bluuebunny/crossref_metadata_2025 huggingface dataset:
Priming and unidirectional language change
Authors: Jäger Gerhard , Rosenbach Anette
Published: September 2008

In this paper we argue that the psycholinguistic mechanism of priming may account for the empirical observation that grammaticalization processes typically proceed in one direction only. It is shown how two well-known unidirectional changes, i.e. the development from spatial to temporal expressions and phonological reduction, may be connected to cases of asymmetric priming as reported in the psycholinguistic literature. In these cases a form or concept A primes a form or concept B, but not vice versa, and this cognitive asymmetry corresponds precisely to the observed unidirectional pathway from A to B in diachronic change. Ultimately, then, we argue that what appears as diachronic trajectories of unidirectional change is decomposable into atomic steps of asymmetric priming in language use. More generally, we also suggest that priming is the ‘missing link’ in evolutionary models of language change in that it provides for a plausible linguistic replicating mechanism, i.e. an ‘amplifier’ of linguistic units.

This is a programmatic paper which should bring to attention the potential of fruitfully applying insights from psycholinguistic research to some central issues of historical linguistics. Specifically, our approach allows for the formulation of falsifiable predictions that can be tested with present-day speakers, under the uniformitarian assumption that the same cognitive mechanisms that we find to be operating in present-day speakers also have operated in past speakers of a language.
Mental Images, Memory Storage, and Composition in the High Middle Ages
Authors: Curruthers Mary J.
Published: September 2008

This essay explores the implications of a commonly held ancient and medieval belief that human memory and invention are, if not exactly the same, the closest thing to it. In order to create, in order to think at all, human beings require both a well-provisioned stock of memory-held knowledge and some mental tool or machine, an engine which lives in the intricate networks of their own memories. In the verbal arts of the trivium students learned the basic principles of memory training: the need for divisio, the need to make a clear, distinct location for each piece of memorized content, and the need to mark items uniquely for secure recollection. Frequently these mental structures took the form of images. Evidence for such memorial and compositional images is common: I focus on a few representative types, including the sermon-related Cherub figure of the later Middle Ages, and accounts by Cassiodorus and others of scholars, even when blind, using their highly structured memories to compose new work.
Spiegelbilder und Ekphrasen. Spekulative Fiktionspoetik im ‚Pfaffen Amis‘ des Strickers
Authors: Klarer Mario
Published: September 2008

Im ‚Pfaffen Amis‘ des Strickers aus der ersten Hälfte des 13. Jahrhunderts finden sich äußerst eigenwillige Bildbeschreibungen, die in der Wort-Bild-Forschung wenig Beachtung erfahren haben. Dies liegt darin begründet, daß es sich um eine Schilderung nicht vorhandener bzw. imaginierter Bilder handelt. Es zeigt sich aber, dass gerade diese so unkonventionelle Ekphrase das mittelalterliche Repräsentations- und Imaginationsverständnis auf signifikante Weise thematisiert. Im vorliegenden Beitrag wird die Beschreibung dieser unsichtbaren imagines einerseits in den größeren Kontext des ‚Pfaffen Amis‘ gestellt und andererseits der paradigmatische, metafiktionale Charakter dieses Textes für das mittelalterliche Repräsentations- und Fiktionsverständnis dargelegt. Hierzu wird die Ekphrase parallel zu mittelalterlichen gehirnanatomischen Texten und zur Zweikörperlehre von Ernst H. Kantorowicz gelesen.
The Evolutionary Rate of Duplicated Genes Under Concerted Evolution
Authors: Mano Shuhei , Innan Hideki
Published: September 2008

The effect of directional selection on the fixation process of a single mutation that spreads in a multigene family by gene conversion is investigated. A simple two-locus model with two alleles, A and a, is first considered in a random-mating diploid population with size N. There are four haplotypes, AA, Aa, aA, and aa, and selection works on the number of alleles A in a diplod (i = 0, 1, 2, 3, 4). Because gene conversion is allowed between the two loci, when the mutation rate is very low, either AA or aa will fix in the population eventually. We consider a situation where a single mutant, A, arises in one locus when a is fixed in both loci. Then, we derive the fixation probability analytically, and the fixation time is investigated by simulations. It is found that gene conversion has an effect to increase the “effective” population size, so that weak selection works more efficiently in a multigene family. With these results, we discuss the effect of gene conversion on the rate of molecular evolution in a multigene family undergoing concerted evolution. We also argue about the applicability of the theoretical results to models of multigene families with more than two loci.
Recombination at Prunus S-Locus Region SLFL1 Gene
Authors: Vieira Jorge , Teles Eliana , Santos Raquel A M , Vieira Cristina P
Published: September 2008

