bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence of the Face Inversion Effect in 4‐Month‐Old Infants
Authors: Turati Chiara , Sangrigoli Sandy , Ruely Josette , de Schonen Scania 
Published: October 2004

AbstractThis study tested the presence of the face inversion effect in 4‐month‐old infants using habituation to criterion followed by a novelty preference paradigm. Results of Experiment 1 confirmed previous findings, showing that when 1 single photograph of a face is presented in the habituation phase and when infants are required to recognize the same photograph, no differences in recognition performance with upright and inverted faces are found. However, Experiment 2 showed that, when infants are habituated to a face shown in a variety of poses and are required to recognize a new pose of the same face, infants' recognition performances were higher for upright than for inverted faces. Overall, results indicate that, under some experimental conditions, 4‐month‐olds process faces differently according to whether faces are presented upright or inverted.
In-vitro transcutaneous delivery of tamoxifen and γ-linolenic acid from borage oil containing ethanol and 1,8-cineole
Authors: Ho Suzanna , Calder Richard J , Thomas Christopher P , Heard Charles M 
Published: October 2004

Abstract
The objective of this study was to examine the effects of ethanol and 1,8-cineole on the transcutaneous delivery of tamoxifen and γ-linolenic acid (GLA) as a two-pronged anti-breast cancer therapy. Formulations containing tamoxifen and varying concentrations of borage oil (∼25% GLA), 1,8-cineole and ethanol were prepared and the simultaneous permeation of tamoxifen and GLA determined across full-thickness pig skin using Franz-type diffusion cells over 48 h. Analysis of tamoxifen and GLA (as methyl ester) were by reverse-phase HPLC. The highest flux of tamoxifen of 488.2 ± 191 times 10−3 μg cm−2 h−1 was observed with a formulation containing 20% 1,8-cineole and 20% ethanol. The same formulation also provided the greatest flux of GLA, 830.6 times 10−3 μg cm−2 h−1. The findings from this work demonstrate the ability of 1,8-cineole and ethanol to enhance the in-vitro permeation of tamoxifen and GLA across the skin and support the plausibility of simultaneously delivering tamoxifen and GLA transcutaneously as a two-pronged anti-breast cancer system.
Antihyperglycaemic and antioxidant effect of hyponidd, an ayurvedic herbomineral formulation in streptozotocin-induced diabetic rats
Authors: Babu P Subash , Prince P Stanely Mainzen 
Published: October 2004

Abstract
Hyponidd is a herbomineral formulation composed of the extracts of ten medicinal plants (Momordica charantia, Melia azadirachta, Pterocarpus marsupium, Tinospora cordifolia, Gymnema sylvestre, Enicostemma littorale, Emblica officinalis, Eugenia jambolana, Cassia auriculata and Curcuma longa). We have investigated hyponidd for its possible antihyperglycaemic and antioxidant effect in diabetic rats. Rats were rendered diabetic by streptozotocin (STZ) (45 mg kg−1 body weight). Oral administration of hyponidd (100 mg kg−1 and 200 mg kg−1) for 45 days resulted in significant lowered levels of blood glucose and significant increased levels of hepatic glycogen and total haemoglobin. An oral glucose tolerance test was also performed in experimental diabetic rats in which there was a significant improvement in blood glucose tolerance in the rats treated with hyponidd. Hyponidd administration also decreased levels of glycosylated haemoglobin, plasma thiobarbituric acid reactive substances, hydroperoxides, ceruloplasmin and α-tocopherol in diabetic rats. Plasma reduced glutathione and vitamin C were significantly elevated by oral administration of hyponidd. The effect of hyponidd at a dose of 200 mg kg−1 was more effective than glibenclamide (600 μg kg−1) in restoring the values to near normal. The results showed that hyponidd exhibits antihyperglycaemic and antioxidant activity in STZ-induced diabetic rats.
Evaluation of khaya gum as a directly compressible matrix system for controlled release
Authors: Odeku Oluwatoyin A , Fell John T 
Published: October 2004

