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PubMed1990

Restoration of the plasticity of binocular maps by NMDA after the critical period in Xenopus.

Visual input during a critical period of development plays a major role in the establishment of orderly connections in the developing visual system. In Xenopus laevis, the matching of visual maps from the two eyes to the optic tectum depends on binocular visual input during the critical period, which extends from late tadpole to early juvenile stages. Alterations in eye position, which produce a mismatch of the tectal maps, normally evoke a compensatory adjustment in the map of the ipsilateral eye only during the critical period. However, continuous application of the glutamate receptor agonist N-methyl-D-aspartate (NMDA) after the normal end of the critical period restores this ability to realign the visual map.

Animals↗
PubMed1996

Structure-activity relationships derived by machine learning: the use of atoms and their bond connectivities to predict mutagenicity by inductive logic programming.

We present a general approach to forming structure-activity relationships (SARs). This approach is based on representing chemical structure by atoms and their bond connectivities in combination with the inductive logic programming (ILP) algorithm PROGOL. Existing SAR methods describe chemical structure by using attributes which are general properties of an object. It is not possible to map chemical structure directly to attribute-based descriptions, as such descriptions have no internal organization. A more natural and general way to describe chemical structure is to use a relational description, where the internal construction of the description maps that of the object described. Our atom and bond connectivities representation is a relational description. ILP algorithms can form SARs with relational descriptions. We have tested the relational approach by investigating the SARs of 230 aromatic and heteroaromatic nitro compounds. These compounds had been split previously into two subsets, 188 compounds that were amenable to regression and 42 that were not. For the 188 compounds, a SAR was found that was as accurate as the best statistical or neural network-generated SARs. The PROGOL SAR has the advantages that it did not need the use of any indicator variables handcrafted by an expert, and the generated rules were easily comprehensible. For the 42 compounds, PROGOL formed a SAR that was significantly (P < 0.025) more accurate than linear regression, quadratic regression, and back-propagation. This SAR is based on an automatically generated structural alert for mutagenicity.

Algorithms↗
PubMed2001

Atypical left atrial flutter after intraoperative radiofrequency ablation of chronic atrial fibrillation: successful ablation using three-dimensional electroanatomic mapping.

Curative treatment of chronic atrial fibrillation (AF) remains a challenging task for electrophysiologists. Eliminating the initiating triggers by focal radiofrequency ablation in a subset of patients with paroxysmal AF and modifying the maintaining substrate by performing linear lesions within the left atrium in patients with prolonged episodes of AF are among the alternative approaches for management of these patients. Recently, a new intraoperative treatment procedure aimed at eliminating left atrial anatomic "anchor" reentrant circuits by induction of contiguous lesions using radiofrequency energy under direct vision was introduced. However, atypical left atrial flutter may occur during follow-up after intraoperative ablation of AF. These arrhythmias most likely are due to discontinuities in linear lesions; therefore, they can be successfully mapped and ablated in a subsequent percutaneous catheter ablation procedure. We report and discuss the case of a patient who underwent successful intraoperative ablation of chronic AF, but who developed atypical left atrial flutter postoperatively. Three-dimensional nonfluoroscopic electroanatomic mapping revealed a gap in the linear lesion line connecting the left upper and right upper pulmonary vein orifices. Ablation at the exit site of the breakthrough was successful.

Aged↗
PubMed2003

Homozygosity mapping of a gene for arterial tortuosity syndrome to chromosome 20q13.

BACKGROUND: Arterial tortuosity syndrome (ATS) is an uncommon connective tissue disorder of unknown aetiology. The most prominent feature is tortuosity of the large arteries, but lengthening, stenosis, and aneurysm formation are also frequent. METHODS: We performed a genomewide screen by homozygosity mapping of three consanguineous multiplex families, two from Morocco, and one from Italy, which included 11 ATS patients. The two families from Morocco may possibly have a common ancestor. RESULTS: We mapped the ATS gene to chromosome 20q13. Recombinations within an extended haplotype of 11 microsatellite markers localised the ATS gene between markers D20S836 and D20S109, an interval of 9.5 cM. CONCLUSIONS: Cloning and completing functional and structural analysis of the ATS gene may provide new insights into the molecular mechanisms of elastogenesis.

