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R C Brown

Publications and source records attributed to R C Brown.

At least 19 recordsLinked to original sources
PubMed2006

Polar organizers and girdling bands of microtubules are associated with gamma-tubulin and act in establishment of meiotic quadripolarity in the hepatic Aneura pinguis (Bryophyta).

Meiosis in Aneura pinguis is preceded by extensive cytoplasmic preparation for quadripartitioning of the diploid sporocyte into a tetrad of haploid spores. In early prophase the four future spore domains are defined by lobing of the cytoplasm and development of a quadripolar prophase spindle focused at polar organizers (POs) centered in the lobes. Cells entering the reproductive phase become isolated and, instead of hooplike cortical microtubules, have endoplasmic microtubule systems centered on POs. These archesporial cells proliferate by mitosis before entering meiosis. In prophase of each mitosis, POs containing a distinct concentration of gamma-tubulin appear de novo at tips of nuclei and initiate the bipolar spindle. Cells entering meiosis become transformed into quadrilobed sporocytes with four POs, one in each lobe. This transition is a complex process encompassing assembly of two opposite POs which subsequently disperse into intersecting bands of microtubules that form around the central nucleus. The girdling bands define the future planes of cytokinesis and the cytoplasm protrudes through the restrictive bands becoming quadrilobed. Two large POs reappear in opposite cleavage furrows. Each divides and the resulting POs migrate into the tetrahedral lobes of cytoplasm. Cones of microtubules emanating from the four POs interact to form a quadripolar microtubule system (QMS) that surrounds the nucleus in meiotic prophase. The QMS is subsequently transformed into a functionally bipolar metaphase spindle by migration of poles in pairs to opposite cleavage furrows. These findings contribute to knowledge of microtubule organization and the role of microtubules in spatial regulation of cytokinesis in plants.

Bryophyta↗
PubMed2005

Peripheral-type benzodiazepine receptor in neurosteroid biosynthesis, neuropathology and neurological disorders.

The peripheral-type benzodiazepine receptor is a mitochondrial protein expressed at high levels in steroid synthesizing tissues, including the glial cells of the brain. Peripheral-type benzodiazepine receptor binds cholesterol with high affinity and is a key element of the cholesterol mitochondrial import machinery responsible for supplying the substrate cholesterol to the first steroidogenic enzyme, thus initiating and maintaining neurosteroid biosynthesis. Neurosteroid formation and metabolism of steroid intermediates are critical components of normal brain function. Peripheral-type benzodiazepine receptor also binds with high affinity various classes of compounds. Upon ligand activation peripheral-type benzodiazepine receptor-dependent cholesterol transport into mitochondria is accelerated leading in increased formation of neuroactive steroids. These steroids, such as allopregnanolone, have been shown to be involved in various neurological disorders, such as anxiety and mood disorders. Thus, peripheral-type benzodiazepine receptor drug ligand-induced neuroactive steroid formation offers a means to regulate brain dysfunction. Peripheral-type benzodiazepine receptor basal expression is upregulated in a number of neuropathologies, including gliomas and neurodegenerative disorders, as well as in various forms of brain injury and inflammation. In Alzheimer's disease pathology neurosteroid biosynthesis is altered and a decrease in the intermediate 22R-hydroxycholesterol levels is observed. This steroid was found to exert neuroprotective properties against beta-amyloid neurotoxicity. Based on this observation, a stable spirostenol derivative showing to display neuroprotective properties was identified, suggesting that compounds developed based on critical intermediates of neurosteroid biosynthesis could offer novel means for neuroprotection. In conclusion, changes in peripheral-type benzodiazepine receptor and neurosteroid levels are part of the phenotype seen in neuropathology and neurological disorders and offer potential targets for new therapies.

Alzheimer Disease↗
PubMed2005

Adsorption of arsenic(V) by activated carbon prepared from oat hulls.

