bluuebunny/crossref_metadata_2025_split huggingface dataset:
One-pot Synthesis of 3-Bromoimidazo[1,2-a]pyridine Derivatives Accompanied by Dimethyl Sulfoxide Oxidation
Authors: Kawano Tomikazu , Kato Nobuo 
Published: February 2006

Abstract
3-Bromoimidazo[1,2-a]pyridine derivatives have been directly synthesized from reaction of 2-aminopyridine derivative with α-haloketone derivatives in DMSO at room temperature, accompanied by DMSO oxidation.
Factors relating to depression after stroke
Authors: Thomas Shirley A. , Lincoln Nadina B. 
Published: February 2006

Objectives. Depression is common after stroke and can impede rehabilitation. The aim of this study was to determine which factors predicted the severity of depression at the time of recruitment to a treatment study and depression 6 months later.Design. A questionnaire‐based longitudinal study.Methods. A total of 123 depressed stroke patients who were between 1 and 6 months post‐stroke and had mild to moderate disabilities were recruited to a randomized controlled trial of cognitive behavioural psychotherapy (CBT) to treat depression (Lincoln & Flannaghan, 2003). At recruitment and at 6 months follow‐up, patients (N=112) were assessed on the Beck Depression Inventory (BDI), General Health Questionnaire‐28 (GHQ‐28), Wakefield Depression Inventory (WDI), Barthel index, Extended activities of daily living scale (EADL), Sheffield Screening Test for Acquired Language Disorders (SST) and Recovery locus of control scale (RLOC).Results. Logistic regression showed that greater communication impairment on the SST at recruitment was predictive of severe depression on the BDI at recruitment (OR=0.72, p=.01). Patients with greater communication impairment (OR=0.69, p<.05) and a more external locus of control (OR=0.89, p<.05) at recruitment were more likely to remain depressed at follow‐up. Patients who remained depressed at follow‐up were more severely depressed at recruitment (p=.001).Conclusions. Locus of control and communication impairment were related to depression. Communication impairment was the strongest predictor of depression severity and prognosis. Mild depression was more likely to resolve. The regression models only accounted for a small proportion of the variance in depression scores. Therefore, further studies of psychosocial factors in a more representative sample are required.
Police Reform: Problems of Governance and Accountability Management Challenges Surrounding Current Proposals for Police Restructuring
Authors: Loveday Barry 
Published: February 2006

This article considers the current decision of the Home Secretary to scrap the 43 police forces and replace them with 12–15 regional strategic police forces. This follows on from the recent report of HMIC, entitled Closing the Gap, published in September 2005, which was to conclude that as currently constituted the police structure for England and Wales was no longer ‘fit for purpose’. Using the ability of police services to provide an effective response to NIM Level 2 crime as a yardstick, HMIC was to find that any force with fewer than 4,000 police officers would be unlikely to be able to provide an adequate response. One consequence of the report and the Home Secretary's response to it has been the request made to all police authorities and forces to present a business case to the Home Office by the end of 2005 identifying the future structure of policing in the region and the pattern of amalgamation they might favour. In the course of this exercise it was to be found that alternatives to amalgamation, collaboration and federation, had both been closed down by the Home Secretary, who has concluded that only the option of amalgamation was now acceptable to his department. Subsequently it was to be learned that a number of factors influencing HMIC's 2005 report obtained that had not been taken into account. These included the decision on the part of HMIC specifically not to include the written section on force collaboration within the final report. Nor, it was also to be discovered, had recognition been given within the report to the expectation that implementation was to be carried out in conjunction with comprehensive Workforce Modernisation. A leaked memorandum from ODPM in late 2005 that local government reform was now under active consideration was also to undermine the earlier assumption on the part of HMIC that no plans for local government reform were currently planned and that unilateral police reorganisation was therefore appropriate.
Osmolality Gaps: Diagnostic Accuracy and Long-Term Variability
Authors: Krahn John , Khajuria Annu 
Published: February 2006

