bluuebunny/crossref_metadata_2025_split huggingface dataset:
41Ca and Accelerator Mass Spectrometry to Monitor Calcium Metabolism in End Stage Renal Disease Patients
Authors: Fitzgerald Robert L , Hillegonds Darren J , Burton Douglas W , Griffin Terrance L , Mullaney Scott , Vogel John S , Deftos Leonard J , Herold David A 
Published: September 2005

AbstractBackground: Monitoring bone resorption with measurements of bone density and biochemical markers is indirect. We hypothesized that bone resorption can be studied directly by serial measurements of the ratio 41Ca/Ca in serum after in vivo labeling of calcium pools with 41Ca. We report the preparation of an intravenous 41Ca dose suitable for humans, an analytical method for determining 41Ca/Ca isotope ratios in biological samples, and studies in human volunteers.Methods: 41Ca was formulated and aliquoted into individual vials, and to the extent possible, the 41Ca doses were tested according to US Pharmacopeia (USP) guidelines. A 10 nCi dose of 41Ca was administered intravenously to 4 end stage renal disease (ESRD) patients on hemodialysis and 4 healthy control individuals. Distribution kinetics were determined over 168 days. Calcium was isolated with 3 precipitation steps and a cation-exchange column, and 41Ca/Ca ratios in serum were then measured by accelerator mass spectrometry.Results: The dosing solution was chemically and radiologically pure, contained &lt;0.1 endotoxin unit/mL, and passed USP sterility tests. Quantification of 41Ca/Ca ratios was linear from 6 × 10−14 to 9.1 × 10−10. The run-to-run imprecision (as CV) of the method was 4% at 4.6 × 10−11 and 6% at 9.1 × 10−10. The area under the curve of 41Ca in the central compartment vs time was significantly less for ESRD patients than for controls (P &lt;0.005).Conclusions: Isotope ratios spanning 5 orders of magnitude can be measured by accelerator mass spectrometry with excellent precision in the range observed in samples collected from patients who have received 10 nCi of 41Ca. The 41Ca at this dose caused no adverse effects in 8 volunteers. This is the first report of the use of 41Ca to monitor differences in bone turnover between healthy individuals and ESRD patients.
Automated Spectrophotometric Analysis of Mitochondrial Respiratory Chain Complex Enzyme Activities in Cultured Skin Fibroblasts
Authors: Kramer Karen A , Oglesbee Devin , Hartman Stacy J , Huey Joe , Anderson Bambi , Magera Mark J , Matern Dietrich , Rinaldo Piero , Robinson Brian H , Cameron Jessie M , Hahn Si Houn 
Published: September 2005

Abstract
Background: Mitochondrial respiratory chain complex (RCC) disorders may occur as commonly as 1 in 8500 individuals. Because of the great variability of phenotypic presentations, measurement of individual RCC enzyme activities is a crucial diagnostic process. Current assay methods are time-consuming and labor-intensive and thus constitute a major impediment to clinical practice. A method with a faster turnaround time would therefore be beneficial.
Method: We developed an automated spectrophotometric method for measuring the respiratory chain enzyme activities of complex I, complex II + III, and complex IV with the Hitachi 912, an automated spectrophotometer. Mitochondrial citrate synthase was also determined for normalization of the RCC activities.
Results: A blinded method comparison with samples from an external testing center yielded a 91% concordance of interpretations. Mean intraassay imprecision (as CV; n = 20) in a single batch analysis of each RCC was 5.9%. Interassay imprecision, evaluated on 2 samples harvested and analyzed 3 times each, gave mean CVs of 10%–18%.
Conclusions: With this automated method, a panel of RCC enzyme activities can be determined in &lt;2 h. In addition, an immunoblot assay using monoclonal antibodies against specific subunits of RCC enzyme complexes can be informative in cases of borderline enzyme activity. Our results suggest that in vitro diagnosis of RCC enzyme deficiencies in skin fibroblasts is an effective alternative to invasive muscle biopsy.
PARK7 and Nucleoside Diphosphate Kinase A as Plasma Markers for the Early Diagnosis of Stroke
Authors: Allard Laure , Burkhard Pierre R , Lescuyer Pierre , Burgess Jennifer A , Walter Nadia , Hochstrasser Denis F , Sanchez Jean-Charles 
Published: September 2005

