Biomedical subjects

M R Dickson

Publications and source records attributed to M R Dickson.

12 recordsLinked to original sources

PubMed2005

Association studies of transforming growth factor-beta 1 and Alzheimer's disease.

Substantial laboratory evidence suggests Transforming Growth Factor-beta1 (TGFB1) is linked to Alzheimer's Disease (AD) pathology. The purpose of the study was to estimate the genetic association of TGFB1 with AD while controlling for apolipoprotein E4 allele (APOE4) status, the only well-established genetic risk factor for AD. Two study populations were genotyped for the TGFB1-509 and +869 single nucleotide polymorphisms (SNPs) that have been associated with TGFB1 levels. Constituting these populations were 203 families from the NIMH AD Genetic Initiative with at least two affected siblings and a normal sibling, and a population of 126 African-American (AA) AD cases versus 93 age matched controls. Results from family-based analyses showed a significant association between the TGFB1 -509 SNP and AD for the entire set of 203 families (P = 0.007), and a subset of these families without a homozygous APOE4 family member (P = 0.026). Results from family-based analyses on the TGFB1 +869 SNP were not significant in the 203 families. While associations for the main effects of the TGFB1 +869 and -509 SNP with AD in the AA case-control study were also not significant, results did indicate that TGFB1 may function as an effect modifier of APOE4 risk. Specifically, the odds of AD associated with having at least one APOE4 allele increased in an additive fashion with one or two copies of the higher producer allele when stratified by TGFB1 -509 genotype and by TGFB1 +869 genotype. Results support a role for TGFB1 in AD pathogenesis.

Aged↗

PubMed2001

Drosophila E2f2 promotes the conversion from genomic DNA replication to gene amplification in ovarian follicle cells.

Drosophila contains two members of the E2F transcription factor family (E2f and E2f2), which controls the expression of genes that regulate the G1-S transition of the cell cycle. Previous genetic analyses have indicated that E2f is an essential gene that stimulates DNA replication. We show that loss of E2f2 is viable, but causes partial female sterility associated with changes in the mode of DNA replication in the follicle cells that surround the developing oocyte. Late in wild-type oogenesis, polyploid follicle cells terminate a program of asynchronous endocycles in which the euchromatin is entirely replicated, and then confine DNA synthesis to the synchronous amplification of specific loci, including two clusters of chorion genes that encode eggshell proteins. E2f2 mutant follicle cells terminate endocycles on schedule, but then fail to confine DNA synthesis to sites of gene amplification and inappropriately begin genomic DNA replication. This ectopic DNA synthesis does not represent a continuation of the endocycle program, as the cells do not complete an entire additional S phase. E2f2 mutant females display a 50% reduction in chorion gene amplification, and lay poorly viable eggs with a defective chorion. The replication proteins ORC2, CDC45L and ORC5, which in wild-type follicle cell nuclei localize to sites of gene amplification, are distributed throughout the entire follicle cell nucleus in E2f2 mutants, consistent with their use at many genomic replication origins rather than only at sites of gene amplification. RT-PCR analyses of RNA purified from E2f2 mutant follicle cells indicate an increase in the level of Orc5 mRNA relative to wild type. These data indicate that E2f2 functions to inhibit widespread genomic DNA synthesis in late stage follicle cells, and may do so by repressing the expression of specific components of the replication machinery.

Animals↗

PubMed1995

Sintering effects on the strength of hydroxyapatite.

Mechanisms underlying temperature-strength interrelations for dense (> 95% dense, pores closed) hydroxyapatite (HAp) were investigated by comparative assessment of temperature effects on tensile strength, Weibull modulus, apparent density, decomposition (HAp:tricalcium phosphate ratio), dehydroxylation and microstructure. Significant dehydroxylation occurred above approximately 800 degrees C. Strength peaked at approximately 80 MPa just before the attainment of closed porosity (approximately 95% dense). For higher temperatures (closed porosity), the strength dropped sharply to approximately 60 MPa due to the closure of dehydroxylation pathways, and then stabilized at approximately 60 MPa. At very high temperatures (> 1350 degrees C), the strength dropped catastrophically to approximately 10 MPa corresponding to the decomposition of HAp to tricalcium phosphate and the associated sudden release of the remaining bonded water.

Chemistry, Physical↗

PubMed1986

Three-dimensional structure of the surface layer protein of Aquaspirillum serpens VHA determined by electron crystallography.

The three-dimensional structure of the protein which forms the S layer of Aquaspirillum serpens strain VHA has been determined by electron microscopy. Structures have been reconstructed to a resolution of about 1.6 nm for single-layered specimens and about 4 nm for two-layered specimens. The structure, which has hexagonal symmetry, consists of a core in the shape of a cup, with six projections arising from the rim of the cup to join adjacent subunits at the threefold symmetry axes. The model is consistent with edge views of the S layer which have been obtained in this and other work. It is now clear from this work and from three-dimensional reconstructions of other bacterial S layers that a wide diversity exists in the morphology of surface layers.

Bacterial Proteins↗

PubMed1979

An electron-microscope study of beta-glucuronidase crystals.

beta-Glucuronidase from rat preputial glands was crystallized as thin sheets having p6 symmetry in projection with a equal 20.2nm. A filtered image was produced by Fourier methods to a resolution of 2.2 nm by averaging information from six areas. This suggests an approximately triangular molecular outline in projection, and this is taken to indicate a probable tetrahedral arrangement of the four subunits of the beta-glucuronidase molecule.

Computers↗

PubMed1979

The preservation of surface-associated micro-organisms prepared for scanning electron microscopy.

Scanning electron microscopy (SEM) has become a popular means of studying micro-organisms which associate with surfaces. However, as yet no detailed examination has been made of the influence of specimen preparation on the number of organisms finally seen on the SEM screen. In this investigation critical assessment is made of the influence of a wide range or preparative factors on the preservation of filamentous bacteria associated with the epithelial surfaces of rat intestine. Organisms were quantitated using a rigorous counting method (transect line analysis); statistical testing of these counts enabled the comparison of different preparative factors. The composition of the fixative was found to significantly influence the number of organisms preserved; of the fifteen fixatives studied, Karnovsky's fixative with ruthenium red best preserved surface-associated organisms. The influence of other factors on the number and appearance of preserved organisms was also examined. These factors included the washing of specimens prior to fixation, the storage of fixed specimens, and the handling and storage of critical point dried specimens. The results are discussed with reference to the optimal methods for preparing specimens for SEM.

Animals↗

PubMed1975

Location of glycogen in spermatids and spermatozoa of the shipworm, Bankia australis (Teredinidae, Bivalvia, Mollusca).

The periodic acid-thiocarbohydrazide-silver proteinate technique and alpha-amylase digestion were used to locate glycogen in the spermatids and sperms of the bivalve Bankia australis. Glycogen was found in the middle piece and around the acrosome in spermatozoa, apparently randomly scattered throughout the cytoplasm of young spermatids, and in a cytoplasmic bead in old spermatids.

Acrosome↗

PubMed1974