[Electrophysiologic characteristics of caudate-thalamic connections].
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Animals↗
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A connected set algorithm for the identification of spatially contiguous regions in crystallographic envelopes.
A simple algorithm is described for the identification of spatially contiguous regions in crystallographic envelopes. In a single pass through the grid points of the envelope map, the occupied points are assigned to a series of locally contiguous sets based on consideration of the connections within single voxels. A spatially contiguous region is identified as the union of all of the locally contiguous sets that share an element in common. Therefore, chains of spatial connectivity are traced implicitly by performing simple set operations. This algorithm has been implemented in the program CNCTDENV as part of the DEMON/ANGEL suite of density-modification programs.
Journal Article↗
Mapping of protein disulfide bonds using negative ion fragmentation with a broadband precursor selection.
Fast mapping of disulfide bonds in proteins containing multiple cysteine residues is often required in order to assess the integrity of the tertiary structure of proteins prone to degradation and misfolding or to detect distinct intermediate states generated in the course of oxidative folding. A new method of rapid detection and identification of disulfide-linked peptides in complex proteolytic mixtures utilizes the tendency of collision-activated peptide ions to lose preferentially side chains of select amino acids in the negative ion mode. Cleavages of cysteine side chains result in efficient dissociation of disulfide bonds and produce characteristic signatures in the fragment ion mass spectra. While cleavages of other side chains result in insignificant loss of mass and full retention of the peptide ion charge, dissociation of external disulfide bonds results in physical separation of two peptides and, therefore, significant changes of both mass and charge of fragment ions relative to the precursor ion. This feature allows the fragment ions generated by dissociation of external disulfide bonds to be easily detected and identified even if multiple precursor ions are activated simultaneously. Such broadband selection of precursor ions for consecutive activation is achieved by lowering the dc/rf amplitude ratio in the first quadrupole filter of a hybrid quadrupole time-of-flight mass spectrometer. The feasibility of the new method is demonstrated by partial mapping of disulfide bridges within a 37-kDa protein containing 16 cysteine residues and complete disulfide mapping within a lysozyme (14.5 kDa) containing 8 cysteine residues. In addition to detecting peptide pairs connected by a single external disulfide, the new method is also shown to be capable of identifying peptides containing both external and internal disulfide bonds. The two major factors determining the efficiency of disulfide mapping using the new methodology are the effectiveness of proteolysis and the ability of the resulting proteolytic fragments to form multiply charged negative ions.
Amino Acid Sequence↗
Percolation clustering: a novel approach to the clustering of gene expression patterns in Dictyostelium development.
We present a novel approach to the clustering of gene expression patterns based on the mutual connectivity of the patterns. Unlike certain widely used methods (e.g., self-organizing maps and K-means) which essentially force gene expression data into a fixed number of predetermined clustering structures, our approach aims to reveal the natural tendency of the data to cluster, in analogy to the physical phenomenon of percolation. The approach is probabilistic in nature, and as such accommodates the possibility that one gene participates in multiple clusters. The result is cast in terms of the connectivity of each gene to a certain number of (significant) clusters. A computationally efficient algorithm is developed to implement our approach. Performance of the method is illustrated by clustering both constructed data and gene expression data obtained from Dictyostelium development.
Algorithms↗
Interconnections of auditory areas in the guinea pig neocortex.
By studying the efferent projections of five auditory areas in the guinea pig cortex, we sought evidence that the larger fields can be divided into subareas based on unique patterns of cortical connections. Small extracellular injections of biocytin were made in combination with evoked potential mapping or single-unit analysis and histochemical determination of cortical landmarks. The two core fields, primary (AI) and dorsocaudal (DC), are partially surrounded by six adjacent belt areas, leaving two gaps: one at the rostral edge of AI and the other at the dorsal edge. All of the areas studied projected to their nearest neighbors, but AI was the only area to project to all seven of the other auditory areas. The caudal, high-frequency (more than 4 kHz) end of AI had different projections from the rostral, low-frequency (less than 1.5 kHz) end, and there was no evidence of connections between the two ends. Each end had separate dorsal and ventral projections. The two ends of AI may be working independently. By contrast, area DC had strong connections between its high- and low-frequency ends and it may be involved in auditory/visual integration. The dorsorostral belt (DRB) was subdivided into two zones on the basis of its projections: the more rostral part appears to overlap the second somatosensory area and be bimodal, while the caudal part has stronger auditory connections. The small belt area (area S) had separate physiological and anatomical properties from the rest of the rostral belt.
