bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of P Elements in Natural Populations of Drosophila willistoni and D. sturtevantiSequence data from this article have been deposited with the GenBank Data Library under accession nos. AY578739, AY578740, AY578741, AY578742, AY578743, AY578744, AY578745, AY578746, AY578747, AY578748, AY578749, AY578750, AY578751, AY578752, AY578753, AY578754, AY578755, AY578756, AY578757, AY578758, AY578759, AY578760, AY578761, AY578762, AY578763, AY578764, AY578765, AY578766, AY578767, AY578768, AY578769, AY578770, AY578771, AY578772, AY578773, AY578774, AY578775, AY578776, AY578777, AY578778, AY578779, AY578780, AY578781, AY578782, AY578783, AY578784.
Authors: Silva Joana C , Kidwell Margaret G
Published: December 2004

To determine how population structure of the host species affects the spread of transposable elements and to assess the strength of selection acting on different structural regions, we sequenced P elements from strains of Drosophila willistoni and Drosophila sturtevanti sampled from across the distributions of these species. Elements from D. sturtevanti exhibited considerable sequence variation, and similarity among them was correlated to geographic distance between collection sites. By contrast, all D. willistoni elements sampled were essentially identical (π < 0.2%) and exhibited patterns typical of a recent population expansion. While the canonical P elements sampled from D. sturtevanti appear to be long-time residents in that species, a rapid expansion of a very young canonical P-element lineage is suggested in D. willistoni, overcoming barriers such as large geographical distances and moderate levels of population subdivision. Between-species comparisons reveal selective constraints on P-element evolution, as indicated by significantly different substitution rates in noncoding, silent, and replacement sites. Most remarkably, in addition to replacement sites, selection pressure appears to be strong in the first and third introns and in the 3′ and 5′ flanking regions.
Evolutionarily Stable Infection by a Male-Killing Endosymbiont in Drosophila innubilaSequence data from this article have been deposited with the EMBL/GenBank Data Libraries under accession nos. AY541089, AY541237 and AY552552, AY552553.
Authors: Dyer Kelly A , Jaenike John
Published: December 2004

Maternally inherited microbes that spread via male-killing are common pathogens of insects, yet very little is known about the evolutionary duration of these associations. The few examples to date indicate very recent, and thus potentially transient, infections. A male-killing strain of Wolbachia has recently been discovered in natural populations of Drosophila innubila. The population-level effects of this infection are significant: ∼35% of females are infected, infected females produce very strongly female-biased sex ratios, and the resulting population-level sex ratio is significantly female biased. Using data on infection prevalence and Wolbachia transmission rates, infected cytoplasmic lineages are estimated to experience a ∼5% selective advantage relative to uninfected lineages. The evolutionary history of this infection was explored by surveying patterns of polymorphism in both the host and parasite genomes, comparing the Wolbachia wsp gene and the host mtDNA COI gene to five host nuclear genes. Molecular data suggest that this male-killing infection is evolutionarily old, a conclusion supported with a simple model of parasite and mtDNA transmission dynamics. Despite a large effective population size of the host species and strong selection to evolve resistance, the D. innubila-Wolbachia association is likely at a stable equilibrium that is maintained by imperfect maternal transmission of the bacteria rather than partial resistance in the host species.
Evolution of Dominance in Metabolic Pathways
Authors: Bagheri Homayoun C , Wagner Günter P
Published: December 2004

Dominance is a form of phenotypic robustness to mutations. Understanding how such robustness can evolve provides a window into how the relation between genotype and phenotype can evolve. As such, the issue of dominance evolution is a question about the evolution of inheritance systems. Attempts at explaining the evolution of dominance have run into two problems. One is that selection for dominance is sensitive to the frequency of heterozygotes. Accordingly, dominance cannot evolve unless special conditions lead to the presence of a high frequency of mutant alleles in the population. Second, on the basis of theoretical results in metabolic control analysis, it has been proposed that metabolic systems possess inherent constraints. These hypothetical constraints imply the default manifestation of dominance of the wild type with respect to the effects of mutations at most loci. Hence, some biologists have maintained that an evolutionary explanation is not relevant to dominance. In this article, we put into question the hypothetical assumption of default metabolic constraints. We show that this assumption is based on an exclusion of important nonlinear interactions that can occur between enzymes in a pathway. With an a priori exclusion of such interactions, the possibility of epistasis and hence dominance modification is eliminated. We present a theoretical model that integrates enzyme kinetics and population genetics to address dominance evolution in metabolic pathways. In the case of mutations that decrease enzyme concentrations, and given the mechanistic constraints of Michaelis-Menten-type catalysis, it is shown that dominance of the wild type can be extensively modified in a two-enzyme pathway. Moreover, we discuss analytical results indicating that the conclusions from the two-enzyme case can be generalized to any number of enzymes. Dominance modification is achieved chiefly through changes in enzyme concentrations or kinetic parameters such as kcat, both of which can alter saturation levels. Low saturation translates into higher levels of dominance with respect to mutations that decrease enzyme concentrations. Furthermore, it is shown that in the two-enzyme example, dominance evolves as a by-product of selection in a manner that is insensitive to the frequency of heterozygotes. Using variation in kcat as an example of modifier mutations, it is shown that the latter can have direct fitness effects in addition to dominance modification effects. Dominance evolution can occur in a frequency-insensitive manner as a result of selection for such dual-effects alleles. This type of selection may prove to be a common pattern for the evolution of phenotypic robustness to mutations.
Rearrangements in the Cf-9 Disease Resistance Gene Cluster of Wild Tomato Have Resulted in Three Genes That Mediate Avr9 ResponsivenessSequence data from this article have been deposited with the GenBank Data Libraries under accession no. AY569331.
Authors: Kruijt Marco , Brandwagt Bas F , de Wit Pierre J G M
Published: December 2004

