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PubMed1990

Proliferative and genotoxic cellular effects in 2-acetylaminofluorene bladder and liver carcinogenesis: biological modeling of the ED01 study.

The development of tumors in relationship to 2-acetylaminofluorene (AAF) dose and time on study has been evaluated in an experiment conducted by the National Center for Toxicological Research (NCTR) using more than 24,000 female BALB/c mice. By using a biologically based model of two-event carcinogenesis accounting explicitly for both genotoxic and nongenotoxic proliferative effects at the cellular level, we provide a unifying explanation for the apparently disparate dose-response results observed in the urinary bladder and liver. Experimental observations of dose-related DNA adduct levels in both tissues and hyperplasia in the bladder were utilized in estimation of model parameters. Analyses demonstrate that tumor prevalence in the liver can be explained entirely by the influence of AAF on the first of two genetic events, and in the bladder by the synergy between AAF genotoxicity affecting both genetic events and cellular proliferation at higher doses. These results are consistent across the entire ED01 data set.

2-Acetylaminofluorene↗
PubMed2006

Selective stabilization and synaptic specificity: a new cell-biological model.

How are appropriate connections between neurons sorted from the overwhelming surplus of potential, yet inappropriate, connections? Despite the apparently improbable nature of the process, brains wire themselves with a high degree of reproducibility that has been conserved across evolutionary history. Here, we outline a viable cell-biological model for generating synaptic specificity that features selection of nascent synapses based on adhesion and recognition. This process uses the highly dynamic and stochastic nature of intracellular trafficking to generate reproducible patterns of synaptic connectivity.

Animals↗
PubMedDate not supplied

Sialoglycoconjugates in Trypanosoma cruzi-host cell interaction: possible biological models--a review [corrected].

A number of glycoconjugates, including glycolipids and glycoproteins, participate in the process of host-cell invasion by Trypanosoma cruzi and one of the most important carbohydrates involved on this interaction is sialic acid. It is known that parasite trans-sialidase participates with sialic acid in a coordinated fashion in the initial stages of invasion. Given the importance of these sialoglycoconjugates, this review sets out various possible biological models for the interaction between the parasite and mammalian cells that possess a sialylated receptor/ligand system.

Animals↗
PubMed1997

Modelling biological gel contraction by cells: mechanocellular formulation and cell traction force quantification.

Traction forces developed by most cell types play a significant role in the spatial organisation of biological tissues. However, due to the complexity of cell-extracellular matrix interactions, these forces are quantitatively difficult to estimate without explicitly considering cell properties and extracellular mechanical matrix responses. Recent experimental devices elaborated for measuring cell traction on extracellular matrix use cell deposits on a piece of gel placed between one fixed and one moving holder. We formulate here a mathematical model describing the dynamic behaviour of the cell-gel medium in such devices. This model is based on a mechanical force balance quantification of the gel visco-elastic response to the traction forces exerted by the diffusing cells. Thus, we theoretically analyzed and simulated the displacement of the free moving boundary of the system under various conditions for cells and gel concentrations. This model is then used as the theoretical basis of an experimental device where endothelial cells are seeded on a rectangular biogel of fibrin cast between two floating holders, one fixed and the other linked to a force sensor. From a comparison of displacement of the gel moving boundary simulated by the model and the experimental data recorded from the moving holder displacement, the magnitude of the traction forces exerted by the endothelial cell on the fibrin gel was estimated for different experimental situations. Different analytical expressions for the cell traction term are proposed and the corresponding force quantifications are compared to the traction force measurements reported for various kind of cells with the use of similar or different experimental devices.

Animals↗
PubMed1990

A new method to measure brain serotonin synthesis in vivo. I. Theory and basic data for a biological model.

We describe here an autoradiographic method to measure the in vivo rate of serotonin synthesis in rat brain. The method is based on the use of the L-tryptophan analogue alpha-methyl-L-tryptophan (alpha-MTrp), which is converted in vivo into alpha-methylserotonin (alpha-M5HT). Since alpha-M5HT is not a substrate for monoamine oxidase, it is accumulated in the brain tissue. Data are presented to confirm time-dependent conversion of alpha-MTrp into alpha-M5HT in the dorsal raphe nucleus and also in the pineal body, an organ outside the blood-brain barrier. It has also been shown that washing brain slices in 10% trichloroacetic acid results in less than 3% incorporation of alpha-MTrp into brain proteins. The rates of synthesis are calculated in several grossly dissected brain structures by using tracer kinetics and a three-compartment biological model. The half-life of the precursor pool is estimated to be approximately 20 min. The rate of serotonin synthesis is highest in the pineal body.

