bluuebunny/crossref_metadata_2025_split huggingface dataset:
From Hypo- to Hypersuppression: Effect of Amino Acid Substitutions on the RNA-Silencing Suppressor Activity of the Tobacco etch potyvirus HC-Pro
Authors: Torres-Barceló Clara , Martín Susana , Daròs José-Antonio , Elena Santiago F 
Published: September 2008

Abstract
RNA silencing participates in several important functions: from the regulation of cell metabolism and organism development to sequence-specific antiviral defense. Most plant viruses have evolved proteins that suppress RNA silencing and that in many cases are multifunctional. Tobacco etch potyvirus (TEV) HC-Pro protein suppresses RNA silencing and participates in aphid-mediated transmission, polyprotein processing, and genome amplification. In this study, we have generated 28 HC-Pro amino acid substitution mutants and quantified their capacity as suppressors of RNA silencing in a transient expression assay. Most mutations either had no quantitative effect or completely abolished silencing suppression (10 in each class), 3 caused a significant decrease in the activity, and 5 significantly increased it, revealing an unexpected high frequency of mutations conferring hypersuppressor activity. A representative set of the mutant alleles, containing both hypo- and hypersuppressors, was further analyzed for their effect on TEV accumulation and the strength of induced symptoms. Whereas TEV variants with hyposuppressor mutants were far less virulent than wild-type TEV, those with hypersuppressor alleles induced symptoms that were not more severe than those characteristic of the wild-type virus, suggesting that there is not a perfect match between suppression and virulence.
Interactions Between Markers Can Be Caused by the Dominance Effect of Quantitative Trait Loci
Authors: Zhang Luyan , Li Huihui , Li Zhonglai , Wang Jiankang 
Published: September 2008

AbstractF2 populations are commonly used in genetic studies of animals and plants. For simplicity, most quantitative trait locus or loci (QTL) mapping methods have been developed on the basis of populations having two distinct genotypes at each polymorphic marker or gene locus. In this study, we demonstrate that dominance can cause the interactions between markers and propose an inclusive linear model that includes marker variables and marker interactions so as to completely control both additive and dominance effects of QTL. The proposed linear model is the theoretical basis for inclusive composite-interval QTL mapping (ICIM) for F2 populations, which consists of two steps: first, the best regression model is selected by stepwise regression, which approximately identifies markers and marker interactions explaining both additive and dominance variations; second, the interval mapping approach is applied to the phenotypic values adjusted by the regression model selected in the first step. Due to the limited mapping population size, the large number of variables, and multicollinearity between variables, coefficients in the inclusive linear model cannot be accurately determined in the first step. Interval mapping is necessary in the second step to fine tune the QTL to their true positions. The efficiency of including marker interactions in mapping additive and dominance QTL was demonstrated by extensive simulations using three QTL distribution models with two population sizes and an actual rice F2 population.
Dynamics and Differential Proliferation of Transposable Elements During the Evolution of the B and A Genomes of Wheat
Authors: Charles Mathieu , Belcram Harry , Just Jérémy , Huneau Cécile , Viollet Agnès , Couloux Arnaud , Segurens Béatrice , Carter Meredith , Huteau Virginie , Coriton Olivier , Appels Rudi , Samain Sylvie , Chalhoub Boulos 
Published: September 2008

