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Inadequate cortical feature maps: a neural circuit theory of autism.

The autistic syndromes are caused by neurological dysfunctions. The capacity of autistic individuals to form representations of previous sensory impressions, useful for the processing of present information, is impaired. Self-organizing feature maps are mathematical models of cortical feature maps and may be used to simulate cortical processing. Dysfunctional self-organization, resulting in disability to extract features from stimuli, is proposed as a neural circuit theory of autism. The nature and a possible cause of dysfunction self-organization are examined. It is shown that impaired feature detection is valid for explaining the memory function in autism, the lack of drive for central coherence according to Frith's theory of autism, and a number of impairments from the diagnostic criteria. Unequal levels of impairment of different cortical feature maps can account for the typically uneven intelligence profile of autistic individuals. Excessive inhibitory lateral feedback synaptic connection strengths are presented as one factor impairing the development of feature maps. Strong or excessive inhibitory lateral feedback synaptic connection strengths also cause high sensory discrimination and abnormal sensory responses, both documented in autism. A neural circuit theory for autism has been presented. For a proof of this neural circuit theory neurological investigations are required.

Autistic Disorder↗

In vivo and in vitro assessment of mitogen activated protein kinase involvement during quail secondary palate formation.

Spatiotemporally regulated cell proliferation and differentiation are crucial for the successful completion of morphogenesis of the vertebrate secondary palate. An understanding of the mechanisms by which these cellular phenomena are regulated during palate development involves the identification of the various signal transduction pathways. In the present study, the presence and activation of mitogen-activated protein (MAP) kinases were investigated during the development of quail secondary palate. The palatal shelves were dissected on days 5-9 of incubation, homogenized, and centrifuged, after which the samples were separated by anion exchange fast protein liquid chromatography. The fractions were analyzed for myelin basic protein (MBP) phosphorylation. In addition, primary cultures of quail palate mesenchymal cells (QPMCs) were treated with epidermal growth factor (EGF) and prepared for MBP phosphorylation assays. A temporally regulated pattern of phosphotransferase activity, characterized by a three-fold increase in phosphotransferase activity toward MBP between days 5 and 8 of incubation, was observed during quail palate development. Western blotting, using MAP kinase antibodies, demonstrated the presence of a 42-kDa isoform between days 5 and 9 of incubation, during which the level of protein remained constant. Antityrosine immunoblotting with 4G10 also detected a 42-kDa protein. Phosphotransferase assays, using either a MAP kinase-specific substrate peptide (S5) or a protein kinase C inhibitor (R3), further confirmed the presence of a MAP kinase in the developing palate of quail. Because diverse biological processes occur concurrently during in vivo palate morphogenesis, the involvement of MAP kinase was explored further in primary cell culture. The data showed that EGF stimulated proliferation and activated 42-kDa MAP kinase in QPMCs. It is suggested that MAP kinase cascade may be involved in growth factor-regulated cell proliferation during morphogenesis of quail secondary palate.

Animals↗

Stochastic analysis to assess the spatial distribution of groundwater nitrate concentrations in the Po catchment (Italy).

A large database including temporal trends of physical, ecological and socio-economic data was developed within the EUROCAT project. The aim was to estimate the nutrient fluxes for different socio-economic scenarios at catchment and coastal zone level of the Po catchment (Northern Italy) with reference to the Water Quality Objectives reported in the Water Framework Directive (WFD 2000/60/CE) and also in Italian legislation. Emission data derived from different sources at national, regional and local levels are referred to point and non-point sources. While non-point (diffuse) sources are simply integrated into the nutrient flux model, point sources are irregularly distributed. Intensive farming activity in the Po valley is one of the main Pressure factors Driving groundwater pollution in the catchment, therefore understanding the spatial variability of groundwater nitrate concentrations is a critical issue to be considered in developing a Water Quality Management Plan. In order to use the scattered point source data as input in our biogeochemical and transport models, it was necessary to predict their values and associated uncertainty at unsampled locations. This study reports the spatial distribution and uncertainty of groundwater nitrate concentration at a test site of the Po watershed using a probabilistic approach. Our approach was based on geostatistical sequential Gaussian simulation used to yield a series of stochastic images characterized by equally probable spatial distributions of the nitrate concentration across the area. Post-processing of many simulations allowed the mapping of contaminated and uncontaminated areas and provided a model for the uncertainty in the spatial distribution of nitrate concentrations.

