bluuebunny/crossref_metadata_2025 huggingface dataset:
Castability of thin walled titanium alloy castings in vertical centrifugal field
Authors: Li C. Y. , Wu S. P. , Guo J. J. , Su Y. Q. , Fu H. Z.
Published: September 2008

Different casting technologies were investigated on the thin walled titanium alloy castings in this paper, and the experimental results show that it is hard for the titanium alloy melts to fill the thin walled cavities in the gravity field. However, with the action of centrifugal force and Coriolis force on the melts in the centrifugal field, the cavities can be fully filled with the molten metal. The castability of thin walled titanium alloy castings was influenced by some casting parameters, such as rotational velocity, rotational radius and solidifying rate. Experimental results indicate that the forming ability of thin walled titanium alloy increases with increasing rotational velocity. However, the filling ability of molten metal changes a little with increasing rotational radius. In addition, under the experimental condition used in this paper, the number of internal defects of the thin walled castings decreases with increasing rotational velocity, but increases with increasing rotational radius. Filling sequence and solidifying rate play important roles in the defect formation of thin walled titanium alloy castings.
Microstructural characterisation and kinetics modelling of vermicular cast irons
Authors: Laneri K. , Bruna P. , Crespo D.
Published: September 2008

Several experimental techniques are used for phase identification and microstructure characterisation of austempered vermicular cast irons (XRD, SEM, TEM and Mössbauer spectroscopy). Acicular structures were found to be composed by ferrite and austenite with average sizes compatible with those reported for bainitic ferrite in steels and austempered ductile iron. An assessment of the free energy change involved in the austenite→bainite transformation assuming a plate-like nucleation shape for bainite gave an average characteristic length close to that observed from statistical length distributions. The kinetics of the transformation was modelled in the Avrami framework; both the diffusion controlled and the diffusionless growth hypotheses were considered to elucidate the mechanism underlying the austempering phase transformation. Results indicated that diffusion of C is responsible for the nucleation process of the bainite sheaves, which appear as a consequence of a localised displacive transformation when the C concentration is adequate, but further growth of the bainite plates is almost suppressed.
A mere measurement effect for anticipated regret: Impacts on cervical screening attendance
Authors: Sandberg Tracy , Conner Mark
Published: September 2008

The mere measurement of cognitions and in particular intentions has been shown to be sufficient to change behaviour. This study assessed the impact of measuring anticipated regret in addition to intentions and other cognitions on recorded cervical smear attendance rates following invitation in a sample of women. A total of 4,277 women received an invitation for cervical screening and information leaflet: 1,500 of whom also received a standard theory of planned behaviour questionnaire in relation to screening (TPB only group) and a further 1,500 of whom also received a TPB questionnaire plus anticipated regret questions in relation to screening (TPB plus regret group). Total recorded attendance rates indicated significantly higher attendance (ps<.05) in the two experimental groups compared to control (Control, 21%; TPB only, 26%; and TPB plus regret, 26%). However, among those returning questionnaires, there was a significantly increased attendance rate (p <.001) in the TPB plus regret group (65%) compared to the TPB only group (44%). Follow up analyses among those completing questionnaires indicated this effect to be moderated by intentions with a significant difference only apparent among strong intenders. The discussion considers the implications for understanding the ‘mere measurement effect’ and the use of anticipated regret to change behaviour.
State institutions and social identity: National representation in soldiers' and civilians' interview talk concerning military service
Authors: Gibson Stephen , Condor Susan
Published: September 2008

Theory and research deriving from social identity or self‐categorization perspectives often starts out with the presumption that social actors necessarily view societal objects such as nations or states as human categories. However, recent work suggests that this may be only one of a number of forms that societal representation may take. For example, nations may be understood variously as peoples, places, or institutions. This paper presents findings from a qualitative interview study conducted in England, in which soldiers and civilians talked about nationhood in relation to military service. Analysis indicated that, in this context, speakers were often inclined to use the terms ‘Britain’, ‘nation’, and ‘country’ as references to a political institution as opposed to a category of people. In addition, there were systematic differences between the ways in which the two samples construed their nation in institutional terms. The civilians were inclined to treat military service as a matter of obedience to the dictates of the Government of the day. In contrast, the soldiers were more inclined to frame military service as a matter of loyalty to state as symbolically instantiated in the body of the sovereign. Implications for work adopting a social identity perspective are discussed.
Cloning and characterization of α-pinene synthase from Chamaecyparis formosensis Matsum
Authors: Chu Fang-Hua , Kuo Pei-Min , Chen Yu-Rong , Wang Sheng-Yang
Published: September 2008

Analyzing the gene sequences of terpene synthase (TPS) may contribute to a better understanding of terpenes biosynthesis and evolution of phylogenetic taxonomy. Chamaecyparis formosensis is an endemic and precious conifer of Taiwan. To understand the biosynthesis mechanism of terpenes in this tree, a full length of putative mono-TPS, named as Cf-Pin (GeneBank accession no. EU099434), was obtained by PCR method and RACE extension. The Cf-Pin has an 1887-bp open reading frame and encodes 628 amino acids. To identify the function of Cf-Pin, the recombinant protein from Escherichia coli was incubated with geranyl diphosphate, produced one major product, the structure of which was elucidated. GC/MS analysis and matching of retention time and mass spectrum with authentic standards revealed that this product is α-pinene. This is the first report of cloning of a mono-TPS and functionally expressed in E. coli and which could be identified as α-pinene synthase from a Cupressaceae conifer.
Die Entstehung der modernen Landschaftswahrnehmung (1580–1730) (The Making of a New Landscape Perception)
Authors: Schramm Manuel
Published: September 2008

