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At least 937 records · Page 52Linked to original sources

PubMed2002

Split-second sequential selective activation in human secondary visual cortex.

This work addressed early selection based on nonspatial visual features, using event-related potentials (ERPs) with high temporal resolution and dipole-source modeling. Subjects were presented rapid sequences of gratings varying in spatial frequency and orientation, and were instructed to attend to gratings with one spatial frequency and ignore those with another. Attention effects started at 120-msec latency as anterior positivity and proceeded as posterior negativity (200 msec) and anterior negativity (265 msec). Dipole-source modeling suggested that these effects reflect the sequential selective activation of, on average, posterior dorsal-medial, posterior ventral-lateral, and anterior medial cortical areas. In contrast, stimulus-specific activity was observed well before 100-msec latency and characterized by dipoles with locations significantly posterior to those of the attention-modulated activity. These results indicate that even with highly discriminable spatial frequencies, selection is not as early as before the 100-msec latency, unlike what is often found for location selection. It is also separated in time and anatomically from the earliest stimulus-specific cortical activity. Reducing discriminability of the selection feature resulted in longer selection latencies, becoming manifest only at 175 msec as an apparent combination of posterior and anterior negativities, and in an elevated criterion for overt responding.

Adult↗

PubMed2026

Thyroid-stimulating hormone receptor mediates peripheral-central neuroimmune crosstalk in autoimmune thyroid diseases.

BACKGROUND: Organ-specific autoimmune diseases, particularly Graves' disease (GD) and its extrathyroidal manifestation, Graves' orbitopathy (GO), are characterized by systemic autoimmunity that may extend its impact to the central nervous system (CNS). While thyroid-stimulating hormone receptor (TSHR) is the primary driver of pathological remodeling in the thyroid and orbital tissues, emerging evidence suggests it is also expressed in the brain and may participate in neuroimmune signaling. However, the molecular mechanisms linking peripheral TSHR-driven autoimmunity to these extended systemic features remain unclear. Thus, GD and GO provide a unique window to investigate how peripheral autoantibodies influence CNS involvement as part of its broader pathological spectrum. METHODS: Genome-wide association studies (GWAS) and post-GWAS analyses were integrated with bulk RNA sequencing, single-cell and spatial transcriptomics, and brain imaging phenotypes to comprehensively characterize peripheral and central alterations in GD and GO. Mendelian randomization was applied to test causal relationships between genetic variants and brain signatures. Structural biology analyses were further conducted including protein-protein docking, small-molecule docking, and normal mode dynamics to identify prospective modulators of TSHR. Immunofluorescence staining was performed in a GO mouse model to validate the colocalization of potential interacted proteins in the specific brain region. RESULTS: Brain imaging-derived phenotypes (IDPs) alterations in GO and GO were systematically analyzed to identify neuroanatomical and functional alterations. TSHR was further identified as a shared genetic driver across peripheral and central compartments. TSHR was expressed in spiny projection neurons, microglia, and peripheral T cells, with cell-cell communication analyses highlighting TSHR-mediated interactions among neurons, endothelial cells, and microglia. Immunofluorescence staining in a GO mouse model confirmed the colocalization of TSHR with FN1 and GNAS in the basal ganglia, providing tissue-level validation of the computationally predicted ligand-receptor interactions. Immune profiling further showed immune alterations in GD and GO. Structural modeling supported plausible physical interfaces between TSHR and interacting proteins, and small-molecule screening identified three repurposable compounds - venetoclax, irinotecan, and dutasteride - with predicted favorable docking scores and stable binding poses in our simulations. CONCLUSIONS: These findings demonstrate that TSHR acts as a molecular hub mediating peripheral-central neuroimmune crosstalk in GD and GO. The results support a broader "disease-molecule axis" framework that links genetic susceptibility with multi-level immune and neural mechanisms. This work provides mechanistic insights relevant to the development of TSHR-targeted therapies, with implications for both peripheral immune modulation and central regulation. However, the limited sample size, lack of longitudinal follow-up, and absence of in vivo validation warrant cautious interpretation and further investigation.

Receptors, Thyrotropin↗

PubMed2004

Significance of prohormone convertase 2, PC2, mediated initial cleavage at the proglucagon interdomain site, Lys70-Arg71, to generate glucagon.

