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Improving the comparative map of porcine chromosome 10 with respect to human chromosomes 1, 9 and 10.

ZOO-FISH mapping shows human chromosomes 1, 9 and 10 share regions of homology with pig chromosome 10 (SSC10). A more refined comparative map of SSC10 has been developed to help identify positional candidate genes for QTL on SSC10 from human genome sequence. Genes from relevant chromosomal regions of the public human genome sequence were used to BLAST porcine EST databases. Primers were designed from the matching porcine ESTs to assign them to porcine chromosomes using the INRA somatic cell hybrid panel (INRA-SCHP) and the INRA-University of Minnesota Radiation Hybrid Panel (IMpRH). Twenty-eight genes from HSA1, 9 and 10 were physically mapped: fifteen to SSC10 (ACO1, ATP5C1, BMI1, CYB5R1, DCTN3, DNAJA1, EPHX1, GALT, GDI2, HSPC177, OPRS1, NUDT2, PHYH, RGS2, VIM), eleven to SSC1 (ADFP, ALDHIB1, CLTA, CMG1, HARC, PLAA, STOML2, RRP40, TESK1, VCP and VLDLR) and two to SSC4 (ALDH9A1 and TNRC4). Two anonymous markers were also physically mapped to SSC10 (SWR1849 and S0070) to better connect the physical and linkage maps. These assignments have further refined the comparative map between SSC1, 4 and 10 and HSA1, 9 and 10.

Animals↗

Quantitation of mapping uncertainty in Wolff-Parkinson-White syndrome. Implications for anatomic characterization and surgical division of accessory atrioventricular connections.

The purpose of this study was to quantitate the uncertainty inherent in the electrophysiologic mapping of ventricular preexcitation as seen in Wolff-Parkinson-White syndrome. An ink-coated needle electrode was constructed to serve as a point source of unipolar stimulation along the atrioventricular junction. Activation times for 11 ventricular mapping sites at the atrioventricular junction were measured for each stimulation point. Maps were successfully completed for 18 right free wall and 14 posterior septal stimulation points. The activation time at the mapping site closest to the stimulation point was termed the index activation time. Activation times identical to the index activation time were noted at 1.3 +/- 0.5 mapping sites for each free wall stimulation point and 1.9 +/- 0.9 mapping sites for each septal stimulation point (p < 0.05, septal versus free wall stimulation points). Activation times falling within 5 msec of the index activation time were noted at 2.4 +/- 1.0 mapping sites for each free wall stimulation point and at 3.9 +/- 1.4 mapping sites for each septal stimulation point (p < 0.05, septal versus free wall stimulation points). The uncertainty of electrophysiologic mapping can be quantitated, and this error should be considered when making inferences regarding the anatomy of accessory pathways based on electrophysiologic data. A knowledge of the uncertainty inherent in the localization of accessory atrioventricular connections by electrophysiologic mapping can be used to plan borders of surgical dissection that will account for this uncertainty at a 95% confidence level.

Animals↗

New concepts in surgery of WHO grade II gliomas: functional brain mapping, connectionism and plasticity--a review.

Despite a recent literature supporting the impact of surgery on the natural history of low-grade glioma (LGG), the indications of resection still remain a matter of debate, especially because of the frequent location of these tumors within eloquent brain areas - thus with a risk to induce a permanent postoperative deficit. Therefore, since the antagonist nature of this surgery is to perform the most extensive glioma removal possible, while preserving the function and the quality of life, new concepts were recently applied to LGG resection in order to optimize the benefit/risk ratio of the surgery.First, due to the development of functional mapping methods, namely perioperative neurofunctional imaging and intrasurgical direct electrical stimulation, the study of cortical functional organization is currently possible for each patient - in addition to an extensive neuropsychological assessment. Such knowledge is essential because of the inter-individual anatomo-functional variability, increased in tumors due to cerebral plasticity phenomena. Thus, brain mapping enables to envision and perform a resection according to individual functional boundaries.Second, since LGG invades not only cortical but also subcortical structures, and shows an infiltrative progression along the white matter tracts, new techniques of anatomical tracking and functional mapping of the subcortical white matter pathways were also used with the goal to study the individual effective connectivity - which needs imperatively to be preserved during the resection.Third, the better understanding of brain plasticity mechanisms, induced both by the slow-growing LGG and by the surgery itself, were equally studied in each patient and applied to the surgical strategy by incorporating individual dynamic potential of reorganization into the operative planning. The integration of these new concepts of individual functional mapping, connectivity and plastic potential to the surgery of LGG has allowed an extent of surgical indications, an optimization of the quality of resection (neuro-oncological benefit), and a minimization of the risk of sequelae (benefit on the quality of life). In addition, such a strategy has also fundamental applications, since it represents a new door to the connectionism and cerebral plasticity.

