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Axonal mapping of the giant peptidergic neurons VD1 and RPD2 located in the CNS of the pond snail Lymnaea stagnalis, with particular reference to the innervation of the auricle of the heart.

VD1 and RPD2 are two giant neuropeptidergic neurons located respectively in the visceral and right parietal ganglion of the central nervous system (CNS) of the pond snail Lymnaea stagnalis. They are the most prominent representatives of a system of neurons expressing a gene that is similar to the gene expressed in R15 of Aplysia californica. Both neuronal systems are involved in the regulation of cardio-respiratory phenomena. In the present study the axonal branches of VD1 and RPD2 were mapped using immunocytochemical and tracer studies. To this end the alpha 1-antiserum (directed to one of the VD1/RPD2 neuropeptides) was used in combination with Lucifer yellow (LY) and Ni-lys tracers. In whole mount preparations of the CNS, immunostained axons of VD1 and RPD2 were observed to run to the pleural, cerebral and pedal ganglia and in several nerves. Upon LY injection of VD1 thin axon branches were observed in the internal right parietal nerve. These run to the skin in the mantle area near the pneumostome and osphradium. The skin of the lips appeared to receive a similar innervation via the lip nerves. Thick LY filled axons of VD1 and RPD2 were observed in the intestinal nerve. They could be traced to the heart region. The pericardial branch of the intestinal nerve innervates the pericardium and heart (Ni-lys tracing). Immunocytochemically, using the alpha 1-antiserum, it was demonstrated that this nerve branch carries the axons of VD1 and RPD2 to the venous side of the auricle, where they enter the pericardial cavity and ramify in the auricle (but not in the ventricle).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Properties of cognitive maps constructed from texts.

Subjects in three experiments read texts describing the locations of landmarks in a fictitious town. Later they drew sketch maps and verified sentences describing the relative locations of the landmarks. We predicted that subjects would develop mental models of the town that were organized around important landmarks ("anchors"), as are cognitive maps constructed through real-world navigation. More specifically, we expected that landmarks used in the text as reference points for describing the locations of some other landmarks would emerge as anchors in the subjects' cognitive maps and would consequently be recalled more accurately. Results showed that subjects represented such reference-point landmarks more accurately than they did the locations of other landmarks. This effect was independent of: (1) the perspective from which the text was written (route or survey); (2) whether or not a map was present at learning; (3) the order of information in the text (linear or anchors-first), and (4) the amount of information available to the subjects while drawing sketch maps (the full text, the landmark names only, or no information).

Adult↗

Analysis of neural mechanisms underlying verbal fluency in cytoarchitectonically defined stereotaxic space--the roles of Brodmann areas 44 and 45.

We investigated neural activations underlying a verbal fluency task and cytoarchitectonic probabilistic maps of Broca's speech region (Brodmann's areas 44 and 45). To do so, we reanalyzed data from a previous functional magnetic resonance imaging (fMRI) [Brain 125 (2002) 1024] and from a cytoarchitectonic study [J. Comp. Neurol. 412 (1999) 319] and developed a method to combine both data sets. In the fMRI experiment, verbal fluency was investigated in 11 healthy volunteers, who covertly produced words from predefined categories. A factorial design was used with factors verbal class (semantic vs. overlearned fluency) and switching between categories (no vs. yes). fMRI data analysis employed SPM99 (Statistical Parametric Mapping). Cytoarchitectonic maps of areas 44 and 45 were derived from histologic sections of 10 postmortem brains. Both the in vivo fMRI and postmortem MR data were warped to a common reference brain using a new elastic warping tool. Cytoarchitectonic probability maps with stereotaxic information about intersubject variability were calculated for both areas and superimposed on the functional data, which showed the involvement of left hemisphere areas with verbal fluency relative to the baseline. Semantic relative to overlearned fluency showed greater involvement of left area 45 than of 44. Thus, although both areas participate in verbal fluency, they do so differentially. Left area 45 is more involved in semantic aspects of language processing, while area 44 is probably involved in high-level aspects of programming speech production per se. The combination of functional data analysis with a new elastic warping tool and cytoarchitectonic maps opens new perspectives for analyzing the cortical networks involved in language.

