PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Pathway analysis”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources
PubMed2004

VitaPad: visualization tools for the analysis of pathway data.

MOTIVATION: Packages that support the creation of pathway diagrams are limited by their inability to be readily extended to new classes of pathway-related data. RESULTS: VitaPad is a cross-platform application that enables users to create and modify biological pathway diagrams and incorporate microarray data with them. It improves on existing software in the following areas: (i) It can create diagrams dynamically through graph layout algorithms. (ii) It is open-source and uses an open XML format to store data, allowing for easy extension or integration with other tools. (iii) It features a cutting-edge user interface with intuitive controls, high-resolution graphics and fully customizable appearance. AVAILABILITY: http://bioinformatics.med.yale.edu CONTACTS: matthew.holford@yale.edu; hongyu.zhao@yale.edu.

Algorithms↗
PubMed2003

Investigation by 13C-NMR and tricarboxylic acid (TCA) deletion mutant analysis of pathways for succinate formation in Saccharomyces cerevisiae during anaerobic fermentation.

NMR isotopic filiation of 13C-labelled aspartate and glutamate was used to explore the tricarboxylic acid (TCA) pathway in Saccharomyces cerevisiae during anaerobic glucose fermentation. The assimilation of [3-13C]aspartate led to the formation of [2,3-13C]malate and [2,3-13C]succinate, with equal levels of 13C incorporation, whereas site-specific enrichment on C-2 and C-3 of succinate was detected only with [3-13C]glutamate. The non-random distribution of 13C labelling in malate and succinate demonstrates that the TCA pathway operates during yeast fermentation as both an oxidative and a reductive branch. The observed 13C distribution suggests that the succinate dehydrogenase (SDH) complex is not active during glucose fermentation. This hypothesis was tested by deleting the SDH1 gene encoding the flavoprotein subunit of the SDH complex. The growth, fermentation rate and metabolite profile of the sdh1 mutant were similar to those of the parental strain, demonstrating that SDH was indeed not active. Filiation experiments indicated the reductive branch of the TCA pathway was the main pathway for succinate production if aspartate was used as the nitrogen source, and that a surplus of succinate was produced by oxidative decarboxylation of 2-oxoglutarate if glutamate was the sole nitrogen source. Consistent with this finding, a kgd1 mutant displayed lower levels of succinate production on glutamate than on other nitrogen sources, and higher levels of oxoglutarate dehydrogenase activity were observed on glutamate. Thus, the reductive branch generating succinate via fumarate reductase operates independently of the nitrogen source. This pathway is the main source of succinate during fermentation, unless glutamate is the sole nitrogen source, in which case the oxidative decarboxylation of 2-oxoglutarate generates additional succinate.

Anaerobiosis↗
PubMed1980

Photosynthesis of Grass Species Differing in Carbon Dioxide Fixation Pathways: IV. ANALYSIS OF REDUCED OXYGEN RESPONSE IN PANICUM MILIOIDES AND PANICUM SCHENCKII.

