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At least 1,027 records · Page 57Linked to original sources
PubMed1995

Dynamical behaviour of biological regulatory networks--II. Immunity control in bacteriophage lambda.

A number of bacterial and viral genes take part in the decision between lysis and lysogenization in temperate bacteriophages. In the lambda case, at least five viral genes (cI, cro, cII, N and cIII) and several bacterial genes are involved. Several attempts have been made to model this complex regulatory network. Our approach is based on a logical method described in the first paper of the series which formalizes the interactions between the elements of a regulatory network in terms of discrete variables, functions and parameters. In this paper two models are described and discussed, the first (two-variable model) focused on cI and cro interactions, the second (four-variable model) considering, in addition, genes cII and N. The treatment presented emphasizes the roles of positive and negative feedback loops and their interactions in the development of the phage. The role of the loops between cI and cro, and of cI on itself (which both have to be positive loops) was discovered earlier; this group's contribution to this aspect mainly deals with the possibility of treating these loops as parts of a more extended network. In contrast, the role of the negative loop of cro on itself had apparently remained unexplained. We realized that this loop buffers the expression of genes cro itself. cII, O and P against the inflation due to the rapid replication of the phage. More generally, negative auto-control of a gene appears an efficient way to render its expression insensitive (or less sensitive) to gene dosage, whereas a simple negative control would not provide this result.

Bacteria↗
PubMed2005

A marvel of mucosal T cells and secretory antibodies for the creation of first lines of defense.

The mucosal immune system acts as a first line of defense against bacterial and viral infections while also playing a crucial role in the establishment and maintenance of mucosal homeostasis between the host and the outside environment. In addition to epithelial cells and antigen-presenting cells (dendritic cells and macrophages), B and T lymphocytes form a dynamic mucosal network for the induction and regulation of secretory IgA (S-IgA) and cytotoxic T lymphocyte (CTL) responses. This review seeks to shed light on the pathways of induction and regulation of these responses and to elucidate the role they simultaneously play in fending off pathogen invasion and maintaining mucosal homeostasis.

Animals↗
PubMed2001

Silicon synaptic depression.

The recent quantitative description of activity-dependent depression in the synaptic transmission between cortical neurons has lead to many interesting suggestions of possible computational implications. Based on a simple biological model, we have constructed an analog circuit that emulates the properties of short-term depressing synapses. The circuit comprises only seven transistors and two capacitors per synapse, and is able to reproduce computational features of depressing synapses such as the 1/F law, the detection of long intervals of presynaptic silence and the sensitivity to redistribution of presynaptic firing rates. It provides a useful basis for implementing neural networks with dynamical synapses.

Computer Simulation↗
PubMed2006

Respondent-driven sampling of injection drug users in two U.S.-Mexico border cities: recruitment dynamics and impact on estimates of HIV and syphilis prevalence.

Respondent-driven sampling (RDS), a chain referral sampling approach, is increasingly used to recruit participants from hard-to-reach populations, such as injection drug users (IDUs). Using RDS, we recruited IDUs in Tijuana and Ciudad (Cd.) Juárez, two Mexican cities bordering San Diego, CA and El Paso, TX, respectively, and compared recruitment dynamics, reported network size, and estimates of HIV and syphilis prevalence. Between February and April 2005, we used RDS to recruit IDUs in Tijuana (15 seeds, 207 recruits) and Cd. Juárez (9 seeds, 197 recruits), Mexico for a cross-sectional study of behavioral and contextual factors associated with HIV, HCV and syphilis infections. All subjects provided informed consent, an anonymous interview, and a venous blood sample for serologic testing of HIV, HCV, HBV (Cd. Juárez only) and syphilis antibody. Log-linear models were used to analyze the association between the state of the recruiter and that of the recruitee in the referral chains, and population estimates of the presence of syphilis antibody were obtained, correcting for biased sampling using RDS-based estimators. Sampling of the targeted 200 recruits per city was achieved rapidly (2 months in Tijuana, 2 weeks in Cd. Juárez). After excluding seeds and missing data, the sample prevalence of HCV, HIV and syphilis were 96.6, 1.9 and 13.5% respectively in Tijuana, and 95.3, 4.1, and 2.7% respectively in Cd. Juárez (where HBV prevalence was 84.7%). Syphilis cases were clustered in recruitment trees. RDS-corrected estimates of syphilis antibody prevalence ranged from 12.8 to 26.8% in Tijuana and from 2.9 to 15.6% in Ciudad Juárez, depending on how recruitment patterns were modeled, and assumptions about how network size affected an individual's probability of being included in the sample. RDS was an effective method to rapidly recruit IDUs in these cities. Although the frequency of HIV was low, syphilis prevalence was high, particularly in Tijuana. RDS-corrected estimates of syphilis prevalence were sensitive to model assumptions, suggesting that further validation of RDS is necessary.

