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At least 793 records · Page 44Linked to original sources
PubMed2006

Global reaction route mapping on potential energy surfaces of formaldehyde, formic acid, and their metal-substituted analogues.

Global reaction route mapping of equilibrium structures, transition structures, and their connections on potential energy surface (PES) has been done for MCHO (M = H, Li, Na, Al, Cu) and HCO2M (M = H, Li). A one-after-another technique based on the scaled hypersphere search method has been successfully applied to exploring unknown chemical structures, transition structures, and reaction pathways for organometallic systems. Upon metal substitution, considerable changes of stable structures, reaction pathways, and relative heights of transition structures have been discovered, though some features are similar among the analogues. Al and Cu atoms were found to behave as very strong scissors to cut the CO double bond in MCHO. Energy profiles of the CO insertion into Li-H and Li-CH3 bonds were found to be very similar, especially around the structures where the Li atom is not directly connected with the methyl group, which indicates little effects of alkyl substitution on the reaction route topology.

Journal Article↗
PubMed2004

Early motor activity drives spindle bursts in the developing somatosensory cortex.

Sensorimotor coordination emerges early in development. The maturation period is characterized by the establishment of somatotopic cortical maps, the emergence of long-range cortical connections, heightened experience-dependent plasticity and spontaneous uncoordinated skeletal movement. How these various processes cooperate to allow the somatosensory system to form a three-dimensional representation of the body is not known. In the visual system, interactions between spontaneous network patterns and afferent activity have been suggested to be vital for normal development. Although several intrinsic cortical patterns of correlated neuronal activity have been described in developing somatosensory cortex in vitro, the in vivo patterns in the critical developmental period and the influence of physiological sensory inputs on these patterns remain unknown. We report here that in the intact somatosensory cortex of the newborn rat in vivo, spatially confined spindle bursts represent the first and only organized network pattern. The localized spindles are selectively triggered in a somatotopic manner by spontaneous muscle twitches, motor patterns analogous to human fetal movements. We suggest that the interaction between movement-triggered sensory feedback signals and self-organized spindle oscillations shapes the formation of cortical connections required for sensorimotor coordination.

Aging↗
PubMed2002

Concept mapping: a tool to bridge the disciplinary divide.

The American College of Women's Health Physicians has been exploring an on-line educational tool-concept mapping-to facilitate the development of an interdisciplinary and woman-centered women's health curriculum, and to implement The Women's Health Care Competencies for Medical Students. By using an on-line concept map of the menstrual cycle, we have built upon a standard piece of curricula that describes a unique aspect of female physiology and transformed it into a knowledge framework that builds capacity. The concept map highlights relationships between concepts and across disciplines, connecting the competencies to enable meaningful learning so that a learner can adapt their knowledge to multiple settings, incorporate new learning, and generate new knowledge to grow the interdisciplinary field of women's health. The on-line format allows access from multiple sites and courses, and allows the curricula to grow organically over time without upsetting current curricular design.

Artificial Intelligence↗
PubMed1980

Path of the polypeptide in bacteriorhodopsin.

An attempt has been made to fit the amino acid sequence of bacteriorhodopsin to the three-dimensional density map of the molecule. First, seven segments of the sequence were selected as being probable transmembrane alpha helices. Then each of the 5040 possible ways of fitting these seven segments into the seven regions of helical density in the map were evaluated based on the criteria of connectivity of the nonhelical link regions, charge neutralization, and total scattering density per helix. A single model that may be experimentally tested emerged as the most probable.

Bacteriorhodopsins↗
PubMed2000

Norepinephrine induces vascular endothelial growth factor gene expression in brown adipocytes through a beta -adrenoreceptor/cAMP/protein kinase A pathway involving Src but independently of Erk1/2.

