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PubMed1994

[Functional imaging of the human brain with conventional MRI].

It was shown in 1991 by Belliveau and co-workers that the activation of the human brain can be visualized in a completely noninvasive way by MRI. First publications coming from the US claimed that very high magnetic field strength or echo planar imaging, both available only at a few research sites, would be necessary to do this job. Recently, it was demonstrated that functional imaging of the human brain can be done with high spatial resolution MRI using conventional FLASH-sequences with the commercial widely available 1,5 Tesla systems. First results have been reported for visual as well as primary motor cortex activation in healthy volunteers. The key to a successful application of the conventional technique lies in the design of extremely low bandwidth, long echo-time FLASH-sequences with high spatial resolution.

Adult↗
PubMed1997

An RGD to LDV motif conversion within the disintegrin kistrin generates an integrin antagonist that retains potency but exhibits altered receptor specificity. Evidence for a functional equivalence of acidic integrin-binding motifs.

Integrin ligands almost invariably employ a variant of either the RGD or LDV motif as a key element of their receptor recognition site. These short acidic peptide sequences collaborate with specific nonhomologous flanking residues and spatially separate "synergy" sequences to determine receptor binding specificity. Although the consensus sequences for RGD and LDV motifs are quite different, their common use suggests that they might share a critical role in receptor-ligand engagement. To date, the effects of interconversion of the two motifs within a natural protein framework have not been tested; however, in this study, we have converted the natural RGD site found in the snake venom disintegrin kistrin into an LDV motif and examined the effects of the change on the specificity of integrin recognition and on disintegrin potency. While an assessment of receptor binding using cell adhesion and purified integrin solid-phase assays demonstrated recognition of recombinant RGD kistrin by alphaVbeta3 and alpha5beta1, a series of LDV kistrin chimeras did not bind to these integrins, but instead were recognized specifically by alpha4beta1. The minimal change to elicit this distinct switch in receptor specificity was found to involve alteration of only three residues within kistrin. Alanine scanning mutagenesis was used to provide further information on the functional contribution of the three residues. More important, the LDV kistrin chimeras also retained much of the characteristic potency of RGD kistrin, indicating that the kistrin scaffold is optimized for presentation of both RGD and LDV sequences. These findings provide evidence for similarities in motif pharmacophore and reinforce the hypothesis that RGD and LDV sites have an equivalent functional role in receptor binding. They also demonstrate the potential for other disintegrin-containing proteins, perhaps from the ADAM family, to employ LDV sequences for integrin binding.

Amino Acid Sequence↗
PubMed1995

SD filtering for enhancement of a nuclear medicine image sequence.

This paper explores the use of an image sequence processing algorithm, called the simultaneous diagonalization (SD) filter, which can be effectively applied to long noisy image sequences. This filter was developed to filter a spatially invariant image sequence to form one new image in which a desired feature is enhanced and one or more undesired features (and noise) are suppressed in the filtered image. This filtering technique, applied to a long noisy image sequence, can be used to achieve significant data compression for image storage and provide surprisingly good enhanced image reconstructions. For this investigation, SD filtering is applied to a temporal image sequence, a renogram, with compression of a very noisy 180-image sequence to a 4-image set. The renogram, a nuclear medicine technique, was chosen due to its low signal-to-noise ratio over a long image sequence. Before the application of the SD filter, classical image processing techniques, median and averaging filtering, are used as a preliminary method to reduce the image sequence noise content. Compared to any of the images in the original image sequence, the reconstructed images are remarkably good. The SD filter with prefiltering, thus, can collect information distributed over a 180-image temporal sequence with low signal-to-noise ratio.

Algorithms↗
PubMed1980

Localization of SV40 genes within supercoiled loop domains.

