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At least 523 records · Page 29Linked to original sources
PubMed2001

New patterns of intracortical projections after focal cortical stroke.

Cortical strokes alter functional maps but associated changes in connections have not been documented. The neuroanatomical tracer biotinylated dextran amine (BDA) was injected into cortex bordering infarcts 3 weeks after focal strokes in rat whisker barrel (somatosensory) cortex. The mirror locus in the opposite hemisphere was injected as a control. After 1 week of survival, brains were processed for cytochrome oxidase (CO)-, Nissl-, and BDA-labeled neurons. Cortex bordering the infarct (peri-infarct cortex) had abnormal CO and Nissl structure. BDA-labeled neurons were plotted and projections were analyzed quantitatively. Animals with small strokes had intracortical projections, arising from peri-infarct cortex, not seen in normal hemispheres: the overall orientation was statistically significantly different from and rotated 157 degrees relative to the controls. Compared to the controls, significantly fewer cells were labeled in the thalamus. Thus, after focal cortical stroke, the peri-infarct cortex is structurally abnormal, loses thalamic connections, and develops new horizontal cortical connections by axonal sprouting.

Action Potentials↗
PubMed2006

Protruding disordered loop of gC1qR is specifically exposed and related to antiapoptotic property in germ cell lineage.

We established a monoclonal antibody (MAb), 5G9, with the use of a fixed seminoma tissue from an archival paraffin-embedded specimen, as an immunogen. Without antigen retrieval, positive 5G9-immunohistochemical staining was confined mostly to primordial germ cells, spermatogonia and various germ cell tumors. 5G9 recognized a mitochondrial 32-kD protein with an isoelectric point of pH 4.2, identified as a multifunctional ubiquitous protein, receptor for globular head of C1q (gC1qR), whose epitope was mapped in a disordered loop connecting the beta3 and the beta4 strands. Reflecting the ubiquitous distribution of gC1qR, with antigen retrieval, 5G9 was found reactive to a wide range of normal and tumor tissues. Since several co-precipitated and phosphorylated bands were observed in various human cell lines but not in germ cell tumor cell lines by in vitro phosphorylation assay, we speculate that the epitope of gC1qR is specifically unmasked in the germ cell lineage. By reducing gC1qR by siRNA, a significant increase was observed in the number of apoptotic cells in ITO-II and TCam-2 cell lines, but to a lesser extent in the Colo201 colon cancer cell line, showing an antiapoptotic property of gC1qR in the germ cells. Since protein-protein interaction is partially preserved by fixation, archival paraffin-embedded specimens can be a valuable source of immunogens for generating monoclonal antibodies (MAbs) that recognize tissue-specific protein conformation.

Antibodies, Monoclonal↗
PubMed1996

Voltage-sensitive dye recording using retrogradely transported dye in the chicken spinal cord: staining and signal characteristics.

We describe a novel method for retrogradely labeling specific neuronal populations using voltage-sensitive dyes. Styryl dyes were injected into the ventral roots of the isolated embryonic chick spinal cord. After waiting several hours, the dye labeled motoneurons and autonomic preganglionic neurons. Neuronal cell bodies, dendrites and axons were labeled; we presume that the dye traveled either by retrograde transport or by diffusion within the membrane of the axon to which the dyes were initially applied. Using either a photodiode array or a photomultiplier, fluorescence changes could be recorded from motoneurons following antidromic or synaptic activation. Several characteristics of the fluorescence changes were measured indicating that the signals did indeed reflect changes in the motoneuron membrane potential. The best labeling and optical signals were obtained using the relatively hydrophobic dyes di-8-ANEPPQ and di-12-ANEPEQ. In the great majority of cases these dyes responded with an increase in fluorescence of 1-3% (delta F/F) in response to synaptic or antidromic depolarization of the motoneurons. We anticipate that these techniques should be useful in the mapping of activity patterns and connectivity in neural networks within a defined population of neurons.

Action Potentials↗
PubMed1986

Unpaired cysteine-54 interferes with the ability of an engineered disulfide to stabilize T4 lysozyme.

