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Topology of gap junction networks in C. elegans.

Gap junctions are prevalent in every nervous system, but their role in information processing remains largely unknown. In C. elegans, the role of gap junctional communication in touch sensitivity has been demonstrated. In this animal, the entire complement of gap junctions in the nervous system is documented, therefore providing a good model for the computational investigation of circuit functions of gap junctions.We explored several hypotheses about the role of gap junctions in the nervous system of C. elegans by systematically analysing an anatomical database with recursive algorithms. We find that gap junctions connect different sets of neurons from those connected by chemical synapses. In addition, when analysing the topology of the gap-junction networks, we find that, surprisingly, most (92%) neurons in the worm are linked in a single gap-junction network. The worm nervous system can only be divided into smaller networks by assuming that two or more gap junctions are necessary for functional coupling or that neural activity has limited propagation. However, these groups, and others identified using algorithms with subsets or combinations of restrictive criteria, do not correspond to any known circuits identified in genetic and behavioral studies. Finally, we notice that the function of some gap junctions appears linked to their precise location on the neuronal processes. We propose that the location of the gap junctions within the neuron determines their functional role.

Animals↗

The cortical connections of area V6: an occipito-parietal network processing visual information.

The aim of this work was to study the cortical connections of area V6 by injecting neuronal tracers into different retinotopic representations of this area. To this purpose, we first functionally recognized V6 by recording from neurons of the parieto-occipital cortex in awake macaque monkeys. Penetrations with recording syringes were performed in the behaving animals in order to inject tracers exactly at the recording sites. The tracers were injected into the central or peripheral field representation of V6 in different hemispheres. Irrespective of whether injections were made in the centre or periphery, area V6 showed reciprocal connections with areas V1, V2, V3, V3A, V4T, the middle temporal area /V5 (MT/V5), the medial superior temporal area (MST), the medial intraparietal area (MIP), the ventral intraparietal area (VIP), the ventral part of the lateral intraparietal area and the ventral part of area V6A (V6AV). No labelled cells or terminals were found in the inferior temporal, mesial and frontal cortices. The connections of V6 with V1, and with all the retinotopically organized prestriate areas, were organized retinotopically. The connection of V6 with MIP suggests a visuotopic organization for this latter. Labelling in V6A and VIP after either central or peripheral V6 injections was very similar in location and extent, as expected on the basis of the nonretinotopic organization of these areas. We suggest that V6 plays a pivotal role in the dorsal visual stream, by distributing the visual information coming from the occipital lobe to the sensorimotor areas of the parietal cortex. Given the functional characteristics of the cells of this network, we suggest that it could perform the fast form and motion analyses needed for the visual guiding of arm movements as well as their coordination with the eyes and the head.

Animals↗

Quantitative analysis of axon collaterals of single neurons in layer IIa of the piriform cortex of the guinea pig.

To study the various types of neurons in layer IIa in the piriform cortex (PC) and the spatial distribution of their axons, axon collaterals of three neurons in layer IIa were labeled and quantitatively analyzed by intracellular injection of biocytin in the guinea pig. Individual neurons have highly distributed axon collaterals, which display a little tendency toward patchy concentrations inside as well as outside the PC. One semilunar cell in the posterior PC had 54-mm-long axon collaterals and 4,200 boutons, out of which 2,100 (49% of the total number of boutons) were distributed in the PC. One semilunar-pyramidal transitional cell in the posterior PC had 256-mm-long axon collaterals and 23,000 boutons, out of which 16,100 (70% of the total number of boutons) and 4,000 (18% of the total number of boutons) were respectively distributed in all layers and in layer Ia of the PC. One multipolar cell in the posterior PC had 188-mm-long axon collaterals and 18,000 boutons, out of which 13,700 (78% of the total number of boutons) were distributed in the PC. Our results revealed that the connection patterns of individual cells in layer IIa have most of the features required for an associative neural network, which may function as a content-addressable memory for the association of odor stimuli.

Animals↗

Magnetic resonance imaging of trabecular bone structure in the distal radius: relationship with X-ray tomographic microscopy and biomechanics.

