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At least 19 recordsLinked to original sources
PubMed2026

ARCADIA reveals spatially dependent transcriptional programs through integration of scRNA-seq and spatial proteomics.

MOTIVATION: Cellular states are strongly influenced by spatial context, but single-cell RNA sequencing (scRNA-seq) loses information about local tissue organization, while spatial proteomic assays capture limited marker panels that constrain transcriptomic inference. Integrating these modalities can elucidate how spatial niches shape transcriptional programs, yet existing approaches depend on either feature-level correspondence such as gene-protein linkage or cell-level barcode pairing, which is often unavailable. RESULTS: We present ARCADIA (ARchetype-based Clustering and Alignment with Dual Integrative Autoencoders), a generative framework for cross-modal integration that operates without cell barcode pairing and does not assume direct feature-to-feature correspondence. ARCADIA identifies modality-specific archetypes, that is, convex combinations of cells representing extreme phenotypic states, and aligns these anchors across modalities by minimizing the discrepancy between their cell-type composition profiles. The aligned archetypes define a shared coordinate system that anchors dual variational autoencoders (VAEs) trained with cross-modal geometric regularization, preserving archetype structure and spatial neighborhood information while enabling bidirectional translation between modalities. On semi-synthetic CITE-seq data, ARCADIA outperforms existing weak-linkage methods. Applied to independent human tonsil scRNA-seq and CODEX data, ARCADIA reconstructs known tissue architecture and reveals spatially dependent transcriptional programs linking B-cell maturation and T-cell activation or exhaustion to microenvironmental niches. AVAILABILITY AND IMPLEMENTATION: Source code is accessible at https://github.com/azizilab/ARCADIA_public. Reproducibility scripts and data are available at https://github.com/azizilab/arcadia_reproducibility.

Proteomics↗
PubMed1992

Spatially dependent deadtime losses in high count rate cardiac PET.

Cardiac PET scans result in nonhomogeneous distributions of activity within the body, which might lead to great variations in singles rates around the detector ring. Conventional deadtime correction algorithms assume that the singles rates are uniform. This paper investigates singles nonuniformities during several typical cardiac scanning protocols (bolus injections of 15O-water and 82Rb, slow infusion of 18F-FDG and static imaging with FDG) and estimates how such nonuniformities might affect quantitative data. Nonuniformity was observed in all studies and was described by an asymmetry index which increased to 58% during bolus water injection, the most inhomogeneous study. These results are valid for any scanner with a ring diameter of approximately 78 cm and are independent of the amount of activity injected. Deadtime losses depend on the amount of activity and on the scanner type. Nonhomogeneities in singles can be shown to produce spatially dependent deadtime correction factors; for our scanner, these were seen to differ by up to 16% from the mean deadtime correction during bolus water injection. To demonstrate the distortions generated by average deadtime correction, the activity distribution during a clinical cardiac study was simulated using a phantom. A simple local deadtime correction and its implementation on our system are described, and the resulting improvements in both absolute and relative quantitation of the phantom study are shown.

Deoxyglucose↗
PubMed1992

Analysis of the temporal and spatial dependence of the eddy current fields in a 40-cm bore magnet.

Eddy current fields, generated in an animal-size superconducting NMR magnet by a nominally rectangular pulsed transverse gradient applied in the vertical direction, have been studied by measuring the offset frequency of the proton NMR signal obtained from a small spherical sample. Measurements were made, after various time delays, at nine different locations in the sample space. Analysis of the data shows that the time-dependent fields at all nine locations are quite well accounted for by the superposition of only four independent exponentially decaying components that have time constants in the range from 9 to 400 ms. Two of these were found to be caused by eddy currents generated in the magnet structure. They generate primarily linear gradients, though one of them also produces a B0 shift, indicating a significant asymmetry about the isocenter of the conducting structure in which the eddy current flows. The other two exponentially decaying components, which had very different time constants from the eddy currents and also initial amplitudes of the opposite sign, were generated by the preemphasis unit. This calls into question the procedure used to adjust the preemphasis unit and an alternative method is proposed.

