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Multisensory visual-auditory object recognition in humans: a high-density electrical mapping study.

Multisensory object-recognition processes were investigated by examining the combined influence of visual and auditory inputs upon object identification--in this case, pictures and vocalizations of animals. Behaviorally, subjects were significantly faster and more accurate at identifying targets when the picture and vocalization were matched (i.e. from the same animal), than when the target was represented in only one sensory modality. This behavioral enhancement was accompanied by a modulation of the evoked potential in the latency range and general topographic region of the visual evoked N1 component, which is associated with early feature processing in the ventral visual stream. High-density topographic mapping and dipole modeling of this multisensory effect were consistent with generators in lateral occipito-temporal cortices, suggesting that auditory inputs were modulating processing in regions of the lateral occipital cortices. Both the timing and scalp topography of this modulation suggests that there are multisensory effects during what is considered to be a relatively early stage of visual object-recognition processes, and that this modulation occurs in regions of the visual system that have traditionally been held to be unisensory processing areas. Multisensory inputs also modulated the visual 'selection-negativity', an attention dependent component of the evoked potential this is usually evoked when subjects selectively attend to a particular feature of a visual stimulus.

Adult↗

Richard P. Bunge memorial lecture. Nerve injury and repair--a challenge to the plastic brain.

Repair and reconstruction of major nerve trunks in the upper extremity is a very challenging surgical problem. Today, there is no surgical repair technique that can assure recovery of tactile discrimination in the hand of an adult patient following nerve repair. In contrast, young individuals usually attain a complete recovery of functional sensibility. The outcome from nerve repair depends mainly on central nervous system factors including functional cortical reorganizational processes caused by misdirection in axonal outgrowth. Deafferentation due to local anesthetic block, amputation or nerve transection in the upper extremity leads to very rapid cortical synaptic remodeling, resulting in a distorted cortical hand representation as well as in enlarged and overlapping cortical receptive fields. Sensory relearning programs are aimed at refinement of these receptive fields to normalize the distorted hand map and improve processing at a high-order cortical level in the context of the 'new language spoken by the hand'. As peripheral nerve repair techniques cannot be further refined, there is a need for new and improved strategies for sensory relearning following nerve repair. We propose the utilization of multimodal capacity of the brain, using another sense (hearing) to substitute for lost hand sensation and to provide an alternate sensory input from the hand early after transection. The purpose was to modulate cortical reorganizations due to deafferentation to preserve cortical hand representation. Preliminary results from a prospective clinical randomized study indicate that the use of a Sensor Glove System, which stereophonically transposes the friction sound elicited by active touch, results in improved recovery of tactile discrimination in the nerve-injured hand. Future strategies for treatment of nerve injuries should promote cellular methods to minimize post-traumatic nerve cell death and to improve axonal outgrowth rate and orientation, but high on the agenda are new strategies for refined sensory relearning following nerve repair.

Adolescent↗

Anti oppressive practice: a route to the empowerment of people with dementia through communication and choice.

This short study looks at the issue of anti oppressive practice and the way that it relates to the care of people with dementia. In particular it considers ways in which people can be empowered and given choices around aspects of day-to-day living in a care setting. The study took place over a period of 6 months and utilized the Dementia Care Mapping (DCM) observation process to assess the level of well being of residents in the setting studied. The results can only be seen as a first stage in the process of understanding ways in which people with dementia may be empowered. It is demonstrated that a change of practice developed over the 6 months between the two observation periods. Areas such as communications and day-to-day activities are examined to identify both problems and strategies for such change. The conclusion highlights the need to continue the mapping exercise as a way of ensuring that change is not only maintained but also advanced.

Activities of Daily Living↗

MAPKs mediate the activation of cytosolic phospholipase A2 by amyloid beta(25-35) peptide in bovine retina pericytes.

