PubMed Health⌕ Search

Biomedical subjects

J S Edwards

Publications and source records attributed to J S Edwards.

At least 19 recordsLinked to original sources
PubMed2003

Suitability and utility of computational analysis tools: characterization of erythrocyte parameter variation.

Systems engineering can provide insights into multivariate regulatory networks and pooling in complex biological networks that cannot be fully interpreted through experiments alone. Herein, we analyzed the use of phase planes, modal and time-lagged correlation (TLC) analyses of the human erythrocyte to explore the utility of these techniques for understanding the effect of single parameter changes on the behavior of a metabolic network. Specifically, several parameters in key regulatory steps in erythrocyte glycolysis, Rapoport-Leubering bypass, pentose phosphate pathway, adenosine metabolism, and membrane transport were perturbed. The most sensitive parameters were identified based on the steady-state metabolite concentration changes and were explored further. Modal analysis identified relevant time scales for each parameter change. These time scales were further explored using phase plane and TLC analyses. Phase plane and TLC both inferred pooling changes, while TLC also identified changes in the regulatory network structure that resulted from various parameter changes. Each method has strengths and weaknesses for exploring and gaining insight into complex biological networks.

Adenosine↗
PubMed2003

Quantitative analysis of Escherichia coli metabolic phenotypes within the context of phenotypic phase planes.

In silico models of Escherichia coli metabolism have been developed to predict metabolic behavior and propose experimentally testable hypotheses. However, a thorough assessment of the metabolic phenotype requires well-designed experimentation and reproducible experimental techniques. A method for the quantitative analysis of E. coli metabolism in vivo within the framework of in silico phenotypic phase plane analysis is presented. Using this approach, we have quantitatively studied E. coli metabolism in various environmental conditions and nutritional media. Our experimental methodology, in combination with steady-state metabolic models, can be used to study biological properties and evaluate the metabolic capabilities of microbes.

Aerobiosis↗
PubMed2001

Metabolic modeling of microbial strains in silico.

The large volume of genome-scale data that is being produced and made available in databases on the World Wide Web is demanding the development of integrated mathematical models of cellular processes. The analysis of reconstructed metabolic networks as systems leads to the development of an in silico or computer representation of collections of cellular metabolic constituents, their interactions and their integrated function as a whole. The use of quantitative analysis methods to generate testable hypotheses and drive experimentation at a whole-genome level signals the advent of a systemic modeling approach to cellular and molecular biology.

Genome↗
PubMed2001

In silico predictions of Escherichia coli metabolic capabilities are consistent with experimental data.

A significant goal in the post-genome era is to relate the annotated genome sequence to the physiological functions of a cell. Working from the annotated genome sequence, as well as biochemical and physiological information, it is possible to reconstruct complete metabolic networks. Furthermore, computational methods have been developed to interpret and predict the optimal performance of a metabolic network under a range of growth conditions. We have tested the hypothesis that Escherichia coli uses its metabolism to grow at a maximal rate using the E. coli MG1655 metabolic reconstruction. Based on this hypothesis, we formulated experiments that describe the quantitative relationship between a primary carbon source (acetate or succinate) uptake rate, oxygen uptake rate, and maximal cellular growth rate. We found that the experimental data were consistent with the stated hypothesis, namely that the E. coli metabolic network is optimized to maximize growth under the experimental conditions considered. This study thus demonstrates how the combination of in silico and experimental biology can be used to obtain a quantitative genotype-phenotype relationship for metabolism in bacterial cells.

Acetates↗
PubMed2001

Dynamic simulation of the human red blood cell metabolic network.

We have developed a Mathematica application package to perform dynamic simulations of the red blood cell (RBC) metabolic network. The package relies on, and integrates, many years of mathematical modeling and biochemical work on red blood cell metabolism. The extensive data regarding the red blood cell metabolic network and the previous kinetic analysis of all the individual components makes the human RBC an ideal 'model' system for mathematical metabolic models. The Mathematica package can be used to understand the dynamics and regulatory characteristics of the red blood cell.

Computer Simulation↗
PubMed2001

Flux-balance analysis of mitochondrial energy metabolism: consequences of systemic stoichiometric constraints.

Mitochondrial metabolism is a critical component in the functioning and maintenance of cellular organs. The stoichiometry of biochemical reaction networks imposes constraints on mitochondrial function. A modeling framework, flux-balance analysis (FBA), was used to characterize the optimal flux distributions for maximal ATP production in the mitochondrion. The model predicted the expected ATP yields for glucose, lactate, and palmitate. Genetic defects that affect mitochondrial functions have been implicated in several human diseases. FBA can characterize the metabolic behavior due to genetic deletions at the metabolic level, and the effect of mutations in the tricarboxylic acid (TCA) cycle on mitochondrial ATP production was simulated. The mitochondrial ATP production is severely affected by TCA-cycle mutations. In addition, the model predicts the secretion of TCA-cycle intermediates, which is observed in clinical studies of mitochondriopathies such as those associated with fumarase deficiency. The model provides a systemic perspective to characterize the effect of stoichiometric constraints and specific metabolic fluxes on mitochondrial function.

