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Rob Davies

Publications and source records attributed to Rob Davies.

10 recordsLinked to original sources
PubMed2006

DNA methylation profiling of human chromosomes 6, 20 and 22.

DNA methylation is the most stable type of epigenetic modification modulating the transcriptional plasticity of mammalian genomes. Using bisulfite DNA sequencing, we report high-resolution methylation profiles of human chromosomes 6, 20 and 22, providing a resource of about 1.9 million CpG methylation values derived from 12 different tissues. Analysis of six annotation categories showed that evolutionarily conserved regions are the predominant sites for differential DNA methylation and that a core region surrounding the transcriptional start site is an informative surrogate for promoter methylation. We find that 17% of the 873 analyzed genes are differentially methylated in their 5' UTRs and that about one-third of the differentially methylated 5' UTRs are inversely correlated with transcription. Despite the fact that our study controlled for factors reported to affect DNA methylation such as sex and age, we did not find any significant attributable effects. Our data suggest DNA methylation to be ontogenetically more stable than previously thought.

5' Untranslated Regions↗
PubMed2006

Attributions for negative events in the partners of adults with type I diabetes: Associations with partners' expressed emotion and marital adjustment.

OBJECTIVES: An attribution-emotion model of reactions to illness was tested in a sample of partners of 60 adult patients with type I diabetes. METHODS: Partners were interviewed using the Camberwell family interview (CFI), from which spontaneous attributions for negative events were extracted and coded. Events were classified into diabetes and non-diabetes events. Partners also completed questionnaire measures of marital adjustment, anxiety and depression. RESULTS: Compared with low expressed emotion (EE) partners, high-EE partners attributed proportionally more negative diabetes events (e.g. patient characteristics and behaviour) to factors controllable by and personal to the patient. High-EE partners were more anxious than low-EE partners, and made more responsibility attributions (attributions rated as both internal and controllable and personal). Partners with poorer marital adjustment made more responsibility attributions, but only for non-diabetes events. CONCLUSION: Whereas attributions for both diabetes and non-diabetes events were related to partners' EE, attributions for diabetes events were not significantly associated with partners' marital adjustment.

Adaptation, Psychological↗
PubMed2006

Idiosyncratic personal explanations for blood glucose events are associated with poorer self-management and glycemic control in adult patients with long-standing type 1 diabetes.

OBJECTIVE: To examine whether spontaneous causal attributions for blood glucose events were associated with blood glucose control (HbA(1c) [A1C]), self-management, and adjustment to diabetes. RESEARCH DESIGN AND METHODS: A total of 62 adults (31 female) with type 1 diabetes, recruited from a diabetes specialist clinic, with a mean age of 42.3 years and a mean illness duration of 19.6 years, were interviewed about the onset, history, course, and management of their diabetes. Spontaneous causal attributions for fluctuations in blood glucose level were extracted from the interviews and coded in accordance with the Leeds Attributional Coding System. Participants completed questionnaire measures of anxiety, depression, and appraisal of diabetes. Glycemic control (A1C) at the time of interview and 1 year later was extracted from notes. RESULTS: Participants who made proportionally more personal, or idiosyncratic, explanations for blood glucose fluctuations or events (such as hypoglycemic episodes) had higher A1C levels at time 1 and 1 year later and were judged to manage their diabetes less well. Furthermore, the association between personal attributions and A1C was partly accounted for by self-management behavior. Participants who made personal and stable attributions appraised their diabetes more negatively. CONCLUSIONS: Clinicians should be sensitive to patients' causal explanations for blood glucose events. Helping patients consider alternative explanations may produce benefits in terms of better management and control of diabetes.

Adult↗
PubMed2005

A genome-wide, end-sequenced 129Sv BAC library resource for targeting vector construction.

The majority of gene-targeting experiments in mice are performed in 129Sv-derived embryonic stem (ES) cell lines, which are generally considered to be more reliable at colonizing the germ line than ES cells derived from other strains. Gene targeting is reliant on homologous recombination of a targeting vector with the host ES cell genome. The efficiency of recombination is affected by many factors, including the isogenicity (H. te Riele et al., 1992, Proc. Natl. Acad. Sci. USA 89, 5128-5132) and the length of homologous sequence of the targeting vector and the location of the target locus. Here we describe the double-end sequencing and mapping of 84,507 bacterial artificial chromosomes (BACs) generated from AB2.2 ES cell DNA (129S7/SvEvBrd-Hprtb-m2). We have aligned these BACs against the mouse genome and displayed them on the Ensembl genome browser, DAS: 129S7/AB2.2. This library has an average insert size of 110.68 kb and average depth of genome coverage of 3.63- and 1.24-fold across the autosomes and sex chromosomes, respectively. Over 97% of the mouse genome and 99.1% of Ensembl genes are covered by clones from this library. This publicly available BAC resource can be used for the rapid construction of targeting vectors via recombineering. Furthermore, we show that targeting vectors containing DNA recombineered from this BAC library can be used to target genes efficiently in several 129-derived ES cell lines.

Animals↗
PubMed2005

A modelling approach to estimate the sensitivity of pooled faecal samples for isolation of Salmonella in pigs.

