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T Cox

Publications and source records attributed to T Cox.

At least 19 recordsLinked to original sources
PubMed2006

Ensembl 2007.

The Ensembl (http://www.ensembl.org/) project provides a comprehensive and integrated source of annotation of chordate genome sequences. Over the past year the number of genomes available from Ensembl has increased from 15 to 33, with the addition of sites for the mammalian genomes of elephant, rabbit, armadillo, tenrec, platypus, pig, cat, bush baby, common shrew, microbat and european hedgehog; the fish genomes of stickleback and medaka and the second example of the genomes of the sea squirt (Ciona savignyi) and the mosquito (Aedes aegypti). Some of the major features added during the year include the first complete gene sets for genomes with low-sequence coverage, the introduction of new strain variation data and the introduction of new orthology/paralog annotations based on gene trees.

Animals↗
PubMed2006

Late-onset metachromatic leukodystrophy: genotype strongly influences phenotype.

BACKGROUND: P426L and I179S are the two most frequent mutations in juvenile and adult metachromatic leukodystrophy (late-onset MLD), which, in contrast to infantile MLD, show marked phenotypic heterogeneity. OBJECTIVE: To search for genotype-phenotype correlations in late-onset MLD. METHODS: The authors reviewed the clinical course of 22 patients homozygous for mutation P426L vs 20 patients heterozygous for mutation I179S, in which the second arylsulfatase A (ASA) mutation had also been determined. RESULTS: P426L homozygotes principally presented with progressive gait disturbance caused by spastic paraparesis or cerebellar ataxia; mental disturbance was absent or insignificant at the onset of disease but became more apparent as the disease evolved. In contrast, compound heterozygotes for I179S presented with schizophrenia-like behavioral abnormalities, social dysfunction, and mental decline, but motor deficits were scarce. Reduced peripheral nerve conduction velocities and less residual ASA activity were present in P426L homozygotes vs I179S heterozygotes. CONCLUSION: The characteristic clinical differences between homozygous P426L and compound heterozygous I179S patients establish a distinct genotype-phenotype correlation in late-onset metachromatic leukodystrophy.

Adolescent↗
PubMed2006

Work design and management in the manufacturing sector: development and validation of the Work Organisation Assessment Questionnaire.

OBJECTIVES: To examine the factor structure, reliability, and validity of a new context-specific questionnaire for the assessment of work and organisational factors. The Work Organisation Assessment Questionnaire (WOAQ) was developed as part of a risk assessment and risk reduction methodology for hazards inherent in the design and management of work in the manufacturing sector. METHOD: Two studies were conducted. Data were collected from 524 white- and blue-collar employees from a range of manufacturing companies. Exploratory factor analysis was carried out on 28 items that described the most commonly reported failures of work design and management in companies in the manufacturing sector. Concurrent validity data were also collected. A reliability study was conducted with a further 156 employees. RESULTS: Principal component analysis, with varimax rotation, revealed a strong 28-item, five factor structure. The factors were named: quality of relationships with management, reward and recognition, workload, quality of relationships with colleagues, and quality of physical environment. Analyses also revealed a more general summative factor. Results indicated that the questionnaire has good internal consistency and test-retest reliability and validity. Being associated with poor employee health and changes in health related behaviour, the WOAQ factors are possible hazards. It is argued that the strength of those associations offers some estimation of risk. Feedback from the organisations involved indicated that the WOAQ was easy to use and meaningful for them as part of their risk assessment procedures. CONCLUSIONS: The studies reported here describe a model of the hazards to employee health and health related behaviour inherent in the design and management of work in the manufacturing sector. It offers an instrument for their assessment. The scales derived which form the WOAQ were shown to be reliable, valid, and meaningful to the user population.

Adolescent↗
PubMed2006

Ensembl 2006.

The Ensembl (http://www.ensembl.org/) project provides a comprehensive and integrated source of annotation of large genome sequences. Over the last year the number of genomes available from the Ensembl site has increased from 4 to 19, with the addition of the mammalian genomes of Rhesus macaque and Opossum, the chordate genome of Ciona intestinalis and the import and integration of the yeast genome. The year has also seen extensive improvements to both data analysis and presentation, with the introduction of a redesigned website, the addition of RNA gene and regulatory annotation and substantial improvements to the integration of human genome variation data.

Animals↗
PubMed2005

Ensembl 2005.

The Ensembl (http://www.ensembl.org/) project provides a comprehensive and integrated source of annotation of large genome sequences. Over the last year the number of genomes available from the Ensembl site has increased by 7 to 16, with the addition of the six vertebrate genomes of chimpanzee, dog, cow, chicken, tetraodon and frog and the insect genome of honeybee. The majority have been annotated automatically using the Ensembl gene build system, showing its flexibility to reliably annotate a wide variety of genomes. With the increased number of vertebrate genomes, the comparative analysis provided to users has been greatly improved, with new website interfaces allowing annotation of different genomes to be directly compared. The Ensembl software system is being increasingly widely reused in different projects showing the benefits of a completely open approach to software development and distribution.

