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Early phase of spatial mismatch negativity is localized to a posterior "where" auditory pathway.

The auditory mismatch negativity (MMN) is an event-related potential that reflects early processing of changes in acoustic stimulus features. Although the MMN has been well characterized by previous work, the number, roles, and anatomical locations of its cortical generators remain unresolved. Here, we report that the MMN elicited by occasional deviations in sound location is comprised of two temporally and anatomically distinct phases: an early phase with a generator posterior to auditory cortex and contralateral to the deviant stimulus, and a later phase with generators that are more frontal and bilaterally symmetric. The posterior location of the early-phase generator suggests the engagement of neurons within a putative "where" pathway for processing spatial auditory information.

Acoustic Stimulation↗

Local pressure-induced metallization of a semiconducting carbon nanotube in a crossed junction.

The electronic and vibrational density of states of a semiconducting carbon nanotube in a crossed junction was investigated by elastic and inelastic scanning tunneling spectroscopy. The strong radial compression of the nanotube at the junction induces local metallization spatially confined to a few nanometers. The local electronic modifications are correlated with the observed changes in the radial breathing and G band phonon modes, which react very sensitively to local mechanical deformation. In addition, the experiments reveal the crucial contribution of the image charges to the contact potential at nanotube-metal interfaces.

Journal Article↗

Upregulation and spatial shift in the localization of the mannose 6-phosphate/insulin-like growth factor II receptor during radiation enteropathy development in the rat.

BACKGROUND AND PURPOSE: Transforming growth factor beta1 (TGF-beta1) appears to play an important role in the pathogenesis of chronic radiation-induced fibrosis in the intestine and several other organs. TGF-beta1 is secreted as a non-biologically active complex and its function depends on activation. In vitro data suggest that the mannose 6-phosphate/insulin-like growth factor-beta (M6P/IGF-II) receptor is involved in the mechanism of TGF-beta1 activation. Thus, we used a rat model of radiation enteropathy to examine the potential role of the M6P/IGF-II receptor in the in vivo regulation of TGF-beta1 activity and localization. MATERIALS AND METHODS: A scrotal hernia containing a loop of small intestine was created in male rats. The intestine in the scrotum was exposed to 0, 12, or 21 Gy single dose X-radiation. Groups of rats were euthanized 1 day and 2, 6 and 26 weeks after irradiation. Histopathologic injury was assessed with a radiation injury score (RIS). Computerized image analysis was used to identify M6P/IGF-II receptor-positive cells and to quantify extracellular matrix-associated TGF-beta1 immunoreactivity. Changes in urokinase plasminogen activator (uPA), tissue-like plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) immunoreactivity were also assessed. RESULTS: In normal (sham-irradiated) intestine, M6P/IGF-II immunoreactivity was confined to relatively weak, but specific epithelial staining. Irradiated intestine exhibited a highly significant time- and dose-dependent increase in the number of M6P/IGF-II receptor-positive cells (P < 0.001). There was a striking spatial shift of M6P/IGF-II receptor immunoreactivity from epithelium during the early post-radiation phase to stromal cells, most notably fibroblasts during the later stages of injury. Irradiated intestine exhibited distinct co-localization of M6P/ IGF-II receptor-positive cells and extracellular matrix-associated TGF-beta1 in areas of histopathologic injury. There were highly significant associations between the number of M6P/IGF-II receptor-positive stromal cells and TGF-beta1 immunoreactivity (P < 0.001), radiation-induced fibrosis (P < 0.001) and RIS (P < 0.001). Endothelial tPA immunoreactivity decreased significantly after irradiation (P < 0.001), whereas uPA and PAI-1 immunoreactivity levels appeared to be unchanged. CONCLUSIONS: M6P/IGF-II receptor upregulation may be a key factor in the in vivo control of TGF-beta1 activity and responsible for the tissue specificity of TGF-beta1 action after irradiation.

Animals↗

Theoretical derivation of SNR, CNR and spatial resolution for a local adaptive strain estimator for elastography.

Conventional techniques in elastography estimate the axial strain as the gradient of the displacement (time-delay) estimates obtained using cross-correlation of pre- and temporally stretched postcompression radiofrequency (RF) A-line segments. The use of a constant stretch factor for stretching the postcompression A-line is not adequate in the presence of heterogeneous targets that are commonly encountered. This led to the development of several adaptive strain estimation techniques in elastography. Yet, a theoretical framework for the image quality of adaptive strain estimation has not been established. In this work, we develop theoretical expressions for the image quality [measured in terms of the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and spatial resolution] of elastograms obtained using an adaptive strain estimator developed by Alam et al. (1998). We show a linear trade-off between the SNR and axial resolution of the strain elastogram with respect to the window length used for strain estimation. The CNR shows a quadratic tradeoff with the axial resolution with respect to the window length. The SNR, CNR and axial resolution are shown to improve with the ultrasonic bandwidth.

