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Biomedical subjects

J C Wilson

Publications and source records attributed to J C Wilson.

At least 19 recordsLinked to original sources
PubMed2005

Phylogeographic evidence for the existence of an ancient biogeographic barrier: the Isthmus of Kra Seaway.

Biogeographic boundaries are characterised by distinct faunal and floral assemblages restricted on either side, but patterns among groups of taxa often vary and may not be discrete. Historical biogeography as a consequence, while providing crucial insights into the relationship between biological diversity and earth history, has some limitations. Patterns of intraspecific molecular variation, however, may show unambiguous evidence for such historical divides, and can be used to test competing biogeographic hypotheses (often based on the dispersal-vicariance debate). Here, we utilise this method to test the hypothesis that a major biogeographic transition zone between the Sundaic and Indochinese biotas, located just north of the Isthmus of Kra in SE Asia, is the result of Neogene marine transgressions that breached the Isthmus in two locations for prolonged periods of time (>1 million year duration). Phylogeographic analyses of a freshwater decapod crustacean, the giant freshwater prawn Macrobrachium rosenbergii, strongly supports the historical existence of the more northerly postulated seaway. Results presented here highlight the power of utilising intraspecific molecular variation in testing biogeographical hypotheses.

Animals↗
PubMed2004

Longitudinal study of MRS metabolites in Rasmussen encephalitis.

This study analyses the evolution of metabolite changes in an 8-year-old boy with focal Rasmussen encephalitis. Five MRI examinations, including magnetic resonance spectroscopy (MRS) were performed over 9 months. Following complex partial status, T2-weighted imaging showed transient dramatic signal increase in the left superior temporal gyrus and mesial temporal structures. Subsequent scans showed resolution of the swelling and signal normalization, with development of slight focal atrophy. MRS after status showed a reduction in N-acetylaspartate, total creatine and trimethylamines. Subsequent scans showed complete resolution of these metabolite abnormalities, followed later by development of further abnormal metabolite values. Lactate and glutamine/glutamate were elevated after status. After surgery, ex vivo high-field (1)H and (31)P MRS confirmed metabolite abnormalities (elevated choline and decreased aspartate, N-acetylaspartate, [(1)H]glutamate together with altered [(31)P]phospholipid ratios. These findings suggested active disease process in the anterior region of the excised superior temporal gyrus. We conclude that Rasmussen encephalitis is a combination of progressive encephalitic damage and fluctuating seizure effects, in which neuronal injury and recovery can occur. MRS measurements at a single time point should consider the fluctuating metabolite profile related to seizure activity.

Child↗
PubMed2003

Particle formation by ion nucleation in the upper troposphere and lower stratosphere.

Unexpectedly high concentrations of ultrafine particles were observed over a wide range of latitudes in the upper troposphere and lower stratosphere. Particle number concentrations and size distributions simulated by a numerical model of ion-induced nucleation, constrained by measured thermodynamic data and observed atmospheric key species, were consistent with the observations. These findings indicate that, at typical upper troposphere and lower stratosphere conditions, particles are formed by this nucleation process and grow to measurable sizes with sufficient sun exposure and low preexisting aerosol surface area. Ion-induced nucleation is thus a globally important source of aerosol particles, potentially affecting cloud formation and radiative transfer.

Journal Article↗
PubMed2003

Recent strategies in the search for new anti-influenza therapies.

Influenza is a highly contagious, acute upper respiratory tract disease caused by influenza virus, a member of the Orthomyxoviridae family. The viral particles have two surface antigens, haemagglutinin and sialidase (neuraminidase) that extensively decorate the surface of the virus and have been implicated in viral attachment and fusion, and the release of virion progeny, respectively. The receptor for haemagglutinin is the terminal sialic acid residue of host cell surface sialyloligosaccharides, while sialidase catalyses the hydrolysis of terminal sialic acid residues from sialyloligosaccharides. Extensive crystallographic studies of both these proteins have revealed that the residues that interact with the sialic acid are strictly conserved. Therefore, these proteins make attractive targets for the design of drugs to halt the progression of the virus. Recent successful efforts in the search for new cures for influenza have led to the development of three clinically-useful anti-influenza drugs. All three are potent, selective inhibitors of influenza virus A and B sialidase. Strategies for the development of haemagglutinin inhibitors have also been devised.

Antiviral Agents↗
PubMed2001

The detection of large HNO3-containing particles in the winter Arctic stratosphere.

