bluuebunny/crossref_metadata_2025_split huggingface dataset:
From natural products to biological tools
Authors: Wipf Peter , Graham Thomas H. , Xiao Jingbo 
Published: April 2007

Abstract
The development of a total synthetic approach for the antimitotic disorazole C1 and the design of a peptide isostere linked to the reactive oxygen scavenger 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) demonstrate established as well as novel strategies for mining the therapeutic potential of natural products.
The c.–292C>T promoter polymorphism increases reticulocyte-type 15-lipoxygenase-1 activity and could be atheroprotective
Authors: Wittwer Jonas , Bayer Mathias , Mosandl Armin , Muntwyler Jörg , Hersberger Martin 
Published: April 2007

AbstractClin Chem Lab Med 2007;45:487–92.
Bayesian Shrinkage Analysis of Quantitative Trait Loci for Dynamic Traits
Authors: Yang Runqing , Xu Shizhong 
Published: April 2007

Abstract
Many quantitative traits are measured repeatedly during the life of an organism. Such traits are called dynamic traits. The pattern of the changes of a dynamic trait is called the growth trajectory. Studying the growth trajectory may enhance our understanding of the genetic architecture of the growth trajectory. Recently, we developed an interval-mapping procedure to map QTL for dynamic traits under the maximum-likelihood framework. We fit the growth trajectory by Legendre polynomials. The method intended to map one QTL at a time and the entire QTL analysis involved scanning the entire genome by fitting multiple single-QTL models. In this study, we propose a Bayesian shrinkage analysis for estimating and mapping multiple QTL in a single model. The method is a combination between the shrinkage mapping for individual quantitative traits and the Legendre polynomial analysis for dynamic traits. The multiple-QTL model is implemented in two ways: (1) a fixed-interval approach where a QTL is placed in each marker interval and (2) a moving-interval approach where the position of a QTL can be searched in a range that covers many marker intervals. Simulation study shows that the Bayesian shrinkage method generates much better signals for QTL than the interval-mapping approach. We propose several alternative methods to present the results of the Bayesian shrinkage analysis. In particular, we found that the Wald test-statistic profile can serve as a mechanism to test the significance of a putative QTL.
Associations Between Sperm Competition and Natural Variation in Male Reproductive Genes on the Third Chromosome of Drosophila melanogaster
Authors: Fiumera Anthony C , Dumont Bethany L , Clark Andrew G 
Published: April 2007

Abstract
We applied association analysis to elucidate the genetic basis for variation in phenotypes affecting postcopulatory sexual selection in a natural population of Drosophila melanogaster. We scored 96 third chromosome substitution lines for nine phenotypes affecting sperm competitive ability and genotyped them at 72 polymorphisms in 13 male reproductive genes. Significant heterogeneity among lines (P &lt; 0.01) was detected for all phenotypes except male-induced refractoriness (P = 0.053). We identified 24 associations (8 single-marker associations, 12 three-marker haplotype associations, and 4 cases of epistasis revealed by single-marker interactions). Fewer than 9 of these associations are likely to be false positives. Several associations were consistent with previous findings [Acp70A with the male's influence on the female's refractoriness to remating (refractory), Esterase-6 with a male's remating probability (remating) and a measure of female offspring production (fecundity)], but many are novel associations with uncharacterized seminal fluid proteins. Four genes showed evidence for pleiotropic effects [CG6168 with a measure of sperm competition (P2′) and refractory, CG14560 with a defensive measure of sperm competition (P1′) and a measure of female fecundity, Acp62F with P2′ and a measure of female fecundity, and Esterase-6 with remating and a measure of female fecundity]. Our findings provide evidence that pleiotropy and epistasis are important factors in the genetic architecture of male reproductive success and show that haplotype analyses can identify associations missed in the single-marker approach.
Shortcut Predictions for Fitness Properties at the Mutation–Selection–Drift Balance and for Its Buildup After Size Reduction Under Different Management Strategies
Authors: García-Dorado Aurora 
Published: April 2007

