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Results for “Enhancer mapping”

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PubMed2000

The utility of intracardiac echocardiography in interventional electrophysiology.

With the mounting of an ultrasound transducer on the end of a percutaneously placed catheter, intracardiac echocardiography is now possible. It has become clear that endocardial anatomy plays a critical role in a variety of cardiac arrhythmias. The ability to visualize this anatomy, and it's relationship to mapping and ablation catheters, may greatly enhance the safety and efficacy of catheter ablation procedures.

Arrhythmias, Cardiac↗

PubMed1995

Methamphetamine-induced dopaminergic hyperactivity is not accompanied with increase in tyrosine hydroxylase mRNA of the rat midbrain.

Tyrosine hydroxylase (TH) mRNA was measured in the midbrain of rats treated repeatedly with methamphetamine (MAP). Male Sprague-Dawley rats were daily injected with MAP (5 mg/kg, i.p., once daily) or saline for 14 days. Progressive augmentation was observed in MAP-induced stereotyped behaviors. After one week of abstinence, the rats were decapitated and the brains were prepared for either in situ hybridization using non-radioactive cRNA probes or Northern blot analysis using 32P-labeled cDNA probes. In situ hybridization showed that the signals of TH mRNA were localized to the dopaminergic perikarya in the midbrain and were reduced in MAP-treated animals compared to the controls. Northern blot analysis revealed that the level of TH mRNA in the midbrain of MAP-treated rats was decreased by 37% compared to the controls, which was close to the statistical significance (P = 0.053). These results indicate that the dopaminergic hyperactivity caused by repeated MAP treatment is not associated with enhanced transcription of the TH gene.

Animals↗

PubMed1976

Neutron scattering for the analysis of membranes.

The advantageous use of neutron scattering techniques for the determination of membrane structures is described. Constituents of biological membranes show much larger differences in their scattering factors for neutrons than for X-rays, permitting the assignment of chemical groups to features in the Fourier map. Deuteration of particular components further enhances this difference and can be used to phase neutron data similar to the heavy atom technique of protein crystallography. Methods of contrast enhancement using H2O and 2H2O exchange, as well as secific deuterations, are outlined with examples from studies of sciatic nerve myelin artificial membranes and retinal rod outer segments.

Animals↗

PubMed2006

Some problems for representations of brain organization based on activation in functional imaging.

Functional brain imaging has overshadowed traditional lesion studies in becoming the dominant approach to the study of brain-behavior relationships. The proponents of functional imaging studies frequently argue that this approach provides an advantage over lesion studies by observing normal brain activity in vivo without the disruptive effects of brain damage. However, the enthusiastic onslaught of brain images, frequently presented as veridical representations of mental function, has sometimes overwhelmed some basic facts about brain organization repeatedly observed over more than a century. In particular, the lateralization of speech and language to the left cerebral hemisphere in over 90% of the right-handed population does not appear to have been taken as a serious constraint in the interpretation of imaging results in studies of these functions. This paper reviews a number of areas in which standard activation assumptions yield results that are at odds with clinical experience. The activation approach will be contrasted with a performance-based analysis of functional image data, which, at least in the case of speech production, yields results in better agreement with lesion data. Functional imaging represents enormous opportunities for understanding brain-behavior relationships, but at the present level of understanding of what is being represented in such images, it is premature to adhere to a single approach based on the strong but questionable assumptions inherent in most activation studies.

Animals↗

PubMed2005

A comparison of three SPRITE techniques for the quantitative 3D imaging of the 23Na spin density on a 4T whole-body machine.

Sodium density maps acquired with three SPRITE-based methods have been compared in terms of the resulting quantitative information as well as image quality and acquisition times. Consideration of factors relevant for the clinical implementation of SPRITE shows that the Conical-SPRITE variant is preferred because of a 20-fold reduction in acquisition time, slightly improved image quality, and no loss of quantitative information. The acquisition of a 3D data set (32x32x16; FOV=256x256x160 mm) for the quantitative determination of sodium density is demonstrated. In vivo Conical-SPRITE 23Na images of the brain of a healthy volunteer were acquired in 30 min with a resolution of 7.5x7.5x7.5 mm and a signal-to-noise ratio of 23 in cerebrospinal fluid and 17 in brain tissue.

