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At least 1,009 records · Page 56Linked to original sources
PubMed2005

Velocity imaging by ex situ NMR.

A pulsed field gradient stimulated spin-echo NMR sequence is combined with imaging methods to spatially resolve velocity distributions and to measure 2D velocity maps ex situ. The implementation of these techniques in open sensors provides a powerful non-invasive tool to measure molecular displacement in a large number of applications inaccessible to conventional closed magnets. The method is implemented on an open tomograph that provides 3D spatial localization by combining slice selection in the presence of a uniform static magnetic field gradient along the depth direction with pulsed field gradients along the two lateral directions. Different pipe geometries are used to demonstrate that the sequence performs well even in the extremely inhomogeneous B0 and B1 fields of these sensors.

Journal Article↗
PubMed2006

Relaxation and diffusion of perfluorocarbon gas mixtures with oxygen for lung MRI.

We report measurements of free diffusivity D(0) and relaxation times T(1) and T(2) for pure C(2)F(6) and C(3)F(8) and their mixtures with oxygen. A simplified relaxation theory is presented and used to fit the data. The results enable spatially localized relaxation time measurements to determine the local gas concentration in lung MR images, so the free diffusivity D(0) is then known. Comparison of the measured diffusion to D(0) will express the extent of diffusion restriction and allow the local surface-to-volume ratio to be found.

Data Interpretation, Statistical↗
PubMed2005

Expression of P2X4 receptor by lesional activated microglia during formalin-induced inflammatory pain.

P2X4 receptor (P2X4R) is an ion channel gated by adenosine 5'-triphosphate. Here we report the presence and the distribution of P2X4R in rat spinal cord by immunohistochemical analysis in an inflammatory pain model. Peripheral inflammation was induced by subcutaneous injection of 4% formalin into the rat hindpaw. Morphology, spatial localization, and activation state of P2X4R+ cells were described at 1, 5, 7, 14, and 28 days after injury. In normal and saline treated control rats, P2X4R was rarely seen. After formalin administration, an increase of P2X4R+ microglia were observed in the spinal cord dorsal horn on the side ipsilateral to the injection, reaching maximal levels by day 7, and then decreasing to normal levels by day 14. This implicates a role of P2X4R in the spinal inflammatory pain process. Furthermore, formalin-induced region-specific increase in activated microglia was confirmed by ED1 and endothelial monocytes activating polypeptide II (EMAP-II) expression. In conclusion, this is the first demonstration that P2X4R is expressed by microglia in the inflammatory pain.

Animals↗
PubMed2026

Nuclear Proteome Map of Mouse Heart Chambers.

Heart specialization involves nuclear programs; however, chamber-specific regulation of the nuclear proteome landscape remains unknown. In this study, we isolated the nucleus from four major anatomical regions of healthy mouse heart (fresh) and employed quantitative mass spectrometry-based proteomics to construct a comprehensive nuclear proteome landscape of left ventricle (LV, 2403 proteins), right ventricle (RV, 2242 proteins), left atrium (LA, 2368 proteins), and right atrium (RA, 1816 proteins). This led to the discovery of nuclear regional proteome signatures (ventricular signature, 297 proteins; atrial signature, 183 proteins) associated with oxidative metabolism and redox regulation, ferroptosis, extracellular-matrix remodeling, SUMO- and stress-responsive control and transcriptional regulation. Chamber-level analyses further identify distinct nuclear features in LV (120 proteins), LA (188 proteins), and RA (72 proteins). In addition, we defined conserved core nuclear proteome (230 proteins) shared across all anatomical regions, enriched for transcription-regulator complexes, nucleolar/ribosome-associated, RNA-processing, and chromatin-organization components. Within this core network, we report 78 transcription factors/co-factors and select nuclear, chromatin and RNA export-associated proteins, including 29 specific factors (e.g., Alpk3, Rbm14, Arglu1, Hmgb1, Myef2, Sf1) associated with the heart. Regionally, we verified spatial localization in heart of H2ac21 and Sun2 in LA and Ptbp2 in LV by immunofluorescence. This study provides insights into the chamber-resolved view of the nuclear proteome in the heart, establishes a framework for linking nuclear proteomic signatures to atrial and ventricular biology, unique features of the heart nuclear proteome landscape relative to other organs, and a baseline for studying nuclear remodeling in cardiac pathophysiology.

