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PubMed1989

Patient classification in neuropsychological research.

In a number of papers we have been concerned with the type of inferences that are legitimate in "experiments of nature" where the experimenter does not and cannot control the modifications to the cognitive system that are introduced by brain damage. We have argued that in such cases very restrictive conditions must be met in order to be able to draw valid inferences about the structure of normal cognitive mechanisms. Two consequences of these conditions are (1) patient classification into syndrome types (e.g., phonological dysgraphia, agrammatism, and so forth) can play no useful role in research concerned with issues about the structure of normal cognitive functioning or its dissolution under conditions of brain damage; and (2) only single-patient studies allow valid inferences about the structure of cognitive mechanisms from the analysis of impaired performance. Zurif, Gardner, and Brownell (1989, Brain and Cognition, 10, 237-255) have taken exception to our conclusions and propose to show the limitations of our arguments. In this paper we respond to their criticisms.

Aphasia↗

PubMed1991

Electrophoretic analysis of neuronal genomic DNA from hypertrophic spinal ganglia during lizard tail regeneration.

Cytoplasmic and nuclear hypertrophy in neurons from the last 3 pairs of sensory ganglia left in situ cranially to the plane of amputation occurs during lizard tail regeneration. Cytophotometry after Feulgen staining demonstrated the presence of some neurons, from hypertrophic ganglia, whose quantity of DNA exceeded the diploid level (hyperdiploid neurons). In the present work agarose gel electrophoresis of total genomic DNA extracted from hypertrophic ganglia showed one or two bands migrating below the high molecular weight DNA, pointing to a selective amplification of discrete DNA segments.

Amputation, Surgical↗

PubMed1988

CLONING: a microcomputer program for cloning simulations.

A comprehensive computational tool is presented that performs cloning simulations using IBM PC/XT/AT or compatible microcomputers. The CLONING program contains a specific data base for restriction sites, gene markers, fragment sources and reference comments. It draws complete linear or circular maps either on the screen or employing conventional dot-matrix printers. The design of new recombinant molecules is a totally interactive process.

Cloning, Molecular↗

PubMed1988

Mapping of Xp21 translocation breakpoints in and around the DMD gene by pulsed field gel electrophoresis.

Balanced translocations with a breakpoint in the Xp21 region are likely to disrupt the giant Duchenne muscular dystrophy (DMD) locus and can be demonstrated in females suffering from the disease. Pulsed field gel electrophoresis allows the positioning of these breakpoints by detecting junction fragments on the derived chromosomes; DNA probes hybridizing to these fragments may be located as many as several hundred kilobases away from the breakpoints. By using this approach, 11 translocation breakpoints from the Xp21 region have been analyzed. The localization of three previously examined breakpoints was confirmed. Six other breakpoints, including a breakpoint flanking the DMD gene and not associated with the DMD phenotype, could be positioned relative to SfiI sites on a 3.5-Mb restriction map of the region.

Cell Line↗

PubMed2004

Central poststroke pain and reduced opioid receptor binding within pain processing circuitries: a [11C]diprenorphine PET study.

Based on concepts that endogenous opioids participate in neural transmission of pain, the present study in central poststroke pain (CPSP) patients investigated changes in opioid receptor (OR) binding in neural structures centrally involved in the processing of pain. Five patients with central pain after lesions in the brain stem, thalamus or parietal cortex and twelve healthy volunteers underwent a [11C]diprenorphine positron emission tomography study. Binding potentials were calculated using a reference region model in all subjects. Statistical parametric mapping was applied for t-statistical analysis on voxel-basis. Binding potential values for each individual were extracted from a volume of interest at each identified significant peak. Spectral analysis was applied for quantification of global values. Significant regional reduced 11C-diprenorphine binding (corrected for multiple tests) was detected in contralateral thalamus, parietal, secondary somatosensory, insular and lateral prefrontal cortices, and along the midline in anterior cingulate, posterior cingulate and midbrain gray matter. Individual extracted binding values disclosed a reduced binding in these regions in all patients independent from the particular lesion site. The poststroke pain syndrome is associated with a characteristic pattern of reduced OR binding within the neural circuitry processing pain. It is suggested that an imbalance of excitatory-inhibitory mechanisms in certain brain structures, as evidenced in decreased [11C]diprenorphine binding, is one of the causes or the consequences of poststroke pain.

