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Abnormal visual input leads to development of abnormal axon trajectories in frogs.

Throughout the normal vertebrate brain, visual maps form the left and right eyes overlap and are in register with one another. Visual input has a major role in the development of the pathways which mediate these binocular projections. A dramatic example of the developmental role of sensory input occurs in the isthmo-tectal projection, which is part of the polysynaptic relay from the eye to the ipsilateral tectum of the frog, Xenopus laevis. If one eye is rotated when the animal is still a tadpole, the isthmic axons respond by changing the topography of their terminations in the tectum; for example, a given isthmo-tectal axon which normally would connect with medial tectum can be induced to terminate in lateral tectum. Such rearrangements bring the ipsilateral visual map into register with the contralateral retinotectal map, even though one eye has been rotated. Indirect evidence has suggested that after early eye rotation, isthmo-tectal axons do not grow directly to their new tectal targets but instead reach those targets by routes which pass through their normal termination zones. Here I have used anterograde horseradish peroxidase labelling of isthmo-tectal fibres to show the trajectories of such axons and to compare them with the routes which axons take when allowed to develop normally. Tracings of individual axons in flat-mounted, unsectioned tecta show that most axons in normal Xenopus follow fairly straight paths in the tectum. In contrast, early eye rotation causes many isthmo-tectal axons to follow crooked, circuitous pathways before they terminate.

Animals↗

A framework based on spin glass models for the inference of anatomical connectivity from diffusion-weighted MR data - a technical review.

A family of methods aiming at the reconstruction of a putative fascicle map from any diffusion-weighted dataset is proposed. This fascicle map is defined as a trade-off between local information on voxel microstructure provided by diffusion data and a priori information on the low curvature of plausible fascicles. The optimal fascicle map is the minimum energy configuration of a simulated spin glass in which each spin represents a fascicle piece. This spin glass is embedded into a simulated magnetic external field that tends to align the spins along the more probable fiber orientations according to diffusion models. A model of spin interactions related to the curvature of the underlying fascicles introduces a low bending potential constraint. Hence, the optimal configuration is a trade-off between these two kind of forces acting on the spins. Experimental results are presented for the simplest spin glass model made up of compass needles located in the center of each voxel of a tensor based acquisition.

Algorithms↗

Mapping chemical gradients within and along a fibrous structural tissue, mussel byssal threads.

The byssal thread of a mussel is an extraorganismic connective tissue that exhibits a striking end-to-end gradient in mechanical properties and thus provides a unique opportunity for studying how gradients are made. Mfp-1 (Mytilus foot protein-1) is a conspicuous component of the protective outer cuticle of byssal threads given its high 3,4-dihydroxyphenylalanine (Dopa) content at 10-15 mol %. Amino acid analysis of mfp-1 extracted from successive foot sections of Mytilus galloprovincialis reveals a post-translationally mediated gradient with highest Dopa levels present in mfp-1 from the accessory gland near the tip of the foot decreasing gradually toward the base. The Dopa content of successive segments of byssal threads decreases from the distal to the proximal end and thus reflects the trend of mfp-1 in the foot. Inductively coupled plasma analysis indicates that certain metal ions including iron follow the trend in Dopa along the thread. Energy-dispersive x-ray spectrometry showed that iron, when present, was concentrated in the cuticle of the threads but sparse in the core. The axial iron gradient appears most closely correlated with the Dopa gradient. The direct incubation of mussels and byssal threads in Fe(3+) supplemented seawater showed that byssal threads are unable to sequester iron from the seawater. Instead, particulate/soluble iron is actively taken up by mussels during filter feeding and incorporated into byssal threads during their secretion. Our results suggest that mussels may exploit the interplay between Dopa and metals to tailor the different parts of threads for specific mechanical properties.

Amino Acid Sequence↗

Nuclear magnetic resonance studies of complex formation between the oligonucleotide d(TATC) covalently linked to an acridine derivative and its complementary sequence d(GATA).