Animals↗
[Quantitative aspects of the formation of a half chromatid chiasma as an intermediate product of genetic recombination in bacteriophages].
Formal genetic consequences of generation and break-up of a half chromatid chiasma have been studied on the basis of a model with the symmetric exchange of two strands between parental DNA molecules. In recombination analysis, generation and break-up of this structure gives rise to a critical frequency R (zeta), which corresponds to recombination between two markers separated by a distance equal to the mean genetic length zeta of the hybrid region at the time of scission of the cross connection. The use of the distance zata as a natural unit of a genetic map is suggested. In the case of bacteriophage T4 under conditions of standard crosses the half chromatid chiasma is characterized by the value R (zata) equal to 3.0-10(-2), the structure acquiring with equal probability either of the two alternative isomeric configurations at the time of scission of the cross connection. About four per cent of the total number of mismatches as a result of break-up to the half chromatid chiasm were repaired.
Chromatids↗
Evidence that the bed nucleus of the stria terminalis contributes to the modulation of hypophysiotropic corticotropin-releasing factor cell responses to systemic interleukin-1beta.
Systemic infection activates the hypothalamic-pituitary-adrenal (HPA) axis, and brainstem catecholamine cells have been shown to contribute to this response. However, recent work also suggests an important role for the central amygdala (CeA). Because direct connections between the CeA and the hypothalamic apex of the HPA axis are minimal, the present study investigated whether the bed nucleus of the stria terminalis (BNST) might act as a relay between them. This was done by using an animal model of acute systemic infection involving intravascular delivery of the proinflammatory cytokine interleukin-1beta (IL-1beta, 1 microg/kg). Unilateral ibotenic acid lesions encompassing the ventral BNST significantly reduced both IL-1beta-induced increases in Fos immunoreactivity in corticotropin-releasing factor (CRF) cells of the hypothalamic paraventricular nucleus (PVN) and corresponding increases in adrenocorticotropic hormone (ACTH) secretion. Similar lesions had no effect on CRF cell responses to physical restraint, suggesting that the effects of BNST lesions were not due to a nonspecific effect on stress responses. In further studies, we examined the functional connections between PVN, BNST, and CeA by combining retrograde tracing with mapping of IL-1beta-induced increases in Fos in BNST and CeA cells. In the case of the BNST, these studies showed that systemic IL-1beta administration recruits ventral BNST cells that project directly to the PVN. In the case of the CeA, the results obtained were consistent with an arrangement whereby lateral CeA cells recruited by systemic IL-1beta could regulate the activity of medial CeA cells projecting directly to the BNST. In conclusion, the present findings are consistent with the hypothesis that the BNST acts as a relay between the CeA and PVN, thereby contributing to CeA modulation of hypophysiotropic CRF cell responses to systemic administration of IL-1beta.
Adrenocorticotropic Hormone↗
Somatotopic mapping of sensory neurons innervating mechanosensory hairs on the larval prolegs of Manduca sexta.
The abdominal prolegs are the principal locomotory appendages of the larval tobacco hornworm, Manduca sexta. The prolegs bear numerous mechanosensory bristle sensilla, each innervated by an afferent neuron that arborizes within the central nervous system (CNS). Based on their positions on the proleg, we have divided the sensilla into planta hairs (PHs), lateral hairs (LHs), and medial hairs (MHs). Previously, we found that PH afferents produce monosynaptic excitatory postsynaptic potentials (EPSPs) in proleg retractor muscle motoneurons, the size of which depends on the position of the hair in the PH array. In this paper we examined the central arbors of the proleg afferents to determine whether there was an anatomical correlate to the pattern of synaptic strengths. We found that the afferent arbors are arranged somatotopically within the CNS in a pattern similar to that for bristle afferents elsewhere on the abdomen; i.e., the anterior-posterior and medial-lateral position of a hair on the proleg was reflected in the location of the afferent arbor along the corresponding axes within sensory neuropil. All afferents terminated within a similar ventral region of neuropil. The arbors of PH, MH, and to a lesser extent, LH afferents, were enlarged as compared to afferents innervating hairs elsewhere on the abdomen. This feature, combined with the dense innervation of the proleg, causes the proleg region to be relatively overrepresented in sensory neuropil. We also examined the afferents innervating a pair of ventral midline hairs (VMHs) present in each abdominal segment, which, unlike the other afferents, showed segment-specific central arbors. We conclude that the somatotopic mapping of afferent arbors may contribute to the specificity of synaptic connections in this system.
