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Biomedical subjects

S Schnell

Publications and source records attributed to S Schnell.

At least 19 recordsLinked to original sources
PubMed2006

A systematic investigation of the rate laws valid in intracellular environments.

Recently there has been significant interest in deducing the form of the rate laws for chemical reactions occurring in the intracellular environment. This environment is typically characterized by low-dimensionality and a high macromolecular content; this leads to a spatial heterogeneity not typical of the well stirred in vitro environments. For this reason, the classical law of mass action has been presumed to be invalid for modeling intracellular reactions. Using lattice-gas automata models, it has recently been postulated [H. Berry, Monte Carlo simulations of enzyme reactions in two dimensions: Fractal kinetics and spatial segregation, Biophys. J. 83 (2002) 1891-1901; S. Schnell, T.E. Turner, Reaction kinetics in intracellular environments with macromolecular crowding: simulations and rate laws, Prog. Biophys. Mol. Biol. 85 (2004) 235-260] that the reaction kinetics is fractal-like. In this article we systematically investigate for the first time how the rate laws describing intracellular reactions vary as a function of: the geometry and size of the intracellular surface on which the reactions occur, the mobility of the macromolecules responsible for the crowding effects, the initial reactant concentrations and the probability of reaction between two reactant molecules. We also compare the rate laws valid in heterogeneous environments in which there is an underlying spatial lattice, for example crystalline alloys, with the rate laws valid in heterogeneous environments where there is no such natural lattice, for example in intracellular environments. Our simulations indicate that: (i) in intracellular environments both fractal kinetics and mass action can be valid, the major determinant being the probability of reaction, (ii) the geometry and size of the intracellular surface on which reactions are occurring does not significantly affect the rate law, (iii) there are considerable differences between the rate laws valid in heterogeneous non-living structures such as crystals and those valid in intracellular environments. Deviations from mass action are less pronounced in intracellular environments than in a crystalline material of similar heterogeneity.

Fractals↗
PubMed2006

A clock and wavefront mechanism for somite formation.

Somitogenesis, the sequential formation of a periodic pattern along the antero-posterior axis of vertebrate embryos, is one of the most obvious examples of the segmental patterning processes that take place during embryogenesis and also one of the major unresolved events in developmental biology. In this article, we develop a mathematical formulation of a new version of the Clock and Wavefront model proposed by Pourquié and co-workers (Dubrulle, J., McGrew, M.J., Pourquié, O., 2001. FGF signalling controls somite boundary position and regulates segmentation clock control of spatiotemporal Hox gene activation. Cell 106, 219-232). Dynamic expression of FGF8 in the presomitic mesoderm constitutes the wavefront of determination which sweeps along the body axis interacting as it moves with the segmentation clock to gate cells into somites. We also show that the model can mimic the anomalies formed when progression of the wavefront is disturbed and make some experimental predictions that can be used to test the hypotheses underlying the model.

Animals↗
PubMed2006

A mathematical investigation of a Clock and Wavefront model for somitogenesis.

Somites are transient blocks of cells that form sequentially along the antero-posterior axis of vertebrate embryos. They give rise to the vertebrae, ribs and other associated features of the trunk. In this work we develop and analyse a mathematical formulation of a version of the Clock and Wavefront model for somite formation, where the clock controls when the boundaries of the somites form and the wavefront determines where they form. Our analysis indicates that this interaction between a segmentation clock and a wavefront can explain the periodic pattern of somites observed in normal embryos. We can also show that a simplification of the model provides a mechanism for predicting the anomalies resulting from perturbation of the wavefront.

Algorithms↗
PubMed2006

Use and abuse of the quasi-steady-state approximation.

The transient kinetic behaviour of an open single enzyme, single substrate reaction is examined. The reaction follows the Van Slyke-Cullen mechanism, a spacial case of the Michaelis-Menten reaction. The analysis is performed both with and without applying the quasi-steady-state approximation. The analysis of the full system shows conditions for biochemical pathway coupling, which yield sustained oscillatory behaviour in the enzyme reaction. The reduced model does not demonstrate this behaviour. The results have important implications in the analysis of open biochemical reactions and the modelling of metabolic systems.

Artifacts↗
PubMed2006

Influence of grape treatment on the wine yeast populations isolated from spontaneous fermentations.