Agriculture↗

New images from human visual cortex.

Recent developments in imaging and histology have greatly clarified our understanding of the nature and organization of human visual cortex. More than ten human cortical visual areas can now be differentiated, compared with the approximately 30 areas described in macaque monkeys. Most human areas and columns described so far appear quite similar to those in macaque but distinctive species differences also exist. Imaging studies suggest two general information-processing streams (parietal and temporal) in human visual cortex, as proposed in macaque. Several human areas are both motion- and direction-selective, and a progression of motion-processing steps can be-inferred from the imaging data. Human visual areas for recognizing form are less well defined but the evidence again suggests a progression of information-processing steps and areas, beginning posterior to the human middle temporal area (or V5), and extending inferiorly then anteriorly. This is consistent with findings from macaque, and with human clinical reports.

Animals↗

[HL7 standard--features, principles, and methodology].

The mission of HL7 Inc. non-profit organization is to provide standards for the exchange, management and integration of data that support clinical patient care, and the management, delivery and evaluation of healthcare services. As the standards developed by HL7 Inc. represent the world's most influential standardization efforts in the field of medical informatics, the HL7 family of standards has been recognized by the technical and scientific community as the foundation for the next generation healthcare information systems. Versions 1 and 2 of HL7 standard have solved many issues, but also demonstrated the size and complexity of health information sharing problem. As the solution complete new methodology has been adopted that is encompassed in the HL7 Version 3 recommendations. This approach standardizes Reference Information Model (RIM), which is the source of all derived domain models and message structures. Message design is now defined in detail, enabling interoperability between loosely coupled systems that are.designed by different vendors and deployed in various environments. At the start of the Primary Healthcare Information System project in the Republic of Croatia in 2002, the decision was to go directly to Version 3. The target scope of work includes clinical, financial and administrative data management in the domain of healthcare processes. By using HL7v3 standardized methodology we were able to completely map the Croatian primary healthcare domain to HL7v3 artefacts. Further refinement processes that are planned for the future will provide semantic interoperability and detailed description of all elements in HL7 messages. Our HL7 Business Component is in constant process of studying different legacy applications, making solid foundation for their integration to HL7-enabled communication environment.

Ambulatory Care Information Systems↗

Mass mapping of cancer cell lysates using two-dimensional liquid separations, electrospray-time of flight-mass spectrometry, and automated data processing.

Intact protein masses from immortal, nontransformed MCF10A, a human breast epithelial cell line, and its malignant derivative MCF10CA1a.cl1 have been mapped using a combination of all-liquid separations and automated data interpretation. Preparative liquid isoelectric focusing combined with nonporous silica reverse-phase high-performance liquid chromatography allows efficient separation of a large number of proteins in complex mixtures such as whole-cell lysates. Molecular weight determination of these proteins is achieved using electrospray-time of flight-mass spectrometry, however, manual data analysis for these separations is both complex and time-consuming. Protein mass mapping can be significantly enhanced by automating deconvolution functions typically performed manually, with resulting reductions in hands-on analysis time from 20-30 h per chromatogram to approximately 15 min. This reduction in analysis time allows for rapid screening of cancer cell lines for potential biomarkers over a wider pI range than would otherwise be possible.

Biomarkers, Tumor↗

Two sequences participating in the autolytic processing of satellite tobacco ringspot virus complementary RNA.

