bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of Pet Ownership and Attachment in Older Adults
Authors: Watt Deidre , Pachana Nancy A. 
Published: February 2008

AbstractAustralia is preparing for a population increase in persons aged over 65 years, which will likely result in increased mental health needs for this group. Sub-clinical levels of depression, anxiety and loneliness are common in older adults. Older adults are also more likely than any other age group to live alone. Research has suggested that older adults living on their own often report companion animals as providing important social support. Thirty-two community-dwelling older adults, between 60 and 75+ years of age, took part in this study examining attachment to pets in an older cohort. Previous or current pet ownership was a requirement for inclusion in the study in order to account for possible bias of nonpet owners on reporting pets as a positive influence on wellbeing. Results found support for the psychometric properties of a relatively new attachment scale designed for older adults. Results also indicated limited support for a relationship between pet attachment and quality of life in the study group. Implications for clinical work with older adults and areas for future research are discussed.
Rescue From Oculocutaneous Albinism Type 4 Using Medaka slc45a2 cDNA Driven by Its Own Promoter
Authors: Fukamachi Shoji , Kinoshita Masato , Tsujimura Taro , Shimada Atsuko , Oda Shoji , Shima Akihiro , Meyer Axel , Kawamura Shoji , Mitani Hiroshi 
Published: February 2008

Abstract
Patients and vertebrate mutants with oculocutaneous albinism type 4 (OCA4) have mutations in the solute carrier family 45 member 2 (slc45a2) gene. However, there is no empirical evidence for this gene–phenotype relationship. There is a unique OCA4 mutant in medaka (b) that exhibits albinism only in the skin, but the mechanism underlying this phenotype is also unknown. In this study, we rescued medaka OCA4 phenotypes, in both the eyes and the skin, by micro-injection of an slc45a2-containing genomic fragment or slc45a2 cDNA driven by its own 0.9-kb promoter. We also identified a spontaneous nucleotide change of 339 bp in the promoter as the b mutation. There are multiple transcription start sites in medaka slc45a2, as in its human ortholog, and only the shortest and eye-specific mRNA is transcribed with the b mutation. Interestingly, we further revealed a conserved pyrimidine (Py)-rich sequence of ∼10 bp in the promoter by medaka–pufferfish comparative genomics and verified that it plays an indispensable role for expression of slc45a2 in the skin. Further studies of the 0.9-kb promoter identified in this study should provide insights into the cis/trans-regulatory mechanisms underlying the ocular and cutaneous expression of slc45a2.
Linkage Disequilibrium Under Skewed Offspring Distribution Among Individuals in a Population
Authors: Eldon Bjarki , Wakeley John 
Published: February 2008

Abstract
Correlations in coalescence times between two loci are derived under selectively neutral population models in which the offspring of an individual can number on the order of the population size. The correlations depend on the rates of recombination and random drift and are shown to be functions of the parameters controlling the size and frequency of these large reproduction events. Since a prediction of linkage disequilibrium can be written in terms of correlations in coalescence times, it follows that the prediction of linkage disequilibrium is a function not only of the rate of recombination but also of the reproduction parameters. Low linkage disequilibrium is predicted if the offspring of a single individual frequently replace almost the entire population. However, high linkage disequilibrium can be predicted if the offspring of a single individual replace an intermediate fraction of the population. In some cases the model reproduces the standard Wright–Fisher predictions. Contrary to common intuition, high linkage disequilibrium can be predicted despite frequent recombination, and low linkage disequilibrium under infrequent recombination. Simulations support the analytical results but show that the variance of linkage disequilibrium is very large.
The Genetics of Domestication of the Azuki Bean (Vigna angularis)
Authors: Kaga Akito , Isemura Takehisa , Tomooka Norihiko , Vaughan Duncan A 
Published: February 2008

