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The posterior parietal cortex: sensorimotor interface for the planning and online control of visually guided movements.

We present a view of the posterior parietal cortex (PPC) as a sensorimotor interface for visually guided movements. Special attention is given to the role of the PPC in arm movement planning, where representations of target position and current hand position in an eye-centered frame of reference appear to be mapped directly to a representation of motor error in a hand-centered frame of reference. This mapping is direct in the sense that it does not require target position to be transformed into intermediate reference frames in order to derive a motor error signal in hand-centered coordinates. Despite being direct, this transformation appears to manifest in the PPC as a gradual change in the functional properties of cells along the ventro-dorsal axis of the superior parietal lobule (SPL), i.e. from deep in the sulcus to the cortical surface. Possible roles for the PPC in context dependent coordinate transformations, formation of intrinsic movement representations, and in online control of visually guided arm movements are also discussed. Overall these studies point to the emerging view that, for arm movements, the PPC plays a role not only in the inverse transformations required to convert sensory information into motor commands but also in 'forward' transformations as well, i.e. in integrating sensory input with previous and ongoing motor commands to maintain a continuous estimate of arm state that can be used to update present and future movement plans. Critically, this state estimate appears to be encoded in an eye-centered frame of reference.

Animals↗

Peroxisomal proteomics, a new tool for risk assessment of peroxisome proliferating pollutants in the marine environment.

In an attempt to improve the detection of peroxisome proliferation as a biomarker in environmental pollution assessment, we have applied a novel approach based on peroxisomal proteomics. Peroxisomal proteins from digestive glands of mussels Mytilus galloprovincialis were analyzed using 2-DE and MS. We have generated a reference 2-DE map from samples obtained in a well-studied reference area and compared this with peroxisomal proteomes from other sequenced genomes. In addition, by comparing 2-DE maps from control samples with samples obtained in a polluted area, we have characterized the peroxisome proliferation expression pattern associated with exposure to a polluted environment. Over 100 spots were reproducibly resolved per 2-DE map; 55 differentially expressed spots were quantitatively detected and analyzed, and 14 of these showed an increase in protein expression of more than fourfold. Epoxide hydrolase, peroxisomal antioxidant enzyme, and sarcosine oxidase (SOX) have been identified by ESI MS/MS, and acyl-CoA oxidase, multifunctional protein, and Cu,Zn-superoxide dismutase were immunolocalized by Western blotting. Our results indicate that a peroxisomal protein pattern associated to marine pollutant exposure can be generated, and this approach may have a greater potential as biomarker than traditional, single-protein markers.

Animals↗

A Simplified Workflow for the Prediction of Putative Viral Reads Using NIPT Data.

OBJECTIVE: Non-invasive prenatal testing (NIPT) identifies fetal chromosomal abnormalities by sequencing cell-free fetal DNA (cffDNA). Recent studies suggest the prediction of viral sequences from NIPT data, but current methods lack cost-effectiveness for routine use. This study develops a straightforward workflow to investigate potential viral signatures in pregnant women using NIPT data from 888 Iranian participants. METHOD: Two bioinformatic workflows were compared for predicting viral reads: the traditional method involved mapping reads to the human genome, followed by mapping unmapped reads to viral references, and a direct mapping approach to viral genomes, as proposed in this research. RESULTS: While maintaining reproducibility comparable to the conventional method, the proposed workflow minimizes computational complexity and time usage for data processing. Ultimately, this analysis suggested viral DNA in 24.2% of samples, encompassing 29 distinct species, implying the diversity of the maternal virome. CONCLUSION: This study presents a computationally efficient workflow for the in silico prediction of viral-like sequences from routine NIPT data. Further experimental validation is essential to verify the presence, viability, or clinical relevance of these sequences.

Humans↗

Mapping approaches to gene identification in humans.