The efficiency of self-manufactured activated carbon (AC) produced from oat hulls in adsorbing arsenic(V) was tested in a batch reactor. The results indicated that the adsorptive capacity of AC was affected by initial pH value, with adsorption capacity decreasing from 3.09 to 1.57 mg As g(-1) AC when the initial pH values increased from 5 to 8. A modified linear driving force model conjugated with a Langmuir isotherm was created to describe the study's kinetics. The test results show that rapid adsorption and slow adsorption exist simultaneously when AC is used to remove arsenic(V).

Adsorption↗
PubMed2005

Gamma-tubulin and microtubule organization during microsporogenesis in Ginkgo biloba.

This is the first report on gamma-tubulin and microtubule arrays during microsporogenesis in a gymnosperm. Meiosis in Ginkgo biloba is polyplastidic, as is typical of the spermatophyte clade, and microtubule arrays are organized at various sites during meiosis and cytokinesis. In early prophase, a cluster of gamma-tubulin globules occurs in the central cytoplasm adjacent to the off-center nucleus. These globules diminish in size and spread over the surface of the nucleus. A system of microtubules focused on the gamma-tubulin forms a reticulate pattern in the cytoplasm. As the nucleus migrates to the center of the microsporocyte, gamma-tubulin becomes concentrated at several sites adjacent to the nuclear envelope. Microtubules organized at these foci of gamma-tubulin give rise to a multipolar prophase spindle. By metaphase I, the spindle has matured into a distinctly bipolar structure with pointed poles. In both first and second meiosis, gamma-tubulin becomes distributed throughout the metaphase spindles, but becomes distinctly polar again in anaphase. In telophase I, gamma-tubulin moves from polar regions to the proximal surface of chromosome groups/nuclei where interzonal microtubules are organized. No cell wall is deposited and the interzonal microtubules embrace a plate of organelles between the two nuclear cytoplasmic domains (NCDs) of the dyad. Following second meiosis, phragmoplasts that form between sister and non-sister nuclei fuse to form a complex six-sided structure that directs simultaneous cytokinesis. Gamma-tubulin becomes associated with nuclei after both meiotic divisions and is especially conspicuous in the distal hemisphere of each young microspore where an unusual encircling system of cortical microtubules develops.

Germ Cells↗
PubMed2005

Survey of the biological effects of refractory ceramic fibres: overload and its possible consequences.

This paper summarizes the biological effects of refractory ceramic fibres (RCFs). RCFs are aluminosilicate glass insulation wools with similar chemical properties to other synthetic vitreous fibres (SVFs) or 'man-made vitreous fibres' (MMVFs). There is concern that RCFs could be significantly more pathogenic than other SVFs. This paper critically reviews the data on which this perception is based. Morbidity studies on workers in RCF manufacturing indicated that, in the United states, RCF exposure was associated with an increased incidence of pleural plaques and in both the united states and Europe with statistically significant changes in some measures of lung function (though not at present exposure levels). No interstitial fibrosis was found. An ongoing mortality study of limited statistical power has failed to indicate any increased incidence of lung cancer or mesothelioma. Findings in several early animal studies led to a large series of inhalation studies where rats exposed to high levels of RCF developed fibrosis and tumours but not those exposed to other SVFs. Similarly hamsters exposed to one sample (RCF1) developed mesothelioma. Subsequent analyses of the data indicated that the RCF used in these experiments had a significantly greater proportion of non-fibrous particles than those present in the other types of SVFs tested or in workplace air. Short-term studies indicated that pulmonary overload occurred at the same as RCF tissue burdens as those in the long-term animal bioassay. When RCFs were prepared in the same way as the other SVFs, a sample resulted with a more representative ratio of particles to fibres; this sample did not produce overload in short-term tests. SVFs have various abilities to persist in the lung tissue and thus accumulate to varying degrees. It is suggested that biopersistence is a key property. While RCFs are among the more persistent they are similar to many other fibre types. The scientific and regulatory implications of these findings are examined.

