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PubMed1992

Properties of reach-related neuronal activity in cortical area 7A.

1. In protocol 1, two macaque monkeys were trained to reach to illuminated buttons with the right arm as reach-related unit activity was monitored in area 7a of the left hemisphere. 2. Of 402 neurons recorded in area 7a, 109 changed their discharge rates during the reach task. The change could occur early or late in the trajectory, or during the return movement of the arm to the rest plate. Spatial preferences were seen in 59/109 reach-related cells, usually for the right or center buttons. 3. In protocol 2, another monkey was trained to reach with either arm to targets displayed on a touch-sensitive video monitor. Of 273 neurons sampled in area 7a (both hemispheres) during the bilateral task performance, 84 were reach-related: 33 responded similarly to reaches of either arm. Most of the rest had a contralateral arm preference. When bilateral reach-related cells had a spatial preference, that preference was the same for both arms. 4. With the use of two target sequences in either protocol, it was found that spatial preferences were observable only for primary reaches from the side of the body up to the target. Relatively few cells responded to other trajectories, and those that did usually failed to discriminate movement direction. Movement extent did not influence discharge rates. 5. Although a total of 125/270 reach cells had observable visual responses, only 4 out of 18 cells tested in both dark and light conditions showed a significant drop in reach-related activity in the dark. Thus visual input from the moving hand probably is responsible for only part of the reach activity in area 7a. 6. Reach-related activity in area 7a appears to signal specific phases of the motor performance and is often restricted to distinct spatial regions. As such, it could be used by the frontal lobe to facilitate upcoming elements of a motor sequence, including terminal corrections.

Animals↗

PubMed1984

Variability and conformation of HLA class I antigens: a predictive approach to the spatial arrangement of polymorphic regions.

Comparison of available sequences of HLA-A and HLA-B antigens shows that variable positions are predominantly localized in four segments spanning residues 63-85, 105-116, 138-156, and 177-194. The fourth segment is unique in that it contains no differences between antigens of the same locus. Secondary folding of HLA heavy chain was estimated by three independent predictive methods and areas of defined structure were correlated with the distribution of local hydrophobicity to outline putative internal and external portions. The three analyses each independently predict a high probability for beta structure in the alpha 1, alpha 2, and alpha 3 domains. A single alpha-helix is predicted within residues 146-160, a segment of likely importance in cytotoxic T cell recognition and graft rejection. Substitutions within this segment are spatially related by the helical turn. Variable residues usually lie in areas of high local hydrophilicity, and therefore they are probably on the surface of the molecule. The model predicts that they are frequently located in beta strands, beta-turns, or the above-mentioned alpha-helix, so that most substitutions would be accommodated within rigid frameworks that may impose structural constraints to variability. The secondary structure of alpha 1, alpha 2, and alpha 3 domains presents some analogies that suggest that they might share common features in their tertiary folding. The predicted structure of alpha 3 is strongly reminiscent of that of immunoglobulin constant domains. Possible arrangements of elements of secondary structure are discussed, as an attempt to situating the polymorphic regions of HLA class I antigens in a spatial context.

Amino Acid Sequence↗

PubMed1998

Combined deficits of saccades and visuo-spatial orientation after cortical lesions.

Functionally, saccadic eye movements are closely linked to visuo-spatial orientation. Anatomically, the network of cortical areas controlling saccades also seems to be involved in spatial attention and orientation. Consequently, lesions should cause deficits in both categories. We investigated this in 34 patients with focal unilateral lesions of the posterior parietal cortex (PPC), the frontal eye fields (FEF), the supplementary motor area (SMA), or the dorsolateral prefrontal cortex (PFC). Saccadic eye movements were recorded using infrared reflection oculography. Visual hemineglect or other visuo-spatial disorders were investigated by a series of standardized paper-pencil tests. Further, the internal spatial coordinates (subjective visual vertical and subjective straight ahead) were assessed psychophysically. Depending on the site of the lesion, different patterns of deficits were identified: lesions of the PPC impaired reflexive exploration of visual space in terms of delayed and hypometric visually triggered saccades into the contralesional hemifield, related to the severity of visual hemineglect. Further, PPC lesions specifically affected basic functions of the perceptual analysis of space, such as the internal spatial coordinates and spatial constancy across saccades. The latter was tested by applying visual double-step stimuli, where saccade-related extraretinal information had to be taken into account for achieving spatial accuracy. Frontal lesions left these functions intact. FEF lesions, however, impaired systematic intentional exploration of space, thus causing an exploratory-motor type of visual hemineglect. Prefrontal (PFC) lesions impaired the working memory for saccade-related spatial information, and SMA lesions affected temporal properties such as the timing of saccadic sequences, but did not cause specific visuo-spatial deficits. In conclusion, patients with frontal or parietal cortical lesions often exhibit combined saccadic and visuo-spatial disorders, most of which are topically specific.

