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At least 1,045 records · Page 58Linked to original sources
PubMed1999

Cell cycling and cell enlargement in developing leaves of Arabidopsis.

Cell cycling plays an important role in plant development, including: (1) organ morphogenesis, (2) cell proliferation within tissues, and (3) cell differentiation. In this study we use a cyclin::beta-glucuronidase reporter construct to characterize spatial and temporal patterns of cell cycling at each of these levels during wild-type development in the model genetic organism Arabidopsis thaliana (Columbia). We show that a key morphogenetic event in leaf development, blade formation, is highly correlated with localized cell cycling at the primordium margin. However, tissue layers are established by a more diffuse distribution of cycling cells that does not directly involve the marginal zone. During leaf expansion, tissue proliferation shows a strong longitudinal gradient, with basiplastic polarity. Tissue layers differ in pattern of proliferative cell divisions: cell cycling of palisade mesophyll precursors is prolonged in comparison to that of pavement cells of the adjacent epidermal layers, and cells exit the cycle at different characteristic sizes. Cell divisions directly related to formation of stomates and of vascular tissue from their respective precursors occur throughout the period of leaf extension, so that differing tissue patterns reflect superposition of cycling related to cell differentiation on more general tissue proliferation. Our results indicate that cell cycling related to leaf morphogenesis, tissue-specific patterns of cell proliferation, and cell differentiation occurs concurrently during leaf development and suggest that unique regulatory pathways may operate at each level.

Arabidopsis↗
PubMed1996

Control of hypertrophic scar growth using antibody-targeted photolysis.

Hypertrophic scar is marked by excess collagen accumulation secondary to an increased vascularization response in the scar and an increase in fibroblast cell density. It is currently the most debilitating long-term complication of the surviving burn patient, and at present, there is no routinely effective form of therapy. In this study, we investigated the potential use of antibody-targeted photolysis (ATPL) in treating hypertrophic scars. An immunoconjugate consisting of a photosensitizer (Sn-chlorin e6) linked to a monoclonal antibody that binds to human myofibroblasts (PR2D3) was prepared, which in response to photoactivation produces singlet oxygen in close proximity to the target cell surface. The model used for these studies consisted of 1-mm 3 human hypertrophic scar tissue implants in athymic mice. These implants increase approximately 20-fold in volume over a period of 15 days. Four days after implantation immunoconjugate was injected directly into scar implants allowed to diffuse throughout for 24 hr before implants were illuminated with laser light at 630 nm (120 J/cm 2). ATPL treatment caused a significant reduction in total growth compared to the untreated controls (P < 0.05). No effect was observed when an irrelevant conjugate (anti-Pseudomonas aeruginosa) was used. Histological examination of the ATPL-treated implants 24 hr post-ATPL revealed the presence of a large number of lipid droplets indicative of massive cell damage and infiltration by mononuclear cells and neutrophils.

Animals↗
PubMed1993

Dynamical role of "protein friction" in the sliding movement of protein motors in vitro.

When protein motors interact with a sliding cytoplasmic-filament through a weak-binding interaction (thus, without ATP splitting), this interaction cycle results in friction opposing the sliding movement. The friction is owing to the flexible nature of the heads of these motors as globular proteins. Under a certain condition, the friction becomes proportional to the sliding velocity. This viscous-like friction by protein motor is called protein friction. Since the protein friction is more than 10 times larger than the hydrodynamic viscous drag, we propose that the sliding velocity in the in vitro motility system is limited when the active sliding force generated by protein motors is balanced by the protein friction. The model of the protein friction hypothesis is consistent with many experimental data of the in vitro motility systems such as those of mixture experiments with different myosins and the ATP-concentration dependence of the sliding velocity. By relating the coefficient of the protein friction to the diffusion coefficient, we show that the model is consistent with the data on the one-dimensional Brownian movement of a microtubule on a dynein-coated glass surface in the presence of vanadate and ATP. The model also shows that the Brownian movement is driven directly by the thermally-generated structural fluctuations of the dynein heads rather than the atomic collision of solvent molecules. Thus, the model implies that the thermal structural fluctuations of the protein motor heads underlie the ATP-induced sliding movement by protein motors and hence protein motors are a Brownian actuator.

