von Thadden

    1999-01-01

    This paper studies product market competition under a strategic transparency decision. Dominant investors can influence information collection in the financial market, and thereby corporate transparency, by affecting market liquidity or the cost of information collection. More transparency on a firm

  12. Dominant investors and strategic transparency

    NARCIS (Netherlands)

    E.C. Perotti; E.-L. von Thadden

    1998-01-01

    This paper studies product market competition under a strategic transparency decision. Dominant investors can influence information collection in the financial market, and thereby corporate transparency, by affecting market liquidity or the cost of information collection. More transparency on a firm

  13. Modeling vapor dominated geothermal reservoirs

    Energy Technology Data Exchange (ETDEWEB)

    Marconcini, R.; McEdwards, D.; Neri, G.; Ruffilli, C.; Schroeder, R.; Weres, O.; Witherspoon, P.

    1977-09-12

    The unresolved questions with regard to vapor-dominated reservoir production and longevity are reviewed. The simulation of reservoir behavior and the LBL computer program are discussed. The geology of Serrazzano geothermal field and its reservoir simulation are described. (MHR)

  14. Restrained roman domination in graphs

    Directory of Open Access Journals (Sweden)

    Roushini Leely Pushpam

    2015-03-01

    Full Text Available A Roman dominating function (RDF on a graph G = (V,E is defined to be a function satisfying the condition that every vertex u for which f(u = 0 is adjacent to at least one vertex v for which f(v = 2. A set S V is a Restrained dominating set if every vertex not in S is adjacent to a vertex in S and to a vertex in . We define a Restrained Roman dominating function on a graph G = (V,E to be a function satisfying the condition that every vertex u for which f(u = 0 is adjacent to at least one vertex v for which f(v = 2 and at least one vertex w for which f(w = 0. The weight of a Restrained Roman dominating function is the value . The minimum weight of a Restrained Roman dominating function on a graph G is called the Restrained Roman domination number of G and denoted by . In this paper, we initiate a study of this parameter.

  15. Biolog phenotype microarrays.

    Science.gov (United States)

    Shea, April; Wolcott, Mark; Daefler, Simon; Rozak, David A

    2012-01-01

    Phenotype microarrays nicely complement traditional genomic, transcriptomic, and proteomic analysis by offering opportunities for researchers to ground microbial systems analysis and modeling in a broad yet quantitative assessment of the organism's physiological response to different metabolites and environments. Biolog phenotype assays achieve this by coupling tetrazolium dyes with minimally defined nutrients to measure the impact of hundreds of carbon, nitrogen, phosphorous, and sulfur sources on redox reactions that result from compound-induced effects on the electron transport chain. Over the years, we have used Biolog's reproducible and highly sensitive assays to distinguish closely related bacterial isolates, to understand their metabolic differences, and to model their metabolic behavior using flux balance analysis. This chapter describes Biolog phenotype microarray system components, reagents, and methods, particularly as they apply to bacterial identification, characterization, and metabolic analysis.

  16. Mathematical modeling of planar cell polarity to understand domineering nonautonomy.

    Science.gov (United States)

    Amonlirdviman, Keith; Khare, Narmada A; Tree, David R P; Chen, Wei-Shen; Axelrod, Jeffrey D; Tomlin, Claire J

    2005-01-21

    Planar cell polarity (PCP) signaling generates subcellular asymmetry along an axis orthogonal to the epithelial apical-basal axis. Through a poorly understood mechanism, cell clones that have mutations in some PCP signaling components, including some, but not all, alleles of the receptor frizzled, cause polarity disruptions of neighboring wild-type cells, a phenomenon referred to as domineering nonautonomy. Here, a contact-dependent signaling hypothesis, derived from experimental results, is shown by reaction-diffusion, partial differential equation modeling and simulation to fully reproduce PCP phenotypes, including domineering nonautonomy, in the Drosophila wing. The sufficiency of this model and the experimental validation of model predictions reveal how specific protein-protein interactions produce autonomy or domineering nonautonomy.

  17. The DFNA10 phenotype.

    NARCIS (Netherlands)

    Leenheer, E. de; Huygen, P.L.M.; Wayne, S.; Smith, R.J.H.; Cremers, C.W.R.J.

    2001-01-01

    We present a detailed analysis of the DFNA10 phenotype based on data from 25 hearing-impaired persons coming from a large American pedigree segregating for deafness at the DFNA10 locus (chromosome 6q22.3-23.2). Cross-sectional analysis of air conduction threshold-on-age data from all available last-

  18. 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.

  19. 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...

  20. Vector-meson dominance revisited

    Directory of Open Access Journals (Sweden)

    Terschlüsen Carla

    2012-12-01

    Full Text Available The interaction of mesons with electromagnetism is often well described by the concept of vector-meson dominance (VMD. However, there are also examples where VMD fails. A simple chiral Lagrangian for pions, rho and omega mesons is presented which can account for the respective agreement and disagreement between VMD and phenomenology in the sector of light mesons.

  1. Dominant resistance against plant viruses

    NARCIS (Netherlands)

    Ronde, de D.; Butterbach, P.B.E.; Kormelink, R.J.M.

    2014-01-01

    To establish a successful infection plant viruses have to overcome a defense system composed of several layers. This review will overview the various strategies plants employ to combat viral infections with main emphasis on the current status of single dominant resistance (R) genes identified agains

  2. Hand dominance in orthopaedic surgeons.

    LENUS (Irish Health Repository)

    Lui, Darren F

    2012-08-01

    Handedness is perhaps the most studied human asymmetry. Laterality is the preference shown for one side and it has been studied in many aspects of medicine. Studies have shown that some orthopaedic procedures had poorer outcomes and identified laterality as a contributing factor. We developed a questionnaire to assess laterality in orthopaedic surgery and compared this to an established scoring system. Sixty-two orthopaedic surgeons surveyed with the validated Waterloo Handedness Questionnaire (WHQ) were compared with the self developed Orthopaedic Handedness Questionnaire (OHQ). Fifty-eight were found to be right hand dominant (RHD) and 4 left hand dominant (LHD). In RHD surgeons, the average WHQ score was 44.9% and OHQ 15%. For LHD surgeons the WHQ score was 30.2% and OHQ 9.4%. This represents a significant amount of time using the non dominant hand but does not necessarily determine satisfactory or successful dexterity transferable to the operating room. Training may be required for the non dominant side.

  3. Dominance and Age in Bilingualism

    Science.gov (United States)

    Birdsong, David

    2014-01-01

    The present article examines the relationship between age and dominance in bilingual populations. Age in bilingualism is understood as the point in development at which second language (L2) acquisition begins and as the chronological age of users of two languages. Age of acquisition (AoA) is a factor in determining which of a bilingual's two…

  4. Ergodic averages via dominating processes

    DEFF Research Database (Denmark)

    Møller, Jesper; Mengersen, Kerrie

    2006-01-01

    We show how the mean of a monotone function (defined on a state space equipped with a partial ordering) can be estimated, using ergodic averages calculated from upper and lower dominating processes of a stationary irreducible Markov chain. In particular, we do not need to simulate the stationary ...

  5. Genetics of the dominant ataxias

    NARCIS (Netherlands)

    Verbeek, Dineke S.; van de Warrenburg, Bart P. C.

    2011-01-01

    The relevant clinical, genetic, and cell biologic aspects of the dominantly inherited spinocerebellar ataxias (SCAs) are reviewed in this article. SCAs are diseases of the entire nervous system; in addition to cerebellar ataxia, the central (but not obligate) disease feature, many noncerebellar comp

  6. 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.

  7. From nature-dominated to human-dominated environmental changes

    Science.gov (United States)

    Messerli, Bruno; Grosjean, Martin; Hofer, Thomas; Núñez, Lautaro; Pfister, Christian

    2000-01-01

    To what extent is it realistic and useful to view human history as a sequence of changes from highly vulnerable societies of hunters and gatherers through periods with less vulnerable, well buffered and highly productive agrarian-urban societies to a world with regions of extreme overpopulation and overuse of life support systems, so that vulnerability to climatic-environmental changes and extreme events is again increasing? This question cannot be fully answered in our present state of knowledge, but at least we can try to illustrate, with three case studies from different continents, time periods and ecosystems, some fundamental changes in the relationship between natural processes and human activities that occur, as we pass from a nature-dominated to a human dominated environment. 1. Early-mid Holocene: Nature dominated environment — human adaptation, mitigation, and migration. In the central Andes, the Holocene climate changed from humid (10,800-8000 BP) to extreme arid (8000-3600 BP) conditions. Over the same period, prehistoric hunting communities adopted a more sedentary pattern of resource use by settling close to the few perennial water bodies, where they began the process of domesticating camelids around 5000 BP and irrigation from about 3100 BP. 2. Historical period: An agrarian society in transition from an "enduring" to an innovative human response. Detailed documentary evidence from Western Europe may be used to reconstruct quite precisely the impacts of climatic variations on agrarian societies. The period considered spans a major transition from an apparently passive response to the vagaries of the environment during the 16th century to an active and innovative attitude from the onset of the agrarian revolution in the late 18th century through to the present day. The associated changes in technology and in agricultural practices helped to create a society better able to survive the impact of climatic extremes. 3. The present day: A human dominated

  8. New Solutions for Synchronized Domineering

    Science.gov (United States)

    Bahri, Sahil; Kruskal, Clyde P.

    Cincotti and Iida invented the game of Synchronized Domineering, and analyzed a few special cases. We develop a more general technique of analysis, and obtain results for many more special cases. We obtain complete results for board sizes 3 ×n, 5 ×n, 7 ×n, and 9 ×n (for n large enough) and partial results for board sizes 2×n, 4 ×n, and 6 ×n.

  9. Dominant perceptions on the age

    OpenAIRE

    Komatina Slavica

    2003-01-01

    Contemporary developed society, despite the fact that it is constantly and intensively ageing, is characterized by deeply rooted numerous negative stereotypes on old people and old age as a life period. The study of dominant perceptions on the age of Belgrade population takes not only the universal character of negative connotation of old age into consideration, but also the concrete unfavorable social context. The delicate problematic of stereotypes on old age and old people has been analyze...

  10. Dominant modes via model error

    Science.gov (United States)

    Yousuff, A.; Breida, M.

    1992-01-01

    Obtaining a reduced model of a stable mechanical system with proportional damping is considered. Such systems can be conveniently represented in modal coordinates. Two popular schemes, the modal cost analysis and the balancing method, offer simple means of identifying dominant modes for retention in the reduced model. The dominance is measured via the modal costs in the case of modal cost analysis and via the singular values of the Gramian-product in the case of balancing. Though these measures do not exactly reflect the more appropriate model error, which is the H2 norm of the output-error between the full and the reduced models, they do lead to simple computations. Normally, the model error is computed after the reduced model is obtained, since it is believed that, in general, the model error cannot be easily computed a priori. The authors point out that the model error can also be calculated a priori, just as easily as the above measures. Hence, the model error itself can be used to determine the dominant modes. Moreover, the simplicity of the computations does not presume any special properties of the system, such as small damping, orthogonal symmetry, etc.

  11. Dominance and gene dosage balance in health and disease: why levels matter!

    Science.gov (United States)

    Veitia, Reiner A; Birchler, James A

    2010-01-01

    The classical concept of genetic dominance is a simplification of a more quantitative reality. This is clearly exemplified by aneuploid syndromes, of which the best known case is trisomy 21. Moreover, there is an increasing number of clinical conditions due to reduced dosage (haploinsufficiency) of genes encoding transcription factors and other proteins involved in signal transduction and macromolecular complexes. In such genetic diseases, a high degree of phenotypic variability is observed, which calls for an explanation. The sources of dominance are heterogeneous and difficult to cover in a brief review. Here, we will focus on the molecular bases of dosage-sensitive syndromes from the perspective of the gene dosage balance hypothesis, which postulates that stoichiometric alterations of macromolecular complexes or cellular networks are responsible for dominant phenotypes, because of the existing non-linear relationships between the genotypic and phenotypic values with which they are associated.

  12. Phenotypic characterization of DFNA24: prelingual progressive sensorineural hearing impairment.

    NARCIS (Netherlands)

    Santos, R.L.; Hafner, F.M.; Huygen, P.L.M.; Linder, T.E.; Schinzel, A.; Spillmann, T.; Leal, S.M.

    2006-01-01

    This article describes the hearing impairment (HI) phenotype which segregates in a large multi-generation Swiss-German family with autosomal dominant nonsyndromic HI. The locus segregating within this pedigree is located on chromosome 4q35-qter and is designated as DFNA24. For this pedigree, audiome

  13. GJA1 mutations, variants, and connexin 43 dysfunction as it relates to the oculodentodigital dysplasia phenotype.

    NARCIS (Netherlands)

    Paznekas, W.A.; Karczeski, B.; Vermeer, S.; Lowry, R.B.; Delatycki, M.; Laurence, F.; Koivisto, P.A.; Maldergem, L. van; Boyadjiev, S.A.; Bodurtha, J.N.; Jabs, E.W.

    2009-01-01

    The predominantly autosomal dominant disorder, oculodentodigital dysplasia (ODDD) has high penetrance with intra- and interfamilial phenotypic variability. Abnormalities observed in ODDD affect the eye, dentition, and digits of the hands and feet. Patients present with a characteristic facial

  14. Estimation of dominance variance in purebred Yorkshire swine.

    Science.gov (United States)

    Culbertson, M S; Mabry, J W; Misztal, I; Gengler, N; Bertrand, J K; Varona, L

    1998-02-01

    We used 179,485 Yorkshire reproductive and 239,354 Yorkshire growth records to estimate additive and dominance variances by Method Fraktur R. Estimates were obtained for number born alive (NBA), 21-d litter weight (LWT), days to 104.5 kg (DAYS), and backfat at 104.5 kg (BF). The single-trait models for NBA and LWT included the fixed effects of contemporary group and regression on inbreeding percentage and the random effects mate within contemporary group, animal permanent environment, animal additive, and parental dominance. The single-trait models for DAYS and BF included the fixed effects of contemporary group, sex, and regression on inbreeding percentage and the random effects litter of birth, dam permanent environment, animal additive, and parental dominance. Final estimates were obtained from six samples for each trait. Regression coefficients for 10% inbreeding were found to be -.23 for NBA, -.52 kg for LWT, 2.1 d for DAYS, and 0 mm for BF. Estimates of additive and dominance variances expressed as a percentage of phenotypic variances were, respectively, 8.8 +/- .5 and 2.2 +/- .7 for NBA, 8.1 +/- 1.1 and 6.3 +/- .9 for LWT, 33.2 +/- .4 and 10.3 +/- 1.5 for DAYS, and 43.6 +/- .9 and 4.8 +/- .7 for BF. The ratio of dominance to additive variances ranged from .78 to .11.

  15. Improvement of prediction ability for genomic selection of dairy cattle by including dominance effects.

    Directory of Open Access Journals (Sweden)

    Chuanyu Sun

    Full Text Available Dominance may be an important source of non-additive genetic variance for many traits of dairy cattle. However, nearly all prediction models for dairy cattle have included only additive effects because of the limited number of cows with both genotypes and phenotypes. The role of dominance in the Holstein and Jersey breeds was investigated for eight traits: milk, fat, and protein yields; productive life; daughter pregnancy rate; somatic cell score; fat percent and protein percent. Additive and dominance variance components were estimated and then used to estimate additive and dominance effects of single nucleotide polymorphisms (SNPs. The predictive abilities of three models with both additive and dominance effects and a model with additive effects only were assessed using ten-fold cross-validation. One procedure estimated dominance values, and another estimated dominance deviations; calculation of the dominance relationship matrix was different for the two methods. The third approach enlarged the dataset by including cows with genotype probabilities derived using genotyped ancestors. For yield traits, dominance variance accounted for 5 and 7% of total variance for Holsteins and Jerseys, respectively; using dominance deviations resulted in smaller dominance and larger additive variance estimates. For non-yield traits, dominance variances were very small for both breeds. For yield traits, including additive and dominance effects fit the data better than including only additive effects; average correlations between estimated genetic effects and phenotypes showed that prediction accuracy increased when both effects rather than just additive effects were included. No corresponding gains in prediction ability were found for non-yield traits. Including cows with derived genotype probabilities from genotyped ancestors did not improve prediction accuracy. The largest additive effects were located on chromosome 14 near DGAT1 for yield traits for both

  16. Facial width-to-height ratio relates to dominance style in the genus Macaca

    Directory of Open Access Journals (Sweden)

    Marta Borgi

    2016-03-01

    Full Text Available Background. Physical, visual, chemical, and auditory cues signalling fighting ability have independently evolved in many animal taxa as a means to resolve conflicts without escalating to physical aggression. Facial width-to-height ratio (fWHR, i.e., the relative width to height of the face has been associated with dominance-related phenotypes both in humans and in other primates. In humans, faces with a larger fWHR are perceived as more aggressive. Methods. We examined fWHR variation among 11 species of the genus Macaca. Macaques have been grouped into four distinct categories, from despotic to tolerant, based on their female dominance style. Female dominance style is related to intra- and inter-sexual competition in both males and females and is the result of different evolutionary pressure across species. We used female dominance style as a proxy of intra-/inter-sexual competition to test the occurrence of correlated evolution between competitive regimes and dominance-related phenotypes. fWHR was calculated from 145 2D photographs of male and female adult macaques. Results. We found no phylogenetic signal on the differences in fWHR across species in the two sexes. However, fWHR was greater, in females and males, in species characterised by despotic female dominance style than in tolerant species. Discussion. Our results suggest that dominance-related phenotypes are related to differences in competitive regimes and intensity of inter- and intra-sexual selection across species.

  17. Learning, tracing, and risk dominance

    DEFF Research Database (Denmark)

    Hendon, Ebbe; Jacobsen, Hans Jørgen; Nielsen, Michael Teit;

    1994-01-01

    This paper presents a learning process which is a generalization of the method of fictitious play of Brown. If the learning process converges, the convergence point is a Nash equilibrium. We study 2 × 2 games. Here the process always converges. The relation between the initial prior, the weight...... assigned to this prior, and the equilibrium selected is examined. As the weight increases, the relation between the prior and the equilibrium selected becomes almost identical to that of the tracing procedure of Harsanyi. In this way the learning process supports the concept of risk dominance of Harsanyi...

  18. Dominant KCNA2 mutation causes episodic ataxia and pharmacoresponsive epilepsy.

    Science.gov (United States)

    Corbett, Mark A; Bellows, Susannah T; Li, Melody; Carroll, Renée; Micallef, Silvana; Carvill, Gemma L; Myers, Candace T; Howell, Katherine B; Maljevic, Snezana; Lerche, Holger; Gazina, Elena V; Mefford, Heather C; Bahlo, Melanie; Berkovic, Samuel F; Petrou, Steven; Scheffer, Ingrid E; Gecz, Jozef

    2016-11-08

    To identify the genetic basis of a family segregating episodic ataxia, infantile seizures, and heterogeneous epilepsies and to study the phenotypic spectrum of KCNA2 mutations. A family with 7 affected individuals over 3 generations underwent detailed phenotyping. Whole genome sequencing was performed on a mildly affected grandmother and her grandson with epileptic encephalopathy (EE). Segregating variants were filtered and prioritized based on functional annotations. The effects of the mutation on channel function were analyzed in vitro by voltage clamp assay and in silico by molecular modeling. KCNA2 was sequenced in 35 probands with heterogeneous phenotypes. The 7 family members had episodic ataxia (5), self-limited infantile seizures (5), evolving to genetic generalized epilepsy (4), focal seizures (2), and EE (1). They had a segregating novel mutation in the shaker type voltage-gated potassium channel KCNA2 (CCDS_827.1: c.765_773del; p.255_257del). A rare missense SCN2A (rs200884216) variant was also found in 2 affected siblings and their unaffected mother. The p.255_257del mutation caused dominant negative loss of channel function. Molecular modeling predicted repositioning of critical arginine residues in the voltage-sensing domain. KCNA2 sequencing revealed 1 de novo mutation (CCDS_827.1: c.890G>A; p.Arg297Gln) in a girl with EE, ataxia, and tremor. A KCNA2 mutation caused dominantly inherited episodic ataxia, mild infantile-onset seizures, and later generalized and focal epilepsies in the setting of normal intellect. This observation expands the KCNA2 phenotypic spectrum from EE often associated with chronic ataxia, reflecting the marked variation in severity observed in many ion channel disorders. © 2016 American Academy of Neurology.

  19. PENCALC: a program for penetrance estimation in autosomal dominant diseases

    Directory of Open Access Journals (Sweden)

    Andréa R.V. Russo Horimoto

    2010-01-01

    Full Text Available We present a computer program developed for estimating penetrance rates in autosomal dominant diseases by means of family kinship and phenotype information contained within the pedigrees. The program also determines the exact 95% credibility interval for the penetrance estimate. Both executable (PenCalc for Windows and web versions (PenCalcWeb of the software are available. The web version enables further calculations, such as heterozygosity probabilities and assessment of offspring risks for all individuals in the pedigrees. Both programs can be accessed and down-loaded freely at the home-page address http://www.ib.usp.br/~otto/software.htm.

  20. Dominant inheritance of retinal ganglion cell resistance to optic nerve crush in mice

    Directory of Open Access Journals (Sweden)

    Schlamp Cassandra L

    2007-03-01

    Full Text Available Abstract Background Several neurodegenerative diseases are influenced by complex genetics that affect an individual's susceptibility, disease severity, and rate of progression. One such disease is glaucoma, a chronic neurodegenerative condition of the eye that targets and stimulates apoptosis of CNS neurons called retinal ganglion cells. Since ganglion cell death is intrinsic, it is reasonable that the genes that control this process may contribute to the complex genetics that affect ganglion cell susceptibility to disease. To determine if genetic background influences susceptibility to optic nerve damage, leading to ganglion cell death, we performed optic nerve crush on 15 different inbred lines of mice and measured ganglion cell loss. Resistant and susceptible strains were used in a reciprocal breeding strategy to examine the inheritance pattern of the resistance phenotype. Because earlier studies had implicated Bax as a susceptibility allele for ganglion cell death in the chronic neurodegenerative disease glaucoma, we conducted allelic segregation analysis and mRNA quantification to assess this gene as a candidate for the cell death phenotype. Results Inbred lines showed varying levels of susceptibility to optic nerve crush. DBA/2J mice were most resistant and BALB/cByJ mice were most susceptible. F1 mice from these lines inherited the DBA/2J phenotype, while N2 backcross mice exhibited the BALB/cByJ phenotype. F2 mice exhibited an intermediate phenotype. A Wright Formula calculation suggested as few as 2 dominant loci were linked to the resistance phenotype, which was corroborated by a Punnett Square analysis of the distribution of the mean phenotype in each cross. The levels of latent Bax mRNA were the same in both lines, and Bax alleles did not segregate with phenotype in N2 and F2 mice. Conclusion Inbred mice show different levels of resistance to optic nerve crush. The resistance phenotype is heritable in a dominant fashion involving

  1. A New Method to Assess Eye Dominance

    Science.gov (United States)

    Valle-Inclan, Fernando; Blanco, Manuel J.; Soto, David; Leiros, Luz

    2008-01-01

    People usually show a stable preference for one of their eyes when monocular viewing is required ("sighting dominance") or under dichoptic stimulation conditions ("sensory eye-dominance"). Current procedures to assess this "eye dominance" are prone to error. Here we present a new method that provides a continuous measure of eye dominance and…

  2. Phenotypic heterogeneity of monogenic frontotemporal dementia

    Directory of Open Access Journals (Sweden)

    Alberto eBenussi

    2015-09-01

    Full Text Available Frontotemporal dementia (FTD is a genetically and pathologically heterogeneous disorder characterized by personality changes, language impairment and deficits of executive functions associated with frontal and temporal lobe degeneration. Different phenotypes have been defined on the basis of presenting clinical symptoms, i.e. the behavioral variant of FTD (bvFTD, the agrammatic variant of Primary Progressive Aphasia (avPPA and the semantic variant of PPA (svPPA. Some patients have an associated movement disorder, either parkinsonism, as in Progressive Supranuclear Palsy (PSP and Corticobasal Syndrome (CBS, or motor neuron disease (FTD-MND. A family history of dementia is found in 40% of cases of FTD and about 10% have a clear autosomal dominant inheritance. Genetic studies have identified several genes associated to monogenic FTD: microtubule-associated protein tau (MAPT, progranulin (GRN, TAR DNA-binding protein 43 (TARBDP, valosin-containing protein (VCP, charged multivesicular body protein 2B (CHMP2B, fused in sarcoma (FUS and the hexanucleotide repeat expansion in intron 1 of the chromosome 9 open reading frame 72 (C9orf72. Patients often present with an extensive phenotypic variability, even among different members of the same kindred carrying an identical disease mutation. The objective of the present work is to review and evaluate available literature data in order to highlight recent advances in clinical, biological and neuroimaging features of monogenic frontotemporal lobar degeneration and try to identify different mechanisms underlying the extreme phenotypic heterogeneity that characterizes this disease.

  3. Dominant perceptions on the age

    Directory of Open Access Journals (Sweden)

    Komatina Slavica

    2003-01-01

    Full Text Available Contemporary developed society, despite the fact that it is constantly and intensively ageing, is characterized by deeply rooted numerous negative stereotypes on old people and old age as a life period. The study of dominant perceptions on the age of Belgrade population takes not only the universal character of negative connotation of old age into consideration, but also the concrete unfavorable social context. The delicate problematic of stereotypes on old age and old people has been analyzed mostly indirectly, through questions on the beginning of old age, advantages and difficulties which we experience during ageing, the first subjective conscious encounter with one’s own ageing, the concept of ideal old age, changes in the persons traits and directly through questions on dominant negative perceptions which prevail on old people in our surrounding. Ageing in the Belgrade milieu is most commonly identified with illness and with the decline of physical potentials, and at the same time a number of other negative qualifications of old age as well. Research results indicate to a pronounced ambivalent standpoint towards ageing, to different observation of one’s own to old age of other people, to different consideration of old age among the sexes and to obvious aversion towards old people. This is expected, taking into consideration that living and ageing are developing nowadays under aggressive influence of contemporary mass culture which affirms youth, beauty, physical strength, health as dominant values, namely everything that is contrary to ageing and old age. On the other hand, our society is today confronted with, as well as in the near past, exceptional political, economic and cultural difficulties which cause specific problems with various age groups, as well as the lowering of the level of mutual endurance and tolerance. The atmosphere of straining the old people and emergence of new antagonisms causes the intensification of

  4. Entropically Dominant State of Proteins

    CERN Document Server

    Li, Wenzhao; Tian, Suyan; Tian, Pu

    2012-01-01

    Configurational entropy is an important factor in the free energy change of many macromolecular recognition and binding processes, and has been intensively studied. Despite great progresses that have been made, the global sampling remains to be a grand challenge in computational analysis of relevant processes. Here we propose and demonstrate an entropy estimation method that is based on physical partition of configurational space and can be readily combined with currently available methodologies. Tests with two globular proteins suggest that for flexible macromolecules with large and complex configurational space, accurate configurational entropy estimation may be achieved simply by considering the entropically most important subspace. This conclusion effectively converts an exhaustive sampling problem into a local sampling one, and defines entropically dominant state for proteins and other complex macromolecules. The conceptional breakthrough is likely to positively impact future theoretical analysis, comput...

  5. Simulation of inverter dominated minigrids

    Energy Technology Data Exchange (ETDEWEB)

    Engler, A.; Osika, O. [Inst. fuer Solare Energieversorgungstechnik (ISET) e.V., Kassel (Germany)

    2003-07-01

    In order to assess the load flow, the transient behaviour and the stability of inverter dominated minigrids, a model for inverters and a transmission system has been developed. The inverters are represented by a frequency and voltage controlled three phase voltage source and the transmission systems consists of switches, overhead lines ({pi}-equivalent), transformers and a load. The inverters operate in parallel via the MV-distribution system and supply an active load. The contribution of each inverter is determined by the setting of the applied droops (similar to conventional power plants). Furthermore an approach for stability assessment of such systems is introduced. This research work is related to the EC-funded project MicroGrids. (orig.)

  6. A Note on Almost Stochastic Dominance

    OpenAIRE

    Guo, Xu; Zhu, Xuehu; Wong, Wing-Keung; Zhu, Lixing

    2013-01-01

    To satisfy the property of expected-utility maximization, Tzeng et al. (2012) modify the almost second-degree stochastic dominance proposed by Leshno and Levy (2002) and define almost higher-degree stochastic dominance. In this note, we further investigate the relevant properties. We define an almost third-degree stochastic dominance in the same way that Leshno and Levy (2002) define second-degree stochastic dominance and show that Leshno and Levy's (2002) almost stochastic dominance has t...

  7. An ontology for microbial phenotypes.

    Science.gov (United States)

    Chibucos, Marcus C; Zweifel, Adrienne E; Herrera, Jonathan C; Meza, William; Eslamfam, Shabnam; Uetz, Peter; Siegele, Deborah A; Hu, James C; Giglio, Michelle G

    2014-11-30

    Phenotypic data are routinely used to elucidate gene function in organisms amenable to genetic manipulation. However, previous to this work, there was no generalizable system in place for the structured storage and retrieval of phenotypic information for bacteria. The Ontology of Microbial Phenotypes (OMP) has been created to standardize the capture of such phenotypic information from microbes. OMP has been built on the foundations of the Basic Formal Ontology and the Phenotype and Trait Ontology. Terms have logical definitions that can facilitate computational searching of phenotypes and their associated genes. OMP can be accessed via a wiki page as well as downloaded from SourceForge. Initial annotations with OMP are being made for Escherichia coli using a wiki-based annotation capture system. New OMP terms are being concurrently developed as annotation proceeds. We anticipate that diverse groups studying microbial genetics and associated phenotypes will employ OMP for standardizing microbial phenotype annotation, much as the Gene Ontology has standardized gene product annotation. The resulting OMP resource and associated annotations will facilitate prediction of phenotypes for unknown genes and result in new experimental characterization of phenotypes and functions.

  8. A complex dominance hierarchy is controlled by polymorphism of small RNAs and their targets.

    Science.gov (United States)

    Yasuda, Shinsuke; Wada, Yuko; Kakizaki, Tomohiro; Tarutani, Yoshiaki; Miura-Uno, Eiko; Murase, Kohji; Fujii, Sota; Hioki, Tomoya; Shimoda, Taiki; Takada, Yoshinobu; Shiba, Hiroshi; Takasaki-Yasuda, Takeshi; Suzuki, Go; Watanabe, Masao; Takayama, Seiji

    2016-12-22

    In diploid organisms, phenotypic traits are often biased by effects known as Mendelian dominant-recessive interactions between inherited alleles. Phenotypic expression of SP11 alleles, which encodes the male determinants of self-incompatibility in Brassica rapa, is governed by a complex dominance hierarchy(1-3). Here, we show that a single polymorphic 24 nucleotide small RNA, named SP11 methylation inducer 2 (Smi2), controls the linear dominance hierarchy of the four SP11 alleles (S44 > S60 > S40 > S29). In all dominant-recessive interactions, small RNA variants derived from the linked region of dominant SP11 alleles exhibited high sequence similarity to the promoter regions of recessive SP11 alleles and acted in trans to epigenetically silence their expression. Together with our previous study(4), we propose a new model: sequence similarity between polymorphic small RNAs and their target regulates mono-allelic gene expression, which explains the entire five-phased linear dominance hierarchy of the SP11 phenotypic expression in Brassica.

  9. High-throughput mouse phenotyping.

    Science.gov (United States)

    Gates, Hilary; Mallon, Ann-Marie; Brown, Steve D M

    2011-04-01

    Comprehensive phenotyping will be required to reveal the pleiotropic functions of a gene and to uncover the wider role of genetic loci within diverse biological systems. The challenge will be to devise phenotyping approaches to characterise the thousands of mutants that are being generated as part of international efforts to acquire a mutant for every gene in the mouse genome. In order to acquire robust datasets of broad based phenotypes from mouse mutants it is necessary to design and implement pipelines that incorporate standardised phenotyping platforms that are validated across diverse mouse genetics centres or mouse clinics. We describe here the rationale and methodology behind one phenotyping pipeline, EMPReSSslim, that was designed as part of the work of the EUMORPHIA and EUMODIC consortia, and which exemplifies some of the challenges facing large-scale phenotyping. EMPReSSslim captures a broad range of data on diverse biological systems, from biochemical to physiological amongst others. Data capture and dissemination is pivotal to the operation of large-scale phenotyping pipelines, including the definition of parameters integral to each phenotyping test and the associated ontological descriptions. EMPReSSslim data is displayed within the EuroPhenome database, where a variety of tools are available to allow the user to search for interesting biological or clinical phenotypes. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. General N-th Degree Stochastic Dominance

    Institute of Scientific and Technical Information of China (English)

    张顺明

    2001-01-01

    This paper examines N-th degree stochastic dominance which isused to compare the risk factor of risky assets after summarizing the definitions of first degree stochastic dominance and second degree stochastic dominance. The paper defines general N-th degree stochastic dominance, presents a sufficient and necessary condition which is the equivalent theorem of general N-th degree stochastic dominance. The feasible utility form is constructed to explain the economic meaning of N-th degree stochastic dominance in the field of financial economics. The equivalent condition is described by the probability distribution functions of risky assets, which are not related to utility functions (preference relations).

  11. Autozygosity reveals recessive mutations and novel mechanisms in dominant genes: implications in variant interpretation

    KAUST Repository

    Monies, Dorota

    2017-04-06

    The purpose of this study is to describe recessive alleles in strictly dominant genes. Identifying recessive mutations in genes for which only dominant disease or risk alleles have been reported can expand our understanding of the medical relevance of these genes both phenotypically and mechanistically. The Saudi population is enriched for autozygosity, which enhances the homozygous occurrence of alleles, including pathogenic alleles in genes that have been associated only with a dominant inheritance pattern.Exome sequencing of patients from consanguineous families with likely recessive phenotypes was performed. In one family, the genotype of the deceased children was inferred from their parents due to lack of available samples.We describe the identification of 11 recessive variants (5 of which are reported here for the first time) in 11 genes for which only dominant disease or risk alleles have been reported. The observed phenotypes for these recessive variants were novel (e.g., FBN2-related myopathy and CSF1R-related brain malformation and osteopetrosis), typical (e.g., ACTG2-related visceral myopathy), or an apparently healthy state (e.g., PDE11A), consistent with the corresponding mouse knockout phenotypes.Our results show that, in the era of genomic sequencing and

  12. Autosomal dominant optic neuropathy and sensorineual hearing loss associated with a novel mutation of WFS1

    NARCIS (Netherlands)

    Hogewind, B.F.T.; Pennings, R.J.E.; Hol, F.A.; Kunst, H.P.M.; Hoefsloot, E.H.; Cruysberg, J.R.M.; Cremers, C.W.R.J.

    2010-01-01

    PURPOSE: To describe the phenotype of a novel Wolframin (WFS1) mutation in a family with autosomal dominant optic neuropathy and deafness. The study is designed as a retrospective observational case series. METHODS: Seven members of a Dutch family underwent ophthalmological, otological, and genetica

  13. Boy with autosomal recessive polycystic kidney and autosomal dominant polycystic liver disease.

    NARCIS (Netherlands)

    Zingg-Schenk, A.; Caduff, J.; Azzarello-Burri, S.; Bergmann, C.; Drenth, J.P.H.; Neuhaus, T.J.

    2012-01-01

    BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) shows a great phenotypic variability between patients, ranging from perinatal demise to mildly affected adults. Autosomal dominant polycystic liver disease (PCLD) does not manifest in childhood. CASE-DIAGNOSIS/TREATMENT: A boy was rep

  14. Dissection of additive, dominance, and imprinting effects for production and reproduction traits in Holstein cattle

    Science.gov (United States)

    Although genome-wide association and genomic selection studies have primarily focused on additive effects, dominance and imprinting effects play an important role in mammalian biology and development. The degree to which these non-additive genetic effects contribute to phenotypic variation and wheth...

  15. [Sighting dominance in patients with macular disease].

    Science.gov (United States)

    Akaza, Eriko; Fujita, Kyoko; Shimada, Hiroyuki; Yuzawa, Mitsuko

    2007-04-01

    To study sighting dominance by comparing macular disease patients undergoing surgical treatment with controls. We studied visual acuity and sighting dominance in 92 macular disease patients, 27 of whom were assessed for both outcomes. We also studied visual acuity and sighting dominance in 412 controls. Sighting dominance was evaluated using the hole-in-card test. Among the controls, 70% showed right sighting dominance, and 30%, left sighting dominance. On the other hand, in patients with macular disease, right sighting dominance was demonstrated in 51%, and left in 49%; that is, 24% showed sighting dominance of the affected eye and 76%, of the fellow eye. During follow-up, sighting dominance of three of the 27 macular disease patients shifted from the affected eye to the fellow eye, which showed improvement in visual acuity. This study raises the possibility of sighting dominance shifting in patients with macular disease. There were differences among cases in the timing of the shift in sighting dominance, indicating that visual acuity may not be the only factor influencing sighting dominance. Further study is needed to confirm the factors contributing to sighting dominance.

  16. Phenotypic and genetic characterization of a novel phenotype in pigs characterized by juvenile hairlessness and age dependent emphysema

    DEFF Research Database (Denmark)

    Bruun, Camilla S.; Jørgensen, Claus B.; Bay, Lene

    2008-01-01

    Background: A pig phenotype characterized by juvenile hairlessness, thin skin and age dependent lung emphysema has been discovered in a Danish pig herd. The trait shows autosomal co-dominant inheritance with all three genotypes distinguishable. Since the phenotype shows resemblance to the integrin...... of musculi arrectores pili, and at puberty or later localized areas of emphysema are seen in the lungs. Comparative mapping predicted that the porcine ITGB6 and ITGAV orthologs map to SSC15. In an experimentall family (n=113), showing segregation of the trait, the candidate region was confirmed by linkage...

  17. Outer-2-independent domination in graphs

    Indian Academy of Sciences (India)

    Marcin Krzywkowski; Doost Ali Mojdeh; Maryem Raoofi

    2016-02-01

    We initiate the study of outer-2-independent domination in graphs. An outer-2-independent dominating set of a graph is a set of vertices of such that every vertex of ()\\ has a neighbor in and the maximum vertex degree of the subgraph induced by ()\\ is at most one. The outer-2-independent domination number of a graph is the minimum cardinality of an outer-2-independent dominating set of . We show that if a graph has minimum degree at least two, then its outer-2-independent domination number equals the number of vertices minus the 2-independence number. Then we investigate the outer-2-independent domination in graphs with minimum degree one. We also prove the Vizing-type conjecture for outer-2-independent domination and disprove the Vizing-type conjecture for outer-connected domination.

  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. 5 CFR 532.305 - Dominant industry.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Dominant industry. 532.305 Section 532... SYSTEMS Determining Rates for Principal Types of Positions § 532.305 Dominant industry. (a)(1) A specialized industry is a “dominant industry” if the number of wage employees in the wage area who are subject...

  1. 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....... This method of detection was used to determine the distribution of SHBG phenotypes in healthy controls of both sexes and in five different pathological conditions characterized by changes in the SHBG level or endocrine disturbances (malignant and benign ovarian neoplasms, hirsutism, liver cirrhosis...... on the experimental values. Differences in SHBG phenotypes do not appear to have any clinical significance and no sex difference was found in the SHBG phenotype distribution....

  2. Global phenotypic characterization of bacteria.

    Science.gov (United States)

    Bochner, Barry R

    2009-01-01

    The measure of the quality of a systems biology model is how well it can reproduce and predict the behaviors of a biological system such as a microbial cell. In recent years, these models have been built up in layers, and each layer has been growing in sophistication and accuracy in parallel with a global data set to challenge and validate the models in predicting the content or activities of genes (genomics), proteins (proteomics), metabolites (metabolomics), and ultimately cell phenotypes (phenomics). This review focuses on the latter, the phenotypes of microbial cells. The development of Phenotype MicroArrays, which attempt to give a global view of cellular phenotypes, is described. In addition to their use in fleshing out and validating systems biology models, there are many other uses of this global phenotyping technology in basic and applied microbiology research, which are also described.

  3. Global phenotypic characterization of bacteria

    Science.gov (United States)

    Bochner, Barry R

    2009-01-01

    The measure of the quality of a systems biology model is how well it can reproduce and predict the behaviors of a biological system such as a microbial cell. In recent years, these models have been built up in layers, and each layer has been growing in sophistication and accuracy in parallel with a global data set to challenge and validate the models in predicting the content or activities of genes (genomics), proteins (proteomics), metabolites (metabolomics), and ultimately cell phenotypes (phenomics). This review focuses on the latter, the phenotypes of microbial cells. The development of Phenotype MicroArrays, which attempt to give a global view of cellular phenotypes, is described. In addition to their use in fleshing out and validating systems biology models, there are many other uses of this global phenotyping technology in basic and applied microbiology research, which are also described. PMID:19054113

  4. Epigenetic dominance of prion conformers.

    Directory of Open Access Journals (Sweden)

    Eri Saijo

    2013-10-01

    Full Text Available Although they share certain biological properties with nucleic acid based infectious agents, prions, the causative agents of invariably fatal, transmissible neurodegenerative disorders such as bovine spongiform encephalopathy, sheep scrapie, and human Creutzfeldt Jakob disease, propagate by conformational templating of host encoded proteins. Once thought to be unique to these diseases, this mechanism is now recognized as a ubiquitous means of information transfer in biological systems, including other protein misfolding disorders such as those causing Alzheimer's and Parkinson's diseases. To address the poorly understood mechanism by which host prion protein (PrP primary structures interact with distinct prion conformations to influence pathogenesis, we produced transgenic (Tg mice expressing different sheep scrapie susceptibility alleles, varying only at a single amino acid at PrP residue 136. Tg mice expressing ovine PrP with alanine (A at (OvPrP-A136 infected with SSBP/1 scrapie prions propagated a relatively stable (S prion conformation, which accumulated as punctate aggregates in the brain, and produced prolonged incubation times. In contrast, Tg mice expressing OvPrP with valine (V at 136 (OvPrP-V136 infected with the same prions developed disease rapidly, and the converted prion was comprised of an unstable (U, diffusely distributed conformer. Infected Tg mice co-expressing both alleles manifested properties consistent with the U conformer, suggesting a dominant effect resulting from exclusive conversion of OvPrP-V136 but not OvPrP-A136. Surprisingly, however, studies with monoclonal antibody (mAb PRC5, which discriminates OvPrP-A136 from OvPrP-V136, revealed substantial conversion of OvPrP-A136. Moreover, the resulting OvPrP-A136 prion acquired the characteristics of the U conformer. These results, substantiated by in vitro analyses, indicated that co-expression of OvPrP-V136 altered the conversion potential of OvPrP-A136 from the S to

  5. [Genetic components and the uncertainty of the phenotypic realization of the mass of newborns in domestic pigs Sus scrofa L].

    Science.gov (United States)

    Nikitin, S V; Kniazev, S P; Ermolaev, V I

    2014-01-01

    In this article, we discuss the features of the genetic determination of a continuous quantitative trait, the mass of newborn offspring in populations of the domestic pig. We defined several components that determine the phenotypic trait, such as the maternal effect, complete dominance, interaction of the parental alleles in the genotype of the offspring, and the uncertainty of phenotypic realization of genotype. We found that a phenotypic trait of high genetic determinacy can also have a maximum range in phenotypic realization, in which case each genotype encountered in the population can realize within the entire range of possible phenotypes.

  6. Neurobehavioral phenotype of Klinefelter syndrome.

    Science.gov (United States)

    Geschwind, D H; Boone, K B; Miller, B L; Swerdloff, R S

    2000-01-01

    A defined genetic syndrome with neurobehavioral components offers an unusual paradigm for the correlation of genetic defects with neurodevelopmental abnormalities. The power of the combination of detailed behavioral, neuroanatomical, and genetic studies has been demonstrated in studies of other conditions involving the sex chromosomes, such as Fragile X syndrome (Mazzocco [2000] Ment Retard Develop Disabil Res Rev. 6:96-106) and Turner syndrome (Ross [2000] Ment Retard Develop Disabil Res Rev. 6:135-141). Although the behavioral and neurologic difficulties that have been identified in Klinefelter syndrome (KS) are in most cases milder than the consequences of many other genetic syndromes, the deficits in KS cause significant morbidity, representing a more common, but poorly understood, subtype of those with learning disabilities. Both as children and as adults, KS subjects appear to offer a powerful genetic model for the study of language and language-based learning disabilities. Although it has been proposed that the language-based learning difficulties of KS boys are similar to those of nonaneuploidic dyslexics [Bender et al., 1986; Geschwind et al., 1998], this is not yet well established. The co-morbid frontal-executive dysfunction observed in KS is also a likely contributor to learning difficulties and, perhaps, social cognition, in many KS patients. It is also proposed that altered left-hemisphere functioning, whether causing, or due to, altered functional and anatomical cerebral dominance, is at the core of KS subjects' language problems. Although X chromosomal loci can provide only part of the picture, the study of KS subjects, a population with a relatively homogeneous etiology for dyslexia/dysphasia and frontal-executive dysfunction, offers many advantages over such a study in the general population, in which both dyslexia and attentional disorders are quite genetically heterogeneous [Decker and Bender, 1988; Pennington, 1990; Grigorenko et al., 1997

  7. On Minus Paired-Domination in Graphs

    Institute of Scientific and Technical Information of China (English)

    邢化明; 孙良

    2003-01-01

    The study of minus paired-domination of a graph G=(V,E) is initiated. Let SV be any paired-dominating set of G, a minus paired-dominating function is a function of the form f∶V→{-1,0,1} such that f(v)=1 for v∈S, f(v)≤0 for v∈V-S, and f(N[v])≥1 for all v∈V. The weight of a minus paired-dominating function f is w(f)=∑f(v), over all vertices v∈V. The minus paired-domination number of a graph G is γ-p(G)=min{w(f)|f is a minus paired-dominating function of G}. On the basis of the minus paired-domination number of a graph G defined, some of its properties are discussed.