Reduced photorespiration has been reported in Panicum milioides on the basis of lower CO(2) compensation concentrations than in C(3) species, lower CO(2) evolution in the light, and less response of apparent photosynthesis to O(2) concentration. The lower response to O(2) in P. milioides could be due to reduced O(2) competition with CO(2) for reaction with ribulose 1,5-bisphosphate, to a reduced loss of CO(2), or to an initial fixation of CO(2) by phosphoenolpyruvate carboxylase. Experiments were carried out with Panicum maximum Jacq., a C(4) species having no apparent photorespiration; tall fescue (Festuca arundinacea Schreb.), a C(3) species; P. milioides Nees ex Trin.; and Panicum schenckii Hack. The latter two species are closely related and have low photorespiration rates. CO(2) exchange was measured at five CO(2) concentrations ranging from 0 to 260 microliters per liter at both 2 and 21% O(2). Mesophyll conductance or carboxylation efficiency was estimated by plotting substomatal CO(2) concentrations against apparent photosynthesis. In the C(4) species P. maximum, mesophyll conductance was 0.96 centimeters per second and was unaffected by O(2) concentration. At 21% O(2) mesophyll conductance of tall fescue was decreased 32% below the value at 2% O(2). Decreases in mesophyll conductance at 21% O(2) for P. milioides and P. schenckii were similar to that for tall fescue. On the other hand, loss of CO(2) in CO(2)-free air, estimated by extrapolating the CO(2) response curve to zero CO(2), was increased from 1.8 to 6.5 milligrams per square decimeter per hour in tall fescue as O(2) was raised from 2-21%. Loss of CO(2) was less than 1 milligram per square decimeter per hour for P. milioides and P. schenckii and was unaffected by O(2). The results suggest that the reduced O(2) response in P. milioides and P. schenckii is due to a lower loss of CO(2) in the light rather than less inhibition of carboxylation by O(2), since the decrease in carboxylation efficiency at 21% O(2) was similar for P. milioides, P. schenckii, and tall fescue. The inhibition of apparent photosynthesis by 21% O(2) in these three species at low light intensities was similar at 31 to 36% which also indicates similar O(2) effects on carboxylation. Apparent photosynthesis at high light intensity was inhibited less by 21% O(2) in P. milioides (16.8%) and P. schenckii (23.8%) than in tall fescue (28.4%). This lower inhibition in the Panicum species may have been due to a higher degree of recycling of photorespired CO(2) in these species than in tall fescue.

Journal Article↗
PubMed1985

Quantitative analysis of pathways of methionine metabolism and their regulation in lemna.

Individual rates of metabolism of the sulfur, methyl, and 4-carbon moieties of methionine were estimated in Lemna paucicostata Hegelm. 6746 growing under standard conditions, and used to quantitate pathways of methionine metabolism. Synthesis of S-adenosylmethionine (AdoMet) is the major pathway for methionine metabolism, with over 4 times as much methionine metabolized by this route as accumulates in protein. More than 90% of AdoMet is used for transmethylation. Methyl groups of choline, phosphatidylcholine, and phosphorylcholine are major end products of this pathway. Flux through methylthio recycling is about one-third the amount of methionine accumulating in protein. Spermidine synthesis accounts for at least 60% of the flux through methylthio recycling. The results obtained here, together with those reported for methionine-supplemented plants (Giovanelli, Mudd, Datko 1981 Biochem Biophys Res Commun 100: 831-839), indicate that methionine supplementation reduced methylneogenesis by no more than the small amount expected from the reduced entry of sulfate sulfur into methionine (Giovanelli, Mudd, Datko, 1985 Plant Physiol 77: 450-455). Methionine supplementation had no significant effect on transmethylation or methylthio recycling. The combined data provide the first comprehensive estimates of the quantitative relationships of major pathways for methionine metabolism and their control in plants.

Journal Article↗
PubMed1980

Electrophysiological analysis of pathways connecting the medial preoptic area with the mesencephalic central grey matter in rats.