Brain Mapping↗

Edge detection in medical images using a genetic algorithm.

An algorithm is developed that detects well-localized, unfragmented, thin edges in medical images based on optimization of edge configurations using a genetic algorithm (GA). Several enhancements were added to improve the performance of the algorithm over a traditional GA. The edge map is split into connected subregions to reduce the solution space and simplify the problem. The edge-map is then optimized in parallel using incorporated genetic operators that perform transforms on edge structures. Adaptation is used to control operator probabilities based on their participation. The GA was compared to the simulated annealing (SA) approach using ideal and actual medical images from different modalities including magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound. Quantitative comparisons were provided based on the Pratt figure of merit and on the cost-function minimization. The detected edges were thin, continuous, and well localized. Most of the basic edge features were detected. Results for different medical image modalities are promising and encourage further investigation to improve the accuracy and experiment with different cost functions and genetic operators.

Algorithms↗

A novel method for nonfluoroscopic catheter-based electroanatomical mapping of the heart. In vitro and in vivo accuracy results.

BACKGROUND: Cardiac mapping is essential for understanding the mechanisms of arrhythmias and for directing curative procedures. A major limitation of the current methods is the inability to accurately relate local electrograms to their spatial orientation. The objective of this study was to present and test the accuracy of a new method for nonfluoroscopic, catheter-based, endocardial mapping. METHODS AND RESULTS: The method is based on using a new locatable catheter connected to an endocardial mapping and navigating system. The system uses magnetic technology to accurately determine the location and orientation of the catheter and simultaneously records the local electrogram from its tip. By sampling a plurality of endocardial sites, the system reconstructs the three-dimensional geometry of the chamber, with the electrophysiological information color-coded and superimposed on the anatomy. The accuracy of the system was tested in both in vitro and in vivo studies and was found to be highly reproducible (SD, 0.16 +/- 0.02 [mean +/- SEM] and 0.74 +/- 0.13 mm) and accurate (mean errors, 0.42 +/- 0.05 and 0.73 +/- 0.03 mm). In further studies, electroanatomical mapping of the cardiac chambers was performed in 34 pigs. Both the geometry and activation sequence were repeatable in all pigs. CONCLUSIONS: The new mapping method is highly accurate and reproducible. The ability to combine electrophysiological and spatial information provides a unique tool for both research and clinical electrophysiology. Consequently, the main shortcomings of conventional mapping-namely, prolonged x-ray exposure, low spatial resolution, and the inability to accurately navigate to a predefined site-can all be overcome with this new method.

Animals↗

Simultaneous mapping of the tricuspid and mitral valve annuli at electrophysiological study.