To define the biological significance of the initial cleavage at the proglucagon (PG) interdomain site, K70-R71 downward arrow, we created two interdomain mutants, K70Q-R71Q and R71A. Cotransfection studies in GH4C1 cells show significant amounts of glucagon production by PC2 along with some glicentin, glicentin-related polypeptide-glucagon (GRPP-glucagon) and oxyntomodulin from wild-type PG. In contrast, a larger peptide, PG 33-158, and low amounts of GRPP-glucagon are predominantly generated from interdomain mutants. HPLC analysis shows a 5-fold increase in glucagon production by PC2 from wild-type PG and a corresponding 4-fold lower accumulation and secretion of unprocessed precursor relative to interdomain mutants. PC2 generates significant levels of glucagon from a glicentin (PG 1-69) expression plasmid, whereas PC1/3 produces only modest amounts of oxyntomodulin. Employing a major PG fragment (PG 72-158) expression plasmid, we show that PC1/3 predominantly generates glucagon-like peptide (GLP)-1, whereas PC2 produces only N-terminally extended GLP-1. Surprisingly, production of GLP-1 and GLP-2 by PC1/3 from interdomain mutants, compared with wild-type PG, is not significantly impaired. In addition to PC2 and PC1/3, PC5/6A and furin are also able to cleave the sites, K70-R71 downward arrow and R107-X-R-R110 downward arrow in PG. We show a much greater ability of furin to cleave the monobasic site, R77 downward arrow, than at the dibasic site, R124-R125 downward arrow, which is also weakly processed by PC5/6A, indicating overlapping specificities of these two convertases mainly with PC1/3. We propose here a trimer-like model of the spatial organization of the hormonal sequences within the PG molecule in which the accessibility to prohormone convertase action of most cleavage sites is restricted with the exception of the interdomain site, K70-R71, which is maximally accessible.

Animals↗

PubMed1988

Developmental patterning of carbohydrate antigens during early embryogenesis of the chick: expression of antigens of the poly-N-acetyllactosamine series.

This report describes a striking temporal and spatial patterning of specific carbohydrate sequences in the developing chick embryo. By using oligosaccharide sequence-specific monoclonal antibodies as immunohistochemical reagents in conjunction with neuraminidase, it was possible to visualize the occurrence, as well as the changes in distribution, of oligosaccharides of the poly-N-acetyllactosamine series. These were (a) long-chain unbranched sequences reactive with anti-i Den, (b) long-chain branched sequences reactive with anti-I Step and (c) short-chain branched sequences reactive with anti-I Ma and (d) their sialylated forms. The salient observations with serial sections of embryos from the unincubated to the 17th stage were as follows. (1) A pronounced anteroposterior patterning appeared during neuroectodermal development, such that the long-chain unbranched and long-chain branched sequences, which were abundant on the ectoderm of the earlier stages, were replaced by short-chain branched sialo-oligosaccharides in the developing brain and anterior neural tube. (2) A striking anteroposterior and mediolateral patterning developed in the subectodermal extracellular spaces. The long-chain linear and short-chain non-sialylated sequences demarcated regions favourable for migration of the lateral plate mesoderm. (3) A distinction was made between the dorsal and ventral routes of the trunk neural crest in that the extracellular matrix of the dorsal route only was associated with long-chain linear and short-chain sialylated branched sequences. (4) A circumscribed perinotochordal distribution of the short-chain sialylated branched sequences was observed in the region of the future centra of the vertebrae. (5) An abundance of long-chain linear and long-chain sialylated branched structures was detected in primordial germ cells which permitted their identification during migration. These observations suggest that oligosaccharides of the poly-N-acetyllactosamine series may have roles as short-range, region-specific information factors during morphogenetic events that take place in the developing embryo, and they open the way to the search for recognition proteins (e.g. endogenous lectins) specific for each of these oligosaccharide structures.

Animals↗

PubMed2006

Gender and limb differences in healthy elite dancers: passé kinematics.

Symmetry of skill development is emphasized in dance training, and many movements are well learned by both genders. The authors conducted a 2-dimensional kinematic analysis of a complex dance movement, the passé, in 12 healthy professional male and female dancers to determine whether there are differences between genders or limbs during the performance of that task. Only peak hip angular displacement differed in men and women. No differences were found between limbs in any of the dependent variables. Dancers displayed consistent temporal and spatial proximal-to-distal sequencing of movement coordination. Despite an indication of limb preference, as defined by gesture or stance limb, there were no differences in proficiency.

Adolescent↗

PubMed2004

[Distinguishing between occluded and low-flow vessels with PROPELLER DWI sequence: a phantom study].