Adolescent↗
PubMed1995

Large-scale cortical networks and cognition.

The well-known parcellation of the mammalian cerebral cortex into a large number of functionally distinct cytoarchitectonic areas presents a problem for understanding the complex cortical integrative functions that underlie cognition. How do cortical areas having unique individual functional properties cooperate to accomplish these complex operations? Do neurons distributed throughout the cerebral cortex act together in large-scale functional assemblages? This review examines the substantial body of evidence supporting the view that complex integrative functions are carried out by large-scale networks of cortical areas. Pathway tracing studies in non-human primates have revealed widely distributed networks of interconnected cortical areas, providing an anatomical substrate for large-scale parallel processing of information in the cerebral cortex. Functional coactivation of multiple cortical areas has been demonstrated by neurophysiological studies in non-human primates and several different cognitive functions have been shown to depend on multiple distributed areas by human neuropsychological studies. Electrophysiological studies on interareal synchronization have provided evidence that active neurons in different cortical areas may become not only coactive, but also functionally interdependent. The computational advantages of synchronization between cortical areas in large-scale networks have been elucidated by studies using artificial neural network models. Recent observations of time-varying multi-areal cortical synchronization suggest that the functional topology of a large-scale cortical network is dynamically reorganized during visuomotor behavior.

Animals↗
PubMed1987

Glial and glycoconjugate boundaries during postnatal development of the central nervous system.

The localization of glycosylated molecules and glia has been studied during early postnatal development in the mouse central nervous system (CNS) using autoradiographic detection of radiolabeled fucose incorporation, and in sections processed either for histochemistry or immunocytochemistry following binding of labeled lectins or an antibody to glial fibrillary acidic protein. Radiolabeled sugar incorporation, lectin binding of glycoconjugates, and glial labeling all reveal borders between nuclei within the diencephalon, midbrain, and brainstem through the first postnatal week. Glycoconjugate and glial boundaries exist throughout the CNS during pattern formation events, and they also are seen in relation to fine aspects of developing functional organization within individual structures (e.g. segmentation associated with the representation of mystacial vibrissae within the brainstem trigeminal complex). The observation that each of the probes employed in this study fails to label boundary organization during later postnatal times suggests that the distribution and chemistry of the glial/glycoconjugate network are dynamic, and they change in accordance with distinct maturational states of the nervous system.

Animals↗
PubMed1994

Distribution of the phosphorylated microtubule-associated protein tau in developing cortical neurons.

During brain development, the microtubule-associated protein tau presents a transient state of high phosphorylation. We have investigated the developmental distribution of the phosphorylated fetal-type tau in the developing rat cortex and in cultures of embryonic cortical neurons, using antibodies which react with tau in a phosphorylation-dependent manner. The phosphorylated fetal-type tau was present in the developing cortex at 20 days but not at 18 days of embryonic life and was not detected before four to five days in neuronal culture. The cyclin-dependent kinase p34cdc2 was expressed only in germinal layers in the embryonic brain and was not co-localized with phosphorylated tau. After 10 days of postnatal life, the phosphorylated tau progressively disappeared from cortical neurons, disappearing first from the deepest cortical layers where neurons are ontogenetically the oldest. Phosphorylated tau was found in axons and dendrites of cortical neurons at all developmental stages whereas unphosphorylated tau tended to disappear from dendrites during development. The timing of appearance of phosphorylated tau in the cortex, by comparison with the expression of other developmental markers, indicates that phosphorylated tau is present at a high level only during the period of intense neuritic outgrowth and that it disappears during the period of neurite stabilization and synaptogenesis, concomitantly to the expression of adult tau isoforms. In control cultures and in cultures treated with colchicine, the phosphorylated tau was not associated to cold-stable and to colchicine-resistant microtubules. These in vivo results suggest that the high expression of phosphorylated tau species is correlated with the presence of a dynamic microtubule network during a period of high plasticity in the developing brain.

