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PubMedDate not supplied

Comparative structural connectivity spectra analysis (CoSCoSA) models of steroids binding to the aromatase enzyme.

A method that combines NMR spectral and structural information into a constructed three-dimensional (3D)-connectivity matrix is developed for modeling biological binding activity of small molecules. The 3D-connectivity matrix for a molecule is defined by associating the distances between all possible carbon-to-carbon connections with their assigned carbon NMR chemical shifts. In this project we selected from the total 3D-connectivity matrix a subset, the two-dimensional (2D) (13)C-(13)C COSY and a theoretical long range 2D (13)C-(13)C distance connectivity spectral plane. Patterns of (13)C chemical shifts observed at these two relative distances for 50 steroids were used to produce a mathematical relationship for the steroids' relative binding affinity (pK(i)) to the aromatase enzyme. We call this technique comparative structural connectivity spectra analysis (CoSCoSA) modeling. Using combinations of the 2D COSY and 2D long-range distance spectra as modeling parameters, we built four CoSCoSA models. One model was made from the 2D COSY spectra alone and another was developed using only the 2D long-range distance spectra. Then the COSY and long-distance spectra were combined in two different ways: starting with the combined principal components (PCs) from the separately calculated COSY and distance spectra or using the combined raw spectra (3D). The best CoSCoSA model was based on the combined PCs from COSY and distance spectra. This model had an r(2) of 0.96 and a leave-one-out cross-validation (q(2)) of 0.92. In general CoSCoSA modeling combines the quantum mechanical information inherent in NMR chemical shifts with internal molecular atom-to-atom distances to give a reliable and straightforward basis for predictive modeling. The technique has the flexibility and accuracy to outperform not only the cross-validated variance q(2) of previously published quantitative structure-activity relationships (QSAR) but also those obtained by related quantitative spectral data-activity relationships (QSDARs) lacking connectivity dimensions.

Aromatase↗
PubMed1982

Formation of novel central and peripheral connections between molluscan central neurons in organ cultured ganglia.

An in vitro organ culture system for buccal ganglia of the adult snail, Helisoma, is described. The system supports: (1) maintenance of characteristic electrophysiological parameters of identified neurons over seven days of culture; (2) choline metabolism including uptake and synthesis over the same duration; (3) sprouting and growth of neurons in response to axotomy; (4) the formation of novel central electrotonic connections between identified neurons as a result of sprouting and growth. These observations on neuronal growth and the formation of connections are similar to those made with in vivo culture. The use of in vitro culture allows precise manipulations not previously possible. When buccal ganglia are cultured in vitro with the cut distal ends of peripheral nerve trunks held closely apposed, axons of neurons 5R and 5L in the nerve trunks are capable of forming electrotonic connections similar to central connections. The capability of these neurons to form electrotonic connections via their peripheral axons implies that special structures (i.e., central neurites) are not required for the formation of connections; and neither are special environments (i.e., the central neuropile) required for these connections.

Animals↗
PubMed1994

Analysis and classification of disulphide connectivity in proteins. The entropic effect of cross-linkage.

An analysis and a classification of protein disulphide connectivity in a set of distinct sequences are presented. We analyse the number of disulphides per sequence, the number of disulphides per residue and the length of disulphide cross-linked loops. Observed connectivities are classified according to the different possible types of arrangement. In addition, we classify disulphide connectivity by physical models describing the arrangement of multiple disulphides. Firstly, we consider whether the features of native connectivity arrangement are describable by the likelihood of diffusive contact in the unfolded state. This is referred to as the diffusion model, and was originated by Kauzmann. A second model, effectively the inverse of the diffusion model, describes native connectivity arrangement as dominated by the entropic stabilisation effect of cross-linkage. This is referred to as the entropic model. Additionally, we compare the distribution of disulphide cross-linked loops and of loops formed by disulphide-like contacts. For short sequences (less than about 75 residues) native connectivities tend to have entropically more-stabilising arrangement features, whilst for longer sequences (greater than about 200 residues) the diffusion model is appropriate. We introduce the concept of arrangement entropy as a measure of the complexity of a connectivity.