Adult↗

Molecular similarity analysis and virtual screening by mapping of consensus positions in binary-transformed chemical descriptor spaces with variable dimensionality.

A novel compound classification algorithm is described that operates in binary molecular descriptor spaces and groups active compounds together in a computationally highly efficient manner. The method involves the transformation of continuous descriptor value ranges into a binary format, subsequent definition of simplified descriptor spaces, identification of consensus positions of specific compound sets in these spaces, and iterative adjustments of the dimensionality of the descriptor spaces in order to discriminate compounds sharing similar activity from others. We term this approach Dynamic Mapping of Consensus positions (DMC) because the definition of reference spaces is tuned toward specific compound classes and their dimensionality is increased as the analysis proceeds. When applied to virtual screening, sets of bait compounds are added to a large screening database to identify hidden active molecules. In these calculations, molecules that map to consensus positions after elimination of most of the database compounds are considered hit candidates. In a benchmark study on five biological activity classes, hits for randomly assembled sets of bait molecules were correctly identified in 95% of virtual screening calculations in a source database containing more than 1.3 million molecules, thus providing a measure of the sensitivity of the DMC technique.

Journal Article↗

Activity of p44/42 MAP kinase in the caudal subnucleus of trigeminal spinal nucleus is increased following perioral noxious stimulation in the mouse.

The extracellular signal-regulated protein kinase-1 and -2 (ERK1 and ERK2), also referred to as the p44/42 mitogen-activated protein kinase (p44/42 MAP kinase), plays an essential role in neuronal signal transduction, but its function involved in nociceptive response has not been deeply studied yet. Here we report immunohistochemical evidence that p44/42 MAPK might be critical in nociceptive response. We found that after formalin was injected into the perioral skin of the upper lip of mice, the number of activated p44/42 MAPK-like immunoreactive neurons was significantly increased in the laminae I and II of the caudal subnucleus of the trigeminal spinal nucleus (Sp5C). The positive neurons and fibers were mostly concentrated in the middle portion of Sp5C dorsoventrally, where the afferent fibers innervating the skin of the upper lip are terminated. The reactive products were localized in perikarya, dendrites, nuclei, and diffusely in the neuropil. The present result suggests that p44/42 MAPK may be important in the transmission and modulation of noxious information in Sp5C.

Animals↗

Bulked segregant analysis using microsatellites: mapping of the dominant white locus in the chicken.

In order to perform a linkage study, the genotypes of a large number of individuals from a segregating population need to be determined. In case the phenotype to be mapped is influenced by a single locus or a major gene, sampling of the DNA from individual animals with the same phenotype into a single pool (bulked segregant) can reduce the number of typings. In this study we used bulked segregant analysis in order to map the Dominant White locus in the chicken. In a pilot experiment, we showed that allele frequencies can be accurately estimated from pooled samples using fluorescently labeled microsatellite markers. A segregating population for the Dominant White locus was obtained by performing a cross between a white male chicken (Genotype li for Dominant White) and a black female chicken (ii). The resulting progeny of 21 white and 18 black chickens were divided in two pools. Genotypes for both the parents and the pools were determined using 168 fluorescently labeled microsatellite markers, of which 68 were informative. The relative allele frequencies between the pools were estimated for these 68 informative markers. One marker (MCW188) was found to segregate with the Dominant White locus. Subsequent typing of all individuals from this cross and an additional 148 animals from five different families showed only two recombinants between the marker and the Dominant White locus, resulting in a LODlinkage score (log10 of odds) of 36. Using the pooled DNA approach, the Dominant White locus was successfully mapped on linkage group 22 of the East Lansing reference family at a distance of 2 cM from MCW188.

