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Biomedical subjects

W J Moore

Publications and source records attributed to W J Moore.

At least 55 records · Page 3Linked to original sources

Conformation of myelin basic protein and its role in myelin formation.

High resolution 13C and 1H NMR spectra of myelin basic protein over a range of pH and concentrations indicate that intramolecular folding of the polypeptide chain occurs in aqueous solution in the region of residues 85 to 116. At pH 4 in D2O solution, the 13C resonances due to nonprotonated carbons of phenylalanine and tryptophan are broadened and chemically shifted compared to the same resonances when the protein is dissolved in 6M guanidinium hydrochloride. These residues occur in the region of the polypeptide chain in which the intramolecular folding may occur. As the pH is raised and the positive charge on the protein reduced from 28 to 18, intermolecular aggregation occurs, which appears to involve these same folded regions. Data on T1 (longitudinal relaxation times) of protons indicate also that amino-acid sidechains vary considerably in their motional freedoms. The concentration dependence of the proton NMR spectra provides further information on association of protein monomers. The region of the protein involved in folding, polymerization and substrate specificities is conservative in various species and we can surmise that it may have a specialized role in protein-lipid interactions in the myelin membrane. We suggest that the protein forms dimers across the cytoplasmic apposition during the formation of myelin. Estimates of the repulsive energies of interaction between approaching membranes suggest that some special mechanism of this kind is required to overcome the repulsive forces due to breakdown of water structure and electrostatic interaction.

Animals↗

Associations in the hominoid facial skeleton.

A comparative study has been made of the correlations between numerous linear and angular dimensions of the facial skeleton of man and the three great apes. The Varimax (rotated orthogonal) factor analysis was found to be an essential aid in analysing the very large correlation matrices obtained. It indicated that three groups of association can be identified in the hominoid skull. The first reflects co-ordonated variation in total skull size; the second, co-ordinated variation within common anatomical regions; the third, co-ordination between the jaws and dentition. A broadly similar pattern was found in each group for all four genera. The principal contrasts between man, on the one hand, and the apes, on the other, were found in groups 1 and 2. The most prominent of these was a generally much tighter degree of association between the size and position of upper and lower jaws in the apes, and a consequently reduced tendency for disruption of the occlusal relationship of the teeth.

Animals↗

Further studies on skull growth in achondroplasic (cn) mice.

The morphology of the basioccipital, basisphenoid and mandibular bones in achondroplasic (cn/cn) mice was compared with that of normal siblings. The two bones of the cranial base were markedly reduced in length but not in width. The percentage reduction in the basisphenoid was twice that in the basioccipital bone and of the same magnitude as that previously observed in the long bones of the limbs. This difference may arise because the basisphenoid, like the long bones, grows in length from two cartilaginous growth sites while the basioccipital grows from one cartilaginous and one periosteal site. The mandible of the cn/cn mice was also reduced in size, although to a lesser extent than were the cranial bones and without the ensuing disproportion. The scale of the mandibular changes suggests that they are largely attributable to regulatory responses to the shortened cranium. The finding that the condylar cartilage of the cn/cn mice is reduced in thickness indicates, however, that the cn gene may have a direct effect on condylar chondrocytes.

Achondroplasia↗

Logarithmic growth of the hominoid mandible.

The growth of the basal unit of the mandible was studied by plotting the position, relative to the median plane, of the oval, mandibular and mental foramina in immature and adult skulls of Man, chimpanzee and gorilla. In Man, the basal unit was found to grow out along a constant logarithmic spiral. In the apes, the basal unit grew along a constant logarithmic spiral, the amount of unfolding being greater in the gorilla than in the chimpanzee. It is argued that the mode of growth seen in the apes evolved, as these forms became more prognathous, because it requires less compensatory rotation of the mandible, while the mode seen in Man is probably closer to that which occurred in common ancestral form.

Adult↗

The development and structure of the chimpanzee mandible.

The sites of growth and remodeling, and the associated changes in cortical bone structure, have been studied in the chimpanzee mandible and compared with those previously reported in the human and macaque mandibles. The location of the principal sites of growth, and the distribution of the areas of deposition and resorption in the ramus, were found to be similar in all three species. In the chimpanzee, unlike Man, the bone being deposited at the condyle, posterior border of the ramus and coronoid process was plexiform in nature, indicating very rapid growth. The pattern of remodeling in the mandibular body, on the other hand, showed marked species differences at the chin and on the submandibular lingual surface, which account for the contrasts seen in the adult morphology of these regions. Although the pattern of distribution of cortical densities differed from that of surface remodeling, the information they give is complementary in analysing bone growth. The densest regions were found to coincide with sites of consistent lamellar deposition, while the least dense regions were those where plexiform bone was formed. Areas where remodeling led to the greatest reorientation of bone tissue within the cortex showed the greatest disparity between the two patterns.

Age Determination by Teeth↗

Subcellular and regional distribution of 125I-labeled alpha-bungarotoxin binding in rat brain and its relationship to acetylcholinesterase and choline acetyltransferase.

