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At least 505 records · Page 28Linked to original sources
PubMed2002

Arabidopsis thaliana, a versatile model system for study of eukaryotic genome-maintenance functions.

The genome of the model plant Arabidopsis thaliana encodes many orthologs of human genome-maintenance proteins, and in several important cases plant DNA repair and mutation-antagonism functions resemble their mammalian counterparts more closely than do those of established microbial models. These orthologs, in conjunction with the powerful tools now available for work with Arabidopsis and the practical advantages of its small size and rapid life cycle, now make it an attractive model system for study of eukaryotic DNA repair and mutagenesis. Already, null mutations that inactivate proteins involved in repair of DNA double-strand breaks or in DNA translesion synthesis and are lethal in mice have proved to be tolerated by plants. This review compares in some detail the genome-maintenance activities encoded by plants, mammals and microbes, and describes important Arabidopsis tools and life cycle characteristics. It concludes with selected examples that illustrate Arabidopsis advantages and/or reveal new insights into genome-maintenance functions of general interest.

Animals↗
PubMed2002

Complex predictive eye pursuit in monkey: a model system for cerebellar studies of skilled movement.

Smooth pursuit eye movements provide a good model system for cerebellar studies of complex motor control in monkeys. First, the pursuit system exhibits predictive control along complex trajectories and this control improves with training. Second, the flocculus/paraflocculus region of the cerebellum appears to generate this control. Lesions impair pursuit and neural activity patterns are closely related to eye motion during complex pursuit. Importantly, neural responses lead eye motion during predictive pursuit and lag eye motion during non-predictable target motions that require visual control. The idea that flocculus/paraflocculus predictive control is non-visual is also supported by a lack of correlation between neural activity and retinal image motion during pursuit. Third, biologically accurate neural network models of the flocculus/paraflocculus allow the exploration and testing of pursuit mechanisms. Our current model can generate predictive control without visual input in a manner that is compatible with the extensive experimental data available for this cerebellar system. Similar types of non-visual cerebellar control are likely to facilitate the wide range of other skilled movements that are observed.

Action Potentials↗
PubMed2003

WinSAAM: a windows-based compartmental modeling system.

Over the last 50 years, complex, dynamic, compartmental models have been used to describe and to make predictions on a host of pharmacokinetic, metabolic, and biological systems. Sophisticated modeling software is required to fit data to such models and to make predictions using these compartmental models. WinSAAM is one such modeling program. The purpose the current report is to describe the features of WinSAAM that make this program suited for modeling all manner of biological systems. We highlight new features, especially those that are unique to WinSAAM, and illustrate with examples how WinSAAM is used to construct models of metabolic systems, to simulate the effects of experiments on systems, and to fit models to data.

Blood Glucose↗
PubMed2002

Can the Neuman Systems Model be adapted to the Malaysian nursing context?

Nursing in Malaysia is still developing as a profession. Issues such as using nursing conceptual models or frameworks in the delivery of nursing care have not been addressed by the majority of nurses. One reason for this has been the level of education and preparation of nurses, while another reason lies with the origins of existing nursing conceptual models. Most nursing conceptual models have their origins in North America. Their utility by nurses of different cultures and academic preparations might not be appropriate. Nursing is a social activity, an interaction between the nurse and the patient. It is carried out in a social environment within a particular culture. Conceptual models developed in one culture might not be readily implanted into another culture. This paper discusses how a conceptual model developed in North America; that is, the Neuman Systems Model, can be adapted into the Malaysian nursing context.

Humans↗
PubMed1993

Membrane currents evoked by afferent fiber stimulation in rat piriform cortex. II. Analysis with a system model.

1. The detailed visualization of membrane currents over time and depth provided by current source-density (CSD) analysis was used as the basis for development of a system model that reproduces the response of piriform cortex to afferent fiber stimulation. This model has allowed the testing and substantial revision of previous hypotheses concerning the sequence of neuronal events underlying this response, has enabled net membrane currents visualized by CSD analysis to be separated into active and passive components, and has generated predictions for important axonal and synaptic parameters as well as for the behavior of piriform cortex as a system. 2. The model was developed in three steps. Activity in excitatory fiber systems was first represented with continuous distributions. The "population conductances" due to the activation of excitatory fiber systems were then computed from the distribution of action-potential arrival times and the conductance waveform for excitatory synapses. Finally, these temporally dispersed excitatory conductances and locally mediated inhibitory conductances were introduced at appropriate locations on a compartmentalized cable that simulated the passive response of the pyramidal cell population. 3. After the simulation of membrane currents at one site, all parameters in the model were fixed so that it could be used to predict the variation in the time course of membrane currents at additional recording sites; comparison with the results of CSD analysis at these sites provided the primary validation of the model. Additional validation included the simulation of membrane potentials derived by intracellular recording, including the effects of manipulating somatic potential with current injection. 4. Several conclusions have emerged from the mathematical description of activity in fiber systems. Propagation of activity in both afferent and association (corticocortical) fiber systems is "dispersive" as a result of a wide spectrum of axon conduction velocities. The characteristically different time courses of afferent and association fiber-mediated responses are largely determined by the focal, shock-evoked origin of the volley in afferent fibers as opposed to the spatially distributed disynaptic origin of activity in association fibers. Conduction velocity distributions for afferent and association fiber systems are skewed and can be approximated with lognormal distributions. 5. General solutions, which relate an arbitrary conduction velocity distribution to arrival time and spatial distributions of action potentials, were used to generate specific solutions describing the effects of dispersive propagation.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMedDate not supplied