Der Aufsatz vertritt die These, daß vor allem das 17. Jahrhundert den Beginn der neuen Naturwahrnehmung in West- und Mitteleuropa markiert, wobei freilich von einer längeren Übergangszeit von ca. 1580–1730 auszugehen ist. In methodischer Hinsicht wird ein breiter Ansatz gewählt, der neuere Erkenntnisse aus der Ideen- und Kunstgeschichte mit technik- und wirtschaftshistorischen Veränderungen im Umgang mit der Natur in Beziehung setzt. Abschnitt I setzt sich mit den Positionen der bisherigen Forschung auseinander, die den Beginn der modernen Naturwahrnehmung entweder in der italienischen Renaissance (14./15. Jahrhundert), der „Wissenschaftlichen Revolution” des 17. Jahrhunderts oder der Romantik des späten 18. Jahrhunderts verorten. Abschnitt II versucht die These zu belegen, daß bereits um 1600 entscheidende Wandlungsprozesse in der Wahrnehmung von Natur und Landschaft in Semantik, Wissenschaft, Technik und Kunst stattfanden. Abschnitt III schildert die weitere Entwicklung in der zweiten Hälfte des 17. und dem ersten Drittel des 18. Jahrhunderts, die besonders durch das Aufkommen der Physikotheologie und der ästhetischen Kategorie des „Erhabenen” geprägt wurde. Abschnitt IV bietet einen kursorischen Ausblick auf die wichtigsten Veränderungen im 19. und 20. Jahrhundert.
Ein soziales „Dramma in musica”?: Verdi, alte Notabeln und neue Eliten im Theater des liberalen Italiens (A Social „Dramma in musica”?: Verdi, Old Notables and New Elites in the Theatre of Liberal Italy)
Authors: Körner Axel
Published: September 2008

Anhand einer Untersuchung von Konflikten um das Theater im liberalen Italien diskutiert der Aufsatz den Einfluß der Eliten des Ancien Régime auf die Stadt- und Kulturverwaltung Bolognas, der ehemaligen Hauptstadt der Päpstlichen Legationen im untergegangenen Kirchenstaat. Ausgangspunkt der Fallstudie sind Reaktionen auf die Musik Giuseppe Verdis. Nicht nur die Idee Verdis als des Barden der italienischen Einigung erweist sich als eine spätere Konstruktion des Komponisten und seiner Anhänger. Darüber hinaus zeigt sich auch, daß viele seiner Werke, die nach 1848 zu Nationalopern wurden, auf Ablehnung stießen. Durch den Wandel des Repertoires im 19. Jahrhundert und auf Grund der städtischen Finanzen nach der italienischen Einigung konnten sich die Theater zudem immer seltener leisten, der Tradition entsprechend, innerhalb eines Opernabends sowohl eine Opera seria als auch ein Ballett zu geben. Das Opernhaus war nicht mehr die Bühne zur Selbstinszenierung des Patriziats, sondern wurde eine Institution der liberalen städtischen Kulturverwaltung. Auch wenn sie sich dem liberalen Italien nicht grundsätzlich entgegenstellten, setzten sich die aus den besten Adelsfamilien der Stadt stammenden Logenbesitzer gegen diese gesellschaftliche Neuordnung mit juristischen und finanziellen Maßnahmen zur Wehr. In Anbetracht dieser Reaktionen stellt sich die Frage, wie solide die liberale Bürgergesellschaft im ehemaligen Kirchenstaat verwurzelt war oder ob sich mit Arno Mayer nicht doch von einem Beispiel der „Persistence of the Old Regime” sprechen läßt.
Das Dritte Reich dauerhaft fest im Blick?: Die Notwendigkeit einer erweiterten Perspektive in der Autobahngeschichte (The Third Reich Permanently in Focus?: The Necessity of an Extended Perspective in the History of the „Autobahn”)
Authors: Ruppmann Reiner
Published: September 2008

Zugleich Besprechung von:

T. Zeller, Driving Germany. The Landscape of the German Autobahn, 1930–1970
Quantitative Trait Loci Mapping and The Genetic Basis of Heterosis in Maize and Rice
Authors: Garcia Antonio Augusto Franco , Wang Shengchu , Melchinger Albrecht E , Zeng Zhao-Bang
Published: September 2008

