bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aberrant Splicing of an Alternative Exon in the Drosophila Troponin-T Gene Affects Flight Muscle Development
Authors: Nongthomba Upendra , Ansari Maqsood , Thimmaiya Divesh , Stark Meg , Sparrow John 
Published: July 2007

Abstract
During myofibrillogenesis, many muscle structural proteins assemble to form the highly ordered contractile sarcomere. Mutations in these proteins can lead to dysfunctional muscle and various myopathies. We have analyzed the Drosophila melanogaster troponin T (TnT) up1 mutant that specifically affects the indirect flight muscles (IFM) to explore troponin function during myofibrillogenesis. The up1 muscles lack normal sarcomeres and contain “zebra bodies,” a phenotypic feature of human nemaline myopathies. We show that the up1 mutation causes defective splicing of a newly identified alternative TnT exon (10a) that encodes part of the TnT C terminus. This exon is used to generate a TnT isoform specific to the IFM and jump muscles, which during IFM development replaces the exon 10b isoform. Functional differences between the 10a and 10b TnT isoforms may be due to different potential phosphorylation sites, none of which correspond to known phosphorylation sites in human cardiac TnT. The absence of TnT mRNA in up1 IFM reduces mRNA levels of an IFM-specific troponin I (TnI) isoform, but not actin, tropomyosin, or troponin C, suggesting a mechanism controlling expression of TnT and TnI genes may exist that must be examined in the context of human myopathies caused by mutations of these thin filament proteins.
Fractioned DNA Pooling: A New Cost-Effective Strategy for Fine Mapping of Quantitative Trait Loci
Authors: Korol A , Frenkel Z , Cohen L , Lipkin E , Soller M 
Published: July 2007

AbstractSelective DNA pooling (SDP) is a cost-effective means for an initial scan for linkage between marker and quantitative trait loci (QTL) in suitable populations. The method is based on scoring marker allele frequencies in DNA pools from the tails of the population trait distribution. Various analytical approaches have been proposed for QTL detection using data on multiple families with SDP analysis. This article presents a new experimental procedure, fractioned-pool design (FPD), aimed to increase the reliability of SDP mapping results, by “fractioning” the tails of the population distribution into independent subpools. FPD is a conceptual and structural modification of SDP that allows for the first time the use of permutation tests for QTL detection rather than relying on presumed asymptotic distributions of the test statistics. For situations of family and cross mapping design we propose a spectrum of new tools for QTL mapping in FPD that were previously possible only with individual genotyping. These include: joint analysis of multiple families and multiple markers across a chromosome, even when the marker loci are only partly shared among families; detection of families segregating (heterozygous) for the QTL; estimation of confidence intervals for the QTL position; and analysis of multiple-linked QTL. These new advantages are of special importance for pooling analysis with SNP chips. Combining SNP microarray analysis with DNA pooling can dramatically reduce the cost of screening large numbers of SNPs on large samples, making chip technology readily applicable for genomewide association mapping in humans and farm animals. This extension, however, will require additional, nontrivial, development of FPD analytical tools.
Early Events in the Evolution of the Silene latifolia Y Chromosome: Male Specialization and Recombination Arrest
Authors: Zluvova Jitka , Georgiev Sevdalin , Janousek Bohuslav , Charlesworth Deborah , Vyskot Boris , Negrutiu Ioan 
Published: July 2007

Abstract
Understanding the origin and evolution of sex chromosomes requires studying recently evolved X–Y chromosome systems such as those in some flowering plants. We describe Y chromosome deletion mutants of Silene latifolia, a dioecious plant with heteromorphic sex chromosomes. The combination of results from new and previously described deletions with histological descriptions of their stamen development defects indicates the presence of two distinct Y regions containing loci with indispensable roles in male reproduction. We determined their positions relative to the two main sex determination functions (female suppressing and the other male promoting). A region proximal to the centromere on the Y p arm containing the putative stamen promoting sex determination locus includes additional early stamen developmental factors. A medial region of the Y q arm carries late pollen fertility factors. Cytological analysis of meiotic X–Y pairing in one of the male-sterile mutants indicates that the Y carries sequences or functions specifically affecting sex chromosome pairing.
Mapping Regions Within Cosmopolitan Inversion In(3R)Payne Associated With Natural Variation in Body Size in Drosophila melanogaster
Authors: Kennington W Jason , Hoffmann Ary A , Partridge Linda 
Published: July 2007

