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Proportional and nonproportional transfer of movement sequences.

Two experiments were designed to determine participants' ability to transfer a learned movement sequence to new spatial locations. A 16-element dynamic arm movement sequence was used in both experiments. The task required participants to move a horizontal lever to sequentially projected targets. Experiment 1 included 2 groups. One group practised a pattern in which targets were located at 20, 40, 60, and 80 degrees from the start position (long sequence). The other group practised a pattern with targets at 20, 26.67, 60, and 80 degrees (mixed sequence). Both groups were tested 24 hours later on the long, mixed, and short sequence. The short sequence was considered a proportional transfer for the long acquisition group because all the amplitudes between targets were reduced by the same proportion. Nonproportional transfer occurred when the amplitudes between targets did not have the same proportions as those for their practice sequence (e.g., long sequence to mixed sequence or vice versa). The results indicated that participants could effectively transfer to new target configurations regardless of whether the transfer required proportional or nonproportional spatial changes to the movement pattern. Experiment 2 assessed the effects of extended practice on proportional and nonproportional spatial transfer. The data indicated that while participants can effectively transfer to both proportional and nonproportional spatial transfer conditions after 1 day of practice, they are only effective at transferring to proportional transfer conditions after 4 days of practice. The results are discussed in terms of the mechanism by which response sequences become increasingly specific over extended practice in an attempt to optimize movement production.

Analysis of Variance↗

Brain GABA editing by localized in vivo (1)H magnetic resonance spectroscopy.

Editing of GABA by (1)H MRS in a specific brain area is a unique tool for in vivo non-invasive investigation of neurotransmission disorders. Selective GABA detection is achieved using sequences based on double quantum coherence (DQC). Our pulse sequence makes accurate measurements without artefacts due to spatial localization. The sequence was tested on a phantom solution. The effect of vigabatrin, a specific inhibitor of GABA transaminase, was measured in rat brain and GABA detection was performed in vivo in monkey brain using this procedure. Rats were split into two groups. In the control group, the rats had access to water and, in the other group (vigabatrin, VGB, rats), animals were allowed free access to drinking water containing vigabatrin. After 3 weeks of treatment, rats were anesthetized for in vivo NMR spectroscopy investigation. At the end of the experiment, brains were quickly removed, freeze-clamped and extracted with 4% perchloric acid. One part of the acid extract was used for GABA concentrations assessment by ion exchange chromatography with ninhydrin detection. The second was used for high-resolution NMR analysis. By chromatography measurements, the GABA concentration was 1.23+/-0.06 micromol/g for controls, while for vigabatrin-treated rats the GABA concentration was 4.89+/-1.60 micromol/g. The NMR in vivo results were closely correlated with the NMR ex vivo (r=0.99, p<0.01) and chromatography results (r=0.98, p<0.01). The correlation between ex vivo results and chromatography results was also high (r=0.99, p<0.001). This pulse sequence performed GABA editing from a 376 microl voxel located on the right basal ganglia area in a non-human primate brain. This in vivo GABA editing scheme can thus be proposed for accurate measurement of brain GABA concentrations.

Administration, Oral↗

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↗

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↗

Metal artifact reduction in musculoskeletal magnetic resonance imaging.

Many strategies can be employed to reduce the size and scale of metal susceptibility artifacts in the vicinity of orthopedic hardware; factors include selection of metal hardware material, patient positioning, and MRI sequence adjustments and techniques. The adjustments to sequence parameters include high spatial resolution fast spin echo sequences with minimal interecho spacing and increased receiver bandwidth. Frequency and phase encoding gradients can be orientated so misregistration artifacts arising from the metal are directed away from areas of anticipated clinical diagnostic interest. Complications arising in the vicinity of metallic hardware, including loosening, can be assessed after implication of these metal artifact reduction techniques.

Artifacts↗

Anterior cingulate activity during routine and non-routine sequential behaviors in macaques.

Anterior cingulate cortex is important in monitoring action for new challenges. We recorded neuron activity in the anterior cingulate sulcus of macaques while they performed a sequential problem-solving task. By trial and error, animals determined the correct sequence for touching three fixed spatial targets. After the sequence was repeated three times, we then changed the correct solution order, requiring a new search. Irrespective of component movements or their kinematics, task-related neurons encoded the serial order of the sequence. Neurons activated with sequence components (68%) differed in activity between search and repetition. Search-related activity occurred when behavioral flexibility was required and ended as soon as the animal accumulated enough information to infer the solution, but had not yet tested it. Repetition-related activity occurred in a regime of memory-based motor performance in which attention to action is less necessary.

Animals↗

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↗

Comparison of hybrid echo-planar imaging and FLASH myocardial perfusion cardiovascular MR imaging.

The purpose of this study was to compare fast single-shot gradient-echo (FLASH) and hybrid echo-planar imaging (EPI) magnetic resonance (MR) technologies regarding the relative contrast-to-noise ratio (CNR), spatiotemporal resolution, size of inducible perfusion defects, and presence of artifacts in patients with coronary artery disease (CAD). Fifteen patients with CAD underwent rest and adenosine stress gadolinium first-pass perfusion cardiovascular MR examinations with EPI and FLASH. The study was approved by the local ethics committee, and each subject gave written informed consent. The spatial resolution of the two sequences was made similar in nine patients, and the temporal resolution was made similar in six. The images were assessed for CNR, artifact, and size of inducible perfusion defects. The CNR was significantly higher with the EPI sequence, whether matched for spatial (32 vs 22 [46%], P < .001) or temporal (35 vs 23 [51%], P < .001) resolution. There was no significant difference in scoring for artifact or area and transmural extent of inducible perfusion defects with EPI and FLASH, whether matched for temporal or spatial resolution. Further work is warranted to determine the relative diagnostic accuracy of the two techniques.

