bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effects of Mismatch Repair and RAD1 Genes on Interchromosomal Crossover Recombination in Saccharomyces cerevisiae
Authors: Nicholson Ainsley , Fabbri Rebecca M , Reeves Jason W , Crouse Gray F 
Published: April 2006

Abstract
We have previously shown that recombination between 400-bp substrates containing only 4-bp differences, when present in an inverted repeat orientation, is suppressed by &gt;20-fold in wild-type strains of S. cerevisiae. Among the genes involved in this suppression were three genes involved in mismatch repair—MSH2, MSH3, and MSH6—and one in nucleotide excision repair, RAD1. We now report the involvement of these genes in interchromosomal recombination occurring via crossovers using these same short substrates. In these experiments, recombination was stimulated by a double-strand break generated by the HO endonuclease and can occur between completely identical (homologous) substrates or between nonidentical (homeologous) substrates. In addition, a unique feature of this system is that recombining DNA strands can be given a choice of either type of substrate. We find that interchromosomal crossover recombination with these short substrates is severely inhibited in the absence of MSH2, MSH3, or RAD1 and is relatively insensitive to the presence of mismatches. We propose that crossover recombination with these short substrates requires the products of MSH2, MSH3, and RAD1 and that these proteins have functions in recombination in addition to the removal of terminal nonhomology. We further propose that the observed insensitivity to homeology is a result of the difference in recombinational mechanism and/or the timing of the observed recombination events. These results are in contrast with those obtained using longer substrates and may be particularly relevant to recombination events between the abundant short repeated sequences that characterize the genomes of higher eukaryotes.
A General Population-Genetic Model for the Production by Population Structure of Spurious Genotype–Phenotype Associations in Discrete, Admixed or Spatially Distributed Populations
Authors: Rosenberg Noah A , Nordborg Magnus 
Published: April 2006

AbstractIn linkage disequilibrium mapping of genetic variants causally associated with phenotypes, spurious associations can potentially be generated by any of a variety of types of population structure. However, mathematical theory of the production of spurious associations has largely been restricted to population structure models that involve the sampling of individuals from a collection of discrete subpopulations. Here, we introduce a general model of spurious association in structured populations, appropriate whether the population structure involves discrete groups, admixture among such groups, or continuous variation across space. Under the assumptions of the model, we find that a single common principle—applicable to both the discrete and admixed settings as well as to spatial populations—gives a necessary and sufficient condition for the occurrence of spurious associations. Using a mathematical connection between the discrete and admixed cases, we show that in admixed populations, spurious associations are less severe than in corresponding mixtures of discrete subpopulations, especially when the variance of admixture across individuals is small. This observation, together with the results of simulations that examine the relative influences of various model parameters, has important implications for the design and analysis of genetic association studies in structured populations.
The Requirements for COMPASS and Paf1 in Transcriptional Silencing and Methylation of Histone H3 in Saccharomyces cerevisiae
Authors: Mueller John E , Canze Megan , Bryk Mary 
Published: April 2006

Abstract
The Set1-containing complex, COMPASS, methylates histone H3 on lysine 4 (K4) in Saccharomyces cerevisiae. Despite the preferential association of K4-trimethylated H3 with regions of the genome that are transcribed by RNA polymerase II, transcriptional silencing is one of the few cases in S. cerevisiae where histone-methylation defects have a clear effect on gene expression. To better understand the role of COMPASS in transcriptional silencing, we have determined which members of COMPASS are required for silencing at the ribosomal DNA locus (rDNA), a telomere, and the silent mating loci (HM) using Northern analyses. Our findings indicate that most members of COMPASS are required for silencing at the rDNA and telomere, while none are required for silencing of endogenous genes at the HM loci. To complement gene-expression analysis, quantitative Western blot experiments were performed to determine the members of COMPASS that are required for methylation of histone H3. While most are required for trimethylation, cells lacking certain COMPASS proteins maintain reduced levels of K4 mono- and dimethylated H3, suggesting that some COMPASS members have redundant function. Finally, we show Paf1 is required for silencing and K4-methylated H3 at the rDNA, suggesting a possible direct role for K4-methylated H3 in gene silencing.
Linkage Disequilibrium Between Incompatibility Locus Region Genes in the Plant Arabidopsis lyrata
Authors: Hagenblad Jenny , Bechsgaard Jesper , Charlesworth Deborah 
Published: April 2006