Animals↗

Image registration with auto-mapped control volumes.

Many image registration algorithms rely on the use of homologous control points on the two input image sets to be registered. In reality, the interactive identification of the control points on both images is tedious, difficult, and often a source of error. We propose a two-step algorithm to automatically identify homologous regions that are used as a priori information during the image registration procedure. First, a number of small control volumes having distinct anatomical features are identified on the model image in a somewhat arbitrary fashion. Instead of attempting to find their correspondences in the reference image through user interaction, in the proposed method, each of the control regions is mapped to the corresponding part of the reference image by using an automated image registration algorithm. A normalized cross-correlation (NCC) function or mutual information was used as the auto-mapping metric and a limited memory Broyden-Fletcher-Goldfarb-Shanno algorithm (L-BFGS) was employed to optimize the function to find the optimal mapping. For rigid registration, the transformation parameters of the system are obtained by averaging that derived from the individual control volumes. In our deformable calculation, the mapped control volumes are treated as the nodes or control points with known positions on the two images. If the number of control volumes is not enough to cover the whole image to be registered, additional nodes are placed on the model image and then located on the reference image in a manner similar to the conventional BSpline deformable calculation. For deformable registration, the established correspondence by the auto-mapped control volumes provides valuable guidance for the registration calculation and greatly reduces the dimensionality of the problem. The performance of the two-step registrations was applied to three rigid registration cases (two PET-CT registrations and a brain MRI-CT registration) and one deformable registration of inhale and exhale phases of a lung 4D CT. Algorithm convergence was confirmed by starting the registration calculations from a large number of initial transformation parameters. An accuracy of approximately 2 mm was achieved for both deformable and rigid registration. The proposed image registration method greatly reduces the complexity involved in the determination of homologous control points and allows us to minimize the subjectivity and uncertainty associated with the current manual interactive approach. Patient studies have indicated that the two-step registration technique is fast, reliable, and provides a valuable tool to facilitate both rigid and nonrigid image registrations.

Algorithms↗

Selection of highly informative and user-friendly microsatellites (SSRs) for genotyping of cultivated potato.

Characterization of nearly 1,000 cultivated potato accessions with simple sequence repeats (SSRs; also referred to as microsatellites) has allowed the identification of a reference set of SSR markers for accurate and efficient genotyping. In addition, 31 SSRs are reported here for a potato genetic map, including new map locations for 24 of them. A first criterion for this proposed reference set was ubiquity of the SSRs in the eight landrace cultivar groups of the potato, Solanum tuberosum. All SSRs tested in the present study displayed the same allele phenotypes and allele size range in the diverse germplasm set as in the advanced potato cultivar germplasm in which they were originally discovered. Thirteen of 13 SSR products from all cultivar groups are shown to cross-hybridize with the corresponding SSR product of the source cultivar to ascertain sequence homology. Other important SSR selection criteria are quality of amplification products, locus complexity, polymorphic index content, and well-dispersed location on a potato genetic map. Screening of 156 SSRs allowed the identification of a highly informative and user-friendly set comprising 18 SSR markers for use in characterization of potato genetic resources. In addition, we have identified true- and pseudo-multiplexing SSRs for even greater efficiency.

Alleles↗

A detailed genetic map of the long arm of chromosome 11.

We describe 14 new restriction fragment length polymorphisms, corresponding to 13 loci on the long arm of chromosome 11. A detailed genetic map of chromosome 11q has been constructed from these and other loci (a total of 31 loci) typed in 59 reference families. The 23 most informative markers were selected to establish a map with a strongly supported order; regional localizations are provided for eight other markers. The loci span 88 cM in males and 148 cM in females and form a dense continuum on 11q. These ordered polymorphic markers will be of help in studying the genes responsible for several diseases that have been localized to this region, including genes responsible for multiple endocrine neoplasia type I (MEN1), ataxia telangiectasia (AT), tuberous sclerosis (TSC), and some forms of asthma and rhinitis.

