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At least 811 records · Page 45Linked to original sources
PubMed2006

Cortical activity pattern computation.

Neural computations are modelled in various ways, but still there is no clear understanding of how the brain performs its computational tasks. This paper presents new results about analysis of neural processes in terms of activity pattern computations. It is shown that it is possible to extract from high-resolution EEG data a first order Markov approximation of a neural communication system employing pattern computations, which is significantly different from similar purely random systems. In our view this result shows that it is likely that neural activity patterns measurable at the macro-level by EEG are correlated with underlying neural computations.

Animals↗
PubMed2005

Slow cortical potential shifts preceding sensorimotor interactions.

It is well known that synchronization of cortical neurons is modulated ("gating") by the chronological interaction between somatosensory and sensorimotor events. This study tested the hypothesis that the anticipatory processes for this interaction increase the synchronization of cortical neurons as revealed by negative event-related potentials (contingent negative variation, CNV). High-resolution electroencephalographic data (128 electrodes) were recorded in 14 subjects. In the "sensorimotor interaction" condition, the subjects were waiting for a galvanic somatosensory stimulation at the left hand concomitant with a Go or NoGo stimulus (50% of Go trials triggering right hand movements). In the control condition, the Go/NoGo stimulus followed the somatosensory stimulation of 1.5s. The electroencephalographic data were spatially enhanced by surface Laplacian estimation. In the control condition, the CNV was observed only in the foreperiod between the somatosensory stimulation and Go/NoGo task (i.e. no CNV before the somatosensory stimuli). It was spatially localized in the primary sensorimotor area contralateral to the possible motor response. In the "sensorimotor interaction" condition, the CNV preceded the concomitant somatosensory stimulation and Go/NoGo task and was distributed to the frontocentral midline other than the contralateral sensorimotor area. These results suggest that the anticipatory processes for sensorimotor interactions increase the synchronization of cortical neurons in the frontocentral midline, possibly due to mechanisms sub-serving top-down attentional processes.

Adult↗
PubMed2026

highSpaClone enables copy number alteration inference and tumor subclone analysis for high-resolution spatial transcriptomics.

High-resolution spatially resolved transcriptomics (SRT) offers unprecedented opportunities to investigate tumor heterogeneity but poses substantial computational and analytical challenges. Here, we present highSpaClone, a computational framework for copy number alteration (CNA) inference and tumor subclone identification from high-resolution SRT data across multiple spatial scales. By integrating spatial constraints into CNA estimation and clonal clustering, highSpaClone enables neighboring spatial locations to share information, thereby improving the robustness of genomic signals and the accuracy of subclone delineation. Across multiple Xenium and Visium HD datasets, highSpaClone revealed unique transcriptional programs, clonal evolutionary trajectories, and distinct tumor-microenvironment interactions. Furthermore, in human colorectal cancer samples, highSpaClone detected CNA events in histologically normal epithelial regions, highlighting early genomic alterations associated with field cancerization. These findings establish highSpaClone as a scalable framework for studying clonal architecture and tumor evolution.

CP: cancer biology↗
PubMed2005

Structure-based systems biology: a zoom lens for the cell.

Systems biology seeks to explain complex biological systems, such as the cell, through the integration of many different types of information. Here, we discuss how the incorporation of high-resolution structural data can provide key molecular details often necessary to understand the complex connection between individual molecules and cell behavior. We suggest a process of zooming on the cell, from global networks through pathways to the precise atomic contacts at the interfaces of interacting proteins.

Animals↗
PubMed2006

Combination of electrocardiographic and angiographic markers of reperfusion in the prediction of infarct size in patients with ST-segment elevation myocardial infarction undergoing successful primary angioplasty.

BACKGROUND: Optimal epicardial recanalization does not guarantee optimal myocardial perfusion. The aim of the current study was to evaluate angiographic and electrocardiographic markers of reperfusion in the prediction of infarct size in patients with STEMI undergoing successful primary angioplasty. METHODS: Our population is represented by 270 STEMI patients with ST successful primary angioplasty (postprocedural TIMI 3 flow and residual stenosis <50%) with available corrected TIMI frame count (cTFC), myocardial blush grade (MBG), ST-segment resolution and enzymatic infarct size (peak CK-MB) analyses. RESULTS: A significant linear relationship with enzymatic infarct size was observed for all markers of reperfusion, except for ST-segment resolution. These data were confirmed even when analyzed as continuous variables in case of cTFC (r=0.13, p=0.035), postprocedural residual cumulative ST-segment elevation (r=0.41, p<0.0001) and deviation (r=0.45, p<0.0001). At multivariate analysis applied to postprocedural angiographic and electrocardiographic markers of reperfusion, cumulative residual ST-segment deviation, myocardial blush grade, and corrected TIMI frame count were independent predictors of enzymatic infarct size. CONCLUSIONS: This study showed that, among patients with STEMI treated by primary angioplasty, cTFC, MBG and cumulative residual ST-segment deviation are independent predictors of infarct size. Therefore, angiography and electrocardiography may provide complementary information in the evaluation of myocardial perfusion.