Brain Diseases↗

PubMed2005

Fractional anisotropy and mean diffusivity measurements on normal human brain: comparison between low-and high-resolution diffusion tensor imaging sequences.

Non-invasive in vivo visualization of white matter fiber tracts is currently feasible by means of diffusion tensor imaging (DTI) techniques. DTI-derived metrics, like fractional anisotropy (FA) and mean diffusivity (MD), have the potential to improve tissue characterization. Technical optimization of diffusion tensor sequences, including signal-to-noise ratio and spatial resolution, was performed for 20 normal subjects. High- and low-resolution DTI sequences were applied on all subjects and FA, MD parametric maps were reconstructed for both protocols. Voxel-based statistical analysis revealed regions with significantly different FA and MD values between the two sequences, while the same type of analysis was performed to illustrate regions with significantly different signal-to-noise ratio. In conclusion, optimized DTI sequences may be applied routinely in clinical practice with a standard MR scanner, while accurate quantification of FA and MD may improve lesion characterization.

Adolescent↗

PubMed2006

Temporal and spatial enumeration processes in the primate parietal cortex.

Humans and animals can nonverbally enumerate visual items across time in a sequence or rapidly estimate the set size of spatial dot patterns at a single glance. We found that temporal and spatial enumeration processes engaged different populations of neurons in the intraparietal sulcus of behaving monkeys. Once the enumeration process was completed, however, another neuronal population represented the cardinality of a set irrespective of whether it had been cued in a spatial layout or across time. These data suggest distinct neural processing stages for different numerical formats, but also a final convergence of the segregated information to form most abstract quantity representations.

Analysis of Variance↗

PubMed1990

Functional dissection of an early Drosophila chorion gene promoter: expression throughout the follicular epithelium is under spatially composite regulation.

We have fused various DNA sequences located upstream of the Drosophila melanogaster s36 chorion gene TATA box to a heterologous basal promoter and reporter gene (hsp70/lacZ). The expression of these constructs, following P-element-mediated germline transformation, was examined in 144 independent lines by histological staining of dissected ovaries for beta-galactosidase activity. A short 84 bp segment of the proximal 5' flanking DNA was sufficient to confer a wild-type gene expression pattern, including temporal specificity for early choriogenic follicles. Surprisingly, initial expression was very localized at the anterior and posterior poles of the follicle. The downstream half of that DNA segment permitted expression at both poles, but especially at the anterior tip, while the upstream half only favored expression in the posterior pole; these results suggested the existence of multiple, spatially specific cis-regulatory elements. When the proximal 84 bp segment was placed 1.5 kb upstream of the basal promoter, beta-galactosidase activity was observed in an altered spatial pattern, indicating that the cis-regulatory element(s) that favor expression in the posterior half of the follicle are position independent, while the element(s) that favor expression elsewhere in the follicle are position sensitive. A distal regulatory segment containing redundant DNA element(s) specific for expression in the anterior pole was identified much further upstream of s36. Thus, the expression of this chorion gene throughout the follicular epithelium is actually composite, occurring in distinct spatial domains under the control of corresponding DNA elements.

Animals↗

PubMed1994

Neuronal activity in the primate supplementary, pre-supplementary and premotor cortex during externally and internally instructed sequential movements.

This study recorded the activity of neurons in the (i) supplementary motor area (SMA), (ii) pre-SMA (the motor area immediately rostral to the SMA), (iii) premotor cortex (PMC) and (iv) primary motor cortex (MI), while the monkey performed a conditional sequential motor task that ensures sequencing of multiple movements to the same manipulandum. This paradigm was chosen in order to prevent the participation of spatial cues in prompting the correct motor sequence. Three different movements (turn-push-pull) were performed under two task conditions: (i) internally determined (I): the monkey had to generate a pre-determined sequence from memory and without visual guidance; (ii) externally triggered (E): the correct sequence of movements was performed by following lights illuminated one after the other. Neuronal activity during the following periods were analyzed: instruction (300 ms following the onset of the auditory instruction signal); delay (interval between the end of the instruction period or the termination of the previous movement and the movement trigger); premovement (interval between the trigger signal and the movement onset); movement (interval between the mechanically-sensed movement onset and the completion of the movement) and reward (500 ms period centered at the time of reward delivery). Pre-SMA neurons were generally more active during the delay and premovement as compared to the movement, instruction and reward periods. Activity in the pre-SMA was more related to E during the pre-movement period, but exhibited a preferential relationship to I in the movement period. SMA neurons were more active when the sequential motor task was internally generated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2005

Fast T1- and T2-weighted pulmonary MR-imaging in patients with bronchial carcinoma.

