bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyclometallated Iridium(III) Complexes with 2-Phenylbenzimidazole Derivatives – Spectroscopic, Electrochemical and Electrochemiluminescence Studies
Authors: Kapturkiewicz A. , Nowacki J. , Borowicz P.
Published: April 2006

Simple synthetic procedure (reactions between iridium trichloride hydrate with a series of fluorine substituted 2-phenyl-N-methyl-benzimidazole derivatives L) leads to the cyclometallated Ir(III) complexes IrL2(acac) and IrL2(pic) where acac = acetylacetonate and pic = α-picolinate anions, respectively. All the investigated complexes exhibit strong absorption in the UV region, due to the spin allowed intra-ligand (IL) transitions, and moderately intense bands in the visible region, due to the metal-to-ligand-charge-transfer (MLCT) transitions. The complexes exhibit also strong luminescence in the deoxygenated 1:1 acetonitrile/dioxane solutions at 298 K as well as in the butyronitrile glasses at 77 K. In both experimental conditions the structured emissions (with the 0–0 transition within the 480–510 nm range of UV-Vis radiation) have been observed. Cyclic voltammetry investigations point out to reversible character of the electrochemical reactions leading to stable IrL2(acac)+ or IrL2(pic)+ cations and IrL2(pic)− anions. The corresponding IrL2(acac)− species have been found to be unstable under the applied experimental conditions (1:1 acetonitrile/dioxane solutions containing 0.1 M (C4H9)4NPF6 as the supporting electrolyte) most probably due to the irreversible electrochemical reduction of the acac− ligand. Appropriate combination of the electrochemical and luminescence properties found for the investigated complexes allows for the electron transfer generation of the excited 3∗IrL2(pic) and 3∗IrL2(acac) species. Triple-potential-step technique was used to create electrochemiluminescence (ECL) emission by annihilation of the electrochemically generated IrL2(acac)+ or IrL2(pic)+ cations and 4,4’-dicyano-biphenyl radical anion. Very high ECL emission efficiencies (close to the excited 3∗IrL2(acac) and 3∗IrL2(pic) luminescence yields) have been found.
ESR-Investigations on the Dynamic Solvent Effects of Degenerate Electron Exchange Reactions. Part I: Cyanobenzenes
Authors: Mladenova Boryana , Kattnig Daniel R. , Grampp Günter
Published: April 2006

The rates of degenerate electron exchange (electron self-exchange) of various cyanobenzenes have been measured by EPR line broadening technique in nine different solvents at room temperature. The molecules studied comprise besides benzene-1,2-dicarbonitrile, benzene-1,4-dicarbonitrile and benzene-1,2,4,5-tetracarbonitrile, the two isomeric tricyanobenzenes, benzene-1,2,3-tricarbonitrile and benzene-1,2,4-tricarbonitrile, the anion radicals of which have not been characterized before.

The experimentally observed rates vary from 4.5 × 108 to 44.0 × 108 M−1 s−1 and show the pronounced dependence on the longitudinal relaxation times, τL, of the solvents. The solvent dynamical effect so manifested is confirmed with remarkable clarity using solvents spanning a wide range of τL-values, which comprise acetonitrile (0.2 ps) and o-dichlorobenzene (6.0 ps) at its extremes. The rate constants are compared with Marcus theory using the continuum model (CM) and the mean spherical approximation (MSA) for the outer sphere reorganization energies and Nelson’s method for the inner sphere reorganization energies. Furthermore, an estimation of the resonance splitting energies, V
RP, is given based on the experimental rates.
Building of an Experimental Cline With Arabidopsis thaliana to Estimate Herbicide Fitness Cost
Authors: Roux Fabrice , Giancola Sandra , Durand Stéphanie , Reboud Xavier
Published: April 2006

Various management strategies aim at maintaining pesticide resistance frequency under a threshold value by taking advantage of the benefit of the fitness penalty (the cost) expressed by the resistance allele outside the treated area or during the pesticide selection “off years.” One method to estimate a fitness cost is to analyze the resistance allele frequency along transects across treated and untreated areas. On the basis of the shape of the cline, this method gives the relative contributions of both gene flow and the fitness difference between genotypes in the treated and untreated areas. Taking advantage of the properties of such migration–selection balance, an artificial cline was built up to optimize the conditions where the fitness cost of two herbicide-resistant mutants (acetolactate synthase and auxin-induced target genes) in the model species Arabidopsis thaliana could be more accurately measured. The analysis of the microevolutionary dynamics in these experimental populations indicated mean fitness costs of ∼15 and 92% for the csr1-1 and axr2-1 resistances, respectively. In addition, negative frequency dependence for the fitness cost was also detected for the axr2-1 resistance. The advantages and disadvantages of the cline approach are discussed in regard to other methods of cost estimation. This comparison highlights the powerful ability of an experimental cline to measure low fitness costs and detect sensibility to frequency-dependent variations.
Disentangling Reasons for Low Y Chromosome Variation in the Greater White-Toothed Shrew (Crocidura russula)
Authors: Lawson Handley Lori J , Berset-Brändli Laura , Perrin Nicolas
Published: April 2006

