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At least 775 records · Page 43Linked to original sources

Temporal dynamics of linguistic processes are reorganized in aphasics' cortex: an EEG mapping study.

Brain lesions are known to elicit reorganization of function in representational cortex. Using linguistic function as an example, we show that (a) injury-related reorganization may also be observed in language-related cortex and (b) this reorganization not only appears in cortical space but also in the dynamic flow of activity. The present study investigated cortical reorganization in a group of 10 nonfluent aphasics who demonstrated partial recovery of linguistic functions. Compared with controls, linguistic functions were organized in an atypical manner, both in terms of spatial structures involved and in the time course of the linguistic processes, from word reading to late stages of word encoding in working memory. For this purpose, event-related potentials were recorded in a two-stimulus design comprising phonological and semantic tasks. Subjects were asked to judge whether two words, separated by a 2-s interval, rhymed (phonological task) or were semantically associated. During word reading of the phonological task, controls showed negativity/activation over occipital sites, whereas patients displayed negativity at left-medial orbitofrontal locations anterior to the common sites of lesion. During the subsequent 2-s interval associated with word encoding, the two groups showed a reversed pattern: significant left-right anterior asymmetry prevailed in controls, whereas lateralization was absent in patients. Aphasics displayed maximum positivity/inhibition over the left frontal regions, at the typical site of lesion. Compared with controls, patients exhibited significant disinhibition (decreased positivity) of right frontal areas and greater activation of left temporal sites. These results suggest that the concept of language plasticity should include, in addition to spatial aspects of linguistic reorganization, the reorganized temporal dynamics associated with recovery of impaired functions.

Adult↗

Toward the neural basis of verbal priming: a cognitive-neuropsychological synthesis.

Repetition priming is a mnemonic phenomenon that has attracted considerable attention from neuropsychologists and cognitive scientists. In an attempt at elucidating the putative mechanisms of priming, the present review draws on evidence from both domains. The review is restricted to verbal priming of visually presented stimuli--an area that accounts for the majority of empirical studies of priming. A number of theoretical accounts are presented. The interim conclusion is that neither multiple systems nor unitary system-multiple process theories can adequately explain the data on priming, although both contain many valid components. An integrative model is proposed to improve the explanation of the empirical evidence. The central assertion of the proposed model is that repetition priming depends on perceptual processes that can be mapped on specific neural systems. It is postulated that individual differences in perceptual processing ability predict variability in memory performance. It is proposed that data-driven priming of verbal stimuli critically depends on the activity of primary and secondary visual cortices in the right hemisphere, whereas conceptually-driven priming is hypothesized to rely on the activities of higher order tertiary association cortices in language areas and more anterior neocortical areas.

Alzheimer Disease↗

Inhibition of p38 MAP kinase as a therapeutic strategy.

Since the discovery of p38 MAP kinase in 1994, our understanding of its biology has progressed dramatically. The key advances include (1) identification of p38 MAP kinase homologs and protein kinases that act upstream and downstream from p38 MAP kinase, (2) identification of interesting and potentially important substrates, (3) elucidation of the role of p38 MAP kinase in cellular processes and (4) the establishment of the mechanism by which the pyridinylimidazole p38 MAP kinase inhibitors inhibit enzyme activity. It is now known that there are four members of the p38 MAP kinase family. They differ in their tissue distribution, regulation of kinase activation and subsequent phosphorylation of downstream substrates. They also differ in terms of their sensitivities toward the p38 MAP kinase inhibitors. The best-studied isoform is p38 alpha, whose activation has been observed in many hematopoietic and non-hematopoietic cell types upon treatment with appropriate stimuli. The pyridinylimidazole compounds, exemplified by SB 203580, were originally prepared as inflammatory cytokine synthesis inhibitors that subsequently were found to be selective inhibitors of p38 MAP kinase. SB 203580 inhibits the catalytic activity of p38 MAP kinase by competitive binding in the ATP pocket. X-ray crystallographic studies of the target enzyme complexed with inhibitor reinforce the observations made from site-directed mutagenesis studies, thereby providing a molecular basis for understanding the kinase selectivity of these inhibitors. The p38 MAP kinase inhibitors are efficacious in several disease models, including inflammation, arthritis and other joint diseases, septic shock, and myocardial injury. In all cases, p38 activation in key cell types correlated with disease initiation and progression. Treatment with p38 MAP kinase inhibitors attenuated both p38 activation and disease severity. Structurally diverse p38 MAP kinase inhibitors have been tested extensively in preclinical studies.