Abstract
We have studied diversity in Arabidopsis lyrata of sequences orthologous to the ARK3 gene of A. thaliana. Our main goal was to test for recombination in the S-locus region. In A. thaliana, the single-copy ARK3 gene is closely linked to the non-functional copies of the self-incompatibility loci, and the ortholog in A. lyrata (a self-incompatible species) is in the homologous genome region and is known as Aly8. It is thus of interest to test whether Aly8 sequence diversity is elevated due to close linkage to the highly polymorphic incompatibility locus, as is theoretically predicted. However, Aly8 is not a single-copy gene, and the presence of paralogs could also lead to the appearance of elevated diversity. We established a typing approach based on different lengths of Aly8 PCR products and show that most A. lyrata haplotypes have a single copy, but some have two gene copies, both closely linked to the incompatibility locus, one being a pseudogene. We determined the phase of multiple haplotypes in families of plants from Icelandic and other populations. Different Aly8 sequence types are associated with different SRK alleles, while haplotypes with the same SRK sequences tend to have the same Aly8 sequence. There is evidence of some exchange of sequences between different Aly8 sequences, making it difficult to determine which ones are allelic or to estimate the diversity. However, the homogeneity of the Aly8 sequences of each S-haplotype suggests that recombination between the loci has been very infrequent over the evolutionary history of these populations. Overall, the results suggest that recombination rarely occurs in the interval between the S-loci and Aly8 and that linkage to the S-loci can probably account for the observed high Aly8 diversity.
Construction of a 10,000-Marker Ultradense Genetic Recombination Map of Potato: Providing a Framework for Accelerated Gene Isolation and a Genomewide Physical Map
Authors: van Os Hans , Andrzejewski Sandra , Bakker Erin , Barrena Imanol , Bryan Glenn J , Caromel Bernard , Ghareeb Bilal , Isidore Edwige , de Jong Walter , van Koert Paul , Lefebvre Véronique , Milbourne Dan , Ritter Enrique , van der Voort Jeroen N A M Rouppe , Rousselle-Bourgeois Françoise , van Vliet Joke , Waugh Robbie , Visser Richard G F , Bakker Jaap , van Eck Herman J 
Published: April 2006

Abstract
An ultradense genetic linkage map with &gt;10,000 AFLP loci was constructed from a heterozygous diploid potato population. To our knowledge, this is the densest meiotic recombination map ever constructed. A fast marker-ordering algorithm was used, based on the minimization of the total number of recombination events within a given marker order in combination with genotyping error-detection software. This resulted in “skeleton bin maps,” which can be viewed as the most parsimonious marker order. The unit of distance is not expressed in centimorgans but in “bins.” A bin is a position on the genetic map with a unique segregation pattern that is separated from adjacent bins by a single recombination event. Putative centromeres were identified by a strong clustering of markers, probably due to cold spots for recombination. Conversely, recombination hot spots resulted in large intervals of up to 15 cM without markers. The current level of marker saturation suggests that marker density is proportional to physical distance and independent of recombination frequency. Most chromatids (92%) recombined once or never, suggesting strong chiasma interference. Absolute chiasma interference within a chromosome arm could not be demonstrated. Two examples of contig construction and map-based cloning have demonstrated that the marker spacing was in accordance with the expected physical distance: approximately one marker per BAC length. Currently, the markers are used for genetic anchoring of a physical map of potato to deliver a sequence-ready minimal tiling path of BAC contigs of specific chromosomal regions for the potato genome sequencing consortium (http://www.potatogenome.net).
Sex Ratio Variation in Iberian Pigs
Authors: Toro M A , Fernández A , García-Cortés L A , Rodrigáñez J , Silió L 
Published: April 2006