PURPOSE: A prospective study to evaluate the diagnostic potential and limitations of three fast MRI sequences in patients with bronchial carcinoma based on the comparison with spiral CT. MATERIAL AND METHODS: Three fast chest MRI sequences from 20 patients with central or peripheral bronchial carcinoma were evaluated by two observers for relation of tumour to adjacent structures, lymph node enlargement, additional pulmonary lesions and artefacts. The information from MR-imaging was compared with the results from spiral CT. MRI comprised a T1-3D-GRE breath-hold examination ("VIBE", TR/TE 4.5/1.9 ms, flip-angle 12 degrees , matrix 502 x 512, 2.5 mm coronal slices), a breath-hold, T2-HASTE sequence (TR/TE 2000/43 ms, matrix 192 x 256, 10 mm coronal slices) and a respiration-triggered T2-TSE sequence (TR/TE 3000-6000/120 ms, matrix 270 x 512, 6 mm transverse slices). The FOV was adapted individually (380-480 mm). RESULTS: The presence of the primary bronchial carcinoma and infiltration of thoracic structures by tumour tissue could be demonstrated by all sequences. VIBE sequence was more suitable for detecting small pulmonary nodules than the other MRI examinations, but compared to CT still 20% of these lesions were missed. Contrary to VIBE and T2-weighted TSE scans, HASTE sequence was limited in imaging mediastinal lymph nodes due to missing relevant findings in 2/20 patients. HASTE images significantly provided the lowest rate of artefacts in imaging lung parenchyma (P < 0.001 in peripheral parenchyma), but spatial resolution was limited in this sequence. Concerning the differentiation between tumour and adjacent atelectasis (n = 8), T2-weighted TSE imaging was superior to CT and VIBE in all cases and to HASTE sequence in 4/8 patients. CONCLUSION: The combination of VIBE and HASTE sequence allows for an adaequate imaging of thoracic processes in patients with bronchial carcinoma, limited only in visualizing small pulmonary nodules. To obtain more detail resolution and to differentiate tumour tissue from adjacent atelectasis, T2-TSE examination may be added in selected cases.

Aged↗

PubMed1995

1/f noise in human cognition.

When a person attempts to produce from memory a given spatial or temporal interval, there is inevitably some error associated with the estimate. The time course of this error was measured in a series of experiments where subjects repeatedly attempted to replicate given target intervals. Sequences of the errors in both spatial and temporal replications were found to fluctuate as 1/f noises. 1/f noise is encountered in a wide variety of physical systems and is theorized to be a characteristic signature of complexity.

Cognition↗

PubMed2001

Characterization of mouse Atp6i gene, the gene promoter, and the gene expression.

Solubilization of bone mineral by osteoclasts depends on the formation of an acidic extracellular compartment through the action of a V-type ATPase. We previously cloned a gene encoding a putative osteoclast-specific proton pump subunit, termed OC-116 kDa, approved mouse Atp6i (ATPase, H+ transporting, [vacuolar proton pump] member I). The function of Atp6i as osteoclast-specific proton pump subunit was confirmed in our mouse knockout study. However, the transcription regulation of Atp6i remains largely unknown. In this study, the gene encoding mouse Atp6i and the promoter have been isolated and completely sequenced. In addition, the temporal and spatial expressions of Atp6i have been characterized. Intrachromosomal mapping studies revealed that the gene contains 20 exons and 19 introns spanning approximately 11 kilobases (kb) of genomic DNA. Alignment of the mouse Atp6i gene exon sequence and predicted amino acid sequence to that of the human reveals a strong homology at both the nucleotide (82%) and the amino acid (80%) levels. Primer extension assay indicates that there is one transcription start site at 48 base pairs (bp) upstream of the initiator Met codon. Analysis of 4 kb of the putative promoter region indicates that this gene lacks canonical TATA and CAAT boxes and contains multiple putative transcription regulatory elements. Northern blot analysis of RNAs from a number of mouse tissues reveals that Atp6i is expressed predominantly in osteoclasts, and this predominant expression was confirmed by reverse-transcription polymerase chain reaction (RT-PCR) assay and immunohistochemical analysis. Whole-mount in situ hybridization shows that Atp6i expression is detected initially in the headfold region and posterior region in the somite stage of mouse embryonic development (E8.5) and becomes progressively restricted to anterior regions and the limb bud by E9.5. The expression level of Atp6i is largely reduced after E10.5. This is the first report of the characterizations of Atp6i gene, its promoter, and its gene expression patterns during mouse development. This study may provide valuable insights into the function of Atp6i, its osteoclast-selective expression, regulation, and the molecular mechanisms responsible for osteoclast activation.

