bluuebunny/crossref_metadata_2025 huggingface dataset:
Universality for generalized Euler products
Authors: Steuding Rasa
Published: May 2007

In the paper, following ideas of Bohr and Bagchi, we present a new equivalent formulation of the Riemann hypothesis for the Riemann zeta-function ζ(
Compositional universality in the N-dimensional ball
Authors: Bernal-González L. , Bonilla A. , Calderón-Moreno M.C.
Published: May 2007

It is proved in this note that a sequence of automorphisms on the
Bayesian Multiple Quantitative Trait Loci Mapping for Complex Traits Using Markers of the Entire Genome
Authors: Huang Hanwen , Eversley Chevonne D , Threadgill David W , Zou Fei
Published: May 2007

A Bayesian methodology has been developed for multiple quantitative trait loci (QTL) mapping of complex binary traits that follow liability threshold models. Unlike most QTL mapping methods where only one or a few markers are used at a time, the proposed method utilizes all markers across the genome simultaneously. The outperformance of our Bayesian method over the traditional single-marker analysis and interval mapping has been illustrated via simulations and real data analysis to identify candidate loci associated with colorectal cancer.
Beneficial Mutation–Selection Balance and the Effect of Linkage on Positive Selection
Authors: Desai Michael M , Fisher Daniel S
Published: May 2007

When beneficial mutations are rare, they accumulate by a series of selective sweeps. But when they are common, many beneficial mutations will occur before any can fix, so there will be many different mutant lineages in the population concurrently. In an asexual population, these different mutant lineages interfere and not all can fix simultaneously. In addition, further beneficial mutations can accumulate in mutant lineages while these are still a minority of the population. In this article, we analyze the dynamics of such multiple mutations and the interplay between multiple mutations and interference between clones. These result in substantial variation in fitness accumulating within a single asexual population. The amount of variation is determined by a balance between selection, which destroys variation, and beneficial mutations, which create more. The behavior depends in a subtle way on the population parameters: the population size, the beneficial mutation rate, and the distribution of the fitness increments of the potential beneficial mutations. The mutation–selection balance leads to a continually evolving population with a steady-state fitness variation. This variation increases logarithmically with both population size and mutation rate and sets the rate at which the population accumulates beneficial mutations, which thus also grows only logarithmically with population size and mutation rate. These results imply that mutator phenotypes are less effective in larger asexual populations. They also have consequences for the advantages (or disadvantages) of sex via the Fisher–Muller effect; these are discussed briefly.
Two-Locus Epistasis With Sexually Antagonistic Selection: A Genetic Parrondo's Paradox
Authors: Reed Floyd A
Published: May 2007

An example is provided where, with antagonistic selection and epistatic interaction of alleles at two loci, an autosomal allele can rise in frequency, persist in the population, and even continue to fixation, despite having an apparently lower average fitness than the alternative allele, in a process similar to Parrondo's paradox.
Patterns of Recombination and MLH1 Foci Density Along Mouse Chromosomes: Modeling Effects of Interference and Obligate Chiasma
Authors: Falque M , Mercier R , Mézard C , de Vienne D , Martin O C
Published: May 2007

Crossover interference in meiosis is often modeled via stationary renewal processes. Here we consider a new model to incorporate the known biological feature of “obligate chiasma” whereby in most organisms each bivalent almost always has at least one crossover. The initial crossover is modeled as uniformly distributed along the chromosome, and starting from its position, subsequent crossovers are placed with forward and backward stationary renewal processes using a chi-square distribution of intercrossover distances. We used our model as well as the standard chi-square model to simulate the patterns of crossover densities along bivalents or chromatids for those having zero, one, two, or three or more crossovers; indeed, such patterns depend on the number of crossovers. With both models, simulated patterns compare very well to those found experimentally in mice, both for MLH1 foci on bivalents and for crossovers on genetic maps. However, our model provides a better fit to experimental data as compared to the standard chi-square model, particularly regarding the distribution of numbers of crossovers per chromosome. Finally, our model predicts an enhancement of the recombination rate near the extremities, which, however, explains only a part of the pattern observed in mouse.
Population Structure and Its Effects on Patterns of Nucleotide Polymorphism in Teosinte (Zea mays ssp. parviglumis)
Authors: Moeller David A , Tenaillon Maud I , Tiffin Peter
Published: May 2007

Surveys of nucleotide diversity in the wild ancestor of maize, Zea mays ssp. parviglumis, have revealed genomewide departures from the standard neutral equilibrium (NE) model. Here we investigate the degree to which population structure may account for the excess of rare polymorphisms frequently observed in species-wide samples. On the basis of sequence data from five nuclear and two chloroplast loci, we found significant population genetic structure among seven subpopulations from two geographic regions. Comparisons of estimates of population genetic parameters from species-wide samples and subpopulation-specific samples showed that population genetic subdivision influenced observed patterns of nucleotide polymorphism. In particular, Tajima's D was significantly higher (closer to zero) in subpopulation-specific samples relative to species-wide samples, and therefore more closely corresponded to NE expectations. In spite of these overall patterns, the extent to which levels and patterns of polymorphism within subpopulations differed from species-wide samples and NE expectations depended strongly on the geographic region (Jalisco vs. Balsas) from which subpopulations were sampled. This may be due to the demographic history of subpopulations in those regions. Overall, these results suggest that explicitly accounting for population structure may be important for studies examining the genetic basis of ecologically and agronomically important traits as well as for identifying loci that have been the targets of selection.
Fine-Tuning of Translation Termination Efficiency inSaccharomyces cerevisiaeInvolves Two Factors in Close Proximity to the Exit Tunnel of the Ribosome
Authors: Hatin Isabelle , Fabret Céline , Namy Olivier , Decatur Wayne A , Rousset Jean-Pierre
Published: May 2007