Cf resistance genes in tomato confer resistance to the fungal leaf pathogen Cladosporium fulvum. Both the well-characterized resistance gene Cf-9 and the related 9DC gene confer resistance to strains of C. fulvum that secrete the Avr9 protein and originate from the wild tomato species Lycopersicon pimpinellifolium. We show that 9DC and Cf-9 are allelic, and we have isolated and sequenced the complete 9DC cluster of L. pimpinellifolium LA1301. This 9DC cluster harbors five full-length Cf homologs, including orthologs of the most distal homologs of the Cf-9 cluster and three central 9DC genes. Two 9DC genes (9DC1 and 9DC2) have an identical coding sequence, whereas 9DC3 differs at its 3′ terminus. From a detailed comparison of the 9DC and Cf-9 clusters, we conclude that the Cf-9 and Hcr9-9D genes from the Cf-9 cluster are ancestral to the first 9DC gene and that the three 9DC genes were generated by subsequent intra- and intergenic unequal recombination events. Thus, the 9DC cluster has undergone substantial rearrangements in the central region, but not at the ends. Using transient transformation assays, we show that all three 9DC genes confer Avr9 responsiveness, but that 9DC2 is likely the main determinant of Avr9 recognition in LA1301.
Compartmentalization of the Yeast Meiotic Nucleus Revealed by Analysis of Ectopic Recombination
Authors: Schlecht Hélène B , Lichten Michael , Goldman Alastair S H
Published: December 2004

As yeast cells enter meiosis, chromosomes move from a centromere-clustered (Rabl) to a telomere-clustered (bouquet) configuration and then to states of progressive homolog pairing where telomeres are more dispersed. It is uncertain at which stage of this process sequences commit to recombine with each other. Previous analyses using recombination between dispersed homologous sequences (ectopic recombination) support the view that, on average, homologs are aligned end to end by the time of commitment to recombination. We have undertaken further analyses incorporating new inserts, chromosome rearrangements, an alternate mode of recombination initiation, and mutants that disrupt nuclear structure or telomere metabolism. Our findings support previous conclusions and reveal that distance from the nearest telomere is an important parameter influencing recombination between dispersed sequences. In general, the farther dispersed sequences are from their nearest telomere, the less likely they are to engage in ectopic recombination. Neither the mode of initiating recombination nor the formation of the bouquet appears to affect this relationship. We suggest that aspects of telomere localization and behavior influence the organization and mobility of chromosomes along their entire length, during a critical period of meiosis I prophase that encompasses the homology search.
Testing Predictions of the Double-Strand Break Repair Model Relating to Crossing Over in Mammalian Cells
Authors: Birmingham Erin C , Lee Shauna A , McCulloch Richard D , Baker Mark D
Published: December 2004

In yeast, four-stranded, biparental “joint molecules” containing a pair of Holliday junctions are demonstrated intermediates in the repair of meiotic double-strand breaks (DSBs). Genetic and physical evidence suggests that when joint molecules are resolved by the cutting of each of the two Holliday junctions, crossover products result at least most of the time. The double-strand break repair (DSBR) model is currently accepted as a paradigm for acts of DSB repair that lead to crossing over. In this study, a well-defined mammalian gene-targeting assay was used to test predictions that the DSBR model makes about the frequency and position of hDNA in recombinants generated by crossing over. The DSBR model predicts that hDNA will frequently form on opposite sides of the DSB in the two homologous sequences undergoing recombination [half conversion (HC); 5:3, 5:3 segregation]. By examining the segregation patterns of poorly repairable small palindrome genetic markers, we show that this configuration of hDNA is rare. Instead, in a large number of recombinants, full conversion (FC) events in the direction of the unbroken chromosomal sequence (6:2 segregation) were observed on one side of the DSB. A conspicuous fraction of the unidirectional FC events was associated with normal 4:4 marker segregation on the other side of the DSB. In addition, a large number of recombinants displayed evidence of hDNA formation. In several, hDNA was symmetrical on one side of the DSB, suggesting that the two homologous regions undergoing recombination swapped single strands of the same polarity. These data are considered within the context of modified versions of the DSBR model.
Mutation and Evolution of Microsatellite Loci in Neurospora
Authors: Dettman Jeremy R , Taylor John W
Published: December 2004

