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Results for “Enhancer mapping”

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At least 613 records · Page 34Linked to original sources

PubMed1994

Caffeine enhances the stimulant effect of methamphetamine, but may not affect induction of methamphetamine sensitization of ambulation in mice.

Methamphetamine (MAP: 1 and 2 mg/kg SC) and caffeine (CAF: 1, 3, 10 and 30 mg/kg SC) dose-dependently increased ambulation in mice. Repeated administration (5 times at 3 to 4-day intervals) of MAP, but not CAF, induced sensitization to its effect. Furthermore, the mice repeatedly receiving CAF showed no significant change in the sensitivity to MAP. Combined administration of MAP with CAF increased the effect. In the combinations of MAP (1 mg/kg) with CAF (3, 10 and 30 mg/kg), and MAP (2 mg/kg) with CAF (1 and 3 mg/kg), the effect was enhanced by the repeated administration. However, MAP sensitization was not modified by the combination with CAF in the repeated administration schedule, except in the combination of MAP (1 mg/kg) with CAF (30 mg/kg). The ambulation-increasing effects of MAP (1 mg/kg), CAF (10 mg/kg) and combination of MAP with CAF were almost equivalently inhibited by SCH 23390 (0.01 and 0.1 mg/kg SC) and YM-09151-2 (0.01 and 0.1 mg/kg SC). However, the inhibitory effects of apomorphine (0.05 mg/kg SC) and N6-(L-phenylisopropyl)-adenosine (0.1 and 0.2 mg/kg SC) were stronger for CAF than for MAP and the combination, and those of alpha-methyl-p-tyrosine (200 mg/kg IP, 4 h before) and reserpine (1 mg/kg SC, 4 h before) were stronger for MAP and CAF alone than for the combination. The present results suggest that, although the combination of MAP and CAF enhances the ambulation-increasing effect through an interaction at dopaminergic system, CAF may not significantly modify the induction of MAP sensitization in mice.

Animals↗

PubMed1999

Application of AFLP markers to genome mapping in poultry.

The amplified fragment length polymorphism (AFLP) technique has been used to enhance marker density in the East Lansing reference chicken genome map, using a backcross family derived from a Red Jungle Fowl by White Leghorn mating with White Leghorn as the recurrent parent. To date, 204 AFLP markers have been added, expanding overall map coverage by about 25%. To the limits of our resolution, AFLP markers are distributed relatively evenly across the EL reference map. AFLP are about 60% as frequent in a cross within White Leghorns (line 7(2) x 6(3)) in comparison to the more divergent reference map population. Based on apparent identity of size, about 40% of the 7(2) x 6(3) cross AFLP fragments were also polymorphic in the reference map cross. Primer pairs in which one primer contains 3' extensions of three selective nucleotides and the other has two selective nucleotides successfully generated AFLP from chicken DNA, but such pairs appeared to amplify only a subset of those fragments to which they have an exact sequence match. Three different restriction enzymes with 4 bp recognition sites (TaqI, HinP1I and MspI) were found to work well with EcoRI as the rarer of the two AFLP restriction enzymes used, with HinP1I being the most effective of the three. AFLP markers are likely to provide an economical method with which to enhance framework linkage maps of chicken and probably other avian genomes.

Animals↗

PubMed2005

Facilitation of gastric compliance and cardiovascular reaction by repeated isobaric distension of the rat stomach.

Gastric distension causes cardiovascular reactions and enhances gastric compliance. Here, we investigated how these responses are related to each other, whether they change upon repeated distension and which neural mechanisms are involved. Mean arterial blood pressure (MAP) in phenobarbital-anaesthetized rats was recorded from a carotid artery and gastric compliance determined with an electronic barostat. Runs of intermittent gastric distension were generated by stepwise increments (5 mmHg) of intragastric (IG) pressure. While gastric compliance peaked at IG pressures of 20 mmHg, the change in MAP (predominantly hypotension) was largest at IG pressures beyond 30 mmHg. Repeated distension enhanced the MAP response to IG pressures beyond 35 mmHg, whereas gastric compliance was facilitated primarily at IG pressures below 20 mmHg. This facilitation of gastric compliance depended on the magnitude of the preceding distension. The MAP response to distension was enhanced by nitric oxide synthase inhibition, inhibited by subdiaphragmatic vagotomy but hardly affected by coeliac ganglionectomy. The facilitation of gastric compliance was changed by vagotomy in a complex manner but left unaltered by the other interventions. These findings show that isobaric gastric distension elicits both MAP and gastric compliance responses whose characteristics, mechanisms and sensitization properties differ profoundly.