Animals↗
PubMed1991

General continuum theory for multiion channel. II. Application to acetylcholine channel.

The general theory (Levitt, D. G. 1990. Biophys. J. 59:271-277) is applied to a model channel that resembles the acetylcholine receptor channel (ACH). The model incorporates the known features of the ACH geometry and fixed charge locations. The channel has a wide mouth facing the outer solution, tapering to a narrow region facing the interior of the cell. Rings of fixed negative charge are placed at the two surfaces where the bilayer begins, corresponding to the known charges at the ends of the M2 segment. It is assumed that the forces acting on the ion are electrostatic: ion-channel wall, ion-ion, Born image and applied voltage. Analytical expressions for these forces are derived that take account of the low dielectric lipid region. In addition, there is a local hard sphere repulsive force that prevents ions from piling up on each other in regions of the channel with a high fixed charge density. A classical continuum theory is used to obtain an expression for the diffusion coefficient in the channel. The model can mimic the major qualitative and, in many cases, quantitative experimental features of the ACH channel: current-voltage relation, conductance versus concentration and interaction between monovalent and divalent ions. The model calculations were also compared with the site directed mutagenesis experiments of Imoto, K., C. Busch, B. Sakmann, M. Mishina, T. Konno, J. Nakai, H. Bujo, Y. Mori, K. Fukuda, and S. Numa. (1988. Nature (Lond.). 335:645-648) in which the charge at the ends of the channel was systematically varied.

Animals↗
PubMed2026

Conditional Diffusion Model-Based Method for Annotation of Antibiotic Resistance Gene Properties.

The crisis of bacterial antibiotic resistance, which has led to a decline in the effectiveness of antibiotics originally used to combat bacterial infections, has emerged as an urgent challenge for public health. Antibiotic resistance genes (ARGs) are one of the key reasons for bacteria to develop resistance to antibiotics. Therefore, accurately identifying and annotating the critical properties of ARGs is of great importance for addressing the antibiotic resistance emergency. Although existing deep learning models demonstrate remarkable effectiveness in extracting local features from sequence data, they still face limitations in the capacity to further gain the enriched latent representations within the data. To address the critical challenge of extracting higher-quality representations from ARGs sequence data, we propose a novel ARGs properties annotation method based on the conditional diffusion model which is used to learn latent representations through domain-specific knowledge injection. Specifically, during the conditional information integration phase, we systematically incorporate ARGs' domain knowledge to guide the diffusion process in generating high-quality latent representations. To overcome information redundancy caused by direct concatenation of conditional information and intermediate features, we design a cross-attention mechanism that enables feature fusion between heterogeneous information sources, thereby enhancing further the quality of obtained representations. Experimental results on widely used data sets demonstrate the framework's effectiveness in achieving superior prediction performance compared to existing methods.

Anti-Bacterial Agents↗
PubMed2006

Direct measurement of the internal electron quasi-Fermi level in dye sensitized solar cells using a titanium secondary electrode.

The spatial dependence of the electron quasi-Fermi level (QFL) in the interior of dye sensitized nanocrystalline solar cells (DSC) under short circuit conditions can be inferred from calculations based on a diffusive electron transport model. The calculations predict that the difference in the QFL between the electrolyte and contact sides of the TiO(2) layer under short circuit conditions at 1 sun could be as much as 0.5-0.7 eV. The predicted QFL profiles depend on assumptions made about energy positions, electron mobility, and the conduction band density of states. In this work, the position of the QFL at the electrolyte side of the dye sensitized TiO(2) film in a DSC has been measured using a thin passivated titanium contact deposited on top of the nanocrystalline TiO(2) by evaporation. The method allows changes in the electron QFL at all points on the IV characteristic of the cell to be monitored under dark and photostationary conditions. In addition, cells incorporating the titanium electrode can give information about the behavior of the QFL under dynamic conditions.