The patterns of mutation and evolution at 13 microsatellite loci were studied in the filamentous fungal genus Neurospora. First, a detailed investigation was performed on five microsatellite loci by sequencing each microsatellite, together with its nonrepetitive flanking regions, from a set of 147 individuals from eight species of Neurospora. To elucidate the genealogical relationships among microsatellite alleles, repeat number was mapped onto trees constructed from flanking-sequence data. This approach allowed the potentially convergent microsatellite mutations to be placed in the evolutionary context of the less rapidly evolving flanking regions, revealing the complexities of the mutational processes that have generated the allelic diversity conventionally assessed in population genetic studies. In addition to changes in repeat number, frequent substitution mutations within the microsatellites were detected, as were substitutions and insertion/deletions within the flanking regions. By comparing microsatellite and flanking-sequence divergence, clear evidence of interspecific allele length homoplasy and microsatellite mutational saturation was observed, suggesting that these loci are not appropriate for inferring phylogenetic relationships among species. In contrast, little evidence of intraspecific mutational saturation was observed, confirming the utility of these loci for population-level analyses. Frequency distributions of alleles within species were generally consistent with the stepwise mutational model. By comparing variation within species at the microsatellites and the flanking-sequence, estimated microsatellite mutation rates were ∼2500 times greater than mutation rates of flanking DNA and were consistent with estimates from yeast and fruit flies. A positive relationship between repeat number and variance in repeat number was significant across three genealogical depths, suggesting that longer microsatellite alleles are more mutable than shorter alleles. To test if the observed patterns of microsatellite variation and mutation could be generalized, an additional eight microsatellite loci were characterized and sequenced from a subset of the same Neurospora individuals.
Genotype-Environment Interactions of Spontaneous Mutations for Vegetative Fitness in the Human Pathogenic Fungus Cryptococcus neoformans
Authors: Xu Jianping
Published: December 2004

Spontaneous mutation is the ultimate source of all genetic variation. By interacting with environmental factors, genetic variation determines the phenotype and fitness of individuals in natural populations. However, except in a few model organisms, relatively little is known about the patterns of genotype-environment interactions of spontaneous mutations. Here I examine the rates of spontaneous mutation and the patterns of genotype-environment interaction of mutations affecting vegetative growth in the human fungal pathogen Cryptococcus neoformans. Eight mutation accumulation (MA) lines were established from a single clone on the nutrient-rich medium YEPD for each of two temperatures, 25° and 37°. Cells from generations 100, 200, 400, and 600 for each of the 16 MA lines were stored and assayed for vegetative growth rates under each of four conditions: (i) 25° on SD (a synthetic dextrose minimal medium); (ii) 25° on YEPD; (iii) 37° on SD; and (iv) 37° on YEPD. Both MA conditions and assay environments for vegetative growth showed significant influence on the estimates of genomic mutation rates, average effect per mutation, and mutational heritability. Significant genotype-environment interactions were detected among the newly accumulated spontaneous mutations. Overall, clones from MA lines maintained at 37° showed less decline in vegetative fitness than those maintained at 25°. The result suggests that a high-temperature environment might be very important for the maintenance of the ability to grow at a high temperature. Results from comparisons between clinical and environmental samples of C. neoformans were consistent with laboratory experimental population analyses. This study calls into question our long-standing view that warm-blooded mammals were only occasional and accidental hosts of this human fungal pathogen.
Maximum-Likelihood Estimation of Demographic Parameters Using the Frequency Spectrum of Unlinked Single-Nucleotide Polymorphisms
Authors: Adams Alison M , Hudson Richard R
Published: December 2004

A maximum-likelihood method for demographic inference is applied to data sets consisting of the frequency spectrum of unlinked single-nucleotide polymorphisms (SNPs). We use simulation analyses to explore the effect of sample size and number of polymorphic sites on both the power to reject the null hypothesis of constant population size and the properties of two- and three-dimensional maximum-likelihood estimators (MLEs). Large amounts of data are required to produce accurate demographic inferences, particularly for scenarios of recent growth. Properties of the MLEs are highly dependent upon the demographic scenario, as estimates improve with a more ancient time of growth onset and smaller degree of growth. Severe episodes of growth lead to an upward bias in the estimates of the current population size, and that bias increases with the magnitude of growth. One data set of African origin supports a model of mild, ancient growth, and another is compatible with both constant population size and a variety of growth scenarios, rejecting greater than fivefold growth beginning >36,000 years ago. Analysis of a data set of European origin indicates a bottlenecked population history, with an 85% population reduction occurring ∼30,000 years ago.
Gene Deletions by Ends-In Targeting in Drosophila melanogaster
Authors: Xie Heng B , Golic Kent G
Published: December 2004

Following the advent of a gene targeting technique in Drosophila, different methods have been developed to modify the Drosophila genome. The initial demonstration of gene targeting in flies used an ends-in method, which generates a duplication of the target locus. The duplicated locus can then be efficiently reduced to a single copy by generating a double-strand break between the duplicated segments. This method has been used to knock out target genes by introducing point mutations. A derivative of this method is reported here. By using different homologous regions for the targeting and reduction steps, a complete deletion of the target gene can be generated to produce a definitive null allele. The breakpoints of the deletion can be precisely controlled. Unlike ends-out targeting, this method does not leave exogenous sequence at the deleted locus. Three endogenous genes, Sir2, Sirt2, and p53 have been successfully deleted using this method.
A Unified Statistical Model for Functional Mapping of Environment-Dependent Genetic Expression and Genotype × Environment Interactions for Ontogenetic Development
Authors: Zhao Wei , Zhu Jun , Gallo-Meagher Maria , Wu Rongling
Published: December 2004