1. An electrophysiological study of ascending and descending connexions between the dorsal raphe region of the mesencephalic periaqueductal grey matter and the medial preoptic area has been performed in dioestrous female rats anaesthetized with urethane. 2. Extracellular action potentials recorded from 208 neurones in the medial preoptic area were analysed for a change in excitability following stimulation of the periaqueductal grey matter. 174 neurones were also tested for changes in excitability following stimulation of the mediobasal hypothalamus. 3. Stimulation of the periaqueductal grey matter at 1 Hz was rarely effective, but short trains of pulses (three at 100 Hz) usually caused an initial inhibition (62.5% of 208) of both projection identified and adjacent neurones of the medial preoptic area, at latencies of 5--90 msec (mean 34.1 +/- 1.4 msec). Inhibition following stimulation of the mediobasal hypothalamus occurred less frequently (34%) and at shorter latency (mean 12.0 +/- 1.8 msec; n = 48). 4. Less frequently (10.6%) periaqueductal grey matter stimulation caused an initial excitation of preoptic neurones at latencies of 15--180 msec, (mean 35.3 +/- 7.2). Initial excitation following mediobasal hypothalamus stimulation was stronger, occurred more frequently (29%) and at shorter latencies (range 3--60 msec, mean 13.1 +/- 1.5). Following such initial excitation, inhibition of spontaneous or ionophoretically evoked activity occurred more frequently following mediobasal hypothalamic stimulation, than after periaqueductal grey matter stimulation. 5. Twenty-four neurones displayed antidromic invasion following periaqueductal grey matter stimulation. Latencies for invasion ranged from 13 to 50 msec (mean 25.5 +/- 2.0 msec) and are suggestive of an unmyelinated projection. Occasionally an abrupt decrease in latency followed an increase in stimulus intensity. Antidromic invasion from mediobasal hypothalamus was characterized by a shorter latency (mean 12.5 +/- 0.7 msec; n = 43). A period of reduced excitability lasting 40--100 msec followed antidromic invasion from either site. 6. Antidromic responses to paired mediobasal hypothalamic or periaqueductal grey matter stimuli at 5 msec intervals revealed an increased latency of invasion of the second response, due to the partial refractory period of the neurone. Five cells showed a decreased latency of invasion at stimulus separations of 10--150 msec, interpreted as evidence of a supranormal period. Changes in conduction velocity during the supranormal period may give rise to a variable latency of invasion of spontaneously active cells. 7. These results provide evidence for direct, reciprocal connexions between the midbrain central grey and the medial preoptic area. These circuits may play a role in controlling neuroendocrine and behavioural aspects of reproductive functions.

Action Potentials↗
PubMed2003

Genetic analysis of pathway specificity during posttranslational protein translocation across the Escherichia coli plasma membrane.

In Escherichia coli, the SecB/SecA branch of the Sec pathway and the twin-arginine translocation (Tat) pathway represent two alternative possibilities for posttranslational translocation of proteins across the cytoplasmic membrane. Maintenance of pathway specificity was analyzed using a model precursor consisting of the mature part of the SecB-dependent maltose-binding protein (MalE) fused to the signal peptide of the Tat-dependent TorA protein. The TorA signal peptide selectively and specifically directed MalE into the Tat pathway. The characterization of a spontaneous TorA signal peptide mutant (TorA*), in which the two arginine residues in the c-region had been replaced by one leucine residue, showed that the TorA*-MalE mutant precursor had acquired the ability for efficiently using the SecB/SecA pathway. Despite the lack of the "Sec avoidance signal," the mutant precursor was still capable of using the Tat pathway, provided that the kinetically favored Sec pathway was blocked. These results show that the h-region of the TorA signal peptide is, in principle, sufficiently hydrophobic for Sec-dependent protein translocation, and therefore, the positively charged amino acid residues in the c-region represent a major determinant for Tat pathway specificity. Tat-dependent export of TorA-MalE was significantly slower in the presence of SecB than in its absence, showing that SecB can bind to this precursor despite the presence of the Sec avoidance signal in the c-region of the TorA signal peptide, strongly suggesting that the function of the Sec avoidance signal is not the prevention of SecB binding; rather, it must be exerted at a later step in the Sec pathway.

Amino Acid Sequence↗
PubMed2005

Expression of a human cytochrome p450 in yeast permits analysis of pathways for response to and repair of aflatoxin-induced DNA damage.

Aflatoxin B1 (AFB1) is a human hepatotoxin and hepatocarcinogen produced by the mold Aspergillus flavus. In humans, AFB1 is primarily bioactivated by cytochrome P450 1A2 (CYP1A2) and 3A4 to a genotoxic epoxide that forms N7-guanine DNA adducts. A series of yeast haploid mutants defective in DNA repair and cell cycle checkpoints were transformed with human CYP1A2 to investigate how these DNA adducts are repaired. Cell survival and mutagenesis following aflatoxin B1 treatment was assayed in strains defective in nucleotide excision repair (NER) (rad14), postreplication repair (PRR) (rad6, rad18, mms2, and rad5), homologous recombinational repair (HRR) (rad51 and rad54), base excision repair (BER) (apn1 apn2), nonhomologous end-joining (NHEJ) (yku70), mismatch repair (MMR) (pms1), translesion synthesis (TLS) (rev3), and checkpoints (mec1-1, mec1-1 rad53, rad9, and rad17). Together our data suggest the involvement of homologous recombination and nucleotide excision repair, postreplication repair, and checkpoints in the repair and/or tolerance of AFB1-induced DNA damage in the yeast model. Rev3 appears to mediate AFB1-induced mutagenesis when error-free pathways are compromised. The results further suggest unique roles for Rad5 and abasic endonuclease-dependent DNA intermediates in regulating AFB1-induced mutagenicity.