Brain↗

PubMed2006

Combined simulated annealing and Shinnar-Le Roux pulse design of slice-multiplexed RF pulses for multi-slice imaging.

Slice-multiplexed RF pulses have recently been introduced for simultaneous multi-slice imaging. Their novel aspect is that each slice is given a different linear phase profile, and hence a different slice-rephasing requirement, by the pulse. During readout, extra slice gradients are applied such that when one slice is rephased, the others are dephased to prevent aliasing. In this paper, an improved method of designing slice-multiplexed RF pulses is presented: component pulses which are optimized with simulated annealing for a specific rephasing are combined using Shinnar-Le Roux methods. In this way, non-linearities at higher flip angles are taken into account and more slices can be excited. Bloch simulations show the phase and amplitude profile of component pulses are faithfully preserved in the multiplexed pulse. Three- and four-slice multiplex pulses are demonstrated in gradient- and spin-echo in-vivo imaging.

Algorithms↗

PubMed2004

Effect of tacrolimus and cyclosporine on renal microcirculation and nitric oxide production.

OBJECTIVES: Cyclosporine (CSA) and tacrolimus (TAC) frequently induce nephrotoxicity and similar pathologic changes. Acute CSA-induced nephrotoxicity has been reported to be mediated by activation of vasoconstrictors such as endothelin. The purpose of the present study was to investigate the acute effects of TAC and CSA on the renal microcirculation and upon a vasodilator such as nitric oxide (NO) production. METHODS: Renal blood flow (RBF) in the microcirculation was measured by a Laser Doppler flow meter in uninephrectomised rats. RBF, mean arterial pressure (MAP), and renal vascular resistance (RVR) were measured in the following groups: (a) TAC (0.1 to 2.0 mg/kg/h, n = 3 approximately 6); CSA (20 and 50 mg/kg/h, n = 5); (b) L-NAME (10 mg/kg), an NO synthase inhibitor, 8 minutes prior to TAC (0.5 and 1.5 mg/kg/h, n = 5), or CSA (20 and 50 mg/kg/h, n = 5). Stable NO end-products, serum NO(2) and NO(3), were measured by the Griess method (n = 5). RESULTS: None of the parameters were changed by TAC alone, whereas TAC with L-NAME significantly reduced RBF (-28 +/- 7%) and increased RVR (46 +/- 17%) in a dose-dependent manner. CSA alone significantly reduced RBF (-37 +/- 6%) and increased RVR (69 +/- 22%) without any changes in MAP. The effects of CSA were enhanced by L-NAME. Serum concentration of NO(2) + NO(3) was significantly reduced by both L-NAME alone and CSA (50 mg/kg) (P < .05), while there were no changes with TAC (1.5 mg/kg). CONCLUSIONS: Blockade of NO production enhance the vasoconstrictive effect of CSA, and unmasked such an effect of TAC. These results suggest that the nephrotoxicity of CSA and TAC may involve the NO system.

Animals↗

PubMed2002

Affinity panning of peptide libraries using anti-streptokinase monoclonal antibodies: selection of an inhibitor of plasmin(ogen) active site.