Adenosine Triphosphatases↗

PubMed2025

SpaceBar enables clone tracing in spatial transcriptomic data.

We report a cellular barcoding strategy, SpaceBar, that enables simultaneous clone tracing and spatial transcriptomics profiling. Our approach uses a library of 96 synthetic barcode sequences that can be robustly detected by imaging based spatial transcriptomics (seqFISH), delivered such that each cell is labeled with a combination of barcodes. We used these barcodes to label melanoma cells in a tumor xenograft model and profiled both clone identity and spatial gene expression in situ. We developed a gene scoring metric that quantifies how strongly gene expression is driven by intrinsic cellular cues or extrinsic environmental signals. Our framework distinguishes between clonal dynamics and environmentally-driven transcriptional regulation in complex tissue contexts.

Journal Article↗

PubMed1993

Primary structure of a variable region of the V kappa I subgroup (ISE) in light chain deposition disease.

Although structural abnormalities of monoclonal immunoglobulin light chains (LC) are suspected to play a determinant role in non-amyloid light chain deposition disease (LCDD), this condition is as yet poorly documented at the molecular level, since only three sequences have been reported to date. In a case of myeloma-associated LCDD, the patient's urine contained an unglycosylated kappa Bence Jones protein made up of dimers and monomers with an apparent molecular mass of 25,000 which was assigned to the V kappa I subgroup by N-terminal amino acid sequencing. The complete variable region sequence of the monoclonal kappa chain produced by the malignant plasma cells was amplified by polymerase chain reaction (PCR) using small amounts of material obtained by bone marrow aspiration. The sequence of three independently amplified cDNA clones derived from a normal-sized kappa messenger RNA was identical to that of the urinary kappa chain. The kappa mRNA had an overall normal structure made up of a V kappa I sequence rearranged to J kappa I. Several unusual features of the variable region (the first complete V kappa I sequence reported in LCDD) included three substitutions that introduced hydrophobic residues at spatially close positions. The strategy associating N-terminal sequence determination and cDNA cloning by PCR could help in accumulating new sequence data and improving our understanding of LCDD pathogenesis.

Amino Acid Sequence↗

PubMed1998

The role of sequences unique to nuclear intermediate filaments in the targeting and assembly of human lamin B: evidence for lack of interaction of lamin B with its putative receptor.

The mechanism by which human nuclear lamin B is targeted and assembled has been studied by transfecting into mammalian cells lamin mutants deleted of three sequences unique to lamins. Nuclear lamins contain an extra 42 amino acids (aa) in their rod domains and NLS and CAAX motifs in their tail domains, which distinguishes them from cytoplasmic IF proteins. These three sequences act in concert to ensure correct temporal and spatial assembly of lamin B. Deletion of any one of these three sequences from lamin B did not significantly disrupt nuclear lamina targeting, but when two or more of these sequences were deleted, targeting was severely compromised. The CAAX motif is necessary for the efficient integration of lamin B into an already formed nuclear lamina, since lamin B CAAX- mutants had reduced targeting to the lamina when arrested in S phase of the cell cycle. CAAX-deficient mutant lamin B proteins were soluble and not associated with membranes at mitosis, proving that the CAAX motif is responsible for association of human lamin B with membranes. In addition, CAAX- mutant lamin B proteins fractionated independently of the lamin B-receptor (LBR), indicating that these two proteins do not bind directly to each other.

3T3 Cells↗

PubMed1999

DNA replication and nuclear organization: prospects for a soluble in vitro system.

The role of nuclear structure in the replication of eukaryotic DNA has been the subject of debate for many decades. The recent demonstration that once-per-cell-cycle replication can take place in vitro without a nucleus, providing sufficiently high concentrations of replication factors are supplied, suggests that one role of the nucleus is to concentrate essential factors. This important finding has paved the way for the establishment of a purified biochemical system for replication of eukaryotic DNA. However, this soluble system, derived from Xenopus egg extracts, initiates replication within any DNA sequence and does not recapitulate the spatial and temporal regulation of DNA replication that is observed in most cells. In both Xenopus and Drosophila embryos, site-specific initiation of replication is not observed until after nuclei become transcriptionally active at the blastula stage of development. Furthermore, programmed changes in both the locations of origins and the time during S-phase at which sequences are replicated accompany key stages of metazoan development. Recent findings indicate that these changes correlate with changes in nuclear organization and that the spatial and temporal program for replication is established early in G1-phase when nuclei are structurally and functionally reorganized after mitosis.