Adenosine Triphosphate↗
PubMed2001

A preliminary assessment of two hospital food service systems using parameters of food safety and consumer opinion.

The goal of any hospital caterer should be to provide food that meets nutritional requirements, satisfies the patient, improves morale and is microbiologically safe. Food distribution to hospital wards plays a critical role. The aim of this study was to compare two hospital food service systems using parameters of food safety and consumer opinion. An NHS hospital was selected where food delivery was due to change from a plated system to a cafeteria trolley system. Samples (50 g) of dishes (n = 27) considered to be high-risk were collected for three consecutive days from breakfast, lunch and supper meals. The samples were taken from a pre-ordered tray (similar to that of a patient) in the plated system and from the trolley on the ward in the cafeteria system of meal delivery (approximately six months after its introduction). Consumer opinions cards (n = 180) were distributed and interviews also conducted. Microbiologically, the quality of food items delivered by both systems was satisfactory. However, concern was raised with the plated system, not for hot foods cooling down but for chilled foods warming up and being sustained in ambient conditions. Overall consumer satisfaction and experience was enhanced with the trolley system. Food was hotter and generally perceived to be of a better quality. Satisfaction with cold desserts was not dependent on the delivery system.

Anecdotes as Topic↗
PubMed2001

The complete phosphotransferase system in Escherichia coli.

We here tabulate and describe all currently recognized proteins of the phosphoenolpyruvate:sugar phosphotransferase system (PTS) and their homologues encoded within the genomes of sequenced E. coli strains. There are five recognized Enzyme I homologues and six recognized HPr homologues. A nitrogen-metabolic PTS phosphoryl transfer chain encoded within the rpoN and ptsP operons and a tri-domain regulatory PTS protein encoded within the dha (dihydroxyacetone catabolic) operon, probably serve regulatory roles exclusively. In addition to several additional putative regulatory proteins, there are 21 (and possibly 22) recognized Enzyme II complexes. Of the 21 Enzyme II complexes, 7 belong to the fructose (Fru) family, 7 belong to the glucose (Glc) family, and 7 belong to the other PTS permease families. All of these proteins are briefly described, and phylogenetic data for the major families are presented.

Escherichia coli↗
PubMed2000

Metabolic flux balance analysis and the in silico analysis of Escherichia coli K-12 gene deletions.

BACKGROUND: Genome sequencing and bioinformatics are producing detailed lists of the molecular components contained in many prokaryotic organisms. From this 'parts catalogue' of a microbial cell, in silico representations of integrated metabolic functions can be constructed and analyzed using flux balance analysis (FBA). FBA is particularly well-suited to study metabolic networks based on genomic, biochemical, and strain specific information. RESULTS: Herein, we have utilized FBA to interpret and analyze the metabolic capabilities of Escherichia coli. We have computationally mapped the metabolic capabilities of E. coli using FBA and examined the optimal utilization of the E. coli metabolic pathways as a function of environmental variables. We have used an in silico analysis to identify seven gene products of central metabolism (glycolysis, pentose phosphate pathway, TCA cycle, electron transport system) essential for aerobic growth of E. coli on glucose minimal media, and 15 gene products essential for anaerobic growth on glucose minimal media. The in silico tpi-, zwf, and pta- mutant strains were examined in more detail by mapping the capabilities of these in silico isogenic strains. CONCLUSIONS: We found that computational models of E. coli metabolism based on physicochemical constraints can be used to interpret mutant behavior. These in silica results lead to a further understanding of the complex genotype-phenotype relation.

Computational Biology↗
PubMed2000

The Escherichia coli MG1655 in silico metabolic genotype: its definition, characteristics, and capabilities.

The Escherichia coli MG1655 genome has been completely sequenced. The annotated sequence, biochemical information, and other information were used to reconstruct the E. coli metabolic map. The stoichiometric coefficients for each metabolic enzyme in the E. coli metabolic map were assembled to construct a genome-specific stoichiometric matrix. The E. coli stoichiometric matrix was used to define the system's characteristics and the capabilities of E. coli metabolism. The effects of gene deletions in the central metabolic pathways on the ability of the in silico metabolic network to support growth were assessed, and the in silico predictions were compared with experimental observations. It was shown that based on stoichiometric and capacity constraints the in silico analysis was able to qualitatively predict the growth potential of mutant strains in 86% of the cases examined. Herein, it is demonstrated that the synthesis of in silico metabolic genotypes based on genomic, biochemical, and strain-specific information is possible, and that systems analysis methods are available to analyze and interpret the metabolic phenotype.

Bacterial Proteins↗
PubMed1999

Systems properties of the Haemophilus influenzae Rd metabolic genotype.

Haemophilus influenzae Rd was the first free-living organism for which the complete genomic sequence was established. The annotated sequence and known biochemical information was used to define the H. influenzae Rd metabolic genotype. This genotype contains 488 metabolic reactions operating on 343 metabolites. The stoichiometric matrix was used to determine the systems characteristics of the metabolic genotype and to assess the metabolic capabilities of H. influenzae. The need to balance cofactor and biosynthetic precursor production during growth on mixed substrates led to the definition of six different optimal metabolic phenotypes arising from the same metabolic genotype, each with different constraining features. The effects of variations in the metabolic genotype were also studied, and it was shown that the H. influenzae Rd metabolic genotype contains redundant functions under defined conditions. We thus show that the synthesis of in silico metabolic genotypes from annotated genome sequences is possible and that systems analysis methods are available that can be used to analyze and interpret phenotypic behavior of such genotypes.