Abstract
Background: The osmolal gap (OG) is a screening test for the detection of toxic volatiles such as methanol and ethylene glycol. We used mean values of patient data to assess the diagnostic accuracy and long-term stability of OG measurements.
Methods: In a prospective study period in 2003, all requests for volatiles had OGs calculated and quality-control samples were analyzed for OG. ROC curves were constructed to determine whether OG could predict the presence of toxic volatiles in serum. This was also done in a retrospective study for data from 1996 to 2004. Our laboratory database was searched for all emergency room patients for the period of 1996 to 2004 who had tests ordered that allowed us to calculate OGs.
Results: For the prospective study period in 2003, the ROC areas indicated that we could accurately predict the presence of toxic volatiles but at markedly different decision cutpoints depending on the formula used. These cutpoints ranged from +10 to +33 mosmol/kg. In the retrospective study, the mean OGs in the patient population for each of the 3 formulas increased by 12 mosmol/kg from 1996 to 2004. For this reason, the diagnostic accuracy was poor when all data were analyzed together.
Conclusions: Under properly controlled conditions, the OG has high sensitivity and specificity for detection of poisoning with some volatiles. Over the long term, however, use of the reference interval of −10 to +10 mosmol/kg yields poor diagnostic accuracy because mean OGs are not constant over time. Bedside calculation is not advisable.
Benchmark for Evaluating the Quality of DNA Sequencing: Proposal from an International External Quality Assessment Scheme
Authors: Patton Simon J , Wallace Andrew J , Elles Rob 
Published: February 2006

Abstract
Background: In the past 15 years, clinical laboratory science has been transformed by the use of technologies that cross the traditional boundaries between laboratory disciplines. However, during this period, issues of quality have not always been given adequate attention. The European Molecular Genetics Quality Network (EMQN) has developed a novel external quality assessment scheme for evaluation of DNA sequencing. We report the results of an international survey of the quality of DNA sequencing among 64 laboratories from 21 countries.
Methods: Current practice for DNA sequence analysis was established by use of an online questionnaire. Participating laboratories were provided with 4 DNA samples of validated genotype. Evaluation of the results included assessing the quality of sequence data, variant genotypes, and mutation nomenclature. To accommodate variations in mutation nomenclature, variants indicated by participants were scored for compliance with 3 acceptable marking schemes.
Results: A total of 346 genotypes were analyzed. Of these, 19 (5%) genotyping errors were made. Of these, 10 (53%) were false-negative and 9 (47%) were false-positive results. A further 27 (8%) errors were made in naming mutations. Results were analyzed for 3 indicators of data quality: PHRED quality scores, Quality Read Length, and Quality Read Overlap. Most laboratories produced results of acceptable diagnostic quality as judged by these indicators. The results were used to calculate a consensus benchmark for DNA sequencing against which individual laboratories could rank their performance.
Conclusions: We propose that the consensus benchmark can be used as a baseline against which the aggregate and individual laboratory standard of DNA sequencing may be tracked from year to year.
Mutations in the extra sex combs and Enhancer of Polycomb Genes Increase Homologous Recombination in Somatic Cells of Drosophila melanogaster
Authors: Holmes Angela M , Weedmark Kelly A , Gloor Gregory B 
Published: February 2006

Abstract
We found that heterozygous mutant alleles of E(Pc) and esc increased homologous recombination from an allelic template in somatic cells in a P-element-induced double-strand break repair assay. Flies heterozygous for mutant alleles of these genes showed increased genome stability and decreased levels of apoptosis in imaginal discs and a concomitant increase in survival following ionizing radiation. We propose that this was caused by a genomewide increase in homologous recombination in somatic cells. A double mutant of E(Pc) and esc had no additive effect, showing that these genes act in the same pathway. Finally, we found that a heterozygous deficiency for the histone deacetylase, Rpd3, masked the radiation-resistant phenotype of both esc and E(Pc) mutants. These findings provide evidence for a gene dosage-dependent interaction between the esc/E(z) complex and the Tip60 histone acetyltransferase complex. We propose that esc and E(Pc) mutants enhance homologous recombination by modulating the histone acetylation status of histone H4 at the double-strand break.
A Linkage Map for Brown Trout (Salmo trutta): Chromosome Homeologies and Comparative Genome Organization With Other Salmonid Fish
Authors: Gharbi Karim , Gautier Angélique , Danzmann Roy G , Gharbi Sonia , Sakamoto Takashi , Høyheim Bjørn , Taggart John B , Cairney Margaret , Powell Richard , Krieg Francine , Okamoto Nobuaki , Ferguson Moira M , Holm Lars-Erik , Guyomard René 
Published: February 2006