In eukaryotes, release factors 1 and 3 (eRF1 and eRF3) are recruited to promote translation termination when a stop codon on the mRNA enters at the ribosomal A-site. However, their overexpression increases termination efficiency only moderately, suggesting that other factors might be involved in the termination process. To determine such unknown components, we performed a genetic screen in Saccharomyces cerevisiae that identified genes increasing termination efficiency when overexpressed. For this purpose, we constructed a dedicated reporter strain in which a leaky stop codon is inserted into the chromosomal copy of the ade2 gene. Twenty-five antisuppressor candidates were identified and characterized for their impact on readthrough. Among them, SSB1 and snR18, two factors close to the exit tunnel of the ribosome, directed the strongest antisuppression effects when overexpressed, showing that they may be involved in fine-tuning of the translation termination level.
Meiotic Parthenogenesis in a Root-Knot Nematode Results in Rapid Genomic Homozygosity
Authors: Liu Qingli L , Thomas Varghese P , Williamson Valerie M
Published: May 2007

Many isolates of the plant-parasitic nematode Meloidogyne hapla reproduce by facultative meiotic parthenogenesis. Sexual crosses can occur, but, in the absence of males, the diploid state appears to be restored by reuniting sister chromosomes of a single meiosis. We have crossed inbred strains of M. hapla that differ in DNA markers and produced hybrids and F2 lines. Here we show that heterozygous M. hapla females, upon parthenogenetic reproduction, produce progeny that segregate 1:1 for the presence or absence of dominant DNA markers, as would be expected if sister chromosomes are rejoined, rather than the 3:1 ratio typical of a Mendelian cross. Codominant markers also segregate 1:1 and heterozygotes are present at low frequency (<3%). Segregation patterns and recombinant analysis indicate that a homozygous condition is prevalent for markers flanking recombination events, suggesting that recombination occurs preferentially as four-strand exchanges at similar locations between both pairs of non-sister chromatids. With this mechanism, meiotic parthenogenesis would be expected to result in rapid genomic homozygosity. This type of high negative crossover interference coupled with positive chromatid interference has not been observed in fungal or other animal systems in which it is possible to examine the sister products of a single meiosis and may indicate that meiotic recombination in this nematode has novel features.
Selective Use of the Primary Literature Transforms the Classroom Into a Virtual Laboratory
Authors: Hoskins Sally G , Stevens Leslie M , Nehm Ross H
Published: May 2007

CREATE (consider, read, elucidate hypotheses, analyze and interpret the data, and think of the next experiment) is a new method for teaching science and the nature of science through primary literature. CREATE uses a unique combination of novel pedagogical tools to guide undergraduates through analysis of journal articles, highlighting the evolution of scientific ideas by focusing on a module of four articles from the same laboratory. Students become fluent in the universal language of data analysis as they decipher the figures, interpret the findings, and propose and defend further experiments to test their own hypotheses about the system under study. At the end of the course students gain insight into the individual experiences of article authors by reading authors' responses to an e-mail questionnaire generated by CREATE students. Assessment data indicate that CREATE students gain in ability to read and critically analyze scientific data, as well as in their understanding of, and interest in, research and researchers. The CREATE approach demystifies the process of reading a scientific article and at the same time humanizes scientists. The positive response of students to this method suggests that it could make a significant contribution to retaining undergraduates as science majors.
A Sensitized PiggyBac-Based Screen for Regulators of Border Cell Migration in Drosophila
Authors: Mathieu Juliette , Sung Hsin-Ho , Pugieux Céline , Soetaert Jan , Rorth Pernille
Published: May 2007

Migration of border cells during Drosophila melanogaster oogenesis is a good model system for investigating the genetic requirements for cell migration in vivo. We present a sensitized loss-of-function screen used to identify new genes required in border cells for their migration. Chromosomes bearing FRTs on all four major autosomal arms were mutagenized by insertions of the transposable element PiggyBac, allowing multiple parallel clonal screens and easy identification of the mutated gene. For border cells, we analyzed homozygous mutant clones positively marked with lacZ and sensitized by expression of dominant-negative PVR, the guidance receptor. We identified new alleles of genes already known to be required for border cell migration, including aop/yan, DIAP1, and taiman as well as a conserved Slbo-regulated enhancer downstream of shg/DE–cadherin. Mutations in genes not previously described to be required in border cells were also uncovered: hrp48, vir, rme-8, kismet, and puckered. puckered was unique in that the migration defects were observed only when PVR signaling was reduced. We present evidence that an excess of JNK signaling is deleterious for migration in the absence of PVR activity at least in part through Fos transcriptional activity and possibly through antagonistic effects on DIAP1.
An Efficient Bayesian Model Selection Approach for Interacting Quantitative Trait Loci Models With Many Effects
Authors: Yi Nengjun , Shriner Daniel , Banerjee Samprit , Mehta Tapan , Pomp Daniel , Yandell Brian S
Published: May 2007