Afferent Pathways↗
Frustrated chaos in biological networks.
The behaviour of three biologically inspired networks is investigated: Immune Idiotypic Network (IIN), Hopfield Network (HN) and Coupled Map Lattice (CML), mainly the effect on the dynamics induced by connecting the network in a frustrated way. Frustration occurs when the global structure is such that local connectivity patterns responsible for stable behaviour are intertwined, leading to mutually competing attractors and chaotic itinerancy among brief appearance of these attractors. Frustration destabilizes the network and provokes an unpredictable "wavering" among the stable dynamic regimes which characterize the same network when it is interconnected in a non-frustrated way. As the main contribution of this paper, an immune idiotypic network in which the prevailing behaviour is oscillatory is studied in detail. It is shown how connecting an elementary three-clone network in a frustrating way transforms the oscillatory regime into a chaotic one. This chaotic regime is further analysed and several interesting aspects are discussed such as the variable homogeneity, the intrinsic chaotic itinerancy among brief oscillatory regimes and the strong unpredictability. In addition, dynamical regimes obtained by frustrating the connectivity of HN and CML are presented and the similarities as well as the differences with the IIN dynamics are emphasized. Common to all these networks is the description of the frustrated chaos as a succession of attempts to relax the network into one of the oscillatory regimes given by a weaker and non-frustrated connectivity, an impossible achievement making the dynamics rambling over brief but repelling orbits.
Animals↗
Spatial and temporal dynamics of hedgerows in three agricultural landscapes of southern Quebec, Canada.
Noncrop areas such as hedgerows in agricultural landscapes can perform several ecological and agronomic functions (e.g., habitat, movement corridors, windbreak, etc.), but their dynamics and drivers of changes are often poorly known. We conducted a study in three agricultural landscapes of southern Quebec, Canada, to assess and compare the spatial and temporal (1958-1997) dynamics of three hedgerow networks in relation to geomorphic conditions (marine, glacial, and mixed deposit) and land-use changes. Hedgerow networks were mapped and described in terms of their structure (density, degree of connectivity, and presence of trees or shrubs) and their relationship to other components of the landscape (connection to woodland). Relationships were assessed in time and space using nonparametric correlation, Mantel test, and principal components analysis (PCA). Results show significant differences between hedgerow structure for the three landscapes and distinct temporal and spatial dynamics that can be related to changes in management practices and agricultural policies. On marine deposits, increases in hedgerow density did not always correspond to an increase in their degree of connectivity, suggesting a possible reduction in network quality. On glacial deposits, hedgerow density declined following abandonment of agricultural land, but rather than disappearing, these linear structures were integrated into adjacent brush or forested areas. Our analysis reveals the complex spatial and temporal dynamics of the hedgerow networks and highlights the need to take into account spatial attributes such as connectivity and connection to woodland to evaluate more accurately overall network quality.
Agriculture↗
Phase image analysis of anomalous ventricular activation in pediatric patients with preexcitation syndromes or ventricular tachycardia.
This prospective study evaluated the accuracy of phase analysis of scintigraphic imaging in defining the site of earliest ventricular activation in pediatric patients with electrophysiologic disorders. Twenty patients (10.8 +/- 5.5 years) with preexcitation (n = 16) or ventricular tachycardia (VT) (n = 4) were independently evaluated by phase image analysis and endocardial catheter mapping. The earliest phase angle (contraction), which was common to three scintigraphic imaging planes during preexcited sinus rhythm or VT, was compared with the earliest retrograde atrial activation during reciprocating tachycardia or the origin of VT, as defined by catheter mapping. Phase analysis of earliest contraction was concordant with catheter mapping of electrical activation in all 13 free-wall accessory connections and in three of four patients with VT. Inconclusive definition of activation occurred only in paraseptal accessory connections or VT. In conclusion, phase analysis accurately defines anomalous ventricular activation that is due to free-wall accessory connections or VT. In patients with complex anatomy or small size, phase analysis allows noninvasive localization of the anatomic substrates of tachycardia.