Animals↗

Angiotensin II regulation of neuromodulation: downstream signaling mechanism from activation of mitogen-activated protein kinase.

Angiotensin II (Ang II) stimulates expression of tyrosine hydroxylase and norepinephrine transporter genes in brain neurons; however, the signal-transduction mechanism is not clearly defined. This study was conducted to determine the involvement of the mitogen-activated protein (MAP) kinase signaling pathway in Ang II stimulation of these genes. MAP kinase was localized in the perinuclear region of the neuronal soma. Ang II caused activation of MAP kinase and its subsequent translocation from the cytoplasmic to nuclear compartment, both effects being mediated by AT1 receptor subtype. Ang II also stimulated SRE- and AP1-binding activities and fos gene expression and its translocation in a MAP kinase-dependent process. These observations are the first demonstration of a downstream signaling pathway involving MAP kinase in Ang II-mediated neuromodulation in noradrenergic neurons.

Angiotensin II↗

Report on seminar: 'designing care'.

The seminar was held under the auspices of the National Demonstration Project, which is a combined effort of the Juran Institute and the Harvard Community Health Plan (HCHP). About 60 delegates attended the conference. Most were from the United States, the rest were from Canada, the Netherlands, the United Kingdom and Australia. The seminar was aimed at introducing those attending to the topic of clinical algorithms. The algorithms were presented as part of a total quality management process concerned with clinical decisions. Algorithms are designed as a pattern, or a map, of a clinical process. It is the aim of an algorithm to ensure stability in a clinical process and to enhance the quality of care given by the process. The seminar was a combination of general sessions and workshop sessions. The general sessions were managed by presenters who had considerable experience in the development of algorithms, and the same presenters then chaired the separate workshop sessions on a group basis. The workshop sessions concentrated on the simulation of algorithm development at the institutions of the attendees.

Algorithms↗

Molecular structures of human argininosuccinate synthetase pseudogenes. Evolutionary and mechanistic implications.

In the human genome there is one expressed gene for argininosuccinate synthetase and 14 pseudogenes. A cDNA coding for human argininosuccinate synthetase was used to screen a human genomic library. Twenty-five unique genomic clones were isolated and extensively characterized. At least seven clones represented processed argininosuccinate synthetase pseudogenes that lost the introns in the expressed gene. Restriction mapping demonstrated that these processed pseudogenes were located in distinct regions of the human genome. Complete nucleotide sequences of two processed pseudogenes, psi AS-1 and psi AS-3, and a partial sequence of psi AS-7 were determined. Both psi AS-1 and psi AS-3 had an adenine-rich region at their 3' end and were flanked by distinct imperfect direct repeats. A comparison of these pseudogene sequences to that of the cDNA demonstrated that psi AS-1 and psi AS-3 were 93% homologous to the cDNA, whereas psi AS-7 was 89% homologous to the cDNA. Therefore, it is estimated that psi AS-1 and psi AS-3 were created 10-11 million years ago, whereas psi AS-7 arose approximately 21 million years ago. We have estimated the evolutionary rate for the expressed argininosuccinate synthetase gene based on the sequences of psi AS-1 and psi AS-3. These data indicate that the expressed argininosuccinate synthetase gene is evolving at a rate similar to that of the beta-globin gene and much faster than the alpha-tubulin gene. Furthermore, a comparison of the sequences of psi AS-1 and psi AS-3 suggests the possibility that these pseudogenes arose from a common intermediate.

Argininosuccinate Synthase↗

Knowing about guessing and guessing about knowing: preschoolers' understanding of indeterminacy.