AbstractTransposable elements (TEs) constitute &gt;80% of the wheat genome but their dynamics and contribution to size variation and evolution of wheat genomes (Triticum and Aegilops species) remain unexplored. In this study, 10 genomic regions have been sequenced from wheat chromosome 3B and used to constitute, along with all publicly available genomic sequences of wheat, 1.98 Mb of sequence (from 13 BAC clones) of the wheat B genome and 3.63 Mb of sequence (from 19 BAC clones) of the wheat A genome. Analysis of TE sequence proportions (as percentages), ratios of complete to truncated copies, and estimation of insertion dates of class I retrotransposons showed that specific types of TEs have undergone waves of differential proliferation in the B and A genomes of wheat. While both genomes show similar rates and relatively ancient proliferation periods for the Athila retrotransposons, the Copia retrotransposons proliferated more recently in the A genome whereas Gypsy retrotransposon proliferation is more recent in the B genome. It was possible to estimate for the first time the proliferation periods of the abundant CACTA class II DNA transposons, relative to that of the three main retrotransposon superfamilies. Proliferation of these TEs started prior to and overlapped with that of the Athila retrotransposons in both genomes. However, they also proliferated during the same periods as Gypsy and Copia retrotransposons in the A genome, but not in the B genome. As estimated from their insertion dates and confirmed by PCR-based tracing analysis, the majority of differential proliferation of TEs in B and A genomes of wheat (87 and 83%, respectively), leading to rapid sequence divergence, occurred prior to the allotetraploidization event that brought them together in Triticum turgidum and Triticum aestivum, &lt;0.5 million years ago. More importantly, the allotetraploidization event appears to have neither enhanced nor repressed retrotranspositions. We discuss the apparent proliferation of TEs as resulting from their insertion, removal, and/or combinations of both evolutionary forces.
Muller's Ratchet and the Degeneration of Y Chromosomes: A Simulation Study
Authors: Engelstädter Jan 
Published: September 2008

Abstract
A typical pattern in sex chromosome evolution is that Y chromosomes are small and have lost many of their genes. One mechanism that might explain the degeneration of Y chromosomes is Muller's ratchet, the perpetual stochastic loss of linkage groups carrying the fewest number of deleterious mutations. This process has been investigated theoretically mainly for asexual, haploid populations. Here, I construct a model of a sexual population where deleterious mutations arise on both X and Y chromosomes. Simulation results of this model demonstrate that mutations on the X chromosome can considerably slow down the ratchet. On the other hand, a lower mutation rate in females than in males, background selection, and the emergence of dosage compensation are expected to accelerate the process.
Retention of Induced Mutations in a Drosophila Reverse-Genetic Resource
Authors: Cooper Jennifer L , Greene Elizabeth A , Till Bradley J , Codomo Christine A , Wakimoto Barbara T , Henikoff Steven 
Published: September 2008

Abstract
Targeting induced local lesions in genomes (TILLING) is a reverse-genetic method for identifying point mutations in chemically mutagenized populations. For functional genomics, it is ideal to have a stable collection of heavily mutagenized lines that can be screened over an extended period of time. However, long-term storage is impractical for Drosophila, so mutant strains must be maintained by continual propagation of live cultures. Here we evaluate a strategy in which ethylmethane sulfonate (EMS) mutagenized chromosomes were maintained as heterozygotes with balancer chromosomes for &gt;100 generations before screening. The strategy yielded a spectrum of point mutations similar to those found in previous studies of EMS-induced mutations, as well as 2.4% indels (insertions and deletions). Our analysis of 1887 point mutations in 148 targets showed evidence for selection against deleterious lesions and differential retention of lesions among targets on the basis of their position relative to balancer breakpoints, leading to a broad distribution of mutational densities. Despite selection and differential retention, the success of a user-funded service based on screening a large collection several years after mutagenesis indicates sufficient stability for use as a long-term reverse-genetic resource. Our study has implications for the use of balancer chromosomes to maintain mutant lines and provides the first large-scale quantitative assessment of the limitations of using breeding populations for repositories of genetic variability.
Cohesin and Recombination Proteins Influence the G1-to-S Transition in Azygotic Meiosis inSchizosaccharomyces pombe
Authors: Doll Eveline , Molnar Monika , Cuanoud Gabriella , Octobre Guillaume , Latypov Vitaly , Ludin Katja , Kohli Jürg 
Published: September 2008

AbstractTo determine whether recombination and/or sister-chromatid cohesion affect the timing of meiotic prophase events, the horsetail stage and S phase were analyzed in Schizosaccharomyces pombe strains carrying mutations in the cohesin genes rec8 or rec11, the linear element gene rec10, the pairing gene meu13, the double-strand-break formation genes rec6, rec7, rec12, rec14, rec15, and mde2, and the recombination gene dmc1. The double-mutant strains rec8 rec11 and rec8 rec12 were also assayed. Most of the single and both double mutants showed advancement of bulk DNA synthesis, start of nuclear movement (horsetail stage), and meiotic divisions by up to 2 hr. Only mde2 and dmc1 deletion strains showed wild-type timing. Contrasting behavior was observed for rec8 deletions (delayed by 1 hr) compared to a rec8 point mutation (advanced by 1 hr). An hypothesis for the role of cohesin and recombination proteins in the control of the G1-to-S transition is proposed. Finally, differences between azygotic meiosis and two other types of fission yeast meiosis (zygotic and pat1-114 meiosis) are discussed with respect to possible control steps in meiotic G1.
Genetic Redundancy in Soybean Photoresponses Associated With Duplication of the Phytochrome A Gene
Authors: Liu Baohui , Kanazawa Akira , Matsumura Hisakazu , Takahashi Ryoji , Harada Kyuya , Abe Jun 
Published: September 2008