Abstract
Khaya gum has been evaluated as a controlled release agent in modified release matrices in comparison with hydroxypropylmethylcellulose (HPMC) using paracetamol (water soluble) and indometacin (water insoluble) as model drugs. Tablets were produced by direct compression and the in-vitro drug release was assessed in conditions mimicking the gastrointestinal system. Khaya gum matrices provided a controlled release of paracetamol for up to 5 h. The release of paracetamol from khaya gum matrices followed time-independent kinetics (n = 1.042) and release rates were dependent on the concentration of the drug present in the matrix. The addition of tablet excipients not only improved the mechanical properties of the tablet, but also altered the dissolution profile, except for dicalcium phosphate where the profile remained unchanged. HPMC could be used to control the drug release rates from khaya gum matrices and a combination of khaya gum and HPMC gave zero-order time-independent release kinetics. Indometacin exhibited a lag time in excess of 2 h, due to its insolubility at low pH, before the zero-order release was observed. Thus khaya gum matrices could be useful in the formulation of sustained release tablets for up to 5 h and the appropriate combination of khaya gum and HPMC could be used to provide a time-independent release for longer periods.
Preventing restenosis in early drug-eluting stent era: recent developments and future perspectives
Authors: Birkenhauer Peter , Yang Zhihong , Gander Bruno 
Published: October 2004

Abstract
Restenosis is the major limitation of the successful therapy of percutaneous coronary intervention (PCI) for patients with coronary artery disease. The problem was appreciated in the late 1970s to early 1980s. Only in recent years, anti-restenotic therapy has achieved a breakthrough with the development of drug-eluting stents. Here, we provide an overview about pathological mechanisms of restenosis after PCI. Present therapeutic approaches to overcome restenosis and recent clinical results are revisited, and some major concerns in the post-drug-eluting stent era are discussed.
Sequencing of Genomic DNA by Combined Amplification and Cycle Sequencing Reaction
Authors: Murphy Kathleen M , Berg Karin D , Eshleman James R 
Published: October 2004

Abstract
Background: Despite considerable advances, DNA sequencing has remained somewhat time-consuming and expensive, requiring three separate steps to generate sequencing products from a template: amplification of the target sequence; purification of the amplified product; and a sequencing reaction. Our aim was to develop a method to routinely combine PCR amplification and cycle sequencing into one single reaction, enabling direct sequencing of genomic DNA.
Methods: Combined amplification and sequencing reactions were set up with Big Dye™ sequencing reagents (Applied Biosystems) supplemented with variable amounts of forward and reverse primers, deoxynucleotide triphosphates (dNTPs), and input DNA. Reactions were thermal-cycled for 35 or 45 cycles. Products were analyzed by capillary electrophoresis to detect sequencing products.
Results: Reactions using two oligonucleotide primers at a ratio of 5:1 (500 nM primer 1 and 100 nM primer 2), 125 μM supplemental dNTPs, and 35–45 thermal cycles optimally supported combined amplification and cycle sequencing reactions. Our results suggest that these reactions are dominated by PCR during early cycles and convert to cycle sequencing in later cycles. We used this technique for a variety of sequencing applications, including the identification of germline mutations/polymorphisms in the Factor V and BRCA2 genes, sequencing of tumor DNA to identify somatic mutations in the DPC4/SMADH4 and FLT3 genes, and sequencing of 16S ribosomal DNA for bacterial speciation.
Conclusions: PCR amplification and cycle sequencing can be combined into a single reaction using the conditions described. This technique allows direct sequencing of genomic DNA, decreasing the cost and labor involved in gene sequencing.
Allelic Diversification at the C (OsC1) Locus of Wild and Cultivated Rice
Authors: Saitoh Kumi , Onishi Kazumitsu , Mikami Ichiho , Thidar Khin , Sano Yoshio 
Published: October 2004