Air Pressure↗

PubMed2000

Parametric mapping of scaled fitting error in dynamic susceptibility contrast enhanced MR perfusion imaging.

The purpose of this study was to examine the benefits of routine generation of a parametric image of scaled curve fitting errors in the analysis of dynamic susceptibility contrast enhanced MR perfusion imaging. We describe the scaled fitting error (SFE), which reflects the magnitude of potential errors in the estimation of perfusion parameters from dynamic susceptibility contrast enhanced studies. The SFE is the root-mean-square error between the observed values in the time course of change of effective transverse relaxation rate (delta R2* (t)) in tissue and the theoretical values derived by gamma variate curve fitting, scaled with a simple function related to the area under the fitted gamma variate curve. The SFE was tested using Monte Carlo simulation and by observations in normal volunteers and patients. This demonstrated that the SFE was linearly related to uncertainties in calculation of the values of relative cerebral blood volume (rCBV) and relative mean transit time (rMTT). High spatial resolution SFE maps were obtained in all volunteers and patients. In normal brain, SFE was consistently higher in white matter than in grey matter. In 54/85 patients with neurodegenerative or vascular brain disease, SFE maps showed focal areas with high values owing to poor signal to noise ratio in delta R2*(t). Increased SFE was also found in 11/54 brain tumours owing to loss of conformance of delta R2*(t) to the gamma variate function. SFE mapping is simple to implement and the computational overhead is negligible. It is concluded that parametric maps of SFE allow visual and quantitative comparison of fitting errors with the theoretical gamma variate model between anatomical regions and provide a quality control device to rapidly assess the reliability of the associated rCBV and rMTT estimations.

Adult↗

PubMed2004

The role of p38 MAP kinase in the synergistic cytotoxic action of calcitriol and TNF-alpha in human breast cancer cells.

Calcitriol, the hormonal form of Vitamin D, potentiates the activity of some agents of the anti-cancer immune system including tumor necrosis factor-alpha (TNF-alpha). Different signaling pathways activated by TNF-alpha may be targets for calcitriol action. Activation of p38 MAP kinase was shown to have both pro- and anti-apoptotic actions in TNF-alpha-induced programmed cell death depending on cell context. Treatment of MCF-7 breast cancer cells with TNF-alpha resulted in activation of p38 MAP kinase that persisted for at least 24h. Whereas calcitriol had no effect on the earlier phase of p38 MAP kinase activation (up to 1h), it inhibited the activation of this pathway between one and 24h after exposure to TNF-alpha. Both calcitriol and the p38 MAP kinase inhibitor SB203580 enhanced TNF-alpha-induced cytotoxicity and drop in mitochondrial membrane potential, but their combined effect was sub-additive. Taken together, these findings suggest that p38 MAP kinase plays an anti-apoptotic role in TNF-alpha-induced cytotoxicity in MCF-7 cells and that the synergistic interaction between TNF-alpha and calcitriol, leading to mitochondrial damage and subsequent cell death, is partially due to modulation of this signaling pathway.

Breast Neoplasms↗

PubMed2001

Epidermal growth factor induction of apolipoprotein A-I is mediated by the Ras-MAP kinase cascade and Sp1.