Abstract
Gene and genome duplications underlie the origins of evolutionary novelty in plants. Soybean, Glycine max, is considered to be a paleopolyploid species with a complex genome. We found multiple homologs of the phytochrome A gene (phyA) in the soybean genome and determined the DNA sequences of two paralogs designated GmphyA1 and GmphyA2. Analysis of the GmphyA2 gene from the lines carrying a recessive allele at a photoperiod insensitivity locus, E4, revealed that a Ty1/copia-like retrotransposon was inserted in exon 1 of the gene, which resulted in dysfunction of the gene. Mapping studies suggested that GmphyA2 is encoded by E4. The GmphyA1 gene was mapped to a region of linkage group O, which is homeologous to the region harboring E4 in linkage group I. Plants homozygous for the e4 allele were etiolated under continuous far red light, but the de-etiolation occurred partially, indicating that the mutation alone did not cause a complete loss of phyA function. The genetic redundancy suggests that the presence of duplicated copies of phyA genes accounts for the generation of photoperiod insensitivity, while protecting against the deleterious effects of mutation. Thus, this phenomenon provides a link between gene duplication and establishment of an adaptive response of plants to environments.
Bursicon Signaling Mutations Separate the Epithelial–Mesenchymal Transition From Programmed Cell Death DuringDrosophila melanogasterWing Maturation
Authors: Natzle Jeanette E , Kiger John A , Green M M 
Published: September 2008

AbstractFollowing eclosion from the pupal case, wings of the immature adult fly unfold and expand to present a flat wing blade. During expansion the epithelia, which earlier produced the wing cuticle, delaminate from the cuticle, and the epithelial cells undergo an epithelial–mesenchymal transition (EMT). The resulting fibroblast-like cells then initiate a programmed cell death, produce an extracellular matrix that bonds dorsal and ventral wing cuticles, and exit the wing. Mutants that block wing expansion cause persistence of intact epithelia within the unexpanded wing. However, the normal progression of chromatin condensation and fragmentation accompanying programmed cell death in these cells proceeds with an approximately normal time course. These observations establish that the Bursicon/Rickets signaling pathway is necessary for both wing expansion and initiation of the EMT that leads to removal of the epithelial cells from the wing. They demonstrate that a different signal can be used to activate programmed cell death and show that two distinct genetic programs are in progress in these cells during wing maturation.
γTub23CInteracts Genetically With Brahma Chromatin-Remodeling Complexes inDrosophila melanogaster
Authors: Vázquez Martha , Cooper Monica T , Zurita Mario , Kennison James A 
Published: September 2008

AbstractThe brahma gene encodes the catalytic subunit of the Drosophila melanogaster BRM chromatin-remodeling complexes. Screening for mutations that interact with brahma, we isolated the dominant-negative Pearl-2 allele of γTub23C. γTub23C encodes one of the two γ-tubulin isoforms in Drosophila and is essential for zygotic viability and normal adult patterning. γ-Tubulin is a subunit of microtubule organizer complexes. We show that mutations in lethal (1) discs degenerate 4, which encodes the Grip91 subunit of microtubule organizer complexes, suppress the recessive lethality and the imaginal phenotypes caused by γTub23C mutations. The genetic interactions between γTub23C and chromatin-remodeling mutations suggest that γ-tubulin might have a role in regulating gene expression.
glo-3, a Novel Caenorhabditis elegans Gene, Is Required for Lysosome-Related Organelle Biogenesis
Authors: Rabbitts Beverley M , Ciotti Marcela K , Miller Natalie E , Kramer Maxwell , Lawrenson Andrea L , Levitte Steven , Kremer Susan , Kwan Elizabeth , Weis Allison M , Hermann Greg J 
Published: September 2008

