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At least 1,297 records · Page 72Linked to original sources
PubMed2006

Visualizing the behavior of human Rad51 at the single-molecule level.

The repair of double-stranded DNA breaks by homologous recombination is essential for maintaining genome integrity. Much of what we know about this DNA repair pathway in eukaryotes has been gleaned from genetics, in vivo experiments with GFP-tagged proteins and traditional biochemical experiments with purified proteins. However, many questions have remained inaccessible to these experimental approaches. Recent technological advances have made it possible to directly visualize the behaviors of individual DNA and protein molecules in vitro, and it is now becoming feasible to apply these technology-driven approaches to complex biochemical systems, such as those involved in the repair of damaged DNA. This report summarizes the use of total internal reflection fluorescence microscopy to probe fundamental aspects of protein-DNA interactions at the single-molecule level, and specific emphasis is placed on our efforts to develop new methods and techniques for studying DNA repair. Using these new approaches we are investigating the DNA-binding behavior of human Rad51 and we have recently demonstrated that this protein can slide on dsDNA via a one-dimensional random walk mechanism driven solely by thermal fluctuations of the surrounding solvent. Here, we highlight some possible implications of this recent finding, and we also briefly discuss the potential benefits of future single-molecule studies in the study of protein-DNA interactions and DNA repair.

DNA↗
PubMed1999

Self-organization of tissue-equivalents: the nature and role of contact guidance.

The morphology and behaviour of tissue cells when surrounded by a network of protein fibres, such as for a tissue-equivalent comprising cells entrapped in a type I collagen gel, is distinct from that when cells are cultured on a rigid surface, and physiologically relevant. The highly elongated and apparently bipolar morphology leads to a 'reversing' type of cell movement in gels, as opposed to a directionally persistent movement characteristic of highly spread, polar cells on surfaces. However, the hallmark of a tissue-equivalent is consolidation of the fibrillar network, or gel compaction, resulting from traction exerted by the cells. When the gel is mechanically constrained from compacting, alignment of the fibrils occurs, inducing cell alignment through a contact guidance response. In order to understand this 'self-organization' of tissue-equivalents, some relevant structural and mechanical properties of collagen gel are considered first, followed by a review of seminal studies of cell traction and tissue-equivalent compaction. Random cell migration in an isotropic gel is then discussed, including a modification of the persistent random walk model used to analyse cell migration on surfaces, followed by a review of contact guidance studies in gels with fibrils having defined alignment. With this background, observations of self-organization of mechanically constrained compacting tissue-equivalents are summarized and explained using a mechanical theory that relates traction-induced compaction to fibre alignment and consequent contact guidance, i.e. a strain-based rather than stress-based cell response to gel compaction. Data in support of this theory obtained from studies involving the controlled applied compression of tissue-equivalents are then presented. Finally, possible mechanisms of contact guidance are discussed.

Cell Adhesion↗
PubMed1998

The relationship between overweight and psychological problems in adult Czech population.

Overweight is often mentioned in causal relationship with various psychological problems and a lack of self-control. 438 randomly chosen subjects (selected from electoral registers or by random walk method)--men and women from Prague and the countryside--were divided according to their body weight into two groups, one with BMI equal or lower that 25, the other one with BMI higher than 25. 92.2 per cent of the subjects were overweight, 8 per cent had BMI higher than 30. Comparison of the two groups with lower and higher body weight based on a self-report questionnaire (GHQ, CAGE and some other items) showed differences between men and women. In men, with growing body weight the self-control in food intake decreased and problems related to lack of self-control increased significantly (smoking, problems with alcohol). On the contrary, women with overweight reported higher self-control in food intake (dieting) and had less problems with alcohol. The relationship between psychological problems (depression, anxiety) and overweight was not unequivocally proved. Men with higher body weight reported significantly less somatic problems in the GHQ. They also suffered comparatively less from depression and anxiety. The overweight women showed slightly more anxiety and significantly higher social dysfunction than women with normal body weight.

