2,635 research outputs found
Competition, monopoly and corporate governance ::essays in honour of Keith Cowling /
No full textCompetition, Monopoly and Corporate Governance covers three broad themes, each associated with a particular strand of Keith Cowling's own writings in industrial economics and each represented by four specially commissioned papers
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Competition, monopoly and corporate governance ::essays in honour of Keith Cowling /
No full textCompetition, Monopoly and Corporate Governance covers three broad themes, each associated with a particular strand of Keith Cowling's own writings in industrial economics and each represented by four specially commissioned papers
Sex differences in Cognitive Abilities Test scores: a UK national picture
No full textBackground and aims. There is uncertainty about the extent or even existence of sex differences in the mean and variability of reasoning test scores ( Jensen, 1998; Lynn, 1994, ; Mackintosh, 1996). This paper analyses the Cognitive Abilities Test (CAT) scores of a large and representative sample of UK pupils to determine the extent of any sex differences.
Sample. A nationally representative UK sample of over 320,000 school pupils aged 11-12 years was assessed on the CAT (third edition) between September 2001 and August 2003. The CAT includes separate nationally standardized tests for verbal, quantitative, and non-verbal reasoning. The size and recency of the sample is unprecedented in research on this issue.
Methods. The sheer size of the sample ensures that any sex difference will achieve statistical significance. Therefore, effect sizes (d) and variance ratios (VR) are employed to evaluate the magnitude of sex differences in mean scores and in score variability, respectively.
Results. The mean verbal reasoning score for girls was 2.2 standard score points higher than the mean for boys, but only 0.3 standard points in favour of girls for non-verbal reasoning (NVR), and 0.7 points in favour of boys for quantitative reasoning (QR). However, for all three tests there were substantial sex differences in the standard deviation of scores, with greater variance among boys. Boys were over represented relative to girls at both the top and the bottom extremes for all tests, with the exception of the top 10% in verbal reasoning.
Conclusions. Given the small differences in means, explanations for sex differences in wider domains such examination attainment at age 16 need to look beyond conceptions of `ability'. Boys tend to be both the lowest and the highest performers in terms of their reasoning abilities, which warns against the danger of stereotyping boys as low achievers
Triplex-directed recognition of a DNA nanostructure assembled by crossover strand exchange
No full textNA has been widely exploited for the self-assembly of nanosized objects and arrays that offer the potential to act as scaffolds for the spatial positioning of molecular components with nanometer precision. Methods that allow the targeting of components to specific locations within these structures are therefore highly sought after. Here we report that the triplex approach to DNA recognition, which relies on the specific binding of an oligonucleotide within the major groove of double-helical DNA, can be exploited to recognize specific loci within a DNA double-crossover tile and array, a nanostructure assembled by crossover strand exchange. The oligonucleotide can be targeted to both crossover and non-crossover strands and, surprisingly, across the region spanning the crossover junction itself. Moreover, by attaching biotin to the end of the oligonucleotide, we show that streptavidin molecules can be recruited to precise locations within a DX array, with an average spacing of 31.9 (±1.3) nm. This is a promising approach that could be exploited to introduce other components compatible with oligonucleotide synthesis into the wide variety of DNA nanostructures assembled by crossover strand exchange, such as those generated by DNA origami.<br/
Comparison of antiparallel A-AT and T-AT triplets within an alternate strand DNA triple helix
No full textWe have examined the formation of alternate strand triple-helices at the target sequence A11(TC)6-(GA)6T11 using the oligonucleotides T11(AG)6 and T11(TG)6, by DNase I footprinting. These third strands were designed so as to form parallel T-AT triplets together with antiparallel G-GC and A-AT or T-AT triplets. We find that, although both oligonucleotides yield clear footprints at similar concentrations (0.3 μM) in the presence of manganese, only T11(TG)6 forms a stable complex in magnesium-containing buffers, albeit at a higher concentration (10-30 μM). Examination of the interaction of (AG)6 and (TG)6 with half the target site confirmed that the complex containing A-AT triplets was only stable in the presence of manganese. In contrast no binding of (TG)6 was detected in the presence of either metal ion, suggesting that the reverse-Hoogsteen T-AT triplet is less stable that GGC. We suggest that, within the context of GGC triplets, the rank order of antiparallel triplet stability is A·AT(Mn2+) > T.AT(Mn2+) > T.AT (Mg2+) > A.AT (Mg2+). Third strands containing a single base substitution in the centre of either the parallel or antiparallel portion showed a (10-fold) weaker interaction in manganese-containing buffers, and no interaction in the presence of magnesium.</p
A fast algorithm for the construction of universal footprinting templates in DNA