Algorithms↗

Spatial proximity and sequence localization of the reactive sulfhydryls of porphobilinogen synthase.

The zinc metalloenzyme porphobilinogen synthase (PBGS) contains several functionally important, but previously unidentified, reactive sulfhydryl groups. The enzyme has been modified with the reversible sulfhydryl-specific nitroxide spin label derivative of methyl methanethiosulfonate (MMTS), (1-oxyl-2,2,5,5-tetramethyl-delta 3-pyrroline-3-methyl)methanethiosulfonate (SL-MMTS) (Berliner, L. J., Grunwald, J., Hankovszky, H. O., & Hideg, K., 1982, Anal. Biochem. 119, 450-455). EPR spectra show that SL-MMTS labels three groups per PBGS subunit (24 per octamer), as does MMTS. EPR signals reflecting nitroxides of different mobilities are observed. Two of the three modified cysteines have been identified as Cys-119 and Cys-223 by sequencing peptides produced by an Asp-N protease digest of the modified protein. Because MMTS-reactive thiols have been implicated as ligands to the required Zn(II), EPR spectroscopy has been used to determine the spatial proximity of the modified cysteine residues. A forbidden (delta m = 2) EPR transition is observed indicating a through-space dipolar interaction between at least two of the nitroxides. The relative intensity of the forbidden and allowed transitions show that at least two of the unpaired electrons are within at most 7.6 A of each other. SL-MMTS-modified PBGS loses all Zn(II) and cannot catalyze product formation. The modified enzyme retains the ability to bind one of the two substrates at each active site. Binding of this substrate has no influence on the EPR spectral properties of the spin-labeled enzyme, or on the rate of release of the nitroxides when 2-mercaptoethanol is added.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Global patterns in human mitochondrial DNA and Y-chromosome variation caused by spatial instability of the local cultural processes.

Because of the widespread phenomenon of patrilocality, it is hypothesized that Y-chromosome variants tend to be more localized geographically than those of mitochondrial DNA (mtDNA). Empirical evidence confirmatory to this hypothesis was subsequently provided among certain patrilocal and matrilocal groups of Thailand, which conforms to the isolation by distance mode of gene diffusion. However, we expect intuitively that the patterns of genetic variability may not be consistent with the above hypothesis among populations with different social norms governing the institution of marriage, particularly among those that adhere to strict endogamy rules. We test the universality of this hypothesis by analyzing Y-chromosome and mtDNA data in three different sets of Indian populations that follow endogamy rules to varying degrees. Our analysis of the Indian patrilocal and the matrilocal groups is not confirmatory to the sex-specific variation observed among the tribes of Thailand. Our results indicate spatial instability of the impact of different cultural processes on the genetic variability, resulting in the lack of universality of the hypothesized pattern of greater Y-chromosome variation when compared to that of mtDNA among the patrilocal populations.

Chromosome Mapping↗

Epitope mapping of the laminin molecule in murine skin basement membrane zone: demonstration of spatial differences in ultrastructural localization.

Results of studies performed to date with polyclonal antilaminin antibodies have been conflicting as to the ultrastructural localization of this glycoprotein in skin basement membrane zone (BMZ). Whereas initial reports suggested its presence solely within the lamina lucida (LL), others have suggested that laminin is instead an exclusive component of the lamina densa (LD). In an attempt to more critically address this issue, we have examined both intact and partially separated (via 1 M NaCl) murine skin BMZ by indirect immunoelectron microscopy via a two-step immunoperoxidase technique on unfixed cryopreserved tissue, utilizing nine well-characterized monoclonal antibodies with binding specificity for laminin. Localization of the sites of the epitopes recognized by these antibodies on isolated laminin molecules was previously determined by rotary shadowing and by biochemical analyses on enzymatic fragments of laminin. Whereas at least faint immunoreactants were detected in both regions with eight of nine antibodies, predominant staining was noted within the LL with three of eight and within (and even sparsely below) the LD in three of eight. One antibody bound solely to the LL; another bound equally within both regions. Although some overlap was noted, it appears that the epitope on the distal portion of the long arm of the laminin molecule resides primarily within the skin LD, whereas epitopes on more central portions of the short arms are present within the LL or within both LL and LD. The findings of stratification of laminin epitopes within skin BMZ supports a similar recent observation in mouse kidney and suggests that portions of the laminin molecule span both LD and LL, and that there may be a non-random spatial orientation for the laminin molecule within murine skin BMZ.

Animals↗

Quantitative evaluation of the lactate signal loss and its spatial dependence in press localized (1)H NMR spectroscopy.

