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At least 703 records · Page 39Linked to original sources

PubMed2002

Mixed-anion complexes with a bipyrazolyl ligand. A new entry to a realm of three-dimensional five-connected coordination topologies.

Cross-linking of corrugated square grid coordination layers by anionic bridging groups generates five-connected coordination networks; the 3D topologies of mixed-anion cobalt(II) and nickel(II) complexes with a tetramethyl-substituted 4,4'-bipyrazolyl ligand are supported by mu-SO4(2-) functions and exist as neutral or cationic five-connected arrays involving additional terminal (NCS-) or non-coordinated (NO3-, ClO4-) groups.

Journal Article↗

PubMed2005

A network of transcriptionally coordinated functional modules in Saccharomyces cerevisiae.

Recent computational and experimental work suggests that functional modules underlie much of cellular physiology and are a useful unit of cellular organization from the perspective of systems biology. Because interactions among modules can give rise to higher-level properties that are essential to cellular function, a complete knowledge of these interactions is necessary for future work in systems biology, including in silico modeling and metabolic engineering. Here we present a computational method for the systematic identification and analysis of functional modules whose activity is coordinated at the level of transcription. We applied this method, Search for Pairwise Interactions (SPIN), to obtain a global view of functional module connectivity in Saccharomyces cerevisiae and to provide insight into the biological mechanisms underlying this coordination. We also examined this global network at higher resolution to obtain detailed information about the interactions of particular module pairs. For instance, our results reveal possible transcriptional coordination of glycolysis and lipid metabolism by the transcription factor Gcr1p, and further suggest that glycolysis and phosphoinositide signaling may regulate each other reciprocally.

Gene Expression Profiling↗

PubMed2001

Designing fault-tolerant distributed archives for picture archiving and communication systems.

PURPOSE: Distributed archives in a picture archiving and communication system (PACS) environment can provide added fault tolerance and fail-over capability, as well as increased load capacity at a more economical price than traditional 'high-availability" systems. Systems can be configured with varying levels of fault tolerance, depending on the amount of redundancy desired. There is, however, a direct correlation between the level of hardware redundancy and cost to implement. This presentation details the system design for fault-tolerant distributed archives as well as several options for redundancy, referencing implementation of a fault-tolerant archive system at the University of Utah. METHODS: The distributed archive system described here is based on Image Devices' image archive software, which can be implemented on multiple individual archive servers in order to distribute archive functionality and operational load. The configuration and implementation of the individual servers together make up the distributed archive system and does not impact the ability of the system to be scaled to meet future requirements. Several implementation and configuration options exist, including the ability for servers to maintain replicated databases containing patient and image information. Thus, each archive can be aware of all information and the location of this information within the distributed archive system. RESULTS: The goal is to produce systems that will still be operational in the event of any single point of failure, ie, a network connection failure between facilities or the failure of a single archive server within the distributed system. During normal operation, workload for image acquisition, image routing and image query requests will be distributed between the archive servers. If the system is deployed in a multifacility environment, each archive server can be configured to be responsible for the acquisition and image distribution management within that server's local facility. If the system is deployed in a single facility environment, load can be distributed evenly between the archive servers based on an understanding of the workload requirements generated be each acquisition and display device in the system. In the event that an archive server fails, other archive servers within the system will have the ability to provide some or all of the failed server's functionality. The degree of fail-over capability is dependent on the archive server's configuration as well as hardware redundancy employed. Three levels of fault-tolerant design can be achieved with this system architecture: (1) duplicate work capability only; (2) duplicate work capability and short-term image cache; (3) duplicate work capability, short-term image cache, and longterm image archival. Using the basic fault-tolerant design above, we have implemented a multifacility distributed archive system at the University of Utah. This system was implemented at a fraction of the cost of true "high-availability" archive architectures yet provides constant up time for the PACS system. If the network connection between the two locations goes down, each site is still fully functional for soft-copy read, as well as image acquisition and distribution. If either of the archive servers goes down, the image sources are redirected to the other archive server. The operational server then handles image distribution for both locations. Access to images in the short-term image cache is available to both archive servers and is not affected by loss of the network connection or remote server. Because there is ony one long-term archive device, the ability to retrieve images from long-term storage is the only function compromised by a network or server failure. CONCLUSION: By implementing distributed archives in a PACS environment, it is possible to achieve a highly fault-tolerant system without the expense of high-availability hardware and software. The design concepts outlined here can be applied to any PACS system that supports distributed archive functionality.

