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At least 487 records · Page 27Linked to original sources
PubMed1999

Separation of propulsive and adhesive traction stresses in locomoting keratocytes.

Strong, actomyosin-dependent, pinching tractions in steadily locomoting (gliding) fish keratocytes revealed by traction imaging present a paradox, since only forces perpendicular to the direction of locomotion are apparent, leaving the actual propulsive forces unresolved. When keratocytes become transiently "stuck" by their trailing edge and adopt a fibroblast-like morphology, the tractions opposing locomotion are concentrated into the tail, leaving the active pinching and propulsive tractions clearly visible under the cell body. Stuck keratocytes can develop approximately 1 mdyn (10,000 pN) total propulsive thrust, originating in the wings of the cell. The leading lamella develops no detectable propulsive traction, even when the cell pulls on its transient tail anchorage. The separation of propulsive and adhesive tractions in the stuck phenotype leads to a mechanically consistent hypothesis that resolves the traction paradox for gliding keratocytes: the propulsive tractions driving locomotion are normally canceled by adhesive tractions resisting locomotion, leaving only the pinching tractions as a resultant. The resolution of the traction pattern into its components specifies conditions to be met for models of cytoskeletal force production, such as the dynamic network contraction model (Svitkina, T.M., A.B. Verkhovsky, K.M. McQuade, and G.G. Borisy. 1997. J. Cell Biol. 139:397-415). The traction pattern associated with cells undergoing sharp turns differs markedly from the normal pinching traction pattern, and can be accounted for by postulating an asymmetry in contractile activity of the opposed lateral wings of the cell.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2003

Myo4p and She3p are required for cortical ER inheritance in Saccharomyces cerevisiae.

Myo4p is a nonessential type V myosin required for the bud tip localization of ASH1 and IST2 mRNA. These mRNAs associate with Myo4p via the She2p and She3p proteins. She3p is an adaptor protein that links Myo4p to its cargo. She2p binds to ASH1 and IST2 mRNA, while She3p binds to both She2p and Myo4p. Here we show that Myo4p and She3p, but not She2p, are required for the inheritance of cortical ER in the budding yeast Saccharomyces cerevisiae. Consistent with this observation, we find that cortical ER inheritance is independent of mRNA transport. Cortical ER is a dynamic network that forms cytoplasmic tubular connections to the nuclear envelope. ER tubules failed to grow when actin polymerization was blocked with the drug latrunculin A (Lat-A). Additionally, a reduction in the number of cytoplasmic ER tubules was observed in Lat-A-treated and myo4Delta cells. Our results suggest that Myo4p and She3p facilitate the growth and orientation of ER tubules.

Actin Cytoskeleton↗
PubMed1998

Mathematical model of the CA1 region of the rat hippocampus.

A mathematical transcription of the intrinsic circuit of the CA1 region of the rat dorsal hippocampus was made and the model parameters adjusted according to experimental data from intracellular recordings and single channel kinetics. This model was able to simulate well the profile of the field potentials recorded extracellularly and the well known phenomenon of the paired-pulse depression. The results suggest that the depression of the second pulse, often interpreted in the literature as resulting from GABA(A) inhibition, can also be due to 'shunting' effects on the CA1 pyramids' membrane. The rhythmic oscillations of the field potential (EEG) was obtained as an emergent property of the network dynamics. The frequency of the field oscillation followed the main synaptic input in the region (Schaffer collaterals).

Animals↗
PubMed1997

Mitochondrial transmission during mating in Saccharomyces cerevisiae is determined by mitochondrial fusion and fission and the intramitochondrial segregation of mitochondrial DNA.