AIM: To study the influence of different methods of grape treatment in wineries on the diversity of the yeast species in spontaneous fermentations. METHODS AND RESULTS: Grapes were crushed and pressed in three different ways followed by spontaneous fermentation. The same grape material picked and crushed aseptically directly in the vineyard served as control. Yeasts isolated at different stages of the fermentation were characterized by 5.8S-ITS-RFLP. Yeasts of the Saccharomyces sensu stricto complex were additionally analysed by microsatellite polymerase chain reaction fingerprinting. The diversity of yeast species isolated from winery fermentations was much greater than from the vineyard fermentation in respect to yeasts of the genus Saccharomyces as well as non-Saccharomyces. CONCLUSIONS: Oenonogical methods alter significantly the yeast diversity in spontaneous fermentations of grape juice. SIGNIFICANCE AND IMPACT OF THE STUDY: Managing spontaneous fermentations successfully depends not only on choosing the suitable grapes but also on the crushing and pressing techniques leading to different yeast populations.

Fermentation↗
PubMed2005

[Selective RPE laser treatment with a scanned cw laser beam in rabbits].

BACKGROUND: Selective RPE laser therapy with sparing of the neurosensory layer is possible by applying repetitive microsecond laser pulses. Macular diseases such as diabetic maculopathy, soft confluent drusen due to age-related macular degeneration or central serous chorioretinopathy were shown to be treated successfully-without concurrent laser scotoma-by this technique. It was the goal of this study to show, if selectivity could also be achieved using a conventional green cw-laser by scanning the beam across the retina during irradiation. MATERIAL AND METHODS: A cw-laser beam at 532 nm was coupled to a slitlamp via a single mode optical fiber. The spot (18 microm) was scanned across the retina of Dutch-belted rabbits through a contact lens using a two-dimensional acusto-optical deflector. The scan-field was 300 microm x 300 microm in size and consisted of six separate scan lines. The scanning speed was adjusted so as to produce 5 micros exposure at each absorber in the center of the scan line. The entire scan pattern was applied 100 times at each site at a frame rate of 100 Hz. Dose response curve was measured by variation of the laser power. ED(50)-thresholds for RPE damage were calculated by fluorescein angiographic leakage in irradiated areas after exposure to different laser intensities. The extent of selectivity was examined by light microscopy. RESULTS: Clinically the selective laser-induced RPE defect was demonstrated by fluorescein angiographic leakage and concurrent absence of ophthalmoscopic visibility. The angiographic ED(50)-damage threshold was 161 mJ/cm(2) (66 mW). Ophthalmoscopic visibility was not noticed even with the maximum available radiant exposure of 438 mJ/cm(2) (180 mW). Thus the safety range between angiographic and ophthalmoscopic thresholds had a factor of at least 2.7. First histological examinations revealed selective RPE destruction with intact photoreceptors for irradiation at laser power levels 2 times above angiographic threshold. CONCLUSION: Selective RPE targeting is feasible with a conventional green cw-laser when scanning the focused laser beam across the fundus with a speed such that every point in exposed RPE is irradiated for duration of 5 micros.

Animals↗
PubMed2005

Genetic basis and risk factors for infectious and noninfectious diseases in US Holsteins. I. Estimation of genetic parameters for single diseases and general health.

Health data collected from 1996 to 1999 from 177 herds in Minnesota and Wisconsin were analyzed to establish genetic basis for infectious and noninfectious diseases. Three types of health traits were targeted. First, available infectious conditions were used to identify animals that are superior in their general immunity (including innate immunity) for infectious diseases. Generalized immunity may be thought of as a combination of immune responses to a variety of immune system challenges. Second, single infectious and noninfectious diseases were analyzed separately. Third, infectious reproductive diseases as one category of related conditions, and cystic ovary disease as one category of 3 related noninfectious ovary disorders were studied. Data were analyzed using a threshold model that included herd, calving year, season of calving, and parity as cross-classified fixed factors; and sire and cow within sires as random effects. Days at risk and days in milk at the beginning of a record were included by fitting the days as continuous covariates in the model. A heritability value of 0.202 +/- 0.083 was estimated for generalized immunity. Heritability values of 0.141 and 0.161 were estimated for uterine infection and mastitis, respectively. Heritability of single noninfectious disorders ranged from 0.087 to 0.349. The amount of additive genetic variance recovered in the underlying scale of noninfectious disorders tended to zero when combining multiple conditions. The study supports combining infectious diseases into categories of interest but we do not recommend the same approach for noninfectious disorders.