Animals↗
PubMed2001

Molecular dynamics simulation of continuous current flow through a model biological membrane channel.

The conductance of sodium ions through a simplified channel-membrane system immersed in a reservoir of 1M NaCl in SPC/E water is examined by molecular dynamics simulation. An applied external potential of 1.1 V drives the ions and water through a channel of length 25 A producing a current of 19.6 pA, in reasonable agreement with experimental findings. The stream of ions and water molecules flows continuously because of the constant applied field and periodic boundary conditions. We also examine the potential profile across the simulation cell, the average density distributions of the various species in the reservoir and radially in the channel, and the ion velocity in the channel.

Biophysical Phenomena↗
PubMed2006

Molluscan natural products as biological models: chemical ecology, histology, and laboratory culture.

The utility of some natural products from molluscs has been known for centuries. However, only recently have modern technologies and advances in the fields of chemistry, chemical ecology, anatomy, histology, and laboratory culture allowed the exploitation of new, unprecedented applications of natural products. Recent studies have dealt with (a) the role that these compounds have in the sea in protecting the animals (e.g., chemical defense), or in mediating their intraspecific communication (e.g., pheromones), (b) the geographical differences in similar or related species (and the implications of this in chemical ecology and phylogeny), and (c) the localization of these metabolites in molluscan tissues (by means of the most modern technologies), among others. The methodology for the laboratory culture of some species has also been established, thus offering new insights into this interesting field. Further applications of all these challenging studies are currently being developed.

Animals↗
PubMed1997

Palliative irradiation for focally symptomatic metastatic renal cell carcinoma: support for dose escalation based on a biological model.

PURPOSE: Renal cell carcinoma has traditionally been regarded as a radioresistant cancer, yet controversy continues as to whether escalation of the palliative radiation dose can overcome the inherent resistance of such tumors when they metastasize. Recently, the linear quadratic model has emerged as a paradigm to assess biologically effective dose of radiotherapy. This study was undertaken to determine the ability of radiotherapy to palliate focally symptomatic metastatic renal cell carcinoma and to assess whether the delivery of higher biologically effective dose was more likely to bring about a palliative response. MATERIALS AND METHODS: Between 1966 and 1995, 107 patients with renal cell metastases at 150 sites were irradiated with palliative intent. Sites irradiated included bone (89), soft tissue (16), brain (20), spinal cord (9) and pulmonary (16). To determine dose effectiveness the biologically effective dose was calculated according to the formula, Gy10 = total dose (1 + fractional dose/alpha-beta), using an alpha-beta of 10. RESULTS: For the entire group 86% of patients derived a palliative response after treatment with irradiation, while 49% derived a complete palliative response. The median duration of palliation was 6 months (range 1 to 150). With respect to overall (that is, complete and partial) response rates, those presenting with high Karnofsky performance status were most likely to respond (status 70 or greater versus less than 70, 88% versus 78%, p < 0.04). With respect to the rate of complete palliative response, performance status (status 70 or greater versus less than 70, 55% versus 31%, p < 0.03) and the use of higher biologically effective doses of irradiation (Gy10 50 or greater versus less than 50, 59% versus 39%, p = 0.001) were associated with a statistically significant increased rate of response. The independent prognostic value of performance status and higher biologically effective doses of irradiation were maintained in multivariate analysis. CONCLUSIONS: Despite the prevailing concept that renal cell carcinoma is generally resistant to radiotherapy, the overwhelming majority of patients seen at our institution in whom metastatic renal cell carcinoma developed were palliated with radiotherapy. A complete palliative response is more likely when higher biologically effective doses of irradiation are delivered, especially to patients with a relatively high performance status.

Aged↗
PubMed2006

BIOCHAM: an environment for modeling biological systems and formalizing experimental knowledge.