Recent studies indicate that eukaryotic DNA is organized into supercoiled loop domains. These loops appear to be anchored at their bases to an insoluble nuclear skeleton or matrix. Most of the DNA in the loops can be released from the matrix by nuclease digestion; the residual DNA remaining with the nuclear matrix represents sequences at the base of the loops, and possibly other sequences which are intimately associated with the nuclear matrix for other reasons. Using a quantitative application of the Southern blotting technique, we have found this residual DNA from SV40 infected 3T3 cells to be enriched in SV40 sequences, indicating that they reside near matrix-DNA attachment points. An enrichment of 3-7 fold relative to total cellular DNA, was found in each of three different lines of SV40 infected 3T3 cells. Control experiments with globin genes showed no such enrichment in this residual matrix DNA. This sequence specificity suggests that the spatial organization of DNA sequences within loops may be related to the functionality of these sequences within the cell.

Animals↗
PubMed1996

Palingol: a declarative programming language to describe nucleic acids' secondary structures and to scan sequence database.

At the DNA/RNA level, biological signals are defined by a combination of spatial structures and sequence motifs. Until now, few attempts had been made in writing general purpose search programs that take into account both sequence and structure criteria. Indeed, the most successful structure scanning programs are usually dedicated to particular structures and are written using general purpose programming languages through a complex and time consuming process where the biological problem of defining the structure and the computer engineering problem of looking for it are intimately intertwined. In this paper, we describe a general representation of structures, suitable for database scanning, together with a programming language, Palingol, designed to manipulate it. Palingol has specific data types, corresponding to structural elements-basically helices-that can be arranged in any way to form a complex structure. As a consequence of the declarative approach used in Palingol, the user should only focus on 'what to search for' while the language engine takes care of 'how to look for it'. Therefore, it becomes simpler to write a scanning program and the structural constraints that define the required structure are more clearly identified.

Base Sequence↗
PubMed1993

A neural gene from Drosophila melanogaster with homology to vertebrate and invertebrate glutamate decarboxylases.

Cross-species hybridization has been used to isolate a second Drosophila gene, with homology to a feline glutamate decarboxylase (Gad) cDNA. The gene differs in sequence, chromosomal location, and spatial expression from the previously reported Drosophila Gad gene, but both encode proteins of 58 kDa. The derived amino acid sequence reveals a typical pyridoxal phosphate binding site and sequence homology consistent with a glutamate decarboxylase function. The protein includes an amino-terminal polyasparagine sequence, and a beta-pleated sheet region, with regularly spaced glutamine and arginine residues, not found in other decarboxylases. Expression in the adult is limited to the neuropil of the first optic ganglion and to regions of the thoracic musculature that may correspond to the location of motor neuron axons. This is consistent with a glial localization for the transcript. There is no overlap with the reported expression of Drosophila Gad. Although the molecular evidence suggests that this gene encodes a pyridoxal phosphate-dependent decarboxylase, glutamate decarboxylase activity associated with this gene could not be demonstrated, and the in vivo substrate is unknown. It is possible that the protein encoded by this gene is novel, not only in sequence and spatial expression, but also in substrate specificity.

Amino Acid Sequence↗
PubMed2025

Stereo-cell: Spatial enhanced-resolution single-cell sequencing with high-density DNA nanoball-patterned arrays.

Single-cell sequencing technologies have advanced our understanding of cellular heterogeneity and biological complexity. However, existing methods face limitations in throughput, capture uniformity, cell size flexibility, and technical extensibility. We present Stereo-cell, a spatial enhanced-resolution single-cell sequencing platform based on high-density DNA nanoball (DNB)-patterned arrays, which enables scalable and unbiased cell capture at a wide input range and supports high-fidelity transcriptome profiling. Stereo-cell further allows integration with imaging-based modalities and multiomics strategies, including immunofluorescence and epitope profiling. This platform is also compatible with profiling extracellular vesicles, microstructures, and large cells, whereas its spatial resolution facilitates in situ analysis of cell-cell interactions, cellular microenvironments, and subcellular transcript localization. Together, Stereo-cell provides a flexible framework for expanding single-cell research applications.

Animals↗
PubMed1986

Transcription initiation of the Saccharomyces cerevisiae iso-1-cytochrome c gene. Multiple, independent T-A-T-A sequences.