Despite its importance to agriculture, the genetic basis of heterosis is still not well understood. The main competing hypotheses include dominance, overdominance, and epistasis. NC design III is an experimental design that has been used for estimating the average degree of dominance of quantitative trait loci (QTL) and also for studying heterosis. In this study, we first develop a multiple-interval mapping (MIM) model for design III that provides a platform to estimate the number, genomic positions, augmented additive and dominance effects, and epistatic interactions of QTL. The model can be used for parents with any generation of selfing. We apply the method to two data sets, one for maize and one for rice. Our results show that heterosis in maize is mainly due to dominant gene action, although overdominance of individual QTL could not completely be ruled out due to the mapping resolution and limitations of NC design III. For rice, the estimated QTL dominant effects could not explain the observed heterosis. There is evidence that additive × additive epistatic effects of QTL could be the main cause for the heterosis in rice. The difference in the genetic basis of heterosis seems to be related to open or self pollination of the two species. The MIM model for NC design III is implemented in Windows QTL Cartographer, a freely distributed software.
Convergent Evolution in the Genetic Basis of Müllerian Mimicry in Heliconius Butterflies
Authors: Baxter Simon W , Papa Riccardo , Chamberlain Nicola , Humphray Sean J , Joron Mathieu , Morrison Clay , ffrench-Constant Richard H , McMillan W Owen , Jiggins Chris D
Published: September 2008

The neotropical butterflies Heliconius melpomene and H. erato are Müllerian mimics that display the same warningly colored wing patterns in local populations, yet pattern diversity between geographic regions. Linkage mapping has previously shown convergent red wing phenotypes in these species are controlled by loci on homologous chromosomes. Here, AFLP bulk segregant analysis using H. melpomene crosses identified genetic markers tightly linked to two red wing-patterning loci. These markers were used to screen a H. melpomene BAC library and a tile path was assembled spanning one locus completely and part of the second. Concurrently, a similar strategy was used to identify a BAC clone tightly linked to the locus controlling the mimetic red wing phenotypes in H. erato. A methionine rich storage protein (MRSP) gene was identified within this BAC clone, and comparative genetic mapping shows red wing color loci are in homologous regions of the genome of H. erato and H. melpomene. Subtle differences in these convergent phenotypes imply they evolved independently using somewhat different developmental routes, but are nonetheless regulated by the same switch locus. Genetic mapping of MRSP in a third related species, the “tiger” patterned H. numata, has no association with wing patterning and shows no evidence for genomic translocation of wing-patterning loci.
Experimental Support for Multiple-Locus Complementary Sex Determination in the Parasitoid Cotesia vestalis
Authors: de Boer Jetske G , Ode Paul J , Rendahl Aaron K , Vet Louise E M , Whitfield James B , Heimpel George E
Published: September 2008

Despite its fundamental role in development, sex determination is highly diverse among animals. Approximately 20% of all animals are haplodiploid, with haploid males and diploid females. Haplodiploid species exhibit diverse but poorly understood mechanisms of sex determination. Some hymenopteran insect species exhibit single-locus complementary sex determination (sl-CSD), where heterozygosity at a polymorphic sex locus initiates female development. Diploid males are homozygous at the sex locus and represent a genetic load because they are inviable or sterile. Inbreeding depression associated with CSD is therefore expected to select for other modes of sex determination resulting in fewer or no diploid males. Here, we investigate an alternative, heretofore hypothetical, mode of sex determination: multiple-locus CSD (ml-CSD). Under ml-CSD, diploid males are predicted to develop only from zygotes that are homozygous at all sex loci. We show that inbreeding for eight generations in the parasitoid wasp Cotesia vestalis leads to increasing proportions of diploid males, a pattern that is consistent with ml-CSD but not sl-CSD. The proportion of diploid males (0.27 ± 0.036) produced in the first generation of inbreeding (mother–son cross) suggests that two loci are likely involved. We also modeled diploid male production under CSD with three linked loci. Our data visually resemble CSD with linked loci because diploid male production in the second generation was lower than that in the first. To our knowledge, our data provide the first experimental support for ml-CSD.
Suppression of Pleiotropic Effects of Functional CRYPTOCHROME Genes by TERMINAL FLOWER 1
Authors: Buchovsky Ana Sabrina , Strasser Bárbara , Cerdán Pablo D , Casal Jorge J
Published: September 2008

TERMINAL FLOWER 1 (TFL1) encodes a protein with similarity to animal phosphatidylethanolamine-binding proteins and is required for normal trafficking to the protein storage vacuole. In Arabidopsis thaliana the tfl1 mutation produces severe developmental abnormalities. Here we show that most aspects of the tfl1 phenotype are lost in the cry1 cry2 double-mutant background lacking cryptochromes 1 and 2. The inhibition of hypocotyl growth by light is reduced in the tfl1 mutant but this effect is absent in the cry1 or cry2 mutant background. Although the promotion of flowering under long rather than short days is a key function of cryptochromes, in the tfl1 background, cryptochromes promoted flowering under short days. Thus, normal CRY control of photoperiod-dependent flowering and hypocotyl growth inhibition requires a functional TFL1 gene.
A General Extreme Value Theory Model for the Adaptation of DNA Sequences Under Strong Selection and Weak Mutation
Authors: Joyce Paul , Rokyta Darin R , Beisel Craig J , Orr H Allen
Published: September 2008