Aged↗

PubMed1997

Molecular dynamics study of time-correlated protein domain motions and molecular flexibility: cytochrome P450BM-3.

Time-correlated atomic motions were used to characterize protein domain boundaries from atomic coordinates generated by molecular dynamics simulations. A novel application of the dynamical cross-correlation matrix (DCCM) analysis tool was used to help identify putative protein domains. In implementing this new approach, several DCCM maps were calculated, each using a different coordinate reference frame from which protein domain boundaries and protein domain residue constituents could be identified. Cytochrome P450BM-3, from Bacillus megaterium, was used as the model protein in this study. The analyses indicated that the simulated protein comprises three distinct domain regions; in contrast, only two protein domains were identified in the original crystal structure report. Specifically, the DCCM analyses showed that the F-G helix region was a separate domain entity and not a part of the alpha domain, as previously designated. The simulations demonstrated that the domain motions of the F-G helix region effected both the size and shape of the enzyme active site, and that the dynamics of the F-G helix domain could possibly control access of substrate to the binding pocket.

Bacillus megaterium↗

PubMed2002

Brain systems engaged in encoding and retrieval of word-pair associates independent of their imagery content or presentation modalities.

In this study, we aimed to characterize commonalities and differences of activation patterns during verbal episodic memory processes across different presentation modalities (visual or auditory) and different imagery content (low or high) of the presented verbal memory items. Twelve right-handed normal male volunteers took part in the study. Each subject underwent six O-15-butanol positron emission tomography scans. In six of the subjects the verbal material was presented visually, and in six subjects auditorily. The subjects had to encode and retrieve two sets of 12 word-pair associates of high (set 1) or low (set 2) imagery content (not semantically related). The presentation of nonsense words served as reference condition. Images were analyzed with statistical parametric mapping. Conjunction analysis was used to identify commonalities, and cognitive subtraction analysis was used to identify differences. The use of conjunction analyses enabled us to identify commonly activated regions involved in episodic encoding and retrieval of verbal material irrespective of the presentation modality or the imagery content. Our results add further evidence to recent findings that bilateral prefrontal activations are important for episodic retrieval and thus the role of the left prefrontal cortex has been underestimated during episodic retrieval. Furthermore, our results support the idea of functionally segregated areas in the prefrontal cortex. Finally, our results provide strong evidence that mesial parietal cortex (precuneus) involvement is not restricted to processes involving imagery.

Adult↗

PubMed1990

Stereological studies of the hippocampus: a comparison of the hippocampal subdivisions of diverse species including hedgehogs, laboratory rodents, wild mice and men.

The volumes of the fascia dentata, hilus, regio inferior, regio superior and subiculum of 9 species that differ significantly in size and degree of forebrain evolution have been compared with the intent of identifying phylogenetic trends in the internal organization of the mammalian hippocampus. The study includes data from the hippocampi of a basal insectivore, 2 species of wild mice, 3 commonly used laboratory rodents and 3 species (including man) that resemble an ascending primate series. In addition to comparisons of the absolute and relative volumes, an allometric approach is used to identify "progressive" size differences not related to body size. Both regio superior and hilus become larger during evolution, while fascia dentata and regio inferior maintain a relationship to body size that is similar to that for the hippocampus in basal insectivores. The inter-species differences are discussed in terms of neuron number and size, for which data are presented from two species, and with reference to a neural model of the cognitive map theory for hippocampal function. Special emphasis is placed on the unique aspects of the human hippocampus. The data represents a quantitative morphological framework within which the observations from physiological, biochemical and behavioral studies in laboratory animals can be related to studies of the human hippocampus.

Animals↗

PubMed2003

Identification of proteins in single-cell capillary electrophoresis fingerprints based on comigration with standard proteins.

