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Linkage mapping of microdissected clones from distal mouse chromosome 16.

A total of 38 unique segments generated by microdissection of mouse chromosome 16 (MMU16), sequence independent amplification (SIA) and cloning were sequentially mapped on the distal portion of the chromosome with two mouse backcross panels. Some reference markers from other sources were retyped in the panels and results integrated with those for our microdissected DNA segments. The clone map is most highly refined in its distal portion, which stretches from reference marker D16Mit71 to D16Mit5, and the highest density of clones is in the region defined by markers D16Mit5 and D16Mit141. This map on distal mouse chromosome 16 should be a useful tool for the mouse genome project and for studies of genes in the region.

Animals↗

Dermatomes and the central organization of dermatomes and body surface regions in the spinal cord dorsal horn in rats.

Dermatomes and the associated central projection fields were studied with the application of fluorescent neurotracer, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI), to 21 reference points on rat trunk and hindlimb skin. Segmental distribution and rostrocaudal central level of dorsal root ganglion (DRG) neurons innervating reference points were examined and DiI-induced fluorescent areas were mapped in the horizontal plane through lamina II of the dorsal horn. Segmental levels of DRG neurons innervating reference points were generally identical to the level determined using dye-extravasation methods. However, innervation of the first digit was situated in the L4 dermatome, not the L3 reported previously using those methods. Generally, afferents from a reference point projected to a single field in the ipsilateral dorsal horn. Reference points on ventral and dorsal median lines of the trunk were represented bilaterally. Afferents from reference points located on the ventral median line of the hindlimb projected to two separate fields: one on the medial margin of spinal cord segments L2-L5 and the other on the medial half of spinal cord segment L5. From the distribution of central projection fields of reference points, central projection fields of dermatomes were revealed as even in shape and located within corresponding spinal cord segments. The arrangement of peripheral and central fields of dermatomes and body surface regions suggests that peripheral and central projection fields of cutaneous afferent fibers are reshaped from the common prototypical pattern that exhibits an orderly and evenly sequenced arrangement.

Afferent Pathways↗

Topographic cortical mapping of EEG sleep stages during daytime naps in normal subjects.

Computer-generated cortical maps of power spectral estimates derived from 16 leads were drawn based on daytime sleep recordings in four normal volunteers. These data were compiled from nine 10-s artifact-free, EEG epochs from awake, stages 1-4 and REM sleep in each volunteer. EEG leads were placed on the left hemisphere and midline according to the 10-20 system with four additional interpolated posterior locations. Magnitude spectral estimates with 1 Hz resolution and adjacent frequencies (delta 2-4, alpha 8-12, beta 13-18) were analyzed with two-way ANOVA (lead by sleep stage). Delta activity was relatively uniform and of low amplitude in awake, eyes-closed subjects, and REM. Delta power increased at the vertex in stage 1. With progressing, non-REM sleep stages, it increased in power and enlarged radially to the intraparietal sulcus posteriorly, and the superior frontal gyrus anteriorly. Comparison of maps with ear and a computed average reference yielded similar topographic patterns. Alpha activity was expectedly maximal occipitally in awake subjects, but surprisingly a frontal area appeared in slow wave sleep. Beta activity in awake subjects was low and maximal parietally; stages 1 and REM showed even lower and more uniform distribution. Stage 2 showed the greatest power, concentrated at the vertex, with stages 3 and 4 diminishing. These data suggest that sleep stages are not completely uniform electrophysiologically across the cortex. This opens the possibility for a new method for the diagnosis of sleep disorders and alternatives in sleep staging.

Adult↗

Identification of QTLs for early blight ( Alternaria solani) resistance in tomato using backcross populations of a Lycopersicon esculentum x L. hirsutum cross.

