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PubMedDate not supplied

[Theoretical study of structural transition in a nucleosome at low ionic strength].

The theoretical analysis of nucleosome stability at low ionic strength has been performed on the basis of consideration of different contributions to the free energy of compact state of the nucleosome DNA terminal regions. The proposed model explains: the fact of low-salt structural change; the transition point (approximately 1.7 mM NaCl) and width (approximately 1 mM); the shift of the transition to the higher salt concentrations in the case of histones tails removal by trypsin. According to the model the increase of electrostatic repulsion between neighbouring turns of DNA superhelix is the main cause of the unwinding of nucleosomal DNA terminal regions in the course of low-salt structural change. The interactions between histone (H2A-H2B) dimer and (H3-H4)2 tetramer provide the compact state of the nucleosomal DNA terminal regions. The existence of electrostatic interactions of nucleosomal DNA terminal regions with tetramer was suggested. These interactions can provide the compact state of nucleosomal DNA at physiological ionic strength even in the absence of (H2A-H2B) dimer.

DNA↗

PubMed1997

Seven helix receptors are enzymes catalysing G protein activation. What is the agonist Kact?

We analysed a model assuming that the G protein activation process is an enzyme catalysed reaction: (i) GGDP recognition, (ii) GDP release, (iii) GTP binding and (iv) activated GGTP (or betagamma followed by alphaGTP) release. This model suggests (1) that the agonists Kact value may decrease with increasing G protein expression. At low G protein concentrations, the agonists Kact value reflects binding to the 'low affinity state'. If the G protein concentration is saturating, the agonists Kact values are correlated but not identical to their KD values for the 'high affinity state' observed in binding studies. (2) All the G proteins recognized by a receptor behave as competitive antagonists with respect to each other. (3) Overexpression of G proteins which recognize only the active receptor state may result in constitutive receptor activation. The rate of G protein activation can be accelerated by facilitating G protein recognition, by increasing the rate of GDP release, or by activating G protein release. Our model explains why guanyl nucleotides are essential for G proteins activation yet inhibit agonist binding, and why the ability of receptor ligands to simulate G protein activation is not always correlated with their ability to distinguish two receptor states, at equilibrium. It can also explain the inhibitory effects of GDP and of the G protein betagamma subunit.

Animals↗

PubMed1991

The subjective evaluation of traffic conflicts based on an internal concept of dangerousness.

Earlier studies concerning subjective judgement of filmed traffic conflicts demonstrated an internal construct of dangerousness. In the present study, two experiments were carried out to investigate the construct further. Since several conflict observation techniques incorporate the impetuosity of an evasive action during a conflict, the relation between inpetuosity and dangerousness was investigated. Although the impetusoity of a conflict predicts the dangerousness of a conflict rather well, it was concluded that the information underlying the judgements differed. In the second experiment the same filmed conflicts were partitioned into a commencement and a manoeuvre stage and judged on a scale of dangerousness. By relating the judgements of the different stages and the overall judgements, the information of relevance for the construct was examined. The results showed that the last part of the conflict, the part that contains most information about the minimal Time to Collision and about the Minimal Distance is of no relevance for judging the dangerousness of a conflict. It was concluded that the construct of dangerousness is based on information contained by the commencement of a convergence and by the onset of an evasive action. Finally, a conjunctive model, explaining the contribution of the two stages to the decision making process, is presented.

Accidents, Traffic↗

PubMed2004

Probabilistic model of decompression sickness based on stochastic models of bubbling in tissues.