We extend our Bayesian model selection framework for mapping epistatic QTL in experimental crosses to include environmental effects and gene–environment interactions. We propose a new, fast Markov chain Monte Carlo algorithm to explore the posterior distribution of unknowns. In addition, we take advantage of any prior knowledge about genetic architecture to increase posterior probability on more probable models. These enhancements have significant computational advantages in models with many effects. We illustrate the proposed method by detecting new epistatic and gene–sex interactions for obesity-related traits in two real data sets of mice. Our method has been implemented in the freely available package R/qtlbim (http://www.qtlbim.org) to facilitate the general usage of the Bayesian methodology for genomewide interacting QTL analysis.
Microhomology-Mediated End Joining in Fission Yeast Is Repressed by Pku70 and Relies on Genes Involved in Homologous Recombination
Authors: Decottignies Anabelle
Published: May 2007

Two DNA repair pathways are known to mediate DNA double-strand-break (DSB) repair: homologous recombination (HR) and nonhomologous end joining (NHEJ). In addition, a nonconservative backup pathway showing extensive nucleotide loss and relying on microhomologies at repair junctions was identified in NHEJ-deficient cells from a variety of organisms and found to be involved in chromosomal translocations. Here, an extrachromosomal assay was used to characterize this microhomology-mediated end-joining (MMEJ) mechanism in fission yeast. MMEJ was found to require at least five homologous nucleotides and its efficiency was decreased by the presence of nonhomologous nucleotides either within the overlapping sequences or at DSB ends. Exo1 exonuclease and Rad22, a Rad52 homolog, were required for repair, suggesting that MMEJ is related to the single-strand-annealing (SSA) pathway of HR. In addition, MMEJ-dependent repair of DSBs with discontinuous microhomologies was strictly dependent on Pol4, a PolX DNA polymerase. Although not strictly required, Msh2 and Pms1 mismatch repair proteins affected the pattern of MMEJ repair. Strikingly, Pku70 inhibited MMEJ and increased the minimal homology length required for efficient MMEJ. Overall, this study strongly suggests that MMEJ does not define a distinct DSB repair mechanism but reflects “micro-SSA.”
Single-Locus Polymorphism in a Heterogeneous Two-Deme Model
Authors: Star Bastiaan , Stoffels Rick J , Spencer Hamish G
Published: May 2007

Environmental heterogeneity has long been considered a likely explanation for the high levels of genetic variation found in most natural populations: selection in a spatially heterogeneous environment can maintain more variation. While this theoretical result has been extensively studied in models with limited parameters (e.g., two alleles, fixed gene flow, and particular selection schemes), the effect of spatial heterogeneity is poorly understood for models with a wider range of parameters (e.g., multiple alleles, different levels of gene flow, and more general selection schemes). We have compared the volume of fitness space that maintains variation in a single-deme model to the volume in a two-deme model for multiple alleles, random selection schemes, and various levels of migration. Furthermore, equilibrium allele-frequency vectors were examined to see if particular patterns of variation are more prevalent than first expected. The two-deme model maintains variation for substantially larger volumes of fitness space with lower heterozygote fitness than the single-deme model. This result implies that selection schemes in the two-deme model can have a wider range of fitness patterns while still maintaining variation. The equilibrium allele-frequency patterns emerging from the two-deme model are more variable and strongly influenced by gene flow.
Increasing the Efficiency of Variance Component Quantitative Trait Loci Analysis by Using Reduced-Rank Identity-by-Descent Matrices
Authors: Rönnegård Lars , Mischenko Kateryna , Holmgren Sverker , Carlborg Örjan
Published: May 2007

Recent technological development in genetics has made large-scale marker genotyping fast and practicable, facilitating studies for detection of QTL in large general pedigrees. We developed a method that speeds up restricted maximum-likelihood (REML) algorithms for QTL analysis by simplifying the inversion of the variance–covariance matrix of the trait vector. The method was tested in an experimental chicken pedigree including 767 phenotyped individuals and 14 genotyped markers on chicken chromosome 1. The computation time in a chromosome scan covering 475 cM was reduced by 43% when the analysis was based on linkage only and by 72% when linkage disequilibrium information was included. The relative advantage of using our method increases with pedigree size, marker density, and linkage disequilibrium, indicating even greater improvements in the future.
Fixation Probabilities When Generation Times Are Variable: The Burst–Death Model
Authors: Hubbarde J E , Wild G , Wahl L M
Published: May 2007

Estimating the fixation probability of a beneficial mutation has a rich history in theoretical population genetics. Typically, to attain mathematical tractability, we assume that generation times are fixed, while the number of offspring per individual is stochastic. However, fixation probabilities are extremely sensitive to these assumptions regarding life history. In this article, we compute the fixation probability for a “burst–death” life-history model. The model assumes that generation times are exponentially distributed, but the number of offspring per individual is constant. We estimate the fixation probability for populations of constant size and for populations that grow exponentially between periodic population bottlenecks. We find that the fixation probability is, in general, substantially lower in the burst–death model than in classical models. We also note striking qualitative differences between the fates of beneficial mutations that increase burst size and mutations that increase the burst rate. In particular, once the burst size is sufficiently large relative to the wild type, the burst–death model predicts that fixation probability depends only on burst rate.
Biochemical and Genetic Analyses Provide Insight Into the Structural and Mechanistic Properties of Actin Filament Disassembly by the Aip1p–Cofilin Complex in Saccharomyces cerevisiae
Authors: Clark Michael G , Amberg David C
Published: May 2007

