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Search Results: 1 - 10 of 480242 matches for " Mark A. Wilson "
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Early large borings from a hardground of Floian-Dapingian age (Early and Middle Ordovician) in northeastern Estonia (Baltica)
Vinn Olev,Wilson Mark A.
Carnets de Géologie , 2010,
Abstract: Large plug- or slightly amphora-shaped borings have been found in the hardground marking the boundary between Early and Middle Ordovician rocks in northeastern Estonia. These borings cut large bioclasts of the trilobite Megistaspis and cannot be assigned with certainty to any known ichnotaxon. They indicate that the diversity of early borings may have been greater than was recognized previously.
Expression and Purification of Chaperone-Active Recombinant Clusterin
Rebecca A. Dabbs, Mark R. Wilson
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0086989
Abstract: Clusterin was the first described secreted mammalian chaperone and is implicated as being a key player in both intra- and extracellular proteostasis. Its unique combination of structural features and biological chaperone activity has, however, previously made it very challenging to express and purify the protein in a correctly processed and chaperone-active form. While there are multiple reports in the literature describing the use of recombinant clusterin, all of these reports suffer from one or more of the following shortcomings: details of the methods used to produce the protein are poorly described, the product is incompletely (if at all) characterised, and purity (if shown) is in many cases inadequate. The current report provides the first well validated method to economically produce pure chaperone-active recombinant clusterin. The method was developed after trialling expression in cultured bacterial, yeast, insect and mammalian cells, and involves the expression of recombinant clusterin from stably transfected HEK293 cells in protein-free medium. The product is expressed at between 7.5 and 10 μg/ml of culture, and is readily purified by a combination of immunoaffinity, cation exchange and size exclusion chromatography. The purified product was shown to be glycosylated, correctly proteolytically cleaved into α- and β-subunits, and have chaperone activity similar to that of human plasma clusterin. This new method creates the opportunity to use mutagenesis and metabolic labelling approaches in future studies to delineate functionally important sites within clusterin, and also provides a theoretically unlimited supply of recombinant clusterin which may in the future find applications in the development of therapeutics.
Methoxylation enhances stilbene bioactivity in Caenorhabditis elegans
Wilson Mark A,Rimando Agnes M,Wolkow Catherine A
BMC Pharmacology , 2008, DOI: 10.1186/1471-2210-8-15
Abstract: Background Stilbenes are 1,2-diphenylethylene congeners produced by plants in response to stress. Many stilbenes also exhibit xenobiotic activities in animal cells, such as inhibition of cancer cell growth, neuroprotection, and immune modulation. In vivo, hydroxylated stilbenes are metabolized by glucuronidation to facilitate excretion. Methoxylated stilbenes are metabolized more slowly, which may have a positive effect on in vivo bioactivity. Here, we have directly compared in vivo bioactivities of methoxylated and hydroxylated stilbenes in a whole organism using the roundworm Caenorhabditis elegans, an advantageous experimental system for such studies due to its rapid lifecycle, genetic amenability and relatively low-cost. Results Toxicity towards C. elegans adults was observed for trimethoxylated and dimethoxylated stilbenes, as well as the monomethoxylated stilbene desoxyrhapontigenin. Toxicity was not observed for the monomethoxylated stilbene, pinostilbene, nor for hydroxylated stilbenes. The methoxylated stilbenes that exhibited toxicity also showed stronger inhibitory effects than the hydroxylated stilbenes on germline tumor growth in gld-1(q485) adults. However, steady-state levels of three inhibitory methoxylated stilbenes did not directly correlate to their relative bioactivities. Conclusion These findings demonstrate that, for the group of stilbenes investigated, methoxylation generally increased bioactivity in vivo in a whole organism, with the exception of pinostilbene. Differences in bioactivity in C. elegans adults did not appear to correlate with differential uptake. Rather, we speculate that methoxylated stilbenes may have increased interactions with biological targets in vivo or may interact with specific targets unaffected by hydroxylated stilbenes. The potent activities of methoxylated stilbenes provide a basis for further investigations to identify in vivo targets for these compounds.
Identification of Functional Subclasses in the DJ-1 Superfamily Proteins
Ying Wei,Dagmar Ringe ,Mark A Wilson,Mary Jo Ondrechen
PLOS Computational Biology , 2007, DOI: 10.1371/journal.pcbi.0030010
Abstract: Genomics has posed the challenge of determination of protein function from sequence and/or 3-D structure. Functional assignment from sequence relationships can be misleading, and structural similarity does not necessarily imply functional similarity. Proteins in the DJ-1 family, many of which are of unknown function, are examples of proteins with both sequence and fold similarity that span multiple functional classes. THEMATICS (theoretical microscopic titration curves), an electrostatics-based computational approach to functional site prediction, is used to sort proteins in the DJ-1 family into different functional classes. Active site residues are predicted for the eight distinct DJ-1 proteins with available 3-D structures. Placement of the predicted residues onto a structural alignment for six of these proteins reveals three distinct types of active sites. Each type overlaps only partially with the others, with only one residue in common across all six sets of predicted residues. Human DJ-1 and YajL from Escherichia coli have very similar predicted active sites and belong to the same probable functional group. Protease I, a known cysteine protease from Pyrococcus horikoshii, and PfpI/YhbO from E. coli, a hypothetical protein of unknown function, belong to a separate class. THEMATICS predicts a set of residues that is typical of a cysteine protease for Protease I; the prediction for PfpI/YhbO bears some similarity. YDR533Cp from Saccharomyces cerevisiae, of unknown function, and the known chaperone Hsp31 from E. coli constitute a third group with nearly identical predicted active sites. While the first four proteins have predicted active sites at dimer interfaces, YDR533Cp and Hsp31 both have predicted sites contained within each subunit. Although YDR533Cp and Hsp31 form different dimers with different orientations between the subunits, the predicted active sites are superimposable within the monomer structures. Thus, the three predicted functional classes form four different types of quaternary structures. The computational prediction of the functional sites for protein structures of unknown function provides valuable clues for functional classification.