Disulfides↗
PubMed2002

Effective connectivity and intersubject variability: using a multisubject network to test differences and commonalities.

This article is about intersubject variability in the functional integration of activity in different brain regions. Previous studies of functional and effective connectivity have dealt with intersubject variability by analyzing data from different subjects separately or pretending the data came from the same subject. These approaches do not allow one to test for differences among subjects. The aim of this work was to illustrate how differences in connectivity among subjects can be addressed explicitly using structural equation modeling. This is enabled by constructing a multisubject network that comprises m regions of interest for each of the n subjects studied, resulting in a total of m x n nodes. Constructing a network of regions from different subjects may seem counterintuitive but embodies two key advantages. First, it allows one to test directly for differences among subjects by comparing models that do and do not allow a particular connectivity parameter to vary over subjects. Second, a multisubject network provides additional degrees of freedom to estimate the model's free parameters. Any neurobiological hypothesis normally addressed by single-subject or group analyses can still be tested, but with greater sensitivity. The common influence of experimental variables is modeled by connecting a virtual node, whose time course reflects stimulus onsets, to the sensory or "input" region in all subjects. Further experimental changes in task or cognitive set enter through modulation of the connections. This approach allows one to model both endogenous (or intrinsic) variance and exogenous effects induced by experimental design. We present a functional magnetic resonance imaging study that uses a multisubject network to investigate intersubject variability in functional integration in the context of single word and pseudoword reading. We tested whether the effect of word type on the reading-related coupling differed significantly among subjects. Our results showed that a number of forward and backward connections were stronger for reading pseudowords than words, and, in one case, connectivity showed significant intersubject variability. The discussion focuses on the implications of our findings and on further applications of the multisubject network analysis.

Adult↗
PubMed1993

Elastic properties of connecting filaments along the sarcomere.

The elasticity of the connecting filament--the filament that anchors the thick filament to the Z-line--has been investigated using rigor release, freeze-break and immunolabelling techniques. When relaxed insect flight muscle was stretched and then allowed to go into rigor, then released, the recoil forces of the connecting filaments caused sarcomeres to shorten. Thin filaments, prevented from sliding by rigor links, were found crumpled against the Z-line. Thus, rigor release experiments demonstrate the spring-like nature of the connecting filaments in insect flight muscle. In vertebrate skeletal muscle, however, the same protocol did not result in sarcomere shortening. Absence of shortening was due to either smaller stiffness of connecting filaments and/or higher stiffness of the thin filaments relative to insect flight muscle. The spring-like nature of the connecting filament was confirmed with the freeze break technique. When the frozen sarcomeres were broken along the A-I junction, the broken connecting filaments retracted to the N1-line level, independently of the thin filaments, demonstrating the basic elastic nature of these filaments. To study the elastic properties of the connecting filaments along the sarcomere, the muscle was labelled with monoclonal antibodies against a titin epitope near the N1-line, and another very near the A-I junction in the I-band. Before labelling, fibers were pre-stretched to varying extents.(ABSTRACT TRUNCATED AT 250 WORDS)

Actin Cytoskeleton↗
PubMed1987

Detection and estimation of neural connectivity based on crosscorrelation analysis.

Crosscorrelation analysis of simultaneously recorded activity of pairs of neurons is a common tool to infer functional neural connectivity. The adequacy of crosscorrelation procedures to detect and estimate neural connectivity has been investigated by means of computer simulations of small networks composed of fairly realistic modelneurons. If the mean interval of neural firings is much larger than the duration of postsynaptic potentials, which will be the case in many central brain areas excitatory connections are easier to detect than inhibitory ones. On the other hand, inhibitory connections are revealed better if the mean firing interval is much smaller than post-synaptic potential duration. In general the effects of external stimuli and the effects of neural connectivity do not add linearly. Furthermore, neurons may exhibit a certain degree of timelock to the stimulus. For these reasons the commonly applied "shift predictor" procedure to separate stimulus and neural effects appears to be of limited value. In case of parallel direct and indirect neural pathways between two neurons crosscorrelation analysis does not estimate the direct connection but instead an effective connectivity, which reflects the combined influences of the parallel pathways.