Artifacts↗
PubMed1976

Electrophysiological basis for the spatial dependence of the inhibitory coupling in the Limulus retina.

A technique for measuring, with total optical isolation, the inhibition between two individual receptor units in the Limulus lateral eye is described. The extracellular responses of pairs of units were recorded, using light piping microelectrodes. The inhibitory coupling between two units was found to be nonlinear and describable by a simple hyperbolic equation written in terms of saturation rate (S), half saturation (H), and threshold (ft). By plotting reciprocal frequencies, the data could be linearized and compared for different pairs of units. The magnitude of inhibition (in terms of S and H) was found to decrease monotonically as the anatomical distance between receptors increased. An electrical model of the inhibitory system was developed which accounts for many of the properties of the observed inhibitory interactions. Using the equations from the model and the experimental data, it is shown that the "electrical distances" (which are computed in terms of space constants lambda) of the inhibitory synapses from the impulse-generating region of the test unit are directly related to the anatomical distance between receptors. It is also shown that "synaptic strength" is relatively constant with separation. The electrical distances of the inhibitory synapses range from about 0.1lambda to 0.25lambda for adjacent units to greater than 0.5lambda for units seven to nine receptors away. It is concluded that the nonlinear character of the inhibitory coupling is attributable to synaptic effects, and that the decrease of inhibition with distance between receptors is caused primarily by an increase in the electrical distance of the inhibitory synapses from the test unit.

Animals↗
PubMed1977

A study of X chromosome linkage with field dependence and spatial visualization.

The purposes of this report are to describe a design for the study of X linkage, to illustrate its application using cognitive test scores, and to offer a linkage hypothesis suggested by these data. Sixty-seven three-son families were examined for two X chromosome marker variables--red-green color vision and Xg(a) blood groups--and given a battery of cognitive tests of field dependence and spatial visualization abilities. Evidence was found to suggest that brothers who are identical in Xg(a) phenotype are more similar to each other in extent of field dependence than brothers who are different in Xg(a) phenotype. This result is tentative because of the small number of informative cases and the many linkage associations examined. If cross-validated, such a finding would be consistent with the proposition that an X chromosome gene contributes to the field dependence cognitive style.

Blood Group Antigens↗
PubMed1992

Effects of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP)-induced hemiparkinsonism on the kinematics of a two-dimensional,multijoint arm movement in the rhesus monkey.

The effects of the selective dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) on the kinematics of two-dimensional arm movements in the primate were studied. Two rhesus monkeys were trained to move a manipulandum at various distances and directions in horizontal space from a centrally located target box. Several kinematic parameters including reaction time, and time and amplitude of peak tangential velocity were analysed. Following an extensive control evaluation period, the animals were unilaterally injected with MPTP into the internal carotid artery. The animals were restudied for up to 289 days following induction of hemiparkinsonism. Larger-amplitude movements (greater than 3.5 cm) were more severely affected than smaller amplitude movements. Both animals exhibited marked changes in the arm movements including increased time-to-peak velocity and decreased peak velocity. The degree of the kinematic changes was spatially dependent, with the decrease in velocity as well as the time-to-peak velocity being more pronounced for the larger, outward movements. Reaction time increased but showed no spatial dependency. Kinematic deficits persisted over the entire time-period studied. Also, the kinematic changes were reduced by levo-3,4 dihydroxyphenylalanine in a dose-dependent manner. Tyrosine hydroxylase immunohistochemistry documented extensive cell loss in the substantia nigra. These results show that both the timing as well as the amplitude of the velocity profiles are disrupted by MPTP consistent with the known akinesia and bradykinesia of parkinsonism. Although abnormalities were present for all directions and distances, a spatial dependency to the deficits was detected. The observation of more pronounced changes for larger, outward movements suggests a role for the basal ganglia in production of larger-amplitude movements directed away from the body.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1992

Stimulus mislocalization depends on spatial frequency.