BACKGROUND: Decompression sickness (DCS) is caused by gas bubbles formed from pre-existing and new microscopic gas nuclei in blood and tissues. Assuming a random pattern of bubbling processes in living tissues, we developed a probabilistic model of DCS. We hypothesized that symptoms of DCS in an individual exposed to decompression appear when the total volume of bubbles in a unit volume of any tissue, w(t), exceeds the critical specific volume of a free gas phase, wcr. Therefore, one may consider the expectation of w(t)/wcr as a measure of the dynamic risk of gas bubble lesion of a given tissue segment. METHODS: Using the standard approach to estimation of various risks and the sum rule of probabilities of joint events, we defined the cumulative probability of DCS onset by the equation Pcum(t) = 1 - exp[Fcum(t)], where Fcum(t) = sigmaVnQnMnc(t), Qn = 1/wncr, where Vn is the volume of a tissue n. The function Mnc(t) coincides with the function Mn(t), defining a time history of the expectation of wn(t) until it achieves its maximum and then becomes a constant. Evaluating Pcum(t) for particular altitude decompressions, we identified the additive cumulative risk function of development of any DCS symptoms, Fcum-tot(t), with the function defining the cumulative risk of any bubble lesion of the "worst" virtual tissue (WVT) of Type A. On the other hand, we identified the additive cumulative risk function of development of intolerable DCS symptoms, Fcum-int(t), with the function defining the cumulative risk of acute bubble lesion of the WVT of Type phi. RESULTS: We found parameters of the curves Pcum-tot(t) and Pcum-int(t) that fit the known empirical curves for the cumulative probability of DCS onset. For men performing mild exercise at 30 kPa after preoxygenation, our estimated parameters for curves Pcum-tot(t) indicate that the WVTs of Type A have nitrogen washout half-times of 260 and 290 min for preoxygenation times of 75 and 135 min, respectively. On the other hand, the parameters of curves Pcum-int(t) show that the WVTs of Type phi in men performing mild exercise at 20-40 kPa after preoxygenation during 0-6 h are virtual tissues with nitrogen washout half-times of 400 to 615 min. CONCLUSION: Our model provides a new approach to predicting DCS risk for various decompression profiles. By demonstrating the dependence of DCS risk on body tissue parameters, the model explains why resistance to DCS in mammals increases with a lower body mass and greater specific blood flow in tissues.

Decompression Sickness↗

PubMed2006

A new approach to epithelial isotonic fluid transport: an osmosensor feedback model.

A model for control of the transport rate and osmolarity of epithelial fluid (isotonic transport) is presented by using an analogy with the control of temperature and flow rate in a shower. The model brings recent findings and theory concerning the role of aquaporins in epithelia together with measurements of epithelial paracellular flow into a single scheme. It is not based upon osmotic equilibration across the epithelium but rather on the function of aquaporins as osmotic sensors that control the tonicity of the transported fluid by mixing cellular and paracellular flows, which may be regarded individually as hyper- and hypo-tonic fluids, to achieve near-isotonicity. The system is built on a simple feedback loop and the quasi-isotonic behavior is robust to the precise values of most parameters. Although the two flows are separate, the overall fluid transport rate is governed by the rate of salt pumping through the cell. The model explains many things: how cell pumping and paracellular flow can be coupled via control of the tight junctions; how osmolarity is controlled without depending upon the precise magnitude of membrane osmotic permeability; and why many epithelia have different aquaporins at the two membranes. The model reproduces all the salient features of epithelial fluid transport seen over many years but also indicates novel behavior that may provide a subject for future research and serve to distinguish it from other schemes such as simple osmotic equilibration. Isotonic transport is freed from constraints due to limited permeability of the membranes and the precise geometry of the system. It achieves near-isotonicity in epithelia in which partial water transport by co-transporters may be present, and shows apparent electro-osmotic effects. The model has been developed with a minimum of parameters, some of which require measurement, but the model is flexible enough for the basic idea to be extended both to complex systems of water and salt transport that still await a clear explanation, such as intestine and airway, and to systems that may lack aquaporins or use other sensors.

Animals↗

PubMedDate not supplied

Head to head dimer model; an alternative model for the strand exchange reaction by RecA protein of Escherichia coli.

The RecA protein of E coli promotes a strand exchange reaction in vitro which appears to be similar to homologous genetic recombination in vivo. A model for the mechanism of strand transfer reaction by RecA protein has been proposed by Howard-Flanders et al based on the assumption that the RecA monomer has two distinctive DNA binding sites both of which can bind to ssDNA as well as dsDNA. Here, I propose an alternative model based on the assumption that RecA monomer has a single domain for binding to a polynucleotide chain with a unique polarity. In addition, the model is based on a few mechanical assumptions that, in the presence of ATP, two RecA molecules form a head to head dimer as the basic binding unit to DNA, and that the binding of RecA protein to a polynucleotide chain induces a structural change of RecA protein that causes a higher state of affinity for another RecA molecule that is expressed as cooperativy. The model explains many of the biochemical capabilities of RecA protein including the polar polymerization of RecA protein on single stranded DNA and polar strand transfer of DNA by the protein as well as the formation of a joint DNA molecule in a paranemic configuration. The model also presents the energetics in the strand transfer reaction.

Adenosine Triphosphate↗

PubMed2005

Binding of C5-dicarboxylic substrate to aspartate aminotransferase: implications for the conformational change at the transaldimination step.