We have introduced an intramolecular disulfide bond into T4 lysozyme and have shown this molecule to be significantly more stable than the wild-type molecule to irreversible thermal inactivation [Perry, L.J., & Wetzel, R. (1984) Science (Washington, D.C.) 226, 555-557]. Wild-type T4 lysozyme contains two free cysteines, at positions 54 and 97, and no disulfide bonds. By directed mutagenesis of the cloned T4 lysozyme gene, we replaced Ile-3 with Cys. Oxidation in vitro generated an intramolecular disulfide bond; proteolytic mapping showed this bond to connect Cys-3 to Cys-97. While this molecule exhibited substantially more stability against thermal inactivation than wild type, its stability was further enhanced by additional modification with thiol-specific reagents. This and other evidence suggest that at basic pH and elevated temperatures Cys-54 is involved in intermolecular thiol/disulfide interchange with the engineered disulfide, leading to inactive oligomers. Mutagenic replacement of Cys-54 with Thr or Val in the disulfide-cross-linked variant generated lysozymes exhibiting greatly enhanced stability toward irreversible thermal inactivation.

Base Sequence↗
PubMed2004

Adiabatic TOBSY in rotating solids.

A MAS solid state NMR approach for achieving efficient scalar coupling mediated through-bond (13)C chemical shift correlations of the aliphatic carbons in uniformly labelled peptides/proteins is described. The method involves the application of a continuous train of adiabatic inversion pulses, as in the adiabatic TOCSY experiments carried out in solution state NMR studies. While rotor synchronised application of adiabatic inversion pulses leads to dipolar correlations, it is shown here via numerical simulations and experimental measurements that asynchronous application of adiabatic pulses can facilitate the mapping of through-bond connectivities. The method employs a suitable phasing scheme for generating the desired isotropic mixing Hamiltonian and requires moderate (13)C RF field strength only.

Carbon Isotopes↗
PubMed1992

Magnetic resonance spectroscopy and imaging of muscle--a physiological approach.

Magnetic resonance spectroscopy (MRS) and imaging (MRI) are now well established techniques for the study of cellular metabolism and gross structure of muscle. Using non-ferrous materials, we have constructed a system for the measurement of isometric force of quadriceps in response to percutaneous electrical stimulation and voluntary effort within the bore of a 48 cm diameter 1.5 T General Electric SIGNA whole body MR system. Using this system we have been able to study the relationship between electromechanical coupling and chemistry of muscle, with 31P MRS for the measurement of high-energy phosphates and pH, during electrically stimulated activity. Image analysis using the Context Vision system enables a distinction to be made, in 1H MRI by T1/T2 mapping, of muscle, fat and connective tissue to give force per unit cross sectional area of muscle. The combination of MR and functional measurements provide a valuable tool for further detailed analysis of human muscle weakness and fatigue.

Electric Stimulation↗
PubMed1996

Subthreshold facilitation and suppression in primary visual cortex revealed by intrinsic signal imaging.

Neurons in primary visual cortex (area 17) respond vigorously to oriented stimuli within their receptive fields; however, stimuli presented outside the suprathreshold receptive field can also influence their responses. Here we describe a fundamental feature of the spatial interaction between suprathreshold center and subthreshold surround. By optical imaging of intrinsic signals in area 17 in response to a stimulus border, we show that a given stimulus generates activity primarily in iso-orientation domains, which extend for several millimeters across the cortical surface in a manner consistent with the architecture of long-range horizontal connections in area 17. By mapping the receptive fields of single neurons and imaging responses from the same cortex to stimuli that include or exclude the aggregate suprathreshold receptive field, we show that intrinsic signals strongly reveal the subthreshold surround contribution. Optical imaging and single-unit recording both demonstrate that the relative contrast of center and surround stimuli regulates whether surround interactions are facilitative or suppressive: the same surround stimulus facilitates responses when center contrast is low, but suppresses responses when center contrast is high. Such spatial interactions in area 17 are ideally suited to contribute to phenomena commonly regarded as part of "higher-level" visual processing, such as perceptual "popout" and "filling-in."

Animals↗
PubMed1999

Adaptor proteins Grb2 and Crk couple Pyk2 with activation of specific mitogen-activated protein kinase cascades.