Recent theoretical studies of the adaptation of DNA sequences assume that the distribution of fitness effects among new beneficial mutations is exponential. This has been justified by using extreme value theory and, in particular, by assuming that the distribution of fitnesses belongs to the Gumbel domain of attraction. However, extreme value theory shows that two other domains of attraction are also possible: the Fréchet and Weibull domains. Distributions in the Fréchet domain have right tails that are heavier than exponential, while distributions in the Weibull domain have right tails that are truncated. To explore the consequences of relaxing the Gumbel assumption, we generalize previous adaptation theory to allow all three domains. We find that many of the previously derived Gumbel-based predictions about the first step of adaptation are fairly robust for some moderate forms of right tails in the Weibull and Fréchet domains, but significant departures are possible, especially for predictions concerning multiple steps in adaptation.
The Generation and Maintenance of Genetic Variation by Frequency-Dependent Selection: Constructing Polymorphisms Under the Pairwise Interaction Model
Authors: Trotter Meredith V , Spencer Hamish G
Published: September 2008

Frequency-dependent selection remains the most commonly invoked heuristic explanation for the maintenance of genetic variation. For polymorphism to exist, new alleles must be both generated and maintained in the population. Here we use a construction approach to model frequency-dependent selection with mutation under the pairwise interaction model. The pairwise interaction model is a general model of frequency-dependent selection at the genotypic level. We find that frequency-dependent selection is able to generate a large number of alleles at a single locus. The construction process generates multiallelic polymorphisms with a wide range of allele-frequency distributions and genotypic fitness relationships. Levels of polymorphism and mean fitness are uncoupled, so constructed polymorphisms remain permanently invasible to new mutants; thus the model never settles down to an equilibrium state. Analysis of constructed fitness sets reveals signatures of heterozygote advantage and positive frequency dependence.
Metabolomic Signatures of Inbreeding at Benign and Stressful Temperatures inDrosophila melanogaster
Authors: Pedersen Kamilla Sofie , Kristensen Torsten Nygaard , Loeschcke Volker , Petersen Bent O , Duus Jens Ø , Nielsen Niels Chr , Malmendal Anders
Published: September 2008

While the population genetics of inbreeding is fairly well understood, the effects of inbreeding on the physiological and biochemical levels are not. Here we have investigated the effects of inbreeding on the Drosophila melanogaster metabolome. Metabolite fingerprints in males from five outbred and five inbred lines were studied by nuclear magnetic resonance spectroscopy after exposure to benign temperature, heat stress, or cold stress. In both the absence and the presence of temperature stress, metabolite levels were significantly different among inbred and outbred lines. The major effect of inbreeding was increased levels of maltose and decreased levels of 3-hydroxykynurenine and a galactoside [1-O-(4-O-(2-aminoethyl phosphate)-β-d-galactopyranosyl)-x-glycerol] synthesized exclusively in the paragonial glands of Drosophila species, including D. melanogaster. The metabolomic effect of inbreeding at the benign temperature was related to gene expression data from the same inbred and outbred lines. Both gene expression and metabolite data indicate that fundamental metabolic processes are changed or modified by inbreeding. Apart from affecting mean metabolite levels, inbreeding led to an increased between-line variation in metabolite profiles compared to outbred lines. In contrast to previous observations revealing interactions between inbreeding and environmental stress on gene expression patterns and life-history traits, the effect of inbreeding on the metabolite profile was similar across the different temperature treatments.
Evolution of Primate Gene Expression: Drift and Corrective Sweeps?
Authors: Chaix R , Somel M , Kreil D P , Khaitovich P , Lunter G A
Published: September 2008

Changes in gene expression play an important role in species' evolution. Earlier studies uncovered evidence that the effect of mutations on expression levels within the primate order is skewed, with many small downregulations balanced by fewer but larger upregulations. In addition, brain-expressed genes appeared to show an increased rate of evolution on the branch leading to human. However, the lack of a mathematical model adequately describing the evolution of gene expression precluded the rigorous establishment of these observations. Here, we develop mathematical tools that allow us to revisit these earlier observations in a model-testing and inference framework. We introduce a model for skewed gene-expression evolution within a phylogenetic tree and use a separate model to account for biological or experimental outliers. A Bayesian Markov chain Monte Carlo inference procedure allows us to infer the phylogeny and other evolutionary parameters, while quantifying the confidence in these inferences. Our results support previous observations; in particular, we find strong evidence for a sustained positive skew in the distribution of gene-expression changes in primate evolution. We propose a “corrective sweep” scenario to explain this phenomenon.
Use of a Drosophila Model to Identify Genes Regulating Plasmodium Growth in the Mosquito
Authors: Brandt Stephanie M , Jaramillo-Gutierrez Giovanna , Kumar Sanjeev , Barillas-Mury Carolina , Schneider David S
Published: September 2008

We performed a forward genetic screen, using Drosophila as a surrogate mosquito, to identify host factors required for the growth of the avian malaria parasite, Plasmodium gallinaceum. We identified 18 presumed loss-of-function mutants that reduced the growth of the parasite in flies. Presumptive mutation sites were identified in 14 of the mutants on the basis of the insertion site of a transposable element. None of the identified genes have been previously implicated in innate immune responses or interactions with Plasmodium. The functions of five Anopheles gambiae homologs were tested by using RNAi to knock down gene function followed by measuring the growth of the rodent parasite, Plasmodium berghei. Loss of function of four of these genes in the mosquito affected Plasmodium growth, suggesting that Drosophila can be used effectively as a surrogate mosquito to identify relevant host factors in the mosquito.
The Chicken (Gallus gallus) Z Chromosome Contains at Least Three Nonlinear Evolutionary Strata
Authors: Nam Kiwoong , Ellegren Hans
Published: September 2008