BACKGROUND: Mapping of the right free wall in patients with accessory pathways is difficult compared with that of the left free wall where the coronary sinus permits stable and accurate location of the electrodes used for endocardial mapping. Furthermore, the sequential roving catheter method is less satisfactory than multiple simultaneous electrode recordings spanning the circumference of the valve annulus. A new method for mapping the tricuspid annulus is described. METHODS: Mapping was performed in nine patients with a suspected right free wall accessory pathway or an atriofascicular connection. The tricuspid annulus was mapped using a specially shaped 1 cm interelectrode 10 pole catheter positioned in the right atrium immediately above the annulus. The coronary sinus was mapped with a 5 mm interelectrode 10 pole catheter and a 2 mm interelectrode 10 pole catheter recorded His bundle activity. Catheter positions were confirmed by multiplane fluoroscopy. Electrograms were digitised and recorded simultaneously using a custom computerised mapping system. The position of the multielectrode catheter around the tricuspid annulus relative to that of the coronary arteries was examined by coronary angiography in three patients. RESULTS: Seven right free wall and two posterior septal accessory pathways, and three atriofascicular connections were detected. Ventricular activation adjacent to both valve annuli was mapped in five patients with pre-excitation. The locations of eight of the nine accessory pathways and the three atriofascicular connections were confirmed at operative mapping. One right free wall accessory pathway in a patient with Ebstein's anomaly was not detected at operative mapping. No additional accessory pathways were found at operative mapping or routine 6 month postoperative electrophysiological study, or during a mean (SD) clinical follow up of 22 (7) months. The tricuspid annulus catheter was located during coronary angiography at a mean (SD) of about 2.5 (0.7) cm above and parallel to the right coronary artery in the right atrioventricular groove. CONCLUSIONS: This new catheter technique permits rapid detailed mapping of atrial and ventricular activation around the tricuspid annulus with a resolution of at least < or = % 1 cm, depending on the number and spacing of electrodes in each catheter. The technique was accurate as judged by mapping at surgery. This method is simple and safe compared with that of others for mapping the right free wall via the right coronary artery. It should facilitate detection and ablation of right free wall accessory pathways and atriofascicular connections.

Adolescent↗

Topographic-specific axon branching controlled by ephrin-As is the critical event in retinotectal map development.

The retinotectal projection is the predominant model for studying molecular mechanisms controlling development of topographic axonal connections. Our analyses of topographic mapping of retinal ganglion cell (RGC) axons in chick optic tectum indicate that a primary role for guidance molecules is to regulate topographic branching along RGC axons, a process that imposes unique requirements on the molecular control of map development. We show that topographically appropriate connections are established exclusively by branches that form along the axon shaft. Initially, RGC axons overshoot their appropriate termination zone (TZ) along the anterior-posterior (A-P) tectal axis; temporal axons overshoot the greatest distance and nasal axons the least, which correlates with the nonlinear increasing A-P gradient of ephrin-A repellents. In contrast, branches form along the shaft of RGC axons with substantial A-P topographic specificity. Topography is enhanced through the preferential arborization of appropriately positioned branches and elimination of ectopic branches. Using a membrane stripe assay and time-lapse microscopy, we show that branches form de novo along retinal axons. Temporal axons preferentially branch on their topographically appropriate anterior tectal membranes. After the addition of soluble EphA3-Fc, which blocks ephrin-A function, temporal axons branch equally on anterior and posterior tectal membranes, indicating that the level of ephrin-As in posterior tectum is sufficient to inhibit temporal axon branching and generate branching specificity in vitro. Our findings indicate that topographic branch formation and arborization along RGC axons are critical events in retinotectal mapping. Ephrin-As inhibit branching along RGC axons posterior to their correct TZ, but alone cannot account for topographic branching and must cooperate with other molecular activities to generate appropriate mapping along the A-P tectal axis.

Animals↗

Mapping of zones of altered morphology and chorionic connective tissue cellular phenotype in human fetal membranes (amniochorion and decidua) overlying the lower uterine pole and cervix before labor at term.

OBJECTIVE: The purpose of this study was to determine the location, frequency, and extent of altered fetal membrane morphology before term labor and its relation to myofibroblast activation in their connective tissue layers. STUDY DESIGN: Fetal membranes that were obtained from 10 women who underwent prelabor cesarean delivery at 38 to 39 weeks of gestation underwent biopsy examination with respect to the internal os of the cervix. The thickness of their constituent layers was measured, and the numbers of alpha-smooth muscle actin immunoreactive cells (ie, marker of myofibroblast activation) within the reticular layer were counted. RESULTS: A region that measured 119+/-21cm(2), that exhibited altered morphology of the fetal membranes from the lower uterine pole, and that was characterized by increased connective tissue thickness and decreased thickness of the cellular layers was demonstrated in all patients. In 8 of 10 patients, this region was centered on the location of the Babcock tissue forceps. Within this region was an area of fetal membranes that exhibited alpha-smooth muscle actin immunoreactivity in the cells of the reticular layer and whose number correlated with parameters of altered morphology. CONCLUSION: All patients before labor at term possess an area of fetal membranes that are located in the lower uterine pole that exhibit altered morphology that is associated with myofibroblastic activation in the chorionic connective tissue.