It was previously reported that briefly presented peripheral stimuli are perceived closer to fixation than continuously presented stimuli at the same eccentricity; this effect has, however, not proved consistently replicable. In this study it was investigated whether the misperception of location might depend upon the spatial frequency content of the stimulus. Spatial-frequency-filtered vertical bars were displayed briefly and their locations were judged relative to continuously visible comparison spots. For monocular stimuli, a significant foveopetal mislocalization of the bar was obtained that increased in size as spatial frequency was lowered. Even larger mislocalizations were obtained for dichoptically presented horizontally disparate pairs of bars, and this effect also increased at low spatial frequencies. Possible underlying mechanisms are discussed, and spatial frequency is suggested to have been the confounding factor in previous studies.

Eye Movements↗
PubMed2026

transFusion: a novel comprehensive platform for integration analysis of single-cell and spatial transcriptomics.

MOTIVATION: Understanding spatial organization, intercellular interactions, and regulatory networks within the spatial context of tissues is crucial for uncovering complex biological processes and disease mechanisms. Spatial transcriptomics technologies have revolutionized this field by enabling the spatially resolved profiling of gene expression. 10× Visium has emerged as the predominant spatial technology, but its low resolution and the complexity of integrating multimodal datasets present significant analytical challenges, particularly for researchers with limited computational and statistical expertise. Current spatial transcriptomics analysis platforms generally fall short of effectively integrating multimodal data and maximizing the utility of spatial information-such as uncovering complex cellular spatial dependencies, multimodal gradient patterns, and spatial coexpression of ligand-receptor pairs and regulatory networks related to disease or biological states-thereby limiting their ability to provide comprehensive end-to-end analytical workflows when analyzing 10× Visium data. RESULTS: To address these limitations, we developed transFusion, a novel, advanced web-based platform specializing in the most comprehensive and effective integration analysis of scRNA-seq and 10× Visium spatial transcriptomics data. transFusion offers 12 key functions, from basic visualization to advanced analyses, including intercellular dependency analysis, ligand-receptor coexpression identification and visualization, and spatial multimodal gradient variation patterns. Two case studies were used to demonstrate transFusion's capabilities in exploring tissue architecture, intercellular communication, dependency networks, and multimodal gradient variation patterns with minimal computational skills and statistical expertise. transFusion provides a flexible and powerful framework for multimodal data integration analysis. AVAILABILITY AND IMPLEMENTATION: transFusion is freely available at https://github.com/WQLin8/transFusion.

Spatial Transcriptomics↗
PubMed2026

A divide and conquer strategy for recapitulating whole genome 3D structure using Hi-C data.

The three dimensional (3D) spatial organization of the genome is closely linked to biological functions and can be captured by Hi-C assays through interrogating genome-wide chromatin interactions. Methodologies for inferring 3D structures from Hi-C data summarized as a two-dimensional (2D) contact matrix can be broadly placed within the paradigms of optimization-based and sampling-based. Many optimization-based methods are capable of constructing whole genome 3D structures but do not account for spatial dependency in the 2D data matrix nor cell heterogeneity in bulk Hi-C data, which provide an average over millions of cells. Sampling-based methods, on the other hand, are probabilistic model-based and can account for not only dependency, heterogeneity, but also other features inherent in Hi-C data, such as over-dispersion and sparsity. However, whole-genome 3D structure recapitulation is too computationally expensive for sampling-based methods, while chromosome-by-chromosome strategies for sampling-based methods ignore important information on inter-chromosomal contacts. To address these issues, we propose the truncated Random effect EXpression-cut and paste (tREX-cap) method, which applies the tREX model within a divide and conquer strategy. The resulting method inherits the good data-feature-cognizant properties of tREX and, in the meantime, can efficiently infer the whole genome 3D structure. We demonstrate the performance of tREX-cap through an extensive simulation study and analyses of a Hi-C lymphoblastoid dataset and a Hi-C IMR90 dataset.

Humans↗
PubMed1977

Perceived lightness depends on perceived spatial arrangement.

The perceived shade of gray depends primarily on the luminance relationship between surfaces percieved to lie in the same plane and not between surfaces that are merely adjacent in the retinal image. This result implies that depth perception must precede lightness perception and that lateral inhibition cannot explain lightness constancy.

