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Biomedical subjects

Michael A Wilson

Publications and source records attributed to Michael A Wilson.

17 recordsLinked to original sources
PubMed2006

Multidimensional liquid chromatography for sample characterisation.

While LC finds enormously widespread use in almost all areas of chemical science, the technique is limited as a means of identification because compounds do not elute with unique retention times. This limitation spurred the growth of hyphenated instrumental methods of analysis, such as LC-MS/MS, which because of the MS/ MS detection became a method of identification. However, techniques like LC-MS/ MS are specialised and require high initial purchase and running costs, inhibiting the more widespread growth of the technique. In an attempt to increase the separation power of LC, multi-dimensional LC was developed. This expanded the separation space and subsequently has allowed the development of methods with fingerprinting ability due to the lower probability of component overlap. The work in this study illustrates the application of 2-D LC as a means of chemical fingerprinting. We employed a sample base of various low molecular weight oligostyrenes and their diastereomers that represent a population of compounds whose selectivities in a one-dimensional separation are almost unity and hence essentially impossible to separate. Yet in a 2-D domain almost all individual components occupy unique 2-D retention times.

Journal Article↗
PubMed2006

Macrophage-stimulating activity of polysaccharides extracted from fruiting bodies of Coriolus versicolor (Turkey Tail Mushroom).

The macrophage-stimulating effect of polysaccharides extracted from Coriolus versicolor (Turkey Tail mushroom) was investigated, and their effectiveness was compared with that of lipopolysaccharide (LPS). The purified polysaccharide (CV-S2-Fr.I) of C. versicolor obtained by Sepharose CL-6B gel chromatography stimulated macrophage lysosomal enzyme activity by 250% at a concentration of 100 microg/mL, which was higher than that of LPS at the same concentration. When CV-S2-Fr.I was used in combination with interferon-gamma, there was a marked cooperative induction of nitric oxide production. However, CV-S2-Fr.I had no effect on nitric oxide production by itself. The proportion of C3-positive macrophages in the CV-S2-Fr.I group increased by 7.2-fold compared with the control group.

Agaricales↗
PubMed2006

The impact of coral bleaching on the pigment profile of the symbiotic alga, Symbiodinium.

Bleaching of corals by loss of symbiotic dinoflagellate algae and/or photosynthetic pigments is commonly triggered by elevated temperatures coupled with high irradiance, and is a first-order threat to coral reef communities. In this study, a high-resolution high-performance liquid chromatography method integrated with mass spectrometry was applied to obtain the first definitive identification of chlorophyll and carotenoid pigments of three clades of symbiotic dinoflagellate algae (Symbiodinium) in corals, and their response to experimentally elevated temperature and irradiance. The carotenoids peridinin, dinoxanthin, diadinoxanthin (Dn), diatoxanthin (Dt) and beta-carotene were detected, together with chlorophylls a and c2, and phaeophytin a, in all three algal clades in unstressed corals. On exposure to elevated temperature and irradiance, three coral species (Montastrea franksi and Favia fragum with clade B algae, and Montastrea cavernosa with clade C) bleached by loss of 50-80% of their algal cells, with no significant impact to chlorophyll a or c2, or peridinin in retained algal cells. One species (Agaricia sp. with clade C) showed no significant reduction in algal cells at elevated temperature and irradiance, but lost substantial amounts of chlorophyll a and carotenoid pigments, presumably through photo-oxidative processes. Two coral species (Porites astreoides and Porites porites both bearing clade A algae) did not bleach. The impact of elevated temperature and irradiance on the levels of the photoprotective xanthophylls (Dn + Dt) and beta-carotene varied among the corals, both in pool size and xanthophyll cycling, and was not correlated to coral bleaching resistance.

Animals↗
PubMed2005

Interactions of sodium montmorillonite with poly(acrylic acid).

The chemical-structural modifications of the natural clay sodium montmorillonite during interaction with poly(acrylic acid) were studied mainly by X-ray photoemission spectroscopy. Samples of modified montmorillonite were prepared from the reaction of sodium montmorillonite ( approximately 0.5 g) and an aqueous solution of poly(acrylic acid) (pH approximately 1.8, 50 g) at varying temperatures. X-ray diffraction indicated that the montmorillonite interlayer space ( approximately 13 A), formed by regular stacking of the silicate layers (dimension approximately 1x1000 nm), expanded to approximately 16 A as the reaction was carried out at room temperature and at 30 degrees C. At 60 degrees C, the interlayer space further expanded to approximately 20 A. The results of X-ray photoemission spectroscopy indicated that poly(acrylic acid) molecules exchange sodium ions on the surface of the silicate layers. These combined results allowed development of a reaction model that explains the dependency of the interlayer expansion with temperature. Information concerning the surface chemical reactions and systematic increases in the interlayer distances is particularly useful if montmorillonite and poly(acrylic acid) are to be used for formation of nanocomposite materials.