Abstract
Gut granules are specialized lysosome-related organelles that act as sites of fat storage in Caenorhabditis elegans intestinal cells. We identified mutations in a gene, glo-3, that functions in the formation of embryonic gut granules. Some glo-3(−) alleles displayed a complete loss of embryonic gut granules, while other glo-3(−) alleles had reduced numbers of gut granules. A subset of glo-3 alleles led to mislocalization of gut granule contents into the intestinal lumen, consistent with a defect in intracellular trafficking. glo-3(−) embryos lacking gut granules developed into adults containing gut granules, indicating that glo-3(+) function may be differentially required during development. We find that glo-3(+) acts in parallel with or downstream of the AP-3 complex and the PGP-2 ABC transporter in gut granule biogenesis. glo-3 encodes a predicted membrane-associated protein that lacks obvious sequence homologs outside of nematodes. glo-3 expression initiates in embryonic intestinal precursors and persists almost exclusively in intestinal cells through adulthood. GLO-3∷GFP localizes to the gut granule membrane, suggesting it could play a direct role in the trafficking events at the gut granule. smg-1(−) suppression of glo-3(−) nonsense alleles indicates that the C-terminal half of GLO-3, predicted to be present in the cytoplasm, is not necessary for gut granule formation. Our studies identify GLO-3 as a novel player in the formation of lysosome-related organelles.
MEANINGS & MOTIVES Experts Debating Tobacco Addiction
Authors: Mars Sarah G. , Ling Pamela M. 
Published: September 2008

Over the last 50 years, tobacco has been excluded from and then included in the category of addictive substances. We investigated influences on these opposing definitions and their application in expert witness testimony in litigation in the 1990s and 2000s. A scientist with ties to the tobacco industry influenced the selection of a definition of addiction that led to the classification of tobacco as a “habituation” in the 1964 Surgeon General's Advisory Committee report. Tobacco was later defined as addictive in the 1988 surgeon general's report. Expert witnesses for tobacco companies used the 1964 report's definition until Philip Morris Tobacco Company publicly changed its position in 1997 to agree that nicotine was addictive. Expert witnesses for plaintiffs suing the tobacco industry used the 1988 report's definition, arguing that new definitions were superior because of scientific advance. Both sides viewed addiction as an objective entity that could be defined more or less accurately.
Ethics in American Health 2: An Ethical Framework for Health System Reform
Authors: Ruger Jennifer Prah 
Published: September 2008

I argue that an ethical vision resting on explicitly articulated values and norms is critical to ensuring comprehensive health reform. Reform requires a consensus on the public good transcending self-interest and narrow agendas and underpinning collective action for universal coverage.In what I call shared health governance, individuals, providers, and institutions all have essential roles in achieving health goals and work together to create a positive environment for health.This ethical paradigm provides (1) reasoned consensus through a joint scientific and deliberative approach to judge the value of a health care intervention; (2) a method for achieving consensus that differs from aggregate tools such as a strict majority vote; (3) combined technical and ethical rationality for collective choice; (4) a joint clinical and economic approach combining efficiency with equity, but with economic solutions following and complementing clinical progress; and (5) protection for disabled individuals from discrimination.
When There's a Heartbeat: Miscarriage Management in Catholic-Owned Hospitals
Authors: Freedman Lori R. , Landy Uta , Steinauer Jody 
Published: September 2008

As Catholic-owned hospitals merge with or take over other facilities, they impose restrictions on reproductive health services, including abortion and contraceptive services. Our interviews with US obstetrician–gynecologists working in Catholic-owned hospitals revealed that they are also restricted in managing miscarriages. Catholic-owned hospital ethics committees denied approval of uterine evacuation while fetal heart tones were still present, forcing physicians to delay care or transport miscarrying patients to non–Catholic-owned facilities. Some physicians intentionally violated protocol because they felt patient safety was compromised. Although Catholic doctrine officially deems abortion permissible to preserve the life of the woman, Catholic-owned hospital ethics committees differ in their interpretation of how much health risk constitutes a threat to a woman's life and therefore how much risk must be present before they approve the intervention.
Smoking Cessation Intervention for Female Prisoners: Addressing an Urgent Public Health Need
Authors: Cropsey Karen , Eldridge Gloria , Weaver Michael , Villalobos Gabriela , Stitzer Maxine , Best Al 
Published: September 2008