Adolescent↗
PubMed1995

Mapping knowledge in chronic illness.

Theory-based nursing practice requires a systematically developed, integrated body of information to deal effectively with the complexities of the human condition. This philosophical research is founded on a complementary knowledge model, valuing diverse views. The burden therefore is on uncovering connections between perspectives. A method is proposed and tested for mapping pluralistic knowledge in chronic illness. Underlying the method development is the premise that all knowledge can be represented as different combinations of ontology (views of the person) and epistemology (nature and aims of science). Based on a review of over 300 references, six major themes (comprised of 20 conceptual categories) are uncovered in the nursing literature. Analysis of the map reveals the influence of trends as well as areas of minimal development (e.g. holism). A key advantage of mapping is the opportunity to know the data in a large substantive area and to begin to identify potential linkages for cumulation. Fatigue, pain, symptom management, day-to-day living with illness, and social support are identified as promising areas to begin building a mid-range theory of chronic illness. Developing a cumulative knowledge base narrows the gap between theory and practice.

Chronic Disease↗
PubMed2003

The structure of the helically perturbed flagellar filament of Pseudomonas rhodos: implications for the absence of the outer domain in other complex flagellins and for the flexibility of the radial spokes.

Bacterial flagella, the organelles of motility, are commonly divided into two classes: 'plain' and 'complex'. The complex filaments are pairwise, helically perturbed forms of the plain filaments and have been reported to occur only in Rhizobium and Pseudomonas. Previously, we reconstructed and analysed the structure of the complex filaments of Rhizobium lupini H13-3 and determined their unique symmetry and origin of the perturbations (Trachtenberg et al., 1986, J Mol Biol 190: 569-576; 1987, 195: 603-620; 1998, 276: 759-773; Cohen-Krausz and Trachtenberg, 1998, J Struct Biol 122: 267-282). Here, we analyse the structure of the flagellar filament of the other known complex filament, that of Pseudomonas rhodos, as reconstructed from electron microscope images. Compared with the filament of R. lupini, the filament of P. rhodos is more flexible, as implied from high-intensity darkfield light microscopy and, although constructed from flagellins of higher molecular weights (59 versus 41 kDa), has similar symmetry. Using cryonegative stained specimens and low-dose, field emission electron microscopy, we reconstructed and averaged 158 filaments each containing 170 statistically significant layer lines. The three-dimensional density maps of P. rhodos clearly suggest, when compared with those of R. lupini and the right-handed Salmonella typhimurium SJW1655, that R. lupini is missing the outer flagellin domain (D3), that the interior of the complex filament is rather similar to that of the plain filament and that the radial spokes (connecting domains D0 and D1), present in individual density maps, average out because of their variability and implied flexibility. Extending the three-start grooves and ridges on the propeller's surface, in the form of an Archimedean screw, may further improve the motility of the cell in viscous environments.

Flagella↗
PubMed1999

The organization and connections of somatosensory cortex in the brush-tailed possum (Trichosurus vulpecula): evidence for multiple, topographically organized and interconnected representations in an Australian marsupial.