Y chromosome variation is determined by several confounding factors including mutation rate, effective population size, demography, and selection. Disentangling these factors is essential to better understand the evolutionary properties of the Y chromosome. We analyzed genetic variation on the Y chromosome, X chromosome, and mtDNA of the greater white-toothed shrew, a species with low variance in male reproductive success and limited sex-biased dispersal, which enables us to control to some extent for life-history effects. We also compared ancestral (Moroccan) to derived (European) populations to investigate the role of demographic history in determining Y variation. Recent colonization of Europe by a small number of founders (combined with low mutation rates) is largely responsible for low diversity observed on the European Y and X chromosomes compared to mtDNA. After accounting for mutation rate, copy number, and demography, the Y chromosome still displays a deficit in variation relative to the X in both populations. This is possibly influenced by directional selection, but the slightly higher variance in male reproductive success is also likely to play a role, even though the difference is small compared to that in highly polygynous species. This study illustrates that demography and life-history effects should be scrutinized before inferring strong selective pressure as a reason for low diversity on the Y chromosome.
A New Method of Estimating the Pollen Dispersal Curve Independently of Effective Density
Authors: Robledo-Arnuncio Juan J , Austerlitz Frédéric , Smouse Peter E
Published: April 2006

We introduce a novel indirect method of estimating the pollen dispersal curve from mother–offspring genotypic data. Unlike an earlier indirect approach (TwoGener), this method is based on a normalized measure of correlated paternity between female pairs whose expectation does not explicitly depend on the unknown effective male population density (de). We investigate the statistical properties of the new method, by comparison with those of TwoGener, considering the sensitivity to reductions of de, relative to census density, resulting from unequal male fecundity and asynchronous flowering. Our main results are: (i) it is possible to obtain reliable estimates of the average distance of pollen dispersal, δ, from indirect methods, even under nonuniform male fecundity and variable flowering phenology; (ii) the new method yields more accurate and more precise δ-estimates than TwoGener under a wide range of sampling and flowering scenarios; and (iii) TwoGener can be used to obtain approximate de estimates, if needed for other purposes. Our results also show that accurately estimating the shape of the tail of the pollen dispersal function by means of indirect methods remains a very difficult challenge.
Assessing the Relative Ages of Admixture in the Bovine Hybrid Zones of Africa and the Near East Using X Chromosome Haplotype Mosaicism
Authors: Freeman Abigail R , Hoggart Clive J , Hanotte O , Bradley Daniel G
Published: April 2006

Historical hybridization events between the two subspecies of cattle, Bos taurus and B. indicus, have occurred in several regions of the world, while other populations have remained nonadmixed. We typed closely linked X chromosome microsatellites in cattle populations with differing histories of admixture from Africa, Europe, the Near East, and India. Haplotype breakdown will occur as admixed populations age, and longer ancestral haplotypes will remain intact in more recently admixed populations compared to older ones. We genotyped male animals from these populations, obtaining unambiguous haplotypes, and measured levels of linkage disequilibrium (LD) and ancestral mosaicism. Extensive LD, likely to be the result of ongoing admixture, was discovered in hybrid cattle populations from the perimeter of the tsetse zone in West Africa. A Bayesian method to assign microsatellite allele ancestry was used to designate the likely origin of each chromosomal segment and assess the relative ages of admixture in the populations. A gradient of the age of admixture in the African continent emerged, where older admixture has produced more fragmented haplotypes in the south, and longer intact haplotypes, indicating more recent hybridization, feature in the northwest.
Evaluation of DNA Pooling for the Estimation of Microsatellite Allele Frequencies: A Case Study Using Striped Bass (Morone saxatilis)
Authors: Skalski Garrick T , Couch Charlene R , Garber Amber F , Weir Bruce S , Sullivan Craig V
Published: April 2006

