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At least 1,351 records · Page 75Linked to original sources
PubMed2005

Use of an artificial neural network to localize accessory pathways of Wolff-Parkinson-White syndrome with 12-lead electrocardiogram.

Today, radio-frequency ablation has been shown to be a safe and effective method to treat paroxysmal tachycardia with Wolff-Parkinson-White syndrome. The many criteria reported for localizing the sites of accessory pathways from a 12-lead electrocardiogram have not proven adequate to differentiate the correct sites of accessory pathways for all situations. This study trained an artificial neural network to differentiate the varied features needed to localize 10 sites of accessory pathways. One hundred fifty patients underwent successful catheter ablation, with manifest single and antegradely conducting accessory pathways. Using the two electrocardiogram features of polarity of delta wave and R wave's share of QRS complex, an artificial neural network learned the characteristics of electrocardiogram waves for each site of the 10 accessory pathways through 90 learning cases, and an applicable network model was developed for testing. In 58 of 60 test cases (96.7%), sites of accessory pathways were localized correctly by the network. Based on the method employed in the present study, it thus becomes possible to predict the sites of accessory pathways with Wolff-Parkinson-White syndrome in more detail by using an artificial neural network with a 12-lead electrocardiogram. In the future, when this method is incorporated into a conventional automatic electrocardiogram system which could analyze delta waves and ORS complex, it will become useful to automatically diagnose the locations of the accessory pathways with Wolff-Parkinson-White syndrome in clinical practice.

Adolescent↗
PubMedDate not supplied

The return of glomerular filtered albumin to the rat renal vein--the albumin retrieval pathway.

BACKGROUND: Recent studies have demonstrated that the normal glomerular capillary wall (GCW) is not charge selective to albumin. This means that albumin flux across the GCW is high. This has been confirmed in studies where albumin uptake by the tubules has been inhibited. Therefore, there must be a high capacity postglomerular retrieval pathway in normal kidneys that returns filtered albumin back to the blood supply. METHODS: This study identifies the presence of glomerular filtered albumin in the renal vein from the analysis of the decrease of radioactivity in the venous effluent after the injection of a pulse of tritium labeled albumin into the renal artery in vivo and in the isolated perfused kidney (IPK). RESULTS: The glomerular filtered albumin is returned to the blood supply by a high capacity pathway that transports this albumin at a rate of 1830+/-292 microg/min rat kidney (n= 14) (mean+/-SEM). This pathway has been identified under physiological conditions in vivo and in the IPK. The pathway is specific for albumin as it does not occur for horseradish peroxidase (HRP). The pathway is inhibited in a non-filtering kidney. The pathway is also inhibited by NH4Cl, an inhibitor of protein uptake. CONCLUSIONS: The high capacity retrieval pathway for albumin is most likely associated with transtubular cell transport. It is also apparent that most albuminuric states could be accounted for by the malfunctioning of this pathway without resorting to any change in glomerular permselectivity.

Albumins↗
PubMed1989

Differing polarity of the constitutive and regulated secretory pathways for von Willebrand factor in endothelial cells.

von Willebrand factor (vWf) is secreted from endothelial cells by one of two pathways-a constitutive pathway and a regulated pathway originating from the Weibel-Palade bodies. The molecular form of vWf from each of these pathways differs, with the most biologically potent molecules being released from Weibel-Palade bodies (Loesberg, C., M. D. Gonsalves, J. Zandbergen, C. Willems, W. G. Van Aken, H. V. Stel, J. A. Van Mourik, and P. G. DeGroot. 1983. Biochim. Biophys. Acta. 763:160-168; Sporn, L. A., V. J. Marder, and D. D. Wagner. 1987. Cell. 46:185-190). We investigated the polarity of the two secretory pathways using human umbilical vein endothelial cells cultured on polycarbonate membrane filters which allowed sampling of media from both the apical and basolateral compartments. After metabolic labeling of cells, vWf (constitutively secreted during a 10-min period or released during a 10-min treatment with a secretagogue) was purified from the apical and basolateral chambers and subjected to gel analysis. Approximately equal amounts of vWf were constitutively secreted into both chambers, and therefore this secretory pathway appeared to be nonpolarized. On the contrary, an average of 90% of vWf released from Weibel-Palade bodies after treatment with the calcium ionophore A23187 or PMA appeared in the basolateral chamber, indicating that the regulated pathway of secretion is highly polarized. Thrombin, a secretagogue which promotes disruption of the endothelial monolayer, led to release of vWf from cells with no apparent polarity. The presence of microtubule-depolymerizing agents nocodazol and colchicine inhibited the polarized release of vWf. Ammonium chloride treatment did not disrupt the polarity of the regulated secretory pathway, indicating that maintenance of low pH in intracellular compartments was not required for the polarized delivery of preformed Weibel-Palade bodies to the plasma membrane.

