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PubMed2003

IndexFinder: a method of extracting key concepts from clinical texts for indexing.

Extracting key concepts from clinical texts for indexing is an important task in implementing a medical digital library. Several methods are proposed for mapping free text into standard terms defined by the Unified Medical Language System (UMLS). For example, natural language processing techniques are used to map identified noun phrases into concepts. They are, however, not appropriate for real time applications. Therefore, in this paper, we present a new algorithm for generating all valid UMLS concepts by permuting the set of words in the input text and then filtering out the irrelevant concepts via syntactic and semantic filtering. We have implemented the algorithm as a web-based service that provides a search interface for researchers and computer programs. Our preliminary experiment shows that the algorithm is effective at discovering relevant UMLS concepts while achieving a throughput of 43K bytes of text per second. The tool can extract key concepts from clinical texts for indexing.

Abstracting and Indexing↗
PubMed2004

Propagation of desynchronous disturbances in synchronized chaotic one-way coupled map lattices.

Propagations of desynchronous perturbations in synchronization processes of spatiotemporal chaos are investigated by considering chaotic one-way coupled map lattices. Under large coupling approximation the desynchronous area in time space is analytically calculated, based on the concepts of comoving Lyapunov exponent and absolute largest Lyapunov exponent. The ideas used in this paper are expected to be applicable to synchronizations of spatiotemporally chaotic systems of coupled maps and coupled oscillators with convective instability.

Journal Article↗
PubMed1994

Distribution and regulation of the candidate prohormone processing enzymes SPC2 and SPC3 in adult rat brain.

A number of candidate mammalian prohormone processing enzymes related to the yeast Kex2 endoprotease have been cloned and demonstrated to cleave several prohormone precursors at single, pairs and tetra basic amino acid processing sites. We have mapped the distribution of the mRNAs encoding two of these endoproteases in adult rat brain. SPC3 message levels showed a more restricted distribution and generally lower levels than SPC2 transcripts. The highest levels of SPC2 mRNA were found in the pyramidal cells of the hippocampus, several thalamic nuclei, the habenula and selected nuclei in the hypothalamus. SPC3 mRNA was most abundant in dentate gyrus granule cells, the habenula and selected hypothalamic nuclei. In the hypothalamus overlapping and unique distributions of the two transcripts were seen in the paraventricular nucleus with SPC3 mRNA predominantly expressed in lateral magnocellular cells. Both SPC2 and SPC3 mRNA were upregulated in the paraventricular and supraoptic hypothalamic nuclei following chronic salt loading. Combined immunocytochemistry/in situ hybridization histochemistry demonstrated that SPC2 and SPC3 transcripts were both expressed in the vasopressinergic subpopulation of magnocellular neurons in the supraoptic nucleus. SPC3 mRNA, but not SPC2 transcripts, also colocalized with immunoreactive vasopressin-associated neurophysin in the suprachiasmatic nucleus. These results remain consistent with roles for SPC2 and SPC3 in the biosynthesis of neuropeptides and for a specific role for SPC3 in the processing of provasopressin. Increased levels of SPC2 and SPC3 transcripts following a chronic osmotic stimulus suggests these proteases are coregulated with prohormone substrates and may be useful as an indicator of peptidergic activity.

Amino Acid Sequence↗
PubMed1996

Monoamine neurotransmitter function and spontaneous recurrence of methamphetamine psychosis.

The process that triggered spontaneous recurrence of methamphetamine (MAP)-induced paranoid-hallucinatory psychosis, a phenomenon known as flashbacks, was studied in 41 subjects with flashbacks, along with 84 subjects with a history of previous MAP psychosis but no flashbacks. Plasma levels of norepinephrine (NE), dopamine, and 5-hydroxytryptamine, and their respective metabolites were assayed in 28 of the 41 flashbackers, 16 of the 84 non-flashbackers, 9 subjects with persistent MAP psychosis, and 28 healthy controls comprised of 20 MAP users and 8 non-users. None of the 28 controls had become psychotic. The 41 flashbackers had experienced significantly greater frequencies of threatening events and frightening paranoid-hallucinatory states during previous MAP use than the 84 non-flashbackers. The dominant factor that triggered flashbacks was a mild fear of other persons. The 41 flashbackers may have encoded threatening experiences as frightening images. Repeated MAP use with threatening experiences may induce sensitization to frightening images. Plasma NE levels during flashbacks were significantly higher than the levels during periods of normalcy, and the NE levels in the 20 user and 8 non-user controls. The 9 subjects with persistent MAP psychosis had significant higher levels of NE than the user and non-user controls. The 16 non-flashbackers had significantly higher MHPG levels than the user controls. The findings suggest that MAP use may induce changes at pharmacological levels in the process underlying sensitization to frightening images. We suggested that when the flashbackers experienced a mild fear of other persons, MAP-induced sensitization to frightening images may have been actualized. Thus, the flashbacks may have been caused through increased noradrenergic hyperactivity.