Although a number of human genes that cause disease have been traced through the defective product, most genetic defects are recognized only by phenotype. When the biochemical defect is unknown, a gene can be located only through molecular approaches based on coinheritance (genetic linkage) of the disease phenotype with a particular allele of a polymorphic DNA marker that has already been mapped to a specific chromosomal region. Linkage studies in affected families have already localized genes for several important diseases, including cystic fibrosis. Finding a genetic linkage in families in which a disease segregates requires that the human genetic map have a large number of polymorphic markers; when the map is dense enough, any disease gene can be located by linkage to a known marker. Many DNA segments with a high degree of polymorphism are being found and mapped as markers in normal reference pedigrees. Genetic linkage mapping has implications even broader than its application to prenatal diagnosis or therapeutic strategy; analyzing mutations in important genes will illuminate basic mechanisms in molecular biology and the early events that lead to cancer and other disorders.

Chromosome Mapping↗

Genetic mapping of the dentinogenesis imperfecta type II locus.

Dentinogenesis imperfecta type II (DGI-II) is an autosomal dominant disorder of dentin formation, which has previously been mapped to chromosome 4q12-21. In the current study, six novel short tandem-repeat polymorphisms (STRPs) have been isolated, five of which show significant evidence of linkage to DGI-II. To determine the order of the STRPs and define the genetic distance between them, nine loci (including polymorphisms for two known genes) were mapped through the CEPH reference pedigrees. The resulting genetic map encompasses 16.3 cM on the sex-averaged map. To combine this map with a physical map of the region, all of the STRPs were mapped through a somatic cell hybrid panel. The most likely location for the DGI-II locus within the fixed marker map is in the D4S2691-D4S2692 interval of 6.6 cM. The presence of a marker that shows no recombination with the DGI-II phenotype between the flanking markers provides an important anchor point for the creation of physical continuity across the DGI-II candidate region.

Base Sequence↗

Advances in cytoarchitectonic mapping of the human cerebral cortex.

The classic cytoarchitectonic maps of the human cerebral cortex (e.g., that of Brodmann [1909]) considerably influenced the concept of localization of function. Although they suffer from drawbacks such as the highly observer-dependent definition of areal borders and the lack of information on intersubject variability of location and size of a cortical area in a spatial reference system, these maps often serve as anatomic references in functional imaging studies. Recent methodologic progress in computerized image analysis of histologic specimens and the development of warping techniques to compensate for intersubject variability of brain structure in the three-dimensional (3-D) space made it possible to overcome these drawbacks. The authors propose a new concept of cytoarchitectonic mapping, which is based on (1) a definition of areal borders using multivariate statistical analysis, (2) a quantitative analysis of similarity and dissimilarity in architecture between cortical areas, and (3) a probabilistic mapping of cytoarchitectonic areas in a 3-D reference system. The combined analysis of architectonic maps and functional imaging data in an identical reference space offers exciting perspectives in the analysis of structural-functional correlations in the living human brain and provides new insights into the architecture of the cerebral cortex.

Animals↗

Using a network menu and the UMLS Information Sources Map to facilitate access to online reference materials.

As computer technology advances, clinicians and biomedical researchers are becoming more dependent upon information from online databases and information systems. By using specially configured computer workstations and high-speed computer networks, it is now possible to access this information in a rapid and straightforward manner. To empower users by providing these capabilities, the authors are assembling a variety of network workstations to be located throughout Yale-New Haven Medical Center. At the heart of the workstation is NetMenu, a program designed to help users connect to a number of important online information systems, including a hospital order entry and results reporting system, a drug reference, bibliographic retrieval systems, and educational programs. In addition, as part of the National Library of Medicine's Unified Medical Language System (UMLS) project, the authors have developed a local prototype of the UMLS Information Sources Map (ISM) and a companion query assistant program to complement the NetMenu in helping users select and connect automatically to information services relevant to a particular question. The ISM query assistant draws from a listing of many online information sources accessible via local and international networks.

