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The potential of Prunus davidiana for introgression into peach [Prunus persica (L.) Batsch] assessed by comparative mapping.

The potential for introgression of Prunus davidiana, a wild species related to peach, was evaluated with respect to problems of non-Mendelian segregation or suppressed recombination which often hamper breeding processes based on interspecific crosses. Three connected (F1, F2 and BC2) populations, derived from a cross between P. davidiana clone P1908 and the peach cultivar Summergrand were used. The intraspecific map of P. davidiana already established using the F1 progeny was complemented, and two interspecific maps, for the F2 and BC2 progenies, were built with a set of markers selected from the Prunus reference map. With the molecular data collected for the F2 map construction, regions with distorted marker segregation were detected on the genome; one third of all loci deviated significantly from the expected Mendelian ratios. However, some of these distorted segregations were probably not due to the interspecific cross. On linkage group 6, a skewed area under gametic selection was most likely influenced by the self-incompatibility gene of P. davidiana. Using anchor loci, a good colinearity between the three maps built and the Prunus reference map was demonstrated. Comparative mapping also revealed that homologous recombination occurred normally between P. davidiana and the Prunus persica genome. This confirmed the closeness of the two species. Higher recombination rates were generally observed between P. davidiana and P. persica than between Prunus amygdalus and P. persica. The consequences for plant breeding strategy are discussed. The three maps of the F1, F2 and BC2 progenies provide useful tools for QTL detection and marker-assisted selection, as well as for assessing the efficiency of the peach breeding scheme applied to introgress P. davidiana genes into peach cultivated varieties.

Breeding↗

Fibrodysplasia ossificans progressiva, a heritable disorder of severe heterotopic ossification, maps to human chromosome 4q27-31.

Fibrodysplasia ossificans progressiva (FOP) is a severely disabling, autosomal-dominant disorder of connective tissue and is characterized by postnatal progressive heterotopic ossification of muscle, tendon, ligament, and fascia and by congenital malformation of the great toes. To identify the chromosomal location of the FOP gene, we conducted a genomewide linkage analysis, using four affected families with a total of 14 informative meioses. Male-to-male transmission of the FOP phenotype excluded X-linked inheritance. Highly polymorphic microsatellite markers covering all human autosomes were amplified by use of PCR. The FOP phenotype is linked to markers located in the 4q27-31 region (LOD score 3.10 at recombination fraction 0). Crossover events localize the putative FOP gene within a 36-cM interval bordered proximally by D4S1625 and distally by D4S2417. This interval contains at least one gene involved in the bone morphogenetic protein-signaling pathway.

Chromosome Mapping↗

Model-based analysis of excitatory lateral connections in the visual cortex.

Excitatory lateral connections within the primary visual cortex are thought to link neurons with similar receptive field properties. Here we studied whether this rule can predict the distribution of excitatory connections in relation to cortical location and orientation preference in the cat visual cortex. To this end, we obtained orientation maps of areas 17 or 18 using optical imaging and injected anatomical tracers into these regions. The distribution of labeled axonal boutons originating from large populations of excitatory neurons was then analyzed and compared with that of individual pyramidal or spiny stellate cells. We demonstrate that the connection patterns of populations of nearby neurons can be reasonably predicted by Gaussian and von Mises distributions as a function of cortical location and orientation, respectively. The connections were best described by superposition of two components: a spatially extended, orientation-specific and a local, orientation-invariant component. We then fitted the same model to the connections of single cells. The composite pattern of nine excitatory neurons (obtained from seven different animals) was consistent with the assumptions of the model. However, model fits to single cell axonal connections were often poorer and their estimated spatial and orientation tuning functions were highly variable. We conclude that the intrinsic excitatory network is biased to similar cortical locations and orientations but it is composed of neurons showing significant deviations from the population connectivity rule.

Animals↗

Theta rhythm of navigation: link between path integration and landmark navigation, episodic and semantic memory.

Five key topics have been reverberating in hippocampal-entorhinal cortex (EC) research over the past five decades: episodic and semantic memory, path integration ("dead reckoning") and landmark ("map") navigation, and theta oscillation. We suggest that the systematic relations between single cell discharge and the activity of neuronal ensembles reflected in local field theta oscillations provide a useful insight into the relationship among these terms. In rats trained to run in direction-guided (1-dimensional) tasks, hippocampal cell assemblies discharge sequentially, with different assemblies active on opposite runs, i.e., place cells are unidirectional. Such tasks do not require map representation and are formally identical with learning sequentially occurring items in an episode. Hebbian plasticity, acting within the temporal window of the theta cycle, converts the travel distances into synaptic strengths between the sequentially activated and unidirectionally connected assemblies. In contrast, place representations by hippocampal neurons in 2-dimensional environments are typically omnidirectional, characteristic of a map. Generation of a map requires exploration, essentially a dead reckoning behavior. We suggest that omnidirectional navigation through the same places (junctions) during exploration gives rise to omnidirectional place cells and, consequently, maps free of temporal context. Analogously, multiple crossings of common junction(s) of episodes convert the common junction(s) into context-free or semantic memory. Theta oscillation can hence be conceived as the navigation rhythm through both physical and mnemonic space, facilitating the formation of maps and episodic/semantic memories.