AbstractBackground: Plasma markers for stroke could be useful in diagnosis and prognosis and in prediction of response of stroke patients to therapy. PARK7 and nucleoside diphosphate kinase A (NDKA) are increased in human postmortem cerebrospinal fluid (CSF), a model of global brain insult, suggesting that measurement in CSF and, more importantly, in plasma may be useful as a biomarker of stroke.Methods: We used ELISA to measure PARK7 and NDKA in plasma in 3 independent European and North American retrospective studies encompassing a total of 622 stroke patients and 165 control individuals.Results: Increases in both biomarkers were highly significant, with sensitivities of 54%–91% for PARK7 and 70%–90% for NDKA and specificities of 80%–97% for PARK7 and 90%–97% for NDKA. The concentrations of both biomarkers increased within 3 h of stroke onset.Conclusions: PARK7 and NDKA may be useful plasma biomarkers for the early diagnosis of stroke. In addition, this study demonstrated the utility of analysis of postmortem CSF proteins as a first step in the discovery of plasma markers of ischemic brain injury.
Lipoprotein(a) Is an Independent Risk Factor for Cardiovascular Disease in Heterozygous Familial Hypercholesterolemia
Authors: Holmes Daniel T , Schick Brian A , Humphries Karin H , Frohlich Jiri 
Published: September 2005

Abstract
Background: The role of lipoprotein(a) [Lp(a)] as a predictor of cardiovascular disease (CVD) in patients with heterozygous familial hypercholesterolemia (HFH) is unclear. We sought to examine the utility of this lipoprotein as a predictor of CVD outcomes in the HFH population at our lipid clinic.
Methods: This was a retrospective analysis of clinical and laboratory data from a large multiethnic cohort of HFH patients at a single, large lipid clinic in Vancouver, Canada. Three hundred and eighty-eight patients were diagnosed with possible, probable, or definite HFH by strict clinical diagnostic criteria. Multivariate Cox regression analysis was used to study the relationship between several established CVD risk factors, Lp(a), and the age of first hard CVD event.
Results: An Lp(a) concentration of 800 units/L (560 mg/L) or higher was a significant independent risk factor for CVD outcomes [hazard ratio (HR) = 2.59; 95% confidence interval (CI), 1.53–4.39; P &lt;0.001]. Other significant risk factors were male sex [HR = 3.19 (1.79–5.69); P &lt;0.001] and ratio of total to HDL-cholesterol [1.18 (1.07–1.30); P = 0.001]. A previous history of smoking or hypertension each produced HRs consistent with increased CVD risk [HR = 1.55 (0.92–2.61) and 1.57 (0.90–2.74), respectively], but neither reached statistical significance (both P = 0.10). LDL-cholesterol was not an independent predictor of CVD risk [HR = 0.85 (0.0.71–1.01); P = 0.07], nor was survival affected by the subcategory of HFH diagnosis (i.e., possible vs probable vs definite HFH).
Conclusion: Lp(a) is an independent predictor of CVD risk in a multiethnic HFH population.
Quantitative Trait Loci for Cuticular Hydrocarbons Associated With Sexual Isolation Between Drosophila simulans and D. sechellia
Authors: Gleason Jennifer M , Jallon Jean-Marc , Rouault Jacques-Deric , Ritchie Michael G 
Published: September 2005