Abstract
Associations between genotypes for inversions and quantitative traits have been reported in several organisms, but little has been done to localize regions within inversions controlling variation in these traits. Here, we use an association mapping technique to identify genomic regions controlling variation in wing size within the cosmopolitan inversion In(3R)Payne in Drosophila melanogaster. Previous studies have shown that this inversion strongly influences variation in wing size, a trait highly correlated with body size. We found three alleles from two separate regions within In(3R)Payne with significant additive effects on wing size after the additional effect of the inversion itself had been taken into account. There were also several alleles with significant genotype-by-inversion interaction effects on wing size. None of the alleles tested had a significant additive effect on development time, suggesting different genes control these traits and that clinal patterns in them have therefore arisen independently. The presence of multiple regions within In(3R)Payne controlling size is consistent with the idea that inversions persist in populations because they contain multiple sets of locally adapted alleles, but more work needs to be done to test if they are indeed coadapted.
Topoisomerase I-Dependent Viability Loss in Saccharomyces cerevisiae Mutants Defective in Both SUMO Conjugation and DNA Repair
Authors: Chen Xiaole L , Silver Hannah R , Xiong Ling , Belichenko Irina , Adegite Caroline , Johnson Erica S 
Published: July 2007

Abstract
Siz1 and Siz2/Nfi1 are the two Siz/PIAS SUMO E3 ligases in Saccharomyces cerevisiae. Here we show that siz1Δ siz2Δ mutants fail to grow in the absence of the homologous recombination pathway or the Fen1 ortholog RAD27. Remarkably, the growth defects of mutants such as siz1Δ siz2Δ rad52Δ are suppressed by mutations in TOP1, suggesting that these growth defects are caused by topoisomerase I activity. Other mutants that affect SUMO conjugation, including a ulp1 mutant and the nuclear pore mutants nup60Δ and nup133Δ, show similar top1-suppressible synthetic defects with DNA repair mutants, suggesting that these phenotypes also result from reduced SUMO conjugation. siz1Δ siz2Δ mutants also display TOP1-independent genome instability phenotypes, including increased mitotic recombination and elongated telomeres. We also show that SUMO conjugation, TOP1, and RAD27 have overlapping roles in telomere maintenance. Top1 is sumoylated, but Top1 does not appear to be the SUMO substrate involved in the synthetic growth defects. However, sumoylation of certain substrates, including Top1 itself and Tri1 (YMR233W), is enhanced in the absence of Top1 activity. Sumoylation is also required for growth of top1Δ cells. These results suggest that the SUMO pathway has a complex effect on genome stability that involves several mechanistically distinct processes.
Rapid Detection of Positive Selection in Genes and Genomes Through Variation Clusters
Authors: Wagner Andreas 
Published: July 2007

Abstract
Positive selection in genes and genomes can point to the evolutionary basis for differences among species and among races within a species. The detection of positive selection can also help identify functionally important protein regions and thus guide protein engineering. Many existing tests for positive selection are excessively conservative, vulnerable to artifacts caused by demographic population history, or computationally very intensive. I here propose a simple and rapid test that is complementary to existing tests and that overcomes some of these problems. It relies on the null hypothesis that neutrally evolving DNA regions should show a Poisson distribution of nucleotide substitutions. The test detects significant deviations from this expectation in the form of variation clusters, highly localized groups of amino acid changes in a coding region. In applying this test to several thousand human–chimpanzee gene orthologs, I show that such variation clusters are not generally caused by relaxed selection. They occur in well-defined domains of a protein's tertiary structure and show a large excess of amino acid replacement over silent substitutions. I also identify multiple new human–chimpanzee orthologs subject to positive selection, among them genes that are involved in reproductive functions, immune defense, and the nervous system.
Major Histocompatibility Complex Heterozygosity Reduces Fitness in Experimentally Infected Mice
Authors: Ilmonen Petteri , Penn Dustin J , Damjanovich Kristy , Morrison Linda , Ghotbi Laleh , Potts Wayne K 
Published: July 2007