Ammonium Chloride↗
PubMed1997

Structural requirements for basolateral sorting of the human transferrin receptor in the biosynthetic and endocytic pathways of Madin-Darby canine kidney cells.

In polarized Madin-Darby canine kidney (MDCK) cells, the transferrin receptor (TR) is selectively delivered to the basolateral surface, where it internalizes transferrin via clathrin-coated pits and recycles back to the basolateral border. Mutant tailless receptors are sorted randomly in both the biosynthetic and endocytic pathways, indicating that the basolateral sorting of TR is dependent upon a signal located within the 61-amino acid cytoplasmic domain. To identify the basolateral sorting signal of TR, we have analyzed a series of mutant human TR expressed in MDCK cells. We find that residues 19-41 are sufficient for basolateral sorting from both the biosynthetic and endocytic pathways and that this is the only region of the TR cytoplasmic tail containing basolateral sorting information. The basolateral sorting signal is distinct from the YTRF internalization signal contained within this region and is not tyrosine based. Detailed functional analyses of the mutant TR indicate that residues 29-35 are the most important for basolateral sorting from the biosynthetic pathway. The structural requirements for basolateral sorting of internalized receptors from the endocytic pathway are not identical. The most striking difference is that alteration of G31DNS34 to YTRF impairs basolateral sorting of newly synthesized receptors from the biosynthetic pathway but not internalized receptors from the endocytic pathway. Also, mutations have been identified that selectively impair basolateral sorting of internalized TRs from the endocytic pathway without affecting basolateral sorting of newly synthesized receptors. These results imply that there are subtle differences in the recognition of the TR basolateral sorting signal by separate sorting machinery located within the biosynthetic and endocytic pathways.

Amino Acid Sequence↗
PubMed2005

The conserved Mec1/Rad53 nuclear checkpoint pathway regulates mitochondrial DNA copy number in Saccharomyces cerevisiae.

How mitochondrial DNA (mtDNA) copy number is determined and modulated according to cellular demands is largely unknown. Our previous investigations of the related DNA helicases Pif1p and Rrm3p uncovered a role for these factors and the conserved Mec1/Rad53 nuclear checkpoint pathway in mtDNA mutagenesis and stability in Saccharomyces cerevisiae. Here, we demonstrate another novel function of this pathway in the regulation of mtDNA copy number. Deletion of RRM3 or SML1, or overexpression of RNR1, which recapitulates Mec1/Rad53 pathway activation, resulted in an approximately twofold increase in mtDNA content relative to the corresponding wild-type yeast strains. In addition, deletion of RRM3 or SML1 fully rescued the approximately 50% depletion of mtDNA observed in a pif1 null strain. Furthermore, deletion of SML1 was shown to be epistatic to both a rad53 and an rrm3 null mutation, placing these three genes in the same genetic pathway of mtDNA copy number regulation. Finally, increased mtDNA copy number via the Mec1/Rad53 pathway could occur independently of Abf2p, an mtDNA-binding protein that, like its metazoan homologues, is implicated in mtDNA copy number control. Together, these results indicate that signaling through the Mec1/Rad53 pathway increases mtDNA copy number by altering deoxyribonucleoside triphosphate pools through the activity of ribonucleotide reductase. This comprises the first linkage of a conserved signaling pathway to the regulation of mitochondrial genome copy number and suggests that homologous pathways in humans may likewise regulate mtDNA content under physiological conditions.

Cell Cycle Proteins↗
PubMed2001

A graph layout algorithm for drawing metabolic pathways.