Explication of the Aip1p/cofilin/actin filament complex may lead to a more detailed understanding of the mechanisms by which Aip1p and cofilin collaborate to rapidly disassemble filaments. We further characterized the actin–Aip1p interface through a random mutagenic screen of ACT1, identifying a novel Aip1p interaction site on actin. This finding is consistent with our current ternary complex model and offers insights into how Aip1p may disturb intersubunit contacts within an actin filament. In addition, site-directed mutagenesis aimed at interfering with salt bridge interactions at the predicted Aip1p–cofilin interface revealed hyperactive alleles of cof1 and aip1 that support the ternary complex model and suggest that conformational changes in cofilin structure may be transmitted to actin filaments, causing increased destabilization. Furthermore, these data support an active role for Aip1p in promoting actin filament turnover.
Centimorgan-Range One-Step Mapping of Fertility Traits Using Interspecific Recombinant Congenic Mice
Authors: L'Hôte David , Serres Catherine , Laissue Paul , Oulmouden Ahmad , Rogel-Gaillard Claire , Montagutelli Xavier , Vaiman Daniel
Published: May 2007

In mammals, male fertility is a quantitative feature determined by numerous genes. Until now, several wide chromosomal regions involved in fertility have been defined by genetic mapping approaches; unfortunately, the underlying genes are very difficult to identify. Here, 53 interspecific recombinant congenic mouse strains (IRCSs) bearing 1–2% SEG/Pas (Mus spretus) genomic fragments disseminated in a C57Bl/6J (Mus domesticus) background were used to systematically analyze male fertility parameters. One of the most prominent advantages of this model is the possibility of analyzing stable phenotypes in living animals. Here, we demonstrate the possibility in one-step fine mapping for several fertility traits. Focusing on strains harboring a unique spretus fragment, we could unambiguously localize two testis and one prostate weight-regulating QTL (Ltw1, Ltw2, and Lpw1), four QTL controlling the sperm nucleus shape (Sh1, Sh2, Sh3, and Sh4), and one QTL influencing sperm survival (Dss1). In several cases, the spretus DNA fragment was small enough to propose sound candidates. For instance, Spata1, Capza, and Tuba7 are very strong candidates for influencing the shape of the sperm head. Identifying new genes implied in mammalian fertility pathways is a necessary prerequisite for clarifying their molecular grounds and for proposing diagnostic tools for masculine infertilities.
A Markov Chain Monte Carlo Approach for Joint Inference of Population Structure and Inbreeding Rates From Multilocus Genotype Data
Authors: Gao Hong , Williamson Scott , Bustamante Carlos D
Published: May 2007

Nonrandom mating induces correlations in allelic states within and among loci that can be exploited to understand the genetic structure of natural populations (Wright 1965). For many species, it is of considerable interest to quantify the contribution of two forms of nonrandom mating to patterns of standing genetic variation: inbreeding (mating among relatives) and population substructure (limited dispersal of gametes). Here, we extend the popular Bayesian clustering approach STRUCTURE (Pritchard  et al. 2000) for simultaneous inference of inbreeding or selfing rates and population-of-origin classification using multilocus genetic markers. This is accomplished by eliminating the assumption of Hardy–Weinberg equilibrium within clusters and, instead, calculating expected genotype frequencies on the basis of inbreeding or selfing rates. We demonstrate the need for such an extension by showing that selfing leads to spurious signals of population substructure using the standard STRUCTURE algorithm with a bias toward spurious signals of admixture. We gauge the performance of our method using extensive coalescent simulations and demonstrate that our approach can correct for this bias. We also apply our approach to understanding the population structure of the wild relative of domesticated rice, Oryza rufipogon, an important partially selfing grass species. Using a sample of n = 16 individuals sequenced at 111 random loci, we find strong evidence for existence of two subpopulations, which correlates well with geographic location of sampling, and estimate selfing rates for both groups that are consistent with estimates from experimental data (s ≈ 0.48–0.70).
Involvement ofEscherichia coliDNA Polymerase IV in Tolerance of Cytotoxic Alkylating DNA Lesionsin Vivo
Authors: Bjedov Ivana , Dasgupta Chitralekha Nag , Slade Dea , Le Blastier Sophie , Selva Marjorie , Matic Ivan
Published: May 2007