The effects of quantitative trait loci (QTL) on phenotypic development may depend on the environment (QTL × environment interaction), other QTL (genetic epistasis), or both. In this article, we present a new statistical model for characterizing specific QTL that display environment-dependent genetic expressions and genotype × environment interactions for developmental trajectories. Our model was derived within the maximum-likelihood-based mixture model framework, incorporated by biologically meaningful growth equations and environment-dependent genetic effects of QTL, and implemented with the EM algorithm. With this model, we can characterize the dynamic patterns of genetic effects of QTL governing growth curves and estimate the global effect of the underlying QTL during the course of growth and development. In a real example with rice, our model has successfully detected several QTL that produce differences in their genetic expression between two contrasting environments. These detected QTL cause significant genotype × environment interactions for some fundamental aspects of growth trajectories. The model provides the basis for deciphering the genetic architecture of trait expression adjusted to different biotic and abiotic environments and genetic relationships for growth rates and the timing of life-history events for any organism.
Genetic Analysis of the Caenorhabditis elegans pax-6 Locus
Authors: Cinar Hediye Nese , Chisholm Andrew D
Published: December 2004

PAX-6 proteins are involved in eye and brain development in many animals. In the nematode Caenorhabditis elegans the pax-6 locus encodes multiple PAX-6 isoforms both with and without a paired domain. Mutations in the C. elegans pax-6 locus can be grouped into three classes. Mutations that affect paired domain-containing isoforms cause defects in epidermal morphogenesis, epidermal cell fates, and gonad cell migration and define the class I (vab-3) complementation group. The class II mutation mab-18(bx23) affects nonpaired domain-containing isoforms and transforms the fate of a sensory organ in the male tail. Class III mutations affect both paired domain and nonpaired domain isoforms; the most severe class III mutations are candidate null mutations in pax-6. Class III mutant phenotypes do not resemble a simple sum of class I and class II phenotypes. A comparison of class I and class III phenotypes indicates that PAX-6 isoforms can interact additively, synergistically, or antagonistically, depending on the cellular context.
An Arabidopsis thaliana Plasma Membrane Proton Pump Is Essential for Pollen Development
Authors: Robertson Whitney R , Clark Katherine , Young Jeffery C , Sussman Michael R
Published: December 2004

The plasma membrane proton pump (H+-ATPase) found in plants and fungi is a P-type ATPase with a polypeptide sequence, structure, and in vivo function similar to the mammalian sodium pump (Na+, K+-ATPase). Despite its hypothetical importance for generating and maintaining the proton motive force that energizes the carriers and channels that underlie plant nutrition, genetic evidence for such a central function has not yet been reported. Using a reverse genetic approach for investigating each of the 11 isoforms in the Arabidopsis H+-ATPase (AHA) gene family, we found that one member, AHA3, is essential for pollen formation. A causative role for AHA3 in male gametogenesis was proven by complementation with a normal transgenic gene and rescue of the mutant phenotype back to wild type. We also investigated the requirement for phosphorylation of the penultimate threonine, which is found in most members of the AHA family and is thought to be involved in regulating catalytic activity. We demonstrated that a T948D mutant form of the AHA3 gene rescues the mutant phenotype in knockout AHA3 plants, but T948A does not, providing the first in planta evidence in support of the model in which phosphorylation of this amino acid is essential.
Genetic Interactions of Drosophila melanogaster arrest Reveal Roles for Translational Repressor Bruno in Accumulation of Gurken and Activity of Delta
Authors: Yan Nan , Macdonald Paul M
Published: December 2004

arrest mutants have pleiotropic phenotypes, ranging from an early arrest of oogenesis to irregular embryonic segmentation defects. One function of arrest is in translational repression of oskar mRNA; this biochemical activity is presumed to be involved in other functions of arrest. To identify genes that could provide insight into how arrest contributes to translational repression or that may be targets for arrest-dependent translational control, we screened deficiency mutants for dominant modification of the arrest phenotype. Only four of the many deficiencies tested, which cover ∼30% of the genome, modified the starting phenotype. One enhancer, identified fortuitously, is the Star gene. Star interaction with arrest results in excess Gurken protein, supporting the model that gurken is a target of repression. Two modifiers were mapped to individual genes. One is Lk6, which encodes a protein kinase predicted to regulate the rate-limiting initiation factor eIF4E. The second is Delta. The interaction between arrest and Delta mimics the phenotype of homozygous Delta mutants, suggesting that arrest could positively control Delta activity. Indeed, arrest mutants have significantly reduced levels of Delta protein at the interface of germline and follicle cells.
Expressive language in children with Kabuki syndrome
Authors: Defloor Truus , van Borsel John , Schrander‐Stumpel Constance T.R.M. , Curfs Leopold M.G.
Published: December 2004