Adolescent↗
PubMed2000

Assessing the roles of change discrimination and luminance integration: evidence for a hybrid race model of perceptual decision making in luminance discrimination.

Many models of perceptual processing assume that participants integrate stimulus evidence over time, for example, random walk models. This class of models is tested in a luminance discrimination paradigm in which the onsets of the stimuli are either instantaneous (stepped) or slowly ramped. The ramped portion of ramped stimuli occurs prior to the stepped stimuli onsets. Consequently, there is more luminance energy in ramped stimuli. Therefore, if participants integrate luminance energy, they should perform better to ramped stimuli. This did not occur in 4 experiments. Participants performed better to stepped stimuli than ramped stimuli in earlier foreperiods and the reverse in later foreperiods. A new model is proposed in which participants monitor both integrated luminance energy and quick temporal changes in luminance, but they do so in a serial fashion. First, participants monitor temporal changes in luminance; later, they monitor integrated luminance energy.

Adult↗
PubMed2001

Amphetamine distorts stimulation-dependent dopamine overflow: effects on D2 autoreceptors, transporters, and synaptic vesicle stores.

Amphetamine (AMPH) is known to raise extracellular dopamine (DA) levels by inducing stimulation-independent DA efflux via reverse transport through the DA transporter and by inhibiting DA re-uptake. In contrast, recent studies indicate that AMPH decreases stimulation-dependent vesicular DA release. One candidate mechanism for this effect is the AMPH-mediated redistribution of DA from vesicles to the cytosol. In addition, the inhibition of stimulation-dependent release may occur because of D2 autoreceptor activation by DA that is released via reverse transport. We used the D2 receptor antagonist sulpiride and mice lacking the D2 receptor to address this issue. To evaluate carefully AMPH effects on release and uptake, we recorded stimulated DA overflow in striatal slices by using continuous amperometry and cyclic voltammetry. Recordings were fit by a random walk simulation of DA diffusion, including uptake with Michaelis-Menten kinetics, that provided estimates of DA concentration and uptake parameters. AMPH (10 microm) promoted the overflow of synaptically released DA by decreasing the apparent affinity for DA uptake (K(m) increase from 0.8 to 32 microm). The amount of DA released per pulse, however, was decreased by 82%. This release inhibition was prevented partly by superfusion with sulpiride (47% inhibition) and was reduced in D2 mutant mice (23% inhibition). When D2 autoreceptor activation was minimal, the combined effects of AMPH on DA release and uptake resulted in an enhanced overflow of exocytically released DA. Such enhancement of stimulation-dependent DA overflow may occur under conditions of low D2 receptor activity or expression, for example as a result of AMPH sensitization.

Amphetamine↗
PubMedDate not supplied

Mobilis in mobile: a probabilistic and chronotopic model of mobility in urban spaces.

In this communication we propose an urban mobility model based on individual random walk driven by a chronotopic action with a deterministic public transportation network. In the absence of chronotopoi the mean field analytic results are found in good agreement with simulations on a computer. When the chronotopoi are switched on, they attract people according to a given law and we obtain a sort of diffusive motion. The model can describe many different kinds of dynamical systems, including biological ones. The work is in progress and the next step will be an empirical test in a concrete case.

City Planning↗
PubMed1975

The statistical analysis of density dependence.

The distrubution of the reciprocal of von Neumann's ratio is considered under the random walk model, x(t+1) rwis;d xt + et, and it is shown how this quantity can be used to test for density dependence in animal populations. Another test is described which is robust under superimposed errors of measurement. The methods are used to analyze data on Canadian fur-bearing mammals.

Animals↗
PubMed2003

Modeling of the detachment of a molecule from a surface: illustration of the "Bell-Evans effect".