Abstract
The identification of genes with large effects on sexual isolation and speciation is an important link between classic evolutionary genetics and molecular biology. Few genes that affect sexual isolation and speciation have been identified, perhaps because many traits influencing sexual isolation are complex behaviors. Cuticular hydrocarbons (CHs) of species of the Drosophila melanogaster group play a large role in sexual isolation by functioning as contact pheromones influencing mate recognition. Some of the genes that play key roles in determining species-specific CHs have been identified. We have performed separate quantitative trait locus (QTL) analyses of 7-tricosene (7-T) and 7,11-heptacosadiene (7,11-HD), the two major female CHs differing between D. simulans and D. sechellia. We find that ∼40% of the phenotypic variance in each CH is associated with two to four chromosomal regions. A region on the right arm of chromosome 3 contains QTL that affect both traits, but other QTL are in distinct chromosomal regions. Epistatic interactions were detected between two pairs of QTL for 7,11-HD such that if either were homozygous for the D. simulans allele, the fly was similar to D. simulans in phenotype, with a low level of 7,11-HD. We discuss the location of these regions with regard to candidate genes for CH production, including those for desaturases.
Likelihoods From Summary Statistics: Recent Divergence Between Species
Authors: Leman Scotland C , Chen Yuguo , Stajich Jason E , Noor Mohamed A F , Uyenoyama Marcy K 
Published: September 2005

Abstract
We describe an importance-sampling method for approximating likelihoods of population parameters based on multiple summary statistics. In this first application, we address the demographic history of closely related members of the Drosophila pseudoobscura group. We base the maximum-likelihood estimation of the time since speciation and the effective population sizes of the extant and ancestral populations on the pattern of nucleotide variation at DPS2002, a noncoding region tightly linked to a paracentric inversion that strongly contributes to reproductive isolation. Consideration of summary statistics rather than entire nucleotide sequences permits a compact description of the genealogy of the sample. We use importance sampling first to propose a genealogical and mutational history consistent with the observed array of summary statistics and then to correct the likelihood with the exact probability of the history determined from a system of recursions. Analysis of a subset of the data, for which recursive computation of the exact likelihood was feasible, indicated close agreement between the approximate and exact likelihoods. Our results for the complete data set also compare well with those obtained through Metropolis-Hastings sampling of fully resolved genealogies of entire nucleotide sequences.
Negative Clonal Selection in Tumor Evolution
Authors: Beckman Robert A , Loeb Lawrence A 
Published: September 2005

Abstract
Development of cancer requires the acquisition of multiple oncogenic mutations and selection of the malignant clone. Cancer evolves within a finite host lifetime and mechanisms of carcinogenesis that accelerate this process may be more likely to contribute to the development of clinical cancers. Mutator mutations are mutations that affect genome stability and accelerate the acquisition of oncogenic mutations. However, mutator mutations will also accelerate the accumulation of mutations that decrease cell proliferation, increase apoptosis, or affect other key fitness parameters. These “reduced-fitness” mutations may mediate “negative clonal selection,” i.e., selective elimination of premalignant mutator clones. Target reduced-fitness loci may be “recessive” (both copies must be mutated to reduce fitness) or “dominant” (single-copy mutation reduces fitness). A direct mathematical analysis is applied to negative clonal selection, leading to the conclusion that negative clonal selection against mutator clones is unlikely to be a significant effect under realistic conditions. In addition, the relative importance of dominant and recessive reduced-fitness mutations is quantitatively defined. The relative predominance of mutator mutations in clinical cancers will depend on several variables, including the tolerance of the genome for reduced-fitness mutations, particularly the number and potency of dominant reduced-fitness loci.
A Novel Chimeric Gene, siren, With Retroposed Promoter Sequence in the Drosophila bipectinata Complex
Authors: Nozawa Masafumi , Aotsuka Tadashi , Tamura Koichiro 
Published: September 2005

Abstract
Retrotransposons often produce a copy of host genes by their reverse transcriptase activity operating on host gene transcripts. Since transcripts normally do not contain promoter, a retroposed gene copy usually becomes a retropseudogene. However, in Drosophila bipectinata and a closely related species we found a new chimeric gene, whose promoter was likely produced by retroposition. This chimeric gene, named siren, consists of a tandem duplicate of Adh and a retroposed fragment of CG11779 containing the promoter and a partial intron in addition to the first exon. We found that this unusual structure of a retroposed fragment was obtained by retroposition of nanos, which overlaps with CG11779 on the complementary strand. The potential of retroposition to produce a copy of promoter and intron sequences in the context of gene overlapping was demonstrated.
Mechanisms of Genetic Exchange Within the Chromosomal Inversions of Drosophila pseudoobscura
Authors: Schaeffer Stephen W , Anderson Wyatt W 
Published: September 2005