PURPOSE: To evaluate the ability of periodically rotated overlapping parallel lines with enhanced reconstruction diffusion-weighted imaging (PROPELLER DWI) to distinguish between vessel occlusion and slow flow. MATERIALS AND METHODS: Using a flow phantom with various velocities (1.37 to 11.1 cm/s), the signal-intensity ratios of the phantom, with the intensity of no flow as baseline, were measured using the following imaging sequences: PROPELLER DWI, spin-echo T1-weighted imaging (SE T1WI), fast-spin-echo T2-weighted imaging (FSE T2WI), two-dimensional phase-contrast imaging (2D PC), and two-dimensional time-of-flight imaging (2D TOF). The b-factor of PROPELLER DWI was varied from 0 to 1000 s/mm(2). The velocity encoding of 2D PC was varied from 2 to 30 cm/s. RESULTS: At the lowest flow velocity (1.37 cm/s) , the signal-intensity ratio was 0.0075 for PROPELLER DWI (b-factor=1000 s/mm(2)), 1.8 for SE T1WI, 0.67 for FSE T2WI, 11 for 2D PC (velocity encoding=2 cm/s), and 1.4 for 2D TOF. The signal-intensity ratio was smallest for PROPELLER DWI, even when the reciprocals of the signal-intensity ratio of 2D PC or 2D TOF were considered. CONCLUSION: The results indicate that PROPELLER DWI provides the best signal intensity-ratio between vessel occlusion and slow flow. Although DWI with single-shot echo-planar imaging (EPI) or multi-shot EPI may have similarly high sensitivity for slow flow, these sequences do not have high spatial resolution or robustness to susceptibility artifacts. PROPELLER DWI would be a better choice for distinguishing between occluded and low-velocity arteries in the skull base or parasellar regions.

Blood Flow Velocity↗

PubMed1999

Tagged MR imaging of intracranial aneurysm models.

We used tagged MR imaging to investigate the flow in two lateral and two terminal saccular intracranial aneurysm models of different neck sizes. Imaging was performed with a 1.5-T superconducting MR system using 2D fast spatial modulation of magnetization (SPAMM) sequences with an intersegmental delay of 25 milliseconds. The flow in the saccular aneurysm models varied with the shape and size of the neck: flow was faster in wider-necked aneurysms than in those with narrower necks.

Intracranial Aneurysm↗

PubMed2001

Organizer and axes formation as a self-organizing process.

It is a widely held view that axis formation is based essentially on pre-localized determinants. However, the robustness of early development, the pattern regulation observed after experimental interferences and the existence of systems that don't require maternal determinants suggest that self-regulating pattern forming systems are also involved. A model is proposed that allows axes formation by a chain of reactions based on local self-enhancement and long-range inhibition. Their appropriate linkage ensures that the intermediary patterns emerge in the correct sequence and have the correct spatial relation to each other. Specifically, the model comprises the following events: the generation of a pole by a pattern-forming process, the formation of a second organizer eccentric to the pole (e.g. the Nieuwkoop center), the ecto-meso-endo subdivision, the generation of the Spemann-Mangold organizer with its anterior-posterior subdivision under the influence of the Nieuwkoop center, the conversion of the Spemann-Mangold organizer (a hot spot) into the notochord (a hot stripe), and the marking of the left side of the organism by a patterning reaction influenced by the midline. The pattern forming reactions do not depend on but can make use of maternally pre-localized determinants or asymmetries. Comparison with known genes and molecules reveals that many of the expected ingredients are present. Computer simulations show that the model accounts for many regulatory features reported in the literature. The computer simulations are available in an animated form at.

Animals↗

PubMed2001

Mapping of atrial fibrillation.

Cardiac mapping has been defined as: "a method by which cardiac signals are recorded from multiple sites of the heart and spatially depicted as a function of time in an integrated manner". It requires determination of the local activation time at each electrode and the creation of activation maps which provide a spatial model of the activation sequence. With respect to atrial fibrillation, mapping is useful to gain insight into the underlying mechanism of atrial fibrillation. In this review, we will discuss the mapping studies of experimental and clinical atrial fibrillation.

Atrial Fibrillation↗

PubMed1983

[Detection of cancer by nuclear magnetic resonance imaging].