Microelectrode mapping techniques were used to determine the organization of somatosensory cortex in the Australian brush-tailed possum (Trichosurus vulpecula). The results of electrophysiological mapping were combined with data on the cyto- and myeloarchitecture, and patterns of corticocortical connections, using sections cut tangential to the pial surface. We found evidence for three topographically organized representations of the body surface that were coextensive with architectonic subdivisions. A large, discontinuous cutaneous representation in anterior parietal cortex was termed the primary somatosensory area (SI). Lateral to SI we found evidence for two further areas, the second somatosensory area (SII) and the parietal ventral area (PV). While neurones in all of these areas were responsive to cutaneous stimulation, those of SI were non-habituating, whereas those in SII and PV often habituated to the stimuli. Moreover, neuronal receptive fields in SII and PV were, in general, larger than those in SI. Neurones in cortex adjacent to the rostral and caudal boundaries of SI, including cortex that interdigitated between the discontinuous SI head and body representations, required stimulation of deep receptors in the periphery to elicit responses. Within the region of cortex containing neurones responsive to stimulation of deep receptors, body parts were represented in a mediolateral progression. Injections of anatomical tracers placed in electrophysiologically identified locations in SI revealed ipsilateral connections with other parts of SI, as well as cortex rostral to, caudal to, and interdigitating between, SI. Injections in SI also resulted in labelling in PV, SII, motor cortex, posterior parietal cortex and perirhinal cortex. The patterns of contralateral projections reflected those of ipsilateral projections, although they were relatively less dense. The present findings support recent observations in other marsupials in which multiple representations of the body surface were described, and suggest that multiple interconnected sensory representations may be a common feature of cortical organization and function in marsupials.

Animals↗
PubMed2005

p21-activated Kinase 1 (Pak1)-dependent phosphorylation of Raf-1 regulates its mitochondrial localization, phosphorylation of BAD, and Bcl-2 association.

Raf-1 protects cells from apoptosis, independently of its signals to MEK and ERK, by translocating to the mitochondria where it binds Bcl-2 and displaces BAD. However, the answer to the question of how Raf-1 is normally lured to the mitochondria and becomes activated remains elusive. p21-activated protein kinases (Paks) are serine/threonine protein kinases that phosphorylate Raf-1 at Ser-338 and Ser-339. Here we elucidate the molecular mechanism through which Pak1 signals to BAD through a Raf-1-activated pathway. Upon phosphorylation by Pak1, Raf-1 translocates to mitochondria and phosphorylates BAD at Ser-112. Moreover, the mitochondrial translocation of Raf-1 and the interaction between Raf-1 and Bcl-2 are regulated by Raf-1 phosphorylation at Ser-338/Ser-339. Notably, we show that formation of a Raf-1-Bcl-2 complex coincides with loss of an interaction between Bcl-2 and BAD. These signals are specific for Pak1, because Src-activated Raf-1 only stimulates the MAP kinase cascade. Thus, our data identify the molecular connections of a Pak1-Raf-1-BAD pathway that is involved in cell survival signaling.

Animals↗
PubMed2004

The supramammillary area: its organization, functions and relationship to the hippocampus.

The supramammillary area of the hypothalamus, although small in size, can have profound modulatory effects on the hippocampal formation and related temporal cortex. It can control hippocampal plasticity and also has recently been shown to contain cells that determine the frequency of hippocampal rhythmical slow activity (theta rhythm). We review here its organization and anatomical connections providing an atlas and a new nomenclature. We then review its functions particularly in relation to its links with the hippocampus. Much of its control of behaviour and its differential activation by specific classes of stimuli is consistent with a tight relationship with the hippocampus. However, its ascending connections involve not only caudal areas of the cortex with close links to the hippocampus but also reciprocal connections with more rostral areas such as the infralimbic and anterior cingulate cortices. These latter areas appear to be the most rostral part of a network that, via the medial septum, hippocampus and lateral septum, is topographically mapped into the hypothalamus. The supramammillary area is thus diffusely connected with areas that control emotion and cognition and receives more topographically specific return information from areas that control cognition while also receiving ascending information from brain stem areas involved in emotion. We suggest that it is a key part of a network that recursively transforms information to achieve integration of cognitive and emotional aspects of goal-directed behaviour.

Animals↗
PubMedDate not supplied

On characterization of dose variations of 2-D proteomics maps by matrix invariants.