Cell Division↗
PubMed1998

Fridtjof Nansen: from the neuron to the North Polar Sea.

Fridtjof Nansen (1861-1930), the Norwegian explorer, oceanographer, statesman, Nobel Peace Prizewinner is best known for his arctic travels. He began his professional career as an invertebrate zoologist at the Bergen Museum in Norway but soon developed an interest in the histological structure of the nervous system. Along with His, Koelliker, Lenhossek and Forel he was a pioneer advocate of what came later to be known as the Neuron Doctrine, but his role is now generally relegated to the footnotes of the history of neuroscience. Comparison with the independent, parallel papers of His and Forel gives Nansen technical priority. The reasons for his relative obscurity as a pioneer neuroscientist are many, but foremost among them must be the persistent failure of Ramón y Cajal to acknowledge Nansen's pioneering insights.

Animals↗
PubMed1998

Sir Vincent Wigglesworth and the coming of age of insect development.

Sir Vincent Wigglesworth (1899-1994), a founder of the discipline of Insect Physiology, was a central figure in the emergence of the concept of postembryonic insect development as sequential polymorphism regulated by endocrine signals. At a time in mid-century when genetics and developmental physiology were severely compartmentalized, he made the conceptual linkage with the recognition that sequential polymorphism must have a genetic basis with gene activation regulated by internal signals.

Animals↗
PubMed1997

The evolution of insect flight: implications for the evolution of the nervous system.

The Insecta encompasses a prodigiously diverse group as measured at the species, family and ordinal levels, but the nervous system bears evidence of conservatism. The early acquisition of flight must have been a major factor in the diversification of body form. Arguments are presented that predator evasion was a primary factor in the origin of flight and that a conserved set of giant interneurons played a key element in the transition.

Animals↗
PubMed1996

Neurogenesis in adult insect mushroom bodies.

The occurrence of neurogenesis in mushroom bodies of adult insects belonging to several orthopteroid and coleopteran families is described. Using injections of 5-bromo, T2'-deoxyuridine, we showed that neuroblasts, which are progenitors of Kenyon cells during preimaginal instars, continue to divide in adult Acheta domesticus. Their progeny constitute a central column in mushroom body cortices of 3-week-old females. Other Gryllidae, Gryllus bimaculatus and Gryllomorpha dalmatina, show the same pattern of neuroblast activity and migration of their progeny. Immunocytochemical staining of glial cells failed to reveal any immunoreactivity, either in proliferating regions or in the resulting cells. In another orthopteran, Locusta migratoria, discrete clusters of cells, located dorsolateral to the Kenyon cells, incorporated 5-bromo, 2'-deoxyuridine, but we could not detect any neuronal progeny migrating to the mushroom body cortices. These cells were strongly labeled with an antiglial antibody, indicating that the replicating cells are glioblasts rather than neuroblasts. In Periplaneta americana (Dictyoptera), cells replicating their DNA were similarly shown to immunoreact with glial antibodies. In contrast, three coleopterans (Tenebrio molitor, Zophobas species, Harmonia axyridis) have two large neuroblasts located in the middle of the mushroom body cortices. These produce cells which migrate within the group of Kenyon cells, their nuclei having the same shape and size as those of surrounding Kenyon cells. In adult insects, neurogenesis in mushroom bodies occurs in Gryllidae and several coleopteran families, but could not be demonstrated in Dictyoptera and Acrididae. Its occurrence and distribution raise the issue of unexpected plasticity in the adult insect brain.

Animals↗
PubMed1996

Comparison of once daily and twice daily nisoldipine as monotherapy in essential hypertension.

Twenty-four patients completed a dose ranging study of the effect of nisoldipine as monotherapy in the treatment of hypertension. This randomized double-blind study consisted of two crossover phases in each of which once and twice daily treatment were compared. In the first treatment phase the total daily dose of nisoldipine was 10 mg, which increased to 20 mg during the second phase. Trough blood pressure measurements were made 12/24 h postdose. During the first phase the blood pressure values following treatment with nisoldipine 5 mg twice daily were significantly lower than with 10 mg once daily. However, when the daily dose was increased to 20 mg there was no significant difference between the two treatment regimens. There was also no significant difference between nisoldipine 5 mg twice daily and 10 mg twice daily but the results for 20 mg once daily were significantly lower than for 10 mg once daily. Four patients withdrew from the study because of adverse events, one while on placebo and three while on nisoldipine therapy. Between 33 percent and 47 percent of patients reported adverse events during nisoldipine treatment but the majority of adverse events reported were mild and did not require treatment withdrawal. Nisoldipine twice daily appeared to be more effective and better tolerated than once daily treatment for 24-h blood pressure control.

Adult↗