Animals↗
PubMed2004

Ensembl 2004.

The Ensembl (http://www.ensembl.org/) database project provides a bioinformatics framework to organize biology around the sequences of large genomes. It is a comprehensive and integrated source of annotation of large genome sequences, available via interactive website, web services or flat files. As well as being one of the leading sources of genome annotation, Ensembl is an open source software engineering project to develop a portable system able to handle very large genomes and associated requirements. The facilities of the system range from sequence analysis to data storage and visualization and installations exist around the world both in companies and at academic sites. With a total of nine genome sequences available from Ensembl and more genomes to follow, recent developments have focused mainly on closer integration between genomes and external data.

Animals↗
PubMed2004

Assessment of a technique for 2D-3D registration of cerebral intra-arterial angiography.

This study assesses the ability of a computer algorithm to perform automated 2D-3D registrations of digitally subtracted cerebral angiograms. The technique was tested on clinical studies of five patients with intracranial aneurysms. The automated procedure was compared against a gold standard manual registration, and achieved a mean registration accuracy of 1.3 mm (SD 0.6 mm). Two registration strategies were tested using coarse (128 x 128 pixel) or fine (256 x 256 pixel) images. The mean registration errors proved similar but registration of the lower resolution images was 3 times quicker (mean registration times 33 s, SD 13 s for low and 150 s SD 48 s for high resolution images). The automated techniques were considerably faster than manual registrations but achieved similar accuracy. The technique has several potential uses but is particularly applicable to endovascular treatment techniques.

Algorithms↗
PubMed2003

Ensembl 2002: accommodating comparative genomics.

The Ensembl (http://www.ensembl.org/) database project provides a bioinformatics framework to organise biology around the sequences of large genomes. It is a comprehensive source of stable automatic annotation of human, mouse and other genome sequences, available as either an interactive web site or as flat files. Ensembl also integrates manually annotated gene structures from external sources where available. As well as being one of the leading sources of genome annotation, Ensembl is an open source software engineering project to develop a portable system able to handle very large genomes and associated requirements. These range from sequence analysis to data storage and visualisation and installations exist around the world in both companies and at academic sites. With both human and mouse genome sequences available and more vertebrate sequences to follow, many of the recent developments in Ensembl have focusing on developing automatic comparative genome analysis and visualisation.

Animals↗
PubMed2003

Epidemiology of hearing impairment at three Flemish Institutes for Deaf and Speech Defective Children.

A retrospective analysis of 190 records of hearing impaired children up to the age of 14, all educated at one of three Flemish Institutes for Deaf and Speech Defective Children in Belgium, was performed. Until 1999, the well-known behavioral test (Ewing test) was used in the Flemish national screening program for hearing losses. Because it presented a lot of disadvantages, it has been replaced by Automated Auditory Brainstem Responses (AABR), enabling the Flemish national neonatal screening program to commence. This study is an extension of the preliminary results of a recently performed retrospective analysis in one Flemish institute of the hearing loss of patients that were diagnosed in the pre-AABR era. The authors analyzed the following data: etiology, risk factors of congenital hearing impairment, the patient's history from the moment of the first suspicion to diagnosis and treatment. The median age of the children was 8.5 years (2-14 year). In 66.5% the parents and/or grandparents were the first to raise suspicion, this was at a median age of approximately 9 months. The diagnosis was often made late, at a median age of 15 months (0-88 months). The etiology was unknown in 32.6% of the cases. The only cast-iron certain diagnoses were pre- and perinatal infections, syndromal and genetic hearing loss, and acquired infections (meningitis and measles). No risk factors of hearing loss, as they are stated by the Joint Committee on Infant Hearing, were found in more than 50% of the cases. Audiometry was performed in all cases, often supplemented with Auditory Brainstem Responses and/or click-evoked otoacoustic emissions, while other diagnostic investigations (imaging, genetics, etc.) were only variably performed. Finally, the authors confirm the need for universal neonatal screening, which only recently started in Belgium, and suggest that a detailed protocol should be established to pursue a coherent diagnostic policy.

Adolescent↗
PubMed2002

Cloned bullfrog skin sodium (fENaC) and xENaC subunits hybridize to form functional sodium channels.