  8. Dominant protein interactions that influence the pathogenesis of conformational diseases.

    Science.gov (United States)

    Wright, Jordan; Wang, Xiaofan; Haataja, Leena; Kellogg, Aaron P; Lee, Jaemin; Liu, Ming; Arvan, Peter

    2013-07-01

    Misfolding of exportable proteins can trigger endocrinopathies. For example, misfolding of insulin can result in autosomal dominant mutant INS gene-induced diabetes of youth, and misfolding of thyroglobulin can result in autosomal recessive congenital hypothyroidism with deficient thyroglobulin. Both proinsulin and thyroglobulin normally form homodimers; the mutant versions of both proteins misfold in the ER, triggering ER stress, and, in both cases, heterozygosity creates potential for cross-dimerization between mutant and WT gene products. Here, we investigated these two ER-retained mutant secretory proteins and the selectivity of their interactions with their respective WT counterparts. In both cases and in animal models of these diseases, we found that conditions favoring an increased stoichiometry of mutant gene product dominantly inhibited export of the WT partner, while increased relative level of the WT gene product helped to rescue secretion of the mutant partner. Surprisingly, the bidirectional consequences of secretory blockade and rescue occur simultaneously in the same cells. Thus, in the context of heterozygosity, expression level and stability of WT subunits may be a critical factor influencing the effect of protein misfolding on clinical phenotype. These results offer new insight into dominant as well as recessive inheritance of conformational diseases and offer opportunities for the development of new therapies.

  9. Homozygosity for dominant mutations increases severity of muscle channelopathies.

    Science.gov (United States)

    Arzel-Hézode, Marianne; Sternberg, Damien; Tabti, Nacira; Vicart, Savine; Goizet, Cyril; Eymard, Bruno; Fontaine, Bertrand; Fournier, Emmanuel

    2010-04-01

    Muscle channelopathies caused by mutations in the SCN4A gene that encodes the muscle sodium channel are transmitted by autosomal-dominant inheritance. We report herein the first cases of homozygous patients for sodium channel mutations responsible for paramyotonia congenita (I1393T) or hypokalemic periodic paralysis (R1132Q). A parallel was drawn between this unprecedented situation and that of myotonia congenita by including patients homozygous or heterozygous for the CLCN1 I556N channel mutation, which is known for incomplete dominance and penetrance. Standardized electromyographic (EMG) protocols combining exercise and cold served as provocative tests to compare homozygotes with heterozygotes for each of the three mutations. Surface-recorded compound muscle action potentials (CMAPs) were used to monitor muscle electrical activity, and myotonic discharges were evaluated by needle EMG. In heterozygous patients, exercise tests disclosed abnormal patterns of CMAP changes, which matched those previously described for similar dominant sodium and chloride channel mutations. Homozygotes showed much more severe clinical features and CMAP changes. We hypothesized that the presence of 100% defective ion channels in the homozygotes could account for the most severe phenotype. This suggests that the severity of muscle channelopathies depends both on the degree of channel impairment caused by the mutation and on the number of mutant channels engaged in the pathophysiological process. Overall, this study has practical consequences for the diagnosis of muscle channelopathies and raises new questions about their pathophysiology.

  10. Ocular Dominance and Handedness in Golf Putting.

    Science.gov (United States)

    Dalton, Kristine; Guillon, Michel; Naroo, Shehzad A

    2015-10-01

    In golf, the impact of eye-hand dominance on putting performance has long been debated. Eye-hand dominance is thought to impact how golfers judge the alignment of the ball with the target and the club with the ball, as well as how golfers visualize the line of the putt when making decisions about the force needed to hit the ball. Previous studies have all measured ocular dominance in primary gaze only, despite golfers spending a significant amount of their time in a putting stance (bent at the hips, head tilted down). Thus, the purpose of this study was to assess ocular dominance in both primary gaze (aligning the ball with the target) and putting gaze (addressing the ball and aligning the club). This study investigated measuring pointing ocular dominance in both primary and putting gaze positions on 31 golfers (14 amateur, 7 club professionals, and 10 top professionals). All players were right-handed golfers, although one reported having no hand dominance and one reported being strongly left hand dominant. The results showed that (1) primary and putting gaze ocular dominances are not equal, nor are they predictive of each other; (2) the magnitude of putting ocular dominance is significantly less than the magnitude of primary gaze ocular dominance; (3) ocular dominance is not correlated with handedness in either primary or putting gaze; and (4) eye-hand dominance is not associated with increased putting skill, although ocular dominance may be associated with increased putting success. It is important that coaches assess golfers' ocular dominance in both primary and putting gaze positions to ensure they have the most accurate information upon which to base their vision strategy decisions.

  11. Phenotypic plasticity, costs of phenotypes, and costs of plasticity

    DEFF Research Database (Denmark)

    Callahan, Hilary S; Maughan, Heather; Steiner, Uli

    2008-01-01

    Why are some traits constitutive and others inducible? The term costs often appears in work addressing this issue but may be ambiguously defined. This review distinguishes two conceptually distinct types of costs: phenotypic costs and plasticity costs. Phenotypic costs are assessed from patterns...... of covariation, typically between a focal trait and a separate trait relevant to fitness. Plasticity costs, separable from phenotypic costs, are gauged by comparing the fitness of genotypes with equivalent phenotypes within two environments but differing in plasticity and fitness. Subtleties associated with both...... types of costs are illustrated by a body of work addressing predator-induced plasticity. Such subtleties, and potential interplay between the two types of costs, have also been addressed, often in studies involving genetic model organisms. In some instances, investigators have pinpointed the mechanistic...

  12. Rationale and Design of the DIPAK 1 Study : A Randomized Controlled Clinical Trial Assessing the Efficacy of Lanreotide to Halt Disease Progression in Autosomal Dominant Polycystic Kidney Disease

    NARCIS (Netherlands)

    Meijer, Esther; Drenth, Joost P. H.; d'Agnolo, Hedwig; Casteleijn, Niek F.; de Fijter, Johan W.; Gevers, Tom J.; Kappert, Peter; Peters, Dorien J. M.; Salih, Mahdi; Soonawala, Darius; Spithoven, Edwin M.; Torres, Vicente E.; Visser, Folkert W.; Wetzels, Jack F. M.; Zietse, Robert; Gansevoort, Ron T.

    Background: There are limited therapeutic options to slow the progression of autosomal dominant polycystic kidney disease (ADPKD). Recent clinical studies indicate that somatostatin analogues are promising for treating polycystic liver disease and potentially also for the kidney phenotype. We report

  13. Rationale and Design of the DIPAK 1 Study: A Randomized Controlled Clinical Trial Assessing the Efficacy of Lanreotide to Halt Disease Progression in Autosomal Dominant Polycystic Kidney Disease

    NARCIS (Netherlands)

    Meijer, E.; Drenth, J.P.H.; d'Agnolo, H.; Casteleijn, N.F.; Fijter, J.W. de; Gevers, T.J.G.; Kappert, P.; Peters, D.J.; Salih, M.; Soonawala, D.; Spithoven, E.M.; Torres, V.E.; Visser, F.W.; Wetzels, J.F.M.; Zietse, R.; Gansevoort, R.T.

    2014-01-01

    BACKGROUND: There are limited therapeutic options to slow the progression of autosomal dominant polycystic kidney disease (ADPKD). Recent clinical studies indicate that somatostatin analogues are promising for treating polycystic liver disease and potentially also for the kidney phenotype. We report

  14. Two clinical phenotypes in polycythemia vera.

    Science.gov (United States)

    Spivak, Jerry L; Considine, Michael; Williams, Donna M; Talbot, Conover C; Rogers, Ophelia; Moliterno, Alison R; Jie, Chunfa; Ochs, Michael F

    2014-08-28

    Polycythemia vera is the ultimate phenotypic consequence of the V617F mutation in Janus kinase 2 (encoded by JAK2), but the extent to which this mutation influences the behavior of the involved CD34+ hematopoietic stem cells is unknown. We analyzed gene expression in CD34+ peripheral-blood cells from 19 patients with polycythemia vera, using oligonucleotide microarray technology after correcting for potential confounding by sex, since the phenotypic features of the disease differ between men and women. Men with polycythemia vera had twice as many up-regulated or down-regulated genes as women with polycythemia vera, in a comparison of gene expression in the patients and in healthy persons of the same sex, but there were 102 genes with differential regulation that was concordant in men and women. When these genes were used for class discovery by means of unsupervised hierarchical clustering, the 19 patients could be divided into two groups that did not differ significantly with respect to age, neutrophil JAK2 V617F allele burden, white-cell count, platelet count, or clonal dominance. However, they did differ significantly with respect to disease duration; hemoglobin level; frequency of thromboembolic events, palpable splenomegaly, and splenectomy; chemotherapy exposure; leukemic transformation; and survival. The unsupervised clustering was confirmed by a supervised approach with the use of a top-scoring-pair classifier that segregated the 19 patients into the same two phenotypic groups with 100% accuracy. Removing sex as a potential confounder, we identified an accurate molecular method for classifying patients with polycythemia vera according to disease behavior, independently of their JAK2 V617F allele burden, and identified previously unrecognized molecular pathways in polycythemia vera outside the canonical JAK2 pathway that may be amenable to targeted therapy. (Funded by the Department of Defense and the National Institutes of Health.).

  15. Two Clinical Phenotypes in Polycythemia Vera

    Science.gov (United States)

    Spivak, Jerry L.; Considine, Michael; Williams, Donna M.; Talbot, Conover C.; Rogers, Ophelia; Moliterno, Alison R.; Jie, Chunfa; Ochs, Michael F.

    2014-01-01

    BACKGROUND Polycythemia vera is the ultimate phenotypic consequence of the V617F mutation in Janus kinase 2 (encoded by JAK2), but the extent to which this mutation influences the behavior of the involved CD34+ hematopoietic stem cells is unknown. METHODS We analyzed gene expression in CD34+ peripheral-blood cells from 19 patients with polycythemia vera, using oligonucleotide microarray technology after correcting for potential confounding by sex, since the phenotypic features of the disease differ between men and women. RESULTS Men with polycythemia vera had twice as many up-regulated or down-regulated genes as women with polycythemia vera, in a comparison of gene expression in the patients and in healthy persons of the same sex, but there were 102 genes with differential regulation that was concordant in men and women. When these genes were used for class discovery by means of unsupervised hierarchical clustering, the 19 patients could be divided into two groups that did not differ significantly with respect to age, neutrophil JAK2 V617F allele burden, white-cell count, platelet count, or clonal dominance. However, they did differ significantly with respect to disease duration; hemoglobin level; frequency of thromboembolic events, palpable splenomegaly, and splenectomy; chemotherapy exposure; leukemic transformation; and survival. The unsupervised clustering was confirmed by a supervised approach with the use of a top-scoring-pair classifier that segregated the 19 patients into the same two phenotypic groups with 100% accuracy. CONCLUSIONS Removing sex as a potential confounder, we identified an accurate molecular method for classifying patients with polycythemia vera according to disease behavior, independently of their JAK2 V617F allele burden, and identified previously unrecognized molecular pathways in polycythemia vera outside the canonical JAK2 pathway that may be amenable to targeted therapy. PMID:25162887

  16. Hand Dominance and Common Hand Conditions.

    Science.gov (United States)

    Lutsky, Kevin; Kim, Nayoung; Medina, Juana; Maltenfort, Mitchell; Beredjiklian, Pedro K

    2016-05-01

    The goals of this study were to (1) assess how frequently patients present for evaluation of common hand disorders in relation to hand dominance and (2) evaluate the effect of hand dominance on function in patients with these conditions. The authors hypothesized that (1) the majority of patients who seek evaluation would have a condition that affects the dominant hand, and (2) disability scores would be worse if the dominant hand is involved. They retrospectively reviewed the records of consecutive patients who presented for treatment to their institution with unilateral symptoms of 5 common disorders of the hand: carpal tunnel syndrome (CTS), de Quervain's tenosynovitis (DEQ), lateral epicondylitis (LE), hand osteoarthritis (OA), and trigger finger (TF). The authors assessed the effect of diagnosis and hand dominance on Disabilities of the Arm, Shoulder and Hand (DASH) scores. The study group comprised 1029 patients (379 men and 650 women) with a mean age of 59.5 years. Ninety percent were right-hand dominant. The dominant and nondominant hands were affected with relatively equal frequency for CTS, DEQ, OA, and TF (range, 45%-53%). Patients with LE had a significantly higher incidence of dominant hand involvement. Men had lower DASH scores than women by an average of 7.9 points, and DASH scores were significantly but slightly higher for the overall group (3.2 points) when the dominant side was affected. Men with LE and women with TF and OA had significantly higher DASH scores when their dominant extremity was affected. Common hand disorders such as CTS, DEQ, OA, and TF affect the dominant and nondominant hands in roughly equivalent proportions, whereas LE is more common on the dominant side. Dominant hand involvement results in significantly worse DASH scores, although the magnitude of this is relatively small. Women have significantly higher DASH scores than men for the conditions evaluated. [Orthopedics. 2016; 39(3):e444-e448.].

  17. Alzheimer disease-like clinical phenotype in a family with FTDP-17 caused by a MAPT R406W mutation

    DEFF Research Database (Denmark)

    Lindquist, S.G.; Holm, I.E.; Schwartz, M.

    2008-01-01

    We report clinical, molecular, neuroimaging and neuropathological features of a Danish family with autosomal dominant inherited dementia, a clinical phenotype resembling Alzheimer's disease and a pathogenic mutation (R406W) in the microtubule associated protein tau (MAPT) gene. Pre-symptomatic an......We report clinical, molecular, neuroimaging and neuropathological features of a Danish family with autosomal dominant inherited dementia, a clinical phenotype resembling Alzheimer's disease and a pathogenic mutation (R406W) in the microtubule associated protein tau (MAPT) gene. Pre...

  18. 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.

  19. Finding our way through phenotypes.

    Science.gov (United States)

    Deans, Andrew R; Lewis, Suzanna E; Huala, Eva; Anzaldo, Salvatore S; Ashburner, Michael; Balhoff, James P; Blackburn, David C; Blake, Judith A; Burleigh, J Gordon; Chanet, Bruno; Cooper, Laurel D; Courtot, Mélanie; Csösz, Sándor; Cui, Hong; Dahdul, Wasila; Das, Sandip; Dececchi, T Alexander; Dettai, Agnes; Diogo, Rui; Druzinsky, Robert E; Dumontier, Michel; Franz, Nico M; Friedrich, Frank; Gkoutos, George V; Haendel, Melissa; Harmon, Luke J; Hayamizu, Terry F; He, Yongqun; Hines, Heather M; Ibrahim, Nizar; Jackson, Laura M; Jaiswal, Pankaj; James-Zorn, Christina; Köhler, Sebastian; Lecointre, Guillaume; Lapp, Hilmar; Lawrence, Carolyn J; Le Novère, Nicolas; Lundberg, John G; Macklin, James; Mast, Austin R; Midford, Peter E; Mikó, István; Mungall, Christopher J; Oellrich, Anika; Osumi-Sutherland, David; Parkinson, Helen; Ramírez, Martín J; Richter, Stefan; Robinson, Peter N; Ruttenberg, Alan; Schulz, Katja S; Segerdell, Erik; Seltmann, Katja C; Sharkey, Michael J; Smith, Aaron D; Smith, Barry; Specht, Chelsea D; Squires, R Burke; Thacker, Robert W; Thessen, Anne; Fernandez-Triana, Jose; Vihinen, Mauno; Vize, Peter D; Vogt, Lars; Wall, Christine E; Walls, Ramona L; Westerfeld, Monte; Wharton, Robert A; Wirkner, Christian S; Woolley, James B; Yoder, Matthew J; Zorn, Aaron M; Mabee, Paula

    2015-01-01

    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. Epigenetics in heart failure phenotypes

    Directory of Open Access Journals (Sweden)

    Alexander Berezin

    2016-12-01

    Full Text Available 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.

  1. The human adult cardiomyocyte phenotype

    NARCIS (Netherlands)

    Bird, SD; Doevendans, PA; van Rooijen, MA; de la Riviere, AB; Hassink, RJ; Passier, R; Mummery, CL

    2003-01-01

    Aim: Determination of the phenotype of adult human atrial and ventricular myocytes based on gene expression and morphology. Methods: Atrial and ventricular cardiomyocytes were obtained from patients undergoing cardiac surgery using a modified isolation procedure. Myocytes were isolated and cultured

  2. EHR Big Data Deep Phenotyping

    National Research Council Canada - National Science Library

    L. J. Frey; L. Lenert; G. Lopez-Campos S. M. Meystre; G. K. Savova; K. C. Kipper-Schuler; J. F. Hurdle J. Zvárová; T. Dostálová; P. Hanzlíc∨ek; Z. Teuberová; M. Nagy; M. Pieš; M. Seydlová; Eliášová; H. Šimková Petra Knaup; Oliver Bott; Christian Kohl; Christian Lovis; Sebastian Garde

    2014-01-01

    Objectives: Given the quickening speed of discovery of variant disease drivers from combined patient genotype and phenotype data, the objective is to provide methodology using big data technology to support...

  3. On trees with total domination number equal to edge-vertex domination number plus one

    Indian Academy of Sciences (India)

    B Krishnakumari; Y B Venkatakrishnan; Marcin Krzywkowski

    2016-05-01

    An edge $e \\in E(G)$ dominates a vertex $v \\in V(G)$ if $e$ is incident with $v$ or $e$ is incident with a vertex adjacent to $v$. An edge-vertex dominating set of a graph $G$ is a set $D$ of edges of $G$ such that every vertex of $G$ is edge-vertex dominated by an edge of $D$. The edge-vertex domination number of a graph $G$ is the minimum cardinality of an edge-vertex dominating set of $G$. A subset $D \\subseteq V(G)$ is a total dominating set of $G$ if every vertex of $G$ has a neighbor in $D$. The total domination number of $G$ is the minimum cardinality of a total dominating set of $G$. We characterize all trees with total domination number equal to edge-vertex domination number plus one.

  4. Electroconvulsive therapy and determination of cerebral dominance

    OpenAIRE

    Dragovic, Milan; Allet, Lindsay; Janca, Aleksandar

    2004-01-01

    Electroconvulsive therapy (ECT) often results in a number of short- and long-time side effects including memory impairment for past and current events, which can last for several months after ECT treatment. It has been suggested that unilateral ECT (uECT) with electrodes placed over the non-dominant (typically right) hemisphere significantly reduces side effects, especially memory disturbances. It is important to note that cerebral dominance equates to speech dominance and avoiding this area ...

  5. Minimum Dominating Tree Problem for Graphs

    Institute of Scientific and Technical Information of China (English)

    LIN Hao; LIN Lan

    2014-01-01

    A dominating tree T of a graph G is a subtree of G which contains at least one neighbor of each vertex of G. The minimum dominating tree problem is to find a dominating tree of G with minimum number of vertices, which is an NP-hard problem. This paper studies some polynomially solvable cases, including interval graphs, Halin graphs, special outer-planar graphs and others.

  6. Eye-dominance, writing hand, and throwing hand.

    Science.gov (United States)

    McManus, I C; Porac, C; Bryden, M P; Boucher, R

    1999-04-01

    Handedness and eye-dominance are undoubtedly associated statistically, although a previous meta-analysis has found that the precise relationship is difficult to explain, with about 35% of right-handers and 57% of left-handers being left eye dominant. Of particular difficulty to genetic or other models is that the proportions are distributed asymmetrically around 50%. The present study asked whether this complicated pattern of association occurred because, following Peters, it is necessary to divide right-and left-handers into consistent handers (who write and throw with the same hand) and inconsistent handers (who write and throw with opposite hands). In an analysis of 10,635 subjects from questionnaire studies, 28.8% of left-handers and 1.6% of right-handers by writing were inconsistent for throwing. Our results also showed that writing hand and throwing hand both relate independently to eyedness, that throwing hand is somewhat more strongly associated with eyedness, and that the awkward asymmetry around 50% is now removed, 24.2% of consistent right-handers being left eye dominant compared with 72.3% of consistent left-handers, and 55.4% of inconsistent right-handers compared with 47.0% of inconsistent left-handers. We conclude that eyedness is phenotypically secondary to writing and throwing handedness. In our discussion we note that eyedness runs in families, we present new data suggesting that writing hand and throwing hand are co-inherited, and we argue that further data are now required to model properly the associations of writing hand, throwing hand, and eyedness, as well as probably also footedness and language dominance.

  7. Semi-strong split domination in graphs

    Directory of Open Access Journals (Sweden)

    Anwar Alwardi

    2014-06-01

    Full Text Available Given a graph $G = (V,E$, a dominating set $D subseteq V$ is called a semi-strong split dominating set of $G$ if $|V setminus D| geq 1$ and the maximum degree of the subgraph induced by $V setminus D$ is 1. The minimum cardinality of a semi-strong split dominating set (SSSDS of G is the semi-strong split domination number of G, denoted $gamma_{sss}(G$. In this work, we introduce the concept and prove several results regarding it.

  8. Neighborhood connected perfect domination in graphs

    Directory of Open Access Journals (Sweden)

    Kulandai Vel M.P.

    2012-12-01

    Full Text Available Let $G = (V, E$ be a connected graph. A set $S$ of vertices in $G$ is a perfect dominating set if every vertex $v$ in $V-S$ is adjacent to exactly one vertex in $S$. A perfect dominating set $S$ is said to be a neighborhood connected perfect dominating set (ncpd-set if the induced subgraph $$ is connected. The minimum cardinality of a ncpd-set of $G$ is called the neighborhood connected perfect domination number of $G$ and is denoted by $\\gamma_{ncp}(G$. In this paper we initiate a study of this parameter.

  9. Autosomal dominant adult neuronal ceroid lipofuscinosis

    NARCIS (Netherlands)

    Nijssen, Peter C.G.

    2011-01-01

    this thesis investigates a family with autosomal dominant neuronal ceroid lipofuscinosis, with chapters on clinical neurology, neuropathology, neurogenetics, neurophysiology, auditory and visual aspects.

  10. Cycles are determined by their domination polynomials

    CERN Document Server

    Akbari, Saieed

    2009-01-01

    Let $G$ be a simple graph of order $n$. A dominating set of $G$ is a set $S$ of vertices of $G$ so that every vertex of $G$ is either in $S$ or adjacent to a vertex in $S$. The domination polynomial of $G$ is the polynomial $D(G,x)=\\sum_{i=1}^{n} d(G,i) x^{i}$, where $d(G,i)$ is the number of dominating sets of $G$ of size $i$. In this paper we show that cycles are determined by their domination polynomials.

  11. Consumers, health insurance and dominated choices.

    Science.gov (United States)

    Sinaiko, Anna D; Hirth, Richard A

    2011-03-01

    We analyze employee health plan choices when the choice set offered by their employer includes a dominated plan. During our study period, one-third of workers were enrolled in the dominated plan. Some may have selected the plan before it was dominated and then failed to switch out of it. However, a substantial number actively chose the dominated plan when they had an unambiguously better choice. These results suggest limitations in the ability of health reform based solely on consumer choice to achieve efficient outcomes and that implementation of health reform should anticipate, monitor and account for this consumer behavior.

  12. The digital revolution in phenotyping

    Science.gov (United States)

    Oellrich, Anika; Collier, Nigel; Groza, Tudor; Rebholz-Schuhmann, Dietrich; Shah, Nigam; Bodenreider, Olivier; Boland, Mary Regina; Georgiev, Ivo; Liu, Hongfang; Livingston, Kevin; Luna, Augustin; Mallon, Ann-Marie; Manda, Prashanti; Robinson, Peter N.; Rustici, Gabriella; Simon, Michelle; Wang, Liqin; Winnenburg, Rainer; Dumontier, Michel

    2016-01-01

    Phenotypes have gained increased notoriety in the clinical and biological domain owing to their application in numerous areas such as the discovery of disease genes and drug targets, phylogenetics and pharmacogenomics. Phenotypes, defined as observable characteristics of organisms, can be seen as one of the bridges that lead to a translation of experimental findings into clinical applications and thereby support ‘bench to bedside’ efforts. However, to build this translational bridge, a common and universal understanding of phenotypes is required that goes beyond domain-specific definitions. To achieve this ambitious goal, a digital revolution is ongoing that enables the encoding of data in computer-readable formats and the data storage in specialized repositories, ready for integration, enabling translational research. While phenome research is an ongoing endeavor, the true potential hidden in the currently available data still needs to be unlocked, offering exciting opportunities for the forthcoming years. Here, we provide insights into the state-of-the-art in digital phenotyping, by means of representing, acquiring and analyzing phenotype data. In addition, we provide visions of this field for future research work that could enable better applications of phenotype data. PMID:26420780

  13. Molecular correlates of social dominance: a novel role for ependymin in aggression.

    Science.gov (United States)

    Sneddon, Lynne U; Schmidt, Rupert; Fang, Yongxiang; Cossins, Andrew R

    2011-04-05

    Theoretical and empirical studies have sought to explain the formation and maintenance of social relationships within groups. The resulting dominance hierarchies have significant fitness and survival consequences dependent upon social status. We hypothesised that each position or rank within a group has a distinctive brain gene expression profile that correlates with behavioural phenotype. Furthermore, transitions in rank position should determine which genes shift in expression concurrent with the new dominance status. We used a custom cDNA microarray to profile brain transcript expression in a model species, the rainbow trout, which forms tractable linear hierarchies. Dominant, subdominant and submissive individuals had distinctive transcript profiles with 110 gene probes identified using conservative statistical analyses. By removing the dominant, we characterised the changes in transcript expression in sub-dominant individuals that became dominant demonstrating that the molecular transition occurred within 48 hours. A strong, novel candidate gene, ependymin, which was highly expressed in both the transcript and protein in subdominants relative to dominants, was tested further. Using antibody injection to inactivate ependymin in pairs of dominant and subdominant zebrafish, the subdominant fish exhibited a substantial increase in aggression in parallel with an enhanced competitive ability. This is the first study to characterise the molecular signatures of dominance status within groups and the first to implicate ependymin in control of aggressive behaviour. It also provides evidence for indirect genetic effect models in which genotype/phenotype of an individual is influenced by conspecific interactions within a group. The variation in the molecular profile of each individual within a group may offer a new explanation of intraspecific variation in gene expression within undefined groups of animals and provides new candidates for empirical study.

  14. Molecular correlates of social dominance: a novel role for ependymin in aggression.

    Directory of Open Access Journals (Sweden)

    Lynne U Sneddon

    Full Text Available Theoretical and empirical studies have sought to explain the formation and maintenance of social relationships within groups. The resulting dominance hierarchies have significant fitness and survival consequences dependent upon social status. We hypothesised that each position or rank within a group has a distinctive brain gene expression profile that correlates with behavioural phenotype. Furthermore, transitions in rank position should determine which genes shift in expression concurrent with the new dominance status. We used a custom cDNA microarray to profile brain transcript expression in a model species, the rainbow trout, which forms tractable linear hierarchies. Dominant, subdominant and submissive individuals had distinctive transcript profiles with 110 gene probes identified using conservative statistical analyses. By removing the dominant, we characterised the changes in transcript expression in sub-dominant individuals that became dominant demonstrating that the molecular transition occurred within 48 hours. A strong, novel candidate gene, ependymin, which was highly expressed in both the transcript and protein in subdominants relative to dominants, was tested further. Using antibody injection to inactivate ependymin in pairs of dominant and subdominant zebrafish, the subdominant fish exhibited a substantial increase in aggression in parallel with an enhanced competitive ability. This is the first study to characterise the molecular signatures of dominance status within groups and the first to implicate ependymin in control of aggressive behaviour. It also provides evidence for indirect genetic effect models in which genotype/phenotype of an individual is influenced by conspecific interactions within a group. The variation in the molecular profile of each individual within a group may offer a new explanation of intraspecific variation in gene expression within undefined groups of animals and provides new candidates for empirical

  15. Octreotide acetate in dominant cystoid macular dystrophy.

    NARCIS (Netherlands)

    Hogewind, B.F.T.; Pieters, G.; Hoyng, C.B.

    2008-01-01

    PURPOSE: Dominant cystoid macular degeneration (DCMD) is an autosomal dominant trait of cystoid macular edema with poor visual prognosis. Until now, no efficient treatments for DCMD have been reported. The authors evaluated a somatostatin-analogue (octreotide acetate) as treatment for DCMD. METHODS:

  16. A note on generalized nonlinear diagonal dominance

    Science.gov (United States)

    Gan, Tai-Bin; Huang, Ting-Zhu; Gao, Jian

    2006-01-01

    In this paper, an open problem, proposed by A. Frommer, about nonlinear generalized diagonal dominance, is solved on some weak restriction, a counterexample is presented if such a restriction is omitted, and some new properties of nonlinear generalized diagonally dominant functions are investigated.

  17. Local surface orientation dominates haptic curvature discrimination

    NARCIS (Netherlands)

    Wijntjes, M.W.A.; Sato, A.; Hayward, V.; Kappers, A.M.L.

    2009-01-01

    Prior studies have shown that local surface orientation is a dominant source of information for haptic curvature perception in static conditions. We show that this dominance holds for dynamic touch, just as was shown earlier for static touch. Using an apparatus specifically developed for this purpos

  18. Pareto-adaptive epsilon-dominance.

    Science.gov (United States)

    Hernández-Díaz, Alfredo G; Santana-Quintero, Luis V; Coello Coello, Carlos A; Molina, Julián

    2007-01-01

    Efficiency has become one of the main concerns in evolutionary multiobjective optimization during recent years. One of the possible alternatives to achieve a faster convergence is to use a relaxed form of Pareto dominance that allows us to regulate the granularity of the approximation of the Pareto front that we wish to achieve. One such relaxed forms of Pareto dominance that has become popular in the last few years is epsilon-dominance, which has been mainly used as an archiving strategy in some multiobjective evolutionary algorithms. Despite its advantages, epsilon-dominance has some limitations. In this paper, we propose a mechanism that can be seen as a variant of epsilon-dominance, which we call Pareto-adaptive epsilon-dominance (paepsilon-dominance). Our proposed approach tries to overcome the main limitation of epsilon-dominance: the loss of several nondominated solutions from the hypergrid adopted in the archive because of the way in which solutions are selected within each box.

  19. English, Language Dominance, and Ecolinguistic Diversity Maintenance

    DEFF Research Database (Denmark)

    Phillipson, Robert; Skutnabb-Kangas, Tove

    2013-01-01

    The chapter analyses how English became dominant and the implications of the expansion of dominant languages for the linguistic and cultural ecology and biodiversity. English has expanded through the imperialist and linguicist policies of the UK, the USA and the World Bank. Key structural and ide...

  20. English, Language Dominance, and Ecolinguistic Diversity Maintenance

    DEFF Research Database (Denmark)

    Phillipson, Robert; Skutnabb-Kangas, Tove

    2017-01-01

    The chapter analyses how English became dominant and the implications of the expansion of dominant languages for the linguistic and cultural ecology and biodiversity. English has expanded through the imperialist and linguicist policies of the UK, the USA and the World Bank. Key structural and ide...

  1. Vision research: losing sight of eye dominance.

    Science.gov (United States)

    Carey, D P

    2001-10-16

    Most people prefer to use their right eye for viewing. New evidence reveals that this dominance is much more plastic than that for one hand or foot: it changes from one eye to the other depending on angle of gaze. Remarkably, sighting dominance depends on the hand being directed towards the visual target.

  2. Modelling dominance in a flexible intercross analysis

    Directory of Open Access Journals (Sweden)

    Besnier Francois

    2009-06-01

    Full Text Available Abstract Background The aim of this paper is to develop a flexible model for analysis of quantitative trait loci (QTL in outbred line crosses, which includes both additive and dominance effects. Our flexible intercross analysis (FIA model accounts for QTL that are not fixed within founder lines and is based on the variance component framework. Genome scans with FIA are performed using a score statistic, which does not require variance component estimation. Results Simulations of a pedigree with 800 F2 individuals showed that the power of FIA including both additive and dominance effects was almost 50% for a QTL with equal allele frequencies in both lines with complete dominance and a moderate effect, whereas the power of a traditional regression model was equal to the chosen significance value of 5%. The power of FIA without dominance effects included in the model was close to those obtained for FIA with dominance for all simulated cases except for QTL with overdominant effects. A genome-wide linkage analysis of experimental data from an F2 intercross between Red Jungle Fowl and White Leghorn was performed with both additive and dominance effects included in FIA. The score values for chicken body weight at 200 days of age were similar to those obtained in FIA analysis without dominance. Conclusion We have extended FIA to include QTL dominance effects. The power of FIA was superior, or similar, to standard regression methods for QTL effects with dominance. The difference in power for FIA with or without dominance is expected to be small as long as the QTL effects are not overdominant. We suggest that FIA with only additive effects should be the standard model to be used, especially since it is more computationally efficient.

  3. Phenotypic screens targeting neurodegenerative diseases.

    Science.gov (United States)

    Zhang, Minhua; Luo, Guangrui; Zhou, Yanjiao; Wang, Shaohui; Zhong, Zhong

    2014-01-01

    Neurodegenerative diseases affect millions of people worldwide, and the incidences increase as the population ages. Disease-modifying therapy that prevents or slows disease progression is still lacking, making neurodegenerative diseases an area of high unmet medical need. Target-based drug discovery for disease-modifying agents has been ongoing for many years, without much success due to incomplete understanding of the molecular mechanisms underlying neurodegeneration. Phenotypic screening, starting with a disease-relevant phenotype to screen for compounds that change the outcome of biological pathways rather than activities at certain specific targets, offers an alternative approach to find small molecules or targets that modulate the key characteristics of neurodegeneration. Phenotypic screens that focus on amelioration of disease-specific toxins, protection of neurons from degeneration, or promotion of neuroregeneration could be potential fertile grounds for discovering therapeutic agents for neurodegenerative diseases. In this review, we will summarize the progress of compound screening using these phenotypic-based strategies for this area, with a highlight on unique considerations for disease models, assays, and screening methodologies. We will further provide our perspectives on how best to use phenotypic screening to develop drug leads for neurodegenerative diseases.

  4. 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.

  5. MME mutation in dominant spinocerebellar ataxia with neuropathy (SCA43).

    Science.gov (United States)

    Depondt, Chantal; Donatello, Simona; Rai, Myriam; Wang, François Charles; Manto, Mario; Simonis, Nicolas; Pandolfo, Massimo

    2016-10-01

    To identify the causative gene mutation in a 5-generation Belgian family with dominantly inherited spinocerebellar ataxia and polyneuropathy, in which known genetic etiologies had been excluded. We collected DNA samples of 28 family members, including 7 living affected individuals, whose clinical records were reviewed by a neurologist experienced in ataxia. We combined linkage data of 21 family members with whole exome sequencing in 2 affected individuals to identify shared heterozygous variants mapping to potentially linked regions. Variants were screened for rarity and for predicted damaging effect. A candidate mutation was confirmed by Sanger sequencing and tested for cosegregation with the disease. Affected individuals presented with late-onset sensorimotor axonal polyneuropathy; all but one also had cerebellar ataxia. We identified a variant in the MME gene, p.C143Y, that was absent from control databases, cosegregated with the phenotype, and was predicted to have a strong damaging effect on the encoded protein by all algorithms we used. MME encodes neprilysin (NEP), a zinc-dependent metalloprotease expressed in most tissues, including the central and peripheral nervous systems. The mutated cysteine 143 forms a disulfide bridge, which is 100% conserved in NEP and in similar enzymes. The recent identification of recessive MME mutations in 10 unrelated individuals from Japan with axonal polyneuropathy further supports the causality of the mutation, despite the dominant mode of inheritance and the presence of cerebellar involvement in our study family. Functional studies are needed to identify the mechanisms underlying these differences.

  6. Electroconvulsive therapy and determination of cerebral dominance.

    Science.gov (United States)

    Dragovic, Milan; Allet, Lindsay; Janca, Aleksandar

    2004-08-12

    Electroconvulsive therapy (ECT) often results in a number of short- and long-time side effects including memory impairment for past and current events, which can last for several months after ECT treatment. It has been suggested that unilateral ECT (uECT) with electrodes placed over the non-dominant (typically right) hemisphere significantly reduces side effects, especially memory disturbances. It is important to note that cerebral dominance equates to speech dominance and avoiding this area of the brain also reduces speech dysfunction after ECT. Traditionally, the routine clinical determination of cerebral dominance has been through the assessment of hand, foot and eye dominance, which is an easy and inexpensive approach that, however, does not ensure accuracy. This review of literature on different methods and techniques for determination of cerebral dominance and provides evidence that functional transcranial Doppler sonography (fTCD) represents a valid and safe alternative to invasive techniques for identifying speech lateralisation. It can be concluded that fTCD, notwithstanding its costs, could be used as a standard procedure prior to uECT treatment to determine cerebral dominance, thereby further reducing cognitive side-effects of ECT and possibly making it more acceptable to both patients and clinicians.

  7. Dominance hierarchy arising from the evolution of a complex small RNA regulatory network.

    Science.gov (United States)

    Durand, Eléonore; Méheust, Raphaël; Soucaze, Marion; Goubet, Pauline M; Gallina, Sophie; Poux, Céline; Fobis-Loisy, Isabelle; Guillon, Eline; Gaude, Thierry; Sarazin, Alexis; Figeac, Martin; Prat, Elisa; Marande, William; Bergès, Hélène; Vekemans, Xavier; Billiard, Sylvain; Castric, Vincent

    2014-12-05

    The prevention of fertilization through self-pollination (or pollination by a close relative) in the Brassicaceae plant family is determined by the genotype of the plant at the self-incompatibility locus (S locus). The many alleles at this locus exhibit a dominance hierarchy that determines which of the two allelic specificities of a heterozygous genotype is expressed at the phenotypic level. Here, we uncover the evolution of how at least 17 small RNA (sRNA)-producing loci and their multiple target sites collectively control the dominance hierarchy among alleles within the gene controlling the pollen S-locus phenotype in a self-incompatible Arabidopsis species. Selection has created a dynamic repertoire of sRNA-target interactions by jointly acting on sRNA genes and their target sites, which has resulted in a complex system of regulation among alleles. Copyright © 2014, American Association for the Advancement of Science.

  8. Predictors of dominance in male Betta splendens.

    Science.gov (United States)

    Bronstein, P M

    1985-03-01

    The formation of dominance/subordinancy relations in pairs of male Siamese fighting fish was examined in six experiments. Dominant animals typically were those fish that built the largest nests and that attacked an image of a live, displaying male most intensely prior to combat. However, pretest performance on an operant task and reaction to an animal's own mirror image were not useful predictors of subsequent dominance. These findings are consistent with the suggestion that domesticated Bettas have a territorial social strategy that includes both nest-building and fighting behaviors.

  9. Height Estimates for Equidimensional Dominant Rational Maps

    CERN Document Server

    Silverman, Joseph H

    2009-01-01

    Let F : W --> V be a dominant rational map between quasi-projective varieties of the same dimension. We give two proofs that h_V(F(P)) >> h_W(P) for all points P in a nonempty Zariski open subset of W. For dominant rational maps F : P^n --> P^n, we give a uniform estimate in which the implied constant depends only on n and the degree of F. As an application, we prove a specialization theorem for equidimensional dominant rational maps to semiabelian varieties, providing a complement to Habegger's recent theorem on unlikely intersections.

  10. Excessive prices as abuse of dominance?

    DEFF Research Database (Denmark)

    la Cour, Lisbeth; Møllgaard, Peter

    2007-01-01

    In previous research, we found that the sole Danish producer of cement holds a dominant position in the Danish market for (grey) cement. We are able to identify an inelastic long-run demand relation that would seem to permit the exercise of market power. We aim to establish whether the dominant...... firm abused its position by charging excessive prices. We also test whether tightening of the Danish competition act has altered the pricing behaviour on the market. We discuss our results in the light of a Danish competition case against the dominant cement producer that was abandoned by the authority...

  11. Total dominator chromatic number of a graph

    Directory of Open Access Journals (Sweden)

    Adel P. Kazemi

    2015-06-01

    Full Text Available Given a graph $G$, the total dominator coloring problem seeks a proper coloring of $G$ with the additional property that every vertex in the graph is adjacent to all vertices of a color class. We seek to minimize the number of color classes. We initiate to study this problem on several classes of graphs, as well as finding general bounds and characterizations. We also compare the total dominator chromatic number of a graph with the chromatic number and the total domination number of it.

  12. The Sound of Dominance: Vocal Precursors of Perceived Dominance during Interpersonal Influence.

    Science.gov (United States)

    Tusing, Kyle James; Dillard, James Price

    2000-01-01

    Determines the effects of vocal cues on judgments of dominance in an interpersonal influence context. Indicates that mean amplitude and amplitude standard deviation were positively associated with dominance judgments, whereas speech rate was negatively associated with dominance judgments. Finds that mean fundamental frequency was positively…

  13. Beethoven, a mouse model for dominant, progressive hearing loss DFNA36.

    Science.gov (United States)

    Vreugde, Sarah; Erven, Alexandra; Kros, Corné J; Marcotti, Walter; Fuchs, Helmut; Kurima, Kiyoto; Wilcox, Edward R; Friedman, Thomas B; Griffith, Andrew J; Balling, Rudi; Hrabé De Angelis, Martin; Avraham, Karen B; Steel, Karen P

    2002-03-01

    Despite recent progress in identifying genes underlying deafness, there are still relatively few mouse models of specific forms of human deafness. Here we describe the phenotype of the Beethoven (Bth) mouse mutant and a missense mutation in Tmc1 (transmembrane cochlear-expressed gene 1). Progressive hearing loss (DFNA36) and profound congenital deafness (DFNB7/B11) are caused by dominant and recessive mutations of the human ortholog, TMC1 (ref. 1), for which Bth and deafness (dn) are mouse models, respectively.

  14. Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency

    OpenAIRE

    Farooqi, I. Sadaf; Yeo, Giles S.H.; Keogh, Julia M.; Aminian, Shiva; Jebb, Susan A; Butler, Gary; Cheetham, Tim; O’Rahilly, Stephen

    2000-01-01

    Over 20 severely obese subjects in 11 independent kindreds have been reported to have pathogenic heterozygous mutations in the gene encoding the melanocortin 4 receptor (MC4R), making this the most common known monogenic cause of human obesity. To date, the detailed clinical phenotype of this dominantly inherited disorder has not been defined, and no homozygous subjects have been described. We determined the nucleotide sequence of the entire coding region of the MC4R gene in 243 subjects with...

  15. Outside finance, dominant investors and strategic transparency

    NARCIS (Netherlands)

    E.C. Perotti; E.-L. von Thadden

    2000-01-01

    This paper studies optimal financial contracts and product market competition under a strategic transparency decision. When firms seeking outside finance resort to actively monitored debt in order to commit against opportunistic behaviour, the dominant lender can influence corporate transparency. Mo

  16. A dynamic domination problem in trees

    Directory of Open Access Journals (Sweden)

    William Klostermeyer

    2015-12-01

    Full Text Available We consider a dynamic domination problem for graphs in which an infinite sequence of attacks occur at vertices with guards and the guard at the attacked vertex is required to vacate the vertex by moving to a neighboring vertex with no guard. Other guards are allowed to move at the same time, and before and after each attack and the resulting guard movements, the vertices containing guards form a dominating set of the graph. The minimum number of guards that can successfully defend the graph against such an arbitrary sequence of attacks is the m-eviction number. This parameter lies between the domination and independence numbers of the graph. We characterize the classes of trees for which the m-eviction number equals the domination number and the independence number, respectively.

  17. States on sharply dominating effect algebras

    Institute of Scientific and Technical Information of China (English)

    Zdenka RIE(C)ANOV(A); WU JunDe

    2008-01-01

    We prove that sharply dominating Archimedean atomic lattice effect algebras can be characterized by the property called basic decomposition of elements. As an application we prove the state smearing theorem for these effect algebras.

  18. States on sharply dominating effect algebras

    Institute of Scientific and Technical Information of China (English)

    Zdenka; RIE■ANOV

    2008-01-01

    We prove that sharply dominating Archimedean atomic lattice effect algebras can be characterized by the property called basic decomposition of elements.As an application we prove the state smearing theorem for these effect algebras.

  19. A Boundary Property for Upper Domination

    KAUST Repository

    AbouEisha, Hassan M.

    2016-08-08

    An upper dominating set in a graph is a minimal (with respect to set inclusion) dominating set of maximum cardinality.The problem of finding an upper dominating set is generally NP-hard, but can be solved in polynomial time in some restricted graph classes, such as P4-free graphs or 2K2-free graphs.For classes defined by finitely many forbidden induced subgraphs, the boundary separating difficult instances of the problem from polynomially solvable ones consists of the so called boundary classes.However, none of such classes has been identified so far for the upper dominating set problem.In the present paper, we discover the first boundary class for this problem.

  20. Testing for Stochastic Dominance with Diversification Possibilities

    NARCIS (Netherlands)

    G.T. Post (Thierry)

    2001-01-01

    textabstractWe derive empirical tests for stochastic dominance that allow for diversification between choice alternatives. The tests can be computed using straightforward linear programming. Bootstrapping techniques and asymptotic distribution theory can approximate the sampling properties of the te

  1. Upper Locating-Domination Numbers of Cycles

    Institute of Scientific and Technical Information of China (English)

    Yan Cai ZHAO; Er Fang SHAN; Ru Zhao GAO

    2011-01-01

    A set D of vertices in a graph G=(V,E) is a locating-dominating set (LDS) if for every two vertices u,v of V\\D the sets N(u)∩ D and N(v)∩ D are non-empty and different.The locating-domination number γL(G) is the minimum cardinality of an LDS of G,and the upper-locating domination number ΓL(G) is the maximum cardinality of a minimal LDS of G.In the present paper,methods for determining the exact values of the upper locating-domination numbers of cycles are provided.