Circular and multimeric forms of the satellite RNA of tobacco ringspot virus and their autolytic processing reactions are well known. They suggest replication models in which key elements are rolling circle transcription and the processing of the resulting multimeric RNA to generate the unit, 'monomeric' satellite RNA sequence. We prepared plasmids bearing two distinct sequences of the satellite RNA. Each was arranged to allow transcription of an oligoribonucleotide (r-oligo) of the polarity that is complementary to encapsidated satellite RNA. One sequence has the autolytic processing phosphodiester bond, ApG, and the other is located at a distance of about 150 nucleotide (nt) residues. The second r-oligo accomplished cleavage of the first, in a catalytic fashion. Analysis of truncated forms showed that 10 nt of the ApG junction-containing r-oligo and 46 of the endoribonucleolytic r-oligo were sufficient for recognition in the cleavage reaction. These results map the sequences involved in autolytic processing of the complementary polarity satellite RNA to two regions.

Base Sequence↗

Use of site-directed mutagenesis to define the limits of sequence variation tolerated for processing of the M13 procoat protein by the Escherichia coli leader peptidase.

Leader peptidase cleaves the leader sequence from the amino terminus of newly made membrane and secreted proteins after they have translocated across the membrane. Analysis of a large number of leader sequences has shown that there is a characteristic pattern of small apolar residues at -1 and -3 (with respect to the cleavage site) and a helix-breaking residue adjacent to the central apolar core in the region -4 to -6. The conserved sequence pattern of small amino acids at -1 and -3 around the cleavage site most likely represents the substrate specificity of leader peptidase. We have tested this by generating 60 different mutations in the +1 to -6 domain of the M13 procoat protein. These mutants were analyzed for in vivo and in vitro processing, as well as for protein insertion into the cytoplasmic membrane. We find that in vivo leader peptidase was able to process procoat with an alanine, a serine, a glycine, or a proline residue at -1 and with a serine, a glycine, a threonine, a valine, or a leucine residue at -3. All other alterations at these sites were not processed, in accordance with predictions based on the conserved features of leader peptides. Except for proline and threonine at +1, all other residues at this position were processed by leader peptidase. None of the mutations at -2, -4, or -5 of procoat (apart from proline at -4) completely abolished leader peptidase cleavage in vivo although there were large effects on the kinetics of processing.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Peptide sequence tag-based blind identification of post-translational modifications with point process model.

UNLABELLED: An important but difficult problem in proteomics is the identification of post-translational modifications (PTMs) in a protein. In general, the process of PTM identification by aligning experimental spectra with theoretical spectra from peptides in a peptide database is very time consuming and may lead to high false positive rate. In this paper, we introduce a new approach that is both efficient and effective for blind PTM identification. Our work consists of the following phases. First, we develop a novel tree decomposition based algorithm that can efficiently generate peptide sequence tags (PSTs) from an extended spectrum graph. Sequence tags are selected from all maximum weighted antisymmetric paths in the graph and their reliabilities are evaluated with a score function. An efficient deterministic finite automaton (DFA) based model is then developed to search a peptide database for candidate peptides by using the generated sequence tags. Finally, a point process model-an efficient blind search approach for PTM identification, is applied to report the correct peptide and PTMs if there are any. Our tests on 2657 experimental tandem mass spectra and 2620 experimental spectra with one artificially added PTM show that, in addition to high efficiency, our ab-initio sequence tag selection algorithm achieves better or comparable accuracy to other approaches. Database search results show that the sequence tags of lengths 3 and 4 filter out more than 98.3% and 99.8% peptides respectively when applied to a yeast peptide database. With the dramatically reduced search space, the point process model achieves significant improvement in accuracy as well. AVAILABILITY: The software is available upon request.

Algorithms↗

Biosynthesis and proteolytic processing of type XI collagen in embryonic chick sterna.