Aflatoxin B1↗
PubMed2000

Dynamic biochemical reaction process analysis and pathway modification predictions.

Recently, the area of model predictive modification of biochemical pathways has received attention with the aim to increase the productivity of microbial systems. In this study, we present a generalization of previous work, where, using a sensitivity study over the fermentation as a dynamic system, the optimal selection of reaction steps for modification (amplification or attenuation) is determined. The influence of metabolites in the activity of enzymes has also been considered (through activation or inhibition). We further introduce a new concept in the dynamic modeling of biochemical reaction systems including a generalized continuous superstructure in which two artificial multiplicative terms are included to account for: (a) enzyme overexpression or underexpression (attenuation or amplification) for the whole enzyme pool; and (b) modification of the apparent order of a kinetic expression with respect to the concentration of a metabolite or any subset of metabolites participating in the pathway. This new formulation allows the prediction of the sensitivity of the pathway performance index (objective function) with respect to the concentration of the enzyme, as well as the interaction of the enzyme with other metabolites. Using this framework, a case study for the production of penicillin V is analyzed, obtaining the most sensitive reaction steps (or bottlenecks) and the most significant regulations of the system, due to the effect of concentration of intracellular metabolites on the activity of each enzyme.

Biochemistry↗
PubMed2003

Irinotecan pathway genotype analysis to predict pharmacokinetics.

PURPOSE: The purpose was to explore the relationships between irinotecan disposition and allelic variants of genes coding for adenosine triphosphate binding cassette transporters and enzymes of putative relevance for irinotecan. EXPERIMENTAL DESIGN: Irinotecan was administered to 65 cancer patients as a 90-min infusion (dose, 200-350 mg/m(2)), and pharmacokinetic data were obtained during the first cycle. All patients were genotyped for variants in genes encoding MDR1 P-glycoprotein (ABCB1), multidrug resistance-associated proteins MRP-1 (ABCC1) and MRP-2 (canalicular multispecific organic anion transporter; ABCC2), breast cancer resistance protein (ABCG2), carboxylesterases (CES1, CES2), cytochrome p450 isozymes (CYP3A4, CYP3A5), UDP glucuronosyltransferase (UGT1A1), and a DNA-repair enzyme (XRCC1), which was included as a nonmechanistic control. RESULTS: Eighteen genetic variants were found in nine genes of putative importance for irinotecan disposition. The homozygous T allele of the ABCB1 1236C>T polymorphism was associated with significantly increased exposure to irinotecan (P = 0.038) and its active metabolite SN-38 (P = 0.031). Pharmacokinetic parameters were not related to any of the other multiple variant genotypes, possibly because of the low allele frequency. The extent of SN-38 glucuronidation was slightly impaired in homozygous variants of UGT1A1*28, although differences were not statistically significant (P = 0.22). CONCLUSIONS: It is concluded that genotyping for ABCB1 1236C>T may be one of the factors assisting with dose optimization of irinotecan chemotherapy in cancer patients. Additional investigation is required to confirm these findings in a larger population and to assess relationships between irinotecan disposition and the rare variant genotypes, especially in other ethnic groups.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

[An electrophysiological analysis of pathways from lateral septum to hippocampal CA1 area in rat].

