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At least 55 records · Page 3Linked to original sources
PubMed1984

Isoelectrophoretic separation and the detection of soluble proteins containing acid-labile phosphate: use of the phosphoenolpyruvate:sugar phosphotransferase system as a model system for N1-P-histidine- and N3-P-histidine-containing proteins.

Procedures have been developed for the detection of acid-labile phosphorylations of proteins. The phosphoproteins were separated by native isoelectric focusing while maintaining the gel at about 0 degree C, and denaturing urea-Nonidet isoelectric focusing gels were adapted to run at -10 degrees C. The proteins of the bacterial phosphoenolpyruvate:sugar phosphotransferase system (PTS), HPr, which contains 1-P-histidine, and factor IIIglc and enzyme I, which contain 3-P-histidine when they are phosphorylated, were used to develop the conditions. Autoradiography of [32P]-labeled phosphoproteins was carried out on frozen gels which had not been acid fixed in order to avoid hydrolysis of the phosphohistidines . The frozen gels were subsequently fixed and stained, and reautoradiography revealed whether the phosphoproteins were acid stable or labile. In addition to the known proteins of the PTS, at least one other protein whose phosphorylation was dependent on enzyme I and HPr was found in Salmonella typhimurium and Escherichia coli [E.B. Waygood , and R.L. Mattoo (1983) Canad . J. Biochem. Cell Biol. 61, 150-153]. Initial experiments with rat tissues have demonstrated acid-labile phosphorylations in proteins which were either [gamma-32P]ATP or [32P]phosphoenolpyruvate dependent. The interconversion of phosphoenolpyruvate and ATP in crude extracts of bacterial cells was examined, and appropriate controls were found. Protein phosphorylation dependent upon phosphoenolpyruvate was much greater in S. typhimurium and E. coli than the corresponding ATP-dependent phosphorylation, while the opposite was found for rat tissues.

Adenosine Triphosphate↗
PubMed1987

Teratological research using in vitro systems. V. Nonmammalian model systems.

In this review of alternative tests to whole-animal rodent studies, the use of sub-mammalian and sub-vertebrate systems is investigated. The history, methodology, known limitations, end points, dose response, and requirements of virus, hydra, planarian, cricket, fish, amphibia, Drosophila, and chicken embryo systems are discussed.

Amphibians↗
PubMedDate not supplied

[Instability and excitation propagation in a catalytic reaction model. II. Distributed system model].

The regime of excitation propagation in monomeric model of active medium is considered. Conditions exist when the phase plane falls into two regions in both of which the equations are linear and their automodel solutions are found analytically. After connecting the solutions a transcendental algebraic equation is obtained, from which the values of excitation propagation rate can be found. The trigger wave has one rate value the propagating impulse--two (physically realised--one). There is a parameter region with four rates (three physically realised ones).

Catalysis↗
PubMed2000

Analyzing sensitivity to model form assumptions of infection transmission system models.

PURPOSE: Transmission system models make restrictive assumptions that might distort the conclusions of model analyses. We propose methods to progressively relax the following assumptions of classical deterministic compartmental models: 1) that the population has an effectively infinite size 2) that contact is instantaneous with no duration, 3) that mixing in this large population is instantaneously thorough after contact.METHODS: Analyses of contact patterns between high and low risk groups on gonorrhea transmission were performed. Initial models were similar to those analyzed by Hethcote and Yorke with compartments corresponding to sets of individuals. The instantaneous contact assumption in these models was relaxed by using continuous deterministic pairing models in the style of models presented by Dietz and Hadelar. That model makes restrictive assumptions about concurrent contacts, population sizes, and instantaneously random mixing. To relax these assumptions, we simulated our GERMS model of discrete individuals forming pairings and transmitting infection in continuous time.RESULTS: Relaxing the instantaneous contact assumption demonstrated a progressively decreased effect of mixing between high and low risk groups as the duration of contact was increased. The GERMS model simulations were shown to effectively reproduce pairing model behavior given the same restrictive assumptions as the pairing model. Further GERMS model analysis then demonstrated that concurrency assumptions alter the effects of contact rates between risk groups in ways that are dependent upon contact parameters. Finally GERMS models were used to structure mixing into four local areas. This affected the dynamics of reaching equilibrium but not the equilibrium value.CONCLUSIONS: Assessing the effects of assumptions in continuous compartmental models of transmission systems is feasible and important.