Escherichia coli PolIV, a DNA polymerase capable of catalyzing synthesis past replication-blocking DNA lesions, belongs to the most ubiquitous branch of Y-family DNA polymerases. The goal of this study is to identify spontaneous DNA damage that is bypassed specifically and accurately by PolIV in vivo. We increased the amount of spontaneous DNA lesions using mutants deficient for different DNA repair pathways and measured mutation frequency in PolIV-proficient and -deficient backgrounds. We found that PolIV performs an error-free bypass of DNA damage that accumulates in the alkA tag genetic background. This result indicates that PolIV is involved in the error-free bypass of cytotoxic alkylating DNA lesions. When the amount of cytotoxic alkylating DNA lesions is increased by the treatment with chemical alkylating agents, PolIV is required for survival in an alkA tag-proficient genetic background as well. Our study, together with the reported involvement of the mammalian PolIV homolog, Polκ, in similar activity, indicates that Y-family DNA polymerases from the DinB branch can be added to the list of evolutionarily conserved molecular mechanisms that counteract cytotoxic effects of DNA alkylation. This activity is of major biological relevance because alkylating agents are continuously produced endogenously in all living cells and are also present in the environment.
Oxidative Stress Enzymes Are Required for DAF-16-Mediated Immunity Due to Generation of Reactive Oxygen Species byCaenorhabditis elegans
Authors: Chávez Violeta , Mohri-Shiomi Akiko , Maadani Arash , Vega Luis Alberto , Garsin Danielle A
Published: May 2007

Caenorhabditis elegans has recently been developed as a model for microbial pathogenesis, yet little is known about its immunological defenses. Previous work implicated insulin signaling in mediating pathogen resistance in a manner dependent on the transcriptional regulator DAF-16, but the mechanism has not been elucidated. We present evidence that C. elegans, like mammalian phagocytes, produces reactive oxygen species (ROS) in response to pathogens. Signs of oxidative stress occur in the intestine—the site of the host–pathogen interface—suggesting that ROS release is localized to this tissue. Evidence includes the accumulation of lipofuscin, a pigment resulting from oxidative damage, at this site. In addition, SOD-3, a superoxide dismutase regulated by DAF-16, is induced in intestinal tissue after exposure to pathogenic bacteria. Moreover, we show that the oxidative stress response genes sod-3 and ctl-2 are required for DAF-16-mediated resistance to Enterococcus faecalis using a C. elegans killing assay. We propose a model whereby C. elegans responds to pathogens by producing ROS in the intestine while simultaneously inducing a DAF-16-dependent oxidative stress response to protect adjacent tissues. Because insulin-signaling mutants overproduce oxidative stress response enzymes, the model provides an explanation for their increased resistance to pathogens.
A Complex Genetic Interaction BetweenArabidopsis thalianaTOC1 and CCA1/LHY in Driving the Circadian Clock and in Output Regulation
Authors: Ding Zhaojun , Doyle Mark R , Amasino Richard M , Davis Seth J
Published: May 2007

It has been proposed that CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY) together with TIMING OF CAB EXPRESSION 1 (TOC1) make up the central oscillator of the Arabidopsis thaliana circadian clock. These genes thus drive rhythmic outputs, including seasonal control of flowering and photomorphogenesis. To test various clock models and to disclose the genetic relationship between TOC1 and CCA1/LHY in floral induction and photomorphogenesis, we constructed the cca1 lhy toc1 triple mutant and cca1 toc1 and lhy toc1 double mutants and tested various rhythmic responses and circadian output regulation. Here we report that rhythmic activity was dramatically attenuated in cca1 lhy toc1. Interestingly, we also found that TOC1 regulates the floral transition in a CCA1/LHY-dependent manner while CCA1/LHY functions upstream of TOC1 in regulating a photomorphogenic process. This suggests to us that TOC1 and CCA1/LHY participate in these two processes through different strategies. Collectively, we have used genetics to provide direct experimental support of previous modeling efforts where CCA1/LHY, along with TOC1, drives the circadian oscillator and have shown that this clock is essential for correct output regulation.
Genetic Dissection of Parallel Sister-Chromatid Cohesion Pathways
Authors: Xu Hong , Boone Charles , Brown Grant W
Published: May 2007

Sister-chromatid cohesion, the process of pairing replicated chromosomes during mitosis and meiosis, is mediated through the essential cohesin complex and a number of nonessential cohesion genes, but the specific roles of these nonessential genes in sister-chromatid cohesion remain to be clarified. We analyzed sister-chromatid cohesion in double mutants of mrc1Δ, tof1Δ, and csm3Δ and identified additive cohesion defects that indicated the existence of at least two pathways that contribute to sister-chromatid cohesion. To understand the relationship of other nonessential cohesion genes with respect to these two pathways, pairwise combinations of deletion and temperature-sensitive alleles were tested for cohesion defects. These data defined two cohesion pathways, one containing CSM3, TOF1, CTF4, and CHL1, and the second containing MRC1, CTF18, CTF8, and DCC1. Furthermore, we found that the nonessential genes are not important for the maintenance of cohesion at G2/M. Thus, our data suggest that nonessential cohesion genes make critical redundant contributions to the establishment of sister-chromatid cohesion and define two cohesion pathways, thereby establishing a framework for understanding the role of nonessential genes in sister-chromatid cohesion.
Manipulating Mitotic Recombination in the Zebrafish Embryo Through RecQ Helicases
Authors: Xie Jing , Bessling Seneca L , Cooper Timothy K , Dietz Harry C , McCallion Andrew S , Fisher Shannon
Published: May 2007

RecQ DNA helicases resolve Rad-51-mediated recombination and suppress aberrant homologous recombination. RecQ gene loss is associated with cancer susceptibility and increased mitotic recombination. We have developed an in vivo assay based on a zebrafish pigment mutant for suppression of RecQ activity, and demonstrate that zebrafish RecQ genes have conserved function in suppressing mitotic recombination.
A Mutant Allele of the Transcription Factor IIH Helicase Gene, RAD3, Promotes Loss of Heterozygosity in Response to a DNA Replication Defect in Saccharomyces cerevisiae
Authors: Navarro Michelle S , Bi Liu , Bailis Adam M
Published: May 2007