Animals↗

In vivo diffusion tensor imaging (DTI) of brain subdivisions and vocal pathways in songbirds.

The neural substrate for song behavior in songbirds, the song control system (SCS), is thus far the best-documented brain circuit in which to study neuroplasticity and adult neurogenesis. Not only does the volume of the key song control nuclei change in size, but also the density of the connections between them changes as a function of seasonal and hormonal influences. This study explores the potentials of in vivo Diffusion-Tensor MRI (DT-MRI or DTI) to visualize the distinct, concentrated connections of the SCS in the brain of the starling (Sturnus vulgaris). In vivo DTI on starling was performed on a 7T MR system using sagittal and coronal slices. DTI was accomplished with diffusion gradients applied in seven non-collinear directions. Fractional Anisotropy (FA)-maps allowed us to distinguish most of the grey matter and white matter-tracts, including the laminae subdividing the avian telencephalon and the tracts connecting the major song control nuclei (e.g., HVC with RA and X). The FA-maps also allowed us to discern a number of song control, auditory and visual nuclei. Fiber tracking was implemented to illustrate the discrimination of all tracts running from and to RA. Because of the remarkable plasticity inherent to the songbird brain, the successful implementation of DTI in this model could represent a useful tool for the in vivo exploration of fiber degeneration and regeneration and the biological mechanisms involved in brain plasticity.

Algorithms↗

Improved neuronal tract tracing using manganese enhanced magnetic resonance imaging with fast T(1) mapping.

There has been growing interest in using manganese-enhanced MRI (MEMRI) to detect neuronal activation, neural architecture, and neuronal connections. Usually Mn(2+) produces a very wide range of T(1) change. In particular, in neuronal tract tracing experiments the site of Mn(2+) injection can have very short T(1) while distant regions have small T(1) reductions, primarily due to dilution of Mn(2+). Most MEMRI studies use T(1)-weighted sequences, which can only give optimal contrast for a narrow range of T(1) changes. To improve sensitivity to the full extent of Mn(2+) concentrations and to optimize detection of low concentrations of Mn(2+), a fast T(1) mapping sequence based on the Look and Locker technique was implemented. Phantom studies demonstrated less than 6.5% error in T(1) compared to more conventional T(1) measurements. Using center-out segmented EPI, whole-brain 3D T(1) maps with 200-microm isotropic resolution were obtained in 2 h from rat brain. Mn(2+) transport from the rat olfactory bulb through appropriate brain structures could be detected to the amygdala in individual animals. The method reliably detected less than 7% reductions in T(1). With this quantitative imaging it should be possible to study more extensive pathways using MEMRI and decrease the dose of Mn(2+) used.

Animals↗

Mapping of multiple B cell epitopes on the 70-kilodalton autoantigen of the U1 ribonucleoprotein complex.

High titer IgG autoantibodies to the 70-kDa polypeptide component (p70) of the U1 ribonucleoprotein (RNP) complex occur in the sera of patients with mixed connective tissue disease, SLE, and related rheumatic diseases. To gain insight into the pathogenesis and diversity of this antibody response we have used recombinant DNA technology to map the linear B cell epitopes on p70. A full length 1.7-kb cDNA clone encoding p70 was isolated from a human placental library and restriction fragments or polymerase chain reaction-generated fragments of the gene subcloned into the bacterial expression vector pGEX. Purified fusion proteins representing specific regions of p70 were immunoblotted with a panel of 70 anti-(U1)RNP+ sera containing anti-p70 antibodies. Six epitopes, four major (A, B, C, and F) and two minor (D and E) were mapped and were located throughout the molecule. The anti-(U1)RNP sera displayed heterogeneity in their pattern of reactivity to the six epitopes although reactivity to epitope C was more frequently associated with SLE rather than mixed connective tissue disease. The identification of multiple B cell epitopes on p70 is consistent with the concept that this self Ag drives the autoantibody response.

Autoantigens↗

Retinal projection in a non-visual area after bilateral tectal ablation in goldfish.

