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Biomedical subjects

A Pines

Publications and source records attributed to A Pines.

At least 19 recordsLinked to original sources
PubMed2005

Time-of-flight flow imaging using NMR remote detection.

A time-of-flight imaging technique is introduced to visualize fluid flow and dispersion through porous media using NMR. As the fluid flows through a sample, the nuclear spin magnetization is modulated by rf pulses and magnetic field gradients to encode the spatial coordinates of the fluid. When the fluid leaves the sample, its magnetization is recorded by a second rf coil. This scheme not only facilitates a time-dependent imaging of fluid flow, it also allows a separate optimization of encoding and detection subsystems to enhance overall sensitivity. The technique is demonstrated by imaging gas flow through a porous rock.

Journal Article↗
PubMed2005

NMR detection using laser-polarized xenon as a dipolar sensor.

Hyperpolarized (129)Xe can be used as a sensor to indirectly detect NMR spectra of heteronuclei that are neither covalently bound nor necessarily in direct contact with the Xe atoms, but coupled through long-range intermolecular dipole-dipole interactions. To reintroduce long-range dipolar couplings the sample symmetry has to be broken. This can be done either by using an asymmetric sample arrangement, or by breaking the symmetry of the spin magnetization with field gradient pulses. Experiments are performed where only a small fraction of the available (129)Xe magnetization is used for each point, so that a single batch of xenon suffices for the point-by-point acquisition of a heteronuclear NMR spectrum. Examples with (1)H as the analyte nucleus show that these methods have the potential to obtain spectra with a resolution that is high enough to determine homonuclear J couplings. The applicability of this technique with remote detection is discussed.

Algorithms↗
PubMed2004

Hyperpolarized xenon nuclear spins detected by optical atomic magnetometry.

We report the use of an atomic magnetometer based on nonlinear magneto-optical rotation with frequency-modulated light to detect nuclear magnetization of xenon gas. The magnetization of a spin-exchange-polarized xenon sample (1.7 c m(3) at a pressure of 5 bars, natural isotopic abundance, polarization 1% ), prepared remotely to the detection apparatus, is measured with an atomic sensor. An average magnetic field of approximately 10 nG induced by the xenon sample on the 10 cm diameter atomic sensor is detected with signal-to-noise ratio approximately 10 , limited by residual noise in the magnetic environment. The possibility of using modern atomic magnetometers as detectors of nuclear magnetic resonance and in magnetic resonance imaging is discussed. Atomic magnetometers appear to be ideally suited for emerging low-field and remote-detection magnetic resonance applications.

Journal Article↗
PubMed2002

The impact of hormonal therapy for infertility on the age at menopause.

OBJECTIVES: To look for possible association between past history of ovulation induction and age at menopause. DESIGN: Women attending our postmenopausal outpatient clinic were asked to fill questionnaires with demographic data, obstetrical history (including treatment for infertility), and medical details related to menopause. PATIENTS: The study group (n=31) consisted of women with a history of ovulation induction, and a control group (n=200) included women who did not experience such intervention. RESULTS: The age at the final menstrual bleeding was 46.4+/-5 in the study group, and 50+/-4 for the control group (P<0.001). This difference was most prominent for women who had induction of ovulation prior to age 35 years: they entered menopause at age 43.8+/-5 years. Smoking had a weak effect on the age at menopause (48.5+/-4 for current, vs. 49.9+/-4 for non- or past-smokers; P<0.03). CONCLUSIONS: This retrospective and preliminary study raises the question whether hormonal manipulations and ovarian over-stimulation during fertility treatments could be a risk factor for premature menopause.

Adult↗
PubMed2002

Two-dimensional NMR correlations of liquid crystals using switched angle spinning.

We present the first application of switched angle spinning (SAS) to correlate the first-order dipolar spectrum of a liquid crystalline sample with the isotropic magic angle spinning (MAS) spectrum in a two-dimensional experiment. In this experiment we are able to select the degree of dipolar couplings introduced via mechanical manipulations of the liquid crystal director in a single oriented sample. The (19)F SAS-COSY correlation of iodotrifluoroethylene, an AMX spin system, dissolved in the nematic liquid crystal 4-octylphenyl-2-chloro-4-(4-heptylbenzoyloxy)-benzoate provides assignment of both the J and dipolar couplings in a single experiment. This work demonstrates the use of oriented samples and sample spinning to resolve homonuclear dipolar couplings using isotropic chemical shifts.