Nuclear magnetic resonance (NMR) imaging for medical diagnosis is rapidly approaching a time of widespread clinical trials. It may ultimately give images a clear as those obtained with computed tomography with a potential for defining tissue chemistry. Perhaps the method can be as free from hazard as is visual observation. The ability to produce coronal and sagittal as well as axial transverse images directly is shown to have important implications for precise lesion assessment. NMR imagings at high magnetic fields demonstrate excellent image quality and high spatial resolution. The variety of sequences possible with NMR allows a choice of images to reflect varying degrees of proton density and blood flow, as well as tissue spin-lattice (T1) and spin-spin relaxation (T2) times.

Brain Neoplasms↗

PubMed1983

[Inversion polymorphism of the malarial mosquito Anopheles messeae. V. The interaction of different chromosomal inversions in the spatial area].

The relations between inversions of chromosome XL, 2R, 3R, 3L from 8 populations of the central part and periphery of the species area were studied. 2-, 3- and 4-factor analysis was carried out. Interaction of inversions XL1, 2R1, 3R1 in central populations (Riga, Moscow, Tomsk) was observed. The nonrandom association of definite inversional genotypes was stationary in spatial - temporary. The phylogenetic initial sequences XL0, 2R0, 3R0 display "+" interaction. The 3-factor analysis of populations of Tomsk shows: 1) interaction of inversions is more essential in males than in females; 2) the statistically significant interaction of 3-4 inversions is not always determined by the effect of 2-factor analysis; 3) the chromosome 3R has a dominance influence on the pattern of association of the multiinversional complex. These data support the hypothesis that differential selection for chromosomes with certain combinations of arrangements is mainly responsible for this phenomenon. In peripheral area populations (Syctyvkar, Irkutsk, Chita), no associations were observed (2R and 3R). When they do take place, their character is changed (Kiev - XL and 3R). This phenomenon may be explained by the influence of frequency-dependent selection.

Animals↗

PubMed1994

[Evaluation and extension of Markov process models for the evolution of DNA].

Markov process models of nucleotide substitution are evaluated. A model proposed by Lanave et al (1984), alleged to need no priori assumption about the substitution pattern, is found to have the assumption of reversibility. Calculations based on the 2-p, 4-p, and 6-p substitution schemes show that site variation of substitution speed leads to serious under-estimation of sequence divergence by various methods. Spatial pattern variation also leads to under-estimation, but the discrepancy is slight. A nonhomogeneous Markov process model is used to study the temporal variations of rates and it is shown that the estimated number of substitutions reflects a rate averaged over time. The implications of those results to evolutionary phylogenetics are discussed.

Biological Evolution↗

PubMed1996

[Three-dimensional echocardiography. Principles and applications].

Three-dimensional echocardiography is based on two methods of retrospective reconstruction from two-dimensional echocardiographic images. The acquisition of the two-dimensional images may be free or imposed, the transducer either carrying an emission-reception system or fixed to an articulated support providing data about its position. In the first system, manual tracing of the contours of the region of interest performed on each frame are superimposed after time sequencing (using the ECG) and spatial repositioning, so enabling three-dimensional visualisation of the contours of the cardiac structures: this approach provides reliable quantitative information (volumes, mass and ejection fractions) and has led to the redefinition of the echocardiographic criteria of mitral valve prolapse. The second system is based on equidistant sections obtained by progressive, controlled two-dimensional scanning (parallel, arc of a circle and rotational) of the structure of interest: a value of grey scale is assigned to the space between two adjacent pixels, enabling the formation of voxels which, when superimposed, give the required effects of volume and surface for three-dimensional imaging. It is then possible to obtain any section of the volume and simulate surgical views of the beating heart. This approach may significantly improve diagnostic accuracy compared with two-dimensional echocardiography and provides access to new quantitative and qualitative parameters.

Echocardiography, Doppler, Color↗

PubMed1997

[Magnetic resonance imaging].

During the last ten years substantial improvement of hardware and software used for the construction of MRI scanners has made available MRI sequences with high temporal and spatial image resolution. Therefore, MR imaging has become an excellent tool and in certain cases the gold standard for the evaluation of cardiovascular diseases. Primary indications for cardiovascular MRI include the assessment of aortic diseases, the arrhythmogenic right ventricle, surgically corrected congenital heart diseases, pericardial disease, intra- and paracardiac tumors and quantification of ventricular function and volumes and myocardial mass. Secondary indications include hypertrophic and dilative cardiomyopathies, valvular and ischemic heart disease. MRI is a totally noninvasive diagnostic technique which is safe and without known harmful potential to biological tissue. The wide diagnostic spectrum providing anatomical, geometrical functional and biochemical information cannot be accomplished by any other diagnostic method.

