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Results for “spatial dependency”

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At least 37 records · Page 2Linked to original sources
PubMed2026

Direct visualization of MCM helicase activation and replisome coupling in situ.

Deciphering the spatial organization of molecular machines that copy the genome remains a fundamental challenge in biology. Essential for eukaryotic DNA replication, Mini-Chromosome Maintenance (MCM2-7) helicases are loaded during G1 as double hexamers (DHs) to license replication origins. Upon activation in S phase, each DH is thought to split into two single hexamers (SHs) that form the active CMG helicases and travel bidirectionally. However, the field has long been divided: biochemical and structural studies define CMG helicases as autonomous, independent motors, while genomic and cellular imaging assays suggest sister replisomes remain physically coupled within replication factories. Here, we use MINFLUX nanoscopy to localize individual MCM complexes down to nanometer precision in situ, directly resolving DHs in human cells and capturing their separation into SHs upon origin firing. We find that the resulting sister replisomes do not diffuse apart: they remain coupled at a characteristic distance of ~40 nm throughout S phase. Depletion experiments identify two distinct contributions to this coupling: local, protein-mediated tethering by the AND1 scaffold, and higher-order spatial confinement dependent on cohesin, which is dispensable for MCM loading in G1 but required to maintain coupling in S phase. By linking the nanometer-scale architecture of the replisome to the genome-wide topology of replication fountains, these findings provide direct spatial evidence that sister forks are coupled during DNA synthesis and define the molecular forces that organize replisomes within their native nuclear context.

DNA replication↗
PubMed1979

Proprioceptive influences on directional hearing: dependence on the movement type.

Proprioceptive effects (PE) on directional hearing, i.e., sound image shifts relatively to the sound source, produced by changes in head position, were studied in their dependence on head movement type in two groups of listeners. The first group included subjects in whom horizontal head deviation to the right or to the left, performed on instruction before the presentation of clicks, caused sound image displacement of 10-15 degrees. When the same sounds were made signals of movement direction, i.e., of pointing with the head at the sound source, PE became fully inhibited in all subjects. The second group included listeners in whom PE was either absent or only very small; substitution of passive head deviations for active turns resulted (in 63 percent of cases) in PEs which presumably had been previously inhibited. Thus identical muscle activities play different roles in auditory spatial perception depending on the type of movement and on the significance of the acoustic signal for the motor act.

Auditory Perception↗
PubMed1977

Influence of hydrogen bonding on the rotamer distribution of the histidine side chain in peptides: 1H NMR and CD studies.

Both 1H NMR and circular dichroism pH titration studies on histidine, His-Gly, Gly-His and Gly-His-Gly indicate that the side-chain spatial orientation depends strongly on the vicinal charges. The arrangement of the imidazole side-chain (rotamer population) is shown by the histidine beta and beta' and the glycine methylene proton chemical shifts as well as the vicinal 1H-1H coupling constants 3JCalpha-H-beta-H, beta'-H. For His-Gly and Gly-His-Gly a good correlation can be found between the ionization of the glycine COOH group and the increase of rotamer III (g-g) which is also visualized by circular dichroism through an enhancement of the ellipticity at 212 nm. In these two peptides a hydrogen bond between the imidazolium and the carboxylate group is supposed to stabilize rotamer III at pH 4-5.

Circular Dichroism↗
PubMed1979

A colour-dependent abnormality in human visual detection of stimulus motion and spatial structure.

We have studied the wavelength dependence of visual responses in a single human subject, M.W., who has an unusual visual defect. It is shown that for red stimuli, both spatial resolution for grating patterns and detection of target movement are grossly abnormal. On the basis of these and other [8] experimental data, we argue that M.W.'s response pattern implies interdependent central visual processing of colour, movement and spatial structure. We examine this conclusion in relation to recent anatomical and electrophysiological findings.

Color Perception↗
PubMed1977

Field-dependence-independence and lateral eye movements following verbal and spatial questions.

In three studies a small positive relationship was found between field-dependent cognitive style and the tendency to give a higher percentage of right lateral eye movements to verbal than to spatial questions. However, in only one of the three studies was the relationship significant (r = .32, n = 52). It is concluded that differences among samples in cognitive style probably cannot account for different patterns of results in studies of lateral eye movement.