Journal Article↗
PubMed2002

APE/Ref-1 is controlled by both redox and cAMP-dependent mechanisms in rat thyroid cells.

APE/Ref-1 is a multifunctional protein possessing both redox and DNA repair functions. Through its redox activity, APE/Ref-1 controls the DNA-binding function of several transcriptional regulators (AP1, NF-kappaB, p53, Pax proteins). We have previously shown that APE/Ref-1 upregulates the transcriptional activity of the thyroid-specific transcription factor Pax8. In thyroid cells, APE/Ref-1 can be detected both in the nuclear and cytoplasmatic compartments. In this study regulatory mechanisms acting on APE/Ref-1 were revealed using the FRTL-5 cell line. TSH induces both cytoplasm-to-nucleus translocation and neosynthesis of APE/Ref-1 protein. Interestingly, only neosynthesis is dependent on cAMP signalling. In contrast, the cytoplasm-to-nucleus translocation is dependent on redox-mediated mechanisms. Based upon the data shown in this study and in others, a bimodal control of APE/Ref-1 by TSH can be delineated.

Animals↗
PubMed2001

An experimental and theoretical investigation of the chemical shielding tensors of (13)C(alpha) of alanine, valine, and leucine residues in solid peptides and in proteins in solution.

We have carried out a solid-state magic-angle sample-spinning (MAS) nuclear magnetic resonance (NMR) spectroscopic investigation of the (13)C(alpha) chemical shielding tensors of alanine, valine, and leucine residues in a series of crystalline peptides of known structure. For alanine and leucine, which are not branched at the beta-carbon, the experimental chemical shift anisotropy (CSA) spans (Omega) are large, about 30 ppm, independent of whether the residues adopt helical or sheet geometries, and are in generally good accord with Omega values calculated by using ab initio Hartree-Fock quantum chemical methods. The experimental Omegas for valine C(alpha) in two peptides (in sheet geometries) are also large and in good agreement with theoretical predictions. In contrast, the "CSAs" (Deltasigma) obtained from solution NMR data for alanine, valine, and leucine residues in proteins show major differences, with helical residues having Deltasigma values of approximately 6 ppm while sheet residues have Deltasigma approximately 27 ppm. The origins of these differences are shown to be due to the different definitions of the CSA. When defined in terms of the solution NMR CSA, the solid-state results also show small helical but large sheet CSA values. These results are of interest since they lead to the idea that only the beta-branched amino acids threonine, valine, and isoleucine can have small (static) tensor spans, Omega (in helical geometries), and that the small helical "CSAs" seen in solution NMR are overwhelmingly dominated by changes in tensor orientation, from sheet to helix. These results have important implications for solid-state NMR structural studies which utilize the CSA span, Omega, to differentiate between helical and sheet residues. Specifically, there will be only a small degree of spectral editing possible in solid proteins since the spans, Omega, for the dominant nonbranched amino acids are quite similar. Editing on the basis of Omega will, however, be very effective for many Thr, Val, and Ileu residues, which frequently have small ( approximately 15-20 ppm) helical CSA (Omega) spans.

Alanine↗
PubMed2001

Solid-state NMR studies of the secondary structure of a mutant prion protein fragment of 55 residues that induces neurodegeneration.

The secondary structure of a 55-residue fragment of the mouse prion protein, MoPrP(89-143), was studied in randomly aggregated (dried from water) and fibrillar (precipitated from water/acetonitrile) forms by (13)C solid-state NMR. Recent studies have shown that the fibrillar form of the P101L mutant of MoPrP(89-143) is capable of inducing prion disease in transgenic mice, whereas unaggregated or randomly aggregated samples do not provoke disease. Through analysis of (13)C chemical shifts, we have determined that both wild-type and mutant sequence MoPrP(89-143) form a mixture of beta-sheet and alpha-helical conformations in the randomly aggregated state although the beta-sheet content in MoPrP(89-143, P101L) is significantly higher than in the wild-type peptide. In a fibrillar state, MoPrP(89-143, P101L) is completely converted into beta-sheet, suggesting that the formation of a specific beta-sheet structure may be required for the peptide to induce disease. Studies of an analogous peptide from Syrian hamster PrP verify that sequence alterations in residues 101-117 affect the conformation of aggregated forms of the peptides.