[Study of volatile substances produced during the melanoidin synthesis in the model system: glyceraldehyde + glycine].

Volatile compounds produced during the synthesis of melanoidins in the model system: glyceraldehyde + glycine were studied. The reactions that resulted in the formation of melanoidins yielded carbon dioxide and trace amounts of ammonia and carbonyl compounds. With a rise in the incubation temperature the browning rate and quantities of gaseous substances increased, although there was no correlation between the two latter parameters. The experiments with 1-14C- and 2-14C-glycine showed that at 80 degrees about 6% and at 37 degrees less than 1% of the amino acid degraded to form CO2. The only source of CO2 was the carboxyl group. No radioactivity occurred in volatile carbonyl compounds. It is suggested that decarboxylation and deamination of the amino acid during its interaction with glyceraldehyde do not play an important part in the mechanism of melanoidin synthesis.

Amino Sugars↗
PubMed2001

Antioxidant and anti-inflammatory activities of Mallotus oppositifolium in model systems.

Chemical analysis of the powdered leaves and root of Mallotus oppositifolium revealed the presence of alkaloids, cardiac glycosides and phenolic compounds with a higher concentration residing in the leaves than in the root. Antioxidant and antiinflammatory activities of the crude extracts in hexane and methanol were evaluated by the beta-carotene linoleate model system and the carrageenan induced rat paw oedema animal model. Both systems identified significant biological activity in the methanolic crude extract of the leaf. Thin layer chromatographic (TLC) analysis of the crude extract in methanol identified four phenolic spots two of which were flavonoid in nature (UV(254nm, 356nm), FeCl3 and AlCl3 visualization).

Animals↗
PubMed1993

The predictive performance of a system model for enflurane closed-circuit inhalational anesthesia.

BACKGROUND: Previously, the authors described a system model for closed-circuit inhalational anesthesia, and demonstrated close agreement between end-tidal isoflurane concentrations measured in their clinical study and those predicted by the model. The predictive performance of their model has not, however, been tested for anesthetics featuring nonpulmonary elimination (NPE). METHODS: The authors quantified the predictive performance of two versions (A and C) of the model in 50 patients by comparing the predicted and the measured alveolar concentration-time profiles after bolus injections of liquid enflurane into the expiratory limb of the closed system. Version A did not incorporate NPE, but version C emulated NPE by adopting the irreversible loss of a fraction of the enflurane present in the arterial hepatic blood flow (0.131, derived from a mass balance study performed by others). For each concentration measured by mass spectrometry, the authors used computer simulations of version A and C to calculate a predicted concentration for both versions. For each patient, the authors calculated the bias (indicating systematic over- or underprediction) and the scatter of the prediction errors (indicating typical error size). RESULTS: The authors administered a total of 379 ml of liquid enflurane via 466 injections. A total of 18,432 alveolar concentrations (one per 10-s period; average concentration = 0.96 vol%) were measured. The bias and the scatter, both given as mean (and SD), were 10.0 (13.1)% and 11.8 (3.9)% for version A and -0.8 (11.4)% and 11.4 (2.8)% for C. The bias for version C was closer to zero; the scatters were similar. CONCLUSIONS: Version C incorporating NPE performs better than version A. The accuracy that was obtained should encourage the use of version C for clinical, teaching, research, economic, and ecologic purposes.

Adult↗
PubMed2005

Re-examination of inhibitor resistance conferred by Qo-site mutations in cytochrome b using yeast as a model system.