Animals↗
PubMed2003

Cell cycle timing and developmental checkpoints in Caulobacter crescentus.

Development in Caulobacter reflects a level of complexity once thought only to exist in eukaryotic cells. The cell cycle and development are not isolated from each other, but are interdependent processes. Checkpoints are in place to ensure that both cell cycle and developmental processes are completed accurately before the next stage is initiated. The timing of these processes is regulated by signal transduction networks that integrate signals from DNA replication, cell division and development. These signal transduction networks achieve precise timing of the cell cycle and development by regulating temporal gene expression, and protein activity by dynamic spatial localization within the cell and timed proteolysis.

Caulobacter crescentus↗
PubMed2004

Large-scale isolation of ESTs from medaka embryos and its application to medaka developmental genetics.

The medaka is becoming an attractive model organism for the study of vertebrate early development and organogenesis and large-scale mutagenesis projects that are aimed at creating developmentally defective mutants are now being conducted by several groups in Japan. To strengthen the study of medaka developmental genetics, we have conducted a large-scale isolation of ESTs from medaka embryos and developed tools that facilitate mutant analysis. In this study, we have characterized a total of 132,082 sequences from both ends of cloned insert cDNAs from libraries generated at different stages of medaka embryo development. Clustering analysis with 3-prime sequences finally identified a total of 12,429 clusters. As a pilot analysis, 924 clusters were subjected to in situ hybridization to determine the spatial localization of their transcripts. Using EST sequence data generated in the present study, a 60-mer oligonucleotide microarray with 8,091 unigenes (Medaka Microarray 8K) was constructed and tested for its usefulness in expression profiling. Furthermore, we have developed a rapid and reliable mutant mapping system using a set of mapped EST markers (M-marker 2003) that covers the entire medaka genome. These resources will accelerate medaka mutant analyses and make an important contribution to the medaka genome project.

Animals↗
PubMed2006

Spatiotemporal analysis of feedback processing during a card sorting task using spatially filtered MEG.

A card sorting paradigm was used to observe the neural correlates of feedback processing in adult participants. Visually presented feedback was used to indicate response accuracy and the requirement to shift response set in a 2-category card sorting task. Magnetoencephalography (MEG) responses to feedback cues were analysed using a beamformer-based spatial filtering algorithm (event-related Synthetic Aperture Magnetometry, erSAM). Analysis of source power revealed activity in rostral anterior cingulate cortex (ACC) only to negative feedback processing, which peaked at 260 ms after stimulus onset. The results are in agreement with both evidence from fMRI on spatial characteristics of negative feedback processing, and evidence from event-related potentials (ERPs) on the temporal profile of this ACC response. The superior temporal gyrus was activated only with positive feedback, reflecting integration of actions with successful outcomes. The present MEG erSAM findings are the first to provide both accurate spatial localization as well as temporal specificity for the neural correlates of feedback processing.

Adult↗
PubMed2005

Structural brain correlates of prepulse inhibition of the acoustic startle response in healthy humans.

Neural regions modulating prepulse inhibition (PPI) of the startle response, an operational measure of sensorimotor gating, are well established from animal studies using surgical and pharmacological procedures. The limbic and cortico-pallido-striato-thalamic circuitry is thought to be responsible for modulation of PPI in the rat. The involvement of this circuitry in human PPI is suggested by observations of deficient PPI in a number of neuropsychiatric disorders characterized by abnormalities at some level in this circuitry and recent functional neuroimaging studies in humans. The current study sought to investigate structural neural correlates of PPI in a sample of twenty-four right-handed, healthy subjects (10 men, 14 women). Subjects underwent magnetic resonance imaging (MRI) at 1.5 T and were assessed (off-line) on acoustic PPI using electromyographic recordings of the orbicularis oculi muscle beneath the right eye. Optimized volumetric voxel-based morphometry (VBM) implemented in SPM99 was used to investigate the relationship of PPI (prepulse onset-to-pulse onset interval 120 ms) to regional grey matter volumes, covarying for sex. Significant positive correlations were obtained between PPI and grey matter volume in the hippocampus extending to parahippocampal gyrus, basal ganglia including parts of putamen, globus pallidus, and nucleus accumbens, superior temporal gyrus, thalamus, and inferior frontal gyrus. These findings identify the relationship between PPI and grey matter availability on a highly spatially localized scale in brain regions shown to be activated in recent functional neuroimaging studies in association with PPI in healthy humans and demonstrate the validity of structural neuroimaging methods in delineating the neural mechanisms underlying human PPI.