In this article we investigate preschool children's understanding of indeterminacy by examining their ability to distinguish between determinate situations--in which the available evidence eliminates all uncertainty about an outcome--and indeterminate situations--in which it does not. We argue that a full understanding of indeterminacy requires the coordination of 3 processes: search, evaluation, and mapping. We describe 3 experiments aimed at discovering the extent to which these processes, each of which has been implicated in previous accounts of indeterminate reasoning, are developed in preschoolers and the extent to which different children organize the processes into different strategies. Experiment 1 examines 5-year-olds' performance on 1- versus 2-solution problems having different configurations of irrelevant information. Experiments 2 and 3 extend the possible sources of indeterminacy from 2 to 4 and vary the amount of consistent, inconsistent, and to-be-discovered evidence. Our results show that 4- and 5-year-old children readily give "Can tell" responses to determinate problems, as well as "Can't tell" responses when they think that the evidence warrants such a response. In addition, we report 2 new findings: (a) different children use different strategies to process determinate evidence, and these strategies, in turn, predict their performance on indeterminate problems; (b) evidence patterns in which a single positive instance is contrasted with 1 or more negative or unknown instances are particularly difficult to resolve. Many children use a decision rule--the Positive Capture rule--that produces consistent errors on this type of problem.

Age Factors↗

Mapping and characterization of an X-linked processed gene related to MYCL1.

A DNA sequence with homology to the myc family of proto-oncogenes has been characterized and found to be a processed gene related to L-MYC (MYCL1). This processed gene (MYCL2) was isolated by cross-hybridization to an oligonucleotide probe synthesized from the C-MYC (MYC) sequence in a highly conserved region of the myc gene family. Sequence analysis of MYCL2 revealed an open reading frame of 1194 bp with no intervening sequences and strong homology to the recently published DNA sequence of MYCL1. Southern and Northern blot analyses of DNAs and RNAs from small cell lung carcinomas confirmed its MYCL1 homology. Mapping of MYCL2 by somatic cell hybrids places this sequence on the long arm of the X chromosome in bands q22----q28.

Animals↗

Development of the nucleus isthmi in Xenopus, II: Branching patterns of contralaterally projecting isthmotectal axons during maturation of binocular maps.

The tectum of Xenopus frogs receives input from both eyes. The contralateral eye's projection reaches the tectum directly, via the optic nerve, and the ipsilateral eye's projection reaches the tectum indirectly, via the nucleus isthmi. Under normal conditions, the topography of the ipsilateral map relayed from the nucleus isthmi is in register with the topography of the retinotectal map from the contralateral eye. During development, the process of aligning the two maps is complicated by the dramatic changes in binocular overlap of the two eyes' visual fields which take place during late tadpole and juvenile stages. The goal of this study is to determine the branching patterns of contralaterally projecting isthmotectal axons before, during, and after the period of rapid eye migration. Isthmotectal axons were filled by anterograde transport of horseradish peroxidase (HRP) from the nucleus isthmi. The results show that crossed isthmotectal axons enter the entire extent of the tectum before binocular overlap begins to increase. Therefore, binocular overlap is not necessary for the initial isthmotectal projection to span the tectum. The density of isthmotectal branches rises dramatically at the same time that the eyes begin to shift. During the period when eye migration is most rapid, many isthmotectal axons form arbors which resemble adult arbors but which extend over greater proportions of the tectal surface. The axons appear to be directed toward appropriate mediolateral positions as they enter the tectum. Their trajectories are roughly rostocaudal, with relatively little change along the mediolateral dimension. These data, when combined with available physiological data, suggest that mediolateral order is initially established by vision-independent mechanisms but can be altered by vision-dependent mechanisms. Rostrocaudal order becomes discernable only at the time when binocular visual cues become available and appears to be established primarily on the basis of the activity of the retinotectal and isthmotectal axons.

Animals↗

Immunolocalization of MAP-2 in routinely formalin-fixed, paraffin-embedded guinea pig brain sections using microwave irradiation: a comparison of different combinations of antibody clones and antigen retrieval buffer solutions.