The contribution of trabecular bone structure to bone strength is of considerable interest in the study of osteoporosis and other disorders characterized by changes in the skeletal system. Magnetic resonance (MR) imaging of trabecular bone has emerged as a promising technique for assessing trabecular bone structure. In this in vitro study we compare the measures of trabecular structure obtained using MR imaging and higher-resolution X-ray tomographic microscopy (XTM) imaging of cubes from human distal radii. The XTM image resolution is similar to that obtained from histomorphometric sections (18 microns isotropic), while the MR images are obtained at a resolution comparable to that achievable in vivo (156 x 156 x 300 microns). Standard histomorphometric measures, such as trabecular bone area fraction (synonymous with BV/TV), trabecular width, trabecular spacing and trabecular number, texture-related measures and three-dimensional connectivity (first Betti number/volume) of the trabecular network have been derived from these images. The variation in these parameters as a function of resolution, and the relationship between the structural parameters, bone mineral density and the elastic modulus are also examined. In MR images, because the resolution is comparable to the trabecular dimensions, partial volume effects occur, which complicate the segmentation of the image into bone and marrow phases. Using a standardized thresholding criterion for all images we find that there is an overestimation of trabecular bone area fraction (approximately 3 times), trabecular width (approximately 3 times), fractal dimension (approximately 1.4 times) and first Betti number/ volume (approximately 10 times), and an underestimation of trabecular spacing (approximately 1.6 times) in the MR images compared with the 18-microns XTM images. However, even for a factor of 9 difference in spatial resolution, the differences in the morphological trabecular structure measures ranged from a factor of 1.4 to 3.0. We have found that trabecular width, area fraction, number, fractal dimension and Betti number/volume measured from the XTM and MR images increases, while trabecular spacing decreases, as the bone mineral density and elastic modulus increase. A preliminary bivariate analysis showed that in addition to bone mineral density alone, the Betti number, trabecular number and spacing contributed to the prediction of the elastic modulus. This preliminary study indicates that measures of trabecular bone structure using MR imaging may play a role in the study of osteoporosis.

Absorptiometry, Photon↗

Puncture-proof picture archiving and communication system.

As we become increasingly dependent on our picture archiving and communications system (PACS) for the clinical practice of medicine, the demand for improved reliability becomes urgent. Borrowing principles from the discipline of Reliability Engineering, we have identified components of our system that constitute single points of failure and have endeavored to eliminate these through redundant components and manual work-around procedures. To assess the adequacy of our preparations, we have identified a set of plausible events that could interfere with the function of one or more of our PACS components. These events could be as simple as the loss of the network connection to a single component or as broad as the loss of our central data center. We have identified the need to continue to operate during adverse conditions, as well as the requirement to recover rapidly from major disruptions in service. This assessment led us to modify the physical locations of central PACS components within our physical plant. We are also taking advantage of actual disruptive events coincident with a major expansion of our facility to test our recovery procedures. Based on our recognition of the vital nature of our electronic images for patient care, we are now recording electronic images in two copies on disparate media. The image database is critical to both continued operations and recovery. Restoration of the database from periodic tape backups with a 24-hour cycle time may not support our clinical scenario: acquisition modalities have a limited local storage capacity, some of which will not contain the daily workload. Restoration of the database from the archived media is an exceedingly slow process, that will likely not meet our requirement to restore clinical operations without significant delay. Our PACS vendor is working on concurrent image databases that would be capable of nearly immediate switchover and recovery.

Computer Systems↗

Development and evaluation of PC-based HIS-RIS-modality-PACS coupling: the results of evaluation of initial stage with personal computer application.

A PC-based HIS/RIS/Modality/PACS coupling was developed and operated where hospital-wide PACS was closely cooperated with the HIS and RIS. Three workstations with a magneto-optical disk (MOD) juke-box for each one were used as PACS servers to collect images from eight computed radiography systems and three CT scanners. An implementation of JPEG compression reduced network load and storage volume. Twenty PACS-terminals can be connected to the PACS servers and get images from them. Functions of the terminals are magnification, tone scale modification and mensuration. The physicians can also get images on HIS-terminals employing improved HIS-terminal functions. This system has many advantages: (1) inexpensive; (2) close cooperation with the HIS and RIS which makes them easy to manage and retrieve images automatically; and (3) it is an open system, which enables us to apply new technologies. As a matter of fact the introduction of a new PC and a new OS made it possible to decrease displaying response time.