The expression of the Saccharomyces cerevisiae CYC1 gene, which encodes iso-1-cytochrome c, produces a family of messenger RNAs whose 5' ends map in the region from position +7 to -93 relative to the first nucleotide at position +1 of the protein-coding DNA sequence. The mechanism of transcription initiation of the CYC1 gene has been examined by using linker-scanning deletions and gene fusions. The various CYC1 derivatives with mutations in the 5' non-coding region were constructed, reintroduced into yeast using a multicopy plasmid, and the mRNA starts mapped by primer extension. The results indicate that four, and possibly five T-A-T-A sequences are located within the 5' non-coding region of the CYC1 gene, and that each T-A-T-A is required for a specific subset of mRNA starts. This conclusion has been confirmed by oligonucleotide mutagenesis of a chromosomal CYC1 T-A-T-A sequence. A loose spatial relationship also exists between the T-A-T-A sequences and the mRNA start sites, and this distance relationship varies from 100 to 60 base-pairs (+/- 15 base-pairs).

Base Sequence↗
PubMed1990

Spatial harmonics and pattern specification in early Drosophila development. Part I. Bifurcation sequences and gene expression.

Molecular probes have now provided an unprecedented wealth of detail revealing the changing spatial patterns of gene products in early Drosophila development. This is examined for dynamic properties which might provide insights into the underlying behaviour of the patterning process. What emerges is that transcripts and protein products of members of the major categories of zygotically active genes involved in segmentation pass through transient spatial patterns that are suggestive of harmonic sequences arising from spatial frequency-doubling bifurcations. That is to say, these patterns are typically periodic in space and show a doubling in the number of domains of spatial expression as development proceeds. One of these patterns reflects the primary functional role of the gene in the establishment of the spatial pattern. The different categories of segmentation gene pass through these transients at different rates, those with the longest functional wavelength progressing most slowly. Each gene in a category has its own unique phase relationship to other members, as well as particular variations on the harmonic sequence theme. The result is that the developing embryo experiences a spatial hierarchy of phase-shifted patterning influences that span the range from the whole embryo to single segments, providing progressively more spatial resolution in the patterning process. The characteristic transients and the dynamic relationships between genes of the different categories suggest that gene products expressed in longer-wavelength patterns act as bifurcation parameters on the dynamic system generating the next shorter wavelength category. Such parametric influences are known to result in frequency-doubling bifurcations in Turing reaction-diffusion systems. A general model is proposed of a hierarchically-nested set of quasi-autonomous dynamic systems involving gene activities that can generate the progressively finer spatial order that emerges during embryogenesis. This model has implications for the general stability properties of evolving epigenetic systems.

Animals↗
PubMed1995

Adapted techniques for clinical MR imaging of tendons.

To determine whether the echo time of magnetic resonance gradient-echo and spin-echo imaging sequences may be important for the occurrence of high signal strength from tendon with pathological alterations, imaging sequences with sufficient spatial resolution and very short echo times were developed for whole-body imagers with standard gradient system. The sequences were applied on the Achilles tendons of five healthy volunteers and seven patients with achillodynia. Some affected regions inside tendon, probably corresponding with tissue with subtle edema in the collagen bundles were only revealed in images recorded with very short echo times TE < 5 ms, whereas stronger affections and protons in liquids between the fiber bundles were also shown in images with longer echo times TE > 10 ms. Gradient-echo methods allow shorter echo times than spin-echo techniques for a given gradient system of the imager and given spatial resolution. So minimum echo time gradient-echo sequences should be used for sensitive imaging of tendon alterations, because no considerable signal dephasing due to susceptibility effects were found in tendon.

Achilles Tendon↗
PubMed1997

Spatial reconstruction of marker trajectories from high-speed video image sequences.