Journal Article↗
PubMed2006

Engineering transport protein function: theoretical and technical considerations using the sugar-transporting phosphotransferase system of Escherichia coli as a model system.

Potential experimental approaches for developing and applying protein-engineering protocols to transmembrane transport systems are described. We specifically consider procedures designed to alter protein function. These procedures are designed for the specific purposes of (1) changing protein interaction specificities and (2) changing a protein's catalytic function. We use sugar-transporting bacterial phosphotransferase systems as model systems to illustrate the proposed approaches. These and other similar procedures are likely to prove to be of utility for biotechnological manipulation of proteins as well as for elucidating potential evolutionary pathways taken for the appearance of novel functions within a protein family.

Bacterial Proteins↗
PubMed2006

Resources for integrative systems biology: from data through databases to networks and dynamic system models.

In systems biology, biologically relevant quantitative modelling of physiological processes requires the integration of experimental data from diverse sources. Recent developments in high-throughput methodologies enable the analysis of the transcriptome, proteome, interactome, metabolome and phenome on a previously unprecedented scale, thus contributing to the deluge of experimental data held in numerous public databases. In this review, we describe some of the databases and simulation tools that are relevant to systems biology and discuss a number of key issues affecting data integration and the challenges these pose to systems-level research.

Animals↗
PubMed2000

Mouse prostate reconstitution model system: A series of in vivo and in vitro models for benign and malignant prostatic disease.

BACKGROUND: An elucidation of the complex, morphological and molecular changes that underlie benign and malignant prostatic disease will likely lead to improved methods of diagnosis and therapy for those disorders. To identify and understand the interrelation of the phenotypic and genetic changes inherent in these important diseases requires the development and use of in vivo and in vitro models that closely mimic specific aspects of the disease process. Once the suspected molecular underpinnings of prostatic disease are uncovered, in vivo and in vitro models will be required for further testing of the functional significance of specific genetic alterations as they are identified. In addition models of prostatic disease are necessary to evaluate novel therapeutic approaches. METHODS: The mouse prostate reconstitution (MPR) model system was developed more than a decade ago with these specific needs in mind. Over the years, specific modifications of the MPR model have demonstrated its versatility and applicability for the study of benign and malignant prostatic disease, including metastatic progression. RESULTS: We discuss various modifications of the MPR model system made for its application to specific aspects of prostatic disease; the clinically relevant information that has been gleaned thus far from the use of this model system; and advances on the horizon for the expansion of its role in prostate research. CONCLUSIONS: The MPR model system has contributed substantially to the understanding and treatment of benign and malignant prostatic diseases. Additional modifications in this series of in vivo and in vitro models will likely lead to further advances.

Animals↗
PubMed1992

A systems model of clinical preventive care: an analysis of factors influencing patient and physician.

An ideal model for clinical preventive care must consider the physician, the patient and the many factors which influence each of them. In this paper, we review existing models, examining their strengths and weaknesses. We then propose a new model, the Systems Model of Clinical Preventive Care. This model is unique in its focus on the patient-physician interaction and details the factors impinging on each that promote or inhibit the completion of preventive care activities. These factors include patient and physician predisposing factors, such as health beliefs and attitudes; enabling factors, such as skills and resources; and reinforcing factors, such as social support. Additional factors include health care system organizational factors, such as access or availability; characteristics of the preventive activity, such as cost; and cues to action, such as symptoms or reminders. The proposed model contains components of behavioral, communication, health education and psychosocial theories. We then apply our model to mammography as an example of a screening activity. Finally, we describe the strengths and weaknesses of the proposed model, and identify areas for future research.