AbstractWithin the area of sex allocation, one of the topics that has attracted a lot of attention is the sex ratio problem. Fisher (1930) proposed that equal numbers of males and females have been promoted by natural selection and it has an adaptive significance. But the empirical success of Fisher's theory remains doubtful because a sex ratio of 0.50 is also expected from the chromosomal mechanism of sex determination. Another way of approaching the subject is to consider that Fisher's argument relies on the underlying assumption that offspring inherit their parent's tendency in biased sex ratio and therefore that genetic variance for this trait exists. Here, we analyzed sex ratio data of 56,807 piglets coming from 550 boars and 1893 dams. In addition to classical analysis of heterogeneity we performed analyses fitting linear and threshold animal models in a Bayesian framework using Gibbs sampling techniques. The marginal posterior mean of heritability was 2.63 × 10−4 under the sire linear model and 9.17 × 10−4 under the sire threshold model. The probability of the hypothesis p(h2 = 0) fitting the last model was 0.996. Also, we did not detect any trend in sex ratio related to maternal age. From an evolutionary point of view, the chromosomal sex determination acts as a constraint that precludes control of offspring sex ratio in vertebrates and it should be included in the general theory of sex allocation. From a practical view that means that the sex ratio in domestic species is hardly susceptible to modification by artificial selection.
N-Terminal Domain of Yeast Hsp104 Chaperone Is Dispensable for Thermotolerance and Prion Propagation but Necessary for Curing Prions by Hsp104 Overexpression
Authors: Hung Guo-Chiuan , Masison Daniel C 
Published: April 2006

Abstract
Hsp104 is a hexameric protein chaperone that resolubilizes stress-damaged proteins from aggregates. Hsp104 promotes [PSI+] prion propagation by breaking prion aggregates, which propagate as amyloid fibers, into more numerous prion “seeds.” Inactivating Hsp104 cures cells of [PSI+] and other amyloid-like yeast prions. Overexpressing Hsp104 also eliminates [PSI+], presumably by completely resolubilizing prion aggregates. Inexplicably, however, excess Hsp104 does not cure the other prions. Here we identify missense mutations in Hsp104's amino-terminal domain (NTD), which is conserved among Hsp100 proteins but whose function is unknown, that improve [PSI+] propagation. Hsp104Δ147, engineered to lack the NTD, supported [PSI+] and functioned normally in thermotolerance and protein disaggregation. Hsp104Δ147 failed to cure [PSI+] when overexpressed, however, implying that excess Hsp104 does not eliminate [PSI+] by direct dissolution of prion aggregates. Curing of [PSI+] by overexpressing catalytically inactive Hsp104 (Hsp104KT), which interferes with endogenous Hsp104, did not require the NTD. We further found that Hsp104 mutants defective in threading peptides through the hexamer pore had reduced ability to support [PSI+] in proportion to protein resolubilization defects, suggesting that [PSI+] propagation depends on this threading and that Hsp104 “breaks” prion aggregates by extracting protein monomers from the amyloid fibers.
Estimating the Genomewide Rate of Adaptive Protein Evolution in Drosophila
Authors: Welch John J 
Published: April 2006