To identify the signaling pathway that mediates the adrenergic stimulation of the expression of the gene for vascular endothelial growth factor (VEGF) during physiologically induced angiogenesis, we examined mouse brown adipocytes in primary culture. The endogenous adrenergic neurotransmitter norepinephrine (NE) induced VEGF expression 3-fold, in a dose- and time-dependent manner (EC(50) approximately 90 nm). Also, the hypoxia-mimicking agent cobalt, as well as serum and phorbol ester, induced VEGF expression, but the effect of NE was additive to each of these factors, implying that a separate signaling mechanism for the NE-mediated induction was activated. The NE effect was abolished by propranolol and mimicked by isoprenaline or BRL-37344 and was thus mediated via beta-adrenoreceptors. The NE-induced VEGF expression was fully cAMP mediated, an effect which was inhibited by H-89 and thus was dependent on protein kinase A activity. Involvement of other adrenergic signaling pathways (alpha(1)-adrenoreceptors, Ca(2+), protein kinase C, alpha(2)-adrenoreceptors, and pertussis toxin-sensitive G(i)-proteins) was excluded. The specific inhibitor of Src tyrosine kinases, PP2, markedly reduced the stimulation by NE, which demonstrates that a cAMP-dependent Src-mediated pathway is positively connected to VEGF expression. However, inhibition of Erk1/2 MAP kinases by PD98059 was without effect. NE did not prolong VEGF mRNA half-life and its effect was thus transcriptional, and was independent of protein synthesis. These results demonstrate that adrenergic stimulation, through beta-adrenoreceptor/cAMP/protein kinase A signaling, recruits a pathway that branches off from the NE-activated Src-Erk1/2 cascade to enhance transcription of the VEGF gene.

Adipose Tissue, Brown↗
PubMed2001

Cytoskeletal mechanisms of neuronal morphogenesis.

The cytoskeleton is the major intracellular structure that determines the morphology of a neuron. Thus, mechanisms that ensure a precisely regulated assembly of cytoskeletal elements in time and space have an important role in the development from a morphologically simple neuronal precursor cell to a complex polarized neuron that can establish contacts to several hundreds of other cells. Here, cytoskeletal mechanisms that underlie the formation of neurites, directed elongation and stabilization of neuronal processes are summarized. It has become evident that different cytoskeletal elements are highly crosslinked with each other by several classes of specific linker proteins. Of these, microtubule-associated proteins (MAPs) appear to have an important role in connecting the microtubule skeleton to other cytoskeletal filaments and plasma membrane components during neuronal morphogenesis. Future experiments will have to elucidate the function and the regulation of the neuronal cytoskeleton in an authentic nervous system environment during development. Recent approaches are discussed at the end of this article.

Journal Article↗
PubMedDate not supplied

Effects of the new antiarrhythmic peptide ZP123 on epicardial activation and repolarization pattern.

Antiarrhythmic peptides such as AAP10 (Gly-Ala-Gly-4Hyp-Pro-Tyr-CONH(2)) have antiarrhythmic properties related to their stimulatory effect on gap junctional coupling. However, most of these peptides are not stable in enzymatic environment which limits studies with these compounds in vivo. ZP123 is a new antiarrhythmic peptide constructed using a retro-all-D-amino acid design of the AAP10 template (Ac-D-Tyr-D-Pro-D-4Hyp-Gly-D-Ala-Gly-NH(2)). The aim of this study was to compare the effects of AAP10 and ZP123 on epicardial activation and repolarization patterns in isolated perfused rabbit hearts. In addition, we tested the effect of these compounds on PKC activation in cultured HeLa-Cx43 cells. Rabbit hearts were perfused according to the Langendorff technique with Tyrode solution at constant pressure (70 cm H(2)O). After 45 min equilibration, either AAP10 (n = 7) or ZP123 (n = 7) was infused intracoronarily in concentrations of 0.1, 1, 10, 100, and 1000 nM (15 min for each concentration) in the presence of 0.05% bovine serum albumine. 256 AgCl electrodes were attached to the hearts surface and connected to the inputs of a 256 channel mapping system in a unipolar circuit (4 kHz/channel, 0.04 mV vertical resolution, 1 mm spatial resolution). For each electrode the activation and repolarization timepoint were determined. We found that both peptides significantly reduced epicardial dispersion by a maximum of about 20% thereby enhancing the homogeneity of epicardial action potential duration, while the action potential duration itself was not affected. The beat-to-beat variability of the epicardial activation pattern was stabilized by both peptides as compared to an untreated time-control series. Other parameters such as LVP, CF, heart rate, or total activation time were not effected by either of the peptides. In a second protocol, rectangular pulses were delivered to the back wall and the propagation velocity was determined longitudinal and transversal to the fiber axis. We found an increase in both longitudinal and transversal conduction velocity. Using a commercial PKC assay on HeLa-Cx43 cells we found that 50 nM AAP10 and 50 nM ZP123 increased activity by 99 +/- 6% and 146 +/- 54%, respectively. The PKC activation induced by either of these compounds was completely blocked using the selective PKCalpha inhibitor GCP54345. We conclude that AAP10 and ZP123 have similar effects in vitro, but the superior enzymatic stability of ZP123 makes this compound the preferred substance for in vivo studies of antiarrhythmic peptides.