Animals↗
PubMed1983

Autoantigens in an immunological network.

An autoantigen network, consisting of all non-lymphoid cells and a subset of peripherally located autoregulatory lymphocytes, is proposed. By equilibrating a web of idiotypic stimulation (helper activity) and antiidiotypic inhibition (suppressor activity) directed at each tissue differentiation antigen, this network quantitatively limits autoantigen expression and thereby regulates the differentiation and growth homeostatic processes these autoantigens mediate. Perturbations of the network's dynamic equilibrium secondary to viral infection, somatic mutation, or interaction with environmental agents would clinically manifest themselves as autoimmune tissue destruction, benign or malignant nonlymphoid neoplasia, and lymphoproliferative disorders.

Antigens↗
PubMed1996

Asymptotic Stationarity of Discrete-time Stochastic Neural Networks.

This paper deals with a class of synchronous discrete-time stochastic neural network models. Dynamic stabilities (or asymptotic stationarities) are analysed for two sub-classes of the models, i.e., a class of stochasticized models from Little, and a class of Hopfield-type stochastic models. Copyright 1996 Elsevier Science Ltd.

Journal Article↗
PubMed1994

Biomechanics of small bowel motility.

A biomechanical model and results of numerical simulation of the propagation of electromechanical waves of deformation along the small bowel are presented. The organ is modelled as a soft orthotropic cylindrical biological shell reinforced by orthogonally interwoven smooth muscle elements, embedded in a connective tissue network. The dynamic reaction starts as a response to the propagation of a depolarization wave along the smooth muscle layers. The muscle layers contract independently but in a coordinated way with the generation of active forces. The mechanical properties of the wall are assumed to be nonlinear. Deformations of the bioshell are finite. The governing system of equations is obtained and solved numerically. The finite-difference method of the second order accuracy over the time and space variables was used. The dynamics of strain distribution in the biological shell and shape changes are analysed.

Biomechanical Phenomena↗
PubMed2006

Escherichia coli as a platform for functional expression of plant P450 carotene hydroxylases.

Carotenoids and their derivatives are essential for growth, development, and signaling in plants and have an added benefit as nutraceuticals in food crops. Despite the importance of the biosynthetic pathway, there remain open questions regarding some of the later enzymes in the pathway. The CYP97 family of P450 enzymes was predicted to function in carotene ring hydroxylation, to convert provitamin A carotenes to non-provitamin A xanthophylls. However, substrate specificity was difficult to investigate directly in plants, which mask enzyme activities by a complex and dynamic metabolic network. To characterize the enzymes more directly, we amplified cDNAs from a model crop, Oryza sativa, and used functional complementation in Escherichia coli to test activity and specificity of members of Clans A and C. This heterologous system will be valuable for further study of enzyme interactions and substrate utilization needed to understand better the role of CYP97 hydroxylases in plant carotenoid biosynthesis.

Amino Acid Sequence↗
PubMed2006

Effects of pore structure and molecular size on diffusion in chromatographic adsorbents.

Two computational approaches, namely Brownian dynamics and network modeling, are presented for predicting effective diffusion coefficients of probes of different sizes in three chromatographic adsorbents, the structural properties of which were determined previously using electron tomography. Three-dimensional reconstructions of the adsorbents provide detailed, explicit characteristics of the pore network, so that no assumptions have to be made regarding pore properties such as connectivity, pore radius and pore length. The diffusivity predictions obtained from the two modeling approaches were compared to experimental diffusivities measured for dextran and protein probes. Both computational methods captured the same qualitative results, while their predictive capabilities varied among adsorbents.

Adsorption↗
PubMed2026

Mechanistic insights into Claudin-14 dysfunction implicated in veins of Galen malformation.