MOTIVATION: A large amount of data on metabolic pathways is available in databases. The ability to visualise the complex data dynamically would be useful for building more powerful research tools to access the databases. Metabolic pathways are typically modelled as graphs in which nodes represent chemical compounds, and edges represent chemical reactions between compounds. Thus, the problem of visualising pathways can be formulated as a graph layout problem. Currently available visual interfaces to biochemical databases either use static images or cannot cope well with more complex, non-standard pathways. RESULTS: This paper presents a new algorithm for drawing pathways which uses a combination of circular, hierarchic and force-directed graph layout algorithms to compute positions of the graph elements representing main compounds and reactions. The algorithm is particularly designed for cyclic or partially cyclic pathways or for combinations of complex pathways. It has been tested on five sample pathways with promising results.

Algorithms↗
PubMed2000

Caenorhabditis elegans has a single pathway to target matrix proteins to peroxisomes.

All eukaryotes so far studied, including animals, plants, yeasts and trypanosomes, have two pathways to target proteins to peroxisomes. These two pathways are specific for the two types of peroxisome targeting signal (PTS) present on peroxisomal matrix proteins. Remarkably, the complete genome sequence of Caenorhabditis elegans lacks the genes encoding proteins specific for the PTS2 targeting pathway. Here we show, by expression of green fluorescent protein (GFP) reporters for both pathways, that the PTS2 pathway is indeed absent in C. elegans. Lack of this pathway in man causes severe disease due to mislocalization of PTS2-containing proteins. This raises the question as to how C. elegans has accommodated the absence of the PTS2 pathway. We found by in silico analysis that C. elegans orthologues of PTS2-containing proteins have acquired a PTS1. We propose that switching of targeting signals has allowed the PTS2 pathway to be lost in the phylogenetic lineage leading to C. elegans.

Alkyl and Aryl Transferases↗
PubMed2001

JNK functions in the non-canonical Wnt pathway to regulate convergent extension movements in vertebrates.

Recent genetic studies in Drosophila identified a novel non-canonical Wnt pathway, the planar cell polarity (PCP) pathway, that signals via JNK to control epithelial cell polarity in Drosophila. Most recently, a pathway regulating convergent extension movements during gastrulation in vertebrate embryos has been shown to be a vertebrate equivalent of the PCP pathway. However, it is not known whether the JNK pathway functions in this non-canonical Wnt pathway to regulate convergent extension movements in vertebrates. In addition, it is not known whether JNK is in fact activated by Wnt stimulation. Here we show that Wnt5a is capable of activating JNK in cultured cells, and present evidence that the JNK pathway mediates the action of Wnt5a to regulate convergent extension movements in Xenopus. Our results thus demonstrate that the non-canonical Wnt/JNK pathway is conserved in both vertebrate and invertebrate and define that JNK has an activity to regulate morphogenetic cell movements.

Amino Acid Sequence↗
PubMed1996

A novel involvement of the PurG and PurI proteins in thiamine synthesis via the alternative pyrimidine biosynthetic (APB) pathway in Salmonella typhimurium.

Thiamine is thought to be synthesized by two alternative pathways, one involving the first four enzymes of the purine pathway and a second that can function independently of the purine pathway. Insertion mutations in purG and purI prevent thiamine synthesis through the alternative pyrimidine biosynthetic (APB) pathway under aerobic but not anaerobic growth conditions. In contrast, point mutations in purG and purI caused one of three distinct phenotypes: Pur- Apb-, Pur- Apb+, or Pur+ Apb-. Analysis of these three mutant classes demonstrated two genetically separable functions for PurG and PurI in thiamine synthesis. In addition to their known enzymatic role in de novo purine synthesis, we propose that PurG and PurI play a novel, possibly nonenzymatic role in the APB pathway. Suppression analysis of Pur- Apb- mutants identified two new genetic loci involved in the APB pathway, apbB and apbD). We show here that mutations in apbB and apbD cause distinct, allele-specific suppression of the thiamine requirement of purG and purI mutants. Our results suggest that PurG and PurI and one or more components of the APB pathway may function as a complex needed for aerobic function of the APB pathway.

Alleles↗
PubMed2000

The Saccharomyces cerevisiae RAD6 group is composed of an error-prone and two error-free postreplication repair pathways.