Most commercial cultivars of tomato, Lycopersicon esculentum Mill., are susceptible to early blight (EB), a devastating fungal ( Alternaria solani Sorauer) disease of tomato in the northern and eastern parts of the U.S. and elsewhere in the world. The disease causes plant defoliation, which reduces yield and fruit quality, and contributes to significant crop loss. Sources of resistance have been identified within related wild species of tomato. The purpose of this study was to identify and validate quantitative trait loci (QTLs) for EB resistance in backcross populations of a cross between a susceptible tomato breeding line (NC84173; maternal and recurrent parent) and a resistant Lycopersicon hirsutum Humb. and Bonpl. accession (PI126445). Sixteen hundred BC(1) plants were grown to maturity in a field in 1998. Plants that were self-incompatible, indeterminant in growth habit, and/or extremely late in maturity, were discarded in order to eliminate confounding effects of these factors on disease evaluation, QTL mapping, and future breeding research. The remaining 145 plants (referred to as the BC(1) population) were genotyped for 141 restriction fragment length polymorphism (RFLP) markers and 23 resistance gene analogs (RGAs), and a genetic linkage map was constructed. BC(1) plants were evaluated for disease symptoms throughout the season, and the area under the disease progress curve (AUDPC) and the final percent defoliation (disease severity) were determined for each plant. BC(1) plants were self-pollinated and produced BC(1)S(1) seed. The BC(1)S(1) population, consisting of 145 BC(1)S(1) families, was grown and evaluated for disease symptoms in replicated field trials in two subsequent years (1999 and 2000) and AUDPC and/or final percent defoliation were determined for each family in each year. Two QTL mapping approaches, simple interval mapping (SIM) and composite interval mapping (CIM), were used to identify QTLs for EB resistance in the BC(1) and BC(1)S(1) populations. QTL results were highly consistent across generations, years and mapping approaches. Approximately ten significant QTLs (LOD >/= 2.4, P </= 0.001) were identified (and validated) for EB resistance, with individual effects ranging from 8.4% to 25.9% and with combined effects of >57% of the total phenotypic variation. All QTLs had the positive alleles from the disease-resistant parent. The good agreement between results of the BC(1) and 2 years of the BC(1)S(1) generations indicated the stability of the identified QTLs and their potential usefulness for improving tomato EB resistance using marker-assisted selection (MAS). Further inspections using SIM and CIM indicated that six of the ten QTLs had independent additive effects and together could account for up to 56.4% of the total phenotypic variation. These complementary QTLs, which were identified in two generations and 3 years, should be the most useful QTLs for MAS and improvement of tomato EB resistance using PI126445 as a gene resource. Furthermore, the chromosomal locations of 10 of the 23 RGAs coincided with the locations of three QTLs, suggesting possible involvement of these RGAs with EB resistance and a potential for identifying and cloning genes which confer EB resistance in tomato.

Journal Article↗

Repetitive self-mutilation among Japanese eating disorder patients with drug use disorder: comparison with patients with methamphetamine use disorder.

Repetitive self-mutilation and drug use disorder are less prevalent in Japan, although the prevalence of eating disorder is comparable with rates in Western countries. However, repetitive self-mutilation has not previously been described in relation to eating disorder and drug use disorder in Japan. Subjects consisted of 19 patients with eating disorders and drug use disorders (ED+DUD) and 12 patients with methamphetamine use disorders (MAP). Subjects were drawn from 180 patients who were referred because of eating disorders and 22 patients who were referred because of methamphetamine-related problems. All subjects underwent a semistructured interview. Repetitive self-mutilation tended to be more prevalent among ED+DUD patients than MAP patients. Conversely, history of oppositional defiant disorder and antisocial personality disorder tended to be more prevalent in MAP patients than in ED+DUD patients. The low prevalence of repetitive self-mutilation appears to be due to low risk factors in Japan, even though the pathogenesis of these behaviors seems to be universal.

Adult↗

[Assessment of myocardial viability by exercise stress-redistribution myocardial scintigraphy with thallium-201: the usefulness of C-map].