In Prunus, the self-incompatibility (S-) locus region is <70 kb. Two genes—the S-RNase, which encodes the functional female recognition component, and the SFB gene, which encodes the pollen recognition component—must co-evolve as a genetic unit to maintain functional incompatibility. Therefore, recombination must be severely repressed at the S-locus. Levels of recombination at genes in the vicinity of the S-locus have not yet been rigorously tested; thus it is unknown whether recombination is also severely repressed at these loci. In this work, we looked at variability levels and patterns at the Prunus spinosa SLFL1 gene, which is physically close to the S-RNase gene. Our results suggest that the recombination level increases near the SLFL1 coding region. These findings are discussed in the context of theoretical models predicting an effect of linked weakly deleterious mutations on the relatedness of S-locus specificities. Moreover, we show that SLFL1 belongs to a gene family of at least five functional genes and that SLFL1 pseudogenes are frequently found in the S-locus region.
Performance of Genomic Selection in Mice
Authors: Legarra Andrés , Robert-Granié Christèle , Manfredi Eduardo , Elsen Jean-Michel
Published: September 2008

Selection plans in plant and animal breeding are driven by genetic evaluation. Recent developments suggest using massive genetic marker information, known as “genomic selection.” There is little evidence of its performance, though. We empirically compared three strategies for selection: (1) use of pedigree and phenotypic information, (2) use of genomewide markers and phenotypic information, and (3) the combination of both. We analyzed four traits from a heterogeneous mouse population (http://gscan.well.ox.ac.uk/), including 1884 individuals and 10,946 SNP markers. We used linear mixed models, using extensions of association analysis. Cross-validation techniques were used, providing assumption-free estimates of predictive ability. Sampling of validation and training data sets was carried out across and within families, which allows comparing across- and within-family information. Use of genomewide genetic markers increased predictive ability up to 0.22 across families and up to 0.03 within families. The latter is not statistically significant. These values are roughly comparable to increases of up to 0.57 (across family) and 0.14 (within family) in accuracy of prediction of genetic value. In this data set, within-family information was more accurate than across-family information, and populational linkage disequilibrium was not a completely accurate source of information for genetic evaluation. This fact questions some applications of genomic selection.
A Misexpression Screen to Identify Regulators of Drosophila Larval Hemocyte Development
Authors: Stofanko Martin , Kwon So Yeon , Badenhorst Paul
Published: September 2008

In Drosophila, defense against foreign pathogens is mediated by an effective innate immune system, the cellular arm of which is composed of circulating hemocytes that engulf bacteria and encapsulate larger foreign particles. Three hemocyte types occur: plasmatocytes, crystal cells, and lamellocytes. The most abundant larval hemocyte type is the plasmatocyte, which is responsible for phagocytosis and is present either in circulation or in adherent sessile domains under the larval cuticle. The mechanisms controlling differentiation of plasmatocytes and their migration toward these sessile compartments are unclear. To address these questions we have conducted a misexpression screen using the plasmatocyte-expressed GAL4 driver Peroxidasin-GAL4 (Pxn-GAL4) and existing enhancer-promoter (EP) and EP yellow (EY) transposon libraries to systematically misexpress ∼20% of Drosophila genes in larval hemocytes. The Pxn-GAL4 strain also contains a UAS-GFP reporter enabling hemocyte phenotypes to be visualized in the semitransparent larvae. Among 3412 insertions screened we uncovered 101 candidate hemocyte regulators. Some of these are known to control hemocyte development, but the majority either have no characterized function or are proteins of known function not previously implicated in hemocyte development. We have further analyzed three candidate genes for changes in hemocyte morphology, cell–cell adhesion properties, phagocytosis activity, and melanotic tumor formation.
Correlation-Based Inference for Linkage Disequilibrium With Multiple Alleles
Authors: Zaykin Dmitri V , Pudovkin Alexander , Weir Bruce S
Published: September 2008

The correlation between alleles at a pair of genetic loci is a measure of linkage disequilibrium. The square of the sample correlation multiplied by sample size provides the usual test statistic for the hypothesis of no disequilibrium for loci with two alleles and this relation has proved useful for study design and marker selection. Nevertheless, this relation holds only in a diallelic case, and an extension to multiple alleles has not been made. Here we introduce a similar statistic, R2, which leads to a correlation-based test for loci with multiple alleles: for a pair of loci with k and m alleles, and a sample of n individuals, the approximate distribution of n(k – 1)(m – 1)/(km)R2 under independence between loci is $\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{{\chi}}_{(k{-}1)(m{-}1)}^{2}\) \end{document}$. One advantage of this statistic is that it can be interpreted as the total correlation between a pair of loci. When the phase of two-locus genotypes is known, the approach is equivalent to a test for the overall correlation between rows and columns in a contingency table. In the phase-known case, R2 is the sum of the squared sample correlations for all km 2 × 2 subtables formed by collapsing to one allele vs. the rest at each locus. We examine the approximate distribution under the null of independence for R2 and report its close agreement with the exact distribution obtained by permutation. The test for independence using R2 is a strong competitor to approaches such as Pearson's chi square, Fisher's exact test, and a test based on Cressie and Read's power divergence statistic. We combine this approach with our previous composite-disequilibrium measures to address the case when the genotypic phase is unknown. Calculation of the new multiallele test statistic and its P-value is very simple and utilizes the approximate distribution of R2. We provide a computer program that evaluates approximate as well as “exact” permutational P-values.
Transmission Dynamics of Heritable Silencing Induced by Double-Stranded RNA inCaenorhabditis elegans
Authors: Alcazar Rosa M , Lin Rueyling , Fire Andrew Z
Published: September 2008

