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Chimeric molecules map and dissociate the potent transforming and secretory properties of PDGF A and PDGF B.

Human platelet-derived growth factor (PDGF) is a connective tissue cell mitogen comprising two related chains encoded by distinct genes. The B chain is the homolog of the v-sis oncogene product. Properties that distinguish these ligands include greater transforming potency of the B chain and more efficient secretion of the A chain. By a strategy involving the generation of PDGF A and B chimeras, these properties were mapped to distinct domains of the respective molecules. Increased transforming efficiency segregated with the ability to activate both alpha and beta PDGF receptors. These findings genetically map PDGF B residues 105 to 144 as responsible for conformational alterations critical to beta PDGF receptor interaction, and provide a mechanistic basis for the greater transforming potency of the PDGF B chain.

Animals↗

Development of callosal topography in visual cortex of normal and enucleated rats.

In normal rats callosal projections in striate cortex connect retinotopically corresponding, nonmirror-symmetric cortical loci, whereas in rats bilaterally enucleated at birth, callosal fibers connect topographically mismatched, mirror-symmetric loci. Moreover, retina input specifies the topography of callosal projections by postnatal day (P)6. To investigate whether retinal input guides development of callosal maps by promoting either the corrective pruning of exuberant axon branches or the specific ingrowth and elaboration of axon branches at topographically correct places, we studied the topography of emerging callosal connections at and immediately after P6. After restricted intracortical injections of anterogradely and retrogradely transported tracers we observed that the normal, nonmirror-symmetric callosal map, as well as the anomalous, mirror-symmetric map observed in neonatally enucleated animals, are present by P6-7, just as collateral branches of simple architecture emerge from their parental axons and grow into superficial cortical layers. Our results therefore do not support the idea that retinal input guides callosal map formation by primarily promoting the large-scale elimination of long, nontopographic branches and arbors. Instead, they suggest that retinal input specifies the sites on the parental axons from which interstitial branches will grow to invade middle and upper cortical layers, thereby ensuring that the location of invading interstitial branches is accurately related to the topographical location of the soma that gives rise to the parental axon. Moreover, our results from enucleated rats suggest that the cues that determine the mirror-symmetric callosal map exert only a weak control on the topography of fiber ingrowth.

Animals↗

Symbol dynamic maps of spatial-temporal chaotic vibrations in a string of impact oscillators.

Spatially complex, temporally chaotic dynamics of N-coupled impact oscillators connected by a string are studied experimentally using a discrete measure of the motion for each of the masses. For N=8, a binary assignment of symbols, corresponding to whether or not the masses impact an amplitude constraint, is used to code the spatial pattern as a binary number and to store its change in time in a computer. A spatial pattern return map is then used to observe the change in spatial patterns with time. Bifurcations in spatial impact patterns are observed in this experiment. An entropy measure is also used to characterize the dynamics. Numerical simulation shows behavior similar to the experimental system.

Journal Article↗

Eph receptor tyrosine kinase-mediated formation of a topographic map in the Drosophila visual system.

Roles for Eph receptor tyrosine kinase signaling in the formation of topographic patterns of axonal connectivity have been well established in vertebrate visual systems. Here we describe a role for a Drosophila Eph receptor tyrosine kinase (EPH) in the control of photoreceptor axon and cortical axon topography in the developing visual system. Although uniform across the developing eye, EPH is expressed in a concentration gradient appropriate for conveying positional information during cortical axon guidance in the second-order optic ganglion, the medulla. Disruption of this graded pattern of EPH activity by double-stranded RNA interference or by ectopic expression of wild-type or dominant-negative transgenes perturbed the establishment of medulla cortical axon topography. In addition, abnormal midline fasciculation of photoreceptor axons resulted from the eye-specific expression of the dominant-negative EPH transgene. These observations reveal a conserved role for Eph kinases as determinants of topographic map formation in vertebrates and invertebrates.

Animals↗

Relationship between intrinsic connections and functional architecture revealed by optical imaging and in vivo targeted biocytin injections in primate striate cortex.

In primate primary visual cortex, neurons sharing similar response properties are clustered together forming functional domains that appear as a mosaic of patches or bands, often traversing the entire cortical depth from the pia to the white matter. Similarly, each cortical site connects laterally through an extensive network of intrinsic projections that are organized in multiple clusters (patches) and reach distances of up to a few millimeters. The relationship between the functional domains and these laterally connected patches has remained a controversial issue despite intensive research efforts. To investigate this relationship, we obtained high-resolution functional maps of the cortical architecture by in vivo optical imaging. Subsequently, extracellular injections of the sensitive anterograde tracer biocytin were targeted into selected functional domains. Within the ocular dominance system, we found that long-range intrinsic connections tended to link the monocular regions of same-eye ocular dominance columns. Furthermore, we discovered that binocular domains formed a separate set of connections in area V1; binocular regions were selectively connected among themselves but were not connected to strictly monocular regions, suggesting that they constitute a distinct columnar system. In the other subsystem subserving orientation preference, patches of intrinsic connections tended to link domains sharing similar orientation preferences. Analyses of the precision of these connections indicated that in both functional subsystems, < 15% of the connections were between domains having orthogonal response properties. However, their selectivity was limited; approximately 30% +/- 10% of the interconnected patches contained neurons exhibiting orientation tuning that differed from those found at the injection sites by at least 45 degrees. At short range (up to 400 microns from the injection site), this casual trend seemed markedly accentuated; the local, synaptic-rich axonal and dendritic arbors crossed freely through columns of diverse functional properties. These complex sets of connections can endow cortical neurons with a rich diversity of response properties and broad tuning.