The RAD6 postreplication repair and mutagenesis pathway is the only major radiation repair pathway yet to be extensively characterized. It has been previously speculated that the RAD6 pathway consists of two parallel subpathways, one error free and another error prone (mutagenic). Here we show that the RAD6 group genes can be exclusively divided into three rather than two independent subpathways represented by the RAD5, POL30, and REV3 genes; the REV3 pathway is largely mutagenic, whereas the RAD5 and the POL30 pathways are deemed error free. Mutants carrying characteristic mutations in each of the three subpathways are phenotypically indistinguishable from a single mutant such as rad18, which is defective in the entire RAD6 postreplication repair/tolerance pathway. Furthermore, the rad18 mutation is epistatic to all single or combined mutations in any of the above three subpathways. Our data also suggest that MMS2 and UBC13 play a key role in coordinating the response of the error-free subpathways; Mms2 and Ubc13 form a complex required for a novel polyubiquitin chain assembly, which probably serves as a signal transducer to promote both RAD5 and POL30 error-free postreplication repair pathways. The model established by this study will facilitate further research into the molecular mechanisms of postreplication repair and translesion DNA synthesis. In view of the high degree of sequence conservation of the RAD6 pathway genes among all eukaryotes, the model presented in this study may also apply to mammalian cells and predicts links to human diseases.

Adenosine Triphosphatases↗
PubMed1995

Proliferation-dependent differential regulation of the dolichol pathway genes in Saccharomyces cerevisiae.

The dolichol pathway serves in the synthesis of the dolichol-linked oligosaccharide precursor for protein N-glycosylation. Recently, we reported that mRNAs of genes that function at the early steps in the dolichol pathway in yeast, ALG7, ALG1 and ALG2, were co-ordinately induced following growth stimulation of G0-arrested cells in a manner similar to that of the transcripts of the early growth response genes (Kukuruzinska, M.A. and Lennon, K. Glycobiology, 4, 437-443, 1994). To determine whether the entire dolichol pathway was co-ordinately regulated with growth, we examined the expression of genes functioning late in the pathway, including two genes encoding oligosaccharyltransferase subunits, at two critical control points in the G1 phase of cell cycle: G0/G1 and START. We show that early in G1, at the G0/G1 transition point, the late ALG genes and the two oligosaccharyltransferase-encoding genes examined were regulated co-ordinately with the early ALG genes: they were downregulated upon exit from the mitotic cell cycle into G0, and they were induced following growth stimulation in the absence of de novo protein synthesis. All the dolichol pathway genes produced transcripts with short half-lives that were rapidly stabilized in the presence of cycloheximide. In contrast, cell division arrest late in G1, at START, was accompanied by a selective downregulation of only the first dolichol pathway gene, ALG7, and not of the genes functioning later in the pathway. These results indicate that, depending on their position in G1, cells either co-ordinately or differentially regulate the dolichol pathway genes.

Base Sequence↗
PubMed2006

Phytohormone signalling pathways interact with sugars during seed germination and seedling development.

Exogenous glucose delays seed germination in Arabidopsis thaliana not only in wild type (WT), but also in a number of mutants in hormone signalling pathways. This study demonstrates that the ABA Insensitive 3 (ABI3) gene in the ABA signalling pathway and the RGA-like 2 (RGL2) and SPINDLY (SPY) genes in the GA signalling pathways all play important roles in the glucose-induced delay of seed germination. Transcription of the ABI3 and RGL2 genes is up-regulated by glucose. This study also supports the idea that different sugars such as the hexose stereoisomers, glucose, and mannose, delay or inhibit seed germination via different branches of the hormone signalling pathways. Analysis of post-germination seedling development of wild-type plants indicates that exogenous glucose supplied after germination may have a concentration-dependent stimulatory effect on root and shoot growth. Comparison of WT and spy seedling growth on different glucose concentrations suggests that the stimulatory effect of glucose is partially exerted via the GA or cytokinin signalling pathways. The effects of glucose on plant growth and development may be stimulatory or inhibitory depending on the developmental stage. The inhibitory effect on seed germination seems to be accomplished via the activation of the ABA signalling pathway, through ABI3, and inactivation of the GA signalling pathway through RGL2 and SPY. On the other hand, the stimulatory effect of glucose on seedling growth may involve the GA and/or cytokinin signalling pathways.