Animals↗
PubMedDate not supplied

Monosynaptic connection: identifiable synapses in the CNS of the edible snail.

The microanatomy of the pre- and postsynaptic neurons and the structure of the monosynaptic connection LPa7-LPa3 are described on the basis of planar reconstruction of sections of preparations of the CNS of the edible snail with neurons marked by heavy metal salts. Some physiological features of the presynaptic neuron and the monosynaptic connection were studied. The criteria for the identification of the LPa7 neuron according to its position in the ganglion, to the physiological reaction of LPa3, and to its microanatomy were determined. The position in the ganglion of three other neurons which form monosynaptic connections with LPa3 is described. The plasticity of the LPa7-LPa3 connection is demonstrated. The possibility of the realization of plasticity through the cutting off of individual synapses composing the connection is hypothesized. The results of 65 experiments on the identification of LPa7, the physiological characteristics of this cell, and its monosynaptic connection with LPa3, are summarized in this study. One preparation with a monosynaptic connection is reconstructed.

Animals↗
PubMedDate not supplied

Neuronal manifestation of two-way connections in conditioning.

Neuronal characteristics of two-way conditional connections were studied in chronic experiments with alert cats during different types of alimentary conditional reflexes. Single unit and multi-unit activities were chronically recorded in the visual and motor cortex and the lateral hypothalamic nucleus. Cross-correlational analysis of neuronal impulse trains was used to characterize the organization of neuron groups in brain structures involved in the formation of a conditional reflex. The experimental data showed an increase in the number of neuronal two-way connections after learning in all three investigated coordinations: visual-motor, visual-hypothalamic, and motor-hypothalamic. With visual-motor interneuronal coordination, the strengthening of two-way connections was due to the enhancement of connections from the motor to the visual neuron (backward connections); with visual- and motor-hypothalamic coordination, the number of interneuronal connections was equal in both directions. In all investigated coordinations, the analysis of the temporal parameters of the interactions between the neurons of different groups showed a dependence of the conditioning procedure on delays of up to 30 ms and a dependence of the motivational state on the interval range of 90-100 ms. The polyfunctional and polycomponent character of two-way neuronal connections in conditioning can be inferred from these data. Evaluation of the activity of neurons of different brain structures suggests the specific organization of intracortical and cortical-subcortical integrity in learning.

Animals↗
PubMed2001

Local lateral connectivity of inhibitory clutch cells in layer 4 of cat visual cortex (area 17).

To characterise spatially a major component of the anatomical basis of local lateral inhibition in layer 4 of cat visual cortex (area 17), we analysed the lateral distribution of neuronal somata postsynaptic to electrophysiologically characterised GABAergic clutch (basket) cell axons (CC1 and CC2). We report two main results. First, the clutch cell axons appear to show isotropic lateral connectivity near their cell body (less than 50 microm radius), but beyond this core region they show anisotropic lateral connectivity, preferring particular angular sectors around their cell body. Second, we estimated the probability of lateral connection for each axon arbor as a function of radial distance from the parent soma. We found that this radial function has a brief rising phase, to a peak at 30-45 microm, and a longer, exponential decaying phase, with a space constant of around 50 microm. The shape of the radial connection probability function suggests that most lateral inhibitory connections of clutch cells are formed with neurons in nearest-neighbour cortical columns. Taken together, the results suggest that these individual layer-4 clutch cell axons may inhibit all (isotropic) nearest-neighbour cortical columns with a relatively high probability of connection, but outside this core region may provide a type of anisotropic lateral inhibition of cortical columns with a radially decreasing probability of connection.

Animals↗
PubMedDate not supplied

Does caval aplanarity influence power losses across in vitro cavopulmonary connections?