Using striped bass (Morone saxatilis) and six multiplexed microsatellite markers, we evaluated procedures for estimating allele frequencies by pooling DNA from multiple individuals, a method suggested as cost-effective relative to individual genotyping. Using moment-based estimators, we estimated allele frequencies in experimental DNA pools and found that the three primary laboratory steps, DNA quantitation and pooling, PCR amplification, and electrophoresis, accounted for 23, 48, and 29%, respectively, of the technical variance of estimates in pools containing DNA from 2–24 individuals. Exact allele-frequency estimates could be made for pools of sizes 2–8, depending on the locus, by using an integer-valued estimator. Larger pools of size 12 and 24 tended to yield biased estimates; however, replicates of these estimates detected allele frequency differences among pools with different allelic compositions. We also derive an unbiased estimator of Hardy–Weinberg disequilibrium coefficients that uses multiple DNA pools and analyze the cost-efficiency of DNA pooling. DNA pooling yields the most potential cost savings when a large number of loci are employed using a large number of individuals, a situation becoming increasingly common as microsatellite loci are developed in increasing numbers of taxa.
Remarkable Site Specificity of Local Transposition Into the Hsp70 Promoter of Drosophila melanogaster
Authors: Shilova Victoria Y , Garbuz David G , Myasyankina Elena N , Chen Bing , Evgen'ev Michael B , Feder Martin E , Zatsepina Olga G
Published: April 2006

Heat-shock genes have numerous features that ought to predispose them to insertional mutagenesis via transposition. To elucidate the evolvability of heat-shock genes via transposition, we have exploited a local transposition technique and Drosophila melanogaster strains with EPgy2 insertions near the Hsp70 gene cluster at 87A7 to produce numerous novel EPgy2 insertions into these Hsp70 genes. More than 50% of 45 independent insertions were made into two adjacent nucleotides in the proximal promoter at positions −96 and −97, and no insertions were into a coding or 3′-flanking sequence. All inserted transposons were in inverse orientation to the starting transposon. The frequent insertion into nucleotides −96 and −97 is consistent with the DNase hypersensitivity, absence of nucleosomes, flanking GAGA-factor-binding sites, and nucleotide sequence of this region. These experimental insertions recapitulated many of the phenotypes of natural transposition into Hsp70: reduced mRNA expression, less Hsp70 protein, and decreased inducible thermotolerance. The results suggest that the distinctive features of heat-shock promoters, which underlie the massive and rapid expression of heat-shock genes upon heat shock, also are a source of evolutionary variation on which natural selection can act.
Characterization and Mapping of a Shattering Mutant in Rice That Corresponds to a Block of Domestication Genes
Authors: Ji Hyeon-So , Chu Sang-Ho , Jiang Wenzhu , Cho Young-Il , Hahn Jang-Ho , Eun Moo-Young , McCouch Susan R , Koh Hee-Jong
Published: April 2006

Easy shattering reduces yield due to grain loss during harvest in cereals. Shattering is also a hindrance in breeding programs that use wild accessions because the shattering habit is often linked to desirable traits. We characterized a shattering mutant line of rice, Hsh, which was derived from a nonshattering japonica variety, Hwacheong, by N-methyl-N-nitrosourea (MNU) treatment. The breaking tensile strength (BTS) of the grain pedicel was measured using a digital force gauge to evaluate the degree of shattering of rice varieties at 5, 10, 15, 20, 25, 30, 35, and 40 days after heading (DAH). The BTS of Hwacheong did not decrease with increasing DAH, maintaining a level of 180–240 gf, while that of Hsh decreased greatly during 10–20 DAH and finally stabilized at 50 gf. Optical microscopy revealed that Hsh had a well-developed abscission layer similar to the wild rice Oryza nivara (accession IRGC105706), while Hwacheong did not produce an abscission layer, indicating that the shattering of Hsh was caused by differentiation of the abscission layer. On the basis of the BTS value and morphology of the abscission layer of F1 plants and segregation data in F2 populations, it was concluded that the easy shattering of Hsh was controlled by the single recessive gene sh-h. The gene sh-h was determined to be located on rice chromosome 7 by bulked segregant analysis. Using 14 SSR markers on rice chromosome 7, the gene sh-h was mapped between the flanking markers RM8262 and RM7161 at distances of 1.6 and 2.0 cM, respectively. An SSR marker Rc17 cosegregated with the gene sh-h. The locus sh-h for shattering was tightly linked to the Rc locus conferring red pericarp, as well as a QTL qSDs-7-1 for seed dormancy, implying that this region might represent a domestication block in the evolutionary pathway of rice.
Dominant Mutants of the Saccharomyces cerevisiae ASF1 Histone Chaperone Bypass the Need for CAF-1 in Transcriptional Silencing by Altering Histone and Sir Protein Recruitment
Authors: Tamburini Beth A , Carson Joshua J , Linger Jeffrey G , Tyler Jessica K
Published: April 2006