Eye Movements↗
PubMed1976

Space representation in unilateral spatial neglect.

Patients with unilateral brain lesions were given a task requiring exploration of space with the hand in order to assess the visual dependency of unilateral spatial neglect. The task was carried out both without visual control and under visual control. Performances were compared with that of normal subjects. Results were :(1) patients with right brain damage with no visual field defect demonstrated left-sided neglect only when the exploration was not controlled visually; (2) patients with left and right brain damage with visual field defect demonstrated contralateral neglect only when the exploration was under visual guidance. The performance of the patients with right brain damage without visual field defect in not clearly understood. The other results suggest that inner spatial representation remains intact in most cases of spatial neglect. The role of parietal lobe damage in the development of this visually induced phenomenon is hypothesised. The dominant position of vision among the senses is indicated.

Adolescent↗
PubMedDate not supplied

[Analysis of spatial frequency characteristics of complex receptive fields].

The difference fB2-fB1=deltaf and ratio fB2/fB1=R of the bandwidth boundary frequencies fB1, fB2 of spatial frequency characteristic of complex receptive field depends on the size of RF and spatial structure of excitatory and inhibitory zones. deltaf and r are independent of the weighting functions of excitatory and inhibitory zones. The theoretical value of r is similar to data which was obtained in psychophysical and physiologycal experiments. The dependence of contrast sensitivity on spatial frequency can be explained by dependence of the envelope of weighting functions of exitatory (inhibitory) zones on the spatial frequency.

Animals↗
PubMed1978

[Electrophysiological methods of assessing myocardial hypoxia].

The potentialitis of the standard electrocardiogram, precordial cartogram and spatial analysis are confronted in 38 patients with extensive anterior or anteroseptal myocardial infarction, acute phase, in order to determine the extent and propagation of the myocardial hypoxia. The determination is performed on the base of the correlation dependence as regards the creatinine-phosphokinase level in blood. The best degree of correlation dependence has the spatial analysis of the changes in the segment ST - Vmax ST sp. r=0.69, as well as the changes in the segment ST reflected in the precordial electrocardiography - nST-0.1 mv. r=0.67. Close is the degree of correlation dependence in the standard electrocardiogram - STv r=0.59. The difference in the correlation coefficients are not statistically significant, allowing their application in the routine work of the three methods.

Acute Disease↗
PubMed1978

Children's use of spatial prepositions in two- and three-dimensional tasks.

This study evaluates children's performance on selected spatial prepositions and determines the age levels these prepositions are acquired in both receptive and expresive language, as revealed in tasks involving both two- and three-dimensional objects. Subjects were 80 children (40 males and 40 females), ranging in age from three years to four years and eleven months. All were native English speakers with no speech, hearing, or neurological disorders, and with normal intelligence. Results indicated a significant difference in test scores according to age (older children perform better than younger), task (comprehension scores higher than production scores), referent (three-dimensional tasks showing higher scores than two-dimensional tasks), and preposition. Children's use of selected spatial prepositions is dependent on the semantic complexity of the preposition. Prepositions whose meanings can be described in terms of simple topological notions are understood and used with greater facility than those involving dimensional or Euclidean spatial notions. When the prepositional variable interacts with age, dimension, task, age + dimension, age + task, dimension + task, and age + dimension + task, overall differential response are likely to occur.

Age Factors↗
PubMed1978

Possible role of transient and sustained visual mechanisms in the determination of similarity judgments.

Two studies examined the role played by transient and sustained visual mechanisms in the determination of similarity judgments produced in response to pairs of geometrical stimuli. In two experiments, subjects were trained to attend to two dimensions of a set of stimuli and to assign similarity ratings with respect to those two dimensions only. An INDSCAL multidimensional scaling analysis of the subsequent similarity ratings showed that subjects emphasized global blob, or low spatial frequency-dependent, dimensions of the stimuli when they were presented for brief durations (20 msec.), irrespective of the dimensions to which the subjects and had been trained to attend. This finding suggested that low spatial frequency selective transient mechanisms dominated the perceptual processes which underlie the similarity judgments. When the stimulus duration was raised to 50 msec. so that sustained mechanisms could also make a signficicant contribution to the perceptual processes underlying the similarity judgments, subjects emphasized only those dimensions on which they had been trained. The implications of the present findings for the concepts of selective attention and automatic activation were discussed.