Amnion↗

Exploring dynamics of protein structure determination and homology-based prediction to estimate the number of superfamilies and folds.

BACKGROUND: As tertiary structure is currently available only for a fraction of known protein families, it is important to assess what parts of sequence space have been structurally characterized. We consider protein domains whose structure can be predicted by sequence similarity to proteins with solved structure and address the following questions. Do these domains represent an unbiased random sample of all sequence families? Do targets solved by structural genomic initiatives (SGI) provide such a sample? What are approximate total numbers of structure-based superfamilies and folds among soluble globular domains? RESULTS: To make these assessments, we combine two approaches: (i) sequence analysis and homology-based structure prediction for proteins from complete genomes; and (ii) monitoring dynamics of the assigned structure set in time, with the accumulation of experimentally solved structures. In the Clusters of Orthologous Groups (COG) database, we map the growing population of structurally characterized domain families onto the network of sequence-based connections between domains. This mapping reveals a systematic bias suggesting that target families for structure determination tend to be located in highly populated areas of sequence space. In contrast, the subset of domains whose structure is initially inferred by SGI is similar to a random sample from the whole population. To accommodate for the observed bias, we propose a new non-parametric approach to the estimation of the total numbers of structural superfamilies and folds, which does not rely on a specific model of the sampling process. Based on dynamics of robust distribution-based parameters in the growing set of structure predictions, we estimate the total numbers of superfamilies and folds among soluble globular proteins in the COG database. CONCLUSION: The set of currently solved protein structures allows for structure prediction in approximately a third of sequence-based domain families. The choice of targets for structure determination is biased towards domains with many sequence-based homologs. The growing SGI output in the future should further contribute to the reduction of this bias. The total number of structural superfamilies and folds in the COG database are estimated as approximately 4000 and approximately 1700. These numbers are respectively four and three times higher than the numbers of superfamilies and folds that can currently be assigned to COG proteins.

Data Interpretation, Statistical↗

Early development of language by hand: composing, reading, listening, and speaking connections; three letter-writing modes; and fast mapping in spelling.

The first findings from a 5-year, overlapping-cohorts longitudinal study of typical language development are reported for (a) the interrelationships among Language by Ear (listening), Mouth (speaking), Eye (reading), and Hand (writing) in Cohort 1 in 1st and 3rd grade and Cohort 2 in 3rd and 5th grade; (b) the interrelationships among three modes of Language by Hand (writing manuscript letters with pen and keyboard and cursive letters with pen) in each cohort in the same grade levels as (a); and (c) the ability of the 1st graders in Cohort 1 and the 3rd graders in Cohort 2 to apply fast mapping in learning to spell pseudowords. Results showed that individual differences in Listening Comprehension, Oral Expression, Reading Comprehension, and Written Expression are stable developmentally, but each functional language system is only moderately correlated with the others. Likewise, manuscript writing, cursive writing, and keyboarding are only moderately correlated, and each has a different set of unique neuropsychological predictors depending on outcome measure and grade level. Results support the use of the following neuropsychological measures in assessing handwriting modes: orthographic coding, rapid automatic naming, finger succession (grapho-motor planning for sequential finger movements), inhibition, inhibition/switching, and phonemes skills (which may facilitate transfer of abstract letter identities across letter formats and modes of production). Both 1st and 3rd graders showed evidence of fast mapping of novel spoken word forms onto written word forms over 3 brief sessions (2 of which involved teaching) embedded in the assessment battery; and this fast mapping explained unique variance in their spelling achievement over and beyond their orthographic and phonological coding abilities and correlated significantly with current and next-year spelling achievement.