The mechanism for the reaction of aspartate aminotransferase with the C4 substrate, l-aspartate, has been well established. The binding of the C4 substrate induces conformational change in the enzyme from the open to the closed form, and the entire reaction proceeds in the closed form of the enzyme. On the contrary, little is known about the reaction with the C5 substrate, l-glutamate. In this study, we analyzed the pH-dependent binding of 2-methyl-l-glutamate to the enzyme and showed that the interaction between the amino group of 2-methyl-l-glutamate and the pyridoxal 5'-phosphate aldimine is weak compared to that between 2-methyl-l-aspartate and the aldimine. The structures of the Michaelis complexes of the enzyme with l-aspartate and l-glutamate were modeled on the basis of the maleate and glutarate complex structures of the enzyme. The result showed that l-glutamate binds to the open form of the enzyme in an extended conformation, and its alpha-amino group points in the opposite direction of the aldimine, while that of l-aspartate is close to the aldimine. These models explain the observations for 2-methyl-l-glutamate and 2-methyl-l-aspartate. The crystal structures of the complexes of aspartate aminotransferase with phosphopyridoxyl derivatives of l-glutamate, d-glutamate, and 2-methyl-l-glutamate were solved as the models for the external aldimine and ketimine complexes of l-glutamate. All the structures were in the closed form, and the two carboxylate groups and the arginine residues binding them are superimposable on the external aldimine complex with 2-methyl-l-aspartate. Taking these facts altogether, it was strongly suggested that the binding of l-glutamate to aspartate aminotransferase to form the Michaelis complex does not induce a conformational change in the enzyme, and that the conformational change to the closed form occurs during the transaldimination step. The hydrophobic residues of the entrance of the active site, including Tyr70, are considered to be important for promoting the transaldimination process and hence the recognition of the C5 substrate.

Amines↗

PubMed1994

DNA double-strand break repair: genetic determinants of flanking crossing-over.

Whether or not homologous interaction of two DNA molecules results in crossing-over of the flanking sequences is an important decision in view of genome organization. Several homologous recombination models, including the double-strand break repair models, explain this decision as choice between two alternative modes of resolution of Holliday-type intermediates. We have demonstrated that a double-strand gap can be repaired through gene conversion copying a homologous duplex, as predicted by the double-strand break repair models, in the RecE pathway of Escherichia coli. This gap repair is often accompanied by crossing-over of the flanking sequences. Mutations in ruvC and recG, whose products interact with Holliday structures in vitro, do not block double-strand gap repair or its association with flanking crossing-over. However, two mutations in the recJ gene, which encodes a single-strand 5'-->3' exonuclease, severely decrease association of flanking crossing-over. Two mutations in the recQ gene, which encodes a helicase, moderately decrease association of flanking crossing-over by themselves and suppress the severe effect of a recJ mutation. Similar relationships of recJ and recQ mutations are observed in cell survival after ultraviolet light irradiation, gamma-ray irradiation, and H2O2 treatment. We discuss how cooperation of the recQ gene product and the recJ gene product brings about double-strand break repair accompanied by flanking crossing-over. We also discuss how this reaction is related to repair of chromosome damages.

Adenosine Triphosphatases↗

PubMed1978

The mechanism of anterior-posterior polarity control in planarians.

The substance which inhibits brain formation in the regenerating planarian Dugesia etrusca was found to be a large molecule, at least in part protein, which electrophoreses as an electronegative moiety in pH 6.8 buffer. A model is presented, based on this finding and previous studies, which proposes an electrochemical mechanism for the control of polarity and possibly for the maintenance of tissue organization in planarians. It is proposed that a bioelectric field exists and moves the electronegative brain-inhibiting substance in a posterior direction, establishing polarity. This model explains the polarity reversal experiments using external fields and many of the previously unexplained classical planarian experiments. Data are presented demonstrating the existence, magnitude, and polarity of this bioelectric field, which is not greatly altered upon decapitation, all in accord with predictions of the model.

Animals↗

PubMed1994

Individual, family, and peer affiliation factors predisposing to early-age onset of alcohol and drug use.