Adolescent↗
Simple microcomputer system for mapping tissue sections with the light microscope.
We describe a method for two-dimensional mapping of tissue sections that makes use of a drawing tube, microscope stage encoders and a microcomputer. The drawing tube views the graphics monitor and superimposes the image of the screen cursor and on-screen menus on the specimen image. Thus, the position of every landmark in each microscopic field can be mapped without stage movement while directly viewing the specimen through the microscope. A mouse is used for data entry and program control. Fields mapped in this way are then assembled into a complete map, which can include line drawings as well as up to 20 landmark types. The coordinate values of all landmarks mapped are stored and remain accessible for editing and analysis. High resolution plots are produced. Specialized functions include grain counting, area and perimeter calculations as well as a perimeter limiter that predefines the area to be mapped. The system uses general purpose hardware that is widely available. Many hitherto time-consuming tasks, such as detailed mapping of cell positions, regions of immunocytochemical staining, degenerating fibers, neuronal connections or any other anatomical feature, can be done in a fraction of the time and effort previously involved. These labor savings can be realized while maintaining the highest resolution and enabling statistical analysis since the data are already in digital form.
Animals↗
Visual spatial integrity in the absence of splenium.
Several lines of evidence have confirmed that visual integrity among the two hemifields is severely impaired following transection of posterior part of the corpus callosum (splenium). But the extent of this impairment differs for various visual functions. Here, in a posterior callosectomized patient (MD), interhemispheric visual spatial integrity is investigated in three experiments. In the first experiment, MD was asked to make decision about horizontal alignment of two balls presented simultaneously in one of three conditions: both in right or left hemifield, or each in one hemifield. We have previously shown that she is not able to perform a shape-matching task for stimuli presented to different hemifields. But in this task, MD was able to compare location of the two bilaterally presented stimuli significantly above chance level. Then we investigated whether attentive visual object tracking across vertical meridian of the visual field is possible in the absence of splenium. MD had to attentively track one bouncing ball among three identical balls, while it crossed the vertical midline in half of trials. Her performance in crossed conditions was significantly above chance level, but it was lower than uncrossed conditions. Finally, we investigated the contribution of simple interhemispheric temporal signals in performing the attentive tracking task. Results suggest that the patient was not using such temporal signals. Our results suggest that interhemispheric connections other than splenium can contribute in making an integral visual map across hemifields. Such an integrated map can be used for bilateral visual spatial comparisons and visual spatial attention.
Adult↗
Reconstructing and deconstructing agonist-induced activation of integrin alphaIIbbeta3.
BACKGROUND: Integrin receptors, composed of transmembrane alpha and beta subunits, are essential for the development and functioning of multicellular animals. Agonist stimulation leads cells to regulate integrin affinity ("activation"), thus controlling cell adhesion and migration, controlling extracellular-matrix assembly, and contributing to angiogenesis, tumor cell metastasis, inflammation, the immune response, and hemostasis. A final step in integrin activation is the binding of talin, a cytoskeletal protein, to integrin beta cytoplasmic domains. Many different signaling molecules that regulate integrin affinity have been described, but a pathway that connects agonist stimulation to talin binding and activation has not been mapped. RESULTS: We used forward, reverse, and synthetic genetics to engineer and order an integrin activation pathway in cells expressing a prototype activatable integrin, platelet alphaIIbbeta3. Phorbol myristate acetate (PMA) activated alphaIIbbeta3 only after the increased expression of both recombinant protein kinase Calpha (PKCalpha) and talin to levels approximating those in platelets. Inhibition of Rap1 GTPase reduced alphaIIbbeta3 activation, whereas activated Rap1A(G12V) bypassed the requirement for PKC, establishing that Rap1 is downstream of PKC. Talin binding to integrins mediates Rap1-induced activation because Rap1A(G12V) failed to activate alphaIIbbeta3 in cells expressing integrin binding-defective talin (W359A). Rap1 activated integrins by forming an integrin-associated complex containing talin in combination with the Rap effector, RIAM. Furthermore, siRNA-mediated knockdown of RIAM blocked integrin activation. CONCLUSIONS: We have, for the first time, ordered a pathway from agonist stimulation to integrin activation and established the Rap1-induced formation of an "integrin activation complex," containing RIAM and talin, that binds to and activates the integrin.