This article deals with the modeling of the detachment of a molecule initially adsorbed on a surface and submitted to an external force whose strength increases with time. By means of an atomic force microscope (AFM), it is possible to measure the force when the molecule separates from the substrate. However, it is known that this force depends to a large extend on the rate at which the pulling force is applied ("Bell-Evans effect"). Two models are described to illustrate this behavior. First, a random walk approach is suggested to reveal the fundamental principle of the escape over a time-dependent energy barrier. Second, a multi bead-and-spring model is proposed to mimic the AFM experiment and numerical simulations, based on Brownian dynamics, are performed.

Binding Sites↗
PubMed2004

A preliminary study of multilevel geographic distribution & prevalence of Aedes aegypti (Diptera: Culicidae) in the state of Goa, India.

BACKGROUND & OBJECTIVES: Dengue virus activity has never been reported in the state of Goa. The present study was carried out to document a multilevel geographic distribution, prevalence and preliminary analysis of risk factors for the invasions of Aedes aegypti in Goa. METHODS: A geographic information system (GIS) based Ae. aegypti surveys were conducted in dry (April 2002) and wet (July 2002) seasons in the rural and urban settlements. The random walk method was used for household coverage. The non-residential area visits included ancillaries of roadways, railways, air-and seaports. Simultaneous adult mosquito collections and one-larva per container technique were adopted. RESULTS: The Ae. aegypti larval and adult prevalence was noted in all the four urban areas in both dry (Density index (DI)= 3 to 6) and wet (DI= 5 to 7) seasons and only one out of 3 villages showed Ae aegypti presence in wet season (DI= 5 to 7). In the residential areas, hutments showed higher relative prevalence indices (Breteau index, BI=100; container index, CI=11.95; adult house index, AHI=13.33) followed by close set cement houses (BI=44.1; CI=12.0; AHI=11.24). Ae aegypti relative prevalence indices were also more for households with pets (BI=85.11; CI=12.5; AHI= 42.85); those with tap had higher risk (larval house index, LHI =32.03; relative risk, RR>2, n=256). Plastic drum was the most preferred breeding place (chi(2) = 19.81; P<0.01; RR=3.41) among domestic containers and rubber tyres (chi(2) = 11.86; P<0.01; RR=3.61)among sundry/rainfilled containers. INTERPRETATION & CONCLUSION: Established Ae aegypti prevalence in the urban settlements during dry and wet seasons and its scattered distribution in a rural settlement spell risk of dengue infection at macro-level. In the residential areas nature and types of the households, tap water supply and storage and communities' attitude and practices contribute to sustained meso-level risk of Ae aegypti prevalence dependant DEN. The non-residential areas offer transient meso-level risk as Ae aegypti prevalence was seasonally unstable and monsoon dependent. Risk at micro-level was due to the preferred larval habitats of Ae aegypti breeding viz., residential plastic-ware and tyres, and transport tyres in non-residential areas.

Aedes↗
PubMed2005

Epileptic transitions: model predictions and experimental validation.

The essence of epilepsy is that a patient displays (long) periods of normal EEG activity (i.e., nonepileptiform) intermingled occasionally with epileptiform paroxysmal activity. The mechanisms of transition between these two types of activity are not well understood. To provide more insight into the dynamics of the neuronal networks leading to seizure generation, the authors developed a computational model of thalamocortical circuits based on relevant patho(physiologic) data. The model exhibits bistability, i.e., it features two operational states, ictal and interictal, that coexist. The transitions between these two states occur according to a Poisson process. An alternative scenario for transitions can be a random walk of network parameters that ultimately leads to a paroxysmal discharge. Predictions of bistable computational model with experimental results from different types of epilepsy are compared.

Adolescent↗
PubMed2006

Tissue engineering templates using minimal surfaces.

The status quo of tissue engineering can be summarized as "a random walk through the design space". The existing scaffold designs based on computeraided design (CAD) and solid freeform fabrication (SFF) are anti-biomorphic and mechanically weak cubic partitions with sharp edges. We introduce minimal surface based unit cells to create biomorphic scaffolds with optimal stress/strain distribution and superior mechanical strength.

Computer Simulation↗
PubMed2006

Isolation by resistance.