Abstract
Divergent phenotypes are often detected in domesticated plants despite the existence of invariant phenotypes in their wild forms. One such example in rice is the occurrence of varying degrees of apiculus coloration due to anthocyanin pigmentation, which was previously reported to be caused by a series of alleles at the C locus. The present study reveals, on the basis of comparison of its maps, that the C gene appears to be the rice homolog (OsC1) of maize C1, which belongs to the group of R2R3-Myb factors. Two different types of deletions causing a frameshift were detected in the third exon, and both of the deleted nucleotides corresponded to the positions of putative base-contacting residues, suggesting that the Indica and Japonica types carry loss-of-function mutations with independent origins. In addition, replacement substitutions were frequently detected in OsC1 of strains carrying the previously defined C alleles. Molecular population analysis revealed that 17 haplotypes were found in 39 wild and cultivated rices, and the haplotypes of most cultivated forms could be classified into one of three distinct groups, with few shared haplotypes among taxa, including Indica and Japonica types. The genealogy of the OsC1 gene suggests that allelic diversification causing phenotypic change might have resulted from mutations in the coding region rather than from recombination between preexisting alleles. The McDonald and Kreitman test revealed that the changes in amino acids might be associated with selective forces acting on the lineage of group A whose haplotypes were carried by most Asian cultivated forms. The results regarding a significant implication for genetic diversity in landraces of rice are also discussed.
Effect of Two- and Three-Locus Linkage Disequilibrium on the Power to Detect Marker/Phenotype Associations
Authors: Nielsen Dahlia M , Ehm Margaret G , Zaykin Dmitri V , Weir Bruce S 
Published: October 2004

AbstractThere has been much recent interest in describing the patterns of linkage disequilibrium (LD) along a chromosome. Most empirical studies that have examined this issue have concentrated on LD between collections of pairs of markers and have not considered the joint effect of a group of markers beyond these pairwise connections. Here, we examine many different patterns of LD defined by both pairwise and joint multilocus LD terms. The LD patterns we considered were chosen in part by examining those seen in real data. We examine how changes in these patterns affect the power to detect association when performing single-marker and haplotype-based case-control tests, including a novel haplotype test based on contrasting LD between affected and unaffected individuals. Through our studies we find that differences in power between single-marker tests and haplotype-based tests in general do not appear to be large. Where moderate to high levels of multilocus LD exist, haplotype tests tend to be more powerful. Single-marker tests tend to prevail when pairwise LD is high. For moderate pairwise values and weak multilocus LD, either testing strategy may come out ahead, although it is also quite likely that neither has much power.
Drosophila Damaged DNA-Binding Protein 1 Is an Essential Factor for Development
Authors: Takata Kei-ichi , Yoshida Hideki , Yamaguchi Masamitsu , Sakaguchi Kengo 
Published: October 2004

Abstract
The damaged DNA-binding protein (DDB) complex, thought to recognize (6-4) photoproducts and other lesions in DNA, has been implicated to have a role in global genomic nucleotide excision repair (NER) and E2F-1-mediated transcription. The complex consists of a heterodimer of p127 (DDB1) and p48 (DDB2), the latter also being known as XPE. We reported previously that in Drosophila expression of the DDB1 (D-DDB1) gene is controlled by the DRE/DREF system, and external injury to DNA is not essential for D-DDB1 function. In the present study of the function of D-DDB1 in a multicellular system, we prepared transgenic flies, which were knocked down for the D-DDB1 gene due to RNA interference (RNAi), and performed immunocytochemistry to ascertain the distribution of D-DDB1 in the eye imaginal disc. It was found to be abundant in the anterior of the morphogenetic furrow (MF). Whole-body overexpression of dsRNA of D-DDB1 in Drosophila using a GAL4-UAS targeted expression system induced melanotic tumors and caused complete lethality. When limited to the eye imaginal disc, a severe rough eye phenotype resulted. Correspondingly, all of the D-DDB1 gene knocked-out flies also died. D-DDB1 therefore appears to be an essential development-associated factor in a multicellular organism.
The HKA Test Revisited
Authors: Wright Stephen I , Charlesworth Brian 
Published: October 2004

Abstract
We present a maximum-likelihood-ratio test of the standard neutral model, using multilocus data on polymorphism within species and divergence between species. The model is based on the Hudson-Kreitman-Aguadé (HKA) test, but allows for an explicit test of selection at individual loci in a multilocus framework. We use coalescent simulations to show that the likelihood-ratio test statistic is conservative, particularly when the assumption of no recombination is violated. Application of the method to polymorphism data from 18 loci from a population of Arabidopsis lyrata provides significant evidence for a balanced polymorphism at a candidate locus thought to be linked to the centromere. The method is also applied to polymorphism data in maize, providing support for the hypothesis of directional selection on genes in the starch pathway.
Connection of Propionyl-CoA Metabolism to Polyketide Biosynthesis in Aspergillus nidulans
Authors: Zhang Yong-Qiang , Brock Matthias , Keller Nancy P 
Published: October 2004

