SEARCH · PubMed Health

Results for “functional network connectivity”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 919 records · Page 51Linked to original sources

PubMed2004

Laser microdissection of immunolabeled astrocytes allows quantification of astrocytic gene expression.

Astrocytes represent the major glial cell population within the central nervous system. In order to elucidate the function of astrocytes under physiological conditions and during the course of neurological disease, astrocytic gene expression profiling is necessary. However, since astrocytes form an intimately connected network with neurons and other cell types in the brain, gene expression analysis of astrocytes with a sufficient degree of cellular specificity is difficult. Here we are presenting a rapid and, thus, RNA preserving immunostaining protocol for the detection of astrocytes in rodent brain. This protocol can readily be combined with laser microdissection (Leica AS LMD platform) and quantitative RT-PCR (qPCR). Employing this method, we studied changes in glial fibrillary acidic protein (GFAP) expression in astrocytes of mouse entorhinal cortex following entorhinal cortex lesion. Using laser microdissection, astrocytes (n = 60) were collected in the tissue surrounding the lesion, the entorhinal cortex contralateral to the lesion, and in unlesioned control animals. Changes in GFAP mRNA were quantified using qPCR. GFAP mRNA levels were 82-fold higher in astrocytes of lesioned animals at the site of the lesion compared to GFAP mRNA levels in entorhinal cortex astrocytes of control mice. GFAP mRNA levels were only slightly elevated at the contralateral side (lesioned animals). This optimized protocol for immunolabeling and laser microdissection of astrocytes followed by qPCR allows quantification of astrocytic gene expression levels with a high degree of cellular specificity. It may similarly be employed in different settings where other cell types need to be identified and microdissected for gene expression profiling.

Animals↗

PubMed1978

Anistropic connectivity and cooperative phenomena as a basis for orientation sensitivity in the visual cortex.

A computer simulation model of the neural circuity underlying orientation sensitivity in cortical neurons is examined. The model consists of a network of 3000 neurons divided into two functionally distinct cell types: excitatory (E-cells) and inhibitory (I-cells). We demonstrate that both orientation sensitivity and shape selectivity can be accounted for by making the following assumptions: 1) thalamic afferents to a sheet of cortical neurons are retinotopically organized; 2) thalamic afferents come from a single neuron, or at most a few neurons, in the lateral geniculate nucleus; 3) cortical activity is cooperative, i.e. largely dependent on intracortical connections, some of which have anisotropies along directions parallel to the pial surface. Anisotropies are specified only by the distribution of cells which are postsynaptic to a particular neuron, without specifying the axonal or dendritic contributions. In this paper, orientation sensitivity arises through cooperative interactions among neurons having anisotropic excitatory, and isotropic inhibitory connections.

Action Potentials↗

PubMed1988

[A mathematical model of the activity of spinal generators of rhythmic movements].

Different organization schemes concerning locomotor and scratching rhythmicity generators are analyzed by means of the mathematical simulation model. A functional group of neurons (half-centre constructed on the stochastically organized neuronal network) is the basis for generator. Some organization schemes concerning locomotor and scratching rhythmicity generators are considered, such as: two half-centres with reciprocal inhibitory connections and tonic excitatory influences on these half-centres: two half-centres with inhibitory-excitatory connections and tonic excitatory influences on one half-centre; ring structures consisting of more than two functional groups of neurons with excitatory and inhibitory connections between them. In all the schemes considered generation of rhythmic activity is possible with time characteristics similar to those of the locomotor and scratching rhythmicity. It is shown that transition from locomotor to scratching rhythmicity can be realized through simply organized actions on generator neurons. Possible principles of construction of spinal generators for locomotor and scratching movements are discussed.

Animals↗

PubMed1986

The brain as a self-organizing system.

Clinical evidence and numerous results from animal experimentation indicate that cognitive functions have to be learned. Brain structures subserving these functions require sensory experience for their maturation. Genetic instructions are in principle not sufficient to specify neuronal connections with sufficient precision. Self-organization processes are implemented in addition which allow to optimize genetically determined blue prints of connectivity by making use of functional criteria. Thus, neuronal activity becomes an important shaping factor in the development of the structural and functional architecture of the forebrain. To the extent that this neuronal activity is modulated by sensory signals, environmental factors can influence the development of neuronal networks. Recent experiments indicate that these shaping processes are additionally controlled by modulatory systems. Both, the noradrenergic projection from the locus coeruleus and the cholinergic projection from the basal forebrain facilitate activity-dependent long-term changes of neuronal connections during development. The activity of these modulatory systems in turn depends on central states such as arousal, attention, and perhaps also motivation. It is inferred from this evidence that experience-dependent self-organization should not be considered as a passive imprinting process but rather as an active dialogue between the brain and its environment. The hypothesis is discussed that many developmental disturbances which are commonly attributed to deprivation are in fact due to defaults of the CNS which either lead to the formulation of wrong questions or to the reduction of exploratory drive.

