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Biomedical subjects

B Adams

Publications and source records attributed to B Adams.

At least 19 recordsLinked to original sources
PubMed2006

Cross-protective immunity can account for the alternating epidemic pattern of dengue virus serotypes circulating in Bangkok.

Dengue virus, the causative agent of dengue fever and its more serious manifestation dengue hemorrhagic fever, is widespread throughout tropical and subtropical regions. The virus exists as four distinct serotypes, all of which have cocirculated in Bangkok for several decades with epidemic outbreaks occurring every 8-10 years. We analyze time-series data of monthly infection incidence, revealing a distinctive pattern with epidemics of serotypes 1, 2, and 3 occurring at approximately the same time and an isolated epidemic of serotype 4 occurring in the intervening years. Phylogenetic analysis of virus samples collected over the same period shows that clade replacement events are linked to the epidemic cycle and indicates that there is an interserotypic immune reaction. Using an epidemic model with stochastic seasonal forcing showing 8- to 10-year epidemic oscillations, we demonstrate that moderate cross-protective immunity gives rise to persistent out-of-phase oscillations similar to those observed in the data, but that strong or weak cross-protection or cross-enhancement only produces in-phase patterns. This behavior suggests that the epidemic pattern observed in Bangkok is the result of cross-protective immunity and may be significantly altered by changes in the interserotypic immune reaction.

Dengue↗
PubMed2006

Assessing reliability of microsatellite genotypes from kit fox faecal samples using genetic and GIS analyses.

Noninvasive faecal DNA sampling has the potential to provide a wealth of information necessary for monitoring and managing endangered species while eliminating the need to capture, handle or observe rare individuals. However, scoring problems, and subsequent genotyping errors, associated with this monitoring method remain a great concern as they can lead to misidentification of individuals and biased estimates. We examined a kit fox scat data set (353 scats; 80 genotypes) for genotyping errors using both genetic and GIS analyses, and evaluated the feasibility of combining both approaches to assess reliability of the faecal DNA results. We further checked the appropriateness of using faecal genotypes to study kit fox populations by describing information about foxes that we could deduce from the 'acceptable' scat genotypes, and comparing it to information gathered with traditional field techniques. Overall, genetic tests indicated that our data set had a low rate of genotyping error. Furthermore, examination of distributions of scat locations confirmed our data set was relatively error free. We found that analysing information on sex primer consistency and scat locations provided a useful assessment of scat genotype error, and greatly limited the amount of additional laboratory work that was needed to identify potentially 'false' scores. 'Acceptable' scat genotypes revealed information on sex ratio, relatedness, fox movement patterns, latrine use, and size of home range. Results from genetic and field data were consistent, supporting the conclusion that our data set had a very low rate of genotyping error and that this noninvasive method is a reliable approach for monitoring kit foxes.

Animals↗
PubMed2003

One-dimensional daisyworld: spatial interactions and pattern formation.

The zero-dimensional daisyworld model of Watson and Lovelock (1983) demonstrates that life can unconsciously regulate a global environment. Here that model is extended to one dimension, incorporating a distribution of incoming solar radiation and diffusion of heat consistent with a spherical planet. Global regulatory properties of the original model are retained. The daisy populations are initially restricted to hospitable regions of the surface but exert both global and local feedback to increase this habitable area, eventually colonizing the whole surface. The introduction of heat diffusion destabilizes the coexistence equilibrium of the two daisy types. In response, a striped pattern consisting of blocks of all black or all white daisies emerges. There are two mechanisms behind this pattern formation. Both are connected to the stability of the system and an overview of the mathematics involved is presented. Numerical experiments show that this pattern is globally determined. Perturbations in one region have an impact over the whole surface but the regulatory properties of the system are not compromised by transient perturbations. The relevance of these results to the Earth and the wider climate modelling field is discussed.

Climate↗
PubMed2003

A protein kinase from Colletotrichum trifolii is induced by plant cutin and is required for appressorium formation.