Insulin induces apolipoprotein A-I, apoA-I gene transcription via a membrane receptor with intrinsic tyrosine kinase activity. This finding prompted us to ask whether the gene is stimulated by epidermal growth factor (EGF), EGF a peptide hormone that binds to another member of the receptor superfamily with tyrosine kinase activity. Our data showed that like insulin, EGF increased abundance of apoA-I protein and transcription of the gene in human hepatoma, Hep G2 cells. The effects of both hormones appeared direct because their induction of apoA-I gene transcription was not affected by the protein synthesis inhibitor, cycloheximide. Although both insulin and EGF stimulate apoA-I expression, each hormone binds to a distinct membrane receptor thus suggesting differential intracellular signaling. Therefore, we used a panel of inhibitors to define the pathway(s) that mediate the actions of these hormones. Whereas, the actions of EGF required only the Ras-mitogen-activated protein, MAP kinase, those of insulin were mediated by equal participation of both the Ras-MAP kinase and protein kinase C, PKC cascades. Despite differences in signaling pathways triggered by each hormone receptor, the activation of apoA-I transcription required the participation of a single transcription factor, Sp1. Furthermore, EGF induction of transcription was attenuated by mutating the MAP kinase site at amino acid, Thr(266) rendering Sp1 phosphorylation deficient. In summary, EGF stimulation of apoA-I expression is mediated solely by the Ras-MAP kinase cascade and enhanced activity of this pathway requires Sp1 with an intact phosphorylation site at Thr(266). However, insulin induction of this gene is different and requires both Ras-MAP kinase and PKC pathways but their actions are also mediated by Sp1.

Amino Acid Sequence↗

PubMed1999

The utility of quantitative body surface isoarea mapping for predicting ventricular tachyarrhythmias.

Noninvasive techniques, such as the signal averaged ECG, have been used to assess risk of ventricular tachyarrhythmias (VT). However, these methods produce false positive and negative results. The purpose of this study was to develop body surface map algorithms which would enhance prediction of susceptibility to VT. Fifty-three patients referred for programmed electrical stimulation were enrolled in this study. All patients underwent signal averaged ECG, body surface map, programmed electrical stimulation. Group I patients had no sustained inducible VT and group II patients had either inducible sustained VT at electrophysiology study or previously documented spontaneous, sustained VT. For body surface map analysis, the difference between extrema on isoarea maps was calculated and defined as the gradient range. An abnormal body surface map was defined as a QRST gradient range < or = 109 mv.ms. The mean QRST gradient range in group II was significantly < that in group I (P < 0.05). By logistic regression analysis, the presence of coronary artery disease, a QRST gradient range < or = 109 mv.ms, an EF < 40% and a signal averaged ECG QRS duration > 114 ms predicted VT. The sensitivity, specificity, positive and negative predictive values for predicting VT susceptibility of an algorithm which combines the signal averaged ECG QRS duration and the QRST gradients were 0.93, 0.76, 0.79, and 0.91, respectively, while those for the signal averaged ECG alone were 0.52, 0.69, 0.63, and 0.59 for VT susceptibility. A combined body surface map-signal averaged ECG algorithm was more sensitive in detecting susceptibility to VT than the signal averaged ECG alone.

Adolescent↗

PubMed2002

Optical imaging of intrinsic signals in ferret auditory cortex: responses to narrowband sound stimuli.

This paper describes optical imaging of the auditory cortex in the anesthetized ferret, particularly addressing optimization of narrowband stimuli. The types of sound stimuli used were tone-pip trains and sinusoidal frequency and amplitude modulated (SFM and SAM) tones. By employing short illumination wavelengths (546 nm), we have successfully characterized the tonotopic arrangement, in agreement with the well-established electrophysiological tonotopic maps of the ferret auditory primary field (AI). The magnitude of the optical signal increased with sound level, was maximal for a modulation frequency (MF) of 2-4 Hz, and was larger for tone-pip trains and SFM sounds than for SAM sounds. Accordingly, an optimal narrowband stimulus was defined. Thus optical imaging can be used successfully to obtain frequency maps in auditory cortex by an appropriate choice of stimulus parameters. In addition, background noise consisting of 0.1-Hz oscillations could be reduced by introduction of blood pressure enhancing drugs. The optical maps were largely independent of 1) the type of narrowband stimulus, 2) the sound level, and 3) the MF. This stability of the optical maps was not predicted from the electrophysiological literature.