  2. Eye dominance in children: a longitudinal study.

    Science.gov (United States)

    Dellatolas, G; Curt, F; Dargent-Paré, C; De Agostini, M

    1998-05-01

    In a sample of 807 normal preschool children aged from 3 to 6, examined eye dominance was not associated with the declared eye dominance of their parents. Forty percent of the children showed left-eyedness. Eyedness was associated with handedness and not significantly related to age group or sex. A strong relationship between the answers of the two parents concerning eye preference was observed. Two hundred forty-four children were followed-up for 2 years. The examinations were carried out once every 6 months. Two thirds of the children showed perfect stability in eye dominance. There was some evidence that stability in eye use tends to increase with age and to be lower in left-handed children with left-handed parents. There is, at present, very little evidence of a positive association between eye dominance in parents and that in their children.

  3. Dominating Manipulations in Voting with Partial Information

    CERN Document Server

    Conitzer, Vincent; Xia, Lirong

    2011-01-01

    We consider manipulation problems when the manipulator only has partial information about the votes of the nonmanipulators. Such partial information is described by an information set, which is the set of profiles of the nonmanipulators that are indistinguishable to the manipulator. Given such an information set, a dominating manipulation is a non-truthful vote that the manipulator can cast which makes the winner at least as preferable (and sometimes more preferable) as the winner when the manipulator votes truthfully. When the manipulator has full information, computing whether or not there exists a dominating manipulation is in P for many common voting rules (by known results). We show that when the manipulator has no information, there is no dominating manipulation for many common voting rules. When the manipulator's information is represented by partial orders and only a small portion of the preferences are unknown, computing a dominating manipulation is NP-hard for many common voting rules. Our results t...

  4. Testing for Stochastic Dominance with Diversification Possibilities

    NARCIS (Netherlands)

    G.T. Post (Thierry)

    2001-01-01

    textabstractWe derive empirical tests for stochastic dominance that allow for diversification between choice alternatives. The tests can be computed using straightforward linear programming. Bootstrapping techniques and asymptotic distribution theory can approximate the sampling properties of the

  5. Olivine-dominated asteroids: Mineralogy and origin

    OpenAIRE

    Sanchez, Juan A.; Reddy, Vishnu; Kelley, Michael S.; Cloutis, Edward A.; Bottke, William F.; Nesvorný, David; Lucas, Michael P.; Hardersen, Paul S.; Gaffey, Michael J.; Abell, Paul A.; Corre, Lucille Le

    2013-01-01

    Olivine-dominated asteroids are a rare type of objects formed either in nebular processes or through magmatic differentiation. The analysis of meteorite samples suggest that at least 100 parent bodies in the main belt experienced partial or complete melting and differentiation before being disrupted. However, only a few olivine-dominated asteroids, representative of the mantle of disrupted differentiated bodies, are known to exist. Due to the paucity of these objects in the main belt their or...

  6. La Domination masculine de Pierre Bourdieu

    Directory of Open Access Journals (Sweden)

    Mileva Filipović

    2008-07-01

    Full Text Available L’objet de cet article est de mettre en evidence quelques questions soulevées par La domination masculine de Pierre Bourdieu: sa construction sociale, sa dehistorisation, et sa naturalisation, sa légitimité, la permanence dans les changements et la révolution dans la connaissance pour transformer le principe de la perpétuation caractérisant ce rapport de domination.

  7. SOME CONSIDERATIONS ON ABUSE OF DOMINANT POSITION

    Directory of Open Access Journals (Sweden)

    Ovidiu Maican

    2007-12-01

    Full Text Available Article 82 (formerly 86 EC contains four essential elements (an undertaking, a dominant position, an abuse of that position and the abuse must affect trade between member states. The term undertakings is subject to the same broad interpretation as that applied to article 81 (formerly 85 EC and covers the same activities, both public and private.The Community interest must be also taken into account. Although it is not clear precisely what this element of article 86 requires, it will clearly curtail the scope of the exception provided under this article. Although abusive behavior of undertakings in a dominant position is prohibited, it must be recalled that merely being in a strong position is not a problem in itself. It is necessary for major players in a market to be aware of their position because practices which would not fall foul of article 82 (formerly 86 EC, where an undertaking is not dominant, will do so where dominance is established. A refusal to deal by a non-dominant undertaking would not be an abuse within article 82 (formerly 86 EC, but it will be so where the undertaking is dominant.

  8. 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

  9. Forensic DNA phenotyping : Regulatory issues

    NARCIS (Netherlands)

    Koops, E.J.; Schellekens, M.H.M.

    2008-01-01

    Forensic DNA phenotyping is an interesting new investigation method: crime-scene DNA is analyzed to compose a description of the unknown suspect, including external and behavioral features, geographic origin and perhaps surname. This method is allowed in some countries but prohibited in a few

  10. Forensic DNA phenotyping : Regulatory issues

    NARCIS (Netherlands)

    Koops, E.J.; Schellekens, M.H.M.

    2008-01-01

    Forensic DNA phenotyping is an interesting new investigation method: crime-scene DNA is analyzed to compose a description of the unknown suspect, including external and behavioral features, geographic origin and perhaps surname. This method is allowed in some countries but prohibited in a few others

  11. Novel SCN9A mutations underlying extreme pain phenotypes: unexpected electrophysiological and clinical phenotype correlations.

    Science.gov (United States)

    Emery, Edward C; Habib, Abdella M; Cox, James J; Nicholas, Adeline K; Gribble, Fiona M; Woods, C Geoffrey; Reimann, Frank

    2015-05-20

    The importance of NaV1.7 (encoded by SCN9A) in the regulation of pain sensing is exemplified by the heterogeneity of clinical phenotypes associated with its mutation. Gain-of-function mutations are typically pain-causing and have been associated with inherited erythromelalgia (IEM) and paroxysmal extreme pain disorder (PEPD). IEM is usually caused by enhanced NaV1.7 channel activation, whereas mutations that alter steady-state fast inactivation often lead to PEPD. In contrast, nonfunctional mutations in SCN9A are known to underlie congenital insensitivity to pain (CIP). Although well documented, the correlation between SCN9A genotypes and clinical phenotypes is still unclear. Here we report three families with novel SCN9A mutations. In a multiaffected dominant family with IEM, we found the heterozygous change L245 V. Electrophysiological characterization showed that this mutation did not affect channel activation but instead resulted in incomplete fast inactivation and a small hyperpolarizing shift in steady-state slow inactivation, characteristics more commonly associated with PEPD. In two compound heterozygous CIP patients, we found mutations that still retained functionality of the channels, with two C-terminal mutations (W1775R and L1831X) exhibiting a depolarizing shift in channel activation. Two mutations (A1236E and L1831X) resulted in a hyperpolarizing shift in steady-state fast inactivation. To our knowledge, these are the first descriptions of mutations with some retained channel function causing CIP. This study emphasizes the complex genotype-phenotype correlations that exist for SCN9A and highlights the C-terminal cytoplasmic region of NaV1.7 as a critical region for channel function, potentially facilitating analgesic drug development studies.

  12. Nigral iron deposition occurs across motor phenotypes of Parkinson's disease.

    Science.gov (United States)

    Jin, L; Wang, J; Jin, H; Fei, G; Zhang, Y; Chen, W; Zhao, L; Zhao, N; Sun, X; Zeng, M; Zhong, C

    2012-07-01

      To investigate whether brain iron deposition correlates with motor phenotypic expressions of Parkinson's disease.   We subtyped patients with Parkinson's disease according to their main motor symptoms (tremor, rigidity/bradykinesia) into three subgroups: tremor-dominant subgroup, akinetic/rigid-dominant subgroup, or mixed subgroup. The iron levels in bilateral substantia nigra, globus pallidus, putamen, the head of caudate, and red nucleus of 87 patients and 50 control subjects were assayed by measuring phase values using susceptibility-weighted phase imaging in a 3-tesla magnetic resonance system. The serum ceruloplasmin levels of all subjects were determined.   The bilateral average phase values of the substantia nigra and all other brain regions examined did not correlate with the main motor symptoms of Parkinson's disease in the total patient group or when patients were grouped according to serum ceruloplasmin levels. Significant correlations between serum ceruloplasmin levels and nigral bilateral average phase values were observed in the tremor and akinetic/rigid-dominant subgroups. Analysis of patients without prior dopaminergic medication exhibited similar results. Increased nigral iron content correlated with disease severity as assayed by the Unified Parkinson's Disease Rating Scale motor scores in the PD(AR) subgroup.   These findings suggest that nigral iron deposition, correlating with decreased serum ceruloplasmin levels, is a risk factor in Parkinson's disease across multiple motor phenotypic expressions. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

  13. A novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia linked to a mutation in the human insulin receptor gene

    DEFF Research Database (Denmark)

    Højlund, Kurt; Hansen, Torben; Lajer, Maria

    2004-01-01

    a missense mutation (Arg1174Gln) in the tyrosine kinase domain of the insulin receptor gene that cosegregated with the disease phenotype (logarithm of odds [LOD] score 3.21). In conclusion, we report a novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia. The findings demonstrate...

  14. Age and group residence but not maternal dominance affect dominance rank in young domestic horses.

    Science.gov (United States)

    Komárková, M; Bartošová, J; Dubcová, J

    2014-11-01

    We present a study focused on those factors influencing dominance position in young horses, with emphasis on the role of the mother. Horses, as other group-living polygynous mammals, form stable linear dominance hierarchies based on agonistic interactions. Higher dominance positions are believed to be connected, in both sexes, to better condition and higher reproductive success. Many variables play a role in forming the dominant-submissive relationships between horses; however, the maternal effect on the dominance position of the offspring still remains unclear, as do the possible mechanisms of transference ("inheritance"). We hypothesized that the maternal dominance position, plus differences in suckling parameters or maternal style, may be responsible for later outcome of the offspring's dominance position, characterized by 2 variables: index of fighting success (CB); and rate of winning encounters (RW). Our study animals were 8 groups of Kladruby horses, loose-housed lactating mares with foals (n = 66 mare-foal pairs); and subsequently 4 groups of the same foals at 3 yr of age. Our results revealed the impact of age on the dominance position of the young horses (P formed via sequential introducing of later-weaned groups of foals. The most dominant horses were mainly recruited from the first-weaned group of the season, and thus were also the oldest individuals in the herd. Further research is needed to discover the role of foal personality and mare style, and their links to possible dominance behaviors in a herd.

  15. Effect of Dominant Versus Non-dominant Vision in Postural Control.

    Science.gov (United States)

    Park, Rae-Young; Kee, Hoi-Sung; Kang, Jung-Ho; Lee, Su-Jin; Yoon, Soe-Ra; Jung, Kwang-Ik

    2011-06-01

    To assess the effect of dominant and non-dominant vision in controlling posture in quiet stance. Twenty-five healthy elderly subjects aged over 60 years old and twenty-five young subjects aged under 30 years old were assessed by computerized dynamic posturography. Postural stability was measured in two conditions; dominant eye open and non-dominant eye open. We used the sensory organization test (SOT) for evaluating sensory impairment. A SOT assessed the subject's ability to use and integrate somatosensory input, vision, and vestibular cues effectively to maintain balance. The SOT was conducted 3 times, and the average value of the 3 trials was used for data analysis. Equilibrium scores reflected the subject's anteroposterior sway. The highest possible score was 100, which indicated that the subject did not sway at all, and a score of 0 indicated a fall from the footplate. Determination of ocular dominance was performed by a hole-in-the card test. For the twenty-five young subjects in this study, equilibrium score in two conditions did not differ. However, for elderly subjects over 60 years, the equilibrium score in dominant vision was higher than in nondominant vision (p<0.05). In young subjects, there were no significant differences in postural control between dominant vision and non-dominant vision. However, in elderly subjects, postural control in non-dominant vision was significantly impaired. Therefore, the evaluation of a dominant eye should be considered in rehabilitation programs for elderly people.

  16. Anomalous dominance, immune parameters, and spatial ability.

    Science.gov (United States)

    Hassler, M

    1993-02-01

    In a sample of male and female subjects in late adolescence, we investigated the relationship of spatial abilities to anomalous dominance and immune parameters as suggested by Geschwind's model of cerebral lateralization (Geschwind & Galaburda, 1985) In addition to the behavioral markers asthma/allergies, migraine, and myopia, we measured IgE and Ig total in blood serum. Atypical handedness, atypical language dominance, and atypical visuospatial dominance were found to be connected with spatial giftedness, and atypical handedness was related to immune vulnerability in males. This outcome provided some support for the Geschwind model in men. In women, spatial giftedness was related to immune vulnerability, but no indicator of anomalous dominance was connected with either giftedness, or immune parameters. Thus, the central thesis of the Geschwind model, i.e., elevated prenatal testosterone effects on the developing brain cause anomalous dominance and, as side effects, spatial giftedness and immune vulnerability, and all these consequences should be related to each other, was not confirmed by our data for females.

  17. The network motif architecture of dominance hierarchies.

    Science.gov (United States)

    Shizuka, Daizaburo; McDonald, David B

    2015-04-01

    The widespread existence of dominance hierarchies has been a central puzzle in social evolution, yet we lack a framework for synthesizing the vast empirical data on hierarchy structure in animal groups. We applied network motif analysis to compare the structures of dominance networks from data published over the past 80 years. Overall patterns of dominance relations, including some aspects of non-interactions, were strikingly similar across disparate group types. For example, nearly all groups exhibited high frequencies of transitive triads, whereas cycles were very rare. Moreover, pass-along triads were rare, and double-dominant triads were common in most groups. These patterns did not vary in any systematic way across taxa, study settings (captive or wild) or group size. Two factors significantly affected network motif structure: the proportion of dyads that were observed to interact and the interaction rates of the top-ranked individuals. Thus, study design (i.e. how many interactions were observed) and the behaviour of key individuals in the group could explain much of the variations we see in social hierarchies across animals. Our findings confirm the ubiquity of dominance hierarchies across all animal systems, and demonstrate that network analysis provides new avenues for comparative analyses of social hierarchies.

  18. Dominant Mutations in the Autoimmune Regulator AIRE Are Associated with Common Organ-Specific Autoimmune Diseases.

    Science.gov (United States)

    Oftedal, Bergithe E; Hellesen, Alexander; Erichsen, Martina M; Bratland, Eirik; Vardi, Ayelet; Perheentupa, Jaakko; Kemp, E Helen; Fiskerstrand, Torunn; Viken, Marte K; Weetman, Anthony P; Fleishman, Sarel J; Banka, Siddharth; Newman, William G; Sewell, W A C; Sozaeva, Leila S; Zayats, Tetyana; Haugarvoll, Kristoffer; Orlova, Elizaveta M; Haavik, Jan; Johansson, Stefan; Knappskog, Per M; Løvås, Kristian; Wolff, Anette S B; Abramson, Jakub; Husebye, Eystein S

    2015-06-16

    The autoimmune regulator (AIRE) gene is crucial for establishing central immunological tolerance and preventing autoimmunity. Mutations in AIRE cause a rare autosomal-recessive disease, autoimmune polyendocrine syndrome type 1 (APS-1), distinguished by multi-organ autoimmunity. We have identified multiple cases and families with mono-allelic mutations in the first plant homeodomain (PHD1) zinc finger of AIRE that followed dominant inheritance, typically characterized by later onset, milder phenotypes, and reduced penetrance compared to classical APS-1. These missense PHD1 mutations suppressed gene expression driven by wild-type AIRE in a dominant-negative manner, unlike CARD or truncated AIRE mutants that lacked such dominant capacity. Exome array analysis revealed that the PHD1 dominant mutants were found with relatively high frequency (>0.0008) in mixed populations. Our results provide insight into the molecular action of AIRE and demonstrate that disease-causing mutations in the AIRE locus are more common than previously appreciated and cause more variable autoimmune phenotypes. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Resolution of Disease Phenotypes Resulting from Multilocus Genomic Variation.

    Science.gov (United States)

    Posey, Jennifer E; Harel, Tamar; Liu, Pengfei; Rosenfeld, Jill A; James, Regis A; Coban Akdemir, Zeynep H; Walkiewicz, Magdalena; Bi, Weimin; Xiao, Rui; Ding, Yan; Xia, Fan; Beaudet, Arthur L; Muzny, Donna M; Gibbs, Richard A; Boerwinkle, Eric; Eng, Christine M; Sutton, V Reid; Shaw, Chad A; Plon, Sharon E; Yang, Yaping; Lupski, James R

    2017-01-05

    Whole-exome sequencing can provide insight into the relationship between observed clinical phenotypes and underlying genotypes. We conducted a retrospective analysis of data from a series of 7374 consecutive unrelated patients who had been referred to a clinical diagnostic laboratory for whole-exome sequencing; our goal was to determine the frequency and clinical characteristics of patients for whom more than one molecular diagnosis was reported. The phenotypic similarity between molecularly diagnosed pairs of diseases was calculated with the use of terms from the Human Phenotype Ontology. A molecular diagnosis was rendered for 2076 of 7374 patients (28.2%); among these patients, 101 (4.9%) had diagnoses that involved two or more disease loci. We also analyzed parental samples, when available, and found that de novo variants accounted for 67.8% (61 of 90) of pathogenic variants in autosomal dominant disease genes and 51.7% (15 of 29) of pathogenic variants in X-linked disease genes; both variants were de novo in 44.7% (17 of 38) of patients with two monoallelic variants. Causal copy-number variants were found in 12 patients (11.9%) with multiple diagnoses. Phenotypic similarity scores were significantly lower among patients in whom the phenotype resulted from two distinct mendelian disorders that affected different organ systems (50 patients) than among patients with disorders that had overlapping phenotypic features (30 patients) (median score, 0.21 vs. 0.36; P=1.77×10(-7)). In our study, we found multiple molecular diagnoses in 4.9% of cases in which whole-exome sequencing was informative. Our results show that structured clinical ontologies can be used to determine the degree of overlap between two mendelian diseases in the same patient; the diseases can be distinct or overlapping. Distinct disease phenotypes affect different organ systems, whereas overlapping disease phenotypes are more likely to be caused by two genes encoding proteins that interact within

  20. Autosomal-dominant osteopetrosis: An incidental finding

    Directory of Open Access Journals (Sweden)

    Rajathi Maria

    2010-01-01

    Full Text Available Osteopetrosis is a descriptive term that refers to a group of rare, heritable disorders of the skeleton. Osteopetrotic conditions vary greatly in their presentation and severity, from just as an incidental finding on radiographs to causing life-threatening complications such as bone marrow suppression. It is caused by failure of osteoclast development and function. Osteopetrosis can be inherited as autosomal-recessive, autosomal-dominant or as X-linked traits, with the most severe forms being the autosomal-recessive ones. The severity of the disease is mild to moderate in the autosomal-dominant forms, with normal life expectancy. Diagnosis is largely based on clinical and radiographic evaluation. The present paper reports a case of autosomal-dominant osteopetrosis complicated by osteomyelitis with a short review of the condition.

  1. Stochastic Dominance under the Nonlinear Expected Utilities

    Directory of Open Access Journals (Sweden)

    Xinling Xiao

    2014-01-01

    Full Text Available In 1947, von Neumann and Morgenstern introduced the well-known expected utility and the related axiomatic system (see von Neumann and Morgenstern (1953. It is widely used in economics, for example, financial economics. But the well-known Allais paradox (see Allais (1979 shows that the linear expected utility has some limitations sometimes. Because of this, Peng proposed a concept of nonlinear expected utility (see Peng (2005. In this paper we propose a concept of stochastic dominance under the nonlinear expected utilities. We give sufficient conditions on which a random choice X stochastically dominates a random choice Y under the nonlinear expected utilities. We also provide sufficient conditions on which a random choice X strictly stochastically dominates a random choice Y under the sublinear expected utilities.

  2. Recent topics on the 0{sup +} dominance

    Energy Technology Data Exchange (ETDEWEB)

    Arima, A [Science Museum, Japan Science Foundation, 2-1 Kitanomaru-Koen, Chiyodaku, Tokyo 102-0091 (Japan); Yoshinaga, N [Department of Physics, Saitama University, Saitama City 338-8570 (Japan); Zhao, Y M [Department of Physics, Shanghai Jiao-Tong University, Shanghai 200030 (China)

    2005-10-01

    The ground states of all even-even nuclei have angular momentum equal to zero, I = 0, and positive parity, {pi} = +. This feature was believed to be a consequence of the attractive short-range interaction between nucleons. However, a predominance of I{sup {pi}} = 0{sup +} ground states was discovered by Johnson, Bertsch and Dean in 1998 using the two-body random ensemble. Since then many efforts have been devoted to understanding and solving this problem by many authors from a lot of view points. Still, the underlying physical origin of the I{sup {pi}} = 0{sup +} dominance has not been fully understood. In this paper, we show our recent progress in understanding the 0{sup +} dominance of many body systems. Some findings related to the I{sup {pi}} = 0{sup +} dominance are also discussed.

  3. Floating plant dominance as a stable state

    Science.gov (United States)

    Scheffer, Marten; Szabó, Sándor; Gragnani, Alessandra; van Nes, Egbert H.; Rinaldi, Sergio; Kautsky, Nils; Norberg, Jon; Roijackers, Rudi M. M.; Franken, Rob J. M.

    2003-01-01

    Invasion by mats of free-floating plants is among the most important threats to the functioning and biodiversity of freshwater ecosystems ranging from temperate ponds and ditches to tropical lakes. Dark, anoxic conditions under thick floating-plant cover leave little opportunity for animal or plant life, and they can have large negative impacts on fisheries and navigation in tropical lakes. Here, we demonstrate that floating-plant dominance can be a self-stabilizing ecosystem state, which may explain its notorious persistence in many situations. Our results, based on experiments, field data, and models, represent evidence for alternative domains of attraction in ecosystems. An implication of our findings is that nutrient enrichment reduces the resilience of freshwater systems against a shift to floating-plant dominance. On the other hand, our results also suggest that a single drastic harvest of floating plants can induce a permanent shift to an alternative state dominated by rooted, submerged growth forms. PMID:12634429

  4. Phenotypic deconstruction of gene circuitry.

    Science.gov (United States)

    Lomnitz, Jason G; Savageau, Michael A

    2013-06-01

    It remains a challenge to obtain a global perspective on the behavioral repertoire of complex nonlinear gene circuits. In this paper, we describe a method for deconstructing complex systems into nonlinear sub-systems, based on mathematically defined phenotypes, which are then represented within a system design space that allows the repertoire of qualitatively distinct phenotypes of the complex system to be identified, enumerated, and analyzed. This method efficiently characterizes large regions of system design space and quickly generates alternative hypotheses for experimental testing. We describe the motivation and strategy in general terms, illustrate its use with a detailed example involving a two-gene circuit with a rich repertoire of dynamic behavior, and discuss experimental means of navigating the system design space.

  5. Phenotypic spectrum of GABRA1

    DEFF Research Database (Denmark)

    Johannesen, Katrine; Marini, Carla; Pfeffer, Siona

    2016-01-01

    myoclonic epilepsy (2), photosensitive idiopathic generalized epilepsy (1), and generalized epilepsy with febrile seizures plus (1) to severe epileptic encephalopathies (11). In the epileptic encephalopathy group, the patients had seizures beginning between the first day of life and 15 months, with a mean...... of 7 months. Predominant seizure types in all patients were tonic-clonic in 9 participants (56%) and myoclonic seizures in 5 (31%). EEG showed a generalized photoparoxysmal response in 6 patients (37%). Four selected mutations studied functionally revealed a loss of function, without a clear genotype......-phenotype correlation. CONCLUSIONS: GABRA1 mutations make a significant contribution to the genetic etiology of both benign and severe epilepsy syndromes. Myoclonic and tonic-clonic seizures with pathologic response to photic stimulation are common and shared features in both mild and severe phenotypes....

  6. 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.

  7. Automated phenotyping of permanent crops

    Science.gov (United States)

    McPeek, K. Thomas; Steddom, Karl; Zamudio, Joseph; Pant, Paras; Mullenbach, Tyler

    2017-05-01

    AGERpoint is defining a new technology space for the growers' industry by introducing novel applications for sensor technology and data analysis to growers of permanent crops. Serving data to a state-of-the-art analytics engine from a cutting edge sensor platform, a new paradigm in precision agriculture is being developed that allows growers to understand the unique needs of each tree, bush or vine in their operation. Autonomous aerial and terrestrial vehicles equipped with multiple varieties of remote sensing technologies give AGERpoint the ability to measure key morphological and spectral features of permanent crops. This work demonstrates how such phenotypic measurements combined with machine learning algorithms can be used to determine the variety of crops (e.g., almond and pecan trees). This phenotypic and varietal information represents the first step in enabling growers with the ability to tailor their management practices to individual plants and maximize their economic productivity.

  8. 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.

  9. Phenotyping jasmonate regulation of senescence.

    Science.gov (United States)

    Seltmann, Martin A; Berger, Susanne

    2013-01-01

    Osmotic stress induces several senescence-like processes in leaves, such as specific changes in gene expression and yellowing. These processes are dependent on the accumulation of jasmonates and on intact jasmonate signaling. This chapter describes the treatment of Arabidopsis thaliana leaves with sorbitol as an osmotic stress agent and the determination of the elicited phenotypes encompassing chlorophyll loss, degradation of plastidial membrane lipids, and induction of genes regulated by senescence and jasmonate.

  10. 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.

  11. Epigenetics of dominance for enzyme activity

    Indian Academy of Sciences (India)

    Kuldip S Trehan; Kulbir S Gill

    2002-03-01

    We have isolated and purified two parental homodimers and a unique heterodimer of acid phosphatase [coded by Acph-11.05() and Acph-10.95()] from isogenic homozygotes and heterozygotes of Drosophila malerkotliana. and produce qualitatively different allozymes and the two alleles are expressed equally within and across all three genotypes and and play an equal role in the epigenetics of dominance. Subunit interaction in the heterodimer over a wide range of H+ concentrations accounts for the epigenetics of dominance for enzyme activity.

  12. Increasing dominance of IT in ICT convergence

    DEFF Research Database (Denmark)

    Henten, Anders; Tadayoni, Reza

    The aim of the paper is to examine the increasing dominance of IT companies in the converging ICT industry and, on the basis of this development, to contribute to extending the theoretical understanding of market and industry convergence in the ICT area.......The aim of the paper is to examine the increasing dominance of IT companies in the converging ICT industry and, on the basis of this development, to contribute to extending the theoretical understanding of market and industry convergence in the ICT area....

  13. Non-domination and democratic legitimacy

    DEFF Research Database (Denmark)

    Rostbøll, Christian F.

    2015-01-01

    While many regard equality as the moral foundation of democracy, republican theory grounds democracy in freedom as non-domination. The grounding of democracy in freedom has been criticized for relying on either an Aristotelian perfectionism or a Rousseauian equation of the people in their collect......While many regard equality as the moral foundation of democracy, republican theory grounds democracy in freedom as non-domination. The grounding of democracy in freedom has been criticized for relying on either an Aristotelian perfectionism or a Rousseauian equation of the people...

  14. Increasing dominance of IT in ICT convergence

    DEFF Research Database (Denmark)

    Henten, Anders; Tadayoni, Reza

    The aim of the paper is to examine the increasing dominance of IT companies in the converging ICT industry and, on the basis of this development, to contribute to extending the theoretical understanding of market and industry convergence in the ICT area.......The aim of the paper is to examine the increasing dominance of IT companies in the converging ICT industry and, on the basis of this development, to contribute to extending the theoretical understanding of market and industry convergence in the ICT area....

  15. 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.

  16. Phenotypic covariance at species’ borders

    Science.gov (United States)

    2013-01-01

    Background Understanding the evolution of species limits is important in ecology, evolution, and conservation biology. Despite its likely importance in the evolution of these limits, little is known about phenotypic covariance in geographically marginal populations, and the degree to which it constrains, or facilitates, responses to selection. We investigated phenotypic covariance in morphological traits at species’ borders by comparing phenotypic covariance matrices (P), including the degree of shared structure, the distribution of strengths of pair-wise correlations between traits, the degree of morphological integration of traits, and the ranks of matricies, between central and marginal populations of three species-pairs of coral reef fishes. Results Greater structural differences in P were observed between populations close to range margins and conspecific populations toward range centres, than between pairs of conspecific populations that were both more centrally located within their ranges. Approximately 80% of all pair-wise trait correlations within populations were greater in the north, but these differences were unrelated to the position of the sampled population with respect to the geographic range of the species. Conclusions Neither the degree of morphological integration, nor ranks of P, indicated greater evolutionary constraint at range edges. Characteristics of P observed here provide no support for constraint contributing to the formation of these species’ borders, but may instead reflect structural change in P caused by selection or drift, and their potential to evolve in the future. PMID:23714580

  17. 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.

  18. Gastric Composite Tumor of Alpha Fetoprotein-Producing Carcinoma/Hepatoid Adenocarcinoma and Endocrine Carcinoma with Reference to Cellular Phenotypes

    Directory of Open Access Journals (Sweden)

    Akira Suzuki

    2012-01-01

    Full Text Available Alpha-fetoprotein-producing carcinoma (AFPC/hepatoid adenocarcinoma (HAC and neuroendocrine carcinoma (NEC are uncommon in the stomach. Composite tumors consisting of these carcinomas and their histologic phenotypes are not well known. Between 2002 and 2007, to estimate the prevalence of composite tumors consisting of tubular adenocarcinoma, AFPC/HAC and NEC, we reviewed specimens obtained from 294 consecutive patients treated surgically for gastric cancer. We examined histological phenotype of tumors of AFPC or NEC containing the composite tumor by evaluating immunohistochemical expressions of MUC2, MUC5AC, MUC6, CDX2, and SOX2. Immunohistochemically, AFPC/HAC dominantly showed the intestinal or mixed phenotype, and NEC frequently showed the gastric phenotype. In the composite tumor, the tubular and hepatoid components showed the gastric phenotype, and the neuroendocrine component showed the mixed type. The unique composite tumor predominantly showed the gastric phenotype, and the hepatoid and neuroendocrine components were considered to be differentiated from the tubular component.

  19. The congenital "ant-egg" cataract phenotype is caused by a missense mutation in connexin46

    DEFF Research Database (Denmark)

    Hansen, Lars; Yao, Wenliang; Eiberg, Hans;

    2006-01-01

    "Ant-egg" cataract is a rare, distinct variety of congenital/infantile cataract that was reported in a large Danish family in 1967. This cataract phenotype is characterized by ant-egg-like bodies embedded in the lens in a laminar configuration and is inherited as an autosomal dominant trait. We...

  20. A novel phenotype associated with cutis laxa, abnormal fat distribution, cardiomyopathy and cataract

    NARCIS (Netherlands)

    Asbeck, E. Van; Wolthuis, D.F.; Mohamed, M.; Wevers, R.A.; Korenke, C.G.; Gardeitchik, T.; Morava, E.

    2014-01-01

    Cutis laxa (CL) is a connective tissue disorder, characterized by loose, inelastic, sagging skin. Both acquired and inherited (dominant, recessive, and X-linked) forms exist. Here, we describe a new phenotype, which overlaps with other known CL syndromes. Our patient has a unique combination of feat

  1. Phenotypic plasticity with instantaneous but delayed switches

    NARCIS (Netherlands)

    Utz, Margarete; Jeschke, Jonathan M.; Loeschcke, Volker; Gabriel, Wilfried

    2014-01-01

    Phenotypic plasticity is a widespread phenomenon, allowing organisms to better adapt to changing environments. Most empirical and theoretical studies are restricted to irreversible plasticity where the expression of a specific phenotype is mostly determined during development. However, reversible pl

  2. Estimation of additive and dominance variance for reproductive traits from different models in Duroc purebred

    Directory of Open Access Journals (Sweden)

    Talerngsak Angkuraseranee

    2010-05-01

    Full Text Available The additive and dominance genetic variances of 5,801 Duroc reproductive and growth records were estimated usingBULPF90 PC-PACK. Estimates were obtained for number born alive (NBA, birth weight (BW, number weaned (NW, andweaning weight (WW. Data were analyzed using two mixed model equations. The first model included fixed effects andrandom effects identifying inbreeding depression, additive gene effect and permanent environments effects. The secondmodel was similar to the first model, but included the dominance genotypic effect. Heritability estimates of NBA, BW, NWand WW from the two models were 0.1558/0.1716, 0.1616/0.1737, 0.0372/0.0874 and 0.1584/0.1516 respectively. Proportionsof dominance effect to total phenotypic variance from the dominance model were 0.1024, 0.1625, 0.0470, and 0.1536 for NBA,BW, NW and WW respectively. Dominance effects were found to have sizable influence on the litter size traits analyzed.Therefore, genetic evaluation with the dominance model (Model 2 is found more appropriate than the animal model (Model 1.

  3. Dominant cataract mutations and specific-locus mutations in mice induced by radiation or ethylnitrosourea

    Energy Technology Data Exchange (ETDEWEB)

    Ehling, U.H.; Favor, J.; Kratochvilova, J.; Neuhaeuser-Klaus, A. (Gesellschaft fuer Strahlen- und Umweltforschung m.b.H. Muenchen, Neuherberg (Germany, F.R.). Inst. fuer Genetik)

    1982-01-01

    In a combined experiment, dominant cataract mutations and specific-locus mutations were scored in the same offspring. In radiation experiments, a total of 15 dominant cataract and 38 specific-locus mutations was scored in 29396 offspring. In experiments with ethylnitrosourea (ENU), a total of 12 dominant cataracts and 54 specific-locus mutations was observed in 12712 offspring. The control frequency for dominant cataracts was 0 in 9954 offspring and for specific-locus mutations 11 in 169955 offspring. The two characteristic features of radiation-induced specific-locus mutations - the augmenting effect of dose fractionation and the quantitative differences in the mutation rates between spermatogonial and post-spermatogonial stages - can also be demonstrated for the induction of dominant cataracts. The dominant cataract mutations recovered can be categorized into 7 phenotypic classes. The only noteworthy difference observed between the radiation- and ENU-induced mutations recovered was that, of the 2 radiation-induced total lens opacities, both were associated with an iris anomaly and microphthalmia whereas the ENU-induced total opacities were not.

  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. Multivariate Analysis of Genotype–Phenotype Association

    Science.gov (United States)

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

    2016-01-01

    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

  6. Stochastic Dominance: Convexity and Some Efficiency Tests

    NARCIS (Netherlands)

    A.M. Lizyayev (Andrey)

    2009-01-01

    textabstractThis paper points out the importance of Stochastic Dominance (SD) efficient sets being convex. We review classic convexity and efficient set characterization results on SD efficiency of a given portfolio relative to a diversified set of assets and generalize them in the following

  7. Co-Roman domination in graphs

    Indian Academy of Sciences (India)

    S Arumugam; Karam Ebadi; Martín Manrique

    2015-02-01

    Let $G = (V,E)$ be a graph and let $f:V→ \\{0, 1, 2\\}$ be a function. A vertex is said to be protected with respect to if $f(u)> 0$ or $f(u)=0$ and is adjacent to a vertex with positive weight. The function is a co-Roman dominating function (CRDF) if: (i) every vertex in is protected, and (ii) each $v \\in V$ with $f(v) > 0$ has a neighbor $u\\in V$ with $f(u)=0$ such that the function $f_{vu}: V→ \\{0,1,2\\}$, defined by $f_{vu}(u)=1$, $f_{vu}(v)=f(v)-1$ and $f_{vu}(x)=f(x)$ for $x\\in V\\backslash \\{u,v\\}$ has no unprotected vertex. The weight of is $w(f)=_{v\\in V} f(v)$. The co-Roman domination number of a graph , denoted by $_{cr}(G)$, is the minimum weight of a co-Roman dominating function on . In this paper we initiate a study of this parameter, present several basic results, as well as some applications and directions for further research. We also show that the decision problem for the co-Roman domination number is NP-complete, even when restricted to bipartite, chordal and planar graphs.

  8. Sedimentation in a river dominated estuary

    CSIR Research Space (South Africa)

    Cooper, JAG

    1993-10-01

    Full Text Available The Mgeni Estuary on the wave dominated cast coast of South Africa occupies a narrow, bedrock confined, alluvial valley and is partially blocked at the coast by an elongate sandy barrier. Fluvial sediment extends to the barrier and marine depositon...

  9. Stochastic dominance and medical decision making.

    Science.gov (United States)

    Leshno, Moshe; Levy, Haim

    2004-08-01

    Stochastic Dominance (SD) criteria are decision making tools which allow us to choose among various strategies with only partial information on the decision makers' preferences. The notion of Stochastic Dominance has been extensively employed and developed in the area of economics, finance, agriculture, statistics, marketing and operation research since the late 1960s. For example, it may tell us which of two medical treatments with uncertain outcomes is preferred in the absence of full information on the patients' preferences. This paper presents a short review of the SD paradigm and demonstrates how the SD criteria may be employed in medical decision making, using the case of small abdominal aortic aneurysms as an illustration. Thus, for instance by assuming risk aversion one can employ second-degree stochastic dominance to divide the set of all possible treatments into the efficient set, from which the decision makers should always choose, and the inefficient (inferior) set. By employing Prospect Stochastic Dominance (PSD) a similar division can be conducted corresponding to all S-shaped utility functions.

  10. Dominance and population structure of freshwater crabs ...

    African Journals Online (AJOL)

    1997-02-06

    Feb 6, 1997 ... systems and fonm a major part of the diet of many vertebrates, little is known about their biology. ... dominant or even keystone species (Power, Tilman, Estes, .... crabs were fed ad lih with Lopis® rabbit pellets every day.

  11. Efficient Diversification According to Stochastic Dominance Criteria

    NARCIS (Netherlands)

    Kuosmanen, T.K.

    2004-01-01

    This paper develops the first operational tests of portfolio efficiency based on the general stochastic dominance (SD) criteria that account for an infinite set of diversification strategies. The main insight is to preserve the cross-sectional dependence of asset returns when forming portfolios by

  12. Google's Long-term Dominance Doubted

    Institute of Scientific and Technical Information of China (English)

    Matt Hines; 张永红

    2004-01-01

    @@ Like Netscape①, Google could lose its market dominance as rivals increasingly adopt its tactics. When it comes to search engines, people overwhelmingly prefer Googlebut increasing competition from a number of rivals could eventually threaten the company's top spot, a study has shown.

  13. Candidate genes in ocular dominance plasticity

    NARCIS (Netherlands)

    M.L. Rietman; J.-P. Sommeijer; C.N. Levelt; J.A. Heimel; A.B. Brussaard; J.G.G. Borst; Y. Elgersma; N. Galjart; G.T. van der Horst; C.M. Pennartz; A.B. Smit; B.M. Spruijt; M. Verhage; C.I. de Zeeuw

    2012-01-01

    Many studies have been devoted to the identification of genes involved in experience-dependent plasticity in the visual cortex. To discover new candidate genes, we have reexamined data from one such study on ocular dominance (OD) plasticity in recombinant inbred BXD mouse strains. We have correlated

  14. MRI of autosomal dominant pure spastic paraplegia

    DEFF Research Database (Denmark)

    Krabbe, K; Nielsen, J E; Fallentin, E

    1997-01-01

    We examined 16 patients with autosomal dominant pure spastic paraplegia (HSP) and 15 normal controls matched for age and sex using MRI of the brain and spinal cord. Images were assessed qualitatively by two independent radiologists, blinded to the clinical diagnosis. Areas of the brain and corpus...

  15. Electromyogram and force during stimulated fatigue tests of muscles in dominant and non-dominant hands

    NARCIS (Netherlands)

    Zijdewind, C; Bosch, W; Goessens, L; Kandou, T W; Kernell, D

    1990-01-01

    Mechanical and electrical properties were studied for the first dorsal interosseous muscle of the dominant (d-FDI) and non-dominant hand (nd-FDI). Observations were made before, during and after a fatigue test, fatigue being evoked by percutaneous electrical stimulation of the ulnar nerve. The test

  16. Electromyogram and force during stimulated fatigue tests of muscles in dominant and non-dominant hands

    NARCIS (Netherlands)

    Zijdewind, C; Bosch, W; Goessens, L; Kandou, T W; Kernell, D

    1990-01-01

    Mechanical and electrical properties were studied for the first dorsal interosseous muscle of the dominant (d-FDI) and non-dominant hand (nd-FDI). Observations were made before, during and after a fatigue test, fatigue being evoked by percutaneous electrical stimulation of the ulnar nerve. The test

  17. A Complex Structural Variation on Chromosome 27 Leads to the Ectopic Expression of HOXB8 and the Muffs and Beard Phenotype in Chickens

    NARCIS (Netherlands)

    Guo, Ying; Gu, Xiaorong; Sheng, Zheya; Wang, Yanqiang; Luo, Chenglong; Liu, Ranran; Qu, Hao; Shu, Dingming; Wen, Jie; Crooijmans, Richard P.M.A.; Carlborg, Örjan; Zhao, Yiqiang; Hu, Xiaoxiang; Li, Ning

    2016-01-01

    Muffs and beard (Mb) is a phenotype in chickens where groups of elongated feathers gather from both sides of the face (muffs) and below the beak (beard). It is an autosomal, incomplete dominant phenotype encoded by the Muffs and beard (Mb) locus. Here we use genome-wide association (GWA) analysis

  18. A Complex Structural Variation on Chromosome 27 Leads to the Ectopic Expression of HOXB8 and the Muffs and Beard Phenotype in Chickens

    NARCIS (Netherlands)

    Guo, Ying; Gu, Xiaorong; Sheng, Zheya; Wang, Yanqiang; Luo, Chenglong; Liu, Ranran; Qu, Hao; Shu, Dingming; Wen, Jie; Crooijmans, Richard P.M.A.; Carlborg, Örjan; Zhao, Yiqiang; Hu, Xiaoxiang; Li, Ning

    2016-01-01

    Muffs and beard (Mb) is a phenotype in chickens where groups of elongated feathers gather from both sides of the face (muffs) and below the beak (beard). It is an autosomal, incomplete dominant phenotype encoded by the Muffs and beard (Mb) locus. Here we use genome-wide association (GWA) analysis

  19. NIH Mouse Metabolic Phenotyping Centers: the power of centralized phenotyping

    Science.gov (United States)

    Kent Lloyd, K. C.; Cline, Gary W.; Wasserman, David H.

    2013-01-01

    The Mouse Metabolic Phenotyping Centers (MMPCs) were founded in 2001 by the National Institutes of Health (NIH) to advance biomedical research by providing the scientific community with standardized, high-quality phenotyping services for mouse models of diabetes, obesity, and their complications. The intent is to allow researchers to take optimum advantage of the many new mouse models produced in labs and in high-throughput public efforts. The six MMPCs are located at universities around the country and perform complex metabolic tests in intact mice and hormone and analyte assays in tissues on a fee-for-service basis. Testing is subsidized by the NIH in order to reduce the barriers for mouse researchers. Although data derived from these tests belong to the researcher submitting mice or tissues, these data are archived after publication in a public database run by the MMPC Coordinating and Bioinformatics Unit. It is hoped that data from experiments performed in many mouse models of metabolic diseases, using standard protocols, will be useful in understanding the nature of these complex disorders. The current areas of expertise include energy balance and body composition, insulin action and secretion, whole-body and tissue carbohydrate and lipid metabolism, cardiovascular and renal function, and metabolic pathway kinetics. In addition to providing services, the MMPC staff provides expertise and advice to researchers, and works to develop and refine test protocols to best meet the community’s needs in light of current scientific developments. Test technology is disseminated by publications and through annual courses. PMID:22940748

  20. 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.

  1. Power, Domination and Kafka’s Castle

    Directory of Open Access Journals (Sweden)

    Yücel Karadaş

    2012-12-01

    Full Text Available The propositions of the Enlightenment philosophy, which valued the individual and his/her freedom, began to lose effect in the middle of the 19th century, with the increasing dominance of the ‘social’ and ‘class’ brought about by the growing industrialization. This dominance, which was the result of the modern capitalist society and the beurocratic state power it gave rise to, drove the intellectuals and thinkers of the time to question the individual freedom ideals of the Enlightenment and the early stages of modernity. In the intellectual sphere this questioning gained speed with Marx but became most apparent in the propositions of the Frankfurt School, which showed a lean on Weber’s idea of beurocratic structures of the modern state. Franz Kafka’s The Castle contributes to this questioning from a literary perspective. The Castle is also important because it was written in Germany where the mechanisms of the beurocratic dominance structures were most overt. The novel strikingly represents how these mechanisms of dominance affect the individuals and the relationships between them. This study handles the individual ideal of the Enlightenment and the criticisms directed to this ideal in the modern times, and it analyzes Kafka’s The Castle in terms of how it takes its place among the criticisms to this ideal with a literary dimension. In his famous work Castle, Kafka, evaluate the modern bureaucracy and its impact on the society in a different perspective from Weber who deal with modern society with the context of rationalization. For a better understanding of the novel, it may be necessary to make a double-layer reading of it. Because, until the last pages of the novel, it is thought that modern bureaucracy as a structure is constructed in the context of “nonsense” not “rationality”. The bureucratic mechanism that woven by hundreds of details in the novel, neither its officality nor its domination built on invididuals, and

  2. Altered fibrinolysis in autosomal dominant thrombomodulin-associated coagulopathy

    Science.gov (United States)

    Burley, Kate; Whyte, Claire S.; Westbury, Sarah K.; Walker, Mary; Stirrups, Kathleen E.; Turro, Ernest; Chapman, Oliver G.; Reilly-Stitt, Christopher; Mutch, Nicola J.