We explore the characterization of 2-D electrophoresis proteomics maps by certain structural invariants derived from matrixes constructed by considering for all pairs of spots in a proteomics maps the shortest (Euclidean) distances and distances measured along zigzag lines connecting protein spots of the neighboring abundance. This paper is a sequel to previous papers in which we outlined the idea of characterizing 2-D proteomics maps by graph-theoretical descriptors. To illustrate the approach, we selected data of Anderson et al. (Anderson, N. L.; Esquer-Blasco, R.; Richardson, F.; Foxworthy, P.; Eacho, P. The effects of peroxisome proliferators on protein abundances in mouse liver. Toxicol. Appl. Pharmacol. 1996, 137, 75-89) on protein abundance in mouse liver under a series of dose of peroxisome proliferator LY1711883. We found strong linear correlation between the experimentally applied doses and the leading eigenvalue of a D/D-type matrix (Randić, M.; Kleiner, A. F.; DeAlba, L. M. Distance/ distance matrices. J. Chem. lnf. Comput. Sci. 1994, 34, 277-286) constructed for the experimental proteomics maps.

Acetophenones↗
PubMed1994

Immunohistochemical localization of gap junction protein channels in hamster sinoatrial node in correlation with electrophysiologic mapping of the pacemaker region.

INTRODUCTION: Gap junction proteins are thought to form the low resistance pathways that connect neighboring cells within the sinoatrial node, and to mediate pacemaker synchronization. METHODS AND RESULTS: We have carried out microelectrode mapping experiments of the hamster sinoatrial region to localize the primary pacemaker area for subsequent light, electron, and immunofluorescence microscopic studies aimed at testing the hypothesis that the major cardiac gap junction protein (connexin43) is present in such an area. The site of earliest activation is unifocal and the pattern of activation, obtained by multiple sequential microelectrode recordings of the sinoatrial region, is qualitatively similar to that previously described for other species. However, quantitatively, the impulse transmission time from the primary pacemaker area to the crista (sulcus) terminalis in the hamster sinoatrial node is about 50% briefer than that of the guinea pig and five times faster than that of the rabbit. Immunolocalization studies in the hamster sinoatrial node using anti-connexin43 antisera demonstrated specific staining at the areas of cell-to-cell apposition and suggested that the apparently high degree of electrical coupling in this tissue is the result of abundant connexin43 expression. The immunofluorescence data were supported by light microscopic studies, which demonstrated the typical morphologic characteristics of sinus nodal cells in the pacemaker area. In addition, an electron microscopic study of the sinoatrial region revealed the presence of gap junctions in the junctional complex at areas of cell-to-cell contact. CONCLUSION: Our results demonstrate that cells in the sinoatrial region of the hamster heart are electrically well coupled and strongly suggest that such coupling is mediated by gap junctional channels formed by connexin43.

Amino Acid Sequence↗
PubMed1989

Quantitative contribution of systemic vascular autoregulation in acute hypertension in conscious dogs.

Experiments were performed in nine conscious dogs to quantitate the contribution of systemic vascular autoregulation to the increases in total peripheral resistance (TPR) and mean arterial pressure (MAP) produced by angiotensin II (ANG II), arginine vasopressin (AVP), and norepinephrine (NE). We hypothesized that if autoregulatory vasoconstriction is significant, then the increase in TPR produced by vasoconstrictor infusion will be greater when MAP is controlled at hypertensive values than when the increase in pressure is prevented by controlling MAP at the animal's normotensive value. Each drug was infused at a dose sufficient to increase MAP by 50%. Then, a constant rate of vasoconstrictor infusion was maintained while MAP was controlled at hypertensive or normotensive levels for 15-min periods using a gravity reservoir connected to the left common carotid artery. During AVP infusion, TPR was significantly greater when MAP was controlled at hypertensive than at normotensive values. This autoregulatory-mediated vasoconstriction accounted for approximately three-fourths of the increase in MAP produced by AVP. No significant autoregulatory component was identified for the increases in TPR and MAP produced by ANG II or NE. We conclude that systemic vascular autoregulation is a powerful physiological property that contributes to the hemodynamic response to pressor doses of AVP.

Angiotensin II↗
PubMed2005

Mapping directed influence over the brain using Granger causality and fMRI.