Animals↗
PubMed2025

NOODAI: a webserver for network-oriented multi-omics data analysis and integration pipeline.

SUMMARY: Omics profiling has proven of great use for unbiased and comprehensive identification of key features that define biological phenotypes and underlie medical conditions. While each omics profile assists characterization of specific molecular components relevant for the studied phenotype, their joint evaluation can offer deeper insights into the overall mechanistic functioning of biological systems. Here, we introduce an approach where, starting from representative traits (e.g. differentially expressed elements) obtained for each omics profile, we construct and analyze joint interaction networks. The resulting networks rely on the existing knowledge of confident interactions among biological entities. We use these maps to identify and describe central elements, which connect multiple entities characteristic of the studied phenotypes and we leverage MONET network decomposition tool in order to highlight functionally connected network modules. In order to enable broad usage of this approach, we developed the NOODAI software platform, which enables integrative omics analysis through a user-friendly interface. The analysis outcomes are presented both as raw output tables as well as informative summary plots and written reports. Since the MONET tool enables the use of algorithms with strong performance in identifying disease-relevant modules, NOODAI software platform can be of a high value for analyzing clinical multi-omics datasets. AVAILABILITY AND IMPLEMENTATION: NOODAI is freely accessible at https://omics-oracle.com. Source code is available under GPL3 at: https://github.com/TotuTiberiu/NOODAI with the DOI: 10.5281/zenodo.17203984.

Software↗
PubMed2006

Bio-Ontology and text: bridging the modeling gap.

MOTIVATION: Natural language processing (NLP) techniques are increasingly being used in biology to automate the capture of new biological discoveries in text, which are being reported at a rapid rate. Yet, information represented in NLP data structures is classically very different from information organized with ontologies as found in model organisms or genetic databases. To facilitate the computational reuse and integration of information buried in unstructured text with that of genetic databases, we propose and evaluate a translational schema that represents a comprehensive set of phenotypic and genetic entities, as well as their closely related biomedical entities and relations as expressed in natural language. In addition, the schema connects different scales of biological information, and provides mappings from the textual information to existing ontologies, which are essential in biology for integration, organization, dissemination and knowledge management of heterogeneous phenotypic information. A common comprehensive representation for otherwise heterogeneous phenotypic and genetic datasets, such as the one proposed, is critical for advancing systems biology because it enables acquisition and reuse of unprecedented volumes of diverse types of knowledge and information from text. RESULTS: A novel representational schema, PGschema, was developed that enables translation of phenotypic, genetic and their closely related information found in textual narratives to a well-defined data structure comprising phenotypic and genetic concepts from established ontologies along with modifiers and relationships. Evaluation for coverage of a selected set of entities showed that 90% of the information could be represented (95% confidence interval: 86-93%; n = 268). Moreover, PGschema can be expressed automatically in an XML format using natural language techniques to process the text. To our knowledge, we are providing the first evaluation of a translational schema for NLP that contains declarative knowledge about genes and their associated biomedical data (e.g. phenotypes). AVAILABILITY: http://zellig.cpmc.columbia.edu/PGschema

Abstracting and Indexing↗
PubMed1993

Non-invasive magnetocardiographic localization of ventricular pre-excitation in the Wolff-Parkinson-White syndrome using a realistic torso model.