AbstractIt is often suggested that heterozygosity at major histocompatibility complex (MHC) loci confers enhanced resistance to infectious diseases (heterozygote advantage, HA, hypothesis), and overdominant selection should contribute to the evolution of these highly polymorphic genes. The evidence for the HA hypothesis is mixed and mainly from laboratory studies on inbred congenic mice, leaving the importance of MHC heterozygosity for natural populations unclear. We tested the HA hypothesis by infecting mice, produced by crossbreeding congenic C57BL/10 with wild ones, with different strains of Salmonella, both in laboratory and in large population enclosures. In the laboratory, we found that MHC influenced resistance, despite interacting wild-derived background loci. Surprisingly, resistance was mostly recessive rather than dominant, unlike in most inbred mouse strains, and it was never overdominant. In the enclosures, heterozygotes did not show better resistance, survival, or reproductive success compared to homozygotes. On the contrary, infected heterozygous females produced significantly fewer pups than homozygotes. Our results show that MHC effects are not masked on an outbred genetic background, and that MHC heterozygosity provides no immunological benefits when resistance is recessive, and can actually reduce fitness. These findings challenge the HA hypothesis and emphasize the need for studies on wild, genetically diverse species.
Dal81 Enhances Stp1- and Stp2-Dependent Transcription Necessitating Negative Modulation by Inner Nuclear Membrane Protein Asi1 in Saccharomyces cerevisiae
Authors: Boban Mirta , Ljungdahl Per O 
Published: July 2007

Abstract
The yeast transcription factors Stp1 and Stp2 are synthesized as latent cytoplasmic precursors. In response to extracellular amino acids, the plasma membrane SPS sensor endoproteolytically excises the N-terminal domains that mediate cytoplasmic retention, enabling the processed forms to efficiently enter the nucleus and induce gene expression. Cytoplasmic retention is not absolute, low levels of full-length Stp1 and Stp2 “leak” into the nucleus, and the concerted action of inner nuclear membrane proteins Asi1, Asi2, and Asi3 restricts their promoter access. In cells lacking Asi function, the precursor forms bind promoters and constitutively induce gene expression. To understand the requirement of Asi-dependent repression, spontaneous mutations in Required for Latent Stp1/2-mediated transcription (RLS) genes that abolish the constitutive expression of SPS sensor-regulated genes in an asi1Δ strain were selected. A single gene, allelic with DAL81, was identified. We show that Dal81 indiscriminately amplifies the transactivation potential of both full-length and processed Stp1 and Stp2 by facilitating promoter binding. In dal81Δ mutants, the repressing activity of the Asi proteins is dispensable, demonstrating that without amplification, the levels of full-length Stp1 and Stp2 that escape cytoplasmic retention are insufficient to activate transcription. Conversely, the high levels of processed Stp1 and Stp2 that accumulate in the nucleus of induced cells activate transcription in the absence of Dal81.
A Linkage Map Reveals a Complex Basis for Segregation Distortion in an Interpopulation Cross in the Moss Ceratodon purpureus
Authors: McDaniel Stuart F , Willis John H , Shaw A Jonathan 
Published: July 2007