AbstractGenetic differences between azuki bean (Vigna angularis var. angularis) and its presumed wild ancestor (V. angularis var. nipponensis) were resolved into QTL for traits associated with adaptation to their respective distinct habits. A genetic linkage map constructed using progenies from a cross between Japanese cultivated and wild azuki beans covers 92.8% of the standard azuki bean linkage map. A reciprocal translocation between cultivated and wild azuki bean parents was identified on the basis of the linkage map having a pseudolinkage group and clustering of seed productivity-related QTL with large effect near the presumed breakpoints. In total, 162 QTL were identified for 46 domestication-related traits. Domestication of azuki bean has involved a trade-off between seed number and seed size: fewer but longer pods and fewer but larger seeds on plants with shorter stature in cultivated azuki bean being at the expense of overall seed yield. Genes found related to germination and flowering time in cultivated azuki bean may confer a selective advantage to the hybrid derivatives under some ecological conditions and may explain why azuki bean has evolved as a crop complex in Japan.
Catalytic-Site Mutations in the MYST Family Histone Acetyltransferase Esa1
Authors: Decker Peter V , Yu David Y , Iizuka Masayoshi , Qiu Qifeng , Smith M Mitchell 
Published: February 2008

AbstractEsa1 is the only essential histone acetyltransferase (HAT) in budding yeast. It is the catalytic subunit of at least two multiprotein complexes, NuA4 and Piccolo NuA4 (picNuA4), and its essential function is believed to be its catalytic HAT activity. To examine the role of Esa1 in DNA damage repair, we isolated viable esa1 mutants with a range of hypersensitivities to the toposide camptothecin. Here we show that the sensitivity of these mutants to a variety of stresses is inversely proportional to their level of histone H4 acetylation, demonstrating the importance of Esa1 catalytic activity for resistance to genotoxic stress. Surprisingly, individual mutations in two residues directly involved in catalysis were not lethal even though the mutant enzymes appear catalytically inactive both in vivo and in vitro. However, the double-point mutant is lethal, demonstrating that the essential function of Esa1 relies on residues within the catalytic pocket but not catalysis. We propose that the essential function of Esa1 may be to bind acetyl-CoA or lysine substrates and positively regulate the activities of NuA4 and Piccolo NuA4.
Maternal Effects as the Cause of Parent-of-Origin Effects That Mimic Genomic Imprinting
Authors: Hager Reinmar , Cheverud James M , Wolf Jason B 
Published: February 2008

Abstract
Epigenetic effects are increasingly recognized as an important source of variation in complex traits and have emerged as the focus of a rapidly expanding area of research. Principle among these effects is genomic imprinting, which has generally been examined in analyses of complex traits by testing for parent-of-origin-dependent effects of alleles. However, in most of these analyses maternal effects are confounded with genomic imprinting because they can produce the same patterns of phenotypic variation expected for various forms of imprinting. Distinguishing between the two is critical for genetic and evolutionary studies because they have entirely different patterns of gene expression and evolutionary dynamics. Using a simple single-locus model, we show that maternal genetic effects can result in patterns that mimic those expected under genomic imprinting. We further demonstrate how maternal effects and imprinting effects can be distinguished using genomic data from parents and offspring. The model results are applied to a genome scan for quantitative trait loci (QTL) affecting growth- and weight-related traits in mice to illustrate how maternal effects can mimic imprinting. This genome scan revealed five separate maternal-effect loci that caused a diversity of patterns mimicking those expected under various modes of genomic imprinting. These results demonstrate that the appearance of parent-of-origin-dependent effects (POEs) of alleles at a locus cannot be taken as direct evidence that the locus is imprinted. Moreover, they show that, in gene mapping studies, genetic data from both parents and offspring are required to successfully differentiate between imprinting and maternal effects as the cause of apparent parent-of-origin effects of alleles.
Synergistic Fitness Interactions and a High Frequency of Beneficial Changes Among Mutations Accumulated Under Relaxed Selection inSaccharomyces cerevisiae
Authors: Dickinson W Joseph 
Published: February 2008