To gain insight into the process of mitochondrial transmission in yeast, we directly labeled mitochondrial proteins and mitochondrial DNA (mtDNA) and observed their fate after the fusion of two cells. To this end, mitochondrial proteins in haploid cells of opposite mating type were labeled with different fluorescent dyes and observed by fluorescence microscopy after mating of the cells. Parental mitochondrial protein markers rapidly redistributed and colocalized throughout zygotes, indicating that during mating, parental mitochondria fuse and their protein contents intermix, consistent with results previously obtained with a single parentally derived protein marker. Analysis of the three-dimensional structure and dynamics of mitochondria in living cells with wide-field fluorescence microscopy indicated that mitochondria form a single dynamic network, whose continuity is maintained by a balanced frequency of fission and fusion events. Thus, the complete mixing of mitochondrial proteins can be explained by the formation of one continuous mitochondrial compartment after mating. In marked contrast to the mixing of parental mitochondrial proteins after fusion, mtDNA (labeled with the thymidine analogue 5-bromodeoxyuridine) remained distinctly localized to one half of the zygotic cell. This observation provides a direct explanation for the genetically observed nonrandom patterns of mtDNA transmission. We propose that anchoring of mtDNA within the organelle is linked to an active segregation mechanism that ensures accurate inheritance of mtDNA along with the organelle.

Cell Division↗
PubMed2005

Evolution of web services in bioinformatics.

Bioinformaticians have developed large collections of tools to make sense of the rapidly growing pool of molecular biological data. Biological systems tend to be complex and in order to understand them, it is often necessary to link many data sets and use more than one tool. Therefore, bioinformaticians have experimented with several strategies to try to integrate data sets and tools. Owing to the lack of standards for data sets and the interfaces of the tools this is not a trivial task. Over the past few years building services with web-based interfaces has become a popular way of sharing the data and tools that have resulted from many bioinformatics projects. This paper discusses the interoperability problem and how web services are being used to try to solve it, resulting in the evolution of tools with web interfaces from HTML/web form-based tools not suited for automatic workflow generation to a dynamic network of XML-based web services that can easily be used to create pipelines.

Computational Biology↗
PubMed2004

Predicting gene regulation by sigma factors in Bacillus subtilis from genome-wide data.

MOTIVATION: Sigma factors regulate the expression of genes in Bacillus subtilis at the transcriptional level. We assess the accuracy of a fold-change analysis, Bayesian networks, dynamic models and supervised learning based on coregulation in predicting gene regulation by sigma factors from gene expression data. To improve the prediction accuracy, we combine sequence information with expression data by adding their log-likelihood scores and by using a logistic regression model. We use the resulting score function to discover currently unknown gene regulations by sigma factors. RESULTS: The coregulation-based supervised learning method gave the most accurate prediction of sigma factors from expression data. We found that the logistic regression model effectively combines expression data with sequence information. In a genome-wide search, highly significant logistic regression scores were found for several genes whose transcriptional regulation is currently unknown. We provide the corresponding RNA polymerase binding sites to enable a straightforward experimental verification of these predictions.

Algorithms↗
PubMed2006

The neural correlates of human working memory for haptically explored object orientations.

Skillful object manipulation requires that haptically explored spatial object characteristics like orientation be adequately represented in working memory. In the current functional magnetic resonance imaging study, healthy right-handed participants explored a bar-shaped reference object with the left hand, memorizing its orientation. After a variable delay (0.5, 5, or 10 s), participants used their right hand to match the orientation by rotating a second, identical object. In the first seconds of the delay, right sensorimotor cortex was active, whereas clusters in left anterior prefrontal cortex (aPFC) (Brodmann area 10) became dominant 2 s after the end of exploration, showing sustained activity for several seconds. In contrast, left parieto-occipital cortex was involved toward the end of the delay interval. Our results indicate that a dynamic network of brain areas subserves hapticospatial information processing in the delay between haptic stimulus exploration and orientation matching. We propose that haptic sensory traces, maintained in contralateral sensorimotor cortex, are transformed into more abstract hapticospatial representations in the early delay stages. Maintenance of these representations engages aPFC and parieto-occipital cortex. Whereas aPFC possibly integrates spatial and motor components of hapticospatial working memory, parieto-occipital cortex might be involved in orientation imagery, supporting working memory, and the preparation of haptic matching.

