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PubMed1992

Collective behaviors in coupled map lattices with local and nonlocal connections.

After having recalled the basic properties of the nontrivial collective dynamics exhibited by lattices of maps with local coupling and synchronous updating, we present the behavior of the same models in which all the connections are random. The mean-field, synchronized limit is shown to be reached only for large enough connectivities and sufficiently strong local chaos. Intermediate models, in which only a few of the connections of each site are taken at random, are then considered. Preliminary results indicate that the nontrivial collective behaviors shown by the regularly connected models may be robust to a small proportion of nonlocal, random connections.

Journal Article↗
PubMed2005

Morphology, electrophysiology and functional input connectivity of pyramidal neurons characterizes a genuine layer va in the primary somatosensory cortex.

Cortical layer V classically has been subdivided into sublayers Va and Vb on cytoarchitectonic grounds. In the analysis of cortical microcircuits, however, layer Va has largely been ignored. The purpose of this study was to investigate pyramidal neurons of layer Va in view of their potential role in integrating information from lemniscal and paralemniscal sources. For this we combined detailed electrophysiological and morphological characterization with mapping of intracortical functional connectivity by caged glutamate photolysis in layer Va of rat barrel cortex in vitro. Electrophysiological characterization revealed pyramidal cells of the regular spiking as well as the intrinsically burst firing type. However, all layer Va pyramidal neurons displayed uniform morphological properties and comparable functional input connectivity patterns. They received most of their excitatory and inhibitory inputs from intracolumnar sources, especially from layer Va itself, but also from layer IV. Those two layers were also the main origin for transcolumnar excitatory inputs. Layer Va pyramidal neurons thus may predominantly integrate information intralaminarly as well as from layer IV. The functional connectivity maps clearly distinguish layer Va from layer Vb pyramidal cells, and suggest that layer Va plays a unique role in intracortical processing of sensory information.

Animals↗
PubMed1995

Scleraxis: a basic helix-loop-helix protein that prefigures skeletal formation during mouse embryogenesis.

Members of the basic helix-loop-helix (bHLH) family of transcription factors have been shown to regulate growth and differentiation of numerous cell types. Cell-type-specific bHLH proteins typically form heterodimers with ubiquitous bHLH proteins, such as E12, and bind a DNA consensus sequence known as an E-box. We used the yeast two-hybrid system to screen mouse embryo cDNA libraries for cDNAs encoding novel cell-type-specific bHLH proteins that dimerize with E12. One of the cDNAs isolated encoded a novel bHLH protein, called scleraxis. During mouse embryogenesis, scleraxis transcripts were first detected between day 9.5 and 10.5 post coitum (p.c.) in the sclerotome of the somites and in mesenchymal cells in the body wall and limb buds. Subsequently, scleraxis was expressed at high levels within mesenchymal precursors of the axial and appendicular skeleton and in cranial mesenchyme in advance of chondrogenesis; its expression pattern in these cell types foreshadowed the developing skeleton. Prior to formation of the embryonic cartilaginous skeleton, scleraxis expression declined to low levels. As development proceeded, high levels of scleraxis expression became restricted to regions where cartilage and connective tissue formation take place. Scleraxis bound the E-box consensus sequence as a heterodimer with E12 and activated transcription of a reporter gene linked to its DNA-binding site. The expression pattern, DNA-binding properties and transcriptional activity of scleraxis suggest that it is a regulator of gene expression within mesenchymal cell lineages that give rise to cartilage and connective tissue.

Amino Acid Sequence↗
PubMed1991

Structure, mapping, and expression of fisp-12, a growth factor-inducible gene encoding a secreted cysteine-rich protein.

We have characterized a growth factor-inducible gene, fisp-12, previously isolated by differential screening of a lambda complementary DNA library of RNA from serum-stimulated NIH 3T3 cells, and have shown that it encodes a cysteine-rich secreted protein of 348 amino acids. The induction of fisp-12 mRNA is rapid and remains for at least 8 h at a high level of expression. The increased level of fisp-12 mRNA following serum stimulation is mainly due to transcriptional activation. Studies on the genomic structure reveal that the fisp-12 transcription unit is 3.1 kilobases long and split into five exons. The 5' flanking region does not contain serum-responsive elements normally found in other immediate early genes. Immunoprecipitation analyses show that the protein is rapidly induced following serum stimulation and that it is efficiently secreted in an unglycosylated form to the medium. The fisp-12 gene maps to the [10A3-10B1] region of the murine genome.