We propose Granger causality mapping (GCM) as an approach to explore directed influences between neuronal populations (effective connectivity) in fMRI data. The method does not rely on a priori specification of a model that contains pre-selected regions and connections between them. This distinguishes it from other fMRI effective connectivity approaches that aim at testing or contrasting specific hypotheses about neuronal interactions. Instead, GCM relies on the concept of Granger causality to define the existence and direction of influence from information in the data. Temporal precedence information is exploited to compute Granger causality maps that identify voxels that are sources or targets of directed influence for any selected region-of-interest. We investigated the method by simulations and by application to fMRI data of a complex visuomotor task. The presented exploratory approach of mapping influences between a region of interest and the rest of the brain can form a useful complement to existing models of effective connectivity.

Attention↗
PubMed2005

SLIM: an alternative Web interface for MEDLINE/PubMed searches - a preliminary study.

BACKGROUND: With the rapid growth of medical information and the pervasiveness of the Internet, online search and retrieval systems have become indispensable tools in medicine. The progress of Web technologies can provide expert searching capabilities to non-expert information seekers. The objective of the project is to create an alternative search interface for MEDLINE/PubMed searches using JavaScript slider bars. SLIM, or Slider Interface for MEDLINE/PubMed searches, was developed with PHP and JavaScript. Interactive slider bars in the search form controlled search parameters such as limits, filters and MeSH terminologies. Connections to PubMed were done using the Entrez Programming Utilities (E-Utilities). Custom scripts were created to mimic the automatic term mapping process of Entrez. Page generation times for both local and remote connections were recorded. RESULTS: Alpha testing by developers showed SLIM to be functionally stable. Page generation times to simulate loading times were recorded the first week of alpha and beta testing. Average page generation times for the index page, previews and searches were 2.94 milliseconds, 0.63 seconds and 3.84 seconds, respectively. Eighteen physicians from the US, Australia and the Philippines participated in the beta testing and provided feedback through an online survey. Most users found the search interface user-friendly and easy to use. Information on MeSH terms and the ability to instantly hide and display abstracts were identified as distinctive features. CONCLUSION: SLIM can be an interactive time-saving tool for online medical literature research that improves user control and capability to instantly refine and refocus search strategies. With continued development and by integrating search limits, methodology filters, MeSH terms and levels of evidence, SLIM may be useful in the practice of evidence-based medicine.

Computer Simulation↗
PubMed2004

Cortical convergence from different frequency domains in the cat primary auditory cortex.

Primary auditory cortex (AI) has a tonotopic map consisting of orderly isofrequency (IF) bands, and cortical connections are commonly supposed to link domains preferring similar characteristic frequencies (CFs) within AI and in auditory association cortex. The interaction of different frequency channels, however, has not fully been understood in terms of anatomical substrates. Here, by injecting two anterograde tracers in different frequency domains of cat AI, without overlap of the injection cores, we attempted to relate the anatomical mapping of cortical outputs to physiologically defined fields in the auditory cortex. Consistent with previous studies, patches of labeled axon terminals were oriented largely along the IF axis. In regions distant from the injection sites, however, terminal patches were divergent in distribution. This divergence resulted in a complex geometry of partial overlap of projections originating from the two injection sites. The relative extent of the overlap tended to vary depending on the distance between the two injection sites. Physiological mapping for tonotopy across auditory fields revealed that projectional overlap was characteristic of dorsal AI and the dorsoposterior field and, to a lesser extent, in the secondary auditory field. Considering the differences in frequency representation in different AI IF bands, the anatomical convergence of projections tuned to different CFs could contribute to the spectral integration of sound components. Furthermore, the different extent of convergence in the functionally distinct fields might reflect field-specific processing of acoustic signals.

Animals↗
PubMed1999

Long-term molecular dynamics simulation of copper azurin: structure, dynamics and functionality.