Abscisic Acid↗
PubMed2000

Induction of apoptosis and inhibition of signalling pathways by alkylated purines.

Addition of growth factors such as EGF and insulin to serum-starved G(0) Chinese hamster fibroblast cells results in activation of the phosphatidylinositol 3-kinase (PI3-K)/p70 S6 kinase (p70(S6K)) pathway and the ras-raf mitogen-activated kinase (MAPK) pathway. Activation of these pathways is usually associated with protection of cells from apoptosis. We have studied the effect of three alkylpurines, O(6)-methylguanine (O6meG), O(6)-ethylguanine (O6etG) and 6-dimethylaminopurine (6DMAP) on two particular steps of these pathways, namely activation of p70(S6K) and of MAPK. Under the same experimental conditions we studied the ability of these alkylpurines to induce apoptosis. Our results show that the three alkylpurines induced apoptosis with increasing efficiency from O6meG to 6DMAP to O6etG. The induction of apoptosis was phase specific, with the G(0)/G(1) phase being most sensitive. A reduced apoptotic response was observed in cells with abnormal nuclear accumulation of mutant or wild-type p53, suggesting that functional p53 was required for the induction of apoptosis. At concentrations inducing apoptosis the three alkylpurines inhibited p70(S6K) activity, while they had the opposite effect on MAPK. Rapamycin, a specific inhibitor of the p70(S6K) pathway, did not induce apoptosis at doses inhibiting p70(S6K) activity, suggesting that p70(S6K) is not directly involved in apoptosis. As expected, and in line with results reported by others, wortmannin, an upstream inhibitor of the p70(S6K) pathway, did induce apoptosis. We propose that activation of the MAPK pathway and simultaneous inhibition of the p70(S6K) pathway induce an apoptotic response in the cell.

Adenine↗
PubMed1981

Multiple ribosomal RNA cleavage pathways in mammalian cells.

The sequence content of mouse L cell pre-rRNA was examined by RNA gel transfer and blot hybridization. Nuclear RNAs were separated by agarose gel electrophoresis, transferred to diazo-paper, and hybridized to twelve different restriction fragments that are complementary to various sections of 45S pre-rRNA. An abundant new 34S pre-rRNA and less abundant new 37S, 26S and 17S pre-rRNAs were detected. The presence of these new pre-rRNAs suggests the existence of at least two new pre-rRNA cleavage pathways. 34S and 26S pre-rRNAs were also detected in HeLa cells suggesting that these new cleavage pathways are characteristic of mammalian cells. Further, an abundant new 12S precursor to 5.8S rRNA was also detected and is common to all the proposed cleavage pathways. The previously identified 45S, 41S, 32S and 20S pre-rRNAs were readily detected and their general structure confirmed. The 20S pre-rRNA is characteristic of the known pathway used by HeLa and other cells, and its presence suggests that growing mouse L cells use this pre-rRNA cleavage pathway. The 36S pre-rRNA characteristic of the previously described mouse L cell cleavage pathway was not detected. In all these cleavage pathways pre-rRNA cleavage sites are apparently identical and occur at or near the termini of the mature 18S, 5.8S and 28S rRNA sequences. The pathways differ only in the temporal order of cleavage at these sites. The position of the 5.8S rRNA sequence was located within the internal transcribed spacer. The known and conserved sequence of 5.8S rRNA from several organisms predicts a characteristic pattern of restriction enzyme sites for 5.8S rDNA. Internal transcribed spacer rDNA was mapped with restriction enzymes, and the characteristic pattern was found near the midpoint of the internal transcribed spacer. This places the 5.8S rRNA sequence at or near the 5' terminus of 32S pre-rRNA.

Animals↗
PubMed2004

MetaCyc: a multiorganism database of metabolic pathways and enzymes.