Acoustic Stimulation↗
PubMed2005

Characterization of event-related designs using BOLD and IRON fMRI.

Despite many desirable characteristics, event-related (ER) stimulus designs for BOLD and IRON suffer from low detection power relative to block designs because the hemodynamic impulse response function (IRF) acts as a low-pass filter on neural activation to attenuate the size of differential responses to alternate stimuli. While the use of exogenous contrast agent (IRON technique) provides an alternative fMRI method in animal models to improve sensitivity and spatial localization, the inherently slower hemodynamic IRF causes IRON detection efficiency to decrease faster than BOLD efficiency as the interstimulus interval (ISI) is shortened. Using simulations based upon assumptions of stimulus-response linearity and experimental data obtained in awake, non-human primates, this study compared detection efficiencies for fixed, random and semi-random ISI distributions for BOLD and IRON techniques. A larger relative gain in detection efficiency at short ISI was obtained by randomized designs using IRON contrast relative to BOLD contrast due to the slower IRF of the IRON method. To quantify tradeoffs between detection efficiency and the predictability of stimulus presentation, the Shannon entropy was introduced as an objective measure of predictability. Small amounts of entropy can be traded for large gains in efficiency, particularly for the IRON method.

Algorithms↗
PubMed2006

fMRI reveals that involuntary visual deviance processing is resource limited.

Previous studies suggest that involuntary auditory attention evoked by unattended auditory stimuli is not influenced by the primary focus of attention. However, prior studies from our laboratory have found that processing of unattended auditory deviant tones in the auditory and frontal regions is modulated by top-down attentional demands and resource availability. Whether processing of unattended visual deviant stimuli is altered by the availability of attentional resources has not been established. The goal of the current study was to examine the automaticity of these activations, their modulation by attentional capacity, and the neuroanatomical distribution of any attentional effects upon visual deviance detection. We designed an event-related functional magnetic resonance imaging (fMRI) study during which subjects performed a continuous perceptual-motor-visual tracking task whose difficulty was modulated by changing the control dynamics of a joystick. Changes in the anatomical localization, spatial distribution, and intensity of the blood oxygenation level-dependent (BOLD) response associated with unattended infrequent visual changes were examined during low- and high-difficulty tracking conditions of the primary visual task. Results revealed that the unattended deviants elicited BOLD activation in the visual, fusiform, and parietal regions. In these regions, the intensity and extent of the activation evoked by the deviants decreased as a function of the demands of the primary visual task. These findings suggest that processing of unattended visual deviant stimuli is restricted by the attentional demands of a primary task, as previously demonstrated for unattended auditory deviant tones.

Adolescent↗
PubMed2006

Spatio-temporal information analysis of event-related BOLD responses.

A new approach for analysis of event-related fMRI (BOLD) signals is proposed. The technique is based on measures from information theory and is used both for spatial localization of task-related activity, as well as for extracting temporal information regarding the task-dependent propagation of activation across different brain regions. This approach enables whole brain visualization of voxels (areas) most involved in coding of a specific task condition, the time at which they are most informative about the condition, as well as their average amplitude at that preferred time. The approach does not require prior assumptions about the shape of the hemodynamic response function (HRF) nor about linear relations between BOLD response and presented stimuli (or task conditions). We show that relative delays between different brain regions can also be computed without prior knowledge of the experimental design, suggesting a general method that could be applied for analysis of differential time delays that occur during natural, uncontrolled conditions. Here we analyze BOLD signals recorded during performance of a motor learning task. We show that, during motor learning, the BOLD response of unimodal motor cortical areas precedes the response in higher-order multimodal association areas, including posterior parietal cortex. Brain areas found to be associated with reduced activity during motor learning, predominantly in prefrontal brain regions, are informative about the task typically at significantly later times.