Evaluation Studies as Topic↗

Environmental cues affecting development.

Multiple receptors connect environmental cues to developmental genes via shortcuts and more tortuous pathways, creating a network of interactive signals in which negative regulators play a key role. The elements of the circuitry, their connections, and their functional significance are being uncovered thanks to the analysis of genetic interactions, protein-protein interactions, sub-cellular localisation and transcriptome patterns.

Arabidopsis Proteins↗

Functional cartography of complex metabolic networks.

High-throughput techniques are leading to an explosive growth in the size of biological databases and creating the opportunity to revolutionize our understanding of life and disease. Interpretation of these data remains, however, a major scientific challenge. Here, we propose a methodology that enables us to extract and display information contained in complex networks. Specifically, we demonstrate that we can find functional modules in complex networks, and classify nodes into universal roles according to their pattern of intra- and inter-module connections. The method thus yields a 'cartographic representation' of complex networks. Metabolic networks are among the most challenging biological networks and, arguably, the ones with most potential for immediate applicability. We use our method to analyse the metabolic networks of twelve organisms from three different superkingdoms. We find that, typically, 80% of the nodes are only connected to other nodes within their respective modules, and that nodes with different roles are affected by different evolutionary constraints and pressures. Remarkably, we find that metabolites that participate in only a few reactions but that connect different modules are more conserved than hubs whose links are mostly within a single module.

Adenosine Triphosphate↗

Using replicator dynamics for analyzing fMRI data of the human brain.

The understanding of brain networks becomes increasingly the focus of current research. In the context of functional magnetic resonance imagery (fMRI) data of the human brain, networks have been mostly detected using standard clustering approaches. In this work, we present a new method of detecting functional networks using fMRI data. The novelty of this method is that these networks have the property that every network member is closely connected with every other member. This definition might to be better suited to model important aspects of brain activity than standard cluster definitions. The algorithm that we present here is based on a concept from theoretical biology called "replicator dynamics."

Algorithms↗

Forming electrical networks in three dimensions by self-assembly

Self-assembly of millimeter-scale polyhedra, with surfaces patterned with solder dots, wires, and light-emitting diodes, generated electrically functional, three-dimensional networks. The patterns of dots and wires controlled the structure of the networks formed; both parallel and serial connections were generated.

Journal Article↗

Suppression of RNA silencing by a geminivirus nuclear protein, AC2, correlates with transactivation of host genes.

Bipartite geminiviruses encode a small protein, AC2, that functions as a transactivator of viral transcription and a suppressor of RNA silencing. A relationship between these two functions had not been investigated before. We characterized both of these functions for AC2 from Mungbean yellow mosaic virus-Vigna (MYMV). When transiently expressed in plant protoplasts, MYMV AC2 strongly transactivated the viral promoter; AC2 was detected in the nucleus, and a split nuclear localization signal (NLS) was mapped. In a model Nicotiana benthamiana plant, in which silencing can be triggered biolistically, AC2 reduced local silencing and prevented its systemic spread. Mutations in the AC2 NLS or Zn finger or deletion of its activator domain abolished both these effects, suggesting that suppression of silencing by AC2 requires transactivation of host suppressor(s). In line with this, in Arabidopsis protoplasts, MYMV AC2 or its homologue from African cassava mosaic geminivirus coactivated >30 components of the plant transcriptome, as detected with Affymetrix ATH1 GeneChips. Several corresponding promoters cloned from Arabidopsis were strongly induced by both AC2 proteins. These results suggest that silencing suppression and transcription activation by AC2 are functionally connected and that some of the AC2-inducible host genes discovered here may code for components of an endogenous network that controls silencing.

DNA, Viral↗

A correlation significance learning scheme for auto-associative memories.