For many years the adult frog skin has been used as a model system to study transepithelial sodium transport. In other sodium transporting tissues the three homologous subunits of the sodium channel have been cloned. The aim of this study was to clone and characterize the amiloride inhibitable sodium channel (ENaC) in adult bullfrog (Rana catesbeiana) skin. Three transcripts corresponding to the alpha, beta, and gamma subunits of ENaC were cloned and sequenced. Co-expression of all three in Xenopus oocytes yielded a functional frog sodium channel (fENaC). Amiloride sensitivity and current voltage relationships suggested that its characteristics were similar to other ENaCs. Subunits from the Xenopus sodium channel (xENaC) and fENaC were combined in all possible triplets. Although functional amiloride inhibitable sodium channels were formed in every case, the amiloride sensitivities were not identical. Subunit combination studies suggested that the alpha subunit made a major contribution to amiloride sensitivity but interactions of beta and gamma were also seen. When the amiloride sensitivities of intact skin from adult R. catesbeiana and Xenopus laevis were compared, Rana also had a consistently higher affinity. Comparison of fENaC and xENaC sequences may provide insight into which amino acids beyond those already identified are critical for amiloride binding.

Amiloride↗
PubMed2002

The Ensembl genome database project.

The Ensembl (http://www.ensembl.org/) database project provides a bioinformatics framework to organise biology around the sequences of large genomes. It is a comprehensive source of stable automatic annotation of the human genome sequence, with confirmed gene predictions that have been integrated with external data sources, and is available as either an interactive web site or as flat files. It is also an open source software engineering project to develop a portable system able to handle very large genomes and associated requirements from sequence analysis to data storage and visualisation. The Ensembl site is one of the leading sources of human genome sequence annotation and provided much of the analysis for publication by the international human genome project of the draft genome. The Ensembl system is being installed around the world in both companies and academic sites on machines ranging from supercomputers to laptops.

Computational Biology↗
PubMed2001

The amount of scurfin protein determines peripheral T cell number and responsiveness.

In the absence of the recently identified putative transcription factor scurfin, mice develop a lymphoproliferative disorder resulting in death by 3 wk of age from a pathology that resembles TGF-beta or CTLA-4 knockout mice. In this report, we characterize mice that overexpress the scurfin protein and demonstrate that these animals have a dramatically depressed immune system. Mice transgenic for the Foxp3 gene (which encodes the scurfin protein) have fewer T cells than their littermate controls, and those T cells that remain have poor proliferative and cytolytic responses and make little IL-2 after stimulation through the TCR. Although thymic development appears normal in these mice, peripheral lymphoid organs, particularly lymph nodes, are relatively acellular. In a separate transgenic line, forced expression of the gene specifically in the thymus can alter thymic development; however, this does not appear to affect peripheral T cells and is unable to prevent disease in mice lacking a functional Foxp3 gene, indicating that the scurfin protein acts on peripheral T cells. The data indicate a critical role for the Foxp3 gene product in the function of the immune system, with both the number and functionality of peripheral T cells under the aegis of the scurfin protein.

Animals↗
PubMed2001

Aldosterone upregulates purinergic responses in larval amphibian skin epithelium.

Bullfrog tadpoles respond to apical application of 100 microM amiloride, acetylcholine (ACh) or ATP with a sharp transient inward (apical to basolateral) cation current. In adult skin, amiloride blockable transepithelial Na+ transport is upregulated by the hormone aldosterone. Tadpoles were treated in vivo with aldosterone and changes in short circuit current (Isc) in response to apical application of ATP were determined. Bullfrog tadpoles were exposed to aldosterone (10(-6) M) for periods ranging from 3 h to 60 h. Skins from 60-h aldosterone-treated animals showed a two- to three-fold increase in apical ATP-activated short circuit current when compared to animals treated with vehicle alone. Sodium replacement with a large, nonpermeable cation resulted in no measurable increase in Isc after exposure to ligand, consistent with ATP activation of an inward cation current and not chloride efflux. Activation/desensitization time courses and treatment with blockers revealed no measurable differences between aldosterone-treated and non-treated skins. Activation by amiloride and ACh gave essentially identical results. Studies with RT/PCR showed significant increases over controls of levels of mRNA associated with P2X channels. Given these data, our working hypothesis is that all three ligands activate the same process that exhibits both purinergic and cholinergic characteristics. These data are consistent with aldosterone upregulation of ATP gated channels expressed in the apical membrane of larval frog skin.

Acetylcholine↗
PubMed2001

Fluconazole for prophylaxis against candidal rectal colonization in the very low birth weight infant.