Standard exercise (Ex)-redistribution (RD) myocardial imaging with thallium-201 (201Tl) may not differentiate viable myocardium from necrosis. This study was intended to clarify whether 201Tl washout rate (WOR) abnormality after Ex can detect myocardial viability in the myocardium with perfusion defect using routine RD image. We performed Ex-RD (three hours after) myocardial tomography with 201Tl in 29 patients with coronary artery disease. From myocardial tomography, 201Tl distribution Bull's-eye maps (Ex and RD) and WOR Bull's-eye map were made. At RD image before PTCA, by referring to the original image, the activity of the myocardial region below 40% to 55% of the maximal 201Tl activity was considered as perfusion defect (RD-Map). Then we constructed a new image (C-Map) by adding the location of WOR abnormality (< or = 30%) to the RD-Map and each map was divided into 17 segments. If the defect-segment in the RD-Map corresponded to WOR abnormality, the segment in the C-Map was judged as viable (no defect). The C-Map and myocardial imaging after PTCA (Post-Map) were compared. In the RD-Map before PTCA, defect was found in 152 segments but in the C-Map they decreased to 59 segments, while defect was found in 62 segments in the Post-Map. In 23 patients the number of defect-segments in the C-Map decreased as compared with those in the RD-Map. And in 22 of them, the Post-Map showed the reduction of defect-segments in comparison with the RD-Map, but in one of them defect did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Isolation of a cDNA encoding the rat MAP-kinase homolog of human p63mapk.

Using a combination of screening, RACE, and RT-PCR, we have isolated a new rat brain cDNA, we refer to as rMNK2, that showed strong homology to known MAP-kinases. The deduced amino acid sequence of rMNK2 indicated that it is the rat homolog of human p63(mapk), showing 94.5% identity. rMNK2 showed 77% homology with rat ERK3 and its human homolog p97(mapk), and 43% homology with both rat genes rMNK1(ERK1) and ERK2, within the kinase domain. This suggest that rMNK2 and ERK3 belong to a separate subfamily within the rat MAP-kinase multigene family. The most interesting difference lies in subdomain VIII, where this new subfamily contain a SEG/SPR motif instead of the TEY/APE found in the ERK subfamily, the TPY/APE found in the JNK/SAPK subfamily or the TGY/APE found in the p38/RK subfamily. The human homologs of ERK3 and rMNK2 (p97(mapk) and p63(mapk)) also show this significant change. Expression of rMNK2 has been detected in brain and to a lesser extent in lung by reverse transcription/PCR (RT-PCR). In situ hybridization of rat brain slices demonstrated a restricted expression of rMNK2 in the choroid plexus and hippocampus. This is interesting because the human homolog p63(mapk) maps to 18q12-21, a region that might be implicated in manic-depressive illness.

Amino Acid Sequence↗

Emergence of self and other in perception and action: an event-control approach.

The present paper analyzes the regularities referred to via the concept 'self.' This is important, for cognitive science traditionally models the self as a cognitive mediator between perceptual inputs and behavioral outputs. This leads to the assertion that the self causes action. Recent findings in social psychology indicate this is not the case and, as a consequence, certain cognitive scientists model the self as being epiphenomenal. In contrast, the present paper proposes an alternative approach (i.e., the event-control approach) that is based on recently discovered regularities between perception and action. Specifically, these regularities indicate that perception and action planning utilize common neural resources. This leads to a coupling of perception, planning, and action in which the first two constitute aspects of a single system (i.e., the distal-event system) that is able to pre-specify and detect distal events. This distal-event system is then coupled with action (i.e., effector-control systems) in a constraining, as opposed to 'causal' manner. This model has implications for how we conceptualize the manner in which one infers the intentions of another, anticipates the intentions of another, and possibly even experiences another. In conclusion, it is argued that it may be possible to map the concept 'self' onto the regularities referred to in the event-control model, not in order to reify 'the self' as a causal mechanism, but to demonstrate its status as a useful concept that refers to regularities that are part of the natural order.

Awareness↗

Electromagnetic tracker measurement error simulation and tool design.