Air Pollutants, Occupational↗
PubMed2004

Gamma-tubulin localization changes from discrete polar organizers to anastral spindles and phragmoplasts in mitosis of Marchantia polymorpha L.

Unlike the astral mitotic spindle that is organized at discrete centriolar centrosomes, the spindle of land plants is typically anastral and its origin has remained obscure. Gamma tubulin (gamma-tubulin), an important component of the centrosome, has been demonstrated at microtubule-nucleating sites in plant cells. Mitotic spindles of certain hepatics are initiated at distinct acentriolar polar organizers (POs) that appear de novo at the onset of mitosis. Data on the relationship of gamma-tubulin to POs and to microtubule arrays throughout the cell cycle were collected from rapidly dividing cells of Marchantia polymorpha (Bryophyta) that were triple-stained for gamma-tubulin, microtubules, and nuclei. POs at opposite ends of the elongated nucleus in early prophase stain brightly for gamma-tubulin and astral microtubules emanating from them initiate the spindle. As the spindle develops, however, the gamma-tubulin becomes dispersed from the highly concentrated spherical form of the POs to more diffusely organized cups at tips of the fusiform nucleus. By the end of prophase, all astral microtubules have disappeared and the gamma-tubulin is located in several minipoles along the now broad polar regions of the spindle. At metaphase, gamma-tubulin extends into the spindle itself. By telophase, the gamma-tubulin has migrated from distal to proximal surfaces of the sister nuclei and extends into the phragmoplast. Upon completion of cytokinesis, gamma-tubulin appears diminished and surrounds the nuclear envelopes. These data show that gamma-tubulin is only briefly concentrated in the PO, migrates in a cell-cycle-specific manner, and is consistently present at all putative sites of microtubule nucleation.

Cell Nucleus↗
PubMed2004

Steam activation of chars produced from oat hulls and corn stover.

Oat hulls and corn stover were used to produce chars at approximately 500 degrees C. The carbon concentrations of oat hull char and corn stover chars produced were 72.3 and 68.0 wt.%, respectively. Both activation burn-off and Brunauer-Emmett-Teller (BET) surface area appear to exhibit a linear relationship with respect to activation time of oat hulls. As to corn stover activated carbons, there is no linear relationship between activation time and BET surface area. However, activation burn-off of and activation time appear to relate in a linear manner for the activated carbons produced from corn stover chars. Oat hull is better than corn stover as a raw material for the production of activated carbon.

Avena↗
PubMed2004

Application of thermophilic enzymes in commercial biotransformation processes.

Biocatalysis is a useful tool in the provision of chiral technology and extremophilic enzymes are just one component in that toolbox. Their role is not always attributable to their extremophilic properties; as with any biocatalyst certain other criteria should be satisfied. Those requirements for a useful biocatalyst will be discussed including issues of selectivity, volume efficiency, security of supply, technology integration, intellectual property and regulatory compliance. Here we discuss the discovery and commercialization of an L-aminoacylase from Thermococcus litoralis, the product of a LINK project between Chirotech Technology and the University of Exeter. The enzyme was cloned into Escherichia coli to aid production via established mesophilic fermentation protocols. A simple downstream process was then developed to assist in the production of the enzyme as a genetically modified-organism-free reagent. The fermentation and downstream processes are operated at the 500 litre scale. Characterization of the enzyme demonstrated a substrate preference for N-benzoyl groups over N-acetyl groups. The operational parameters have been defined in part by substrate-concentration tolerances and also thermostability. Several examples of commercial biotransformations will be discussed including a process that is successful by virtue of the enzyme's thermotolerance.

Amidohydrolases↗
PubMed2003

Events during the first four rounds of mitosis establish three developmental domains in the syncytial endosperm of Arabidopsis thaliana.