The biosynthesis and proteolytic processing of type XI procollagen was examined using pulse-chase labelling of 17-day embryonic chick sterna in organ culture with [3H]proline. Products of biosynthesis were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with and without prior reduction of disulfide bonds. Pro-alpha chains, intermediates, and matrix forms were identified by cyanogen bromide or Staphylococcus aureus V8 protease digestion. The results show that type XI pro-alpha chains assemble into trimeric molecules with interchain disulfide bonds. Proteolytic processing begins at least 40 min after the start of labeling which is later than that of type II procollagen (25 min). This first processing step involves the loss of the domain containing the interchain disulfide bonds which most likely is the carboxyl propeptide. In the case of the pro-alpha 3 chain, this generates the matrix form, m alpha 3, which retains its amino propeptide. For the pro-alpha 1 and pro-alpha 2 chains, this step generates intermediate forms, p alpha 1 and p alpha 2, which undergo a second proteolytic conversion to m alpha 1 and m alpha 2, and yet retain a pepsin-labile domain. The conversion of p alpha 2 to m alpha 2 is largely complete 2 h after labeling. p alpha 1 is converted to m alpha 1 very slowly and is 50% complete after 18 h of chase in organ culture. The apparent proteolytic processing within the amino propeptide, and the differential rate of processing between two chains in the same molecule are unusual and distinguish type XI from collagen types I, II, and III. It is possible that the extremely slow processing of p alpha 1 affects the formation of the heterotypic cartilage collagen fibrils and may be related to the function of type XI collagen.

Animals↗

Pheromonal and host-odor processing in the insect antennal lobe: how different?

In the olfactory bulb of vertebrates and the antennal lobe of insects, precise connections between sensory receptor cells and olfactory glomeruli form the basis of a highly organized chemotopic map at the first stage of central processing in the brain. Beyond this basic level of organization, the olfactory system is typically separated into two subsystems: a 'main' olfactory pathway that detects and processes information about most environmental odorants, and an 'accessory' olfactory pathway that is devoted to information about social signals such as sex pheromones. A growing number of studies show, however, that it is not always possible to draw clear functional distinctions between the two subsystems. These findings have led some to speculate that the organizational principles by which olfactory stimuli are represented across glomeruli may be more similar in these two olfactory subsystems than previously thought.

Animals↗

RNA processing errors in patients with beta-thalassemia.

We have developed a method that permits rapid identification of the consequences of mutations that alter beta-globin RNA processing in erythroid cells. S1 nuclease mapping techniques were used to analyze total bone marrow RNA obtained fron 15 patients who are clinically homozygous for beta-thalassemia and from 5 patients with erythroid hyperplasia from other causes. This analysis was facilitated by the use of single-stranded uniformly labeled DNA probes of high specific activity that were prepared by using recombinant phage M13-beta-globin DNA templates. Two abnormalities of RNA processing were found to occur with high frequency in these patients. Nine thalassemic patients were found to have increased levels of an RNA species that retains all sequences transcribed from intervening sequence 1, implying the presence of mutations that decrease the correct splicing of this intron. Seven of 15 thalassemic patients were found to have an abnormally processed RNA species that retains 19 nucleotides transcribed from the 3' end of intron 1; this abnormality is caused by the G leads to A substitution in intron 1 that is known to create an alternative splice acceptor site.

Base Sequence↗

Visual scan paths are abnormal in deluded schizophrenics.

One explanation for delusion formation is that they result from distorted appreciation of complex stimuli. The study investigated delusions in schizophrenia using a physiological marker of visual attention and information processing, the visual scan path-a map tracing the direction and duration of gaze when an individual views a stimulus. The aim was to demonstrate the presence of a specific deficit in processing meaningful stimuli (e.g. human faces) in deluded schizophrenics (DS) by relating this to abnormal viewing strategies. Visual scan paths were measured in acutely-deluded (n = 7) and non-deluded (n = 7) schizophrenics matched for medication, illness duration and negative symptoms, plus 10 age-matched normal controls. DS employed abnormal strategies for viewing single faces and face pairs in a recognition task, staring at fewer points and fixating non-feature areas to a significantly greater extent than both control groups (P < 0.05). The results indicate that DS direct their attention to less salient visual information when viewing faces. Future paradigms employing more complex stimuli and testing DS when less-deluded will allow further clarification of the relationship between viewing strategies and delusions.

Adult↗

Riddling, bubbling, and Hopf bifurcation in coupled map systems.

In a simple coupled-map system, we show that the desynchronization of the chaotic attractor occurs through a series of Hopf bifurcations. As a result of the accumulation of these processes, the blowout bifurcation of this coupled map system is a new kind of Hopf bifurcation from a chaotic attractor. Riddling, bubbling, and characters of this particular manifestation of Hopf bifurcation from a chaotic attractor are studied in this paper.