The Earliest Giant Osprioneides Borings from the Sandbian (Late Ordovician) of Estonia
Olev Vinn, Mark A. Wilson, Mari-Ann M?tus
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0099455
Abstract: The earliest Osprioneides kampto borings were found in bryozoan colonies of Sandbian age from northern Estonia (Baltica). The Ordovician was a time of great increase in the quantities of hard substrate removed by single trace makers. Increased predation pressure was most likely the driving force behind the infaunalization of larger invertebrates such as the Osprioneides trace makers in the Ordovician. It is possible that the Osprioneides borer originated in Baltica or in other paleocontinents outside of North America.
Recent Outbursts from the Transient X-Ray Pulsar Cep X-4 (GS 2138+56)
Colleen A. Wilson,Mark H. Finger,D. Matthew Scott
Physics , 1998, DOI: 10.1086/306660
Abstract: We report on X-ray observations of the 66 s period transient X-ray pulsar Cep X-4 (GS 2138+56) with the Burst and Transient Source Experiment (BATSE) on the Compton Gamma-Ray Observatory (CGRO) and with the Rossi X-ray Timing Explorer (RXTE). Two outbursts from Cep X-4 were observed with BATSE in 1993 June-July and 1997 July. Pulse frequencies of 15.0941 +/- 0.0002 mHz on 1993 June 25 (MJD 49,163) and 15.0882 +/- 0.0002 mHz on 1997 July 12 (MJD 50,641) were each measured from 2 day spans of BATSE data near each outburst's peak. Cep X-4 showed an average spin down rate of (-4.14 +/- 0.08)*10^(-14) Hz/s between the 1993 and 1997 outbursts. After BATSE could no longer detect Cep X-4, public observations were performed on 1997 July 18 & 25 with the Proportional Counter Array (PCA) on RXTE. A pulse frequency of 15.088 +/- 0.004 mHz was measured from observations on 1997 July 18 (MJD 50,647). Significant aperiodic noise, with an rms variance of ~18% in the frequency range 0.01-1.0 Hz was observed on both days. Energy and intensity dependent pulse shape variations were also seen in these data. Recently published optical observations associate Cep X-4 with a Be companion star. If all 4 outbursts observed from Cep X-4 are assumed to occur at the same orbital phase, we find that the orbital period is between 23 days and 147.3 days.
Characterization of the Crab Pulsar's Timing Noise
D. Matthew Scott,Mark H. Finger,Colleen A. Wilson
Physics , 2003, DOI: 10.1046/j.1365-8711.2003.06825.x
Abstract: We present a power spectral analysis of the Crab pulsar's timing noise, mainly using radio measurements from Jodrell Bank taken over the period 1982-1989. The power spectral analysis is complicated by nonuniform data sampling and the presence of a steep red power spectrum that can distort power spectra measurement by causing severe power ``leakage''. We develop a simple windowing method for computing red noise power spectra of uniformly sampled data sets and test it on Monte Carlo generated sample realizations of red power-law noise. We generalize time-domain methods of generating power-law red noise with even integer spectral indices to the case of noninteger spectral indices. The Jodrell Bank pulse phase residuals are dense and smooth enough that an interpolation onto a uniform time series is possible. A windowed power spectrum is computed revealing a periodic or nearly periodic component with a period of about 568 days and a 1/f^3 power-law noise component with a noise strength of 1.24 +/- 0.067 10^{-16} cycles^2/sec^2 over the analysis frequency range 0.003 - 0.1 cycles/day. This result deviates from past analyses which characterized the pulse phase timing residuals as either 1/f^4 power-law noise or a quasiperiodic process. The analysis was checked using the Deeter polynomial method of power spectrum estimation that was developed for the case of nonuniform sampling, but has lower spectral resolution. The timing noise is consistent with a torque noise spectrum rising with analysis frequency as f implying blue torque noise, a result not predicted by current models of pulsar timing noise. If the periodic or nearly periodic component is due to a binary companion, we find a companion mass > 3.2 Earth masses.