Developing electromagnetically (EM) tracked tools can be very time consuming. Tool design traditionally takes many iterations, each of which requires construction of a physical tool and performing lengthy experiments. We propose a simulator that allows tools to be virtually designed and tested before ever being physically built. Both tool rigid body (RB) configurations and reference RB configurations are configured; the reference RB can be located anywhere in the field, and the tool is virtually moved around the reference in user-specified pattern. Sensor measurements of both RBs are artificially distorted according to a previously acquired error field mapping, and the 6-DOF frames of the Tool and Reference are refit to the distorted sensors. It is possible to predict the tool tip registration error for a particular tool and coordinate reference frame (CRF) in a particular scenario before ever even building the tools.

Computer Simulation↗

Conformation polymorphisms and targeted marker development.

Genetic markers were developed for three targeted bovine loci using both single-stranded and double-stranded DNA conformation polymorphisms. Eight of nine DNA fragments exhibited single-stranded conformation polymorphisms while only one of nine exhibited a double-strand conformation polymorphism. All but one of the polymorphic fragments exhibited two allelic forms, with the exception being a single-stranded conformation polymorphism with three alleles. Utility of conformation polymorphisms relative to microsatellite markers for linkage map development and quantitative trait loci (QTL) mapping was assessed by comparing frequency of heterozygote parents from reference and resource families. Heterozygosity was greater for microsatellite markers (P < 0.01) and reference family parents (P < 0.01), though the disparity between marker types tended to be less dramatic for the reference family parents (P < 0.09). These results suggest conformation polymorphisms will be a useful tool for targeted marker development in linkage map and comparative map development provided genetically diverse families are studied.

Animals↗

A microsatellite-based multipoint index map of human chromosome 22.

Utilizing the CEPH (Centre d'Etude du Polymorphism Humain) reference panel and genotyping data for 24 simple tandem repeat polymorphism (STRP) markers, we have constructed a 15-locus multipoint genetic framework map of human chromosome 22. The markers form a continuous linkage group of 51 cM in males and 81 cM in females. Likely genetic locations are provided for 9 additional STRP sequences. The map was constructed employing the CRIMAP computational methodology to build the multipoint map via a stepwise algorithm. The quality of the framework map was evaluated using a battery of statistical diagnostics that suggest a typing error frequency of 0.1% for markers within the map.

Base Sequence↗

Path integration and the neural basis of the 'cognitive map'.

The hippocampal formation can encode relative spatial location, without reference to external cues, by the integration of linear and angular self-motion (path integration). Theoretical studies, in conjunction with recent empirical discoveries, suggest that the medial entorhinal cortex (MEC) might perform some of the essential underlying computations by means of a unique, periodic synaptic matrix that could be self-organized in early development through a simple, symmetry-breaking operation. The scale at which space is represented increases systematically along the dorsoventral axis in both the hippocampus and the MEC, apparently because of systematic variation in the gain of a movement-speed signal. Convergence of spatially periodic input at multiple scales, from so-called grid cells in the entorhinal cortex, might result in non-periodic spatial firing patterns (place fields) in the hippocampus.

Animals↗

Spatial analysis of evoked potentials in man--a review.

Steps in brain information processing are reflected on the scalp as changes of the electric potential which is evoked by the stimulus. However, for a given recording point on the scalp, there is no absolute amplitude or phase information of the electric brain potential. This means that the shape of an evoked potential waveform which is recorded from a given scalp location crucially depends on the location of the chosen reference. Only unbiased results of evoked potential data evaluation can be hoped to elucidate or map successfully into information processing models established by other methods, e.g. behavior measurements. Conventional recordings vs a common reference contain only one of many possible sets of waveshapes. In order to avoid ambiguities or bias of results, the entire evoked potential data set firstly must be analysed over space, and reference-independent parameters must be extracted. For each time point, the spatial distribution of the potentials is viewed as field map. The parameter extraction in a direct approach at each time point includes, e.g. locations of field peaks and troughs, voltage and gradient between them, and global electrical field power; or, parameters via the first or second spatial derivative of the electric field. In the second step, changes of these reference-independent field measurements are analysed over time. At component latency which is defined by maximal, global field power or by voltage range, mapped field distributions can be compared using maximal/minimal field value locations or complete maps. Significantly different field configurations establish the activity of non-identical neural generators. Classification of the field configurations (examination of orbits of field extrema over time) leads to the segmentation of series of field maps (multichannel EP data) into short epochs of stationary spatial configurations (i.e. spatially characterized components) with equal consideration of all recording points, and without the amplitude criterion. The application of these principles to the following problems is discussed: comparison of evoked potentials between different analysis times, in particular pre-stimulus and post-stimulus electric brain states; zero baseline for measurement; reference electrode; identification of evoked components in time and space. Illustrations of these problems include functional differences of input-analysing sub-systems, and the topography of cognition- and speech-related electric brain activity.