Abstract
For populations at the mutation–selection–drift (MSD) balance, I develop approximate analytical expressions giving expectations for the number of deleterious alleles per gamete, the number of loci at which any individual is homozygous for deleterious alleles, the inbreeding depression rate, and the additive and dominant components of fitness variance. These predictions are compared to diffusion ones, showing good agreement under a wide range of situations. I also give approximated analytical predictions for the changes in mean and additive variance for fitness when a population approaches a new equilibrium after its effective size is reduced to a stable value. Results are derived for populations maintained with equal family contribution or with no management after size reduction, when selection acts through viability or fertility differences. Predictions are compared to previously published results obtained from transition matrices or stochastic simulations, a good qualitative fit being obtained. Predictions are also obtained for populations of various sizes under different sets of plausible mutational parameters. They are compared to available empirical results for Drosophila, and conservation implications are discussed.
Asymmetric Postmating Isolation: Darwin's Corollary to Haldane's Rule
Authors: Turelli Michael , Moyle Leonie C 
Published: April 2007

AbstractAsymmetric postmating isolation, where reciprocal interspecific crosses produce different levels of fertilization success or hybrid sterility/inviability, is very common. Darwin emphasized its pervasiveness in plants, but it occurs in all taxa assayed. This asymmetry often results from Dobzhansky–Muller incompatibilities (DMIs) involving uniparentally inherited genetic factors (e.g., gametophyte–sporophyte interactions in plants or cytoplasmic–nuclear interactions). Typically, unidirectional (U) DMIs act simultaneously with bidirectional (B) DMIs between autosomal loci that affect reciprocal crosses equally. We model both classes of two-locus DMIs to make quantitative and qualitative predictions concerning patterns of isolation asymmetry in parental species crosses and in the hybrid F1 generation. First, we find conditions that produce expected differences. Second, we present a stochastic analysis of DMI accumulation to predict probable levels of asymmetry as divergence time increases. We find that systematic interspecific differences in relative rates of evolution for autosomal vs. nonautosomal loci can lead to different expected F1 fitnesses from reciprocal crosses, but asymmetries are more simply explained by stochastic differences in the accumulation of U DMIs. The magnitude of asymmetry depends primarily on the cumulative effects of U vs. B DMIs (which depend on heterozygous effects of DMIs), the average number of DMIs required to produce complete reproductive isolation (more asymmetry occurs when fewer DMIs are required), and the shape of the function describing how fitness declines as DMIs accumulate. Comparing our predictions to data from diverse taxa indicates that unidirectional DMIs, specifically involving sex chromosomes, cytoplasmic elements, and maternal effects, are likely to play an important role in postmating isolation.
Evidence forde NovoEvolution of Testis-Expressed Genes in theDrosophila yakuba/Drosophila erectaClade
Authors: Begun David J , Lindfors Heather A , Kern Andrew D , Jones Corbin D 
Published: April 2007

AbstractThe mutational origin and subsequent evolution of de novo genes, which are hypothesized to be genes of recent origin that are not obviously related to ancestral coding sequence, are poorly understood. However, accumulating evidence suggests that such genes may often function in male reproduction. Here we use testis-derived expressed sequence tags (ESTs) from Drosophila yakuba to identify genes that have likely arisen either in D. yakuba or in the D. yakuba/D. erecta ancestor. We found several such genes, which show testis-biased expression and are often X-linked. Comparative data indicate that three of these genes have very short open reading frames, which suggests the possibility that a significant number of testis-biased de novo genes in the D. yakuba/D. erecta clade may be noncoding RNA genes. These data, along with previously published data from D. melanogaster, support the idea that many de novo Drosophila genes function in male reproduction and that a small region of the X chromosome in the melanogaster subgroup may be a hotspot for the evolution of novel testis-biased genes.
Yct1p, a Novel, High-Affinity, Cysteine-Specific Transporter From the Yeast Saccharomyces cerevisiae
Authors: Kaur Jaspreet , Bachhawat Anand K 
Published: April 2007