Depth Perception↗
PubMed1992

Effects of variations in the duration of diffusible-tracer infusions on calculated values of global and local cerebral blood flow.

Using dual tracer quantitative digital autoradiography and iodoantipyrine (IAP), we compared local cerebral blood flow (LCBF) measurements using two different infusion times within the same animal. Rats were given concurrent infusions of 14C-IAP and 123I-IAP; one tracer was administered over 20 seconds and the other over 40 seconds. Pairs of autoradiograms, one representing predominantly 123I and the other 14C, were then produced from 20 micron-thick brain sections and images from each section were digitized and processed to produce pairs of digital images of LCBF. The corresponding LCBF images were compared quantitatively on a pixel-by-pixel basis. Global LCBF values were greater (28%) at 20 seconds compared to 40 seconds, consistent with the previously reported "falling flow" phenomenon. Perhaps more importantly, the actual pattern of LCBF differed in certain regions such as the cortex, hippocampus, thalamus, and cerebellum between the two time points. In other words, the quantitative patterns of calculated LCBF values were dependent upon the duration of tracer infusion, even when the infusion times were kept below recommended limits (45 seconds). Thus, errors in LCBF measurements may occur in certain structures even in brief experiments. Because these errors are spatially dependent rather than blood flow dependent, there is presently no model which can be globally applied to the brain to correct them.

Animals↗
PubMed1992

Oscillations in a model of repression with external control.

A mathematical model for control by repression by an extracellular substance is developed, including diffusion and time delays. The model examines how active transport of a nutrient can produce either oscillatory or stable responses depending on a variety of parameters, such as diffusivity, cell size, or nutrient concentration. The system of equations for the mathematical model is reduced to a system of delay differential equations and linear Volterra equations. After linearizing these equations and forming the limiting Volterra equations, the resulting linear system no longer has any spatial dependence. Local stability analysis of the radially symmetric model shows that the system of equations can undergo Hopf bifurcations for certain parameter values, while other ranges of the parameters guarantee asymptotic stability. One numerical study shows that the model can exhibit intracellular biochemical oscillations with increasing extracellular concentrations of the nutrient, which suggests a possible trigger mechanism for morphogenesis.

Bacterial Physiological Phenomena↗
PubMed2026

A host-encoded prophage targets a Candidate Phyla Radiation bacterium and shapes episymbiotic interactions.

The Patescibacteriota, also known as the Candidate Phyla Radiation (CPR), represent a large lineage of ultrasmall bacteria with highly reduced genomes and obligate dependence on bacterial hosts. Although genomic analyses have revealed CRISPR-Cas and restriction-modification systems in many CPR genomes, no cognate bacteriophages (phages) have been isolated, leaving CPR-phage interactions unexplored. Nanosynbacter lyticus TM7x, the first cultivated CPR bacterium, grows episymbiotically on its host, Schaalia odontolytica XH001, in the human oral microbiome. Here, we identify Xhp1, an inducible prophage of XH001 that is preferentially activated during episymbiosis with TM7x. Released Xhp1 particles infect prophage-free XH001 via distinct strategies determined by host growth mode, establishing lysogeny under planktonic conditions but driving lytic infection during surface-associated growth. Xhp1 also binds efficiently to TM7x and exhibits limited infection under the conditions tested, indicating direct phage-CPR interactions. Importantly, TM7x modulates Xhp1 availability in a spatially dependent manner. In planktonic culture, free-floating TM7x reduces lysogenic conversion of XH001ΔXhp1, consistent with TM7x acting as a phage sink that lowers effective phage concentration. In contrast, during surface-associated growth, TM7x increases XH001ΔXhp1 susceptibility to lytic infection, likely by locally concentrating phage particles within a constrained niche. These results demonstrate that CPR bacteria can regulate viral encounter rates through spatial organization. In spatially structured environments such as oral biofilms, such modulation may shape infection dynamics and community structure. Together, this work characterizes the first CPR-targeting phage and reveals a an important role for phages in CPR-host bacteria interactions.