Cytochrome b from yeast (Saccharomyces cerevisiae Meyer ex Hansen) provides a convenient model system for the study of Qo-site inhibitor (QoI) resistance mutations from a variety of organisms. QoI resistance mutations from fungal plant pathogens (G143A and F129L), malaria agent Plasmodium sp (Y279C/S), and Pneumocystis carinii (L275F), an opportunistic pathogenic fungus of man, were introduced into yeast cytochrome b and their effect on the binding of a variety of natural (myxothiazol and stigmatellin) and synthetic (atovaquone, azoxystrobin and pyraclostrobin) inhibitors to the bc1 complex monitored. L275S (from a myxothiazol-resistant yeast) was also re-examined. Stigmatellin binding was relatively unaffected by the introduction of these mutations. Significant increases in resistance were observed for the strobilurin-class inhibitors myxothiazol, azoxystrobin and pyraclostrobin, with the largest increase in resistance conferred by G143A. In contrast, atovaquone binding was most effected by Y279C/S and L275S. Notably, F129L, G143A and L275S had a minor effect on bc1 activity, and so are unlikely to confer significant fitness penalties in vivo. These data are discussed in the light of the atomic structures for myxothiazol- and azoxystrobin-inhibited bovine bc1 which have recently become available. We propose that QoI resistance due to G143A arises from steric hindrance between the inhibitor and cytochrome b, whereas the mechanism of resistance for the other mutations is due to an increase in binding energy between the protein and inhibitor molecule. Site-directed mutagenesis was also used to model selected regions of the mammalian Qo site in yeast cytochrome b in order to further understand the differential efficacy of these QoI in the mammalian and pathogen bc1 complexes.

Amino Acid Sequence↗
PubMed1988

The effects of inhalation anesthetics on calcium-stimulated exocytosis in a natural membrane model system.

Sea urchin egg cortices were used as an in vitro natural membrane model system to determine the effects of inhalation anesthetics on the Ca2+-regulated exocytotic fusion of cortical vesicles with the egg plasma membrane. When Ca2+ was either absent or present in amounts below the threshold for exocytosis, methoxyflurane, halothane, enflurane, isoflurane, chloroform and fluoroxene, at concentrations up to 5 mM, had no effect on the fusion of cortical vesicles with the plasma membrane. However, when Ca2+ was present at or above threshold levels for exocytosis, each of the tested anesthetics caused an inhibition of cortical vesicle fusion. Exocytosis was inhibited most effectively by methoxyflurane (55%), followed by halothane (30%), while fluoroxene consistently had the least effect (less than 5%). These observations support the view that volatile anesthetics can impair the Ca2+-regulated fusogenic activities of natural membranes and are consistent with other data showing that inhalational agents inhibit secretory processes in intact cells.

Anesthesia, Inhalation↗
PubMed1980

A new mouse tumor model system (RIF-1) for comparison of end-point studies.

A new tumor model system (RIF-1) was developed that is very suitable for studies in which clonogenic survival is compared with growth delay and control probability following various forms of treatment. The tumor was a radiation-induced sarcoma in the inbred female C3H/Km mouse. It had a low median tumor dose, had a satisfactory plating efficiency direct from in vivo to in vitro, was nonimmunogenic or minimally immunogenic, and metastasized only at a relatively advanced stage of growth. The cell line grew either as a monolayer on plastic dishes, as tumor spheroids in spinner culture, as lung nodules following injection of a single-cell suspension into the tail veins of syngeneic mice, or as a solid tumor. Both diploid and tetraploid clonogenic cells were found in monolayer cultures of the RIF-1 line.

Animals↗
PubMed1995

Identification of differentially expressed genes in T-lymphoid malignancies in an animal model system.

The molecular events characterizing lymphoid malignancy have been examined in an animal model system, specifically, the retroviral induction of leukemia and lymphoma in the domestic cat following infection with feline leukemia virus (FeLV). Genes differentially expressed in FeLV-induced lymphomas were isolated using a strategy of differential hybridization. Six genes were identified which demonstrate a higher level of expression in an FeLV-induced feline thymic tumor as compared with normal thymus. The differentially expressed genes encode the feline homologues of ribosomal proteins S3a, S4, S17, and L41, elongation factor-1 alpha, and cytochrome oxidase sub-unit I. Northern-blot analysis and quantification by phosphorimaging demonstrates that these genes are expressed at levels from 1.5- to 3.1-fold higher in J5-1 thymic tumor as compared with normal thymus. Expression of the selected ribosomal protein mRNA was further examined in a series of human and feline tissues, including normal tissues, malignant tumors and cell lines. Our data reveal that elevation of the selected ribosomal protein mRNA is associated with all FeLV-induced thymic lymphomas examined. The differentially expressed ribosomal protein mRNA accumulates in a balanced manner in thymic lymphomas. By contrast, the elevation in ribosomal protein mRNA levels is not associated uniformly with hematopoietic malignancy. T-lymphoid malignancy, solid tumors or actively proliferating cells. Rather, the elevation appears to be a uniform and distinctive feature of T-cell malignancy of this particular type. The elevated expression of these genes may be causally related to the neoplastic process.

Adult↗
PubMed1984

Selenite biotransformation to volatile metabolites in an isolated hepatocyte model system.