Attention↗
PubMed2026

Emerging Principles in Spatial Functional Genomics.

Spatial transcriptomic and proteomic atlases have enabled mapping of gene programs within intact tissues, but these measurements remain largely descriptive and do not define the mechanisms controlling tissue biology. Pooled CRISPR screening provides scalable causal interrogation of gene function but remains largely confined to dissociated systems that lack spatial context. In vivo spatial functional genomics (SFG) bridges these approaches by integrating genetic perturbations with in situ transcriptomic and proteomic readouts to measure gene function within intact tissue ecosystems. By preserving spatial organization, SFG enables interpretation of perturbations through effects on cell-cell interactions, diffusible signals, multicellular niches, and tissue architecture. Here, we outline key design axes of SFG: perturbation strategy, barcoding strategy, and phenotypic readout. We discuss computational challenges, including spatial autocorrelation, neighborhood dependence, and context-aware null modeling, and highlight how SFG reveals non-cell-autonomous, architecture-dependent mechanisms of gene function, advancing toward predictive models of tissue organization and gene function.

Genomics↗
PubMed1976

[Conformational heterogeneity of tRNA, detected in the reaction of guanine bases with ketoxal].

The study of kinetic characteristics of the reaction of tRNA guanine bases with kethoxal has shown that temperature, ionic strength and Mg2+ ions, i.e. factors directly affecting the spatial structure of tRNA, influence also on its internal modification. The modification degree under stabilized spatial tRNA structure depends also on the concentration of kethoxal and is expressed in fractional values of the number of modified guanosine residues per tRNA molecule, which indicates the heterogeneity of tRNA for the modification degree. Chromatography of tRNA1 Val preparation on BD cellulose after the exhaustive modification with kethoxal under conditions of stabilized spatial structure has revealed a fraction of molecules completely resistant to the modificator, and a fraction containing differently modified tRNA molecules. tRNA heterogeneity after the reaction with kethoxal (the presence of resistant and reactive forms) indicates conformational heterogeneity of tRNA, expressed in the simultaneous presence of at least two conformer families.

Aldehydes↗
PubMed2026

Impact of spatial distribution of M2 macrophages on prognosis and neoadjuvant chemotherapy resistance in gastric cancer.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is a crucial treatment for locally advanced gastric cancer; however, approximately 30-40% of patients experience primary resistance, the mechanisms of which urgently require elucidation. The tumor microenvironment exhibits a high degree of spatial heterogeneity. M2 macrophages, as critical immune cells within this environment, are typically associated with poor prognosis. Yet, whether their spatial distribution impacts chemotherapy efficacy remains unclear. This study aims to investigate the relationship between the in situ spatial distribution characteristics of M2 macrophages and chemoresistance in gastric cancer. METHODS: Based on The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) cohort, the association between M2 markers (CD163, MRC1) and histological grade as well as overall survival (OS) was evaluated. Spearman correlation and functional enrichment analyses were conducted to explore the mechanistic link between M2 macrophages and stromal barrier construction. Multiplex immunofluorescence (mIF) and digital pathology image analysis were utilized to calculate the areal density of M2 macrophages in the intratumoral core and the peritumoral stroma, respectively. The tumor-to-peritumoral ratio (TPR) was constructed, followed by a rank correlation analysis between TPR and the tumor regression grade (TRG). RESULTS: TCGA-STAD results confirmed that patients with high expression of M2 markers had worse OS (P=0.03), and the expression levels of M2 markers increased with histological grade. MRC1 was highly significantly and positively correlated with the pro-fibrotic factor TGFB1 (rho=0.447, P<0.001), with the gene set significantly enriched in pathways such as positive regulation of cytokine production and myeloid leukocyte activation. Histological examination revealed that in chemoresistant patients (TRG 3), M2 macrophages were primarily retained in the peritumoral stroma, with a median TPR of 0.50; in chemosensitive patients (TRG 1-2), a massive influx of M2 macrophages into the tumor core was observed, with a median TPR of 6.67. TPR was negatively correlated with TRG (rs=-0.65, P=0.043). CONCLUSIONS: The clinical impact of M2 macrophages in the gastric cancer microenvironment is highly dependent on their spatial distribution. The peritumoral-enriched pattern (TPR <1) mediates primary chemoresistance, whereas high infiltration in the core objectively reflects the pathological footprint following effective chemotherapy. The TPR serves as a novel tool for assessing neoadjuvant chemosensitivity in gastric cancer.