Despite growing interest in the effects of landscape heterogeneity on genetic structuring, few tools are available to incorporate data on landscape composition into population genetic studies. Analyses of isolation by distance have typically either assumed spatial homogeneity for convenience or applied theoretically unjustified distance metrics to compensate for heterogeneity. Here I propose the isolation-by-resistance (IBR) model as an alternative for predicting equilibrium genetic structuring in complex landscapes. The model predicts a positive relationship between genetic differentiation and the resistance distance, a distance metric that exploits precise relationships between random walk times and effective resistances in electronic networks. As a predictor of genetic differentiation, the resistance distance is both more theoretically justified and more robust to spatial heterogeneity than Euclidean or least cost path-based distance measures. Moreover, the metric can be applied with a wide range of data inputs, including coarse-scale range maps, simple maps of habitat and nonhabitat within a species' range, or complex spatial datasets with habitats and barriers of differing qualities. The IBR model thus provides a flexible and efficient tool to account for habitat heterogeneity in studies of isolation by distance, improve understanding of how landscape characteristics affect genetic structuring, and predict genetic and evolutionary consequences of landscape change.

Biological Evolution↗
PubMed1988

Analysis of models of single-file diffusion.

Theoretical models of single-file transport in a homogeneous channel are considered. Three levels of channel populations were specified for which different approximations could be used. The results of these approximations are in good agreement with the results of a computer experiment (Aityan and Portnov 1986). At low populations, the pair correlation functions were negligibly small and allowed the use of linear approximation for unidirectional fluxes and populations. The value of the pair correlation function and the respective approximation for fluxes was obtained by the two-particles random-walk technique. At extremely high populations, the "divider" technique was proposed to describe the single-file transport. The divider technique allowed to explain the exponential shape of the pair correlation function FABn, n + 1 profile at extremely high populations. At medium populations the finite difference superposition approximation was valid.

Computer Simulation↗
PubMedDate not supplied

Issues involved in the transmission of chemical signals through the brain extracellular space.

Two classes of substances exist within the extracellular space: energetic and informational. Examples of the former are glucose, dissolved oxygen and CO2 while the latter include excitatory amino acids, cathecholamines and opiates. The simple ions Na+ and Cl- are generally associated with energetic processes while extracellular K+ and Ca2+ tend to be informational in function. Local release of an informational substance brings about a concentration gradient that causes the substance to be dispersed in the extracellular space by diffusion. This process is modified relative to a free aqueous medium by the constraints of volume fraction, tortuosity and uptake. Volume fraction is defined simply as the fraction of a brain region that is extracellular. If a given quantity of substance is released into a region with a reduced volume fraction then the substance will reach a higher concentration than it would in a free medium. Tortuosity is related to the increase in the path length of the random walk of a diffusing particle due to the necessity to navigate around cellular obstructions. Tortuosity manifests itself as a decrease in the diffusion coefficient. Uptake represents the movement of a substance from the extracellular space to the intracellular. Since initially a concentration gradient exists in this direction and all membranes have some permeability some concentration-dependent uptake always occurs. In addition there exist specific carrier-mediated uptake processes for some substances such as amino acids or catecholamines. In some regions the dispersal process can be dominated by uptake rather than diffusion. While volume fraction, tortuosity and uptake have all been demonstrated by a technique based on the use of radiolabels and other methods, these classical techniques have limited spatial and temporal resolution. The advent of methods based on micro-injection of substances by iontophoresis or pressure and subsequent detection with ion-selective microelectrodes (ISMs) or voltammetric microsensors (VMs) has opened a new window onto the dynamic local behavior of the extracellular space. In the last decade our laboratory and others have studied the migration of the test substances tetramethylammonium, tetraethylammonium, AsF6- and alpha naphthalene sulfonate, the endogenous ions K+ and Ca2+, the epileptogenic agent penicillin and the neurotransmitter dopamine. These studies have been carried out on the cerebellum and some other regions in a variety of species that include rat, turtle, skate and an intervertebrate, the cuttlefish.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1977

Assessment of cardiac blood pools in radiocardiography by various indicator dilution models.