Endosperm begins development as a single fertilized cell that undergoes many rounds of mitosis without cytokinesis resulting in a syncytium. The multinucleate cytoplasm is organized by nucleus-based radial microtubule systems into nuclear-cytoplasmic domains. When microtubules are organized into mitotic spindles, the integrity of the common cytoplasm is maintained by an unaltered network of filamentous actin. The first four rounds of mitosis result in the establishment of three developmental domains within the common cytoplasm. The spindles of the first two rounds of mitosis are oriented parallel to the long axis of the central cell, resulting in four nuclear-cytoplasmic domains in a filamentous arrangement. A switch in spindle orientation occurs in the third round of mitosis; all four spindles are oriented perpendicular to the long axis resulting in eight nuclear-cytoplasmic domains arranged in two adjacent files. Whereas the first three rounds of mitosis are synchronous, the fourth occurs as a wave of successive mitoses that begins at the micropylar pole. By the 16-nuclei stage, differences in nuclear shape, cytoskeletal arrays, and cytoplasmic characteristics mark the differentiation of the syncytium into micropylar, central, and chalazal developmental chambers. Nuclei in the micropylar chamber are fusiform and sheathed by parallel microtubules that flare from their tips, while those in the central and chalazal chambers are spherical. Nuclei in the central chamber are surrounded by radial microtubule systems, while those in the chalaza are enmeshed in a reticulum of microtubules. Whereas the cytoplasm in both micropylar and chalazal chambers is dense and nearly nonvacuolate, the syncytium in the central chamber consists of a single layer of evenly spaced nuclear-cytoplasmic domains surrounding a large central vacuole.

Arabidopsis↗
PubMed2003

A dose-response model for refractory ceramic fibers.

Refractory ceramic fibers (RCFs) are man-made vitreous fibers commonly used in insulation applications above 1000 degrees C. Although they have been subjected to considerable toxicologic evaluation, only the pooled results from two rat inhalation studies provide data that may be suitable for performing a numerical risk assessment. Even in these inhalation studies, good evidence exists that the maximum tolerated dose (MTD) was exceeded and that pulmonary overload occurred, a condition that will cause tumors whatever the dust responsible. Indeed, a significant yield of tumors was only obtained at the highest dose tested. If these results are omitted, there is no statistically significant evidence of carcinogenicity within the RCF results. Although there is little evidence that overload-related tumors are relevant to human risk, we adopted a conservative approach to obtain the estimates of risk regardless of overload, using a biologically based model, the two-stage clonal expansion model, as well as various statistical models, including the benchmark dose model. We argue that the data favor the use of a biologically based model, which gives the best fit when the highest dose RCF exposures are omitted. Continuing with this model, we show that available data from the RCF experiment, less outliers, coupled with results from other experiments with man-made mineral fibers (MMVFs), demonstrate that all MMVFs are potentially carcinogenic, with any risk mediated by the fibers' biopersistence. Application of this "all MMVF data set" model yields a maximum likely estimate for RCF excess unit risk of 4.6 x 10(-5) (95% upper confidence limit = 9.2 x 10(-5) per fiber/ml). This implies that the risk from occupational exposure to RCFs at 1 fiber/ml for a typical working lifetime would not exceed 10(-4).

Administration, Inhalation↗
PubMed2003

TETRASPORE encodes a kinesin required for male meiotic cytokinesis in Arabidopsis.

A key step in pollen formation is the segregation of the products of male meiosis into a tetrad of microspores, each of which develops into a pollen grain. Separation of microspores does not occur in tetraspore (tes) mutants of Arabidopsis thaliana, owing to the failure of male meiotic cytokinesis. tes mutants thus generate large 'tetraspores' containing all the products of a single meiosis. Here, we report the positional cloning of the TES locus and details of the role played by the TES product in male cytokinesis. The predicted TES protein includes an N-terminal domain homologous to kinesin motors and a C-terminus with little similarity to other proteins except for a small number of plant kinesins. These include the Arabidopsis HINKEL protein and NACK1 and two from tobacco (Nishihama et al., 2002), which are involved in microtubule organization during mitotic cytokinesis. Immunocytochemistry shows that the characteristic radial arrays of microtubules associated with male meiotic cytokinesis fail to form in tes mutants. The TES protein therefore is likely to function as a microtubule-associated motor, playing a part either in the formation of the radial arrays that establish spore domains following meiosis, or in maintaining their stability.