Birds have female heterogamety with Z and W sex chromosomes. These evolved from different autosomal precursor chromosomes than the mammalian X and Y. However, previous work has suggested that the pattern and process of sex chromosome evolution show many similarities across distantly related organisms. Here we show that stepwise restriction of recombination between the protosex chromosomes of birds has resulted in regions of the chicken Z chromosome showing discrete levels of divergence from W homologs (gametologs). The 12 genes analyzed fall into three levels of estimated divergence values, with the most recent divergence (dS = 0.18–0.21) displayed by 6 genes in a region on the Z chromosome corresponding to the interval 1–11 Mb of the assembled genome sequence. Another 4 genes show intermediate divergence (dS = 0.27–0.38) and are located in the interval 16–53 Mb. Two genes (at positions 42 and 50 Mb) with higher dS values are located proximal to the most distal of the 4 genes with intermediate divergence, suggesting an inversion event. The distribution of genes and their divergence indicate at least three evolutionary strata, with estimated times for cessation of recombination between Z and W of 132–150 (stratum 1), 71–99 (stratum 2), and 47–57 (stratum 3) million years ago. An inversion event, or some other form of intrachromosomal rearrangement, subsequent to the formation of strata 1 and 2 has scrambled the gene order to give rise to the nonlinear arrangement of evolutionary strata currently seen on the chicken Z chromosome. These observations suggest that the progressive restriction of recombination is an integral feature of sex chromosome evolution and occurs also in systems of female heterogamety.
A Simple Method to Account for Natural Selection When Predicting Inbreeding Depression
Authors: García-Dorado Aurora
Published: September 2008

It has been widely appreciated that natural selection opposes the progress of inbreeding in small populations, thus limiting the actual inbreeding depression for fitness traits. However, no method to account for the consequences of this process has been given so far. I give a simple and intuitive method to predict inbreeding depression, taking into account the increase in selection efficiency against recessive alleles during inbreeding. It is based on the use of a “purged inbreeding coefficient” gt that accounts for the reduction of the probability of the deleterious homozygotes caused by the excess d of detrimental effect for deleterious alleles in the homozygous condition over its additive expectation. It is shown that the effect of purging can be important even for relatively small populations. For between-loci variable deleterious effects, accurate predictions can be obtained using the effective homozygous deleterious excess de, which can be estimated experimentally and is robust against variation of the ancestral effective population size. The method can be extended to any trait and it is used to predict the evolution of the mean viability or fecundity in a conservation program with equal or random family contributions.
Selective Transcriptional Profiling and Data Analysis Strategies for Expression Quantitative Trait Loci Mapping in Outbred F2 Populations
Authors: Cardoso Fernando F , Rosa Guilherme J M , Steibel Juan P , Ernst Catherine W , Bates Ronald O , Tempelman Robert J
Published: September 2008

Genetic analysis of transcriptional profiling experiments is emerging as a promising approach for unraveling genes and pathways that underlie variation of complex biological traits. However, these genetical genomics approaches are currently limited by the high cost of microarrays. We studied five different strategies to optimally select subsets of individuals for transcriptional profiling, including (1) maximizing genetic dissimilarity between selected individuals, (2) maximizing the number of recombination events in selected individuals, (3) selecting phenotypic extremes within inferred genotypes of a previously identified quantitative trait locus (QTL), (4) purely random selection, and (5) profiling animals with the highest and lowest phenotypic values within each family–gender subclass. A simulation study was conducted on the basis of a linkage map and marker genotypes were derived from data on chromosome 6 for 510 F2 animals from an existing pig resource population and on a simulated biallelic QTL with pleiotropic effects on performance and gene expression traits. Bivariate analyses were conducted for selected subset sample sizes of 80, 160, and 240 individuals under three different correlation scenarios between the two traits. The genetic dissimilarity and phenotypic extremes within genotype methods had the smallest mean square error on QTL effects and maximum sensitivity on QTL detection, thereby outperforming all other selection strategies, particularly at the smallest proportion of samples selected for gene expression profiling (80/510).
Mixed Effects Models for Quantitative Trait Loci Mapping With Inbred Strains
Authors: Bauman Lara E , Sinsheimer Janet S , Sobel Eric M , Lange Kenneth
Published: September 2008

Fixed effects models have dominated the statistical analysis of genetic crosses between inbred strains. In spite of their popularity, the traditional models ignore polygenic background and must be tailored to each specific cross. We reexamine the role of random effect models in gene mapping with inbred strains. The biggest difficulty in implementing random effect models is the lack of a coherent way of calculating trait covariances between relatives. The standard model for outbred populations is based on premises of genetic equilibrium that simply do not apply to crosses between inbred strains since every animal in a strain is genetically identical and completely homozygous. We fill this theoretical gap by introducing novel combinatorial entities called strain coefficients. With an appropriate theory, it is possible to reformulate QTL mapping and QTL association analysis as an application of mixed models involving both fixed and random effects. After developing this theory, our first example compares the mixed effects model to a standard fixed effects model using simulated advanced intercross line (AIL) data. Our second example deals with hormone data. Here multivariate traits and parameter identifiability questions arise. Our final example involves random mating among eight strains and vividly demonstrates the versatility of our models.
Maximum-Likelihood Estimation of Site-Specific Mutation Rates in Human Mitochondrial DNA From Partial Phylogenetic Classification
Authors: Rosset Saharon , Wells R Spencer , Soria-Hernanz David F , Tyler-Smith Chris , Royyuru Ajay K , Behar Doron M ,   The Genographic Consortium
Published: September 2008

