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PubMed1996

Spatial imagery preserves temporal order.

Line drawings were presented in either a spatial or a nonspatial format. Subjects recalled each of four sets of 24 items in serial order. Amount recalled in the correct serial order and sequencing errors were scored. In Experiment 1 items appeared either in consecutive locations of a matrix or in one central location. Subjects who saw the items in different locations made fewer sequencing errors than those who saw each item in a central location, but serial recall levels for these two conditions did not differ. When items appeared in nonconsecutive locations in Experiment 2, the advantage of the spatial presentation on sequencing errors disappeared. Experiment 3 included conditions in which both the consecutive and nonconsecutive spatial formats were paired with retrieval cues that either did or did not indicate the sequence of locations in which the items had appeared. Spatial imagery aided sequencing when, and only when, the order of locations in which the stimuli appeared could be reconstructed at retrieval.

Cognition↗
PubMed2006

Processing the spatial configuration of complex actions involves right posterior parietal cortex: An fMRI study with clinical implications.

The left hemispheric dominance for complex motor behavior is undisputed. Clinical observations of complex motor deficits in patients with right hemispheric lesions, however, suggest an additional contribution of the right hemisphere to higher motor control. We assessed, using functional MRI (fMRI), which brain regions are implicated in processing the spatial aspects of complex, object-related actions. Using a blocked, factorial design, 17 healthy volunteers were asked to detect either spatial or sequential errors (factor ERROR) in complex activities of daily living, presented as video sequences with the appropriate object(s) or as pantomimes (factor STIMULUS). Observing complex actions (irrespective of stimulus type) activated a bilateral frontoparietal network. Observing actions with objects (relative to pantomimes) differentially increased neural activity in the fusiform gyrus and inferior occipital cortex bilaterally. Observing pantomimes, i.e., the same actions but without any object, differentially activated right prefrontal cortex, anterior cingulate cortex, the precuneus, and left cerebellum. The left cingulate cortex was differentially activated when subjects assessed the sequencing of actions. By contrast, assessing the spatial configuration of complex actions differentially increased neural activity in right posterior parietal cortex. A significant interaction of ERROR and STIMULUS was revealed for the right inferior parietal cortex only. These findings suggest a specific role of the right hemisphere, especially of right posterior parietal cortex, in processing spatial aspects of complex actions and thus provide a physiological basis for the observed apraxic motor deficits in patients with right hemispheric damage.

Activities of Daily Living↗
PubMed2004

Calcium transients induce spatially coordinated increases in traction force during the movement of fish keratocytes.

The coordination of protrusion with retraction is essential for continuous cell movement. In fish keratocytes the activation of stretch-activated calcium channels, and the resulting increase in intracellular calcium, trigger release of the rear cell margin when forward movement is impeded. Although it is likely that retraction involves a calcium-dependent increase in cytoskeletal contractility, it is not known how the timing, magnitude and localization of contractile forces are organized during retraction. We have addressed this question using a new gelatin traction force assay in combination with calcium imaging to determine what changes in cytoskeletal force production accompany calcium-induced retraction. We find that individual calcium transients are followed within seconds by a rapid increase in traction stress that is maintained, or increases in a stepwise manner, until retraction occurs. Increases in traction stress are accompanied by a distinct sequence of changes in the spatial distribution of large traction stresses. Regions of increased traction stress enlarge at the lateral cell margins and expand forward along the cell margin. In particular, rearward facing propulsive' tractions at the leading edge of the cell, which are normally very low, increase several fold. Following retraction, a precipitous drop in traction stress is observed. Such distinct variations in traction stress are not observed in cells when calcium transients are absent. These results suggest a mechanism by which global increases in intracellular calcium can locally regulate contractile force production, in order to maintain a rapid highly directed mode of movement.

Animals↗
PubMed2005

[A preparation technique for quantitative investigation of SPIO-containing solutions and SPIO-labelled cells by MRI].