Age Factors↗

Differential responses of single reticulospinal cells to spatially localized stimulation of the optic tectum in a teleost fish, Salmo trutta.

To determine whether the topographically organized retinal input to the optic tectum is subsequently mapped onto the reticular formation, the responses of antidromically identified reticulospinal cells to tectal surface stimulation were investigated in 45 decerebrated, paralysed trout. The tectum was stimulated through a silver ball surface electrode at 24 different locations, and extracellular recordings were made from the rhombencephalic brainstem with glass microelectrodes filled with a 10% solution of horseradish peroxidase (HRP) in Tris buffer (pH 7.4). After recording, the HRP was, in some cases, iontophoretically expelled from the pipette to identify its location and visualized in histological sections by a modified Hanker-Yates method. Individual reticulospinal neurons discharged 1-4 spikes at short latency in response to stimulation of each of the 24 tectal locations. From one tectal location per cell, this initial response was followed by a late, sustained burst. With a short stimulus train (6 pulses, 55 Hz) the burst could last for over a second with discharge rates of up to 500 Hz. Sometimes this burst could be evoked from neighbouring tectal locations, but only by greatly increasing the stimulus strength. We conclude that the reticular formation receives a highly divergent monosynaptic connection from all locations of the tectum and that the longer latency, sustained burst response is due to a mapped connection between the tectum and the reticular formation. Since the late burst could be preceded by a silent period lasting for approximately 32 ms, we cannot rule out a dependence on interneurons situated between the tectum and the reticulospinal cells.

Animals↗

Aber Lenken Sie Auch? (But do they also guide?).

One of the most intriguing problems in developmental neurobiology is that of how growing axons find the correct way to their proper target cells. Often axonal connections are organized in topographic maps, where neighboring cells of the projecting area are connected to neighboring cells in the target area, thus allowing a faithful transfer of positionally stored information from one area to another. The retinotectal projection is the classical model system for studying topographic projections.

Animals↗

Determining anatomical connectivities between cortical and brainstem pain processing regions in humans: a diffusion tensor imaging study in healthy controls.

Neuroimaging methods have so far identified various structures in the brain involved in the processing of pain and its control. However, our understanding of their anatomical connectivities is relatively weak. Diffusion tensor imaging (DTI), a magnetic resonance imaging-based method, allows in vivo mapping of the anatomical connections in the human brain and was used to investigate the white matter connections originating from the periaquaductal grey (PAG) and nucleus cuneiformis (NCF). We performed DTI on 8 healthy right-handed male volunteers. Group analysis showed that tract paths could be defined and their likelihood quantified for connections between the PAG and separately for the NCF, to the prefrontal cortex, amygdala, thalamus, hypothalamus and rostroventral medial medulla bilaterally. The connections identified confirm the existence of an anatomical circuitry for the functionally characterised top-down influences on pain processing via brainstem structures in humans.

Adult↗

Molecular interaction map of the p53 and Mdm2 logic elements, which control the Off-On switch of p53 in response to DNA damage.

The molecular network that controls responses to genotoxic stress is centered at p53 and Mdm2. Recent findings have shown this network to be more complex than previously envisioned. Using a notation specifically designed for circuit diagram-like representations of bioregulatory networks, we have prepared an updated molecular interaction map of the immediate connections of p53 and Mdm2, which are described as logic elements of the network. We use the map as the basis for a comprehensive review of current concepts of signal processing by these logic elements (an interactive version of the maps-eMIMs can be examined at ). We also used molecular interaction maps to propose a p53 Off-On switch in response to DNA damage.

Apoptosis↗

Anomalous origin of the left coronary artery from the pulmonary trunk: elucidation with colour Doppler flow mapping.