A new concept called correlation significance for expanding the attraction regions around all the stored vectors (attractors) of an asynchronous auto-associative memory is introduced. Since the well known outer product rule adopts equally-weighted correlation matrix for the neuron connections, the attraction region around each attractor is not maximized. In order to maximize these attraction regions, we devise a rule that all the correlations between two different components of two different stored patterns should be unequally weighted. By this formalism, the connection matrix T of the asynchronous neural network is designed by using the gradient descent approach. Additionally, an exponential type error function is constructed such that the number of successfully stored vectors can be directly examined during the entire learning process. Finally, computer simulations demonstrate the efficiency and capability of this scheme.

Computer Simulation↗

New approaches to mechanism analysis for drug discovery using DNA microarray data combined with KeyMolnet.

We have developed a comprehensive information platform, named KeyMolnet, for drug discovery and life science research in the post-genome era. Using KeyMolnet, we show new approaches to research into the biological mechanism in DNA microarray analysis. Thanks to the DNA microarray technology, it is now possible to obtain very large quantities of gene expression data at a time. However, it is still difficult to extract meaningful information from such large quantities of data and to analyze the relationship between gene expression data and biological function. We therefore developed an advanced tool that can generate molecular networks upon demand, and beyond signaling "cross-talks," can connect them to physiological phenomena and medical and drug information. Here we show the methods of mechanism analysis using the DNA microarray data and KeyMolnet, as well as the possible mechanism of inducing apoptosis in the human promyelocytic leukemia cell line, HL-60, treated with 12-O-tetradecanoylphorbol 13-acetate (TPA), using the time series of gene expression data from DNA microarray experiments. KeyMolnet enables practical approaches to research into biological mechanisms, which in turn contribute to new discoveries in the medical, pharmaceutical and life sciences.

Apoptosis↗

Plasmodesmata: gateways for information transfer.

Intercellular communication in plants has evolved to occur via elongated cytoplasmic bridges, called plasmodesmata, that traverse the thick cell walls that surround plant cells. Historically, plasmodesmata have been assigned the mostly passive role of creating cytoplasmic continuity between plant cells enabling free transport of the wealth of small plant metabolites and growth hormones under 1 kDa. When it was discovered that plant viruses pirate plasmodesmata for movement of viral genomes during infection, it was proposed that viruses modified plasmodesmata for transport of very large molecules. Now, there is compelling evidence that plasmodesmata are inherently dynamic, rapidly altering their dimensions to increase their transport capabilities, upon contact with viral as well as developmentally important plant proteins. Further, the study of intercellular transport has prompted analyses of intracellular transport pathways, implicating the cytoskeleton as a major tracking system to plasmodesmata. Thus, plasmodesmata form a three-dimensional network of transportation channels and major checkpoints for information transfer. In the following, current knowledge about structure and function of these connective organelles, and about routing of molecules towards plasmodesmata, will be summarized.

Biological Transport↗

[Blood vessels of the periodontium of incisors and molars of the lower jaw of the white rat].

By means of injective and noninjective methods, the structural organization of the incisor and molar blood bed has been studied in the white rat mandible. For the periodontal blood bed, distinguishing by a pronounced organo-specificity, distribution of arterial and venous vessels between collagenous fiber bundles and a reticular arrangement of the capillaries is peculiar. A definite connection is clearly seen between angioarchitectonics of different segments of the periodontium, its structure and function. Unequal density of the capillary networks in the area of the epithelial dental organ and difference of the periodontal angioarchitectonics with the lingual and labial surfaces of the incisors are noted. The area of the epithelial dental organ, having a peculiar functional importance, is characterized by multiple pathways of blood inflow and outflow, by concentration of structural-functional adaptations which increase expansiveness, capacity and diffusive surface of metabolic microvessels, by a small critical thickness of the tissue layer between neighbouring capillaries.

Animals↗

[Background and evoked neuronal activity of ganglia in the submucous plexus of the small intestine].