1. The subcellular distribution of binding sites for 125I-labeled alpha-bungarotoxin was studied in rat cerebral cortex. Primary fractions showing higher specific activity than homogenate were P2 (crude mitochondria and nerve endings) and P3-P2 was subfractionated on a Ficoll gradient with the P2B (nerve ending) subfraction exhibiting the greatest recovery (65%) and enrichment of toxin binding. Toxin binding showed a distribution similar to that of acetylcholinesterase, choline acetyltransferase, and sodium and potassium ion-activated ATPase. 2. P2B and P3 were subfractionated on five-step discontinuous sucrose gradients. The highest specific activity of toxin binding and acetylcholinesterase was associated with fractions of relatively low buoyant density, while choline acetyltransferase activity was associated with fractions of higher density. 3. Toxin binding, acetylcholinesterase, and choline acetyltransferase activities were relatively high in olfactory lobes, cerebral cortex, thalamic region, caudate nucleus, and brain stem; intermediate in hippocampus; low in cerebellum. 4. The relationship of toxin binding to the putative acetylcholine receptor in brain is discussed.

Acetylcholinesterase↗

Synthesis of membrane protein in slices of rat cerebral cortex.

Protein synthesis was studied in slices from rat cerebral cortex and localized in various purified subcellular membrane fractions isolated after incubation with L-leucine. A synaptosomal fraction isolated from a several times washed crude mitochondrial pellet showed very little contamination by free membranes, and the synaptic membrane fraction isolated from it was estimated to c +ain about 50% of this component. Leucine incorporation into all fractions was highly sensitive (greater than 95%) to emetine except for the cell and synaptic mitochondrial subfractions. They were only 60 to 70% inhibited by emetine and showed 10 to 20% inhibition by chloramphenicol which probably was due to those proteins synthesized in situ by the mitochondria. The net rate of incorporation of labeled protein into the synaptosomal and synaptic membrane subfractions was low, and axonal flow was excluded as a significant source of this label. On the basis of autoradiography it was concluded that the majority of the protein label was contributed by free and membrane-enclosed ribosome-containing contaminants in these fractions. Unlabeled and labeled subcellular fractions were also analyzed by electrophoresis in the presence of sodium dodecyl sulfate. The staining profiles of the microsomal and synaptic membrane subfractions were nearly identical, whereas those of synaptic mitochondria and the soluble proteins of the cell bodies were unique. The labeling of all proteins was blocked by emetine, except for the synaptic mitochondria (cell mitochondria were not examined). These products of mitochondrial protein synthesis exhibited three labeling peaks, the major one with a molecular weight of approximately 38,000. In the absence of emetine, slices incorporated amino acids into soluble and microsomal proteins with high specific activity. The labeled proteins of the soluble fraction were more highly concentrated in the range of molecular weights smaller than 50,000 than were those in the microsomal fraction, and it was concluded that a considerable portion of the protein-synthesizing machinery of the brain is geared to form soluble proteins. The gel patterns of labeled microsomal and synaptic membranes were consistent with contamination by the former contributing most of the protein label in the latter.

Animals↗

Anatomical differences in the femur and tibia between Negroids and Caucasoids antheir effects upon locomotion.

Nine variables of length, width and circumference of the femur and tibia were measured on post-cranial remains of 28 Caucasoids and 45 Negroids. The distance from the point of tibial attachment of the patellar ligament to the head of the tibia (PLID) was also determined. It was found that the Negroid has a significantly longer and narrower femur and tibia than the Caucasoid, although PLID did not vary between the two groups. Thus PLID, relative to the length of the tibia, was less in Negroids than Caucasoids. A factor analysis was carried out in order to examine the relation between PLID and the other variables. It appeared that the same three factors governed the ten variables in both races. In Caucasoids, PLID did not load on either the "length" or "width" factors and appeared unique. In Negroids, PLID loaded on Factor III with two width measures, and this factor correlated positively with the "width" factor. It is suggested that in Caucasoids PLID does not relate to length or width dimensions of the leg but in Negroids it is related to width rather than length.

Anthropometry↗

Biomechanical appraisal of some skeletal features associated with head balance and posture in the Hominoidea.

The condylar position index, condylar angle and the area of insertion of the nuchal musculature corrected for condylar position, direction of muscle pull and skull size were determined in Homo sapiens, Gorilla, Pan and the casts of two Neanderthal and two australopithecine crania. In all three attributes, the values of H. sapiens exceeded, by statistically significant amounts, those for the ape genera. The greater value for the condylar position index indicates a better balance of the head, that for the condylar angle reflects the more vertical orientation of the vertebral column while that for the corrected nuchal area suggests a less effective nuchal musculature in H. sapiens as compared to the apes. In the casts of the Neanderthal crania, the values all came within, or close to, the ranges for H. sapiens. In the australopithecine casts, the condylar angle cane within the ranges for H. sapiens while the condylar position index and the corrected nuchal area were intermediate in value between H. sapiens and the extant apes. These findings are consistent with observations from other skeletal regions that while Australopithecus had an upright posture, this creature was, in the complex of posturally significant morphological features, distinct from extant hominoids.

Animals↗