Abstract
When polymorphism and divergence data are available for multiple loci, extended forms of the McDonald–Kreitman test can be used to estimate the average proportion of the amino acid divergence due to adaptive evolution—a statistic denoted $\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{{\bar{{\alpha}}}}\) \end{document}$. But such tests are subject to many biases. Most serious is the possibility that high estimates of $\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{{\bar{{\alpha}}}}\) \end{document}$ reflect demographic changes rather than adaptive substitution. Testing for between-locus variation in α is one possible way of distinguishing between demography and selection. However, such tests have yielded contradictory results, and their efficacy is unclear. Estimates of $\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{{\bar{{\alpha}}}}\) \end{document}$ from the same model organisms have also varied widely. This study clarifies the reasons for these discrepancies, identifying several method-specific biases in widely used estimators and assessing the power of the methods. As part of this process, a new maximum-likelihood estimator is introduced. This estimator is applied to a newly compiled data set of 115 genes from Drosophila simulans, each with each orthologs from D. melanogaster and D. yakuba. In this way, it is estimated that $\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{{\bar{{\alpha}}}}{\approx}0.4{\pm}0.1\) \end{document}$, a value that does not vary substantially between different loci or over different periods of divergence. The implications of these results are discussed.
Crosslinks Rather Than Strand Breaks Determine Access to Ancient DNA Sequences From Frozen Sediments
Authors: Hansen Anders J , Mitchell David L , Wiuf Carsten , Paniker Lakshmi , Brand Tina B , Binladen Jonas , Gilichinsky David A , Rønn Regin , Willerslev Eske 
Published: April 2006

Abstract
Diagenesis was studied in DNA obtained from Siberian permafrost (permanently frozen soil) ranging from 10,000 to 400,000 years in age. Despite optimal preservation conditions, we found the sedimentary DNA to be severely modified by interstrand crosslinks; single- and double-stranded breaks; and freely exposed sugar, phosphate, and hydroxyl groups. Intriguingly, interstrand crosslinks were found to accumulate ∼100 times faster than single-stranded breaks, suggesting that crosslinking rather than depurination is the primary limiting factor for ancient DNA amplification under frozen conditions. The results question the reliability of the commonly used models relying on depurination kinetics for predicting the long-term survival of DNA under permafrost conditions and suggest that new strategies for repair of ancient DNA must be considered if the yield of amplifiable DNA from permafrost sediments is to be significantly increased. Using the obtained rate constant for interstrand crosslinks the maximal survival time of amplifiable 120-bp fragments of bacterial 16S ribosomal DNA was estimated to be ∼400,000 years. Additionally, a clear relationship was found between DNA damage and sample age, contradicting previously raised concerns about the possible leaching of free DNA molecules between permafrost layers.
Genomic Analysis of the Opi− Phenotype
Authors: Hancock Leandria C , Behta Ryan P , Lopes John M 
Published: April 2006

Abstract
Most of the phospholipid biosynthetic genes of Saccharomyces cerevisiae are coordinately regulated in response to inositol and choline. Inositol affects the intracellular levels of phosphatidic acid (PA). Opi1p is a repressor of the phospholipid biosynthetic genes and specifically binds PA in the endoplasmic reticulum. In the presence of inositol, PA levels decrease, releasing Opi1p into the nucleus where it represses transcription. The opi1 mutant overproduces and excretes inositol into the growth medium in the absence of inositol and choline (Opi− phenotype). To better understand the mechanism of Opi1p repression, the viable yeast deletion set was screened to identify Opi− mutants. In total, 89 Opi− mutants were identified, of which 7 were previously known to have the Opi− phenotype. The Opi− mutant collection included genes with roles in phospholipid biosynthesis, transcription, protein processing/synthesis, and protein trafficking. Included in this set were all nonessential components of the NuA4 HAT complex and six proteins in the Rpd3p–Sin3p HDAC complex. It has previously been shown that defects in phosphatidylcholine synthesis (cho2 and opi3) yield the Opi− phenotype because of a buildup of PA. However, in this case the Opi− phenotype is conditional because PA can be shuttled through a salvage pathway (Kennedy pathway) by adding choline to the growth medium. Seven new mutants present in the Opi− collection (fun26, kex1, nup84, tps1, mrpl38, mrpl49, and opi10/yol032w) were also suppressed by choline, suggesting that these affect PC synthesis. Regulation in response to inositol is also coordinated with the unfolded protein response (UPR). Consistent with this, several Opi− mutants were found to affect the UPR (yhi9, ede1, and vps74).
Telomeric Silencing of an Open Reading Frame in Saccharomyces cerevisiae
Authors: Barton Arnold B , Kaback David B 
Published: April 2006