Computer Communication Networks↗

Comparative mapping of the chicken genome using the East Lansing reference population.

The annotation of known genes on linkage maps provides an informative framework for synteny mapping. In comparative gene mapping, conserved synteny is broadly defined as groups of two or more linked markers that are also linked in two or more species. Although many anonymous markers have been placed on the chicken genome map, locating known genes will augment the number of conserved syntenic groups and consolidate linkage groups. In this report, 21 additional genes have been assigned to linkage groups or chromosomes; five syntenic groups were identified. Ultimately, conserved syntenic groups may help to pinpoint important quantitative trait loci.

Animals↗

Physical mapping of BglII, BamHI, EcoRI, HindIII and PstI restriction fragments of bacteriophage P1 DNA.

A cleavage map of bacteriophage P1 DNA was established by reciprocal double digestion with various restriction endonucleases. The enzymes used and, in parenthesis, the number of their cleavage sites on the P1clts genome are: PstI (1), HindIII(3), BglII (11), BamHI (14) and EcoRI (26). The relative order of the PstI, HindIII and BglII sites, as well as the order of 13 out of the 14 BamHI sites and of 17 out of the 26 EcoRI sites was determined. The P1 genome was divided into 100 map units and the PstI site was arbitrarily chosen as reference point at map unit 20. DNA packaging into phage heads starts preferentially at map unit 92 and it proceeds towards higher map units. The two inverted repeat sequences of P1 DNA map about at units 30 and 34.

Base Sequence↗

Bit-mapped color imaging of human evoked potentials with reference to the N20, P22, P27 and N30 somatosensory responses.

Bit-mapped color imaging of scalp potential fields evoked by sensory stimulation in humans disclosed significant features not identified by mere inspection of multichannel traces. Methodological problems are considered in detail for early cortical SEPs which include several components with sharp rise times occurring at spatially distinct scalp locations. A manageable yet efficient imaging system requires recording electrodes in adequate number and scalp locations, bandpass fidelity to resolve slow and fast components, consistency of bioelectric input data, optimal interpolation and mapping algorithms, and consistent color scaling. Critical steps in these procedures were investigated in conjunction with new evidence on the scalp topography and neural generators of the N20, P20, P22, P27 and N30 SEP components. It is concluded that N20-P20 reflect a tangential equivalent dipole in parietal area 3b while P22 reflects a radial equivalent dipole in motor area 4.

Adult↗

Sensitive and fast T1 mapping based on two inversion recovery images and a reference image.

We developed a fast method to obtain T1 relaxation maps in magnetic resonance imaging (MRI) based on two inversion recovery acquisitions and a reference acquisition, while maintaining high sensitivity by utilizing the full dynamic range of the MRI signal. Optimal inversion times for estimating T1 in the human brain were predicted using standard error propagation theory. In vivo measurements on nine healthy volunteers yielded T1 values of 1094+/-18 ms in gray matter and 746+/-40 ms in white matter, in reasonable agreement with literature values using conventional approaches. The proposed method should be useful for clinical studies because the T1 maps can be obtained within a few seconds.

Algorithms↗

Enzyme cytochemical techniques for metabolic mapping in living cells, with special reference to proteolysis.

Specific enzymes play key roles in many pathophysiological processes and therefore are targets for therapeutic strategies. The activity of most enzymes is largely determined by many factors at the post-translational level. Therefore, it is essential to study the activity of target enzymes in living cells and tissues in a quantitative manner in relation to pathophysiological processes to understand its relevance and the potential impact of its targeting by drugs. Proteases, in particular, are crucial in every aspect of life and death of an organism and are therefore important targets. Enzyme activity in living cells can be studied with various tools. These can be endogenous fluorescent metabolites or synthetic chromogenic or fluorogenic substrates. The use of endogenous metabolites is rather limited and nonspecific because they are involved in many biological processes, but novel chromogenic and fluorogenic substrates have been developed to monitor activity of enzymes, and particularly proteases, in living cells and tissues. This review discusses these substrates and the methods in which they are applied, as well as their advantages and disadvantages for metabolic mapping in living cells.