Adult↗
PubMed2001

Motion correction of parametric fMRI data from multi-slice single-shot multi-echo acquisitions.

Fast parametric imaging using multi-echo techniques has been proven to yield quantitative parameter maps with high stability for functional MRI (fMRI). Due to the different contrasts and signal-to-noise ratios (SNRs) in the various images, motion correction of the echo images or the resulting parameter maps is not a straightforward process. 3D motion correction of parametric imaging data has not yet been examined thoroughly. However, motion correction is an essential step in fMRI data processing. In this study several possible motion detection methods were tested and compared. Motion parameters can be estimated from the different echo images as well as from the parameter maps. The accuracy of the different methods was examined in simulations and in in vivo experiments. Motion parameters should be estimated from the I(0)-parameter maps and subsequently applied to the T(*)(2)-parameter maps.

Brain↗
PubMed1991

Substitution of asparagine for serine-406 of the immunoglobulin mu heavy chain alters glycosylation at asparagine-402.

Previous work suggested that the substitution of Asn for Ser at position 406 of the mu heavy chain of mouse IgM results in aberrant glycosylation at Asn402. In order to characterise the apparently abnormal glycosylation process more precisely, the mutant and wildtype mu chains were fragmented by cleavage with cyanogen bromide, and the resulting glycopeptides were analysed further. Measurements of lectin binding specificity as well as glycosidase sensitivity suggest that the oligosaccharide at Asn402 of wildtype mu is a hybrid type which does not contain terminal alpha(2-6) or alpha(2-3) linked sialic acid. By contrast, the corresponding oligosaccharide on Asn402 of mutant mu is complex and contains terminal sialic acid linked alpha(2-6) to galactose. The structural features for specifying the abnormal glycosylation are present in monomeric mutant IgM.

Amino Acid Sequence↗
PubMed2002

Evaluation of myocardial ischemia in Kawasaki disease using an isointegral map on magnetocardiogram.

The authors have recently reported on the usefulness of the isointegral mapping technique using magnetocardiography (MCG) for the diagnosis of adult ischemic heart disease. This study evaluated myocardial ischemia in patients with Kawasaki disease (KD). The ischemia has been considered difficult to diagnose with a standard ECG. The study included 32 patients (age 3 +/- 22 years, mean 12.9 +/- 4.1 years, +/- SD) with a history of KD and 21 age-matched healthy children. Coronary arterial lesions were present in 13 patients of the KD group, MCG was carried out at rest with a multichannel superconducting quantum interference device (SQUID) system. The integral value was computed for each channel and isointegral maps were constructed during depolarization and repolarization processes. In all subjects of the control group, the integral value of repolarization was higher than that of depolarization and the isointegral map of these two processes showed similar patterns. However, the integral value of repolarization in four cases with KD (one with a history of myocardial infarction, two with a stenotic lesion in the left coronary artery, one with an aneurysmal and stenotic lesion in the right coronary artery) was lower than that of depolarization, and abnormal patterns were evident in the isointegral map. All but the case with myocardial infarction showed only mild abnormalities or almost normal on the ECG. Although sensitivity of the method for detection of myocardial ischemia was not fully assessed because of the small number of cases with significant coronary arterial stenosis, noninvasive isointegral mapping technique using the MCG could be useful for evaluation of myocardial ischemia in patients with KD.

Adolescent↗
PubMed1996

The premotor cortex and nonstandard sensorimotor mapping.

We often gaze at and attend to an object while preparing to reach toward and grasp it, and continue doing so when the plan is executed. Elaborate machinery, much of it in the brainstem and spinal cord, provides control systems for the spatially congruent guidance of the eyes, limbs, and body toward targets in visual space. We will use the term standard mapping for the sensorimotor transformations that underlie such behavior. Despite the common sense character of standard mapping, the targets of gaze, attention, and reaching can be dissociated from each other. We can attend to stimuli in locations that differ from the target of action. We can gaze in one direction while reaching in another. And we can guide spatial action with nonspatial stimuli, such as when, in conditional motor tasks, the color of an object instructs a movement elsewhere in space. All of these situations, and many others, call for a process that we term nonstandard mapping, wherein the central nervous system must reject the commonplace correspondences among visuospatial stimuli, gaze, attention, and reaching movements. We focus in this article on the possibility that premotor cortex underlies nonstandard mapping and, therefore, the behavioral flexibility that such a process allows.