Computer Systems↗

PubMed1997

Critical role of W60d in thrombin allostery.

Mutation of residue W60d of thrombin, located 17 A from the Na+ binding site, suppresses Na+ binding and the functional differences between the slow and fast forms. The molecular basis for the long-range effect of this mutation is provided by a conspicuous network of water molecules which connects the Na+ binding environment to the specificity sites S1 and S2 of the enzyme. The mutation appears to stabilize thrombin in a hybrid conformation that is overall similar to the slow form, but with the fibrinogen recognition site functioning as in the fast form. It also affects the switch in specificity from fibrinogen to protein C linked to the release Na+ and the fast-->slow conversion. Under physiological conditions of pH, temperature and NaCl concentration, the W60dS mutant behaves as an anticoagulant. It has a reduced activity toward fibrinogen by 22-fold, while the reduction of protein C activation in the presence of saturating concentrations of thrombomodulin is less than 2-fold. Even more remarkable is the cleavage of fibrin I monomer leading to release of fibrinopeptide B, which is reduced by more than 130-fold. This property is reminiscent of the snake venom ancrod, which only releases fibrinopeptide A, and adds substantially to the anticoagulant potency of the W60dS mutant. In fact, the clotting time in the presence of this mutant is prolonged more than 40-fold compared to the wild-type.

Allosteric Regulation↗

PubMed2025

Exploring the transmission of cognitive task information through optimal brain pathways.

Understanding the large-scale information processing that underlies complex human cognition is the central goal of cognitive neuroscience. While emerging activity flow models demonstrate that cognitive task information is transferred by interregional functional or structural connectivity, graph-theory-based models typically assume that neural communication occurs via the shortest path of brain networks. However, whether the shortest path is the optimal route for empirical cognitive information transmission remains unclear. Based on a large-scale activity flow mapping framework, we found that the performance of activity flow prediction with the shortest path was significantly lower than that with the direct path. The shortest path routing was superior to other network communication strategies, including search information, path ensembles, and navigation. Intriguingly, the shortest path outperformed the direct path in activity flow prediction when the physical distance constraint and asymmetric routing contribution were simultaneously considered. This study not only challenges the shortest path assumption through empirical network models but also suggests that cognitive task information routing is constrained by the spatial and functional embedding of the brain network.

Humans↗

PubMed2004

Acquired disorders of elastic tissue: part I. Increased elastic tissue and solar elastotic syndromes.

Elastic fibers in the extracellular matrix are an integral component of dermal connective tissue. The resilience and elasticity required for normal structure and function of the skin may be attributed to the network of elastic tissue. Advances in our understanding of elastic tissue physiology provide a foundation for studying the pathogenesis of elastic tissue disorders. Many acquired disorders are nevertheless poorly understood due to the paucity of reported cases. Several acquired disorders in which accumulation or elastotic degeneration of dermal elastic fibers produces prominent clinical and histopathologic features have recently been described. They include elastoderma, linear focal elastosis, and late-onset focal dermal elastosis and must be differentiated from better-known disorders, among them acquired pseudoxanthoma elasticum, elastosis perforans serpiginosa, and Favré-Racouchot syndrome. Learning objective At the conclusion of this learning activity, participants should understand the similarities and differences between acquired disorders of elastic tissue that are characterized by an increase in elastic tissue, as well as the spectrum of solar elastotic dermatoses.