Optimally designed cavopulmonary connections are desirable to reduce transanastomotic power loss. Since aplanarity of the total cavopulmonary connections results from the natural anterior-posterior position of the superior vena cava and the right pulmonary artery, the aim of this study was to investigate the influence of aplanarity of caval offset on transanastomotic power losses. Two types of cavopulmonary connections, a planar cross-like connection and a nonplanar V-shaped anastomosis, were studied in a mock circulation, comparing for each type native porcine vessels and Perspex glass models. Total flow varied between 1200 and 6000 ml/min at superior to inferior caval flow ratios of SVC/IVC = 50/50% and 33/67%, respectively. Pressures and flows were measured and power losses calculated. No significant differences in power losses were found between the planar and aplanar connections for native vessels or for Perspex glass models. Power losses across the native preparations in each configuration were significantly higher than those in the corresponding Perspex glass model. The simulation of the natural aplanar V-shaped caval offset in total cavopulmonary connections used to bypass the right ventricle seems to have no relevant additional effect on in vitro power losses compared to planar connections.

Adolescent↗
PubMed2005

Embryonic electrical connections appear to pre-figure a behavioral circuit in the leech CNS.

During development, many embryos show electrical coupling among neurons that is spatially and temporally regulated. For example, in vertebrate embryos extensive dye coupling is seen during the period of circuit formation, suggesting that electrical connections could pre-figure circuits, but it has been difficult to identify which neuronal types are coupled. We have used the leech Hirudo medicinalis to follow the development of electrical connections within the circuit that produces local bending. This circuit consists of three layers of neurons: four mechanosensory neurons (P cells), 17 identified interneurons, and approximately 24 excitatory and inhibitory motor neurons. These neurons can be identified in embryos, and we followed the spatial and temporal dynamics as specific connections developed. Injecting Neurobiotin into identified cells of the circuit revealed that electrical connections were established within this circuit in a precise manner from the beginning. Connections first appeared between motor neurons; mechanosensory neurons and interneurons started to connect at least a day later. This timing correlates with the development of behaviors, so the pattern of emerging connectivity could explain the appearance first of spontaneous behaviors (driven by a electrically coupled motor network) and then of evoked behaviors (when sensory neurons and interneurons are added to the circuit).

Animals↗
PubMed1990

Usefulness of combined propranolol and verapamil for evaluation of surgical ablation of accessory atrioventricular connections in patients without structural heart disease.

Successful surgical ablation of atrioventricular (AV) accessory connections may be confirmed during postoperative electrophysiologic testing by the absence of accessory connection conduction in both the anterograde and retrograde directions. Whereas the former may be readily apparent by examination of the surface electrocardiogram during sinus rhythm or atrial pacing, assessment of the latter may be complicated by the frequent presence of enhanced retrograde AV nodal conduction in the postoperative period. Consequently, availability of interventions that selectively affect AV nodal conduction and refractoriness without concomitant effects on accessory connections may be helpful for assessing the success of the surgical procedure. In this study the effects of combined propranolol and verapamil administration on electrophysiologic properties of the AV node and the accessory AV connection were assessed both pre- and postoperatively in 17 patients (12 men and 5 women, mean age 33 years) undergoing surgical ablation of accessory connections. Preoperatively, electrophysiologic characteristics of all but 1 of the accessory AV connections were unaffected by propranolol and verapamil administration. Postoperatively, on the other hand, propranolol and verapamil significantly prolonged both the retrograde AV node effective refractory period (baseline: 272 +/- 34 ms vs after drugs: 384 +/- 70 ms [p less than 0.0001]) and the shortest cycle length maintaining 1:1 ventriculoatrial conduction (baseline: 357 +/- 99 ms vs after drugs: 485 +/- 64 ms [p less than 0.0001]). Late postoperative electrophysiologic evaluation (7 +/- 3 weeks) revealed no evidence of residual accessory AV connection conduction, and all patients remain asymptomatic at 21 +/- 10 months follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

The connections of area PG, 7a, with cortex in the parietal, occipital and temporal lobes of the monkey.