UNLABELLED: PURPOSE. This work aims to present a preparation technique for ex-vivo MR examination of SPIO (superparamagnetic iron oxide) containing solutions or SPIO labeled cells. Accumulations of SPIO particles and labeled cells were prepared in different concentrations using agar gel phantoms. Signal extinction around accumulations of magnetic material was examined systematically by gradient echo sequences with variable echo times and spatial resolution. The correlation between local iron concentration and diameter of signal extinction in MR gradient echo images was investigated. METHODS: Resovist, (SHU 555A) was used as superparamagnetic contrast medium. Different concentrations of SPIO-containing solutions (0.75 - 15 mg Fe/10 ml) and magnetically labeled SK-Mel28 cells (25,000-1,000,000 cells/10 ml) were accommodated inside a defined volume in an agar matrix. Diameters of signal void were assessed in dependence on local iron concentration, echo time (5-25 ms) and isotropic spatial resolution (length of voxel 0.25 - 0.60 mm). Measurements were performed on a clinical MR whole body scanner (3 Tesla) using a spoiled gradient echo sequence (FLASH). RESULTS: For the present experimental conditions sensitivity to detect the magnetic label was maximized using TE 25 ms. In contrast, the area of signal cancellation was minimized using TE 5 ms and isotropic resolution of 0.25 mm. In the latter case the image indicated the area of magnetic material most precisely. Diameter of signal cancellation was a logarithmic function on local iron concentration. In the presented set-up detection of concentrations as low as 0.75 mg Fe/10 ml in SPIO-containing solution or 1.25 mg Fe/10 ml in SPIO-labeled SK-Mel28 cells was certainly possible. CONCLUSION: The proposed preparation strategy with a well defined spatial distribution of the magnetic material in an agar gel phantom produced reliable results and appears clearly superior compared to set-ups with randomly distributed material in glass tubes. The diameter of the signal extinction in gradient echo images was significantly affected by the choice of echo time and spatial resolution. The calibration of signal cancellation versus iron concentrations may be valuable to assess SPIO concentrations and possibly numbers of labeled cells under specific conditions in vitro or even in vivo.

Cell Line, Tumor↗
PubMed1996

Postelectrophoresis capillary scanning method for DNA sequencing.

A postelectrophoresis capillary scanning method for increasing the throughput of DNA sequencing has been developed. The method features a spatially and temporally separated arrangement between capillary gel electrophoresis separation of DNA sequencing fragments and the visualization of the separation pattern. Fluroescently labeled DNA sequencing fragments of pBluescript SK(-) were produced in enzymatic chain-termination reactions and separated by capillary gel electrophoresis using a 110 cm fused silica capillary with a transparent polymer coating. A partial sequence from the DNA was then determined by repeated scanning of the capillary at a rate of 8.39 cm/s, with changing excitation wavelengths and spectral filter sets.

Base Sequence↗
PubMed1992

The regulation of the murine Hox-2.5 gene expression during cell differentiation.

The mouse Hox-2.5 gene containing a Drosophila Antennapedia-type homeobox sequence is expressed in a spatially and temporally restricted manner during embryogenesis. We found that the mouse embryonal carcinoma cell line P19 expresses Hox-2.5 during differentiation by the treatment with retinoic acid (RA). Expression of the Hox-2.5 gene was not detected in undifferentiated P19 cells, but detected 72 hours after treatment with RA. In order to analyze this inductive response, we first identified the Hox-2.5 transcription initiation site and a possible promoter region. Subsequently, we prepared constructs containing various Hox-2.5 DNA fragments fused to a firefly luciferase reporter gene and transfected these into undifferentiated or differentiating P19 cells. These studies have demonstrated that a region -279 to +15 with respect to the transcription initiation site has a differentiation-responsive promoter activity. Deletion analysis suggests that the sequences responsible for this induction are located in several distinct domains within the 294 bp promoter region. Two of the possible differentiation-responsive elements were identified by analysis of DNA-protein interactions, and in vivo competition assays lend support to the notion that these regions are involved in the differential expression of Hox-2.5 promoter activity.

Animals↗
PubMed2002

Measurements of MTF and SNR(f) using a subtraction method in MRI.

A method was developed for accurate measurement of the modulation transfer function (MTF) and signal-to-noise ratio in the spatial frequency domain (SNR(f)) of magnetic resonance images (MRI). The MTF was calculated from the complex images of a line object which were obtained by the subtraction of two separately acquired data sets of a specially designed phantom with a sliding sheet. Moreover, the SNR(f) was calculated from the MTF and Wiener spectrum, both of which were determined using the same phantom configuration. The MTFs and SNR(f)s in the conventional spin-echo (SE) and turbo SE, in which the effective echo time was set to the first echo, were evaluated by changing the T2 of the phantom and the echo train length. The MTFs in the positive and negative frequencies indicated the effect of the k-space trajectory for each pulse sequence. SNR(f)s gave spatial frequency information that was not obtained with conventional methods. In this method, the influence of image nonuniformity and unwanted artefacts (edge and ghost) could be eliminated. An analysis of the MTF and the SNR in the spatial frequency domain provides additional information for the assessment of image quality in MRI.