Large particles containing nitric acid (HNO3) were observed in the 1999/2000 Arctic winter stratosphere. These in situ observations were made over a large altitude range (16 to 21 kilometers) and horizontal extent (1800 kilometers) on several airborne sampling flights during a period of several weeks. With diameters of 10 to 20 micrometers, these sedimenting particles have significant potential to denitrify the lower stratosphere. A microphysical model of nitric acid trihydrate particles is able to simulate the growth and sedimentation of these large sizes in the lower stratosphere, but the nucleation process is not yet known. Accurate modeling of the formation of these large particles is essential for understanding Arctic denitrification and predicting future Arctic ozone abundances.

Journal Article↗
PubMed2001

Formulations and processing of yogurt affect the microbial quality of carbonated yogurt.

Carbonation, flavor, culture type, pH, and storage time were varied to investigate the effects of these variables and their interactions on the growth of both typical and nontypical yogurt cultures and some contaminating bacteria. Two types of yogurt cultures (YC-470 and YC-180) were used as the source of typical yogurt bacteria, Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus. In addition, Lactobacillus acidophilus (LA-K) and Bifidobacterium longum ATCC 15707 were added as nontypical yogurt cultures to make sweetened low fat (1%) Swiss-style plain, strawberry, and lemon yogurts. Samples were incubated at 43 degrees C until pH values of 5.0 or 4.2 were reached. Strawberry yogurts at low (4.2) and high (5.0) pHs were divided into three portions, which were separately inoculated with contaminating bacteria, Bacillus licheniformis ATCC 14580, Escherichia coli ATCC 11775, and Listeria monocytogenes Scott A. After incorporation of carbon dioxide (1.10 to 1.27 volume of CO2 gas dissolved in water), the yogurt was stored at 4 degrees C for a 90-d period. Carbon dioxide did not affect the growth of typical or nontypical yogurt bacteria. Also, CO2 did not inhibit the growth of undesirable microorganisms. In general, low levels of CO2 did not affect the bacterial population in yogurt. The microflora of yogurt were influenced by culture type, pH, flavor type, and storage time or their interactions.

Bacillus↗
PubMed2000

Synthesis and evaluation of C-9 modified N-acetylneuraminic acid derivatives as substrates for N-acetylneuraminic acid aldolase.

Several C-9 modified N-acetylneuraminic acid derivatives have been synthesised and evaluated as substrates of N-acetylneuraminic acid aldolase. Simple C-9 acyl or ether modified derivatives of N-acetylneuraminic acid were found to be accepted as substrates by the enzyme, albeit being transformed more slowly than Neu5Ac itself. 1H NMR spectroscopy was used to evaluate the extent of the enzyme catalysed transformation of these compounds. Interestingly, the chain-extended Neu5Ac derivative 16 is not a substrate for N-acetylneuraminate lyase and behaves as an inhibitor of the enzyme.

Bacterial Proteins↗
PubMed2000

The conformational and biological analysis of a cyclic anti-obesity peptide from the C-terminal domain of human growth hormone.

The three-dimensional solution structure of antiobesity drug (AOD), a 15-residue, disulfide-bonded, cyclic peptide, cyclo(6,13)-H2N-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe-OH, derived from the C-terminal domain of the human growth hormone (hGH) (residues 177-191) was determined using two-dimensional 1H NMR spectroscopy. AOD stimulates lipolysis and inhibits lipogenesis, in vitro, in rodent, porcine and human adipose tissues. These biological effects suggest that AOD is a potential therapeutic candidate for the treatment of obesity. Conformational studies of AOD were conducted in aqueous solution and in water/dimethylsulfoxide mixtures. In general, spectral quality was superior in the water/ dimethylsulfoxide mixtures. The cyclic region of AOD in water/dimethylsulfoxide adopts type I beta-turns at residues Ser8-Val9-Glu10-Gly11 and Ser12-Cys13-Gly14-Phe15, each preceded by loop-like structures. Comparison of the conformation of this peptide with residues 177-191 in the native hGH protein X-ray crystal structure indicates that the synthetic peptide retains some structural similarity to the intact protein. This study provides evidence that the C-terminal region of hGH is a specific functional domain of the multifunctional hGH protein.

Adipose Tissue↗
PubMed1999

Investigation of the stability of thiosialosides toward hydrolysis by sialidases using NMR spectroscopy.

[formula: see text] 1H NMR spectroscopy has been used to investigate whether the alpha(2-->6)-linked thiosialoside 3 and the alpha(2-->3)-linked thiosialoside 9 are hydrolyzed in the presence of Vibrio cholerae sialidase. Similarly, the hydrolysis of the O-ketosides Neu5Ac-2-O-alpha-(2-->3)-Gal beta Me (4) and the alpha-(2-->6)-sialyllactoside 7, representing natural alpha(2-->3)- and alpha(2-->6)-linked sialosides, respectively, was investigated. The results of the 1H NMR experiments clearly demonstrate that the thiosialosides are not hydrolyzed by Vibrio cholerae sialidase. As expected, the O-sialosides are hydrolyzed to give N-acetyl-alpha-D-neuraminic acid as the first product of substrate cleavage.

