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In vivo validation of an experimental adaptive quantitative coronary angiography algorithm to circumvent overestimation of small luminal diameters.

The reliability of quantitative coronary angiography (QCA) measurements is of fundamental importance for the study and practice of interventional cardiology. In vivo validation results have consistently reported a tendency for QCA systems to overestimate small luminal diameters. Such a systematic error may result in the underestimation of luminal gain during intracoronary procedures and in the underestimation of progression of coronary artery disease during longitudinal studies. We report the in vivo validation results of an experimental adaptive edge-detection algorithm that was developed to reduce overestimation of small luminal diameters by incorporating a dynamic function of variable kernel size of the derivative operator and variable weighting of the first and second derivatives of the brightness profile. The results of the experimental algorithm were compared to those of the conventional parent edge detection algorithm with fixed parameters. Dynamic adjustment of the edge-detection algorithm parameters was found to improve measurements of small (< 0.8-mm) luminal diameters as evidenced by an intercept of +.07 mm for the algorithm with variable weighting compared to +0.21 mm for the parent algorithm with fixed weighting. A slope of < 1 was found for both the parent and experimental algorithms with subsequent underestimation of large luminal diameters. Systematic errors in a QCA system can be identified and corrected by the execution of objective in vivo validation studies and the consequent refinement of edge-detection algorithms. The overestimation of small luminal diameters may be overcome by the incorporation of a dynamic edge-detection algorithm.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗

A comparison of mathematical models for estimating right ventricular volumes in animals and man.

Volume of 19 right ventricular canine casts and 11 right ventricular human casts were obtained by water displacement and compared to three different mathematical models for estimating right ventricular volumes by biplane cineangiography. In the canine studies, significant linear correlation coefficients were obtained using the longest measured length method (r = 0.92), the triangular modification of Simpson's rule (r = 0.93), and the elliptical modification of Simpson's rule (r = 0.93). The human studies resulted in similar significant correlation coefficients of 0.96, 0.97, and 0.97, respectively. Although the highest correlation with the lowest standard error of estimate was obtained using the triangular model, all three mathematical models produced volume estimations that feel within acceptabe biological limits of accuracy.

Animals↗

Mesostriatal and mesolimbic projections of midbrain neurons immunoreactive for estrogen receptor beta or androgen receptors in rats.

The dopamine (DA) inputs to the caudate putamen, the nucleus accumbens, and the amygdala in rats are sensitive to circulating estrogens and androgens. One mechanism for the hormone modulation of these systems may be via actions at cognate intracellular estrogen and androgen receptors. However, although it is known that specific subsets of midbrain DA neurons are immunopositive for estrogen receptor beta (ERbeta) or androgen receptors (ARs), it is not known where these receptor-bearing cells project. To address this issue, we combined double-label immunocytochemistry with retrograde tract tracing to identify the forebrain projections of ERbeta- or AR-immunoreactive (IR) midbrain neurons. Specifically, Fluoro-Gold and/or cholera toxin were injected into discrete subregions of the caudate-putamen, the nucleus accumbens, or the amygdala. Evaluations of the resultant midbrain labeling revealed that ERbeta-IR neurons sent collateral projections mainly to both the ventral caudate-putamen and the amygdala, but not to the dorsal caudate or nucleus accumbens. In contrast, AR-IR neurons projected either to the amygdala or the nucleus accumbens but not to the caudate-putamen. The organization of these forebrain projections concurs with some of the known hormone sensitivities of mesostriatal and mesolimbic DA systems in rats and provides an anatomical model that predicts separate influences for androgens and estrogens over mesostriatal and mesolimbic DA systems.

Amygdala↗

Frontotemporal and dopaminergic control of idea generation and creative drive.

This article presents a three-factor anatomical model of human idea generation and creative drive, focusing on interactions between the temporal lobes, frontal lobes, and limbic system. Evidence is drawn from functional imaging, drug studies, and lesion analysis. Temporal lobe changes, as in hypergraphia, often increase idea generation, sometimes at the expense of quality. Frontal lobe deficits may decrease idea generation, in part because of rigid judgments about an idea's worth. These phenomena are clearest in verbal creativity, and roughly parallel the pressured communication of temporal lobe epilepsy, mania, and Wernicke's aphasia-compared to the sparse speech and cognitive inflexibility of depression, Broca's aphasia, and other frontal lobe lesions. The phenomena also shape non-linguistic creativity, as in that of frontotemporal dementia. The appropriate balance between frontal and temporal activity is mediated by mutually inhibitory corticocortical interactions. Mesolimbic dopamine influences novelty seeking and creative drive. Dopamine agonists and antagonists have opposite effects on goal-directed behavior and hallucinations. Creative drive is not identical to skill-the latter depends more on neocortical association areas. However, drive correlates better with successful creative output than skill does. Traditional neuroscientific models of creativity, such as the left brain - right brain hemispheric model, emphasize skills primarily, and stress art and musical skill at the expense of language and mathematics. The three-factor model proposed here predicts findings in a broad range of normal and pathological states and can be tested in many experimental paradigms.