Animals↗

Preliminary linkage map of the chicken (Gallus domesticus) genome based on microsatellite markers: 77 new markers mapped.

Microsatellite polymorphisms are finding increasing use in genetics. The objectives of this study were 1) to enlarge the number of markers to contribute to a well-defined linkage map of the chicken genome; and 2) to create a preliminary linkage map only based on microsatellite markers. The need for microsatellite markers is high for performing a whole genome scan for the identification of quantitative trait loci. Seventy-seven newly developed microsatellite markers that were polymorphic on either one or both of the reference populations were mapped and in combination with all previously described markers, used to construct a preliminary linkage map of the chicken genome. The 128 microsatellite markers mapped thus far cover 23 of the 38 linkage groups of the East Lansing reference population. In the case of the Compton reference population, 20 linkage groups out of 40 are covered with microsatellite markers. No linkage was found in the East Lansing population with five markers, and in the case of the Compton population four markers were unlinked. About 42 and 32% of the East Lansing and Compton maps, respectively, were covered by the 128 microsatellite markers. The microsatellite markers are well dispersed among the various linkage groups and there was no evidence for clustering of the markers within the map. With the 38 markers that were mapped on both reference populations, 10 of the East Lansing linkage groups could be associated with 13 of the Compton linkage groups.

Animals↗

Partial cloning of a squid microtubule-associated protein (MAP H1) and the identification of the microtubule binding domain.

An approximately 420-kDa ATP binding protein, referred to as MAP H1, has previously been shown to be involved in microtubule-dependent vesicle motility in the squid giant axon. To gain further insight into the structure and function of this protein, partially overlapping cDNA clones encoding approximately a quarter of the MAP H1 molecule were identified from two squid optic lobe libraries using affinity-purified antibodies to squid MAP H1. One clone in particular (KS18), which hybridizes to an approximately 13-kb message, encodes a series of almost identical repeats of a 16-amino-acid sequence that is tandemly repeated. The sequence of clone KS18 is unique and does not correspond to any nucleotide or amino acid sequence in the data base. The presence of repeated elements within the microtubule binding domain of several other MAPs prompted us to investigate whether the MAP H1 repeats are involved in microtubule binding. In-vitro-synthesized polypeptides containing these repeats sediment with taxol-stabilized microtubules in a microtubule binding assay. The predicted secondary structure of the 16-amino-acid repeat region of MAP H1 contains alternating beta-sheets and turns and could form the globular domain seen in negative-stain electron micrographs of MAP H1.

Amino Acid Sequence↗

Development of EST-derived CAPS and AFLP markers linked to a gene for resistance to ryegrass blast (Pyricularia sp.) in Italian ryegrass (Lolium multiflorum Lam.).

Ryegrass blast, also called gray leaf spot, is caused by the fungus Pyricularia sp. It is one of the most serious diseases of Italian ryegrass (Lolium multiflorum Lam.) in Japan. We analyzed segregation of resistance in an F(1) population from a cross between a resistant and a susceptible cultivar. The disease severity distribution in the F(1) population suggested that resistance was controlled by a major gene (Lm Pi1). Analysis of amplified fragment length polymorphisms with bulked segregant analysis identified several markers tightly linked to Lm Pi1. To identify other markers linked to Lm Pi1, we used expressed sequence tag-cleaved amplified polymorphic sequence (EST-CAPS) markers mapped in a reference population of Italian ryegrass. Of the 30 EST-CAPS markers screened, one marker, p 56, flanking the Lm Pi1 locus was found. The restriction pattern of p 56 amplification showed a unique fragment corresponding to the resistant allele at the Lm Pi1 locus. A linkage map constructed from the reference population showed that the Lm Pi1 locus was located in linkage group 5 of Italian ryegrass. Genotype results obtained from resistant and susceptible cultivars indicate that the p 56 marker is useful for introduction of the Lm Pi1 gene into susceptible germ plasm in order to develop ryegrass cultivars with enhanced resistance to ryegrass blast.