Brain↗

Learning-induced neural plasticity associated with improved identification performance after training of a difficult second-language phonetic contrast.

Adult native Japanese speakers have difficulty perceiving the English /r-l/ phonetic contrast even after years of exposure. However, after extensive perceptual identification training, long-lasting improvement in identification performance can be attained. This fMRI study investigates localized changes in brain activity associated with 1 month of extensive feedback-based perceptual identification training by native Japanese speakers learning the English /r-l/ phonetic contrast. Before and after training, separate functional brain imaging sessions were conducted for identification of the English /r-l/ contrast (difficult for Japanese speakers), /b-g/ contrast (easy), and /b-v/ contrast (difficult), in which signal-correlated noise served as the reference control condition. Neural plasticity, denoted by exclusive enhancement in brain activity for the /r-l/ contrast, does not involve only reorganization in brain regions concerned with acoustic-phonetic processing (superior and medial temporal areas) but also the recruitment of additional bilateral cortical (supramarginal gyrus, planum temporale, Broca's area, premotor cortex, supplementary motor area) and subcortical regions (cerebellum, basal ganglia, substantia nigra) involved with auditory-articulatory (perceptual-motor) mappings related to verbal speech processing and learning. Contrary to what one may expect, brain activity for perception of a difficult contrast does not come to resemble that of an easy contrast as learning proceeds. Rather, the results support the hypothesis that improved identification performance may be due to the acquisition of auditory-articulatory mappings allowing for perception to be made in reference to potential action.

Brain↗

Radiofrequency catheter ablation of ectopic atrial tachycardia using paced activation sequence mapping.

OBJECTIVES: Although ectopic atrial tachycardia is infrequent, it can be an important clinical challenge. We sought to define an alternative therapeutic approach to this refractory problem. BACKGROUND: Radiofrequency energy catheter ablation has been used to treat a variety of ventricular and supraventricular arrhythmias but has not been proved efficacious in the management of ectopic atrial tachycardia. METHODS: Ten patients (14 to 47 years of age) referred with refractory ectopic atrial tachycardia were studied. Mapping techniques included identification of earliest atrial activation, confirmation of concordance of P wave configuration during spontaneous tachycardia and pacing from the ablation catheter, and paced activation sequence mapping. The paced activation sequence mapping compared the activation sequence at multiple atrial sites during spontaneous tachycardia with that recorded during pacing from the ablation catheter. The catheter was steered to a point where pacing reproduced the spontaneous activation sequence. RESULTS: Foci were right atrial in eight patients and left atrial in two. In 8 of 10 patients, 514 +/- 97 (SE) J and 5.7 +/- 2.3 (SD) J radiofrequency energy applications ablated the ectopic focus. Seven of these eight patients presented with one focus and one had two discrete and stable foci. Ablation was unsuccessful in two patients with multiple foci. No complications occurred. An arrhythmia focus recurred in two patients and one patient underwent successful repeat ablation. The other patient was managed medically. All seven patients with successful ablation are symptom free after 6.5 +/- 3.8 months. CONCLUSIONS: Our preliminary experience suggests that with the use of both paced activation sequence mapping and standard techniques, radiofrequency ablation of ectopic atrial tachycardia may be a safe and effective form of therapy.