Animals↗

PubMed1988

Spatial organization and genetic information in brain development.

In the course of brain development neurons acquire qualitative and quantitative biochemical and morphological properties which depend on the position of the cells within the nervous system. In the dimensions tangential to multilayered cell sheets mechanisms contributing to spatial order include induction by adjacent tissue as well as internal generation of morphogenetic fields (presumably by reactions involving autocatalysis and lateral inhibition). In the dimensions across the sheet cells of different types are produced in one layer and sort into another layer, guided presumably by contact mediated cell interaction. Positional and directional cues encoded in the developing brain are essentially involved in axonal guidance and the formation of neuronal connections. In mammals and man, the number of neurons and their connections in the brain is much higher than the number of genes. This is possible because there are repetitive neuronal circuits in the brain, and there is topographic order of connections between different brain areas. For instance, few quantitatively graded markers would suffice for specifying the projection of one area of the nervous system onto another, generating spatial order for a large number of fibers while requiring only a limited amount of genetic information. Higher brain functions, such as learning and memory, may logically require only a neural network consisting of repetitive subunits. On the other hand, it is an evolutionary advantage for an organism to be endowed, from the outset, with a pattern of neural connections which is subtly and quantitatively tuned for efficiency in dealing with the environment, while remaining flexible for change and adaptation in the course of learning.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed2004

Coexpression analysis of human genes across many microarray data sets.

We present a large-scale analysis of mRNA coexpression based on 60 large human data sets containing a total of 3924 microarrays. We sought pairs of genes that were reliably coexpressed (based on the correlation of their expression profiles) in multiple data sets, establishing a high-confidence network of 8805 genes connected by 220,649 "coexpression links" that are observed in at least three data sets. Confirmed positive correlations between genes were much more common than confirmed negative correlations. We show that confirmation of coexpression in multiple data sets is correlated with functional relatedness, and show how cluster analysis of the network can reveal functionally coherent groups of genes. Our findings demonstrate how the large body of accumulated microarray data can be exploited to increase the reliability of inferences about gene function.

Cluster Analysis↗

PubMed2004

Analysis of beta-1,3-glucan assembly in Saccharomyces cerevisiae using a synthetic interaction network and altered sensitivity to caspofungin.

Large-scale screening of genetic and chemical-genetic interactions was used to examine the assembly and regulation of beta-1,3-glucan in Saccharomyces cerevisiae. Using the set of deletion mutants in approximately 4600 nonessential genes, we scored synthetic interactions with genes encoding subunits of the beta-1,3-glucan synthase (FKS1, FKS2), the glucan synthesis regulator (SMI1/KNR4), and a beta-1,3-glucanosyltransferase (GAS1). In the resulting network, FKS1, FKS2, GAS1, and SMI1 are connected to 135 genes in 195 interactions, with 26 of these genes also interacting with CHS3 encoding chitin synthase III. A network core of 51 genes is multiply connected with 112 interactions. Thirty-two of these core genes are known to be involved in cell wall assembly and polarized growth, and 8 genes of unknown function are candidates for involvement in these processes. In parallel, we screened the yeast deletion mutant collection for altered sensitivity to the glucan synthase inhibitor, caspofungin. Deletions in 52 genes led to caspofungin hypersensitivity and those in 39 genes to resistance. Integration of the glucan interaction network with the caspofungin data indicates an overlapping set of genes involved in FKS2 regulation, compensatory chitin synthesis, protein mannosylation, and the PKC1-dependent cell integrity pathway.

Antifungal Agents↗

PubMed1991

Patterns of connectivity in the cat sensory-motor cortex: a light and electron microscope analysis of the projection arising from area 3a.