Acrylic Resins↗
PubMed2005

Precursor decomposition and nucleation kinetics during platelike apatite synthesis.

Self-organization of calcium and phosphorus precursors in solution containing acetic acid and ethylene glycol produces a nanosized lamellar acetate-phosphonate hybrid containing two acetate and one phosphonate components. The lamellar morphology of the hybrid precursor is responsible the formation of platelike apatite product after thermal treatment at or above 400 degrees C. However a preliminary preheating stage (300 degrees C, 24 h) is crucial in determining the morphology of the apatite. Activation energy measurements by nonisothermal thermogravimetric analysis show that decomposition of the hybrid precursor involves at least two steps. Among the three components, it appears that the calcium acetate bidentate chelate component is stable below or at 300 degrees C. However, the calcium phosphonate and calcium acetate monodentate components are decomposed at this temperature. Above 360 degrees C, nuclear magnetic resonance and infrared spectroscopic data reveal the decomposition of more stable calcium acetate bidentate chelate. It is evident that the bond rupture of the bidentate calcium acetate species in the precursor results in the start of crystalline apatite formation but the other components must be decomposed by heating prior to this critical step in order to produce platelike apatite.

Apatites↗
PubMed2005

Study of the selectivity of reversed-phase columns for the separation of polycarboxylic acids and polyphenol compounds.

A systematic investigation was undertaken into the relative separation performance of five reversed-phase chromatography columns including some commercially new hybrid packed columns for a series of polycarboxylic acids and polyphenol compounds. Information theory (IT) and factor analysis (FA), together with a basic evaluation of retention information (band shape, retention factor and elution order) were used to compare four columns to a conventional C18 column. The results revealed very little difference in retention behaviour between the Phenomenex Aqua C18 column, the Waters XTerra RP C18 column, and the conventional Phenomenex Luna C18 column. However, there were notable differences in the retention processes between the Phenomenex Synergi polar-RP column, which is an ether-linked phenyl base with polar endcapping, and the Luna C18 column. The most significant differences were observed between the Luna C18 column and a Phenomenex Luna Cyano column. However, the limited degree of retention of the polycarboxylic acids and polyphenol compounds on the Luna Cyano column permits only limited use for the separation of these types of compounds. Overall, the Phenomenex Synergi polar-RP column exhibited the best performance for the separation of the test solutes compared to that of the conventional C18 column, with IT yielding an Informational Similarity of 0.99 and FA a moderate correlation coefficient of 0.70. The Phenomenex Synergi polar-RP column gave the best peak shape and offered substantial selectivity differences thereby providing a good alternative over the conventional C18 column for separating polycarboxylic acids and polyphenols.

Adsorption↗
PubMed2005

Gene expression in mice infected with West Nile virus strains of different neurovirulence.

West Nile virus causes febrile illness in humans with a proportion of cases progressing to meningoencephalitis, encephalitis, hepatitis, and death. Isolates of the virus fall into two genetic lineages, with differences in neuroinvasiveness for mice occurring between strains within both lineages. We used DNA microarrays to compare gene expression in mice infected peripherally with seven lineage 1 and 2 strains confirmed to be of either high or low neuroinvasiveness in mice and associated with severe or benign infection in humans and birds. The 4 strains with highest neuroinvasiveness induced increased expression of 47 genes in the brain, 111 genes in the liver, and 70 genes in the spleen, relative to the 3 least neuroinvasive strains. Genes involved in interferon signaling pathways, protein degradation, T-cell recruitment, MHC class I and II antigen presentation, and apoptosis were identified that may have both pathogenic and protective effects, but increased expression of certain acute proteins, central nervous system specific proteins and proteins associated with T-cell hepatitis, implicate mechanisms related to exalted virulence.

Animals↗
PubMed2005

Atmospheric pressure chemical ionisation liquid chromatography/multistage mass spectrometry for assignment of sedimentary bacteriochlorophyll derivatives.