When certain phytopathogenic fungi contact plant surfaces, specialized infection structures (appressoria) are produced that facilitate penetration of the plant external barrier; the cuticle. Recognition of this hydrophobic host surface must be sensed by the fungus, initiating the appropriate signaling pathway or pathways for pathogenic development. Using polymerase chain reaction and primers designed from mammalian protein kinase C sequences (PKC), we have isolated, cloned, and characterized a protein kinase from Colletotrichum trifolii, causal agent of alfalfa anthracnose. Though sequence analysis indicated conserved sequences in mammalian PKC genes, we were unable to induce activity of the fungal protein using known activators of PKC. Instead, we show that the C. trifolii gene, designated LIPK (lipid-induced protein kinase) is induced specifically by purified plant cutin or long-chain fatty acids which are monomeric constituents of cutin. PKC inhibitors prevented appressorium formation and, to a lesser extent, spore germination. Overexpression of LIPK resulted in multiple, abnormally shaped appressoria. Gene replacement of lipk yielded strains which were unable to develop appressoria and were unable to infect intact host plant tissue. However, these mutants were able to colonize host tissue following artificial wounding, resulting in typical anthracnose lesions. Taken together, these data indicate a central role in triggering infection structure formation for this protein kinase, which is induced specifically by components of the plant cuticle. Thus, the fungus is able to sense and use host surface chemistry to induce a protein kinase-mediated pathway that is required for pathogenic development.

Amino Acid Sequence↗
PubMed2003

Injury prevention attitudes and awareness in New Zealand.

OBJECTIVES: This study was designed to obtain New Zealand data on beliefs related to a broad spectrum of injuries and their prevention. METHODS: A cross sectional phone survey was conducted of approximately 400 randomly selected households from each of 13 territorial local authorities across New Zealand, giving a total of 5282. Respondents were asked questions on awareness and attitudes to injury prevention, ownership and use of safety equipment, safety behaviours, and incidence of self reported injury. RESULTS: 84% agreed with the statement that "Most injuries are preventable" and 91% rated their homes as "very safe" or "reasonably safe". A high proportion of homes had smoke alarms (81%) and first aid kits (81%), and more than half (56%) had turned down the temperature of their hot water to 55 degrees C or lower. However, less than half of the respondents said that they practised the other safety behaviours. Significant associations were found between the practise of safety behaviours and respondents' home safety ratings. There was a significant association between home safety ratings and the incidence of injury occurring in all settings (p<0.0001), however there was no discernable association between home safety ratings and injury occurring in the home. CONCLUSIONS: Although this survey found that most respondents believed that injuries are preventable and considered their homes to be safe, the public need to be further encouraged to adopt common safety practices and behaviours in the home.

Accidents, Home↗
PubMed2002

Performance deficits of mGluR8 knockout mice in learning tasks: the effects of null mutation and the background genotype.

mGluR8 is a G-protein coupled metabotropic glutamate receptor expressed in the mammalian brain. Members of the mGluR family have been shown to be modulators of neural plasticity and learning and memory. Here we analyze the consequences of a null mutation at the mGluR8 gene locus generated using homologous recombination in embryonic stem cells by comparing the learning performance of the mutants with that of wild type controls in the Morris water maze (MWM) and the context and cue dependent fear conditioning (CFC). Our results revealed robust performance deficits associated with the genetic background, the ICR outbred strain, in both mGluR8 null mutant and the wild type control mice. Mice of this strain origin suffered from impaired vision as compared to CD1 or C57BL/6 mice, a significant impediment in MWM, a visuo-spatial learning task. The CFC task, being less dependent on visual cues, allowed us to reveal subtle performance deficits in the mGluR8 mutants: novelty induced hyperactivity and temporally delayed and blunted responding to shocks and temporally delayed responding to contextual stimuli were detected. The role of mGluR8 as a presynaptic autoreceptor and its contribution to cognitive processes are hypothesized and the utility of gene targeting as compared to pharmacological methods is discussed.

Animals↗
PubMed2001

A novel tetratricopeptide repeat (TPR) containing PP5 serine/threonine protein phosphatase in the malaria parasite, Plasmodium falciparum.