Animals↗
PubMed2000

Cotranscription of 5S rRNA-tRNA(Arg)(ACG) from Brassica napus chloroplasts and processing of their intergenic spacer.

S1 mapping showed that at least a significant portion of the 5S rRNA and tRNA(Arg)(ACG) is co-transcribed in canola chloroplast, making trnR the last gene transcribed in an operon of which the final sequence is 5'-16S-tRNA(Ile)-tRNA(Ala)-23S-4.5S-5S-tRNA(Arg)-3'. Various RNA termini representing RNA processing sites at several parts of the 5S rRNA-tRNA(Arg) area were detected. This gene spacer is substantially conserved among various species compared here, and a secondary structure model for this chloroplast region in canola applies to other plant sequences. The conservation of this intergenic sequence suggests a functional role, possibly by providing recognition structures for endogenous RNases involved in its maturing process.

Base Sequence↗
PubMed1999

Processing of the N termini of nascent polypeptide chains requires deformylation prior to methionine removal.

N-formyl-methionine termini are formed in the initiation reaction of bacterial protein synthesis and processed during elongation of the nascent polypeptide chain. We report that the formyl group must be removed before the methionine residue can be cleaved by methionine aminopeptidase. This has long been implicitly assumed, but that assumption was based on inconclusive data and was in apparent conflict with more recently published data. We demonstrate that the Salmonella typhimurium methionine aminopeptidase is totally inactive on an N-formyl-methionyl peptide in vitro, and present a detailed characterization of the substrate specificity of this key enzyme by use of a very sensitive and quantitative assay. Finally, a reporter protein expressed in a strain lacking peptide deformylase was shown to retain the formyl group confirming the physiological role of the deformylase.

Amino Acid Sequence↗
PubMed2003

A suffix tree approach to the interpretation of tandem mass spectra: applications to peptides of non-specific digestion and post-translational modifications.

MOTIVATION: Tandem mass spectrometry combined with sequence database searching is one of the most powerful tools for protein identification. As thousands of spectra are generated by a mass spectrometer in one hour, the speed of database searching is critical, especially when searching against a large sequence database, or when the peptide is generated by some unknown or non-specific enzyme, even or when the target peptides have post-translational modifications (PTM). In practice, about 70-90% of the spectra have no match in the database. Many believe that a significant portion of them are due to peptides of non-specific digestions by unknown enzymes or amino acid modifications. In another case, scientists may choose to use some non-specific enzymes such as pepsin or thermolysin for proteolysis in proteomic study, in that not all proteins are amenable to be digested by some site-specific enzymes, and furthermore many digested peptides may not fall within the rang of molecular weight suitable for mass spectrometry analysis. Interpreting mass spectra of these kinds will cost a lot of computational time of database search engines. OVERVIEW: The present study was designed to speed up the database searching process for both cases. More specifically speaking, we employed an approach combining suffix tree data structure and spectrum graph. The suffix tree is used to preprocess the protein sequence database, while the spectrum graph is used to preprocess the tandem mass spectrum. We then search the suffix tree against the spectrum graph for candidate peptides. We design an efficient algorithm to compute a matching threshold with some statistical significance level, e.g. p = 0.01, for each spectrum, and use it to select candidate peptides. Then we rank these peptides using a SEQUEST-like scoring function. The algorithms were implemented and tested on experimental data. For post-translational modifications, we allow arbitrary number of any modification to a protein. AVAILABILITY: The executable program and other supplementary materials are available online at: http://hto-c.usc.edu:8000/msms/suffix/.

Algorithms↗
PubMed1992

Conservation and characterisation of spatial features in a new method of data compression for body surface potential maps.