Delivery of Health Care↗
PubMed2004

Characterizing complex peptide mixtures using a multi-dimensional liquid chromatography-mass spectrometry system: Saccharomyces cerevisiae as a model system.

A rugged, reproducible, multi-dimensional LC-MS system was developed to identify and characterize proteins involved in protein-protein interactions and/or protein complexes. Our objective was to optimize chromatographic parameters for complex protein mixture analyses using automated peptide sequence recognition as an analytical end-point. The chromatographic system uses orthogonal separation mechanisms by employing strong cation exchange (SCX) in the first dimension and reversed phase (RP) in the second dimension. The system is fully automated and sufficiently robust to handle direct injections of protein digests. This system incorporates a streamlined post analysis results comparison, called DBParser, which permitted comprehensive evaluation of sample loading and chromatographic conditions to optimize the performance and reproducibility. Peptides obtained from trypsin digestion of a yeast soluble extract provided an open-ended model system containing a wide variety and dynamic range of components. Conditions are described that resulted in an average (n = 4) of 1489 unique peptide identifications, corresponding to 459 non-redundant protein sequence database records (SDRs) in the 20 microg soluble fraction digest.

Chromatography, Liquid↗
PubMed1992

Comparison of the accuracy and reproducibility of the keratometer and the EyeSys Corneal Analysis System Model I.

The EyeSys Corneal Analysis System Model I measures corneal topography using digital image analysis of placido rings reflected off the cornea. With three observers, we compared the accuracy and reproducibility (precision) of the Marco Keratometer Model 1 and EyeSys Corneal Analysis System Model I using four poly(methyl methacrylate) spheres (37.50, 42.51, 47.54, and 55.06 diopters [D]), three steel spheres (40.50, 42.50, and 44.75 D), and 20 normal human eyes (41.50 to 46.00 D). For the spheres, the standard deviations of intra-observer and overall reproducibility for both devices were less than 0.12 D; the absolute mean differences between the measurements of the seven spheres and the known values were 0.25 D or more for two spheres as measured by the keratometer and none as measured by the EyeSys. For the normal corneas, the standard deviations of intra-observer and overall reproducibility for dioptric measurements were 0.07 D and 0.14 D for the keratometer and 0.13 D and 0.19 D for the EyeSys. The EyeSys Corneal Analysis System Model I exceeds keratometer accuracy in reading calibrated spheres and approaches keratometer reproducibility in measuring the 3-mm zone of normal human corneas.

Cornea↗
PubMed1991

A study of deoxyribonucleotide metabolism and its relation to DNA synthesis. Supercomputer simulation and model-system analysis.

A model system (1) was established to analyze purine and pyrimidine metabolism. This system has been expanded to include macrosimulation of DNA synthesis and the study of its regulation by terminal deoxynucleoside triphosphates (dNTPs) via a complex set of interactions. Computer experiments reveal that our model exhibits adequate and reasonable sensitivity in terms of dNTP pool levels and rates of DNA synthesis when inputs to the system are varied. These simulation experiments reveal that in order to achieve maximum DNA synthesis (in terms of purine metabolism), a proper balance is required in guanine and adenine input into this metabolic system. Excessive inputs will become inhibitory to DNA synthesis. In addition, studies are carried out on rates of DNA synthesis when various parameters are changed quantitatively. The current system is formulated by 110 differential equations.

Animals↗
PubMed1984

Mutagen formation in browning model systems.