Abstract
We report the construction of a linkage map for the moss Ceratodon purpureus (n = 13), based on a cross between geographically distant populations, and provide the first experimental confirmation of maternal chloroplast inheritance in bryophytes. From a mapping population of 288 recombinant haploid gametophytes, genotyped at 121 polymorphic AFLP loci, three gene-based nuclear loci, one chloroplast marker, and sex, we resolved 15 linkage groups resulting in a map length of ∼730 cM. We estimate that the map covers more than three-quarters of the C. purpureus genome. Approximately 35% of the loci were sex linked, not including those in recombining pseudoautosomal regions. Nearly 45% of the loci exhibited significant segregation distortion (α = 0.05). Several pairs of unlinked distorted loci showed significant deviations from multiplicative genotypic frequencies, suggesting that distortion arises from genetic interactions among loci. The distorted autosomal loci all exhibited an excess of the maternal allele, suggesting that these interactions may involve nuclear–cytoplasmic factors. The sex ratio of the progeny was significantly male biased, and the pattern of nonrandom associations among loci indicates that this results from interactions between the sex chromosomes. These results suggest that even in interpopulation crosses, multiple mechanisms act to influence segregation ratios.
Cost-effectiveness of Alternative Strategies for Tuberculosis Screening Before Kindergarten Entry
Authors: Flaherman Valerie J. , Porco Travis C. , Marseille Elliot , Royce Sarah E. 
Published: July 2007

OBJECTIVE. We undertook a decision analysis to evaluate the economic and health effects and incremental cost-effectiveness of using targeted tuberculin skin testing, compared with universal screening or no screening, before kindergarten.METHODS. We constructed a decision tree to determine the costs and clinical outcomes of using targeted testing compared with universal screening or no screening. Baseline estimates for input parameters were taken from the medical literature and from California health jurisdiction data. Sensitivity analyses were performed to determine plausible ranges of associated outcomes and costs. We surveyed California health jurisdictions to determine the prevalence of mandatory universal tuberculin skin testing.RESULTS. In our base-case scenario, the cost to prevent an additional case of tuberculosis by using targeted testing, compared with no screening, was $524897. The cost to prevent an additional case by using universal screening, compared with targeted testing, was $671398. The incremental cost of preventing a case through screening remained above $100000 unless the prevalence of tuberculin skin testing positivity increased to &gt;10%. More than 51% of children entering kindergarten in California live where tuberculin skin testing is mandatory.CONCLUSIONS. The cost to prevent a case of tuberculosis by using either universal screening or targeted testing of kindergarteners is high. If targeted testing replaced universal tuberculin skin testing in California, then $1.27 million savings per year would be generated for more cost-effective strategies to prevent tuberculosis. Improving the positive predictive value of the risk factor tool or applying it to groups with higher prevalence of latent tuberculosis would make its use more cost-effective. Universal tuberculin skin testing should be discontinued, and targeted testing should be considered only when the prevalence of risk factor positivity and the prevalence of tuberculin skin testing positivity among risk factor–positive individuals are high enough to meet acceptable thresholds for cost-effectiveness.
Prenatal Cocaine and Tobacco Effects on Children's Language Trajectories
Authors: Lewis Barbara A. , Kirchner H. Lester , Short Elizabeth J. , Minnes Sonia , Weishampel Paul , Satayathum Sudtida , Singer Lynn T. 
Published: July 2007

OBJECTIVE. The objective of this study was to examine the effects of prenatal cocaine and polydrug exposure on language development of preschool children using a prospective longitudinal model, controlling for confounders.
METHODS. Children who were exposed to cocaine in utero (n = 209) and nonexposed children (n = 189) were followed prospectively at birth and at 1, 2, 4, and 6 years of age and were compared on receptive, expressive, and total language scores across time using random coefficient models, controlling for confounders.
RESULTS. A significant, stable effect of cocaine exposure on language development was observed over time for all language domains, with cocaine exposure related to poorer language performance. Cigarette exposure was related to lower receptive language scores. Environmental influences on language scores were also observed. Both the cocaine-exposed and nonexposed children declined in language performance over time.
CONCLUSIONS. Prenatal cocaine exposure has a stable negative effect on language skills during the first 6 years of life. Both cocaine-exposed and nonexposed children showed decreased language growth over time; however, cocaine-exposed children demonstrated linguistic deficits compared with nonexposed peers and did not catch up. Cigarette and environmental influences were also noted.
Obesity Risk for Female Victims of Childhood Sexual Abuse: A Prospective Study
Authors: Noll Jennie G. , Zeller Meg H. , Trickett Penelope K. , Putnam Frank W. 
Published: July 2007