Heritable silencing effects are gene suppression phenomena that can persist for generations after induction. In the majority of RNAi experiments conducted in Caenorhabditis elegans, the silencing response results in a hypomorphic phenotype where the effects recede after the F1 generation. F2 and subsequent generations revert to the original phenotype. Specific examples of transgenerational RNAi in which effects persist to the F2 generation and beyond have been described. In this study, we describe a systematic pedigree-based analysis of heritable silencing processes resulting from initiation of interference targeted at the C. elegans oocyte maturation factor oma-1. Heritable silencing of oma-1 is a dose-dependent process where the inheritance of the silencing factor is unequally distributed among the population. Heritability is not constant over generational time, with silenced populations appearing to undergo a bottleneck three to four generations following microinjection of RNA. Transmission of silencing through these generations can be through either maternal or paternal gamete lines and is surprisingly more effective through the male gametic line. Genetic linkage tests reveal that silencing in the early generations is transmitted independently of the original targeted locus, in a manner indicative of a diffusible epigenetic element.
Different Strategies to Persist: The pogo-Like Lemi1 Transposon Produces Miniature Inverted-Repeat Transposable Elements or Typical Defective Elements in Different Plant Genomes
Authors: Guermonprez Hélène , Loot Céline , Casacuberta Josep M
Published: September 2008

Miniature inverted-repeat transposable elements (MITEs) are a particular type of defective class II elements present in genomes as high-copy-number populations of small and highly homogeneous elements. While virtually all class II transposon families contain non-autonomous defective transposon copies, only a subset of them have a related MITE family. At present it is not known in which circumstances MITEs are generated instead of typical class II defective transposons. The ability to produce MITEs could be an exclusive characteristic of particular transposases, could be related to a particular structure of certain defective class II elements, or could be the consequence of particular constraints imposed by certain host genomes on transposon populations. We describe here a new family of pogo-like transposons from Medicago truncatula closely related to the Arabidopsis Lemi1 element that we have named MtLemi1. In contrast to the Arabidopsis Lemi1, present as a single-copy element and associated with hundreds of related Emigrant MITEs, MtLemi1 has attained >30 copies and has not generated MITEs. This shows that a particular transposon can adopt completely different strategies to colonize genomes. The comparison of AtLemi1 and MtLemi1 reveals transposase-specific domains and possible regulatory sequences that could be linked to the ability to produce MITEs.
Gene Conversion and End-Joining-Repair Double-Strand Breaks in the Caenorhabditis elegans Germline
Authors: Robert Valérie J , Davis M Wayne , Jorgensen Erik M , Bessereau Jean-Louis
Published: September 2008

Excision of a Mos1 transposon in the germline of Caenorhabditis elegans generates a double-strand break in the chromosome. We demonstrate that breaks are most prominently repaired by gene conversion from the homolog, but also rarely by nonhomologous end-joining. In some cases, gene conversion events are resolved by crossing over. Surprisingly, expression of the transposase using an intestine-specific promoter can induce repair, raising the possibility that activation of transposase expression in somatic cells can lead to transposition of Mos1 in the germline.
Survival of the Currently Fittest: Genetics of Rainbow Trout Survival Across Time and Space
Authors: Vehviläinen Harri , Kause Antti , Quinton Cheryl , Koskinen Heikki , Paananen Tuija
Published: September 2008

As a fitness trait, survival is assumed to exhibit low heritability due to strong selection eroding genetic variation and/or spatio-temporal variation in mortality agents reducing genetic and increasing residual variation. The latter phenomenon in particular may contribute to low heritability in multigeneration data, even if certain cohorts exhibit significant genetic variation. Analysis of survival data from 10 year classes of rainbow trout reared at three test stations showed that treating survival as a single trait across all generations resulted in low heritability (h2 = 0.08–0.17). However, when heritabilities were estimated from homogeneous generation and test station-specific cohorts, a wide range of heritability values was revealed (h2 = 0.04–0.71). Of 64 genetic correlations between different cohorts, 20 were positive, but 16 were significantly negative, confirming that genetic architecture of survival is not stable across generations and environments. These results reveal the existence of hidden genetic variation for survival and demonstrate that treating survival as one trait over several generations may not reveal its true genetic architecture. Negative genetic correlations between cohorts indicate that overall survival has limited potential to predict general resistance, and care should be taken when using it as selection criterion.
Bacteriophage Adsorption Rate and Optimal Lysis Time
Authors: Shao Yongping , Wang Ing-Nang
Published: September 2008