We have previously shown that, in bovine retina pericytes, amyloid beta(1-42) and its truncated form containing amino acids 25-35, after 24 h treatment, stimulate arachidonic acid (AA) release and phosphatidylcholine hydrolysis, by activation of both cytosolic (cPLA(2)) and Ca(2+)-independent (iPLA(2)) phospholipase A(2). A putative role for MAP kinases in this process emerged. Here we studied the role of the MAP-kinase family as well as both cPLA(2) and iPLA(2) mRNA expression by a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in the same sublethal model of amyloid-beta (Abeta) damage to pericytes in vitro. Abeta(25-35) peptide evoked AA release as well as stimulated phosphorylation of ERK1/2, p38 MAPKs and cPLA(2), but not c-Jun N-terminal kinase (JNK/SAPK). PD98059, an inhibitor of ERK-activating kinase MEK-1, and SB203580, an inhibitor of p38 protein kinase, abolished the stimulation of AA release and MAPK activities. In cells stimulated by Abeta(25-35) peptide, Western blotting and confocal microscopy analyses confirmed either an increase in the phosphorylated form of ERKs and p38 or their nuclear translocation. A complete inhibition of MAPK activation and AA release was also observed when pericytes were treated with GF109203X, a general PKC inhibitor, indicating the important role of both PKC and the two MAPKs in mediating the Abeta peptide response. Compared with samples untreated or treated with reverse Abeta(35-25) peptide, pretreatment with 50 microM Abeta(25-35) for 24 h significantly increased the level of constitutively expressed iPLA(2) mRNA by 25%, which seems to depend on the activation of kinases. By contrast, the level of cPLA(2) mRNA remained unchanged. Together, these data link either the stimulation of PKC-ERK-p38 cascades or PLA(2) activity by Abeta peptide to prooxidant mechanism induced by amyloid, which may initially stimulate the cell reaction as well as metabolic repair, such as during inflammation.

Amyloid beta-Peptides↗

A sensorimotor map: modulating lateral interactions for anticipation and planning.

Experimental studies of reasoning and planned behavior have provided evidence that nervous systems use internal models to perform predictive motor control, imagery, inference, and planning. Classical (model-free) reinforcement learning approaches omit such a model; standard sensorimotor models account for forward and backward functions of sensorimotor dependencies but do not provide a proper neural representation on which to realize planning. We propose a sensorimotor map to represent such an internal model. The map learns a state representation similar to self-organizing maps but is inherently coupled to sensor and motor signals. Motor activations modulate the lateral connection strengths and thereby induce anticipatory shifts of the activity peak on the sensorimotor map. This mechanism encodes a model of the change of stimuli depending on the current motor activities. The activation dynamics on the map are derived from neural field models. An additional dynamic process on the sensorimotor map (derived from dynamic programming) realizes planning and emits corresponding goal-directed motor sequences, for instance, to navigate through a maze.

Action Potentials↗

Differential recruitment of the splicing machinery during transcription predicts genome-wide patterns of mRNA splicing.

The splicing machinery associates with genes to facilitate efficient cotranscriptional mRNA processing. We have mapped these associations by genome localization analysis to ascertain how splicing is achieved and regulated on a system-wide scale. Our data show that factors important for intron recognition sample nascent mRNAs and are retained specifically at intron-containing genes via RNA-dependent interactions. Spliceosome assembly proceeds cotranscriptionally but completes posttranscriptionally in most cases. Some intron-containing genes were not bound by the spliceosome, including several developmentally regulated genes. On this basis, we predicted and verified regulated splicing and observed a role for nuclear mRNA surveillance in monitoring those events. Finally, we present evidence that cotranscriptional processing events determine the recruitment of specific mRNA export factors. Broadly, our results provide mechanistic insights into the coordinated regulation of transcription, mRNA processing, and nuclear export in executing complex gene expression programs.

Adenosine Triphosphatases↗

Nanoimaging and spectroscopic analysis of rubber/ZnO interfaces by energy-filtering transmission electron microscopy.