Animals↗

Connections between the quality of consultations and patient compliance in general practice.

The aim of the study was to generate and test a theory about connections between the quality of consultations and patient compliance in general practice. The theory was empirically based on patient interviews in order to understand the patient's perceptions and behaviour, and on development of a list for mapping of consultations, which in turn allowed coherent descriptions of consultations and compliance. The theory suggests and explains that compliance is connected with the fulfillment of six relatively simple criteria for the quality of consultations. The theory was tested by comparing predictions of compliance derived from analyses of 63 consultations with patient questionnaire based measurements of compliance. The difference between proportions of patients who were complaint after consultations fulfilling and not fulfilling respectively the criteria was 44%. The 95% confidence limits of this difference were 21% and 67%.

Family Practice↗

The Drosophila melanogaster dodecasatellite sequence is closely linked to the centromere and can form connections between sister chromatids during mitosis.

We have used fluorescence in situ hybridisation to wild-type and rearranged mitotic chromosomes to map the Drosophila melanogaster dodecasatellite sequence. It is located at a unique site, within the pericentric heterochromatin of the right arm of the third chromosome, closely linked to the primary constriction. In polytene chromosomes, dodecasatellite is found as one or a few dots in the central region of the chromocentre. In untreated diploid cells, dodecasatellite sequences are found as one or two dots throughout the cell cycle. This distribution can be altered in a cell cycle-dependent manner in two ways. Firstly, in interphase cells, hypotonic shock promotes the decondensation of the genomic region containing this satellite, resulting in a string-like structure. Secondly, some of the precociously separated sister chromatids produced by colchicine treatment show dodecasatellite within the intervening space connecting the main dodecasatellite signals of each chromatid. The distribution of dodecasatellite seems to be rather constant between individuals of the same species, as indicated by the lack of any detectable variations in its pattern amongst individuals from six geographically distant strains of D. melanogaster. On the other hand, the distribution of dodecasatellite shows a remarkable degree of variation amongst closely related species of the melanogaster subgroup ranging from a non-detectable signal in Drosophila yakuba and Drosophila teissieri, to staining in the X, second and third chromososomes of Drosophila mauritiana.

Animals↗

Genetic mapping of the Sorghum bicolor vp1 gene and its relationship with preharvest sprouting resistance.

The plant vp1 gene encodes a transcription factor originally identified in maize that participates in the control of the transition from embryogenesis to seed germination. Different lines of evidence suggest that vp1 participates in preharvest sprouting (PHS) resistance in cereals, but the genetic relationship is not yet established. Thus, the aim of this study was to investigate if there is a connection between vp1 and the formerly documented quantitative trait loci for PHS in Sorghum bicolor. This gene was mapped in sorghum using two well-studied inbred lines displaying contrasting PHS phenotypes. Linkage analysis revealed that the S. bicolor vp1 (Sbvp1) locus is linked to markers located on chromosomes 3 and 8 in maize. Analysis indicated that this gene is not correlated with PHS at a statistically significant level. Structural analysis of the Sbvp1 gene from both inbred lines showed a high degree of overall conservation (low polymorphism), even in the promoter region. These findings, taken together with the previously observed correlation between the pattern of expression of this gene and PHS performance, suggest that Sbvp1 might act downstream in the signalling pathway that leads to seed germination, or even be differentially regulated as a consequence rather than as a cause of the phenotypic behaviour.

Chromosome Mapping↗

Crystallographic threading.

Crystallographic studies play a major role in current efforts towards protein structure determination. Despite recent advances in computational tools for molecular modeling and graphics, the construction of a three-dimensional protein backbone model from crystallographic data remains complex and time-consuming. This paper describes a unique contribution to an automated approach to protein model construction and evaluation, where a model is represented as an annotated trace (or partial trace) of a structure. Candidate models are derived through a topological analysis of the electron density map of a protein. Using sequence alignment techniques, we determine an optimal threading of the known sequence onto the candidate protein structure models. In this threading, connected nodes on the model are associated with adjacent amino acids in the sequence and a fitness score is assigned based on features extracted from the electron density map for the protein. Experimental results demonstrate that crystallographic threading provides an effective means for evaluating the "goodness" of experimentally derived protein models.