The first step of bacteriophage (phage) infection is the attachment of the phage virion onto a susceptible host cell. This adsorption process is usually described by mass-action kinetics, which implicitly assume an equal influence of host density and adsorption rate on the adsorption process. Therefore, an environment with high host density can be considered as equivalent to a phage endowed with a high adsorption rate, and vice versa. On the basis of this assumption, the effect of adsorption rate on the evolution of phage optimal lysis time can be reinterpreted from previous optimality models on the evolution of optimal lysis time. That is, phage strains with a higher adsorption rate would have a shorter optimal lysis time and vice versa. Isogenic phage λ-strains with different combinations of six different lysis times (ranging from 29.3 to 68 min), two adsorption rates (9.9 × 10−9 and 1.3 × 10−9 phage−1 cell−1 ml−1 min−1), and two markers (resulting in “blue” or “white” plaques) were constructed. Various pairwise competitions among these strains were conducted to test the model prediction. As predicted by the reinterpreted model, the results showed that the optimal lysis time is shorter for phage strains with a high adsorption rate and vice versa. Competition between high- and low-adsorption strains also showed that, under current conditions and phenotype configurations, the adsorption rate has a much larger impact on phage relative fitness than the lysis time.
Human Endogenous Retrovirus (HERVK9) Structural Polymorphism With Haplotypic HLA-A Allelic Associations
Authors: Kulski Jerzy K , Shigenari Atsuko , Shiina Takashi , Ota Masao , Hosomichi Kazuyoshi , James Ian , Inoko Hidetoshi
Published: September 2008

The frequency and HLA-A allelic associations of a HERVK9 DNA structural polymorphism located in close proximity to the highly polymorphic HLA-A gene within the major histocompatibility complex (MHC) genomic region were determined in Japanese, African Americans, and Australian Caucasians to better understand its human population evolutionary history. The HERVK9 insertion or deletion was detected as a 3′ LTR or a solo LTR, respectively, by separate PCR assays. The average insertion frequency of the HERVK9.HG was significantly different (P < 1.083e−6) between the Japanese (0.59) and the African Americans (0.34) or Australian Caucasians (0.37). LD analysis predicted a highly significant (P < 1.0e−5) linkage between the HLA-A and HERVK9 alleles, probably as a result of hitchhiking (linkage). Evolutionary time estimates of the solo, 5′ and 3′ LTR nucleotide sequence divergences suggest that the HERVK9 was inserted 17.3 MYA with the first structural deletion occurring 15.1 MYA. The LTR/HLA-A haplotypes appear to have been formed mostly during the past 3.9 MY. The HERVK9 insertion and deletion, detected by a simple and economical PCR method, is an informative genetic and evolutionary marker for the study of HLA-A haplotype variations, human migration, the origins of contemporary populations, and the possibility of disease associations.
A Genomewide Linkage Scan for Quantitative Trait Loci Influencing the Craniofacial Complex in Baboons (Papio hamadryas spp.)
Authors: Sherwood Richard J , Duren Dana L , Havill Lorena M , Rogers Jeff , Cox Laura A , Towne Bradford , Mahaney Michael C
Published: September 2008

Numerous studies have detected significant contributions of genes to variation in development, size, and shape of craniofacial traits in a number of vertebrate taxa. This study examines 43 quantitative traits derived from lateral cephalographs of 830 baboons (Papio hamadryas) from the pedigreed population housed at the Southwest National Primate Research Center. Quantitative genetic analyses were conducted using the SOLAR analytic platform, a maximum-likelihood variance components method that incorporates all familial information for parameter estimation. Heritability estimates were significant and of moderate to high magnitude for all craniofacial traits. Additionally, 14 significant quantitative trait loci (QTL) were identified for 12 traits from the three developmental components (basicranium, splanchnocranium, and neurocranium) of the craniofacial complex. These QTL were found on baboon chromosomes (and human orthologs) PHA1 (HSA1), PHA 2 (HSA3), PHA4 (HSA6), PHA11 (HSA12), PHA13 (HSA2), PHA16 (HSA17), and PHA17 (HSA13) (PHA, P. hamadryas; HSA, Homo sapiens). This study of the genetic architecture of the craniofacial complex in baboons provides the groundwork needed to establish the baboon as an animal model for the study of genetic and nongenetic influences on craniofacial variation.
A Random Mutagenesis Approach to Isolate Dominant-Negative Yeastsec1Mutants Reveals a Functional Role for Domain 3a in Yeast and Mammalian Sec1/Munc18 Proteins
Authors: Boyd Alan , Ciufo Leonora F , Barclay Jeff W , Graham Margaret E , Haynes Lee P , Doherty Mary K , Riesen Michèle , Burgoyne Robert D , Morgan Alan
Published: September 2008

SNAP receptor (SNARE) and Sec1/Munc18 (SM) proteins are required for all intracellular membrane fusion events. SNAREs are widely believed to drive the fusion process, but the function of SM proteins remains unclear. To shed light on this, we screened for dominant-negative mutants of yeast Sec1 by random mutagenesis of a GAL1-regulated SEC1 plasmid. Mutants were identified on the basis of galactose-inducible growth arrest and inhibition of invertase secretion. This effect of dominant-negative sec1 was suppressed by overexpression of the vesicle (v)-SNAREs, Snc1 and Snc2, but not the target (t)-SNAREs, Sec9 and Sso2. The mutations isolated in Sec1 clustered in a hotspot within domain 3a, with F361 mutated in four different mutants. To test if this region was generally involved in SM protein function, the F361-equivalent residue in mammalian Munc18-1 (Y337) was mutated. Overexpression of the Munc18-1 Y337L mutant in bovine chromaffin cells inhibited the release kinetics of individual exocytosis events. The Y337L mutation impaired binding of Munc18-1 to the neuronal SNARE complex, but did not affect its binary interaction with syntaxin1a. Taken together, these data suggest that domain 3a of SM proteins has a functionally important role in membrane fusion. Furthermore, this approach of screening for dominant-negative mutants in yeast may be useful for other conserved proteins, to identify functionally important domains in their mammalian homologs.
The Cellular, Developmental and Population-Genetic Determinants of Mutation-Rate Evolution
Authors: Lynch Michael
Published: September 2008