Energy-filtering transmission electron microscopy (EFTEM) was employed for investigating interactions between rubber and ZnO particles in the accelerated vulcanization process. Combining elemental mapping and electron energy loss spectroscopy (EELS) by EFTEM enabled the characterization of the interfaces with spatial resolutions of less than 10 nm and with high elemental detection sensitivity. We found that a sulfur- and zinc-rich compound was generated around ZnO particles, and that product was then revealed to be ZnS-generated as a byproduct in the accelerated vulcanization process. Through this study, it is indicated that the accelerated vulcanization with ZnO does not occur uniformly in the rubber matrix; it occurs locally around ZnO particles at a higher reaction rate, implying that the rubber network structure is not uniform on the nanoscale.

Journal Article↗

Role of MAP kinase signalling pathways in the mode of action of peroxisome proliferators.

Peroxisome proliferators (PPs) are a class of non-genotoxic chemicals that cause rodent liver enlargement and hepatocarcinogenesis. In primary rat hepatocytes, PPs cause cell proliferation, suppression of apoptosis and peroxisome proliferation. We have investigated the role of different families of mitogen-activated protein (MAP) kinases in the mode of action of PPs. Addition of 50 microM nafenopin to primary rat hepatocyte cultures caused weak activation of extracellular signal regulated kinases and p38 MAP kinase. However, incubation of primary hepatocytes with the p38 MAP kinase inhibitor SB203580 or the MAP kinase kinase (MEK) inhibitor PD098059 prevented the induction of DNA synthesis and the suppression of transforming growth factor beta(1)-induced apoptosis by the PP nafenopin. In contrast, in the presence of these MAP kinase inhibitors, nafenopin still induced palmitoyl CoA oxidation, a measure of peroxisome proliferation. We have shown previously that PPs such as nafenopin require tumour necrosis factor alpha (TNF-alpha) to exert their effects on cellular proliferation and apoptosis. Here we show that treatment of primary rat hepatocyte cultures with nafenopin causes an increase in bioactive TNF-alpha and that this process requires p38 MAP kinase activity.

Animals↗

Characterization of three maize bacterial artificial chromosome libraries toward anchoring of the physical map to the genetic map using high-density bacterial artificial chromosome filter hybridization.

Three maize (Zea mays) bacterial artificial chromosome (BAC) libraries were constructed from inbred line B73. High-density filter sets from all three libraries, made using different restriction enzymes (HindIII, EcoRI, and MboI, respectively), were evaluated with a set of complex probes including the 185-bp knob repeat, ribosomal DNA, two telomere-associated repeat sequences, four centromere repeats, the mitochondrial genome, a multifragment chloroplast DNA probe, and bacteriophage lambda. The results indicate that the libraries are of high quality with low contamination by organellar and lambda-sequences. The use of libraries from multiple enzymes increased the chance of recovering each region of the genome. Ninety maize restriction fragment-length polymorphism core markers were hybridized to filters of the HindIII library, representing 6x coverage of the genome, to initiate development of a framework for anchoring BAC contigs to the intermated B73 x Mo17 genetic map and to mark the bin boundaries on the physical map. All of the clones used as hybridization probes detected at least three BACs. Twenty-two single-copy number core markers identified an average of 7.4 +/- 3.3 positive clones, consistent with the expectation of six clones. This information is integrated into fingerprinting data generated by the Arizona Genomics Institute to assemble the BAC contigs using fingerprint contig and contributed to the process of physical map construction.

Blotting, Southern↗

The short transcript of Leishmania RNA virus is generated by RNA cleavage.