Creativity↗

Columnar projections from the cholinergic nucleus isthmi to the optic tectum in chicks (Gallus gallus): a possible substrate for synchronizing tectal channels.

The cholinergic division of the avian nucleus isthmi, the homolog of the mammalian nucleus parabigeminalis, is composed of the pars parvocellularis (Ipc) and pars semilunaris (SLu). Ipc and SLu were studied with in vivo and in vitro tracing and intracellular filling methods. 1) Both nuclei have reciprocal homotopic connections with the ipsilateral optic tectum. The SLu connection is more diffuse than that of Ipc. 2) Tectal inputs to Ipc and SLu are Brn3a-immunoreactive neurons in the inner sublayer of layer 10. Tectal neurons projecting on Ipc possess "shepherd's crook" axons and radial dendritic fields in layers 2-13. 3) Neurons in the mid-portion of Ipc possess a columnar spiny dendritic field. SLu neurons have a large, nonoriented spiny dendritic field. 4) Ipc terminals form a cylindrical brush-like arborization (35-50 microm wide) in layers 2-10, with extremely dense boutons in layers 3-6, and a diffuse arborization in layers 11-13. SLu neurons terminate in a wider column (120-180 microm wide) lacking the dust-like boutonal features of Ipc and extend in layers 4c-13 with dense arborizations in layers 4c, 6, and 9-13. 5) Ipc and SLu contain specialized fast potassium ion channels. We propose that dense arborizations of Ipc axons may be directed to the distal dendritic bottlebrushes of motion detecting tectal ganglion cells (TGCs). They may provide synchronous activation of a group of adjacent bottlebrushes of different TGCs of the same type via their intralaminar processes, and cross channel activation of different types of TGCs within the same column of visual space.

Acetylcholine↗

Multiple olfactory receptor neurons and their axonal projections in the antennal lobe of the honeybee Apis mellifera.

The poreplate sensilla of honeybees are equipped with multiple olfactory receptor neurons (ORNs), which innervate glomeruli of the antennal lobe (AL). We investigated the axonal projection pattern in glomeruli of the AL (glomerular pattern), formed by the multiple ORNs of individual poreplate sensilla. We used the different glomerular patterns to draw conclusions about the equipment of poreplate sensilla with different ORN types. ORNs of single poreplate sensilla were stained and analyzed by laser-scanning confocal microscopy and 3D software (AMIRA). In 13 specimens we found between 7 and 23 ORNs. This is in accordance with data found in the literature (5-35 ORNs) suggesting that all ORNs of the single poreplate sensilla were stained. The ORNs innervate the AL via all four sensory tracts (T1-T4), and glomeruli of the anterior part of the AL are more often innervated. Each ORN innervates a single glomerulus (uniglomerular), and all ORNs of one poreplate sensillum project to different glomeruli. Visual inspection and individual identification of glomeruli, based on the honeybee digital AL atlas, were used to evaluate mapping of glomeruli by a rigid transformation of the experimental ALs onto a reference AL. ORNs belonging to individual poreplate sensilla form variable glomerular patterns, and we did not find a common organization of glomerular patterns. We conclude that poreplate sensilla are equipped with different ORN types but that the same ORN types can be found in different poreplate sensilla. The equipment of poreplate sensilla with ORNs is overlapping. The mapping of glomeruli by rigid transformation is revealed to be a powerful tool for comparative neuroanatomy.

Animals↗

Morphological assessment of neuronal aggregates in the striatum of the rat.