Artifacts↗
PubMed1992

Activin A induced expression of a fork head related gene in posterior chordamesoderm (notochord) of Xenopus laevis embryos.

A gene family encoding the fork head/HNF-3 domain has been identified in the South African clawed frog, Xenopus laevis. Screening of genomic DNA and gastrula stage derived cDNA libraries with a DNA fragment encoding the Drosophila fork head domain led to the isolation of a number of different clones encoding this motif. While one of the Xenopus fork head sequences, XFD-3, represents the Xenopus counterpart to rat HNF-3 beta, all other sequences encode novel types of fork head related proteins. Here we report on XFD-1, a DNA binding protein which can bind to the HNF-3 alpha target sequence. Analysis of temporal and spatial expression revealed that the gene is activated at blastula stage and that transcripts are localized in a rather thin stripe of cells invaginating the dorsal blastopore lip (organizer) during gastrulation. XFD-1 mRNA is localized within the notochord and, by the end of neurulation, is no longer detectable. In the animal cap assay the gene is activated by incubation with the vegetalizing factor (activin A) but not with bFGF.

Activins↗
PubMed2006

Moving from spatially segregated to transparent motion: A modelling approach.

Motion transparency, in which patterns of moving elements group together to give the impression of lacy overlapping surfaces, provides an important challenge to models of motion perception. It has been suggested that we perceive transparent motion when the shape of the velocity histogram of the stimulus is bimodal. To investigate this further, random-dot kinematogram motion sequences were created to simulate segregated (perceptually spatially separated) and transparent (perceptually overlapping) motion. The motion sequences were analysed using the multi-channel gradient model (McGM) to obtain the speed and direction at every pixel of each frame of the motion sequences. The velocity histograms obtained were found to be quantitatively similar and all were bimodal. However, the spatial and temporal properties of the velocity field differed between segregated and transparent stimuli. Transparent stimuli produced patches of rightward and leftward motion that varied in location over time. This demonstrates that we can successfully differentiate between these two types of motion on the basis of the time varying local velocity field. However, the percept of motion transparency cannot be based simply on the presence of a bimodal velocity histogram.

Models, Theoretical↗
PubMed2026

Multi-omics and spatial transcriptomics reveal that S100A10 drives CD8+ T-cell exhaustion and immune evasion in hepatocellular carcinoma through cPLA2-5-LOX-mediated arachidonic acid metabolism and ferroptosis.

Immune evasion in hepatocellular carcinoma (HCC) represents a major biological barrier limiting the efficacy of immunotherapy, yet its molecular basis remains incompletely understood. Increasing evidence indicates that tumor metabolic reprogramming and ferroptosis-related signaling play critical roles in shaping an immunosuppressive tumor microenvironment (TME); however, the specific regulatory factors involved remain unclear. This study aims to systematically elucidate the functional role of S100 calcium-binding protein A10 (S100A10) in immune evasion in HCC, with a particular focus on the molecular mechanisms by which S100A10 regulates CD8+ T-cell exhaustion through arachidonic acid (AA) metabolism and ferroptosis, as well as its potential therapeutic implications. To this end, data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) cohort are integrated to analyze the expression patterns of S100A10, its prognostic value, and its association with the immune microenvironment. S100A10 overexpression and knockout models are established in HCCLM3 and MHCC97L cell lines, and S100A10-mediated metabolic pathway reprogramming is characterized using transcriptomic profiling, untargeted metabolomics, and ferroptosis-related functional assays. In parallel, single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics are employed to delineate the cell-type specificity and spatial distribution of S100A10. Furthermore, human CD8+ T-cell co-culture systems and orthotopic mouse HCC models are used to evaluate the impact of S100A10 on immune function and responsiveness to anti-programmed cell death protein 1 (anti-PD-1) therapy. The results demonstrate that S100A10 is significantly upregulated in HCC and is closely associated with poor prognosis and an immunosuppressive state. Mechanistically, S100A10 activates cytosolic phospholipase A2-arachidonate 5-lipoxygenase (cPLA2-5-LOX)-mediated AA oxidative metabolism, leading to the accumulation of lipid peroxidation products and ferroptosis-associated signals, thereby driving CD8+ T-cell exhaustion and promoting immune evasion. Significantly, inhibition of S100A10 reshapes the tumor immune microenvironment (TIME) and enhances the therapeutic efficacy of anti-PD-1 treatment. Collectively, these findings identify S100A10 as a critical regulator of metabolic-immune coupling in HCC and provide a theoretical basis for combinatorial strategies targeting metabolism and immunotherapy.