Connective Tissue Diseases↗

PubMed2005

Topographical maps as complex networks.

The neuronal networks in the mammalian cortex are characterized by the coexistence of hierarchy, modularity, short and long range interactions, spatial correlations, and topographical connections. Particularly interesting, the latter type of organization implies special demands on developing systems in order to achieve precise maps preserving spatial adjacencies, even at the expense of isometry. Although the object of intensive biological research, the elucidation of the main anatomic-functional purposes of the ubiquitous topographical connections in the mammalian brain remains an elusive issue. The present work reports on how recent results from complex network formalism can be used to quantify and model the effect of topographical connections between neuronal cells over the connectivity of the network. While the topographical mapping between two cortical modules is achieved by connecting nearest cells from each module, four kinds of network models are adopted for implementing intramodular connections, including random, preferential-attachment, short-range, and long-range networks. It is shown that, though spatially uniform and simple, topographical connections between modules can lead to major changes in the network properties in some specific cases, depending on intramodular connections schemes, fostering more effective intercommunication between the involved neuronal cells and modules. The possible implications of such effects on cortical operation are discussed.

Animals↗

PubMed2004

The insular lobe of Reil--its anatamico-functional, behavioural and neuropsychiatric attributes in humans--a review.

There is considerable clinical and experimental research to explore the anatamico-functional correlations of the limbic lobe to establish its relevance in modern neuroscience. The insula being a pivotal structure in the concept of the greater limbic lobe, we have attempted to highlight in this review the topographical anatomy and development, the remarkable heterogeneity of the insular cortical architecture, the widespread multifaceted spectrum of functional connectivity patterns and how this is translated to its behavioural specialisation in humans. The insula serves as an intergration cortex for multimodal convergence of distributed neural networks such as the somesthetic-limbic, insulo-limbic, insulo-orbito-temporal and the prefrontal-striato-pallidal-basal forebrain. This provides the conceptual framework to facilitate functional and clinical considerations relevant to the various behavioural and neuropsychiatric disorders outlined in this review. The functional role of the insula in these disorders with particular reference to the current functional neuroimaging data has been also reviewed in this article.

Cerebral Cortex↗

PubMedDate not supplied

Brain-periphery connections: do they play a role in mediating the effect of centrally injected interleukin-1 beta on gonadal function?

The immune system and several endocrine axes communicate with each other through a network of molecules which collectively produce a coordinated response to immune challenges. This phenomenon, necessary for the survival of the organism, is thought to involve the release, by activated cells in the periphery, of proteins, called cytokines, which inform the brain about immune activation. The brain then organizes a series of neuroendocrine responses which participate in the regulation of the host response. With regard to the influence of cytokines on the hypothalamic-pituitary-gonadal axis, we know that the injection of these proteins lowers gonadotropin-releasing hormone release, which in turn inhibits luteinizing hormone (LH) secretion. These changes would be expected to decrease sex steroid production and, indeed, estrogens and testosterone are low in female and male rats, respectively, following acute intracerebroventricular (i.c.v.) injection of interleukin (IL)-1 beta. There is, however, another possibility that central cytokines could alter ovarian and testicular function independently of changes in gonadotropin levels. Prolonged i.c.v. infusion of the cytokine into the female rat brain produced a dramatic rise in progesterone levels. The absence of a comparable change in the progesterone release rate of males infused with IL-1 beta, and the presence of marked surges of prolactin (PRL) in the females, suggests that IL-1 beta altered ovarian function, and that the persistence of large corpora lutea induced PRL release. The possibility that the cytokine might stimulate the brain circuits that regulate PRL release, while possible, appears remote, because male rats injected with IL-1 beta showed significantly blunted PRL levels. In intact adult male rats, i.c.v. IL-1 beta administration caused the expected decrease in LH and testosterone levels, but was also accompanied by a loss of testicular responsiveness to gonadotropins. Though elevated levels of corticosteroids are known to interfere with normal gonadal steroidogenesis, blockade of IL-1-induced corticosterone release did not reverse the inhibitory influence of the cytokine. One mechanism that deserves attention is the possibility that i.c.v. injection of IL-1 beta might increase circulating cytokine levels, and indeed plasma IL-6 concentrations were significantly elevated in rats treated with IL-1 beta. This humoral mechanism may disrupt testicular function through the documented inhibitory effects of blood-borne cytokines on Leydig cell function. In addition, brain cytokines might influence a variety of peripheral events through direct (neural?) connections. This brief review discusses the hypothesis that there are brain-to-gonad connections that bypass the pituitary, and presents results that might support the possibility that central injection of IL-1 beta decreases testosterone secretion independently of blunted LH levels.