Acoustic Stimulation↗

PubMed2006

Pulmonary fissure segmentation on CT.

A pulmonary fissure is a boundary between the lobes in the lungs. Its segmentation is of clinical interest as it facilitates the assessment of lung disease on a lobar level. This paper describes a new approach for segmenting the major fissures in both lungs on thin-section computed tomography (CT). An image transformation called "ridge map" is proposed for enhancing the appearance of fissures on CT. A curve-growing process, modeled by a Bayesian network, is described that is influenced by both the features of the ridge map and prior knowledge of the shape of the fissure. The process is implemented in an adaptive regularization framework that balances these influences and reflects the causal dependencies in the Bayesian network using an entropy measure. The method effectively alleviates the problem of inappropriate weights of regularization terms, an effect that can occur with static regularization methods. The method was applied to segment and visualize the lobes of the lungs on chest CT of 10 patients with pulmonary nodules. Only 78 out of 3286 left or right lung regions with fissures (2.4%) required manual correction. The average distance between the automatically segmented and the manually delineated "ground-truth" fissures was 1.01 mm, which was similar to the average distance of 1.03 mm between two sets of manually segmented fissures. The method has a linear-time worst-case complexity and segments the upper lung from the lower lung on a standard computer in less than 5 min.

Algorithms↗

PubMed2000

A conserved docking site in MEKs mediates high-affinity binding to MAP kinases and cooperates with a scaffold protein to enhance signal transmission.

The recognition of mitogen-activated protein kinases (MAPKs) by their upstream activators, MAPK/ERK kinases (MEKs), is crucial for the effective and accurate transmission of many signals. We demonstrated previously that the yeast MAPKs Kss1 and Fus3 bind with high affinity to the N terminus of the MEK Ste7, and proposed that a conserved motif in Ste7, the MAPK-docking site, mediates this interaction. Here we show that the corresponding sequences in human MEK1 and MEK2 are necessary and sufficient for the direct binding of the MAPKs ERK1 and ERK2. Mutations in MEK1, MEK2, or Ste7 that altered conserved residues in the docking site diminished binding of the cognate MAPKs. Furthermore, short peptides corresponding to the docking sites in these MEKs inhibited MEK1-mediated phosphorylation of ERK2 in vitro. In yeast cells, docking-defective alleles of Ste7 were modestly compromised in their ability to transmit the mating pheromone signal. This deficiency was dramatically enhanced when the ability of the Ste5 scaffold protein to associate with components of the MAPK cascade was also compromised. Thus, both the MEK-MAPK docking interaction and binding to the Ste5 scaffold make mutually reinforcing contributions to the efficiency of signaling by this MAPK cascade in vivo.

Adaptor Proteins, Signal Transducing↗

PubMed1997

Value of simulated body surface potential maps as templates in localizing sites of ectopic activation for radiofrequency ablation.

Body surface potential maps recorded during catheter pace mapping can facilitate the localization of the site of origin of ventricular tachycardia. In this study, we investigated the value of a realistic computer model of the human ventricular myocardium in generating body surface potential maps as templates for identifying sites of ectopic activation. Our model features an anatomically accurate geometry and an anisotropy due to transmural fibre rotation, that were reconstructed with a spatial resolution of 0.5 mm. It simulates the electrotonic interactions of cardiac cells by solving a nonlinear parabolic partial differential equation, but it behaves as a cellular automaton when the transmembrane potential exceeds the threshold value. We successfully validated our model by comparing the simulated activation sequences--described by isochronal maps, epicardial potential maps and body surface potential maps--with the measured sequences of epicardial and body surface maps reported in the literature. By systematically pacing the left ventricular and right ventricular endocardial surfaces in our ventricular model, we generated a database of 155 QRS-integral maps, which provides a high-resolution reference frame for localizing distinct endocardial pacing sites. This database promises to be a useful tool in improving the performance of catheter pace mapping used in combination with body surface potential mapping. Overall, the results demonstrate that our computer model of the human ventricular myocardium is well suited for complementing a database of QRS-integral maps obtained during clinical pace mapping and can help enhance the efficacy of the ablative treatment of ventricular arrhythmias.