Carbohydrate Sequence↗
PubMed1999

Children's recall 1 or 2 years after an event.

In Study 1, children were reinterviewed about an event they had taken part in 2 years earlier when they were 6 years old (M.-E. Pipe & J. C. Wilson, 1994). In Study 2, children were reinterviewed about an event in which they had participated 1 year earlier when they were 6 or 9 years of age (S. Gee & M.-E. Pipe, 1995). Interviews were conducted with or without cue items and distractors, as in the original studies. The amount of information reported in free recall decreased over the 1- or 2-year delays, and for 6-year-olds, there was also a small decrease in accuracy of free recall. Reinstating specific cue items in Study 2 maintained recall when attention was drawn to them, but prompting children led to a decrease in accuracy. Whereas information repeated across interviews was highly accurate, information reported for the first time at the long delays was not.

Child↗
PubMed1999

Viscoelasticity of randomly branched polymers in the vulcanization class.

We report viscosity, recoverable compliance, and molar mass distribution for a series of randomly branched polyester samples with long linear chain sections between branch points. Molecular structure characterization determines tau=2.47+/-0.05 for the exponent controlling the molar mass distribution, so this system belongs to the vulcanization (mean-field) universality class. Consequently, branched polymers of similar size strongly overlap and form interchain entanglements. The viscosity diverges at the gel point with an exponent s=6.1+/-0.3, that is significantly larger than the value of 1.33 predicted by the branched polymer Rouse model (bead-spring model without entanglements). The recoverable compliance diverges at the percolation threshold with an exponent t=3.2+/-0.2. This effect is consistent with the idea that each branched polymer of size equal to the correlation length stores k(B)T of elastic energy. Near the gel point, the complex shear modulus is a power law in frequency with an exponent u=0.33+/-0.05. The measured rheological exponents confirm that the dynamic scaling law u=t/(s+t) holds for the vulcanization class. Since s is larger and u is smaller than the Rouse values observed in systems that belong to the critical percolation universality class, we conclude that entanglements profoundly increase the longest relaxation time. Examination of the literature data reveals clear trends for the exponents s and u as functions of the chain length between branch points. These dependencies, qualitatively explained by hierarchical relaxation models, imply that the dynamic scaling observed in systems that belong to the vulcanization class is nonuniversal.

Journal Article↗
PubMed1997

Reciprocal regulation of the early promoter region of bacteriophage HP1 by the Cox and Cl proteins.

We have identified a transcriptional switch at the early promoter region of bacteriophage HP1. This switch controls the transcription of the early lytic operon from the P(R1) and P(R2) promoters and the transcription of the lysogenic operon from the P(L) promoter. The start sites of the three promoters were mapped, and using a chloramphenicol acetyl transferase assay, we have investigated the levels of transcription from the promoters in the absence or in the presence of two phage-encoded transcription factors: HP1 Cox and HP1 Cl. The HP1 Cox protein repressed the production of P(L) transcripts 30-fold, while the HP1 Cl protein repressed lytic transcription at least 70-fold. Binding sites for HP1 Cox and Cl were identified in the early promoter region; mutations of these sites eliminated transcriptional repression. In addition, a mutant Cl protein was isolated which is temperature sensitive for repression. Taken together, these data demonstrate the reciprocal regulation of a transcriptional switch in which the actions of the two phage-encoded proteins at the phage early promoters determine the choice between lytic and lysogenic growth.

Bacteriophages↗
PubMed1997

Crystal structure of vipoxin at 2.0 A: an example of regulation of a toxic function generated by molecular evolution.

Vipoxin is the main toxic component in the venom of the Bulgarian snake Vipera ammodytes meridionalis, the most toxic snake in Europe. Vipoxin is a complex between a toxic phospholipase A2 (PLA2) and a non-toxic protein inhibitor. The structure is of genetic interest due to the high degree of sequence homology (62%) between the two functionally different components. The structure shows that the formation of the complex in vipoxin is significantly different to that seen in many known structures of phospholipases and contradicts the assumptions made in earlier studies. The modulation of PLA2 activity is of great pharmacological interest, and the present structure will be a model for structure-based drug design.

Amino Acid Sequence↗
PubMed1997

A conformational study of the human and rat encephalitogenic myelin oligodendrocyte glycoprotein peptides 35-55.