In the previous paper in this Journal, we reported the use of capillary sieving electrophoresis to characterize proteins expressed by single cancer cells at specific phases in the cell cycle. Analysis of the data revealed one component with cell cycle-dependent changes in expression at the 99% confidence limit. However, the amount of protein present in a single cell is far too small to allow its direct identification by mass spectrometry. In this paper, we report a method by which such proteins can be tentatively identified. We perform standard SDS-PAGE electrophoresis of the proteins contained within a homogenate prepared from an HT29 cell culture. Proteins extracted from bands in the gel are identified by mass spectrometry. The proteins also provide a set of standards that can be used to spike the sample before capillary sieving electrophoresis (CSE) separation; comigration is taken as evidence for the identity of the target protein. In a proof-of-principle experiment, a single band migrating at approximately 47 kDa was isolated from the SDS-PAGE gel generated from the HT29 cell line. Proteins extracted from this band were used to spike a CSE separation of the same extract. This band comigrated with a cell cycle-dependent component identified from single-cell analysis. In-gel digestion and LC/MS/MS were used to identify five proteins, including cytokeratin 18, which is the product of the most highly expressed gene in this cell line.

Amino Acid Sequence↗

PubMed1996

A novel X-linked gene, DDP, shows mutations in families with deafness (DFN-1), dystonia, mental deficiency and blindness.

In 1960, progressive sensorineural deafness (McKusick 304,700, DFN-1) was shown to be X-linked based on a description of a large Norwegian pedigree. More recently, it was shown that this original DFN-1 family represented a new type of recessive neurodegenerative syndrome characterized by postlingual progressive sensorineural deafness as the first presenting symptom in early childhood, followed by progressive dystonia, spasticity, dysphagia, mental deterioration, paranoia and cortical blindness. This new disorder, termed Mohr-Tranebjaerg syndrome (referred to here as DFN-1/MTS) was mapped to the Xq21.3-Xq22 region2. Using positional information from a patient with a 21-kb deletion in chromosome Xq22 and sensorineural deafness along with dystonia, we characterized a novel transcript lying within the deletion as a candidate for this complex syndrome. We now report small deletions in this candidate gene in the original DFN-1/MTS family, and in a family with deafness, dystonia and mental deficiency but not blindness. This gene, named DDP (deafness/ dystonia peptide), shows high levels of expression in fetal and adult brain. The DDP protein demonstrates striking similarity to a predicted Schizosaccharomyces pombe protein of no known function. Thus, is it likely that the DDP gene encodes an evolutionarily conserved novel polypeptide necessary for normal human neurological development.

Abnormalities, Multiple↗

PubMed2003

Haplotype block partition with limited resources and applications to human chromosome 21 haplotype data.

Recent studies have shown that the human genome has a haplotype block structure such that it can be decomposed into large blocks with high linkage disequilibrium (LD) and relatively limited haplotype diversity, separated by short regions of low LD. One of the practical implications of this observation is that only a small fraction of all the single-nucleotide polymorphisms (SNPs) (referred as "tag SNPs") can be chosen for mapping genes responsible for human complex diseases, which can significantly reduce genotyping effort, without much loss of power. Algorithms have been developed to partition haplotypes into blocks with the minimum number of tag SNPs for an entire chromosome. In practice, investigators may have limited resources, and only a certain number of SNPs can be genotyped. In the present article, we first formulate this problem as finding a block partition with a fixed number of tag SNPs that can cover the maximal percentage of the whole genome, and we then develop two dynamic programming algorithms to solve this problem. The algorithms are sufficiently flexible to permit knowledge of functional polymorphisms to be considered. We apply the algorithms to a data set of SNPs on human chromosome 21, combining the information of coding and noncoding regions. We study the density of SNPs in intergenic regions, introns, and exons, and we find that the SNP density in intergenic regions is similar to that in introns and is higher than that in exons, results that are consistent with previous studies. We also calculate the distribution of block break points in intergenic regions, genes, exons, and coding regions and do not find any significant differences.

Chromosomes, Human, Pair 21↗

PubMed1993

Diagnostic imaging as a measuring device for stereotactic neurosurgery.

A wide range of diagnostic imaging techniques are used as positional measuring devices for the localization stage of stereotactic neurosurgery. Positional mapping from the image system to the surgical reference frame is achieved using a variety of designs of fiduciary systems. Standard projection radiography, computed tomography, digital radiography and fluoroscopy, and magnetic resonance imaging are used to plan and accurately guide interventional neurosurgical procedures. A general summary of the applications of stereotactic techniques is presented. The techniques involved and the design principles of the fiduciary systems used are discussed, along with the scientific limitations and accuracies of the various systems.