Abstract
The endmost chromosome I ORF is silenced by a natural telomere position effect. YAR073W/IMD1 was found to be transcribed at much higher levels in sir3 mutants and when its adjacent telomere was removed from it. These results suggest that telomeres play a role in silencing actual genes.
Pediatric Hospitalists: Report of a Leadership Conference
Authors: Lye Patricia S. , Rauch Daniel A. , Ottolini Mary C. , Landrigan Christopher P. , Chiang Vincent W. , Srivastava Rajendu , Muret-Wagstaff Sharon , Ludwig Stephen 
Published: April 2006

OBJECTIVES. To summarize a meeting of academic pediatric hospitalists and to describe the current state of the field.
METHODS. The Ambulatory Pediatric Association sponsored a meeting for academic pediatric hospitalists in November 2003. The purpose of the meeting was to discuss and to define roles of academic pediatric hospitalists, including their roles as clinicians, educators, and researchers, and to discuss organizational issues and unique hospitalist issues within general academic pediatrics. Workshops were held in the areas of organization and administration, academic life, research, and education. A literature review was also conducted in the areas discussed.
RESULTS. More than 130 physicians attended. Thirteen workshops were held, and all information was summarized in large-group sessions for all attendees.
CONCLUSIONS. Pediatric hospital medicine is a rapidly growing field, with an estimated 800 to 1000 pediatric hospitalists currently practicing. Initial work has defined the clinical environment and has begun to stake out a unique knowledge and skill set. The Pediatric Hospitalists in Academic Settings conference demonstrated the audience for additional development and the resources to move forward.
Oral Sildenafil in Infants With Persistent Pulmonary Hypertension of the Newborn: A Pilot Randomized Blinded Study
Authors: Baquero Hernando , Soliz Amed , Neira Freddy , Venegas Maria E. , Sola Augusto 
Published: April 2006

BACKGROUND. Persistent pulmonary hypertension (PPHN) occurs in as many as 6.8 of 1000 live births. Mortality is ∼10% to 20% with high-frequency ventilation, surfactant, inhaled nitric oxide, and extracorporeal membrane oxygenation but is much higher when these therapies are not available. Sildenafil is a phosphodiesterase inhibitor type 5 that selectively reduces pulmonary vascular resistance.
OBJECTIVE. Our goal was to evaluate the feasibility of using oral sildenafil and its effect on oxygenation in PPHN.
DESIGN. This study was a proof-of-concept, randomized, masked study in infants &gt;35.5 weeks' gestation and &lt;3 days old with severe PPHN and oxygenation index (OI) &gt;25 admitted to the NICU (Hospital Niño Jesús, Barranquilla, Colombia). The sildenafil solution was prepared from a 50-mg tablet. The first dose (1 mg/kg) or placebo was given by orogastric tube &lt;30 minutes after randomization and every 6 hours. Preductal saturation and blood pressure were monitored continuously. OI was calculated every 6 hours. The main outcome variable was the effect of oral sildenafil on oxygenation. Sildenafil or placebo was discontinued when OI was &lt;20 or if there was no significant change in OI after 36 hours.
RESULTS. Six infants with an OI of &gt;25 received placebo, and 7 received oral sildenafil at a median age of 25 hours. All infants were severely ill, on fraction of inspired oxygen 1.0, and with similar ventilatory parameters. Intragastric sildenafil and placebo were well tolerated. In the treatment group, OI improved in all infants within 6 to 30 hours, all showed a steady improvement in pulse oxygen saturation over time, and none had noticeable effect on blood pressure; 6 of 7 survived. In the placebo group, 1 of 6 infants survived.
CONCLUSIONS. Oral sildenafil was administered easily and tolerated as well as placebo and improved OI in infants with severe PPHN, which suggests that oral sildenafil may be effective in the treatment of PPHN and underscores the need for a large, controlled trial.