The MetaCyc database (see URL http://MetaCyc.org) is a collection of metabolic pathways and enzymes from a wide variety of organisms, primarily microorganisms and plants. The goal of MetaCyc is to contain a representative sample of each experimentally elucidated pathway, and thereby to catalog the universe of metabolism. MetaCyc also describes reactions, chemical compounds and genes. Many of the pathways and enzymes in MetaCyc contain extensive information, including comments and literature citations. SRI's Pathway Tools software supports querying, visualization and curation of MetaCyc. With its wide breadth and depth of metabolic information, MetaCyc is a valuable resource for a variety of applications. MetaCyc is the reference database of pathways and enzymes that is used in conjunction with SRI's metabolic pathway prediction program to create Pathway/Genome Databases that can be augmented with curation from the scientific literature and published on the world wide web. MetaCyc also serves as a readily accessible comprehensive resource on microbial and plant pathways for genome analysis, basic research, education, metabolic engineering and systems biology. In the past 2 years the data content and the Pathway Tools software used to query, visualize and edit MetaCyc have been expanded significantly. These enhancements are described in this paper.

Biochemical Phenomena↗
PubMed2005

ArrayXPath II: mapping and visualizing microarray gene-expression data with biomedical ontologies and integrated biological pathway resources using Scalable Vector Graphics.

SUMMARY: ArrayXPath (http://www.snubi.org/software/ArrayXPath/) is a web-based service for mapping and visualizing microarray gene-expression data with integrated biological pathway resources using Scalable Vector Graphics (SVG). Deciphering the crosstalk among pathways and integrating biomedical ontologies and knowledge bases may help biological interpretation of microarray data. ArrayXPath is empowered by integrating gene-pathway, disease-pathway, drug-pathway and pathway-pathway correlations with integrated Gene Ontology, Medical Subject Headings and OMIM Morbid Map-based annotations. We applied Fisher's exact test and relative risk to evaluate the statistical significance of the correlations. ArrayXPath produces Javascript-enabled SVGs for web-enabled interactive visualization of gene-expression profiles integrated with gene-pathway-disease interactions enriched by biomedical ontologies.

Cluster Analysis↗
PubMed2006

Topology-based cancer classification and related pathway mining using microarray data.

Cancer classification is the critical basis for patient-tailored therapy, while pathway analysis is a promising method to discover the underlying molecular mechanisms related to cancer development by using microarray data. However, linking the molecular classification and pathway analysis with gene network approach has not been discussed yet. In this study, we developed a novel framework based on cancer class-specific gene networks for classification and pathway analysis. This framework involves a novel gene network construction, named ordering network, which exhibits the power-law node-degree distribution as seen in correlation networks. The results obtained from five public cancer datasets showed that the gene networks with ordering relationship are better than those with correlation relationship in terms of accuracy and stability of the classification performance. Furthermore, we integrated the ordering networks, classification information and pathway database to develop the topology-based pathway analysis for identifying cancer class-specific pathways, which might be essential in the biological significance of cancer. Our results suggest that the topology-based classification technology can precisely distinguish cancer subclasses and the topology-based pathway analysis can characterize the correspondent biochemical pathways even if there are subtle, but consistent, changes in gene expression, which may provide new insights into the underlying molecular mechanisms of tumorigenesis.

Gene Expression Profiling↗
PubMed2006

PANTHER version 6: protein sequence and function evolution data with expanded representation of biological pathways.

PANTHER is a freely available, comprehensive software system for relating protein sequence evolution to the evolution of specific protein functions and biological roles. Since 2005, there have been three main improvements to PANTHER. First, the sequences used to create evolutionary trees are carefully selected to provide coverage of phylogenetic as well as functional information. Second, PANTHER is now a member of the InterPro Consortium, and the PANTHER hidden markov Models (HMMs) are distributed as part of InterProScan. Third, we have dramatically expanded the number of pathways associated with subfamilies in PANTHER. Pathways provide a detailed, structured representation of protein function in the context of biological reaction networks. PANTHER pathways were generated using the emerging Systems Biology Markup Language (SBML) standard using pathway network editing software called CellDesigner. The pathway collection currently contains approximately 1500 reactions in 130 pathways, curated by expert biologists with authorship attribution. The curation environment is designed to be easy to use, and the number of pathways is growing steadily. Because the reaction participants are linked to subfamilies and corresponding HMMs, reactions can be inferred across numerous different organisms. The HMMs can be downloaded by FTP, and tools for analyzing data in the context of pathways and function ontologies are available at http://www.pantherdb.org.

Animals↗