Four infants and children with anomalous connection of the left coronary artery to the pulmonary trunk were studied with colour Doppler flow mapping. In three the diagnosis was only suspected when the colour Doppler study showed dilated intraseptal and epicardial vessels and an abnormal flow signal into the pulmonary artery in diastole; this latter signal localised the exact site of communication, which was not apparent on angiocardiography. Two of these patients had previously had operations for severe mitral regurgitation, the diagnosis of anomalous left coronary artery having been previously considered in one but missed despite aortic root angiography. The colour study in the fourth was largely confirmatory, operation without catheterisation being undertaken on the basis of the echocardiographic images. By contrast in two infants subsequently seen with congestive cardiomyopathy the demonstration of flow direction in the left coronary artery confirmed that it was normally connected to the aorta. Colour Doppler flow mapping can show flow direction in the left coronary artery and from the mouth of an anomalous coronary artery into the pulmonary artery, thus simplifying the diagnosis and allowing the site of the connection of the left coronary artery to the pulmonary artery to be determined with precision.

Cardiomyopathy, Dilated↗

Functional topography: multidimensional scaling and functional connectivity in the brain.

In neuroimaging, functional mapping usually implies mapping function into an anatomical space, for example, using statistical parametric mapping to identify activation foci, or the characterization of distributed changes with spatial modes (eigenimages or principal components) (Friston et al., 1993a). This article is about a complementary approach, namely, mapping anatomy into a functional space. We describe a simple variant of multidimensional scaling (principal coordinates analysis; Gower, 1966) that uses functional connectivity as its metric. The scaling transformation maps anatomy into a functional space. The topography, or proximity relationships, in this space embody the functional connectivity among brain regions. The higher the functional connectivity, the closer the regions. Functional connectivity is defined here as the correlation between remote neurophysiological events. The technique represents a descriptive characterization of anatomically distributed changes in the brain that reveals the structure of corticocortical interactions in terms of functional correlations. To illustrate the approach we have analyzed data from normal subjects and schizophrenic patients obtained with PET during the performance of word generation tasks. In particular, we focus on prefrontotemporal integration in normal subjects and show that, in schizophrenia, the left temporal regions and prefrontal cortex evidence abnormal functional connectivity.

Brain↗

Target recognition and visual maps in the thalamus of achiasmatic dogs.

Vision is dependent on ordered neuronal representations or maps of visual space. These maps depend on precise connections between retinal axons and their targets cells. In mammals, nerve fibres from right and left eyes produce congruent maps of contralateral visual space in adjacent layers of the lateral geniculate nucleus (LGN). We have identified an autosomal recessive mutation in Belgian sheepdogs that eliminates the optic chiasm. In these mutants, all retinal axons project into the ipsilateral optic tract, including those originating in the nasal hemiretina that normally cross midline. These animals exhibit a pronounced horizontal nystagmus. The abnormal ipsilaterally directed nasal fibres innervate the LGN as if they had successfully crossed the midline, terminating in the appropriate layer of the nucleus. As a consequence, the LGN contains non-congruent, mirror-image maps of visual space in adjacent layers. These results show that there is a robust affinity between nasal and temporal retinal axons and specific LGN layers even when all retinal axons originate from a single eye.

Animals↗

Detecting functional connectivity in the resting brain: a comparison between ICA and CCA.

Independent component analysis (ICA) and cross-correlation analysis (CCA) are general tools for detecting resting-state functional connectivity. In this study, we jointly evaluated these two approaches based on simulated data and in vivo functional magnetic resonance imaging data acquired from 10 resting healthy subjects. The influence of the number of independent components (maps) on the results of ICA was investigated. The influence of the selection of the seeds on the results of CCA was also examined. Our results reveal that significant differences between these two approaches exist. The performance of ICA is superior as compared with that of CCA; in addition, the performance of ICA is not significantly affected by structured noise over a relatively large range. The results of ICA could be affected by the number of independent components if this number is too small, however. Converting the spatially independent maps of ICA into z maps for thresholding tends to overestimate the false-positive rate. However, the overestimation is not very severe and may be acceptable in most cases. The results of CCA are dependent on seeds location. Seeds selected based on different criteria will significantly affect connectivity maps.

Adolescent↗