Abstract
Propionyl-CoA is an intermediate metabolite produced through a variety of pathways including thioesterification of propionate and catabolism of odd chain fatty acids and select amino acids. Previously, we found that disruption of the methylcitrate synthase gene, mcsA, which blocks propionyl-CoA utilization, as well as growth on propionate impaired production of several polyketides—molecules typically derived from acetyl-CoA and malonyl-CoA—including sterigmatocystin (ST), a potent carcinogen, and the conidiospore pigment. Here we describe three lines of evidence that demonstrate that excessive propionyl-CoA levels in the cell can inhibit polyketide synthesis. First, inactivation of a putative propionyl-CoA synthase, PcsA, which converts propionate to propionyl-CoA, restored polyketide production and reduced cellular propionyl-CoA content in a ΔmcsA background. Second, inactivation of the acetyl-CoA synthase, FacA, which is also involved in propionate utilization, restored polyketide production in the ΔmcsA background. Third, fungal growth on several compounds (e.g., heptadecanoic acid, isoleucine, and methionine) whose catabolism includes the formation of propionyl-CoA, were found to inhibit ST and conidiospore pigment production. These results demonstrate that excessive propionyl-CoA levels in the cell can inhibit polyketide synthesis.
Analysis of the Estimators of the Average Coefficient of Dominance of Deleterious Mutations
Authors: Fernández B , García-Dorado A , Caballero A 
Published: October 2004

Abstract
We investigate the sources of bias that affect the most commonly used methods of estimation of the average degree of dominance (h) of deleterious mutations, focusing on estimates from segregating populations. The main emphasis is on the effect of the finite size of the populations, but other sources of bias are also considered. Using diffusion approximations to the distribution of gene frequencies in finite populations as well as stochastic simulations, we assess the behavior of the estimators obtained from populations at mutation-selection-drift balance under different mutational scenarios and compare averages of h for newly arisen and segregating mutations. Because of genetic drift, the inferences concerning newly arisen mutations based on the mutation-selection balance theory can have substantial upward bias depending upon the distribution of h. In addition, estimates usually refer to h weighted by the homozygous deleterious effect in different ways, so that inferences are complicated when these two variables are negatively correlated. Due to both sources of bias, the widely used regression of heterozygous on homozygous means underestimates the arithmetic mean of h for segregating mutations, in contrast to their repeatedly assumed equality in the literature. We conclude that none of the estimators from segregating populations provides, under general conditions, a useful tool to ascertain the properties of the degree of dominance, either for segregating or for newly arisen deleterious mutations. Direct estimates of the average h from mutation-accumulation experiments are shown to suffer some bias caused by purging selection but, because they do not require assumptions on the causes maintaining segregating variation, they appear to give a more reliable average dominance for newly arisen mutations.
A Functional Analysis Reveals Dependence on the Anaphase-Promoting Complex for Prolonged Life Span in Yeast
Authors: Harkness Troy A A , Shea Kyla A , Legrand Charmaine , Brahmania Mayur , Davies Gerald F 
Published: October 2004

Abstract
Defects in anaphase-promoting complex (APC) activity, which regulates mitotic progression and chromatin assembly, results in genomic instability, a hallmark of premature aging and cancer. We investigated whether APC-dependent genomic stability affects aging and life span in yeast. Utilizing replicative and chronological aging assays, the APC was shown to promote longevity. Multicopy expression of genes encoding Snf1p (MIG1) and PKA (PDE2) aging-pathway components suppressed apc5CA phenotypes, suggesting their involvement in APC-dependent longevity. While it is known that PKA inhibits APC activity and reduces life span, a link between the Snf1p-inhibited Mig1p transcriptional modulator and the APC is novel. Our mutant analysis supports a model in which Snf1p promotes extended life span by inhibiting the negative influence of Mig1p on the APC. Consistent with this, we found that increased MIG1 expression reduced replicative life span, whereas mig1Δ mutations suppressed the apc5CA chronological aging defect. Furthermore, Mig1p and Mig2p activate APC gene transcription, particularly on glycerol, and mig2Δ, but not mig1Δ, confers a prolonged replicative life span in both APC5 and acp5CA cells. However, glucose repression of APC genes was Mig1p and Mig2p independent, indicating the presence of an uncharacterized factor. Therefore, we propose that APC-dependent genomic stability is linked to prolonged longevity by the antagonistic regulation of the PKA and Snf1p pathways.
A Novel Solution for the Time-Dependent Probability of Gene Fixation or Loss Under Natural Selection
Authors: Wang Ying , Rannala Bruce 
Published: October 2004