If, in the adult goldfish, one optic tectum is ablated, the regenerating optic axons from the contralateral retina innervate the remaining tectum, where they form a retinotopically ordered map. The pathway for this induced ipsilateral projection coincides with many of the pathways which normally connect the two tecta, but early in regeneration the optic fibres also enter non-visual centres to which there are degenerating tectal efferent pathways to follow. We have therefore now investigated the fate of regenerating optic axons in goldfish from which both optic tecta have been removed; they are found to innervate non-visual centres, where again they generate a retinotopic map.

Animals↗

The effect of arterial pressure on the ocular pressure-volume relationship in the rabbit.

The purpose of this study was to quantify the effect of mean arterial pressure (MAP) on the ocular pressure-volume relationship. The experiments were performed in pentobarbital anesthetized rabbits instrumented with occluders on the thoracic aorta and inferior vena cava to control MAP which was measured via a cannula in the central ear artery. To vary the ocular volume and measure the intraocular pressure (IOP), two 23 gauge needles were inserted through the pars plana into the vitreous: one needle was connected to a saline-filled syringe and the other needle was connected to a pressure transducer. In one group of animals (n = 5), pressure-volume curves were determined at MAPs of 100, 80, 60, 40 and 20 mmHg and post mortem by cumulative saline injections (2 microliters) every 1-1.5 sec. In a second group (n = 7), pressure-volume curves were obtained at MAPs of 80, 60 and 40 mmHg and post mortem by saline infusion at 0.5 microliter sec-1 until the IOP reached 100 mmHg. The infusion protocol was repeated in a third group (n = 11) where the choroidal flux and the concentration of moving blood cells (CMBC) were measured by a laser Doppler flowmeter as indices of choroidal blood flow and the blood volume, respectively. MAP had three primary effects on the ocular pressure-volume relationship: (1) the baseline IOP varied exponentially with MAP, (2) the steepness of the initial portion of the pressure-volume curves was MAP-dependent and (3) the curves exhibited a 'plateau' as the IOP approached the prevailing MAP at MAPs > or = 40 mmHg. All of the curves in the living eye intersected and became indistinguishable from the post mortem curve when the IOP exceeded the prevailing MAP. The flux and CMBC measurements indicated that the MAP-dependence of the initial portion of the curves was due to failure of choroidal autoregulation and diminished increases in choroidal blood volume at the lower MAPs, and that the plateau portion of the curves was due to expulsion of blood from the eye. It is concluded that MAP has a significant effect on the ocular pressure-volume relationship.

Animals↗

Interhemispheric connections of visual cortex in the owl monkey, Aotus trivirgatus, and the bushbaby, Galago senegalensis.

Anatomical techniques have been used to map within visual cortex th pattern of degenerating axonal terminals produced by surgical section of the splenium of the corpus callosum in the owl monkey, Aotus trivirgatus, and the bushbaby, Galago senegalensis. Previous studies in other species have shown that callosal inputs terminate preferentially in regions where the vertical meridian of the visual field is represented. Such a correspondence can serve as a useful aid for locating the boundaries of visual areas. The goals of this study have been (1) to assess the degree of correspondence between callosal inputs and previously identified vertical meridian representations in the owl monkey and bushbaby, and (2) to gain information from the pattern of callosal inputs concerning the existence and organization of as yet unidentified extrastriate visual areas. In both the owl monkey and the bushbaby, a discrete band of degenerating axonal terminals corresponds precisely to the vertical meridian representation at the V1-V2 border, and a less precise increase in the density of degenerating axonal terminals corresponds to the vertical meridian representation of extrastriate area MT. A well-defined band of degeneration on the ventral surface of the owl monkey's cerebral hemisphere corresponds to a previously unknown vertical meridian representation which is shared by two newly identified extrastriate visual areas. Elsewhere in visual cortex the pattern of callosal connections is more complex. Although this pattern may still reflect visual topography, it is not immediately useful for distinguishing areal boundaries.

Animals↗

See your brands through your customers' eyes.