Amino Acid Sequence↗
PubMed1997

The connectionist simulation of aphasic naming.

The simulation of language disorders using interactive activation (IA) networks and connectionist systems is discussed. An existing IA account of aphasic naming is described, in which two network parameters (decay rate and connection strength) are varied to fit the error production of an aphasic patient. Fairly similar results can be obtained through modification of additional parameters, including the so-called "shared weight increase factor" linking lexical and semantic units. This leads us to consider simulation of aphasic naming using connectionist networks which do not require explicit variation of network parameters. A modular connectionist architecture is presented, in which semantic-lexical and phonological knowledge are instantiated using self-organizing Kohonen maps, while connections between them are implemented using Hebbian networks; a linear connectionist network (Madaline) is used to simulate nonword repetition. The Hebbian connections are lesioned in order to reproduce the patient's naming errors.

Aphasia↗
PubMed2001

Only one nemo-like kinase gene homologue in invertebrate and mammalian genomes.

The nemo-like kinase (Nlk) connects the MAP kinase and Wnt signalling pathways. We have found that invertebrate (Caenorhabditis elegans, Drosophila melanogaster) and mammalian genomes (Mus musculus and Homo sapiens) each contain only a single functional Nlk gene. The mouse genome also harbours a transcriptionally silent processed Nlk pseudogene residing on chromosome 2. Thus, while genes encoding upstream (such as Wnts and frizzelds) and downstream (such as TCF/LEF) components of the Wnt signalling pathway have been extensively diversified during evolution, genes encoding components of the common core of the connecting signalling structure (such as beta-catenin, GSK beta and Nlk) have been maintained in single copies.

Amino Acid Sequence↗
PubMed2003

Diffusion MRI of complex neural architecture.

While functional brain imaging methods can locate the cortical regions subserving particular cognitive functions, the connectivity between the functional areas of the human brain remains poorly understood. Recently, investigators have proposed a method to image neural connectivity noninvasively using a magnetic resonance imaging method called diffusion tensor imaging (DTI). DTI measures the molecular diffusion of water along neural pathways. Accurate reconstruction of neural connectivity patterns from DTI has been hindered, however, by the inability of DTI to resolve more than a single axon direction within each imaging voxel. Here, we present a novel magnetic resonance imaging technique that can resolve multiple axon directions within a single voxel. The technique, called q-ball imaging, can resolve intravoxel white matter fiber crossing as well as white matter insertions into cortex. The ability of q-ball imaging to resolve complex intravoxel fiber architecture eliminates a key obstacle to mapping neural connectivity in the human brain noninvasively.

Cerebral Cortex↗
PubMed2006

Noninvasive quantification of fluid mechanical energy losses in the total cavopulmonary connection with magnetic resonance phase velocity mapping.

A major determinant of the success of surgical vascular modifications, such as the total cavopulmonary connection (TCPC), is the energetic efficiency that is assessed by calculating the mechanical energy loss of blood flow through the new connection. Currently, however, to determine the energy loss, invasive pressure measurements are necessary. Therefore, this study evaluated the feasibility of the viscous dissipation (VD) method, which has the potential to provide the energy loss without the need for invasive pressure measurements. Two experimental phantoms, a U-shaped tube and a glass TCPC, were scanned in a magnetic resonance (MR) imaging scanner and the images were used to construct computational models of both geometries. MR phase velocity mapping (PVM) acquisitions of all three spatial components of the fluid velocity were made in both phantoms and the VD was calculated. VD results from MR PVM experiments were compared with VD results from computational fluid dynamics (CFD) simulations on the image-based computational models. The results showed an overall agreement between MR PVM and CFD. There was a similar ascending tendency in the VD values as the image spatial resolution increased. The most accurate computations of the energy loss were achieved for a CFD grid density that was too high for MR to achieve under current MR system capabilities (in-plane pixel size of less than 0.4 mm). Nevertheless, the agreement between the MR PVM and the CFD VD results under the same resolution settings suggests that the VD method implemented with a clinical imaging modality such as MR has good potential to quantify the energy loss in vascular geometries such as the TCPC.

Biomechanical Phenomena↗
PubMed1995

Homeobox genes and connective tissue patterning.