Localized (1)H NMR spectroscopy using the 90 degrees -t(1)-180 degrees -t(1)+t(2)-180 degrees -t(2)-Acq. PRESS sequence can lead to a signal loss for the lactate doublet compared with signals from uncoupled nuclei which is dependent on the choice of t(1) and t(2). The most striking signal loss of up to 78% of the total signal occurs with the symmetrical PRESS sequence (t(1)=t(2)) at an echo time of 2/J (approximately 290 ms). Calculations have shown that this signal loss is related to the pulse angle distributions produced by the two refocusing pulses which leads to the creation of single quantum polarization transfer (PT) as well as to not directly observable states (NDOS) of the lactate AX(3) spin system: zero- and multiple-quantum coherences, and longitudinal spin orders. In addition, the chemical shift dependent voxel displacement (VOD) leads to further signal loss. By calculating the density operator for various of the echo times TE=n/J, n=1, 2, 3,..., we calculated quantitatively the contributions of these effects to the signal loss as well as their spatial distribution. A maximum signal loss of 75% can be expected from theory for the symmetrical PRESS sequence and TE=2/J for Hamming filtered sinc pulses, whereby 47% are due to the creation of NDOS and up to 28% arise from PT. Taking also the VOD effect into account (2 mT/m slice selection gradients, 20-mm slices) leads to 54% signal loss from NDOS and up to 24% from PT, leading to a maximum signal loss of 78%. Using RE-BURP pulses with their more rectangular pulse angle distributions reduces the maximum signal loss to 44%. Experiments at 1.5 T using a lactate solution demonstrated a maximum lactate signal loss for sinc pulses of 82% (52% NDOS, 30% PT) at TE=290 ms using the symmetrical PRESS sequence. The great signal loss and its spatial distribution is of importance for investigations using a symmetrical PRESS sequence at TE=2/J.

Acetic Acid↗

Hydrogen clearance method for determining local cerebral blood flow. I. Spatial resolution.

To define the effective spatial resolution of the hydrogen clearance method, serial local CBF (LCBF) measurements were performed at different distances from the cortico-white matter junction of the cat brain. Twenty-five platinum-wire microelectrodes with a sensitive surface of 0.07 mm2 were inserted into the cerebral cortex of three cats through burr holes in the skull and advanced toward the ear-to-ear level in 1- or 0.1-mm steps. Most electrodes passed from high-perfusion regions into low-perfusion areas, indicating that the cortico-white matter junction had been traversed. Whereas within the gray and white matter the LCBF values were fairly constant, a striking decrease of CBF was registered at the cortico-white matter junction. Here the mean LCBF from 12 electrodes showed significant differences in flow between two locations 1 mm apart. On two occasions, a significant difference in CBF was found for locations only 0.1 mm apart. Despite this high spatial resolution, monoexponential clearance curves were detected only in the vicinity of the cortico-white matter junction. It is therefore assumed that factors other than flow might influence H2 clearance.

Animals↗

Spatial distribution of inputs and local receptive field properties of a wide-field, looming sensitive neuron.

The lobula giant movement detector (LGMD) in the locust visual system and its target neuron, the descending contralateral movement detector (DCMD), respond to approaching objects looming on a collision course with the animal. They thus provide a good model to study the cellular and network mechanisms underlying the sensitivity to this specific class of behaviorally relevant stimuli. We determined over an entire locust eye the density distribution of optical axes describing the spatial organization of local inputs to the visual system and compared it with the sensitivity distribution of the LGMD/DCMD to local motion stimuli. The density of optical axes peaks in the equatorial region of the frontal eye. Local motion sensitivity, however, peaks in the equatorial region of the caudolateral visual field and only correlates positively with the dorso-ventral density of optical axes. On local stimulation, both the velocity tuning and the response latency of the LGMD/DCMD depend on stimulus position within the visual field. Spatial and temporal integration experiments in which several local motion stimuli were activated either simultaneously or at fixed delays reveal that the LGMD processes local motion in a strongly sublinear way. Thus the neuron's integration properties seem to depend on several factors including its dendritic morphology, the local characteristics of afferent fiber inputs, and inhibition mediated by different pathways or by voltage-gated conductances. Our study shows that the selectivity of this looming sensitive neuron to approaching objects relies on more complex biophysical mechanisms than previously thought.

Action Potentials↗

Spatial relationship of source localizations in patients with focal epilepsy: Comparison of MEG and EEG with a three spherical shells and a boundary element volume conductor model.