To select sequences complementary to their binding sites, two anti-streptokinase (SK) monoclonal antibodies (mAbs), A4.5 and A5.5, were used in biopanning of 15-mer and hexamer phage-displayed peptide libraries, respectively. mAb A4.5 inhibits the catalytic activity of streptokinase-plasminogen activator complex (SKPAC), the binding of plasminogen to SK and the binding of human anti-SK polyclonal Abs to SK. All clones selected from the 15-mer peptide library by mAb A4.5 had identical nucleotide and amino acid sequences, RSVYRCSPFVGCWFG. An 11-mer peptide (peptide A4.5, YRCSPFVGCWF) derived from this sequence inhibited the binding of mAb A4.5 and human anti-SK polyclonal Abs to SK as well as the catalytic activity of both SKPAC and plasmin. The binding of the second mAb (mAb A5.5) to SK is lost upon interaction of SK with plasminogen, suggesting that sequences selected by this mAb are likely associated with the C-terminal cleavage site of SK. Biopanning of a hexamer peptide library with mAb A5.5 selected the sequence RYLQDY that is homologous to residues 324-328, adjacent to one possible C-terminal cleavage site in SK. A 10-mer synthetic peptide (LDFRDLYDPR) corresponding to residues 321-330 in SK specifically inhibited the binding of mAb A5.5 to SK. The selection and characterization of these two peptides enhances our understanding of SK structure, maps an antigenic epitope, and identifies a peptide inhibitor of plasminogen activation.

Amino Acid Sequence↗

PubMedDate not supplied

Behavioral and brain imaging studies of saccadic performance in schizophrenia.

Data are reviewed from a series of saccadic studies demonstrating that schizophrenia subjects have normal performance on some types, and abnormal performance on other types, of tasks. Normal refixation saccade characteristics and BOLD signal change among schizophrenia subjects suggest that basic saccade generating circuitry is functionally intact among these subjects. Schizophrenia patients and their relatives, however, demonstrate difficulty with saccadic inhibition, a function ostensibly mediated by DLPFC circuitry. We review additional evidence for saccadic inhibition being associated with prefrontal circuitry provided by EEG and fMRI data. Minimum norm analysis of EEG data suggests that dipolar activity preceding correct antisaccades occurred preferentially in prefrontal cortex. Furthermore, there is an indication from the fMRI data that prefrontal activity may be increased in normal, but not in schizophrenia, subjects during antisaccade tasks. These data suggest that a research program relying on multiple functional imaging technologies may be helpful for furthering our understanding of schizophrenia's essential neuropathology.

Brain Mapping↗

PubMed1997

BDNF and NT-3 modulate expression and threonine phosphorylation of microtubule-associated protein 2 analogues, and alter their distribution in the developing rat cerebral cortex.

Effects of brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-3 on the expression of structural or synapse-associated proteins were examined in the developing rat cerebral cortex. Following ventricular administration of BDNF or NT-3 at embryonic day (E) 16, expression of microtubule-associated protein (MAP) 2 of 280 kDa was enhanced at E18 and/or E20, and threonine phosphorylation of MAP2 analogues of 120 and 66 kDa was modulated in different ways. NT-3 basically altered the distribution of MAP2 proteins at E20. These findings suggest that NT-3 and BDNF play a role in regulating production and phosphorylation of MAP2 analogues during development of the rat cerebral cortex.

Animals↗

PubMed2001

A quantitative comparison of motion detection algorithms in fMRI.

An important step in the analysis of fMRI time-series data is to detect, and as much as possible, correct for subject motion during the course of the scanning session. Several public domain algorithms are currently available for motion detection in fMRI. This paper compares the performance of four commonly used programs: AIR 3.08, SPM99, AFNI98, and the pyramid method of Thévenaz, Ruttimann, and Unser (TRU). The comparison is based on the performance of the algorithms in correcting a range of simulated known motions in the presence of various degrees of noise. SPM99 provided the most accurate motion detection amongst the algorithms studied. AFNI98 provided only slightly less accurate results than SPM99, however, it was several times faster than the other programs. This algorithm represents a good compromise between speed and accuracy. AFNI98 was also the most robust program in presence of noise. It yielded reasonable results for very low signal to noise levels. For small initial misalignments, TRU's performance was similar to SPM99 and AFNI98. However, its accuracy diminished rapidly for larger misalignments. AIR was found to be the least accurate program studied.