BACKGROUND: Candidal infections are an important cause of morbidity and mortality in the very low birth weight (VLBW) infant. Current intervention focuses on treatment once candidal septicemia is either suspected or diagnosed. Studies have suggested that colonization with candidal species is an important risk factor for subsequent infection. OBJECTIVE: To determine whether prophylactic fluconazole for the first 28 days of life results in a decreased incidence of candidal colonization in the VLBW infant. RESEARCH DESIGN: Prospective, randomized, controlled, intention-to-treat design comparing prophylaxis with fluconazole versus placebo for the first 28 days of life. SETTING: A tertiary level intensive care nursery in a major teaching hospital in Charleston, South Carolina. PATIENTS: One hundred three infants with a birth weight of <1500 g, either inborn or outborn, who were admitted to the intensive care nursery between January 1998 and February 1999. METHODS: Infants were enrolled within 72 hours of life with rectal cultures performed on the day of randomization (DOR), as well as day of life (DOL) 7, 14, and 28. Those infants with a birth weight of <1250 g had additional cultures on DOL 35, 49, and 56. Cultures were plated on selective media for isolation of candidal organisms. Infants were randomized to receive either fluconazole (6 mg/kg) or placebo on the DOR. Subsequent doses were given every 72 hours until DOL 7 and then every 24 hours until DOL 28. Medication was given either intravenously or by feeding tube once the infant had been gavage feeding for a 48-hour period without feeding intolerance. Aspartate aminotransferase and alanine aminotransferase levels were obtained on DOR and DOL 7, 14, and 28 to assess for fluconazole toxicity. The minimal inhibitory concentration to fluconazole was determined for all positive cultures to assess the development of resistance. RESULTS: The infants who received fluconazole (n = 53) and placebo (n = 50) had no statistical difference in the major risk factors known to increase the chances of candidal septicemia in the VLBW infant. Rectal colonization by candidal species was detected in 8 of the 53 fluconazole-treated patients (15.1%) and in 23 of the 50 infants treated with placebo (46%). Fluconazole significantly reduced rectal colonization from DOL 14 through DOL 56 in all infants with a birth weight of <1250 g, and from DOL 14 through DOL 56 in all infants with a birth weight of 1250 to 1500 g. Alanine aminotransferase levels were higher in the fluconazole versus the placebo-treated group on DOL 14 (18.1 IU/L vs 15 IU/L), but no clinically significant abnormalities were observed. Candida albicans was the most common species isolated. There was no increase in species of Candida noted for their intrinsic resistance to fluconazole, and there was no statistically significant difference in the minimal inhibitory concentrations to fluconazole for all C albicans isolates in either group at any period. CONCLUSION: Prophylactic administration of fluconazole to the VLBW infant for the first 28 days of life is safe and results in a decreased risk of rectal colonization by candidal species. Larger studies to determine the effect of prophylaxis on candidal septicemia and development of resistance in such a selective high-risk group are warranted before initiation of routine prophylaxis.fluconazole, very low birth weight infant, prophylaxis, candidal sepsis, sensitivities to fluconazole.

Antifungal Agents↗
PubMed2000

N-Acetylaspartate and creatine levels measured by (1)H MRS relate to recognition memory.

OBJECTIVES: To investigate the relationship between recognition memory and metabolite levels in medial structures of the temporal lobes in the living human brain. METHODS: Proton MRS ((1)H MRS) and the intracarotid amobarbital test were performed in 16 epileptic patients found suitable for temporal lobectomy. All patients had mesial temporal sclerosis. Metabolite ratios between N:-acetylaspartate (NAA), creatine and phosphocreatine (Cr + PCr), and choline-containing compounds (Cho) [NAA/(Cr + PCr), NAA/Cho, and NAA/(Cr + PCr + Cho)] were calculated for (1)H MRS voxels that included the amygdala, anterior half of the hippocampus, and underlying subiculum. Metabolite ratios were correlated with unilateral memory scores estimated by the intracarotid amobarbital test for words, objects, faces, and total score. RESULTS: The total memory score, memory for objects and faces, and NAA/(Cr + PCr) were significantly lower for the hemisphere ipsilateral to the resection. The asymmetry indexes for NAA/(Cr + PCr) correlated with asymmetry indexes for words (rho = 0.82, p = 0.0001) and total memory (rho = 0. 72, p = 0.002). Analysis of memory scores and metabolite ratios from all 32 hemispheres revealed a correlation between NAA/(Cr + PCr) and memory for words (rho = 0.45, p = 0.009). A correlation between memory for words and NAA/(Cr + PCr) existed in the contralateral (rho = 0.58, p = 0.019) and in the right (rho = 0.51, p = 0.045) hemispheres, and a trend was found in the left hemispheres (rho = 0. 48, p = 0.06). CONCLUSION: There is a correlation between memory for words and the NAA/(Cr + PCr) ratio from medial temporal structures in patients with mesial temporal sclerosis. The findings suggest that medial temporal structures and adjacent neocortex play a significant role in recognition memory in humans, particularly for words.

Adolescent↗