Arachidonic acid metabolism↗
PubMed1994

DNA class organization on maize Adh1 yeast artificial chromosomes.

The organization of higher plant genomes is poorly understood. These genomes are typified by their large size and extensive repetitive DNA component. To further our understanding of the composition and arrangement of genomic DNA sequences, we have performed a detailed analysis of a contiguous interval of 280 kb surrounding the Adh1 locus of maize. A series of overlapping lambda subclones was isolated, and individual fragments were characterized with respect to their genomic copy number. Cross-hybridization analyses were used to define a minimum of 37 repetitive DNA classes within the 280-kb interval. Hybridizations with highly repetitive DNAs cloned from other regions of the maize genome suggested that > 50% of all highly repetitive elements in maize are represented on this single yeast artificial chromosome. These repeated sequences were found in an organizational pattern not previously observed; individual repetitive elements are interspersed with one another in an apparently random fashion and are spatially separate from single copy number sequences. Extensive tandem arrays were not found. Sequences from one end of the 280-kb interval were used to isolate overlapping yeast artificial chromosome clones, representing the first step in a chromosome walk.

Alcohol Dehydrogenase↗
PubMed1982

Relationship between the total size of exons and introns in protein-coding genes of higher eukaryotes.

We have attempted to ascertain the correlation between the genetic information content in the exons and the surrounding intron sequences with regard to their spatial arrangement within a gene. A comparison is made of the sizes, taken from recent publications, of exons and introns of approximately equal to 80 different protein-coding chromosomal genes, mostly from higher eukaryotes. The exons of these genes do not show very marked variation in size and can be classified into three major discrete and two minor additional size groups, whereas individual introns vary considerably in size within and between genes. Notwithstanding, the overall length of all introns present within a given gene is a function of the total size, mostly corresponding to the total genetic information content, of the exons. Three cases that violate this exon-size dependency of introns are genes coding for (i) histone H1, feather keratin, and interferons, (ii) tubulin and actin, and (iii) silk fibroin. The exons of these genes are larger than 0.7 kilobase pair in total size and the genes show a strong sequence homogeneity among the repetitious family members or internal repeats of coding sequences within the gene. We propose that conservation of sequences, which is required by the family members, internal repeats, or the entire gene, would actually motivate the removal of introns.

Animals↗
PubMed2000

Synthetic peptide mimics of a predicted topographical interaction surface: the cytochrome P450 2B1 recognition domain for NADPH-cytochrome P450 reductase.

In order to identify the cytochrome P450-binding domain for NADPH-cytochrome P450 reductase, synthetic peptide mimics of predicted surface regions of rat cytochrome P450 2B 1 were constructed and evaluated for inhibition of the P450-reductase interaction. A peptide corresponding to residues 116-134, which includes the C helix, completely inhibited reductase-mediated benzphetamine demethylation by purified P450 2B1. Replacement of Arg-125 by Glu yielded a noninhibitory peptide, suggesting that this residue significantly contributes to the reductase-P450 interaction. Additional P450 peptides were prepared which correspond to combinations of regions distant in primary sequence, but predicted to be spatially proximate. A peptide derived from segments of the C and L helices was a more potent inhibitor than peptides derived from either segment alone. This topographically designed peptide not only inhibited P450 2B1 in its purified form, but also when membrane-bound in rat liver microsomes. The peptide also inhibited microsomal aryl hydrocarbon hydroxylase, aniline hydroxylase, and erythromycin demethylase activities derived from other P450s. These results indicate that the C and L helices contribute to a reductase-binding site common to multiple P450s, and present a peptide mimic for this region that is useful for inhibition of P450-mediated microsomal activities.

Amino Acid Sequence↗
PubMed2025

Spatial mutual nearest neighbors for spatial transcriptomics data.