Algorithms↗

PubMed1998

Optimization of the ultrafast Look-Locker echo-planar imaging T1 mapping sequence.

The Look-Locker echo-planar imaging (LL-EPI) sequence has been numerically optimized in terms of the signal-to-noise ratio in the measured value of T1, for both single-shot (repetition time (TR) = infinity), and dynamically repeated T1 measurements. The sequence is optimized for the normal biologic range of T1 (0.2 s to 2.0 s) and for a range of sequence parameters found on most magnetic resonance (MR) scanners. Both linearly and geometrically spaced magnetization sample pulse intervals were considered. For single-shot measurements, the sequence with 24 linearly spaced sample pulses, an inversion time of 0.01 s, an inter-sample pulse delay of 0.10 s, and a sample radiofrequency (RF) pulse flip angle of 25 degrees was found to be optimum. When the number of sample pulses was limited due to hardware limitations, different pulse sequence parameters were indicated. The optimization procedures used are appropriate for any single-shot T1 mapping sequence variant and for any rapid T1 mapping application. The use of an optimized Look-Locker echo-planar imaging sequence is demonstrated by an example of dynamic contrast-enhanced scanning in the brain using fast T1 mapping.

Brain↗

PubMed1992

Identification of region-specific yeast artificial chromosomes using pools of Alu element-mediated polymerase chain reaction probes labeled via linear amplification.

The ability to identify large numbers of yeast artificial chromosomes (YACs) specific to any given genomic region rapidly and efficiently enhances both the construction of clone maps and the isolation of region-specific landmarks (e.g., polymorphic markers). We describe a method of preparing region-specific single-stranded hybridization probes from Alu element-mediated polymerase chain reaction (Alu-PCR) products of somatic cell hybrids for YAC library screening. Pools of up to 50 cloned Alu-PCR products from an irradiation-reduced hybrid containing 22q11.2-q13.1 were labeled to high specific activity by linear amplification using a single vector primer. The resulting single-stranded probes were extensively competed to remove repetitive sequences, while retaining the full complexity of the probe. Extensive coverage of the region by YACs using multiple probe pools was demonstrated as many YACs were detected more than once. In situ analysis using chosen YACs confirmed that the clones were specific for the region. Thus, this pooled probe approach constitutes a rapid method to identify large numbers of YACs relevant to a large chromosomal region.

Base Sequence↗

PubMed2000

Regulation of neuregulin signaling by PSD-95 interacting with ErbB4 at CNS synapses.

Neuregulins (NRGs) and their receptors, the ErbB protein tyrosine kinases, are essential for neuronal development, but their functions in the adult CNS are unknown. We report that ErbB4 is enriched in the postsynaptic density (PSD) and associates with PSD-95. Heterologous expression of PSD-95 enhanced NRG activation of ErbB4 and MAP kinase. Conversely, inhibiting expression of PSD-95 in neurons attenuated NRG-mediated activation of MAP kinase. PSD-95 formed a ternary complex with two molecules of ErbB4, suggesting that PSD-95 facilitates ErbB4 dimerization. Finally, NRG suppressed induction of long-term potentiation in the hippocampal CA1 region without affecting basal synaptic transmission. Thus, NRG signaling may be synaptic and regulated by PSD-95. A role of NRG signaling in the adult CNS may be modulation of synaptic plasticity.

Animals↗

PubMed2000

Characterization of the regulatory elements controlling neuronal expression of the A-isoform of the ecdysone receptor gene of Drosophila melanogaster.

During the development of the adult central nervous system (CNS) of the fruitfly Drosophila melanogaster, the A-isoform of the ecdysone receptor (EcR-A), a typical nuclear hormone receptor, is expressed at high levels in the Type II neurons, a set of neurons that die shortly after the emergence of the adult. To understand the role that transcriptional regulation of nuclear receptor genes plays in CNS development, we have dissected the region controlling the transcription of EcR-A by analyzing the ability of this region to drive the expression of reporter genes in transgenic animals. These analyses have demonstrated that the Type II neurons are a heterogeneous collection of neurons that utilize different regulatory elements to coordinate the expression of the same transcript.