Objectives. We tested the efficacy of a combined pharmacologic and behavioral smoking cessation intervention among women in a state prison in the southern United States. Methods. The study design was a randomized controlled trial with a 6-month waitlist control group. The intervention was a 10-week group intervention combined with nicotine replacement therapy. Two hundred and fifty participants received the intervention, and 289 were in the control group. Assessments occurred at baseline; end of treatment; 3, 6, and 12 months after treatment; and at weekly sessions for participants in the intervention group. Results. The intervention was efficacious compared with the waitlist control group. Point prevalence quit rates for the intervention group were 18% at end of treatment, 17% at 3-month follow-up, 14% at 6-month follow-up, and 12% at 12-month follow-up, quit rates that are consistent with outcomes from community smoking-cessation interventions. Conclusions. Female prisoners are interested in smoking cessation interventions and achieved point-prevalence quit rates similar to community samples. Augmenting tobacco control policies in prison with smoking cessation interventions has the potential to address a significant public health need.
Household Smoking Bans and Adolescent Antismoking Attitudes and Smoking Initiation: Findings From a Longitudinal Study of a Massachusetts Youth Cohort
Authors: Albers Alison B. , Biener Lois , Siegel Michael , Cheng Debbie M. , Rigotti Nancy 
Published: September 2008

Objectives. We sought to determine whether adolescents living in households in which smoking was banned were more likely to develop antismoking attitudes and less likely to progress to smoking compared with those living in households in which smoking was not banned. Methods. We completed a longitudinal 4-year, 3-wave study of a representative sample of 3834 Massachusetts youths aged 12 to 17 years at baseline; 2791 (72.8%) were reinterviewed after 2 years, and 2217 (57.8%) were reinterviewed after 4 years. We used a 3-level hierarchical linear model to analyze the effect of a household ban on antismoking attitudes and smoking behaviors. Results. The absence of a household smoking ban increased the odds that youths perceived a high prevalence of adult smoking, among both youths living with a smoker (odds ratio [OR] = 1.56; 95% confidence interval [CI] = 1.15, 2.13) and those living with nonsmokers (OR = 1.75; 95% CI = 1.29, 2.37). Among youths who lived with nonsmokers, those with no home ban were more likely to transition from nonsmoking to early experimentation (OR = 1.89; 95% CI = 1.30, 2.74) than were those with a ban. Conclusions. Home smoking bans may promote antismoking attitudes among youths and reduce progression to smoking experimentation among youths who live with nonsmokers.
Medical Liability Insurance as a Barrier to the Provision of Abortion Services in Family Medicine
Authors: Dehlendorf Christine E. , Grumbach Kevin 
Published: September 2008

Family physicians who wish to provide abortions have been subject to both denial of coverage by medical liability insurers and the imposition of large premium increases. These policy decisions by insurance companies raise questions about the role of family physicians in abortion care and about the autonomy of medical specialties in defining their scope of practice. We review the issues specific to abortion services in the primary care setting and examine the broader implications for the medical profession. Finally, we review how advocacy and improved regulation of the insurance industry could help to ensure that clinicians who are trained and willing to provide services to their patients are not limited by the decisions of medical liability insurers.
HIV and Pregnancy Intentions: Do Services Adequately Respond to Women's Needs?
Authors: Gruskin Sofia , Firestone Rebecca , MacCarthy Sarah , Ferguson Laura 
Published: September 2008

Too little is known about how an HIV diagnosis and access to care and treatment affect women's childbearing intentions. As access to antiretroviral therapy improves, greater numbers of HIV-positive women are living longer, healthier lives, and many want to have children. Effectively supporting women's reproductive decisionmaking in the context of HIV requires understanding how pregnancy, reproduction, and HIV intersect and asking questions that bridge the biomedical and social sciences. Considering women to be at the center of decisions on health policy and service delivery can help provide an appropriate constellation of services. A clear research agenda is needed to create a more coordinated approach to policies and programs supporting the pregnancy intentions of women with HIV.