Myelin oligodendrocyte glycoprotein (MOG), is considered an important central-nervous system-specific target autoantigen for primary demyelination in autoimmune diseases like multiple sclerosis. We have recently demonstrated that MOG or its derived peptide, MOG-(35-55)-peptide, are able to produce in animals, clinicopathologic signs that mimic multiple sclerosis. The rat MOG sequence spanning amino acids 35-55 [rMOG-(35-55)-peptide] differs from the human sequence [hMOG-(35-55)-peptide] by a single amino acid substitution, i.e. Pro42-->Ser. Mice injected with rMOG-(35-55)-peptide showed severe inflammation and demyelination throughout the central nervous system but, interestingly, mice injected with hMOG-(35 -55)-peptide showed only a few foci of mild inflammation with no demyelination. Circular dichroism and nuclear magnetic resonance spectroscopy have been used to structurally characterise the bioactive peptides hMOG-(35-55)-peptide and rMOG-(35-55)-peptide. In 0.1 M K2HPO4/KOH, 90% H2O/D2O solutions, these derived peptides have been shown, by NMR spectroscopy, to adopt detectable levels of short-range structure in equilibrium with unfolded conformers. On addition of 2,2,2-trifluoro-(2H3)ethanol, rMOG-(35-55)-peptide and hMOG-(35-55)-peptide adopt folded structures which have nuclear Overhauser enhancements characteristic of a poorly defined alpha-helix over residues 44-51. There are some indications of secondary structure also evident in the N-terminal region of rMOG-(35-55)-peptide. CD spectroscopy has revealed that in aqueous solution both peptides are unfolded but in 2.2.2-trifluoroethanol and, at micellar concentrations of sodium dodecyl sulfate, rMOG-(35-55)-peptide and, to a lesser extent, hMOG-(35-55)-peptide adopt helical conformations. In contrast, at non-micellar concentrations of SDS rMOG-(35-55)-peptide and hMOG-(35-55)-peptide adopt, according to CD spectroscopy, a beta-structure indicating that the peptides change conformation depending on the microenvironment of the amino acids.

Amino Acid Sequence↗
PubMed1997

Catalysis by a new sialidase, deaminoneuraminic acid residue-cleaving enzyme (KDNase Sm), initially forms a less stable alpha-anomer of 3-deoxy-D-glycero-D-galacto-nonulosonic acid and is strongly inhibited by the transition state analogue, 2-deoxy-2, 3-didehydro-D-glycero-D-galacto-2-nonulopyranosonic acid, but not by 2-deoxy-2,3-didehydro-N-acetylneuraminic acid.

Deaminoneuraminic acid residue-cleaving enzyme (KDNase Sm) is a new sialidase that has been induced and purified from Sphingobacterium multivorum. Catalysis by this new sialidase has been studied by enzyme kinetics and 1H NMR spectroscopy. Vmax/Km values determined for synthetic and natural substrates of KDNase Sm reveal that 4-methylumbelliferyl-KDN (KDNalpha2MeUmb, Vmax/Km = 0.033 min-1) is the best substrate for this sialidase, presumably because of its good leaving group properties. The transition state analogue, 2, 3-didehydro-2,3-dideoxy-D-galacto-D-glycero-nonulosonic acid, is a strong competitive inhibitor of KDNase Sm (Ki = 7.7 microM versus Km = 42 microM for KDNalpha2MeUmb). 2-Deoxy-2, 3-didehydro-N-acetylneuraminic acid and 2-deoxy-2, 3-didehydro-N-glycolylneuraminic acid are known to be strong competitive inhibitors for bacterial sialidases such as Arthrobacter ureafaciens sialidase; however, KDNase Sm activity is not significantly inhibited by these compounds. This observation suggests that the hydroxyl group at C-5 is important for recognition of the inhibitor by the enzyme. Reversible addition of water molecule (or hydroxide ion) to the reactive sialosyl cation, presumably formed at the catalytic site of KDNase Sm, eventually gives rise to two different adducts, the alpha- and beta-anomers of free 3-deoxy-D-glycero-D-galacto-nonulosonic acid. 1H NMR spectroscopic studies clearly demonstrate that the thermodynamically less stable alpha-form is preferentially formed as the first product of the cleavage reaction and that isomerization rapidly follows, leading to an equilibrium mixture of the two isomers, the beta-isomer being the major species at equilibrium. Therefore, we propose that KDNase Sm catalysis proceeds via a mechanism common to the known exosialidases, but the recognition of the substituent at C-5 by the enzyme differs.

Flavobacterium↗
PubMed1997

Platelet-derived growth factor in human brain tumors.

This paper initially reviews ligand and receptor systems for the PDGF family and the signalling systems they use as well as their role in neural developments. It then describes the putative role of this family in astrocytoma, meningioma, and pituitary adenoma pathogenesis. Potential therapies with receptor antagonists or dominant negative mutants are discussed in the final sections.

Animals↗