Although the matter has been subject to considerable theoretical study, there are numerous open questions regarding the mechanisms driving the mutation rate in various phylogenetic lineages. Most notably, empirical evidence indicates that mutation rates are elevated in multicellular species relative to unicellular eukaryotes and prokaryotes, even on a per-cell division basis, despite the need for the avoidance of somatic damage and the accumulation of germline mutations. Here it is suggested that multicellularity discourages selection against weak mutator alleles for reasons associated with both the cellular and the population-genetic environments, thereby magnifying the vulnerability to somatic mutations (cancer) and increasing the risk of extinction from the accumulation of germline mutations. Moreover, contrary to common belief, a cost of fidelity need not be invoked to explain the lower bound to observed mutation rates, which instead may simply be set by the inability of selection to advance very weakly advantageous antimutator alleles in finite populations.
Fixation Probability for Lytic Viruses: The Attachment-Lysis Model
Authors: Patwa Z , Wahl L M
Published: September 2008

The fixation probability of a beneficial mutation is extremely sensitive to assumptions regarding the organism's life history. In this article we compute the fixation probability using a life-history model for lytic viruses, a key model organism in experimental studies of adaptation. The model assumes that attachment times are exponentially distributed, but that the lysis time, the time between attachment and host cell lysis, is constant. We assume that the growth of the wild-type viral population is controlled by periodic sampling (population bottlenecks) and also include the possibility that clearance may occur at a constant rate, for example, through washout in a chemostat. We then compute the fixation probability for mutations that increase the attachment rate, decrease the lysis time, increase the burst size, or reduce the probability of clearance. The fixation probability of these four types of beneficial mutations can be vastly different and depends critically on the time between population bottlenecks. We also explore mutations that affect lysis time, assuming that the burst size is constrained by the lysis time, for experimental protocols that sample either free phage or free phage and artificially lysed infected cells. In all cases we predict that the fixation probability of beneficial alleles is remarkably sensitive to the time between population bottlenecks.
Efficient Ends-Out Gene Targeting In Drosophila
Authors: Huang Juan , Zhou Wenke , Watson Annie M , Jan Yuh-Nung , Hong Yang
Published: September 2008

In this report, we describe several approaches to improve the scalability and throughput of major genetic crosses in ends-out gene targeting. We generated new sets of targeting vectors and fly stocks and introduced a novel negative selection marker that drastically reduced the frequency of false-positive targeting candidates.
Requirement of Rad5 for DNA Polymerase ζ-Dependent Translesion Synthesis in Saccharomyces cerevisiae
Authors: Pagès Vincent , Bresson Anne , Acharya Narottam , Prakash Satya , Fuchs Robert P , Prakash Louise
Published: September 2008

In yeast, Rad6–Rad18-dependent lesion bypass involves translesion synthesis (TLS) by DNA polymerases η or ζ or Rad5-dependent postreplication repair (PRR) in which error-free replication through the DNA lesion occurs by template switching. Rad5 functions in PRR via its two distinct activities—a ubiquitin ligase that promotes Mms2–Ubc13-mediated K63-linked polyubiquitination of PCNA at its lysine 164 residue and a DNA helicase that is specialized for replication fork regression. Both these activities are important for Rad5's ability to function in PRR. Here we provide evidence for the requirement of Rad5 in TLS mediated by Polζ. Using duplex plasmids carrying different site-specific DNA lesions—an abasic site, a cis–syn TT dimer, a (6-4) TT photoproduct, or a G-AAF adduct—we show that Rad5 is needed for Polζ-dependent TLS. Rad5 action in this role is likely to be structural, since neither the inactivation of its ubiquitin ligase activity nor the inactivation of its helicase activity impairs its role in TLS.
mei-38 Is Required for Chromosome Segregation During Meiosis in Drosophila Females
Authors: Wu Changjian , Singaram Vinod , McKim Kim S
Published: September 2008

Meiotic chromosome segregation occurs in Drosophila oocytes on an acentrosomal spindle, which raises interesting questions regarding spindle assembly and function. One is how to organize a bipolar spindle without microtubule organizing centers at the poles. Another question is how to orient the chromosomes without kinetochore capture of microtubules that grow from the poles. We have characterized the mei-38 gene in Drosophila and found it may be required for chromosome organization within the karyosome. Nondisjunction of homologous chromosomes occurs in mei-38 mutants primarily at the first meiotic division in females but not in males where centrosomes are present. Most meiotic spindles in mei-38 oocytes are bipolar but poorly organized, and the chromosomes appear disorganized at metaphase. mei-38 encodes a novel protein that is conserved in the Diptera and may be a member of a multigene family. Mei-38 was previously identified (as ssp1) due to a role in mitotic spindle assembly in a Drosophila cell line. MEI-38 protein localizes to a specific population of spindle microtubules, appearing to be excluded from the overlap of interpolar microtubules in the central spindle. We suggest MEI-38 is required for the stability of parallel microtubules, including the kinetochore microtubules.
Genetic Basis of Evolutionary Adaptation by Escherichia coli to Stressful Cycles of Freezing, Thawing and Growth
Authors: Sleight Sean C , Orlic Christian , Schneider Dominique , Lenski Richard E
Published: September 2008