The oligodeoxynucleotide d(TATC) was covalently attached to the 9-amino group of 2-methoxy-6-chloro-9-aminoacridine (Acr) through its 3'-phosphate via a pentamethylene linker (m5). Complex formation between d(TATC)m5Acr and the complementary strand d(GATA) in aqueous solution was investigated by nuclear magnetic resonance. The COSY and NOESY connectivities allowed us to assign all the proton resonances of the bases, the sugars (except the overlapping 5'/5'' resonances), the acridine, and the pentamethylene chain. Structural informations derived from relative intensities of COSY and NOESY maps revealed that the duplex d(TATC)-d(GATA) adopts a B-type conformation and that the deoxyriboses preferentially adopt a 2'-endo conformation. The NOE connectivities observed between the protons of the bases or of the sugars and the protons of the dye and of the pentamethylene chain led us to propose a model involving an equilibrium between two families of configurations. In the first family, the acridine derivative is intercalated between base pairs C4-G4 and T3-A3. In the second family, the acridine derivative is sandwiched between two aggregated duplexes. The structure of the intercalated complex as well as that of the aggregated species is discussed.

Acridines↗

[Mapping of the genetic locus determining the degree of natural resistance to erythromycin in Salmonella].

The locus which determines ordinary (natural--ery or) level of resistance to erythromycin in Salmonella has been mapped. According to the results of conjugation mating and the analysis of the properties' transfer gradient this region is localized next to his--locus, the gene order being; trp--his--eryor. However, no contransduction of eryor--locus with his--gene has been demonstrated. An assumption on a possible mechanism of alteration of natural level of erythromycin resistance in S. typhimurium mutants Er-4 and Es-1 (received earlier) has been made. This mechanism is connected with alterations in cell permeability.

Cell Membrane Permeability↗

Antibody mapping and tissue localization of globular and cysteine-rich regions of perlecan domain III.

Perlecan is the best-characterized basement membrane heparan sulfate proteoglycan. It has a large (approximately 400 KD) core protein consisting of five distinct domains. Domain III, a centrally located domain, contains three globular domains separated by cysteine-rich epidermal growth factor (EGF)-like repeats. Domain III has overall homology with the N-terminus of the laminin alpha 1-chain. The aim of this study was to map a library of nine rat monoclonal antibodies (MAbs) against murine perlecan core protein, using recombinant whole Domain III and defined subdomains of Domain III. ELISA and Western blotting showed that six of the nine MAbs recognized Domain III of perlecan, three of them mapping to globular Subdomain IIIc, and the other three recognized epitopes within the cysteine-rich regions. All six MAbs stained every basement membrane of several mouse organs as well as some connective tissues, including cartilage. Therefore, several distinct epitopes of perlecan Domain III are present in most if not all basement membranes and are not obscured by intermolecular interactions. These precisely mapped antibodies may therefore be useful in understanding the function of perlecan and its core protein.

Animals↗

UVB-irradiated human keratinocytes and interleukin-1alpha indirectly increase MAP kinase/AP-1 activation and MMP-1 production in UVA-irradiated dermal fibroblasts.