Leishmania RNA virus 1 produces a short viral RNA transcript corresponding to the 5' end of positive-sense single-stranded RNAs both in virally infected cells and in in vitro polymerase assays. We hypothesized that this short transcript was generated via cleavage of full-length positive-sense single-stranded RNA. A putative cleavage site was mapped by primer extension analysis to nucleotide 320 of the viral genome. To address the hypothesis that the short transcript is generated via cleavage at this site, two substrate RNAs that possessed viral sequence encompassing the putative cleavage site were created. When incubated with sucrose-purified viral particles, these substrate RNAs were site-specifically cleaved. The cleavage site of the in vitro-processed RNAs also mapped to viral nucleotide 320. The short-transcript-generating activity could be specifically abolished by proteinase K treatment of sucrose-purified viral particles and high concentrations of EGTA [ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid], suggesting that the activity requires a proteinaceous factor and possibly intact viral particles. The cleavage activity is directly associated with short-transcript-generating activity, since only viral particle preparations which were capable of generating the short transcript in polymerase assays were also active in the cleavage assay. Furthermore, the short-transcript-generating activity is independent of the viral polymerase's transcriptase and replicase activities. We present a working model whereby cleavage of Leishmaniavirus RNA transcripts functions in the maintenance of a low-level persistent infection.

Animals↗

The site of 3' end formation of histone messenger RNA is a fixed distance from the downstream element recognized by the U7 snRNP.

Two conserved elements direct the 3' end processing of histone messenger RNA: a stem-loop structure immediately upstream of the site of cleavage and the histone downstream element (HDE), located 12-19 nucleotides downstream of the stem-loop in the premessenger RNA. We studied the role of these two elements by systematically inserting up to 10 C residues between them in the mouse H2A-614 histone pre-mRNA. 3' End mapping of RNAs processed in vitro demonstrated that as the HDE is move downstream, the site of cleavage correspondingly moves 3'. In addition, the efficiency of processing declines. In the wild-type substrate, cleavage occurs 3' of an A residue; modest increases in the efficiency of processing of the insertion mutants were observed when an A residue was placed at the new cleavage site. The results of psoralen cross-linking studies and immunoprecipitations using anti-trimethylguanosine antibodies indicated that the decreased processing efficiency of the insertion mutants is not due to impaired binding of the U7 small nuclear ribonucleoprotein (snRNP). We conclude that the mammalian U7 snRNP acts as a molecular ruler, targeting enzymatic components of cleave histone pre-mRNAs a fixed distance from its binding site, the HDE.

Animals↗

Mapping and characterization of the mouse and human SS18 genes, two human SS18-like genes and a mouse Ss18 pseudogene.

We have previously isolated and characterized a mouse cDNA orthologous to the human synovial sarcoma associated SS18 (formerly named SSXT and SYT) cDNA. Here, we report the characterization of the genomic structure of the mouse Ss18 gene. Through in silico methods with sequence information contained in the public databases, we did the same for the human SS18 gene and two human SS18 homologous genes, SS18L1 and SS18L2. In addition, we identified a mouse Ss18 processed pseudogene and mapped it to chromosome 1, band A2-3. The mouse Ss18 gene, which is subject to extensive alternative splicing, is made up of 11 exons, spread out over approximately 45 kb of genomic sequence. The human SS18 gene is also composed of 11 exons with similar intron-exon boundaries, spreading out over about 70 kb of genomic sequence. One alternatively spliced exon, which is not included in the published SS18 cDNA, corresponds to a stretch of sequence which we previously identified in the mouse Ss18 cDNA. The human SS18L1 gene, which is also made up of 11 exons with similar intron-exon boundaries, was mapped to chromosome 20 band q13.3. The smaller SS18L2 gene, which is composed of three exons with similar boundaries as the first three exons of the other three genes, was mapped to chromosome 3 band p21. Through sequence and mutation analyses this gene could be excluded as a candidate gene for 3p21-associated renal cell cancer. In addition, we created a detailed BAC map around the human SS18 gene, placing it unequivocally between the CA-repeat marker AFMc014wf9 and the dihydrofolate reductase pseudogene DHFRP1. The next gene in this map, located distal to SS18, was found to be the TBP associated factor TAFII-105 (TAF2C2). Further analogies between the mouse Ss18 gene, the human SS18 gene and its two homologous genes were found in the putative promoter fragments. All four promoters resemble the promoters of housekeeping genes in that they are TATA-less and embedded in canonical CpG islands, thus explaining the high and widespread expression of the SS18 genes.