Amino Acid Sequence↗
PubMed2001

Functionalized xenon as a biosensor.

The detection of biological molecules and their interactions is a significant component of modern biomedical research. In current biosensor technologies, simultaneous detection is limited to a small number of analytes by the spectral overlap of their signals. We have developed an NMR-based xenon biosensor that capitalizes on the enhanced signal-to-noise, spectral simplicity, and chemical-shift sensitivity of laser-polarized xenon to detect specific biomolecules at the level of tens of nanomoles. We present results using xenon "functionalized" by a biotin-modified supramolecular cage to detect biotin-avidin binding. This biosensor methodology can be extended to a multiplexing assay for multiple analytes.

Avidin↗
PubMed2001

Approach to high-resolution ex situ NMR spectroscopy.

Nuclear magnetic resonance (NMR) experiments are typically performed with samples immersed in a magnet shimmed to high homogeneity. However, there are many circumstances in which it is impractical or undesirable to insert objects or subjects into the bore of a high-field magnet. Here we present a methodology based on an adaptation of nutation echoes that provides resolved spectra in the presence of matched inhomogeneous static and radiofrequency fields, thereby opening the way to high-resolution ex situ NMR. The observation of chemical shifts is regained through the use of multiple-pulse sequences of correlated, composite z-rotation pulses, producing resolved NMR spectra of liquid samples.

Magnetic Resonance Spectroscopy↗
PubMed2001

Mitochondrial localization of APE/Ref-1 in thyroid cells.

Mutations of mitochondrial DNA (mtDNA) are associated with different human diseases, including cancer and aging. Reactive oxygen species produced during oxidative phosphorylation are a major source of mtDNA damage. It is not clear, however, whether DNA repair mechanisms, able to abolish effects due to oxidative damage, are present in mitochondria. APE/Ref-1 is a nuclear protein possessing both redox activity (by which activates, "in vitro", the DNA-binding functions of several transcription factors) and DNA repair activity over apurinic/apyrimidinic sites. Immunohistochemical evidences indicate that in follicular thyroid cells, APE/Ref-1 is located in both nucleus and cytoplasm. Electronmicroscopy immunocytochemistry performed in the rat thyroid FRTL-5 cell line, indicates that part of the cytoplasmatic APE/Ref-1 is located in mitochondria. The presence of APE/Ref-1 inside mitochondria is further demonstrated by western blot analysis after cell fractionation. In the Kimol cell line (which is derived from FRTL-5, transformed by the Ki-ras oncogene) the amount of mitochondrial APE/Ref-1 is reduced by three to fourfold with respect to the normal FRTL-5 cells. These results suggest that: (i) a machinery capable of repairing DNA damaged by oxidative stress is present in mitochondria and (ii) mtDNA repair mechanisms may be impaired during cell transformation.

Animals↗
PubMed2001

Characterization of the effects of nonspecific xenon-protein interactions on (129)Xe chemical shifts in aqueous solution: further development of xenon as a biomolecular probe.

The sensitivity of (129)Xe chemical shifts to weak nonspecific xenon-protein interactions has suggested the use of xenon to probe biomolecular structure and interactions. The realization of this potential necessitates a further understanding of how different macromolecular properties influence the (129)Xe chemical shift in aqueous solution. Toward this goal, we have acquired (129)Xe NMR spectra of xenon dissolved in amino acid, peptide, and protein solutions under both native and denaturing conditions. In general, these cosolutes induce (129)Xe chemical shifts that are downfield relative to the shift in water, as they deshield the xenon nucleus through weak, diffusion-mediated interactions. Correlations between the extent of deshielding and molecular properties including chemical identity, structure, and charge are reported. Xenon deshielding was found to depend linearly on protein size under denaturing solution conditions; the denaturant itself has a characteristic effect on the (129)Xe chemical shift that likely results from a change in the xenon solvation shell structure. In native protein solutions, contributions to the overall (129)Xe chemical shift arise from the presence of weak xenon binding either in cavities or at the protein surface. Potential applications of xenon as a probe of biological systems including the detection of conformational changes and the possible quantification of buried surface area at protein-protein interfaces are discussed.

Amino Acids↗