Since the description of Kabuki syndrome in 1981 over 300 cases from a variety of countries have been reported. Only a limited number of these reports, however, provided data on speech language development. Ghent University Hospital (J. Van Borsel, T. Defloor) and the Department of Clinical Genetics, Academic Hospital Maastricht (C.T.R.M. Schrander‐Stumpel, L.M.G. Curfs) are directing research on the specific nature of communicative development in persons with Kabuki syndrome. The aim of the present study was to delineate the language difficulties in the syndrome. The subjects were six Dutch‐speaking children (three male, three female), with chronological age ranging from 4.4 to 10.6 years (mean = 8.1). Spontaneous speech samples were collected, subjected to a consensus orthographic transcription, and analyzed by means of TOAST [Moerman‐Coetsier and Van Besien, 1987], a Dutch standardized diagnostic instrument to investigate different aspects of spontaneous language production. In all the children, expressive language abilities were impaired. Poor morphosyntactic abilities were consistently demonstrated. Lexical and pragmatic difficulties were also present, whereas phonological development was less often affected. © 2004 Wiley‐Liss, Inc.
Supernumerary ring chromosome 7 mosaicism: Case report, investigation of the gene content, and delineation of the phenotype
Authors: Lichtenbelt K.D. , Hochstenbach R. , van Dam W.M. , Eleveld M.J. , Poot M. , Beemer F.A.
Published: December 2004

We report a girl with severe retardation of expressive speech development carrying a small, supernumerary ring chromosome derived from the proximal region of the long arm of chromosome 7. The r(7) chromosome is present in 50% of lymphocytes. We also review the six additional cases with a supernumerary r(7) chromosome reported in the literature. Among these patients, a severe retardation of productive language capabilities is seen as a shared clinical feature, irrespective of the degree of mosaicism as detected in blood. The dysmorphisms in these patients are minor and no shared congenital abnormalities seen. We, therefore, recommend chromosomal investigations in children with unexplained, disproportionately retarded expressive speech performance. Because speech and language acquisition are subject to genetic influences, we investigated whether there are genes on the r(7) chromosome that may affect brain development or function in a dosage‐dependent manner. We found that both in our patient and in four patients described by others, the supernumerary r(7) chromosome contains the region from the centromere up to marker D7S613 located at 7q11.23. We speculate that the effects on speech acquisition are mediated by the supernumerary copies of the STX1A and LIMK1 genes, which are both located in this region and known to suppress neurite growth when overexpressed in vitro. © 2004 Wiley‐Liss, Inc.
Kabuki syndrome is not caused by an 8p duplication: A cytogenetic study in 20 patients
Authors: Engelen John J.M. , Loneus Wim H. , Vaes‐Peeters Gerrie , Schrander‐Stumpel Constance T.R.M.
Published: December 2004

Kabuki syndrome is charcterized by a typical facial gestalt in combination with hypotonia and joint laxity, developmental delay, persistent fetal fingertip pads, and structural abnormalities mainly of the palate and the heart. Cytogenetic conditions may present with features of the syndrome. Recently, Milunsky and Huang [2003], reported an 8p duplication at chromosome 8p22‐8p23.1 in 6 patients with Kabuki syndrome. We studied 20 individuals with Kabuki syndrome and were not able to confirm this finding. Kabuki syndrome remains a clinical diagnosis in the majority of cases. © 2004 Wiley‐Liss, Inc.
Fine mapping of a region on chromosome 8p gives evidence for a QTL contributing to individual differences in an anxiety‐related personality trait: TPQ harm avoidance
Authors: Dina Christian , Nemanov Lubov , Gritsenko Inga , Rosolio Naama , Osher Yamima , Heresco‐Levy Uri , Sariashvilli Emma , Bachner‐Melman Rachel , Zohar Ada H. , Benjamin Jonathan , Belmaker Robert H. , Ebstein Richard P.
Published: December 2004

The chromosome 8p region is of interest in human behavioral genetics since it harbors a susceptibility region not only for schizophrenia but also for anxiety‐related personality traits such as harm avoidance and neuroticism. Towards verifying our preliminary linkage finding of a QTL for TPQ harm avoidance at chromosome 8p, we have now genotyped altogether 24 micro‐satellite markers in 377 families. Using three methods (maximum likelihood binomial or MLB, MERLIN, and an associated one parameter model), we observed significant results (P values from 0.002 to 0.0004) for linkage to harm avoidance in this region. A peak multipoint LOD score of 2.76 (P value 0.0002) was obtained with the MLB method. The region‐wide empirical P value was 0.002 [0.001–0.0046]. Although, the peak position varied somewhat according to the method (D8S1048 for MLB, D8S1463 for the two other methods), for three methods D8S1810 (∼60 cM) is within 1–2 cM of the peak for harm avoidance. This marker is of particular interest since it is proximate (<0.5 cM) of the core haplotype that in several recent studies show significant association with schizophrenia near neuroregulin 1. Although association studies with microsatellite markers need to be interpreted cautiously, using the Haplotype Trend Regression test one marker, D8S499 (∼60 cM), showed an empirical P value of 2 × 10−5 for allele 3, which confers a decreased harm avoidance score. Altogether, the current linkage and association results suggest the possibility that the same locus near the neuroregulin 1 gene on chromosome 8p confers risk for both an anxiety‐related personality trait as well as schizophrenia. We hypothesize that this common genetic factor may contribute to emotional liability during early development, which constitutes a predisposing factor for major psychosis. © 2004 Wiley‐Liss, Inc.
Quantitative trait locus analysis of candidate gene alleles associated with attention deficit hyperactivity disorder (ADHD) in five genes: DRD4, DAT1, DRD5, SNAP‐25, and 5HT1B
Authors: Mill Jonathan , Xu Xiaohui , Ronald Angelica , Curran Sarah , Price Tom , Knight Jo , Craig Ian , Sham Pak , Plomin Robert , Asherson Philip
Published: December 2004