Abstract
We have used the inversion system of Drosophila pseudoobscura to investigate how genetic flux occurs among the gene arrangements. The patterns of nucleotide polymorphism at seven loci were used to infer gene conversion events between pairs of different gene arrangements. We estimate that the average gene conversion tract length is 205 bp and that the average conversion rate is 3.4 × 10−6, which is 2 orders of magnitude greater than the mutation rate. We did not detect gene conversion events between all combinations of gene arrangements even though there was sufficient nucleotide variation for detection and sufficient opportunity for exchanges to occur. Genetic flux across the inverted chromosome resulted in higher levels of differentiation within 0.1 Mb of inversion breakpoints, but a slightly lower level of differentiation in central inverted regions. No gene conversion events were detected within 17 kb of an inversion breakpoint suggesting that the formation of double-strand breaks is reduced near rearrangement breakpoints in heterozygotes. At least one case where selection rather than proximity to an inversion breakpoint is responsible for reduction in polymorphism was identified.
Marker-Based Quantitative Genetics in the Wild?: The Heritability and Genetic Correlation of Chemical Defenses in Eucalyptus
Authors: Andrew R L , Peakall R , Wallis I R , Wood J T , Knight E J , Foley W J 
Published: September 2005

Abstract
Marker-based methods for estimating heritability and genetic correlation in the wild have attracted interest because traditional methods may be impractical or introduce bias via G × E effects, mating system variation, and sampling effects. However, they have not been widely used, especially in plants. A regression-based approach, which uses a continuous measure of genetic relatedness, promises to be particularly appropriate for use in plants with mixed-mating systems and overlapping generations. Using this method, we found significant narrow-sense heritability of foliar defense chemicals in a natural population of Eucalyptus melliodora. We also demonstrated a genetic basis for the phenotypic correlation underlying an ecological example of conditioned flavor aversion involving different biosynthetic pathways. Our results revealed that heritability estimates depend on the spatial scale of the analysis in a way that offers insight into the distribution of genetic and environmental variance. This study is the first to successfully use a marker-based method to measure quantitative genetic parameters in a tree. We suggest that this method will prove to be a useful tool in other studies and offer some recommendations for future applications of the method.
The Yeast Histone Chaperone Chromatin Assembly Factor 1 Protects Against Double-Strand DNA-Damaging Agents
Authors: Linger Jeffrey , Tyler Jessica K 
Published: September 2005

Abstract
The removal of histones from DNA and their subsequent replacement is likely to be necessary for all processes that require access to the DNA sequence in eukaryotic cells. The histone chaperone chromatin assembly factor 1 (CAF-1) mediates histone H3-H4 assembly during DNA replication and nucleotide excision repair in vitro. We have found that budding yeast deleted for the genes encoding CAF-1 are highly sensitive to double-strand DNA-damaging agents. Our genetic analyses indicate that CAF-1 plays a role in both homologous recombination and nonhomologous end-joining pathways and that the function of CAF-1 during double-strand repair is distinct from that of another histone H3-H4 chaperone, anti-silencing function 1 (ASF1). CAF-1 does not protect the genome by assembling it into a damage-resistant chromatin structure, because induction of CAF-1 after DNA damage is sufficient to restore viability. Furthermore, CAF-1 is not required for repair of the DNA per se or for DNA damage checkpoint function. CAF-1-mediated resistance to DNA damage is dependent on the ability of CAF-1 to bind PCNA, indicating that PCNA may recruit CAF-1 to sites of double-strand DNA repair. We propose that CAF-1 has an essential role in assembling chromatin during double-strand-DNA repair.
Drosophila starvin Encodes a Tissue-Specific BAG-Domain Protein Required for Larval Food Uptake
Authors: Coulson Michelle , Robert Stanley , Saint Robert 
Published: September 2005