Letter↗
PubMed2004

Micropatterned composite membranes of polymerized and fluid lipid bilayers.

Micropatterned composite membranes of polymerized and fluid lipid bilayers were constructed on solid substrates. Lithographic photopolymerization of a diacetylene-containing phospholipid, 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DiynePC), and subsequent removal of nonreacted monomers by a detergent solution (0.1 M sodium dodecyl sulfate (SDS)) yielded a patterned polymeric bilayer matrix on the substrate. Fluid lipid bilayers of phosphatidylcholine from egg yolk (egg-PC) were incorporated into the lipid-free wells surrounded by the polymeric bilayers through the process of fusion and reorganization of suspended small unilamellar vesicles. Spatial distribution of the fluid bilayers in the patterned bilayer depended on the degree of photopolymerization that in turn could be modulated by varying the applied UV irradiation dose. The polymeric bilayer domains blocked lateral diffusion of the fluid lipid bilayers and confined them in the defined areas (corrals), if the polymerization was conducted with a sufficiently large UV dose. On the other hand, lipid molecules of the fluid bilayers penetrated into the polymeric bilayer domains, if the UV dose was relatively small. A direct correlation was observed between the applied UV dose and the lateral diffusion coefficient of fluorescent marker molecules in the fluid bilayers embedded within the polymeric bilayer domains. Artificial control of lateral diffusion by polymeric bilayers may lead to the creation of complex and versatile biomimetic model membrane arrays.

Diffusion↗
PubMed2002

Intestinal patches for oral drug delivery.

PURPOSE: Oral route offers an attractive mode of drug administration, although its applications are limited by poor stability of peptides and proteins in the gastrointestinal tract. In this article, we report a novel method based on intestinal patches for oral drug delivery. This method involves the use of millimeter size mucoadhesive patches that adhere to the intestinal wall and direct solute diffusion towards the wall similar to that observed in the case of a transdermal patch. METHODS: Intestinal patches were prepared by sandwiching a film of cross-linked bovine serum albumin microspheres between a film of ethyl cellulose and Carbopol/pectin. Delivery of three model drugs, sulforhodamine B. phenol red, and dextran was assessed in vitro using rat intestine. RESULTS: In vitro tests confirmed substantial unidirectional diffusion of model drugs from the patch across the intestinal wall. The presence of ethyl cellulose layer minimized release from the edges as well as from the back side of the patch into the intestinal lumen. In vitro experiments with rat intestine showed that patches were effective in delivering model drugs across the intestine. Trans-lumenal flux of model drugs from intestinal patches was about 100-fold higher compared to that from a solution due to localization of the solute near the intestinal wall and due to minimization of drug loss into the intestinal lumen. CONCLUSIONS: Intestinal patches offer a novel approach for oral drug delivery.

Adhesives↗
PubMed2004

Increased site 1 affinity improves biopotency of porcine growth hormone. Evidence against diffusion dependent receptor dimerization.

Based on phage display optimization studies with human growth hormone (GH), it is thought that the biopotency of GH cannot be increased. This is proposed to be a result of the affinity of the first receptor for hormone far exceeding that which is required to trap the hormone long enough to allow diffusion of the second receptor to form the ternary complex, which initiates signaling. We report here that despite similar site 1 kinetics to the hGH/hGH receptor interaction, the potency of porcine GH for its receptor can be increased up to 5-fold by substituting hGH residues involved in site 1 binding into pGH. Based on extensive mutations and BIAcore studies, we show that the higher potency and site 1 affinity of hGH for the pGHR is primarily a result of a decreased off-rate associated with residues in the extended loop between helices 1 and 2 that interact with the two key tryptophans Trp104 and Trp169 in the receptor binding hot spot. Our mutagenic analysis has also identified a second determinant (Lys165), which in addition to His169, restricts the ability of non-primate hormones to activate hGH receptor. The increased biopotency of GH that we observe can be explained by a model for GH receptor activation where subunit alignment is critical for effective signaling.