Journal Article↗

Enhancing palliative care education in medical school curricula: implementation of the palliative education assessment tool.

The authors report the results of a Robert Wood Johnson Foundation-funded project that catalyzed New York State medical schools to develop and implement strategic plans for curricular change to enhance palliative care education. The project used the Palliative Education Assessment Tool for curricular mapping of palliative care education throughout each school's four-year curriculum and used site visits to facilitate strategic planning within each institution. Of the 14 New York State medical schools, 13 participated in the project. Ten provided strategic plans for change, with a total of 71 specific goals (median = 5 per school). Of these goals, 67 (94.4%) had been implemented or were in the active-planning process one year after the plans were created. Overall, palliative care content was enhanced in four curricular areas: basic science courses, ethics and humanities courses, clerkship rotations, and faculty development in palliative care. The process of self-assessment, curriculum mapping of a specific thematic area, and strategic planning for change appears to have successfully enhanced the palliative care content in the medical schools' curricula.

Curriculum↗

A STAP algorithm approach to fMRI: a simulation study.

PURPOSE: To adapt the space-time adaptive processing (STAP) algorithm, previously developed in the field of sensor array processing and applied to radar signal processing, for use in construction of brain activation maps in functional magnetic resonance imaging (fMRI). MATERIALS AND METHODS: STAP is a two-dimensional filter in which both the spatial and temporal responses are controlled adaptively. It processes space-time data as a complete spatiotemporal set. Unlike presently used fMRI techniques, STAP locates activated regions both spatially and in frequency. RESULTS: Computer simulations incorporating actual MRI noise indicate that STAP exhibits a high degree of accuracy in detecting the small signal intensity changes inherent in fMRI. CONCLUSION: Because STAP processes space-time data as a single data matrix, it exhibits potential over currently available fMRI methods in providing a measure of the full spatiotemporal extent of a task-related activity.

Algorithms↗

Ribosomal S6 kinase (RSK) regulates phosphorylation of filamin A on an important regulatory site.

The Ras-mitogen-activated protein (Ras-MAP) kinase pathway regulates various cellular processes, including gene expression, cell proliferation, and survival. Ribosomal S6 kinase (RSK), a key player in this pathway, modulates the activities of several cytoplasmic and nuclear proteins via phosphorylation. Here we report the characterization of the cytoskeletal protein filamin A (FLNa) as a membrane-associated RSK target. We show that the N-terminal kinase domain of RSK phosphorylates FLNa on Ser(2152) in response to mitogens. Inhibition of MAP kinase signaling with UO126 or mutation of Ser(2152) to Ala on FLNa prevents epidermal growth factor (EGF)-stimulated phosphorylation of FLNa in vivo. Furthermore, phosphorylation of FLNa on Ser(2152) is significantly enhanced by the expression of wild-type RSK and antagonized by kinase-inactive RSK or specific reduction of endogenous RSK. Strikingly, EGF-induced, FLNa-dependent migration of human melanoma cells is significantly reduced by UO126 treatment. Together, these data provide substantial evidence that RSK phosphorylates FLNa on Ser(2152) in vivo. Given that phosphorylation of FLNa on Ser(2152) is required for Pak1-mediated membrane ruffling, our results suggest a novel role for RSK in the regulation of the actin cytoskeleton.

Amino Acid Sequence↗

The TIGER system: automating the geographic structure of the United States census.

The success of a census rests not only on how well the Bureau of the Census collects data, but also on how well the Census Bureau links those data to geographic areas. Problems with the geographic materials produced for the 1980 census caused confusion on the part of the Census Bureau's field staff, the staff processing the collected data, and the users of the resulting information. To avoid similar problems in 1990, the Geography Division of the Census Bureau is developing an automated geographic system that will support numerous Census Bureau operations beginning with the 1990 Decennial Census. A major component of this automated system is the computer-readable map data being developed in cooperation with the US Geological Survey using their 1:100-000-scale map series as the source.

Americas↗