Animals↗

PubMed2001

[Involvement of WT1 gene expression in regulation of P53 and MDM2 proteins function in acute lymphoblastic leukemia].

Using sensitive techniques such as reverse transcription polymerase chain reaction (RT-PCR) the expression of WT1 gene in acute lymphoblastic leukemias (ALL) is indicated. High level of mRNA WT1 was only observed in ALL cases with leukemic cells characterized by P53- and MDM2-positive staining in cytometric analysis. The overexpression of P53 protein has not been induced by P53 gene abnormalities and MDM2 protein synthesis was independent from respective gene amplification. The data suggest that WT1 may play a distinct role in the pathophysiology of acute leukemias. It can regulate the function of the main oncoprotein network factors--P53 and MDM2 proteins. There was concluded that the most important mechanism of tissue P53-immunopositivity was connected with the P53 interactions with other oncoproteins, especially with MDM2 and WT1. They have caused different effects in particular cases and several phenotypes of leukemic cells were described. However, the negative tissue staining with anti-P53 monoclonal antibodies can not be evidence of the proper P53 protein function. The immunohistochemical estimations of the P53 level in the cells are insufficient for diagnostic and clinical evaluations. Molecular analyses of P53 and MDM2 genes, as well the WT1 gene transcription, are necessary for the proper characterisation of functional and structural status of P53.

Case-Control Studies↗

PubMed1996

Synaptic organizations and dynamical properties of weakly connected neural oscillators. II. Learning phase information.

This is the second of two articles devoted to analyzing the relationship between synaptic organizations (anatomy) and dynamical properties (function) of networks of neural oscillators near multiple supercritical Andronov-Hopf bifurcation points. Here we analyze learning processes in such networks. Regarding learning dynamics, we assume (1) learning is local (i.e. synaptic modification depends on pre- and postsynaptic neurons but not on others), (2) synapses modify slowly relative to characteristic neuron response times, (3) in the absence of either pre- or postsynaptic activity, the synapse weakens (forgets). Our major goal is to analyze all synaptic organizations of oscillatory neural networks that can memorize and retrieve phase information or time delays. We show that such network have the following attributes: (1) the rate of synaptic plasticity connected with learning is determined locally by the presynaptic neurons, (2) the excitatory neurons must be long-axon relay neurons capable of forming distant connections with other excitatory and inhibitory neurons, (3) if inhibitory neurons have long axons, then the network can learn, passively forget and actively unlearn information by adjusting synaptic plasticity rates.

Learning↗

PubMed1999

Cognitive dysfunction in schizophrenia: unifying basic research and clinical aspects.