BACKGROUND: Solar ultraviolet (UV) irradiation induces the production of matrix metalloproteinases (MMPs) by activating cellular signalling transduction pathways. MMPs are responsible for the degradation and/or inhibition of synthesis of collagenous extracellular matrix in connective tissues. We mimicked the action of environmental ultraviolet on skin and investigated the effects of UVB-irradiated human keratinocytes HaCaT and IL-1alpha on mitogen activated protein (MAP) kinase activation, c-Jun and c-Fos (AP-1 is composed of Jun and Fos proteins) mRNA expression and MMP-1 production in UVA-irradiated dermal fibroblasts. METHODS: Following UVA irradiation, the culture medium of fibroblasts was replaced by culture medium from UVB-irradiated HaCaT, or replaced by the complete culture medium with interleukin (IL)-1alpha. MAP kinase activity expression in fibroblasts was detected by Western blot. c-Jun and c-Fos mRNA expressions were determined by reverse transcriptional polymerase chain reaction (RT-PCR); MMP-1 production in culture medium was detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Culture medium from UVB-irradiated keratinocytes increased MAP kinase activity and c-Jun mRNA expression in UVA-irradiated fibroblasts. IL-1alpha increased MAP kinase activity and c-Jun mRNA expression, IL-1alpha also increased c-Fos mRNA expression. Both culture media from UVB-irradiated human keratinocytes and externally applied IL-1alpha increased MMP-1 production in UVA-irradiated fibroblasts. CONCLUSIONS: UVB-irradiated keratinocytes and IL-1alpha indirectly promote MMP-1 production in UVA-irradiated fibroblasts by increasing MAP kinase/AP-1 activity. IL-1 may play an important role in the paracrine activation and dermal collagen excessive degradation leading to skin photoaging.

Cell Line↗

Experience-dependent amelioration of motor impairments in adulthood following neonatal medial frontal cortex injury in rats is accompanied by motor map expansion.

One of the most common, and disruptive, neurological symptoms following neonatal brain injury is a motor impairment. Neonatal medial frontal cortical lesions in rats produce enduring motor impairments, and it is thought that lesion-induced abnormal cortical morphology and connectivity may underlie the motor deficits. In order to investigate the functional consequences of the lesion-induced anatomical abnormalities in adulthood, we used intracortical microstimulation to determine the neurophysiologic organization of motor maps within the lesion hemisphere. In addition, groups of neonatal lesion rats were given reach training or complex housing rehabilitation in adulthood and then mapped with intracortical microstimulation. The results demonstrate that neonatal medial frontal cortex lesions produce motor deficits in adulthood that are associated with abnormal motor maps. Further, adult behavioral treatment promoted partial recovery that was supported by reorganization of the motor maps whereby there were increases in the size of the forelimb motor maps. The experience-induced expansion of the forelimb motor maps in adulthood provides a neural mechanism for the experience-dependent improvements in motor performance.

Analysis of Variance↗

How spiking neurons give rise to a temporal-feature map: from synaptic plasticity to axonal selection.

A temporal-feature map is a topographic neuronal representation of temporal attributes of phenomena or objects that occur in the outside world. We explain the evolution of such maps by means of a spike-based Hebbian learning rule in conjunction with a presynaptically unspecific contribution in that, if a synapse changes, then all other synapses connected to the same axon change by a small fraction as well. The learning equation is solved for the case of an array of Poisson neurons. We discuss the evolution of a temporal-feature map and the synchronization of the single cells' synaptic structures, in dependence upon the strength of presynaptic unspecific learning. We also give an upper bound for the magnitude of the presynaptic interaction by estimating its impact on the noise level of synaptic growth. Finally, we compare the results with those obtained from a learning equation for nonlinear neurons and show that synaptic structure formation may profit from the nonlinearity.

Journal Article↗

Human platelet basic protein/connective tissue activating peptide-III maps in a gene cluster on chromosome 4q12-q13 along with other genes of the beta-thromboglobulin superfamily.

Pro-platelet basic protein (pro-PBP) is the precursor of the two platelet alpha-granule proteins, PBP and connective tissue activating peptide-III. Upon platelet activations they are released and further processed in plasma to beta-thromboglobulin and neutrophil-activating peptide-2. The gene encoding pro-PBP is mapped in this study to chromosome 4q12-q13. At least four other members of this family of small inducible cytokines, including NAP-1/Il-8 and platelet factor 4, reside within the same locus, indicating a gene cluster for the beta-thromboglobulin family.

Chemokines↗

White matter pathway asymmetry underlies functional lateralization.