Abstract
Cysteine transport in the yeast Saccharomyces cerevisiae is mediated by at least eight different permeases, none of which are specific for cysteine. We describe a novel, high-affinity, (Km = 55 μm), cysteine-specific transporter encoded by the ORF YLL055w that was initially identified by a combined strategy of data mining, bioinformatics, and genetic analysis. Null mutants of YLL055w, but not of the other genes encoding for transporters that mediate cysteine uptake such as GAP1, GNP1, MUP1, or AGP1 in a met15Δ background, resulted in a growth defect when cysteine, at low concentrations, was provided as the sole sulfur source. Transport experiments further revealed that Yll055wp was the major contributor to cysteine transport under these conditions. The contributions of the other transporters became relevant only at higher concentrations of cysteine or when YLL055w was either deleted or repressed. YLL055w expression was repressed by organic sulfur sources and was mediated by the Met4p-dependent sulfur regulatory network. The results reveal that YLL055w encodes the principal cysteine transporter in S. cerevisiae, which we have named YCT1 (yeast cysteine transporter). Interestingly, Yct1p belongs to the Dal5p family of transporters rather than the amino acid permease family to which all the known amino acid transporters belong.
A Novel NonnullZIP1Allele Triggers Meiotic Arrest With Synapsed Chromosomes inSaccharomyces cerevisiae
Authors: Mitra Neal , Roeder G Shirleen 
Published: April 2007

AbstractDuring meiotic prophase, assembly of the synaptonemal complex (SC) brings homologous chromosomes into close apposition along their lengths. The Zip1 protein is a major building block of the SC in Saccharomyces cerevisiae. In the absence of Zip1, SC fails to form, cells arrest or delay in meiotic prophase (depending on strain background), and crossing over is reduced. We created a novel allele of ZIP1, zip1-4LA, in which four leucine residues in the central coiled-coil domain have been replaced by alanines. In the zip1-4LA mutant, apparently normal SC assembles with wild-type kinetics; however, crossing over is delayed and decreased compared to wild type. The zip1-4LA mutant undergoes strong checkpoint-induced arrest in meiotic prophase; the defect in cell cycle progression is even more severe than that of the zip1 null mutant. When the zip1-4LA mutation is combined with the pch2 checkpoint mutation, cells sporulate with wild-type efficiency and crossing over occurs at wild-type levels. This result suggests that the zip1-4LA defect in recombination is an indirect consequence of cell cycle arrest. Previous studies have suggested that the Pch2 protein acts in a checkpoint pathway that monitors chromosome synapsis. We hypothesize that the zip1-4LA mutant assembles aberrant SC that triggers the synapsis checkpoint.
Identification of Mom7, a Novel Modifier of ApcMin/+ on Mouse Chromosome 18
Authors: Kwong Lawrence N , Shedlovsky Alexandra , Biehl Bryan S , Clipson Linda , Pasch Cheri A , Dove William F 
Published: April 2007

Abstract
The ApcMin mouse model of colorectal cancer provides a discrete, quantitative measurement of tumor multiplicity, allowing for robust quantitative trait locus analysis. This advantage has previously been used to uncover polymorphic modifiers of the Min phenotype: Mom1, which is partly explained by Pla2g2a; Mom2, a spontaneous mutant modifier; and Mom3, which was discovered in an outbred cross. Here, we describe the localization of a novel modifier, Mom7, to the pericentromeric region of chromosome 18. Mom7 was mapped in crosses involving four inbred strains: C57BL/6J (B6), BTBR/Pas (BTBR), AKR/J (AKR), and A/J. There are at least two distinct alleles of Mom7: the recessive, enhancing BTBR, AKR, and A/J alleles and the dominant, suppressive B6 allele. Homozygosity for the enhancing alleles increases tumor number by approximately threefold in the small intestine on both inbred and F1 backgrounds. Congenic line analysis has narrowed the Mom7 region to within 7.4 Mb of the centromere, 28 Mb proximal to Apc. Analysis of SNP data from various genotyping projects suggests that the region could be as small as 4.4 Mb and that there may be five or more alleles of Mom7 segregating among the many strains of inbred mice. This has implications for experiments involving ApcMin and comparisons between different or mixed genetic backgrounds.
Retrotransposons Influence the Mouse Transcriptome: Implication for the Divergence of Genetic Traits
Authors: Horie Kyoji , Saito Ei-suke , Keng Vincent W , Ikeda Ryuji , Ishihara Hiroshi , Takeda Junji 
Published: April 2007