Abstract
Kimura (1955b) proposed a solution for the time-dependent probability of fixation, or loss, of a gene under selection. Example calculations suggest the formulas are prone to numerical inaccuracies. An alternative solution is proposed; the correctness of the solution is confirmed by numerically solving the Kolmogorov backward equation and by simulation.
Fixation Probability Favors Increased Fecundity Over Reduced Generation Time
Authors: Wahl L M , DeHaan C S 
Published: October 2004

Abstract
The cornerstone of population genetics is a probabilistic understanding of the ultimate fate—survival or extinction—of rare mutations. If a mutation is beneficial, it enables its carrier to reproduce faster than native wild-type individuals. In classic derivations and in the considerable body of research that has followed, “faster” has been defined mathematically to mean “able to produce more surviving offspring per generation.” Many organisms, however, may increase their reproductive rate by producing the same number of offspring in a shorter generation time: a mutant bacterium, for example, may complete the cell cycle and produce two offspring more quickly than the wild type. We find that the ultimate fixation probability of a mutation conferring a shorter generation time differs from that of a mutation conferring more offspring by a factor of 2 ln(2)—nearly 40%. This predicts a reduction in the overall substitution rate for any mutation that decreases the generation time: fixation probability is biased toward increased offspring number.
Genes Encoding Vitamin-K Epoxide Reductase Are Present in Drosophila and Trypanosomatid Protists
Authors: Robertson Hugh M 
Published: October 2004

Abstract
Vitamin-K epoxide reductase is encoded by the VKORC1 gene in mammals and other vertebrates, which also have a paralog, VKORC1L1. Single homologs are present in basal deuterostome and insect genomes, including Drosophila, and three trypanosomatid protists. VKOR is therefore an ancient gene/protein that can be studied in the Drosophila model system.
Mutation Rate and Predicted Phenotypic Target Sizes in Ethylnitrosourea-Treated Mice
Authors: Concepcion Dorothy , Seburn Kevin L , Wen Gen , Frankel Wayne N , Hamilton Bruce A 
Published: October 2004

Abstract
Chemical mutagenesis of the mouse is ongoing in several centers around the world, with varying estimates of mutation rate and number of sites mutable to phenotype. To address these questions, we sequenced ∼9.6 Mb of DNA from G1 progeny of ethylnitrosourea-treated mice in a large, broad-spectrum screen. We identified 10 mutations at eight unique sites, including six nonsynonymous coding substitutions. This calibrates the nucleotide mutation rate for two mutagenesis centers, implies significance criteria for positional cloning efforts, and provides working estimates of effective genetic target sizes for selected phenotypes.
CREB Binding Protein Functions During Successive Stages of Eye Development in Drosophila
Authors: Kumar Justin P , Jamal Tazeen , Doetsch Alex , Turner F Rudolf , Duffy Joseph B 
Published: October 2004

Abstract
During the development of the compound eye of Drosophila several signaling pathways exert both positive and inhibitory influences upon an array of nuclear transcription factors to produce a near-perfect lattice of unit eyes or ommatidia. Individual cells within the eye are exposed to many extracellular signals, express multiple surface receptors, and make use of a large complement of cell-subtype-specific DNA-binding transcription factors. Despite this enormous complexity, each cell will make the correct developmental choice and adopt the appropriate cell fate. How this process is managed remains a poorly understood paradigm. Members of the CREB binding protein (CBP)/p300 family have been shown to influence development by (1) acting as bridging molecules between the basal transcriptional machinery and specific DNA-binding transcription factors, (2) physically interacting with terminal members of signaling cascades, (3) acting as transcriptional coactivators of downstream target genes, and (4) playing a key role in chromatin remodeling. In a screen for new genes involved in eye development we have identified the Drosophila homolog of CBP as a key player in both eye specification and cell fate determination. We have used a variety of approaches to define the role of CBP in eye development on a cell-by-cell basis.