Aged↗
PubMed2005

The role of topical nasal steroids in the treatment of children with otitis media with effusion and/or adenoid hypertrophy.

OBJECTIVES: Topical steroid treatment can be a powerful alternative to surgery in controlling adenoid hypertrophy and otitis media with effusion (OME). METHODS: A prospective, controlled, randomized, clinical study in an academic tertiary care center. A total of 122 children (3-15-year-old) on the waiting list for an adenoidectomy and/or ventilation tube placement were enrolled into the study and control groups. The study group (67 patients with adenoid hypertrophy, 34 of them with otitis media with effusion) received intranasal mometasone furoate monohydrate 100 mcg/day, and the control group (55 patients with adenoid hypertrophy, 29 of them with otitis media with effusion) was followed up without any treatment. All patients were evaluated at 0 and 6 weeks. The assessment of each patient included history, a symptom questionnaire, a skin prick test, a tympanogram, if possible a pure tone audiogram, and otoscopic and endoscopic examinations. The size of adenoid tissue was graded as a percentage according to obliteration of the choanae. The adenoid/choana ratio (A/C) was recorded for each patient. Symptoms were scored as 0 (absent), 1 (intermittent/periodic), or 2 (continuous). The data were analyzed with the "Statistical Package for the Social Sciences" (SPSS 9.0) using the appropriate nonparametric tests for nominal and ordinal data. RESULTS: Resolution of otitis media with effusion in the study group (42.2%) was significantly higher than that in the control group (14.5%) (p<0.001). Forty-five patients (67.2%) with adenoid hypertrophy in the study group showed a significant decrease in adenoid size according to the endoscopic evaluation compared to the control group (p<0.001). A significant improvement in obstructive symptoms was seen in the study group (p<0.001). The endoscopically measured adenoid/choana ratio and degree of obstructive symptoms showed a significant correlation (r=0.838 p<0.001, r=0.879 p<0.001, r=0.838 p<0.001, r=0.879 p<0.001). The adenoid/choana ratio improved significantly in atopic patients in the study group (p<0.05), whereas in atopic patients in the control group there was no change (p=0.221). CONCLUSION: Nasal mometasone furoate monohydrate treatment can significantly reduce adenoid hypertrophy and eliminate obstructive symptoms. It is a useful alternative to surgery, at least in the short term, for otitis media with effusion.

Academic Medical Centers↗
PubMed2006

A temperature-profile method for estimating flow in geologic heat pipes.

Above-boiling temperature conditions, as encountered, for example, in geothermal reservoirs and in geologic repositories for the storage of heat-producing radioactive wastes, may induce strong liquid and gas flow processes in porous subsurface environments. The magnitude of these flow processes is extremely hard to measure in the field. We therefore propose a simple temperature-profile method that uses high-resolution temperature data for deriving such information. The energy that is transmitted with the vapor and water flow creates a nearly isothermal zone maintained at about the boiling temperature, referred to as a heat pipe. Characteristic features of measured temperature profiles, such as the differences in the gradients inside and outside of the heat-pipe regions, are used to derive the approximate magnitude of the liquid and gas fluxes in the subsurface.

Air Movements↗
PubMed2006

Abnormal intra-QRS potentials associated with percutaneous transluminal coronary angiography-induced transient myocardial ischemia.