Structural and functional asymmetry of the human brain has been well documented using techniques such as magnetic resonance imaging (MRI). However, asymmetry of underlying white matter connections is less well understood. We applied an MRI technique known as diffusion tensor tractography to reveal the morphology of the white matter in vivo by mapping directions of maximum water diffusion in brain tissue. White matter pathway asymmetry was investigated in a normalized image data set of 30 right-handed young healthy individuals. We identified, for the first time, a rightwardly asymmetric pathway connecting the posterior temporal lobe to the superior parietal lobule. This pathway may be related to auditory spatial attention and working memory for which there is evidence for a rightward laterality from functional imaging studies. Additional leftward asymmetries connecting the parietal and frontal lobes to the temporal lobe may be more closely related to laterality of language.

Adult↗

[Strategies for data analysis of brain activation studies with functional MR tomography].

The sensitivity of gradient-echo magnetic resonance imaging (MRI) to changes in cerebral blood oxygenation has been introduced for mapping functional brain activation. To benefit from the high spatial and temporal resolution of the respective dynamic MRI data sets, their analysis requires algorithms that are capable of both precisely delineating task-related activation patterns and demonstrating functional connectivity of interacting areas. Here, we present various strategies for data evaluation by means of correlational analyses that surpass the quality of subtraction-based activation maps by improving both sensitivity and robustness. On a pixel-by-pixel basis the approach correlates signal time courses with a reference function, reflecting the temporal sequence of activated and control states. Extended versions employ the calculation of auto- or cross-correlation functions that increase sensitivity, but require periodic stimulations. Following individual correction for non-specific but correlated signal fluctuations, mapping of task-related coherent activation can be improved using neighborhood principles. Such refined strategies are expected to enhance the usefulness of oxygenation-sensitive MRI for studying the functional anatomy of the human brain under both physiological and pathological conditions.

Algorithms↗

Functional demarcation of a border between areas V6 and V6A in the superior parietal gyrus of the macaque monkey.

We have compared physiological data recorded from three alert macaque monkeys with separate observations of local connectivity, to locate and characterize the functional border between two related but distinct visual areas on the caudal face of the superior parietal gyrus. We refer to these areas as V6 and V6A. The occupy almost the entire extent of the anterior bank of the parieto-occipital sulcus, V6A being the more dorsal. These two areas are strongly interconnected. Anatomically, we have defined the border as the point at which labelled axon terminals first adopt a recognizably 'descending' pattern in their laminar characteristics, after injections of wheatgerm agglutinin-horseradish peroxidase into the dorsal half of the gyrus (in presumptive V6A). A similar principle was used to recognize the same border by the pattern of input from area V5, except that in this case the relevant transition in laminar characteristics is that between an 'intermediate' pattern (in V6) and an 'ascending' pattern (in V6A). V6A was found to be distinct from V6 in a number of its physiological properties. Unlike V6, it contains visually unresponsive cells as well as units with craniotopic receptive fields ('real-position' cells), units tuned to very slow stimulus speeds, units with complex visual selectivities and units with activity related to attention. V6A was also found to have a larger mean receptive field size and scatter than V6. By contrast, response properties related to the basic orientation and direction of moving bar stimuli were indistinguishable between V6 and V6A, as was the influence of gaze direction on cell activity in the two areas. Two-dimensional maps of the recording sites allowed reconstruction of the V6/V6A border. For comparison, the anatomical results were rendered on two-dimensional maps of identical format to those used to summarize the physiological data. After normalizing for relative size, the physiological and connectional estimates of the border between V6 and V6A were found to coincide, at least within the range of individual variation between hemispheres. An architectonic map in the same format was also made from a hemisphere stained for myelin and Nissl substance. Area PO, defined by its general density of myelination was not distinct in this material, but several architectural features were traceable and one of these was also found to approximate the V6/V6A border. The particular criteria that distinguish V6 from V6A differ from a recent description of areas PO and POd in the Cebus monkey; we believe it most likely that PO and POd together may correspond to V6.

Analysis of Variance↗