BACKGROUND: The malarial parasite, Plasmodium falciparum (Pf), is responsible for nearly 2 million deaths worldwide. However, the mechanisms of cellular signaling in the parasite remain largely unknown. Recent discovery of a few protein kinases and phosphatases point to a thriving reversible phosphorylation system in the parasite, although their function and regulation need to be determined. RESULTS: We provide biochemical and sequence evidence for a protein serine/threonine phosphatase type PP5 in Plasmodium falciparum, and named it PfPP5. The 594-amino acid polypeptide was encoded by a 1785 nucleotide long intronless gene in the parasite. The recombinant protein, expressed in bacteria, was indistinguishable from native PfPP5. Sequencing comparison indicated that the extra-long N-terminus of PfPP5 outside the catalytic core contained four tetratricopeptide repeats (TPRs), compared to three such repeats in other PP5 phosphatases. The PfPP5 N-terminus was required for stimulation of the phosphatase activity by polyunsaturated fatty acids. Co-immunoprecipitation demonstrated an interaction between native PfPP5 and Pf heat shock protein 90 (hsp90). PfPP5 was expressed in all the asexual erythrocytic stages of the parasite, and was moderately sensitive to okadaic acid. CONCLUSIONS: This is the first example of a TPR-domain protein in the Apicomplexa family of parasites. Since TPR domains play important roles in protein-protein interaction, especially relevant to the regulation of PP5 phosphatases, PfPP5 is destined to have a definitive role in parasitic growth and signaling pathways. This is exemplified by the interaction between PfPP5 and the cognate chaperone hsp90.

Amino Acid Sequence↗
PubMed2001

Coherent control of pulsed X-ray beams.

Synchrotrons produce continuous trains of closely spaced X-ray pulses. Application of such sources to the study of atomic-scale motion requires efficient modulation of these beams on timescales ranging from nanoseconds to femtoseconds. However, ultrafast X-ray modulators are not generally available. Here we report efficient subnanosecond coherent switching of synchrotron beams by using acoustic pulses in a crystal to modulate the anomalous low-loss transmission of X-ray pulses. The acoustic excitation transfers energy between two X-ray beams in a time shorter than the synchrotron pulse width of about 100 ps. Gigahertz modulation of the diffracted X-rays is also observed. We report different geometric arrangements, such as a switch based on the collision of two counter-propagating acoustic pulses: this doubles the X-ray modulation frequency, and also provides a means of observing a localized transient strain inside an opaque material. We expect that these techniques could be scaled to produce subpicosecond pulses, through laser-generated coherent optical phonon modulation of X-ray diffraction in crystals. Such ultrafast capabilities have been demonstrated thus far only in laser-generated X-ray sources, or through the use of X-ray streak cameras.

Journal Article↗
PubMed2001

Reactions of dimethylsulfoxide reductase in the presence of dimethyl sulfide and the structure of the dimethyl sulfide-modified enzyme.

The bis-molybdopterin enzyme dimethylsulfoxide reductase (DMSOR) from Rhodobacter capsulatus catalyzes the conversion of dimethyl sulfoxide (DMSO) to dimethyl sulfide (DMS), reversibly, in the presence of suitable e(-)-donors or e(-)-acceptors. The catalytically significant intermediate formed by reaction of DMSOR with DMS ('the DMS species') and a damaged enzyme form derived by reaction of the latter with O(2) (DMS-modified enzyme, DMSOR(mod)D) have been investigated. Evidence is presented that Mo in the DMS species is not, as widely assumed, Mo(IV). Formation of the DMS species is reversed on removing DMS or by addition of an excess of DMSO. Equilibrium constants for the competing reactions of DMS and DMSO with the oxidized enzyme (K(d) = 0.07 +/- 0.01 and 21 +/- 5 mM, respectively) that control these processes indicate formation of the DMS species occurs at a redox potential that is 80 mV higher than that required, according to the literature, for reduction of Mo(VI) to Mo(IV) in the free enzyme. Specificity studies show that with dimethyl selenide, DMSOR yields a species analogous to the DMS species but with the 550 nm peak blue-shifted by 27 nm. It is concluded from published redox potential data that this band is due to metal-to-ligand charge transfer from Mo(V) to the chalcogenide. Since the DMS species gives no EPR signal in the normal or parallel mode, a free radical is presumed to be in close proximity to the metal, most likely on the S. The species is thus formulated as Mo(V)-O-S(*)Me(2). Existing X-ray crystallographic and Raman data are consistent with this structure. Furthermore, 1e(-) oxidation of the DMS species with phenazine ethosulfate yields a Mo(V) form without an -OH ligand, since its EPR signal shows no proton splittings. This form presumably arises via dissociation of DMSO. The structure of DMSOR(mod)D has been determined by X-ray crystallography. All four thiolate ligands and Ogamma of serine-147 remain coordinated to Mo, but there are no terminal oxygen ligands and Mo is Mo(VI). Thus, it is a dead-end species, neither oxo group acceptance nor e(-)-donation being possible. O(2)-dependent formation of DMSOR(mod)D represents noncatalytic breakdown of the DMS species by a pathway alternative to that in turnover, with oxidation to Mo(VI) presumably preceding product release. Steps in the forward and backward catalytic cycles are discussed in relation to earlier stopped-flow data. The finding that in the back-assay the Mo(IV) state may at least in part be by-passed via two successive 1e(-) reactions of the DMS species with the e(-)-acceptor, may have implications in relation to the existence of separate molybdopterin enzymes catalyzing DMSO reduction and DMS oxidation, respectively.