In this study, a multifactorial model of liability to early-age alcohol and drug use was elucidated on a sample of sons of substance-abusing fathers (n = 59) and sons of normal fathers (n = 71) at time 1 when the boys were 10-12 years of age. Three hierarchical regression analyses were computed to test models to identify salient risk characteristics associated with sons' perception of family dysfunction unconventional activities among peers, and affiliation with peers engaged in delinquent behaviors. The respective models explained 28% of the variance on sons' Dysfunctional Family Index scores, 21% of the variance on sons' Conventional Activities of Friends Scale scores, and 53% of the variance was accounted for on sons' Peer Delinquency Scale scores. In subsequent logistic regression analyses, a multifactorial model comprised of individual, family, and peer risk characteristics obtained at time 1 correctly predicted 83.7% of sons who had used alcohol and/or drugs by time 2 when they were 12-14 years old. The findings also suggest that temperament phenotype influences family interaction patterns that in turn influence the psychosocial development of the child.

Alcoholism↗

PubMed2006

Predicting density of Ixodes pacificus nymphs in dense woodlands in Mendocino County, California, based on geographic information systems and remote sensing versus field-derived data.

Ixodes pacificus nymphs are the primary vectors to humans of Borrelia burgdorferi, the etiologic agent of Lyme disease, in California. We used a supervised classification model, based on remote sensing (RS) data from multi-seasonal Landsat TM 5 images, to identify the key habitat in Mendocino County where humans are exposed to I. pacificus nymphs (woodlands carpeted with leaf litter). The model, based on the normalized difference vegetation index (NDVI), brightness, and wetness, separated the nymphal risk habitat (52.6% of the county) from other habitat types with > 93% user and producer accuracies. Next, we determined the density of questing nymphs in 62 woodland-leaf areas located throughout Mendocino County and created forward-stepwise regression models explaining the variation in nymphal density based on traits attainable by a lay-person in the field (e.g., tree species present, deer signs; r(2) = 0.43, P < 0.0001), or geographic information systems (GIS)/RS-based environmental data (r(2) = 0.50, P < 0.0001). The GIS/RS model, using July NDVI, November greenness, a coastal influence category, May solar insolation, November hours of sunlight, and dominant hydrologic grouping as input variables, was 22% more accurate in predicting nymphal density at 16 validation sites (r(2) = 0.72) than the field-derived data model (r(2) = 0.50). The habitat classification and GIS/RS models were combined to create a continuous nymphal density surface for the entirety of Mendocino County. This risk surface showed that 11.9% of the county was classified as habitat posing at least moderate risk of human exposure to nymphs (> 6.4 nymphs per 100 m(2)). Furthermore, high-risk areas (> 10.5 nymphs per 100 m(2); 1.7% of the county) tended to cluster in the central interior and most heavily populated region of Mendocino County, but were rare in the proximity of coastal population centers.

Animals↗

PubMed2006

Determinants of health promotion action: comparative analysis of local voluntary associations in four municipalities in Finland.

The World Health Organization makes a case for the importance of voluntary organizations in promoting health at local levels. The purpose of this paper is to contribute to understanding which factors explain local voluntary associations (LVAs) participation in health promotion in local contexts. It does so through (i) identifying indicators that represent determinants of health promotion action which were reported by LVAs and by (ii) comparing their actions with these determinants. The data reported are from a questionnaire survey of all registered LVAs in four municipalities in Finland. Principal component analysis revealed four determinants of health promotion action. Four factors in the final multivariate model explained over half of the variance of LVAs engagement in health promotion action: competence, values 'healthy' and also opportunities and municipality. There is some evidence to support a model of health promotion action which has not been tested empirically in relation to these types of organization. More detailed studies of determinants of health promotion action are needed to shape strategies in local communities.

Community Health Planning↗

PubMed2000

Too early to explain all experimental data with a single model.

The target article by Prilutsky gives an excellent overview of the predictions of the Crowninshield and Brand model and about the relevant literature about muscle coordination. However, we do not agree with the claim that the Crowninshield and Brand model can explain the coordination between one-joint and two-joint muscles. In this commentary we will make three claims: (a) The Crowninshield and Brand model cannot explain all aspects of muscle coordination, (b) there is good experimental evidence that different constraints and models may be necessary to explain muscle coordination in different motor tasks, and (c) the reason for the lack of quantitative fits between predictions about muscle force and experimental data is that it is hard to measure muscle force in man. As a compromise one has to rely on EMG activity as a measure of muscle force. Because of the complex relationship between EMG and muscle force, a quantitative test of models is difficult.

Humans↗

PubMed1992

Health effects of unemployment--I. Long-term unemployed men in a rural and an urban setting.