Heart blood pools were evaluated by different indicator dilution models from single detector 113mIn radiocardiographic measurements on healthy subjects. It appeared that generally accepted mathematical expressions based on the nth moments of the radiocardiographic dilution curve overestimate the heart volumes by 30-40%. The study suggests that the indicator dispersion within the heart chambers is an essential parameter affecting the central circulatory dilution process, which ought to be included in the radiocardiographic models. Dispersion models based on the random walk equation, probability density function and the gamma variate model produced consistent heart volumes. The suitability of the dispersion models for clinical routine use is discussed briefly.

Adolescent↗
PubMed1988

Chemotactic factor-induced polarization, receptor redistribution, and locomotion of human blood monocytes.

The locomotor response of human blood monocytes to chemotactic factors was studied using a polarization assay on cells in suspension and by filming locomotion on albumin-coated glass. Cells in optimal (5 x 10(-9) M) but uniform concentrations of N-formyl-methionyl-leucyl-phenylalanine (FMLP) polarized well and showed a 'persistent random walk' type of locomotion, whereas in supraoptimal concentrations (10(-7) M), the cells took erratic paths and polarized poorly, suggesting that monocytes cannot develop an anteroposterior polarity if hit by ligand molecules at many points on the cell surface simultaneously. Monocyte polarization in chemotactic factors at 37 degrees was transient and was gradually lost after 15-20 min. Likewise, the ability to form Fc rosettes after this time was gradually lost, suggesting loss of functional receptors from the cell surface with time. In optimally polarized cells, Fc rosettes were frequently localized at the head of the cell. This localization also was lost with time. Using pure chemotactic factors (FMLP, C5a, leukotriene B4) we found, as reported earlier (Cianciolo & Snyderman 1981), that polarization was restricted to a subpopulation (approximately 60% of cells) that responded to multiple attractants. However, 80-90% of monocytes polarized in response to combinations of any of the above pure attractants with candida-activated serum. This suggests that the subpopulation that lacks receptors for classical chemotactic factors nevertheless has locomotor capacity and can respond to undefined factors in activated serum, and that the great majority of blood monocytes is motile if appropriately stimulated.

Chemotactic Factors↗
PubMed1987

Terminal distributions along a 'knight's line' for a stochastic epidemic.

The model under consideration relates to the spread of a disease in a finite population where removal of infectives is allowed to occur. It is equivalent to a restricted random walk over a discrete grid of points interior to a trapezium. We consider an artificial barrier on the grid at which the epidemic ceases. The barrier is a semi-diagonal resembling the path of the knight in chess and allows some simplification of the analysis. In particular, we investigate the probability distribution along this barrier when time is infinite. Recursive relations are obtained for these terminal distributions and are used to develop an exact numerical method for their computation. In certain cases, a slight modification of the binomial distribution provides a good approximation to the actual distribution. A direct recursive method for calculating moments of the distribution is given and we show how the whole distribution may be recovered from these moments.

Disease Outbreaks↗
PubMed1985

Theoretical approach to active dispersal and colonization of houses by Triatoma infestans.

Dispersive flight by Triatoma infestans was modelled by assuming either unidirectional flight in a straight line, or that flight followed a pattern of 'random walk' analogous to two-dimensional Brownian motion. Parameter estimates for the models were derived from previous fieldwork in Argentina and Brazil. Calculated probabilities of houses becoming infested over a 1 year period were compared with actual changes of house infestation in a small farming community in central Brazil. It was found that infestation could be explained partly by the dispersive flight of the bugs according to the distances between houses, and partly by the predisposition of houses to infestation by virtue of their construction, since houses with cracked mud walls were particularly susceptible to infestation. Infested houses lying more than 200 m from uninfested houses appeared to make an almost negligible contribution to infestation of the uninfested houses. This suggests that buffer zones of this size around treated areas could help to minimize the risk of reinfestation after treatment.

Animals↗