Increased mitotic recombination enhances the risk for loss of heterozygosity, which contributes to the generation of cancer in humans. Defective DNA replication can result in elevated levels of recombination as well as mutagenesis and chromosome loss. In the yeast Saccharomyces cerevisiae, a null allele of the RAD27 gene, which encodes a structure-specific nuclease involved in Okazaki fragment processing, stimulates mutation and homologous recombination. Similarly, rad3-102, an allele of the gene RAD3, which encodes an essential helicase subunit of the core TFIIH transcription initiation and DNA repairosome complexes confers a hyper-recombinagenic and hypermutagenic phenotype. Combining the rad27 null allele with rad3-102 dramatically stimulated interhomolog recombination and chromosome loss but did not affect unequal sister-chromatid recombination, direct-repeat recombination, or mutation. Interestingly, the percentage of cells with Rad52-YFP foci also increased in the double-mutant haploids, suggesting that rad3-102 may increase lesions that elicit a response by the recombination machinery or, alternatively, stabilize recombinagenic lesions generated by DNA replication failure. This net increase in lesions led to a synthetic growth defect in haploids that is relieved in diploids, consistent with rad3-102 stimulating the generation and rescue of collapsed replication forks by recombination between homologs.
Frequency-Dependent Selection and the Maintenance of Genetic Variation: Exploring the Parameter Space of the Multiallelic Pairwise Interaction Model
Authors: Trotter Meredith V , Spencer Hamish G
Published: May 2007

When individuals' fitnesses depend on the genetic composition of the population in which they are found, selection is then frequency dependent. Frequency-dependent selection (FDS) is often invoked as a heuristic explanation for the maintenance of large numbers of alleles at a locus. The pairwise interaction model is a general model of FDS via intraspecific competition at the genotypic level. Here we use a parameter-space approach to investigate the full potential for the maintenance of multiallelic equilibria under the pairwise interaction model. We find that FDS maintains full polymorphism more often than classic constant-selection models and produces more skewed equilibrium allele frequencies. Fitness sets with some degree of rare advantage maintained full polymorphism most often, but a wide variety of nonobvious fitness patterns were also found to have positive potential for polymorphism. An example is put forth suggesting possible explanations for multiallelic polymorphisms maintained despite positive FDS on individual alleles.
Genetic Load in Sexual and Asexual Diploids: Segregation, Dominance and Genetic Drift
Authors: Haag Christoph R , Roze Denis
Published: May 2007

In diploid organisms, sexual reproduction rearranges allelic combinations between loci (recombination) as well as within loci (segregation). Several studies have analyzed the effect of segregation on the genetic load due to recurrent deleterious mutations, but considered infinite populations, thus neglecting the effects of genetic drift. Here, we use single-locus models to explore the combined effects of segregation, selection, and drift. We find that, for partly recessive deleterious alleles, segregation affects both the deterministic component of the change in allele frequencies and the stochastic component due to drift. As a result, we find that the mutation load may be far greater in asexuals than in sexuals in finite and/or subdivided populations. In finite populations, this effect arises primarily because, in the absence of segregation, heterozygotes may reach high frequencies due to drift, while homozygotes are still efficiently selected against; this is not possible with segregation, as matings between heterozygotes constantly produce new homozygotes. If deleterious alleles are partly, but not fully recessive, this causes an excess load in asexuals at intermediate population sizes. In subdivided populations without extinction, drift mostly occurs locally, which reduces the efficiency of selection in both sexuals and asexuals, but does not lead to global fixation. Yet, local drift is stronger in asexuals than in sexuals, leading to a higher mutation load in asexuals. In metapopulations with turnover, global drift becomes again important, leading to similar results as in finite, unstructured populations. Overall, the mutation load that arises through the absence of segregation in asexuals may greatly exceed previous predictions that ignored genetic drift.
Phosphorylation of the Sic1 Inhibitor of B-Type Cyclins in Saccharomyces cerevisiae Is Not Essential but Contributes to Cell Cycle Robustness
Authors: Cross Frederick R , Schroeder Lea , Bean James M
Published: May 2007

In budding yeast, B-type cyclin (Clb)-dependent kinase activity is essential for S phase and mitosis. In newborn G1 cells, Clb kinase accumulation is blocked, in part because of the Sic1 stoichiometric inhibitor. Previous results strongly suggested that G1 cyclin-dependent Sic1 phosphorylation, and its consequent degradation, is essential for S phase. However, cells containing a precise endogenous gene replacement of SIC1 with SIC1-0P (all nine phosphorylation sites mutated) were fully viable. Unphosphorylatable Sic1 was abundant and nuclear throughout the cell cycle and effectively inhibited Clb kinase in vitro. SIC1-0P cells had a lengthened G1 and increased G1 cyclin transcriptional activation and variable delays in the budded part of the cell cycle. SIC1-0P was lethal when combined with deletion of CLB2, CLB3, or CLB5, the major B-type cyclins. Sic1 phosphorylation provides a sharp link between G1 cyclin activation and Clb kinase activation, but failure of Sic1 phosphorylation and proteolysis imposes a variable cell cycle delay and extreme sensitivity to B-type cyclin dosage, rather than a lethal cell cycle block.
Interleukin 22 Is a Candidate Gene forTmevp3, a Locus Controlling Theiler's Virus-Induced Neurological Diseases
Authors: Levillayer F , Mas M , Levi-Acobas F , Brahic M , Bureau J F
Published: May 2007