In vertebrates, limb tendons are derived from cells that migrate from the lateral plate mesoderm during early development. While some of the developmental steps leading to the formation of these tissues are known, little is known about the molecular mechanisms controlling them. We have identified two murine homeobox-containing genes, Six 1 and Six 2, which are expressed in a complementary fashion during the development of limb tendons. Transcripts for both genes are found in different sets of phalangeal tendons. Six 1 and Six 2 also are expressed in skeletal and smooth muscle, respectively. These genes may participate in the patterning of the distal tendons of the limb phalanges by setting positional values along the limb axes.

Amino Acid Sequence↗
PubMed2004

Differential expression of fibrillin-3 adds to microfibril variety in human and avian, but not rodent, connective tissues.

The human genome contains three fibrillins: FBN1 and FBN2, both well characterized, and FBN3, reported only as a cDNA sequence. Like FBN2, the highest expression levels of FBN3 were found in fetal tissues, with only low levels in postnatal tissues. Immunolocalization demonstrated fibrillin-3 in extracellular microfibrils abundant in developing skeletal elements, skin, lung, kidney, and skeletal muscle. Unlike the other two fibrillins, FBN3 expression is high in brain, and FBN3 is alternatively spliced, removing the exon encoding cbEGF2. Like FBN1, FBN3 contains three alternate exons in the 5' UTR. While FBN3 orthologs were identified in cow and chicken, Fbn3 appears to have been inactivated in the mouse genome, perhaps during chromosome fission events. Located on chromosome 19p13.3-13.2, FBN3 is a candidate gene for Weill-Marchesani syndrome.

Alternative Splicing↗
PubMed1996

A tandem duplication within the fibrillin 1 gene is associated with the mouse tight skin mutation.

Mice carrying the Tight skin (Tsk) mutation have thickened skin and visceral fibrosis resulting from an accumulation of extracellular matrix molecules. These and other connective tissue abnormalities have made Tskl + mice models for scleroderma, hereditary emphysema, and myocardial hypertrophy. Previously we localized Tsk to mouse chromosome 2 in a region syntenic with human chromosome 15. The microfibrillar glycoprotein gene, fibrillin 1 (FBN1), on human chromosome 15q, provided a candidate for the Tsk mutation. We now demonstrate that the Tsk chromosome harbors a 30- to 40-kb genomic duplication within the Fbn1 gene that results in a larger than normal in-frame Fbn1 transcript. These findings provide hypotheses to explain some of the phenotypic characteristics of Tskl + mice and the lethality of Tsk/Tsk embryos.

Amino Acid Sequence↗
PubMed1996

Molecular markers near the mouse brachymorphic (bm) gene, which affects connective tissues and bleeding time.

Several inherited skeletal/connective tissue defects are associated with hemorrhagic disorders in humans. Accordingly, three mouse mutants (brachymorphic [bm], hemimelic extra toes [Hx], and ulnaless [Ul]), with inherited skeletal abnormalities, were analyzed for hemorrhagic tendencies. All three had prolonged bleeding times. Platelet numbers, size, and function, as well as common soluble plasma clotting factors, were not measurably affected. To further define the bm mutation, its chromosomal location relative to 19 other molecular markers was determined to a high resolution in a large interspecific backcross. Several microsatellite markers were found to be very closely linked to bm and should provide useful entry points for the eventual identification of this gene by positional/candidate cloning techniques. These results suggest that inherited skeletal abnormalities and bleeding tendencies are associated more frequently in both humans and animal models than is commonly recognized. Identification of these genes may reveal novel relationships between osteogenesis and hemostasis.

Animals↗
PubMed2004

Neural regulation of the hepatic circadian rhythm.

A microarray analysis experiment has revealed that there are many genes, including so-called clock genes, expressing a circadian rhythm in the liver. The clock genes mentioned above are expressed not only in the suprachiasmatic nucleus (SCN) of the hypothalamus, where the master clock exists, but also in other brain regions and various peripheral tissues. In the liver, clock genes are abundantly expressed and show a clear circadian rhythm. Thus, clock genes seem to play a critical role in the molecular clockworks of both the SCN and the liver. Although oscillation of clock genes in the liver is controlled under the circadian clock mechanism in the SCN, we do not know the resetting signals on liver clock function. Over the past few years, use of the pseudorabies virus, a transsynaptic tract tracer, has allowed us to map neural connections between the SCN and peripheral tissues in several physiological systems. Communication between the SCN and peripheral tissues occurs through autonomic nervous systems involving the sympathetic and parasympathetic neurons. This review mainly describes both anatomical and physiological experiments to reveal the sympathetic control over liver clock function. Although further study is necessary to produce the precise mechanism underlying neural control of liver clock systems, evolution of this mechanism will help our understanding of liver clock functions such as drug metabolism and energy metabolism.