A browning model system, consisting of diacetyl and ammonia, produced frameshift and base-pair substitution mutagens when the system was heated over 20 min and 120 min, respectively. The major product was 2,4,5- trimethylimidazole , which showed no mutagenicity toward Salmonella typhimurium strains TA98 and TA100 with or without metabolic activation. When furfural was reacted with nitrate under mild conditions (for 30 min to 3 h at 0-25 degrees C and pH 2-7), it did not produce mutagenic nitrofuran derivatives. However, the ethyl ether extract obtained from the reaction mixture of furfural and nitrate with hydrochloric acid exhibited strong mutagenic activities toward S. typhimurium strains TA98 and TA100 in the presence of metabolic activation. The major product of this reaction mixture, 4- nitrofurfural , exhibited no mutagenicity toward tester strains TA98 and TA100 with or without metabolic activation. Pure active mutagen(s) was (were) not, however, identified in either system.

Ammonia↗
PubMed2003

Progressive neurodegeneration in Drosophila: a model system.

The Drosophila model system has been used to study neurodegenerative diseases by expression of human disease genes in transgenic flies. A different approach is to isolate and characterize Drosophila mutants with progressive neurodegeneration to find novel genes required for brain integrity. Mammalian homologues of these genes might be the genetic basis for some of the various progressive neurodegeneration diseases in humans. Here we describe several such mutants. Some of them reveal degeneration in specific parts of the brain while others affect all brain regions. Cell death can occur through apoptosis or necrosis. In one case, mutant flies show abnormal behavior prior to obvious degeneration while most other mutants reveal such defects only in later stages. These mutants offer a new approach to study basic mechanisms of neurodegeneration and for developing fly models for human diseases.

Animals↗
PubMed2006

Coupling of a 3D finite element model of cardiac ventricular mechanics to lumped systems models of the systemic and pulmonic circulation.

In this study we present a novel, robust method to couple finite element (FE) models of cardiac mechanics to systems models of the circulation (CIRC), independent of cardiac phase. For each time step through a cardiac cycle, left and right ventricular pressures were calculated using ventricular compliances from the FE and CIRC models. These pressures served as boundary conditions in the FE and CIRC models. In succeeding steps, pressures were updated to minimize cavity volume error (FE minus CIRC volume) using Newton iterations. Coupling was achieved when a predefined criterion for the volume error was satisfied. Initial conditions for the multi-scale model were obtained by replacing the FE model with a varying elastance model, which takes into account direct ventricular interactions. Applying the coupling, a novel multi-scale model of the canine cardiovascular system was developed. Global hemodynamics and regional mechanics were calculated for multiple beats in two separate simulations with a left ventricular ischemic region and pulmonary artery constriction, respectively. After the interventions, global hemodynamics changed due to direct and indirect ventricular interactions, in agreement with previously published experimental results. The coupling method allows for simulations of multiple cardiac cycles for normal and pathophysiology, encompassing levels from cell to system.

Animals↗
PubMed1985

Towards understanding paternal extragenic contributions to early amphibian pattern specification: the axolotl ts-1 gene as a model system.

As a model system for understanding the role sperm extragenic components might play in early embryogenesis the genetics and phenotype of the ts-1 axolotl (Ambystoma mexicanum) mutant gene are reviewed. That mutant gene displays parental effects. It exhibits both maternal (egg-mediated) as well as paternal (sperm-mediated) phenotypic effects. A variety of possible modes of action of the ts-1 gene are reviewed. Comparisons of various precedents to the ts-1 genetic data are made. In addition, novel models which account for the ts-1 phenotypic data are presented.

Ambystoma↗
PubMed1993

Protein traffic in polarized epithelial cells: the polymeric immunoglobulin receptor as a model system.

As a model system to study protein traffic in polarized epithelial cells, we have used the polymeric immunoglobulin receptor. This receptor travels first to the basolateral surface, where it can bind polymeric IgA or IgM. The receptor is then endocytosed and delivered to endosomes. The receptor is sorted into transcytotic vesicles, which are exocytosed at the apical surface. The 103-amino acid cytoplasmic domain of the receptor contains several sorting signals. The 17 residues closest to the membrane are an autonomous signal that is necessary and sufficient for basolateral sorting. For rapid endocytosis there are two independent signals, both of which contain critical tyrosine residues. Finally, transcytosis is signaled by phosphorylation of a particular serine.

Animals↗