The protein tyrosine kinase Pyk2 acts as an upstream regulator of mitogen-activated protein (MAP) kinase cascades in response to numerous extracellular signals. The precise molecular mechanisms by which Pyk2 activates distinct MAP kinase pathways are not yet fully understood. In this report, we provide evidence that the protein tyrosine kinase Src and adaptor proteins Grb2, Crk, and p130Cas act as downstream mediators of Pyk2 leading to the activation of extracellular signal-regulated kinase (ERK) and c-Jun amino-terminal kinase (JNK). Pyk2-induced activation of Src is necessary for phosphorylation of Shc and p130Cas and their association with Grb2 and Crk, respectively, and for the activation of ERK and JNK cascades. Expression of a Grb2 mutant with a deletion of the amino-terminal Src homology 3 domain or the carboxyl-terminal tail of Sos strongly reduced Pyk2-induced ERK activation, with no apparent effect on JNK activity. Grb2 with a deleted carboxyl-terminal Src homology 3 domain partially blocked Pyk2-induced ERK and JNK pathways, whereas expression of dominant interfering mutants of p130Cas or Crk specifically inhibited JNK but not ERK activation by Pyk2. Taken together, our data reveal specific pathways that couple Pyk2 with MAP kinases: the Grb2/Sos complex connects Pyk2 to the activation of ERK, whereas adaptor proteins p130Cas and Crk link Pyk2 with the JNK pathway.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Molecular cloning and functional characterization of chicken toll-like receptors. A single chicken toll covers multiple molecular patterns.

Toll-like receptors (TLR) in the innate immune system have not been identified in non-mammalian vertebrates. Two types of TLR were cloned from a chicken bursa cDNA library using degenerate primers based on the consensus sequences of mouse and Drosophila Toll and designated as chicken TLR (chTLR) type 1 and type 2. Of the nine human TLRs reported to date, these chTLRs showed the highest homology to human TLR2. The extracellular regions of type 1 and type 2 contained a distinct approximately 200-amino acid stretch and were 45.3 and 46.3% homologous to that of human TLR2. The intracellular Toll/interleukin-1R homology domain of type 1 and type 2 was perfectly identical to each other and highly homologous (80.7%) to that of human TLR2. Both types were widely detected by reverse transcriptase-polymerase chain reaction and immunoblotting in various chicken organs, especially those rich in connective tissue. Both genes were mapped to chromosome 4q1.1, suggesting that they arose by gene duplication. By reporter gene assay, type 2 and to a lesser extent type 1, selectively signaled the presence of mycoplasma macrophage-activating lipopeptide-2/M161Ag in the human embryonic kidney 293 cell system. Cotransfection of type 2 and human CD14 or MD-2 into human embryonic kidney 293 cells allowed the response to Escherichia coli lipopolysaccharide (LPS), whereas type 1 did not signal LPS or any other microbial components tested. These results indicated that chTLR type 2 covers two major microbe patterns, lipoproteins and LPS, which are regulated by TLR2 and TLR4 in mammals. In oviparous animals, the duplicated TLRs in the pattern-recognition system may function for host-pathogen discrimination in a manner that is distinct from that in mammals.

Alleles↗
PubMed2005

Functional analysis of RNA binding by the hepatitis C virus RNA-dependent RNA polymerase.

Protein-RNA interaction plays a critical role in regulating RNA synthesis by the hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp). RNAs of 7 nucleotides (nt) or longer had affinities 5-fold better than an RNA of 5 nt, suggesting a minimal length required for binding. To identify RNA contact sites on the HCV RdRp, a biotinylated 7-nt RNA capable of directing de novo initiation was used in a process that coupled reversible formaldehyde cross-linking, RNA affinity chromatography, and mass spectrometry. By this process, we identified 18 peptides cross-linked to the 7-nt RNA. When these identified peptides were overlaid on the three-dimensional structures of NS5B, most mapped to the fingers subdomain, connecting loops between fingers and thumb subdomains and in the putative RNA binding channel. Two of the identified peptides resided in the active site cavity of the RdRp. Recombinant HCV RdRp with single residue changes in likely RNA contact sites were generated and characterized for effects on HCV RdRp activity. Mutant proteins had significant effects on cross-linking to 7-nt RNA and reduced RNA synthesis in vitro by 2- to 20-fold compared with wild type protein. When the mutations were tested for the replication of HCV RNA in the context of the cells transfected with the HCV subgenomic replicon, all except one prevented colony formation, indicating a defect in HCV RNA replication. These biochemical and functional analyses identified a number of residues in the HCV RdRp that are important for HCV RNA synthesis.