It has been widely postulated that the categorical diagnosis of attention deficit hyperactivity disorder (ADHD) should be seen as the extreme end of a set of traits quantitatively distributed in the general population. A consequence of this is that the genes associated with DSM‐IV ADHD should also influence these underlying traits in non‐affected individuals. The aim of this study was to examine if specific candidate loci previously shown to be associated with DSM‐IV ADHD, also act as quantitative trait loci (QTLs) for ADHD‐symptoms in the general population. We have genotyped five candidate markers in a population‐based sample of male dizygous twin‐pairs (n = 329 pairs). We found little evidence to support a role for the previously‐nominated alleles of a DRD4 VNTR, a 5HT1B SNP, or a microsatellite marker near to DRD5, in the distribution of ADHD‐symptoms scores; however, we found some evidence to suggest that the DAT1 3′UTR VNTR and weak evidence that a microsatellite in SNAP‐25 may have a role in continuous measures of ADHD‐symptoms hyperactivity above and beyond their role in clinical ADHD. © 2004 Wiley‐Liss, Inc.
The 3111T/C polymorphism of hClock is associated with evening preference and delayed sleep timing in a Japanese population sample
Authors: Mishima Kazuo , Tozawa Takuma , Satoh Kohtoku , Saitoh Hidetomo , Mishima Yumiko
Published: December 2004

Sleep timing is influenced by the circadian system. Morningness‐eveningness (ME) preference in humans is affected by the free‐running period, which is determined by circadian clock‐relevant genes. In this study, we investigated association between the 3111T/C polymorphism in the 3′‐flanking region of hClock (Homo sapiens Clock homolog) and ME preference in 421 Japanese subjects. The Horne–Ostberg ME questionnaire (MEQ) scores showed normal distribution, with mean score of 51.2 ± 1.4 (range, 25–73), and scores were positively correlated with sleep onset time (r = 0.541, P < 0.001) and wake time (r = 0.513, P < 0.001). MEQ scores were significantly lower in subjects with 3111C/C (n = 12) than in subjects with 3111T/C (n = 106, P < 0.001) or 3111T/T (n = 303, P < 0.001), suggesting a stronger eveningness preference in 3111C/C homozygotes. This group also showed significantly delayed sleep onset (P < 0.001), shorter sleep time (P < 0.001), and greater daytime sleepiness (P < 0.001) in comparison to parameters in the subjects with the 3111T allele. There was no significant difference in any of these parameters between the 3111C/T and 3111T/T genotypes. The influence of the 3111T/C polymorphism on ME preferences in Caucasian populations remains controversial. The present findings in a Japanese population sample, which should have a relatively low risk of population stratification effects, suggest the significance of the association of the 3111C/C allele of hClock with evening preference. © 2004 Wiley‐Liss, Inc.
Dopamine receptor D4 (DRD4) gene in Han Chinese children with attention‐deficit/hyperactivity disorder (ADHD): Increased prevalence of the 2‐repeat allele
Authors: Leung Patrick W.L. , Lee C.C. , Hung S.F. , Ho T.P. , Tang C.P. , Kwong S.L. , Leung S.Y. , Yuen S.T. , Lieh‐Mak F. , Oosterlaan Jaap , Grady Deborah , Harxhi Ante , Ding Y.C. , Chi H.C. , Flodman Pamela , Schuck Sabrina , Spence M. Anne , Moyzis Robert , Swanson James
Published: December 2004

There is an increased prevalence of the 7‐repeat (7R) allele of the dopamine receptor D4 (DRD4) gene in attention‐deficit/hyperactivity disorder (ADHD). However, the population prevalence of the 7R allele varies considerably across ethnicity and is very low in Asians. To test whether this 7R allele/ADHD association still held in a Chinese clinical sample, 32 Han Chinese children with a confirmed ADHD diagnosis and normal IQ who were methylphenidate‐responders were genotyped. None of them had a DRD4 7R allele. Instead, we observed a significantly increased prevalence of the 2‐repeat (2R) allele in this clinical sample (33%) compared to ethnically‐matched controls (20%) (χ2(1d.f.) = 5.90, P = 0.015). This approximately 1.65‐fold increase of the 2R allele in our probands is close to the observed increase of the 7R allele in European‐ancestry ADHD children. Recent genetic studies have indicated that the 2R allele in Asians is likely derived from the 7R allele. Further, available biochemical data indicate that both the 2R and 7R protein have blunted responses to dopamine compared to the 4R protein. Based on these results, we propose that the observed increased prevalence of the 2R allele in our Han Chinese ADHD probands is still consistent with the 7R allele hypothesis of ADHD in European‐ancestry children. Recent studies have suggested that any variant from the conserved ancestral 4R allele might potentially alter biochemistry/phenotype. We hypothesize that an increased frequency of any non‐4R allele may define the association of the DRD4 gene with ADHD that holds across ethnicity. The present findings, however, obtained with a small ADHD sample size, should be replicated. © 2004 Wiley‐Liss, Inc.
A flexible interface design for Web directories to accommodate different cognitive styles
Authors: Chen Sherry Y. , Magoulas George D. , Dimakopoulos Dionisios
Published: December 2004