Seeking to unite psychological and biological approaches, this paper links cognitive and cellular hypotheses and data about thought and language abnormalities in schizophrenia. The common thread, it is proposed, is a dysregulated suppression of associations (at the behavioral and functional neural systems level), paralleled by abnormalities of inhibition at the cellular and molecular level, and by an abnormal anatomical substrate (reduced MRI gray matter volume) in areas subserving language. At the level of behavioral experiments and connectionist modeling, data suggest an abnormal semantic network connectivity (strength of associations) in schizophrenia, but not an abnormality of network size (number of associates). This connectivity abnormality is likely to be a preferential processing of the dominant (strongest) association, with the neglect of preceding contextual information. At the level of functional neural systems, the N400 event-related potential amplitude is used to index the extent of "search" for a semantic match to a word. In a short stimulus-onset-asynchrony condition, both schizophrenic and schizotypal personality disorder subjects showed, compared with controls, a reduced N400 amplitude to the target words that were related to cues, e.g. cat-dog, a result compatible with behavioral data. Other N400 data strongly and directly suggest that schizophrenics do not efficiently utilize context.

Brain↗

PubMed2002

Cortical network reorganization guided by sensory input features.

Sensory experience alters the functional organization of cortical networks. Previous studies using behavioral training motivated by aversive or rewarding stimuli have demonstrated that cortical plasticity is specific to salient inputs in the sensory environment. Sensory experience associated with electrical activation of the basal forebrain (BasF) generates similar input specific plasticity. By directly engaging plasticity mechanisms and avoiding extensive behavioral training, BasF stimulation makes it possible to efficiently explore how specific sensory features contribute to cortical plasticity. This review summarizes our observations that cortical networks employ a variety of strategies to improve the representation of the sensory environment. Different combinations of receptive-field, temporal, and spectrotemporal plasticity were generated in primary auditory cortex neurons depending on the pitch, modulation rate, and order of sounds paired with BasF stimulation. Simple tones led to map expansion, while modulated tones altered the maximum cortical following rate. Exposure to complex acoustic sequences led to the development of combination-sensitive responses. This remodeling of cortical response characteristics may reflect changes in intrinsic cellular mechanisms, synaptic efficacy, and local neuronal connectivity. The intricate relationship between the pattern of sensory activation and cortical plasticity suggests that network-level rules alter the functional organization of the cortex to generate the most behaviorally useful representation of the sensory environment.

Acetylcholine↗

PubMed2005

Mechanisms of axon guidance in the developing nervous system.

The human brain assembles an incredible network of over a billion neurons. Understanding how these connections form during development in order for the brain to function properly is a fundamental question in biology. Much of this wiring takes place during embryonic development. Neurons are generated in the ventricular zone, migrate out, and begin to differentiate. However, neurons are often born in locations some distance from the target cells with which they will ultimately form connections. To form connections, neurons project long axons tipped with a specialized sensing device called a growth cone. The growing axons interact directly with molecules within the environment through which they grow. In order to find their targets, axonal growth cones use guidance molecules that can either attract or repel them. Understanding what these guidance cues are, where they are expressed, and how the growth cone is able to transduce their signal in a directionally specific manner is essential to understanding how the functional brain is constructed. In this chapter, we review what is known about the mechanisms involved in axonal guidance. We discuss how the growth cone is able to sense and respond to its environment and how it is guided by pioneering cells and axons. As examples, we discuss current models for the development of the spinal cord, the cerebral cortex, and the visual and olfactory systems.

Animals↗

PubMed2004

Bayesian analysis of signaling networks governing embryonic stem cell fate decisions.

MOTIVATION: Signaling events that direct mouse embryonic stem (ES) cell self-renewal and differentiation are complex and accordingly difficult to understand in an integrated manner. We address this problem by adapting a Bayesian network learning algorithm to model proteomic signaling data for ES cell fate responses to external cues. Using this model we were able to characterize the signaling pathway influences as quantitative, logic-circuit type interactions. Our experimental dataset includes measurements for 28 signaling protein phosphorylation states across 16 different factorial combinations of cytokine and matrix stimuli as reported previously. RESULTS: The Bayesian network modeling approach allows us to uncover previously reported signaling activities related to mouse ES cell self-renewal, such as the roles of LIF and STAT3 in maintaining undifferentiated ES cell populations. Furthermore, the network predicts novel influences such as between ERK phosphorylation and differentiation, or RAF phosphorylation and differentiated cell proliferation. Visualization of the influences detected by the Bayesian network provides intuition about the underlying physiology of the signaling pathways. We demonstrate that the Bayesian networks can capture the linear, nonlinear and multistate logic interactions that connect extracellular cues, intracellular signals and consequent cell functional responses.

