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Biomedical subjects

Christopher A Brown

Publications and source records attributed to Christopher A Brown.

11 recordsLinked to original sources

Microscale correlation between surface chemistry, texture, and the adhesive strength of Staphylococcus epidermidis.

Staphylococcus epidermidis is among the most commonly isolated microbes from medical implant infections, particularly in the colonization of blood-contacting devices. We explored the relationships between surface wettability and root-mean-square roughness (Rq) on microbial adhesive strength to a substrate. Molecular-level interactions between S. epidermidis and a variety of chemically and texturally distinct model substrata were characterized using a cellular probe and atomic force microscopy (AFM). Substrata included gold, aliphatic and aromatic self-assembled monolayers, and polymeric and proteinaceous materials. Substrate hydrophobicity, described in terms of the water contact angle, was an insufficient parameter to explain the adhesive force of the bacterium for any of the surfaces. Correlations between adhesion forces and Rq showed weak relationships for most surfaces. We used an alternate methodology to characterize the texture of the surface that is based on a fractal tiling algorithm applied to images of each surface. The relative area as a function of the scale of observation was calculated. The discrete bonding model (DBM) was applied, which describes the area available for bonding interactions over the full range of observational scales contained in the measured substrate texture. Weak negative correlations were obtained between the adhesion forces and the area available for interaction, suggesting that increased roughness decreases bacterial adhesion when nano- to micrometer scales are considered. We suggest that modification of the DBM is needed in order to include discontinuous bonding. The adhesive strength is still related to the area available for bonding on a particular scale, but on some very fine scales, the bacteria may not be able to conform to the valleys or pits of the substrate. Therefore, the bonding between the bacterium and substrate becomes discontinuous, occurring only on the tops of ridges or asperities.

Algorithms↗

Dental microwear texture analysis: technical considerations.

Dental microwear analysis is commonly used to infer aspects of diet in extinct primates. Conventional methods of microwear analysis have usually been limited to two-dimensional imaging studies using a scanning electron microscope and the identification of apparent individual features. These methods have proved time-consuming and prone to subjectivity and observer error. Here we describe a new methodological approach to microwear: dental microwear texture analysis, based on three-dimensional surface measurements taken using white-light confocal microscopy and scale-sensitive fractal analysis. Surface parameters for complexity, scale of maximum complexity, anisotropy, heterogeneity, and textural fill volume offer repeatable, quantitative characterizations of three-dimensional surfaces, free of observer measurement error. Some results are presented to illustrate how these parameters distinguish extant primates with different diets. In this case, microwear surfaces of Cebus apella and Lophocebus albigena, which consume some harder food items, have higher average values for complexity than do folivores or soft fruit eaters.

Alouattinae↗

Rearrangements in icosahedral boranes and carboranes revisited.

The structure, stability, and intermolecular rearrangements between ortho-, meta-, and para-C2B10H12 and were investigated using the hybrid density functional B3LYP/6-31G(d) for vibrational frequencies, as well as B3LYP/6-311+G(2d,p) for single-point electronic energies. The general trends in free energies of rearrangement between ortho-C2B10H12 to meta-C2B10H12 and meta-C2B10H12 to para-C2B10H12 presented here are consistent with experimental reaction temperatures. In addition, the majority of the rearrangements can be viewed in terms of concerted diamond-square-diamond steps and triangular face rotations.

Boranes↗

The influence of later-arriving sounds on the ability of listeners to judge the lateral position of a source.

This study examined the deleterious effects of a later-arriving sound on the processing of interaural differences of time (IDTs) from a preceding sound. A correlational analysis assessed the relative weight given to IDTs of source and echo clicks for echo delays of 1-64 ms when the echo click was attenuated relative to the source click (0-36 dB). Also measured were proportion correct and the proportion of responses predicted from the weights. The IDTs of source and echo clicks were selected independently from Gaussian distributions (mu=0 s, sigma = 100/s). Listeners were instructed to indicate the laterality of the source click. Equal weight was given to the source and echo clicks for echo delays of 64 ms with no echo attenuation. For echo delays of 16-64 ms, attenuating the echo had no substantial effect on source weight or proportion correct until the echo was attenuated by 18-30 dB. At echo delays < or =4 ms, source weights and proportions correct remained high regardless of echo attenuation. The proportions of responses predicted from the weights were lower at echo delays > or =16 ms. Results were discussed in terms of backward recognition masking and binaural sluggishness and compared to measurements of echo disturbance.

Humans↗

Dental microwear texture analysis shows within-species diet variability in fossil hominins.

Reconstructing the diets of extinct hominins is essential to understanding the paleobiology and evolutionary history of our lineage. Dental microwear, the study of microscopic tooth-wear resulting from use, provides direct evidence of what an individual ate in the past. Unfortunately, established methods of studying microwear are plagued with low repeatability and high observer error. Here we apply an objective, repeatable approach for studying three-dimensional microwear surface texture to extinct South African hominins. Scanning confocal microscopy together with scale-sensitive fractal analysis are used to characterize the complexity and anisotropy of microwear. Results for living primates show that this approach can distinguish among diets characterized by different fracture properties. When applied to hominins, microwear texture analysis indicates that Australopithecus africanus microwear is more anisotropic, but also more variable in anisotropy than Paranthropus robustus. This latter species has more complex microwear textures, but is also more variable in complexity than A. africanus. This suggests that A. africanus ate more tough foods and P. robustus consumed more hard and brittle items, but that both had variable and overlapping diets.