MOTIVATION: Mutual nearest neighbors (MNN) is a widely used computational tool to perform batch correction for single-cell RNA-sequencing data. However, in applications such as spatial transcriptomics, it fails to take into account the 2D spatial information. RESULTS: Here, we present spatialMNN, an algorithm that integrates multiple spatial transcriptomic samples and identifies spatial domains. Our approach begins by building a k-nearest neighbors (kNN) graph based on the spatial coordinates, prunes noisy edges, and identifies niches to act as anchor points for each sample. Next, we construct a MNN graph across the samples to identify similar niches. Finally, the spatialMNN graph can be partitioned using existing algorithms, such as the Louvain algorithm to predict spatial domains across the tissue samples. We demonstrate the performance of spatialMNN using large datasets, including one with N = 31 10x Genomics Visium samples. We also evaluate the computing performance of spatialMNN to other popular spatial clustering methods. AVAILABILITY AND IMPLEMENTATION: Our software package is available on GitHub (https://github.com/Pixel-Dream/spatialMNN). The code is available on Zenodo (https://doi.org/10.5281/zenodo.15073963).

Algorithms↗
PubMed2002

Circadian Transcription. Thinking outside the E-Box.

The E-Box is a widely used DNA control element. Despite its brevity and broad distribution the E-Box is a remarkably versatile sequence that affects many different genetic programs, including proliferation, differentiation, tissue-specific responses, and cell death. The circadian clock is one of the latest pathways shown to employ this element. In this context, E-Boxes are likely to play a key role in establishing the robust waves of gene expression characteristic of circadian transcription. The regulatory flexibility of the E-Box hinges on the sequence ambiguity allowed at its core, the strong influence of the surrounding sequences, and the recruitment of spatially and temporally regulated E-Box-binding factors. Therefore, understanding how a particular E-Box can accomplish a specific task entails the identification and systematic analysis of these cis- and trans-acting E-Box modifiers. In the present study we compared the E-Box-containing minimal promoters of vasopressin and cyclin B1, two genes that can respond to the transcriptional oscillators driving the circadian clock and cell cycle, respectively. Results of this comparison will help elucidate the manner in which discreet DNA modules associate to either augment or restrain the activation of potential circadian E-Boxes in response to competing regulatory signals.

3T3 Cells↗
PubMed2026

Mycosis Fungoides-Like Atopic Dermatitis Represents a Th22-Dominant Inflammatory Endotype.

BACKGROUND: Early-stage mycosis fungoides (MF) often presents diagnostic challenges because of its clinical overlap with atopic dermatitis (AD). In clinical practice, we encountered a subset of patients with severe AD who fulfilled the MF diagnostic criteria yet remained clinically indistinguishable from AD and presented refractoriness to advanced therapies. We termed this ambiguous entity "mycosis fungoides-like AD" (mfAD) and sought to determine whether it represents malignant transformation or a distinct inflammatory endotype of AD. METHODS: Skin biopsies were obtained from 7 patients with AD and 11 patients with mfAD. We performed paired single-cell RNA sequencing and single-cell T-cell receptor sequencing analyses. Publicly available MF and AD datasets were integrated for comparative analysis. Spatial transcriptomic profiling was used to contextualize single-cell findings within the tissue architecture. RESULTS: Comparative transcriptomic analysis revealed that T cells in mfAD were aligned with those in AD and lacked genomic instability. High-resolution profiling showed that mfAD was characterized by oligoclonal Th22 expansion rather than a single dominant malignant clone. Notably, all patients with mfAD achieved rapid clinical remission with selective JAK1 inhibition, indicating the therapeutic response characteristics of inflammatory dermatoses. CONCLUSION: Our findings demonstrate that mfAD is not a true malignancy, but rather a Th22-driven inflammatory endotype of AD. These results redefine mfAD as an inflammatory subtype within the AD spectrum, providing a mechanistic explanation for both the "pseudo-monoclonality" that leads to MF misdiagnosis and the failure of dupilumab. This study establishes a rationale for the use of JAK inhibitors in precision medicine for this patient population.

JAK inhibitor↗
PubMed2004

3D DT-MRI using a reduced-FOV approach and saturation pulses.

Diffusion tensor imaging (DTI) can provide vital insights into brain connectivity, and may become an important tool for the diagnosis and treatment of neurological disease. However, DTI's intrinsic low signal-to-noise ratio (SNR) and vulnerability to ghosting artifacts can result in poor image quality with low spatial resolution, which limits its clinical applications. In this study, a new double-shot EPI sequence (half-FOV EPI) with high spatial resolution was developed. This method enables DT measurements to be obtained with high isotropic spatial resolution and whole-brain coverage. To avoid ghosting artifacts, the data are combined in image space rather than in k-space.

Adult↗