Through its complex network of interconnections, each of the functionally specialized subdivisions in the cat primary somatosensory cortex may provide the motor cortex with different input and thus play a unique role in motor behavior. Areas 2 and 3a receive separate peripheral information. Cells in both regions project directly to the cat motor cortex but are thought to target different populations of neurons. In this study the morphology and distribution patterns of the area 3a projection to the motor cortex were compared to previous findings on the projection from area 2. Also, details of the projection from area 3a to area 2 were studied. Injections of Phaseolus vulgaris leucoagglutinin were made into area 3a and fixed brain tissue was processed for immunohistochemical staining of this anterograde tracer. Tissue was examined with the light microscope to determine the patterns of the 3a projections to area 2 and motor cortex, area 4. Axons arising from cells in area 3a terminated in multiple column-like clusters in both motor cortex and area 2. The small number of cells labeled at the injection sites suggested that multiple foci of the 3a fibers are formed by collateral axonal branches of the same neurons. The topography of the projection from area 3a to the motor cortex was more clearly defined than that from area 3a to area 2. Electron microscope analysis determined the laminar distribution and types of synapses formed between area 3a efferents and their target neurons. A high proportion of synapses was found in layer III in both target regions. However, unlike in area 4, labeled terminals were sparse in laminae I and II of area 2. Axospinous synapses were slightly more numerous than axodendritic synapses, but both were distributed similarly throughout the thickness of the cortex. In area 2 the axospinous synapses accounted for 63% of synapses and in area 4 for 57% of synapses. No axosomatic synapses were detected.

Animals↗

PubMed1991

Neural network programming in bioprocess variable estimation and state prediction.

A neural network program with efficient learning ability for bioprocess variable estimation and state prediction was developed. A 3 layer, feed-forward neural network architecture was used, and the program was written in Quick C ver 2.5 for an IBM compatible computer with a 80486/33 MHz processor. A back propagation training algorithm was used based on learning by pattern and momentum in a combination as used to adjust the connection of weights of the neurons in adjacent layers. The delta rule was applied in a gradient descent search technique to minimize a cost function equal to the mean square difference between the target and the network output. A non-linear, sigmoidal logistic transfer function was used in squashing the weighted sum of the inputs of each neuron to a limited range output. A good neural network prediction model was obtained by training with a sequence of past time course data of a typical bioprocess. The well trained neural network estimated accurately and rapidly the state variables with or without noise even under varying process dynamics.

Algorithms↗

PubMed2002

Dynamics of Boolean networks controlled by biologically meaningful functions.

The remarkably stable dynamics displayed by randomly constructed Boolean networks is one of the most striking examples of the spontaneous emergence of self-organization in model systems composed of many interacting elements (Kauffman, S., J. theor. Biol.22, 437-467, 1969; The Origins of Order, Oxford University Press, Oxford, 1993). The dynamics of such networks is most stable for a connectivity of two inputs per element, and decreases dramatically with increasing number of connections. Whereas the simplicity of this model system allows the tracing of the dynamical trajectories, it leaves out many features of real biological connections. For instance, the dynamics has been studied in detail only for networks constructed by allowing all theoretically possible Boolean rules, whereas only a subset of them make sense in the material world. This paper analyses the effect on the dynamics of using only Boolean functions which are meaningful in a biological sense. This analysis is particularly relevant for nets with more than two inputs per element because biological networks generally appear to be more extensively interconnected. Sets of the meaningful functions were assembled for up to four inputs per element. The use of these rules results in a smaller number of distinct attractors which have a shorter length, with relatively little sensitivity to the size of the network and to the number of inputs per element. Forcing away the activator/inhibitor ratio from the expected value of 50% further enhances the stability. This effect is more pronounced for networks consisting of a majority of activators than for networks with a corresponding majority of inhibitors, indicating that the former allow the evolution of larger genetic networks. The data further support the idea of the usefulness of logical networks as a conceptual framework for the understanding of real-world phenomena.

Algorithms↗

PubMed1994

The influence of limited presynaptic growth and synapse removal on adaptive synaptogenesis.

This report continues our research into the effectiveness of adaptive synaptogenesis in constructing feed-forward networks which perform good transformations on their inputs. Good transformations are characterized by the maintenance of input information and the removal of statistical dependence. Adaptive synaptogenesis stochastically builds and sculpts a synaptic connectivity in initially unconnected networks using two mechanisms. The first, synaptogenesis, creates new, excitatory, feed-forward connections. The second, associative modification, adjusts the strength of existing synapses. Our previous implementations of synaptogenesis only incorporated a postsynaptic regulatory process, receptivity to new innervation (Adelsberger-Mangan and Levy 1993a, b). In the present study, a presynaptic regulatory process, presynaptic avidity, which regulates the tendency of a presynaptic neuron to participate in a new synaptic connection as a function of its total synaptic weight, is incorporated into the synaptogenesis process. In addition, we investigate a third mechanism, selective synapse removal. This process removes synapses between neurons whose firing is poorly correlated. Networks that are constructed with the presynaptic regulatory process maintain more information and remove more statistical dependence than networks constructed with postsynaptic receptivity and associative modification alone. Selective synapse removal also improves network performance, but only when implemented in conjunction with the presynaptic regulatory process.