The objective of this study was to develop and parametrize a mathematical model of the sensitivity of pooled sampling of faeces to detect Salmonella infection in pigs. A mathematical model was developed to represent the effect of pooling on the probability of Salmonella isolation. Parameters for the model were estimated using data obtained by collecting 50 faecal samples from each of two pig farms. Each sample was tested for Salmonella at individual sample weights of 0.1, 0.5, 1, 10 and 25 g and pools of 5, 10 and 20 samples were created from the individual samples. The highest test sensitivity for individual samples was found at 10 g (90% sensitivity), with the 25 g test sensitivity equal to 83%. For samples of less than 10 g, sensitivity was found to reduce with sample weight. Incubation for 48 h was found to produce a more sensitive test than incubation for 24 h. Model results found increasing sensitivity with more samples in the pool, with the pools of 5, 10 and 20 being more sensitive than individual sampling, and the pools of 20 being the most sensitive of those considered.

Animals↗
PubMed2005

Complex haplotypes, copy number polymorphisms and coding variation in two recently divergent mouse strains.

Inbred mouse strains provide the foundation for mouse genetics. By selecting for phenotypic features of interest, inbreeding drives genomic evolution and eliminates individual variation, while fixing certain sets of alleles that are responsible for the trait characteristics of the strain. Mouse strains 129Sv (129S5) and C57BL/6J, two of the most widely used inbred lines, diverged from common ancestors within the last century, yet very little is known about the genomic differences between them. By comparative genomic hybridization and sequence analysis of 129S5 short insert libraries, we identified substantial structural variation, a complex fine-scale haplotype pattern with a continuous distribution of diversity blocks, and extensive nucleotide variation, including nonsynonymous coding SNPs and stop codons. Collectively, these genomic changes denote the level and direction of allele fixation that has occurred during inbreeding and provide a basis for defining what makes these mouse strains unique.

Animals↗
PubMed2005

The genome of the protist parasite Entamoeba histolytica.

Entamoeba histolytica is an intestinal parasite and the causative agent of amoebiasis, which is a significant source of morbidity and mortality in developing countries. Here we present the genome of E. histolytica, which reveals a variety of metabolic adaptations shared with two other amitochondrial protist pathogens: Giardia lamblia and Trichomonas vaginalis. These adaptations include reduction or elimination of most mitochondrial metabolic pathways and the use of oxidative stress enzymes generally associated with anaerobic prokaryotes. Phylogenomic analysis identifies evidence for lateral gene transfer of bacterial genes into the E. histolytica genome, the effects of which centre on expanding aspects of E. histolytica's metabolic repertoire. The presence of these genes and the potential for novel metabolic pathways in E. histolytica may allow for the development of new chemotherapeutic agents. The genome encodes a large number of novel receptor kinases and contains expansions of a variety of gene families, including those associated with virulence. Additional genome features include an abundance of tandemly repeated transfer-RNA-containing arrays, which may have a structural function in the genome. Analysis of the genome provides new insights into the workings and genome evolution of a major human pathogen.

Animals↗
PubMed2005

The effect of atorvastatin on serum lipoproteins in acromegaly.

OBJECTIVE: Acromegaly is associated with long-term adverse effects on cardiovascular mortality and morbidity. Reducing growth hormone secretion improves well-being and symptoms, but may not significantly improve the lipoprotein profile. An additional approach to cardiovascular risk reduction in acromegaly may therefore be to target lipoprotein metabolism directly. In this study we investigated the effect of statin treatment. DESIGN: Double blind, placebo-controlled, crossover study of the effects on circulating lipoproteins of atorvastatin 10 mg daily vs. placebo. Each treatment was given for 3 months in random order. SUBJECTS: Eleven patients with acromegaly. MEASUREMENTS: Lipids, lipoproteins, apolipoproteins, enzyme activity and calculated cardiovascular risk. RESULTS: Atorvastatin treatment compared to placebo resulted in a significant decrease in serum cholesterol (5.85 +/- 1.04 mmol/l vs. 4.22 +/- 0.69 mmol/l; mean +/- SD; P < 0.001), low-density lipoprotein (LDL) cholesterol (2.95 +/- 1.07 mmol/l vs. 1.82 +/- 0.92 mmol/l; P < 0.001), very low-density lipoprotein (VLDL) cholesterol (0.31 (0.21-0.47) mmol vs. 0.23 (0.13-0.30) mmol/l median (interquartile range); P < 0.05), apolipoprotein B (111 +/- 28 mg/dl vs. 80 +/- 18 mg/dl; P < 0.001), and calculated coronary heart disease risk (6.8 (3.3-17.9) vs. 2.8 (1.5-5.7)% over next 10 years; P < 0.01). Serum triglyceride was 1.34 (1.06-1.71) mmol/l on placebo and 1.14 (0.88-1.48) mmol/l on atorvastatin (ns). HDL cholesterol, apolipoprotein A1 and Lp(a) concentrations and cholesteryl ester transfer protein and lecithin: cholesterol acyl transferase activities were also not significantly altered. CONCLUSION: Atorvastatin treatment was safe, well tolerated and effective in improving the atherogenic lipoprotein profile in acromegaly.

Acromegaly↗
PubMed2004

Mutagenic insertion and chromosome engineering resource (MICER).

Embryonic stem cell technology revolutionized biology by providing a means to assess mammalian gene function in vivo. Although it is now routine to generate mice from embryonic stem cells, one of the principal methods used to create mutations, gene targeting, is a cumbersome process. Here we describe the indexing of 93,960 ready-made insertional targeting vectors from two libraries. 5,925 of these vectors can be used directly to inactivate genes with an average targeting efficiency of 28%. Combinations of vectors from the two libraries can be used to disrupt both alleles of a gene or engineer larger genomic changes such as deletions, duplications, translocations or inversions. These indexed vectors constitute a public resource (Mutagenic Insertion and Chromosome Engineering Resource; MICER) for high-throughput, targeted manipulation of the mouse genome.

Animals↗