Abstract
Massive accumulation of retrotransposons, comprising &gt;40% of human and mouse genomes, is one of the major events in the evolution of the genome. However, most retrotransposons have lost retrotransposition competency, which makes studying their role in genome evolution elusive. Intracisternal A-particle (IAP) elements are long terminal repeat (LTR)-type mouse retrotransposons consisting of full-length and internally deleted types. Some are retrotransposition competent and their upregulated activity has been reported in mutant mice deficient in genome defense systems, suggesting that IAP elements provide a unique platform for studying the interaction between retrotransposons and mammalian genomes. Using the IAP element as a model case, here we show that mobilization of retrotransposons alters the mouse transcriptome. Retrotransposition assay in cultured cells demonstrated that a subset of internally deleted IAP elements, called IΔ1 type, retrotranspose efficiently when supplied with functional IAP proteins. Furthermore, the IΔ1 type IAP element exhibited substantial transcription-inducing activity in the flanking region. Genomewide transcript analysis of embryonic stem (ES) cells identified IAP-induced transcripts, including fusion transcripts between IAP sequence and endogenous genes. Unexpectedly, nearly half of these IAP elements obtained from ES cells derived from 129 mouse strain were absent in the C57BL/6 genome, suggesting that IAP-driven transcription contributes to the unique trait of the individual mouse strain. On the basis of these data, we propose that retrotransposons are one of the drivers that shape the mammalian transcriptome.
A Bayesian Multilocus Association Method: Allowing for Higher-Order Interaction in Association Studies
Authors: Albrechtsen Anders , Castella Sofie , Andersen Gitte , Hansen Torben , Pedersen Oluf , Nielsen Rasmus 
Published: April 2007

AbstractFor most common diseases with heritable components, not a single or a few single-nucleotide polymorphisms (SNPs) explain most of the variance for these disorders. Instead, much of the variance may be caused by interactions (epistasis) among multiple SNPs or interactions with environmental conditions. We present a new powerful statistical model for analyzing and interpreting genomic data that influence multifactorial phenotypic traits with a complex and likely polygenic inheritance. The new method is based on Markov chain Monte Carlo (MCMC) and allows for identification of sets of SNPs and environmental factors that when combined increase disease risk or change the distribution of a quantitative trait. Using simulations, we show that the MCMC method can detect disease association when multiple, interacting SNPs are present in the data. When applying the method on real large-scale data from a Danish population-based cohort, multiple interactions are identified that severely affect serum triglyceride levels in the study individuals. The method is designed for quantitative traits but can also be applied on qualitative traits. It is computationally feasible even for a large number of possible interactions and differs fundamentally from most previous approaches by entertaining nonlinear interactions and by directly addressing the multiple-testing problem.
The Genetic Architecture of Shoot Branching in Arabidopsis thaliana: A Comparative Assessment of Candidate Gene Associations vs. Quantitative Trait Locus Mapping
Authors: Ehrenreich Ian M , Stafford Phillip A , Purugganan Michael D 
Published: April 2007

Abstract
Association mapping focused on 36 genes involved in branch development was used to identify candidate genes for variation in shoot branching in Arabidopsis thaliana. The associations between four branching traits and moderate-frequency haplogroups at the studied genes were tested in a panel of 96 accessions from a restricted geographic range in Central Europe. Using a mixed-model association-mapping method, we identified three loci—MORE AXILLARY GROWTH 2 (MAX2), MORE AXILLARY GROWTH 3 (MAX3), and SUPERSHOOT 1 (SPS1)—that were significantly associated with branching variation. On the basis of a more extensive examination of the MAX2 and MAX3 genomic regions, we find that linkage disequilibrium in these regions decays within ∼10 kb and trait associations localize to the candidate genes in these regions. When the significant associations are compared to relevant quantitative trait loci (QTL) from previous Ler × Col and Cvi × Ler recombinant inbred line (RIL) mapping studies, no additive QTL overlapping these candidate genes are observed, although epistatic QTL for branching, including one that spans the SPS1, are found. These results suggest that epistasis is prevalent in determining branching variation in A. thaliana and may need to be considered in linkage disequilibrium mapping studies of genetically diverse accessions.
Why Are There Still Over 1000 Uncharacterized Yeast Genes?
Authors: Peña-Castillo Lourdes , Hughes Timothy R 
Published: April 2007