Abstract
We report on the construction of a linkage map for brown trout (Salmo trutta) and its comparison with those of other tetraploid-derivative fish in the family Salmonidae, including Atlantic salmon (Salmo salar), rainbow trout (Oncorhynchus mykiss), and Arctic char (Salvelinus alpinus). Overall, we identified 37 linkage groups (2n = 80) from the analysis of 288 microsatellite polymorphisms, 13 allozyme markers, and phenotypic sex in four backcross families. Additionally, we used gene–centromere analysis to approximate the position of the centromere for 20 linkage groups and thus relate linkage arrangements to the physical morphology of chromosomes. Sex-specific maps derived from multiple parents were estimated to cover 346.4 and 912.5 cM of the male and female genomes, respectively. As previously observed in other salmonids, recombination rates showed large sex differences (average female-to-male ratio was 6.4), with male crossovers generally localized toward the distal end of linkage groups. Putative homeologous regions inherited from the salmonid tetraploid ancestor were identified for 10 pairs of linkage groups, including five chromosomes showing evidence of residual tetrasomy (pseudolinkage). Map alignments with orthologous regions in Atlantic salmon, rainbow trout, and Arctic char also revealed extensive conservation of syntenic blocks across species, which was generally consistent with chromosome divergence through Robertsonian translocations.
In Vivo Analysis of a Gain-of-Function Mutation in the Drosophila eag-Encoded K+ Channel
Authors: Cardnell Robert J G , Dalle Nogare Damian E , Ganetzky Barry , Stern Michael 
Published: February 2006

Abstract
Neuronal Na+ and K+ channels elicit currents in opposing directions and thus have opposing effects on neuronal excitability. Mutations in genes encoding Na+ or K+ channels often interact genetically, leading to either phenotypic suppression or enhancement for genes with opposing or similar effects on excitability, respectively. For example, the effects of mutations in Shaker (Sh), which encodes a K+ channel subunit, are suppressed by loss-of-function mutations in the Na+ channel structural gene para, but enhanced by loss-of-function mutations in a second K+ channel encoded by eag. Here we identify two novel mutations that suppress the effects of a Sh mutation on behavior and neuronal excitability. We used recombination mapping to localize both mutations to the eag locus, and we used sequence analysis to determine that both mutations are caused by a single amino acid substitution (G297E) in the S2–S3 linker of Eag. Because these novel eag mutations confer opposite phenotypes to eag loss-of-function mutations, we suggest that eagG297E causes an eag gain-of-function phenotype. We hypothesize that the G297E substitution may cause premature, prolonged, or constitutive opening of the Eag channels by favoring the “unlocked” state of the channel.
The Hitchhiking Effect on Linkage Disequilibrium Between Linked Neutral Loci
Authors: Stephan Wolfgang , Song Yun S , Langley Charles H 
Published: February 2006