Adolescent↗

High-resolution MRI reflects myeloarchitecture and cytoarchitecture of human cerebral cortex.

Maps of cytoarchitectonically defined cortical areas have proven to be a valuable tool for anatomic localization of activated brain regions revealed by functional imaging studies. However, architectonic data require observations in a sample of postmortem brains. They can only be used reliably for comparison with functional data as probabilistic maps after spatial normalization to a common reference space. The complete architectonic analysis of an individual living brain has not been achievable to date, because the relationship remains unclear between laminar gray value changes of cerebral cortex in magnetic resonance (MR) images and those of cyto- and myeloarchitectonic histologic sections. We examined intensity profiles through the cortex in five imaging modalities: in vivo T1 and postmortem T2 MRI, one cell body stain, and two myelin stains. After visualizing the dissimilarities in the shapes of these profiles using a canonical analysis, differences between the profiles from the different image modalities were compared quantitatively. Subsequently, the profiles extracted from the in vivo T1-weighted images were estimated from profiles extracted from cyto- and myeloarchitectonic sections using linear combinations. We could verify statistically the mixed nature of the cortical T1 signal obtained in vivo: The MR intensity profiles were significantly more similar to myeloarchitectonic than to cytoarchitectonic profiles, but a weighted sum of both fitted the T1 profiles best.

Brain Mapping↗

Proteomic analysis of normal human urinary proteins isolated by acetone precipitation or ultracentrifugation.

BACKGROUND: Proteomic techniques have recently become available for large-scale protein analysis. The utility of these techniques in identification of urinary proteins is poorly defined. We constructed a proteome map of normal human urine as a reference protein database by using two differential fractionated techniques to isolate the proteins. METHODS: Proteins were isolated from urine obtained from normal human volunteers by acetone precipitation or ultracentrifugation, separated by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and identified by matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry followed by peptide mass fingerprinting. RESULTS: A total of 67 protein forms of 47 unique proteins were identified, including transporters, adhesion molecules, complement, chaperones, receptors, enzymes, serpins, cell signaling proteins and matrix proteins. Acetone precipitated more acidic and hydrophilic proteins, whereas ultracentrifugation fractionated more basic, hydrophobic, and membrane proteins. Bioinformatic analysis predicted glycosylation to be the most common explanation for multiple forms of the same protein. CONCLUSIONS: Combining two differential isolation techniques magnified protein identification from human urine. Proteomic analysis of urinary proteins is a promising tool to study renal physiology and pathophysiology and to determine biomarkers of renal disease.

Acetone↗

An in vivo validation of quantitative blood flow imaging in arteries and veins using magnetic resonance phase-shift techniques.

Magnetic resonance (MR) techniques have recently been introduced, allowing quantitative measurement of blood flow with high spatial and temporal resolutions. These techniques are based on the phase of the MR signal rather than on the amplitude, and are referred to as MR phase or velocity mapping. Clinical validation is still lacking. We therefore performed an in vivo validation of such a technique in 17 healthy volunteers. Velocity maps were acquired at 50 ms intervals over the cardiac cycle in the aorta, superior and inferior vena cava. Plots were made of flow velocity and volume flow vs time and used for calculation of left ventricular stroke volume (SV), cardiac output (CO) and venous return. Comparison with Doppler ultrasound (x) yielded y = -7.5 + 1.1x (r = 0.76) for SV measurements (ml), and y = 0.3 + 0.9x (r = 0.86) for CO calculations (1 min-1). Comparison between MR SV (x) and MR determination of venous return (y), obtained by summation of the flow volumes per cardiac cycle in the superior and inferior vena cava, was close to identity, y = 1.3 + 1.0x (r = 0.91). Also, preliminary applications are presented in patients with aortic diseases. The findings of this study show that magnetic resonance velocity imaging can be accurately applied in vivo as a non-invasive means of measuring flow.

Aortic Dissection↗