Chromosome Mapping↗

Cutaneous lymphatic drainage in patients with grossly involved nodal basins.

BACKGROUND: The development of lymphatic mapping techniques has facilitated the identification of the sentinel lymph node (SLN), the first node in the regional basin into which cutaneous lymphatics flow from a particular skin area. Previous studies have shown that SLN histology reflects the histology of the entire basin, because melanoma metastases progress in an orderly fashion, involving the SLN before higher nodes in the basin become involved with metastatic disease. It is uncertain whether these orderly cutaneous lymphatic flow patterns are maintained in grossly involved basins. Lymphatic mapping was performed in a population of melanoma patients with clinically palpable lymphadenopathy to address this question. We aimed to determine whether the presence of gross nodal disease in the basin alters lymphatic flow into that basin so that lymphatic mapping techniques are not applicable, and, in patients referred with a grossly involved basin, whether preoperative lymphoscintigraphy should be performed to identify other regional basins at risk for metastases. METHODS: Eight patients presented with grossly palpable disease in the regional basin and underwent preoperative lymphoscintigraphy. All patients with palpable disease and all basins indicated by lymphoscintigraphy to be at risk were dissected. Three patients presented with clinically palpable nodes at the time of diagnosis, and five developed nodal disease on clinical follow-up after undergoing initial wide local excision only. A total of 10 basins in the eight patients were dissected. Of these, eight of the basins had grossly palpable regional nodal disease, and the other two basins were identified by preoperative lymphoscintigraphy as being at risk for metastases. The SLN was identified with intraoperative mapping, harvested, and submitted to pathology. Complete therapeutic lymph node dissections were performed following the SLN harvest in the basins with grossly palpable disease. SLN biopsy alone was performed in the two basins that did not have clinically palpable adenopathy but showed cutaneous lymphatic flow from the scintigram. RESULTS: Sixteen SLNs were harvested from these eight basins with grossly palpable disease, and 14 (87.5%) contained tumor. In each case, one of the SLNs was the grossly palpable node, and in six of the basins (75%) it was the only site of melanoma metastases. An additional 190 higher level, non-SLNs were removed, 32 (16.8%) of which contained microscopic foci of metastatic melanoma (P = .015). The null hypothesis that melanoma nodal metastasis is a random event is rejected. Two patients with trunk melanoma primary sites were identified to have other basins at risk for metastatic disease on lymphoscintigraphy. SLN biopsies were performed in these two patients, and one had microscopic nodal disease in the SLN. CONCLUSIONS: These data support the fact that cutaneous lymphatic drainage patterns are maintained in patients with grossly involved basins, thus buttressing the idea that the SLN is the node most likely to develop metastatic disease. Gross disease in the basin does not significantly alter cutaneous lymphatic flow into the regional basin, as the sentinel lymph node identified under these circumstances is the same as with the grossly involved node. Preoperative lymphoscintigraphy in patients who present with grossly involved nodes in one basin may identify other regional basins with micrometastatic disease and deserves further study in this setting.

Adult↗

Searching for names in two city street maps.

Two experiments investigated the speed with which names could be found on maps from two London street atlases. Differences in grid referencing between the maps accounted for large differences in search times. However, small statistically significant differences were still present when grid references were not being used, and these cannot be explained in terms of map scale, nor in terms of greater familiarity with the faster map. Several design differences could have contributed to this effect and it is likely that the use of lower case type on the faster map was an important factor. Implications for the map designer are discussed.

Journal Article↗

A circle map model of human circadian rhythms.

