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Biomedical subjects

M C Lawrence

Publications and source records attributed to M C Lawrence.

31 records · Page 2Linked to original sources

The three-dimensional structure of the seed storage protein phaseolin at 3 A resolution.

The polypeptides of the trimeric seed storage protein phaseolin comprise two structurally similar units each made up of a beta-barrel and an alpha-helical domain. The beta-barrel has the 'jelly-roll' folding topology of the viral coat proteins and the alpha-helical domain shows structural similarity to the helix-turn-helix motif found in certain DNA-binding proteins.

Amino Acid Sequence↗

Modelling the surface lattice of alpha-keratin filaments.

A recently-proposed model for the distribution of scattering material on the surface lattice of alpha-keratin intermediate filaments in dry porcupine quill is examined in detail. It is shown that, while retaining the basic form of the model (namely a dislocated helix with finite lattice spacing of 198.2 A), alternative meridonal distributions of scattering material within the finite lattice unit cell can be obtained which are consistent with the low-angle meridional X-ray pattern. The Gaussian shape function used to demonstrate the finite lattice in the model is questioned. The meridional diffraction pattern from hydrated porcupine quill is also examined and, apart from the intense fifth order reflection, can be modelled by distortion of the dry species scattering material distribution.

Animals↗

The application of the maximum entropy method to electron microscopic tomography.

The maximum entropy method has been applied to single axis tilt electron microscopic tomography. Its application requires that the problem be correctly formulated and that the model for the noise in electron micrographs be developed. A suitable noise model was determined empirically. The maximum entropy method was applied to a reconstruction of a test object from projections to which noise had been added. These reconstructions were superior to those obtained by reciprocal space weighted back protection. The method was also robust towards the incorrect specification of the noise, the penalty being an increase in the time required for convergence rather than degradation of the quality of the reconstructed image. In the reconstruction of negatively stained chromatin fibres it was possible to obtain satisfactory images utilizing all the information in the projections, in contrast to conventional methods in which high resolution data are removed by the application of Fourier space filters.

Algorithms↗

A method for monitoring the collapse of plastic sections as a function of electron dose.

We present a method for monitoring the collapse of plastic sections when irradiated in the electron microscope. The two surfaces of the section are separately coated with colloidal gold particles. The section is then tilted to an angle of 45 degrees in the microscope and a series of micrographs recorded, corresponding to increasing total electron dose. The collapse of the specimen normal to the plane of the section causes a relative movement in the image of the two sets of particles marking the two surfaces. By measuring the positions of a few gold particles on each side of the section in each exposure of the series, the collapse and also the in-plane shrinkage can be computed. The sections exhibit a rapid initial collapse, followed by a much slower phase of thinning. These effects should be taken into account when producing quantitative three-dimensional maps from tilt series of sectioned material.

Animals↗

Dose-related effects of isoflurane on superior mesenteric vasoconstriction induced by endotoxemia in the rat.

To investigate the interplay between endotoxin-induced circulatory shock and the cardiovascular effects of different doses of isoflurane, mean aortic pressure (MAP), central venous pressure (CVP), mean pulmonary arterial pressure (MPAP), heart rate (HR), cardiac output and superior mesenteric artery flow (SMAF), were monitored in rats anesthetized with either 1.4% or 2.0% isoflurane in oxygen. Cardiac index (Cl), total peripheral vascular resistance (TPR) and superior mesenteric vascular resistance (SMVR) were derived. During continuous administration of isoflurane, endotoxin (LD90, 40 mg X kg-1 iv) was given after a 30-min baseline period, and data were collected for an additional 2-h period. Sham-challenged (saline) animals served as controls. The response to endotoxin in the systemic circulation showed a decrease in Cl and MAP, while HR and TPR increased. MPAP and CVP were essentially unchanged. There were no significant differences in the systemic circulation variables between endotoxin groups, apart from a more pronounced HR increase during 1.4% isoflurane. Regionally, however, SMAF was lower and SMVR was higher in the 2.0% versus the 1.4% isoflurane group following endotoxin. To conclude, the degree of mesenteric vasoconstriction during endotoxemia was dependent on the dose of isoflurane. This dose-related effect seems to be mediated through interaction with intrinsic vascular control, a higher dose allowing a more pronounced local blood flow reduction.

Animals↗

Crystallographic structure of allosterically inhibited phosphofructokinase at 7 A resolution.

The structure of the allosterically inhibited form of phosphofructokinase from Bacillus stearothermophilus has been determined by X-ray crystallography to 7 A resolution by molecular replacement using the known structure of the active state as a starting model. Comparing the inhibited state with the active state, the tetramer is twisted about its long axis such that one pair of subunits in the tetramer rotates relative to the other pair by about 8 degrees around one of the molecular dyad axes. This rotation partly closes the binding site for the co-operative substrate fructose-6-phosphate, explaining its weaker binding to this conformational state. Within the subunit, one domain rotates relative to the other by 4.5 degrees, which further closes the fructose-6-phosphate site, without closing the cleft between the domains of the same subunit: this motion causes little change to the catalytic site. This T-state model is consistent with the simple allosteric kinetic scheme in which the active and the inhibited conformations differ in their affinities for fructose-6-phosphate, but not in their catalytic rates. It does not explain the heterotropic allosteric effects.

Allosteric Site↗

The nature of heme-aniline interactions during hemin-mediated oxygen activation and insertion reactions.

The interaction of aniline with hemin during oxygen activation and insertion mediated by the metalloporphyrin has been studied by a combined theoretical, semiempirical, and experimental approach. Results indicate that association is via a planar pi bonding interaction between the aromatic pi electrons of the amine and tetrapyrrole ring system. The effect of very high concentrations of hydroxyl radical scavengers on the system is discussed.

Aniline Compounds↗

Four universal forms of chlorophyll a.

We have matched the red absorption band measured at -196 C in a variety of chloroplast preparations with four major component curves representing forms of chlorophyll a having peaks at 661.6, 669.6, 677.1, and 683.7 nanometers. Chloroplast fractions enriched in one or the other of the two photochemical systems both contain these four major components, but system 1 preparations contain relatively more chlorophyll a 684. Chlorophyll a 677 and chlorophyll a 684 have greater bandwidths in system 1. Bands at longer wavelengths near 693 and 704 nanometers also often occur, but with far smaller heights than the above major bands. The longer wavelength bands are more common in system 1 than in system 2. In system 1 the half-widths of the four major bands in typical spectra average 11.3, 10.0, 10.3, and 10.8 nanometers while in system 2 they are 11.6, 9.8, 9.4, and 9.6 nanometers. Some spectra with sharper and some with wider bands were found, but the wavelengths were identical.

Journal Article↗