Adult↗
PubMed2005

Critical branching captures activity in living neural networks and maximizes the number of metastable States.

Recent experimental work has shown that activity in living neural networks can propagate as a critical branching process that revisits many metastable states. Neural network theory suggests that attracting states could store information, but little is known about how a branching process could form such states. Here we use a branching process to model actual data and to explore metastable states in the network. When we tune the branching parameter to the critical point, we find that metastable states are most numerous and that network dynamics are not attracting, but neutral.

Animals↗
PubMed2000

A Jini service to reconstruct tomographic data.

Distributed computing that uses dynamic networks will change the way we work and communicate thanks to the interaction of devices and services, that are automatically added and removed from the network as needed. The Jini technology, which is built atop the Java programming language, provides a homogenous view of the network and extends the ability of code to migrate in Java. This software design model simplifies the configuration and access to hardware devices and software services in a network. Thus, it becomes possible to execute new services without pre-installing software on client machines. This new programming paradigm is especially important in medical applications, where the reliable transmission of information is essential. This paper demonstrates how single photon emission computerized tomography data can be iteratively reconstructed using a Jini service.

Computer Communication Networks↗
PubMed2004

Theta-modulated feedforward network generates rate and phase coded firing in the entorhino-hippocampal system.

Principal cells of the hippocampus and of its only cortical input region, the entorhinal cortex exhibit place specific activity in the freely moving rat. While entorhinal cells have widely tuned place fields, hippocampal place fields are more localized and determine not only the rate but also the timing of place cell spikes. Several models have successfully attempted to explain this fine tuning making use of intrahippocampal attractor network dynamics provided by the recurrent collaterals of hippocampal area CA3. Recent experimental evidence shows that CA1 place cells preserve their tuning curves even in the absence of input from CA3. We propose a model in which entorhinal and hippocampal pyramidal cell populations are only connected via feedforward connections. Synaptic transmission in our sytem is gated by a class of interneurons inhibiting specifically the entorhino-hippocampal pathway. Theta rhythm modulates the activity of each component. Our results show that rhythmic shunting inhibition endows entorhinal cells with a novel type of temporal code conveyed by the phase jitter of individual spikes. This converts coarsely tuned place-specific activity in the entorhinal cortex to velocity-dependent postsynaptic excitation and, thus, provides hippocampal place cells with an input that has recently been proposed to account for their rate and phase coded firing. Hippocampal place fields are generated through this mechanism and also shown to be robust against variations in the level of tonic inhibition.

Action Potentials↗
PubMed1997

The structure and function of the cutaneous vasculature.

The cutaneous vasculature is a dynamic network that responds to its environment depending upon specific demands in time and space. Changes in its functional role can be observed as changes in gross structure, or by alterations in specific gene expression or function. The improved understanding in mechanisms by which EC participate in inflammatory, neoplastic, and reparative processes will likely reap great benefits in our understanding and treatment of cutaneous disease.

Endothelium↗
PubMed2004

Visualization of protein interactions in living plant cells using bimolecular fluorescence complementation.

Dynamic networks of protein-protein interactions regulate numerous cellular processes and determine the ability to respond appropriately to environmental stimuli. However, the investigation of protein complex formation in living plant cells by methods such as fluorescence resonance energy transfer has remained experimentally difficult, time consuming and requires sophisticated technical equipment. Here, we report the implementation of a bimolecular fluorescence complementation (BiFC) technique for visualization of protein-protein interactions in plant cells. This approach relies on the formation of a fluorescent complex by two non-fluorescent fragments of the yellow fluorescent protein brought together by association of interacting proteins fused to these fragments (Hu et al., 2002). To enable BiFC analyses in plant cells, we generated different complementary sets of expression vectors, which enable protein interaction studies in transiently or stably transformed cells. These vectors were used to investigate and visualize homodimerization of the basic leucine zipper (bZIP) transcription factor bZIP63 and the zinc finger protein lesion simulating disease 1 (LSD1) from Arabidopsis as well as the dimer formation of the tobacco 14-3-3 protein T14-3c. The interaction analyses of these model proteins established the feasibility of BiFC analyses for efficient visualization of structurally distinct proteins in different cellular compartments. Our investigations revealed a remarkable signal fluorescence intensity of interacting protein complexes as well as a high reproducibility and technical simplicity of the method in different plant systems. Consequently, the BiFC approach should significantly facilitate the visualization of the subcellular sites of protein interactions under conditions that closely reflect the normal physiological environment.