Animals↗
Cortical cartography using the discrete conformal approach of circle packings.
Cortical flattening algorithms are becoming more widely used to assist in visualizing the convoluted cortical gray matter sheet of the brain. Metric-based approaches are the most common but suffer from high distortions. Conformal, or angle-based algorithms, are supported by a comprehensive mathematical theory. The conformal approach that uses circle packings is versatile in the manipulation and display of results. In addition, it offers some new and interesting metrics that may be useful in neuroscientific analysis and are not available through numerical partial differential equation conformal methods. In this paper, we begin with a brief description of cortical "flat" mapping, from data acquisition to map displays, including a brief review of past flat mapping approaches. We then describe the mathematics of conformal geometry and key elements of conformal mapping. We introduce the mechanics of circle packing and discuss its connections with conformal geometry. Using a triangulated surface representing a cortical hemisphere, we illustrate several manipulations available using circle packing methods and describe the associated "ensemble conformal features" (ECFs). We conclude by discussing current and potential uses of conformal methods in neuroscience and computational anatomy.
Algorithms↗
Cryptic causation of human disease: reading between the (germ) lines.
Most cases of complex human diseases arise sporadically. However, usually there is a significant level of familial aggregation of risk and genetic mapping has identified the responsible gene in a few mendelian cases. Although a disease can be causally genetic, intensified mapping efforts have so far been unable to identify genes that account for more than a small fraction of the familial risk, perhaps because the responsible variation arises by somatic mutation (SM). SM explains the kind of epidemiological pattern seen in cancer, and might have a comparable role in many other diseases. For example, in epilepsy, which has largely defied mapping analysis, the underlying disease pathology, undamped neuronal signaling, is closely connected to gene function. Better technologies to detect and characterize SM are becoming available. However, until it is studied directly, SM will remain a cryptic etiological force, even for diseases that are essentially "genetic".
Animals↗
[Contribution of color Doppler in the diagnosis of bilateral ductus arteriosus].
We report a neonate with distal bilateral ductus arteriosus origin of nonconfluent pulmonary arteries which was only diagnosed accurately by 2-D echo Doppler color flow mapping in the context of situs ambiguous, univentricular A-V connection and pulmonary atresia with normal systemic/pulmonary venous drainage. The color flow appearance of this singular vascular anatomy was enhanced after prostaglandin administration, which, allowed us to see an image resembling a "moustache morphology". At 36 months of age, and after a successful bilateral 4 mm modified Blalock Taussig shunt implantation by sequential approach, the patient is waiting for the next surgical step which will include a restoration of the confluence of the pulmonary arteries with bidirectional Glenn operation. Brief embryological and differential diagnosis comments are discussed.
Anastomosis, Surgical↗
Engineered metal binding sites map the heterogeneous folding landscape of a coiled coil.
To address whether proteins fold along multiple pathways, i,i+4 bi-histidine metal binding sites are introduced into dimeric and crosslinked versions of the leucine zipper region of the growth control transcription factor, GCN4. Divalent metal ion binding enhances both the equilibrium and folding activation free energies for GCN4. The enhancement of folding rates quantifies the fraction of molecules that have the binding site in a helical geometry in the transition state. Hence, this new method, termed Psi-analysis, identifies the degree of pathway heterogeneity for a protein that folds in a two-state manner, a capability that is generally unavailable even with single molecule methods. Adjusting metal ion concentration continuously varies the stability of the bi-histidine region without additional structural perturbation to the protein. For dimeric and crosslinked versions, the accompanying changes in kinetic barrier heights at each metal ion concentration maps the folding landscape as well as establishes the importance of connectivity in pathway selection. Furthermore, this method can be generalized to other biophysical studies, where the ability to continuously tune the stability of a particular region with no extraneous structural perturbation is advantageous.
Amino Acid Sequence↗