Amino Acid Substitution↗
PubMed2006

Identification of metabolic units induced by environmental signals.

MOTIVATION: Biological cells continually need to adapt the activity levels of metabolic functions to changes in their living environment. Although genome-wide transcriptional data have been gathered in a large variety of environmental conditions, the connections between the expression response to external changes and the induction or repression of specific metabolic functions have not been investigated at the genome scale. RESULTS: We present here a correlation-based analysis for identifying the expression response of genes involved in metabolism to specific external signals, and apply it to analyze the transcriptional response of Saccharomyces cerevisiae to different stress conditions. We show that this approach leads to new insights about the specificity of the genomic response to given environmental changes, and allows us to identify genes that are particularly sensitive to a unique condition. We then integrate these signal-induced expression data with structural data of the yeast metabolic network and analyze the topological properties of the induced or repressed subnetworks. They reveal significant discrepancies from random networks, and in particular exhibit a high connectivity, allowing them to be mapped back to complete metabolic routes.

Adaptation, Physiological↗
PubMed2006

Emergence of coherence in complex networks of heterogeneous dynamical systems.

We present a general theory for the onset of coherence in collections of heterogeneous maps interacting via a complex connection network. Our method allows the dynamics of the individual uncoupled systems to be either chaotic or periodic, and applies generally to networks for which the number of connections per node is large. We find that the critical coupling strength at which a transition to synchrony takes place depends separately on the dynamics of the individual uncoupled systems and on the largest eigenvalue of the adjacency matrix of the coupling network. Our theory directly generalizes the Kuramoto model of equal strength all-to-all coupled phase oscillators to the case of oscillators with more realistic dynamics coupled via a large heterogeneous network.

Computer Communication Networks↗
PubMed1999

Estimating unobserved reflection intensities in Laue diffraction by the maximum-entropy method.

In protein crystallography, the use of low-resolution reflections is important in defining the molecular mask and polypeptide backbone. However, in Laue data collection, the loss of low-resolution reflection data (>2dmin) can be as high as 40-50%, even after the deconvolution of multiples. To estimate the reflection intensities that are not recorded in data collection, a new method is presented based on maximizing the entropy of the Patterson function subject to the constraints imposed by the intensities of the observed reflections. The method has been tested with Laue diffraction data from hen egg-white lysozyme. All unobserved reflections within 5 A resolution were estimated, and their inclusion in the electron-density-map calculation significantly improved the connectivity. This method could also be applied to improve the completeness of monochromatic data.

Animals↗
PubMed1994

Posttranslational processing of human alpha 2-HS glycoprotein (human fetuin). Evidence for the production of a phosphorylated single-chain form by hepatoma cells.

alpha 2-HS glycoprotein (alpha 2-HS) is a major protein occurring in human blood and calciferous tissues. Due to extensive sequence identity, alpha 2-HS has been grouped with the fetuins, a family of proteins that occur in fetal plasma in high concentrations. Native alpha 2-HS undergoes a series of posttranslational modifications including proteolytic processing, multiple N-glycosylations and O-glycosylations, and sulfation of the carbohydrate side chains. Various two-chain forms of alpha 2-HS have been prepared from human plasma, however, the single-chain precursor has not yet been isolated. Here, we have studied the biosynthesis of alpha 2-HS by a human hepatoma cell line, HepG2. We demonstrate that a single-chain form and the two-chain form of alpha 2-HS are secreted by this cell line. The alpha 2-HS forms are further modified by phosphorylation on multiple serine residues. Mapping studies indicate that the connecting peptide region releasable from the heavy chain of alpha 2-HS contains at least one such phosphorylation site. Our results identify proteolytic trimming and/or phosphorylation as modifications possibly regulating the biological effects of alpha 2-HS and the homologous fetuins.

Amino Acid Sequence↗
PubMed1999

Simulation of ultrasonic pulse propagation, distortion, and attenuation in the human chest wall.