    2016-01-01

    Thrombomodulin-associated coagulopathy (TM-AC) is a newly recognized dominant bleeding disorder in which a p.Cys537Stop variant in the thrombomodulin (TM) gene THBD, results in high plasma TM levels and protein C-mediated suppression of thrombin generation. Thrombin in complex with TM also activates thrombin-activatable fibrinolysis inhibitor (TAFI). However, the effect of the high plasma TM on fibrinolysis in TM-AC is unknown. Plasma from TM-AC cases and high-TM model control samples spiked with recombinant soluble TM showed reduced tissue factor–induced thrombin generation. Lysis of plasma clots from TM-AC cases was significantly delayed compared with controls but was completely restored when TM/thrombin-mediated TAFI activation was inhibited. Clots formed in blood from TM-AC cases had the same viscoelastic strength as controls but also showed a TAFI-dependent delay in fibrinolysis. Delayed fibrinolysis was reproduced in high-TM model plasma and blood samples. Partial restoration of thrombin generation with recombinant activated factor VII or activated prothrombin complex concentrate did not alter the delayed fibrinolysis in high-TM model blood. Our finding of a previously unrecognized fibrinolytic phenotype indicates that bleeding in TM-AC has a complex pathogenesis and highlights the pivotal role of TM as a regulator of hemostasis. PMID:27436851

  3. A possible dominant white gene in Jersey cattle

    Directory of Open Access Journals (Sweden)

    Sponenberg D Phillip

    2001-01-01

    Full Text Available Abstract A white heifer ("Snow" was born in 1991 from coloured registered Jersey parents. She produced six calves sired by coloured Jersey bulls: three white bull calves, two white heifer calves, and one coloured bull calf. One of the white bull calves was mated with 40 Hereford × Friesian yearling heifers (white face, predominantly black body with some white patches. The 38 resulting calves included 16 white and 22 coloured calves. Twelve of the 16 white calves were heifers and four were bulls. Red or black spotting was recorded on some white calves. The results are consistent with an autosomal dominant mutant causing the white phenotype. The mutation appears to have arisen spontaneously in Snow, then passing to her white progeny and white grand-progeny. The white individuals varied from entirely white in a few cases, to most having some residual small areas of red or black pigmentation in patterns not typical of other reported white spotting patterns of cattle.

  4. The flux-summation theorem and the 'evolution of dominance'.

    Science.gov (United States)

    Agutter, Paul S

    2008-10-21

    The flux-summation theorem (FST) is a central principle of metabolic control analysis. It describes how the control of flux through any metabolic pathway of arbitrary complexity is distributed among the component reaction steps. Two issues concerning the FST are discussed in this paper. First, it has been suggested that the theorem could, in principle, be inapplicable under certain conditions, i.e. the sum of the control coefficients of all the enzymes supporting a pathway could exceed unity. Such conditions have not been found in any species so far studied, so in practice the FST is always applicable. I argue that applicability of the FST is a precondition for phenotypic robustness and therefore for survival. Second, the FST provides a basis for explaining dominance that renders Fisher's 'modifier genes' hypothesis otiose. Some recent misunderstandings of metabolic control analysis have led to the claim that this explanation is flawed and therefore that Fisher's hypothesis can and should be reinstated. Here, these suggestions are refuted.

  5. Phenotype of normal hairline maturation.

    Science.gov (United States)

    Rassman, William R; Pak, Jae P; Kim, Jino

    2013-08-01

    Hairlines change shape with age, starting at birth. A good head of hair is frequently present some time after ages 3 to 5 years. The look of childhood has its corresponding hairline, and, as the child grows and develops into adulthood, facial morphology migrate changes from a childlike look to a more mature look. This article discusses the dynamics of hairline evolution and the phenotypic variations of the front and side hairlines in men and women. A modeling system is introduced that provides a common language to define the various anatomic points of the full range of hairlines.

  6. Phenotypic MicroRNA Microarrays

    OpenAIRE

    2013-01-01

    Microarray technology has become a very popular approach in cases where multiple experiments need to be conducted repeatedly or done with a variety of samples. In our lab, we are applying our high density spots microarray approach to microscopy visualization of the effects of transiently introduced siRNA or cDNA on cellular morphology or phenotype. In this publication, we are discussing the possibility of using this micro-scale high throughput process to study the role of microRNAs in the bio...

  7. 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

  8. A nonsense mutation in CRYGC associated with autosomal dominant congenital nuclear cataract in a Chinese family.

    Science.gov (United States)

    Yao, Ke; Jin, Chongfei; Zhu, Ning; Wang, Wei; Wu, Renyi; Jiang, Jin; Shentu, Xingchao

    2008-07-09

    To identify the genetic defect associated with autosomal dominant congenital nuclear cataract in a Chinese family. Family history and phenotypic data were recorded, and the phenotypes were documented by slit lamp photography. The genomic DNA was extracted from peripheral blood leukocytes. All the exons and flanking intronic sequences of CRYGC and CRYGD were amplified by polymerase chain reaction (PCR) and screened for mutation by direct DNA sequencing. Structural models of the wild type and mutant gammaC-crystallin were generated and analyzed by SWISS-MODEL. Sequencing of the coding regions of CRYGC and CRYGD showed the presence of a heterozygous C>A transversion at c.327 of the coding sequence in exon 3 of CRYGC (c.327C>A), which results in the substitution of a wild type cysteine to a nonsense codon (C109X). One and a half Greek key motifs at the COOH-terminus were found to be absent in the structural model of the mutant truncated gammaC-crystallin. A novel nonsense mutation in CRYGC was detected in a Chinese family with consistent autosomal dominant congenital nuclear cataract, providing clear evidence of a relationship between the genotype and the corresponding cataract phenotype.

  9. Cluster analysis of obesity and asthma phenotypes.

    Directory of Open Access Journals (Sweden)

    E Rand Sutherland

    Full Text Available BACKGROUND: Asthma is a heterogeneous disease with variability among patients in characteristics such as lung function, symptoms and control, body weight, markers of inflammation, and responsiveness to glucocorticoids (GC. Cluster analysis of well-characterized cohorts can advance understanding of disease subgroups in asthma and point to unsuspected disease mechanisms. We utilized an hypothesis-free cluster analytical approach to define the contribution of obesity and related variables to asthma phenotype. METHODOLOGY AND PRINCIPAL FINDINGS: In a cohort of clinical trial participants (n = 250, minimum-variance hierarchical clustering was used to identify clinical and inflammatory biomarkers important in determining disease cluster membership in mild and moderate persistent asthmatics. In a subset of participants, GC sensitivity was assessed via expression of GC receptor alpha (GCRα and induction of MAP kinase phosphatase-1 (MKP-1 expression by dexamethasone. Four asthma clusters were identified, with body mass index (BMI, kg/m(2 and severity of asthma symptoms (AEQ score the most significant determinants of cluster membership (F = 57.1, p<0.0001 and F = 44.8, p<0.0001, respectively. Two clusters were composed of predominantly obese individuals; these two obese asthma clusters differed from one another with regard to age of asthma onset, measures of asthma symptoms (AEQ and control (ACQ, exhaled nitric oxide concentration (F(ENO and airway hyperresponsiveness (methacholine PC(20 but were similar with regard to measures of lung function (FEV(1 (% and FEV(1/FVC, airway eosinophilia, IgE, leptin, adiponectin and C-reactive protein (hsCRP. Members of obese clusters demonstrated evidence of reduced expression of GCRα, a finding which was correlated with a reduced induction of MKP-1 expression by dexamethasone CONCLUSIONS AND SIGNIFICANCE: Obesity is an important determinant of asthma phenotype in adults. There is heterogeneity in

  10. The biology of habitat dominance; can microbes behave as weeds?

    Science.gov (United States)

    Cray, Jonathan A; Bell, Andrew N W; Bhaganna, Prashanth; Mswaka, Allen Y; Timson, David J; Hallsworth, John E

    2013-09-01

    Competition between microbial species is a product of, yet can lead to a reduction in, the microbial diversity of specific habitats. Microbial habitats can resemble ecological battlefields where microbial cells struggle to dominate and/or annihilate each other and we explore the hypothesis that (like plant weeds) some microbes are genetically hard-wired to behave in a vigorous and ecologically aggressive manner. These 'microbial weeds' are able to dominate the communities that develop in fertile but uncolonized--or at least partially vacant--habitats via traits enabling them to out-grow competitors; robust tolerances to habitat-relevant stress parameters and highly efficient energy-generation systems; avoidance of or resistance to viral infection, predation and grazers; potent antimicrobial systems; and exceptional abilities to sequester and store resources. In addition, those associated with nutritionally complex habitats are extraordinarily versatile in their utilization of diverse substrates. Weed species typically deploy multiple types of antimicrobial including toxins; volatile organic compounds that act as either hydrophobic or highly chaotropic stressors; biosurfactants; organic acids; and moderately chaotropic solutes that are produced in bulk quantities (e.g. acetone, ethanol). Whereas ability to dominate communities is habitat-specific we suggest that some microbial species are archetypal weeds including generalists such as: Pichia anomala, Acinetobacter spp. and Pseudomonas putida; specialists such as Dunaliella salina, Saccharomyces cerevisiae, Lactobacillus spp. and other lactic acid bacteria; freshwater autotrophs Gonyostomum semen and Microcystis aeruginosa; obligate anaerobes such as Clostridium acetobutylicum; facultative pathogens such as Rhodotorula mucilaginosa, Pantoea ananatis and Pseudomonas aeruginosa; and other extremotolerant and extremophilic microbes such as Aspergillus spp., Salinibacter ruber and Haloquadratum walsbyi. Some microbes

  11. The Human Phenotype Ontology in 2017

    Science.gov (United States)

    Köhler, Sebastian; Vasilevsky, Nicole A.; Engelstad, Mark; Foster, Erin; McMurry, Julie; Aymé, Ségolène; Baynam, Gareth; Bello, Susan M.; Boerkoel, Cornelius F.; Boycott, Kym M.; Brudno, Michael; Buske, Orion J.; Chinnery, Patrick F.; Cipriani, Valentina; Connell, Laureen E.; Dawkins, Hugh J.S.; DeMare, Laura E.; Devereau, Andrew D.; de Vries, Bert B.A.; Firth, Helen V.; Freson, Kathleen; Greene, Daniel; Hamosh, Ada; Helbig, Ingo; Hum, Courtney; Jähn, Johanna A.; James, Roger; Krause, Roland; F. Laulederkind, Stanley J.; Lochmüller, Hanns; Lyon, Gholson J.; Ogishima, Soichi; Olry, Annie; Ouwehand, Willem H.; Pontikos, Nikolas; Rath, Ana; Schaefer, Franz; Scott, Richard H.; Segal, Michael; Sergouniotis, Panagiotis I.; Sever, Richard; Smith, Cynthia L.; Straub, Volker; Thompson, Rachel; Turner, Catherine; Turro, Ernest; Veltman, Marijcke W.M.; Vulliamy, Tom; Yu, Jing; von Ziegenweidt, Julie; Zankl, Andreas; Züchner, Stephan; Zemojtel, Tomasz; Jacobsen, Julius O.B.; Groza, Tudor; Smedley, Damian; Mungall, Christopher J.; Haendel, Melissa; Robinson, Peter N.

    2017-01-01

    Deep phenotyping has been defined as the precise and comprehensive analysis of phenotypic abnormalities in which the individual components of the phenotype are observed and described. The three components of the Human Phenotype Ontology (HPO; www.human-phenotype-ontology.org) project are the phenotype vocabulary, disease-phenotype annotations and the algorithms that operate on these. These components are being used for computational deep phenotyping and precision medicine as well as integration of clinical data into translational research. The HPO is being increasingly adopted as a standard for phenotypic abnormalities by diverse groups such as international rare disease organizations, registries, clinical labs, biomedical resources, and clinical software tools and will thereby contribute toward nascent efforts at global data exchange for identifying disease etiologies. This update article reviews the progress of the HPO project since the debut Nucleic Acids Research database article in 2014, including specific areas of expansion such as common (complex) disease, new algorithms for phenotype driven genomic discovery and diagnostics, integration of cross-species mapping efforts with the Mammalian Phenotype Ontology, an improved quality control pipeline, and the addition of patient-friendly terminology. PMID:27899602

  12. Connectivity editing for quad-dominant meshes

    KAUST Repository

    Peng, Chihan

    2013-08-01

    We propose a connectivity editing framework for quad-dominant meshes. In our framework, the user can edit the mesh connectivity to control the location, type, and number of irregular vertices (with more or fewer than four neighbors) and irregular faces (non-quads). We provide a theoretical analysis of the problem, discuss what edits are possible and impossible, and describe how to implement an editing framework that realizes all possible editing operations. In the results, we show example edits and illustrate the advantages and disadvantages of different strategies for quad-dominant mesh design. © 2013 The Author(s) Computer Graphics Forum © 2013 The Eurographics Association and John Wiley & Sons Ltd.

  13. 0{sup +} dominance with random interactions

    Energy Technology Data Exchange (ETDEWEB)

    Arima, A [Science Museum, Japan Science Foundation, 2-1 Kitanomaru-Koen, Chiyodaku, Tokyo 102-0091 (Japan); Yoshinaga, N [Department of Physics, Saitama University, Saitama City 338-8570 (Japan); Zhao, Y M [Department of Physics, Shanghai Jiao-Tong University, Shanghai 200030 (China)

    2005-01-01

    The ground states of all even-even nuclei have angular momentum equal to zero, I = 0, and positive parity, {pi} = +. This feature was believed to be a consequence of the attractive short-range interaction between nucleons. However, a predominance of I{sup {pi}} = 0{sup +} ground states was discovered in 1998 using the two-body random ensemble. Since then many efforts have been devoted to understanding and solving this problem from a lot of viewpoints. Still, the underlying physical origin of the I{sup {pi}} = 0{sup +} dominance has not been fully understood. Our recent progress in understanding the 0{sup +}dominance of many-body systems is shown.

  14. On the Dominance of Attitude Emotionality.

    Science.gov (United States)

    Rocklage, Matthew D; Fazio, Russell H

    2016-02-01

    Many situations in our lives require us to make relatively quick decisions as whether to approach or avoid a person or object, buy or pass on a product, or accept or reject an offer. These decisions are particularly difficult when there are both positive and negative aspects to the object. How do people go about navigating this conflict to come to a summary judgment? Using the Evaluative Lexicon (EL), we demonstrate across three studies, 7,700 attitude expressions, and nearly 50 different attitude objects that when positivity and negativity conflict, the valence that is based more on emotion is more likely to dominate. Furthermore, individuals are also more consistent in the expression of their univalent summary judgments when they involve greater emotionality. In sum, valence that is based on emotion tends to dominate when resolving ambivalence and also helps individuals to remain consistent when offering quick judgments.

  15. Mean Field Games with a Dominating Player

    Energy Technology Data Exchange (ETDEWEB)

    Bensoussan, A., E-mail: axb046100@utdallas.edu [The University of Texas at Dallas, International Center for Decision and Risk Analysis, Jindal School of Management (United States); Chau, M. H. M., E-mail: michaelchaumanho@gmail.com; Yam, S. C. P., E-mail: scpyam@sta.cuhk.edu.hk [The Chinese University of Hong Kong, Department of Statistics (Hong Kong, People’s Republic of China) (China)

    2016-08-15

    In this article, we consider mean field games between a dominating player and a group of representative agents, each of which acts similarly and also interacts with each other through a mean field term being substantially influenced by the dominating player. We first provide the general theory and discuss the necessary condition for the optimal controls and equilibrium condition by adopting adjoint equation approach. We then present a special case in the context of linear-quadratic framework, in which a necessary and sufficient condition can be asserted by stochastic maximum principle; we finally establish the sufficient condition that guarantees the unique existence of the equilibrium control. The proof of the convergence result of finite player game to mean field counterpart is provided in Appendix.

  16. EXTRASOLAR REFRACTORY-DOMINATED PLANETESIMALS: AN ASSESSMENT

    Energy Technology Data Exchange (ETDEWEB)

    Jura, M.; Xu, S., E-mail: jura@astro.ucla.edu, E-mail: sxu@astro.ucla.edu [Department of Physics and Astronomy, University of California, Los Angeles, CA 90095-1562 (United States)

    2013-02-01

    Previously published observations of 60 externally polluted white dwarfs show that none of the stars have accreted from intact refractory-dominated parent bodies composed mainly of Al, Ca, and O, although planetesimals with such a distinctive composition have been predicted to form. We propose that such remarkable objects are not detected by themselves because, unless they are scattered outward from their initial orbit, they are engulfed and destroyed during the star's asymptotic giant branch evolution. As yet, there is at most only weak evidence supporting a scenario where the composition of any extrasolar minor planet can be explained by blending of an outwardly scattered refractory-dominated planetesimal with an ambient asteroid.

  17. Autosomal dominant rolandic epilepsy with speech dyspraxia.

    Science.gov (United States)

    Scheffer, I E

    2000-01-01

    Autosomal Dominant Rolandic Epilepsy with Speech Dyspraxia (ADRESD) is a rare disorder which highlights the relationship between Benign Rolandic Epilepsy (BRE) and speech and language disorders. Subtle speech and language disorders have recently been well characterised in BRE. ADRESD is associated with long term, more severe speech and language difficulties. The time course of rolandic epilepsy in ADRESD is typical of that of BRE. ADRESD is inherited in an autosomal dominant manner with anticipation. It is postulated that the anticipation may be due to an, as yet unidentified, triplet repeat expansion in a gene for rolandic epilepsy. BRE follows complex inheritance but it is possible that ADRESD may hold some valuable clues to the pathogenesis of BRE.

  18. Clustering in a neutrino-dominated universe

    Energy Technology Data Exchange (ETDEWEB)

    White, S.D.M.; Frenk, C.S.; Davis, M.

    1983-11-01

    We have simulated the nonlinear growth of structure in a universe dominated by massive neutrinos using initial conditions derived from detailed linear calculations of earlier evolution. Codes based on a direct N-body integrator and on a fast Fourier transform Poisson solver produce very similar results. The coherencce length of the neutrino distribution at early times is directly related to the mass of the neutrino and thence to the present density of the universe. We find this length to be too large to be consistent with the observed clustering scale of galaxies if other cosmological parameters are to remain within their accepted ranges. The conventional neutrino-dominated picture appears to be ruled out.

  19. Synthesis of Greedy Algorithms Using Dominance Relations

    Science.gov (United States)

    Nedunuri, Srinivas; Smith, Douglas R.; Cook, William R.

    2010-01-01

    Greedy algorithms exploit problem structure and constraints to achieve linear-time performance. Yet there is still no completely satisfactory way of constructing greedy algorithms. For example, the Greedy Algorithm of Edmonds depends upon translating a problem into an algebraic structure called a matroid, but the existence of such a translation can be as hard to determine as the existence of a greedy algorithm itself. An alternative characterization of greedy algorithms is in terms of dominance relations, a well-known algorithmic technique used to prune search spaces. We demonstrate a process by which dominance relations can be methodically derived for a number of greedy algorithms, including activity selection, and prefix-free codes. By incorporating our approach into an existing framework for algorithm synthesis, we demonstrate that it could be the basis for an effective engineering method for greedy algorithms. We also compare our approach with other characterizations of greedy algorithms.

  20. Adaptive computation for convection dominated diffusion problems

    Institute of Scientific and Technical Information of China (English)

    CHEN Zhiming; JI Guanghua

    2004-01-01

    We derive sharp L∞(L1) a posteriori error estimate for the convection dominated diffusion equations of the form αu/αt+div(vu)-εΔu=g. The derived estimate is insensitive to the diffusionparameter ε→0. The problem is discretized implicitly in time via the method of characteristics and in space via continuous piecewise linear finite elements. Numerical experiments are reported to show the competitive behavior of the proposed adaptive method.

  1. Mathias Klotz: Restaurante Dominó, Santiago

    OpenAIRE

    Klotz,Mathias

    2010-01-01

    El proyecto consiste en la construcción de un local icónico para Dominó, una de las más conocidas fuentes de soda de Santiago, que cuenta con casi 60 años de existencia. El directorio de la empresa decidió inaugurar un nuevo local en calle Isidora Goyenechea, ubicada en el barrio El Golf, nuevo centro financiero de Santiago.

  2. Hydrogen dominant metallic alloys: high temperature superconductors?

    Science.gov (United States)

    Ashcroft, N W

    2004-05-07

    The arguments suggesting that metallic hydrogen, either as a monatomic or paired metal, should be a candidate for high temperature superconductivity are shown to apply with comparable weight to alloys of metallic hydrogen where hydrogen is a dominant constituent, for example, in the dense group IVa hydrides. The attainment of metallic states should be well within current capabilities of diamond anvil cells, but at pressures considerably lower than may be necessary for hydrogen.

  3. Core Dominance Parameter for -Ray Loud Blazars

    Indian Academy of Sciences (India)

    S. H. Li; J. H. Fan; D. X. Wu

    2014-09-01

    In this paper, we compiled 572 blazars that have known core dominance parameter (log ), out of which 121 blazars are -ray loud blazars. We compared log between 121 blazars and the rest with non -ray detections, and found that -ray loud blazars showed a different distribution, and their average value of log is greater than that for non -ray blazars. Our analysis suggests that the -ray emissions are strongly beamed.

  4. Photosynthesis in Hydrogen-Dominated Atmospheres

    Science.gov (United States)

    Bains, William; Seager, Sara; Zsom, Andras

    2014-01-01

    The diversity of extrasolar planets discovered in the last decade shows that we should not be constrained to look for life in environments similar to early or present-day Earth. Super-Earth exoplanets are being discovered with increasing frequency, and some will be able to retain a stable, hydrogen-dominated atmosphere. We explore the possibilities for photosynthesis on a rocky planet with a thin H2-dominated atmosphere. If a rocky, H2-dominated planet harbors life, then that life is likely to convert atmospheric carbon into methane. Outgassing may also build an atmosphere in which methane is the principal carbon species. We describe the possible chemical routes for photosynthesis starting from methane and show that less energy and lower energy photons could drive CH4-based photosynthesis as compared with CO2-based photosynthesis. We find that a by-product biosignature gas is likely to be H2, which is not distinct from the hydrogen already present in the environment. Ammonia is a potential biosignature gas of hydrogenic photosynthesis that is unlikely to be generated abiologically. We suggest that the evolution of methane-based photosynthesis is at least as likely as the evolution of anoxygenic photosynthesis on Earth and may support the evolution of complex life. PMID:25411926

  5. Photosynthesis in Hydrogen-Dominated Atmospheres

    Directory of Open Access Journals (Sweden)

    William Bains

    2014-11-01

    Full Text Available The diversity of extrasolar planets discovered in the last decade shows that we should not be constrained to look for life in environments similar to early or present-day Earth. Super-Earth exoplanets are being discovered with increasing frequency, and some will be able to retain a stable, hydrogen-dominated atmosphere. We explore the possibilities for photosynthesis on a rocky planet with a thin H2-dominated atmosphere. If a rocky, H2-dominated planet harbors life, then that life is likely to convert atmospheric carbon into methane. Outgassing may also build an atmosphere in which methane is the principal carbon species. We describe the possible chemical routes for photosynthesis starting from methane and show that less energy and lower energy photons could drive CH4-based photosynthesis as compared with CO2-based photosynthesis. We find that a by-product biosignature gas is likely to be H2, which is not distinct from the hydrogen already present in the environment. Ammonia is a potential biosignature gas of hydrogenic photosynthesis that is unlikely to be generated abiologically. We suggest that the evolution of methane-based photosynthesis is at least as likely as the evolution of anoxygenic photosynthesis on Earth and may support the evolution of complex life.

  6. Olivine-dominated Asteroids: Mineralogy and Origin

    CERN Document Server

    Sanchez, Juan A; Kelley, Michael S; Cloutis, Edward A; Bottke, William F; Nesvorný, David; Lucas, Michael P; Hardersen, Paul S; Gaffey, Michael J; Abell, Paul A; Corre, Lucille Le

    2013-01-01

    Olivine-dominated asteroids are a rare type of objects formed either in nebular processes or through magmatic differentiation. The analysis of meteorite samples suggest that at least 100 parent bodies in the main belt experienced partial or complete melting and differentiation before being disrupted. However, only a few olivine-dominated asteroids, representative of the mantle of disrupted differentiated bodies, are known to exist. Due to the paucity of these objects in the main belt their origin and evolution have been a matter of great debate over the years. In this work we present a detailed mineralogical analysis of twelve olivine-dominated asteroids. Within our sample we distinguish two classes, one that we call pure-olivine asteroids and another referred to as olivine-rich asteroids. For the pure-olivine asteroids the olivine chemistry was found to range from ~ Fo49 to Fo70, consistent with the values measured for brachinites and R chondrites. In the case of the olivine-rich asteroids we determined thei...

  7. 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

  8. 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.

  9. Phenotypic variability in Patau syndrome.

    Science.gov (United States)

    Caba, Lavinia; Rusu, Cristina; Butnariu, Lacramioara; Panzaru, Monica; Braha, Elena; Volosciuc, M; Popescu, Roxana; Gramescu, Mihaela; Bujoran, C; Martiniuc, Violeta; Covic, M; Gorduza, E V

    2013-01-01

    Patau syndrome has an incidence of 1/10.000-20.000, the clinical diagnosis being suggested by the triad cleft lip and palate, microphthalmia/anophthalmia and postaxial polydactyly. Most frequent cytogenetic abnormality is free and homogeneous trisomy 13 (80.0%), rarely being detected trisomy mosaics or Robertsonian translocations. The objective of the study was to identify phenotypic features of trisomy 13. The retrospective study was conducted on a trial group of 14 cases diagnosed cytogenetically with trisomy 13 between January 2000 and December 2012 at lasi Medical Genetics Centre. Of the 14 cases, 3 were evaluated pathologically (two aborted foetuses and one stillborn), 8 cases were detected in the neonatal period, and 3 in infancy. Clinical diagnosis was supported by the identification of a model of abnormal development, mainly characterized by: maxillary cleft (lip and palate--5 cases; lip--1 case), ocular abnormalities (microphthalmia/anophthalmia--7 cases; cyclopia--1 case), postaxial polydactyly (7 cases), scalp defects (6 cases), congenital heart anomalies (10 cases, 6 patients with atrial septal defect), complete holoprosencephaly (4 cases), ear abnormalities (11 cases), broad nasal root (10 cases). An important issue in confirming the phenotypic variability of Patau syndrome is that the classic clinical triad was identified only in one case. Patau syndrome is a disease with variable expression and is characterized by a pattern of abnormal prenatal development characterized by facial dysmorphia, polydactyly and severe birth defects (heart, brain) that generate an increased in utero and perinatal mortality.

  10. Divergent sensory phenotypes in nonspecific arm pain: comparisons with cervical radiculopathy.

    Science.gov (United States)

    Moloney, Niamh; Hall, Toby; Doody, Catherine

    2015-02-01

    To investigate whether distinct sensory phenotypes were identifiable in individuals with nonspecific arm pain (NSAP) and whether these differed from those in people with cervical radiculopathy. A secondary question considered whether the frequency of features of neuropathic pain, kinesiophobia, high pain ratings, hyperalgesia, and allodynia differed according to subgroups of sensory phenotypes. Cross-sectional study. Higher education institution. Forty office workers with NSAP, 17 people with cervical radiculopathy, and 40 age- and sex-matched healthy controls (N=97). Not applicable. Participants were assessed using quantitative sensory testing (QST) comprising thermal and vibration detection thresholds and thermal and pressure pain thresholds; clinical examination; and relevant questionnaires. Sensory phenotypes were identified for each individual in the patient groups using z-score transformation of the QST data. Individuals with NSAP and cervical radiculopathy present with a spectrum of sensory abnormalities; a dominant sensory phenotype was not identifiable in individuals with NSAP. No distinct pattern between clinical features and questionnaire results across sensory phenotypes was identified in either group. When considering sensory phenotypes, neither individuals with NSAP nor individuals with cervical radiculopathy should be considered homogeneous. Therefore, people with either condition may warrant different intervention approaches according to their individual sensory phenotype. Issues relating to the clinical identification of sensory hypersensitivity and the validity of QST are highlighted. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  11. Phenotypic covariance structure and its divergence for acoustic mate attraction signals among four cricket species.

    Science.gov (United States)

    Bertram, Susan M; Fitzsimmons, Lauren P; McAuley, Emily M; Rundle, Howard D; Gorelick, Root

    2012-01-01

    The phenotypic variance-covariance matrix (P) describes the multivariate distribution of a population in phenotypic space, providing direct insight into the appropriateness of measured traits within the context of multicollinearity (i.e., do they describe any significant variance that is independent of other traits), and whether trait covariances restrict the combinations of phenotypes available to selection. Given the importance of P, it is therefore surprising that phenotypic covariances are seldom jointly analyzed and that the dimensionality of P has rarely been investigated in a rigorous statistical framework. Here, we used a repeated measures approach to quantify P separately for populations of four cricket species using seven acoustic signaling traits thought to enhance mate attraction. P was of full or almost full dimensionality in all four species, indicating that all traits conveyed some information that was independent of the other traits, and that phenotypic trait covariances do not constrain the combinations of signaling traits available to selection. P also differed significantly among species, although the dominant axis of phenotypic variation (p(max)) was largely shared among three of the species (Acheta domesticus, Gryllus assimilis, G. texensis), but different in the fourth (G. veletis). In G. veletis and A. domesticus, but not G. assimilis and G. texensis, p(max) was correlated with body size, while p(max) was not correlated with residual mass (a condition measure) in any of the species. This study reveals the importance of jointly analyzing phenotypic traits.

  12. Hemispheric dominance and cell phone use.

    Science.gov (United States)

    Seidman, Michael D; Siegel, Bianca; Shah, Priyanka; Bowyer, Susan M

    2013-05-01

    A thorough understanding of why we hold a cell phone to a particular ear may be of importance when studying the impact of cell phone safety. To determine if there is an obvious association between sidedness of cell phone use and auditory hemispheric dominance (AHD) or language hemispheric dominance (LHD). It is known that 70% to 95% of the population are right-handed, and of these, 96% have left-brain LHD. We have observed that most people use their cell phones in their right ear. An Internet survey was e-mailed to individuals through surveymonkey.com. The survey used a modified Edinburgh Handedness Inventory protocol. Sample questions surveyed which hand was used to write with, whether the right or left ear was used for phone conversations, as well as whether a brain tumor was present. General community. An Internet survey was randomly e-mailed to 5000 individuals selected from an otology online group, patients undergoing Wada testing and functional magnetic resonance imaging, as well as persons on the university listserv, of which 717 surveys were completed. Determination of hemispheric dominance based on preferred ear for cell phone use. A total of 717 surveys were returned. Ninety percent of the respondents were right handed, and 9% were left handed. Sixty-eight percent of the right-handed people used the cell phone in their right ear, 25% in the left ear, and 7% had no preference. Seventy-two of the left-handed respondents used their left ear, 23% used their right ear, and 5% had no preference. Cell phone use averaged 540 minutes per month over the past 9 years. An association exists between hand dominance laterality of cell phone use (73%) and our ability to predict hemispheric dominance. Most right-handed people have left-brain LHD and use their cell phone in their right ear. Similarly, most left-handed people use their cell phone in their left ear. Our study suggests that AHD may differ from LHD owing to the difference in handedness and cell phone ear use

  13. Autosomal-Dominant Multiple Pterygium Syndrome Is Caused by Mutations in MYH3.

    Science.gov (United States)

    Chong, Jessica X; Burrage, Lindsay C; Beck, Anita E; Marvin, Colby T; McMillin, Margaret J; Shively, Kathryn M; Harrell, Tanya M; Buckingham, Kati J; Bacino, Carlos A; Jain, Mahim; Alanay, Yasemin; Berry, Susan A; Carey, John C; Gibbs, Richard A; Lee, Brendan H; Krakow, Deborah; Shendure, Jay; Nickerson, Deborah A; Bamshad, Michael J

    2015-05-01

    Multiple pterygium syndrome (MPS) is a phenotypically and genetically heterogeneous group of rare Mendelian conditions characterized by multiple pterygia, scoliosis, and congenital contractures of the limbs. MPS typically segregates as an autosomal-recessive disorder, but rare instances of autosomal-dominant transmission have been reported. Whereas several mutations causing recessive MPS have been identified, the genetic basis of dominant MPS remains unknown. We identified four families affected by dominantly transmitted MPS characterized by pterygia, camptodactyly of the hands, vertebral fusions, and scoliosis. Exome sequencing identified predicted protein-altering mutations in embryonic myosin heavy chain (MYH3) in three families. MYH3 mutations underlie distal arthrogryposis types 1, 2A, and 2B, but all mutations reported to date occur in the head and neck domains. In contrast, two of the mutations found to cause MPS in this study occurred in the tail domain. The phenotypic overlap among persons with MPS, coupled with physical findings distinct from other conditions caused by mutations in MYH3, suggests that the developmental mechanism underlying MPS differs from that of other conditions and/or that certain functions of embryonic myosin might be perturbed by disruption of specific residues and/or domains. Moreover, the vertebral fusions in persons with MPS, coupled with evidence of MYH3 expression in bone, suggest that embryonic myosin plays a role in skeletal development.

  14. Clinical variability in hereditary optic neuropathies: Two novel mutations in two patients with dominant optic atrophy and Wolfram syndrome.

    Science.gov (United States)

    Galvez-Ruiz, Alberto

    2015-01-01

    Dominant optic atrophy (DOA) and Wolfram syndrome share a great deal of clinical variability, including an association with hearing loss and the presence of optic atrophy at similar ages. The objective of this paper was to discuss the phenotypic variability of these syndromes with respect to the presentation of two clinical cases. We present two patients, each with either DOA or Wolfram syndrome, and contribute to the research literature through our findings of two novel mutations. The overlapping of several clinical characteristics in hereditary optic neuropathies can complicate the differential diagnosis. Future studies are needed to better determine the genotype-phenotype correlation for these diseases.

  15. Phenotypic plasticity: molecular mechanisms and adaptive significance.

    Science.gov (United States)

    Kelly, Scott A; Panhuis, Tami M; Stoehr, Andrew M

    2012-04-01

    Phenotypic plasticity can be broadly defined as the ability of one genotype to produce more than one phenotype when exposed to different environments, as the modification of developmental events by the environment, or as the ability of an individual organism to alter its phenotype in response to changes in environmental conditions. Not surprisingly, the study of phenotypic plasticity is innately interdisciplinary and encompasses aspects of behavior, development, ecology, evolution, genetics, genomics, and multiple physiological systems at various levels of biological organization. From an ecological and evolutionary perspective, phenotypic plasticity may be a powerful means of adaptation and dramatic examples of phenotypic plasticity include predator avoidance, insect wing polymorphisms, the timing of metamorphosis in amphibians, osmoregulation in fishes, and alternative reproductive tactics in male vertebrates. From a human health perspective, documented examples of plasticity most commonly include the results of exercise, training, and/or dieting on human morphology and physiology. Regardless of the discipline, phenotypic plasticity has increasingly become the target of a plethora of investigations with the methodological approaches utilized ranging from the molecular to whole organsimal. In this article, we provide a brief historical outlook on phenotypic plasticity; examine its potential adaptive significance; emphasize recent molecular approaches that provide novel insight into underlying mechanisms, and highlight examples in fishes and insects. Finally, we highlight examples of phenotypic plasticity from a human health perspective and underscore the use of mouse models as a powerful tool in understanding the genetic architecture of phenotypic plasticity.

  16. Role of GLI2 in hypopituitarism phenotype.

    Science.gov (United States)

    Arnhold, Ivo J P; França, Marcela M; Carvalho, Luciani R; Mendonca, Berenice B; Jorge, Alexander A L

    2015-06-01

    GLI2 is a zinc-finger transcription factor involved in the Sonic Hedgehog pathway. Gli2 mutant mice have hypoplastic anterior and absent posterior pituitary glands. We reviewed the literature for patients with hypopituitarism and alterations in GLI2. Twenty-five patients (16 families) had heterozygous truncating mutations, and the phenotype frequently included GH deficiency, a small anterior pituitary lobe and an ectopic/undescended posterior pituitary lobe on magnetic resonance imaging and postaxial polydactyly. The inheritance pattern was autosomal dominant with incomplete penetrance and variable expressivity. The mutation was frequently inherited from an asymptomatic parent. Eleven patients had heterozygous non-synonymous GLI2 variants that were classified as variants of unknown significance, because they were either absent from or had a frequency lower than 0.001 in the databases. In these patients, the posterior pituitary was also ectopic, but none had polydactyly. A third group of variants found in patients with hypopituitarism were considered benign because their frequency was ≥ 0.001 in the databases. GLI2 is a large and polymorphic gene, and sequencing may identify variants whose interpretation may be difficult. Incomplete penetrance implies in the participation of other genetic and/or environmental factors. An interaction between Gli2 mutations and prenatal ethanol exposure has been demonstrated in mice dysmorphology. In conclusion, a relatively high frequency of GLI2 mutations and variants were identified in patients with congenital GH deficiency without other brain defects, and most of these patients presented with combined pituitary hormone deficiency and an ectopic posterior pituitary lobe. Future studies may clarify the relative role and frequency of GLI2 alterations in the aetiology of hypopituitarism.

  17. Dominant transmission of de novo KIF1A motor domain variant underlying pure spastic paraplegia.

    Science.gov (United States)

    Ylikallio, Emil; Kim, Doyoun; Isohanni, Pirjo; Auranen, Mari; Kim, Eunjoon; Lönnqvist, Tuula; Tyynismaa, Henna

    2015-10-01

    Variants in family 1 kinesin (KIF1A), which encodes a kinesin axonal motor protein, have been described to cause variable neurological manifestations. Recessive missense variants have led to spastic paraplegia, and recessive truncations to sensory and autonomic neuropathy. De novo missense variants cause developmental delay or intellectual disability, cerebellar atrophy and variable spasticity. We describe a family with father-to-son transmission of de novo variant in the KIF1A motor domain, in a phenotype of pure spastic paraplegia. Structural modeling of the predicted p.(Ser69Leu) amino acid change suggested that it impairs the stable binding of ATP to the KIF1A protein. Our study reports the first dominantly inherited KIF1A variant and expands the spectrum of phenotypes caused by heterozygous KIF1A motor domain variants to include pure spastic paraplegia. We conclude that KIF1A should be considered a candidate gene for hereditary paraplegias regardless of inheritance pattern.

  18. The cost of dominance: suppressing subordinate reproduction affects the reproductive success of dominant female banded mongooses.

    Science.gov (United States)

    Bell, M B V; Nichols, H J; Gilchrist, J S; Cant, M A; Hodge, S J

    2012-02-07

    Social species show considerable variation in the extent to which dominant females suppress subordinate reproduction. Much of this variation may be influenced by the cost of active suppression to dominants, who may be selected to balance the need to maximize the resources available for their own offspring against the costs of interfering with subordinate reproduction. To date, the cost of reproductive suppression has received little attention, despite its potential to influence the outcome of conflict over the distribution of reproduction in social species. Here, we investigate possible costs of reproductive suppression in banded mongooses, where dominant females evict subordinates from their groups, thereby inducing subordinate abortion. We show that evicting subordinate females is associated with substantial costs to dominant females: pups born to females who evicted subordinates while pregnant were lighter than those born after undisturbed gestations; pups whose dependent period was disrupted by an eviction attained a lower weight at independence; and the proportion of a litter that survived to independence was reduced if there was an eviction during the dependent period. To our knowledge, this is the first empirical study indicating a possible cost to dominants in attempting to suppress subordinate breeding, and we argue that much of the variation in reproductive skew both within and between social species may be influenced by adaptive variation in the effort invested in suppression by dominants.

  19. Forecasting cyanobacteria dominance in Canadian temperate lakes.

    Science.gov (United States)

    Persaud, Anurani D; Paterson, Andrew M; Dillon, Peter J; Winter, Jennifer G; Palmer, Michelle; Somers, Keith M

    2015-03-15

    Predictive models based on broad scale, spatial surveys typically identify nutrients and climate as the most important predictors of cyanobacteria abundance; however these models generally have low predictive power because at smaller geographic scales numerous other factors may be equally or more important. At the lake level, for example, the ability to forecast cyanobacteria dominance is of tremendous value to lake managers as they can use such models to communicate exposure risks associated with recreational and drinking water use, and possible exposure to algal toxins, in advance of bloom occurrence. We used detailed algal, limnological and meteorological data from two temperate lakes in south-central Ontario, Canada to determine the factors that are closely linked to cyanobacteria dominance, and to develop easy to use models to forecast cyanobacteria biovolume. For Brandy Lake (BL), the strongest and most parsimonious model for forecasting % cyanobacteria biovolume (% CB) included water column stability, hypolimnetic TP, and % cyanobacteria biovolume two weeks prior. For Three Mile Lake (TML), the best model for forecasting % CB included water column stability, hypolimnetic TP concentration, and 7-d mean wind speed. The models for forecasting % CB in BL and TML are fundamentally different in their lag periods (BL = lag 1 model and TML = lag 2 model) and in some predictor variables despite the close proximity of the study lakes. We speculate that three main factors (nutrient concentrations, water transparency and lake morphometry) may have contributed to differences in the models developed, and may account for variation observed in models derived from large spatial surveys. Our results illustrate that while forecast models can be developed to determine when cyanobacteria will dominate within two temperate lakes, the models require detailed, lake-specific calibration to be effective as risk-management tools.

  20. Dominant Correlogram Based Particle Filter Tracking

    Institute of Scientific and Technical Information of China (English)

    MAO Yan-fen; SHI Peng-fei

    2005-01-01

    A novel dominant correlogram based particle filter was proposed for an object tracking in visual surveillance. Particle filter outperforms the Kalman filter in non-linear and non-Gaussian estimation problem. This paper proposed incorporating spatial information into visual feature, and yields a reliable likelihood description of the observation and prediction. A similarity-ratio is defined to evaluate the effectivity of different similarity measurements in weighing samples. The experimental results demonstrate the effective and robust performance compared with the histogram based tracking in traffic scenes.

  1. Autosomal dominant craniosynostosis of the sutura metopica.

    Science.gov (United States)

    Hennekam, R C; Van den Boogaard, M J

    1990-11-01

    Trigonocephaly due to craniosynostosis of the sutura metopica was found in two sibs with normal intelligence. Both were microcephalic. The father had a sloping forehead and possibly partial metopic craniosynostosis. The paternal grandfather had a bony ridge at the upper half of the metopic suture without significant head deformity. A paternal sister was possibly also affected. None of the affected persons showed significant other anomalies. Craniosynostosis of the metopic suture may be an autosomal dominantly inherited disorder, not associated with functional brain or other abnormalities.

  2. Translating Dominant Institutional Logics in Practice

    DEFF Research Database (Denmark)

    Agger Nielsen, Jeppe; Jensen, Tina Blegind

    In this paper we examine the proliferation of a new mobile technology in a structured setting of home care in Denmark, focusing on how actions at multiple levels interact to enable technology diffusion and institutionalization. The case study shows how a dominating field level logic...... of the efficient mobile technology system becomes transformed and institutionalized through translation mechanisms as organizations reformulate and interpret the organizational practices of mobile technology use during the process of adoption. Our study offers a multilevel view on these processes and suggests...

  3. Radiation-dominated area metric cosmology

    CERN Document Server

    Schuller, Frederic P

    2007-01-01

    We provide further crucial support for a refined, area metric structure of spacetime. Based on the solution of conceptual issues, such as the consistent coupling of fermions and the covariant identification of radiation fields on area metric backgrounds, we show that the radiation-dominated epoch of area metric cosmology is equivalent to that epoch in standard Einstein cosmology. This ensures, in particular, successful nucleosynthesis. This surprising result complements the previously derived prediction of a small late-time acceleration of an area metric universe.

  4. Phenotypic checkpoints regulate neuronal development.

    Science.gov (United States)

    Ben-Ari, Yehezkel; Spitzer, Nicholas C

    2010-11-01

    Nervous system development proceeds by sequential gene expression mediated by cascades of transcription factors in parallel with sequences of patterned network activity driven by receptors and ion channels. These sequences are cell type- and developmental stage-dependent and modulated by paracrine actions of substances released by neurons and glia. How and to what extent these sequences interact to enable neuronal network development is not understood. Recent evidence demonstrates that CNS development requires intermediate stages of differentiation providing functional feedback that influences gene expression. We suggest that embryonic neuronal functions constitute a series of phenotypic checkpoint signatures; neurons failing to express these functions are delayed or developmentally arrested. Such checkpoints are likely to be a general feature of neuronal development and constitute presymptomatic signatures of neurological disorders when they go awry.

  5. Phenotypic Plasticity and Species Coexistence.

    Science.gov (United States)

    Turcotte, Martin M; Levine, Jonathan M

    2016-10-01

    Ecologists are increasingly interested in predicting how intraspecific variation and changing trait values impact species interactions and community composition. For many traits, much of this variation is caused by phenotypic plasticity, and thus the impact of plasticity on species coexistence deserves robust quantification. Partly due to a lack of sound theoretical expectations, empirical studies make contradictory claims regarding plasticity effects on coexistence. Our critical review of this literature, framed in modern coexistence theory, reveals that plasticity affects species interactions in ways that could impact stabilizing niche differences and competitive asymmetries. However, almost no study integrates these measures to quantify the net effect of plasticity on species coexistence. To address this challenge, we outline novel empirical approaches grounded in modern theory.

  6. Estrogen, inflammation, and platelet phenotype.

    Science.gov (United States)

    Miller, Virginia M; Jayachandran, Muthuvel; Hashimoto, Kazumori; Heit, John A; Owen, Whyte G

    2008-01-01

    Although exogenous estrogenic therapies increase the risk of thrombosis, the effects of estrogen on formed elements of blood are uncertain. This article examines the genomic and nongenomic actions of estrogen on platelet phenotype that may contribute to increased thrombotic risk. To determine aggregation, secretion, protein expression, and thrombin generation, platelets were collected from experimental animals of varying hormonal status and from women enrolled in the Kronos Early Estrogen Prevention Study. Estrogen receptor beta predominates in circulating platelets. Estrogenic treatment in ovariectomized animals decreased platelet aggregation and adenosine triphosphate (ATP) secretion. However, acute exposure to 17beta-estradiol did not reverse decreases in platelet ATP secretion invoked by lipopolysaccharide. Thrombin generation was positively correlated to the number of circulating microvesicles expressing phosphatidylserine. Assessing the effect of estrogen treatments on blood platelets may lead to new ways of identifying women at risk for adverse thrombotic events with such therapies.