This article introduces a novel concept of abnormal intra-QRS potentials (AIQPs) associated with myocardial ischemia. AIQPs are microvolt-level potentials--subtle alterations in the QRS of the high-resolution electrocardiogram (ECG)--isolated from the unfiltered signal-averaged ECG (SAECG) by a method of mathematical modeling. The aims of the study were (1) to determine the characteristics of potentials in the SAECG related to ischemically altered activation during percutaneous transluminal coronary angiography (PTCA), (2) to determine their relationship with standard 12-lead ECG variables, and (3) to investigate whether AIQPs have a specific pathophysiologic basis in myocardial ischemia. Continuous high-resolution ECG data were acquired from 12 patients before, during, and after PTCA. SAECGs were computed every 60 seconds using an enhanced method of signal averaging. AIQP, ST-segment deviation, and changes in standard ECG QRS duration were measured in each 1-minute SAECG. AIQP amplitudes increased significantly during balloon inflation, compared with the preinflation state. AIQPs exhibited a greater prevalence (12 of 12 patients) than ST-segment deviation changes of more than 100 microV (7 of 12 patients), or measurable changes in standard QRS duration (4 of 12 patients). In patients with significant changes in 12-lead ECG variables during balloon inflation, AIQPs were strongly correlated with both ST-segment and QRS-duration changes. AIQP timing was correlated with the artery occluded, suggesting a specific, ischemia-influenced origin of the signal. AIQPs show promise as a time-localized, sensitive new ECG marker of ischemically altered ventricular activation.

Angioplasty, Balloon, Coronary↗
PubMed2003

The crystallographic structure of Na,K-ATPase N-domain at 2.6A resolution.

The structure of the N-domain of porcine alpha(2) Na,K-ATPase was determined crystallographically to 3.2A resolution by isomorphous heavy-atom replacement using a single mercury derivative. The structure was finally refined against 2.6A resolution synchrotron data. The domain forms a seven-stranded antiparallel beta-sheet with two additional beta-strands forming a hairpin and five alpha-helices. Approximately 75% of the residues were superimposable with residues from the structure of Ca-ATPase N-domain, and a structure-based sequence alignment is presented. The positions of key residues are discussed in relation to the pattern of hydrophobicity, charge and sequence conservation of the molecular surface. The structure of a hexahistidine tag binding to nickel ions is presented.

Amino Acid Sequence↗
PubMed2005

Determining protein topology from skeletons of secondary structures.

We report a novel computational procedure for determining protein native topology, or fold, by defining loop connectivity based on skeletons of secondary structures that can usually be obtained from low to intermediate-resolution density maps. The procedure primarily involves a knowledge-based geometry filter followed by an energetics-based evaluation. It was tested on a large set of skeletons covering a wide range of protein architecture, including one modeled from an experimentally determined 7.6A cryo-electron microscopy (cryo-EM) density map. The results showed that the new procedure could effectively deduce protein folds without high-resolution structural data, a feature that could also be used to recognize native fold in structure prediction and to interpret data in fields like structure genomics. Most importantly, in the energetics-based evaluation, it was revealed that, despite the inevitable errors in the artificially constructed structures and limited accuracy of knowledge-based potential functions, the average energy of an ensemble of structures with slightly different configurations around the native skeleton is a much more robust parameter for marking native topology than the energy of individual structures in the ensemble. This result implies that, among all the possible topology candidates for a given skeleton, evolution has selected the native topology as the one that can accommodate the largest structural variations, not the one rigidly trapped in a deep, but narrow, conformational energy well.

Algorithms↗
PubMed2006

Crystal structure of a multi-domain immunophilin from Arabidopsis thaliana: a paradigm for regulation of plant ABC transporters.

FKBP42 is a membrane-anchored immunophilin playing a critical role in morphogenesis and development of higher plants. We present the X-ray structure of the cytoplasmic portion of FKBP42 comprising both the FKBP-like domain and the TPR domain at 2.85 A resolution. The data shed light on the probable binding modes of key interaction partners, including HSP90 and two classes of ABC transporters. The resulting models provide a structural background for further investigation of the unique biological properties of this protein.

ATP-Binding Cassette Transporters↗
PubMed2005

Induction of suppressors of cytokine signaling (SOCS) in the retina during experimental autoimmune uveitis (EAU): potential neuroprotective role of SOCS proteins.

Suppressors of cytokine signaling (SOCS) are implicated in immunopathogenic mechanisms of autoimmune diseases. We show here that SOCS expression in retina is temporarily correlated with progression of experimental autoimmune uveitis (EAU), an organ-specific autoimmune disease that serves as model of human uveitis. Peak of EAU correlates with highest SOCS genes expression while disease resolution coincides with their down-regulation. Surprisingly, SOCS5 is constitutively expressed in retina. SOCS5 expression increases significantly during EAU and remains elevated even after disease resolution. Our data suggest that cytokine-inducible SOCS members may be involved in negative regulation of inflammatory cytokines activities during EAU, while constitutively expressed SOCS5 may have neuroprotective functions.

Animals↗
PubMed2006

Anticipatory electroencephalography alpha rhythm predicts subjective perception of pain intensity.