A long-term molecular dynamics simulation (1.1 ns), at 300 K, of fully hydrated azurin has been performed to put into relationship the protein dynamics to functional properties with particular attention to those structural elements involved in the electron transfer process. A detailed analysis of the root mean square deviations and fluctuations and of the intraprotein H-bonding pattern has allowed us to demonstrate that a rigid arrangement of the beta-stranded protein skeleton is maintained during the simulation run, while a large mobility is registered in the solvent-exposed connecting regions (turns) and in the alpha-helix. Moreover, the structural elements, likely involved in the electron transfer path, show a stable H-bonding arrangement and low fluctuations. Analysis of the dynamical cross-correlation map has revealed the existence of correlated motions among residues connected by hydrogen bonds and of correlated and anti-correlated motions between regions which are supposed to be involved in the functional process, namely the hydrophobic patch and the regions close to the copper reaction center. The results are briefly discussed also in connection to the current through-bond tunneling model for the electron transfer process. Finally, a comparison with the structural and the dynamical behaviour of plastocyanin, whose structure and functional role are very similar to those of azurin, has been performed.

Journal Article↗
PubMed2004

The use of concept mapping to enlighten the knowledge networks of diabetic children: a pilot study.

OBJECTIVE: The value of concept mapping in enlightening nature and organization of knowledge was shown with adult diabetic or obese patients. Our objectives were to ascertain the relevance and feasability of concept mapping in diabetic children during an educational program. METHOD: This qualitative research was performed in 5 children from 8 to 13 years. Concept maps were drawn at the beginning (Phase 1) and at the end (Phase 2) of an educational program. During the interview each child was invited to express himself starting from the central concept: "diabetes", and to express his/her knowledge, representations, and life experience. RESULTS: The ten maps analysis shows: an increase of knowledge between phase 1 and phase 2 (+34%), towards a deepening of initial knowledge and an addition of new knowledge (43% and 41% of the added knowledge); a decrease of inaccurate knowledge in phase 2; an enrichment of the knowledge networks (+16 cross links); an increase of knowledge related to the ways to behave knowledge (+42%). CONCLUSION: This preliminary report demonstrated that concept maps were feasible, useful and relevant in therapeutic education of children. This method allowed us to show how every child connected his knowledge and how it was modified by an educational intervention. Concept maps therefore contributed to individual educational diagnosis and assessment of new knowledge integration.

Adolescent↗
PubMed2000

A Differential Geometric Description of the Relationships among Perceptions.

We present a differential geometric method for measuring and characterizing the perceptions of an observer of a continuum of stimuli. Because the method is not based on a model of perceptual mechanisms, it can potentially be applied to a wide variety of observers and to many types of visual and auditory stimuli. The observer is asked to identify which small transformation of one stimulus is perceived to be equivalent to a small transformation of a second stimulus, differing from the first stimulus by a third small transformation. The observer's identification of a number of such transformations can be used to calculate an affine connection on the stimulus manifold. This quantity describes how the observer encodes an evolving stimulus as a perceived sequence of "reference" transformations. This type of encoding is a multidimensional generalization of Fechner's method and reduces to his psychophysical scale when the stimulus manifold is one dimensional and the reference transformation is chosen to be a just noticeable difference. The intrinsic aspects of the nature of the observer's perceptions can be characterized by the curvature and torsion tensors derived from the connection. The multidimensional analogues of psychophysical scale functions exist if and only if these quantities vanish. Differences between the affine connections of two observers characterize differences between their perceptions of the same evolving stimuli. The affine connections of two observers can also be used to map a stimulus perceived by one observer onto another stimulus, perceived in the same way by the other observer. Unlike multidimensional scaling techniques, this method does not assume that the observer has a sense of distance (a metric) or that he/she can otherwise compare stimulus pairs that are oriented along perceptually different directions in the manifold. The method was used to measure the affine connections of observers of a dot moving on different background graphics; e.g., a blank screen, a grid, or two converging lines similar to those used to create the Ponzo illusion. The results comprise quantitative measurements of the background graphic's influence on each observer's perceptions of straightness, parallelism, and distance. The measurements demonstrate differences between the perceptions of the two observers. Copyright 2000 Academic Press.

Journal Article↗