Algorithms↗

An experimental system for auditory image representations.

This paper presents an experimental system for the conversion of images into sound patterns. The system was designed to provide auditory image representations within some of the known limitations of the human hearing system, possibly as a step towards the development of a vision substitution device for the blind. The application of an invertible (1-to-1) image-to-sound mapping ensures the preservation of visual information. The system implementation involves a pipelined special purpose computer connected to a standard television camera. The time-multiplexed sound representations, resulting from a real-time image-to-sound conversion, represent images up to a resolution of 64 x 64 pixels with 16 gray-tones per pixel. A novel design and the use of standard components have made for a low-cost portable prototype conversion system having a power dissipation suitable for battery operation. Computerized sampling of the system output and subsequent calculation of the approximate inverse (sound-to-image) mapping provided the first convincing experimental evidence for the preservation of visual information in the sound representations of complicated images. However, the actual resolution obtainable with human perception of these sound representations remains to be evaluated.

Acoustics↗

Some telencephalic connections in the frog, Rana pipiens.

Some afferent, efferent and intrinsic connections of the telencephalon of Rana pipiens were studied using a horseradish peroxidase method. Afferents to the telencephalon from thalamic and brain stem cell groups were demonstrated. These findings, taken together with the results of previous studies, indicate that separate thalamic cell groups project visual, auditory and somatosensory information onto the striatum. A separate thalamic cell group projects to the medial telencephalic wall and probably conveys visual and somatosensory information. These telencephalic afferent systems do not appear to be directly comparable to those of birds and reptiles. Additionally, some telencephalic afferents demonstrated in previous studies using anterograde degeneration techniques were confirmed, and some intratelencephalic connections were identified.

Amygdala↗

The cytoarchitecture of the interfascicular nucleus and ventral tegmental area of Tsai in the rat.

The cytoarchitecture of the ventral tegmental area of Tsai (VTA) has been studied in detail in the rat with the acid of both conventional techniques and glyoxylic acid-fluorescence histochemistry. Three main dopamine containing cells groups can be distinguished: nucleus paranigralis, nucleus parabrachialis pigmentosus, nucleus linearis raphe caudalis. Nucleus parabrachialis pigmentosus lies dorsally, and nucleus paranigaralis ventrally in the VTA, while nucleus linearis continues posteriorly and medially from VTA and extends dorsally in the midline up towards the dorsal raphe nucleus. Fluorescent neurons in these three groups correspond to the A10 group. In addition to these previously described findings, the present study shows evidence for further small but cytoarchitecturally distinct dopaminergic group called the interfascicular necleus. This lies anteriorly and ventrally in the ventral tegmentum in the midline, dorsal to the rostral portion of the interpeduncular nucleus and interpeduncular fossa. The significance of these cytoarchitectural findings is discussed in relation to the known connections of the region.

Animals↗

The organization of prefrontocaudate projections and their laminar origin in the macaque monkey: a retrograde study using HRP-gel.

The organization of the prefrontocaudate connection in the macaque monkey was studied with a polyacrylamide gel of horseradish peroxidase that was injected, after callosotomy, into the head of the caudate nucleus. Tissues were processed for peroxidase activity with tetramethylbenzidine. Retrogradely labeled cells appeared bilaterally in the prefrontal cortex, and ipsilaterally in the premotor area, frontal operculum, insula, and rostral region of the temporal cortex. In the prefrontal cortex, labeled cells were located in cortical layers 2-6. In layer 2, labeled cells were occasionally seen. In layer 3, a considerable number of labeled cells were seen and were mainly distributed in its lower part. They were pyramidal cells. Layer 4 contained a considerable number of labeled cells that were pyramidal or round. Somal sizes of these labeled cells were from 5 to 15 micron, but none of the cells less than 5 micron were labeled. Layer 5 was densely packed with labeled cells, though at a higher density in its upper part (5a). They were pyramidal cells. In layer 6, pyramidal or fusiform cells were labeled at a lower density than in layer 5. The laminar pattern and density of labeled cells were different among various regions of the prefrontal cortex, but, in general, the supragranular labeling tended to frequently occur in the regions containing the numerous labeled cells. There was a topographical relationship between the prefrontal regions containing the majority of labeled cells and the injection sites in the head of the caudate nucleus: the medial orbitofrontal cortex and the medial surface extending downward from the rostral sulcus project ipsilaterally to the medialmost portion of the ventromedial part of the head of the nucleus, the lateral orbitofrontal cortex projects to the ventromedial part of the head of the nucleus, and the dorsolateral prefrontal cortex ventral to the principal sulcus projects to the central part of the head of the nucleus. Our findings in the macaque monkey indicate that the corticocaudate connection is similar in laminar organization of efferent neurons to the corticocortical connections.

Animals↗