UNLABELLED: This high-resolution electroencephalography (EEG) study tested the hypothesis that the suppression of rolandic alpha power before predictable painful stimulation affects the subject's subsequent evaluation of pain intensity, as a reflection of the influence of expectancy processes on painful stimulus processing. High-resolution EEG data were recorded (126 channels) from 10 healthy adult volunteers during the expectancy of a painful CO(2)-laser stimulation at the right wrist. Surface laplacian estimation enhanced the EEG spatial information content over 6 scalp regions of interest (left frontal, right frontal, left central, right central, left parietal, and right parietal areas). Spectral power was computed for 3 alpha sub-bands with reference to the individual alpha frequency peak (about 5-7 Hz for alpha 1, 7-9 Hz for alpha 2, and 9-11 Hz for alpha 3). The suppression of the alpha power before the painful stimulation [as reflected by the event-related desynchronization (ERD)] indexed the anticipatory cortical processes. Results showed maximum (negative) correlations between the alpha 2 and alpha 3 ERD amplitude at the left central area and the subjective evaluation of pain intensity (P < .001). The stronger the anticipatory alpha 2 and alpha 3 ERD, the higher the subjective evaluation of pain intensity. For alpha 3, that correlation was confirmed even when the effect of habituation across the recording session was taken into account. These results suggest that the anticipatory suppression of the alpha rhythms over the contralateral primary sensorimotor cortex predicts subsequent subjects' evaluation of pain intensity, in line with its crucial role for the discrimination of that intensity. PERSPECTIVE: This electroencephalographic study showed that anticipatory activation/deactivation of sensorimotor cortex roughly predicts subjective evaluation of pain. This motivates further investigation on possible implications for the understanding of central chronic pain. Chronic pain patients might exaggerate the anticipatory activation of sensorimotor cortex to negligible pain stimuli.

Adult↗
PubMed2004

Sequence context and modified hydrophobic moment plots help identify 'horizontal' surface helices in transmembrane protein structure prediction.

Transmembrane proteins make up at least one-fifth of the genome of most organisms and are critical components of key pathways for cell survival and interactions with the environment. The function of helices found at the membrane surface in transmembrane proteins has not been greatly explored, but it is likely that they play an ancillary role to membrane spanning helices and are analogous to the surface active helices of peripheral membrane proteins, being involved in: lipid association, membrane perturbation, transmembrane signal transduction and regulation, and transmembrane helical bundle formation. Due to the difficulties in obtaining high-resolution structural data for this class of proteins, structure-from-sequence predictive methods continue to be developed as a means to obtain structural models for these largely intractable systems. A simple but effective variant of the hydrophobic moment analysis of amino acid sequences is described here as part of a protocol for distinguishing helical sequences that are parallel to or 'horizontal' at the membrane bilayer/aqueous phase interface from helices that are membrane-embedded or located in extra-membranous domains. This protocol when tested on transmembrane spanning protein amino acid sequences not used in its development, was found to be 84-91% accurate when the results were compared to the partition locations in the corresponding structures determined by X-ray crystallography, and 72% accurate in determining which helices lie horizontal or near horizontal at the lipid interface.

Algorithms↗
PubMed2006

Controlled 2D crystallization of membrane proteins using methyl-beta-cyclodextrin.

High-resolution structural data of membrane proteins can be obtained by studying 2D crystals by electron crystallography. Finding the right conditions to produce these crystals is one of the major bottlenecks encountered in 2D crystallography. Many reviews address 2D crystallization techniques in attempts to provide guidelines for crystallographers. Several techniques including new approaches to remove detergent like the biobeads technique and the development of dedicated devices have been described (dialysis and dilution machines). In addition, 2D crystallization at interfaces has been studied, the most prominent method being the 2D crystallization at the lipid monolayer. A new approach based on detergent complexation by cyclodextrins is presented in this paper. To prove the ability of cyclodextrins to remove detergent from ternary mixtures (lipid, detergent and protein) in order to get 2D crystals, this method has been tested with OmpF, a typical beta-barrel protein, and with SoPIP2;1, a typical alpha-helical protein. Experiments over different time ranges were performed to analyze the kinetic effects of detergent removal with cyclodextrins on the formation of 2D crystals. The quality of the produced crystals was assessed with negative stain electron microscopy, cryo-electron microscopy and diffraction. Both proteins yielded crystals comparable in quality to previous crystallization reports.

Aquaporins↗
PubMed2006

V(D)J recombination in zebrafish: Normal joining products with accumulation of unresolved coding ends and deleted signal ends.