Amino Acid Sequence↗
PubMed2002

Kinetics and equilibrium in insulin radioimmunoassay.

The kinetics of insulin reaction has been studied with its specific antibody immobilized on the inner wall of the reaction tube; the radioimmunoanalytical determination of such a substance is based on the reaction. Independent variables were labelled and unlabelled insulin concentrations, temperature, viscosity, and the medium's ionic strength. Biexponential kinetics was found to be dependent on the concentrations fitted to the models discussed in the paper. The effect of temperature shows activation parameters similar to the viscous flow energy of water, which suggests that the reaction is diffusion-controlled. The results of the viscosity analysis points at the clearly negative influence of viscosity upon the direct reaction rate. Ionic strength has a noticeable, though not relevant, effect which seems to indicate that the variation resulting from the glycerol addition is not due to the influence of the dielectric constant in the solutions used.

Biochemistry↗
PubMed1980

[The adhesive process. Part II: Research on pathogenesis (author's transl)].

In adhesive middle ears the rate of recidives after operation is very high - irrespective of the tube function (part I). This may be caused by changed middle ear pressure and other pressure determinating factors like the tube function, the elasticity of the tympanic membrane, the volume of the middle ear space and gas diffusion. Registration of the tube function by pressure equalisation test as well as the direct, continous measurement of the middle ear pressure shows, that in 30-40% of the patients examined, a physiological tube function with normal pressure was found before and after tympanoplasty. In model studies we could demonstrate, that even in normal middle ear pressure tympanograms may be achieved, which are typical for adhesive processes, with a peak in the negative pressure area. The volumes of the middle ear spaces after tympanoplastics are larger (4,3 ml on an average) then preoperatively, but smaller than normal. Continuous registration of the middle ear pressure shows that in adhesive middle ears that development of negative pressure is diminished - compared with a collective of patients with normal elasticity of the tympanic membrane. This difference can only be explained by decreased elasticity of the membrane, found with adhesive processes and after tympanoplatics. Recidives after tympanoplastics in atelectatic ears may be caused by the development of negative pressure due to tube dysfunction. In cases of normal tube function (30-40% of the patients) and normal pressure, the rate of recidives is mostly caused by decreased elasticity of the tympanic membrane together with the smaller volume of the middle ear spaces.

Acoustic Impedance Tests↗
PubMed1990

Epithelial transport of drugs in cell culture. I: A model for studying the passive diffusion of drugs over intestinal absorptive (Caco-2) cells.

A human intestinal cell line, Caco-2, was used as a model to study the passive diffusion of drugs across intestinal epithelium. The cells formed continuous monolayers when grown on permeable filters of polycarbonate. After 10 days in culture, the monolayers had a transmembrane resistance of approximately 260 ohms.cm2 and a cell density of 0.9 x 10(6) cells/cm2. At this time the cells were impermeable to [14C]polyethyleneglycol (MW 4000). These characteristics remained constant for 20 days (i.e., from day 10 to day 30). Six beta-blocking agents with a 2000-fold range of lipophilicity were studied for their transepithelial transport properties. The transport parameters were independent of drug concentration and transport direction. The apparent permeability coefficients ranged from 41.91 +/- 4.31 x 10(-6) cm/s for the most lipophilic drug, propranolol, to 0.203 +/- 0.004 x 10(-6) cm/s for the most hydrophilic drug, atenolol. The transport parameters were compared with those published for rat ileum. The transport rates were similar for four out of five drugs. Atenolol was transported at a slower rate in the Caco-2 model, which may be explained by the fact that the Caco-2 cells form a tighter epithelium than the rat ileal enterocytes. The findings of this paper indicate that Caco-2 cells may be used to model the intestinal absorption of drugs.