Brain↗
PubMed2005

Border ownership from intracortical interactions in visual area v2.

A border between two image regions normally belongs to only one of the regions; determining which one it belongs to is essential for surface perception and figure-ground segmentation. Border ownership is signaled by a class of V2 neurons, even though its value depends on information coming from well outside their classical receptive fields. I use a model of V2 to show that this visual area is able to generate the ownership signal by itself, without requiring any top-down mechanism or external explicit labels for figures, T junctions, or corners. In the model, neurons have spatially local classical receptive fields, are tuned to orientation, and receive information (from V1) about the location and orientation of borders. Border ownership signals that model physiological observations arise through finite range, intraareal interactions. Additional effects from surface features and attention are discussed. The model licenses testable predictions.

Algorithms↗
PubMed2005

Ins(1,4,5)P3 receptors and inositol phosphates in the heart-evolutionary artefacts or active signal transducers?

The generation of the second messenger inositol 1,4,5-trisphosphate (Ins(1,4,5)P(3)) and its associated release of Ca(2+) from internal stores is a highly conserved module in intracellular signaling from Drosophila to mammals. Many cell types, often nonexcitable cells, depend on this pathway to couple external signals to intracellular Ca(2+) release. However, despite the presence of the requisite Ins(1,4,5)P(3) signaling machinery, excitable cells such as cardiac myocytes employ a robust alternate system of intracellular Ca(2+) release, namely, a coupled system of Ca(2+) influx, followed by Ca(2+) release via the IP(3)R-related ryanodine receptors. In these systems, Ins(1,4,5)P(3) signaling pathways appear to be largely dormant. In this review, we consider the general features of inositol phosphate (InsP) responses in cardiac myocytes and the molecules mediating these responses. The spatial localization of Ins(1,4,5)P(3) generation and Ins(1,4,5)P(3) receptor (IP(3)Rs) is likely of key importance, and we examine the state of knowledge in atrial, ventricular, and Purkinje myocytes. Several studies have implicated Ins(1,4,5)P(3) generation in both arrhythmogenic and hypertrophic responses, and possible mechanisms involving Ins(1,4,5)P(3) are discussed. While Ins(1,4,5)P(3) is unlikely to be a key player in cardiac excitation-contraction (EC) coupling, its potential role in an alternate Ca(2+) release system to signal changes in gene transcription warrants further investigation. Such studies will help to determine whether cardiac Ins(1,4,5)P(3) generation represents a vestigial pathway or plays an active role in cardiac signaling.

Animals↗
PubMed2004

Single-molecule spectroscopic methods.

Being praised for the mere fact of enabling the detection of individual fluorophores a dozen years ago, single-molecule techniques nowadays represent standard methods for the elucidation of the structural rearrangements of biologically relevant macromolecules. Single-molecule-sensitive techniques, such as fluorescence correlation spectroscopy, allow real-time access to a multitude of molecular parameters (e.g. diffusion coefficients, concentration and molecular interactions). As a result of various recent advances, this technique shows promise even for intracellular applications. Fluorescence imaging can reveal the spatial localization of fluorophores on nanometer length scales, whereas fluorescence resonance energy transfer supports a wide range of different applications, including real-time monitoring of conformational rearrangements (as in protein folding). Still in their infancy, single-molecule spectroscopic methods thus provide unprecedented insights into basic molecular mechanisms.

Molecular Structure↗
PubMed2004

Cu, Pb and Zn contamination in Nuuanu watershed, Oahu, Hawaii.

