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Biomedical subjects

R P Millane

Publications and source records attributed to R P Millane.

6 recordsLinked to original sources

Ordered water in hydrated solid-state polysaccharide systems.

Water molecules within a monolayer or so of macromolecular surfaces are often located in well-defined positions and have restricted mobility. These ordered water molecules play a role in stabilizing polysaccharide ordered structures and intermolecular interactions that are the basis of the rheological properties utilized in food systems. X-ray fiber diffraction can be used to determine the three-dimensional structures of polysaccharides in solid, but well-hydrated, polycrystalline fibers. In favorable cases, difference Fourier synthesis can be used to locate ordered water molecules in these systems, allowing one to visualize their functionally important interactions. These studies provide relevant evidence regarding water interactions in more hydrated systems and in solution. The functionality of ordered water in some polysaccharides used in food systems, as well as in some connective tissue glycosaminoglycans where the ordered water has been defined in considerable detail, as determined by fiber diffraction, is described in this chapter. These structures allow one to derive some general features of the role of ordered water in such systems.

Carbohydrate Sequence

Effects of disorder on fibre diffraction patterns.

Diffraction patterns from oriented polycrystalline specimens of fibrous polymers sometimes contain features indicating that the constituent microcrystallites are disordered. Such disorder affects the relationship between the crystal structure and the diffracted intensities. Therefore, the effects of disorder must be considered when determining structures from fibre diffraction data. Theory is developed here that describes the intensities diffracted by disordered polycrystalline fibres, and is used to calculate diffraction patterns from stimulated specimens with various kinds of disorder. The results show how Bragg and continuous diffraction are distributed on such diffraction patterns, and implications for structure determination are discussed.

Crystallization

A model of atrioventricular nodal conduction.

A model of cardiac impulse propagation through the atrioventricular node is described. The model is based on a synthesis of various experimentally determined characteristics of atrioventricular nodal conduction. The model can be set up to mimic a particular patient's atrioventricular node, by using data collected during routine electrophysiological studies. It can also be used as a component in a larger model of the cardiac conduction system, to simulate cardiac arrhythmias.

Arrhythmias, Cardiac

A re-examination of the crystal structure of A-DNA using fiber diffraction data.

Classical A-DNA helices with h = 0.25 nm may represent the greatest mass per unit length attainable by polynucleotide duplexes. The X-ray diffraction pattern from polycrystalline and well-oriented fibers of calf thymus DNA in its A-form has been carefully re-examined. Indexing on the basis of a C-face-centered monoclinic unit cell of dimensions a = 2.170 nm, b = 3.990 nm, c = 2.803 nm and beta = 96.82 degrees is superior to alternatives that have been proposed. Two right-handed. Watson-Crick base-paired, helical DNA chains with 2 X 11 nucleotides per 2.803 nm pitch, each carrying C3'-endo furanose rings, pass through the unit cell. The crystallography requires the two chains in the duplex to be antiparallel and conformationally identical but the 11 nucleotides in each pitch may be distinct. However, a secondary structure with a mononucleotide asymmetric unit provides as good an X-ray agreement as one with 11 distinct nucleotides. This relative lack of variability is quite different from what is observed in fibrous B-DNAs.

Animals

Structure of the alpha-form of poly[d(A)].poly[d(T)] and related polynucleotide duplexes.

The alpha-form of poly[d(A)].poly[d(T)], observed in fibers at high (greater than 80%) relative humidity, is a 10-fold double-helical structure of pitch 3.2 nm. This new X-ray analysis shows that the two strands of the double helix are of the same kind conformationally and both B-like in containing C-2'-endo-puckered deoxyribose rings. Nevertheless, the two strands are different enough for the overall morphology of the duplex to resemble that of the heteromerous model for the drier (beta) form of poly[d(A)].poly[d(T)] in which one strand has C-2'-endo rings and the other C-3'-endo. Since the orientations of the bases in poly[d(A)].poly[d(T)] are persistently different from those of classical B-DNA it is likely that there will be local bending (about 10 degrees) at the junctions between general sequence tracts and the oligo[d(A)].oligo[d(T)] tracts that occur in some native DNAs. The conclusions about the structure of alpha-poly[d(A)].poly[d(T)] are reinforced by independent analyses of similar X-ray diffraction patterns from poly[d(A)].poly[d(U)] and poly[d(A-I)].poly[d(C-T)].

Models, Molecular

DNA-RNA hybrid secondary structures.

DNA-RNA and DNA-DNA duplexes are even more polymorphic than observed previously. DNA-RNA hybrids can have secondary structures like A-DNA or A-RNA, but double helices of the synthetic DNA-RNA hybrids poly(dA) X poly(rU) and poly(dI) X poly(rC), respectively, form 11-fold and 10-fold double-helical structures in which the two chains have quite different conformations. Extensive X-ray fiber diffraction analyses show that in both structures the DNA chains have C-2'-endo-puckered furanose rings, while the anti-parallel RNA chains have C-3'-endo-puckered rings. The bidirectional properties of such duplexes may be important in the transfer of biological information from nucleic acids.

Base Composition