Algorithms↗

PubMed2006

Domains, motifs, and scaffolds: the role of modular interactions in the evolution and wiring of cell signaling circuits.

Living cells display complex signal processing behaviors, many of which are mediated by networks of proteins specialized for signal transduction. Here we focus on the question of how the remarkably diverse array of eukaryotic signaling circuits may have evolved. Many of the mechanisms that connect signaling proteins into networks are highly modular: The core catalytic activity of a signaling protein is physically and functionally separable from molecular domains or motifs that determine its linkage to both inputs and outputs. This high degree of modularity may make these systems more evolvable-in principle, novel circuits, and therefore highly innovative regulatory behaviors, can arise from relatively simple genetic events such as recombination, deletion, or insertion. In support of this hypothesis, recent studies show that such modular systems can be exploited to engineer nonnatural signaling proteins and pathways with novel behavior.

Animals↗

PubMed2002

Specific ablation of the nidogen-binding site in the laminin gamma1 chain interferes with kidney and lung development.

Basement membrane assembly is of crucial importance in the development and function of tissues and during embryogenesis. Nidogen 1 was thought to be central in the assembly processes, connecting the networks formed by collagen type IV and laminins, however, targeted inactivation of nidogen 1 resulted in no obvious phenotype. We have now selectively deleted the sequence coding for the 56 amino acid nidogen-binding site, gamma1III4, within the Lamc1 gene by gene targeting. Here, we show that mice homozygous for the deletion die immediately after birth, showing renal agenesis and impaired lung development. These developmental defects were attributed to locally restricted ruptures in the basement membrane of the elongating Wolffian duct and of alveolar sacculi. These data demonstrate that an interaction between two basement membrane proteins is required for early kidney morphogenesis in vivo.

Animals↗

PubMed2006

Distinct electrical and chemical connectivity maps in the thalamic reticular nucleus: potential roles in synchronization and sensation.

GABAergic neurons of the thalamic reticular nucleus (nRt) provide thalamocortical relay neurons with feedback inhibition that influences sensory processing and thalamocortical rhythm generation. Mutual interactions between reticular neurons coordinate oscillatory activities developed within the network during normal sleep and in absence epilepsy, but the chemical versus electrical nature of these connections and their functional influence remain controversial. Here, we investigated the incidence and spatial extent of intra-nRt connectivity in vitro in horizontal and coronal thalamic slices from rat. Laser scanning photostimulation activated presynaptic nRt cells during patch-clamp recordings of postsynaptic neurons. Photolysis of caged glutamate evoked GABAergic IPSCs and/or depolarizing events (spikelets, mediated via electrical coupling) in a large proportion of neurons, thus indicating connectivity with presynaptic cell(s). Synaptic inputs were organized along the major axis of the nucleus in the same orientation as, but commonly exceeding the extent of, dendritic arborization of the postsynaptic neuron. In the anteroposterior (horizontal) plane, chemical connectivity had higher incidence (60% of recorded neurons vs 40% in vertical plane) and longer spatial extent, whereas in the dorsoventral (vertical) plane, electrical coupling dominated (47% incidence vs 37% in horizontal plane) and was more widely distributed. These data demonstrate that both electrical and chemical synapses are prominent within nRt and suggest different roles for the two types of connections. We thus propose that, along the vertical plane, electrical connectivity will promote coordinated rhythmic activity of sleep and/or thalamocortical epilepsy, whereas along the horizontal plane, chemical connectivity will oppose widespread thalamocortical synchronization and modulate sensory throughput.

Animals↗