Atmospheric pressure chemical ionisation liquid chromatography/multistage mass spectrometry (APCI-LC/MSn) provides a rapid, on-line method for the assignment of individual bacteriophaeophorbide c and d methyl esters (BPMEs) in complex mixtures. The MS2 spectrum for each component is diagnostic of the type of BPME (c or d), and characteristic losses in MS5 and MS6 permit assignment of the alkyl substituents at positions C-8 and C-12 of the macrocycle. MS5 mass chromatograms permit the deconvolution of coeluting isobaric BPMEs, revealing the true profiles of the individual components. The distributions are different in lake sediments from la Salada de Chiprana (Spain) and Kirisjes Pond (Antarctica), and a novel BPME c with a neo-pentyl substituent has been observed in the Kirisjes Pond sediment.

Bacteriochlorophylls↗
PubMed2005

The origin and early evolution of membrane channels.

The origin and early evolution of ion channels are considered from the point of view that the transmembrane segments of membrane proteins are structurally quite simple and do not require specific sequences to fold. We argue that the transport of solute species, especially ions, required an early evolution of efficient transport mechanisms, and that the emergence of simple ion channels was protobiologically plausible. We also argue that, despite their simple structure, such channels could possess properties that, at the first sight, appear to require markedly greater complexity. These properties can be subtly modulated by local modifications to the sequence rather than global changes in molecular architecture. In order to address the evolution and development of ion channels, we focus on identifying those protein domains that are commonly associated with ion channel proteins and are conserved throughout the three main domains of life (Eukarya, Bacteria, and Archaea). We discuss the potassium-sodium-calcium superfamily of voltage-gated ion channels, mechanosensitive channels, porins, and ABC-transporters and argue that these families of membrane channels have sufficiently universal architectures that they can readily adapt to the diverse functional demands arising during evolution.

Evolution, Molecular↗
PubMed2005

Mystery in the basement.

56 year-old male presented to the University of Mississippi Medical Center emergency department (ED) with complaints of progressive shortness of breath, productive cough, fever, and malaise. His past medical history was significant for hypertension as well as a 60 pack-year history of smoking. Upon arrival to the ED he had a temperature of 103.6 degrees F, blood pressure of 80/40 mm Hg, a pulse of 110 beats per minute, respirations of 28 per minute, and an oxygen saturation of 50% on room air. He appeared to be in significant respiratory distress. Lung examination revealed diffuse bilateral rhonchi and wheezes in all lung fields. He was emergently intubated. Chest radiograph demonstrated a miliary pattern scattered throughout all lung fields in addition to parenchymal opacities. A complete blood count revealed a white blood cell count of 33,500 10(3)/microL, hematocrit of 37%, and platelets of 906,000 10(3)/uL. Blood urea nitrogen and creatinine were 27 mg/dL and 1.0 mg/dL, respectively. Initial ABG on 100% oxygen showed pH 7.15, pCO2 82 mm Hg, and pO2 62 mm Hg. Troponin I was negative. An electrocardiogram demonstrated sinus tachycardia. Blood and urine cultures were obtained.

Antifungal Agents↗
PubMed2004

The transcriptional responses of Mycobacterium tuberculosis to inhibitors of metabolism: novel insights into drug mechanisms of action.

The differential transcriptional response of Mycobacterium tuberculosis to drugs and growth-inhibitory conditions was monitored to generate a data set of 430 microarray profiles. Unbiased grouping of these profiles independently clustered agents of known mechanism of action accurately and was successful at predicting the mechanism of action of several unknown agents. These predictions were validated biochemically for two agents of previously uncategorized mechanism, pyridoacridones and phenothiazines. Analysis of this data set further revealed 150 underlying clusters of coordinately regulated genes offering the first glimpse at the full metabolic potential of this organism. A signature subset of these gene clusters was sufficient to classify all known agents as to mechanism of action. Transcriptional profiling of both crude and purified natural products can provide critical information on both mechanism and detoxification prior to purification that can be used to guide the drug discovery process. Thus, the transcriptional profile generated by a crude marine natural product recapitulated the mechanistic prediction from the pure active component. The underlying gene clusters further provide fundamental insights into the metabolic response of bacteria to drug-induced stress and provide a rational basis for the selection of critical metabolic targets for screening for new agents with improved activity against this important human pathogen.

Antipsychotic Agents↗
PubMed2004

Meteors do not break exogenous organic molecules into high yields of diatomics.