Cardiovascular Diseases↗

PubMedDate not supplied

Visualization of barrier tree sequences.

Dynamical models that explain the formation of spatial structures of RNA molecules have reached a complexity that requires novel visualization methods that help to analyze the validity of these models. Here, we focus on the visualization of so-called folding landscapes of a growing RNA molecule. Folding landscapes describe the energy of a molecule as a function of its spatial configuration; thus they are huge and high dimensional. Their most salient features, however, are encapsulated by their so-called barrier tree that reflects the local minima and their connecting saddle points. For each length of the growing RNA chain there exists a folding landscape. We visualize the sequence of folding landscapes by an animation of the corresponding barrier trees. To generate the animation, we adapt the foresight layout with tolerance algorithm for general dynamic graph layout problems. Since it is very general, we give a detailed description of each phase: constructing a supergraph for the trees, layout of that supergraph using a modified DoT algorithm, and presentation techniques for the final animation.

Base Sequence↗

PubMed2006

Evidence of the activity of dissimilatory sulfate-reducing prokaryotes in nonsulfidogenic tropical mobile muds.

In spite of the nonsulfidic conditions and abundant reactive iron(III) commonly found in mobile tropical deltaic muds, genes encoding dissimilatory sulfite reductase (dsr) were successfully amplified from the upper approximately 1 m of coastal deposits sampled along French Guiana and in the Gulf of Papua. The dsr sequences retrieved were highly diverse, were generally represented in both study regions and fell into six large phylogenetic groupings: Deltaproteobacteria, Thermodesulfovibrio groups, Firmicutes and three groups without known cultured representatives. The spatial and temporal distribution of dsr sequences strongly supports the contention that the sulfate-reducing prokaryote communities in mobile mud environments are cosmopolitan and stable over a period of years. The decrease in the (35)SO(4) (2-) tracer demonstrates that, despite abundant reactive sedimentary iron(III) ( approximately 350-400 mumol g(-1)), the sulfate-reducing prokaryotes present are active, with the highest levels of sulfide being generated in the upper zones of the cores (0-30 cm). Both the time course of the (35)S-sulfide tracer activity and the lack of reduced sulfur in sediments demonstrate virtually complete anaerobic loss of solid phase sulfides. We propose a pathway of organic matter oxidation involving at least 5-25% of the remineralized carbon, wherein sulfide produced by sulfate-reducing prokaryotes is cyclically oxidized biotically or abiotically by metal oxides.

Anaerobiosis↗

PubMed1994

Transcriptional regulation of string (cdc25): a link between developmental programming and the cell cycle.

During postblastoderm embryogenesis in Drosophila, cell cycles progress in an invariant spatiotemporal pattern. Most of these cycles are differentially timed by bursts of transcription of string (cdc25), a gene encoding a phosphatase that triggers mitosis by activating the Cdc2 kinase. An analysis of string expression in 36 pattern-formation mutants shows that known patterning genes act locally to influence string transcription. Embryonic expression of string gene fragments shows that the complete pattern of string transcription requires extensive cis-acting regulatory sequences (> 15.3 kb), but that smaller segments of this regulatory region can drive proper temporal expression in defined spatial domains. We infer that string upstream sequences integrate many local signals to direct string's transcriptional program. Finally, we show that the spatiotemporal progression of string transcription is largely unaffected in mutant embryos specifically arrested in G2 of cycles 14, 15, or 16, or G1 of cycle 17. Thus, there is a regulatory hierarchy in which developmental inputs, not cell cycle inputs, control the timing of string transcription and hence cell cycle progression.

Animals↗

PubMed1986

[Cognition of binary-event-sequences: its relation to the sequential attributes].

Sixty subjects were asked to evaluate the degree of similarity among 15 binary-event-sequences which were generated through the Bernoulli process. The averaged similarity matrix of 50 subjects (ten omitted) was analysed by the Hayashi's Quantification Method IV, and the dimensions yielded were compared with the theoretically derived dimensions for the operational interpretation. The result showed that the run structure--the number of runs and the length of the longest run--and the number of one event in a sequence were the important attributes in cognition of binary-event-sequences. These attributes were most frequently employed by subjects, although other attributes and their combinations may be relevant. It was pointed out that the general tendency of judgments, i.e., dependence on the spatial and visual aspects of given sequences, proved subjects' inattention to the characteristics of the probabilistic generation process of sequences.

Cognition↗