A novel method is presented for the spatial reconstruction of marker trajectories, which describe the motion of articulating segments of the human or animal body or of a technical construction. In human motion analysis, such markers may be attached to landmark points defining the configuration of the subject. A high-speed video-recording system comprising two cameras is used for motion data acquisition. The particular images are composed of the synchronous recordings of both cameras; the resolution of one image is 239 x 192 pixels, which is comparatively low. To obtain high precision, a new centre estimation method has been developed to calculate the image coordinates of the centres of the recorded spherical markers to subpixel precision. Image coordinates of the centres in subsequent frames are obtained by first applying a tracing algorithm, which calculates the position of a marker to pixel precision, and then using the new centre estimation method. The reconstruction of the spatial coordinates from the image coordinates is based on a three-dimensional photogrammetric calibration and results in deviations of about 0.1%. The instantaneous acceleration of a falling ball has been calculated. The average deviation from the gravitational constant was comparatively small. From the accuracy of the results, it can be concluded that the novel method is applicable in connection with the high-speed video-recording system presently used. Moreover, the techniques are suitable for reconstructing three-dimensional marker trajectories from any low-resolution video image sequences recorded simultaneous with at least two cameras.

Algorithms↗
PubMed1984

The effects of visual and spatial interference on spatial working memory.

Baddeley and Lieberman (1980) have shown that processing within spatial working memory is disrupted by a spatial secondary task, but not significantly by a visual processing secondary task. In the present study their experiment was replicated under broadly similar circumstances. The spatial and verbal primary tasks involved remembering descriptions of spatially arranged or nonsense sequences of digits, respectively. The secondary visual and spatial tasks involved either judging the level of brightness or pressing an unseen matrix of buttons in a predetermined sequence. In contrast to the finding of Baddeley and Lieberman, both the visual and spatial secondary tasks significantly impaired spatial working memory. Neither of these secondary tasks significantly interfered with concurrent verbal processing. The present findings suggest that spatial working memory draws from resources from both visual and spatial quarters.

Adult↗
PubMed2025

scBSP: a fast and accurate tool for identifying spatially variable features from high-resolution spatial omics data.

MOTIVATION: Emerging spatial omics technologies empower comprehensive exploration of biological systems from multi-omics perspectives in their native tissue location in 2D and 3D space. However, the limited sequencing depth, increasing spatial resolution, and growing spatial spots in spatial omics technologies present significant computational challenges in identifying biologically meaningful molecules with variable spatial distributions across various omics modalities. RESULTS: We introduce scBSP, an open-source, versatile, and user-friendly package for identifying spatially variable features in large-scale spatial omics data. scBSP demonstrates significantly enhanced computational efficiency, processing high-resolution spatial omics data within seconds, and exhibits robust cross-platform performance by consistently identifying spatially variable features with high reproducibility across various sequencing platforms. AVAILABILITY AND IMPLEMENTATION: scBSP is available for download from R CRAN at https://cran.r-project.org/web/packages/scBSP/index.html and PyPI at https://pypi.org/project/scbsp/.

Software↗
PubMed1994

Automatic detection of spatial and dynamic heterogeneity of repolarization.

Heterogeneity of ventricular repolarization is associated with the development of life-threatening ventricular arrhythmias. Temporal heterogeneity of repolarization may be manifest in an individual beat (spatial heterogeneity) or in a sequence of beats (dynamic heterogeneity). Spatial inhomogeneity of repolarization throughout the myocardium may be expressed electrocardiographically as dispersion of repolarization durations computed in simultaneously recorded leads. The beat-to-beat changes in the repolarization pattern (duration and/or amplitude) may account for a dynamic (time-dependent) dimension of heterogeneity, occasionally seen as T-wave alternans. A visual detection of heterogeneous repolarization is a time-consuming, observer-dependent, and frequently inaccurate process. Therefore, we developed computer algorithms designed to detect automatically (1) dispersion of repolarization and (2) nonvisible T-wave alternans from digitally recorded (1,000 Hz) X, Y, and Z electrocardiogram leads. This automatic approach was subsequently tested in 10 patients with idiopathic long QT syndrome and in 10 age-matched normal subjects. Long QT syndrome patients presented with significantly higher indices of heterogeneity in comparison with the control subjects; the dispersion of repolarization was 44 +/- 11 and 13 +/- 6 ms, respectively (P < .01), and T-wave alternans index was 0.40 +/- 0.37 and 0.03 +/- 0.06, respectively (P < .01). Simultaneous evaluation of spatial (dispersion of repolarization) and dynamic (T-wave alternans) aspects of repolarization provides new insight into heterogeneity of electrical recovery after myocardial depolarization. The automatic detection of repolarization dispersion and T-wave alternans in digital electrocardiogram recordings provides a practical method to evaluate heterogeneity of repolarization and may be useful for stratifying patients at risk of ventricular arrhythmias.