The cortico-cortical connections of area PG, 7a, in the parietal, occipital and temporal lobes have been studied after injections of HRP in this area and in certain of the areas connected with it. After such injections in PG there are labelled cells in architectonic areas OA and PE (visual area PO), the cingulate and retrosplenial areas situated medial to PG; posteriorly labelled cells are present in OA, visual areas MST, MT, V2, V3, V4 and in the walls and floor of the lower part of the superior temporal sulcus. Injections in PE and V4 show that these connections are reciprocal. Small injections in PG result in cell labelling in different parts of the areas connected to PG, suggesting that the connections are well organized and that there may be an ordered representation of the visual field in PG. In the lower wall of the lower part of the superior temporal sulcus there is overlap of the two visual pathways in the cortex, that to the temporal lobe with that to the parietal lobe; and in a restricted part of this sulcus there is convergence and overlap of the sequences of cortico-cortical connections related to the visual, somatic and auditory sensory systems. There may be certain common principles in the sequences of cortical connections to the parietal and temporal lobes from the primary visual and somatic sensory areas; in both there are well organized hierarchical and parallel pathways, and both are related to the superior temporal sulcus and to the cingulate cortex.

Animals↗
PubMed1984

Electron microscopic studies on the connections between capsomers in the adenovirus capsid.

Electron microscopic observation of negatively stained virions suggests that the interhexonal spaces within the adenovirus capsid are bridged by interhexonal connective elements. Similar connections are also detected between pentons and the five peripentonal hexons. Examinations of electron micrographs by Markham's rotational integration technique reveals the presence of a regular network of the connective elements between the capsomers in the whole capsid. The length of these connections corresponds to about one-third of the diameter of the hexons. The connections consist of two approximately parallel elements, thus every hexon is joined to its six nearest neighbours by 12 connections. A possible mutual orientation pattern of the connective elements in the whole capsid is presented on a tentative virus model.

Adenoviridae↗
PubMedDate not supplied

The descending auditory pathway and acousticomotor systems: connections with the inferior colliculus.

In this review the following major points are emphasized. First, the descending auditory system includes 3 separate, but parallel pathways connecting the AC, MGB and IC. Each pathway makes a strong set of connections with a distinctive area from each of 3 auditory centers. The three sets of connections are mutually exclusive, such that the pathways describe 3 separate corticocolliculo-geniculate systems. Thus, multiple feedback loops between the AC and the IC are formed which create a great capacity for parallel processing of auditory information. Second, the IC projects to the SOC and, in particular, to the source of olivocochlear efferent neurons. The connections of the IC with the AC rostrally, and with the olivocochlear neurons caudally, imply a descending trisynaptic pathway from the cortex to the cochlea whose travel time could better that of the ascending pathway and thus provide an efficient feedback mechanism. It is probable that the IC influences cochlear signal processing. The reciprocal connectivity between any two of either the IC, SOC or the CN, again, affords to the auditory system remarkable parallel processing capabilities. Finally, the descending auditory, and 'extra-auditory' connections of the IC bestow a functional separateness to the 3 nuclei of the IC, a view that is best illustrated by description of the ICX as an acousticomotor nucleus, having connections with the SC, cerebellum and somatosensory and vocalization systems. More sophisticated questions about the descending auditory system will incorporate these present observations and test functional implications to which they allude.

Animals↗
PubMed1988

Organization of the afferent connections of the mediodorsal thalamic nucleus in the rat, related to the mediodorsal-prefrontal topography.