Regional variations in cell-packing density, culminating in the formation of cell clusters, is now a recognized morphological characteristic of the striatum that has been correlated, in some instances, with either regional histochemical variations or the distribution pattern of afferent fiber systems, or both. Within these cluster regions a further level of organization exists, in the form of discrete neuronal aggregates. The light microscopic morphology of these neurons and the nature of their intercellular contacts at the electron microscope level form the focus of this report. The neurons composing such aggregates are characterized by contiguous soma-somatic or soma-dendritic contact with extended regions of junctionlike symmetrical and consistent contacts where the distance between the cytoplasmic membranes of apposing neurons narrows to as close as 7 nm. Coated vesicles close to the contact areas are common. Three-dimensional computer reconstructions of serial 1 micron sections through aggregates in either the caudatoputamen or nucleus accumbens reveal "chains" of contiguous cells that frequently involve as many as 60 neurons. These contiguous cell aggregates are discrete entities within the larger clusters or islands. It is postulated that the cellular aggregates may represent the fundamental level of striatal organization and may be local modules for intrinsic information processing, modifying extrinsic data processed through the biochemical compartmentalization of the striatum imparted by striosomes, neuropeptides, and dopaminergic, thalamic and cortical afferents.

Animals↗

Anatomy and fine structure of neurons in the deutocerebral projection pathway of the crayfish olfactory system.

Golgi impregnation and neurobiotin injection were used to examine details of the neural pathways in the olfactory system of the freshwater crayfish, Procambarus clarkii. Deutocerebral projection neurons (globuli cells) were directly injected with neurobiotin. These neurons have dendritic arborizations in the ipsilateral olfactory and accessory lobes, and they project axons to the lateral protocerebrum, where they terminate in microglomeruli of the hemi-ellipsoid body. The axons of the deutocerebral projection neurons are readily impregnated by Golgi procedures, and they terminate as an expanded membranous knot about 5 microns in diameter. Electron microscopy on Golgi-stained terminals has revealed that each knot makes several hundred synapses with small spine-like or shaft-like processes of postsynaptic neurons. Injection of neurobiotin into local interneurons of the hemi-ellipsoid body and subsequent examination of stained preparations with the electron microscope reveals that these cells are a major postsynaptic target of the deutocerebral projection neurons. Furthermore, the local interneurons make extensive efferent synaptic connections with unidentified neurons in the terminal medulla.

Animals↗

Pigment pattern formation in zebrafish during late larval stages: a model based on local interactions.

We present a model to explain pigment cell pattern formation in the late larval stages of zebrafish, Danio rerio, and its mutants, based on new time sequence experimental data. The model stresses the importance of differential intercellular adhesion and the mechanisms of stem cell regulation to explain pigment pattern formation in zebrafish. All interactions included in the model are local in contrast to the previous models for pattern formation, which are based on long range interactions. The hypotheses of the model are tested through a mathematical (cellular automaton) model. Simulations show that differential cellular adhesion together with an appropriate mechanism of stem cell regulation are able to reproduce the main characteristics of pattern formation in the wild-type zebrafish and mutants. The results obtained with the simulations are compared with experimental data and specific experimental tests to the predictions of the model are provided.

Algorithms↗

Roles of JUMONJI in mouse embryonic development.

Cardiac development is a complex biological process requiring the integration of cell specification, differentiation, migration, proliferation, and morphogenesis. Although significant progress has been made recently in understanding the molecular basis of cardiac development, mechanisms of transcriptional control of cardiac development remain largely unknown. In search for the developmentally important genes, the jumonji gene (jmj) was identified by gene trap technology and characterized as a critical nuclear factor for mouse embryonic development. Jmj has been shown to play important roles in cardiovascular development, neural tube fusion process, hematopoiesis, and liver development in mouse embryos. The amino acid sequence of the JUMONJI protein (JMJ) reveals that JMJ belongs to the AT-rich interaction domain transcription factor family and more recently has been described as a member of the JMJ transcription factor family. Here, we review the roles of jmj in multiple organ development with a focus on cardiovascular development in mice.

Animals↗

Peripheral blood fibrocytes contribute to the formation of the avian spleen.

Chick-quail chimeric studies were made to determine the origin of the cells of splenic ellipsoid. The ellipsoid is formed by supporting and phagocytic cells, which are embedded in a well-organized extracellular matrix. Splenic and bursal anlage of 6- to 6.5-day-old quail embryos were transplanted into the coelomic cavity of 3-day-old chick embryos and further incubated for 17 days. CD45+ chicken hemopoietic cells colonized both organs. They formed the cells of the ellipsoid and the periellipsoidal white pulp of the transplanted quail spleen. Chicken-specific collagen III was produced only in the donor quail spleen, but not in the bursa of Fabricius. The CD45+/collagen I+/collagen III+ cells are probably identical with the mammalian peripheral blood fibrocytes and contribute to the formation of supporting cells, whereas the CD45+/74.2+ ellipsoid-associated macrophages are of monocytic origin. We provide, for the first time, experimental evidence that peripheral blood fibrocytes exist in the avian species; they are present in the circulation of the chicken embryo and contribute to the organogenesis of the spleen.