Electron Spin Resonance Spectroscopy↗
PubMed2001

Intron conservation in the DNA polymerase gene encoded by Chlorella viruses.

Previously we reported that 19 of 42 viruses that infect Chlorella strain NC64A (NC64A viruses) contain a short, nuclear-located, spliceosomal-processed intron in a pyrimidine dimer-specific glycosylase/apyrimidine lyase (pdg) gene. Surprisingly, the nucleotide sequence of the intron region is more conserved than the exon regions of the gene (L. Sun et al., 2000, J. Mol. Evol. 50, 82-92). For comparative purposes, we determined the nucleotide sequence of a similar intron type and its flanking coding regions in the DNA polymerase (dnapol) gene from the same 42 NC64A viruses and also 5 viruses that infect Chlorella strain Pbi. Thirty-eight of the 42 NC64A viruses contained a 101-nucleotide intron and the remaining 4 had an 86-nucleotide intron located in the same position in dnapol. The 4 viruses with the smaller intron in dnapol also have a smaller intron in their pdg gene. There was no intron in the dnapol gene of the 5 Pbi viruses. Phylogenetic analyses indicate that the dnapol genes containing the 86-nucleotide intron represent the ancestral condition among the NC64A viruses. The intron in the dnapol gene is phase 0 (keeps codons intact), which differs from the phase 1 intron in the pdg gene. The intron in the dnapol gene, unlike the pdg intron, was conserved (83 to 100% identical) to about the same extent as the coding regions of the gene (78 to 100% identical).

Amino Acid Sequence↗
PubMed2000

Muscarinic stimulation of alpha1E Ca channels is selectively blocked by the effector antagonist function of RGS2 and phospholipase C-beta1.

Neuronal alpha1E Ca channel subunits are widely expressed in mammalian brain, where they are thought to form R-type Ca channels. Recent studies have demonstrated that R-type channels contribute to neurosecretion and dendritic Ca influx, but little is known concerning their modulation. Here we show that alpha1E channels are strongly stimulated, and only weakly inhibited, through M1 muscarinic acetylcholine receptors. Both forms of channel modulation are mediated by pertussis toxin-insensitive G-proteins. Channel stimulation is blocked by regulator of G-protein signaling 2 (RGS2) or the C-terminal region of phospholipase C-beta1 (PLCbeta1ct), which have been previously shown to function as GTPase-activating proteins for Galphaq. In contrast, RGS2 and PLCbeta1ct do not block inhibition of alpha1E through M1 receptors. Inhibition is prevented, however, by the C-terminal region of beta-adrenergic receptor kinase 1, which sequesters Gbetagamma dimers. Thus, stimulation of alpha1E is mediated by a pertussis toxin-insensitive Galpha subunit (e.g., Galphaq), whereas inhibition is mediated by Gbetagamma. The ability of RGS2 and PLCbeta1ct to selectively block stimulation indicates these proteins functioned primarily as effector antagonists. In support of this interpretation, RGS2 prevented stimulation of alpha1E with non-hydrolyzable guanosine 5'-0-(3-thiotriphosphate). We also report strong muscarinic stimulation of rbE-II, a variant alpha1E Ca channel that is insensitive to voltage-dependent inhibition. Our results predict that Galphaq-coupled receptors predominantly stimulate native R-type Ca channels. Receptor-mediated enhancement of R-type Ca currents may have important consequences for neurosecretion, dendritic excitability, gene expression, or other neuronal functions.

Animals↗
PubMed2000

Reversible dissociation of thiolate ligands from molybdenum in an enzyme of the dimethyl sulfoxide reductase family.