This study was performed to evaluate the accuracy of magnetocardiography in non-invasive localization of the ventricular pre-excitation site in patients suffering from the Wolff-Parkinson-White (WPW) syndrome. Twelve WPW patients were studied, in whom the pre-excitation caused serious supraventricular arrhythmias refractory to drug therapy. Magnetocardiographic measurements were performed in a magnetically shielded room, and non-invasive localization was computed from preprocessed magnetic signals using a current dipole source in a realistically shaped digital torso. All patients underwent intra-operative multicatheter mapping and subsequent dissection of the accessory atrioventricular connection. The intra-operative localization results were marked on magnetic resonance images of the heart, where magnetocardiographic results were also superimposed to allow comparison. The average of the three-dimensional differences between the magnetocardiographic and the invasive results was 2.1 +/- 0.9 cm. In all cases, the computed localization result was in the same or adjacent anatomical region as the intra-operative result. The present results show that the magnetocardiographic method using a realistic torso model is capable of localizing pre-excitation sites with sufficient accuracy to provide extra information so that non-pharmacological therapeutic interventions can be applied.

Adult↗
PubMed1988

Reentry as a cause of ventricular tachycardia in patients with chronic ischemic heart disease: electrophysiologic and anatomic correlation.

In this report we describe electrophysiologic and histologic findings in hearts and endocardially resected preparations from patients with sustained ventricular tachycardias in the chronic phase of myocardial infarction. We recorded simultaneously from 64 endocardial sites during tachycardia in 72 patients that were operated on for medically intractable ventricular tachycardias. Two other patients underwent heart transplantation, and mapping was performed on the explanted isolated heart connected to a Langendorff perfusion set-up. During operation 139 tachycardias with different morphologies could be induced. Although the majority of evidence supports the concept of a reentrant mechanism for these tachycardias, we found that 105 tachycardias appeared to arise at a focal area of less than 1.4 cm2. In only three cases macroreentry around the infarction scar could be detected. Of 21 tachycardias in which the "origin" appeared to be focal, earliest subendocardial activation was preceded by discrete electrograms of low amplitude (presystolic activity). In three tachycardias presystolic activity was detected at several sites, permitting reconstruction of its route. Histology of the endocardial resected preparation in one of these cases revealed separate zones of viable myocardial fibers in areas in which presystolic activity was recorded. These zones were located intramurally and subendocardially, supporting the concept that reentry occurred via isolated bundles of surviving myocytes at the border of the infarct and the larger subendocardial muscle mass. Conduction velocity through the isolated tracts was on the order of 25 cm/sec. Similar reentrant pathways were found in the two isolated hearts. Extracellular and intracellular recordings were made from 20 endocardial preparations that were excised from areas in which tachycardia originated. Preparations were superfused in a tissue bath. These experiments showed that action potentials were usually close to normal, but occasionally action potentials with reduced amplitude and slow upstrokes were found. In addition, there were cells that exhibited both fast and slow upstrokes, depending on the direction of the wavefront. Histology of seven resected preparations and the isolated hearts showed subendocardially as well as intramurally located zones of viable myocardium. Fractionation of extracellular electrograms and slow conduction were found in areas where surviving muscle fibers and strands of fibrous tissue were interwoven, and in zones where muscle fibers were oriented in parallel but isolated by strands of connective tissue.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1999

A sequence-ready BAC clone contig of a 2.2-Mb segment of human chromosome 1q24.

Human chromosomal region 1q24 encodes two cloned disease genes and lies within large genetic inclusion intervals for several disease genes that have yet to be identified. We have constructed a single bacterial artificial chromosome (BAC) clone contig that spans over 2 Mb of 1q24 and consists of 78 clones connected by 100 STSs. The average density of mapped STSs is one of the highest described for a multimegabase region of the human genome. The contig was efficiently constructed by generating STSs from clone ends, followed by library walking. Distance information was added by determining the insert sizes of all clones, and expressed sequence tags (ESTs) and genes were incorporated to create a partial transcript map of the region, providing candidate genes for local disease loci. The gene order and content of the region provide insight into ancient duplication events that have occurred on proximal 1q. The stage is now set for further elucidation of this interesting region through large-scale sequencing.