Animals↗

PubMed1999

Single large DNA molecule analysis using fluorescence microscopy.

A large DNA analysis method which enable to obtain spatial information of positions of specific sequences along DNA molecule has been developed. Making use of the phenomenon that large DNA molecule is elongated stably under alternative current field in a concentrated linear polymer solution, direct observation of elongated individual lambda DNA molecules with fluorescence probes was carried out using fluorescence microscopy. Then, the spatial positions of the fluorescence spot of the probe on the DNA molecule were determined by image analysis.

Bacteriophage lambda↗

PubMed1993

Nuclear DNA sequence divergence between parapatric subspecies of the grasshopper Chorthippus parallelus.

Sequence data from a non-coding nuclear DNA segment (Cpnl-1) was used to investigate the divergence between Spanish and French subspecies of the grasshopper Chorthippus parallus which form a hybrid zone in the Pyrenees. The spatial distribution of eighteen Cpnl-1 sequence haplotypes from eighteen French and fifteen Spanish populations and phylogenetic analyses using both distance and parsimony procedures provide strong evidence that the Pyrenean hybrid zone was formed by postglacial secondary contact and that the French subspecies arose by range expansion from a Balkan or Italian refugium. In addition, the data provide evidence for subdivision between grasshoppers from Northern Spain and those from Central and Pyrenean Spanish populations.

Animals↗

PubMedDate not supplied

[Cognitive deterioration in Huntington disease].

OBJECTIVES: To review, summarize and update data on the pattern of cognitive deterioration in Huntington's disease (HD). DEVELOPMENT: HD represents a paradigm of frontostriatal dementia in which cognitive deterioration affects three large domains: memory, executive and visual-spatial functions. Episodic explicit memory deficit mainly affects the processes of information recovery, whilst changes in implicit memory are impaired in learning procedures but not in priming. Executive dysfunction constitutes an essential characteristic, affecting the working memory, attention, sequencing and planning. Complex visual-spatial functions are severely affected and this may affect recognition of complex figures and facial gestures. Some of these mental changes may be detected during preclinical stages. At the present time, since it is possible to make a definite genetic diagnosis and there is neuropathological data on HD, this condition is considered to be an excellent clinical model for the study of the cognitive functions carried out by the cortico-striatal circuits. CONCLUSIONS: Using a multidisciplinary approach a cognitive model has been established in which the corpus striatum is considered to be the basic structure for selection of information which will generate the appropriate response, both motor and behavioral, for the context involved. Loss of this capacity leads to mental rigidity and perseveration in conduct, which are typical of the cognitive disorders of HD.

Attention↗

PubMed2026

Spatially confined electrochemical strategy with DNA-assembled nanogaps for SNP detection.

Accurate detection of low-abundance single nucleotide polymorphisms (SNPs) against a large excess of homologous wild-type sequences requires both selective molecular recognition and effective transduction of small sequence differences into measurable signals. Here, we report a spatially confined electrochemical strategy that couples sequence-selective recognition with size-dependent mass-transport gating. DNA-hybridization-driven self-assembly of gold nanoparticles (AuNPs) forms a three-dimensional self-assembled electrode (3D-SAE) with a DNA-defined interparticle architecture. Competitive probes (SP/WP) convert single-base recognition into distinct molecular-size states: the SNP-associated pathway preferentially triggers a hybridization chain reaction (HCR), generating bulky AuNP-anchored HCR/methylene blue complexes (Au@HCR/MB) with reduced electrochemical accessibility through the porous 3D-SAE, whereas the wild-type pathway does not trigger HCR and maintains a high-current response from more readily accessible MB-containing species. Thus, sequence recognition is translated into a molecular-size difference and subsequently into an electrochemical signal through differential mass transport. Under buffer conditions, the platform achieved a statistically estimated detection limit of ∼0.47 fM and a quantitative range of 1 fM-100 pM. It discriminated a 0.1% mutant abundance in a fragmented genomic-DNA background. The downstream signal-transduction chemistry is enzyme-free and isothermal. This work establishes a mechanistical recognition-size-conversion-mass-transport-gating architecture for electrochemical nucleic acid analysis.

Polymorphism, Single Nucleotide↗