Body surface potential maps consist of a huge amount of data represented as a series of three-dimensional maps, which are time consuming to process and expensive to store. In spite of the continuous interest in body surface potential maps, their use has not become common and they are of no practical use in the clinics. This is due to the overwhelming amount of measured data required to generate the maps and the lack of quantitative methods to analyse them. Data compression or reduction may solve these deficiencies. Such a procedure must conserve the fine spatial details of the maps, which are usually extracted from low level surface potentials, as these are reported to be significant in diagnostic electrocardiography. A technique is presented for data reduction, that implements two-level thresholding and conserves the fine significant spatial features of each map. A sequence of annuli thus produced is shown to describe the dynamic nature of the underlying process. This sequence is further processed and characterised by features which quantify its dynamic behaviour: time of annuli sequence appearance, its duration, three-dimensional loci of centres of mass of the annuli, distances between successive centres of mass and cross-correlation coefficients between successive annuli. To test the data reduction procedure and the usefulness of the features, maps from 20 subjects are studied (both normal patients and those with various pathologies). It is found that the use of annuli instead of the whole measured information allows simple storage, display and calculations; the features, which vary in time, represent closely the changes in location of the annuli and their dynamic variations of shape. The features are also found to be grouped together for the maps of the normal patients and for each pathology. Thus, body surface potential maps may become more commonly used in clinics by being represented by a set of features, which conserve their dynamic and spatial nature, and which may serve for classification of cardiac pathologies.

Action Potentials↗
PubMed2004

Real-time monitoring of ubiquitination in living cells by BRET.

Ubiquitin has emerged as an important regulator of protein stability and function in organisms ranging from yeast to mammals. The ability to detect in situ changes in protein ubiquitination without perturbing the physiological environment of cells would be a major step forward in understanding the ubiquitination process and its consequences. Here, we describe a new method to study this dynamic post-translational modification in intact human embryonic kidney cells. Using bioluminescence resonance energy transfer (BRET), we measured the ubiquitination of beta-arrestin 2, a regulatory protein implicated in the modulation of G protein-coupled receptors. In addition to allowing the detection of basal and GPCR-regulated ubiquitination of beta-arrestin 2 in living cells, real-time BRET measurements permitted the recording of distinct ubiquitination kinetics that are dictated by the identity of the activated receptor. The ubiquitination BRET assay should prove to be a useful tool for studying the dynamic ubiquitination of proteins and for understanding which cellular functions are regulated by this post-translational event.

Arrestins↗
PubMed2005

Requirement of the MAP kinase signaling pathways for mouse preimplantation development.

Mammalian preimplantation development involves several crucial events, such as compaction and blastocyst formation, but little is known about essential genes that regulate this developmental process. Here, we have focused on MAP kinase signaling pathways as potential regulatory pathways for the process. Our results show that inhibition of the JNK pathway or of the p38 MAP kinase pathway, but not of the ERK pathway, results in inhibition of cavity formation, and that JNK and p38 are active during mouse preimplantation development. Our subsequent microarray analyses show that, of about 39,000 transcripts analyzed, the number of those genes whose expression level is sensitive to the inhibition of the JNK or the p38 pathway, but insensitive to the inhibition of the ERK pathway, is only 156. Moreover, of the 156 genes, expression of 10 genes (two genes upregulated and eight genes downregulated) is sensitive to either inhibition of the JNK or p38 pathways. These 10 genes include several genes known for their function in axis and pattern formation. Downregulation of some of the 10 genes simultaneously using siRNA leads to abnormality in cavity formation. Thus, this study has successfully narrowed down candidate genes of interest, detailed analysis of which will probably lead to elucidation of the molecular mechanism of preimplantation development.

Animals↗
PubMed2002

The photomorphogenesis regulator DET1 binds the amino-terminal tail of histone H2B in a nucleosome context.

Light provides a major source of information from the environment during plant growth and development. Recent results suggest that the key events controlling light-regulated gene expression in plants are translocation of the phytochrome photoreceptors into the nucleus, followed by their binding to transcription factors such as PIF3. Coupled with this, the degradation of positively acting intermediates such as the transcription factor HY5 by COP1 and the COP9 signalosome appears to be an important process whereby photomorphogenesis is repressed in darkness (e.g., ). Genetic analyses in Arabidopsis and tomato have revealed that the nuclear protein DET1 also plays a key role in the repression of photomorphogenesis. However, the function of this protein has remained a mystery. In a series of in vitro experiments, we provide persuasive evidence that DET1 binds to nonacetylated amino-terminal tails of the core histone H2B in the context of the nucleosome. Furthermore, we have utilized FRET (fluorescence resonance energy transfer) imaging with GFP variants to demonstrate this interaction within the nucleus of living plant cells. Given the dramatic photomorphogenic phenotypes of det1 mutants, we propose that chromatin remodeling plays a heretofore unsuspected role in regulating gene expression during photomorphogenesis.

Acetylation↗
PubMed1999

Do hippocampal pyramidal cells signal non-spatial as well as spatial information?