Abomasum↗
PubMed2004

Distributions-per-level: a means of testing level detectors and models of patch-clamp data.

Level or jump detectors generate the reconstructed time series from a noisy record of patch-clamp current. The reconstructed time series is used to create dwell-time histograms for the kinetic analysis of the Markov model of the investigated ion channel. It is shown here that some additional lines in the software of such a detector can provide a powerful new means of patch-clamp analysis. For each current level that can be recognized by the detector, an array is declared. The new software assigns every data point of the original time series to the array that belongs to the actual state of the detector. From the data sets in these arrays distributions-per-level are generated. Simulated and experimental time series analyzed by Hinkley detectors are used to demonstrate the benefits of these distributions-per-level. First, they can serve as a test of the reliability of jump and level detectors. Second, they can reveal beta distributions as resulting from fast gating that would usually be hidden in the overall amplitude histogram. Probably the most valuable feature is that the malfunctions of the Hinkley detectors turn out to depend on the Markov model of the ion channel. Thus, the errors revealed by the distributions-per-level can be used to distinguish between different putative Markov models of the measured time series.

Algorithms↗
PubMed2004

Stochastic approaches for modelling in vivo reactions.

In recent years, stochastic modelling has emerged as a physically more realistic alternative for modelling in vivo reactions. There are numerous stochastic approaches available in the literature; most of these assume that observed random fluctuations are a consequence of the small number of reacting molecules. We review some important developments of the stochastic approach and consider its suitability for modelling intracellular reactions. We then describe recent efforts to include the fluctuation effects caused by the structural organisation of the cytoplasm and the limited diffusion of molecules due to macromolecular crowding.

Algorithms↗
PubMed2004

Mathematical and computational techniques to deduce complex biochemical reaction mechanisms.

Time series data can now be routinely collected for biochemical reaction pathways, and recently, several methods have been proposed to infer reaction mechanisms for metabolic pathways and networks. In this paper we provide a survey of mathematical techniques for determining reaction mechanisms for time series data on the concentration or abundance of different reacting components, with little prior information about the pathways involved.

Algorithms↗
PubMed2004

A mathematical formulation for the cell-cycle model in somitogenesis: analysis, parameter constraints and numerical solutions.

In this work we present an analysis, supported by numerical simulations, of the formulation of the cell-cycle model for somitogenesis proposed in Collier et al. (J. Theor Biol. 207 (2000), 305-316). The analysis indicates that by introducing appropriate parameter constraints on model parameters the cell-cycle mechanism can indeed give rise to the periodic pattern of somites observed in normal embryos. The analysis also provides a greater understanding of the signalling process controlling somite formation and allows us to understand which parameters influence somite length.

Animals↗
PubMed2004

High neuroticism and depressive temperament are associated with dysfunctional regulation of the hypothalamic-pituitary-adrenocortical system in healthy volunteers.

OBJECTIVE: Elevated neuroticism, depressive temperament and dysfunctional regulation of the hypothalamic-pituitary-adrenocortical (HPA) system are considered as risk factors for unipolar depression. An interaction of these vulnerability factors was suggested, but controversially discussed. In absence of other informative studies we set out for a replication test and for elucidation of the underlying mechanism. METHOD: Ninety-two subjects recruited in the community-performed assessments of personality and temperament as well as measurement of HPA function with the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test. RESULTS: Cortisol levels subsequent to Dex/CRH challenge were associated with neuroticism; high-neuroticism subjects revealed a higher HPA activation. This difference was mainly because of male subjects >/=25 years. A similar relationship was observed for depressive temperament. CONCLUSION: This constellation may propose that HPA dysregulation is the endocrinological basis for neuroticism and depressive temperament; this result supports the view that distinct personality factors and HPA vulnerability interact in mediating depression.

Adrenal Cortex Hormones↗
PubMed2004

Correlations among body condition scores from various sources, dairy form, and cow health from the United States and Denmark.