The present study was designed to evaluate the efficacy of different microwave pretreatment methods to retrieve microtubule-associated protein 2 (MAP-2) immunoreactivity in formalin-fixed, paraffin-embedded guinea pig brain sections. Brain sections, microwave pretreated in boiling sodium citrate, citric acid, Tris hydrochloride, and EDTA buffers of pH 4, 6, and 8, were labeled with four different clones of MAP-2 monoclonal antibodies. No MAP-2 immunoreactivity was observed in control sections processed without microwave pretreatment. Optimal MAP-2 immunoreactivity was observed only when MAP-2 antibody clone AP18 was used in conjunction with citric acid buffer of pH 6.0. Using this combination, brain sections from nerve agent soman-exposed guinea pigs were found to exhibit marked reduction in MAP-2 immunostaining in the hippocampus. These observations suggest that the clone of the antibody in addition to the type and pH of antigen retrieval (AR) solution are important variables to be considered for establishing an optimal AR technique. When studying counterpart antigens of species other than that to which the antibodies were originally raised, different antibody clones must be tested in combination with different microwave-assisted AR (MAR) methods. This MAR method makes it possible to conduct retrospective studies on archival guinea pig brain paraffin blocks to evaluate changes in neuronal MAP-2 expression as a consequence of chemical warfare nerve agent toxicity.

Animals↗

The polycistronic mRNA of the Zymomonas mobilis glf-zwf-edd-glk operon is subject to complex transcript processing.

The full-length 6.14-kb polycistronic glf-zwf-edd-glk mRNA from Zymomonas mobilis appears to be processed by endonucleolytic cleavage, resulting in the formation of several discrete transcripts. Northern analysis and transcript mapping revealed that the processed transcripts correspond to functional mono-, di-, or tricistronic messages. The relative abundance of the gene-specific, functional messages was measured. Expression of zwf and edd correlated well with functional message levels. Disproportionally high levels of the glk-specific mRNAs might compensate for the instability of glucokinase by allowing increased translation. The relative abundance of the discrete transcripts was shown to be a function of their respective decay rates. Northern analysis of the fate of the 6.14-kb transcript after inhibition of transcription by rifampin showed that the abundance of shorter, more stable transcripts increased at the expense of longer, less stable transcripts. This is suggestive of endonucleolytic mRNA processing. The most abundant 5' and 3' transcript ends were found to lie within secondary structures that probably impart stability to the most abundant mRNAs.

Base Sequence↗

Multisensory auditory-visual interactions during early sensory processing in humans: a high-density electrical mapping study.

Integration of information from multiple senses is fundamental to perception and cognition, but when and where this is accomplished in the brain is not well understood. This study examined the timing and topography of cortical auditory-visual interactions using high-density event-related potentials (ERPs) during a simple reaction-time (RT) task. Visual and auditory stimuli were presented alone and simultaneously. ERPs elicited by the auditory and visual stimuli when presented alone were summed ('sum' ERP) and compared to the ERP elicited when they were presented simultaneously ('simultaneous' ERP). Divergence between the 'simultaneous' and 'sum' ERP indicated auditory-visual (AV) neural response interactions. There was a surprisingly early right parieto-occipital AV interaction, consistent with the finding of an earlier study [J. Cogn. Neurosci. 11 (1999) 473]. The timing of onset of this effect (46 ms) was essentially simultaneous with the onset of visual cortical processing, as indexed by the onset of the visual C1 component, which is thought to represent the earliest cortical visual evoked potential. The coincident timing of the early AV interaction and C1 strongly suggests that AV interactions can affect early visual sensory processing. Additional AV interactions were found within the time course of sensory processing (up to 200 ms post stimulus onset). In total, this system of AV effects over the scalp was suggestive of both activity unique to multisensory processing, and the modulation of 'unisensory' activity. RTs to the stimuli when presented simultaneously were significantly faster than when they were presented alone. This RT facilitation could not be accounted for by probability summation, as evidenced by violation of the 'race' model, providing compelling evidence that auditory-visual neural interactions give rise to this RT effect.

Acoustic Stimulation↗

Filling-in in schizophrenia: a high-density electrical mapping and source-analysis investigation of illusory contour processing.