It is generally agreed that the rat hippocampus is involved in spatial memory. Whether this is its sole or primary function, or merely one component of a broader function, is still debated. It has been suggested, for example, that the hippocampus stores information about flexible relations between stimuli, both spatial and non-spatial. In this paper, I reiterate the basic tenet of the cognitive map theory that the processing and storage of spatial information is the primary and perhaps the exclusive role of the hippocampus in the rat, and that data that appear to contradict this have been misinterpreted. These data are found in reports of non-spatial correlates of unit activity recorded in the awake animals and reports of deficits on non-spatial tasks following hippocampal lesions. In this paper, I examine both claims and suggest alternative explanations of the data. The first part of the paper contains a review of some of the properties of hippocampal place cells, which might be misinterpreted as non-spatial in "non-spatial" tasks. For example, if an animal is trained to carry out a sequence of stereotyped actions in different parts of an environment, there will be a strong correlation between the performance of each behaviour and the animal's location, and it is necessary to rule out the locational correlate as the cause of the firing pattern. The second part of the paper looks at the results of experiments on conditioning and non-spatial discrimination tasks and concludes that the results are less supportive of a more general relational theory of hippocampal function than has been suggested. Furthermore, there is often a discrepancy between the correlates of unit firing in non-spatial tasks and the absence of an effect of hippocampal damage on these same or similar tasks. It is concluded that, contrary to the claims of its detractors, the cognitive map theory is still the theory of hippocampal function that is most clearly specified, makes the most testable predictions, and for which there is the strongest experimental support.

Animals↗
PubMed1984

Polymorphism of tubulin oligomers in the presence of microtubule-associated proteins. Implications in microtubule assembly.

The interaction between tubulin and microtubule-associated proteins (MAPs) in solutions of cycled microtubule protein has been studied by using radioactively labeled MAPs. Kinetic data of MAP association to microtubules in the polymerization process indicate that an oligomer P of tubulin and MAPs is the polymerizing species. Analysis of MAP binding to microtubules formed from solutions in which the ratio MAPs/tubulin was varied shows evidence for a polymorphism of tubulin-MAP oligomers. When the ratio MAPs/tubulin is decreased by addition of dimeric tubulin to 3 times cycled microtubule protein, an oligomer P' less rich in MAPs than P and unable to incorporate in microtubules is formed. The data further show that while tau, MAP1, and MAP2 can bind to oligomer P, only MAP1 and MAP2 can bind to oligomer P'. Therefore, the interactions of tau factor and of MAP1 and MAP2 with tubulin follow different patterns.

Animals↗
PubMedDate not supplied

Characteristics of human medulloblastoma cell line TE-671 under different growth conditions in vitro: a morphological and immunohistochemical study.

The human medulloblastoma cell line, TE-671, was studied in vitro both in monolayer culture and in a three-dimensional culture system using gelfoam as the supporting matrix. Flow cytometry studies of cells grown in monolayer culture revealed a unimodal, tetraploid DNA content. Most cells in both in vitro systems contained neuron-specific enolase (NSE), actin, and tubulin, while only occasional cells or cell clusters contained the 68,000 molecular weight subunit of neurofilaments (NF mol. wt 68,000) or microtubule-associated protein 2 (MAP-2). In monolayer culture, long cellular processes containing NSE, NF mol. wt 68,000 and MAP-2, which were present at 2 days, were nearly absent by 7 days. All antigens were present at 4 days in the organ culture system; by 72 days, cells still stained positively for NF mol. wt 68 000 and MAP-2, but staining for NSE, actin, and beta-tubulin was diminished as compared to 4 days. Retinoic acid (RA) in the 13-cis isomer form at 10(-6) M was applied to monolayer cultures at day 1 for 6 days and to gelfoam cultures at day 1 for 28 days. RA did not significantly alter cell proliferation up to 7 days in vitro and did not appreciably affect cellular expression of NSE, NF mol. wt 68 000, MAP-2, beta-tubulin, or actin in either system. By electron microscopy, most cells grown under different culture conditions with or without RA treatment appeared to be undifferentiated and polygonal, with occasional cytoplasmic annulate lamellae. The immunohistochemical and ultrastructural features reported indicate that the TE-671 medulloblastoma line is composed primarily of primitive neuroepithelial cells with a limited potential for neuronal differentiation. This differentiation was not promoted by RA or by an in vitro system known to favour differentiation in a number of human and animal nervous system tumours. The findings suggest that the cells of the TE-671 line lack either receptors for retinoic acid or the capacity to respond to bound retinoic acid.

Actins↗