UNLABELLED: BIOCHAM (the BIOCHemical Abstract Machine) is a software environment for modeling biochemical systems. It is based on two aspects: (1) the analysis and simulation of boolean, kinetic and stochastic models and (2) the formalization of biological properties in temporal logic. BIOCHAM provides tools and languages for describing protein networks with a simple and straightforward syntax, and for integrating biological properties into the model. It then becomes possible to analyze, query, verify and maintain the model with respect to those properties. For kinetic models, BIOCHAM can search for appropriate parameter values in order to reproduce a specific behavior observed in experiments and formalized in temporal logic. Coupled with other methods such as bifurcation diagrams, this search assists the modeler/biologist in the modeling process. AVAILABILITY: BIOCHAM (v. 2.5) is a free software available for download, with example models, at http://contraintes.inria.fr/BIOCHAM/.

Algorithms↗
PubMed1996

Biological model of ED01 hepatocarcinogenesis.

The ED01 bioassay on 2-acetylaminofluorene (2-AAF)-induced hepatocarcinogenesis in BALB/c mice was analyzed using a biologically based, two-mutation model of the oncogenic process. Computer simulations indicate that 2-AAF-induced hepatocarcinogenesis has both genotoxic and promotional components. However, contrary to the current paradigm, we find that the genotoxic component of 2-AAF plays a minor role in its carcinogenicity. The ED01 hepatocarcinogenicity can be explained almost entirely to result from the promotional influence of 2-AAF on an existing pool of spontaneously initiated cells.

2-Acetylaminofluorene↗
PubMed2006

Biological models: measuring variability with classical and quantum information.

This essay proposes methods to analyse the variability of biological data. The idea is to express the state of a biological system as a linear combination of base states in a Hilbert space. Coefficients of the linear combination can be interpreted as probabilities and informational entropy is associated to each state allowing the definition of a classical variability measure. Besides, state transition matrices can also be calculated and their norms express the dynamics of the system organization and a quantum variability measure. As the examples show, the classical measure expresses a structural variability and the quantum measure expresses a functional variability.

Computational Biology↗
PubMed2001

Stochastic noise interferes coherently with a model biological clock and produces specific dynamic behaviour.

The influence of noise is unavoidable in all living systems. Its impact on a model of a biological clock, normally running in regular oscillating modes, is examined. It is shown that in a specific system in which endogenous rhythmicity is produced by a beat oscillator acting on a feedback coupled metabolic pool system, noise can act coherently to produce unexpected dynamic behaviour, running from regular over pseudo-regular to irregular time-structures. If the biological system consists of a set of identical weakly coupled cells, stochasticity may lead to phase decoupling producing irregular spatio-temporal patterns. Synchronization via phase resetting can be achieved by external short-time temperature pulses. Explicit results are obtained for the well-studied circadian photosynthesis oscillations in plants performing crassulacean acid metabolism. Because of the generic structure of the underlying nonlinear dynamics they can, however, be regarded as a general property of the influence of noise on nonlinear excitable systems with fixed points occuring close to limit cycles.

Biological Clocks↗
PubMedDate not supplied

Modelling biological depth perception in binocular vision: the local disparity estimation.

This paper presents an approach to solving the correspondence problem in binocular vision and to computing the local horizontal disparity map using a biologically inspired algorithm. A computer application was developed as a tool for implementing, developing, and testing computational models for stereopsis, and also as a framework for integrating the disparity map with other perspective clues. Two models for stereopsis have been implemented. One of them is biologically inspired (it models the behaviour of simple and complex cells from the striate cortex) and the other is the 'classical' model of David Marr and Tomaso Poggio, implemented in order to have a comparison term for the simulation results. The paper details the results obtained on random-dot stereograms and on pairs of real images.

Algorithms↗
PubMed2005

Worms in space? A model biological dosimeter.

Although it is well known that radiation causes mutational damage, little is known about the biological effects of long-term exposure to radiation in space. Exposure to radiation can result in serious heritable defects in experimental animals, and in humans, susceptibility to cancer, radiation-sickness, and death at high dosages. It is possible to do ground controlled studies of different types of radiation on experimental animals and to physically measure radiation on the space station or on space probes. However, the actual biological affects of long-term exposure to the full range of space radiation have not been studied, and little information is available about the biological consequences of solar flares. Biological systems are not simply passive recording instruments. They respond differently under different conditions, and thus it is important to be able to collect data from a living animal. There are technical difficulties that restrict the placement of an experimental organism in a space environment for long periods of time, in a manner that allows for the recovery of genetic data. Use of the self-fertilizing hermaphroditic nematode, Caenorhabditis elegans offers potential for the design of a biological dosimeter. In this paper, we describe the advantages of this model system and review the literature of C. elegans in space.

Animals↗