Anisotropy↗

PubMed2002

Treasure hunting in a new era: genotyping of single nucleotide polymorphisms and the search for complex disease genes by association scans.

Genotyping single nucleotide polymorphisms by technologies like those described in this issue are propelling us towards a new era in the study of human genetics. This new era promises improved prospects for mapping genes responsible for complex human diseases and other complex traits. In this article, I sketch empirical results and statistical theory that together form the scientific rationale for anticipating enhanced success in gene mapping in the new era that is now approaching.

Genetic Diseases, Inborn↗

PubMed2005

Mapping brains without coordinates.

Brain mapping has evolved considerably over the last century. While most emphasis has been placed on coordinate-based spatial atlases, coordinate-independent parcellation-based mapping is an important technique for accessing the multitude of structural and functional data that have been reported from invasive experiments, and provides for flexible and efficient representations of information. Here. we provide an introduction to motivations, concepts, techniques and implications of coordinate-independent mapping of microstructurally or functionally defined brain structures. In particular, we explain the problems of constructing mapping paths and finding adequate heuristics for their evaluation. We then introduce the three auxiliary concepts of acronym-based mapping (AM), of a generalized hierarchy (GM ontology), and of a topographically oriented regional map (RM) with adequate granularity for mapping between individual brains with different cortical folding and between humans and non-human primates. Examples from the CoCoMac database of primate brain connectivity demonstrate how these concepts enhance coordinate-independent mapping based on published relational statements. Finally, we discuss the strengths and weaknesses of spatial coordinate-based versus coordinate-independent microstructural brain mapping and show perspectives for a wider application of parcellation-based approaches in the integration of multi-model structural, functional, and clinical data.

Anatomy, Comparative↗

PubMed1995

YAC analysis and minimal tiling path construction for chromosome 21q.

We have undertaken a detailed analysis of several hundred YACs from widely available YAC libraries which map to human chromosome 21 with the goal of improving the physical map of chromosome 21 and determining the feasibility of producing a minimal tiling path of well characterized, stable, non-chimeric YACs spanning the long arm of the chromosome (21q). We report information on over 500 YACs known to contain STS from 21q including information on size, stability, chimerism, marker content, and NotI restriction sites. YACs derive from the CEPH and St. Louis YAC libraries, and STSs include the set of 198 markers originally used do assemble a YAC contig of 21q, as well as additional anonymous probes and gene markers. This information has assisted in refinements of STS order, has defined a region of general instability in 2lq22.3, has identified an increased number of NotI restriction sites, and has defined cryptic gaps, particularly in 2lq2l, for which few or no markers are available. These results have allowed us to develop and assess a minimal tiling path of overlapping YACs consisting of 59 YACs (and two PI clones), largely non chimeric, stable, and of verified STS content. They total 30 mb of non-overlapping DNA, and contain all chromosome 21 specific STSs originally used to define the 810 YAC 21q YAC contig. When integrated with the analysis of a somatic cell hybrid mapping panel of chromosome 21 reported in the accompanying manuscript, a greatly enhanced understanding of the physical map of chromosome 21 is obtained.

Chromosome Mapping↗

PubMed1998

SUR-8, a conserved Ras-binding protein with leucine-rich repeats, positively regulates Ras-mediated signaling in C. elegans.

We describe the identification and characterization of a novel gene, sur-8, that positively regulates Ras-mediated signal transduction during C. elegans vulval development. Reduction of sur-8 function suppresses an activated ras mutation and dramatically enhances phenotypes of mpk-1 MAP kinase and ksr-1 mutations, while increase of sur-8 dosage enhances an activated ras mutation. sur-8 appears to act downstream of or in parallel to ras but upstream of raf. sur-8 encodes a conserved protein that is composed predominantly of leucine-rich repeats. The SUR-8 protein interacts directly with Ras but not with the Ras(P34G) mutant protein, suggesting that SUR-8 may mediate its effects through Ras binding. A structural and functional SUR-8 homolog in humans specifically binds K-Ras and N-Ras but not H-Ras in vitro.