AbstractSpontaneous mutations were accumulated for ∼4800 generations in 48 lines of yeast protected from effective selection by frequent passage through single-cell bottlenecks. Changes in fitness were evaluated by direct competition with matched parental stocks differing only at a selectively neutral marker locus. Average fitness declined by ∼5% over the course of the experiment. The rate of change increased sharply in later generations, strongly suggesting synergistic epistasis. Divergence among lines increased rapidly relative to the change in average fitness and also at an accelerating pace. Both results are well matched by a model assuming that fitness cost increases exponentially (approximately second order) with the number of accumulated mutations. This result is consistent with fitness loss due primarily to interactions between specific pairs of gene products. I also estimate that ∼25% of the mutations with detectable fitness effects were beneficial. This result can be explained by the fact that the effects of most mutations are small relative to the distance from a local fitness optimum.
Bayesian Variable Selection for Detecting Adaptive Genomic Differences Among Populations
Authors: Riebler Andrea , Held Leonhard , Stephan Wolfgang 
Published: February 2008

AbstractWe extend an Fst-based Bayesian hierarchical model, implemented via Markov chain Monte Carlo, for the detection of loci that might be subject to positive selection. This model divides the Fst-influencing factors into locus-specific effects, population-specific effects, and effects that are specific for the locus in combination with the population. We introduce a Bayesian auxiliary variable for each locus effect to automatically select nonneutral locus effects. As a by-product, the efficiency of the original approach is improved by using a reparameterization of the model. The statistical power of the extended algorithm is assessed with simulated data sets from a Wright–Fisher model with migration. We find that the inclusion of model selection suggests a clear improvement in discrimination as measured by the area under the receiver operating characteristic (ROC) curve. Additionally, we illustrate and discuss the quality of the newly developed method on the basis of an allozyme data set of the fruit fly Drosophila melanogaster and a sequence data set of the wild tomato Solanum chilense. For data sets with small sample sizes, high mutation rates, and/or long sequences, however, methods based on nucleotide statistics should be preferred.
Functional Interactions Between Sae2 and the Mre11 Complex
Authors: Kim Hee-Sook , Vijayakumar Sangeetha , Reger Mike , Harrison Jacob C , Haber James E , Weil Clifford , Petrini John H J 
Published: February 2008

Abstract
The Mre11 complex functions in double-strand break (DSB) repair, meiotic recombination, and DNA damage checkpoint pathways. Sae2 deficiency has opposing effects on the Mre11 complex. On one hand, it appears to impair Mre11 nuclease function in DNA repair and meiotic DSB processing, and on the other, Sae2 deficiency activates Mre11-complex-dependent DNA-damage-signaling via the Tel1–Mre11 complex (TM) pathway. We demonstrate that SAE2 overexpression blocks the TM pathway, suggesting that Sae2 antagonizes Mre11-complex checkpoint functions. To understand how Sae2 regulates the Mre11 complex, we screened for sae2 alleles that behaved as the null with respect to Mre11-complex checkpoint functions, but left nuclease function intact. Phenotypic characterization of these sae2 alleles suggests that Sae2 functions as a multimer and influences the substrate specificity of the Mre11 nuclease. We show that Sae2 oligomerizes independently of DNA damage and that oligomerization is required for its regulatory influence on the Mre11 nuclease and checkpoint functions.
Accelerated Mitochondrial Evolution and “Darwin's Corollary”: Asymmetric Viability of Reciprocal F1 Hybrids in Centrarchid Fishes
Authors: Bolnick Daniel I , Turelli Michael , López-Fernández Hernán , Wainwright Peter C , Near Thomas J 
Published: February 2008