  7. The genetic basis of hair whorl, handedness, and other phenotypes

    Science.gov (United States)

    Hatfield, J.S.

    2006-01-01

    Evidence is presented that RHO, RHCE, and other RH genes, may be interesting candidates to consider when searching for the genetic basis of hair whorl rotation (i.e., clockwise or counterclockwise), handedness (i.e., right handed, left handed or ambidextrous), speech laterality (i.e., right brained or left brained), speech dyslexia (e.g., stuttering), sexual orientation (i.e., heterosexual, homosexual, bisexual, or transsexual), schizophrenia, bipolar disorder, and autism spectrum disorder. Such evidence involves the need for a genetic model that includes maternal immunization to explain some of the empirical results reported in the literature. The complex polymorphisms present among the maternally immunizing RH genes can then be used to explain other empirical results. Easily tested hypotheses are suggested, based upon genotypic (but not phenotypic) frequencies of the RH genes. In particular, homozygous dominant individuals are expected to be less common or lacking entirely among the alternative phenotypes. If it is proven that RH genes are involved in brain architecture, it will have a profound effect upon our understanding of the development and organization of the asymmetrical vertebrate brain and may eventually lead to a better understanding of the developmental processes which occur to produce the various alternative phenotypes discussed here. In addition, if RH genes are shown to be involved in the production of these phenotypes, then the evolutionary studies can be performed to demonstrate the beneficial effect of the recessive alleles of RHO and RHCE, and why human evolution appears to be selecting for the recessive alleles even though an increase in the frequency of such alleles may imply lower average fecundity among some individuals possessing them.

  8. Evolution of phenotypic plasticity in colonizing species.

    Science.gov (United States)

    Lande, Russell

    2015-05-01

    I elaborate an hypothesis to explain inconsistent empirical findings comparing phenotypic plasticity in colonizing populations or species with plasticity from their native or ancestral range. Quantitative genetic theory on the evolution of plasticity reveals that colonization of a novel environment can cause a transient increase in plasticity: a rapid initial increase in plasticity accelerates evolution of a new optimal phenotype, followed by slow genetic assimilation of the new phenotype and reduction of plasticity. An association of colonization with increased plasticity depends on the difference in the optimal phenotype between ancestral and colonized environments, the difference in mean, variance and predictability of the environment, the cost of plasticity, and the time elapsed since colonization. The relative importance of these parameters depends on whether a phenotypic character develops by one-shot plasticity to a constant adult phenotype or by labile plasticity involving continuous and reversible development throughout adult life. © 2014 John Wiley & Sons Ltd.

  9. FYPO: the fission yeast phenotype ontology.

    Science.gov (United States)

    Harris, Midori A; Lock, Antonia; Bähler, Jürg; Oliver, Stephen G; Wood, Valerie

    2013-07-01

    To provide consistent computable descriptions of phenotype data, PomBase is developing a formal ontology of phenotypes observed in fission yeast. The fission yeast phenotype ontology (FYPO) is a modular ontology that uses several existing ontologies from the open biological and biomedical ontologies (OBO) collection as building blocks, including the phenotypic quality ontology PATO, the Gene Ontology and Chemical Entities of Biological Interest. Modular ontology development facilitates partially automated effective organization of detailed phenotype descriptions with complex relationships to each other and to underlying biological phenomena. As a result, FYPO supports sophisticated querying, computational analysis and comparison between different experiments and even between species. FYPO releases are available from the Subversion repository at the PomBase SourceForge project page (https://sourceforge.net/p/pombase/code/HEAD/tree/phenotype_ontology/). The current version of FYPO is also available on the OBO Foundry Web site (http://obofoundry.org/).

  10. Metabolomic phenotyping of a cloned pig model

    DEFF Research Database (Denmark)

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

    2011-01-01

    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...

  11. Phenotypic plasticity and diversity in insects

    OpenAIRE

    Moczek, Armin P.

    2010-01-01

    Phenotypic plasticity in general and polyphenic development in particular are thought to play important roles in organismal diversification and evolutionary innovation. Focusing on the evolutionary developmental biology of insects, and specifically that of horned beetles, I explore the avenues by which phenotypic plasticity and polyphenic development have mediated the origins of novelty and diversity. Specifically, I argue that phenotypic plasticity generates novel targets for evolutionary pr...

  12. 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.

  13. Geographic atrophy phenotype identification by cluster analysis.

    Science.gov (United States)

    Monés, Jordi; Biarnés, Marc

    2017-07-20

    To identify ocular phenotypes in patients with geographic atrophy secondary to age-related macular degeneration (GA) using a data-driven cluster analysis. This was a retrospective analysis of data from a prospective, natural history study of patients with GA who were followed for ≥6 months. Cluster analysis was used to identify subgroups within the population based on the presence of several phenotypic features: soft drusen, reticular pseudodrusen (RPD), primary foveal atrophy, increased fundus autofluorescence (FAF), greyish FAF appearance and subfoveal choroidal thickness (SFCT). A comparison of features between the subgroups was conducted, and a qualitative description of the new phenotypes was proposed. The atrophy growth rate between phenotypes was then compared. Data were analysed from 77 eyes of 77 patients with GA. Cluster analysis identified three groups: phenotype 1 was characterised by high soft drusen load, foveal atrophy and slow growth; phenotype 3 showed high RPD load, extrafoveal and greyish FAF appearance and thin SFCT; the characteristics of phenotype 2 were midway between phenotypes 1 and 3. Phenotypes differed in all measured features (p≤0.013), with decreases in the presence of soft drusen, foveal atrophy and SFCT seen from phenotypes 1 to 3 and corresponding increases in high RPD load, high FAF and greyish FAF appearance. Atrophy growth rate differed between phenotypes 1, 2 and 3 (0.63, 1.91 and 1.73 mm(2)/year, respectively, p=0.0005). Cluster analysis identified three distinct phenotypes in GA. One of them showed a particularly slow growth pattern. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  14. Analysing Olympic Games through dominance networks

    Science.gov (United States)

    Calzada-Infante, Laura; Lozano, Sebastián

    2016-11-01

    The aim of this paper is to assess the results/performance of countries in the Olympic Games, taking into account their size and resources. A complex network analysis approach is proposed. The first step is to build the dominance network, which is a weighted directed graph in which nodes represent the participating nations and the arc length between any two nations measures the weighted difference in the number of medals won by both countries. An arc from a country to another b exists only if the latter has won more medals than the former and, in addition, it is smaller in population and in terms of GDP. In other words, an arc between two nodes exists if the origin nation performs worse than the destination when, given the population and GDP of both countries, it should have performed better (or at least equally). This dominance network has transitive links and a layered structure and, apart from being visualized, it can be characterized using different complex network measures. The results of the Beijing 2008 Olympic Games are used to illustrate the proposed approach.

  15. A stem cell niche dominance theorem

    Directory of Open Access Journals (Sweden)

    Shibata Darryl K

    2011-01-01

    Full Text Available Abstract Background Multilevelness is a defining characteristic of complex systems. For example, in the intestinal tissue the epithelial lining is organized into crypts that are maintained by a niche of stem cells. The behavior of the system 'as a whole' is considered to emerge from the functioning and interactions of its parts. What we are seeking here is a conceptual framework to demonstrate how the "fate" of intestinal crypts is an emergent property that inherently arises from the complex yet robust underlying biology of stem cells. Results We establish a conceptual framework in which to formalize cross-level principles in the context of tissue organization. To this end we provide a definition for stemness, which is the propensity of a cell lineage to contribute to a tissue fate. We do not consider stemness a property of a cell but link it to the process in which a cell lineage contributes towards tissue (malfunction. We furthermore show that the only logically feasible relationship between the stemness of cell lineages and the emergent fate of their tissue, which satisfies the given criteria, is one of dominance from a particular lineage. Conclusions The dominance theorem, conceived and proven in this paper, provides support for the concepts of niche succession and monoclonal conversion in intestinal crypts as bottom-up relations, while crypt fission is postulated to be a top-down principle.

  16. Are quasar jets dominated by Poynting flux?

    CERN Document Server

    Sikora, M; Madejski, G M; Lasota, J P; Sikora, Marek; Begelman, Mitchell C.; Madejski, Greg M.; Lasota, Jean-Pierre

    2005-01-01

    The formation of relativistic astrophysical jets is presumably mediated by magnetic fields threading accretion disks and central, rapidly rotating objects. As it is accelerated by magnetic stresses, the jet's kinetic energy flux grows at the expense of its Poynting flux. However, it is unclear how efficient is the conversion from magnetic to kinetic energy and whether there are any observational signatures of this process. We address this issue in the context of jets in quasars. Using data from all spatial scales, we demonstrate that in these objects the conversion from Poynting-flux-dominated to matter-dominated jets is very likely to take place closer to the black hole than the region where most of the Doppler boosted radiation observed in blazars is produced. We briefly discuss the possibility that blazar activity can be induced by global MHD instabilities, e.g., via the production of localized velocity gradients that lead to dissipative events such as shocks or magnetic reconnection, where acceleration of...

  17. Cyclic dominance in evolutionary games: A review

    CERN Document Server

    Szolnoki, Attila; Jiang, Luo-Luo; Szczesny, Bartosz; Rucklidge, Alastair M; Perc, Matjaz

    2014-01-01

    Rock is wrapped by paper, paper is cut by scissors, and scissors are crushed by rock. This simple game is popular among children and adults to decide on trivial disputes that have no obvious winner, but cyclic dominance is also at the heart of predator-prey interactions, the mating strategy of side-blotched lizards, the overgrowth of marine sessile organisms, and the competition in microbial populations. Cyclical interactions also emerge spontaneously in evolutionary games entailing volunteering, reward, punishment, and in fact are common when the competing strategies are three or more regardless of the particularities of the game. Here we review recent advances on the rock-paper-scissors and related evolutionary games, focusing in particular on pattern formation, the impact of mobility, and the spontaneous emergence of cyclic dominance. We also review mean-field and zero-dimensional rock-paper-scissors models and the application of the complex Ginzburg-Landau equation, and we highlight the importance and use...

  18. Divergent clonal selection dominates medulloblastoma at recurrence

    Science.gov (United States)

    Morrissy, A. Sorana; Garzia, Livia; Shih, David J. H.; Zuyderduyn, Scott; Huang, Xi; Skowron, Patryk; Remke, Marc; Cavalli, Florence M. G.; Ramaswamy, Vijay; Lindsay, Patricia E.; Jelveh, Salomeh; Donovan, Laura K.; Wang, Xin; Luu, Betty; Zayne, Kory; Li, Yisu; Mayoh, Chelsea; Thiessen, Nina; Mercier, Eloi; Mungall, Karen L.; Ma, Yusanne; Tse, Kane; Zeng, Thomas; Shumansky, Karey; Roth, Andrew J. L.; Shah, Sohrab; Farooq, Hamza; Kijima, Noriyuki; Holgado, Borja L.; Lee, John J. Y.; Matan-Lithwick, Stuart; Liu, Jessica; Mack, Stephen C.; Manno, Alex; Michealraj, K. A.; Nor, Carolina; Peacock, John; Qin, Lei; Reimand, Juri; Rolider, Adi; Thompson, Yuan Y.; Wu, Xiaochong; Pugh, Trevor; Ally, Adrian; Bilenky, Mikhail; Butterfield, Yaron S. N.; Carlsen, Rebecca; Cheng, Young; Chuah, Eric; Corbett, Richard D.; Dhalla, Noreen; He, An; Lee, Darlene; Li, Haiyan I.; Long, William; Mayo, Michael; Plettner, Patrick; Qian, Jenny Q.; Schein, Jacqueline E.; Tam, Angela; Wong, Tina; Birol, Inanc; Zhao, Yongjun; Faria, Claudia C.; Pimentel, José; Nunes, Sofia; Shalaby, Tarek; Grotzer, Michael; Pollack, Ian F.; Hamilton, Ronald L.; Li, Xiao-Nan; Bendel, Anne E.; Fults, Daniel W.; Walter, Andrew W.; Kumabe, Toshihiro; Tominaga, Teiji; Collins, V. Peter; Cho, Yoon-Jae; Hoffman, Caitlin; Lyden, David; Wisoff, Jeffrey H.; Garvin, James H.; Stearns, Duncan S.; Massimi, Luca; Schüller, Ulrich; Sterba, Jaroslav; Zitterbart, Karel; Puget, Stephanie; Ayrault, Olivier; Dunn, Sandra E.; Tirapelli, Daniela P. C.; Carlotti, Carlos G.; Wheeler, Helen; Hallahan, Andrew R.; Ingram, Wendy; MacDonald, Tobey J.; Olson, Jeffrey J.; Van Meir, Erwin G.; Lee, Ji-Yeoun; Wang, Kyu-Chang; Kim, Seung-Ki; Cho, Byung-Kyu; Pietsch, Torsten; Fleischhack, Gudrun; Tippelt, Stephan; Ra, Young Shin; Bailey, Simon; Lindsey, Janet C.; Clifford, Steven C.; Eberhart, Charles G.; Cooper, Michael K.; Packer, Roger J.; Massimino, Maura; Garre, Maria Luisa; Bartels, Ute; Tabori, Uri; Hawkins, Cynthia E.; Dirks, Peter; Bouffet, Eric; Rutka, James T.; Wechsler-Reya, Robert J.; Weiss, William A.; Collier, Lara S.; Dupuy, Adam J.; Korshunov, Andrey; Jones, David T. W.; Kool, Marcel; Northcott, Paul A.; Pfister, Stefan M.; Largaespada, David A.; Mungall, Andrew J.; Moore, Richard A.; Jabado, Nada; Bader, Gary D.; Jones, Steven J. M.; Malkin, David; Marra, Marco A.; Taylor, Michael D.

    2016-01-01

    The development of targeted anti-cancer therapies through the study of cancer genomes is intended to increase survival rates and decrease treatment-related toxicity. We treated a transposon–driven, functional genomic mouse model of medulloblastoma with ‘humanized’ in vivo therapy (microneurosurgical tumour resection followed by multi-fractionated, image-guided radiotherapy). Genetic events in recurrent murine medulloblastoma exhibit a very poor overlap with those in matched murine diagnostic samples (<5%). Whole-genome sequencing of 33 pairs of human diagnostic and post-therapy medulloblastomas demonstrated substantial genetic divergence of the dominant clone after therapy (<12% diagnostic events were retained at recurrence). In both mice and humans, the dominant clone at recurrence arose through clonal selection of a pre-existing minor clone present at diagnosis. Targeted therapy is unlikely to be effective in the absence of the target, therefore our results offer a simple, proximal, and remediable explanation for the failure of prior clinical trials of targeted therapy. PMID:26760213

  19. Modelling of clumpy photon dominated regions

    Science.gov (United States)

    Cubick, M.; Röllig, M.; Ossenkopf, V.; Kramer, C.; Stutzki, J.

    Observations of the interstellar medium (ISM) reveal its fractal structure over a large range of scales. The quantitative description shows that the ISM consists mainly of surfaces, so that the stellar UV-radiation can deeply penetrate into the ISM and in consequence dominates its physical and chemical conditions. Thus, the bulk of the ISM can be identified as photon dominated regions (PDRs). A simple model with the proper fractal characteristics is that of an ensemble of spherical clumps with a power-law mass spectrum and a power-law mass-size relation. Hence, we model the FIR line emission of the molecular gas by the integrated emission of such an ensemble, calculating the emission of individual clumps with the KOSMA-τ PDR code. This clumpy PDR-model, with observationally constrained parameters, is fitted to the CO, [C i], and [O i] emission along the Galactic plane as observed by the FIRAS instrument abord the COBE satellite. The FIR line intensity distribution with Galactic longitude is reproduced within factors of about 2. The predicted [C ii] 158 μm line intensity and FIR continuum emission also coincide with the observations.

  20. Are Quasar Jets Dominated by Poynting Flux?

    Energy Technology Data Exchange (ETDEWEB)

    Sikora, M

    2005-02-02

    The formation of relativistic astrophysical jets is presumably mediated by magnetic fields threading accretion disks and central, rapidly rotating objects. As it is accelerated by magnetic stresses, the jet's kinetic energy flux grows at the expense of its Poynting flux. However, it is unclear how efficient is the conversion from magnetic to kinetic energy and whether there are any observational signatures of this process. We address this issue in the context of jets in quasars. Using data from all spatial scales, we demonstrate that in these objects the conversion from Poynting-flux-dominated to matter-dominated jets is very likely to take place closer to the black hole than the region where most of the Doppler boosted radiation observed in blazars is produced. We briefly discuss the possibility that blazar activity can be induced by global MHD instabilities, e.g., via the production of localized velocity gradients that lead to dissipative events such as shocks or magnetic reconnection, where acceleration of relativistic particles and production of non-thermal flares is taking place.

  1. Systemic factors dominate mammal protein evolution.

    Science.gov (United States)

    Vinogradov, Alexander E

    2010-05-07

    Proteins encoded by highly expressed genes evolve more slowly. This correlation is thought to arise owing to purifying selection against toxicity of misfolded proteins (that should be more crucial for highly expressed genes). It is now widely accepted that this individual (by-gene) effect is a dominant cause in protein evolution. Here, I show that in mammals, the evolutionary rate of a protein is much more strongly related to the evolutionary rate of coexpressed proteins (and proteins of the same biological pathway) than to the expression level of its encoding gene. The complexity of gene regulation (estimated by the numbers of transcription factor targets and regulatory microRNA targets in the encoding gene) is another important cause, which is much stronger than gene expression level. Proteins encoded by complexly regulated genes evolve more slowly. The intronic length and the ratio of intronic to coding sequence lengths also correlate negatively with protein evolutionary rate (which contradicts the expectation from the negative link between expression level and evolutionary rate). One more important factor, which is much stronger than gene expression level, is evolutionary age. More recent proteins evolve faster, and expression level of an encoding gene becomes quite a minor cause in the evolution of mammal proteins of metazoan origin. These data suggest that, in contrast to a widespread opinion, systemic factors dominate mammal protein evolution.

  2. 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

  3. 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.

  4. The phenotypic variance gradient - a novel concept.

    Science.gov (United States)

    Pertoldi, Cino; Bundgaard, Jørgen; Loeschcke, Volker; Barker, James Stuart Flinton

    2014-11-01

    Evolutionary ecologists commonly use reaction norms, which show the range of phenotypes produced by a set of genotypes exposed to different environments, to quantify the degree of phenotypic variance and the magnitude of plasticity of morphometric and life-history traits. Significant differences among the values of the slopes of the reaction norms are interpreted as significant differences in phenotypic plasticity, whereas significant differences among phenotypic variances (variance or coefficient of variation) are interpreted as differences in the degree of developmental instability or canalization. We highlight some potential problems with this approach to quantifying phenotypic variance and suggest a novel and more informative way to plot reaction norms: namely "a plot of log (variance) on the y-axis versus log (mean) on the x-axis, with a reference line added". This approach gives an immediate impression of how the degree of phenotypic variance varies across an environmental gradient, taking into account the consequences of the scaling effect of the variance with the mean. The evolutionary implications of the variation in the degree of phenotypic variance, which we call a "phenotypic variance gradient", are discussed together with its potential interactions with variation in the degree of phenotypic plasticity and canalization.

  5. Phenotypic screening: the future of antibody discovery.

    Science.gov (United States)

    Gonzalez-Munoz, Andrea L; Minter, Ralph R; Rust, Steven J

    2016-01-01

    Most antibody therapeutics have been isolated from high throughput target-based screening. However, as the number of validated targets diminishes and the target space becomes increasingly competitive, alternative strategies, such as phenotypic screening, are gaining momentum. Here, we review successful phenotypic screens, including those used to isolate antibodies against cancer and infectious agents. We also consider exciting advances in the expression and phenotypic screening of antibody repertoires in single cell autocrine systems. As technologies continue to develop, we believe that antibody phenotypic screening will increase further in popularity and has the potential to provide the next generation of therapeutic antibodies.

  6. Suppressing Autoimmunity in Arabidopsis thalianawith Dominant Negative Immune Receptors

    DEFF Research Database (Denmark)

    Greeff, Michael Christiaan

    . CAMTA3 was previously shown to be a negative regulator of plant defense by inhibiting transcription of EDS1 and NDR1, important downstream signaling components of R-protein signaling. We found that two dominant negative alleles, DSC-D and DSC2-D, can suppress all tested camta3-1 phenotypes. We...... hypothesize that like acd11 and other autoimmune mutants, the increased levels of defense genes like EDS1 in camta3-1 might be a consequence of R protein activation and not merely as a result of negative regulation of plant defense responses as was previously proposed. DSC and CAMTA3 are part of a nuclear...

  7. Genotype phenotype correlation in Wilson's disease within families-a report on four south Indian families

    Institute of Scientific and Technical Information of China (English)

    S Santhosh; GM Chandy; RV Shaji; CE Eapen; V Jayanthi; S Malathi; P Finny; N Thomas; M Chandy; G Kurian

    2008-01-01

    AIM: To study the genotype phenotype correlation inWilson's disease (WD) patients with in families.METHODS: We report four unrelated families from South India with nine members affected withWD. Phenotype was classified as per international consensus phenotypic classification of WD. DNA was extracted from peripheral blood and 21 exons of ATP7B gene and flanking introns were amplified by polymerase chain reaction (PCR). The PCR products were screened for mutations and the aberrant products noted on screening were sequenced.RESULTS: Four separate ATP7B mutations were found in the four families. ATP7B mutations were identical amongst affected members within each family.Three families had homozygous mutations of ATP7B gene while one family had compound heterozygous mutation, of which only one mutation was identified.We noted concordance between ATP7B gene mutation and Wilson's disease phenotype amongst members within each family. The age of onset of symptoms orof detection of asymptomatic disease, baseline serum ceruloplasmin and baseline urinary copper levelswere also similar in affected members of each family.Minor differences in phenotype and baseline serumceruloplasmin level were noted in one family.CONCLUSION: We report concordance between ATP7B mutation and WD phenotype within each familywith > 1 member affected with WD. Homozygous ATP7B mutation was present in 3 of the 4 families studied. Our report supports allelic dominance as adeterminant of WD phenotype. However, in one familywith compound heterozygous mutation, there was a similar WD phenotype which suggests that there may be other factors determining the phenotype.

  8. Multidrug resistance as a dominant molecular marker in transformation of wine yeast.

    Science.gov (United States)

    Kozovska, Z; Maraz, A; Magyar, I; Subik, J

    2001-12-14

    Pure wine yeast cultures are increasingly used in winemaking to perform controlled fermentations and produce wine of reproducible quality. For the genetic manipulation of natural wine yeast strains dominant selective markers are obviously useful. Here we demonstrate the successful use of the mutated PDR3 gene as a dominant molecular marker for the selection of transformants of prototrophic wine yeast Saccharomyces cerevisiae. The selected transformants displayed a multidrug resistance phenotype that was resistant to strobilurin derivatives and azoles used to control pathogenic fungi in agriculture and medicine, respectively. Random amplification of DNA sequences and electrophoretic karyotyping of the host and transformed strains after microvinification experiments resulted in the same gel electrophoresis patterns. The chemical and sensory analysis of experimental wines proved that the used transformants preserved all their useful winemaking properties indicating that the pdr3-9 allele does not deteriorate the technological properties of the transformed wine yeast strain.

  9. Bethlem myopathy: An autosomal dominant myopathy with flexion contractures, keloids, and follicular hyperkeratosis

    Directory of Open Access Journals (Sweden)

    Aralikatte Onkarappa Saroja

    2013-01-01

    Full Text Available Bethlem myopathy and Ullrich congenital muscular dystrophy form a spectrum of collagenopathies caused by genetic mutations encoding for any of the three subunits of collagen VI. Bethlem phenotype is relatively benign and is characterized by proximal dominant myopathy, keloids, contractures, distal hyperextensibility, and follicular hyperkeratosis. Three patients from a single family were diagnosed to have Bethlem myopathy based on European Neuromuscular Centre Bethlem Consortium criteria. Affected father and his both sons had slowly progressive proximal dominant weakness and recurrent falls from the first decade. Both children aged 18 and 20 years were ambulant at presentation. All had flexion contractures, keloids, and follicular hyperkeratosis without muscle hypertrophy. Creatinine kinase was mildly elevated and electromyography revealed myopathic features. Muscle imaging revealed severe involvement of glutei and vasti with "central shadow" in rectus femoris. Muscle biopsy in the father showed dystrophic changes with normal immmunostaining for collagen VI, sarcoglycans, and dysferlin.

  10. [Clinical and molecular study in a family with autosomal dominant hypohidrotic ectodermal dysplasia].

    Science.gov (United States)

    Callea, Michele; Cammarata-Scalisi, Francisco; Willoughby, Colin E; Giglio, Sabrina R; Sani, Ilaria; Bargiacchi, Sara; Traficante, Giovanna; Bellacchio, Emanuele; Tadini, Gianluca; Yavuz, Izzet; Galeotti, Angela; Clarich, Gabriella

    2017-02-01

    Hypohidrotic ectodermal dysplasia (HED) is a rare disease characterized by deficiency in development of structure derived from the ectoderm and is caused by mutations in the genes EDA, EDAR, or EDARADD. Phenotypes caused by mutations in these three may exhibit similar clinical features, explained by a common signaling pathway. Mutations in EDA gene cause X linked HED, which is the most common form. Mutations in EDAR and EDARADD genes cause autosomal dominant and recessive form of HED. The most striking clinical findings in HED are hypodontia, hypotrichosis and hypohidrosis that can lead to episodes of hyperthermia. We report on clinical findings in a child with HED with autosomal dominant inheritance pattern with a heterozygous mutation c.1072C>T (p.Arg358X) in the EDAR gene. A review of the literature with regard to other cases presenting the same mutation has been carried out and discussed.

  11. Evidence for the existence of a fourth dominantly inherited spinocerebellar ataxia locus

    Energy Technology Data Exchange (ETDEWEB)

    Lopes-Cendes, I. (Montreal General Hospital Research Institute, Quebec (Canada) Montreal Neurological Institute and Hospital, Quebec (Canada) McGill Univ., Quebec (Canada)); Andermann, E. (Montreal Neurological Institute and Hospital, Quebec (Canada) McGill Univ., Quebec (Canada)); Rouleau, G.A. (Montreal General Hospital Research Institute, Quebec (Canada) Montreal Neurological Institute and Hospital, Quebec (Canada))

    1994-05-01

    The autosomal dominantly inherited spinocerebellar ataxias (SCAs) are a heterogeneous group of disorders. To date, three loci have been identified: The SCA1 locus (on chr 6p), the SCA2 locus (on chr 12q), and more recently a Machado-Joseph disease (MJD) locus (on chr 14q). The authors have studied one large French-Canadian kindred with four generations of living affected individuals segregating an autosomal dominant form of SCA. Linkage analysis using anonymous DNA markers that flank the three previously described loci significantly exclude the French-Canadian kindred from the SCA1, SCA2, and MJD loci. Therefore, a fourth, still unmapped SCA locus remains to be identified. In addition, the unique clinical phenotype present in all affected individuals of the French-Canadian kindred might be characteristic of this still unmapped SCA locus. 34 refs., 2 figs., 2 tabs.

  12. Characterization of two new dominant ClC-1 channel mutations associated with myotonia

    DEFF Research Database (Denmark)

    Grunnet, Morten; Jespersen, Thomas; Colding-Jørgensen, Eskild

    2003-01-01

    Voltage-gated ClC-1 chloride channels encoded by the CLCN1 gene have a major role in setting the membrane potential in skeletal muscle. More than 60 CLCN1 mutations have been associated with myotonia congenita. These mutations are traditionally classified as recessive (Becker's disease) or dominant...... (Thomsen's disease). In this study, we have electrophysiologically characterized two new dominant ClC-1 mutations, thereby elucidating the observed phenotype in patients. The two ClC-1 mutants M128V and E193K were identified, and the DNA was isolated from patients and subsequently expressed in Xenopus...... revealed a change in reversal potential compared to wild-type channels. This finding supports the notion that the E193 amino acid is an important determinant in the selectivity filter of the human ClC-1 channel. The electrophysiological behavior of both mutants demonstrates a severe reduction in ClC-1...

  13. Machado-Joseph disease is genetically different from Holguin dominant ataxia (SCA2)

    Energy Technology Data Exchange (ETDEWEB)

    Silveria, I.; Manaia, A. (Univ. Porto (Portugal) Hopital Necker-Enfants Malades, Paris (France)); Melki, J.; Burlet, P.; Rozet, J.M.; Munnich, A. (Hopital Necker-Enfants Malades, Paris (France)); Magarino, C.; Gispert, S. (Univ. Porto (Portugal) Centro Nacional Genetica Medica, Havana (Cuba)); Lunkes, A.; Auburger, G. (Univ. Hospital, Duesseldorf (Germany))

    1993-09-01

    Machado-Joseph disease (MJD) and Holguin ataxia (SCA2) are autosomal dominant multisystem degenerations with spinocerebellar involvement that are predominant among people of Portuguese-Azorean and of Cuban descent, respectively. Their clinical distinction may at times be difficult to make in individual patients, due to significant phenotypic overlapping (similar overall age-of-onset and duration of cerebellar ataxia, eye movement, and, often, other common problems). The recent mapping of SCA2 to chromosome 12q provided another candidate region for linkage studies of MJD. Original data on 10 families with Holguin ataxia show that the locus of phenylalanine hydroxylase (PAH) on chromosome 12q is linked to SCA2 at 4 cM and is thus far its closest marker. The exclusion of linkage 15 cM on each side of PAH in 16 families with MJD shows that these two forms of dominant ataxia are genetically distinct and at different chromosomal locations (nonallelic). 20 refs., 2 tabs.

  14. Long Island Sound: a Human Dominated Environment

    Science.gov (United States)

    Thomas, E.; Varekamp, J. C.

    2006-05-01

    Long Island Sound (LIS) is a marginally marine urban estuary, with Long Island (NY) as its southern coastline, New York and Connecticut along its northern coast. LIS has a narrow opening to the West (East River), but most exchange with the ocean occurs at its eastern end, resulting in an east-west gradient in salinity. There is also an east-west gradient in indicators of contamination in the surface sediments (e.g., trace metals). Western LIS is close to the main population center (New York City), but also is a focusing region for fine- grained sediments. Since the 1970s, western LIS and to a lesser extent, central LIS, suffer summer hypoxia or even anoxia. We used sediment cores in westernmost and central LIS to document environmental changes over the last millennium, including the time of European settlement, using microfossil, geochemical, sedimentological, and trace element proxies. Sediment ages were determined using metal pollution records and radiometric carbon dating. Before European settlement, the low-diversity benthic faunas were dominated by Elphidium excavatum (feeding on diatoms) at shallow depths (human population growth in the region, with a marked decrease in salinity in westernmost LIS, and with the beginning of low oxygen conditions as indicated by carbon isotope values in foraminiferal tests. At the same time, accumulation rates of organic carbon and nitrogen increased several fold, most extremely so in westernmost LIS. These data thus all indicate that humans influenced LIS and its ecosystems from the mid 19th century on, causing eutrophication, increased fresh water run-off due to urbanization and possibly re-routing of fresh water through waste water treatment plants, and increased organic carbon and trace metal storage in the sediments. A period of additional faunal changes started in the late 1960s, when overall foraminiferal abundance decreased, but Ammonia parkinsoniana, formerly absent or rare, became common to dominant especially in

  15. On a conjecture about inverse domination in graphs

    DEFF Research Database (Denmark)

    Frendrup, Allan; Henning, Michael A.; Randerath, Bert

    Let G = (V,E) be a graph with no isolated vertex. A classical observation in domination theory is that if D is a minimum dominating set of G, then V \\D is also a dominating set of G. A set D′ is an inverse dominating set of G if D′ is a dominating set of G and D′ ⊆ V \\D for some minimum dominating...... domination number of G is at most the independence number of G. We prove this conjecture for special families of graphs, including claw-free graphs, bipartite graphs, split graphs, very well covered graphs, chordal graphs and cactus graphs....

  16. Molecular and cellular pathogenesis of autosomal dominant polycystic kidney disease

    Directory of Open Access Journals (Sweden)

    A.P. Bastos

    2011-07-01

    Full Text Available Autosomal dominant polycystic kidney disease (ADPKD is one of the most common human life-threatening monogenic disorders. The disease is characterized by bilateral, progressive renal cystogenesis and cyst and kidney enlargement, often leading to end-stage renal disease, and may include extrarenal manifestations. ADPKD is caused by mutation in one of two genes, PKD1 and PKD2, which encode polycystin-1 (PC1 and polycystin-2 (PC2, respectively. PC2 is a non-selective cation channel permeable to Ca2+, while PC1 is thought to function as a membrane receptor. The cyst cell phenotype includes increased proliferation and apoptosis, dedifferentiation, defective planar polarity, and a secretory pattern associated with extracellular matrix remodeling. The two-hit model for cyst formation has been recently extended by the demonstration that early gene inactivation leads to rapid and diffuse development of renal cysts, while inactivation in adult life is followed by focal and late cyst formation. Renal ischemia/reperfusion, however, can function as a third hit, triggering rapid cyst development in kidneys with Pkd1 inactivation induced in adult life. The PC1-PC2 complex behaves as a sensor in the primary cilium, mediating signal transduction via Ca2+ signaling. The intracellular Ca2+ homeostasis is impaired in ADPKD, being apparently responsible for the cAMP accumulation and abnormal cell proliferative response to cAMP. Activated mammalian target for rapamycin (mTOR and cell cycle dysregulation are also significant features of PKD. Based on the identification of pathways altered in PKD, a large number of preclinical studies have been performed and are underway, providing a basis for clinical trials in ADPKD and helping the design of future trials.

  17. Interactions Dominate the Dynamics of Visual Cognition

    Science.gov (United States)

    Stephen, Damian G.; Mirman, Daniel

    2010-01-01

    Many cognitive theories have described behavior as the summation of independent contributions from separate components. Contrasting views have emphasized the importance of multiplicative interactions and emergent structure. We describe a statistical approach to distinguishing additive and multiplicative processes and apply it to the dynamics of eye movements during classic visual cognitive tasks. The results reveal interaction-dominant dynamics in eye movements in each of the three tasks, and that fine-grained eye movements are modulated by task constraints. These findings reveal the interactive nature of cognitive processing and are consistent with theories that view cognition as an emergent property of processes that are broadly distributed over many scales of space and time rather than a componential assembly line. PMID:20070957

  18. Numerical Models of Blackbody-Dominated GRBs

    CERN Document Server

    Cuesta-Martínez, Carlos F; Mimica, Petar; Thöne, Christina C; de Ugarte-Postigo, Antonio

    2015-01-01

    Blackbody-dominated (BBD) gamma-ray bursts (GRBs) are events characterized by the absence of a typical afterglow, long durations and the presence of a significant thermal component following the prompt gamma-ray emission. GRB 101225A (the `Christmas burst') is a prototype of this class. A plausible progenitor system for it, and for the BBD-GRBs, is the merger of a neutron star (NS) and a helium core of an evolved, massive star. Using relativistic hydrodynamic simulations we model the propagation of an ultrarelativistic jet through the enviroment created by such a merger and we compute the whole radiative signature, both thermal and non-thermal, of the jet dynamical evolution. We find that the thermal emission originates from the interaction between the jet and the hydrogen envelope ejected during the NS/He merger.

  19. Changing the Dominant Paradigm in Economics

    Directory of Open Access Journals (Sweden)

    Maria de Lourdes Mollo

    2015-10-01

    Full Text Available This article addresses the discussion proposed by the World Academy of Art & Science (WAAS about the need to build a new paradigm to confront the challenges of the global society and to move across to a New Society discussing specific problems related to economic globalization and proposing changes. The ways in which economic orthodoxy and heterodoxy analyze the role of the State and the question of sustainability of development and the problems of environmental sustainability depend on their different views or theoretical arguments about the role of the market. The article contrasts the mainstream economics arguments to support the free market context of globalization with Post-Keynesian and Marxist’s skeptical or critical views. Finally, it proposes some strategies to face the critical aspects analyzed making suggestions to move to another dominant economic paradigm.

  20. The right brain is dominant in psychotherapy.

    Science.gov (United States)

    Schore, Allan N

    2014-09-01

    This article discusses how recent studies of the right brain, which is dominant for the implicit, nonverbal, intuitive, holistic processing of emotional information and social interactions, can elucidate the neurobiological mechanisms that underlie the relational foundations of psychotherapy. Utilizing the interpersonal neurobiological perspective of regulation theory, I describe the fundamental role of the early developing right brain in relational processes, throughout the life span. I present interdisciplinary evidence documenting right brain functions in early attachment processes, in emotional communications within the therapeutic alliance, in mutual therapeutic enactments, and in therapeutic change processes. This work highlights the fact that the current emphasis on relational processes is shared by, cross-fertilizing, and indeed transforming both psychology and neuroscience, with important consequences for clinical psychological models of psychotherapeutic change.

  1. Dark energy domination in the Virgocentric flow

    CERN Document Server

    Chernin, A D; Nasonova, O G; Teerikorpi, P; Valtonen, M J; Dolgachev, V P; Domozhilova, L M; Byrd, G G

    2010-01-01

    The standard \\LambdaCDM cosmological model implies that all celestial bodies are embedded in a perfectly uniform dark energy background, represented by Einstein's cosmological constant, and experience its repulsive antigravity action. Can dark energy have strong dynamical effects on small cosmic scales as well as globally? Continuing our efforts to clarify this question, we focus now on the Virgo Cluster and the flow of expansion around it. We interpret the Hubble diagram, from a new database of velocities and distances of galaxies in the cluster and its environment, using a nonlinear analytical model which incorporates the antigravity force in terms of Newtonian mechanics. The key parameter is the zero-gravity radius, the distance at which gravity and antigravity are in balance. Our conclusions are: 1. The interplay between the gravity of the cluster and the antigravity of the dark energy background determines the kinematical structure of the system and controls its evolution. 2. The gravity dominates the qu...

  2. Apical-dominant particle swarm optimization

    Institute of Scientific and Technical Information of China (English)

    Zhihua Cui; Xingjuan Cai; Jianchao Zeng; Guoji Sun

    2008-01-01

    Particle swarm optimization (PSO) is a new stochastic population-based search methodology by simulating the animal social behaviors such as birds flocking and fish schooling.Many improvements have been proposed within the framework of this biological assumption.However,in this paper,the search pattern of PSO is used to model the branch growth process of natural plants.It provides a different poten-tial manner from artificial plant.To illustrate the effectiveness of this new model,apical dominance phenomenon is introduced to construct a novel variant by emphasizing the influence of the phototaxis.In this improvement,the population is divided into three different kinds of buds associated with their performances.Furthermore,a mutation strategy is applied to enhance the ability escaping from a local optimum.Sim-ulation results demonstrate good performance of the new method when solving high-dimensional multi-modal problems.

  3. Isoniazid induced motor-dominant neuropathy.

    Science.gov (United States)

    Arsalan, Rabeeya; Sabzwari, Saniya

    2015-10-01

    Isoniazid though a very effective treatment for tuberculosis can cause severe motor-dominant neuropathy which can be reversible with pyridoxine supplementation. A 45-year-old female diagnosed with psoas abscess, culture positive for mycobacterium tuberculosis, was started on anti- tuberculous treatment with four drugs, including isoniazid at a dose of 5 mg/kg/day. Three months later she developed severe motor weakness of lower limbs with loss of ankle and knee reflexes. She was treated with vitamin B6 injections and isoniazid treatment was continued. Her motor weakness gradually improved in a few months, but mild sensory impairment persisted even after two years. There is need for vigilance regarding neurological effects of isoniazid in seemingly low-risk individuals in whom development of symptoms should raise the suspicion about slow acetylator status. Timely therapeutic intervention with high-dose vitamin B6 can reduce the long-term morbidity associated with this easily reversible condition.

  4. Low frequency groans indicate larger and more dominant fallow deer (Dama dama males.

    Directory of Open Access Journals (Sweden)

    Elisabetta Vannoni

    Full Text Available BACKGROUND: Models of honest advertisement predict that sexually selected calls should signal male quality. In most vertebrates, high quality males have larger body sizes that determine higher social status and in turn higher reproductive success. Previous research has emphasised the importance of vocal tract resonances or formant frequencies of calls as cues to body size in mammals. However, the role of the acoustic features of vocalisations as cues to other quality-related phenotypic characteristics of callers has rarely been investigated. METHODOLOGY/PRINCIPAL FINDINGS: We examined whether the acoustic structure of fallow deer groans provides reliable information on the quality of the caller, by exploring the relationships between male quality (body size, dominance rank, and mating success and the frequency components of calls (fundamental frequency, formant frequencies, and formant dispersion. We found that body size was not related to the fundamental frequency of groans, whereas larger males produced groans with lower formant frequencies and lower formant dispersion. Groans of high-ranking males were characterised by lower minimum fundamental frequencies and to a lesser extent, by lower formant dispersions. Dominance rank was the factor most strongly related to mating success, with higher-ranking males having higher mating success. The minimum fundamental frequency and the minimum formant dispersion were indirectly related to male mating success (through dominance rank. CONCLUSION/SIGNIFICANCE: Our study is the first to show that sexually selected vocalisations can signal social dominance in mammals other than primates, and reveals that independent acoustic components encode accurate information on different phenotypic aspects of male quality.

  5. Enamelin and autosomal-dominant amelogenesis imperfecta.

    Science.gov (United States)

    Hu, J C-C; Yamakoshi, Y

    2003-01-01

    Dental enamel forms as a progressively thickening extracellular layer by the action of proteins secreted by ameloblasts. The most abundant enamel protein is amelogenin, which is expressed primarily from a gene on the X-chromosome (AMELX). The two most abundant non-amelogenin enamel proteins are ameloblastin and enamelin, which are expressed from the AMBN and ENAM genes, respectively. The human AMBN and ENAM genes are located on chromosome 4q13.2. The major secretory products of the human AMELX, AMBN, and ENAM genes have 175, 421, and 1103 amino acids, respectively, and are all post-translationally modified, secreted, and processed by proteases. Mutations in AMELX have been shown to cause X-linked amelogenesis imperfecta (AI), which accounts for 5% of AI cases. Mutations in ENAM cause a severe form of autosomal-dominant smooth hypoplastic AI that represents 1.5%, and a mild form of autosomal-dominant local hypoplastic AI that accounts for 27% of AI cases in Sweden. The discovery of mutations in the ENAM gene in AI kindreds proved that enamelin is critical for proper dental enamel formation and that it plays a role in human disease. Here we review how enamelin was discovered, what is known about enamelin protein structure, post-translational modifications, processing by proteases, and its potentially important functional properties such as its affinity for hydroxyapatite and influence on crystal growth in vitro. The primary structures of human, porcine, mouse, and rat enamelin are compared, and the human enamelin gene, its structure, chromosomal localization, temporal and spatial patterns of expression, and its role in the etiology of amelogenesis imperfecta are discussed.

  6. Lifestyle dominates cardiovascular risks in Malaysia

    Directory of Open Access Journals (Sweden)

    Khalib A. Latiff

    2008-03-01

    Full Text Available Cardiovascular problem is one of the leading cause of death in Malaysia and now invaded to the sub-urban and rural areas. To prevent and control of this problem, several main risk factors needed to be known and shall be reexamined and ranked according to the priority. The objectives of this research paper was to identify several dominant risk factor related to cardiovascular problem. A cross sectional study was carried out from March 2000 – June 2001 on a total of 8159 rural population aged 18 and above to measure the prevalence of the common cardiovascular risk factors. Those risk factors are systolic blood pressure, diastolic blood pressure, serum cholesterol level, obesity index, blood glucose level, smoking, physical activity and mental stress. Overall prevalence of common cardiovascular risk factors were higher, dominated by physical inactivity (65.7%, hypercholesterolemia – TC:HC (62.3%, mental stress (55.5% and obesity (53.7%. Smoking was also high at 49.9% especially among men. However systolic hypertension, diastolic hypertension and diabetes mellitus; although increased by age, its prevalence is relatively low at 23.7%, 19.2%, and 6.3% respectively. Cardiovascular risk factors related to lifestyle are much evidenced as compared to risk factors related to the biological influence. Therefore, all initiatives in community health intervention should be mobilized specifically on prevention and control of lifestyle-related risk factors. (Med J Indones 2008; 17: 50-6Keywords: cardiovascular problem, community intervention, lifestyle-linked risk factors

  7. Symptom onset in autosomal dominant Alzheimer disease

    Science.gov (United States)

    Acosta-Baena, Natalia; Aisen, Paul S.; Bird, Thomas; Danek, Adrian; Fox, Nick C.; Goate, Alison; Frommelt, Peter; Ghetti, Bernardino; Langbaum, Jessica B.S.; Lopera, Francisco; Martins, Ralph; Masters, Colin L.; Mayeux, Richard P.; McDade, Eric; Moreno, Sonia; Reiman, Eric M.; Ringman, John M.; Salloway, Steve; Schofield, Peter R.; Sperling, Reisa; Tariot, Pierre N.; Xiong, Chengjie; Morris, John C.; Bateman, Randall J.