Computer Simulation↗

PubMed1989

Nodular organization and differential intrametastatic distribution of the fluorescent dye Hoechst 33342 in B16 melanoma liver metastasis.

The development of B16F10 liver metastases as related to its vascular organization was studied by morphological and functional methods, using the DNA-binding fluorochrome, Hoechst 33342. Experimental metastases were produced by intrasplenic injection of B16F10 melanoma cells, and the animals were sacrificed 3-7 days after tumor cell injection. The results show that early metastases are made up of avascular nodules of tumor cells, which subsequently developed lacunae which are not lined by endothelial cells and usually contain blood cells. A more developed metastasis seems to be made up of several nodules with or without lacunae. Between the nodules, vessels connected to blood circulation were usually observed. A functional study with a fluorescent dye showed that early metastases stained negatively, while more developed metastases showed a reticular fluorescent pattern, coincident with the intrametastatic vascular network and displaying a nodular image. In this case, the fluorescence displayed a gradient of intensity decreasing from the vessels towards the lacunae, where the tumor cells showed no fluorescence. In summary, our results suggest that B16 liver metastases have a nodular growth pattern, which is characterized by the formation, during their development, of lacunae not connected to the general circulation and that tumor cells have poor access to small molecules delivered from the blood.

Animals↗

PubMed1987

Morphologic and biochemical evidence for a contractile cell network within the rat intestinal mucosa.

Subepithelial and pericryptal fibroblastlike cells form a two-dimensional network immediately subjacent to the epithelial basal lamina in the small intestine and colon in several mammalian species. Stellate-shaped cells with similar, but not identical characteristics, form a three-dimensional network deep within the villar lamina propria. Electron microscopic studies indicate that these cells contain a putative contractile apparatus, are attached to each other and to apparently organized elements of the extracellular matrix by typical adhesive devices, and form gap junctions with each other. Comparative in situ immunoperoxidase localization studies document the presence in these cells of four contraction-associated proteins (smooth muscle isotropomyosin, cyclic guanosine monophosphate-dependent protein kinase, both nonmuscle and smooth muscle isomyosin, and actin) in amounts generally greater than those found in connective tissue fibroblasts, but less than in smooth muscle cells. Taken together, these results strongly suggest a smooth muscle-like, contractile function for these cells and indicate that this cellular network may provide a supportive tonus for the epithelium, as well as provide the force needed for active movement of the villus, expulsion of crypt secretion products, and propulsion of absorption products in the lamina propria, the microvasculature, and lacteals of the intestinal villus.

Animals↗

PubMed1999

"Mutagenesis" by peptide aptamers identifies genetic network members and pathway connections.

We selected peptide aptamers from combinatorial libraries that disrupted cell-cycle arrest caused by mating pheromone in yeast. We used these aptamers as baits in two-hybrid hunts to identify genes involved in cell-cycle arrest. These experiments identified genes known to function in the pathway, as well as a protein kinase, the CBK1 product, whose function was not known. We used a modified two-hybrid system to identify specific interactions disrupted by these aptamers. These experiments demonstrate a means to perform "genetics" on the protein complement of a cell without altering its genetic material. Peptide aptamers can be identified that disrupt a process. These aptamers can then be used as affinity reagents to identify individual proteins and protein interactions needed for the process. Forward genetic analysis with peptide aptamer "mutagens" should be particularly useful in elucidating genetic networks in organisms and processes for which classical genetics is not feasible.

Amino Acid Sequence↗

PubMed1982

Functional arrangement of connective tissue in striated muscle with emphasis on cardiac muscle.

The presence and arrangement of connective tissue associated with cardiac and skeletal muscle and composed principally of collagen is clearly demonstrable by scanning and high voltage electron microscopy. The basic organization consists of a perimysium composed of bundles of collagen fibers that connect the epimysium to the endomysium. The endomysium has at least 4 components: (1) a dense weave network that surrounds myocytes, (2) myocyte-myocyte collagen struts that connect adjacent myocytes, (3) myocyte-capillary struts that connect capillaries and myocytes, and (4) a complex of single collagen fibers, glycoproteins, and glycosaminoglycans. The amount of collagen in each component varies with the function of the muscle. Different types of skeletal muscles contain different amounts of collagen depending upon the function and composition of the particular muscle. In cardiac muscle the amount of collagen varies with different species. Different regions of the heart show differences in the amount of collagen due to different functional requirements of those regions. Thus, the amount of collagen in atria is different than in the ventricles due to differences in pressure and volume of these components of the heart.