The objectives of this study were to estimate genetic correlations among body condition scores (BCS) from various sources, dairy form, and measures of cow health. Body condition score and dairy form evaluated during routine type appraisal was obtained from the Holstein Association USA, Inc. A second set of BCS was obtained from Dairy Records Managements Systems (DRMS) and was recorded by producers that use PCDART dairy management software. Disease observations were obtained from recorded veterinarian treatments in several dairy herds in the United States. Estimated breeding values for diseases in Denmark were also obtained. Genetic correlations among BCS, dairy form, and cow health traits in the United States were generated with sire models. Models included fixed effects for age, DIM, and contemporary group. Random effects included sire, permanent environment, herd-year season for health traits, and error. Predicted transmitting abilities (PTA) for BCS and dairy form were correlated with estimated breeding values for disease in Denmark. The genetic correlation estimate between BCS from DRMS and BCS from the Holstein Association USA, Inc., was 0.85. The genetic correlation estimate between BCS and a composite of all diseases in the United States was -0.79, and PTA for BCS was favorably correlated with an index of resistance to disease other than mastitis in Denmark (0.27). Dairy form was positively correlated with a composite of all diseases in the United States (0.85) and was unfavorably correlated with an index for resistance to disease other than mastitis in Denmark (-0.29). Adjustment for protein yield PTA had a minimal affect on correlations between PTA for BCS or dairy form and disease in Denmark. Selection for higher body condition or lower dairy form with continued selection for yield may slow deterioration in cow health as a correlated response to selection for increased yield.

Animals↗
PubMed2003

[Effect of iron oxide addition on hydrogen, carbon dioxide and methane geneses in paddy soil].

Paddy soil is an important contributor for atmospheric methane. The methanogenesis is related to the production of acetate, hydrogen and carbon dioxide during the decomposition of organic matter under anaerobic conditions. As electron acceptors, iron (III) oxides can effectively compete with electrons in the transformation of organic matter into methane. Its mechanism maybe relates to the consumption of H2 and CO2. After added ferrihydrite and lepidocrocite, the H2, CO2 and CH4 were determined during the anaerobic incubation of slurries at 25 degrees C for 105 days. The results indicated that the addition of ferrihydrite and lepidocrocite could greatly decrease the concentration of H2, CO2 and CH4, and ferrihydrite had a stronger effect than lepidocrocite. In this system, the balance of organic-C was disturbed, CH4-C and CO2-C were reduced, but the CO3(2-)-C fixed by slurry was greatly increased.

Carbon Dioxide↗
PubMed2001

Lentivirus-transduced human monocyte-derived dendritic cells efficiently stimulate antigen-specific cytotoxic T lymphocytes.

Dendritic cells (DCs) are professional antigen-presenting cells that are highly effective adjuvants for immunizing against pathogens and tumor antigens. The potential merit of genetic approaches to loading DCs with antigens is to express high and sustained levels of proteins that can be subsequently processed and presented to T lymphocytes. Replication-defective oncoretroviruses are able to efficiently transduce CD34(+) progenitor-derived DCs but not monocyte-derived DCs. Here, it is shown that efficient gene transfer is obtained using a human immunodeficiency virus-1-derived lentiviral vector deleted of all structural and accessory genes. Infection of immature DCs with the lentiviral vector at a multiplicity of infection of 20 resulted in stable gene expression in 30% to 40% of the matured DCs. Proviral DNA was detectable by Alu polymerase chain reaction for the lentiviral but not the oncoretroviral vector. Most importantly, it is demonstrated that lentivirus-transduced DCs were fully functional and effectively activated autologous HLA A2.1(+) peripheral blood cytotoxic T lymphocytes (CTLs). DCs expressing lentiviral vector-encoded Flu peptide were at least as efficient as DCs pulsed with the same peptide in stimulating specific CTLs. The efficacy of the lentivirus-transduced DCs was further demonstrated by their ability to directly activate freshly harvested peripheral blood Flu-specific CTLs in the absence of CD4(+) T-cell help and exogenous cytokines. The availability of a stable gene delivery system based on a multiply attenuated lentivirus that does not encode any viral protein and that allows sustained antigen presentation by DCs derived from blood monocytes will be very useful for the biologic investigation of DCs and the improvement of immunotherapeutic strategies involving DCs.

CD4-Positive T-Lymphocytes↗
PubMed2001

A fast method to estimate kinetic constants for enzyme inhibitors.

We present a method to determine the reaction type and kinetic constants for enzyme inhibitors that decreases the number of experimental assays by at least a factor of five. It is based on a new theoretical formalism in terms of concentrations that dismisses the requirement of estimating initial velocities. Expressions for the time evolution of the concentrations of all the reactants are also given.

Algorithms↗