Evidence is accumulating that patients with schizophrenia exhibit relatively severe deficits in early visual sensory processing within the dorsal stream, while processing within the ventral stream appears to be relatively more intact. Here, illusory contour (IC) processing was investigated in a cohort of schizophrenia patients and age-matched healthy controls using high-density visual evoked potentials (VEPs), spatiotemporal topographic analyses and the Local Auto-Regressive Average distributed linear inverse source estimation. IC processing was assessed because it is now known to be an excellent metric of early processing within regions of the ventral visual stream. Results in the present study show that IC processing (106-194 ms) is spared in patients with schizophrenia, providing strong evidence that early ventral stream processing is essentially normal. This is so despite equally strong evidence that early dorsal stream processing is severely impaired in this population, as indexed by a robust decrement in amplitude of the P1 component in patients and a large topographic difference between groups for this component (54-104 ms). Source analysis confirmed that the flow of activity into the dorsal stream was substantially decreased in patients. As such, these results suggest that some aspects of early ventral processing are not entirely reliant on intact inputs from the dorsal stream. Lastly, we show that later phases of visual processing (240-400 ms) also rely on the activity of different brain networks in controls and patients, with the latter recruiting strong frontal activity perhaps as compensation for impaired ventral stream processing during this period. We interpret the present findings in the context of a two-stage processing model. Under this model, it is suggested that the second stage of ventral stream processing is dependent on the fidelity of inputs from the dorsal visual stream and that impairment of this critical modulatory input may underlie the failure of 'higher-level' ventral stream processes in this population.

Adult↗

A second generation radiation hybrid map to aid the assembly of the bovine genome sequence.

BACKGROUND: Several approaches can be used to determine the order of loci on chromosomes and hence develop maps of the genome. However, all mapping approaches are prone to errors either arising from technical deficiencies or lack of statistical support to distinguish between alternative orders of loci. The accuracy of the genome maps could be improved, in principle, if information from different sources was combined to produce integrated maps. The publicly available bovine genomic sequence assembly with 6x coverage (Btau_2.0) is based on whole genome shotgun sequence data and limited mapping data however, it is recognised that this assembly is a draft that contains errors. Correcting the sequence assembly requires extensive additional mapping information to improve the reliability of the ordering of sequence scaffolds on chromosomes. The radiation hybrid (RH) map described here has been contributed to the international sequencing project to aid this process. RESULTS: An RH map for the 30 bovine chromosomes is presented. The map was built using the Roslin 3000-rad RH panel (BovGen RH map) and contains 3966 markers including 2473 new loci in addition to 262 amplified fragment-length polymorphisms (AFLP) and 1231 markers previously published with the first generation RH map. Sequences of the mapped loci were aligned with published bovine genome maps to identify inconsistencies. In addition to differences in the order of loci, several cases were observed where the chromosomal assignment of loci differed between maps. All the chromosome maps were aligned with the current 6x bovine assembly (Btau_2.0) and 2898 loci were unambiguously located in the bovine sequence. The order of loci on the RH map for BTA 5, 7, 16, 22, 25 and 29 differed substantially from the assembled bovine sequence. From the 2898 loci unambiguously identified in the bovine sequence assembly, 131 mapped to different chromosomes in the BovGen RH map. CONCLUSION: Alignment of the BovGen RH map with other published RH and genetic maps showed higher consistency in marker order and chromosome assignment than with the current 6x sequence assembly. This suggests that the bovine sequence assembly could be significantly improved by incorporating additional independent mapping information.

Animals↗

[The data processing of neurophysiological examination and the diagnostic support system].

Neurophysiological examinations include EEG, EMG, Evoked Potential (EP) and ENG. In this paper, EEG and EP data processing, and the diagnostic support system using these findings were discussed. The FFT and AR model for analysis of frequency, and the pattern recognition for spike or spindle detection are the technical methods for application to EEG data processing of the first order. Amplitude or phase mapping techniques, as a second order data processing, were not only applied to the diagnosis of neurological disorders, but also used for detection of electrical equivalent dipole source localization which was inversely reconstructed in the cerebral cortex from the distribution of EEG potentials on the scalp. The averaging technique was used for detection of small evoked potentials (EP) such as SEP or ABR. The following items were included in the diagnostic support system applied to data processing. 1) Topographic analysis in the brain mapping of SEP to median nerve stimulation was applied to the identification of the central sulcus during a neurosurgical procedure to maintain the QOL of patient. 2) The usefulness of EEG automatic reporting system with Japanese sentences and brain topographic mapping was described. 3) Digital EEG in a data filing system using magneto optical disks was used for data analysis and diagnostic support system after EEG examination.