Aged↗

Temporal processing in poor adult readers.

The aim of this study was to investigate the relationships between two different temporal processing tasks and word identification performance in skilled, dyslexic and poor adult readers. In Experiment 1 spatial and temporal sequencing tasks were conducted. It was found that adult dyslexics were significantly less accurate than skilled readers across all conditions in the temporal sequencing task, and when higher numbers of stimuli were presented in the spatial task. Experiment 2 replicated Experiment 1 in the temporal sequencing task and also found that poor readers had significantly higher motion coherence thresholds than those found in the skilled reader group. Ten percent of the variance in coherence thresholds was accounted for by performance on the temporal sequencing task. Multiple regression analyses determined that performance on the two temporal tasks could explain seventy percent of the variance in word identification scores, with the temporal sequencing task making the larger independent contribution. Experiment 3 replicated the findings of Experiment 2, while taking into account IQ, verbal memory and processing speed. Three things were concluded. First, the temporal tasks measure different aspects of temporal processing. The contribution to performance of higher-level perceptual and attentional components of the temporal sequencing task accounts for the relatively weak correlation found between the two measures. While sensory sensitivity to motion is measured at MT, the involvement of this area and PPC in higher-level perceptual and attentional processes is suggested by the findings of this study. Second, the association between temporal sequencing and reading skills may provide a stronger link between neural processing and poor reading skills than basic sensory processing measures alone, suggesting that a sensory magnocellular (M) system deficit cannot fully explain the relationship found between reading and visual neural processing. Third, problems with rapid sequential processing are predicted to be a generalised problem in poor adult readers, whether they are formally classified as dyslexic, or are poor performers on measures of word identification. Temporal processing may follow a distribution similar to that found for word identification skills.

Adolescent↗

Strategic grouping in the spatial span memory task.

Spatial short-term memory performance was examined in relation to participants' strategies. A total of 20 adult participants viewed and reproduced sequences of locations that varied in length (five, six, seven, or eight locations) and spatial separability (a manipulation of the configurations). In trial-by-trial self-reports, participants described five types of strategies. Chunking the spatial sequences into groups of three or four locations was the sole strategy associated with increased accuracy. Participants demonstrated considerable variability in the strategies that they selected, suggesting that cognitive resources are allocated to strategy selection, execution, and monitoring in the spatial span task. Spatially separable sequences were more accurately recalled than nonseparable sequences, independent of strategic grouping, suggesting two levels of grouping in the spatial span task.

Adult↗

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↗

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↗

Fast imaging of phosphocreatine in the normal human myocardium using a three-dimensional RARE pulse sequence at 4 Tesla.

PURPOSE: To investigate the use of a three-dimensional rapid acquisition with relaxation enhancement (RARE) pulse sequence for direct acquisition of phosphocreatine (PCr) images of the human myocardium. MATERIALS AND METHODS: A short elliptical birdcage radiofrequency (RF) body coil was constructed to produce a uniform flip angle throughout the chest cavity. In vivo images using a spectrally-selective RARE sequence with a spatial resolution of 1.2 cm x 1.2 cm x 2.5 cm (4 cm(3)) were acquired in nine minutes and 40 seconds. RESULTS: Scans of phantoms demonstrated excellent spectral selectivity. The signal-to-noise ratio in the myocardium ranged from 12.6 in the anterior wall to 5.3 in the mid septum. CONCLUSION: This study demonstrates that PCr data can be acquired using a three-dimensional RARE sequence with greater spatial and temporal resolution than spectroscopic techniques.

Humans↗

Sequence learning in Parkinson's disease: the effect of spatial stimulus-response compatibility.

Patients with Parkinson's disease (PD) have repeatedly demonstrated reduced sequence-specific learning effects in serial reaction time tasks (SRTs). Previous research with PD patients has mainly employed the 'classical' SRT task, involving a spatially compatible assignment of stimuli and responses. From cognitive research, it is known that spatial compatibility triggers rapid, automatic responses in the direction of the stimulus. Automatic responding has shown to be disinhibited in PD patients and may therefore interfere with stimulus anticipation during the learning process. The aim of the present study was to test this hypothesis by investigating if reduced sequence-specific learning depends on spatial stimulus-response compatibility. PD patients and age-matched controls were examined either with an SRT variant involving central stimulus presentation, thereby preventing automatic linking of stimulus and response locations, or with a spatially compatible SRT task. Patients showed reduced sequence-specific learning effects only when the stimulus-response assignment was spatially compatible. This pattern of results confirms the hypothesis that sequence learning deficits in PD may result from a predominance of automatic response activation over learning-based stimulus anticipations during the learning phase.

Female↗

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↗

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↗

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↗

Multi-echo imaging in highly inhomogeneous magnetic fields.

A new pulsed field gradient multi-echo imaging technique to encode position in the phase of every echo generated by a CPMG sequence in the presence of a strongly inhomogeneous static magnetic field is presented. It was applied to improve the sensitivity in an imaging experiment by adding the echo train acquired during the CPMG sequence and to spatially resolve relaxation times of inhomogeneous specimens using single-sided probes. The sequence was implemented in a new bar-magnet MOUSE equipped with a gradient coil system to apply a pulsed magnetic field with a constant gradient along one spatial coordinate. An important reduction by a factor larger than two orders of magnitude in the acquisition time was obtained compared to the previously published single-point imaging technique.

Algorithms↗