In preparations of the cat small intestine, presence of three types of cells was revealed: 1st--with single spikes, 2nd--with slow, and 3rd--with fast bursts of spontaneous activity as well as groups of silent neurons. The 1st and the 2nd type cells and some silent cells receive activating influence from adjacent ganglia. Silent neurons included mechanosensitive cells responding with specific series of discharges to mechanical deformation of the ganglion and to electric stimulation of adjacent ganglia. The interneuronal relationships within the ganglion and connections between cells of adjacent ganglia were revealed which suggests that all neurons of the plexus are involved in a functional network.

Acetylcholine↗

Gravitational neuromorphology.

This review shows that morphological studies of the central, peripheral and autonomic nervous system of animals exposed to altered gravity yield data which are extremely significant for our understanding of the mechanisms of adaptation of the nervous system, and of the mammalian organism as a whole, to increased and decreased loading. Neuromorphological studies, correlating structure and function, indicate a decreased activity in weightlessness for spinal ganglia neurons and motoneurons of the spinal cord, as well as the neurons of the hypothalamic nuclei producing arginine vasopressin and growth hormone releasing factor. Structural changes of the somatosensory cortex and spinal ganglia suggest a decreased afferent flow to the somatosensory cortex in microgravity. The results characterize the mechanisms of structural adaptation to a decreased afferent flow in microgravity by the neurons in the hemisphere cortex and brain stem nuclei. There is also morphological evidence for an increased sensitivity of the otolith apparatus and for the development of a hyponoradrenergic syndrome in weightlessness. These studies have shown that both microgravity and the simulation of microgravity effects by tail suspension-induced structural changes in the large neurons of lumbar spinal ganglia and motoneurons of the lumbar spinal cord, which occur under conditions of nerve cell hypoactivity. The structural changes, and consequently the development of neuron hypoactivity, are expressed more extensively after microgravity than after tail suspension for the same length of time. The influence of microgravity and hypergravity on animals is expressed by opposing changes in nervous tissue structure in the spinal ganglia, spinal cord, and nodulus of cerebellar vermis. These changes indicate neuron hypoactivity under microgravity and neuron hyperactivity under 2 G. Morphological assessment of the functional state of other structures of the brain under hypergravity will require further study. Can all structural changes which occur in nerve tissue under microgravity or under hypergravity be explained on the basis of increased or decreased activity of its structural elements? The presently available data regarding the correlation of structure and functional state of cells in brain and spinal cord suggest an affirmative answer. Ultrastructural studies of the nodular cortex of the cerebellum in rats after different duration spaceflights provide what appears to be a convincing example. However, it should be pointed out that the criteria for the morphological assessment of the functional state of single nerve cells will certainly be different from those for groups of neurons connected in a nerve cell network.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

High-frequency oscillations in the output networks of the hippocampal-entorhinal axis of the freely behaving rat.

Population bursts of the CA3 network, which occur during eating, drinking, awake immobility, and slow-wave sleep, produce a large field excitatory postsynaptic potential throughout stratum radiatum of the CA1 field (sharp wave). The CA3 burst sets into motion a short-lived, dynamic interaction between CA1 pyramidal cells and interneurons, the product of which is a 200 Hz oscillatory field potential (ripple) and phase-related discharge of the CA1 network. Although many CA1 pyramidal neurons discharge during the time (50-100 msec) of each sharp wave, each wave of a ripple (approximately 5 msec) reflects the synchronization of more discrete subsets of CA1 neurons. When we used multi-site recordings in freely behaving rats, we observed ripples throughout the longitudinal extent (approximately 4-5 mm) of the dorsal CA1 region that were coherent for multiple cycles of each ripple. High-frequency ripples were also observed throughout the hippocampal-entorhinal output pathway that were concurrent but less coherent on a cycle-by-cycle basis. Single and multiunit neuronal activity was phase-related to local ripples throughout the hippocampal-entorhinal output pathway. Entorhinal ripples occurred 5-30 msec after the CA1 ripples and were related to the occurrence of an entorhinal sharp wave. Thus, during each hippocampal sharp wave, there is powerful synchronization among the neuronal networks that connect the hippocampus to the neocortex. We suggest that this population interaction (1) biologically constrains theoretical models of hippocampal function and dysfunction and (2) has the capacity to support an "off-line" memory consolidation process.

Animals↗