Biomedical subjects

Jeanine J Prompers

Publications and source records attributed to Jeanine J Prompers.

6 recordsLinked to original sources

PubMed2006

Regional variations in intramyocellular lipid concentration correlate with muscle fiber type distribution in rat tibialis anterior muscle.

1H MR spectroscopy (MRS) has proved to be a valuable noninvasive tool to measure intramyocellular lipids (IMCL) in research focused on insulin resistance and type II diabetes in both humans and rodents. An important determinant of IMCL is the muscle fiber type, since oxidative type I fibers can contain up to three times more IMCL than glycolytic type II muscle fibers. Because these different muscle fiber types are inhomogeneously distributed in rodent muscle, in the present study we investigated the distribution of IMCL within the rat tibialis anterior muscle (TA) in vivo using single-voxel 1H MRS along with the muscle fiber distribution in the TA ex vivo determined from immunohistological assays. IMCL levels in the TA differed by up to a factor of 3 depending on the position of the voxel. The distribution of IMCL over the TA cross section was not random, but emerged in a pattern similar to the distribution of the predominantly oxidative muscle fiber types. Dietary interventions, such as high-fat feeding and 15 hr of fasting, did not significantly change this typical fiber type-dependent pattern of IMCL content. These results stress the importance of voxel positioning when single-voxel 1H MRS is used to study IMCL in rodent muscle.

Animal Feed↗

PubMed2006

Dynamic MRS and MRI of skeletal muscle function and biomechanics.

MR is a powerful technique for studying the biomechanical and functional properties of skeletal muscle in vivo in health and disease. This review focuses on 31P, 1H and 13C MR spectroscopy for assessment of the dynamics of muscle metabolism and on dynamic 1H MRI methods for non-invasive measurement of the biomechanical and functional properties of skeletal muscle. The information thus obtained ranges from the microscopic level of the metabolism of the myocyte to the macroscopic level of the contractile function of muscle complexes. The MR technology presented plays a vital role in achieving a better understanding of many basic aspects of muscle function, including the regulation of mitochondrial activity and the intricate interplay between muscle fiber organization and contractile function. In addition, these tools are increasingly being employed to establish novel diagnostic procedures as well as to monitor the effects of therapeutic and lifestyle interventions for muscle disorders that have an increasing impact in modern society.

Adenosine Triphosphate↗

PubMed2003

Cross-correlation suppressed T1 and NOE experiments for protein side-chain 13CH2 groups.

Relaxation measurements of side-chain 13CH2-groups of uniformly 13C labeled human ubiquitin were performed at 600 MHz and 800 MHz magnetic field strength at 30 degrees C. Dipole-dipole cross-correlated relaxation effects in T1 experiments were suppressed by the combination of radio-frequency pulses and pulsed field gradients during the relaxation delay leading to monoexponential relaxation decays that allow a more accurate extraction of the 13C T1 relaxation times. Heteronuclear [1H]-13C NOEs obtained by using different proton saturation schemes indicate that the influence of cross-correlation is small. The experimental T1 and NOE data were interpreted in a model-free way in terms of a generalized order parameter and an internal correlation time.

Amino Acids↗

PubMed2002

General framework for studying the dynamics of folded and nonfolded proteins by NMR relaxation spectroscopy and MD simulation.

A general framework is presented for the interpretation of NMR relaxation data of proteins. The method, termed isotropic reorientational eigenmode dynamics (iRED), relies on a principal component analysis of the isotropically averaged covariance matrix of the lattice functions of the spin interactions responsible for spin relaxation. The covariance matrix, which is evaluated using a molecular dynamics (MD) simulation, is diagonalized yielding reorientational eigenmodes and amplitudes that reveal detailed information about correlated protein dynamics. The eigenvalue distribution allows one to quantitatively assess whether overall and internal motions are statistically separable. To each eigenmode belongs a correlation time that can be adjusted to optimally reproduce experimental relaxation parameters. A key feature of the method is that it does not require separability of overall tumbling and internal motions, which makes it applicable to a wide range of systems, such as folded, partially folded, and unfolded biomolecular systems and other macromolecules in solution. The approach was applied to NMR relaxation data of ubiquitin collected at multiple magnetic fields in the native form and in the partially folded A-state using MD trajectories with lengths of 6 and 70 ns. The relaxation data of native ubiquitin are well reproduced after adjustment of the correlation times of the 10 largest eigenmodes. For this state, a high degree of separability between internal and overall motions is present as is reflected in large amplitude and collectivity gaps between internal and overall reorientational modes. In contrast, no such separability exists for the A-state. Residual overall tumbling motion involving the N-terminal beta-sheet and the central helix is observed for two of the largest modes only. By adjusting the correlation times of the 10 largest modes, a high degree of consistency between the experimental relaxation data and the iRED model is reached for this highly flexible biomolecule.

Computer Simulation↗

PubMed2002

Dynamic and structural analysis of isotropically distributed molecular ensembles.

An efficient new method is presented for the characterization of motional correlations derived from a set of protein structures without requiring the separation of overall and internal motion. In this method, termed isotropically distributed ensemble (IDE) analysis, each structure is represented by an ensemble of isotropically distributed replicas corresponding to the situation found in an isotropic protein solution. This leads to a covariance matrix of the cartesian atomic positions with elements proportional to the ensemble average of scalar products of the position vectors with respect to the center of mass. Diagonalization of the covariance matrix yields eigenmodes and amplitudes that describe concerted motions of atoms, including overall rotational and intramolecular dynamics. It is demonstrated that this covariance matrix naturally distinguishes between "rigid" and "mobile" parts without necessitating a priori selection of a reference structure and an atom set for the orientational alignment process. The method was applied to the analysis of a 5-ns molecular dynamics trajectory of native ubiquitin and a 40-ns trajectory of a partially folded state of ubiquitin. The results were compared with essential dynamics analysis. By taking advantage of the spherical symmetry of the IDE covariance matrix, more than a 10-fold speed up is achieved for the computation of eigenmodes and mode amplitudes. IDE analysis is particularly suitable for studying the correlated dynamics of flexible and large molecules.

Computer Simulation↗

PubMed2002

Assignment strategy for proteins with known structure.

In protein NMR the assignment of nuclear spin resonances is a prerequisite for all subsequent applications, such as studies of ligand binding, protein-DNA interactions, and dynamics. Resonance assignment is a time consuming step even when the 3D x-ray structure of the protein is available. A new strategy is presented to solve the "inverse" assignment problem, which is the determination of the NMR resonance assignment from a known 3D protein structure. The protocol employs NMR data in the form of residual dipolar couplings and chemical shifts, while it does not require any sequential NMR connectivity information. The assignment problem is mathematically formulated in terms of a weighted matching problem that can be computationally efficiently solved by a combinatorial optimization algorithm. The protocol is applied to ubiquitin using two or three residual dipolar couplings per amino acid measured in Pfl phage medium together with chemical shift information. The algorithm yields for more than 90% of the protein backbone resonances the correct assignment.

Algorithms↗