Claudin-14 (CLDN14) is a key component of tight junctions (TJs) critical for maintaining paracellular barrier function. Variants of CLDN14 have been linked to Vein of Galen malformations (VOGMs), a rare cerebrovascular disorder; however, the molecular mechanisms underlying their pathogenicity remain unknown. Here, we investigate the mechanistic effects of two VOGM-associated mutations, A113P and V143M, using reinforcement-learning driven enhanced sampling molecular dynamics simulations combined with DiffNets-based deep learning and independent trajectory-wide structural analyses. Our analysis reveals that A113P induces broader structural disruption of CLDN14, perturbing paracellular sealing, pore symmetry, and inter-protomer communication, whereas V143M induces structural rearrangements centred around TM3 and the TM3-ECL2 region. In both cases, mutation-specific alterations are observed in structural stability and interfacial organization across oligomeric assemblies. Notably, these effects are qualitatively consistent across different modelled architectures, despite variability in local responses. In the absence of experimentally resolved structures, the structural perturbations reported here provide a mechanistic understanding of how VOGM-associated variants may influence CLDN14 structure and dynamics.

Aneurysm↗
PubMed2004

A cross-platform model for secure Electronic Health Record communication.

During the past decade, there have been many regional, national and European projects focused on the development of platforms for secure access and sharing of distributed patient information. A platform is needed because present local or enterprise-wide information systems are typically not intended for cross-organisational secure access of patient data. Most of the present secure platforms are local or regional. Commonly used platform types in the health care environment vary from secure point-to-point communication systems to internet-based portals. This paper defines an enhanced cross-security platform which makes it possible for different kinds of local, regional, and national health information systems to communicate in a secure way. The proposed evolutionary way interconnects regional or national security domains with the help of a cross-platform zone. A more revolutionary model based on peer-to-peer Grid like networks and dynamic security credentials is also discussed. The proposed evolutionary model uses cross-domain security and interoperability services to ensure secure communication and interoperability between different security domains. The platform supports both communication defined beforehand and adhoc dynamic access to distributed electronic health records (EHRs). The internet is proposed as the "glue" between different regional or national security domains.

Access to Information↗
PubMed2006

Effects of rapid and slow potassium repolarization currents and calcium dynamics on hysteresis in restitution of action potential duration.

We used a mathematical model to investigate effects of repolarizing currents I(kr) and I(ks), calcium (Ca) current I(CaL), and Ca dynamics in network sarcoplasmic reticulum and junctional sarcoplasmic reticulum (JSR) on hysteresis in restitution of action potential duration. Enhanced I(kr) increased slope of restitution, hysteresis loop thickness, and delay between peaks of diastolic intervals and action potential duration. Increase in I(ks) decreased loop thickness and peak delay. Decrease in I(CaL) had effects similar to increasing I(kr), except slope of restitution decreased markedly. Uptake of Ca into the network sarcoplasmic reticulum had less effect on hysteresis than transfer of Ca into JSR. Faster transfer of Ca into JSR markedly decreased loop thickness and peak delay. Our results provide insight into mechanisms responsible for this newly identified property of restitution. Such information will be valuable in studies where modification of hysteresis is used to investigate its role in arrhythmogenesis.

Action Potentials↗
PubMedDate not supplied

Crossmodal integration for perception and action.

The integration of information from different sensory modalities has many advantages for human observers, including increase of salience, resolution of perceptual ambiguities, and unified perception of objects and surroundings. Several behavioral, electrophysiological and neuroimaging data collected in various tasks, including localization and detection of spatial events, crossmodal perception of object properties and scene analysis are reviewed here. All the results highlight the multiple faces of crossmodal interactions and provide converging evidence that the brain takes advantages of spatial and temporal coincidence between spatial events in the crossmodal binding of spatial features gathered through different modalities. Furthermore, the elaboration of a multimodal percept appears to be based on an adaptive combination of the contribution of each modality, according to the intrinsic reliability of sensory cue, which itself depends on the task at hand and the kind of perceptual cues involved in sensory processing. Computational models based on bayesian sensory estimation provide valuable explanations of the way perceptual system could perform such crossmodal integration. Recent anatomical evidence suggest that crossmodal interactions affect early stages of sensory processing, and could be mediated through a dynamic recurrent network involving backprojections from multimodal areas as well as lateral connections that can modulate the activity of primary sensory cortices, though future behavioral and neurophysiological studies should allow a better understanding of the underlying mechanisms.

Animals↗
PubMed2005

The dynamics of histone H1 function in chromatin.

Over 80% of the nucleosomes in chromatin contain histone H1, a protein family known to affect the structure and activity of chromatin. Genetic studies and in vivo imaging experiments are changing the traditional view of H1 function and mechanism of action. H1 variants are partially redundant, mobile molecules that interact with nucleosomes as members of a dynamic protein network and serve as fine tuners of chromatin function.

Animals↗