Transcriptional silencing involves the formation of specialized repressive chromatin structures. Previous studies have shown that the histone H3–H4 chaperone known as chromatin assembly factor 1 (CAF-1) contributes to transcriptional silencing in yeast, although the molecular basis for this was unknown. In this work we have identified mutations in the nonconserved C terminus of antisilencing function 1 (Asf1) that result in enhanced silencing of HMR and telomere-proximal reporters, overcoming the requirement for CAF-1 in transcriptional silencing. We show that CAF-1 mutants have a drastic reduction in DNA-bound histone H3 levels, resulting in reduced recruitment of Sir2 and Sir4 to the silent loci. C-terminal mutants of another histone H3–H4 chaperone Asf1 restore the H3 levels and Sir protein recruitment to the silent loci in CAF-1 mutants, probably as a consequence of the weakened interaction between these Asf1 mutants and histone H3. As such, these studies have identified the nature of the molecular defect in the silent chromatin structure that results from inactivation of the histone chaperone CAF-1.
Genetic Control of X Chromosome Inactivation in Mice: Definition of theXceCandidate Interval
Authors: Chadwick Lisa Helbling , Pertz Lisa M , Broman Karl W , Bartolomei Marisa S , Willard Huntington F
Published: April 2006

In early mammalian development, one of the two X chromosomes is silenced in each female cell as a result of X chromosome inactivation, the mammalian dosage compensation mechanism. In the mouse epiblast, the choice of which chromosome is inactivated is essentially random, but can be biased by alleles at the X-linked X controlling element (Xce). Although this locus was first described nearly four decades ago, the identity and precise genomic localization of Xce remains elusive. Within the X inactivation center region of the X chromosome, previous linkage disequilibrium studies comparing strains of known Xce genotypes have suggested that Xce is physically distinct from Xist, although this has not yet been established by genetic mapping or progeny testing. In this report, we used quantitative trait locus (QTL) mapping strategies to define the minimal Xce candidate interval. Subsequent analysis of recombinant chromosomes allowed for the establishment of a maximum 1.85-Mb candidate region for the Xce locus. Finally, we use QTL approaches in an effort to identify additional modifiers of the X chromosome choice, as we have previously demonstrated that choice in Xce heterozygous females is significantly influenced by genetic variation present on autosomes (Chadwick and Willard 2005). We did not identify any autosomal loci with significant associations and thus show conclusively that Xce is the only major locus to influence X inactivation patterns in the crosses analyzed. This study provides a foundation for future analyses into the genetic control of X chromosome inactivation and defines a 1.85-Mb interval encompassing all the major elements of the Xce locus.
Differential Roles of Transcriptional Mediator Complex Subunits Crsp34/Med27, Crsp150/Med14 and Trap100/Med24 During Zebrafish Retinal Development
Authors: Dürr Katrin , Holzschuh Jochen , Filippi Alida , Ettl Anne-Kathrin , Ryu Soojin , Shepherd Iain T , Driever Wolfgang
Published: April 2006

The transcriptional mediator complex has emerged as an important component of transcriptional regulation, yet it is largely unknown whether its subunits have differential functions in development. We demonstrate that the zebrafish mutation m885 disrupts a subunit of the mediator complex, Crsp34/Med27. To explore the role of the mediator in the control of retinal differentiation, we employed two additional mutations disrupting the mediator subunits Trap100/Med24 and Crsp150/Med14. Our analysis shows that loss of Crsp34/Med27 decreases amacrine cell number, but increases the number of rod photoreceptor cells. In contrast, loss of Trap100/Med24 decreases rod photoreceptor cells. Loss of Crsp150/Med14, on the other hand, only slightly reduces dopaminergic amacrine cells, which are absent from both crsp34m885 and trap100lessen mutant embryos. Our data provide evidence for differential requirements for Crsp34/Med27 in developmental processes. In addition, our data point to divergent functions of the mediator subunits Crsp34/Med27, Trap100/Med24, and Crsp150/Med14 and, thus, suggest that subunit composition of the mediator contributes to the control of differentiation in the vertebrate CNS.
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

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 >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

In 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

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

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

An ultradense genetic linkage map with >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