Arabidopsis↗
PubMed2006

Does stress exacerbate liver diseases?

Although anecdotal comments on detrimental effects of psychosocial stress on liver diseases can be found even in the early literature, only recently has scientific evidence been reported. The present article reviewed such evidence to demonstrate how stress exacerbates liver diseases. A search of the literature from the last two decades was performed using MEDLINE by pairing 'psychological stress' with 'liver' or 'hepatitis.' Additional research was conducted by screening the bibliographies of articles retrieved in the MEDLINE search. The search results showed that the principal effectors of the activated hypothalamic-pituitary-adrenal (HPA) axis, glucocorticoids, can exert a facilitative effect on the hepatic inflammatory response and even increase the risk of developing hepatocellular carcinoma. For certain liver diseases, defective HPA axis activation, which probably contributed to the exacerbation of the liver disease, has been reported. The efferent sympathetic/adrenomedullary system mainly contributes to the stress-induced exacerbation of liver diseases via its neurotransmitters, the catecholamines. In contrast, the efferent parasympathetic nervous system elicits an inhibitory effect on the development of hepatic inflammation. In conclusion, the pathophysiological interaction between stress and the liver appears to be regulated by the complex, dynamic networks of both the endocrine and autonomic nervous systems, which implies a further need for basic research into the involved mechanisms and for clinical evidence to apply psychosocial support to patients with chronic liver diseases.

Animals↗
PubMed2004

The role of early visual cortex in visual integration: a neural model of recurrent interaction.

This paper presents a model on the potential functional roles of the early visual cortex in the primate visual system. Our hypothesis is that early visual areas, such as V1, are important for continual interaction among various higher order visual areas during visual processing. The interaction is mediated by recurrent connections between higher order visual areas and V1, manifested in the long-latency context-sensitive activities often observed in neurophysiological experiments, and is responsible for the re-integration of information analysed by the higher visual areas. Specifically, we considered the case of integrating 'what' and 'where' information from the ventral and dorsal streams. We found that such a cortical architecture provides simple solutions and fresh insights into the problems of attentional routing and visual search. The computational viability of this architecture was tested by simulating a large-scale neural dynamical network.

Attention↗
PubMed2006

Cell culture models to investigate the selective vulnerability of motoneuronal mitochondria to familial ALS-linked G93ASOD1.

Mitochondrial damage induced by superoxide dismutase (SOD1) mutants has been proposed to have a causative role in the selective degeneration of motoneurons in amyotrophic lateral sclerosis (ALS). In order to investigate the basis of the tissue specificity of mutant SOD1 we compared the effect of the continuous expression of wild-type or mutant (G93A) human SOD1 on mitochondrial morphology in the NSC-34 motoneuronal-like, the N18TG2 neuroblastoma and the non-neuronal Madin-Darby Canine Kidney (MDCK) cell lines. Morphological alterations of mitochondria were observed in NSC-34 expressing the G93A mutant (NSC-G93A) but not the wild-type SOD1, whereas a ten-fold greater level of total expression of the mutant had no effect on mitochondria of non-motoneuronal cell lines. Fragmented network, swelling and cristae remodelling but not vacuolization of mitochondria or other intracellular organelles were observed only in NSC-G93A cells. The mitochondrial alterations were not explained by a preferential localization of the mutant within NSC-G93A mitochondria, as a higher amount of the mutant SOD1 was found in mitochondria of MDCK-G93A cells. Our results suggest that mitochondrial vulnerability of motoneurons to G93ASOD1 is recapitulated in NSC-34 cells, and that peculiar features in network dynamics may account for the selective alterations of motoneuronal mitochondria.