Animals↗

Role of a spatial distribution of IP3 receptors in the Ca2+ dynamics of the Xenopus embryo at the mid-blastula transition stage.

Periodic calcium activity correlates temporally with the onset of gene expression in the embryo, suggesting a causal relation between these two events. Calcium transients are elicited by the action of fibroblast growth factor (FGF) through the activation of phospholipase C. In this work, we present a reaction-diffusion model that extends our previous results on the generation of calcium oscillations for a single and two coupled blastomere cells to a meridian of the Xenopus embryo at the mid-blastula transition. In the model, all cells are subject to the same amount of FGF and contain the same concentration of intracellular components, except for the amount of IP(3) receptors (IP3R). A bell-shaped distribution of IP3R produces the correct shape of the calcium transients experimentally observed in the Xenopus blastula at stage 8 (mid-blastula transition stage). The model is also capable of predicting period and amplitude values close to the experimental values. In our model, calcium transients induce spatially localized ERK periodic transients that could activate specific nuclear genes, allowing for the regional differentiation of the cells in the zone under the influence of the calcium signal.

Animals↗

Setting the stage for development: mRNA translation and stability during oocyte maturation and egg activation in Drosophila.

Early animal development is controlled by maternally encoded RNAs and proteins, which are loaded into the egg during oogenesis. Oocyte maturation and egg activation trigger changes in the translational status and the stability of specific maternal mRNAs. Whereas both maturation and activation have been studied in depth in amphibians and echinoderms, only recently have these processes begun to be dissected using the powerful genetic and molecular tools available in Drosophila. This review focuses on the mechanisms and functions of regulated maternal mRNA translation and stability in Drosophila--and compares these mechanisms with those elucidated in other animal models, particularly Xenopus--beginning late in oogenesis and continuing to the mid-blastula transition, when developmental control is transferred to zygotically synthesized transcripts.

Animals↗

Embryonic staging system for the short-tailed fruit bat, Carollia perspicillata, a model organism for the mammalian order Chiroptera, based upon timed pregnancies in captive-bred animals.

There are approximately 4,800 extant species of mammals that exhibit tremendous morphological, physiological, and developmental diversity. Yet embryonic development has been studied in only a few mammalian species. Among mammals, bats are second only to rodents with regard to species number and habitat range and are the most abundant mammals in undisturbed tropical regions. Bat development, though, remains relatively unstudied. Here, we describe and illustrate a staging series of embryonic development for the short-tailed fruit bat, Carollia perspicillata, based on embryos collected at timed intervals after captive matings. As Carollia can be readily maintained and propagated in captivity and is extremely abundant in the wild, it offers an attractive choice as a chiropteran model organism. This staging system provides a framework for studying Carollia embryogenesis and should prove useful as a guide for embryological studies of other bat species and for comparisons with other orders of mammals.

Animals↗

Misexpression screen for genes altering the olfactory map in Drosophila.

Despite the identification of a number of guidance molecules, a comprehensive picture has yet to emerge to explain the precise anatomy of the olfactory map. From a misexpression screen of 1,515 P{GS} lines, we identified 23 genes that, when forcibly expressed in the olfactory receptor neurons, disrupted the stereotyped anatomy of the Drosophila antennal lobes. These genes, which have not been shown previously to control olfactory map development, encode novel proteins as well as proteins with known roles in axonal outgrowth and cytoskeletal remodeling. We analyzed Akap200, which encodes a Protein Kinase A-binding protein. Overexpression of Akap200 resulted in fusion of the glomeruli, while its loss resulted in misshapen and ectopic glomeruli. The requirement of Akap200 validates our screen as an effective approach for recovering genes controlling glomerular map patterning. Our finding of diverse classes of genes reveals the complexity of the mechanisms that underlie olfactory map development.

A Kinase Anchor Proteins↗

Olfactory ensheathing cells and olfactory nerve fibroblasts maintain continuous open channels for regrowth of olfactory nerve fibres.