Prophages↗
PubMed1992

Phase delay of pulmonary acoustic transmission from trachea to chest wall.

The frequency-dependent propagation time, or phase delay tau (f), of sonic noise transmission from the trachea to the chest wall was estimated over the 100-600 Hz frequency range using a phase estimation technique from measurements performed on eight healthy subjects. Since tau (f) can be greater than one period of the input signal at frequencies greater than 100 Hz, the unambiguous phase estimate at 100 Hz was used as a starting-point to determine the phase angle H(f) and tau (f) at higher frequencies under the constraint that the spectra did not exhibit large point-to-point discontinuities. The resulting tau (f) range of 0.9-4.1 ms is consistent with sound propagation to the chest wall through both airways and surrounding parenchyma. The frequency and spatial dependence of tau (f) indicates that with increasing frequency more sonic energy travels further into the branching airway structure before coupling into the parenchyma. These results suggest that information concerning distinct regional lung structures may be obtained by probing the system acoustically over selected frequency bands.

Acoustics↗
PubMed1992

Intensity artifacts in MRI caused by gradient switching in an animal-size NMR magnet.

The switching of magnetic field gradients in MRI gives rise to eddy currents in the structural components of superconducting magnet systems. The associated magnetic fields cause intensity artifacts which are particularly severe in some animal-size systems. We treat theoretically three mechanisms which cause intensity artifacts in one-dimensional projection images obtained by a spin-echo technique. The first is an off-resonance effect, caused by applying the refocusing pulse before the read compensation gradient pulse has decayed sufficiently. The other two mechanisms are caused by a spatial dependence of the phase accumulated by the spins at the time of formation of the echo, as a result of the eddy current fields. First, interference causes a loss of transverse magnetization because of a variation in the phase of spins which lie on the same isochromat during the read gradient pulse. Second, a variation of the phase of the spins in a direction orthogonal to the isochromats causes spins throughout the sample to refocus at different times. These two mechanisms are fundamentally different, since interference can occur even if the main magnetic field is homogeneous, whereas improper refocusing does not. It is shown that there is no loss of intensity by the interference mechanism if phase encoding is used to form two-dimensional images. This may well be a major reason why images obtained by 2DFT have been found to be generally superior to those obtained by projection reconstruction. Experimentally, the distribution of intensity in one-dimensional projection images of a square slice phantom is compared with theoretical intensities, estimated using eddy current field reported in the preceding paper.

Artifacts↗
PubMed1992

Sarcolemmal calcium binding sites in heart: II. Mathematical model for diffusion of calcium released from the sarcoplasmic reticulum into the diadic region.

We present a model for predicting the temporal and spatial dependence of [Ca] in the cardiac subsarcolemmal diadic region (cleft), following Ca release from the "feet" of the sarcoplasmic reticulum. This region is modeled as a disc 10 nm thick, 430 nm in radius, with or without Ca binding sites and open at its periphery to the cytosol. [Ca] is computed for three diffusion coefficients (100, 20 and 4% of aqueous diffusion), following release of a 20-msec square pulse sufficient to produce 50% maximal contractile force, or repetitive release (400/min) of such pulses. Numerical solutions are obtained for the general diffusion/binding problem and analytic solutions for the case of no binding sites. For the middle value of diffusion coefficient, and in the absence of binding sites, [Ca] rises to approximately 1.5 mM in 20-msec and then falls to approximately 0.1 microM in less than 3 msec. Adding binding sites reduces peak [Ca] to approximately 0.6 mM but prolongs its decline, requiring approximately 200 msec to reach 20 microM. For repetitive release [Ca] is greater than 100 microM for roughly half of each cycle. Two major implications of the predicted [Ca] are: (i) The effect of Ca binding sites on [Ca] will cause Ca efflux from the cleft via the Na-Ca exchanger (Km(Ca) approximately 20 microM) to continue at a significant level for greater than 200 msec. (ii) The time constant for inactivation of release from the "feet" must be much greater than for activation if Ca-induced Ca release is to continue for greater than 1-2 msec.

Animals↗