Biomedical subjects

Helen Jenkins

Publications and source records attributed to Helen Jenkins.

7 recordsLinked to original sources

PubMed2006

MeMo: a hybrid SQL/XML approach to metabolomic data management for functional genomics.

BACKGROUND: The genome sequencing projects have shown our limited knowledge regarding gene function, e.g. S. cerevisiae has 5-6,000 genes of which nearly 1,000 have an uncertain function. Their gross influence on the behaviour of the cell can be observed using large-scale metabolomic studies. The metabolomic data produced need to be structured and annotated in a machine-usable form to facilitate the exploration of the hidden links between the genes and their functions. DESCRIPTION: MeMo is a formal model for representing metabolomic data and the associated metadata. Two predominant platforms (SQL and XML) are used to encode the model. MeMo has been implemented as a relational database using a hybrid approach combining the advantages of the two technologies. It represents a practical solution for handling the sheer volume and complexity of the metabolomic data effectively and efficiently. The MeMo model and the associated software are available at http://dbkgroup.org/memo/. CONCLUSION: The maturity of relational database technology is used to support efficient data processing. The scalability and self-descriptiveness of XML are used to simplify the relational schema and facilitate the extensibility of the model necessitated by the creation of new experimental techniques. Special consideration is given to data integration issues as part of the systems biology agenda. MeMo has been physically integrated and cross-linked to related metabolomic and genomic databases. Semantic integration with other relevant databases has been supported through ontological annotation. Compatibility with other data formats is supported by automatic conversion.

Computer Simulation↗

PubMed2005

Positive and negative effects of widespread badger culling on tuberculosis in cattle.

Human and livestock diseases can be difficult to control where infection persists in wildlife populations. For three decades, European badgers (Meles meles) have been culled by the British government in a series of attempts to limit the spread of Mycobacterium bovis, the causative agent of bovine tuberculosis (TB), to cattle. Despite these efforts, the incidence of TB in cattle has risen consistently, re-emerging as a primary concern for Britain's cattle industry. Recently, badger culling has attracted controversy because experimental studies have reached contrasting conclusions (albeit using different protocols), with culled areas showing either markedly reduced or increased incidence of TB in cattle. This has confused attempts to develop a science-based management policy. Here we use data from a large-scale, randomized field experiment to help resolve these apparent differences. We show that, as carried out in this experiment, culling reduces cattle TB incidence in the areas that are culled, but increases incidence in adjoining areas. These findings are biologically consistent with previous studies but will present challenges for policy development.

Animals↗

PubMed2005

Efficient deletion of normal Brca2-deficient intestinal epithelium by poly(ADP-ribose) polymerase inhibition models potential prophylactic therapy.

The genes encoding the BRCA1 and BRCA2 tumor suppressors are the most commonly mutated in human familial breast cancers. Both have separate roles in the maintenance of genomic stability through involvement in homologous recombination, an error-free process enabling cells to repair DNA double-strand breaks. We have previously shown that cre-mediated conditional deletion of Brca2 within the mouse small intestine sensitizes the tissue to DNA damage. Eventually, the tissue repopulates via stem cells in which recombination at the floxed Brca2 allele has not taken place. In this study, we have treated Brca2-deficient small intestine with a potent small-molecule inhibitor of poly(ADP-ribose) polymerase 1 (PARP1), an enzyme predominantly involved in the recognition of DNA single-strand breaks. Brca2 deficiency rendered otherwise normal cells exquisitely sensitive to PARP inhibition, resulting in very high levels of apoptosis as early as 6 hours after treatment, with evidence for repopulation of the tissue at 12 hours. Furthermore, the intestines of animals treated with serial injections of the inhibitor repopulated very rapidly in comparison with those from untreated mice. Our results represent the first in vivo demonstration that inhibition of PARP1 activity confers exquisite sensitivity to death in physiologically normal Brca2-deficient cells, suggesting that such a regimen may be extremely potent prophylactically in women heterozygous for the BRCA2 gene, as well as against established tumors lacking functional BRCA2.

Animals↗

PubMed2005

Toward supportive data collection tools for plant metabolomics.

Over recent years, a number of initiatives have proposed standard reporting guidelines for functional genomics experiments. Associated with these are data models that may be used as the basis of the design of software tools that store and transmit experiment data in standard formats. Central to the success of such data handling tools is their usability. Successful data handling tools are expected to yield benefits in time saving and in quality assurance. Here, we describe the collection of datasets that conform to the recently proposed data model for plant metabolomics known as ArMet (architecture for metabolomics) and illustrate a number of approaches to robust data collection that have been developed in collaboration between software engineers and biologists. These examples also serve to validate ArMet from the data collection perspective by demonstrating that a range of software tools, supporting data recording and data upload to central databases, can be built using the data model as the basis of their design.

Arabidopsis↗

PubMed2004

SGS742: the first GABA(B) receptor antagonist in clinical trials.

The GABA(B) receptor antagonist SGS742 (CGP36742) displays pronounced cognition enhancing effects in mice, young and old rats and in Rhesus monkeys in active and passive avoidance paradigms, in an eight-arm radial maze and a Morris water maze and in a social learning task. SGS742 blocks the late inhibitory postsynaptic potential and the paired-pulse inhibition of population spikes recorded from CA1 pyramidal neurons of the hippocampus of rats in vitro and in vivo. SGS742 significantly enhances the release of glutamate, aspartate, glycine and somatostatin in vivo. Chronic administration of SGS742 causes an up-regulation of GABA(B) receptors in the frontal cortex of rats. Single doses cause a significant enhancement of the mRNA and protein levels of NGF and BDNF in the cortex and hippocampus of rats. The observed antidepressant effects of SGS742 in rats may be explained by these findings. SGS742 was well tolerated in experimental animals as well as in young and elderly human volunteers with an absolute bioavailability in humans of 44%. In a Phase II double-blind, placebo-controlled study in 110 patients with mild cognitive impairment (MCI), oral administration of SGS742 at a dose of 600 mg t.i.d. for 8 weeks significantly improved attention, in particular choice reaction time and visual information processing as well as working memory measured as pattern recognition speed. A second Phase II clinical trial in 280 Alzheimer's disease patients is underway.

Adult↗

PubMed2004

A proposed framework for the description of plant metabolomics experiments and their results.

The study of the metabolite complement of biological samples, known as metabolomics, is creating large amounts of data, and support for handling these data sets is required to facilitate meaningful analyses that will answer biological questions. We present a data model for plant metabolomics known as ArMet (architecture for metabolomics). It encompasses the entire experimental time line from experiment definition and description of biological source material, through sample growth and preparation to the results of chemical analysis. Such formal data descriptions, which specify the full experimental context, enable principled comparison of data sets, allow proper interpretation of experimental results, permit the repetition of experiments and provide a basis for the design of systems for data storage and transmission. The current design and example implementations are freely available (http://www.armet.org/). We seek to advance discussion and community adoption of a standard for metabolomics, which would promote principled collection, storage and transmission of experiment data.

Database Management Systems↗

PubMed2003

Synthesis of the reported structure of pogostol and a total aynthesis of (+/-)-kessane without the use of protecting groups.

[reaction: see text] A short racemic synthesis of kessane from 4-hydroxy-4-methyl-2-cyclohexenone is described using a route that also resulted in the synthesis of the reported structure of pogostol. The key step involves an Fe(III)-mediated tandem radical ring-expansion/cyclization of the cyclopropylsilyl ether 9. No protecting groups are used in the entire sequence. Comparison of the NMR data of synthetic pogostol to that in the literature indicates that the structure originally proposed is incorrect.

Journal Article↗