Abstract
We describe a developmental, genetic, and molecular analysis of the sole Drosophila member of the BAG family of genes, which is implicated in stress response and survival in mammalian cells. We show that the gene, termed starvin (stv), is expressed in a highly tissue-specific manner, accumulating primarily in tendon cells following germ-band retraction and later in somatic muscles and the esophagus during embryonic stage 15. We show that stv expression falls within known tendon and muscle cell transcriptional regulatory cascades, being downstream of stripe, but not of another tendon transcriptional regulator, delilah, and downstream of the muscle regulator, mef-2. We generated a series of stv alleles and, surprisingly, given the muscle and tendon-specific embryonic expression of stv, found that the gross morphology and function of somatic muscles is normal in stv mutants. Nonetheless, stv mutant larvae exhibit a striking and fully penetrant mutant phenotype of failure to grow after hatching and a severely impaired ability to take up food. Our study provides the first report of an essential, developmentally regulated BAG-family gene.
A Test of Founder Effect Speciation Using Multiple Loci in the Auklets (Aethia spp.)
Authors: Walsh H E , Jones I L , Friesen V L 
Published: September 2005

Abstract
Whether speciation results more frequently from the genetic consequences of founder events or from gradual genetic divergence of large populations is a matter of debate. In this study, multiple analyses were applied to data from three loci (cytochrome b, α-enolase intron VIII, and MHC class II B) to test for founder effects associated with speciation in Aethia (Aves: Alcidae), a genus of seabirds thought to have undergone a rapid founder-induced radiation. Effective population sizes (Ne) were derived from estimators of θ based on allelic diversity and the coalescent and from data on trans-species polymorphism. Results indicated that Ne has been on the order of 105–106 individuals throughout the evolutionary histories of least and crested auklets (A. pusilla and A. cristatella, respectively) and that Ne of the ancestral species was at least 16,000 individuals. Computer simulations of MHC evolution indicated that a single-generation bottleneck at speciation could not have involved &lt;85 individuals for each species. More moderate simulation scenarios indicated that population size could not have dropped below 2000 individuals at the time of species founding. Demographic history appears to have been stable for the auklets throughout the past several million years, and a founder effect associated with their speciation is unlikely.
Loss-of-Function Mutations in a Glutathione S-Transferase Suppress the prune-Killer of prune Lethal Interaction
Authors: Provost Elayne , Hersperger Grafton , Timmons Lisa , Ho Wen Qi , Hersperger Evelyn , Alcazar Rosa , Shearn Allen 
Published: September 2005

Abstract
The prune gene of Drosophila melanogaster is predicted to encode a phosphodiesterase. Null alleles of prune are viable but cause an eye-color phenotype. The abnormal wing discs gene encodes a nucleoside diphosphate kinase. Killer of prune is a missense mutation in the abnormal wing discs gene. Although it has no phenotype by itself even when homozygous, Killer of prune when heterozygous causes lethality in the absence of prune gene function. A screen for suppressors of transgenic Killer of prune led to the recovery of three mutations, all of which are in the same gene. As heterozygotes these mutations are dominant suppressors of the prune-Killer of prune lethal interaction; as homozygotes these mutations cause early larval lethality and the absence of imaginal discs. These alleles are loss-of-function mutations in CG10065, a gene that is predicted to encode a protein with several zinc finger domains and glutathione S-transferase activity.
An Integrated Genetic and Physical Map for the Malaria Vector Anopheles funestus
Authors: Wondji Charles S , Hunt Richard H , Pignatelli Patricia , Steen Keith , Coetzee Maureen , Besansky Nora , Lobo Neil , Collins Frank H , Hemingway Janet , Ranson Hilary 
Published: September 2005

Abstract
We have constructed a genetic map of the major African malaria vector, Anopheles funestus, using genetic markers segregating in F2 progeny from crosses between two strains colonized from different field sites. Genotyping was performed on 174 progeny from three families using 33 microsatellite markers, a single RFLP, and 15 single nucleotide polymorphism (SNP) loci. Four linkage groups were resolved and these were anchored to chromosomes X and 2 and chromosomal arms 3R and 3L by comparison with a physical map of this species. Five markers were linked to the X chromosome, 16 markers to chromosome 2, and 10 and 11 markers to chromosomal arms 3R and 3L, respectively. This significantly increases the number of chromosomally defined genetic markers for this species and will facilitate the identification of genes controlling epidemiologically important traits such as resistance to insecticides or vector competence.