Base Sequence↗

Automatic re-contouring in 4D radiotherapy.

Delineating regions of interest (ROIs) on each phase of four-dimensional (4D) computed tomography (CT) images is an essential step for 4D radiotherapy. The requirement of manual phase-by-phase contouring prohibits the routine use of 4D radiotherapy. This paper develops an automatic re-contouring algorithm that combines techniques of deformable registration and surface construction. ROIs are manually contoured slice-by-slice in the reference phase image. A reference surface is constructed based on these reference contours using a triangulated surface construction technique. The deformable registration technique provides the voxel-to-voxel mapping between the reference phase and the test phase. The vertices of the reference surface are displaced in accordance with the deformation map, resulting in a deformed surface. The new contours are reconstructed by cutting the deformed surface slice-by-slice along the transversal, sagittal or coronal direction. Since both the inputs and outputs of our automatic re-contouring algorithm are contours, it is relatively easy to cope with any treatment planning system. We tested our automatic re-contouring algorithm using a deformable phantom and 4D CT images of six lung cancer patients. The proposed algorithm is validated by visual inspections and quantitative comparisons of the automatic re-contours with both the gold standard segmentations and the manual contours. Based on the automatic delineated ROIs, changes of tumour and sensitive structures during respiration are quantitatively analysed. This algorithm could also be used to re-contour daily images for treatment evaluation and adaptive radiotherapy.

Aged↗

Taxonomic map of the schizophrenias, with special reference to puerperal psychosis.

Data collected by a single observer on 147 schizophrenic patients were subjected to clustering analysis. The results produced the hypothesis that schizophrenic illnesses directly after childbirth are a separate disease entity. This hypothesis was not disproved by experimental testing. Several disease entities may be included in the term schizophrenia. If this is so, the methods used in generating and testing the hypothesis that puerperal schizophrenia is a separate disease may provide a systematic method of classifying the various illnesses.

Bipolar Disorder↗

Histone H4 from cuttlefish testis is sequentially acetylated. Comparison with acetylation of calf thymus histone H4.

The differently acetylated subfractions of histone H4 isolated from cuttlefish testis and from calf thymus were separated by ion exchange chromatography on sulfopropyl-Sephadex, using a shallow linear gradient of guanidine hydrochloride in the presence of 6 M urea at pH 3.0. The tetra-, tri-, di-, mono-, and nonacetylated forms of cuttlefish H4 represent 2, 6.4, 18, 32.2, and 41.4% of the whole histone, respectively. The di-, mono-, and nonacetylated forms of calf H4 represent 11.7, 41.3, and 44% of the whole histone, respectively. The acetylation sites were determined in each subfraction by identification of the acetylated peptides. In each acetylated H4 subfraction, the acetylated tryptic peptides were identified by peptide mapping and amino acid analysis with reference to the peptide map of nonacetylated H4. In cuttlefish testis H4, lysine 12 is the main site of acetylation in the monoacetylated subfraction; lysines 5 and 12 are found acetylated in diacetylated H4; lysines 5, 12, and 16 are found acetylated in triacetylated H4. From these results and the stoichiometry of the different H4 subfractions, it can be concluded that lysine 5 is acetylated after lysine 12. In calf thymus, lysine 16 is the only site of acetylation in the monoacetylated subfraction. All the diacetylated forms are acetylated in lysine 16, the second site of acetylation being, in decreasing order, lysine 12, lysine 5, or lysine 8. These observations suggest that acetylation occurs in a sequential manner. Moreover, the sites of acetylation depend upon the biological event in which acetylation is involved.

Acetylation↗