Molecular Signals and Skeletal Muscle Adaptation to Exercise
Mark Wilson
International Journal of Applied Exercise Physiology , 2013,
Abstract: The phenotypic plasticity of skeletal muscle affords a considerable degree of adaptability not seen in other bodily tissues. The mechanical properties of skeletal muscle are highly dependent on loading conditions. The extent of skeletal muscle plasticity is distinctly highlighted by a loss of muscle mass, or atrophy, after a period of reduced weight-bearing activity, for example during periods of extended bed rest, space flight and in spinal cord injury. On the other hand, increased mechanical loading, or resistance training, induces muscle growth, or hypertrophy. Endurance exercise performance is also dependent on the adaptability of skeletal muscle, especially muscles that contribute to posture, locomotion and the mechanics of breathing. However, the molecular pathways governing skeletal muscle adaptations are yet to be satisfactorily delineated and require further investigation. Researchers in the areas of exercise physiology, physiotherapy and sports medicine are endeavoring to translate experimental knowledge into effective, innovative treatments and regimens in order to improve physical performance and health in both elite athletes and the general community. The efficacy of the translation of molecular biological paradigms in experimental exercise physiology has long been underappreciated. Indeed, molecular biology tools can now be used to answer questions regarding skeletal muscle adaptation in response to exercise and provide new frameworks to improve physical performance. Furthermore, transgenic animal models, knockout animal models and in vivo studies provide tools to test questions concerned with how exercise initiates adaptive changes in gene expression. In light of these perceived deficiencies, an attempt is made here to elucidate the molecular mechanisms of skeletal muscle adaptation to exercise. An examination will be made of the functional capacity of skeletal muscle to respond to a variety of exercise conditions, namely endurance and resistance exercise training. Through the critical evaluation of relevant scientific literature, it is hoped that an overview of the current status of this important area of exercise physiology is achieved.
Co-Regulation of the DAF-16 Target Gene, cyp-35B1/dod-13, by HSF-1 in C. elegans Dauer Larvae and daf-2 Insulin Pathway Mutants
Wendy B. Iser,Mark A. Wilson,William H. Wood III,Kevin Becker,Catherine A. Wolkow
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0017369
Abstract: Insulin/IGF-I-like signaling (IIS) has both cell autonomous and non-autonomous functions. In some cases, targets through which IIS regulates cell-autonomous functions, such as cell growth and metabolism, have been identified. In contrast, targets for many non-autonomous IIS functions, such as C. elegans dauer morphogenesis, remain elusive. Here, we report the use of genomic and genetic approaches to identify potential non-autonomous targets of C. elegans IIS. First, we used transcriptional microarrays to identify target genes regulated non-autonomously by IIS in the intestine or in neurons. C. elegans IIS controls expression of a number of stress response genes, which were differentially regulated by tissue-restricted IIS. In particular, expression of sod-3, a MnSOD enzyme, was not regulated by tissue-restricted IIS on the microarrays, while expression of hsp-16 genes was rescued back to wildtype by tissue restricted IIS. One IIS target regulated non-autonomously by age-1 was cyp-35B1/dod-13, encoding a cytochrome P450. Genetic analysis of the cyp-35B1 promoter showed both DAF-16 and HSF-1 are direct regulators. Based on these findings, we propose that hsf-1 may participate in the pathways mediating non-autonomous activities of age-1 in C. elegans.
Summer Diatom Blooms in the North Pacific Subtropical Gyre: 2008–2009
Tracy A. Villareal, Colbi G. Brown, Mark A. Brzezinski, Jeffrey W. Krause, Cara Wilson
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0033109
Abstract: The summertime North Pacific subtropical gyre has widespread phytoplankton blooms between Hawaii and the subtropical front (~30°N) that appear as chlorophyll (chl) increases in satellite ocean color data. Nitrogen-fixing diatom symbioses (diatom-diazotroph associations: DDAs) often increase 102–103 fold in these blooms and contribute to elevated export flux. In 2008 and 2009, two cruises targeted satellite chlorophyll blooms to examine DDA species abundance, chlorophyll concentration, biogenic silica concentration, and hydrography. Generalized observations that DDA blooms occur when the mixed layer depth is < 70 m are supported, but there is no consistent relationship between mixed layer depth, bloom intensity, or composition; regional blooms between 22–34°N occur within a broader temperature range (21–26°C) than previously reported. In both years, the Hemiaulus-Richelia and Rhizosolenia-Richelia DDAs increased 102–103 over background concentrations within satellite-defined bloom features. The two years share a common trend of Hemiaulus dominance of the DDAs and substantial increases in the >10 μm chl a fraction (~40–90+% of total chl a). Integrated diatom abundance varied 10-fold over <10 km. Biogenic silica concentration tracked diatom abundance, was dominated by the >10 μm size fraction, and increased up to 5-fold in the blooms. The two years differed in the magnitude of the surface chl a increase (2009>2008), the abundance of pennate diatoms within the bloom (2009>2008), and the substantially greater mixed layer depth in 2009. Only the 2009 bloom had sufficient chl a in the >10 μm fraction to produce the observed ocean color chl increase. Blooms had high spatial variability; ocean color images likely average over numerous small events over time and space scales that exceed the individual event scale. Summertime DDA export flux noted at the Hawaii time-series Sta. ALOHA is probably a generalized feature of the eastern N. Pacific north to the subtropical front.
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