After intracerebral inoculation, Theiler's virus induces in its natural host, the mouse, an acute encephalomyelitis followed, in susceptible animals, by chronic inflammation and primary demyelination. Susceptibility to demyelination among strains of laboratory mice is explained by the capacity of the immune system to control viral load during persistence. Also, differences of susceptibility to viral load between the susceptible SJL strain and the resistant B10.S strain are mainly due to two loci, Tmevp2 and Tmevp3, located close to the Ifng locus on chromosome 10. In this article, we show that the Tmevp3 locus controls both mortality during the acute encephalomyelitis and viral load during persistence. Most probably, two genes located in the Tmevp3 interval control these two different phenotypes with efficiencies that depend on the age of the mouse at inoculation. Il22, a member of the IL-10 cytokine family, is a candidate gene for the control of mortality during the acute encephalomyelitis.
Reducing DNA Polymerase α in the Absence of Drosophila ATR Leads to P53-Dependent Apoptosis and Developmental Defects
Authors: LaRocque Jeannine R , Dougherty Diana L , Hussain Sumreen K , Sekelsky Jeff
Published: May 2007

The ability to respond to DNA damage and incomplete replication ensures proper duplication and stability of the genome. Two checkpoint kinases, ATM and ATR, are required for DNA damage and replication checkpoint responses. In Drosophila, the ATR ortholog (MEI-41) is essential for preventing entry into mitosis in the presence of DNA damage. In the absence of MEI-41, heterozygosity for the E(mus304) mutation causes rough eyes. We found that E(mus304) is a mutation in DNApol-α180, which encodes the catalytic subunit of DNA polymerase α. We did not find any defects resulting from reducing Polα by itself. However, reducing Polα in the absence of MEI-41 resulted in elevated P53-dependent apoptosis, rough eyes, and increased genomic instability. Reducing Polα in mutants that lack downstream components of the DNA damage checkpoint (DmChk1 and DmChk2) results in the same defects. Furthermore, reducing levels of mitotic cyclins rescues both phenotypes. We suggest that reducing Polα slows replication, imposing an essential requirement for the MEI-41-dependent checkpoint for maintenance of genome stability, cell survival, and proper development. This work demonstrates a critical contribution of the checkpoint function of MEI-41 in responding to endogenous damage.
The Evolution of Condition-Dependent Sex in the Face of High Costs
Authors: Hadany Lilach , Otto Sarah P
Published: May 2007

Facultatively sexual organisms often engage in sex more often when in poor condition. We show that such condition-dependent sex carries evolutionary advantages and can explain the evolution of sexual reproduction even when sex entails high costs. Specifically, we show that alleles promoting individuals of low fitness to have sex more often than individuals of high fitness spread through a population. Such alleles are more likely to segregate out of bad genetic backgrounds and onto good genetic backgrounds, where they tend to remain. This “abandon-ship” mechanism provides a plausible model for the evolution and maintenance of facultative sex.
Mutational Bias for Body Size in Rhabditid Nematodes
Authors: Ostrow Dejerianne , Phillips Naomi , Avalos Arián , Blanton Dustin , Boggs Ashley , Keller Thomas , Levy Laura , Rosenbloom Jeffrey , Baer Charles F
Published: May 2007

Mutational bias is a potentially important agent of evolution, but it is difficult to disentangle the effects of mutation from those of natural selection. Mutation-accumulation experiments, in which mutations are allowed to accumulate at very small population size, thus minimizing the efficiency of natural selection, are the best way to separate the effects of mutation from those of selection. Body size varies greatly among species of nematode in the family rhabditidae; mutational biases are both a potential cause and a consequence of that variation. We report data on the cumulative effects of mutations that affect body size in three species of rhabditid nematode that vary fivefold in adult size. Results are very consistent with previous studies of mutations underlying fitness in the same strains: two strains of Caenorhabditis briggsae decline in body size about twice as fast as two strains of C. elegans, with a concomitant higher point estimate of the genomic mutation rate; the confamilial Oscheius myriophila is intermediate. There is an overall mutational bias, such that mutations reduce size on average, but the bias appears consistent between species. The genetic correlation between mutations that affect size and those underlying fitness is large and positive, on average.
Knowledge-Dependent Pattern Classification of Human Nasal Profiles
Authors: Tanikawa Chihiro , Kakiuchi Yasuhiro , Yagi Masakazu , Miyata Kayoko , Takada Kenji
Published: May 2007

Objective: (1) To determine feature vector representations (geometric pattern parameters) that are effective in describing human nasal profiles, (2) to determine the number of code vectors (typical nasal patterns) that are mathematically optimized by applying the vector quantization method to each feature vector extracted for each subject, and (3) to determine the morphological traits of each code.