Alleles↗
PubMed2002

Cytoskeletal organization of the micropylar endosperm in Coronopus didymus L. (Brassicaceae).

The micropylar chamber of the mustard Coronopus didymus is a developmental domain distinct from the contiguous central chamber and the more extreme chalazal chamber. Early in syncytial development the micropylar endosperm surrounding the embryo becomes populated with unusual fusiform to multilobed nuclei. These nuclei are sheathed by unique parallel arrays of microtubules that focus at tips of the nuclei and flare to connect with a reticulate network in the common cytoplasm. F-actin does not closely invest the nuclei but instead forms an extensive but separate cytoplasmic reticulum. When the embryo is in the early heart stage, the cytoskeleton of the endosperm undergoes a remarkable transition in preparation for cellularization. Microtubules become reorganized into radial arrays emanating from the nuclei, which themselves become spherical. Radial microtubule systems (RMSs), which replace both the parallel microtubules and the cytoplasmic reticulum, organize the common cytoplasm into evenly spaced nuclear cytoplasmic domains (NCDs). F-actin gradually becomes coaligned with the RMSs. Phragmoplasts are initiated adventitiously at the interfaces of opposing RMSs in the absence of mitosis. Cell plate deposition, which is initiated at multiple sites, results in a network of walls formed more or less simultaneously around the densely packed NCDs. The walls, which are rich in 1-3-beta-glucans, join with one another and with the existing walls of both the central cell and embryo to complete cellularization in the micropylar chamber. In the adjacent central chamber where the syncytium is restricted to a thin peripheral layer by the large central vacuole, basic organization of the syncytium into NCDs is followed by alternating cycles of alveolation and periclinal cell division resulting in cellularization.

Brassicaceae↗
PubMed2001

C-H insertion approach to the synthesis of endo,exo-furofuranones: synthesis of (+/-)-asarinin, (+/-)-epimagnolin A, and (+/-)-fargesin.

A series of novel 5-aryl-4-aryloxymethyl-3-diazotetrahydrofuran-2-ones (12, 24, and 35a/b) have been prepared and found to undergo regio- and stereoselective C-H insertion reactions to afford 2,6-diaryl-3,7-dioxabicyclo[3.3.0]octane-8-ones (18, 26, and 36a/b) with endo,exo stereochemistry. Subsequent reduction of the lactone ring and cyclization of the resulting diols 27 and 37a/b permitted the synthesis of three endo,exo-furofuran lignans: asarinin (2), fargesin (3), and epimagnolin A (4). En route to the key diazo compounds 24 and 35a/b, a modified procedure for the Ghosez keteniminium-olefin cyclization was developed, which was required to minimize the decomposition of acid-sensitive functional groups such as electron-rich benzylic ethers that were present in the target compounds 2-4.

Anti-Allergic Agents↗
PubMed2001

RANTES production from CD4+ lymphocytes correlates with host genotype and rates of human immunodeficiency virus type 1 disease progression.

Several chemokine and chemokine receptor parameters were measured in peripheral blood mononuclear cells obtained from patients before they became infected with human immunodeficiency virus type 1 (HIV-1). After HIV-1 infection, the parameters were compared with plasma HIV-1 RNA levels and with rates of CD4(+) lymphocyte decline. Patients who were heterozygous for the Delta32CCR5 allele had significantly higher levels of RANTES production from their CD4(+) lymphocytes than did patients who did not carry the Delta32CCR5 allele (P=.01). Higher RANTES production levels from ex vivo-activated CD4(+)-enriched lymphocytes, but not CD8(+) lymphocytes, correlated with lower plasma HIV-1 RNA levels 9-12 months after infection (P= .01) and with slower rates of CD4(+) lymphocyte decline (P= .002). CCR5 expression levels on ex vivo-activated CD4(+) lymphocytes did not correlate with markers of disease progression. These results further support the hypothesis that chemokine production levels are associated with HIV-1 replication in vivo.