Microbial evolution experiments offer a powerful approach for coupling changes in complex phenotypes, including fitness and its components, with specific mutations. Here we investigate mutations substituted in 15 lines of Escherichia coli that evolved for 1000 generations under freeze–thaw–growth (FTG) conditions. To investigate the genetic basis of their improvements, we screened many of the lines for mutations involving insertion sequence (IS) elements and identified two genes where multiple lines had similar mutations. Three lines had IS150 insertions in cls, which encodes cardiolipin synthase, and 8 lines had IS150 insertions in the uspA-uspB intergenic region, encoding two universal stress proteins. Another line had an 11-bp deletion mutation in the cls gene. Strain reconstructions and competitions demonstrated that this deletion is beneficial under the FTG regime in its evolved genetic background. Further experiments showed that this cls mutation helps maintain membrane fluidity after freezing and thawing and improves freeze–thaw (FT) survival. Reconstruction of isogenic strains also showed that the IS150 insertions in uspA/B are beneficial under the FTG regime. The evolved insertions reduce uspB transcription and increase both FT survival and recovery, but the physiological mechanism for this fitness improvement remains unknown.
Diploid/Polyploid Syntenic Shuttle Mapping and Haplotype-Specific Chromosome Walking Toward a Rust Resistance Gene (Bru1) in Highly Polyploid Sugarcane (2n ∼ 12x ∼ 115)
Authors: Le Cunff Loïc , Garsmeur Olivier , Raboin Louis Marie , Pauquet Jérome , Telismart Hugues , Selvi Athiappan , Grivet Laurent , Philippe Romain , Begum Dilara , Deu Monique , Costet Laurent , Wing Rod , Glaszmann Jean Christophe , D'Hont Angélique
Published: September 2008

The genome of modern sugarcane cultivars is highly polyploid (∼12x), aneuploid, of interspecific origin, and contains 10 Gb of DNA. Its size and complexity represent a major challenge for the isolation of agronomically important genes. Here we report on the first attempt to isolate a gene from sugarcane by map-based cloning, targeting a durable major rust resistance gene (Bru1). We describe the genomic strategies that we have developed to overcome constraints associated with high polyploidy in the successive steps of map-based cloning approaches, including diploid/polyploid syntenic shuttle mapping with two model diploid species (sorghum and rice) and haplotype-specific chromosome walking. Their applications allowed us (i) to develop a high-resolution map including markers at 0.28 and 0.14 cM on both sides and 13 markers cosegregating with Bru1 and (ii) to develop a physical map of the target haplotype that still includes two gaps at this stage due to the discovery of an insertion specific to this haplotype. These approaches will pave the way for the development of future map-based cloning approaches for sugarcane and other complex polyploid species.
Preservation of a Pseudogene by Gene Conversion and Diversifying Selection
Authors: Takuno Shohei , Nishio Takeshi , Satta Yoko , Innan Hideki
Published: September 2008

Interlocus gene conversion is considered a crucial mechanism for generating novel combinations of polymorphisms in duplicated genes. The importance of gene conversion between duplicated genes has been recognized in the major histocompatibility complex and self-incompatibility genes, which are likely subject to diversifying selection. To theoretically understand the potential role of gene conversion in such situations, forward simulations are performed in various two-locus models. The results show that gene conversion could significantly increase the number of haplotypes when diversifying selection works on both loci. We find that the tract length of gene conversion is an important factor to determine the efficacy of gene conversion: shorter tract lengths can more effectively generate novel haplotypes given the gene conversion rate per site is the same. Similar results are also obtained when one of the duplicated genes is assumed to be a pseudogene. It is suggested that a duplicated gene, even after being silenced, will contribute to increasing the variability in the other locus through gene conversion. Consequently, the fixation probability and longevity of duplicated genes increase under the presence of gene conversion. On the basis of these findings, we propose a new scenario for the preservation of a duplicated gene: when the original donor gene is under diversifying selection, a duplicated copy can be preserved by gene conversion even after it is pseudogenized.
The Influence of Gene Conversion on Linkage Disequilibrium Around a Selective Sweep
Authors: Jones Danielle A , Wakeley John
Published: September 2008

In a 2007 article, McVean studied the effect of recombination on linkage disequilibrium (LD) between two neutral loci located near a third locus that has undergone a selective sweep. The results demonstrated that two loci on the same side of a selected locus might show substantial LD, whereas the expected LD for two loci on opposite sides of a selected locus is zero. In this article, we extend McVean's model to include gene conversion. We show that one of the conclusions is strongly affected by gene conversion: when gene conversion is present, there may be substantial LD between two loci on opposite sides of a selective sweep.
A Genetic Screen Identifies New Regulators of Steroid-Triggered Programmed Cell Death in Drosophila
Authors: Wang Lei , Evans Janelle , Andrews Hillary K , Beckstead Robert B , Thummel Carl S , Bashirullah Arash
Published: September 2008