Materials and Methods: Lateral facial photographs of 200 Japanese women recorded for orthodontic diagnosis were selected. Five anatomic landmarks were identified on each image together with a set of data points that constituted the contour of the facial profile. An eight-dimensional feature vector effective in distinguishing differences in nasal profile patterns was extracted from the data set using experts' knowledge of the anatomic traits of the nose. The vector quantization technique was applied to the feature vectors to provide the optimum number of nasal profile patterns.

Results: The number of code vectors mathematically optimized was six, and the differences between vectors were maximized by morphological traits of the root, dorsum, tip, and base of the nose. Proportions of the number of image records classified into each code were 25.5%, 24.5%, 21.5%, 15.0%, 10.0%, and 3.5% from code 1 to code 6, respectively.

Conclusions: Classifying nasal profile patterns based on knowledge from a linguistic description was found to be more effective than a method based on uniform sectioning. The differences between vectors were maximized by morphological traits of the root, the dorsum, the tip, and the base of the nose.
Mandibular Symphyseal Distraction Osteogenesis Using a Bone-Supported Distractor
Authors: Bayram Mehmet , Özer Mete , Alkan Alper
Published: May 2007

Increases in mandibular width by symphyseal distraction osteogenesis have recently been shown to be an acceptable and stable treatment option for transverse deficiencies. This case report presents the application of symphyseal distraction osteogenesis for increasing mandibular width using a bone-supported distractor as part of the orthodontic treatment of a 14-year-old male with a tapered shaped mandible and severe mandibular anterior crowding.
Thin-plate Spline Analysis of Craniofacial Growth in Class I and Class II Subjects
Authors: Franchi Lorenzo , Baccetti Tiziano , Stahl Franka , McNamara James A.
Published: May 2007

Objective: To compare the craniofacial growth characteristics of untreated subjects with Class II division 1 malocclusion with those of subjects with normal (Class I) occlusion from the prepubertal through the postpubertal stages of development.

Materials and Methods: The Class II division 1 sample consisted of 17 subjects (11 boys and six girls). The Class I sample also consisted of 17 subjects (13 boys and four girls). Three craniofacial regions (cranial base, maxilla, and mandible) were analyzed on the lateral cephalograms of the subjects in both groups by means of thin-plate spline analysis at T1 (prepubertal) and T2 (postpubertal). Both cross-sectional and longitudinal comparisons were performed on both size and shape differences between the two groups.

Results: The results showed an increased cranial base angulation as a morphological feature of Class II malocclusion at the prepubertal developmental phase. Maxillary changes in either shape or size were not significant. Subjects with Class II malocclusion exhibited a significant deficiency in the size of the mandible at the completion of active craniofacial growth as compared with Class I subjects.

Conclusion: A significant deficiency in the size of the mandible became apparent in Class II subjects during the circumpubertal period and it was still present at the completion of active craniofacial growth.
Root Resorption on Torqued Human Premolars Shown by Tartrate-Resistant Acid Phosphatase Histochemistry and Transmission Electron Microscopy
Authors: Casa Mauricio A. , Faltin Rolf M. , Faltin Kurt , Arana-Chavez Victor E.
Published: May 2007

Objective: To identify clastic cells on the root surfaces of torqued human premolars.

Materials and Methods: A continuous force of 600 cNmm was applied to upper first premolars in patients 13–16 years of age by using a precise biomechanical model with superelastic wires (NiTi-SE). The 28 teeth in 14 patients were divided into five groups (control [nonmoved], and moved for either 1, 2, 3, or 4 weeks) and processed for tartrate-resistant acid phosphatase (TRAP) histochemistry and transmission electron microscopy.

Results: Mononuclear TRAP-positive cells appeared at 2 weeks, wheras large multinucleated TRAP-positive cells were numerous at 3 and 4 weeks. Ultrastructural examination revealed many clastic cells in contact with resorption lacunae. In addition, some cementoblast-like cells appeared secreting new cementum over previously resorbed lacunae.

Conclusions: In general, resorption lacunae and the number of clastic cells, which increased with the duration of the applied force, were found on the cementum surface at the pressure areas. Some signs of cementum repair were also noticed, even with the maintenance of the level of the force.
Orthodontic and Periodontal Outcomes of Treated Impacted Maxillary Canines
Authors: Crescini Aldo , Nieri Michele , Buti Jacopo , Baccetti Tiziano , Pini Prato Giovan Paolo
Published: May 2007

Objective: To evaluate the influence of pretreatment radiographic features (α-angle, d-distance, and s-sector) on (1) the duration of active orthodontic traction and (2) the posttreatment periodontal status (pocket depth [PD] and keratinized tissue width [KT]) of impacted maxillary canines treated by a combined surgical (flap approach) and orthodontic (direct traction to the center of the ridge) treatment.

Material and Methods: A study population of 168 patients (168 canines) was evaluated. Multiple regression analysis was used.

Results: Pretreatment radiographic variables were associated significantly with the duration of orthodontic traction. Age, sex, and site of impaction did not significantly affect the duration of traction. No significant differences in PD and KT were present at the end of surgical-orthodontic treatment with respect to any of the variables considered. The analysis of PD and KT variables after orthodontic treatment revealed a healthy periodontium.

Conclusions: α-angle, d-distance, and s-sector are valid indicators for the duration of orthodontic traction. They are not prognostic indicators of final periodontal status of orthodontically-repositioned canines.