The aim of the present study was to determine the organization of the afferents of the mediodorsal thalamic nucleus in relation to the reciprocal connections of this nucleus with different areas of the prefrontal cortex. For this purpose injections of horseradish peroxidase, or horseradish peroxidase conjugated to wheatgerm agglutinin were placed in different parts of the mediodorsal nucleus. These experiments revealed the organization of the reciprocal mediodorsal-prefrontal connections since wheatgerm agglutinin-horseradish peroxidase is transported effectively in anterograde and retrograde directions. Injections of wheatgerm agglutinin-horseradish peroxidase or fluorescent tracers were placed in different portions of the prefrontal cortex, and the lectin Phaseolus vulgaris leucoagglutinin was injected in the mediodorsal nucleus in order to verify in more detail the point-to-point relationship in the mediodorsal-prefrontal connections. The organization of a number of the subcortical afferents to the mediodorsal nucleus was determined in detail using injections of Phaseolus vulgaris leucoagglutinin, wheatgerm agglutinin-horseradish peroxidase, or tritiated amino acids in areas identified as a source of mediodorsal afferents in the retrograde tracing experiments. These anterograde tracers were injected in different parts of the pallidal complex, the amygdala, the lateral hypothalamus, the lateral entorhinal cortex, the ventral mesencephalon, the superior colliculus and the dorsal tegmental region. The results of the present experiments indicate that the mediodorsal nucleus, on the basis of its cyto-, myelo- and chemoarchitecture as well as the organization of its reciprocal connections with the prefrontal cortex, can be subdivided into a medial, a central, a lateral and a paralamellar segment. Apart from this subdivision along a mediolateral axis, rostrocaudal and dorsoventral differences are also evident in the structural organization and connectivity of the mediodorsal nucleus. A number of subcortical structures send fibres to all parts of the mediodorsal nucleus. The reticular thalamic nucleus projects to the mediodorsal nucleus in a topographical way such that its rostral part is connected with the rostral part of the nucleus, whereas more caudal and ventral areas in the reticular thalamic nucleus are connected with more caudal parts of the mediodorsal nucleus. Regions in the brainstem that project to all parts of the mediodorsal nucleus include the mesencephalic raphé nuclei, the locus coeruleus, the rostral part of the central gray substance and the reticular formation.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1989

Functional consequences of modification of callosal connections by perinatal enucleation in rat visual cortex.

The effects of neonatal monocular enucleation (right eye) on the callosal connections in the rat visual cortex were studied by physiological and morphological methods. Evoked activity was recorded in the left hemisphere, i.e. contralaterally to the enucleated eye. After enucleation, trans-callosally evoked responses were recorded in a widened stripe of the lateral visual cortex. Compared with the controls, the responsive area was expanded laterally and medially, i.e. into the lateral part of the primary visual area and within the secondary visual cortex (lateral part). Within about 0.5 mm of the expansion, the responses did not differ from those recorded in areas with "normal" callosal connections. Morphological evidence is presented suggesting that this expansion of evoked responses with high amplitudes and short latencies corresponds to an extension of callosal connections with a high density of axon terminals in layers two and three. Further medially within the primary visual cortex, callosally evoked responses with low amplitudes and longer latencies were recorded. The main types of unit responses and characteristic interactions between visually and callosally evoked responses are shown and discussed. These results suggest that following neonatal enucleation (1) the callosal connections expand and form functional synapses in the lateral part of the visual cortex, (2) these connections can activate cortical neurons either directly or by mediation of associational connections between the lateral secondary and primary visual cortex areas and (3) callosal connections can interact with visually evoked potentials and unit responses.

Animals↗
PubMed1991

Repolarization abnormalities after catheter ablation of accessory atrioventricular connections with radiofrequency current.

The purpose of this study was to evaluate the serial changes in T wave configuration in patients undergoing successful radiofrequency catheter ablation of accessory atrioventricular (AV) connections. Twenty-nine consecutive patients with overt preexcitation and 16 patients with a concealed accessory atrioventricular (AV) connection were included. An electrocardiogram (ECG) was recorded before ablation and 15 min, 1 or 2 days and 1 and 3 months after ablation. Postablation T wave abnormalities occurred in 22 (76%) of the 29 patients who had overt pre-excitation but in none of the 16 patients with a concealed accessory AV connection. The T wave abnormalities were not related to myocardial necrosis or echocardiographic abnormalities. The ECG location and severity of T wave changes were dependent on the accessory AV connection location and degree of baseline pre-excitation, respectively. Fourteen of 19 patients with a posteriorly located AV connection (left, right or septal) had T wave inversion or flattening in the inferior leads and 3 patients had precordial T wave peaking. Two patients with an anteroseptal AV accessory connection had both inferior T wave inversion or flattening and precordial T wave peaking. Among seven patients with a manifest left lateral accessory AV connection, two had lateral T wave inversion or flattening and two had precordial T wave peaking. There was 95% concordance between the directional change of the T wave after ablation and the direction of the delta wave on the baseline ECG.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