Amyotrophic Lateral Sclerosis↗
PubMed2006

Differential expression of otoferlin in brain, vestibular system, immature and mature cochlea of the rat.

Mutations of the human otoferlin gene lead to an autosomal recessive nonsyndromic form of prelingual, sensorineural deafness (deafness autosomal recessive 9, DFNB9). Several studies have demonstrated expression of otoferlin in the inner ear and brain, and suggested a role of otoferlin in Ca(2+)-triggered exocytosis. So far, otoferlin expression profiles were solely based on the detection of mRNA. Here, we analysed the expression of otoferlin protein and mRNA using immunohistochemistry, in situ hybridization and RT-PCR in neonatal and mature Wistar rat tissue. In agreement with previous studies, otoferlin expression was found in the brain and in inner and vestibular hair cells. Otoferlin mRNA and protein was, however, also detected in mature outer hair cells of low-frequency processing cochlear turns and in auditory nerve fibres. In outer, inner and vestibular hair cells, otoferlin was subcellularly localized at a considerable distance from the presumed active release sites. Double-staining with the synaptic ribbon marker, C-terminal binding protein 2 (CtBP2), or the presynaptic Ca(2+)-channel, Ca(v)1.3, both assumed to mark the sites of vesicle fusion and transmitter release, did not colocalize with otoferlin expression and thus do not necessarily support a selected role of otoferlin in Ca(2+)-triggered exocytosis. The widespread distribution of otoferlin in neurons, nerve fibres and hair cells, and its subcellular distribution extending beyond the regions of synaptic vesicle fusion, i.e. coenrichment with the cytosolic Golgi matrix protein 130 (GM130) in inner hair cells or the early endosomal autoantigen 1 (EEA1) in outer hair cells support instead the idea of a more ubiquitous role of otoferlin in early/recycling endosome trans-Golgi network dynamics.

Age Factors↗
PubMed2006

Allometric scaling enhances stability in complex food webs.

Classic local stability theory predicts that complex ecological networks are unstable and are unlikely to persist despite empiricists' abundant documentation of such complexity in nature. This contradiction has puzzled biologists for decades. While some have explored how stability may be achieved in small modules of a few interacting species, rigorous demonstrations of how large complex and ecologically realistic networks dynamically persist remain scarce and inadequately understood. Here, we help fill this void by combining structural models of complex food webs with nonlinear bioenergetic models of population dynamics parameterized by biological rates that are allometrically scaled to populations' average body masses. Increasing predator-prey body mass ratios increase population persistence up to a saturation level that is reached by invertebrate and ectotherm vertebrate predators when being 10 or 100 times larger than their prey respectively. These values are corroborated by empirical predator-prey body mass ratios from a global data base. Moreover, negative effects of diversity (i.e. species richness) on stability (i.e. population persistence) become neutral or positive relationships at these empirical ratios. These results demonstrate that the predator-prey body mass ratios found in nature may be key to enabling persistence of populations in complex food webs and stabilizing the diversity of natural ecosystems.

Animals↗
PubMed1989

Establishment and functional implications of B-cell connectivity.

We have discussed some aspects of the structure of the normal immune system, particularly the B-cell compartment. We have argued: that a basic property of the natural antibody repertoire is constituted by high degrees of connectivity within the immune system as well as between the system and other components of the organism; that the complementarities constituting this connectivity are based on self-self interactions, high degrees of degeneracy or somatically selected interactions and that these properties are conserved through evolution, to ensure self-reference; that by evolutionary selection, antibody V-genes encoding such structural properties are ensured to be expressed early in ontogeny. The set of highly connected cells will be kept through ontogeny and form the basis for a compartment of naturally-activated lymphocytes making up 10-15% of the total lymphocyte population. As suggested before, this pool of connected cells may be responsible for maintenance of normal network dynamics and prevention of autoaggression.

Amino Acid Sequence↗