Chromosome Mapping↗
PubMed1999

An approach for access differentiation design in medical distributed applications built on databases.

A formalized "top to bottom" design approach was described in [1] for distributed applications built on databases, which were considered as a medium between virtual and real user environments for a specific medical application. Merging different components within a unified distributed application posits new essential problems for software. Particularly protection tools, which are sufficient separately, become deficient during the integration due to specific additional links and relationships not considered formerly. E.g., it is impossible to protect a shared object in the virtual operating room using only DBMS protection tools, if the object is stored as a record in DB tables. The solution of the problem should be found only within the more general application framework. Appropriate tools are absent or unavailable. The present paper suggests a detailed outline of a design and testing toolset for access differentiation systems (ADS) in distributed medical applications which use databases. The appropriate formal model as well as tools for its mapping to a DMBS are suggested. Remote users connected via global networks are considered too.

Computer Communication Networks↗
PubMed1975

The isocortex of the ox (Bos taurus). I. The sulci and gyri.

A simplified scheme of the functionally important gyri and the sulci delimiting these areas, in the ox, is presented. The criteria used are the cyto- and myelo-architecture of the different areas and their correlation with the available physiological information of the nearest ungulates. The preparation of the brain map and experimental studies to determine the thalamocortical connections and later electrophysiological studies are thus possible. The following conclusions have been drawn: 1. The coronoansate sulci are the equivalents of the central sulcus of man. 2. The cruciate sulcus delimits the motor cortex caudally. 3. The equivalent of the calcarine sulcus of man, is the caudal part of the intralimbic sulcus, the axial sulcus of the striate area. 4. The suprasylvian sulcus forms the equivalent of the parietooccipital fissure of man. 5. The equivalent gyri of the isocortical areas of man are defined and the mechanical processes involved in the deformation pattern of the sagittaly oriented gyri of the subprimate mammals resulting in the coronal gyral pattern of man, are described.

Animals↗
PubMed2006

[Processing of spatial information by hippocampal place cells].

Hippocampal place cells can process the environmental inputs and make up a cognitive map in the hippocampus, or strengthen the synaptic connections within an association cortical cell assembly,thus creating a permanent engram for a spatial site. Outputs from the hippocampus are then integrated with other inputs within the nucleus accumbens and finally initiate a goal-directed behavior through the motor circuit.

Animals↗
PubMed1994

Quality of periodontal healing. IV: Enzyme histochemical evidence for an osteoblast origin of reparative cementum.

The aim of the present study was to map the distribution of healing gingival and periodontal connective tissue well as osteoblastic activity in marginal periodontal wound healing using activity of alkaline phosphatases as markers. Activity of non-specific alkaline phosphatase (NSAP) was abundant in periodontal but not in gingival connective tissue. Activity of vanadate-resistant alkaline phosphatase (VRAP) had a preferential localisation to periosteal and endosteal bone surfaces but was not detectable in cementoblasts along root surfaces. However, following spontaneous marginal healing of exposed dentine surfaces, activity of VRAP was also found on healing dentine surfaces. It was concluded that osteoblasts rather than cementoblasts form reparative cementum on exposed dentine surfaces during marginal periodontal healing.

Alkaline Phosphatase↗
PubMed2000

Radiofrequency ablation of a right atrial appendage-ventricular accessory pathway by transcutaneous epicardial instrumentation.

Epicardial location of accessory AV pathways may be responsible for the failure of conventional endocardial radiofrequency catheter ablation. Transcutaneous epicardial instrumentation provides access to the normal pericardium with no need for invasive thoracotomy or thoracoscopy. We report the case of successful epicardial mapping and ablation of a right atrial appendage-ventricular connection using a percutaneous epicardial approach, after repeated failure of endocardial ablation attempts.

Adult↗