Meteoroids that dominate the Earth's extraterrestrial mass influx (50-300 microm size range) may have contributed a unique blend of exogenous organic molecules at the time of the origin of life. Such meteoroids are so large that most of their mass is ablated in the Earth's atmosphere. In the process, organic molecules are decomposed and chemically altered to molecules differently from those delivered to the Earth's surface by smaller (<50 microm) micrometeorites and larger (>10 cm) meteorites. The question addressed here is whether the organic matter in these meteoroids is fully decomposed into atoms or diatomic compounds during ablation. If not, then the ablation products made available for prebiotic organic chemistry, and perhaps early biology, might have retained some memory of their astrophysical nature. To test this hypothesis we searched for CN emission in meteor spectra in an airborne experiment during the 2001 Leonid meteor storm. We found that the meteor's light-emitting air plasma, which included products of meteor ablation, contained less than 1 CN molecule for every 30 meteoric iron atoms. This contrasts sharply with the nitrogen/iron ratio of 1:1.2 in the solid matter of comet 1P/Halley. Unless the nitrogen content or the abundance of complex organic matter in the Leonid parent body, comet 55P/Tempel-Tuttle, differs from that in comet 1P/Halley, it appears that very little of that organic nitrogen decomposes into CN molecules during meteor ablation in the rarefied flow conditions that characterize the atmospheric entry of meteoroids approximately 50 microm-10 cm in size. We propose that the organics of such meteoroids survive instead as larger compounds.

Meteoroids↗
PubMed2004

The mass and speed dependence of meteor air plasma temperatures.

The speed and mass dependence of meteor air plasma temperatures is perhaps the most important data needed to understand how small meteoroids chemically change the ambient atmosphere in their path and enrich the ablated meteoric organic matter with oxygen. Such chemistry can play an important role in creating prebiotic compounds. The excitation conditions in various air plasma emissions were measured from high-resolution optical spectra of Leonid storm meteors during NASA's Leonid Multi-Instrument Aircraft Campaign. This was the first time a sufficient number and range of temperature measurements were obtained to search for meteoroid mass and speed dependencies. We found slight increases in temperature with decreasing altitude, but otherwise nearly constant values for meteoroids with speeds between 35 and 72 km/s and masses between 10(-5) g and 1 g. We conclude that faster and more massive meteoroids produce a larger emission volume, but not a higher air plasma temperature. We speculate that the meteoric plasma may be in multiphase equilibrium with the ambient atmosphere, which could mean lower plasma temperatures in a CO(2)-rich early Earth atmosphere.

Air↗
PubMed2003

Membrane peptides and their role in protobiological evolution.

How simple membrane peptides performed such essential protocellular functions as transport of ions and organic matter across membranes separating the interior of the cell from the environment, capture and utilization of energy, and transduction of environmental signals, is a key question in protobiological evolution. On the basis of detailed, molecular-level computer simulations we explain how these peptides fold at water-membrane interfaces, insert into membranes, self-assemble into higher-order structures and acquire functions. We have investigated the interfacial behavior and folding of several peptides built of leucine and glutamine residues and have demonstrated that many of them tend to adopt ordered structures. Further, we have studied the insertion of an alpha-helical peptide containing leucine (L) and serine (S) of the form (LSLLLSL)3 into a model membrane. The transmembrane state is metastable, and approximately 15 kcal mol(-1) is required to insert the peptide into the membrane. Investigations of dimers formed by (LSLLLSL)3 and glycophorin A demonstrate how the favorable free energy of helix association can offset the unfavorable free energy of insertion, leading to self-assembly of peptide helices in the membrane. An example of a self-assembled structure is the tetrameric transmembrane pore of the influenza virus M2 protein, which is an efficient and selective voltage-gated proton channel. Our simulations explain the gating mechanism and provide guidelines how to re-engineer the channel to act as a simple proton pump. In general, emergence of integral membrane proteins appears to be quite feasible and may be easier to envision than the emergence of water-soluble proteins.

Amino Acids↗
PubMed2002

Carbon exchange in hot alkaline degradation of glucose.

The decomposition of 1-13C-D-glucose, 6-13C-D-glucose, and 1-13C-sodium lactate has been studied in hot (145 +/- 3 degrees C) alkaline (3.5 M) sodium hydroxide solution in order to understand the mechanisms of carbon exchange in the alkaline degradation of glucose. The results show that in the formation of lactate from glucose the carboxylate (COO-) carbon is formed preferentially from C1 carbons but methyl (CH3) carbon is formed preferentially from C6 carbons. However, on further decomposition of lactate to ethanol and carbonate, 13C-labeled carboxylate (COO-) is scrambled equally among carbonate and both carbons in product ethanol molecules. In the production of glycolate, the labeled C1 carbon mainly ends up as carboxylate (COO-) carbon, while for C6-labeled glucose the labeled carbon mainly ends up as alcoholic (CH2OH) carbon. In the production of acetate and formate there is also discrimination between C1 and C6 label.

Acetates↗