Abstract
We analyzed a three-locus model of genetic hitchhiking with one locus experiencing positive directional selection and two partially linked neutral loci. Following the original hitchhiking approach by Maynard Smith and Haigh, our analysis is purely deterministic. In the first half of the selected phase after a favored mutation has entered the population, hitchhiking may lead to a strong increase of linkage disequilibrium (LD) between the two neutral sites if both are &lt;0.1s away from the selected site (where s is the selection coefficient). In the second half of the selected phase, the main effect of hitchhiking is to destroy LD. This occurs very quickly (before the end of the selected phase) when the selected site is between both neutral loci. This pattern cannot be attributed to the well-known variation-reducing effect of hitchhiking but is a consequence of secondary hitchhiking effects on the recombinants created in the selected phase. When the selected site is outside the neutral loci (which are, say, &lt;0.1s apart), however, a fast decay of LD is observed only if the selected site is in the immediate neighborhood of one of the neutral sites (i.e., if the recombination rate r between the selected site and one of the neutral sites satisfies $\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(r{\ll}0.1s\) \end{document}$). If the selected site is far away from the neutral sites (say, r &gt; 0.3s), the decay rate of LD approaches that of neutrality. Averaging over a uniform distribution of initial gamete frequencies shows that the expected LD at the end of the hitchhiking phase is driven toward zero, while the variance is increased when the selected site is well outside the two neutral sites. When the direction of LD is polarized with respect to the more common allele at each neutral site, hitchhiking creates more positive than negative linkage disequilibrium. Thus, hitchhiking may have a distinctively patterned LD-reducing effect, in particular near the target of selection.
Substitution Mapping of dth1.1, a Flowering-Time Quantitative Trait Locus (QTL) Associated With Transgressive Variation in Rice, Reveals Multiple Sub-QTL
Authors: Thomson Michael J , Edwards Jeremy D , Septiningsih Endang M , Harrington Sandra E , McCouch Susan R 
Published: February 2006

Abstract
A quantitative trait locus (QTL), dth1.1, was associated with transgressive variation for days to heading in an advanced backcross population derived from the Oryza sativa variety Jefferson and an accession of the wild rice relative Oryza rufipogon. A series of near-isogenic lines (NILs) containing different O. rufipogon introgressions across the target region were constructed to dissect dth1.1 using substitution mapping. In contrast to the late-flowering O. rufipogon parent, O. rufipogon alleles in the substitution lines caused early flowering under both short- and long-day lengths and provided evidence for at least two distinct sub-QTL: dth1.1a and dth1.1b. Potential candidate genes underlying these sub-QTL include genes with sequence similarity to Arabidopsis GI, FT, SOC1, and EMF1, and Pharbitis nil PNZIP. Evidence from families with nontarget O. rufipogon introgressions in combination with dth1.1 alleles also detected an early flowering QTL on chromosome 4 and a late-flowering QTL on chromosome 6 and provided evidence for additional sub-QTL in the dth1.1 region. The availability of a series of near-isogenic lines with alleles introgressed from a wild relative of rice provides an opportunity to better understand the molecular basis of transgressive variation in a quantitative trait.
Dynamics of Gene Introgression in the African Malaria Vector Anopheles gambiae
Authors: Zhong Daibin , Temu Emmanuel A , Guda Tom , Gouagna Louis , Menge David , Pai Aditi , Githure John , Beier John C , Yan Guiyun 
Published: February 2006

Abstract
Anopheles gambiae is a major malaria vector in Africa and a popular model species for a variety of ecological, evolutionary, and genetic studies on vector control. Genetic manipulation of mosquito vectorial capacity is a promising new weapon for the control of malaria. However, the release of exotic transgenic mosquitoes will bring in novel alleles in addition to the parasite-inhibiting genes, which may have unknown effects on the local population. Therefore, it is necessary to develop methodologies that can be used to evaluate the spread rate of introduced genes in A. gambiae. In this study, the effects and dynamics of genetic introgression between two geographically distinct A. gambiae populations from western Kenya (Mbita) and eastern Tanzania (Ifakara) were investigated with amplified fragment length polymorphisms (AFLPs) and microsatellite markers. Microsatellites and polymorphic cDNA markers revealed a large genetic differentiation between the two populations (average FST = 0.093, P &lt; 0.001). When the two strains were crossed in random mating between the two populations, significant differences in the rate of genetic introgression were found in the mixed populations. Allele frequencies of 18 AFLP markers (64.3%) for Mbita and of 26 markers (92.9%) for Ifakara varied significantly from F5 to F20. This study provides basic information on how a mosquito release program would alter the genetic makeup of natural populations, which is critical for pilot field testing and ecological risk evaluation of transgenic mosquitoes.
Saccharomyces cerevisiae Polymerase ζ Functions in Mitochondria
Authors: Zhang Hengshan , Chatterjee Aditi , Singh Keshav K 
Published: February 2006