Alternative Splicing↗

Partial blocking of NMDA receptors reduces plastic changes induced by short-lasting classical conditioning in the SI barrel cortex of adult mice.

The effect of blockade of N-methyl-D-aspartate (NMDA) receptors in the barrel cortex upon the learning-induced changes of the cortical body map was examined in adult mice. We have previously found that three sensory conditioning sessions, in which stimulation of a row of vibrissae was paired with a tail shock, produced an enlargement of the functional representation of a row of vibrissae stimulated during training. Implantation of the slow release polymer Elvax, containing 2-amino-5-phosphonovalerate (APV, 50 mM), in the vicinity of the barrel cortex was performed 1 day before conditioning to block NMDA receptors. The cortical representation of a trained row of vibrissae was visualized with 2-deoxyglucose (2DG) functional brain mapping 1 day after the completion of the conditioning procedure. The partial blockade of NMDA receptors within the barrel cortex reduced (by half) the expansion of the cortical representation of a trained row of vibrissae as compared to the enlargement of the cortical representation of a trained row found in untreated (60%) and Elvax-PBS implanted (47%) mice. The results provide evidence that the learning-induced processes of cortical map reorganization involve mechanisms that depend on NMDA receptor activation.

2-Amino-5-phosphonovalerate↗

Intracardiac echocardiography (9 MHz) in humans: methods, imaging views and clinical utility.

A new low-frequency (9 MHz, 9 Fr) catheter-based ultrasound (US) transducer has been designed that allows greater depth of cardiac imaging. To demonstrate the imaging capability and clinical utility, intracardiac echocardiography (ICE) using this lower frequency catheter was performed in 56 patients undergoing invasive electrophysiological procedures. Cardiac imaging and monitoring were performed with the catheter transducer placed in the superior vena cava (SVC), right atrium (RA) and/or right ventricle (RV). In all patients, ICE identified distinct endocardial structures with excellent resolution and detail, including the crista terminalis, RA appendage, caval and coronary sinus orifices, fossa ovalis, pulmonary vein orifices, ascending aorta and its root, pulmonary artery, RV and all cardiac valves. The left atrium and ventricle were imaged with the transducer at the limbus fossa ovalis of the interatrial septum and in the RV, respectively. ICE was important in identifying known or unanticipated aberrant anatomy in 11 patients (variant Eustachian valve, atrial septal aneurysm and defect, lipomatous hypertrophy, Ebstein's anomaly, ventricular septal defect, tetralogy of Fallot, transposition of the great arteries, disrupted chordae tendinae and pericardial effusion) or in detecting procedure-related abnormalities (narrowing of SVC-RA junction orifice or pulmonary venous lumen, atrial thrombus, interatrial communication). In patients with inappropriate sinus tachycardia, ICE was the primary ablation catheter-guidance technique for sinus node modification. With ICE monitoring, the evolution of lesion morphology with the three imaging features including swelling, dimpling and crater formation was observed. In all patients, ICE was contributory to the mapping and ablation process by guiding catheters to anatomically distinct sites and/or assessing stability of the electrode-endocardial contact. ICE was also used to successfully guide atrial septal puncture (n = 9) or RA basket catheter placement (n = 4). Thus, ICE with a new 9-MHz catheter-based transducer has better imaging capability with a greater depth. Normal and abnormal cardiac anatomy can be readily identified. ICE proved useful during electrophysiological mapping and ablation procedures for guiding interatrial septal puncture, assessing placement and contact of mapping and ablation catheters, monitoring ablation lesion morphological changes, and instantly diagnosing cardiac complications.