Adaptor Proteins, Signal Transducing↗

PubMed1998

Effects of L-NAME and L-Arg on arterial blood pressure in normotensive and hypertensive streptozotocin diabetic rats.

The present study was designed to examine blood pressure response to nitric oxide synthase-pathway inhibition and stimulation in normotensive and hypertensive diabetic rats. Rats treated with streptozotocin (60 mg/Kg i.p.) developed high blood glucose, polyuria and slow weight gain compared with control. One group of diabetic rats developed hypertension, consequently we studied three experimental groups: control rats (C), normotensive diabetic rats (ND) and hypertensive diabetic rats (HD). Mean arterial pressure (MAP), systolic blood pressure, diastolic blood pressure and heart rate were recorded: baseline time, 30 after L-nitro arginine methyl ester (L-NAME: 1 mg/Kg i.v.) and post L-arginine (L-arg: 250 mg/Kg i.v.) injection. L-NAME induced a significantly increase in MAP in all groups. This enhancement was smaller in diabetic than in control rats. The increase in MAP in HD was significantly lower than that in ND L-arg induced a significantly decrease in MAP in all groups. This decrease was significantly attenuated in diabetic compared with control rats. The degree of hypotension in response to L-arg in diabetic groups was lower in hypertensive than that in normotensive diabetic rats. These data suggest that an impairment of nitric oxide formation could be involved in the development of hypertension in this model.

Analysis of Variance↗

PubMed1997

Bombesin and zinc enhance the synergistic mitogenic effects of insulin and phosphocholine by a MAP kinase-dependent mechanism in Swiss 3T3 cells.

Simultaneous treatment of serum-starved (24 h) Swiss 3T3 cells with insulin (500 nM) and phosphocholine (PCho) (0.25-1 mM) resulted in synergistic stimulation of DNA synthesis via a mitogen activated protein (MAP) kinase-independent rapamycin-sensitive mechanism. Co-treatment of cells with bombesin (10 nM) or zinc (25 microM) enhanced the combined mitogenic effects of insulin and PCho 2-3-fold; however, in the presence of bombesin or zinc the combined effects of insulin and PCho were not inhibited by rapamycin. The potentiating effects of bombesin and zinc on insulin plus PCho-induced DNA synthesis were accompanied by large stimulation of p42 MAP kinase activity. The results indicate that in Swiss 3T3 cell cultures, synergistic stimulation of DNA synthesis by extracellular insulin and PCho via a p42 MAP kinase-dependent mechanism requires the presence of other growth regulatory agents, such as bombesin or zinc.

3T3 Cells↗

PubMed2005

Vegetation mapping for change detection on an arid-zone river.

A vegetation mapping system for change detection was tested at the Havasu National Wildlife Refuge (HNWR) on the Lower Colorado River. A low-cost, aerial photomosaic of the 4200 ha, study area was constructed utilizing an automated digital camera system, supplemented with oblique photographs to aid in determining species composition and plant heights. Ground-truth plots showed high accuracy in distinguishing native cottonwood (Populus fremontii) and willow (Salix gooddingii) trees from other vegetation on aerial photos. Marsh vegetation (mainly cattails, Typha domengensis) was also easily identified. However, shrubby terrestrial vegetation, consisting of saltcedar (Tamarix ramosissima), arrowweed (Pluchea sericea), and mesquite trees (Prosopis spp.), could not be accurately distinguished from each other and were combined into a single shrub layer on the final vegetation map. The final map took the form of a base, shrub and marsh layer, which was displayed as a Normalized Difference Vegetation Index map from a Landsat Enhanced Thematic Mapper (ETM+) image to show vegetation intensity. Native willow and cottonwood trees were digitized manually on the photomosaic and overlain on the shrub layer in a GIS. By contrast to present, qualitative mapping systems used on the Lower Colorado River, this mapping system provides quantitative information that can be used for accurate change detection. However, better methods to distinguish between saltcedar, mesquite, and arrowweed are needed to map the shrub layer.

Desert Climate↗