Animals↗

Interrelationship of growth differentiation factor 9 and inhibin in early folliculogenesis and ovarian tumorigenesis in mice.

To investigate the interrelationship of inhibin alpha and growth differentiation factor 9 (GDF9) during early folliculogenesis, we generated mice lacking both inhibin alpha and GDF9. Our findings on these Inha Gdf9 double-mutant mice are as follows: 1). females develop ovarian tumors and a cachexia-like wasting syndrome, resembling mice lacking inhibin alpha alone. This indicates that the granulosa cells are competent to proliferate despite the lack of GDF9; 2). follicular development progresses to multiple-layer follicle stages before tumorigenesis. This demonstrates that the up-regulation of inhibin alpha in the Gdf9 knockout ovary directly prevents the proliferation of the granulosa cells at the primary follicle stage, an effect that is released in the absence of inhibin alpha; 3). a morphological theca forms around the preantral follicles with no detectable selective theca markers [i.e. 17alpha-hydroxylase (Cyp17), LH receptor (Lhr), and Kit]. These results indicate that the theca recruitment can occur independently of GDF9, but the differentiation of thecal cells is blocked; and 4). inhibin/activin subunits betaA, betaB, and Kit ligand (Kitl) mRNA are highly up-regulated, suggesting that the increased activins and KITL play functional roles in early folliculogenesis. Thus, GDF9 appears to function indirectly to regulate early granulosa cell proliferation and theca recruitment in vivo.

Activins↗

Zygote arrest 1 (Zar1) is an evolutionarily conserved gene expressed in vertebrate ovaries.

Zygote arrest 1 (ZAR1) is an ovary-specific maternal factor that plays essential roles during the oocyte-to-embryo transition. In mice, the Zar1 mRNA is detected as a 1.4-kilobase (kb) transcript that is synthesized exclusively in growing oocytes. To further understand the functions of ZAR1, we have cloned the orthologous Zar1 cDNA and/or genes for mouse, rat, human, frog, zebrafish, and pufferfish. The entire mouse Zar1 gene and a related pseudogene span approximately 4.0 kb, contain four exons, and map to adjacent loci on mouse chromosome 5. The human ZAR1 orthologous gene similarly consists of four exons and resides on human chromosome 4p12, which is syntenic with the mouse Zar1 chromosomal locus. Rat (Rattus norvegicus) and pufferfish (Fugu rubripes) Zar1 genes were recognized by database mining and deduced protein alignment analysis. The rat Zar1 gene also maps to a region that is syntenic with the mouse Zar1 gene locus on rat chromosome 14. Frog (Xenopus laevis) and zebrafish (Danio rerio) Zar1 orthologs were cloned by reverse transcription-polymerase chain reaction and rapid amplification of cDNA ends analysis of ovarian mRNA. Unlike mouse and human, the frog Zar1 is detected in multiple tissues, including lung, muscle, and ovary. The Zar1 mRNA appears in the cytoplasm of oocytes and persists until the tailbud stage during frog embryogenesis. Mouse, rat, human, frog, zebrafish, and pufferfish Zar1 genes encode proteins of 361, 361, 424, 295, 329, and 320 amino acids, respectively, and share 50.8%-88.1% amino acid identity. Regions of the N-termini of these ZAR1 orthologs show high sequence identity among these various proteins. However, the C-terminal 103 amino acids of these proteins, encoded by exons 2-4, contain an atypical eight-cysteine Plant Homeo Domain motif and are highly conserved, sharing 80.6%-98.1% identity among these species. These findings suggest that the carboxyl-termini of these ZAR1 proteins contain an important functional domain that is conserved through vertebrate evolution and that may be necessary for normal female reproduction in the transition from oocyte to embryonic life.

Amino Acid Sequence↗

Offspring size-number trade-offs in scorpions: an empirical test of the van Noordwijk and de Jong model.

Life-history traits are expected to exhibit negative phenotypic trade-offs, but often do not. In a seminal paper, van Noordwijk and de Jong (1986) provided an answer to this seeming paradox. According to their model, trade-offs will be more difficult to detect if variation in resource acquisition (or investment) is high relative to variation in resource allocation to the traits under consideration. Despite its influence on subsequent life-history studies, this model has rarely been tested. I use data from 10 species of scorpion (a total of 30 datasets, including multiple populations or years for some species) to test the van Noordwijk-de Jong model as modified to examine the relationship between offspring size and number. For both the overall data and a subset, including only the species Centruroides vittatus, I found that the correlation between offspring size and number within a population was significantly negatively correlated with the ratio of allocation variance to investment variance. That is, strong trade-offs were found when the investment variance was low relative to the allocation variance. These results were robust to the particular measure of offspring size and to whether offspring data were adjusted for female size variation. My results therefore provide strong evidence in support of the van Noordwijk and de Jong model.