The mitochondrial DNA hypervariable segment I (HVS-I) is widely used in studies of human evolutionary genetics, and therefore accurate estimates of mutation rates among nucleotide sites in this region are essential. We have developed a novel maximum-likelihood methodology for estimating site-specific mutation rates from partial phylogenetic information, such as haplogroup association. The resulting estimation problem is a generalized linear model, with a nonstandard link function. We develop inference and bias correction tools for our estimates and a hypothesis-testing approach for site independence. We demonstrate our methodology using 16,609 HVS-I samples from the Genographic Project. Our results suggest that mutation rates among nucleotide sites in HVS-I are highly variable. The 16,400–16,500 region exhibits significantly lower rates compared to other regions, suggesting potential functional constraints. Several loci identified in the literature as possible termination-associated sequences (TAS) do not yield statistically slower rates than the rest of HVS-I, casting doubt on their functional importance. Our tests do not reject the null hypothesis of independent mutation rates among nucleotide sites, supporting the use of site-independence assumption for analyzing HVS-I. Potential extensions of our methodology include its application to estimation of mutation rates in other genetic regions, like Y chromosome short tandem repeats.
Molecular Marker Systems for Oenothera Genetics
Authors: Rauwolf Uwe , Golczyk Hieronim , Meurer Jörg , Herrmann Reinhold G , Greiner Stephan
Published: September 2008

The genus Oenothera has an outstanding scientific tradition. It has been a model for studying aspects of chromosome evolution and speciation, including the impact of plastid nuclear co-evolution. A large collection of strains analyzed during a century of experimental work and unique genetic possibilities allow the exchange of genetically definable plastids, individual or multiple chromosomes, and/or entire haploid genomes (Renner complexes) between species. However, molecular genetic approaches for the genus are largely lacking. In this study, we describe the development of efficient PCR-based marker systems for both the nuclear genome and the plastome. They allow distinguishing individual chromosomes, Renner complexes, plastomes, and subplastomes. We demonstrate their application by monitoring interspecific exchanges of genomes, chromosome pairs, and/or plastids during crossing programs, e.g., to produce plastome–genome incompatible hybrids. Using an appropriate partial permanent translocation heterozygous hybrid, linkage group 7 of the molecular map could be assigned to chromosome 9·8 of the classical Oenothera map. Finally, we provide the first direct molecular evidence that homologous recombination and free segregation of chromosomes in permanent translocation heterozygous strains is suppressed.
A Novel Septin-Associated Protein, Syp1p, Is Required for Normal Cell Cycle-Dependent Septin Cytoskeleton Dynamics in Yeast
Authors: Qiu Wenjie , Neo Suat Peng , Yu Xianwen , Cai Mingjie
Published: September 2008

Septins are a family of GTP-binding proteins whose heterooligomeric complex is the basic structural element of the septin filaments found in many eukaryotic organisms. In budding yeast, septins are mainly confined at the mother–daughter junction and are required for cell morphogenesis and division. Septins undergo assembly and disassembly in accordance with the progression of the cell cycle. In this report, we identified the yeast protein Syp1p as a new regulator of septin dynamics. Syp1p colocalizes with septins throughout most of the cell cycle. Syp1p interacts with the septin subunit Cdc10p and can be precipitated by Cdc10p and Cdc12p. In the syp1Δ mutant, both formation of a complete septin ring at the incipient bud site and disassembly of the septin ring in later stages of cell division are significantly delayed. In addition, overexpression of Syp1p causes marked acceleration of septin disassembly. The fluorescence recovery after photobleaching (FRAP) assay further showed that Syp1p promotes septin turnover in different cell cycle stages. These results suggest that Syp1p is involved in the regulation of cell cycle-dependent dynamics of the septin cytoskeleton in yeast.
Components of the RNAi Machinery That Mediate Long-Distance Chromosomal Associations Are Dispensable for Meiotic and Early Somatic Homolog Pairing inDrosophila melanogaster
Authors: Blumenstiel Justin P , Fu Roxana , Theurkauf William E , Hawley R Scott
Published: September 2008

Homolog pairing is indispensable for the proper segregation of chromosomes in meiosis but the mechanism by which homologs uniquely pair with each other is poorly understood. In Drosophila, somatic chromosomes also undergo full homolog pairing by an unknown mechanism. It has been recently demonstrated that both insulator function and somatic long-distance interactions between Polycomb response elements (PREs) are stabilized by the RNAi machinery in Drosophila. This suggests the possibility that long-distance pairing interactions between homologs, either during meiosis or in the soma, may be stabilized by a similar mechanism. To test this hypothesis, we have characterized meiotic and early somatic chromosome pairing of homologous chromosomes in flies that are mutant for various components of the RNAi machinery. Despite the identification of a novel role for the piRNA machinery in meiotic progression and synaptonemal complex (SC) assembly, we have found that the components of the RNAi machinery that mediate long-distance chromosomal interactions are dispensable for homologous chromosome pairing. Thus, there appears to be at least two mechanisms that bring homologous sequences together within the nucleus: those that act between dispersed homologous sequences and those that act to align and pair homologous chromosomes.
Cross-Species Bacterial Artificial Chromosome–Fluorescence in Situ Hybridization Painting of the Tomato and Potato Chromosome 6 Reveals Undescribed Chromosomal Rearrangements
Authors: Tang Xiaomin , Szinay Dóra , Lang Chunting , Ramanna Munikote S , van der Vossen Edwin A G , Datema Erwin , Lankhorst René Klein , de Boer Jan , Peters Sander A , Bachem Christian , Stiekema Willem , Visser Richard G F , de Jong Hans , Bai Yuling
Published: September 2008