Animals↗

PubMed2006

The photodissociation dynamics of O2 at 193 nm: an O3PJ angular momentum polarization study.

In the following paper we present translational anisotropy and angular momentum polarization data for O((3)P(1)) and O((3)P(2)) products of the photodissociation of molecular oxygen at 193 nm. The data were obtained using polarized laser photodissociation coupled with resonantly enhanced multiphoton ionization and velocity-map ion imaging. Under the jet-cooled conditions employed, absorption is believed to be dominated by excitation into the Herzberg continuum. The experimental data are compared with previous experiments and theoretical calculations at this and other wavelengths. Semi-classical calculations performed by Groenenboom and van Vroonhoven [J. Chem. Phys, 2002, 116, 1965] are used to estimate the alignment parameters arising from incoherent excitation and dissociation and these are shown to agree qualitatively well with the available experimental data. Following the work of Alexander et al. [J. Chem. Phys, 2003, 118, 10566], orientation and alignment parameters arising from coherent excitation and dissociation are modelled more approximately by estimating phase differences generated subsequent to dissociation via competing adiabatic pathways leading to the same asymptotic products. These calculations lend support to the view that large values of the coherent alignment moments, but small values of the corresponding orientation moments, could arise from coherent excitation of (and subsequent dissociation via) parallel and perpendicular components of the Herzberg I, II and III transitions.

Anisotropy↗

PubMed2005

[Clinical highfield MR].

MRI-imaging using a field strength above 2 Tesla -- recently termed "highfield MRI" -- has come into clinical use in the last three years. For technical reasons, the initial application of highfield MRI concentrated on examinations of the brain. By improving the technology and solving specific problems, it has now become possible to perform total body scans. Only a few studies have been carried out to determine whether the use of highfield MRI is advantageous compared to scanning at the usual field strengths, and what these advantages might be. MR-angiography of cerebral vessels as well as certain aspects of structural imaging of the brain seem to benefit. BOLD contrast fMRI, perfusion analysis and spectroscopy all seem to improve. For total body scanning, it is already possible to examine certain areas in "1.5 Tesla quality", in some cases shortening scanning time considerably. This survey summarises the present state of knowledge, realising that the presentation might not be all-comprising since progress in this field is very dynamic.

Brain↗

PubMed2005

Enhanced hypotensive effects of the essential oil of Ocimum gratissimum leaves and its main constituent, eugenol, in DOCA-salt hypertensive conscious rats.

The cardiovascular effects of intravenous (i.v.) treatment with the essential oil of Ocimum gratissimum (EOOG) and its main constituent, eugenol (Eug) were investigated in the experimental model of deoxycorticosterone acetate (DOCA-salt)-hypertensive rats. In both conscious DOCA-salt hypertensive rats and their uninephrectomized controls, i.v. bolus injections of EOOG (1 - 20 mg/kg) or Eug (1 - 10 mg/kg) induced dose-dependent hypotension and bradycardia. Treatment with DOCA-salt significantly enhanced the maximal decreases in mean aortic pressure (MAP) elicited by hexamethonium (30 mg/kg, i.v.) as well as the hypotensive responses to both EOOG and Eug without affecting the bradycardia. However, the enhancement of EOOG-induced hypotension in hypertensive rats remained unaffected by i.v. pretreatment with either hexamethonium (30 mg/kg) or methylatropine (1 mg/kg). These results show that i.v. treatment with EOOG or Eug dose-dependently decreased blood pressure in conscious DOCA-salt hypertensive rats, and this action is enhanced when compared with uninephrectomized controls. This enhancement appears related mainly to an increase in EOOG-induced vascular smooth relaxation rather than to enhanced sympathetic nervous system activity in this hypertensive model.

Animals↗