No full textWe introduce and give a complete description of a new graph to be used for DNA sequencing questions. This graph has the advantage over the classical de Bruijn graph that it fully accounts for the double stranded nature of DNA, rather than dealing with single strands. Technically, our graph may be thought of as the quotient of the de Bruijn graph under the natural involution of sending a DNA strand to its complementary strand. However, this involution has fixed points, and this complicates the structure of the quotient graph which we have therefore modified herein. As an application and motivating example, we give an efficient algorithm for constructing universal footprinting templates for n-mers. This problem may be formulated as the task of finding a shortest possible segment of DNA which contains every possible sequence of base pairs of some fixed length n. Previous work by Kwan et al has attacked this problem from a numerical point of view and generated minimal length universal footprinting templates for n=2, 3, 5, 7, together with unsubstantiated candidates for the case n=4. We show that their candidates for n=4 are indeed minimal length universal footprinting templates
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XRCC1 and DNA strand break repair
No full textDNA single-strand breaks can arise indirectly, as normal intermediates of DNA base excision repair, or directly from damage to deoxyribose. Because single-strand breaks are induced by endogenous reactive molecules such as reactive oxygen species, these lesions pose a continuous threat to genetic integrity. XRCC1 protein plays a major role in facilitating the repair of single-strand breaks in mammalian cells, via an ability to interact with multiple enzymatic components of repair reactions. Here, the protein¿protein interactions facilitated by XRCC1, and the repair processes in which these interactions operate, are reviewed. Models for the repair of single-strand breaks during base excision repair and at direct breaks are presented
Secondary binding sites for triplex-forming oligonucleotides containing bulges, loops, and mismatches in the third strand
No full textWe have used DNase I footprinting to examine the binding of five different 17-mer oligonucleotides to a 53-base oligopurine tract containing four pyrimidine interruptions. Although all the expected triplexes formed with high affinity (Kd 10-50 nM), one oligonucleotide produced a footprint at a second site with about 20-fold lower affinity. We have explored the nature of this secondary binding site and suggest that it arises when each end of the third strand forms a 7-mer triplex with adjacent regions on the duplex, generating a contiguous 14-base triplex with a bulge in the center of the third strand oligonucleotide. This unusual binding mode was examined by use of oligonucleotides that were designed with the potential to form different length third-strand loops of various base composition. We find that triplexes containing single-base bulges are generally more stable than those with dinucleotide loops, though triplexes can be formed with loops of up to nine thymines, generating complexes with submicromolar dissociation constants. These structures are much more stable than those formed by adding two separate 7-mer oligonucleotides, which do not generate DNase I footprints, though a stable complex is generated when the two halves are covalently joined by a hexa(ethylene glycol) linker. MPE produces less clear footprints, presumably because this cleavage agent binds to triplex DNA, but confirms that the oligonucleotides can bind in unexpected places. These results suggest that extra care needs to be taken when designing long triplex-forming oligonucleotides so as to avoid triplex formation at shorter secondary sites
MRE11 facilitates the removal of human topoisomerase II complexes from genomic DNA
No full textTopoisomerase II creates a double-strand break intermediate with topoisomerase covalently coupled to the DNA via a 5'-phosphotyrosyl bond. These intermediate complexes can become cytotoxic protein-DNA adducts and DSB repair at these lesions requires removal of topoisomerase II. To analyse removal of topoisomerase II from genomic DNA we adapted the trapped in agarose DNA immunostaining assay. Recombinant MRE11 from 2 sources removed topoisomerase IIalpha from genomic DNA in vitro, as did MRE11 immunoprecipitates isolated from A-TLD or K562 cells. Basal topoisomerase II complex levels were very high in A-TLD cells lacking full-length wild type MRE11, suggesting that MRE11 facilitates the processing of topoisomerase complexes that arise as part of normal cellular metabolism. In K562 cells inhibition of MRE11, PARP or replication increased topoisomerase IIalpha and beta complex levels formed in the absence of an anti-topoisomerase II dru
Phosphorylation of Exo1 modulates homologous recombination repair of DNA double-strand breaks
No full textDNA double-strand break (DSB) repair via the homologous recombination pathway is a multi-stage process, which results in repair of the DSB without loss of genetic information or fidelity. One essential step in this process is the generation of extended single-stranded DNA (ssDNA) regions at the break site. This ssDNA serves to induce cell cycle checkpoints and is required for Rad51 mediated strand invasion of the sister chromatid. Here, we show that human Exonuclease 1 (Exo1) is required for the normal repair of DSBs by HR. Cells depleted of Exo1 show chromosomal instability and hypersensitivity to ionising radiation (IR) exposure. We find that Exo1 accumulates rapidly at DSBs and is required for the recruitment of RPA and Rad51 to sites of DSBs, suggesting a role for Exo1 in ssDNA generation. Interestingly, the phosphorylation of Exo1 by ATM appears to regulate the activity of Exo1 following resection, allowing optimal Rad51 loading and the completion of HR repair. These data establish a role for Exo1 in resection of DSBs in human cells, highlighting the critical requirement of Exo1 for DSB repair via HR and thus the mainte-nance of genomic stability
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