OBJECTIVE. Efforts are under way to articulate environmental, psychosocial, and biological conditions that may predispose the development and maintenance of obesity. There is increasing evidence that adverse childhood experiences such as childhood abuse may be implicated in the development of obesity. Given the dearth of prospective evidence for this link, the objective of this study was to track body mass across development (from childhood, through adolescence, and into young adulthood [ie, ages 6–27]) in a prospective, longitudinal study of abused and nonabused female subjects.
METHODS. Height and weight were obtained for 84 female subjects with substantiated childhood sexual abuse and 89 demographically similar comparison female subjects at 6 points during development. Obesity status was examined at various stages during development, and body-mass growth trajectories were contrasted across the 2 groups. It was hypothesized that, in comparison with their nonabused peers, abused female subjects would be more likely to (1) manifest obesity by early adulthood and (2) manifest high-risk growth trajectories throughout development.
RESULTS. Obesity rates were not different across groups in childhood or adolescence. By young adulthood (ages 20–27), abused female subjects were significantly more likely to be obese (42.25%) than were comparison female subjects (28.40%). Hierarchical linear modeling growth-trajectory analyses indicated that abused female subjects, on average, acquired body mass at a significantly steeper rate from childhood through young adulthood than did comparison female subjects after controlling for minority status and parity.
CONCLUSIONS. Psychosocial difficulties (eg, depression) and psychobiological conditions (eg, hypothalamic-pituitary-adrenal axis dysregulation) that have been shown to be related to both childhood abuse and obesity may help to explain these results. The identification of high-risk growth trajectories may improve health outcomes for victims. Systematic study of the mechanistic pathways and mediating processes that would help to explain the connection between childhood sexual abuse and later obesity is encouraged.
Use of Complementary and Alternative Medicine in a General Pediatric Clinic
Authors: Jean Dany , Cyr Claude 
Published: July 2007

BACKGROUND. Use of complementary and alternative medical therapies is common and increasing, particularly for children with chronic disease.OBJECTIVES. The purpose of this work was to describe the use of complementary and alternative medicine by children and to identify factors that may influence the use of complementary and alternative medicine.PATIENTS AND METHODS. We conducted a cross-sectional descriptive study with children who were visiting a pediatric outpatient clinic. Parent's satisfaction about primary care was evaluated with the Parent's Perceptions of Pediatric Primary Care Quality questionnaire.RESULTS. Fifty-four percent of children used ≥1 type of complementary and alternative medicine in the previous year. No sociodemographic characteristic difference was found between user and nonuser groups. Children most often used complementary and alternative medicine to treat musculoskeletal problems (27%), psychological problems (24%), or infections (20%). Factors that influenced complementary and alternative medicine use were “word of mouth” (36%), “reference by a physician” (28%), “personal experience by parents” (28%), and “no adequate resources in ‘traditional’ medicine” (21%). Forty-seven percent of complementary and alternative medicine users used prescribed medications simultaneously. Most users (75%) believed that complementary and alternative medicine had no potential adverse effects or interactions with prescribed medication. Only 44% of complementary and alternative users were known as such by their physician. The primary care satisfaction was significantly lower in complementary and alternative users versus nonusers. Parents of complementary and alternative users were less satisfied in the areas of accessibility, knowledge of the patient, and communication.CONCLUSIONS. Complementary and alternative medicine was used by 54% of the children in our cohort. Complementary and alternative medicine users were less satisfied with primary care than nonusers. Only 44% of complementary and alternative medicine users were known by their physician. It is important that physicians systematically elicit families' expectations of treatment and be aware of the range of therapies used by children.