Epilepsy surgery is an option for patients with pharmacoresistant focal epilepsies, but it requires a precise focus localization procedure. Magnetoencephalography (MEG) and electroencephalography (EEG) can be used for analysis of interictal activity. The aim of this prospective study was to compare clusters of source localization results with MEG and EEG using a three spherical shells (3SS) and a boundary element method (BEM) volume conductor model. The study was closed when 100 patients met the inclusion criteria. Simultaneous MEG and EEG were recorded during presurgical evaluation. Epileptiform signals were analyzed using an equivalent current dipole model. Centroids of source localizations from MEG, EEG, 3SS, and BEM in their respective combinations were compared. In a 3SS model, MEG source localizations were 5.6 mm inferior to those obtained by EEG, while in a BEM model MEG source localizations were 6.3 mm anterior and 4.8 mm superior. The mean scattering of source localizations between both volume conductor models was 19.5 mm for EEG and 9.6 mm for MEG. For MEG no systematic difference between BEM and 3SS source localizations was found. For EEG, source localizations with BEM were 5.9 mm posterior and 11.7 mm inferior to those determined using 3SS. No differences were found between the 46 temporal and the 54 extratemporal lobe epilepsy patients. The observed systematic differences of source localizations of epileptic spikes due to the applied source signal modality and volume conductor model should be considered in presurgical evaluation when only one source signal and volume conductor model is available.

Adult↗

Spatial variation of the local tissue oxygen diffusion coefficient measured in situ in the cat retina and cornea.

A method for measuring the local oxygen diffusion coefficient (D) in an intact tissue, in situ, in a living cat is described. Values of D were calculated from nonlinear regression analysis of the polarographic (turn-on) transients using a semi-empirical model for the retina and a theoretical one for the cornea. Two types of microelectrodes were employed: in the retina, ones with extremely short recesses; and in the cornea, bare metal needles. The local D in the cat retina was practically homogeneous with a mean of 1.97 +/- 0.11.10(-5) cm2/s, at its body temperature of 37-38 degrees C, 70.6 +/- 3.3 percent of that in isotonic saline at 37 degrees C. In the cat corneal stroma, at its normal temperature in situ of 33 degrees C, D was also virtually homogeneous with a mean of 1.19 +/- 0.20.10(-5) cm2/s, 42.8 +/- 7.3 percent of that in isotonic saline at 37 degrees C.

Animals↗

Localized hedgehog activity controls spatial limits of wingless transcription in the Drosophila embryo.

Cell patterning in the body segments of the Drosophila embryo requires activity of the segment polarity genes, a molecularly heterogeneous group defined by a generic mutant phenotype. Two of these genes, wingless (wg) and hedgehog (hh), encode proteins that enter the secretory pathway, implicating them as signals that instruct the fates of neighbouring cells. Genetic analysis has identified wg transcription as one of the targets of hh activity and it has been suggested that the spatial control of wg expression depends on the limited range of the hh signal and the differential competence of responding cells. I have tested this model by driving ubiquitous expression of the hh gene using the Hsp70 promoter. Here I report that, as predicted, this causes the ectopic activation of wg in only a subset of the cells of each parasegment. Using another target of hh activity as a probe, I demonstrate that the competence of cells to express wg is independent of their ability to receive the hh signal. Finally, I show that wg activation requires the function of the segment polarity gene fused, suggesting that the putative hh signal is transduced by the serine/threonine kinase that fused encodes.

Animals↗

Spatial, temporal and subcellular localization of islet-brain 1 (IB1), a homologue of JIP-1, in mouse brain.

Islet-brain 1 (IB1) was recently identified as a DNA-binding protein of the GLUT2 gene promoter. The mouse IB1 is the rat and human homologue of the Jun-interacting protein 1 (JIP-1) which has been recognized as a key player in the regulation of c-Jun amino-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) pathways. JIP-1 is involved in the control of apoptosis and may play a role in brain development and aging. Here, IB1 was studied in adult and developing mouse brain tissue by in situ hybridization, Northern and Western blot analysis at cellular and subcellular levels, as well as by immunocytochemistry in brain sections and cell cultures. IB1 expression was localized in the synaptic regions of the olfactory bulb, retina, cerebral and cerebellar cortex and hippocampus in the adult mouse brain. IB1 was also detected in a restricted number of axons, as in the mossy fibres from dentate gyrus in the hippocampus, and was found in soma, dendrites and axons of cerebellar Purkinje cells. After birth, IB1 expression peaks at postnatal day 15. IB1 was located in axonal and dendritic growth cones in primary telencephalon cells. By biochemical and subcellular fractionation of neuronal cells, IB1 was detected both in the cytosolic and membrane fractions. Taken together with previous data, the restricted neuronal expression of IB1 in developing and adult brain and its prominent localization in synapses suggest that the protein may be critical for cell signalling in developing and mature nerve terminals.

Adaptor Proteins, Signal Transducing↗