Brain↗

PubMed1991

Multiple representations contribute to body knowledge processing. Evidence from a case of autotopagnosia.

Body schema disturbances were studied in a 62-yr-old woman with Alzheimer's disease. She was severely impaired in verbal and nonverbal tasks requiring her to localize body parts (on her own body, the examiner's body or a doll's body) even though she correctly named the same parts when pointed at by the examiner. Pointing responses were misdirected mainly to parts contiguous with the target area and, to a lesser extent, to functionally equivalent body parts. We also found that the patient was able to define body part names functionally but not spatially. In another series of tasks, and in contrast to the above results, performances were normal when small objects, attached to the patient's body, served as pointing targets. Furthermore, on subsequent testing she pointed correctly at the remembered position of these objects. The fact that the same point in 'body space' is localized correctly when it corresponds to an external object and erroneously when it corresponds to a body part contradicts the idea of the body schema as a unitary function. Learning the position of objects on the body surface requires access to some form of body-reference system on which this information can be mapped. We argue that such a system can be available in autotopagnosia and is independent from the visuospatial representations of the body structure that are postulated to be damaged or inaccessible in this syndrome. An integrated account of the present results and of those reported by other authors suggests that multiple levels of representation (e.g., sensorimotor, visuospatial, semantic) are involved in the organization of body knowledge.

Agnosia↗

PubMed1998

FlyBase: a Drosophila database.

FlyBase (http://flybase.bio.indiana.edu/) is a comprehensive database of genetic and molecular data concerning Drosophila . FlyBase is maintained as a relational database (in Sybase) and is made available as html documents and flat files. The scope of FlyBase includes: genes, alleles (with phenotypes), aberrations, transposons, pointers to sequence data, gene products, maps, clones, stock lists, Drosophila workers and bibliographic references.

Animals↗

PubMed2002

The European database on small subunit ribosomal RNA.

The European database on SSU rRNA can be consulted via the World WideWeb at http://rrna.uia.ac.be/ssu/ and compiles all complete or nearly complete small subunit ribosomal RNA sequences. Sequences are provided in aligned format. The alignment takes into account the secondary structure information derived by comparative sequence analysis of thousands of sequences. Additional information such as literature references, taxonomy, secondary structure models and nucleotide variability maps, is also available.

Animals↗

PubMed2004

TropGENE-DB, a multi-tropical crop information system.

TropGENE-DB, is a crop information system created to store genetic, molecular and phenotypic data of the numerous yet poorly documented tropical crop species. The most common data stored in TropGENE-DB are information on genetic resources (agro-morphological data, parentages, allelic diversity), molecular markers, genetic maps, results of quantitative trait loci analyses, data from physical mapping, sequences, genes, as well as the corresponding references. TropGENE-DB is organized on a crop basis with currently three running modules (sugarcane, cocoa and banana), with plans to create additional modules for rice, cotton, oil palm, coconut, rubber tree, pineapple, taro, yam and sorghum. The TropGENE-DB information system is accessible for consultation via the internet at http://tropgenedb.cirad.fr. Specific web consultation interfaces have been designed to allow quick consultations as well as complex queries.

Computational Biology↗

PubMed2004

Radon mapping in south Tyrol: comparison between two different procedures.

In this paper two different procedures for radon mapping have been compared on the same database referring to indoor radon records of South Tyrol. The first procedure is based on descriptive statistics applied to administrative units while the second one implies a more complicated statistical analysis applied to a regular grid: it involves floor level normalization of radon data, filling and smoothing algorithms for the territory cells.

Air Pollutants, Radioactive↗

PubMed2000

Discrete homoclinic orbits in a laser with feedback

We provide experimental evidence of the discrete character of homoclinic chaos in a laser with feedback. We show that the narrow chaotic windows are distributed exponentially as a function of a control parameter. The number of consecutive chaotic regions corresponds to the number of loops around the saddle focus responsible for Shilnikov chaos. The characterization of homoclinic chaos is also done through the return map of the return times at a suitable reference point.

Journal Article↗