Adrenergic beta-Antagonists↗
PubMed2003

A two-locus gene conversion model with selection and its application to the human RHCE and RHD genes.

A two-locus gene conversion model with selection is developed. Under the joint action of selection, mutation, gene conversion, recombination, and random genetic drift, approximate formulas for the expectations of the moments of allele frequencies and the expected amounts of variation within and between two loci are obtained by a diffusion method assuming relatively strong selection. It is shown that the pattern of allelic variation is mainly determined by the balance between gene conversion and selection, because these two mechanisms act in opposite directions. As an application of the theoretical results, the human RHCE and RHD genes are considered. The very high level of amino acid divergence between the two genes is observed only in a short region around exon 7. It is known that exon 7 encodes amino acids that characterize the difference between the RHCE and RHD antigens. The observed pattern of DNA variation in this region is consistent with the selection model developed in this article, suggesting that strong selection might be working to maintain the RHCE/RHD antigen variation in the two-locus system. The selection intensity is estimated on the basis of the theoretical result.

Alleles↗
PubMed1995

Hepatic transport of rose bengal by perfused rabbit liver: the effect of albumin binding on the unidirectional rate constants.

The effect of albumin on the unidirectional rate constants for the hepatic transport of rose bengal was studied using perfused rabbit livers. Rabbit livers were perfused in a recirculating system with albumin concentrations between 10 and 600 microM and the disappearance of I-125 rose bengal following a bolus injection was recorded. A distributed model of hepatic transport was used to estimate the rate constants for influx into cells, efflux from cells to plasma and biliary excretion. When the rate constants were corrected for albumin binding, the influx, but not the efflux or excretion constant, was a steeply rising function of the perfusate albumin concentration. The result that the influx but not efflux constant is albumin dependent suggests that the phenomenon is not due to slow diffusion across an unstirred fluid layer or to nonequilibrium binding within such a layer. The possibility that the albumin-dependent influx is due to a direct exchange of rose bengal between albumin and a membrane carrier protein is also considered. The independence of the efflux constant and the albumin concentration makes this hypothesis less tenable. However, these data are consistent with the facilitation of albumin-ligand dissociation by liver cells. This analysis represents the first reduction to practice of distributed modeling of disappearance curves. The fact that the excretion constant is independent of the perfusate albumin concentration serves to validate the model that has previously only been considered on theoretical grounds.

Animals↗
PubMed2005

Contrasting effects of chloride on the toxicity of silver to two green algae, Pseudokirchneriella subcapitata and Chlamydomonas reinhardtii.

Short-term silver toxicity was determined for two freshwater algae, Pseudokirchneriella subcapitata and Chlamydomonas reinhardtii, in the presence and absence of chloride. Silver speciation in the exposure media was controlled and algal growth was measured over 6 h. For P. subcapitata, an alga with low Ag uptake fluxes, silver toxicity could be predicted on the basis of the free Ag+ concentration, in the presence or absence of significant complexation by chloride ions, as predicted by the biotic ligand model (BLM). For C. reinhardtii, an alga with high Ag uptake fluxes, silver toxicity was better predicted by the concentration of all labile dissolved Ag species than by free silver, a result that is consistent with diffusion through the unstirred layer surrounding the cell surface being the rate-limiting step in silver uptake. For both species, growth inhibition could be predicted on the basis of the Ag intracellular quota in the presence or absence of chloride, indicating that silver toxicity is a direct result of intracellular accumulation rather than cell surface interactions.