A finite-difference time-domain model for ultrasonic pulse propagation through soft tissue has been extended to incorporate absorption effects as well as longitudinal-wave propagation in cartilage and bone. This extended model has been used to simulate ultrasonic propagation through anatomically detailed representations of chest wall structure. The inhomogeneous chest wall tissue is represented by two-dimensional maps determined by staining chest wall cross sections to distinguish between tissue types, digitally scanning the stained cross sections, and mapping each pixel of the scanned images to fat, muscle, connective tissue, cartilage, or bone. Each pixel of the tissue map is then assigned a sound speed, density, and absorption value determined from published measurements and assumed to be representative of the local tissue type. Computational results for energy level fluctuations and arrival time fluctuations show qualitative agreement with measurements performed on the same specimens, but show significantly less waveform distortion than measurements. Visualization of simulated tissue-ultrasound interactions in the chest wall shows possible mechanisms for image aberration in echocardiography, including effects associated with reflection and diffraction caused by rib structures. A comparison of distortion effects for varying pulse center frequencies shows that, for soft tissue paths through the chest wall, energy level and waveform distortion increase markedly with rising ultrasonic frequency and that arrival-time fluctuations increase to a lesser degree.

Acoustics↗
PubMed1995

Adult plasticity in the visual system.

When visual cortical neurons in adult mammals are deprived of their normal afferent input from retinae, they are capable of acquiring new receptive fields by modifying the effectiveness of existing intrinsic connections, a basis for topographic map reorganization. To gain insights into the underlying mechanisms and functional significance of this adult plasticity, we measured the spatial limits and time course of retinotopic map reorganization. We also determined whether reactivated neurons exhibit normal receptive field properties. We found that virtually all units in the denervated zone of cortex acquired new receptive fields (i.e., there were no silent areas in the cortex) and map reorganization can take place within hours of deafferentation provided that retinal lesions are relatively small (< 5 degrees). Furthermore, after long periods of recovery, reactivated units exhibited strikingly normal selectivity to stimulus orientation, direction of movement, and spatial frequency if relatively high contrast stimuli were used. However, responsiveness of these neurons, measured in terms of the maximum response amplitude and the contrast threshold, was clearly reduced. Thus, contrary to traditional belief, the adult visual cortex is capable of exhibiting considerable plasticity, and reactivated neurons are capable of contributing to an analysis of a visual scene.

Animals↗
PubMed2004

Comparison of oculomotor neuronal activity in paralaminar and mediodorsal thalamus in the rhesus monkey.

We previously reported that neurons in the mediodorsal thalamic nucleus (MD) are topographically organized and express spatial and nonspatial coding properties similar to those of the prefrontal areas with which they are connected. In the course of mapping the dorsal thalamus, we also studied neurons in a subset of thalamic nuclei (the caudal part of the ventral lateral nucleus (VLc), the oral part of the ventral posterior lateral nucleus (VPLo), the parvocellular part of the ventral anterior nucleus (VApc)) lateral to the MD and just across the internal medullary lamina. We compared these "paralaminar" neurons to MD neurons by having monkeys perform the same spatial and nonspatial cognitive tasks as those used to investigate the MD; these included two saccadic tasks-one requiring delayed and the other immediate responses-and one picture fixation task. Of the paralaminar thalamic neurons modulated by the saccadic tasks, a majority had saccade-related activity, and this was nearly always spatially tuned. Also, for about half of these neurons, the saccade-related activity occurred exclusively during the delayed-response task. No neurons with event-related activity in the saccadic tasks were preferentially modulated by specific picture stimuli, although other neurons were. All of these results were similar to what we had found for MD neurons. However, in contrast to the high proportion of presaccadic responses observed in the MD, the majority of saccade-related neurons in paralaminar thalamus exhibited mid- or postsaccadic activity, i.e., that started during or after the saccade. Our findings suggest that neurons in the paralaminar thalamus may be possible conduits of oculomotor feedback signals, especially during memory-guided saccades.

Animals↗
PubMed2005

Music and video iconicity: theory and experimental design.

Experimental studies on the relationship between quasi-musical patterns and visual movement have largely focused on either referential, associative aspects or syntactical, accent-oriented alignments. Both of these are very important, however, between the referential and areferential lays a domain where visual pattern perceptually connects to musical pattern; this is iconicity. The temporal syntax of accent structures in iconicity is hypothesized to be important. Beyond that, a multidimensional visual space connects to musical patterning through mapping of visual time/space to musical time/magnitudes. Experimental visual and musical correlates are presented and comparisons to previous research provided.

Attention↗