Upon stimulating the lateral septal region, a population spike could be recorded in the stratum pyramidale of hippocampal CA1 together with a recordable EPSP in the apical dendrites (stratum radiatum). After destruction of hippocampal CA3, CA4 pyramidal cells by intraventricular microinjection of kainic acid, electrical stimulation of the lateral septum could no longer evoke EPSP in the apical dendrites. This experiment suggests that the neural connection of the lateral septo-CA1 apical dendrites is mediated by the collaterals of the ipsilateral CA3 pyramidal cells. But after the destruction of CA3, CA4, electric stimulation of lateral septum could still evoke EPSP in the basal dendrites (stratum oriends). The neural connection mediating the response of the lateral septo-CA1 basal dendrites was not reported before, but the neural pathway remains to be investigated.

Animals↗
PubMed2006

Laser microdissection and microarray analysis of breast tumors reveal ER-alpha related genes and pathways.

About 70-80% of breast cancers express estrogen receptor alpha (ER-alpha), and estrogens play important roles in the development and growth of hormone-dependent tumors. Together with lymph node metastasis, tumor size, and histological grade, ER status is considered as one of the prognostic factors in breast cancer, and an indicator for hormonal treatment. To investigate genes and pathways that are associated with ER status and epithelial cells in breast tumor, we applied laser capture microdissection (LCM) technology to capture epithelial tumor cells from 28 lymph node-negative breast tumor samples, in which 17 patients had ER-alpha+ tumors, and 11 patients have ER-alpha- tumors. Gene expression profiles were analysed on Affymetrix Hu133A GeneChip. Meanwhile, gene profiles using total RNA isolated from bulk tumors of the same 28 patients were also generated. In total, 146 genes and 112 genes with significant P-value and having significant differential expression between ER-alpha+ and ER-alpha- tumors were identified from the LCM data set and bulk tissue data set, respectively. A total of 61 genes were found to be common in both data sets, while 85 genes were unique to the LCM data set and 51 genes were present only in the bulk tumor data set. Pathway analysis with the 85 genes using Gene Ontology suggested that genes involved in endocytosis, ceramide generation, Ras/ERK/Ark cascade, and JAT-STAT pathways may play roles related to ER. The gene profiling with LCM-captured tumor cells provides a unique approach to study epithelial tumor cells and to gain an insight into signaling pathways associated with ER.

Breast Neoplasms↗
PubMedDate not supplied

Functional development of the corticocortical pathway for motion analysis in the macaque monkey: a 14C-2-deoxyglucose study.

The corticocortical pathway for motion analysis transmits visual information from striate cortex (V1) via V2, V3d, superior temporal sulcal areas MT, MST, and FST to motion-sensitive areas in the floor and upper bank of the anterior part of the superior temporal sulcus (AST). We studied the functional development of this pathway by applying the 14C-2-deoxyglucose method to rhesus monkeys (Macaca mulatta) ranging in age from 2 d to 3-4 years. A comparison of local cerebral glucose utilization (LCGU) in an intact and a visually deafferented hemisphere in each animal across the age range revealed that this pathway, immature at birth, reaches adult-like levels at 3 months of age. This developmental time course is reflected both in absolute LCGU and in the interhemispheric LCGU differences in all the areas of the pathway. At all ages, the interhemispheric difference in LCGU is largest in V1 and gradually declines along the pathway until a minimum is reached in AST. This decline likely reflects an increasing proportion of nonvisual inputs to the higher-order areas of the pathway. Measurements like those above taken in areas of inferior parietal cortex indicate that they mature at the same rate as those in the motion analysis pathway. However, comparison with findings on the functional development of the temporal areas of the occipitotemporal pathway for object vision (Bachevalier et al., 1991) suggests that areas along the motion analysis pathway and those in parietal cortex mature about 1 month earlier.

Age Factors↗
PubMed1997

[Instrumental analysis of sagittal condylar motion pathway].

An analysis of protrusive jaw movement was carried out using Quick-Axis mandibular motion analyser. The condylar path tracings were recorded of 46 individuals (21 women and 25 men). Three recordings were performed on each side and a tangent to the condylar curves was drawn to calculate the condylar angle. Considering all dates the mean value of angulation was 52.2 degrees. There were no statistically significant differences between the two sexes and sides. The authors' findings suggest it is advisable to perform three consecutive registrations on each side and calculate a mean condylar angle to gain a better result.

Adult↗