Much is unknown concerning the role of thiolate ligands of molybdenum in molybdopterin enzymes. It has been suggested that thiolate dissociation from molybdenum is part of the catalytic mechanism of bis-molybdopterin enzymes of the dimethyl sulfoxide reductase (DMSOR) family. For DMSOR from Rhodobacter capsulatus, thiolate dissociation has therefore been investigated crystallographically, by UV/visible spectroscopy, and by enzyme assays. When crystallized from sodium citrate, all four thiolates of DMSOR are within bonding distance of Mo, but after extended exposure to Na(+)-Hepes, a pair of thiolates dissociates, a mixture of structures being indicated after shorter exposures to this buffer. DMSOR is stable in sodium citrate and other buffers but unstable aerobically although not anaerobically in Na(+)-Hepes. Aerobically in Na(+)-Hepes, a first-order reaction (k = 0.032 hr(-)(1) at 37 degrees C) leads to loss of activity in the backward but not the forward (dimethyl sulfoxide reduction) assay and loss of absorption at lambda > approximately 450 nm. This reaction can be reversed by a cycle of reduction and reoxidation ("redox-cycling"). Slower irreversible loss of activity in the forward assay and cofactor dissociation follow. Spectral analogy with a mono-molybdopterin enzyme supports the conclusion that in the Hepes-modified DMSOR form, only two cofactor dithiolene sulfur atoms are coordinated to molybdenum. Loss of activity provides the first clear evidence that sulfur ligand dissociation is an artifact, not part of the catalytic cycle. Clearly, structural data on DMSOR samples extensively exposed to Hepes is not directly relevant to the native enzyme. The nature of the oxygen ligands detected crystallographically is discussed, as is the specificity of Hepes and the mechanism whereby its effects are achieved. DMSOR forms complexes with Na(+)-Hepes and other buffer ions. For DMSOR crystallized from Hepes, electron density in the substrate binding channel suggests that buffers bind in this site. Like the as-prepared enzyme, the modified form (DMSOR(mod)D), known to arise on extended aerobic exposure to dimethyl sulfide, is susceptible to a further degradative reaction, although this is not buffer-dependent. It involves loss of absorption at lambda > approximately 450 nm and, presumably, dissociation of thiolate ligands. Evidence is presented that, as a result of O(2) damage, DMSOR samples not submitted to redox-cycling may be contaminated with DMSOR(mod)D and with material absorbing in the region of 400 nm, analogous to the Hepes-modified enzyme. Since the latter lacks absorption at lambda > approximately 450 nm, its presence may escape detection.

Buffers↗
PubMed2000

Temperature-dependent interfacial stiffness of the disorder layer in a thin Cu3Au alloy film

The order-disorder transition in a 170 A thick Cu3Au(111) epitaxial alloy film is examined using x-ray diffraction techniques. Below the transition temperature T0, a disordered surface layer of thickness l is detected. This layer exhibits wetting behavior, i.e., l increases, obeying a logarithmic growth law on approach to T0. We show by a detailed analysis of the order parameter profiles that the stiffness of the order-disorder interface is temperature dependent, resulting in a nonuniversality of the wetting transition.

Journal Article↗
PubMed2000

A novel experimental technique for atomic X-ray holography.

A new experimental technique for reciprocal X-ray holography has been developed. The experimental set-up makes it possible to measure a reciprocal hologram without unwanted mixture of the X-ray fluorescence holography signal. The data are recorded during continuous rotation of the sample, and are accumulated over many revolutions. Thus the sensitivity to fluctuations of the source characteristics is reduced. A very high resolution over a large angular range is also achieved, which allows recording of X-ray standing-wave shapes near Bragg angles. The reconstruction of the measured hologram of a Cu(3)Au crystal gives positions of the nearest and next-nearest neighbours of a fluorescing Cu atom.

Journal Article↗
PubMed2000

Parametric down conversion of X-ray photons.

Parametric down conversion of X-ray photons in diamond crystals was detected in two experiments, both using the phase-matching scheme first employed in the X-ray regime by Eisenberger & McCall [Phys. Rev. Lett. (1971), 26, 684-688]. The conversion events were detected by a combination of time-correlation spectroscopy and energy discrimination, using Si drift-chamber detectors. The time-correlation spectra give a direct comparison of the conversion rate over the accidental coincidence rate. Mechanisms for possible detection of false events and ways to cross check against them are discussed in detail.

Journal Article↗