    2014-01-01

    Objective: To identify factors influencing age at symptom onset and disease course in autosomal dominant Alzheimer disease (ADAD), and develop evidence-based criteria for predicting symptom onset in ADAD. Methods: We have collected individual-level data on ages at symptom onset and death from 387 ADAD pedigrees, compiled from 137 peer-reviewed publications, the Dominantly Inherited Alzheimer Network (DIAN) database, and 2 large kindreds of Colombian (PSEN1 E280A) and Volga German (PSEN2 N141I) ancestry. Our combined dataset includes 3,275 individuals, of whom 1,307 were affected by ADAD with known age at symptom onset. We assessed the relative contributions of several factors in influencing age at onset, including parental age at onset, age at onset by mutation type and family, and APOE genotype and sex. We additionally performed survival analysis using data on symptom onset collected from 183 ADAD mutation carriers followed longitudinally in the DIAN Study. Results: We report summary statistics on age at onset and disease course for 174 ADAD mutations, and discover strong and highly significant (p 0.38) correlations between individual age at symptom onset and predicted values based on parental age at onset and mean ages at onset by mutation type and family, which persist after controlling for APOE genotype and sex. Conclusions: Significant proportions of the observed variance in age at symptom onset in ADAD can be explained by family history and mutation type, providing empirical support for use of these data to estimate onset in clinical research. PMID:24928124

  8. Right parietal dominance in spatial egocentric discrimination.

    Science.gov (United States)

    Loayza, F R; Fernández-Seara, M A; Aznárez-Sanado, M; Pastor, M A

    2011-03-15

    Egocentric tactile perception is crucial for skilled hand motor control. In order to better understand the brain functional underpinnings related to this basic sensorial perception, we performed a tactile perception functional magnetic resonance imaging (fMRI) experiment with two aims. The first aim consisted of characterizing the neural substrate of two types of egocentric tactile discrimination: the spatial localization (SLD) and simultaneity succession discrimination (SSD) in both hands to define hemispheric dominance for these tasks. The second goal consisted of characterizing the brain activation related to the spatial attentional load, the functional changes and their connectivity patterns induced by the psychometric performance (PP) during SLD. We used fMRI in 25 right-handed volunteers, applying pairs of sinusoidal vibratory stimuli on eight different positions in the palmar surface of both hands. Subjects were required either to identify the stimulus location with respect to an imaginary midline (SLD), to discriminate the simultaneity or succession of a stimuli pair (SSD) or to simply respond to stimulus detection. We found a fronto-parietal network for SLD and frontal network for SSD. During SLD we identified right hemispheric dominance with increased BOLD activation and functional interaction of the right supramarginal gyrus with contralateral intra-parietal sulcus for right and left hand independently. Brain activity correlated to spatial attentional load was found in bilateral structures of intra-parietal sulcus, precuneus extended to superior parietal lobule, pre-supplementary motor area, frontal eye fields and anterior insulae for both hands. We suggest that the right supramarginal gyrus and its interaction with intra-parietal lobule may play a pivotal role in the phenomenon of tactile neglect in right fronto-parietal lesions. Copyright © 2010 Elsevier Inc. All rights reserved.

  9. Some notes on the Roman domination number and Italian domination number in graphs

    Science.gov (United States)

    Hajibaba, Maryam; Jafari Rad, Nader

    2017-09-01

    An Italian dominating function (or simply, IDF) on a graph G = (V, E) is a function f : V → {0, 1, 2} that satisfies the property that for every vertex v ∈ V, with f(v) = 0, Σ u∈N(v) f(u) ≥ 2. The weight of an Italian dominating function f is defined as w(f) = f(V ) = Σ u∈V f(u). The minimum weight among all of the Italian dominating functions on a graph G is called the Italian domination number of G, and is denoted by γI (G). A double Roman dominating function (or simply, DRDF) is a function f : V → {0, 1, 2, 3} having the property that if f(v) = 0 for a vertex v, then v has at least two adjacent vertices assigned 2 under f or one adjacent vertex assigned 3 under f, and if f(v) = 1, then v has at least one neighbor with f(w) ≥ 2. The weight of a DRDF f is defined as the sum f(V) = Σ v∈V f(v), and the minimum weight of a DRDF on G is the double Roman domination number of G, denoted by γdR (G). In this paper we show that γdR (G)/2 ≤ γI (G) ≤ 2γdR (G)/3, and characterize all trees T with γI (T) = 2γdR (T)/3.

  10. Invasive ecosystem engineer selects for different phenotypes of an associated native species.

    Science.gov (United States)

    Wright, Jeffrey T; Gribben, Paul E; Byers, James E; Monro, Keyne

    2012-06-01

    Invasive habitat-forming ecosystem engineers modify the abiotic environment and thus represent a major perturbation to many ecosystems. Because native species often persist in these invaded habitats but have no shared history with the ecosystem engineer, the engineer may impose novel selective pressure on native species. In this study, we used a phenotypic selection framework to determine whether an invasive habitat-forming ecosystem engineer (the seaweed Caulerpa taxifolia) selects for different phenotypes of a common co-occurring native species (the bivalve Anadara trapezia). Compared to unvegetated habitat, Caulerpa habitat has lower water flow, lower dissolved oxygen, and sediments are more silty and anoxic. We determined the performance consequences of variation in key functional traits that may be affected by these abiotic changes (shell morphology, gill mass, and palp mass) for Anadara transplanted into Caulerpa and unvegetated habitat. Both linear and nonlinear performance gradients in Anadara differed between habitats, and these gradients were stronger in Caulerpa compared to unvegetated sediment. Moreover, in Caulerpa alternate phenotypes performed well, and these phenotypes were different from the dominant phenotype in unvegetated sediment. By demonstrating that phenotype-performance gradients differ between habitats, we have highlighted a role for Caulerpa as an agent of selection on native species.

  11. Phenotypic plasticity and modularity allow for the production of novel mosaic phenotypes in ants

    OpenAIRE

    Londe, Sylvain; Monnin, Thibaud; Cornette, Raphaël; Debat, Vincent; Brian L Fisher; Molet, Mathieu

    2015-01-01

    International audience; Background: The origin of discrete novelties remains unclear. Some authors suggest that qualitative phenotypic changes may result from the reorganization of preexisting phenotypic traits during development (i.e., developmental recombination) following genetic or environmental changes. Because ants combine high modularity with extreme phenotypic plasticity (queen and worker castes), their diversified castes could have evolved by developmental recombination. We performed...

  12. 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

  13. The need for agriculture phenotyping: "moving from genotype to phenotype".

    Science.gov (United States)

    Boggess, Mark V; Lippolis, John D; Hurkman, William J; Fagerquist, Clifton K; Briggs, Steve P; Gomes, Aldrin V; Righetti, Pier Giorgio; Bala, Kumar

    2013-11-20

    Increase in the world population has called for the increased demand for agricultural productivity. Traditional methods to augment crop and animal production are facing exacerbating pressures in keeping up with population growth. This challenge has in turn led to the transformational change in the use of biotechnology tools to meet increased productivity for both plant and animal systems. Although many challenges exist, the use of proteomic techniques to understand agricultural problems is steadily increasing. This review discusses the impact of genomics, proteomics, metabolomics and phenotypes on plant, animal and bacterial systems to achieve global food security and safety and we highlight examples of intra and extra mural research work that is currently being done to increase agricultural productivity. This review focuses on the global demand for increased agricultural productivity arising from population growth and how we can address this challenge using biotechnology. With a population well above seven billion humans, in a very unbalanced nutritional state (20% overweight, 20% risking starvation) drastic measures have to be taken at the political, infrastructure and scientific levels. While we cannot influence politics, it is our duty as scientists to see what can be done to feed humanity. Hence we highlight the transformational change in the use of biotechnology tools over traditional methods to increase agricultural productivity (plant and animal). Specifically, this review deals at length on how a three-pronged attack, namely combined genomics, proteomics and metabolomics, can help to ensure global food security and safety. This article is part of a Special Issue entitled: Translational Plant Proteomics. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Identiifcation of a novel male sterile wheat mutant dms conferring dwarf status and multi-pistils

    Institute of Scientific and Technical Information of China (English)

    DUAN Zong-biao; SHEN Chun-cai; LI Qiao-yun; L Gui-zhen; NI Yong-jing; YU Dong-yan; NIU Ji-shan

    2015-01-01

    Plant height and fertility are two important traits of wheat (Triticum aestivum L.), whose mutants are ideal materials for studies on molecular mechanisms of stem and lforal organ development. In this study, we identiifed a dwarf, multi-pistil and male sterile (dms hereafter) wheat mutant from Zhoumai 18. Simple sequence repeat (SSR) marker assay with 181 primer pairs showed that only one locus of GWM148-2B was divergent between Zhoumai 18 and dms. There were three typical phenotypes in the progeny of dms, tal (T;ca. 0.8 m), semi-dwarf (M;ca. 0.6 m) and dwarf (D;under 0.3 m) plants. Morphological investigation indicated that the internode length of M was shortened by about 20–50 mm each;the internode number of D was 2 less than that of T and Zhoumai 18, and its internode length was shorter also. The pol en vigor and hybridization test demonstrated that dms mutant was male sterility. Segregated phenotypes in progeny of M suggested that the multi-pistils and sterility were control ed by one recessive gene locus which was designated as dms temporarily, and the plant height was control ed by a semi-dominant gene locus Dms. Therefore, progeny individuals of the dms had three genotypes, DmsDms for tal plants, Dmsdms for semi-dwarf plants and dmsdms for dwarf plants. The mutant progenies were individual y selected and propagated for more than 6 generations, thus a set of near isogenic lines of T, M and D for dms were developed. This study provides a set germplasms for studies on molecular mechanisms of wheat stem and spike development.

  15. Identification of a novel male sterile wheat mutant dms conferring dwarf status and multi-pistils

    Institute of Scientific and Technical Information of China (English)

    DUAN Zong-biao[1; SHEN Chun-cai[1; LI Qiao-yun[1; LU Gui-zhen[1; NI Yong-jing[2; YU Dong-yan[1; NIU Ji-shan[1

    2015-01-01

    Plant height and fertility are two important traits of wheat (Triticum aesfivum L.), whose mutants are ideal materials for studies on molecular mechanisms of stem and floral organ development. In this study, we identified a dwarf, multi-pistil and male sterile (dms hereafter) wheat mutant from Zhoumai 18. Simple sequence repeat (SSR) marker assay with 181 primer pairs showed that only one locus of GWM148-2B was divergent between Zhoumai 18 and dins. There were three typical phenotypes in the progeny of dms, tall (T; ca. 0.8 m), semi-dwarf (M; ca. 0.6 m) and dwarf (D; under 0.3 m) plants. Morphological investigation indicated that the intemode length of M was shortened by about 20-50 mm each; the intemode number of D was 2 less than that ofT and Zhoumai 18, and its internode length was shorter also. The pollen vigor and hybridization test demonstrated that dms mutant was male sterility. Segregated phenotypes in progeny of M suggested that the multi-pistils and sterility were controlled by one recessive gene locus which was designated as dms temporarily, and the plant height was controlled by a semi-dominant gene locus Dms. Therefore, progeny individuals of the dms had three genotypes, DmsDms for tall plants, Dmsdms for semi-dwarf plants and dmsdms for dwarf plants. The mutant progenies were individually selected and propagated for more than 6 generations, thus a set of near isogenic lines of T, M and D for dms were developed. This study provides a set germplasms for studies on molecular mechanisms of wheat stem and spike development.

  16. Dominância coronariana na síndrome da hipoplasia do coração esquerdo Coronary dominance patterns in hypoplastic left heart syndrome

    Directory of Open Access Journals (Sweden)

    Decio Cavalet Soares Abuchaim

    2011-12-01

    Full Text Available INTRODUÇÃO: Apesar de a síndrome do coração esquerdo hipoplásico (SCEH ser extensamente estudada, esta doença ainda apresenta mortalidade elevada se comparada a outras doenças tratadas como fisiologia univentricular. Assim, diferenças morfológicas entre fenótipos dentro do espectro da SCEH podem ser fatores de risco e sua identificação pode auxiliar na escolha terapêutica entre os subgrupos anatômicos. OBJETIVOS: Determinar a forma mais frequente de dominância coronariana em corações com SCEH nos subgrupos com atresia (AM e estenose mitral (EM. MÉTODOS: Análise da anatomia coronariana de acordo com a distribuição dos ramos epicárdicos e o padrão de dominância, classificadas em direita, esquerda ou balanceada. O grupo controle foi composto por nove peças de corações morfologicamente normais. O grupo SCEH constituiu-se de nove peças com AM e 24 peças com EM. Para análise estatística foi utilizado o teste do qui-quadrado. RESULTADOS: Houve diferença significativa entre os dois grupos em relação à dominância coronariana (x²= 9,298; P=0,01. A dominância esquerda esteve presente em 75% dos casos de EM, e a balanceada só foi observada na EM. No grupo controle, observou-se dominância direita em todos os casos (PINTRODUCTION: Although hypoplastic left heart syndrome (HLHS be extensively studied, this disease still has a high mortality rate compared to other diseases treated as univentricular physiology. In this way, morphological differences between phenotypes within the spectrum of HLHS may be risk factors and their identification can assist in choosing treatment between subgroups. OBJECTIVE: To identify the most prevalent form of coronary artery dominance in hearts with HLHS groups with mitral atresia (MA and mitral stenosis (MS. METHODS: Analysis of coronary anatomy according to the distribution of epicardial branches and the pattern of dominance, classified as right, left or balanced. The control group was

  17. 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…

  18. Emerging semantics to link phenotype and environment

    Directory of Open Access Journals (Sweden)

    Anne E. Thessen

    2015-12-01

    Full Text Available Understanding the interplay between environmental conditions and phenotypes is a fundamental goal of biology. Unfortunately, data that include observations on phenotype and environment are highly heterogeneous and thus difficult to find and integrate. One approach that is likely to improve the status quo involves the use of ontologies to standardize and link data about phenotypes and environments. Specifying and linking data through ontologies will allow researchers to increase the scope and flexibility of large-scale analyses aided by modern computing methods. Investments in this area would advance diverse fields such as ecology, phylogenetics, and conservation biology. While several biological ontologies are well-developed, using them to link phenotypes and environments is rare because of gaps in ontological coverage and limits to interoperability among ontologies and disciplines. In this manuscript, we present (1 use cases from diverse disciplines to illustrate questions that could be answered more efficiently using a robust linkage between phenotypes and environments, (2 two proof-of-concept analyses that show the value of linking phenotypes to environments in fishes and amphibians, and (3 two proposed example data models for linking phenotypes and environments using the extensible observation ontology (OBOE and the Biological Collections Ontology (BCO; these provide a starting point for the development of a data model linking phenotypes and environments.

  19. 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…

  20. Effects of polyandry on male phenotypic diversity.

    Science.gov (United States)

    Barbosa, M; Dornelas, M; Magurran, A E

    2010-11-01

    Polyandry has the potential to affect the distribution of phenotypes and to shape the direction of sexual selection. Here, we explore this potential using Trinidadian guppies as a model system and ask whether polyandry leads to directional and/or diversifying selection of male phenotypic traits. In this study, we compare the phenotypic diversity of offspring from multiply and singly sired broods. To quantify phenotypic diversity, we first combine phenotypic traits using multivariate methods, and then take the dispersion of individuals in multivariate space as our measure of diversity. We show that, when each trait is examined separately, polyandry generates offspring with a higher proportion of bright coloration, indicating directional selection. However, our multivariate approach reveals that this directionality is accompanied by an increase in phenotypic diversity. These results suggest that polyandry (i) selects for the production of sons with the preferred brighter colour phenotypes whereas (ii) enhancing the diversity of male sexual traits. Promoting phenotypic diversity may be advantageous in coping with environmental and reproductive variability by increasing long-term fitness. © 2010 The Authors. Journal Compilation © 2010 European Society For Evolutionary Biology.

  1. Disc degeneration-related clinical phenotypes.

    Science.gov (United States)

    Battié, Michele C; Lazáry, Aron; Fairbank, Jeremy; Eisenstein, Stephen; Heywood, Chris; Brayda-Bruno, Marco; Varga, Péter Pál; McCall, Iain

    2014-06-01

    The phenotype, or observable trait of interest, is at the core of studies identifying associated genetic variants and their functional pathways, as well as diagnostics. Yet, despite remarkable technological developments in genotyping and progress in genetic research, relatively little attention has been paid to the equally important issue of phenotype. This is especially true for disc degeneration-related disorders, and the concept of degenerative disc disease, in particular, where there is little consensus or uniformity of definition. Greater attention and rigour are clearly needed in the development of disc degeneration-related clinical phenotypes if we are to see more rapid advancements in knowledge of this area. When selecting phenotypes, a basic decision is whether to focus directly on the complex clinical phenotype (e.g. the clinical syndrome of spinal stenosis), which is ultimately of interest, or an intermediate phenotype (e.g. dural sac cross-sectional area). While both have advantages, it cannot be assumed that associated gene variants will be similarly relevant to both. Among other considerations are factors influencing phenotype identification, comorbidities that are often present, and measurement issues. Genodisc, the European research consortium project on disc-related clinical pathologies has adopted a strategy that will allow for the careful characterisation and examination of both the complex clinical phenotypes of interest and their components.

  2. Regulatory mechanisms link phenotypic plasticity to evolvability

    NARCIS (Netherlands)

    van Gestel, Jordi; Weissing, Franz J

    2016-01-01

    Organisms have a remarkable capacity to respond to environmental change. They can either respond directly, by means of phenotypic plasticity, or they can slowly adapt through evolution. Yet, how phenotypic plasticity links to evolutionary adaptability is largely unknown. Current studies of plasticit

  3. The Neuroanatomy of the Autistic Phenotype

    Science.gov (United States)

    Fahim, Cherine; Meguid, Nagwa A.; Nashaat, Neveen H.; Yoon, Uicheul; Mancini-Marie, Adham; Evans, Alan C.

    2012-01-01

    The autism phenotype is associated with an excess of brain volume due in part to decreased pruning during development. Here we aimed at assessing brain volume early in development to further elucidate previous findings in autism and determine whether this pattern is restricted to idiopathic autism or shared within the autistic phenotype (fragile X…

  4. 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.

  5. Phenotypic screening for developmental neurotoxicity ...

    Science.gov (United States)

    There are large numbers of environmental chemicals with little or no available information on their toxicity, including developmental neurotoxicity. Because of the resource-intensive nature of traditional animal tests, high-throughput (HTP) methods that can rapidly evaluate chemicals for the potential to affect the developing brain are being explored. Typically, HTP screening uses biochemical and molecular assays to detect the interaction of a chemical with a known target or molecular initiating event (e.g., the mechanism of action). For developmental neurotoxicity, however, the mechanism(s) is often unknown. Thus, we have developed assays for detecting chemical effects on the key events of neurodevelopment at the cellular level (e.g., proliferation, differentiation, neurite growth, synaptogenesis, network formation). Cell-based assays provide a test system at a level of biological complexity that encompasses many potential neurotoxic mechanisms. For example, phenotypic assessment of neurite outgrowth at the cellular level can detect chemicals that target kinases, ion channels, or esterases at the molecular level. The results from cell-based assays can be placed in a conceptual framework using an Adverse Outcome Pathway (AOP) which links molecular, cellular, and organ level effects with apical measures of developmental neurotoxicity. Testing a wide range of concentrations allows for the distinction between selective effects on neurodevelopmental and non-specific

  6. Bronchiectasis: Phenotyping a Complex Disease.

    Science.gov (United States)

    Chalmers, James D

    2017-03-15

    Bronchiectasis is a long-neglected disease currently experiencing a surge in interest. It is a highly complex condition with numerous aetiologies, co-morbidities and a heterogeneous disease presentation and clinical course. The past few years have seen major advances in our understanding of the disease, primarily through large real-life cohort studies. The main outcomes of interest in bronchiectasis are symptoms, exacerbations, treatment response, disease progression and death. We are now more able to identify clearly the radiological, clinical, microbiological and inflammatory contributors to these outcomes. Over the past couple of years, multidimensional scoring systems such as the Bronchiectasis Severity Index have been introduced to predict disease severity and mortality. Although there are currently no licensed therapies for bronchiectasis, an increasing number of clinical trials are planned or ongoing. While this emerging evidence is awaited, bronchiectasis guidelines will continue to be informed largely by real-life evidence from observational studies and patient registries. Key developments in the bronchiectasis field include the establishment of international disease registries and characterisation of disease phenotypes using cluster analysis and biological data.

  7. Identification of a Locus for Autosomal Dominant Polycystic Liver Disease, on Chromosome 19p13.2-13.1

    OpenAIRE

    Reynolds, David M.; Falk, Cathy T.; Li, Airong; King, Bernard F.; Kamath, Patrick S.; Huston III, John; Shub, Clarence; Iglesias, Diana M.; Martin, Rodolfo S.; Pirson, Yves; Torres, Vicente E.; Somlo, Stefan

    2000-01-01

    Polycystic liver disease (PCLD) is characterized by the growth of fluid-filled cysts of biliary epithelial origin in the liver. Although the disease is often asymptomatic, it can, when severe, lead to complications requiring surgical therapy. PCLD is most often associated with autosomal dominant polycystic kidney disease (ADPKD); however, families with an isolated polycystic liver phenotype without kidney involvement have been described. The clinical presentation and histological features of ...

  8. Geographic Variation in Genetic Dominance of the Color Morphs of the Red-Backed Salamander, PLETHODON CINEREUS.

    Science.gov (United States)

    Highton, R

    1975-06-01

    Female parent-offspring phenotypic data on color morph frequencies in the red-backed salamander, Plethodon cinereus, were obtained from two Virginia localities (164 broods from Greene County and 97 broods from Giles County). The color morph data indicate that the striped morph is genetically dominant in Giles County and recessive in Greene County. It is suggested that epistatic interaction of two or more loci is responsible for the difference between the localities.

  9. The Inflammatory Phenotype in Failed Metal-On-Metal Hip Arthroplasty Correlates with Blood Metal Concentrations.

    Directory of Open Access Journals (Sweden)

    Erja-Leena Paukkeri

    Full Text Available Hip arthroplasty is the standard treatment of a painful hip destruction. The use of modern metal-on-metal (MOM bearing surfaces gained popularity in total hip arthroplasties during the last decade. Recently, worrisome failures due to adverse reaction to metal debris (ARMD, including pseudotumor response, have been widely reported. However, the pathogenesis of this reaction remains poorly understood. The aim of the present study was to investigate the ARMD response by flow cytometry approach.Sixteen patients with a failed Articular Surface Replacement (ASR hip prosthesis were included in the study. Samples of pseudotumor tissues collected during revision surgery were degraded by enzyme digestion and cells were typed by flow cytometry. Whole blood chromium and cobalt concentrations were analyzed with mass spectrometry before revision surgery.Flow cytometry analysis showed that the peri-implant pseudotumor tissue expressed two principal phenotypes, namely macrophage-dominated and T-lymphocyte-dominated response; the average portions being 54% (macrophages and 25% (T-lymphocytes in macrophage-dominated inflammation and 20% (macrophages and 54% (T-lymphocytes in T-lymphocyte-dominated response. The percentages of B-lymphocytes and granulocytes were lower in both phenotypes. Interestingly, the levels of blood chromium and cobalt were significantly higher in patients with macrophage-dominated response.The results suggest that the adverse tissue reactions induced by MOM wear particles contain heterogeneous pathogeneses and that the metal levels are an important factor in the determination of the inflammatory phenotype. The present results support the hypothesis that higher metal levels cause cytotoxicity and tissue injury and macrophages are recruited to clear the necrotic debris. On the other hand, the adverse response developed in association with lower metal levels is T-lymphocyte-dominated and is likely to reflect hypersensitivity reaction.

  10. Sex Differences in the Perceived Dominance and Prestige of Women With and Without Cosmetics.

    Science.gov (United States)

    Mileva, Viktoria R; Jones, Alex L; Russell, Richard; Little, Anthony C

    2016-10-01

    Women wearing cosmetics have been associated with a higher earning potential and higher status jobs. However, recent literature suggests that status can be accrued through two distinct routes: dominance and prestige. In two experiments, we applied a standardized amount of cosmetics to female faces using computer software. We then asked participants to rate faces with and without cosmetics for various traits including attractiveness, dominance, and prestige. Men and women both rated the faces with cosmetics added as higher in attractiveness. However, only women rated faces with cosmetics as higher in dominance, while only men rated them as higher in prestige. In a follow-up study, we investigated whether these enhanced perceptions of dominance from women were caused by jealousy. We found that women experience more jealousy toward women with cosmetics, and view these women as more attractive to men and more promiscuous. Our findings suggest that cosmetics may function as an extended phenotype and can alter other's perceptions differently depending on the perceiver's sex.

  11. Physiological phenotyping of plants for crop improvement.

    Science.gov (United States)

    Ghanem, Michel Edmond; Marrou, Hélène; Sinclair, Thomas R

    2015-03-01

    Future progress in crop breeding requires a new emphasis in plant physiological phenotyping for specific, well-defined traits. Success in physiological phenotyping to identify parents for use in breeding efforts for improved cultivars has been achieved by employing a multi-tier screening approach with different levels of sophistication and trait resolution. Subsequently, cultivar development required an integrated mix of classical breeding approaches and one or more tiers of phenotyping to identify genotypes expressing the desired trait. The role of high throughput systems can be useful; here, we emphasize that this approach is likely to offer useful results at an initial tier of phenotyping and will need to be complemented with more directed tiers of phenotyping. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. A novel heterozygous mutation in cardiac calsequestrin causes autosomal dominant catecholaminergic polymorphic ventricular tachycardia

    Science.gov (United States)

    Gray, Belinda; Bagnall, Richard D.; Lam, Lien; Ingles, Jodie; Turner, Christian; Haan, Eric; Davis, Andrew; Yang, Pei-Chi; Clancy, Colleen E.; Sy, Raymond W.; Semsarian, Christopher

    2017-01-01

    Background Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal inherited arrhythmia syndrome characterized by adrenergically stimulated ventricular tachycardia. Mutations in the cardiac ryanodine receptor gene (RYR2) cause an autosomal dominant form of CPVT, while mutations in the cardiac calsequestrin 2 gene (CASQ2) cause an autosomal recessive form. Objective The aim of this study was to clinically and genetically evaluate a large family with severe autosomal dominant CPVT. Methods Clinical evaluation of family members was performed, including detailed history, physical examination, electrocardiogram, exercise stress test, and autopsy review of decedents. We performed genome-wide linkage analysis in 12 family members and exome sequencing in 2 affected family members. In silico models of mouse and rabbit myocyte electrophysiology were used to predict potential disease mechanisms. Results Severe CPVT with dominant inheritance in 6 members was diagnosed in a large family with 2 sudden deaths, 2 resuscitated cardiac arrests, and multiple appropriate implantable cardioverter-defibrillator shocks. A comprehensive analysis of cardiac arrhythmia genes did not reveal a pathogenic variant. Exome sequencing identified a novel heterozygous missense variant in CASQ2 (Lys180Arg) affecting a highly conserved residue, which cosegregated with disease and was absent in unaffected family members. Genome-wide linkage analysis confirmed a single linkage peak at the CASQ2 locus (logarithm of odds ratio score 3.01; θ = 0). Computer simulations predicted that haploinsufficiency was unlikely to cause the severe CPVT phenotype and suggested a dominant negative mechanism. Conclusion We show for the first time that a variant in CASQ2 causes autosomal dominant CPVT. Genetic testing in dominant CPVT should include screening for heterozygous CASQ2 variants. PMID:27157848

  13. Motor unit number index examination in dominant and non-dominant hand muscles.

    Science.gov (United States)

    Li, Xiaoyan; He, Wensheng; Li, Charles; Wang, Ying-Chih; Slavens, Brooke A; Zhou, Ping

    2015-01-01

    This study investigated the effect of handedness on motor unit number index (MUNIX). Maximal hand strength, compound muscle action potential (CMAP) and voluntary surface electromyography (EMG) signals were measured bilaterally for the first dorsal interosseous (FDI) and thenar muscles in 24 right-handed and 2 left-handed healthy subjects. Mean (±standard error) grip and pinch forces in the dominant hand were 43.99 ± 2.36 kg and 9.36 ± 0.52 kg respectively, significantly larger than those in the non-dominant hand (grip: 41.37 ± 2.29 kg, p muscles. In addition, there was a lack of correlation between the strength and myoelectric parameters in regression analysis. However, strong correlations were observed between dominant and non-dominant hand muscles in both strength and myoelectric measures. Our results indicate that the population of motor units or spinal motor neurons as estimated from MUNIX may not be associated with handedness. Such findings help understand and interpret the MUNIX during its application for clinical or laboratory investigations.

  14. 2D : 4D in Men Is Related to Aggressive Dominance but Not to Sociable Dominance

    NARCIS (Netherlands)

    van der Meij, Leander; Almela, Mercedes; Buunk, Abraham P.; Dubbs, Shelli; Salvador, Alicia

    2012-01-01

    It has been shown that a smaller ratio between the length of the second and fourth digit (2D:4D) is an indicator of the exposure to prenatal testosterone (T). This study measured the 2D:4D of men and assessed dominance as a personality trait to investigate indirectly if the exposure to prenatal T is

  15. On the Informativeness of Dominant and Co-Dominant Genetic Markers for Bayesian Supervised Clustering

    DEFF Research Database (Denmark)

    Guillot, Gilles; Carpentier-Skandalis, Alexandra

    2011-01-01

    We study the accuracy of a Bayesian supervised method used to cluster individuals into genetically homogeneous groups on the basis of dominant or codominant molecular markers. We provide a formula relating an error criterion to the number of loci used and the number of clusters. This formula...

  16. Anomia-Pathological Verbal Dominance. Agnosic Behavior in Anomia: A Case of Pathological Verbal Dominance

    Science.gov (United States)

    McGlannan, Frances, Ed.

    1975-01-01

    Summarized are three articles concerned with research on neurological aspects of learning disabilities entitled "Anomia-A Case of Pathological Verbal Dominance;""Brain--Right Hemisphere--Man's So Called 'Minor Hemisphere;""Neurology-A Special Neurological Examination of Children with Learning Disabilities". (DB)

  17. Characterization of mutations in 22 females with X-linked dominant chondrodysplasia punctata (Happle syndrome).

    Science.gov (United States)

    Herman, Gail E; Kelley, Richard I; Pureza, V; Smith, D; Kopacz, Kevin; Pitt, James; Sutphen, Rebecca; Sheffield, Leslie J; Metzenberg, Aida B

    2002-01-01

    Human X-linked dominant chondrodysplasia punctata (CDPX2) or Happle syndrome is associated with mutations in the human emopamil binding protein (EBP), a delta8-delta7-sterol isomerase involved in cholesterol biosynthesis. The purpose of the current study was to determine the spectrum of EBP mutations in females with CDPX2 and the utility of biochemical screening for the disorder by analysis of plasma sterols. Genomic sequencing of the coding exons of the human delta8-delta7-sterol isomerase gene was performed on DNA from 26 females with suspected X-linked dominant chondrodysplasia punctata. Clinical data and sterol analyses were obtained for 24 and 23 of the patients, respectively. Mutations in the human EBP delta8-delta7-sterol isomerase gene were found in 22 (85%) of 26 females studied, including 20 (91%) of 22 patients who demonstrated an abnormal sterol profile. Thirteen of the mutations have not been reported previously. All of the females in whom mutations were found demonstrated typical skin manifestations of CDPX2, and all but one had a skeletal dysplasia. Plasma sterol analysis was a highly specific and sensitive indicator of the presence of an EBP mutation in females with suspected CDPX2, including a clinically unaffected mother of a sporadic case. No clear genotype/phenotype correlations were ascertained, probably because phenotypic expression is influenced substantially by the pattern of X-inactivation in an affected female.

  18. A note on mate allocation for dominance handling in genomic selection

    Directory of Open Access Journals (Sweden)

    Toro Miguel A

    2010-08-01

    Full Text Available Abstract Estimation of non-additive genetic effects in animal breeding is important because it increases the accuracy of breeding value prediction and the value of mate allocation procedures. With the advent of genomic selection these ideas should be revisited. The objective of this study was to quantify the efficiency of including dominance effects and practising mating allocation under a whole-genome evaluation scenario. Four strategies of selection, carried out during five generations, were compared by simulation techniques. In the first scenario (MS, individuals were selected based on their own phenotypic information. In the second (GSA, they were selected based on the prediction generated by the Bayes A method of whole-genome evaluation under an additive model. In the third (GSD, the model was expanded to include dominance effects. These three scenarios used random mating to construct future generations, whereas in the fourth one (GSD + MA, matings were optimized by simulated annealing. The advantage of GSD over GSA ranges from 9 to 14% of the expected response and, in addition, using mate allocation (GSD + MA provides an additional response ranging from 6% to 22%. However, mate selection can improve the expected genetic response over random mating only in the first generation of selection. Furthermore, the efficiency of genomic selection is eroded after a few generations of selection, thus, a continued collection of phenotypic data and re-evaluation will be required.

  19. Women in academic profession and male domination

    Directory of Open Access Journals (Sweden)

    Tomić Marta

    2010-01-01

    Full Text Available This paper presents a case study of women in the academic teaching profession in the context of the Criminal Police Academy, a Belgrade higher education institution of a typically male-dominant type. The aim of the paper is to describe and analyze women's current position and upward career mobility, as well as to discover the causes and mechanisms limiting their weaker (slower professional recognition. Multiple case method was deployed, on the basis of data collected from various sources: relevant literature on gender inequality of women in the academic profession, official documents of the institution in which the study was conducted, and personal life stories of women research subjects taken through in-depth semi-structured interviews. The results indicate that women who are part of a masculine climate in their academic teaching profession and in their personal life, are arguably in a subordinate position compared to men, and accept their position as quite natural. The research was limited to six typical cases, so that the conclusions may be generalized only with the greatest care; however, researchers who are interested in checking the study's objectivity and validity are provided with the adequate basis for further testing. The research shows that personal perspectives and testimonies of women can contribute to a deeper understanding of their disadvantage in academia, while at the same time contributing to the sociology of the 'individual' and the 'qualitative' by expanding the database on gender issues.

  20. Dominant Vortex Structures in Transverse Jets

    Directory of Open Access Journals (Sweden)

    Seyfettin Bayraktar

    2016-01-01

    Full Text Available In this paper, formation and development of one of the most dominant vortex structures, namely, counter-rotating vortex pair (CVP which is seen in the jet in crossflow are investigated numerically. Influences of the inclination angles between the nozzle(s and channel on the CVP are presented for three inclination angles, =30, 60 and 90 at velocity ratio, R=2.0. Effects of the number of the nozzles on the evolution of CVP is analyzed by considering the single and three side-by-side positioned circular nozzles. In addition to the CVP, some secondary vortices are also reported by considered relatively a narrow channel because their existence cannot be showed in wider channel. Simulations reveal that higher the inclination angle the more jet penetration into the channel in all directions and increasing the inclination angle causes larger CVPs in size. Although the flow structure of the CVP formed in the single and three side-by-side nozzles are similar their evolution is quite different.

  1. Interactions in dendronized polymers: intramolecular dominates intermolecular.

    Science.gov (United States)

    Córdova-Mateo, Esther; Bertran, Oscar; Zhang, Baozhong; Vlassopoulos, Dimitris; Pasquino, Rossana; Schlüter, A Dieter; Kröger, Martin; Alemán, Carlos

    2014-02-21

    In an attempt to relate atomistic information to the rheological response of a large dendritic object, interand intramolecular hydrogen bonds and p,p-interactions have been characterized in a dendronized polymer (DP) that consists of a polymethylmethacrylate backbone with tree-like branches of generation four (PG4) and contains both amide and aromatic groups. Extensive atomistic molecular dynamics simulations have been carried out on (i) an isolated PG4 chain and (ii) ten dimers formed by two PG4 chains associated with different degrees of interpenetration. Results indicate that the amount of nitrogen atoms involved in hydrogen bonding is ~11% while ~15% of aromatic groups participate in p,pinteractions. Furthermore, in both cases intramolecular interactions clearly dominate over intermolecular ones, while exhibiting markedly different behaviors. Specifically, the amount of intramolecular hydrogen bonds increases when the interpenetration of the two chains decreases, whereas intramolecular p,pinteractions remain practically insensitive to the amount of interpenetration. In contrast, the strength of the corresponding two types of intermolecular interactions decreases with interpenetration. Although the influence of complexation on the density and cross-sectional radius is relatively small, interpenetration affects significantly the molecular length of the DP. These results support the idea of treating DPs as long colloidal molecules.

  2. Nonlinear transient analysis of joint dominated structures

    Science.gov (United States)

    Chapman, J. M.; Shaw, F. H.; Russell, W. C.

    1987-01-01

    A residual force technique is presented that can perform the transient analyses of large, flexible, and joint dominated structures. The technique permits substantial size reduction in the number of degrees of freedom describing the nonlinear structural models and can account for such nonlinear joint phenomena as free-play and hysteresis. In general, joints can have arbitrary force-state map representations but these are used in the form of residual force maps. One essential feature of the technique is to replace the arbitrary force-state maps describing the nonlinear joints with residual force maps describing the truss links. The main advantage of this replacement is that the incrementally small relative displacements and velocities across a joint are not monitored directly thereby avoiding numerical difficulties. Instead, very small and 'soft' residual forces are defined giving a numerically attractive form for the equations of motion and thereby permitting numerically stable integration algorithms. The technique was successfully applied to the transient analyses of a large 58 bay, 60 meter truss having nonlinear joints. A method to perform link testing is also presented.

  3. Dominance and Transmissions in Supertropical Valuation Theory

    CERN Document Server

    Izhakian, Zur; Rowen, Louis

    2011-01-01

    This paper is a sequel of [IKR1], where we defined supervaluations on a commutative ring $R$ and studied a dominance relation $\\phi \\geq \\psi$ between supervaluations $\\phi$ and $\\psi$ on $R$, aiming at an enrichment of the algebraic tool box for use in tropical geometry. A supervaluation $\\phi:R \\to U$ is a multiplicative map from $R$ to a supertropical semiring $U$, cf. [IR1], [IR2], [IKR1], with further properties, which mean that $\\phi$ is a sort of refinement, or covering, of an m-valuation (= monoid valuation) $v: R \\to M$. In the most important case, that $R$ is a ring, m-valuations constitute a mild generalization of valuations in the sense of Bourbaki [B], while $\\phi \\geq \\psi$ means that $\\psi: R \\to V$ is a sort of coarsening of the supervaluation $\\phi$. If $\\phi(R)$ generates the semiring $U$, then $\\phi \\geq \\psi$ iff there exists a "transmission" $\\alpha: U \\to V$ with $\\psi = \\alpha \\circ \\phi$. Transmissions are multiplicative maps with further properties, cf. [IKR1, Sec. 5]. Every semiring ...

  4. Front propagation in vortex-dominated flows

    Science.gov (United States)

    O'Malley, Garrett; Winokur, Justin; Solomon, Tom

    2008-11-01

    We present experiments that explore how the propagation of a reaction front is affected by a two-dimensional flow dominated by vortices. The reaction is the excitable Belousov-Zhabotinsky chemical reaction. The flow is driven by the interaction between an electrical current passing through the fluid and a spatially-varying magnetic field produced by an array of magnets below the fluid. For some of the experiments, the forcing is strong enough to produce a weakly turbulent flow. Measurements are made both of the enhanced diffusion coefficient D^* describing transport in the flow and of the propagation speed v of a reaction front in the same flow. Scaling of v versus D^* is compared with that for the standard Fisher-Kolmogorov-Petrovsky-Piskunov prediction v ˜√D (with D as the molecular diffusion coefficient) for the reaction-diffusion limit with no fluid advection. We also study the effects of superdiffusive transport and Lévy flights on front propagation in a time-dependent vortex array with wavy jet regions.

  5. MRI of autosomal dominant pure spastic paraplegia

    Energy Technology Data Exchange (ETDEWEB)

    Krabbe, K.; Fallentin, E.; Herning, M. [Danish Research Center of Magnetic Resonance, Hvidovre Hospital, Kettegaard alle 30, DK-2650 Hvidovre (Denmark); Nielsen, J.E.; Fenger, K. [Institute of Medical Biochemistry and Genetics, Laboratory of Medical Genetics, Section of Neurogenetics, University of Copenhagen (Denmark)

    1997-10-01

    We examined 16 patients with autosomal dominant pure spastic paraplegia (HSP) and 15 normal controls matched for age and sex using MRI of the brain and spinal cord. Images were assessed qualitatively by two independent radiologists, blinded to the clinical diagnosis. Areas of the brain and corpus callosum on one midsagittal slice and the area of the brain on one axial slice were measured and a ``corpus-callosum index`` expressing the size of the corpus callosum relative to that of the brain was calculated. Cross-sectional areas and anteroposterior and transverse diameters of the spinal cord at the levels of C 2, C 5, T 3, T 6, T 9 and T 11 were measured. No significant differences between patients and controls were found on qualitative evaluation of the images. The patients had a significantly smaller corpus callosum and ``corpus-callosum index`` than controls. This finding, not reported previously, might indicate that the disease process in pure HSP is not confined to the spinal cord. The anteroposterior diameters of the spinal cord at T 3 and T 9 were significantly smaller in patients than in controls. This might correspond to the degeneration of the pyramidal tracts and the dorsal columns described at neuropathological examination. (orig.). With 1 fig., 3 tabs.

  6. On a Conjecture about Inverse Domination in Graphs

    DEFF Research Database (Denmark)

    Frendrup, Allan; Henning, Michael A.; Randerath, Bert

    2010-01-01

    Let G = (V, E) be a graph with no isolated vertex. A classical observation in domination theory is that if D is a minimum dominating set of G, then V \\ D is also a dominating set of G. A set D' is an inverse dominating set of G if D' is a dominating set of G and D' subset of V \\ D for some minimum...... domination number of G is at most the independence number of G. We prove this conjecture for special families of graphs, including claw-free graphs, bipartite graphs, split graphs, very well covered graphs, chordal graphs and cactus graphs....

  7. Total and paired domination numbers of toroidal meshes

    CERN Document Server

    Hu, Fu-Tao

    2011-01-01

    Let $G$ be a graph without isolated vertices. The total domination number of $G$ is the minimum number of vertices that can dominate all vertices in $G$, and the paired domination number of $G$ is the minimum number of vertices in a dominating set whose induced subgraph contains a perfect matching. This paper determines the total domination number and the paired domination number of the toroidal meshes, i.e., the Cartesian product of two cycles $C_n$ and $C_m$ for any $n\\ge 3$ and $m\\in\\{3,4\\}$, and gives some upper bounds for $n, m\\ge 5$.

  8. A note on neighborhood total domination in graphs

    Indian Academy of Sciences (India)

    Nader Jafari Rad

    2015-08-01

    Let = ( ,) be a graph without isolated vertices. A dominating set of is called a neighborhood total dominating set (or just NTDS) if the induced subgraph [()] has no isolated vertex. The minimum cardinality of a NTDS of is called the neighborhood total domination number of and is denoted by nt(). In this paper, we obtain sharp bounds for the neighborhood total domination number of a tree. We also prove that the neighborhood total domination number is equal to the domination number in several classes of graphs including grid graphs.

  9. 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...

  10. Phenotypic plasticity of southern ocean diatoms: key to success in the sea ice habitat?

    Directory of Open Access Journals (Sweden)

    Olivia Sackett

    Full Text Available Diatoms are the primary source of nutrition and energy for the Southern Ocean ecosystem. Microalgae, including diatoms, synthesise biological macromolecules such as lipids, proteins and carbohydrates for growth, reproduction and acclimation to prevailing environmental conditions. Here we show that three key species of Southern Ocean diatom (Fragilariopsis cylindrus, Chaetoceros simplex and Pseudo-nitzschia subcurvata exhibited phenotypic plasticity in response to salinity and temperature regimes experienced during the seasonal formation and decay of sea ice. The degree of phenotypic plasticity, in terms of changes in macromolecular composition, was highly species-specific and consistent with each species' known distribution and abundance throughout sea ice, meltwater and pelagic habitats, suggesting that phenotypic plasticity may have been selected for by the extreme variability of the polar marine environment. We argue that changes in diatom macromolecular composition and shifts in species dominance in response to a changing climate have the potential to alter nutrient and energy fluxes throughout the Southern Ocean ecosystem.

  11. Genotype-phenotype correlation in Chinese patients with spinal and bulbar muscular atrophy.

    Directory of Open Access Journals (Sweden)

    Wang Ni

    Full Text Available Spinal and bulbar muscular atrophy (SBMA is an X-linked recessive motor neuron disease characterized by slowly progressive weakness and atrophy of proximal limbs and bulbar muscles. To assess the genotype-phenotype correlation in Chinese patients, we identified 155 patients with SBMA and retrospectively examined available data from laboratory tests and neurophysiological analyses. Correlations between genotype and phenotype were analyzed. There was an inverse correlation between the length of CAG repeats and age at first muscle weakness (p<0.0001. The serum creatine kinase level showed a significant inverse correlation with disease duration and the age at examination (p=0.019 and p=0.004, respectively. Unlike previous classification of motor- and sensory-dominant phenotypes, all findings of nerve conduction, except the amplitudes of median nerve compound motor action potential, were positively correlated to the length of CAG repeats. A significant decline in sensory nerve action potential amplitudes may assist differential diagnosis of SBMA.

  12. Autosomal dominant erythermalgia associated with a novel mutation in the voltage-gated sodium channel alpha subunit Nav1.7.

    NARCIS (Netherlands)

    Michiels, J.J.M.; Morsche, R.H.M. te; Jansen, J.B.M.J.; Drenth, J.P.H.

    2005-01-01

    BACKGROUND: Autosomal dominant primary erythermalgia is a rare disorder characterized by recurrent attacks of red, warm, and painful hands and/or feet. OBJECTIVE: To describe the phenotypes and molecular data of a 10-member family with 5 symptomatic living patients with erythermalgia. RESULTS: The

  13. Neonatal onset autosomal dominant polycystic kidney disease (ADPKD) in a patient homozygous for a PKD2 missense mutation due to uniparental disomy.

    NARCIS (Netherlands)

    Losekoot, M.; Ruivenkamp, C.A.; Tholens, A.P.; Grimbergen, J.E.; Vijfhuizen, L.; Vermeer, S.; Dijkman, H.B.P.M.; Cornelissen, E.A.M.; Bongers, M.H.F.; Peters, D.J.