Trace metal contamination in urban aquatic ecosystems in Hawaii is a significant problem, especially in terms of Cu, Pb, and Zn. These trace metals are linked to automobile usage. An in-depth study was designed to determine the influence of road sediments and storm sewers on bioavailable (0.5 M HCl) trace metal concentrations in bed sediments of Nuuanu stream, Oahu. Lead was the most enriched trace metal in the watershed. Compared to baseline Pb concentrations of <3 mg/kg, road sediments averaged 186 mg/kg, with a maximum value of 3140 mg/kg. Stream bed sediments had average Pb values of 122 mg/kg, with a maximum of 323 mg/kg. Al-normalized enrichment ratios (ERs) for the <63 microm fraction indicated that the watershed was significantly polluted in the lower, urbanized reaches, with maximum ER values of 560 and 94 for Pb in road sediments and stream sediments, respectively. Median ER values for Cu, Pb, and Zn in stream sediments were 2, 36, and 5, respectively. Rainfall events prior to sediment sampling masked any influence that storm sewer outlets might have had on the localized spatial distribution of metals associated with bed sediments. However, there was a general pattern of increasing trace metal concentrations downstream as the fluvial network traversed residential areas and commercial, highly trafficked areas in the lower portions of the watershed.

Biological Availability↗
PubMed2005

Repair after cholestatic liver injury correlates with neutrophil infiltration and matrix metalloproteinase 8 activity.

BACKGROUND: Although timely surgical treatment of liver disease can interrupt inflammation and reduce fibrosis, the mechanisms of repair are unknown. We questioned whether these mechanisms of repair include changes in the inflammatory infiltrate and associated biological activity of matrix metalloproteinases (MMPs) 8 and 2. METHODS: Rats (n >or= 3) underwent biliary ductal suspension for 7 days followed by decompression. Livers were collected after 7 days of obstruction (d0) and after 2, 5, and 7 days of repair (d2, d5, d7, respectively), and assessed morphometrically for collagen, polymorphonuclear cells (PMNs), Kupffer cells (KCs), and inflammatory mononuclear phagocytes (MNPs). In situ zymography was performed by using fluorogenic substrates for MMP-8 and MMP-2 to spatially localize enzymatic activity. RESULTS: Cholestatic injury resulted in significantly elevated (P <or= .001) collagen deposition (3-fold), and elevated numbers of MNPs (10-fold), KCs (5-fold), and PMNs (4-fold), compared with shams. PMNs remained elevated through d7, while collagen deposition, KCs, and MNPs returned to sham levels by d2. In situ zymography showed no significant changes in MMP-2 activity after cholestatic injury and repair. MMP-8 activity was significantly (P <or= .05) elevated only during repair. Activity was localized to fibrotic portal triads containing PMNs. CONCLUSIONS: Cholestatic injury results in increased fibrosis, MNPs, KCs, and PMNs but no MMP-2 or MMP-8 activity. Biliary decompression results in increased MMP-8 activity co-localized to areas of portal fibrosis and PMN accumulation. We conclude that secretion of MMP-8 by neutrophils may play a critical role in resolving the fibrotic scar generated during cholestasis.

Animals↗
PubMed2005

For K+ channels, Na+ is the new Ca2+.

Although K+ channels activated by Ca2+ have long been known to shape neuronal excitability, evidence is accumulating that K+ channels sensitive to intracellular Na+, termed K(Na) channels, have an equally significant role. K(Na) channels contribute to adaptation of firing rate and to slow afterhyperpolarizations that follow repetitive firing. In certain neurons, they also appear to be activated by Na+ influx accompanying a single spike. Two genes encoding these channels, Slick and Slack, are expressed throughout the brain. The spatial localization of K(Na) channels along axons, dendrites and somata appears to be highly cell-type specific. Their molecular properties also suggest that these channels contribute to the response of neurons to hypoxia.

Action Potentials↗
PubMed2006

Space, time and dopamine.

In recent years, dopamine has emerged as a key neurotransmitter that is crucially involved in incentive motivation and reinforcement learning. Dopamine release is evoked by rewards. The extensive divergence of outputs from a small number of dopaminergic neurons suggests a spatially nonselective action of dopamine, but it reinforces the specific actions that led to reward. How is this achieved? We propose that the selectivity of dopamine effects is achieved by the timing of dopamine release in relation to the activity of glutamatergic synapses, rather than by spatial localization of the dopamine signal to specific synaptic contacts. The synaptic mechanisms of these actions are unknown but reduced levels of dopamine, for example in Parkinson's disease, leads to a paucity of behavioural output, whereas its excess production has been associated with psychiatric problems. Clearly, there are therapeutic imperatives that require a better understanding of how dopamine functions at a synaptic level.

Animals↗