Chlorides↗
PubMed2002

Neuroprotective gene therapy for Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease characterised by a progressive loss of the dopaminergic neurones in the substantia nigra pars compacta. Accumulating evidence indicates that apoptosis contributes to neuronal cell death in PD patients' brain. Excitotoxicity, oxidative stress, and mitochondrial respiratory failure are thought to be the key inducers of the apoptotic cascade. Even though the initial cause and the mechanism of degeneration are poorly understood, neuroprotection can be achieved by interfering with neuronal cell death either directly or by preventing neuronal dysfunction. Potential agents for neuroprotection are neurotrophic factors, inhibitors of apoptosis or anti-oxidative agents. However, the existence of the blood-brain barrier precludes systemic delivery of these factors. In situ gene delivery provides strategies for local and sustained administration of protective factors at physiologically relevant doses. Viral vectors mediating stable gene expression in the central nervous system exist and are still under development. Efficacy of these vectors has repeatedly been demonstrated in the animal models both ex vivo and in vivo. Ex vivo gene delivery could furthermore be combined with cell replacement therapies by transplanting genetically modified cells compensating for the lost neuronal cell population in order to provide neuroprotection to both the grafted cells and degenerating host neurones. However, several aspects of gene transfer, such as uncontrolled diffusion, axonal transport, unpredictable site of integration and immunological responses, still raise safety concerns and justify further development of viral and non-viral vectors as well as genetic elements with tightly controlled gene expression. Various relevant animal models for Parkinson's disease are available for the evaluation of gene therapy strategies. These include induction of cell death in specific neurone population through administration of toxins either directly in the brain or systemically, as well as transgenic mice expressing human disease-associated mutations.

Animals↗
PubMed2004

Absorber's effect projected directly above improves spatial resolution in near infrared backscattered imaging.

The spatial resolution of near infrared spectroscopic imaging in brain function mapping studies needs to be improved. Most near infrared spectroscopic imaging systems use optical fibers that are arranged like a lattice. The light source and the detector have one-on-one correspondence at intervals of about 3 cm. In this study, we apply several detectors against one source to improve spatial resolution. We assume that a local absorber within a strong scattering medium is a model for local cerebral activation. When we calculate absorbance, which is used to spectroscopically calculate hemoglobin concentration, the peak position shifts away from above the position where an absorber is located. As far as absorbance is calculated, we cannot obtain spatial information about the absorber even if many detectors are used against one source. When we calculate the difference between detected light intensities, however, we demonstrate that an absorber projected onto the measuring surface has an influence directly above it. We predict this property from a light diffusion equation and also prove it experimentally through measurements of a uniform resinous phantom with an absorber. This is one of the basic principles supporting the achievement of higher spatial resolutions with near infrared spectroscopic imaging.

Absorption↗
PubMed2006

Computed pore potentials of the nicotinic acetylcholine receptor.

Electrostatic surface potentials in the vestibule of the nicotinic acetylcholine receptor (nAChR) were computed from structural models using the University of Houston Brownian Dynamics program to determine their effect on ion conduction and ionic selectivity. To further determine whether computed potentials accurately reflect the electrostatic environment of the channel, the potentials were used to predict the rate constants for diffusion-enhanced fluorescence energy transfer; the calculated energy transfer rates are directly comparable with those determined experimentally (see companion article by Meltzer et al. in this issue). To include any effects on the local potentials by the bound acceptor fluorophore crystal violet, its binding site was first localized within the pore by fluorescence energy transfer measurements from dansyl-C6-choline bound to the agonist sites and also by simulations of binding using Autodock. To compare the computed potentials with those determined experimentally, we used the predicted energy transfer rates from Tb3+ chelates of varying charge to calculate an expected potential using the Boltzmann relationship. This expected potential (from -20 to -40 mV) overestimates the values determined experimentally (from -10 to -25 mV) by two- to fourfold at similar conditions of ionic strength. Although the results indicate a basic discrepancy between experimental and computed surface potentials, both methods demonstrate that the vestibular potential has a relatively small effect on conduction and selectivity.

Cell Membrane↗