Alleles↗
PubMed2001

Long man-made fibers and lung cancer risk.

We show that available experimental data from long-term oncogenicity experiments in Fisher rats are consistent with the hypothesis that the oncogenic potential of long man-made mineral fibers is determined mainly by their biopersistence. We present analyses of these data within the initiation-promotion-progression paradigm of carcinogenesis. Our method of analysis can take the temporal pattern of the burden of long fibers in the lungs of individual animals into explicit account. For this analysis, the temporal pattern of lung burden for each animal was imputed from the information obtained from sacrificed animals. The data are consistent with the hypothesis that fibers act as initiators in the rat lung. We present an estimate of the dose-dependent initiation parameter that is based on all the available data.

Animals↗
PubMed2001

The power of the European Union protocol to test for carcinogenicity of inhaled fibers.

We evaluate the power of a recent protocol proposed by the European Union (EU) for testing the carcinogenicity of inhaled fibers. We assume that every fiber has oncogenic potential determined by its biopersistence. We use a recently estimated potency for the oncogenic potential of fibers together with experimentally determined "weighted" half-lives (WHL) of a dozen fibers to generate simulations of long-term bioassays conducted according to the EU protocol. We analyze these experiments using standard statistical techniques and determine the number of tests that would have yielded significant results. We conclude that the EU protocol will readily detect the carcinogenic effect of long-lived fibers, such as amosite with a WHL of more than 450 days, and usually detect the effect of fibers, such as RCF1a, with WHL of about 40-50 days. However, the EU protocol has very low power to detect effects of short-lived fibers, such as X607, with WHL of about 10 days.

Biological Assay↗
PubMed2001

The cytoskeleton and spatial control of cytokinesis in the plant life cycle.

One of the intriguing aspects of development in plants is the precise control of division plane and subsequent placement of walls resulting in the specific architecture of tissues and organs. The placement of walls can be directed by either of two microtubule cycles. The better known microtubule cycle is associated with control of the future division plane in meristematic growth where new cells become part of tissues. The future daughter domains are determined before the nucleus enters prophase and the future site of cytokinesis is marked by a preprophase band (PPB) of cortical microtubules. The spindle axis is then organized in accordance with the PPB and, following chromosome movement, a phragmoplast is initiated in the interzone and expands to join with parental walls at the site previously occupied by the PPB. The alternative microtubule cycle lacks both the hooplike cortical microtubules of interphase and the PPB. Wall placement is determined by a radial microtubule system that defines a domain of cytoplasm either containing a nucleus or destined to contain a nucleus (the nuclear cytoplasmic domain) and controls wall placement at its perimeter. This more flexible system allows for cytoplasmic polarization and migration of nuclei in coenocytes prior to cellularization. The uncoupling of cytokinesis from karyokinesis is a regular feature of the reproductive phase in plants and results in specific, often unusual, patterns of cells which reflect the position of nuclei at the time of cellularization (e.g., the arrangement of spores in a tetrad, cells of the male and female gametophytes of angiosperms, and the distinctive cellularization of endosperm). Thus, both microtubule cycles are required for completion of plant life cycles from bryophytes to angiosperms. In angiosperm seed development, the two methods of determining the boundaries of domains where walls will be deposited are operative side by side. Whereas the PPB cycle drives embryo development, the radial-microtubule-system cycle drives the common nuclear type of endosperm development from the syncytial stage through cellularization. However, a switch to the PPB cycle can occur in endosperm, as it does in barley, when peripheral cells divide to produce a multilayered aleurone. The triggers for the switch between microtubule cycles, which are currently unknown, are key to understanding plant development.

Arabidopsis↗