V(D)J recombination proceeds from a site-specific cleavage to an imprecise end joining, via generation and resolution of recombination ends. Although rearranged antigen receptor genes isolated from zebrafish (Danio rerio) resemble those made in mammals, differences may arise during evolution from lower to higher vertebrates, in regard to efficiency, fidelity and regulation of this recombination. To elucidate the V(D)J recombination reaction in zebrafish, we characterized recombination ends transiently produced by zebrafish lymphocytes, as well as joining products. Similar to their mammalian counterpart, zebrafish lymphocytes make perfect signal joints and normal coding joints, indicating their competent end resolution machinery. However, recombination ends recovered from the same zebrafish lymphoid tissues exhibit some features that are not readily seen in normal mammalian counterpart: deleted signal ends and accumulation of opened coding ends. These results indicate that the recombination reaction in zebrafish lymphocytes is inefficient and less stringently regulated, which may result from unstable post-cleavage complexes, and/or slow transition from cleavage to resolution. Our data suggests that the V(D)J recombination machinery may have undergone evolution selection to become more efficient in higher jawed vertebrates.

Animals↗
PubMed2004

Evaluation of [123I]IBZM pinhole SPECT for the detection of striatal dopamine D2 receptor availability in rats.

Single photon emission computed tomography (SPECT) and MRI coregistration have been assessed to characterize striatal dopamine D2/D3 receptor (D2/D3R) availability in rats following injection of the D2 and D3R radioligand [123I] iodobenzamide ([123I]IBZM). High-resolution SPECT data were obtained with a pinhole collimator. In order to precisely estimate brain regions of low radioligand uptake, SPECT images were coregistered onto a MRI template with high accuracy (maximum mismatch 1.1 mm). To evaluate an adequate dose of radioligand to be administered without exceeding the radioligand-to-receptor occupancy >5% and to define an appropriate time period for image acquisition, three untreated groups of animals received 29.6, 37, and 44.4 MBq of [123I]IBZM and underwent five consecutive SPECT acquisitions lasting 64 min each. Ratio calculations between specific striatal radioligand uptake and nondisplaceable cerebellar uptake revealed a secular equilibrium between 75 and 355 min post-tracer application in all three animal groups. Consequently, since the highest regional uptake values were obtained in the animal group receiving 44.4 MBq [123I]IBZM, this injection dose was considered to be appropriate. Finally, the capacity of the imaging method to detect distinct severity levels of striatal dopamine D2/D3 receptor loss was tested in a low, medium, and high dose quinolinic acid (QA) animal model of Huntington's disease. Motor impairment indicative of striatal dysfunction was monitored using amphetamine-induced rotational behavior and locomotor activity. Loss of striatal D2/D3R bearing medium-sized spiny neurons was assessed by DARPP-32 immunohistochemistry and compared to [123I]IBZM binding. Optical density measures of DARPP-32 immunohistochemistry demonstrated QA dose-dependent mild to subtotal unilateral striatal lesions ranging from 29.4% to 96.9% when compared to the nonlesioned side. Linear regression analysis showed that measurements of striatal DARPP-32 optical density and striatal [123I]IBZM uptake of the lesioned side were highly correlated (r2=0.83; P<0.001) whereas correlation with locomotor activity was less tight (r2=0.23; P<0.05; amphetamine-induced rotational behavior was not significantly correlated). This is the first study to demonstrate that in vivo [123I]IBZM SPECT and MRI coregistration are highly sensitive and, in contrast to behavioral measures, accurately detect mild to subtotal striatal lesions by measuring loss of D2/D3R availability. SPECT-MRI-based estimation of regional [123I]IBZM uptake provides a cost effective and widely available in vivo imaging technique for assessing striatal integrity in animal studies.

Animals↗
PubMed2004

Protein binding and disruption by Clp/Hsp100 chaperones.

Clp/Hsp100 chaperones work with other cellular chaperones and proteases to control the quality and amounts of many intracellular proteins. They employ an ATP-dependent protein unfoldase activity to solubilize protein aggregates or to target specific classes of proteins for degradation. The structural complexity of Clp/Hsp100 proteins combined with the complexity of the interactions with their macromolecular substrates presents a considerable challenge to understanding the mechanisms by which they recognize and unfold substrates and deliver them to downstream enzymes. Fortunately, high-resolution structural data is now available for several of the chaperones and their functional partners, which together with mutational data on the chaperones and their substrates has provided a glimmer of light at the end of the Clp/Hsp100 tunnel.

Endopeptidase Clp↗