Between 1983 and 1987 in an urban and a rural Dutch area employed and long-term unemployed men, between 30 and 50 years old, have been interviewed. The main topics of the study were the independent health effects of unemployment, the factors related to these health effects and socio-cultural differences. Long-term unemployment is considered to be a social phenomenon that restructures individual's social positions into multiple deprived positions. The characteristics of this restructuring are a relative lack of socio-structural resources, low social participation and emotional problems. Independent effects on the health status (perceived somatic and depressive complaints and self reported chronic disease) have been found to exist among both the rural and the urban unemployed. There is no clear effect of unemployment on health care use, but regional differences in health care use among rural and urban unemployed have been found. Between the urban and rural unemployed there are more similarities than differences in the factors and models explaining ill-health. The most important factors are: loneliness, disadvantageous consequences of unemployment, money worries and ill-health prior to job loss (health selection at the labour market). One important difference is that among the urban unemployed the perceived size of the network is an explanatory factor, but among the rural unemployed perceived stigmatization is more important. In general, ill-health can be better explained for the rural unemployed than for the urban unemployed.

Adult↗

PubMed2000

The anomalous mole fraction effect in Chara: gating at the edge of temporal resolution.

The anomalous mole fraction effect (AMFE) of the K(+) channel in excised patches of the tonoplast of Chara showed a minimum of apparent open-channel current at 20 mM Tl(+) and 230 mM K(+). Time series obtained at a sampling rate of 100 kHz (filter 25 kHz) were analyzed by three methods to find out whether the AMFE results from an effect on gating or on the conductivity of the open state. Fitting the amplitude histograms by a superposition of gaussians showed a broadening in the presence of Tl(+). Dwell-time analysis based on an O-O-C-C-C model failed to evaluate rate constants above the filter frequency. Thus, the absence of any reduction of apparent open-channel current in time series simulated with the evaluated rate constants could not be taken as evidence against the hypothesis of gating. Finally, a direct fit of the measured time series using five different 5-state Hidden Markov models revealed that the presence of Tl(+) changed the rate constants in such a way that the number of transitions into the short-lived open state (30 micros) increased strongly compared to those in the absence of Tl(+). These models explain 25% reduction of apparent single-channel current amplitude through a rapid gating mechanism.

Electrophysiology↗

PubMed2006

Predicting the emergence of human hantavirus disease using a combination of viral dynamics and rodent demographic patterns.

The paper proposes a model explaining the spatial variation in incidence of nephropathia epidemica in Europe. We take into account the rodent dynamic features and the replicative dynamics of the virus in animals, high in the acute phase of newly infected animals and low in the subsequent chronic phase. The model revealed that only vole populations with multi-annual fluctuations allow for simultaneously high numbers of infected rodents and high proportions of those rodents in the acute excretion phase during the culminating phase of population build-up. This leads to a brief peak in exceptionally high concentrations of virus in the environment, and thereby, to human exposure. Such a mechanism suggests that a slight ecological disturbance in animal-parasite systems could result in the emergence of human diseases. Thus, the potential risk for public health due to several zoonotic diseases may be greater than previously believed, based solely on the distribution of human cases.

Animals↗

PubMed1985

A recursive model of economic well-being in retirement.

Although investigators have identified some of the social and economic forces that influence levels of economic resources among elderly adults, little has been done to organize these factors into predictive lifespan models of economic well-being. Applying path analysis to data on retiring workers from the Panel Study of Income Dynamics, the present research offers a beginning recursive model. It traces the influences of demographic/family background, human capital, and work-related characteristics on economic position in retirement. Controlling for differences in labor force participation and other human capital measures, race and family background lose their direct significance, whereas sex remains directly significant in predicting economic resource levels for recently retired workers. In addition, the model estimates the direct and indirect effects played by industrial sector location and social class position. In total the structurally based capital attainment model explains 65% of the variance in a measure of economic well-being that includes retirement income and wealth.

Aged↗

PubMed2004

A mathematical model of immunohistochemical preparations, which provides quantitative predictions.

A mathematical model of the reaction between primary antibody and epitope is described using the Law of Mass Action to define the reaction quantitatively. The model explains some of the peculiar properties of immunohistochemical preparations. It also predicts that antibody excess over epitope will not increase staining intensity for very avid primary antibodies. This property can be exploited to measure the amount of epitope in histological sections. The assumptions of the model are not specific to immunohistochemistry, and such reasoning should be widely applicable to tests based on highly avid detection systems with high amplification of the initial signal.

Antibodies↗