    2012-01-01

    Autosomal dominant polycystic kidney disease (ADPKD), due to a heterozygous mutation in PKD1 or PKD2, is usually an adult onset disease. Renal cystic disease is generally milder in PKD2 patients than in PKD1 patients. Recently, several PKD1 patients with a severe renal cystic phenotype due to a seco

  14. 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.

  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. 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. © 2014 The Authors. Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

  17. CAG repeat size correlates to electrophysiological motor and sensory phenotypes in SBMA.

    Science.gov (United States)

    Suzuki, Keisuke; Katsuno, Masahisa; Banno, Haruhiko; Takeuchi, Yu; Atsuta, Naoki; Ito, Mizuki; Watanabe, Hirohisa; Yamashita, Fumitada; Hori, Norio; Nakamura, Tomohiko; Hirayama, Masaaki; Tanaka, Fumiaki; Sobue, Gen

    2008-01-01

    Spinal and bulbar muscular atrophy (SBMA) is an adult-onset, lower motor neuron disease caused by an aberrant elongation of a CAG repeat in the androgen receptor (AR) gene. The main symptoms are weakness and atrophy of bulbar, facial and limb muscles, but sensory disturbances are frequently found in SBMA patients. Motor symptoms have been attributed to the accumulation of mutant AR in the nucleus of lower motor neurons, which is more profound in patients with a longer CAG repeat. We examined nerve conduction properties including F-waves in a total of 106 patients with genetically confirmed SBMA (mean age at data collection = 53.8 years; range = 31-75 years) and 85 control subjects. Motor conduction velocities (MCV), compound muscle action potentials (CMAP), sensory conduction velocities (SCV) and sensory nerve action potentials (SNAP) were significantly decreased in all nerves examined in the SBMA patients compared with that in the normal controls, indicating that axonal degeneration is the primary process in both motor and sensory nerves. More profound abnormalities were observed in the nerves of the upper limbs than in those of the lower limbs. F-waves in the median nerve were absent in 30 of 106 cases (28.3%), but no cases of absent F-waves were observed in the tibial nerve. From an analysis of the relationship between CMAPs and SNAPs, patients were identified with different electrophysiological phenotypes: motor-dominant, sensory-dominant and non-dominant phenotypes. The CAG repeat size and the age at onset were significantly different among the patients with motor- and sensory-dominant phenotypes, indicating that a longer CAG repeat is more closely linked to the motor-dominant phenotype and a shorter CAG repeat is more closely linked to the sensory-dominant phenotype. Furthermore, when we classified the patients by CAG repeat size, CMAP values showed a tendency to be decreased in patients with a longer CAG repeat (> or =47), while SNAPs were significantly

  18. Stickler syndrome caused by COL2A1 mutations: genotype-phenotype correlation in a series of 100 patients

    DEFF Research Database (Denmark)

    Hoornaert, Kristien P; Vereecke, Inge; Dewinter, Chantal;

    2010-01-01

    Stickler syndrome is an autosomal dominant connective tissue disorder caused by mutations in different collagen genes. The aim of our study was to define more precisely the phenotype and genotype of Stickler syndrome type 1 by investigating a large series of patients with a heterozygous mutation ...

  19. Achondroplasia: from genotype to phenotype.

    Science.gov (United States)

    Richette, Pascal; Bardin, Thomas; Stheneur, Chantal

    2008-03-01

    This review focuses on the rheumatological features of achondroplasia, which is the most common skeletal dysplasia and the most frequent cause of short-limbed dwarfism. It is inherited in an autosomal dominant manner but results in the majority of cases of de novo mutations. The disease is related to a mutation in the fibroblast growth factor receptor-3 (FGFR3) gene encoding one member of the FGFR subfamily of tyrosine kinase receptors, which results in constitutive activation of the receptor. Biochemical studies of FGFR3 combined with experiments in knock-out mice have demonstrated that FGFR3 is a negative regulator of chondrocytes proliferation and differentiation in growth plate. This mutation induces a disturbance of endochondral bone formation. The diagnosis of achondroplasia is based on typical clinical and radiological features including short stature, macrocephaly with frontal bossing, midface hypoplasia and rhizomelic shortening of the limbs. The most common rheumatological complications of achondroplasia are medullar and radicular compressions due to spinal stenosis and deformities of the lower limbs. Current treatment and future therapies are discussed.

  20. Complex inheritance of ABCA4 disease: four mutations in a family with multiple macular phenotypes.

    Science.gov (United States)

    Lee, Winston; Xie, Yajing; Zernant, Jana; Yuan, Bo; Bearelly, Srilaxmi; Tsang, Stephen H; Lupski, James R; Allikmets, Rando

    2016-01-01

    Over 800 mutations in the ABCA4 gene cause autosomal recessive Stargardt disease. Due to extensive genetic heterogeneity, observed variant-associated phenotypes can manifest tremendous variability of expression. Furthermore, the high carrier frequency of pathogenic ABCA4 alleles in the general population (~1:20) often results in pseudo-dominant inheritance patterns further complicating the diagnosis and characterization of affected individuals. This study describes a genotype/phenotype analysis of an unusual family with multiple macular disease phenotypes spanning across two generations and segregating four distinct ABCA4 mutant alleles. Complete sequencing of ABCA4 discovered two known missense mutations, p.C54Y and p.G1961E. Array comparative genomic hybridization revealed a large novel deletion combined with a small insertion, c.6148-698_c.6670del/insTGTGCACCTCCCTAG, and complete sequencing of the entire ABCA4 genomic locus uncovered a new deep intronic variant, c.302+68C>T. Patients with the p.G1961E mutation had the mildest, confined maculopathy phenotype with peripheral flecks while those with all other mutant allele combinations exhibited a more advanced stage of generalized retinal and choriocapillaris atrophy. This family epitomizes the clinical and genetic complexity of ABCA4-associated diseases. It contained variants from all classes of mutations, in the coding region, deep intronic, both single nucleotide variants and copy number variants that accounted for varying phenotypes segregating in an apparent dominant fashion. Unequivocally defining disease-associated alleles in the ABCA4 locus requires a multifaceted approach that includes advanced mutation detection methods and a thorough analysis of clinical phenotypes.

  1. Autosomal dominant pseudohypoaldosteronism type 1 with a novel splice site mutation in MR gene

    Directory of Open Access Journals (Sweden)

    Kaito Hiroshi

    2009-11-01

    Full Text Available Abstract Background Autosomal dominant pseudohypoaldosteronism type 1 (PHA1 is a rare inherited condition that is characterized by renal resistance to aldosterone as well as salt wasting, hyperkalemia, and metabolic acidosis. Renal PHA1 is caused by mutations of the human mineralcorticoid receptor gene (MR, but it is a matter of debate whether MR mutations cause mineralcorticoid resistance via haploinsufficiency or dominant negative mechanism. It was previously reported that in a case with nonsense mutation the mutant mRNA was absent in lymphocytes because of nonsense mediated mRNA decay (NMD and therefore postulated that haploinsufficiency alone can give rise to the PHA1 phenotype in patients with truncated mutations. Methods and Results We conducted genomic DNA analysis and mRNA analysis for familial PHA1 patients extracted from lymphocytes and urinary sediments and could detect one novel splice site mutation which leads to exon skipping and frame shift result in premature termination at the transcript level. The mRNA analysis showed evidence of wild type and exon-skipped RT-PCR products. Conclusion mRNA analysis have been rarely conducted for PHA1 because kidney tissues are unavailable for this disease. However, we conducted RT-PCR analysis using mRNA extracted from urinary sediments. We could demonstrate that NMD does not fully function in kidney cells and that haploinsufficiency due to NMD with premature termination is not sufficient to give rise to the PHA1 phenotype at least in this mutation of our patient. Additional studies including mRNA analysis will be needed to identify the exact mechanism of the phenotype of PHA.

  2. Phenotypic insights into ADCY5‐associated disease

    Science.gov (United States)

    Chang, Florence C.F.; Westenberger, Ana; Dale, Russell C.; Smith, Martin; Pall, Hardev S.; Perez‐Dueñas, Belen; Grattan‐Smith, Padraic; Ouvrier, Robert A.; Mahant, Neil; Hanna, Bernadette C.; Hunter, Matthew; Lawson, John A.; Max, Christoph; Sachdev, Rani; Meyer, Esther; Crimmins, Dennis; Pryor, Donald; Morris, John G.L.; Münchau, Alex; Grozeva, Detelina; Carss, Keren J.; Raymond, Lucy; Kurian, Manju A.; Klein, Christine

    2016-01-01

    ABSTRACT Background Adenylyl cyclase 5 (ADCY5) mutations is associated with heterogenous syndromes: familial dyskinesia and facial myokymia; paroxysmal chorea and dystonia; autosomal‐dominant chorea and dystonia; and benign hereditary chorea. We provide detailed clinical data on 7 patients from six new kindreds with mutations in the ADCY5 gene, in order to expand and define the phenotypic spectrum of ADCY5 mutations. Methods In 5 of the 7 patients, followed over a period of 9 to 32 years, ADCY5 was sequenced by Sanger sequencing. The other 2 unrelated patients participated in studies for undiagnosed pediatric hyperkinetic movement disorders and underwent whole‐exome sequencing. Results Five patients had the previously reported p.R418W ADCY5 mutation; we also identified two novel mutations at p.R418G and p.R418Q. All patients presented with motor milestone delay, infantile‐onset action‐induced generalized choreoathetosis, dystonia, or myoclonus, with episodic exacerbations during drowsiness being a characteristic feature. Axial hypotonia, impaired upward saccades, and intellectual disability were variable features. The p.R418G and p.R418Q mutation patients had a milder phenotype. Six of seven patients had mild functional gain with clonazepam or clobazam. One patient had bilateral globus pallidal DBS at the age of 33 with marked reduction in dyskinesia, which resulted in mild functional improvement. Conclusion We further delineate the clinical features of ADCY5 gene mutations and illustrate its wide phenotypic expression. We describe mild improvement after treatment with clonazepam, clobazam, and bilateral pallidal DBS. ADCY5‐associated dyskinesia may be under‐recognized, and its diagnosis has important prognostic, genetic, and therapeutic implications. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society PMID:27061943

  3. Polk Mutant Mice Have a Spontaneous Mutator Phenotype

    Science.gov (United States)

    Stancel, J. Nicole Kosarek; McDaniel, Lisa D.; Velasco, Susana; Richardson, James; Guo, Caixia; Friedberg, Errol C.

    2009-01-01

    Mice defective in the Polk gene (which encodes DNA polymerase kappa) are viable and do not manifest obvious phenotypes. The present studies document a spontaneous mutator phenotype in Polk−/− mice. The initial indication of enhanced spontaneous mutations in these mice came from the serendipitous observation of a postulated founder mutation that manifested in multiple disease states among a cohort of mice comprising all three possible Polk genotypes. Polk−/− and isogenic wild type controls carrying a reporter transgene (the λ-phage cII gene) were used for subsequent quantitative and qualitative studies on mutagenesis in various tissues. We observed significantly increased mutation frequencies in the kidney, liver, and lung of Polk−/− mice, but not in the spleen or testis. G:C base pairs dominated the mutation spectra of the kidney, liver, and lung. These results are consistent with the notion that Polκ is required for accurate translesion DNA synthesis past naturally occurring polycyclic guanine adducts, possibly generated by cholesterol and/or its metabolites. PMID:19783230

  4. Otopalatodigital spectrum disorders: refinement of the phenotypic and mutational spectrum.

    Science.gov (United States)

    Moutton, Sébastien; Fergelot, Patricia; Naudion, Sophie; Cordier, Marie-Pierre; Solé, Guilhem; Guerineau, Elodie; Hubert, Christophe; Rooryck, Caroline; Vuillaume, Marie-Laure; Houcinat, Nada; Deforges, Julie; Bouron, Julie; Devès, Sylvie; Le Merrer, Martine; David, Albert; Geneviève, David; Giuliano, Fabienne; Journel, Hubert; Megarbane, André; Faivre, Laurence; Chassaing, Nicolas; Francannet, Christine; Sarrazin, Elisabeth; Stattin, Eva-Lena; Vigneron, Jacqueline; Leclair, Danielle; Abadie, Caroline; Sarda, Pierre; Baumann, Clarisse; Delrue, Marie-Ange; Arveiler, Benoit; Lacombe, Didier; Goizet, Cyril; Coupry, Isabelle

    2016-08-01

    Otopalatodigital spectrum disorders (OPDSD) constitute a group of dominant X-linked osteochondrodysplasias including four syndromes: otopalatodigital syndromes type 1 and type 2 (OPD1 and OPD2), frontometaphyseal dysplasia, and Melnick-Needles syndrome. These syndromes variably associate specific facial and extremities features, hearing loss, cleft palate, skeletal dysplasia and several malformations, and show important clinical overlap over the different entities. FLNA gain-of-function mutations were identified in these conditions. FLNA encodes filamin A, a scaffolding actin-binding protein. Here, we report phenotypic descriptions and molecular results of FLNA analysis in a large series of 27 probands hypothesized to be affected by OPDSD. We identified 11 different missense mutations in 15 unrelated probands (n=15/27, 56%), of which seven were novel, including one of unknown significance. Segregation analyses within families made possible investigating 20 additional relatives carrying a mutation. This series allows refining the phenotypic and mutational spectrum of FLNA mutations causing OPDSD, and providing suggestions to avoid the overdiagnosis of OPD1.

  5. Surgical Treatment of Patients with Lennox-Gastaut Syndrome Phenotype

    Directory of Open Access Journals (Sweden)

    Shi-Yong Liu

    2012-01-01

    Full Text Available Lennox-Gastaut syndrome (LGS is a devastating and refractory generalized epilepsy affecting children and adolescents. In this study we report the results of resective surgery in 18 patients with LGS phenotype who underwent single-lobe/lesionectomy or multilobe resection plus multiple subpial transection and/or callosotomy. After surgery, seven patients became completely seizure-free (Engel Class I and five almost seizure-free (Engel Class II. Additional four had significant seizure control (Engel Class III, and two had no change in seizure frequency (Engel Class IV. Of the 4 patients without any lesion on brain MRI, 2 ended with Engel Class II, 1 with III and the other with IV in Engels’ classification. Mean intelligence quotient (IQ increased from 56.1 ± 8.1 (mean ± SD before operation to 67.4 ± 8.2 (mean ± SD after operation, a significant improvement (P=0.001. Results also indicated that the younger the patient at surgery, or the shorter the interval between onset of seizure and resective operation, the better the intellectual outcome. Our data suggest that resective epilepsy surgery can be successful in patients with LGS phenotype as long as the EEG shows dominance of discharges in one hemisphere and corresponding ipsilateral imaging findings, even with contralateral ictal discharges.

  6. Oral phenotype and variation in focal dermal hypoplasia.

    Science.gov (United States)

    Wright, John Timothy; Puranik, Chaitanya P; Farrington, Frank

    2016-03-01

    Focal dermal hypoplasia (FDH) or Goltz Syndrome (OMIM# 305600) is an X-linked dominant ectodermal dysplasia caused by mutations in the PORCN gene. This gene encodes an endoplasmic reticulum transmembrane protein that is involved in processing the embryonically critical WNT signaling proteins. Individuals diagnosed with FDH were recruited to participate in the study through the National Foundation for Ectodermal Dysplasia. Individuals were evaluated to characterize the FDH phenotype. Each participant completed a brief dental survey and oral evaluation using artificial light. To identify the oral soft and hard tissue findings 19 individuals (16 female and 3 male) participated with a median age of 10 years (range 2-56 years). Soft and hard tissue defects were present in 68% (13) and 94% (18) of the patients, respectively. Dental anomalies were highly prevalent with 68% (13) demonstrating vertical enamel grooving, 52% (10) having peg shaped tooth deformities, and 78% (15) having enamel hypoplasia with or without discoloration. Cleft lip and cleft palate presented in 15% (3) of the participants. Other findings included 57% (11) having intra-oral lipoma or papilloma with no site predilection. Dental malocclusions were common with 63% (12) having some degree of malocclusion with 15% (3) of participants having class III malocclusion with an anterior dental cross bite. Participants frequently reported speech problems or difficulty with chewing (73%; N = 14). This study shows there is marked variation in the oral phenotype of individuals with FDH and underscores the important role of WNT signaling in oro-facial development.

  7. Toward a defense-dominated world

    Energy Technology Data Exchange (ETDEWEB)

    Wood, L.

    1993-08-01

    Maintaining the large-scale peace in a defense-dominated world necessarily will require not only passive but also active defenses against large-scale aggression that are technically feasible, practical and easy to employ -- and robust against perversion into support of aggression. Such peace maintenance tool-sets will feature means for effectively rebuking aggression as well as providing timely and very widely available seaming of aggression underway anywhere. This report discusses the technology base which currently exists to provide world-wide, high-quality imagery at moderate (5--10 meter) spatial resolution or imagery of 1% of the Earth`s land surface at high ({le} 1 meter) resolution no less frequently than daily, at a total cost of the order of $1 B, with operational capability in the later `90s. Such systems could provide timely warning of aggressive actions anywhere. Similarly, space-based means of defeating aggression conducted with even quite short-range ballistic missiles anywhere in the world could be brought into existence by the end of the `90s for a total cost of about $10 B, and small high-altitude, long flight-duration robotic aircraft carrying high-performance sensors and interceptor missilery could provide both seaming and active defenses against attacks conducted with very short range ballistic missiles, as well as attacks launched with air-breathing threats such as bombers and cruise missiles, for a cost per defended area of the order of $10/km{sup 2}. It appears that all of the associated sensors can find apt dual-use as high-performance systems for monitoring physical aspects of the human environment.

  8. Dark Energy Domination In The Virgocentric Flow

    Science.gov (United States)

    Byrd, Gene; Chernin, A. D.; Karachentsev, I. D.; Teerikorpi, P.; Valtonen, M.; Dolgachev, V. P.; Domozhilova, L. M.

    2011-04-01

    Dark energy (DE) was first observationally detected at large Gpc distances. If it is a vacuum energy formulated as Einstein's cosmological constant, Λ, DE should also have dynamical effects at much smaller scales. Previously, we found its effects on much smaller Mpc scales in our Local Group (LG) as well as in other nearby groups. We used new HST observations of member 3D distances from the group centers and Doppler shifts. We find each group's gravity dominates a bound central system of galaxies but DE antigravity results in a radial recession increasing with distance from the group center of the outer members. Here we focus on the much larger (but still cosmologically local) Virgo Cluster and systems around it using new observations of velocities and distances. We propose an analytic model whose key parameter is the zero-gravity radius (ZGR) from the cluster center where gravity and DE antigravity balance. DE brings regularity to the Virgocentric flow. Beyond Virgo's 10 Mpc ZGR, the flow curves to approach a linear global Hubble law at larger distances. The Virgo cluster and its outer flow are similar to the Local Group and its local outflow with a scaling factor of about 10; the ZGR for Virgo is 10 times larger than that of the LG. The similarity of the two systems on the scales of 1 to 30 Mpc suggests that a quasi-stationary bound central component and an expanding outflow applies to a wide range of groups and clusters due to small scale action of DE as well as gravity. Chernin, et al 2009 Astronomy and Astrophysics 507, 1271 http://arxiv.org/abs/1006.0066 http://arxiv.org/abs/1006.0555

  9. 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.

  10. Adding Asymmetrically Dominated Alternatives: Violations of Regularity & the Similarity Hypothesis.

    Science.gov (United States)

    1981-07-01

    target but not by the competitor. ADDING ASYMMET-.ICALLY DOMINATED ALTERNATIVES EXHIBIT 1 PLACEMIENT OF ASYMETRICALLY DOMINATED DECOY (P re i. C t2r cc...adding the decoy. Thus, .... " ADDING ASYMETRICALLY DOMINATED ALTERNATIVES 16 EXHIBIT 3 VIOLATIONS OF REGULARITY DUE TO ADDING DECOY Probability of...expanding A.DDING ASYMETRICALLY DOMINATED ALTERNATIVES 22 the degree of the range extention, suggests that a simple range extention ex- planation is not

  11. A Generalised Concept of Dominance in Linear Programming Models

    OpenAIRE

    Drynan, Ross G.

    1987-01-01

    The notion of dominance most familiar to agricultural economists is perhaps the decision theoretic concept entailed in comparing one risky prospect to others. But dominance concepts are also relevant in the linear programming context, for example in identifying redundant constraints. In this note, the standard concept of dominance in linear programming is generalized by defining dominance with respect to differing levels of information about the programming problem.

  12. Sensorimotor performance as a function of eye dominance and handedness.

    Science.gov (United States)

    Coren, S

    1999-04-01

    Performance on a speeded target striking task was significantly associated with eye dominance and handedness for a sample of 30 subjects. They showed the expected higher performance with the dominant hand but also showed an effect of eye of input. Highest performance was obtained with binocular viewing, next best used the dominant eye, and poorest performance the nondominant eye. Effects were additive with no interaction between hand and eye dominance.

  13. New Criteria for Judging Generalized Strictly Diagonally Dominant Matrix

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jin-song

    2015-01-01

    Generalized strictly diagonally dominant matrices play a wide and important role in computational mathematics, mathematical physics, theory of dynamical systems, etc. But it is difficult to judge a matrix is or not generalized strictly diagonally dominant matrix. In this paper, by using the properties of α-chain diagonally dominant matrix, we obtain new criteria for judging generalized strictly diagonally dominant matrix, which enlarge the identification range.

  14. The Mammalian Phenotype Ontology as a unifying standard for experimental and high-throughput phenotyping data.

    Science.gov (United States)

    Smith, Cynthia L; Eppig, Janan T

    2012-10-01

    The Mammalian Phenotype Ontology (MP) is a structured vocabulary for describing mammalian phenotypes and serves as a critical tool for efficient annotation and comprehensive retrieval of phenotype data. Importantly, the ontology contains broad and specific terms, facilitating annotation of data from initial observations or screens and detailed data from subsequent experimental research. Using the ontology structure, data are retrieved inclusively, i.e., data annotated to chosen terms and to terms subordinate in the hierarchy. Thus, searching for "abnormal craniofacial morphology" also returns annotations to "megacephaly" and "microcephaly," more specific terms in the hierarchy path. The development and refinement of the MP is ongoing, with new terms and modifications to its organization undergoing continuous assessment as users and expert reviewers propose expansions and revisions. A wealth of phenotype data on mouse mutations and variants annotated to the MP already exists in the Mouse Genome Informatics database. These data, along with data curated to the MP by many mouse mutagenesis programs and mouse repositories, provide a platform for comparative analyses and correlative discoveries. The MP provides a standard underpinning to mouse phenotype descriptions for existing and future experimental and large-scale phenotyping projects. In this review we describe the MP as it presently exists, its application to phenotype annotations, the relationship of the MP to other ontologies, and the integration of the MP within large-scale phenotyping projects. Finally we discuss future application of the MP in providing standard descriptors of the phenotype pipeline test results from the International Mouse Phenotype Consortium projects.

  15. Stochasticity and efficiency of convection-dominated vs. SASI-dominated supernova explosions

    CERN Document Server

    Cardall, Christian Y

    2015-01-01

    We present an initial report on 160 simulations of a highly simplified model of the post-bounce supernova environment in three spatial dimensions (3D). We set different values of a parameter characterizing the impact of nuclear dissociation at the stalled shock in order to regulate the post-shock fluid velocity, thereby determining the relative importance of convection and the stationary accretion shock instability (SASI). While our convection-dominated runs comport with the paradigmatic notion of a `critical neutrino luminosity' for explosion at a given mass accretion rate (albeit with a nontrivial spread in explosion times just above threshold), the outcomes of our SASI-dominated runs are much more stochastic: a sharp threshold critical luminosity is `smeared out' into a rising probability of explosion over a $\\sim 20\\%$ range of luminosity. We also find that the SASI-dominated models are able to explode with 3 to 4 times less efficient neutrino heating, indicating that progenitor properties, and fluid and ...

  16. A broad phenotypic screen identifies novel phenotypes driven by a single mutant allele in Huntington's disease CAG knock-in mice.

    Directory of Open Access Journals (Sweden)

    Sabine M Hölter

    Full Text Available Huntington's disease (HD is an autosomal dominant neurodegenerative disorder caused by the expansion of a CAG trinucleotide repeat in the HTT gene encoding huntingtin. The disease has an insidious course, typically progressing over 10-15 years until death. Currently there is no effective disease-modifying therapy. To better understand the HD pathogenic process we have developed genetic HTT CAG knock-in mouse models that accurately recapitulate the HD mutation in man. Here, we describe results of a broad, standardized phenotypic screen in 10-46 week old heterozygous HdhQ111 knock-in mice, probing a wide range of physiological systems. The results of this screen revealed a number of behavioral abnormalities in HdhQ111/+ mice that include hypoactivity, decreased anxiety, motor learning and coordination deficits, and impaired olfactory discrimination. The screen also provided evidence supporting subtle cardiovascular, lung, and plasma metabolite alterations. Importantly, our results reveal that a single mutant HTT allele in the mouse is sufficient to elicit multiple phenotypic abnormalities, consistent with a dominant disease process in patients. These data provide a starting point for further investigation of several organ systems in HD, for the dissection of underlying pathogenic mechanisms and for the identification of reliable phenotypic endpoints for therapeutic testing.

  17. A broad phenotypic screen identifies novel phenotypes driven by a single mutant allele in Huntington's disease CAG knock-in mice.

    Science.gov (United States)

    Hölter, Sabine M; Stromberg, Mary; Kovalenko, Marina; Garrett, Lillian; Glasl, Lisa; Lopez, Edith; Guide, Jolene; Götz, Alexander; Hans, Wolfgang; Becker, Lore; Rathkolb, Birgit; Rozman, Jan; Schrewed, Anja; Klingenspor, Martin; Klopstock, Thomas; Schulz, Holger; Wolf, Eckhard; Wursta, Wolfgang; Gillis, Tammy; Wakimoto, Hiroko; Seidman, Jonathan; MacDonald, Marcy E; Cotman, Susan; Gailus-Durner, Valérie; Fuchs, Helmut; de Angelis, Martin Hrabě; Lee, Jong-Min; Wheeler, Vanessa C

    2013-01-01

    Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by the expansion of a CAG trinucleotide repeat in the HTT gene encoding huntingtin. The disease has an insidious course, typically progressing over 10-15 years until death. Currently there is no effective disease-modifying therapy. To better understand the HD pathogenic process we have developed genetic HTT CAG knock-in mouse models that accurately recapitulate the HD mutation in man. Here, we describe results of a broad, standardized phenotypic screen in 10-46 week old heterozygous HdhQ111 knock-in mice, probing a wide range of physiological systems. The results of this screen revealed a number of behavioral abnormalities in HdhQ111/+ mice that include hypoactivity, decreased anxiety, motor learning and coordination deficits, and impaired olfactory discrimination. The screen also provided evidence supporting subtle cardiovascular, lung, and plasma metabolite alterations. Importantly, our results reveal that a single mutant HTT allele in the mouse is sufficient to elicit multiple phenotypic abnormalities, consistent with a dominant disease process in patients. These data provide a starting point for further investigation of several organ systems in HD, for the dissection of underlying pathogenic mechanisms and for the identification of reliable phenotypic endpoints for therapeutic testing.

  18. Exploring the Bilingualism of a Migrant Community through Language Dominance

    Science.gov (United States)

    Santello, Marco

    2014-01-01

    This study outlines a linguistic profile of two subgroups of Italian English circumstantial bilinguals - one dominant in English and the other dominant in Italian--by exploring for the first time their linguistic repertoire through the Gradient Bilingual Dominance Scale (Dunn & Fox Tree, 2009). The scale takes into account language…

  19. Carnival and Domination: Pedagogies of Neither Care Nor Justice.

    Science.gov (United States)

    Sidorkin, Alexander M.

    1997-01-01

    Discusses the need to overcome domination in education, arguing that such cultural phenomena as carnival could do a better job of overcoming domination than the ethics of justice and care, and suggesting that the concept of domination belongs to the language of freedom rather than the language of morality. (SM)

  20. Signed and Minus Domination in Complete Multipartite Graphs

    CERN Document Server

    Liang, Hongyu

    2012-01-01

    In this paper we determine the exact values of the signed domination number, signed total domination number, and minus domination number of complete multipartite graphs, which substantially generalizes some previous results obtained for special subclasses of complete multipartite graphs such as cliques and complete bipartite graphs.

  1. Trait dominance promotes reflexive staring at masked angry body postures

    NARCIS (Netherlands)

    Hortensius, R.; van Honk, J.; De Gelder, B.; Terburg, D.

    2014-01-01

    It has been shown that dominant individuals sustain eye-contact when non-consciously confronted with angry faces, suggesting reflexive mechanisms underlying dominance behaviors. However, dominance and submission can be conveyed and provoked by means of not only facial but also bodily features. So fa

  2. The Relationship Between Lateral Dominance and Divergent Cognitive Thought.

    Science.gov (United States)

    Williams, Barbara B.

    This study was designed to explore the relationship of lateral dominance to divergent cognitive thought. According to the screening results of the Harris Tests of Lateral Dominance, 36 subjects ranging from 9-12 years were divided equally into three groups of left, right, and mixed lateral dominance. In order to measure divergent cognitive…

  3. Factors affecting the reproductive success of dominant male meerkats.

    Science.gov (United States)

    Spong, Göran F; Hodge, Sarah J; Young, Andrew J; Clutton-Brock, Tim H

    2008-05-01

    Identifying traits that affect the reproductive success of individuals is fundamental for our understanding of evolutionary processes. In cooperative breeders, a dominant male typically restricts mating access to the dominant female for extended periods, resulting in pronounced variation in reproductive success among males. This may result in strong selection for traits that increase the likelihood of dominance acquisition, dominance retention and reproductive rates while dominant. However, despite considerable research on reproductive skew, few studies have explored the factors that influence these three processes among males in cooperative species. Here we use genetic, behavioural and demographic data to investigate the factors affecting reproductive success in dominant male meerkats (Suricata suricatta). Our data show that dominant males sire the majority of all offspring surviving to 1 year. A male's likelihood of becoming dominant is strongly influenced by age, but not by weight. Tenure length and reproductive rate, both important components of dominant male reproductive success, are largely affected by group size and composition, rather than individual traits. Dominant males in large groups have longer tenures, but after this effect is controlled, male tenure length also correlates negatively to the number of adult females in the group. Male reproductive rate also declines as the number of intra- and extra-group competitors increases. As the time spent in the dominant position and reproductive rate while dominant explain > 80% of the total variance in reproductive success, group composition thus has major implications for male reproductive success.

  4. Mixed Dominance and the Manner of Holding a Pencil.

    Science.gov (United States)

    Lovell, Virginia K.

    1982-01-01

    Reports on an informal study that revealed that a significant number of people who hold a pencil with two fingers and a thumb have mixed cerebral dominance, that more females than males have mixed dominance, and that those with mixed dominance tend to be more imaginative. (FL)

  5. 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.

  6. 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.

  7. Counsel the genotype, treat the phenotype

    NARCIS (Netherlands)

    van der Zwaag, Paul A.; van Tintelen, J. Peter

    2011-01-01

    This editorial refers to 'Novel correlations between the genotype and the phenotype of hypertrophic and dilated cardiomyopathy: results from the German Competence Network Heart Failure' by S. Waldmuller et al., published in this issue on pages 1185-1192.

  8. Catecholamine metabolomic and secretory phenotypes in phaeochromocytoma

    NARCIS (Netherlands)

    Eisenhofer, G.; Pacak, K.; Huynh, T.T.; Qin, N.; Bratslavsky, G.; Linehan, W.M.; Mannelli, M.; Friberg, P.; Grebe, S.K.; Timmers, H.J.L.M.; Bornstein, S.R.; Lenders, J.W.M.

    2011-01-01

    Phaeochromocytomas and paragangliomas (PPGLs) are highly heterogeneous tumours with variable catecholamine biochemical phenotypes and diverse hereditary backgrounds. This analysis of 18 catecholamine-related plasma and urinary biomarkers in 365 patients with PPGLs and 846 subjects without PPGLs

  9. 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.

  10. 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.

  11. Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency.

    Science.gov (United States)

    Farooqi, I S; Yeo, G S; Keogh, J M; Aminian, S; Jebb, S A; Butler, G; Cheetham, T; O'Rahilly, S

    2000-07-01

    Over 20 severely obese subjects in 11 independent kindreds have been reported to have pathogenic heterozygous mutations in the gene encoding the melanocortin 4 receptor (MC4R), making this the most common known monogenic cause of human obesity. To date, the detailed clinical phenotype of this dominantly inherited disorder has not been defined, and no homozygous subjects have been described. We determined the nucleotide sequence of the entire coding region of the MC4R gene in 243 subjects with severe, early-onset obesity. A novel two-base pair GT insertion in codon 279 was found in two unrelated subjects, and four novel missense mutations, N62S, R165Q, V253I, C271Y, and one mutation (T112M) reported previously were found in five subjects. N62S was found in homozygous form in five children with severe obesity from a consanguineous pedigree. All four heterozygous carriers were nonobese. Several features of the phenotype, e.g. hyperphagia, tendency toward tall stature, hyperinsulinemia, and preserved reproductive function, closely resemble those reported previously in Mc4r knock-out mice. In addition, a marked increase in bone mineral density was seen in all affected subjects. In transient transfection assays, the N62S mutant receptor showed a responsiveness to alphaMSH that was intermediate between the wild-type receptor and mutant receptors carrying nonsense and missense mutations associated with dominantly inherited obesity. Thus MC4R mutations result in a syndrome of hyperphagic obesity in humans that can present with either dominant or recessive patterns of inheritance.

  12. Convergent Adaptation in the Dominant Global Hospital Clone ST239 of Methicillin-Resistant Staphylococcus aureus

    Science.gov (United States)

    Baines, Sarah L.; Holt, Kathryn E.; Schultz, Mark B.; Seemann, Torsten; Howden, Brian O.; Jensen, Slade O.; van Hal, Sebastiaan J.; Coombs, Geoffrey W.; Firth, Neville; Powell, David R.; Stinear, Timothy P.

    2015-01-01

    ABSTRACT Infections caused by highly successful clones of hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) are a major public health burden. The globally dominant sequence type 239 (ST239) HA-MRSA clone has persisted in the health care setting for decades, but the basis of its success has not been identified. Taking a collection of 123 ST239 isolates spanning 32 years, we have used population-based functional genomics to investigate the evolution of this highly persistent and successful clone. Phylogenetic reconstruction and population modeling uncovered a previously unrecognized distinct clade of ST239 that was introduced into Australia from Asia and has perpetuated the epidemic in this region. Functional analysis demonstrated attenuated virulence and enhanced resistance to last-line antimicrobials, the result of two different phenomena, adaptive evolution within the original Australian ST239 clade and the introduction of a new clade displaying shifts in both phenotypes. The genetic diversity between the clades allowed us to employ genome-wide association testing and identify mutations in other essential regulatory systems, including walKR, that significantly associate with and may explain these key phenotypes. The phenotypic convergence of two independently evolving ST239 clades highlights the very strong selective pressures acting on HA-MRSA, showing that hospital environments have favored the accumulation of mutations in essential MRSA genes that increase resistance to antimicrobials, attenuate virulence, and promote persistence in the health care environment. Combinations of comparative genomics and careful phenotypic measurements of longitudinal collections of clinical isolates are giving us the knowledge to intelligently address the impact of current and future antibiotic usage policies and practices on hospital pathogens globally. PMID:25736880

  13. Candidate genes in ocular dominance plasticity

    Directory of Open Access Journals (Sweden)

    M. Liset Rietman

    2012-02-01

    Full Text Available The objective of this study was to identify new candidate genes involved in experience-dependent plasticity. To this aim, we combined previously obtained data from recombinant inbred BXD strains on ocular dominance (OD plasticity and gene expression levels in the neocortex. We validated our approach using a list of genes which alter OD plasticity when inactivated. The expression levels of one fifth of these genes correlated with the amount of OD plasticity. Moreover, the two genes with the highest relative inter-strain differences were among the correlated genes. This suggests that correlation between gene expression levels and OD plasticity is indeed likely to point to genes with a causal role in modulating or generating plasticity in the visual cortex. After this validation on known plasticity genes, we identified new candidate genes by a multi-step approach. First, a list was compiled of all genes of which the expression level in BXD strains correlate with the amount of OD plasticity. To narrow this list to the more promising candidates, we took its cross-section with a list of genes co-regulated with the sensitive period for OD plasticity and a list of genes associated with pathways implicated in OD plasticity. This analysis resulted in a list of 32 candidate genes. The list contained unproven, but not surprising, candidates, such as the genes for IGF-1, NCAM1, NOGO-A, the gamma2 subunit of the GABA(A receptor, acetylcholine esterase and the catalytic subunit of cAMP-dependent protein kinase A. This was indicative of the viability of our approach, but more interesting were the novel candidate genes: Akap7, Akt1, Camk2d, Cckbr, Cd44, Crim1, Ctdsp2, Dnajc5, Gnai1, Itpka, Mapk8, Nbea, Nfatc3, Nlk, Npy5r, Phf21a, Phip, Ppm1l, Ppp1r1b, Rbbp4, Slc1a3, Slit2, Socs2, Spock3, St8sia1, Zfp207. The possible role of some of these candidates is discussed in the article.

  14. Novel CREB3L3 Nonsense Mutation in a Family With Dominant Hypertriglyceridemia.

    Science.gov (United States)

    Cefalù, Angelo B; Spina, Rossella; Noto, Davide; Valenti, Vincenza; Ingrassia, Valeria; Giammanco, Antonina; Panno, Maria D; Ganci, Antonina; Barbagallo, Carlo M; Averna, Maurizio R

    2015-12-01

    Cyclic AMP responsive element-binding protein 3-like 3 (CREB3L3) is a novel candidate gene for dominant hypertriglyceridemia. To date, only 4 kindred with dominant hypertriglyceridemia have been found to be carriers of 2 nonsense mutations in CREB3L3 gene (245fs and W46X). We investigated a family in which hypertriglyceridemia displayed an autosomal dominant pattern of inheritance. The proband was a 49-year-old woman with high plasma triglycerides (≤1300 mg/dL; 14.68 mmol/L). Her father had a history of moderate hypertriglyceridemia, and her 51-year-old brother had triglycerides levels as high as 1600 mg/dL (18.06 mmol/L). To identify the causal mutation in this family, we analyzed the candidate genes of recessive and dominant forms of primary hypertriglyceridemia by direct sequencing. The sequencing of CREB3L3 gene led to the discovery of a novel minute frame shift mutation in exon 3 of CREB3L3 gene, predicted to result in the formation of a truncated protein devoid of function (c.359delG-p.K120fsX20). Heterozygosity for the c.359delG mutation resulted in a severe phenotype occurring later in life in the proband and her brother and a good response to diet and a hypotriglyceridemic treatment. The same mutation was detected in a 13-year-old daughter who to date is normotriglyceridemic. We have identified a novel pathogenic mutation in CREB3L3 gene in a family with dominant hypertriglyceridemia with a variable pattern of penetrance. © 2015 American Heart Association, Inc.

  15. 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...... of atypical inflammatory bowel disease (IBD) patients. Our aim was to identify the prevalence of atypical disease patterns in new-onset pediatric UC using the Paris classification....

  16. 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...... facilitated the analysis of structural variants in human populations and model systems in unprecedented detail. In this Review, we describe how structural variants can affect molecular and cellular processes, leading to complex organismal phenotypes, including human disease. We further present advances...

  17. 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 ...

  18. Searching for the phenotypes of schizophrenia.

    Science.gov (United States)

    Cromwell, R L; Elkins, I J; McCarthy, M E; O'Neil, T S

    1994-01-01

    Use of clinical diagnosis as the phenotype for genetic study is discussed, and criteria for appropriate alternative phenotypes are presented. Then, recent research on four alternatives is discussed: (a) resistance to interference from an associative prime, (b) reaction time crossover, (c) creativity, and (d) socioeconomic achievement. It is concluded that resistance to interference from an associative prime and reaction time crossover at 3-sec. preparatory interval level are the most promising of these candidates.

  19. Radiographic Structural Damage Is Worse in the Dominant than the Non-Dominant Hand in Individuals with Early Rheumatoid Arthritis

    National Research Council Canada - National Science Library

    Koh, Jung Hee; Jung, Seung Min; Lee, Jennifer Jooha; Kang, Kwi Young; Kwok, Seung-Ki; Park, Sung-Hwan; Ju, Ji Hyeon

    2015-01-01

    ...) in the dominant and non-dominant hand. Data from 194 patients recently diagnosed with seropositive RA, and with hand radiographs taken at the time of diagnosis and at 2-year follow-up, were analyzed retrospectively...

  20. Phenex: ontological annotation of phenotypic diversity.

    Directory of Open Access Journals (Sweden)

    James P Balhoff

    Full Text Available BACKGROUND: Phenotypic differences among species have long been systematically itemized and described by biologists in the process of investigating phylogenetic relationships and trait evolution. Traditionally, these descriptions have been expressed in natural language within the context of individual journal publications or monographs. As such, this rich store of phenotype data has been largely unavailable for statistical and computational comparisons across studies or integration with other biological knowledge. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe Phenex, a platform-independent desktop application designed to facilitate efficient and consistent annotation of phenotypic similarities and differences using Entity-Quality syntax, drawing on terms from community ontologies for anatomical entities, phenotypic qualities, and taxonomic names. Phenex can be configured to load only those ontologies pertinent to a taxonomic group of interest. The graphical user interface was optimized for evolutionary biologists accustomed to working with lists of taxa, characters, character states, and character-by-taxon matrices. CONCLUSIONS/SIGNIFICANCE: Annotation of phenotypic data using ontologies and globally unique taxonomic identifiers will allow biologists to integrate phenotypic data from different organisms and studies, leveraging decades of work in systematics and comparative morphology.

  1. [Variant phenotype of Lesch-Nyhan syndrome].

    Science.gov (United States)

    Torres Jiménez, Rosa; García García, Marta; García Puig, Juan

    2011-01-29

    Lesch-Nyhan syndrome (LNS) and LNS variants are due to mutations in the HPRT1 gene causing HPRT enzymatic activity deficiency. We report a patient presenting a variant phenotype and a major genetic defect. The mutation has been previously reported as always associated with complete Lesch-Nyhan phenotype. We analyzed the presence of complete HPRT mRNA in this patient, in two patients with the complete Lesch Nyhan syndrome phenotype, and in control subjects. We found a minor amount of normal HPRT mRNA in the present patient but also in the two patients with splice mutation and the complete Lesch Nyhan syndrome phenotype. To our knowledge, this patient is the first report of a major genetic defect, with no detectable enzymatic activity, and a partial HPRT deficiency phenotype. Our results question the hypothesis of a normally spliced HPRT cDNA as the sole cause of the patient partial phenotype. Copyright © 2010 Elsevier España, S.L. All rights reserved.

  2. Phenotypic consequences of aneuploidy in Arabidopsis thaliana.

    Science.gov (United States)

    Henry, Isabelle M; Dilkes, Brian P; Miller, Eric S; Burkart-Waco, Diana; Comai, Luca

    2010-12-01

    Aneuploid cells are characterized by incomplete chromosome sets. The resulting imbalance in gene dosage has phenotypic consequences that are specific to each karyotype. Even in the case of Down syndrome, the most viable and studied form of human aneuploidy, the mechanisms underlying the connected phenotypes remain mostly unclear. Because of their tolerance to aneuploidy, plants provide a powerful system for a genome-wide investigation of aneuploid syndromes, an approach that is not feasible in animal systems. Indeed, in many plant species, populations of aneuploid individuals can be easily obtained from triploid individuals. We phenotyped a population of Arabidopsis thaliana aneuploid individuals containing 25 different karyotypes. Even in this highly heterogeneous population, we demonstrate that certain traits are strongly associated with the dosage of specific chromosome types and that chromosomal effects can be additive. Further, we identified subtle developmental phenotypes expressed in the diploid progeny of aneuploid parent(s) but not in euploid controls from diploid lineages. These results indicate long-term phenotypic consequences of aneuploidy that can persist after chromosomal balance has been restored. We verified the diploid nature of these individuals by whole-genome sequencing and discuss the possibility that trans-generational phenotypic effects stem from epigenetic modifications passed from aneuploid parents to their diploid progeny.

  3. The Genetics of Phenotypic Plasticity. XIV. Coevolution.

    Science.gov (United States)

    Scheiner, Samuel M; Gomulkiewicz, Richard; Holt, Robert D

    2015-05-01

    Plastic changes in organisms' phenotypes can result from either abiotic or biotic effectors. Biotic effectors create the potential for a coevolutionary dynamic. Through the use of individual-based simulations, we examined the coevolutionary dynamic of two species that are phenotypically plastic. We explored two modes of biotic and abiotic interactions: ecological interactions that determine the form of natural selection and developmental interactions that determine phenotypes. Overall, coevolution had a larger effect on the evolution of phenotypic plasticity than plasticity had on the outcome of coevolution. Effects on the evolution of plasticity were greater when the fitness-maximizing coevolutionary outcomes were antagonistic between the species pair (predator-prey interactions) than when those outcomes were augmenting (competitive or mutualistic). Overall, evolution in the context of biotic interactions reduced selection for plasticity even when trait development was responding to just the abiotic environment. Thus, the evolution of phenotypic plasticity must always be interpreted in the full context of a species' ecology. Our results show how the merging of two theory domains--coevolution and phenotypic plasticity--can deepen our understanding of both and point to new empirical research.