Peculiar relationships between the sleep-wake cycle and temperature rhythm have been found during free-run situations, i.e. internal synchronization, internal desynchronization and phase trapping. The periods of both rhythms and the phase relationships between them could well characterize the above behavioral states. In this paper, firstly, our mathematical interpretations for them are proposed. According to these interpretations, a new circadian system model is developed. Our model consists of two circle maps, one for the dynamics of sleep-onset phase and the other wake-onset phase in reference to the temperature rhythm. The model dynamics is controlled mainly by the map for sleep-onsets which simultaneously determines behavior of wake-onsets. The model parameters are uniquely estimated based on the experimental results. The diverse behavior of the sleep-wake cycle associated with the synchronized and desynchronized states is suggested to be understood as bifurcation phenomena of the model dynamics. The bifurcation of the model dynamics is controlled by a single parameter, whose quantitative characteristics are investigated in detail. The results shown here could provide a novel framework to understand the human circadian rhythms systematically.

Body Temperature↗

[Introduction of rapid HIV tests to a public health center in Japan and evaluation of its effects].

OBJECTIVE: As an attempt to make HIV testing more accessible to many people, rapid HIV tests were introduced to a public health center. We evaluated logistic issues and effects of the introduction. METHODS: In January 2003, the Tochigi Prefectural Kennan Public Health and Welfare Center introduced rapid HIV tests simultaneously with conventional HIV tests. We studied the number and types of the clients before and after its introduction as well as comparing them with those of other public centers. Information on rapid HIV test practices was uploaded on the website, "HIV Kensa-Soudan Map" and its effects were also evaluated. RESULTS: The public health center had performed 130 conventional HIV tests in 2002 prior to the introduction of rapid HIV tests but performed 453 HIV tests in 2003 (250% increase). Of those, 404 clients (94%) preferred the rapid tests. Out of the 404 rapid HIV tests performed, five were tested positive but only one was confirmed to be positive (false positive rate 1%). The introduction of rapid HIV tests had a negative impact on other sexually transmitted infection (STI) tests. The access rates to TP antibody tests (rapid tests) and Chlamydia antibody tests (non rapid tests) offered to HIV test recipients declined from 77% to 63% and from 76% to 33%, respectively. However, the actual number of these STI tests increased due to the increased number of HIV tests. Sixty-one per cent of those who came to take the HIV tests referred to the website "HIV Kensa-Soudan Map". During the same time period, the increase rate in the number of those who took the non rapid HIV tests provided at other public health centers in Tochigi prefecture was 0% and the increase rate nationwide was 20%. CONCLUSIONS: The introduction of these tests to public health centers greatly increases access to HIV testing. It was found that the website "HIV Kensa-Soudan Map" was a useful information source for HIV testing. However, because of high false positive rate (about 1%), it is important to establish an effective pre- and post-test counseling system. It is also necessary to prevent the number of tests for other STIs from declining when rapid HIV tests are implemented simultaneously.

Adolescent↗

SWISS-2DPAGE: a database of two-dimensional gel electrophoresis images.

This publication presents the SWISS-2DPAGE database which gathers data on proteins identified on various two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) maps. Each SWISS-2DPAGE entry contains data on one protein, including mapping procedures, physiological and pathological data and bibliographical references, as well as several 2-D PAGE images showing the protein location. Links are also provided to other databases such as SWISS-PROT, EMBL, PROSITE and OMIM. The database has been set up on a server which may be accessed from any computer connected to the internet and it also makes it possible to display the theoretical location of proteins, the positions of which are not yet known on the 2-D PAGE.

Databases, Factual↗

Automated enhancement of description logic-defined terminologies to facilitate mapping to ICD9-CM.

Compositional (post-coordinated) terminologies are one potential solution to the problem of content completeness. However, they have the potential to render data incomparable. For computers to determine that compositional expressions are comparable, the relations between the composed components that are understood implicitly by human readers must be represented explicitly for computer manipulation. We discuss a technique for discovering and formalizing the implicit semantic relationships in two vocabularies: the International Classification of Disease Version 9 Clinical Modification (ICD9-CM), and SNOMED-Reference Terminology (SNOMED-RT). The results of this technique are used to augment the existing SNOMED-RT relation ontology, which is a necessary step in automated concept mapping between systems. The reference terminology must contain all the semantics implicit in the classification in order to map concepts between the two representations. We also provide an explicit representation of the implied semantics of ICD9-CM. This tabulation will be useful for other knowledge engineering efforts involving ICD9-CM.