Animals↗

PubMed2006

Foraging biology predicts food web complexity.

Food webs, the networks of feeding links between species, are central to our understanding of ecosystem structure, stability, and function. One of the key aspects of food web structure is complexity, or connectance, the number of links expressed as a proportion of the total possible number of links. Connectance (complexity) is linked to the stability of webs and is a key parameter in recent models of other aspects of web structure. However, there is still no fundamental biological explanation for connectance in food webs. Here, we propose that constraints on diet breadth, driven by optimal foraging, provide such an explanation. We show that a simple diet breadth model predicts highly constrained values of connectance as an emergent consequence of individual foraging behavior. When combined with features of real food web data, such as taxonomic and trophic aggregation and cumulative sampling of diets, the model predicts well the levels of connectance and scaling of connectance with species richness, seen in real food webs. This result is a previously undescribed synthesis of foraging theory and food web theory, in which network properties emerge from the behavior of individuals and, as such, provides a mechanistic explanation of connectance currently lacking in food web models.

Animals↗

PubMed2002

Multiple neural systems controlling food intake and body weight.

Discovery of the leptin receptor and its downstream peptidergic pathways has reconfirmed the crucial role of the hypothalamus in the regulation of food intake and energy balance. Strategically located in the midst of the mammalian neuraxis, the hypothalamus receives at least three distinct types of relevant information via direct or indirect neural connections as well as hormone receptors and substrate sensors bestowed on hypothalamic neurons. First, the medial and to a lesser extent the lateral hypothalamus receive a rich mix of information pertaining to the internal state of relative energy repletion/depletion. Second, specific hypothalamic nuclei receive information about the behavioral state, such as diurnal clock, physical activity-level, reproductive cycle, developmental stage, as well as imminent (e.g. fight and flight) and chronic (e.g. infection) stressors, that can potentially impact on short-term availability of fuels and long-term energy balance. Third, the hypothalamus, particularly its lateral aspects, receives information from areas in the forebrain involved in the acquisition, storage, and retrieval of sensory representations of the external food space and internal food experience, as well as from the executive forebrain involved in behavior selection and initiation. In addition, rich intrahypothalamic connections facilitate further distribution of incoming information to various hypothalamic nuclei. On the other hand, the hypothalamus has widespread neural projections to the same cortical areas it receives inputs, and many hypothalamic neurons are one synapse away from most endocrine systems and from both sympathetic and parasympathetic effector organs involved in the flux, storage, mobilization, and utilization of fuels. It is argued that processing within cortico-limbic areas and communication with hypothalamic areas are particularly important in human food intake control that is more and more guided by cognitive rather than metabolic aspects in the obesigenic environment of affluent societies. A distributed neural network for the control of food intake and energy balance consisting of a central processor and several parallel processing loops is hypothesized. Detailed neurochemical, anatomical, and functional analysis of reciprocal connections of the numerous peptidergic neuron populations in the hypothalamus with extrahypothalamic brain areas will be necessary to better understand what hypothalamus, forebrain, and brainstem tell each other and who is in charge under specific conditions of internal and external nutrient availability.

Animals↗

PubMed2003

Information transfer in the penta-EF-hand protein sorcin does not operate via the canonical structural/functional pairing. A study with site-specific mutants.

Sorcin is a typical penta-EF-hand protein that participates in Ca2+-regulated processes by translocating reversibly from cytosol to membranes, where it interacts with different target proteins in different tissues. Binding of two Ca2+/monomer triggers translocation, although EF1, EF2, and EF3 are potentially able to bind calcium at micromolar concentrations. To identify the functional pair, the conserved bidentate -Z glutamate in these EF-hands was mutated to yield E53Q-, E94A-, and E124A-sorcin, respectively. Limited structural perturbations occur only in E124A-sorcin due to involvement of Glu-124 in a network of interactions that comprise the long D helix connecting EF3 to EF2. The overall affinity for Ca2+ and for two sorcin targets, annexin VII and the ryanodine receptor, follows the order wild-type > E53Q- > E94A- > E124A-sorcin, indicating that disruption of EF3 has the largest functional impact and that disruption of EF2 and EF1 has progressively smaller effects. Based on this experimental evidence, EF3 and EF2, which are not paired in the canonical manner, are the functional EF-hands. Sorcin is proposed to be activated upon Ca2+ binding to EF3 and transmission of the conformational change at Glu-124 via the D helix to EF2 and from there to EF1 via the canonical structural/functional pairing. This mechanism may be applicable to all penta-EF-hand proteins.

Amino Acid Sequence↗