Ongoing genomics projects of tomato (Solanum lycopersicum) and potato (S. tuberosum) are providing unique tools for comparative mapping studies in Solanaceae. At the chromosomal level, bacterial artificial chromosomes (BACs) can be positioned on pachytene complements by fluorescence in situ hybridization (FISH) on homeologous chromosomes of related species. Here we present results of such a cross-species multicolor cytogenetic mapping of tomato BACs on potato chromosomes 6 and vice versa. The experiments were performed under low hybridization stringency, while blocking with Cot-100 was essential in suppressing excessive hybridization of repeat signals in both within-species FISH and cross-species FISH of tomato BACs. In the short arm we detected a large paracentric inversion that covers the whole euchromatin part with breakpoints close to the telomeric heterochromatin and at the border of the short arm pericentromere. The long arm BACs revealed no deviation in the colinearity between tomato and potato. Further comparison between tomato cultivars Cherry VFNT and Heinz 1706 revealed colinearity of the tested tomato BACs, whereas one of the six potato clones (RH98-856-18) showed minor putative rearrangements within the inversion. Our results present cross-species multicolor BAC–FISH as a unique tool for comparative genetic studies across Solanum species.
Genetic Analysis of MraY Inhibition by the ϕX174 Protein E
Authors: Zheng Yi , Struck Douglas K , Bernhardt Thomas G , Young Ry
Published: September 2008

Protein E, the lysis protein of bacteriophage ϕX174, is a specific inhibitor of MraY, the phospho-MurNAc-pentapeptide translocase that catalyzes the synthesis of lipid I in the conserved pathway for peptidoglycan biosynthesis. The original evidence for this inhibition was the isolation of two spontaneous E-resistance mraY mutants. Here we report further genetic studies aimed at dissecting the interaction between E and MraY, using a genetic strategy that is facile, rapid, and does not depend on the availability of purified E, purified MraY, or its substrates. This system relies on the ability of mraY or its enzymatically inactive D267N allele to protect cells from lysis after induction of a chimeric λ∷E prophage. Using this approach, the MraY protein from Bacillus subtilis, which shares 43% sequence identity with the Escherichia coli enzyme, was found to interact weakly, if at all, with E. A potential E binding site defined by transmembrane domains 5 and 9 has been identified by isolating more mraY mutants resistant to E inhibition. Genetic analysis indicates that these E-resistant alleles fall into three classes on the basis of the affinity of the encoded proteins for MraY.
Accurate Discovery of Expression Quantitative Trait Loci Under Confounding From Spurious and Genuine Regulatory Hotspots
Authors: Kang Hyun Min , Ye Chun , Eskin Eleazar
Published: September 2008

In genomewide mapping of expression quantitative trait loci (eQTL), it is widely believed that thousands of genes are trans-regulated by a small number of genomic regions called “regulatory hotspots,” resulting in “trans-regulatory bands” in an eQTL map. As several recent studies have demonstrated, technical confounding factors such as batch effects can complicate eQTL analysis by causing many spurious associations including spurious regulatory hotspots. Yet little is understood about how these technical confounding factors affect eQTL analyses and how to correct for these factors. Our analysis of data sets with biological replicates suggests that it is this intersample correlation structure inherent in expression data that leads to spurious associations between genetic loci and a large number of transcripts inducing spurious regulatory hotspots. We propose a statistical method that corrects for the spurious associations caused by complex intersample correlation of expression measurements in eQTL mapping. Applying our intersample correlation emended (ICE) eQTL mapping method to mouse, yeast, and human identifies many more cis associations while eliminating most of the spurious trans associations. The concordances of cis and trans associations have consistently increased between different replicates, tissues, and populations, demonstrating the higher accuracy of our method to identify real genetic effects.
A Targeted Deleterious Allele of the Splicing Factor SCNM1 in the Mouse
Authors: Howell Viive M , de Haan Georgius , Bergren Sarah , Jones Julie M , Culiat Cymbeline T , Michaud Edward J , Frankel Wayne N , Meisler Miriam H
Published: September 2008