The ensheathing cells of the olfactory nerves are arranged end-to-end to form a continuous channel enclosing the olfactory axons from their origin in the olfactory mucosa to their termination in the olfactory bulb. On their outer surface, the olfactory ensheathing cell channels have a basal lamina and an outer encirclement of olfactory nerve fibroblasts. We present an anatomical model of the ensheathing arrangements for the entire transit of the olfactory axons from the horizontal basal cells of the mucosa through the nerves to the superficial astrocytes of the bulb. We used intracranial section of the olfactory nerves to induce a rapid retrograde loss of olfactory neurons and degeneration of their axons, followed by replacement of the neurons from stem cells in the mucosa and growth of the newly formed axons along the olfactory nerves. The olfactory ensheathing cells survive and play a vital role in this process. Unlike Schwann cells in damaged peripheral nerve, the olfactory ensheathing cells neither divide nor migrate. They are actively phagocytic for removal of the degenerating axons, and provide continuous stable open channels along which adventitious cells such as erythrocytes and macrophages can travel, and along which the newly formed axons can regenerate. We suggest that the persistence of these open channels is an important element in the effectiveness of the regeneration. These properties, which the olfactory ensheathing cells exert in collaboration with olfactory nerve fibroblasts, may also be involved in the reparative effects of these cells when transplanted into lesions of the spinal cord.

Animals↗

Linear inverse source estimate of combined EEG and MEG data related to voluntary movements.

A method for the modeling of human movement-related cortical activity from combined electroencephalography (EEG) and magnetoencephalography (MEG) data is proposed. This method includes a subject's multi-compartment head model (scalp, skull, dura mater, cortex) constructed from magnetic resonance images, multi-dipole source model, and a regularized linear inverse source estimate based on boundary element mathematics. Linear inverse source estimates of cortical activity were regularized by taking into account the covariance of background EG and MEG sensor noise. EEG (121 sensors) and MEG (43 sensors) data were recorded in separate sessions whereas normal subjects executed voluntary right one-digit movements. Linear inverse source solution of EEG, MEG, and EEG-MEG data were quantitatively evaluated by using three performance indexes. The first two indexes (Dipole Localization Error [DLE] and Spatial Dispersion [SDis]) were used to compute the localization power for the source solutions obtained. Such indexes were based on the information provided by the column of the resolution matrix (i.e., impulse response). Ideal DLE values tend to zero (the source current was correctly retrieved by the procedure). In contrast, high DLE values suggest severe mislocalization in the source reconstruction. A high value of SDis at a source space point mean that such a source will be retrieved by a large area with the linear inverse source estimation. The remaining performance index assessed the quality of the source solution based on the information provided by the rows of the resolution matrix R, i.e., resolution kernels. The i-th resolution kernels of the matrix R describe how the estimation of the i-th source is distorted by the concomitant activity of all other sources. A statistically significant lower dipole localization error was observed and lower spatial dispersion in source solutions produced by combined EEG-MEG data than from EEG and MEG data considered separately (P < 0.05). These effects were not due to an increased number of sensors in the combined EEG-MEG solutions. They result from the independence of source information conveyed by the multimodal measurements. From a physiological point of view, the linear inverse source solution of EEG-MEG data suggested a contralaterally preponderant bilateral activation of primary sensorimotor cortex from the preparation to the execution of the movement. This activation was associated with that of the supplementary motor area. The activation of bilateral primary sensorimotor cortical areas was greater during the processing of afferent information related to the ongoing movement than in the preparation for the motor act. In conclusion, the linear inverse source estimate of combined MEG and EEG data improves the estimate of movement-related cortical activity.

Dura Mater↗

Hepatic enzymic zonation: a reevaluation of the concept of the liver acinus.

The distribution pattern of a periportal enzyme (carbamoylphosphate synthetase) and a pericentral enzyme (glutamine synthetase) in human and rat liver has provided an objective parameter to delineate the zonal boundaries of the liver acinus. On sections, the pericental zone (zone 3) is circular and discrete rather than star-like and reticular, as predicted by the acinar concept, whereas the periportal zone (zone 1) is reticular, i.e. contiguous between adjacent acini rather than discrete. Three-dimensionally, the composite of pericentral zones (the pericentral compartment) follows the branching pattern of the terminal hepatic (central) vein, whereas the composite of periportal zones (the periportal compartment) envelops the pericentral compartment as a three-dimensional network (reticulum). This modified concept that is based upon the three-dimensional distribution of hepatocyte-specific enzymes is supported by data from the literature regarding the three-dimensional angioarchitecture of the liver, the perfusion pattern of the liver and the three-dimensional pattern of tissue oxygenation. Hence, a unified concept of the liver architecture that is based upon the observed distribution pattern of blood flow, of gene expression and of metabolism can be established.

Adult↗