Abstract
The yeast genetics community has embraced genomic biology, and there is a general understanding that obtaining a full encyclopedia of functions of the ∼6000 genes is a worthwhile goal. The yeast literature comprises over 40,000 research papers, and the number of yeast researchers exceeds the number of genes. There are mutated and tagged alleles for virtually every gene, and hundreds of high-throughput data sets and computational analyses have been described. Why, then, are there &gt;1000 genes still listed as uncharacterized on the Saccharomyces Genome Database, 10 years after sequencing the genome of this powerful model organism? Examination of the currently uncharacterized gene set suggests that while some are small or newly discovered, the vast majority were evident from the initial genome sequence. Most are present in multiple genomics data sets, which may provide clues to function. In addition, roughly half contain recognizable protein domains, and many of these suggest specific metabolic activities. Notably, the uncharacterized gene set is highly enriched for genes whose only homologs are in other fungi. Achieving a full catalog of yeast gene functions may require a greater focus on the life of yeast outside the laboratory.
Outcome of and complications associated with tube cystostomy in dogs and cats: 76 cases (1995–2006)
Authors: Beck Alison L. , Grierson James M. , Ogden Daniel M. , Hamilton Michael H. , Lipscomb Victoria J. 
Published: April 2007

Abstract
Objective—To determine indications for cystostomy tube use in dogs and cats, complications associated with their use, and outcome of dogs and cats in which cystostomy tubes had been inserted.
Design—Retrospective case series.
Animals—37 dogs and 39 cats.
Procedures—Information was obtained from medical records.Long-term follow-up information was obtained by use of a client questionnaire.
Results—Indications for cystostomy tube placement were bladder dysfunction, urinary tract rupture, obstructive urinary tract neoplasia, urinary diversion following urogenital surgery, obstructive urolithiasis, and feline lower urinary tract disease.Median time tubes were in place was 11 days, but duration of tube use was significantly longer for animals with blad-der dysfunction than for animals with urinary tract trauma, urinary diversion, or urinary tract obstruction.Thirty-seven (49%) animals had tube complications.Development of complica tions was not significantly associated with species, age, body weight, duration of tube use, or tube type, except that animals were significantly more likely to develop complications following long-rather than short-term use.In 42 animals, the underlying condition resolved and the tube was removed; 22 animals died or were euthanatized with the tube in place.
Conclusions and Clinical Relevance—Results suggested that cystostomy tubes may be used for animals with various conditions related to problems with urine outflow.Nearly half the animals in the study developed complications related to the cystostomy tube, suggesting that potential complications should be discussed with owners prior to tube placement. However, most complications were easily resolved.
Comparison of classic hypoadrenocorticism with glucocorticoid-deficient hypoadrenocorticism in dogs: 46 cases (1985–2005)
Authors: Thompson Ann L. , Scott-Moncrieff J. Catharine , Anderson Johnna D. 
Published: April 2007

Abstract
Objective—To compare dogs with glucocorticoid-deficient hypoadrenocorticism (GDH) with those with mineralocorticoid- and glucocorticoid-deficient hypoadrenocorticism (MGDH) and determine prevalence, historical and clinicopathologic markers, and outcome of dogs with GDH.
Design—Retrospective case series.
Animals—46 dogs with hypoadrenocorticism.
Procedures—Records in the veterinary medical database at Purdue University were searched for dogs in which hypoadrenocorticism had been diagnosed at the Veterinary Teaching Hospital from 1985 to 2005. Data pertaining to signalment, history, a minimum clinicopathologic database, treatment, and outcome were collected. Dogs with hypoadrenocorticism were classified as having MGDH if hyponatremia, hyperkalemia, or both were detected and as having GDH if hyponatremia and hyperkalemia were absent. Dogs were excluded if they had ever been treated with mitotane or had been treated with > 1 dose of corticosteroids within a month prior to the ACTH-stimulation test.
Results—35 dogs with MGDH and 11 dogs with GDH met the inclusion criteria. Dogs with GDH were older at the time of diagnosis and had a longer duration of clinical signs prior to diagnosis than those with MGDH. Dogs with GDH were more likely to be anemic, hypoalbuminemic, and hypocholesterolemic than dogs with MGDH.
Conclusions and Clinical Relevance—GDH was more common than reported in a referral hospital population of dogs with primary hypoadrenocorticism. Definitive diagnosis of GDH remains a clinical challenge. Absence of a stress leukogram in dogs with signs of illness (especially relating to the gastrointestinal tract) warrants further investigation. Most dogs with primary cortisol deficiency do not develop mineralocorticoid deficiency.