Animals↗
PubMed2001

Auditory and lateral line inputs to the midbrain of an aquatic anuran: neuroanatomic studies in Xenopus laevis.

Computation of rate in auditory signals is essential to call recognition in anurans. This task is ascribed to a group of central nervous system nuclei in the dorsal midbrain or torus semicircularis, homologous to the inferior colliculus of mammals. We have mapped the connections of the subnuclei of the torus semicircularis in Xenopus laevis to determine which receive auditory and which receive lateral line information. Relative to terrestrial anurans, the torus of X. laevis is hypertrophied and occupies the entire caudal, dorsal midbrain. Auditory input to the torus, that arising directly from the dorsal medullary nucleus, is present only in the laminar nucleus. The principal and magnocellular nuclei receive their input from the lateral line nucleus of the medulla. All three nuclei of the torus also have reciprocal connections with the superior olive and the nucleus of the lateral lemniscus. Ascending efferents from all three nuclei of the torus innervate central and lateral thalamic nuclei, and all have a weak reciprocal connection with the posterior thalamus. The laminar and magnocellular nuclei have reciprocal connections with the ventral thalamus, and all three nuclei of the torus receive descending input from the anterior entopeduncular nucleus. The laminar and magnocellular nuclei also receive descending input from the preoptic area. Based on our identification of toral nuclei and these results we assign a major function for the detection of water-borne sounds to the laminar nucleus and a major function for the detection of near field disturbances in water pressure to the principal and magnocellular nuclei.

Animals↗
PubMed1996

Genomic structure and chromosomal mapping of the mouse nov gene.

The nov gene encodes a cysteine-rich protein that is overexpressed in avian nephroblastomas. It is a member of the CCN family of proteins, all of which are involved in cell growth. Genomic and cDNA clones encompassing the mouse nov gene have been isolated and characterized. The mouse nov gene is highly conserved with the human and chick nov genes at the level of nucleotide sequence and genomic organization. The exon structure reflects the modular organization of the NOV protein in a number of structural domains. These are highly conserved with other members of the CCN family, as is the distribution of 38 of its 40 cysteine residues. The nov gene maps to chromosome 15, between D15 Mit 153 and D15 Mit 183, in a region of conserved synteny with human chromosome 8.

Amino Acid Sequence↗
PubMed1993

Assignment of the human aggrecan gene AGC1 to 15q25-->q26.2 by in situ hybridization.

The human aggrecan gene (AGC1) has been localized to 15q25-->q26.2 by in situ hybridization. Although no genetic diseases of connective tissue map to this location, the malignant melanoma-associated surface antigen mel-CSPG is located here; mel-CSPG is a chondroitin sulfate proteoglycan. This raises the possibility that AGC1 and mel-CSPG may be the same gene.

Aggrecans↗
PubMed2005

Hot spots of perforated forest in the eastern United States.

National assessments of forest fragmentation satisfy international biodiversity conventions, but they do not identify specific places where ecological impacts are likely. In this article, we identify geographic concentrations (hot spots) of forest located near holes in otherwise intact forest canopies (perforated forest) in the eastern United States, and we describe the proximate causes in terms of the non-forest land-cover types contained in those hot spots. Perforated forest, defined as a 0.09-ha unit of forest that is located at the center of a 7.29-ha neighborhood containing 60-99% forest with relatively low connectivity, was mapped over the eastern United States by using land-cover maps with roads superimposed. Statistically significant (P < 0.001) hot spots of high perforation rate (perforated area per unit area of forest) were then located by using a spatial scan statistic. Hot spots were widely distributed and covered 20.4% of the total area of the 10 ecological provinces examined, but 50.1% of the total hot-spot area was concentrated in only two provinces. In the central part of the study area, more than 90% of the forest edge in hot spots was attributed to anthropogenic land-cover types, whereas in the northern and southern parts it was more often associated with semi-natural land cover such as herbaceous wetlands.

Conservation of Natural Resources↗