Abstract
The MtArg8 reversion assay, which measures point mutation in mtDNA, indicates that in budding yeast Saccharomyces cerevisiae, DNA polymerase ζ and Rev1 proteins participate in the mitochondrial DNA mutagenesis. Supporting this evidence, both polymerase ζ and Rev1p were found to be localized in the mitochondria. This is the first report demonstrating that the DNA polymerase ζ and Rev1 proteins function in the mitochondria.
Tracing Nonlegume Orthologs of Legume Genes Required for Nodulation and Arbuscular Mycorrhizal Symbioses
Authors: Zhu Hongyan , Riely Brendan K , Burns Nicole J , Ané Jean-Michel 
Published: February 2006

Abstract
Most land plants can form a root symbiosis with arbuscular mycorrhizal (AM) fungi for assimilation of inorganic phosphate from the soil. In contrast, the nitrogen-fixing root nodule symbiosis is almost completely restricted to the legumes. The finding that the two symbioses share common signaling components in legumes suggests that the evolutionarily younger nitrogen-fixing symbiosis has recruited functions from the more ancient AM symbiosis. The recent advances in cloning of the genes required for nodulation and AM symbioses from the two model legumes, Medicago truncatula and Lotus japonicus, provide a unique opportunity to address biological questions pertaining to the evolution of root symbioses in plants. Here, we report that nearly all cloned legume genes required for nodulation and AM symbioses have their putative orthologs in nonlegumes. The orthologous relationship can be clearly defined on the basis of both sequence similarity and microsyntenic relationship. The results presented here serve as a prelude to the comparative analysis of orthologous gene function between legumes and nonlegumes and facilitate our understanding of how gene functions and signaling pathways have evolved to generate species- or family-specific phenotypes.
Functions of Multiple Exonucleases Are Essential for Cell Viability, DNA Repair and Homologous Recombination inrecDMutants ofEscherichia coli
Authors: Ðermić Damir 
Published: February 2006

AbstractHeterotrimeric RecBCD enzyme unwinds and resects a DNA duplex containing blunt double-stranded ends and directs loading of the strand-exchange protein RecA onto the unwound 3′-ending strand, thereby initiating the majority of recombination in wild-type Escherichia coli. When the enzyme lacks its RecD subunit, the resulting RecBC enzyme, active in recD mutants, is recombination proficient although it has only helicase and RecA loading activity and is not a nuclease. However, E. coli encodes for several other exonucleases that digest double-stranded and single-stranded DNA and thus might act in consort with the RecBC enzyme to efficiently promote recombination reactions. To test this hypothesis, I inactivated multiple exonucleases (i.e., exonuclease I, exonuclease X, exonuclease VII, RecJ, and SbcCD) in recD derivatives of the wild-type and nuclease-deficient recB1067 strain and assessed the ability of the resultant mutants to maintain cell viability and to promote DNA repair and homologous recombination. A complex pattern of overlapping and sometimes competing activities of multiple exonucleases in recD mutants was thus revealed. These exonucleases were shown to be essential for cell viability, DNA repair (of UV- and γ-induced lesions), and homologous recombination (during Hfr conjugation and P1 transduction), which are dependent on the RecBC enzyme. A model for donor DNA processing in recD transconjugants and transductants was proposed.
Coalescent Processes When the Distribution of Offspring Number Among Individuals Is Highly Skewed
Authors: Eldon Bjarki , Wakeley John 
Published: February 2006

Abstract
We report a complex set of scaling relationships between mutation and reproduction in a simple model of a population. These follow from a consideration of patterns of genetic diversity in a sample of DNA sequences. Five different possible limit processes, each with a different scaled mutation parameter, can be used to describe genetic diversity in a large population. Only one of these corresponds to the usual population genetic model, and the others make drastically different predictions about genetic diversity. The complexity arises because individuals can potentially have very many offspring. To the extent that this occurs in a given species, our results imply that inferences from genetic data made under the usual assumptions are likely to be wrong. Our results also uncover a fundamental difference between populations in which generations are overlapping and those in which generations are discrete. We choose one of the five limit processes that appears to be appropriate for some marine organisms and use a sample of genetic data from a population of Pacific oysters to infer the parameters of the model. The data suggest the presence of rare reproduction events in which ∼8% of the population is replaced by the offspring of a single individual.