The biotransformation of selenite to dimethylselenide was studied in an oxygenated hepatocyte model system. The concentrations of selenite used were 20-100 microM. A lag period of one hour or more, during which no net formation of selenide could be detected characterized the system. The maximal rate of volatilization was recorded during the second hour and was 0.13 nmoles/10(6) cells/min with 50 microM selenite. The rate then declined and volatilization eventually ceased. Two-thirds of the added amount of Se was lost within 4 hr. Oxidation of glutathione (GSH) by cumene hydroperoxide delayed volatilization. An inhibitor of gluconeogenesis, p-tert-butylbenzoic acid (3 microM) prevented volatilization. There were indications that GSSG reductase dependent metabolism was the only major metabolic pathway in hepatocytes under the conditions studied. During the lag period Se accumulated in cells, but was subsequently partially released during volatilization. The accumulation of Se was paralleled by an increase in oxygen uptake. The above mentioned inhibitors of volatilization prolonged the phase of accumulation. With 50 microM selenite the rate of accumulation was 0.06 nmoles/10(6) cells/min and maximally 30-35% of the added dose was retained in the cells. The results are compatible with the assumption that Se mainly accumulated as Se-glutathione complexes. The possibility that such complexes autooxidized and entered futile redox cycles during the lag period is discussed.

Animals↗
PubMed1999

Object-oriented biomedical system modelling--the language.

The paper describes a new object-oriented biomedical continuous system modelling language (OOBSML). It is fully object-oriented and supports model inheritance, encapsulation, and model component instantiation and behaviour polymorphism. Besides the traditional differential and algebraic equation expressions the language includes also formal expressions for documenting models and defining model quantity types and quantity units. It supports explicit definition of model input-, output- and state quantities, model components and component connections. The OOBSML model compiler produces self-contained, independent, executable model components that can be instantiated and used within other OOBSML models and/or stored within model and model component libraries. In this way complex models can be structured as multilevel, multi-component model hierarchies. Technically the model components produced by the OOBSML compiler are executable computer code objects based on distributed object and object request broker technology. This paper includes both the language tutorial and the formal language syntax and semantic description.

Algorithms↗
PubMed2000

Effect of enzymatic and chemical oxidation on the antioxidant capacity of catechin model systems and apple derivatives.

Changes in the chain-breaking activity of catechin model systems and apple derivatives were studied as a consequence of enzymatic and chemical oxidation. Although in different time scales, both enzymatic and chemical oxidations of catechin promoted an initial increase and a following decrease in the chain-breaking activity. The latter was associated with the formation of brown pigments. Similar changes were detected during storage at -18 degrees C of nonoxidized and enzymatically oxidized apple purees. The initial increase in antioxidant activity upon oxidation was attributed to the formation of procyanidins with larger aromatic structure and to synergy effects among them. The formation of tannins, the reactivity of which is sterically hindered, was proposed as a possible explanation for the decrease in antioxidant capacity in the advanced phases of oxidation.

Antioxidants↗
PubMed1997

The regulation by phosphorylation of 'priming' of phospholipase A2 activity in the neutrophil model system, differentiated HL60 cells.

1 Differential HL60 cells have been utilized as a model system to examine the 'priming' of neutrophil phospholipase A2 activity. In control cells activation of phospholipase A2 by a 5 min stimulation with the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (100 nM) was essentially undetectable. When cells were primed by preincubation with 5 microns cytochalasin B for 5 min arachidonate release, a measure of phospholipase A2 activation, was observed within 20 s. 2 Priming by cytochalasin B did not involve or require a change in intracellular free calcium concentration. 3 Priming was associated with an increase in general protein tyrosine phosphorylation and could also be induced by the receptor tyrosine kinase agonist granulocyte macrophage colony-stimulating factor (GM-CSF, 20 ng ml-1) and be mimicked by treatment with the phosphotyrosine phosphatase inhibitor perhydrovanadate (0.5 mM). However, increase in MAP kinase activity was not involved in the priming process. 4 Western blot analysis demonstrated that phospholipase A2 was phosphorylated in both control and primed cells, but that an increase in the amount of membrane associated enzyme was found in the primed cells. 5 Thus priming appears to be due to membrane association of the phospholipase and this may be regulated by tyrosine kinase activities.

Arachidonic Acid↗
PubMed2004

Prevention of mutagen formation in heated meats and model systems.

Possible means for preventing mutagen formation in cooked meats and in heated model systems are described. One way to reduce mutagenicity in cooked meats is to control cooking temperature, time and method. Another way is to increase water content or to avoid loss of water in meats during cooking. Addition of an excessive amount of reducing sugars to meats before cooking is effective in minimizing mutagen formation, which may be due to suppression of generation of the pyrazine cation radical Maillard intermediate of heterocyclic amines. Addition of a small amount of ascorbate or erythorbate is also effective, which may be the result of scavenging the intermediary pyrazine cation radical.

Animals↗