Gastric cancer (GC)↗
PubMed2026

A systematic review and meta-analysis of visuospatial attentional deficits in Parkinson's patients.

Parkinson's disease (PD) is a neurodegenerative condition primarily characterized by motor deficits, yet cognitive impairments are increasingly recognized. While deficits in executive functioning are well documented even in the absence of cognitive decline, evidence of attentional deficits in PD remains inconsistent, and the role of motor symptom lateralization is unclear. In this systematic review and meta-analysis, we examined visual attention in right-handed, cognitively unimpaired idiopathic PD patients, focusing on the canonical attentional domains (sustained, selective, divided) and processes (alerting, endogenous and exogenous orienting, reorienting), as well as visuospatial bias. Four databases were searched for studies comparing PD patients with healthy controls. Meta-analytic estimates were derived using Hedges' g within random-effects models, and studies that could not be quantitatively integrated were summarized narratively. In addition, studies directly comparing patients with left- and right-predominant motor symptoms (LPD vs. RPD) were reviewed qualitatively. Across 51 studies, PD patients exhibited deficits in sustained, selective, and divided attention. Among attentional processes, only exogenous orienting was impaired, whereas alerting, endogenous orienting, and reorienting were preserved. Findings from the few studies examining visuospatial bias indicated small, context-dependent shifts in spatial attention rather than a consistent directional bias. These findings indicate that PD patients show visual-attentional impairments, particularly under high-demand conditions, while basic alertness and voluntary orienting appear preserved. Exogenous orienting deficits and subtle rightward spatial tendencies in LPD suggest disruption of right-hemisphere attentional networks. These results have implications for early cognitive assessment, rehabilitation strategies, and understanding the neural bases of attentional dysfunction in PD.

Humans↗
PubMed1979

Pattern and flicker detection examined in terms of the nasal-temporal division of the retina.

Contrast thresholds for the detection of flicker and the detection of pattern were measured for nasal and temporal retinae of each eye separately. While confirming that these two types of threholds can differ, depending on the spatial frequency, the results provide no support for hemiretinal or hemispheric asymmetries in the distribution of the putative pattern and movement channels.

Discrimination Learning↗
PubMed1975

Antibody nature of circulating inhibitor of plasma von Willebrand factor.

A circulating plasma inhibitor of the "von Willebrand factor" was observed in a multiply tranfused subject with severe von Willebrand's disease. The platelet-active von Willebrand factor is associated with a plasma protein macromolecular complex that is deficient in the disease. The inhibitor appears to be an IgG antibody, kappa type, based on neutralization tests with goat antisera to specific human immunoglobulins. The IgG and inhibitor separated out together in plasma fractions obtained by "salting-out" and chromatographic procedures. Two separate inhibitor neutralization tests for the platelet-active factor, one with human plasma and ristocetin, the other with bovine plasma, gave similar results, based on the macroscopic aggregation time test of fixed human platelets. With cryoprecipitate transfusions the inhibitor was transiently neutralized with the temporary appearance of von Willebrand factor, factor VIII, and factor VIII-like antigen in the plasma. The plasma inhibitor level increased after transfusion, suggesting an anamnestic response. Lower titer inhibitor plasmas neutralized only the platelet activity. Highest titer plasma also neutralized human factor VIII, but only in part; it did not neutralize either bovine factor VIII or the human small active factor VIII fragment. The anti-factor VIII activity of the von Willebrand factor inhibitor may be due to steric hindrance, dependent on the spatial relationship of factor VIII sites on the macromolecular complex.

Animals↗