Automation↗

Alignment of the PiGMaP and USDA linkage maps of porcine chromosomes 3 and 9.

The European Pig Gene Mapping Project (PiGMaP) and United States Department of Agriculture (USDA) porcine linkage maps for chromosomes 3 and 9 have been aligned by typing three USDA microsatellites from chromosome 3 and five from chromosome 9 on the PiGMaP reference families. Using the CRIMAP linkage analysis package, revised multipoint linkage maps were constructed for chromosome 3 and 9. Inclusion of these USDA markers in the multipoint analysis resulted in an increase in length of 47% and 33% respectively for these two PiGMaP linkage groups. This increase in size is mainly the result of extension of the ends of both linkage groups.

Animals↗

Gene-specific universal mammalian sequence-tagged sites: application to the canine genome.

We are developing a genetic map of the dog based partly upon markers contained within known genes. In order to facilitate the development of these markers, we have used polymerase chain reaction (PCR) primers designed to conserved regions of genes that have been sequenced in at least two species. We have refined the method for designing primers to maximize the number that produce successful amplifications across as many mammalian species as possible. We report the development of primer sets for 11 loci in detail: CFTR, COL10A1, CSFIR, CYP1A1, DCN1, FES, GHR, GLB1, PKLR, PVALB, and RB1. We also report an additional 75 primer sets in the appendices. The PCR products were sequenced to show that the primers amplify the expected canine genes. These primer sets thus define a class of gene-specific sequence-tagged sites (STSs). There are a number of uses for these STSs, including the rapid development of various linkage tools and the rapid testing of genomic and cDNA libraries for the presence of their corresponding genes. Six of the eleven gene targets reported in detail have been proposed to serve as "anchored reference loci" for the development of mammalian genetic maps [O'Brien, S. J., et al., Nat. Genet. 3:103, 1993]. The primer sets should cover a significant portion of the canine genome for the development of a linkage map. In order to determine how useful these primer sets would be for the other genome projects, we tested the 11 primer sets on the DNA from species representing five mammalian orders. Eighty-four percent of the gene-species combinations amplified successfully. We have named these primer sets "universal mammalian sequence-tagged sites" because they should be useful for many mammalian genome projects.

Amino Acid Sequence↗

Successful release of entrapped circumferential mapping catheters in patients undergoing pulmonary vein isolation for atrial fibrillation.

OBJECTIVES: The purpose of this study was to demonstrate a method for successful and safe release of an entrapped circular catheter. BACKGROUND: Segmental pulmonary vein (PV) isolation is widely practiced for patients with symptomatic drug-refractory atrial fibrillation. A circular mapping catheter is sometimes used with this technique to map the electrical connection between the left atrium (LA) and the PVs. This catheter reportedly can become entrapped in the mitral valve apparatus. Attempts to free the entrapped catheter can result in serious complications, including damage to the mitral valve chordae tendineae or fracture of the catheter itself. METHODS: Three patients were referred for PV isolation for atrial fibrillation. A circular mapping catheter was used to map the sites of LA-PV electrical connections. RESULTS: During the procedure, the circular mapping catheter became entrapped in the mitral valve apparatus in two patients and in the PV in one patient. A series of maneuvers, which included use of another catheter and guiding sheaths as well as pushing forward rather than pulling back on the entrapped catheter, allowed safe and successful release of the entrapped catheter in all patients. CONCLUSIONS: Entrapment of the circular mapping in the mitral valve apparatus or the PVs during PV isolation is a rare complication associated with use this catheter. We describe a series of maneuvers that may allow safe and successful release of the entrapped catheter.

Adult↗