Arrhythmias, Cardiac↗
PubMed1995

Visuo-spatial working memory: structures and variables affecting a capacity measure.

The present paper examines the issue of the capacity of visuo-spatial working memory. A series of experiments test the hypothesis that two different components are critical in visuo-spatial working memory (passive store and active imagery operations), and, thereafter, attempt to specify the variables that affect the capacity of the passive store component. In the experiments, congenitally blind and sighted participants were asked to remember the spatial positions of target objects in two-dimensional matrices, with or without simultaneously performing a sequence of spatially-based imagery operations. We considered both the positions recall performance (the passive storage component) and the sequential imagery processing performance (the active processing component). We suggest that the two components of visuo-spatial working memory are independent. We also propose that both the number of relevant matrices and the number of target objects within each matrix affect the capacity of visuo-spatial working memory, with the latter factor possibly playing a greater role than the former one.

Adult↗
PubMed1999

The 69 bp circadian regulatory sequence (CRS) mediates per-like developmental, spatial, and circadian expression and behavioral rescue in Drosophila.

The period (per) gene is an essential component of the circadian timekeeping mechanism in Drosophila. This gene is expressed in a circadian manner, giving rise to a protein that feeds-back to regulate its own transcription. A 69 bp clock regulatory sequence (CRS) has been identified previously upstream of the period gene. The CRS confers wild-type mRNA cycling when used to drive a lacZ reporter gene in transgenic flies. To determine whether the CRS also mediates proper developmental and spatial expression and behavioral rescue, we used the CRS to drive either lacZ or per in transgenic flies. The results show that the CRS is able to activate expression in pacemaker neuron precursors in larvae and essentially all tissues that normally express per in pupae and adults. The CRS is sufficient to rescue circadian feedback loop function and behavioral rhythms in per01 flies. However, the period of locomotor activity rhythms shortens if a stronger basal promoter is used. This study shows that regulatory elements sufficient for clock-dependent and tissue-specific per expression in larvae, pupae, and adults are present in the CRS and that the period of adult locomotor activity rhythms is dependent, in part, on the overall level of per transcripts.

Animals↗
PubMed1998

Four-kilobase sequence of the mouse CNP gene directs spatial and temporal expression of lacZ in transgenic mice.

The gene encoding 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) is one of the earliest myelin genes to be expressed in the brain. It is expressed at basal levels in some non-neural tissues but at much higher levels in the nervous system, and its relevance and mechanism are unknown. Using transgenic mice, we examined the expression pattern conferred by a 4-kilobase (-kb) 5'-flanking sequence of the mouse CNP gene coupled to the bacterial lacZ reporter gene. Here we report that this 4-kb fragment contains sufficient information to direct expression of the transgene to the tissue and/or cell type, in which CNP is normally expressed. In the central nervous system (CNS), CNP-lacZ expression was regulated in a temporal manner, consistent with endogenous CNP expression. Transgene expression was detected in embryonic brain and spinal cord in immature oligodendrocytes, and it significantly increased with age. In adult mice, beta-galactosidase activity (which appeared to be oligodendrocyte specific) was found essentially in white matter areas of the CNS. Moreover, the transgene was expressed in peripheral nervous system, testis, and thymus-tissues that normally express CNP. Taken together, our results provide strong evidence that cis-acting regulatory elements, necessary to direct spatial and temporal expression of the transgene in oligodendrocytes, are located within the 4-kb 5'-flanking sequence of the mouse CNP gene. This promoter could be a valuable tool to target specific expression of other transgenes to oligodendrocytes, and may provide important new insights into myelination or dysmyelination.

Aging↗