Analysis of Variance↗

Nuclear Overhauser enhancement spectroscopy cross-relaxation rates and ethanol distribution across membranes.

Measurement of nuclear Overhauser enhancement spectroscopy cross-relaxation rates between ethanol and palmitoyloleoylphosphatidylcholine bilayers was combined with atomic-level molecular dynamics simulations. The molecular dynamics trajectories yielded autocorrelation functions of proton dipole-dipole interactions, and, consequently, relaxation times and cross-relaxation rates. These analyses allow the measured cross-relaxation rates to be interpreted in terms of relative interaction strengths with the various segments of the lipid molecule. We determined that cross-relaxation between ethanol and specific lipid resonances is primarily determined by the sites of interaction with some modulation due to lipid disorder and to local differences in intramolecular lipid dynamics. The rates scale linearly with the lifetime of temporary ethanol-lipid associations. Ethanol interacts with palmitoyloleoylphosphatidylcholine bilayers primarily via hydrophilic interactions, in particular the formation of hydrogen bonds to the lipid phosphate group. There is a weak contribution to binding from hydrophobic interaction with lipid chain segments near the glycerol. However, the strength of hydrophobic interactions is insufficient to compensate for the energetic loss of locating ethanol in an exclusively hydrophobic environment, resulting in a probability of locating ethanol in the bilayer center that is three orders of magnitude lower than locating ethanol at the lipid/water interface. The low cross-relaxation rates between terminal methyl protons of hydrocarbon chains and ethanol are as much the result of infrequent chain upturns as of brief excursions of ethanol into the region of lipid hydrocarbon chains near the glycerol. The combination of nuclear magnetic resonance measurements and molecular dynamics simulations offers a general pathway to study the interaction of small molecules with the lipid matrix at atomic resolution.

Biophysics↗

Quantification of dental microwear by tandem scanning confocal microscopy and scale-sensitive fractal analyses.

Dental microwear analysis is among the most commonly used approaches to reconstructing the diets of extinct animal species and past peoples. The usual procedure involves imaging tooth wear surfaces by scanning electron microscopy (SEM). Surfaces are characterized quantitatively by measurement of individual wear features (pits and scratches) on photomicrographs. Recent studies of living animals have shown associations between diets on one hand and patterns of dental microwear on the other. Furthermore, patterns on fossil teeth have been used to reconstruct diets in extinct forms. However, conventional methods for microwear analysis are limited. Scanning electron microscopy does not provide a true representation of these surfaces in three dimensions, and identification and measurement of individual features is time consuming, subjective, and subject to high interobserver error. This paper describes a new approach to the analysis of dental microwear using tandem scanning confocal microscopy and scale-sensitive fractal analyses. The instrument used in this study provides three-dimensional coordinates representing surfaces at a resolution equivalent to that employed by most SEM microwear studies. Fractal analyses offer objective, repeatable, quantitative characterization of surfaces. This approach eliminates major sources of error and increases power to resolve differences between species. Moreover, rapid surface characterization will allow examination of large samples to assess within species variation and to make finer distinctions between species.

Animals↗

Direct assessment of profilometric roughness variability from typical implant surface types.

PURPOSE: Protocols for quantifying the surface roughness of implants are varied and dependent upon the roughness parameter produced by the particular measurement device. The objective of this study was to examine the accuracy and precision of typical roughness characterization instruments used in the dental implant industry. MATERIALS AND METHODS: The average roughness (Ra) was measured using 2 common surface characterization instruments: an interferometer and a stylus profilometer. Titanium disks were prepared to represent 4 typical dental implant surfaces: machined, acid-etched, hydroxyapatite-coated, and titanium plasma-sprayed. Repeated measurements from multiple sites on each surface were undertaken to establish statistical inferences. Qualitative images of the surfaces were also acquired using a laser scanning confocal microscope. After surface measurements were conducted, the disks were diametrically cut and cross-sectional profiles were examined using a scanning electron microscope (SEM) as a comparative measure of surface topography. An analysis of variance was applied to isolate the effects of the measurement site, measurement sequence, surface treatment, and instrument type on Ra values. RESULTS: The results indicated that surface treatment (P = .0001) and instrument (P = .0001) strongly influenced Ra data. By design, measurement site (diametrical: P = .9859; area: P = .9824) and measurement sequence (P = .9990) did not influence roughness. In the assessment of individual instrument accuracy, the interferometer was the most accurate in predicting SEM-based roughness (P = .6688) compared with the stylus (P = .0839). As a measure of aggregate precision over all measurements, the most repeatable instrument was the stylus (coefficient of variation [CV] = 0.108), followed by the interferometer (CV = 0.125) and SEM (CV = 0.273). DISCUSSION: These results indicate dependencies in accuracy and precision related to the surface characterization technique. CONCLUSION: Instrument variability may obscure functional correlations between implant surface topography and osseointegration.

Acid Etching, Dental↗