Search engines are very popular tools for collecting information from distributed resources. They provide not only search facilities, but they also offer directories for users to browse content divided into groups. In this paper, we've adopted an individual differences approach to explore user's attitudes towards various interface features provided by existing Web directories. Among a variety of individual differences, cognitive style is a particularly important characteristic that influences the effectiveness of information seeking. Empirical results indicate that users' cognitive styles influence their reactions to the organization of subject categories, presentation of the results, and screen layout. We developed a set of design guidelines on the basis of these results, and propose a flexible interface that adopts these guidelines to accommodate the preferences of different cognitive style groups.
Scatter of journals and literature obsolescence reflected in document delivery requests
Authors: Tonta Yaşar , Ünal Yurdagül
Published: December 2004

In this paper we investigate the scattering of journals and literature obsolescence reflected in more than 137,000 document delivery requests submitted to a national document delivery service. We first summarize the major findings of the study with regards to the performance of the service. We then identify the “core” journals from which article requests were satisfied and address the following research questions: (a) Does the distribution of (core) journals conform to the Bradford's Law of Scattering? (b) Is there a relationship between usage of journals and impact factors, journals with high impact factors being used more often than the rest? (c) Is there a relationship between usage of journals and total citation counts, journals with high total citation counts being used more often than the rest? (d) What is the median age of use (half‐life) of requested articles in general? (e) Do requested articles that appear in core journals get obsolete more slowly? (f) Is there a relationship between obsolescence and journal impact factors, journals with high impact factors being obsolete more slowly? (g) Is there a relationship between obsolescence and total citation counts, journals with high total citation counts being obsolete more slowly? Based on the analysis of findings, we found that the distribution of highly and moderately used journal titles conform to Bradford's Law. The median age of use was 8 years for all requested articles. Ninety percent of the articles requested were 21 years of age or younger. Articles that appeared in 168 core journal titles seem to get obsolete slightly more slowly than those of all titles. We observed no statistically significant correlations between the frequency of journal use and ISI journal impact factors, and between the frequency of journal use and ISI‐ (Institute for Scientific Information, Philadelphia, PA) cited half‐lives for the most heavily used 168 core journal titles. There was a weak correlation between usage of journals and ISI‐reported total citation counts. No statistically significant relationship was found between median age of use and journal impact factors and between median age of use and total citation counts. There was a weak negative correlation between ISI journal impact factors and cited half‐lives of 168 core journals, and a weak correlation between ISI citation half‐lives and use half‐lives of core journals. No correlation was found between cited half‐lives of 168 core journals and their corresponding total citation counts as reported by ISI. Findings of the current study are discussed along with those of other studies.
Trust‐based secure information sharing between federal government agencies
Authors: Liu Peng , Chetal Amit
Published: December 2004

The September 11 attack and the following investigations show that there is a serious information sharing problem among the relevant federal government agencies, and the problem can cause substantial deficiencies in terrorism attack detection. In this paper we provide a systematic analysis of the causes of this problem; and conclude that existing secure information sharing technologies and protocols cannot provide enough incentives for government agencies to share information with each other without worrying that their own interests can be jeopardized. Although trust‐based information access is well studied in the literature, the existing trust models, which are based on certified attributes, cannot support effective information sharing among government agencies, which requires an interest‐based trust model. To solve this information sharing problem, we propose an innovative interest‐based trust model and a novel information sharing protocol, where a family of information sharing policies are integrated, and information exchange and trust negotiation are interleaved with and interdependent upon each other. In addition, an implementation of this protocol is presented using the emerging technology of XML Web Services. The implementation is totally compatible with the Federal Enterprise Architecture reference models and can be directly integrated into existing E‐Government systems.
Exploring the Active‐Site of a Rationally Redesigned Lipase for Catalysis of Michael‐Type Additions
Authors: Carlqvist Peter , Svedendahl Maria , Branneby Cecilia , Hult Karl , Brinck Tore , Berglund Per
Published: December 2004

Michael‐type additions of various thiols and α,β‐unsaturated carbonyl compounds were performed in organic solvent catalyzed by wild‐type and a rationally redesigned mutant of Candida antarctica lipase B. The mutant lacks the nucleophilic serine 105 in the active‐site; this results in a changed catalytic mechanism of the enzyme. The possibility of utilizing this mutant for Michael‐type additions was initially explored by quantum‐chemical calculations on the reaction between acrolein and methanethiol in a model system. The model system was constructed on the basis of docking and molecular‐dynamics simulations and was designed to simulate the catalytic properties of the active site. The catalytic system was explored experimentally with a range of different substrates. The kcat values were found to be in the range of 10−3 to 4 min−1, similar to the values obtained with aldolase antibodies. The enzyme proficiency was 107. Furthermore, the Michael‐type reactions followed saturation kinetics and were confirmed to take place in the enzyme active site.
Metallophilicity versus π–π Interactions: Ligand‐Unsupported Argentophilicity/Cuprophilicity in Oligomers‐of‐Dimers [M2L2]n (M=CuI or AgI, L=tridentate ligand)
Authors: Zhang Jie‐Peng , Wang Yi‐Bo , Huang Xiao‐Chun , Lin Yan‐Yong , Chen Xiao‐Ming
Published: December 2004