Adult↗

The further construction of the two-dimensional database of common human proteins.

The master two-dimensional gel database (D. Burggraf et al., Electrophoresis 1992, 13, 729-732) [1] of common human proteins has been expanded to include detailed protein characteristics. Human cellular proteins from 5 cell lines and different cell organelles representing various tissues (muscle, nervous, connective, epithelial blood) and germ layers (ectoderm, endoderm and mesoderm), were separated by two-dimensional gel electrophoresis (2-DE). According to a recently developed algorithm, master gels of these different cells were established by computer-aided image processing. An expanded map with protein-chemical information of the polypeptides common to all human cells is shown. The synthetic, common human protein-map represents 856 spots resolved with an accuracy of 4 cm/pI unit. The protein spots were characterized either by their isoelectric point, molecular mass, integrated intensity, background-corrected optical density, spot area, or cellular distribution. About 80 proteins were further characterized and identified by protein name, amino acid composition analysis, N-terminal sequencing, enzymatic digest and subsequent peptide sequencing. Additionally the proteins of the common human protein map were identified by Western blotting. Specific information regarding glycosylation and quantitation of expression levels after chemical, biological and mechanical stimulation is included in the database.

Amino Acid Sequence↗

Experimentation with a transcranial magnetic stimulation system for functional brain mapping.

We describe functional brain mapping experiments using a transcranial magnetic stimulation (TMS) device. This device, when placed on a subject's scalp, stimulates the underlying neurons by generating focused magnetic field pulses. A brain mapping is then generated by measuring responses of different motor and sensory functions to this stimulation. The key process in generating this mapping is the association of the 3-D positions and orientations of the TMS probe on the scalp to a 3-D brain reconstruction such as is feasible with a magnetic resonance image (MRI). We have developed a registration system which not only generates functional brain maps using such a device, but also provides real-time feedback to guide the technician in placing the probe at appropriate points on the head to achieve the desired map resolution. Functional areas we have mapped are the motor and visual cortex. Validation experiments focus on repeatability tests for mapping the same subjects several times. Applications of the technique include neuroanatomy research, surgical planning and guidance, treatment and disease monitoring, and therapeutic procedures.

Brain Mapping↗

Automated DNA sequencing and analysis of the human genome.

In the past few years, striking advances have been made in automating DNA sequence analysis. Currently, efforts are underway to automate and improve DNA purification, mapping, and data processing procedures. The predictable advances in these technologies should soon place us in a position to sequence the entire human genome. The information derived from this project will have profound implications for basic biology and clinical medicine alike.

Base Sequence↗

Spatially filtered magnetoencephalographic analysis of cortical oscillatory changes in basic brain rhythms during the Japanese 'Shiritori' Word Generation Task.

BACKGROUND: 'Shiritori' (capping verses) is a traditional Japanese word generation game, and is very familiar to native Japanese speakers. The shiritori task is expected to more strongly activate temporal language-related regions than conventional word generation to letters because of its characteristic way to make cue letters. OBJECTIVES: The aim of this study was to examine the cortical oscillatory changes in basic brain rhythms during silently performing a shiritori task. METHODS: Using synthetic aperture magnetometry (SAM) analysis of magnetoencephalography, we estimated the tomographic distributions of the statistically significant differences of the power in the alpha and beta frequency bands between the resting and the task periods. RESULTS: Significant event-related desynchronization (ERD) in the 8- to 25-Hz band, thought to reflect neural activation, was localized within task-related cortical regions with left-side dominance. The significant ERDs were estimated in both the frontal and temporal language-related regions encompassing Broca's and Wernicke's areas, although previous neuroimaging studies using word generation to letters showed neural activation predominantly in frontal regions. CONCLUSIONS: Our results show the potential of SAM analysis for reliable brain mapping of language processing, and suggest that the shiritori task might be more suitable for examining the language-related network in the brain than conventional word generation to letters.

Adult↗