Algorithms↗

Transcription and processing of RNA from mouse ribosomal DNA transfected into hamster cells.

Transcription of mouse genes coding for rRNA in CHO cells was promoter dependent at levels 3 to 10% of that of endogenous rRNA synthesis. Northern (RNA) and S1 nuclease mapping analyses demonstrated that transcription proceeds through the entire gene segment coding for rRNA in transfected constructs and continues, at least in some cases, into the adjoining plasmid sequences. S1 nuclease mapping also detected some processing cleavages in the transcripts, including those at the 3' terminus of 18S rRNA, those at the rapidly cleaved site at +650 in the external transcribed spacer, and those at a previously uncharacterized, rapidly cleaved site in the internal transcribed spacer. Deletion of sequences upstream or downstream from the promoter generally had no measurable effect on the level of transcription, but deletion of a 300-base-pair XhoI-XhoI fragment starting 1,287 base pairs from the transcription start site sharply increased the steady-state level of rRNA. Effects on processing were harder to test, because many intermediates are too unstable to detect even by S1 nuclease mapping; however, the data suggest that RNAs with deletions in the external transcribed spacer are processed poorly at distal sites. Processing at some sites may thus depend on interactions involving distant segments of rRNA.

Animals↗

High-resolution spot-scan electron microscopy of microcrystals of an alpha-helical coiled-coil protein.

We describe the electron microscopy of a crystalline assembly of an alpha-helical coiled-coil protein extracted from the ootheca of the praying mantis. Electron diffraction patterns of unstained crystals show crystal lattice sampling of the coiled-coil molecular transform to a resolution beyond 1.5 A. Using a "spot-scan" method of electron imaging, micrographs of unstained crystals have been obtained that visibly diffract laser light from crystal spacings as small as 4.3 A. A projection map was calculated to 4 A using electron diffraction amplitudes and phases from computer-processed images. The projection map clearly shows modulations in density arising from the 5.1 A alpha-helical repeat, the first time this type of modulation has been revealed by electron microscopy. The crystals have p2 plane group symmetry with a = 92.4 A, b = 150.7 A, y = 92.4 degrees. Examination of tilted specimens shows that c is approximately 18 A, indicating that the unit cell is only one molecule thick. A preliminary interpretation shows tightly packed molecules some 400 A long lying with their long axes in the plane of the projection. The molecules have a coiled-coil configuration for most of their length. The possible modes of packing of the molecules in three dimensions are discussed.

Animals↗

Site-specific integrated pest management for high value crops: sample units for map generation using the Colorado potato beetle (Coleoptera: Chrysomelidae) as a model system.

Site-specific agriculture uses maps to optimize within-field placement of agricultural practices. This technology introduces the potential to optimize pest management by varying pesticide or other inputs to better match within-field variation in pest density. Current sampling plans are designed to estimate mean density and may not be suitable for mapping, although useful sampling plans could be developed for map generation for integrated pest management. Using Colorado potato beetle, Leptinotarsa decemlineata (Say), adults, larvae, and egg masses as model systems, the influence of the sample unit on map validity was explored. Adapting currently used sampling plans for potato integrated pest management by spatially referencing each sampled stem failed to resolve spatial dependence and resulted in maps with poor reliability. Increasing the sample unit improved resolution of spatial dependence and map reliability for each life stage. A distance-walk sample unit for adult and late instar Colorado potato beetles which has high potential for map generation is introduced. Using this sample unit, generalizations about Colorado potato beetle spatial dependence are made to discuss issues of developing sampling programs for map generation. An iterative process of sampling, spatial analysis, and error analysis is suggested for evaluating sample units for mapping pest density in high value crops.

Animals↗