The auxiliary spliceosomal protein SCNM1 contributes to recognition of nonconsensus splice donor sites. SCNM1 was first identified as a modifier of the severity of a sodium channelopathy in the mouse. The most severely affected strain, C57BL/6J, carries the variant allele SCNM1R187X, which is defective in splicing the mutated donor site in the Scn8amedJ transcript. To further probe the in vivo function of SCNM1, we constructed a floxed allele and generated a mouse with constitutive deletion of exons 3–5. The SCNM1Δ3-5 protein is produced and correctly localized to the nucleus, but is more functionally impaired than the C57BL/6J allele. Deficiency of SCNM1 did not significantly alter other brain transcripts. We characterized an ENU-induced allele of Scnm1 and evaluated the ability of wild-type SCNM1 to rescue lethal mutations of I-mfa and Brunol4. The phenotypes of the Scnm1Δ3-5 mutant confirm the role of this splice factor in processing the Scn8amedJ transcript and provide a new allele of greater severity for future studies.
A Simple Polymerase Chain Reaction-Based Method for the Construction of Recombinase-Mediated Cassette Exchange Donor Vectors
Authors: Bateman Jack R , Wu C-ting
Published: September 2008

Here we describe a simple method for generating donor vectors suitable for targeted transgenesis via recombinase-mediated cassette exchange (RMCE) using the ΦC31 integrase. This PCR-based strategy employs small attB “tails” on the primers used to amplify a sequence of interest, permitting the rapid creation of transgenes for in vivo analysis.
Nonsense-Mediated Decay of ash1 Nonsense Transcripts in Saccharomyces cerevisiae
Authors: Zheng Wei , Finkel Jonathan S , Landers Sharon M , Long Roy M , Culbertson Michael R
Published: September 2008

Nonsense-mediated mRNA decay (NMD) performs two functions in eukaryotes, one in controlling the expression level of a substantial subset of genes and the other in RNA surveillance. In the vast majority of genes, nonsense mutations render the corresponding transcripts prone to surveillance and subject to rapid degradation by NMD. To examine whether some classes of nonsense transcripts escape surveillance, we asked whether NMD acts on mRNAs that undergo subcellular localization prior to translation. In Saccharomyces cerevisiae, wild-type ASH1 mRNA is one of several dozen transcripts that are exported from the mother-cell nucleus during mitotic anaphase, transported to the bud tip on actin cables, anchored at the bud tip, and translated. Although repressed during transport, translation is a prerequisite for NMD. We found that ash1 nonsense mutations affect transport and/or anchoring independently of NMD. The nonsense transcripts respond to NMD in a manner dependent on the position of the mutation. Maximal sensitivity to NMD occurs when transport and translational repression are simultaneously impaired. Overall, our results suggest a model in which ash1 mRNAs are insensitive to NMD while translation is repressed during transport but become sensitive once repression is relieved.
Differential Gene Expression between Fall‐ and Spring‐Run Chinook Salmon Assessed by Long Serial Analysis of Gene Expression
Authors: Bernier Jeremiah C. , Birkeland Shanda R. , Cipriano Michael J. , McArthur Andrew G. , Banks Michael A.
Published: September 2008

Of all Pacific salmonids, Chinook salmon Oncorhynchus tshawytscha display the greatest variability in return times to freshwater. The molecular mechanisms of these differential return times have not been well described. Current methods, such as long serial analysis of gene expression (LongSAGE) and microarrays, allow gene expression to be analyzed for thousands of genes simultaneously. To investigate whether differential gene expression is observed between fall‐ and spring‐run Chinook salmon from California's Central Valley, LongSAGE libraries were constructed. Three libraries containing between 25,512 and 29,372 sequenced tags (21 base pairs/tag) were generated using messenger RNA from the brains of adult Chinook salmon returning in fall and spring and from one ocean‐caught Chinook salmon. Tags were annotated to genes using complementary DNA libraries from Atlantic salmon Salmo salar and rainbow trout O. mykiss. Differentially expressed genes, as estimated by differences in the number of sequence tags, were found in all pairwise comparisons of libraries (freshwater versus saltwater = 40 genes; fall versus spring = 11 genes; and spawning versus nonspawning = 51 genes). The gene for ependymin, an extracellular glycoprotein involved in behavioral plasticity in fish, exhibited the most differential expression among the three groupings. Reverse transcription polymerase chain reaction analysis verified the differential expression of ependymin between the fall‐ and spring‐run samples. These LongSAGE libraries, the first reported for Chinook salmon, provide a window of the transcriptional changes during Chinook salmon return migration to freshwater and spawning and increase the amount of expressed sequence data.
Duplication of Accessory Phallic Urethra (Urethra Triplication) in the Female, Signaling Mesenchymal Interruptions of the Cloacal Membrane as a Cause for Sagittal Urethral Duplications
Authors: van der Putte Sebastian C.J.
Published: September 2008

A specimen of accessory phallic urethra duplication (triplication) in a 32.5-week gestation female was studied histologically. The specimen demonstrated an anterior “phallic urethra” ending inside a penoclitoral organ in a megalourethra-like dilatation with a narrow epispadiac meatus and “anterior urethrocutaneous fistula” and a posterior canal opening with the anal canal. With histology suggestive of a split persistent urogenital sinus, correlation to normal development strongly suggests an error in the formation of the cloacal membrane and developing superficial cloaca at 26 to 29 days' ovulation age (2 to 4 mm), causing an isolated interruption of the membrane by mesenchyme, which by participating in the growth of the early cloaca may extend as far as the vaginal orifice later. Differences in number, position, and size of such mesenchymal interruptions can explain other duplications and triplications and offer a single alternative for the many current theories of pathogenesis, none of which are compatible with new insights in normal development.