Subaru markets an L.L. Bean Outback station wagon. Dell stamps Microsoft and Intel logos on its computers. Such inter-weaving of different companies' brands is now commonplace. But one of the central tools of brand management-portfolio mapping--has not kept pace with changes in the marketplace. Most conventional brand maps include only those brands owned by a company, arranged along organizational lines with little regard for how the brands influence customer perceptions. In this article, the authors present a new mapping tool--the brand portfolio molecule--that reveals the way brands appear to customers. The brand portfolio molecule includes all the brands that factor into a consumer's decision to buy, whether or not the company owns them. The first step in creating a brand portfolio molecule is to determine which brands should or should not be included. The second step is to classify each brand by asking five key questions: 1) How important is this brand to customers' purchase decisions about the brand you're mapping? 2) Is its influence positive or negative? 3) What market position does this brand occupy relative to the other brands in the portfolio? 4) How does this brand connect to the other brands in the portfolio? 5) How much control do you have over this brand? The last step is to map the molecule using a 3-D modeling program or by hand with pen and paper. Individual brands take the form of atoms, and they're clustered in ways that reflect how customers see them. The usefulness of the tool lies in its ability to show the many forces that influence a customer's buying decision--and to provide a powerful new way to think about brand strategy.

Commerce↗

A geodesic framework for analyzing molecular similarities.

A fast self-organizing algorithm for extracting the minimum number of independent variables that can fully describe a set of observations was recently described (Agrafiotis, D. K.; Xu, H. Proc. Natl. Acad. Sci.U.S.A. 2002, 99, 15869-15872). The method, called stochastic proximity embedding (SPE), attempts to generate low-dimensional Euclidean maps that best preserve the similarities between a set of related objects. Unlike conventional multidimensional scaling (MDS) and nonlinear mapping (NLM), SPE preserves only local relationships and, by doing so, reveals the intrinsic dimensionality and metric structure of the data. Its success depends critically on the choice of the neighborhood radius, which should be consistent with the local curvature of the underlying manifold. Here, we describe a procedure for determining that radius by examining the tradeoff between the stress function and the number of connected components in the neighborhood graph and show that it can be used to produce meaningful maps in any embedding dimension. The power of the algorithm is illustrated in two major areas of computational drug design: conformational analysis and diversity profiling of large chemical libraries.

Journal Article↗

Neural substrata underlying tectal eye movement codification in goldfish.

The optic tectum encodes orienting eye saccades in a spatially ordered map. To investigate whether the functional properties of each tectal site are related to a particular pattern of connectivity with downward structures in the brainstem, two sets of experiments were carried out. First, biotinylated dextran amine (BDA) was injected at different tectal sites along the anteroposterior axis. Electrical stimulation at these sites evoked saccades whose horizontal component amplitudes increased with the distance to the rostral pole. In the second experiment, BDA and fluoro-ruby (FR) were injected at different tectal sites along the mediolateral axis. Electrical stimulation here evoked saccades with different upward and downward directions, but similar horizontal component amplitudes. A major finding of the first experiment was that a topographic link of the tectum exists with the mesencephalic reticular formation, but that such a connection was absent or very attenuated for the rhombencephalic reticular formation. In the second set of experiments, the clusters of BDA and FR boutons left by the mediolateral tectal sites were separated in the rostral mesencephalon, at the level of the nucleus of the medial longitudinal fasciculus, but overlapped in the caudal mesencephalon and rhombencephalon. These data provide evidence that decodification of tectal motor commands is based, at least in part, on the connectivity of each tectal locus on downward structures with the brainstem.

Animals↗

Head direction cells: properties and functional significance.

The strong signal carried by head direction cells in the postsubiculum complements the positional signal carried by hippocampal place cells; together, the directional and positional signals provide the information necessary to permit rats to generate and carry out intelligent, efficient solutions to spatial problems. Our opinion is that the hippocampal positional system acts as a cognitive map and that the role of the directional system is to put the map into register with the environment. In this way, paths found using the map can be properly executed. Head direction cells have recently been discovered in parts of the thalamus reciprocally connected with the postsubiculum; such cells provide important clues to the organization of the directional system.

Animals↗

Genomics and homeostasis.

The Cannon lecture this year illustrates how knowledge of DNA sequences of complex living organisms is beginning to shape the landscape of physiology in the 21st century. Enormous challenges and opportunities now exist for physiologists to relate the galaxy of genes to normal and pathological functions. The first extensive genomic systems biology map for cardiovascular and renal function was completed last year as well as a new hypothesis-generating tool ("physiological profiling") that enables us to hypothesize relationships between specific genes responsible for the regulation of regulatory pathways. Techniques of chromosomal substitution (consomic and congenic rats) are beginning to confirm statistical results from linkage analysis studies, narrow the regions of genetic interest for positional cloning, and provide genetically well-defined control strains for physiological studies. Patterns of gene expression identified by microarray and mapping of expressed genes to chromosomal sites are adding to the understanding of systems physiology. The previously unimaginable goal of connecting approximately 36,000 genes to the complex functions of mammalian systems is indeed well underway.