The steroid hormone ecdysone triggers the rapid and massive destruction of larval tissues through transcriptional cascades that culminate in rpr and hid expression and caspase activation. Here we describe the use of genetic screens to further our understanding of this steroid-triggered programmed cell death response. Pupal lethal mutants were screened for specific defects in larval salivary gland destruction. A pilot screen using existing P-element collections resulted in the identification of mutations in known cell death regulators, E74 and hid, as well as multiple alleles in CBP (nejire) and dTrf2. A large-scale EMS mutagenesis screen on the third chromosome resulted in the recovery of 48 mutants. These include seven multiallelic complementation groups, at least five of which do not map to regions or genes previously associated with cell death. Five mutants display defects in the transcriptional induction of rpr and hid, and all display a penetrant block in caspase activation. Three were mapped to specific genes: CG5146, which encodes a protein of unknown function, Med24, which encodes a component of the RNA polymerase II mediator complex, and CG7998, which encodes a putative mitochondrial malate dehydrogenase. These genetic screens provide new directions for understanding the regulation of programmed cell death during development.
Evaluation of Community-Based Health Projects: The Healthy Tomorrows Experience
Authors: Ruch-Ross Holly , Keller David , Miller Nicole , Bassewitz Jane , Melinkovich Paul
Published: September 2008

OBJECTIVES. To address the “millennial morbidities,” pediatricians must partner with community-based organizations to develop interventions. Little is known about the capacity of the resulting programs for program evaluation or the importance of evaluation in project success and sustainability. The objective of this study was to examine the capacity of community-based health programs to conduct project evaluations and determine the impact of project evaluation on project outcome.

METHODS. Project directors from 149 community-based programs funded from 1989 to 2003 through the Healthy Tomorrows Partnership for Children Program were surveyed regarding their project experience with evaluation and documentation of project outcomes and the current status of their project.

RESULTS. Program directors from 123 (83%) programs completed the survey. Despite barriers to the evaluation process, 83% of the respondents indicated that their evaluations produced useful information. Programs that were described by respondents as “well evaluated” were more likely to report that the evaluation was implemented as planned and that the evaluation included outcome measures. Projects were more likely to be sustained in their original form when at least 1 outcome was reported on the survey.

CONCLUSIONS. Evaluation of community-based programs, although challenging, is beneficial to project success and sustainability. Policy makers and funding agencies should consider ways to encourage community partnerships to incorporate evaluation into their planning process.
Health-Related Quality of Life for Extremely Low Birth Weight Adolescents in Canada, Germany, and the Netherlands
Authors: Verrips Erik , Vogels Ton , Saigal Saroj , Wolke Dieter , Meyer Renate , Hoult Lorraine , Verloove-Vanhorick S. Pauline
Published: September 2008

OBJECTIVE. The goal was to compare health-related quality of life of 12- to 16-year-old adolescents born at an extremely low birth weight in regional cohorts from Ontario (Canada), Bavaria (Germany), and the Netherlands.

METHODS. Patients were extremely low birth weight survivors from Canada, Germany, and the Netherlands. Health-related quality of life was assessed with Health Utilities Index 3. Missing data were substituted by proxy reports. Differences in mean Health Utilities Index 3 scores were tested by using analysis of variance. Differences in the numbers of children with affected attributes were tested by using logistic regression analyses.

RESULTS. Survival rates were similar; response rates varied between 71% and 90%. Significant differences in health-related quality of life were found between the cohorts, with Dutch children scoring highest on Health Utilities Index 3 and German children scoring lowest, independent of birth weight, gestational age, and cerebral palsy. Differences in mean utility scores were mainly attributable to differences in the cognition health attribute. Most of the results were corroborated by logistic regression analyses.

CONCLUSIONS. There were significant differences between the 3 cohorts in health-related quality of life, not related to differences in birth weight, gestational age, or cerebral palsy. Survival and response rates alone cannot explain these differences.
Elevated Temperature After Hypoxic-Ischemic Encephalopathy: Risk Factor for Adverse Outcomes
Authors: Laptook Abbot , Tyson Jon , Shankaran Seetha , McDonald Scott , Ehrenkranz Richard , Fanaroff Avroy , Donovan Edward , Goldberg Ronald , O'Shea T. Michael , Higgins Rosemary D. , Poole W. Kenneth ,   and the National Institute of Child Health and Human Development Neonatal Research Network
Published: September 2008

OBJECTIVE. The goal was to determine whether the risk of death or moderate/severe disability in term infants with hypoxic-ischemic encephalopathy increases with relatively high esophageal or skin temperature occurring between 6 and 78 hours after birth.

METHODS. This was an observational secondary study within the National Institute of Child Health and Human Development Neonatal Research Network randomized trial comparing whole-body cooling and usual care (control) for term infants with hypoxic-ischemic encephalopathy. Esophageal and skin temperatures were recorded serially for 72 hours. Each infant's temperatures for each site were rank ordered. The high temperature was defined for each infant as the mean of all temperature measurements in the upper quartile. The low temperature was similarly defined as the mean of the lower quartile. Outcomes were related to temperatures in 3 logistic regression analyses for the high, median, and low temperatures at each temperature site for each group, with adjustment for the level of encephalopathy, gender, gestational age, and race.