To verify whether attractive metallophilic interactions exist in the dimer‐of‐dimers [Cu2(ophen)2]2 (Hophen=1H‐[1,10]phenanthrolin‐2‐one) (1), we designed and synthesized a series of such [M2L2]2 structures by varying the d10 metal and/or the ligand (M=CuI or AgI, L=ophen or obpy; Hobpy=1H‐[2,2′]bipyridinyl‐6‐one), and have successfully obtained three dimers‐of‐dimers: [Ag2(ophen)2]2⋅6 H2O (2), [Cu2(obpy)2]2 (3), and [Ag2(obpy)2]2⋅4.5 H2O⋅0.5 DMF (4). X‐ray analyses of these structures show that interdimer MM separations in [Ag2(ophen)2]2 (3.199 Å) are remarkably shorter than those in [Cu2(ophen)2]2 (3.595 Å). Shorter interdimer MM separations are found in the structures of [M2(obpy)2]2 (2.986 and 2.993 Å in [Cu2(obpy)2]2, 3.037 to 3.093 Å in [Ag2(obpy)2]2), in which the π systems are smaller than in the complexes with the ophen ligand. Detailed structural comparison of these dimers‐of‐dimers indicates that the interdimer, face‐to‐face π–π interactions repulse rather than support the interdimer metal–metal attractive interactions. This study also yields qualitative comparison of the strengths between argentophilic, cuprophilic, and face‐to‐face π–π interactions. DFT calculations on the four dimers‐of‐dimers further support the above deduction. The structure of a trimer‐of‐dimers [Ag2(obpy)2]3 (AgAg 3.171 to 3.274 Å) is further evidence that the oligomerization of the [M2L2] molecules is favored by stronger metallophilic and weaker face‐to‐face π–π interactions.
Molecular characterization and developmental expression pattern of the chicken apolipoprotein D gene: Implications for the evolution of vertebrate lipocalins
Authors: Ganfornina María D. , Sánchez Diego , Pagano Aldo , Tonachini Laura , Descalzi‐Cancedda Fiorella , Martínez Salvador
Published: December 2004

The insect Lazarillo and the mammalian apolipoprotein D (ApoD) are orthologous members of the lipocalin protein family. We report the cloning and embryonic expression of chicken ApoD, the first molecularly characterized nonmammalian ApoD. We also report the ApoD expression in mouse during postnatal development and some novel aspects of the expression of the paralogous lipocalin prostaglandin D‐synthase (PGDS) and discuss these results in view of the lipocalin family evolution in vertebrates. ApoD is expressed in subsets of central nervous system (CNS) neurons and glia during late chicken embryogenesis. Contrary to mouse ApoD, no expression appears in neural crest‐derived cephalic mesenchyme and blood vessel pericytes. Also, ApoD is expressed in developing chicken feathers. These expressions are corroborated by quantitative reverse transcriptase‐polymerase chain reaction profiles. ApoD is expressed during mouse postnatal development in a subset of CNS neurons, astrocytes and oligodendrocytes, but also in meninges and pericytes. Chicken PGDS is expressed in brain meninges and perivascular cells. Our results suggest that the amniote last common ancestor expressed ApoD and PGDS in the brain during embryogenesis. ApoD appears restricted to ectodermal derivatives, whereas PGDS is expressed by derivatives of the three germ layers. Developmental Dynamics 232:191–199, 2005. © 2004 Wiley‐Liss, Inc.
Abnormal development of the intercostal muscles and the rib cage inMyf5−/− embryos leads to pulmonary hypoplasia
Authors: Inanlou Mohammad Reza , Kablar Boris
Published: December 2004

The aim of our study was to investigate the importance of pulmonary distension and fetal breathing‐like movements executed by the contractile activity of the intercostal respiratory muscles for proper lung growth and maturation. Lung development inMyf5−/−embryos, lacking the rib cage and functional intercostal musculature, was compared with wild‐type controls at embryonic days 14.5, 16.5, and 18.5. Our data revealed thatMyf5−/−embryos suffered from pulmonary hypoplasia in part due to the decreased number of proliferating lung cells and in part due to the increased number of terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) ‐positive cells. In addition, the proximal‐to‐distal expression gradient of thyroid transcription factor‐1 observed in wild‐type embryos was not maintained inMyf5−/−embryos. The number of lung cells expressing platelet‐derived growth factor‐BB, its receptor and insulin growth factor‐I was significantly decreased in the hypoplastic lung. By contrast, no difference in the expression pattern of surfactant associated proteins or Clara cells marker was detected between wild‐type andMyf5−/−embryos. Collectively, our data suggest that the mechanochemical signal transduction pathway used in vitro is also effective in vivo influencing lung growth but not lung cell maturation and resulting in lung hypoplasia. These data affirm the role of fetal breathing‐like movements in lung organogenesis. Developmental Dynamics 232:43–54, 2005. © 2004 Wiley‐Liss, Inc.