Within 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

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

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

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

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

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.
Do Differences in the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists Positions on the Ethics of Maternal–Fetal Interventions Reflect Subtly Divergent Professional Sensitivities to Pregnant Women and Fetuses?
Authors: Brown Stephen D. , Truog Robert D. , Johnson Judith A. , Ecker Jeffrey L.
Published: April 2006

As therapeutic interventions that are designed for the direct benefit of the fetus have evolved, pediatric specialists along with obstetricians have become increasingly engaged in the management of pregnancies that are complicated by fetal disorders. Do the 2 groups of medical specialists hold differing “world views” on the nature of the maternal–fetal relationship that could have an impact on decision-making? A direct comparison of the positions of the ethics committees of the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists concerning maternal–fetal conflicts and fetal therapy reveals subtle but telling differences. Compared with the American College of Obstetricians and Gynecologists policy, the American Academy of Pediatrics statement accords somewhat less weight to maternal decision-making and is more tolerant of overriding maternal refusal of interventions that are recommended for fetal benefit. In doing so, it may oblige pregnant patients to assume greater risk and tolerate diminished autonomy. We urge leaders from both disciplines to meet and seek consensus so that a common approach and language can guide treatment of the patients whom we share.
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 >35.5 weeks' gestation and <3 days old with severe PPHN and oxygenation index (OI) >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 <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 <20 or if there was no significant change in OI after 36 hours.

RESULTS. Six infants with an OI of >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.
A Randomized, Controlled Trial of an Interactive Educational Computer Package for Children With Asthma
Authors: McPherson Amy C. , Glazebrook Cristine , Forster Debra , James Claire , Smyth Alan
Published: April 2006

OBJECTIVE. The purpose of this study was to evaluate the impact and acceptability of an educational multimedia program designed to promote self-management skills in children with asthma.

METHODS. We conducted a randomized, controlled trial with measures at baseline and 1- and 6-month follow-up. The trial was conducted in pediatric outpatient respiratory clinics in 3 United Kingdom hospitals. Participants included 101 children aged 7 to 14 years under the care of hospital-based asthma services. The children were randomly assigned to receive an asthma information booklet alone or the booklet plus The Asthma Files, an interactive CD-ROM for children with asthma. Asthma knowledge was the primary outcome measure. Other measures included asthma locus of control, lung function, use of oral steroids, and school absence.

RESULTS. At the 1-month follow-up (n = 99), children in the computer group had improved knowledge compared with the control group and a more internal locus of control. There were no differences in objective lung-function measures, hospitalizations, or oral steroid use. The study participants were positive in their evaluation of the intervention. At the 6-month follow-up (n = 90), significantly fewer children in the intervention group had required oral steroids and had had time off school for asthma in the previous 6 months. The difference did not reach statistical significance in the intention-to-treat analysis for both steroid use and school absence.

CONCLUSION. The Asthma Files was found to be an effective and popular health education tool for promoting asthma self-management skills within pediatric care.
Transcutaneous Bilirubin Levels in the First 96 Hours in a Normal Newborn Population of ≥35 Weeks' Gestation
Authors: Maisels M. Jeffrey , Kring Elizabeth
Published: April 2006

OBJECTIVE. To obtain transcutaneous bilirubin (TcB) measurements, at 6-hour intervals, in the first 96 hours after birth in a normal newborn population (gestational age: ≥35 weeks).

METHODS. We performed 9397 TcB measurements on 3984 healthy newborn infants (gestational age: ≥35 weeks) from 6 to 96 hours of age. All measurements were performed in the well-infant nursery with a Draeger Air-Shields transcutaneous jaundice meter (model JM-103), within 2 hours of the designated time.

RESULTS. There was a distinct pattern to the velocity of the increase in TcB levels over different time periods. TcB levels increased in a linear manner most rapidly in the first 6 to 18 hours and then less rapidly from 18 to 42 hours, followed by a much slower increase until peak levels occurred. Decreasing gestational age was associated significantly with higher TcB levels.

CONCLUSIONS. We provide data on neonatal bilirubinemia, based on TcB levels determined in a large, predominately white and breastfed, North American population. Infants who require closer evaluation and observation initially are those whose bilirubin levels are ≥95th percentile, ie, increasing more rapidly than 0.22 mg/dL per hour in the first 24 hours, 0.15 mg/dL per hour between 24 and 48 hours, and 0.06 mg/dL per hour after 48 hours. These data should be useful for detecting aberrant trends, identifying infants who need additional evaluation, and planning appropriate follow-up for jaundiced newborns.