  4. Directional dominance on stature and cognition in diverse human populations

    Science.gov (United States)

    Mattsson, Hannele; Eklund, Niina; Gandin, Ilaria; Nutile, Teresa; Jackson, Anne U.; Schurmann, Claudia; Smith, Albert V.; Zhang, Weihua; Okada, Yukinori; Stančáková, Alena; Faul, Jessica D.; Zhao, Wei; Bartz, Traci M.; Concas, Maria Pina; Franceschini, Nora; Enroth, Stefan; Vitart, Veronique; Trompet, Stella; Guo, Xiuqing; Chasman, Daniel I.; O’Connel, Jeffery R.; Corre, Tanguy; Nongmaithem, Suraj S.; Chen, Yuning; Mangino, Massimo; Ruggiero, Daniela; Traglia, Michela; Farmaki, Aliki-Eleni; Kacprowski, Tim; Bjonnes, Andrew; van der Spek, Ashley; Wu, Ying; Giri, Anil K.; Yanek, Lisa R.; Wang, Lihua; Hofer, Edith; Rietveld, Cornelius A.; McLeod, Olga; Cornelis, Marilyn C.; Pattaro, Cristian; Verweij, Niek; Baumbach, Clemens; Abdellaoui, Abdel; Warren, Helen R.; Vuckovic, Dragana; Mei, Hao; Bouchard, Claude; Perry, John R.B.; Cappellani, Stefania; Mirza, Saira S.; Benton, Miles C.; Broeckel, Ulrich; Medland, Sarah E.; Lind, Penelope A.; Malerba, Giovanni; Drong, Alexander; Yengo, Loic; Bielak, Lawrence F.; Zhi, Degui; van der Most, Peter J.; Shriner, Daniel; Mägi, Reedik; Hemani, Gibran; Karaderi, Tugce; Wang, Zhaoming; Liu, Tian; Demuth, Ilja; Zhao, Jing Hua; Meng, Weihua; Lataniotis, Lazaros; van der Laan, Sander W.; Bradfield, Jonathan P.; Wood, Andrew R.; Bonnefond, Amelie; Ahluwalia, Tarunveer S.; Hall, Leanne M.; Salvi, Erika; Yazar, Seyhan; Carstensen, Lisbeth; de Haan, Hugoline G.; Abney, Mark; Afzal, Uzma; Allison, Matthew A.; Amin, Najaf; Asselbergs, Folkert W.; Bakker, Stephan J.L.; Barr, R. Graham; Baumeister, Sebastian E.; Benjamin, Daniel J.; Bergmann, Sven; Boerwinkle, Eric; Bottinger, Erwin P.; Campbell, Archie; Chakravarti, Aravinda; Chan, Yingleong; Chanock, Stephen J.; Chen, Constance; Chen, Y.-D. Ida; Collins, Francis S.; Connell, John; Correa, Adolfo; Cupples, L. Adrienne; Smith, George Davey; Davies, Gail; Dörr, Marcus; Ehret, Georg; Ellis, Stephen B.; Feenstra, Bjarke; Feitosa, Mary F.; Ford, Ian; Fox, Caroline S.; Frayling, Timothy M.; Friedrich, Nele; Geller, Frank; Scotland, Generation; Gillham-Nasenya, Irina; Gottesman, Omri; Graff, Misa; Grodstein, Francine; Gu, Charles; Haley, Chris; Hammond, Christopher J.; Harris, Sarah E.; Harris, Tamara B.; Hastie, Nicholas D.; Heard-Costa, Nancy L.; Heikkilä, Kauko; Hocking, Lynne J.; Homuth, Georg; Hottenga, Jouke-Jan; Huang, Jinyan; Huffman, Jennifer E.; Hysi, Pirro G.; Ikram, M. Arfan; Ingelsson, Erik; Joensuu, Anni; Johansson, Åsa; Jousilahti, Pekka; Jukema, J. Wouter; Kähönen, Mika; Kamatani, Yoichiro; Kanoni, Stavroula; Kerr, Shona M.; Khan, Nazir M.; Koellinger, Philipp; Koistinen, Heikki A.; Kooner, Manraj K.; Kubo, Michiaki; Kuusisto, Johanna; Lahti, Jari; Launer, Lenore J.; Lea, Rodney A.; Lehne, Benjamin; Lehtimäki, Terho; Liewald, David C.M.; Lind, Lars; Loh, Marie; Lokki, Marja-Liisa; London, Stephanie J.; Loomis, Stephanie J.; Loukola, Anu; Lu, Yingchang; Lumley, Thomas; Lundqvist, Annamari; Männistö, Satu; Marques-Vidal, Pedro; Masciullo, Corrado; Matchan, Angela; Mathias, Rasika A.; Matsuda, Koichi; Meigs, James B.; Meisinger, Christa; Meitinger, Thomas; Menni, Cristina; Mentch, Frank D.; Mihailov, Evelin; Milani, Lili; Montasser, May E.; Montgomery, Grant W.; Morrison, Alanna; Myers, Richard H.; Nadukuru, Rajiv; Navarro, Pau; Nelis, Mari; Nieminen, Markku S.; Nolte, Ilja M.; O’Connor, George T.; Ogunniyi, Adesola; Padmanabhan, Sandosh; Palmas, Walter R.; Pankow, James S.; Patarcic, Inga; Pavani, Francesca; Peyser, Patricia A.; Pietilainen, Kirsi; Poulter, Neil; Prokopenko, Inga; Ralhan, Sarju; Redmond, Paul; Rich, Stephen S.; Rissanen, Harri; Robino, Antonietta; Rose, Lynda M.; Rose, Richard; Sala, Cinzia; Salako, Babatunde; Salomaa, Veikko; Sarin, Antti-Pekka; Saxena, Richa; Schmidt, Helena; Scott, Laura J.; Scott, William R.; Sennblad, Bengt; Seshadri, Sudha; Sever, Peter; Shrestha, Smeeta; Smith, Blair H.; Smith, Jennifer A.; Soranzo, Nicole; Sotoodehnia, Nona; Southam, Lorraine; Stanton, Alice V.; Stathopoulou, Maria G.; Strauch, Konstantin; Strawbridge, Rona J.; Suderman, Matthew J.; Tandon, Nikhil; Tang, Sian-Tsun; Taylor, Kent D.; Tayo, Bamidele O.; Töglhofer, Anna Maria; Tomaszewski, Maciej; Tšernikova, Natalia; Tuomilehto, Jaakko; Uitterlinden, Andre G.; Vaidya, Dhananjay; van Hylckama Vlieg, Astrid; van Setten, Jessica; Vasankari, Tuula; Vedantam, Sailaja; Vlachopoulou, Efthymia; Vozzi, Diego; Vuoksimaa, Eero; Waldenberger, Melanie; Ware, Erin B.; Wentworth-Shields, William; Whitfield, John B.; Wild, Sarah; Willemsen, Gonneke; Yajnik, Chittaranjan S.; Yao, Jie; Zaza, Gianluigi; Zhu, Xiaofeng; Project, The BioBank Japan; Salem, Rany M.; Melbye, Mads; Bisgaard, Hans; Samani, Nilesh J.; Cusi, Daniele; Mackey, David A.; Cooper, Richard S.; Froguel, Philippe; Pasterkamp, Gerard; Grant, Struan F.A.; Hakonarson, Hakon; Ferrucci, Luigi; Scott, Robert A.; Morris, Andrew D.; Palmer, Colin N.A.; Dedoussis, George; Deloukas, Panos; Bertram, Lars; Lindenberger, Ulman; Berndt, Sonja I.; Lindgren, Cecilia M.; Timpson, Nicholas J.; Tönjes, Anke; Munroe, Patricia B.; Sørensen, Thorkild I.A.; Rotimi, Charles N.; Arnett, Donna K.; Oldehinkel, Albertine J.; Kardia, Sharon L.R.; Balkau, Beverley; Gambaro, Giovanni; Morris, Andrew P.; Eriksson, Johan G.; Wright, Margie J.; Martin, Nicholas G.; Hunt, Steven C.; Starr, John M.; Deary, Ian J.; Griffiths, Lyn R.; Tiemeier, Henning; Pirastu, Nicola; Kaprio, Jaakko; Wareham, Nicholas J.; Pérusse, Louis; Wilson, James G.; Girotto, Giorgia; Caulfield, Mark J.; Raitakari, Olli; Boomsma, Dorret I.; Gieger, Christian; van der Harst, Pim; Hicks, Andrew A.; Kraft, Peter; Sinisalo, Juha; Knekt, Paul; Johannesson, Magnus; Magnusson, Patrik K.E.; Hamsten, Anders; Schmidt, Reinhold; Borecki, Ingrid B.; Vartiainen, Erkki; Becker, Diane M.; Bharadwaj, Dwaipayan; Mohlke, Karen L.; Boehnke, Michael; van Duijn, Cornelia M.; Sanghera, Dharambir K.; Teumer, Alexander; Zeggini, Eleftheria; Metspalu, Andres; Gasparini, Paolo; Ulivi, Sheila; Ober, Carole; Toniolo, Daniela; Rudan, Igor; Porteous, David J.; Ciullo, Marina; Spector, Tim D.; Hayward, Caroline; Dupuis, Josée; Loos, Ruth J.F.; Wright, Alan F.; Chandak, Giriraj R.; Vollenweider, Peter; Shuldiner, Alan; Ridker, Paul M.; Rotter, Jerome I.; Sattar, Naveed; Gyllensten, Ulf; North, Kari E.; Pirastu, Mario; Psaty, Bruce M.; Weir, David R.; Laakso, Markku; Gudnason, Vilmundur; Takahashi, Atsushi; Chambers, John C.; Kooner, Jaspal S.; Strachan, David P.; Campbell, Harry; Hirschhorn, Joel N.; Perola, Markus

    2015-01-01

    Homozygosity has long been associated with rare, often devastating, Mendelian disorders1 and Darwin was one of the first to recognise that inbreeding reduces evolutionary fitness2. However, the effect of the more distant parental relatedness common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity, ROH), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power3,4. Here we use ROH to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts and find statistically significant associations between summed runs of homozygosity (SROH) and four complex traits: height, forced expiratory lung volume in 1 second (FEV1), general cognitive ability (g) and educational attainment (nominal p<1 × 10−300, 2.1 × 10−6, 2.5 × 10−10, 1.8 × 10−10). In each case increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing convincing evidence for the first time that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples5,6, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein (LDL) cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection7, this study provides evidence that increased stature and cognitive function have been

  5. Advanced phenotyping and phenotype data analysis for the study of plant growth and development

    Science.gov (United States)

    Rahaman, Md. Matiur; Chen, Dijun; Gillani, Zeeshan; Klukas, Christian; Chen, Ming

    2015-01-01

    Due to an increase in the consumption of food, feed, fuel and to meet global food security needs for the rapidly growing human population, there is a necessity to breed high yielding crops that can adapt to the future climate changes, particularly in developing countries. To solve these global challenges, novel approaches are required to identify quantitative phenotypes and to explain the genetic basis of agriculturally important traits. These advances will facilitate the screening of germplasm with high performance characteristics in resource-limited environments. Recently, plant phenomics has offered and integrated a suite of new technologies, and we are on a path to improve the description of complex plant phenotypes. High-throughput phenotyping platforms have also been developed that capture phenotype data from plants in a non-destructive manner. In this review, we discuss recent developments of high-throughput plant phenotyping infrastructure including imaging techniques and corresponding principles for phenotype data analysis. PMID:26322060

  6. Minimum 2-Tuple Dominating Set of an Interval Graph

    Directory of Open Access Journals (Sweden)

    Tarasankar Pramanik

    2011-01-01

    Full Text Available The k-tuple domination problem, for a fixed positive integer k, is to find a minimum size vertex subset such that every vertex in the graph is dominated by at least k vertices in this set. The case when k=2 is called 2-tuple domination problem or double domination problem. In this paper, the 2-tuple domination problem is studied on interval graphs from an algorithmic point of view, which takes O(n2 time, n is the total number of vertices of the interval graph.

  7. -Taking a Dominant Design Perspective on ERP Companies-

    OpenAIRE

    Schmidt, Henrik

    2002-01-01

    The dominant design concept describes the evolution from one dominant design to a new one, or in a new industry, the evolution to a set of standards and features that becomes a dominant design for that particular product or sector. Typically the dominant design is used to describe industry trends. This thesis takes the bottom up perspective, i.e. the company's perspective, to identify if, or what parts, of the dominant design model that can be used as an explanatory tool of innovation in the ...

  8. The Vulnerability of Some Networks including Cycles via Domination Parameters

    Directory of Open Access Journals (Sweden)

    Tufan Turaci

    2016-01-01

    Full Text Available Let G=(V(G,E(G be an undirected simple connected graph. A network is usually represented by an undirected simple graph where vertices represent processors and edges represent links between processors. Finding the vulnerability values of communication networks modeled by graphs is important for network designers. The vulnerability value of a communication network shows the resistance of the network after the disruption of some centers or connection lines until a communication breakdown. The domination number and its variations are the most important vulnerability parameters for network vulnerability. Some variations of domination numbers are the 2-domination number, the bondage number, the reinforcement number, the average lower domination number, the average lower 2-domination number, and so forth. In this paper, we study the vulnerability of cycles and related graphs, namely, fans, k-pyramids, and n-gon books, via domination parameters. Then, exact solutions of the domination parameters are obtained for the above-mentioned graphs.

  9. The dominant mechanisms of hyporheic exchange

    Science.gov (United States)

    McCluskey, Alexander H.; Stewardson, Michael J.; Grant, Stanley B.

    2013-04-01

    plane beds due to coherent turbulence primarily scales with the Reynolds number and the shear Peclet number, while exchange with bedforms also depends on bed depth and permeability. This suggests that while turbulence is ubiquitous in exchange across the SWI, enhanced rates of hyporheic exchange observed due to bedforms results from variation of dynamic head at the SWI alone. Our meta-analysis has shown changing dominance of exchange mechanisms. However, the dynamic relationship of the two mechanisms will not be understood until measurements of the turbulent structures and pressure fluctuations in flume experiments are correlated to existing models derived from flume studies. We are undertaking investigations coupling experimental techniques in measuring exchange flows to further understand the dynamic nature of these exchange mechanisms. This work will be essential in quantifying rates of hyporheic exchange relative to specific controls in natural and regulated streams. Ultimately, this will be an important step in predicting the impact of changes to stream and bed conditions on benthic organisms and aquatic ecology more broadly.

  10. Genetic testing in familial AD and FTD: mutation and phenotype spectrum in a Danish cohort.

    Science.gov (United States)

    Lindquist, S G; Schwartz, M; Batbayli, M; Waldemar, G; Nielsen, J E

    2009-08-01

    Autosomal dominantly transmitted Alzheimer's disease (AD) and frontotemporal dementia (FTD) are genetically heterogeneous disorders. To date, three genes have been identified in which mutations cause early-onset autosomal dominant inherited AD: APP, PSEN1, and PSEN2. Mutations in two genes on chromosome 17, the MAPT and the PGRN genes, are associated with autosomal dominant inherited FTD. The aim of this study was to characterize the mutation spectrum and describe genotype-phenotype correlations in families with inherited dementia. The identification of novel mutations and/or atypical genotype-phenotype correlations contributes to further characterizing the disorders. DNA-samples from the 90 index cases from a Danish referral-based cohort representing families with presumed autosomal dominant inherited AD or FTD were screened for mutations in the known genes with sequencing, denaturing high-performance liquid chromatography (DHPLC) and multiplex ligation-dependent probe amplification (MLPA) techniques. Seven presumed pathogenic mutations (two PSEN1, one PSEN2, one APP, one MAPT, and two PGRN) were identified, including a novel PSEN2 mutation (V393M). No dosage aberrations were identified.

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

    Science.gov (United States)

    Moore, Mark W.

    2013-01-01

    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 production and phenotyping. PMID:22940749

  12. Dominance from the perspective of gene-gene and gene-chemical interactions.

    Science.gov (United States)

    Gladki, Arkadiusz; Zielenkiewicz, Piotr; Kaczanowski, Szymon

    2016-02-01

    In this study, we used genetic interaction (GI) and gene-chemical interaction (GCI) data to compare mutations with different dominance phenotypes. Our analysis focused primarily on Saccharomyces cerevisiae, where haploinsufficient genes (HI; genes with dominant loss-of-function mutations) were found to be participating in gene expression processes, namely, the translation and regulation of gene transcription. Non-ribosomal HI genes (mainly regulators of gene transcription) were found to have more GIs and GCIs than haplosufficient (HS) genes. Several properties seem to lead to the enrichment of interactions, most notably, the following: importance, pleiotropy, gene expression level and gene expression variation. Importantly, after these properties were appropriately considered in the analysis, the correlation between dominance and GI/GCI degrees was still observed. Strikingly, for the GCIs of heterozygous strains, haploinsufficiency was the only property significantly correlated with the number of GCIs. We found ribosomal HI genes to be depleted in GIs/GCIs. This finding can be explained by their high variation in gene expression under different genetic backgrounds and environmental conditions. We observed the same distributions of GIs among non-ribosomal HI, ribosomal HI and HS genes in three other species: Schizosaccharomyces pombe, Drosophila melanogaster and Homo sapiens. One potentially interesting exception was the lack of significant differences in the degree of GIs between non-ribosomal HI and HS genes in Schizosaccharomyces pombe.

  13. Retroviral vector insertion sites associated with dominant hematopoietic clones mark "stemness" pathways.

    Science.gov (United States)

    Kustikova, Olga S; Geiger, Hartmut; Li, Zhixiong; Brugman, Martijn H; Chambers, Stuart M; Shaw, Chad A; Pike-Overzet, Karin; de Ridder, Dick; Staal, Frank J T; von Keudell, Gottfried; Cornils, Kerstin; Nattamai, Kalpana Jekumar; Modlich, Ute; Wagemaker, Gerard; Goodell, Margaret A; Fehse, Boris; Baum, Christopher

    2007-03-01

    Evidence from model organisms and clinical trials reveals that the random insertion of retrovirus-based vectors in the genome of long-term repopulating hematopoietic cells may increase self-renewal or initiate malignant transformation. Clonal dominance of nonmalignant cells is a particularly interesting phenotype as it may be caused by the dysregulation of genes that affect self-renewal and competitive fitness. We have accumulated 280 retrovirus vector insertion sites (RVISs) from murine long-term studies resulting in benign or malignant clonal dominance. RVISs (22.5%) are located in or near (up to 100 kb [kilobase]) to known proto-oncogenes, 49.6% in signaling genes, and 27.9% in other or unknown genes. The resulting insertional dominance database (IDDb) shows substantial overlaps with the transcriptome of hematopoietic stem/progenitor cells and the retrovirus-tagged cancer gene database (RTCGD). RVISs preferentially marked genes with high expression in hematopoietic stem/progenitor cells, and Gene Ontology revealed an overrepresentation of genes associated with cell-cycle control, apoptosis signaling, and transcriptional regulation, including major "stemness" pathways. The IDDb forms a powerful resource for the identification of genes that stimulate or transform hematopoietic stem/progenitor cells and is an important reference for vector biosafety studies in human gene therapy.

  14. Characterization of the dominant inheritance mechanism of Episodic Ataxia type 2.

    Science.gov (United States)

    Dorgans, Kevin; Salvi, Julie; Bertaso, Federica; Bernard, Ludivine; Lory, Philippe; Doussau, Frederic; Mezghrani, Alexandre

    2017-10-01

    Episodic Ataxia type 2 (EA2) is an autosomal dominant neuronal disorder linked to mutations in the Cav2.1 subunit of P/Q-type calcium channels. In vitro studies have established that EA2 mutations induce loss of channel activity and that EA2 mutants can exert a dominant negative effect, suppressing normal Cav2.1 activity through protein misfolding and trafficking defects. To date, the role of this mechanism in the disease pathogenesis is unknown because no animal model exists. To address this issue, we have generated a mouse bearing the R1497X nonsense mutation in Cav2.1 (Cav2.1(R1497X)). Phenotypic analysis of heterozygous Cav2.1(R1497X) mice revealed ataxia associated with muscle weakness and generalized absence epilepsy. Electrophysiological studies of the cerebellar circuits in heterozygous Cav2.1(R1497X) mice highlighted severe dysregulations in synaptic transmission of the two major excitatory inputs as well as alteration of the spontaneous activity of Purkinje cells. Moreover, these neuronal dysfunctions were associated with a strong suppression of Cav2.1 channel expression in the cerebellum of heterozygous Cav2.1(R1497X) mice. Finally, the presence of Cav2.1 in cerebellar lipid raft microdomains was strongly impaired in heterozygous Cav2.1(R1497X) mice. Altogether, these results reveal a pathogenic mechanism for EA2 based on a dominant negative activity of mutant channels. Copyright © 2017. Published by Elsevier Inc.

  15. The diminishing dominance of the dominant hemisphere: Language fMRI in focal epilepsy.

    Science.gov (United States)

    Tailby, Chris; Abbott, David F; Jackson, Graeme D

    2017-01-01

    "Which is the dominant hemisphere?" is a question that arises frequently in patients considered for neurosurgery. The concept of the dominant hemisphere implies uniformity of language lateralisation throughout the brain. It is increasingly recognised that this is not the case in the healthy control brain, and it is especially not so in neurological diseases such as epilepsy. In the present work we adapt our published objective lateralisation method (based on the construction of laterality curves) for use with sub-lobar cortical, subcortical and cerebellar regions of interest (ROIs). We apply this method to investigate regional lateralisation of language activation in 12 healthy controls and 18 focal epilepsy patients, using three different block design language fMRI paradigms, each tapping different aspects of language processing. We compared lateralisation within each ROI across tasks, and investigated how the quantity of data collected affected the ability to robustly estimate laterality across ROIs. In controls, lateralisation was stronger, and the variance across individuals smaller, in cortical ROIs, particularly in the Inferior Frontal (Broca) region. Lateralisation within temporal ROIs was dependent on the nature of the language task employed. One of the healthy controls was left lateralised anteriorly and right lateralised posteriorly. Consistent with previous work, departures from normality occurred in ~ 15-50% of focal epilepsy patients across the different ROIs, with atypicality most common in the Lateral Temporal (Wernicke) region. Across tasks and ROIs the absolute magnitude of the laterality estimate increased and its across participant variance decreased as more cycles of task and rest were included, stabilising at ~ 4 cycles (~ 4 min of data collection). Our data highlight the importance of considering language as a complex task where lateralisation varies at the subhemispheric scale. This is especially important for presurgical planning for

  16. On Trees with Double Domination Number Equal to the 2-Outer-Independent Domination Number Plus One

    Institute of Scientific and Technical Information of China (English)

    Marcin KRZYWKOWSKI

    2012-01-01

    A vertex of a graph is said to dominate itself and all of its neighbors.A double dominating set of a graph G is a set D of vertices of G,such that every vertex of G is dominated by at least two vertices of D.The double domination number of a graph G is the minimum cardinality of a double dominating set of G.For a graph G =(V,E),a subset D (∈) V(G) is a 2-dominating set if every vertex of V(G) \\ D has at least two neighbors in D,while it is a 2-outer-independent dominating set of G if additionally the set V(G)\\D is independent.The 2-outer-independent domination number of G is the minimum cardinality of a 2-outer-independent dominating set of G.This paper characterizes all trees with the double domination number equal to the 2-outer-independent domination number plus one.

  17. Transition from avalanche dominated transport to drift-wave dominated transport in a basic laboratory experiment

    Science.gov (United States)

    van Compernolle, Bart; Morales, George; Maggs, James; Sydora, Richard

    2016-10-01

    Results of a basic heat transport experiment involving an off-axis heat source are presented. Experiments are performed in the Large Plasma Device (LAPD) at UCLA. A ring-shaped electron beam source injects low energy electrons (below ionization energy) along a strong magnetic field into a preexisting, large and cold plasma. The injected electrons are thermalized by Coulomb collisions within a short distance and provide an off-axis heat source that results in a long, hollow, cylindrical region of elevated plasma pressure embedded in a colder plasma, and far from the machine walls. The off-axis source is active for a period long compared to the density decay time, i.e. as time progresses the power per particle increases. Two distinct regimes are observed to take place, an initial regime dominated by avalanches, identified as sudden intermittent rearrangements of the pressure profile, and a second regime dominated by sustained drift-Alfvén wave activity. The transition between the two regimes is sudden, affects the full radial profile and is preceded by the growth of drift Alfvén waves. Langmuir probe data will be shown on the evolution of the density, temperature and flow profiles during the transition. The character of the sustained drift wave activity will also be presented. Work supported by NSF/DOE Grant 1619505, and performed at the Basic Plasma Science Facility, sponsored jointly by DOE and NSF.

  18. Emerging trends in evolving networks: Recent behaviour dominant and non-dominant model

    Science.gov (United States)

    Abbas, Khushnood; Shang, Mingsheng; Luo, Xin; Abbasi, Alireza

    2017-10-01

    Novel phenomenon receives similar attention as popular one. Therefore predicting novelty is as important as popularity. Emergence is the side effect of competition and ageing in evolving systems. Recent behaviour or recent link gain in networks plays an important role in emergence. We exploited this wisdom and came up with two models considering different scenarios and systems. Where recent behaviour dominates over total behaviour (total link gain) in the first one, and recent behaviour is as important as total behaviour for future link gain in the second one. It supposes that random walker walks on a network and can jump to any node, the probability of jumping or making a connection to other node is based on which node is recently more active or receiving more links. In our assumption, the random walker can also jump to the node which is already popular but recently not popular. We are able to predict emerging nodes which are generally suppressed under preferential attachment effect. To show the performance of our model we have conducted experiments on four real data sets namely, MovieLens, Netflix, Facebook and Arxiv High Energy Physics paper citation. For testing our model we used four information retrieval indices namely Precision, Novelty, Area Under Receiving Operating Characteristic (AUC) and Kendal's rank correlation coefficient. We have used four benchmark models for validating our proposed models. Although our model does not perform better in all the cases but, it has theoretical significance in working better for recent behaviour dominated systems.

  19. Dominating sets and ego-centered decompositions in social networks

    CERN Document Server

    Boudourides, Moses A

    2016-01-01

    Our aim here is to address the problem of decomposing a whole network into a minimal number of ego-centered subnetworks. For this purpose, the network egos are picked out as the members of a minimum dominating set of the network. However, to find such an efficient dominating ego-centered construction, we need to be able to detect all the minimum dominating sets and to compare all the corresponding dominating ego-centered decompositions of the network. To find all the minimum dominating sets of the network, we are developing a computational heuristic, which is based on the partition of the set of nodes of a graph into three subsets, the always dominant vertices, the possible dominant vertices and the never dominant vertices, when the domination number of the network is known. To compare the ensuing dominating ego-centered decompositions of the network, we are introducing a number of structural measures that count the number of nodes and links inside and across the ego-centered subnetworks. Furthermore, we are ...

  20. Roman domination in Cartesian product graphs and strong product graphs

    CERN Document Server

    Yero, Ismael G

    2011-01-01

    A set $S$ of vertices of a graph $G$ is a dominating set for $G$ if every vertex outside of $S$ is adjacent to at least one vertex belonging to $S$. The minimum cardinality of a dominating set for $G$ is called the domination number of $G$. A map $f : V \\rightarrow \\{0, 1, 2\\}$ is a Roman dominating function on a graph $G$ if for every vertex $v$ with $f(v) = 0$, there exists a vertex $u$, adjacent to $v$, such that $f(u) = 2$. The weight of a Roman dominating function is given by $f(V) =\\sum_{u\\in V}f(u)$. The minimum weight of a Roman dominating function on $G$ is called the Roman domination number of $G$. In this article we study the Roman domination number of Cartesian product graphs and strong product graphs. More precisely, we study the relationships between the Roman domination number of product graphs and the (Roman) domination number of the factors.

  1. [Quantification of ocular dominance for better management of eye disease].

    Science.gov (United States)

    Chaumillon, R; Alahyane, N; Senot, P; Vergne, J; Lemoine, C; Doré-Mazars, K; Blouin, J; Vergilino-Perez, D; Guillaume, A

    2015-04-01

    The dominant eye is defined as the one we unconsciously choose when we have to perform monocular tasks. In the field of clinical neuro-ophthalmology, it is well-established that ocular dominance plays a key role in several eye diseases. Furthermore, the accurate quantification of ocular dominance is crucial with regard to certain surgical techniques. However, classical preoperative tests cannot determine the amount of ocular dominance. In order to obtain further insight into the phenomenon of ocular dominance, we study its influence at behavioral and neurophysiological levels (experiments 1 and 2). Based on these new data, we suggest a method to improve quantification of ocular dominance (experiment 3). We demonstrate that ocular dominance has an influence on hand movements and on interhemispheric transfer time. Moreover, we show that an analysis of the dynamics of saccades allows us to sort out participants with strong or weak ocular dominance. In conclusion, this better understanding of the phenomenon of ocular dominance, coupled with the analysis of saccadic dynamics, might, in the short or medium term, lead to the establishment of a quick and straightforward battery of tests allowing determination of the amount of ocular dominance for each patient. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  2. An efficient non-dominated sorting method for evolutionary algorithms.

    Science.gov (United States)

    Fang, Hongbing; Wang, Qian; Tu, Yi-Cheng; Horstemeyer, Mark F

    2008-01-01

    We present a new non-dominated sorting algorithm to generate the non-dominated fronts in multi-objective optimization with evolutionary algorithms, particularly the NSGA-II. The non-dominated sorting algorithm used by NSGA-II has a time complexity of O(MN(2)) in generating non-dominated fronts in one generation (iteration) for a population size N and M objective functions. Since generating non-dominated fronts takes the majority of total computational time (excluding the cost of fitness evaluations) of NSGA-II, making this algorithm faster will significantly improve the overall efficiency of NSGA-II and other genetic algorithms using non-dominated sorting. The new non-dominated sorting algorithm proposed in this study reduces the number of redundant comparisons existing in the algorithm of NSGA-II by recording the dominance information among solutions from their first comparisons. By utilizing a new data structure called the dominance tree and the divide-and-conquer mechanism, the new algorithm is faster than NSGA-II for different numbers of objective functions. Although the number of solution comparisons by the proposed algorithm is close to that of NSGA-II when the number of objectives becomes large, the total computational time shows that the proposed algorithm still has better efficiency because of the adoption of the dominance tree structure and the divide-and-conquer mechanism.

  3. Domination parameters of a graph with added vertex

    Directory of Open Access Journals (Sweden)

    Maciej Zwierzchowski

    2004-01-01

    Full Text Available Let \\(G=(V,E\\ be a graph. A subset \\(D\\subseteq V\\ is a total dominating set of \\(G\\ if for every vertex \\(y\\in V\\ there is a vertex \\(x\\in D\\ with \\(xy\\in E\\. A subset \\(D\\subseteq V\\ is a strong dominating set of \\(G\\ if for every vertex \\(y\\in V-D\\ there is a vertex \\(x\\in D\\ with \\(xy\\in E\\ and \\(\\deg _{G}(x\\geq\\deg _{G}(y\\. The total domination number \\(\\gamma _{t}(G\\ (the strong domination number \\(\\gamma_{S}(G\\ is defined as the minimum cardinality of a total dominating set (a strong dominating set of \\(G\\. The concept of total domination was first defined by Cockayne, Dawes and Hedetniemi in 1980 [Cockayne E. J., Dawes R. M., Hedetniemi S. T.: Total domination in graphs. Networks 10 (1980, 211–219], while the strong domination was introduced by Sampathkumar and Pushpa Latha in 1996 [Pushpa Latha L., Sampathkumar E.: Strong weak domination and domination balance in a graph. Discrete Mathematics 161 (1996, 235–242]. By a subdivision of an edge \\(uv\\in E\\ we mean removing edge \\(uv\\, adding a new vertex \\(x\\, and adding edges \\(ux\\ and \\(vx\\. A graph obtained from \\(G\\ by subdivision an edge \\(uv\\in E\\ is denoted by \\(G\\oplus u_{x}v_{x}\\. The behaviour of the total domination number and the strong domination number of a graph \\(G\\oplus u_{x}v_{x}\\ is developed.

  4. Association of alkaline phosphatase phenotypes with arthritides

    Directory of Open Access Journals (Sweden)

    Padmini A

    2004-01-01

    Full Text Available Arthritides, a symmetrical polyarticular disease of the bone are a heterogenous group of disorders in which hereditary and environmental factors in combination with an altered immune response appear to play a causative and pathogenic role in its occurrence. Alkaline phosphatase (ALP is an enzyme found in all tissues, with particularly high concentrations of ALP observed in the liver, bile ducts, placenta, and bone.Alkaline phosphatase is an orthophosphoric monoester phosphohydrolase catalyzing the hydrolysis of organic esters at alkaline pH, indicating that alkaline phosphatase is involved in fundamental biological processes.1 The present study envisages on identifying the specific electromorphic association of alkaline phosphatase with arthritides. Phenotyping of serum samples was carried out by PAGE (Polyacrylamide gel electrophoresis following Davies (19642 protocol on 41 juvenile arthritis, 150 rheumatoid arthritis and 100 osteo arthritis apart from, 25 normal children and 100 adult healthy subjects. Phenotyping of alkaline phosphatase revealed an increase in preponderance of p+ and p++ phenotypes in juvenile, rheumatoid and osteo arthritic patients. However a significant association of these phenotypes was observed only with rheumatoid arthritis condition (c2:17.46. Similarly, a significant increase of p+ phenotypes in female rheumatoid arthritis patients was observed (c2:14.973, suggesting that the decrease in p° (tissue non specific synthesis/secretion of alkaline phosphatase could be associated with decreased mineralization and ossification process in arthritis condition.

  5. Phenotypic plasticity and diversity in insects.

    Science.gov (United States)

    Moczek, Armin P

    2010-02-27

    Phenotypic plasticity in general and polyphenic development in particular are thought to play important roles in organismal diversification and evolutionary innovation. Focusing on the evolutionary developmental biology of insects, and specifically that of horned beetles, I explore the avenues by which phenotypic plasticity and polyphenic development have mediated the origins of novelty and diversity. Specifically, I argue that phenotypic plasticity generates novel targets for evolutionary processes to act on, as well as brings about trade-offs during development and evolution, thereby diversifying evolutionary trajectories available to natural populations. Lastly, I examine the notion that in those cases in which phenotypic plasticity is underlain by modularity in gene expression, it results in a fundamental trade-off between degree of plasticity and mutation accumulation. On one hand, this trade-off limits the extent of plasticity that can be accommodated by modularity of gene expression. On the other hand, it causes genes whose expression is specific to rare environments to accumulate greater variation within species, providing the opportunity for faster divergence and diversification between species, compared with genes expressed across environments. Phenotypic plasticity therefore contributes to organismal diversification on a variety of levels of biological organization, thereby facilitating the evolution of novel traits, new species and complex life cycles.

  6. Phenotypic analysis and molecular characterization of an allelic mutant of the D61 gene in rice

    Institute of Scientific and Technical Information of China (English)

    Yanan; Gao; Guangquan; Wang; Shoujiang; Yuan; Yanling; Qin; Jinfeng; Zhao; Yanpei; Zhang; Wenhui; Zhang; Xueyong; Li

    2014-01-01

    Brassinosteroids(BRs) are a class of plant-specific steroidal hormones that play important roles in multiple biological processes. In this paper, a classic rice mutant gsor300084,showing erect leaves and semi-dwarf stature, was characterized. Morphological analysis in darkness showed that the mesocotyl of the gsor300084 mutant did not elongate when grown in darkness. Coleoptile elongation and root growth were less affected by the exogenous application of brassinolide(BL), the most active form of BR, in gsor300084 than in the wild-type rice variety Matsumae. Lamina joint bending analysis also showed that gsor300084 was less sensitive to exogenous BL than Matsumae. These results suggested that the gsor300084 mutant is defective in BR sensitivity. Map-based cloning indicated that gsor300084 is a novel allelic mutant of the DWARF61(D61) gene, which encodes the putative BR receptor OsBRI1. A single-base mutation appears in the LRR domain of OsBRI1, changing the 444 th amino acid from tryptophan(W) to arginine(R). Subcellular localization analysis suggested that both the wild-type and mutant OsBRI1 protein are localized at the cytoplasmic membrane. Structure modeling revealed that the W444 R substitution may affect the perception of BRs by the LRR domain.

  7. Phenotypic analysis and molecular characterization of an allelic mutant of the D61 gene in rice

    Directory of Open Access Journals (Sweden)

    Yanan Gao

    2014-08-01

    Full Text Available Brassinosteroids (BRs are a class of plant-specific steroidal hormones that play important roles in multiple biological processes. In this paper, a classic rice mutant gsor300084, showing erect leaves and semi-dwarf stature, was characterized. Morphological analysis in darkness showed that the mesocotyl of the gsor300084 mutant did not elongate when grown in darkness. Coleoptile elongation and root growth were less affected by the exogenous application of brassinolide (BL, the most active form of BR, in gsor300084 than in the wild-type rice variety Matsumae. Lamina joint bending analysis also showed that gsor300084 was less sensitive to exogenous BL than Matsumae. These results suggested that the gsor300084 mutant is defective in BR sensitivity. Map-based cloning indicated that gsor300084 is a novel allelic mutant of the DWARF61 (D61 gene, which encodes the putative BR receptor OsBRI1. A single-base mutation appears in the LRR domain of OsBRI1, changing the 444th amino acid from tryptophan (W to arginine (R. Subcellular localization analysis suggested that both the wild-type and mutant OsBRI1 protein are localized at the cytoplasmic membrane. Structure modeling revealed that the W444R substitution may affect the perception of BRs by the LRR domain.

  8. 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

  9. 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.

  10. The overshoot and phenotypic equilibrium in characterizing cancer dynamics of reversible phenotypic plasticity.

    Science.gov (United States)

    Chen, Xiufang; Wang, Yue; Feng, Tianquan; Yi, Ming; Zhang, Xingan; Zhou, Da

    2016-02-07

    The paradigm of phenotypic plasticity indicates reversible relations of different cancer cell phenotypes, which extends the cellular hierarchy proposed by the classical cancer stem cell (CSC) theory. Since it is still questionable if the phenotypic plasticity is a crucial improvement to the hierarchical model or just a minor extension to it, it is worthwhile to explore the dynamic behavior characterizing the reversible phenotypic plasticity. In this study we compare the hierarchical model and the reversible model in predicting the cell-state dynamics observed in biological experiments. Our results show that the hierarchical model shows significant disadvantages over the reversible model in describing both long-term stability (phenotypic equilibrium) and short-term transient dynamics (overshoot) in cancer cell populations. In a very specific case in which the total growth of population due to each cell type is identical, the hierarchical model predicts neither phenotypic equilibrium nor overshoot, whereas the reversible model succeeds in predicting both of them. Even though the performance of the hierarchical model can be improved by relaxing the specific assumption, its prediction to the phenotypic equilibrium strongly depends on a precondition that may be unrealistic in biological experiments. Moreover, it still does not show as rich dynamics as the reversible model in capturing the overshoots of both CSCs and non-CSCs. By comparison, it is more likely for the reversible model to correctly predict the stability of the phenotypic mixture and various types of overshoot behavior.

  11. 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.

  12. The 2-Domination and 2-Bondage Numbers of Grid Graphs

    CERN Document Server

    Lu, You

    2012-01-01

    Let $p$ be a positive integer and $G=(V,E)$ be a simple graph. A subset $D\\subseteq V$ is a $p$-dominating set if each vertex not in $D$ has at least $p$ neighbors in $D$. The $p$-domination number $\\g_p(G)$ is the minimum cardinality among all $p$-dominating sets of $G$. The $p$-bondage number $b_p(G)$ is the cardinality of a smallest set of edges whose removal from $G$ results in a graph with a $p$-domination number greater than the $p$-domination number of $G$. In this note we determine the 2-domination number $\\g_2$ and 2-bondage number $b_2$ for the grid graphs $G_{m,n}=P_m\\times P_n$ for $2\\leq m\\leq 4$.

  13. Ocular dominance affects magnitude of dipole moment: an MEG study.

    Science.gov (United States)

    Shima, Hiroshi; Hasegawa, Mitsuhiro; Tachibana, Osamu; Nomura, Motohiro; Yamashita, Junkoh; Ozaki, Yuzo; Kawai, Jun; Higuchi, Masanori; Kado, Hisashi

    2010-08-23

    To investigate whether the ocular dominance affects laterality in the activity of the primary visual cortex, we examined the relationship between the ocular dominance and latency or dipole moment measured by checkerboard-pattern and magnetoencephalography in 11 right-handed healthy male participants. Participants with left-eye dominance showed a dipole moment of 21.5+/-6.1 nAm with left-eye stimulation and 16.1+/-3.6 nAm with right, whereas those with right-eye dominance showed a dipole moment of 18.0+/-5.2 and 21.5+/-2.7 nAm with left-eye and right-eye stimulation of the infero-medial quadrant visual field, respectively. Thus, the dipole moment was higher when the dominant eye was stimulated, which implies that ocular dominance is regulated by the ipsilateral occipital lobe.

  14. Neurocognitive Phenotypes in Severe Childhood Psychiatric Disorders.

    Science.gov (United States)

    Kavanaugh, Brian C; Dupont-Frechette, Jennifer A; Tellock, Perrin P; Maher, Isolde D; Haisley, Lauren D; Holler, Karen A

    2016-10-01

    This study investigated the presence of potential neurocognitive phenotypes within a severe childhood psychiatric sample. A medical chart review was conducted for 106 children who received a neuropsychological evaluation during children's psychiatric inpatient program hospitalization. A hierarchical cluster analysis was conducted to identify distinct clinical clusters based on neurocognitive measures. Cluster analysis identified four distinct clusters, subsequently labeled neurocognitive phenotypes: "intact cognition" (27%), "global dysfunction" (20%), "organization/planning" (21%), and "inhibition-memory" (32%). Significant differences were identified in history of legal involvement and antipsychotic medications at hospital admission. Differences between none-minimal and moderate-high neurocognitive dysfunction were identified in age, amount of diagnoses and antipsychotic medications at admission, and hospital length of stay. Current findings provide preliminary evidence of underlying neurocognitive phenotypes within severe childhood psychiatric disorders. Findings highlight the importance of neuropsychological evaluation in the treatment of childhood psychiatric disorders.

  15. Regulatory mechanisms link phenotypic plasticity to evolvability.

    Science.gov (United States)

    van Gestel, Jordi; Weissing, Franz J

    2016-04-18

    Organisms have a remarkable capacity to respond to environmental change. They can either respond directly, by means of phenotypic plasticity, or they can slowly adapt through evolution. Yet, how phenotypic plasticity links to evolutionary adaptability is largely unknown. Current studies of plasticity tend to adopt a phenomenological reaction norm (RN) approach, which neglects the mechanisms underlying plasticity. Focusing on a concrete question - the optimal timing of bacterial sporulation - we here also consider a mechanistic approach, the evolution of a gene regulatory network (GRN) underlying plasticity. Using individual-based simulations, we compare the RN and GRN approach and find a number of striking differences. Most importantly, the GRN model results in a much higher diversity of responsive strategies than the RN model. We show that each of the evolved strategies is pre-adapted to a unique set of unseen environmental conditions. The regulatory mechanisms that control plasticity therefore critically link phenotypic plasticity to the adaptive potential of biological populations.

  16. 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.

  17. Phenotypic and molecular assessment of seven patients with 6p25 deletion syndrome: Relevance to ocular dysgenesis and hearing impairment

    Directory of Open Access Journals (Sweden)

    Ritch Robert

    2004-06-01

    Full Text Available Abstract Background Thirty-nine patients have been described with deletions involving chromosome 6p25. However, relatively few of these deletions have had molecular characterization. Common phenotypes of 6p25 deletion syndrome patients include hydrocephalus, hearing loss, and ocular, craniofacial, skeletal, cardiac, and renal malformations. Molecular characterization of deletions can identify genes that are responsible for these phenotypes. Methods We report the clinical phenotype of seven patients with terminal deletions of chromosome 6p25 and compare them to previously reported patients. Molecular characterization of the deletions was performed using polymorphic marker analysis to determine the extents of the deletions in these seven 6p25 deletion syndrome patients. Results Our results, and previous data, show that ocular dysgenesis and hearing impairment are the two most highly penetrant phenotypes of the 6p25 deletion syndrome. While deletion of the forkhead box C1 gene (FOXC1 probably underlies the ocular dysgenesis, no gene in this region is known to be involved in hearing impairment. Conclusions Ocular dysgenesis and hearing impairment are the two most common phenotypes of 6p25 deletion syndrome. We conclude that a locus for dominant hearing loss is present at 6p25 and that this locus is restricted to a region distal to D6S1617. Molecular characterization of more 6p25 deletion patients will aid in refinement of this locus and the identification of a gene involved in dominant hearing loss.

  18. Bounds on the hop domination number of a tree

    Indian Academy of Sciences (India)

    S K Ayyaswamy; B Krishnakumari; C Natarajan; Y B Venkatakrishnan

    2015-11-01

    A hop dominating set of a graph is a set of vertices of if for every vertex of () \\ D, there exists $u \\in D$ such that (, ) = 2. The hop domination number of a graph , denoted by ℎ(), is the minimum cardinality of a hop dominating set of . We prove that for every tree of order with leaves and support vertices we have (−− +4)/3 ≤ ℎ() ≤ /2, and characterize the trees attaining each of the bounds.

  19. Upper bounds for domination related parameters in graphs on surfaces

    Directory of Open Access Journals (Sweden)

    Vladimir Samodivkin

    2016-08-01

    Full Text Available In this paper we give tight upper bounds on the total domination number, the weakly connected domination number and the connected domination number of a graph in terms of order and Euler characteristic. We also present upper bounds for the restrained bondage number, the total restrained bondage number and the restricted edge connectivity of graphs in terms of the orientable/nonorientable genus and maximum degree.

  20. Multidimensional first-order dominance comparisons of population wellbeing

    DEFF Research Database (Denmark)

    Arndt, Thomas Channing; Siersbæk, Nikolaj; Østerdal, Lars Peter Raahave

    In this paper, we convey the concept of first-order dominance (FOD) with particular focus on applications to multidimensional population welfare comparisons. We give an account of the fundamental equivalent definitions of FOD, illustrated with simple numerical examples. An implementable method...... for detecting dominances is explained along with a bootstrapping procedure that yields additional information relative to what can be obtained from dominance comparisons alone. We discuss strengths and weaknesses of FOD, compared to other multidimensional population comparison concepts, and describe practical...