Animals↗

Integration of physical, genetic and cytogenetic maps of human chromosome 7: isolation and analysis of yeast artificial chromosome clones for 117 mapped genetic markers.

An important goal for the human genome project is to assemble fully integrated physical, genetic and cytogenetic maps for each human chromosome. Towards that end, we have isolated yeast artificial chromosome (YAC) clones containing 117 of the 119 genetic markers that constitute a recently constructed, detailed genetic map of human chromosome 7. Analysis of these clones reveals numerous examples where adjacent genetic markers have been physically connected, either in individual YACs or in multi-YAC contigs. At present, the 117 genetic markers are contained in fewer than 80 YAC contigs, with most of these contigs uniquely ordered relative to one another based on the genetic map positions of the corresponding markers. These YACs and YAC contigs are estimated to contain approximately 60-85% of the DNA from human chromosome 7. YACs representing 36 genetic markers were mapped by fluorescence in situ hybridization (FISH) to metaphase chromosomes, allowing assignment of these genetic markers to cytogenetic bands along chromosome 7 and placement of the centromere within the genetic map. Together, these studies provide genetically and cytogenetically anchored YAC clones covering the majority of chromosome 7 that will be useful both for the positional cloning of genes and as a framework for assembling a complete YAC-based physical map of the chromosome.

Chromosome Mapping↗

Macaque red nucleus: origins of spinal and olivary projections and terminations of cortical inputs.

The cerebellar, spinal, bulbar, and cortical connections of the mammalian red nucleus imply a motor role. However, what information the red nucleus receives, processes, and distributes is poorly understood, partly because the rubral microcircuitry, especially in primates, remains incompletely defined. Multiple retrogradely transported fluorescent tracers were injected into the spinal cord and inferior olive of the macaque to label rubrospinal and rubroolivary neuron populations, respectively. Anterograde dextran amines were used to label the terminals of corticorubral neurons. These data provided the topographic framework for examining the morphology of rubral neurons in the accompanying paper (Burman et al. [2000]). Soma profiles of rubrospinal and rubro-olivary neurons were respectively segregated in the magnocellular and parvocellular nuclei. A subpopulation of neurons (DL-spinal cells) with their somas immediately dorsolateral to the rostral magnocellular nucleus and its capsule, also projected to the spinal cord, as did clusters of neurons in the periaqueductal grey matter. Terminals of corticorubral axons originating from ipsilateral primary motor area 4 (the densest projection), the supplementary motor area, cingulate area 24, area 8, and posterior parietal area 5, were each mapped in the parvocellular red nucleus. Only area 4 projected to the magnocellular red nucleus, and this projection as small. DL-spinal neurons had no cortical input. The somatotopic organization of rubral connections was examined only in (a) the corticorubral input from motor area 4, and (b) the rubrospinal and DL-spinal projections. These connections and their somatotopic alignment, were mapped in a 3-dimensional reconstruction of the red nucleus.

Animals↗

Reentry and the problem of integrating multiple cortical areas: simulation of dynamic integration in the visual system.

Studies of the cerebral cortex, particularly those of the visual system, demonstrate the existence of multiple, anatomically segregated and functionally specialized cortical areas. There is no evidence that these areas, which are linked by a network of reciprocal connections, are coordinated by a higher-order center. The visual image that we perceive, however, seems to be unified and coherent. In this article, we address the problem of integration posed by these observations. In an extension of our previous work, we develop a dynamic model of reentry. Reentry is a process of parallel and recursive signaling along ordered anatomical connections that achieves integration by giving rise to constructive and correlative properties within and among maps. We present and test a computer model simulating nine functionally segregated visual areas organized into three streams for form, color, and motion. The model receives visual input consisting of camera images of objects of different shapes and colors. We show the specialized response properties of the areas in the three streams. A computational strategy involving a phase variable is introduced to represent explicitly the dynamics of short-term temporal correlations among thousands of units distributed across different areas. We then illustrate constructive and correlative consequences of reentry within a system of reciprocal intra- and interareal connections by two examples taken from psychophysics: generation of form from motion and motion capture. The model solves the so-called "binding problem" through short-term correlations, which serve to link similar object features within a simulated cortical area and to bind multiple attributes of one or more objects across several areas, including a nontopographic one. Integration emerges from cooperative effects within and among the specialized areas. These effects lead to a simple output, a simulated foveation response, that is used as a basis for conditioning. Reward is mediated by the activation of a saliency system that is modeled on diffuse projection systems in the brain. As a result, the visual cortical model carries out foveation responses to input stimuli that require the dynamic conjunction and discrimination of form, color, and location for successful performance.

Animals↗