Abstract
Reciprocal crosses between species can yield hybrids with different viabilities. The high frequency of this asymmetric hybrid viability (“Darwin's corollary”) places it alongside Haldane's rule and the “large-X effect” as a general feature of postmating reproductive isolation. Recent theory suggests that reciprocal cross asymmetries can arise from stochastic substitutions in uniparentally inherited loci such as mitochondrial genomes, although large systematic differences in mitochondrial substitution rates can also contribute to asymmetries. Although the magnitude of asymmetry will be relatively insensitive to unequal rates of mitochondrial evolution in diverging species, we show here that rate asymmetries can have a large effect on the direction of viability asymmetries. In reciprocal crosses between species, the maternal parent with faster mitochondrial evolution will tend to produce less viable F1 hybrids owing to an increased probability of mito-nuclear incompatibilities. We test this prediction using data on reciprocal hybrid viability and molecular evolution rates from a clade of freshwater fishes, Centrarchidae. As predicted, species with accelerated mitochondrial evolution tend to be the worse maternal parent for F1 hybrids, providing the first comparative evidence for a systematic basis to Darwin's corollary. This result is consistent with the hypothesis that mito-nuclear incompatibilities can play an important role in reproductive isolation. Such asymmetrical reproductive isolation may help explain the asymmetrical mitochondrial introgression observed between many hybridizing species. However, as with any comparative study, we cannot rule out the possibility that our results arise from a mutual correlation with a third variable such as body size.
Drosophila Importin α1 Performs Paralog-Specific Functions Essential For Gametogenesis
Authors: Ratan R , Mason D A , Sinnot B , Goldfarb D S , Fleming R J 
Published: February 2008

Abstract
Importin α's mediate nuclear transport by linking nuclear localization signal (NLS)-containing proteins to importin β1. Animal genomes encode three conserved groups of importin α's, α1's, α2's, and α3's, each of which are competent to bind classical NLS sequences. Using Drosophila melanogaster we describe the isolation and phenotypic characterization of the first animal importin α1 mutant. Animal α1's are more similar to ancestral plant and fungal α1-like genes than to animal α2 and α3 genes. Male and female importin α1 (Dα1) null flies developed normally to adulthood (with a minor wing defect) but were sterile with defects in gametogenesis. The Dα1 mutant phenotypes were rescued by Dα1 transgenes, but not by Dα2 or Dα3 transgenes. Genetic interactions between the ectopic expression of Dα1 and the karyopherins CAS and importin β1 suggest that high nuclear levels of Dα1 are deleterious. We conclude that Dα1 performs paralog-specific activities that are essential for gametogenesis and that regulation of subcellular Dα1 localization may affect cell fate decisions. The initial expansion and specialization of the animal importin α-gene family may have been driven by the specialized needs of gametogenesis. These results provide a framework for studies of the more complex mammalian importin α-gene family.
An Investigation of Heterochromatin Domains on the Fourth Chromosome ofDrosophila melanogaster
Authors: Riddle Nicole C , Leung Wilson , Haynes Karmella A , Granok Howard , Wuller Jo , Elgin Sarah C R 
Published: February 2008

AbstractThe banded portion of Drosophila melanogaster chromosome 4 exhibits euchromatic and heterochromatic characteristics. Reminiscent of heterochromatin, it contains a high percentage of repetitive elements, does not undergo recombination, and exhibits high levels of HP1 and histone-3 lysine-9 dimethylation. However, in the distal 1.2 Mb, the gene density is typical of euchromatin, and this region is polytene in salivary gland nuclei. Using P-element reporters carrying a copy of hsp70-white, alternative chromatin packaging domains can be distinguished by the eye color phenotype. Mapping studies identified the repetitive element 1360 as a candidate for heterochromatin targeting in the fourth chromosome Hcf region. We report here two new screens using this reporter to look for additional heterochromatin target sites. We confirm that reporter elements within 10 kb of 1360 are usually packaged as heterochromatin; however, heterochromatin packaging occurs in the sv region in the absence of 1360. Analyses of the sequences adjacent to P-element reporters show no simple association between specific repeated elements and transgene expression phenotype on a whole chromosome level. The data require that heterochromatin formation as a whole depends on a more complex pattern of sequence organization rather than the presence of a single sequence element.
Neuropathology in Drosophila Mutants With Increased Seizure Susceptibility
Authors: Fergestad Tim , Olson Lisa , Patel Khelan P , Miller Rosie , Palladino Michael J , Ganetzky Barry 
Published: February 2008