RESULTS. In control infants, the mean esophageal temperature was 37.2 ± 0.7°C over the 72-hour period, and 63%, 22%, and 8% of all temperatures were >37°C, >37.5°C, and >38°C, respectively. The mean skin temperature was 36.5 ± 0.8°C, and 12%, 5%, and 2% of all temperatures were >37°C, >37.5°C, and >38°C, respectively. The odds of death or disability were increased 3.6–4 fold for each 1°C increase in the highest quartile of skin or esophageal temperatures. There were no associations between temperatures and outcomes in the cooling-treated group.

CONCLUSIONS. Relatively high temperatures during usual care after hypoxia-ischemia were associated with increased risk of adverse outcomes. The results may reflect underlying brain injury and/or adverse effects of temperature on outcomes.
Identifying Postpartum Depression: Are 3 Questions as Good as 10?
Authors: Kabir Karolyn , Sheeder Jeanelle , Kelly Lisa S.
Published: September 2008

BACKGROUND. Postpartum depression is the most common medical problem that new mothers face. Anxiety is a more prominent feature of postpartum depression than of depression that occurs at other times in life. Routine, universal screening significantly improves detection in primary health care settings. Thus, an ultrabrief scale that could be incorporated into a general health survey or interview would be useful.

OBJECTIVE. We tested the hypothesis that, during the first 6 postpartum months, the 3-item anxiety subscale of the Edinburgh Postpartum Depression Scale is a better ultrabrief depression screener than 2 Edinburgh Postpartum Depression Scale questions that are almost identical to the widely used Patient Health Questionnaire.

METHODS. A cohort of 199 14- to 26-year-old participants in an adolescent-oriented maternity program completed the Edinburgh Postpartum Depression Scale at well-child visits during the first 6 postpartum months. Three subscales of the Edinburgh Postpartum Depression Scale were examined as ultrabrief alternatives: the anxiety subscale (3 items; Edinburgh Postpartum Depression Scale-3), the depressive symptoms subscale (7 items; Edinburgh Postpartum Depression Scale-7), and 2 questions that resemble the Patient Health Questionnaire (Edinburgh Postpartum Depression Scale-2). The reliability, stability, and construct validity of the Edinburgh Postpartum Depression Scale and 3 subscales were compared. Criterion validity was assessed by comparison with a score of ≥10 on the full, 10-item Edinburgh Postpartum Depression Scale.

RESULTS. A total of 41 mothers (20.6%) met study criteria for referral for evaluation of depression (Edinburgh Postpartum Depression Scale-10 score ≥ 10). The Edinburgh Postpartum Depression Scale-3 exhibited the best screening performance characteristics, with sensitivity at 95% and negative predictive value at 98%. It identified 16% more mothers as depressed than the Edinburgh Postpartum Depression Scale did. The performance of the Edinburgh Postpartum Depression Scale-2 was markedly inferior, with sensitivity at 48% to 80%. Moreover, the Edinburgh Postpartum Depression Scale-2 was unreliable for mothers who had not been depressed in the past.

CONCLUSION. The brevity, reliability, and operating characteristics of the Edinburgh Postpartum Depression Scale-3 make it an attractive postpartum depression screening tool for primary health care settings in which the goal is to detect depression, not to assess its severity. Validation by diagnostic psychiatric interview is needed.
Incidence of Fractures Attributable to Abuse in Young Hospitalized Children: Results From Analysis of a United States Database
Authors: Leventhal John M. , Martin Kimberly D. , Asnes Andrea G.
Published: September 2008

OBJECTIVE. The goal was to assess the proportion of children with fractures attributable to abuse and the incidence of fractures caused by abuse among children <36 months of age who were hospitalized in the United States.

METHODS. We used the Kids' Inpatient Database, which has discharge data on 80% of acute pediatric hospitalizations in the United States, for 3 time periods (1997, 2000, and 2003). Fractures attributable to abuse in children <36 months of age were identified by both an International Classification of Diseases, Ninth Revision, Clinical Modification code for fracture and a diagnosis external-cause-of-injury code for abuse. Weighted estimates of the incidence were calculated.

RESULTS. Among children <36 months of age who were hospitalized with fractures, the proportions of cases attributable to abuse were 11.9% in 1997, 11.9% in 2000, and 12.1% in 2003. The proportions of cases attributable to abuse decreased with increasing age; for example, in 2003, the proportions attributable to abuse were 24.9% for children <12 months of age, 7.2% for children 12 to 23 months of age, and 2.9% for children 24 to 35 months of age. In 2003, the incidence of fractures caused by abuse was 15.3 cases per 100000 children <36 months of age. The incidence was 36.1 cases per 100000 among children <12 months of age; this decreased to 4.8 cases per 100000 among 12- to 23-month-old children and 4.8 cases per 100000 among 24- to 35-month-old children.

CONCLUSIONS. The Kids' Inpatient Database can be used to provide reasonable estimates of the incidence of hospitalization with fractures attributable to child abuse. For children <12 months of age, the incidence was 36.1 cases per 100000, a rate similar to that of inflicted traumatic brain injury (25–32 cases per 100000).