AbstractGenetic factors are known to contribute to seizure susceptibility, although the long-term effects of these predisposing factors on neuronal viability remain unclear. To examine the consequences of genetic factors conferring increased seizure susceptibility, we surveyed a class of Drosophila mutants that exhibit seizures and paralysis following mechanical stimulation. These bang-sensitive seizure mutants exhibit shortened life spans and age-dependent neurodegeneration. Because the increased seizure susceptibility in these mutants likely results from altered metabolism and since the Na+/K+ ATPase consumes the majority of ATP in neurons, we examined the effect of ATPα mutations in combination with bang-sensitive mutations. We found that double mutants exhibit strikingly reduced life spans and age-dependent uncoordination and inactivity. These results emphasize the importance of proper cellular metabolism in maintaining both the activity and viability of neurons.
A Drosophila Gain-of-Function Screen for Candidate Genes Involved in Steroid-Dependent Neuroendocrine Cell Remodeling
Authors: Zhao Tao , Gu Tingting , Rice Heather C , McAdams Kathleen L , Roark Kimberly M , Lawson Kaylan , Gauthier Sebastien A , Reagan Kathleen L , Hewes Randall S 
Published: February 2008

Abstract
The normal functioning of neuroendocrine systems requires that many neuropeptidergic cells change, to alter transmitter identity and concentration, electrical properties, and cellular morphology in response to hormonal cues. During insect metamorphosis, a pulse of circulating steroids, ecdysteroids, governs the dramatic remodeling of larval neurons to serve adult-specific functions. To identify molecular mechanisms underlying metamorphic remodeling, we conducted a neuropeptidergic cell-targeted, gain-of-function genetic screen. We screened 6097 lines. Each line permitted Gal4-regulated transcription of flanking genes. A total of 58 lines, representing 51 loci, showed defects in neuropeptide-mediated developmental transitions (ecdysis or wing expansion) when crossed to the panneuropeptidergic Gal4 driver, 386Y-Gal4. In a secondary screen, we found 29 loci that produced wing expansion defects when crossed to a crustacean cardioactive peptide (CCAP)/bursicon neuron-specific Gal4 driver. At least 14 loci disrupted the formation or maintenance of adult-specific CCAP/bursicon cell projections during metamorphosis. These include components of the insulin and epidermal growth factor signaling pathways, an ecdysteroid-response gene, cabut, and an ubiquitin-specific protease gene, fat facets, with known functions in neuronal development. Several additional genes, including three micro-RNA loci and two factors related to signaling by Myb-like proto-oncogenes, have not previously been implicated in steroid signaling or neuronal remodeling.
Multiple Pathways Influence Mitochondrial Inheritance in Budding Yeast
Authors: Frederick Rebecca L , Okamoto Koji , Shaw Janet M 
Published: February 2008

AbstractYeast mitochondria form a branched tubular network. Mitochondrial inheritance is tightly coupled with bud emergence, ensuring that daughter cells receive mitochondria from mother cells during division. Proteins reported to influence mitochondrial inheritance include the mitochondrial rho (Miro) GTPase Gem1p, Mmr1p, and Ypt11p. A synthetic genetic array (SGA) screen revealed interactions between gem1Δ and deletions of genes that affect mitochondrial function or inheritance, including mmr1Δ. Synthetic sickness of gem1Δ mmr1Δ double mutants correlated with defective mitochondrial inheritance by large buds. Additional studies demonstrated that GEM1, MMR1, and YPT11 each contribute to mitochondrial inheritance. Mitochondrial accumulation in buds caused by overexpression of either Mmr1p or Ypt11p did not depend on Gem1p, indicating these three proteins function independently. Physical linkage of mitochondria with the endoplasmic reticulum (ER) has led to speculation that distribution of these two organelles is coordinated. We show that yeast mitochondrial inheritance is not required for inheritance or spreading of cortical ER in the bud. Moreover, Ypt11p overexpression, but not Mmr1p overexpression, caused ER accumulation in the bud, revealing a potential role for Ypt11p in ER distribution. This study demonstrates that multiple pathways influence mitochondrial inheritance in yeast and that Miro GTPases have conserved roles in mitochondrial distribution.