Evolutionary analysis of the TPP-dependent enzyme family

The evolutionary relationships of the thiamine pyrophosphate (TPP)-dependent family of enzymes was investigated by generation of a neighbor joining phylogenetic tree using sequences from the conserved pyrophosphate (PP) and pyrimidine (Pyr) binding domains of 17 TPP-dependent enzymes. This represents the most comprehensive analysis of TPP-dependent enzyme evolution to date. The phylogeny was shown to be robust by comparison with maximum likelihood trees generated for each individual enzyme and also broadly confirms the evolutionary history proposed recently from structural comparisons alone (Duggleby 2006). The phylogeny is most parsimonious with the TPP enzymes having arisen from a homotetramer which subsequently diverged into an α2β2 heterotetramer. The relationship between the PP- and Pyr-domains and the recruitment of additional protein domains was examined using the transketolase C-terminal (TKC)-domain as an example. This domain has been recruited by several members of the family and yet forms no part of the active site and has unknown function. Removal of the TKC-domain was found to increase activity toward β-hydroxypyruvate and glycolaldehyde. Further truncations of the Pyr-domain yielded several variants with retained activity. This suggests that the influence of TKC-domain recruitment on the evolution of the mechanism and specificity of transketolase (TK) has been minor, and that the smallest functioning unit of TK comprises the PP- and Pyr-domains, whose evolutionary histories extend to all TPP-dependent enzymes

Some special Kahler metrics on SL(2,C) and their holomorphic quantization

The group SU(2)*SU(2) acts naturally on SL(2,C) by simultaneous right and left multiplication. We study the Kahler metrics invariant under this action using global Kahler potentials. The volume growth and various curvature quantities are then explicitly computable. Examples include metrics of positive, negative and zero Ricci curvature, and the 1-lump metric of the CP^1-model on a sphere. We then look at the holomorphic quantization of these metrics, where some physically satisfactory results on the dimension of the Hilbert space can be obtained. These give rise to an interesting geometrical conjecture, regarding the dimension of this space for general Stein manifolds in the semi-classical limit.Comment: 28 pages, no figure

Supercurrent coupling in the Faddeev-Skyrme model

Motivated by the sigma model limit of multicomponent Ginzburg-Landau theory, a version of the Faddeev-Skyrme model is considered in which the scalar field is coupled dynamically to a one-form field called the supercurrent. This coupled model is investigated in the general setting where physical space is an oriented Riemannian manifold and the target space is a Kaehler manifold. It is shown that supercurrent coupling destroys the topological stability enjoyed by the usual Faddeev-Skyrme model, so that there can be no globally stable knot solitons in this model. Nonetheless, local energy minimizers may still exist. The first variation formula is derived and used to construct three families of static solutions of the model, all on compact domains. In particular, a coupled version of the unit-charge hopfion on a three-sphere of arbitrary radius is found. The second variation formula is derived, and used to analyze the stability of some of these solutions. A family of stable solutions is identified, though these may exist only in spaces of even dimension. Finally, it is shown that, in contrast to the uncoupled model, the coupled unit hopfion on the three-sphere of radius R is unstable for all R. This gives an explicit, exact example of supercurrent coupling destabilizing a stable solution of the uncoupled Faddeev-Skyrme model, and casts doubt on the conjecture of Babaev, Faddeev and Niemi that knot solitons should exist in the low-energy regime of two-component superconductors.Comment: 17 page

Martian sub-surface ionising radiation: biosignatures and geology

The surface of Mars, unshielded by thick atmosphere or global magnetic field, is exposed to high levels of cosmic radiation. This ionising radiation field is deleterious to the survival of dormant cells or spores and the persistence of molecular biomarkers in the subsurface, and so its characterisation is of prime astrobiological interest. Here, we present modelling results of the absorbed radiation dose as a function of depth through the Martian subsurface, suitable for calculation of biomarker persistence. A second major implementation of this dose accumulation rate data is in application of the optically stimulated luminescence technique for dating Martian sediments. We present calculations of the dose-depth profile in the Martian subsurface for various scenarios: variations of surface composition (dry regolith, ice, layered permafrost), solar minimum and maximum conditions, locations of different elevation (Olympus Mons, Hellas basin, datum altitude), and increasing atmospheric thickness over geological history. We also model the changing composition of the subsurface radiation field with depth compared between Martian locations with different shielding material, determine the relative dose contributions from primaries of different energies, and discuss particle deflection by the crustal magnetic fields

Resuscitation-promoting factors possess a lysozyme-like domain

The novel bacterial cytokine family – resuscitation-promoting factors (Rpfs) – share a conserved domain of uncharacterized function. Predicting the structure of this domain suggests that Rpfs possess a lysozyme-like domain. The model highlights the good conservation of residues involved in catalysis and substrate binding. A lysozyme-like function makes sense for this domain in the light of experimental characterization of the biological function of Rpfs

Identification of T. gondii myosin light chain-1 as a direct target of TachypleginA-2, a small-molecule inhibitor of parasite motility and invasion

This work was supported by US Public Health Service grant AI054961 (GEW/NJW), a University Research Fellowship from the Royal Society (NJW) and funding for the mass spectrometry analysis was provided by the Vermont Genetics Network/NIH Grant 8P20GM103449 from the INBRE program of the NIGMS.Motility of the protozoan parasite Toxoplasma gondii plays an important role in the parasite's life cycle and virulence within animal and human hosts. Motility is driven by a myosin motor complex that is highly conserved across the Phylum Apicomplexa. Two key components of this complex are the class XIV unconventional myosin, TgMyoA, and its associated light chain, TgMLC1. We previously showed that treatment of parasites with a small-molecule inhibitor of T. gondii invasion and motility, tachypleginA, induces an electrophoretic mobility shift of TgMLC1 that is associated with decreased myosin motor activity. However, the direct target(s) of tachypleginA and the molecular basis of the compound-induced TgMLC1 modification were unknown. We show here by ''click'' chemistry labelling that TgMLC1 is a direct and covalent target of an alkyne-derivatized analogue of tachypleginA. We also show that this analogue can covalently bind to model thiol substrates. The electrophoretic mobility shift induced by another structural analogue, tachypleginA-2, was associated with the formation of a 225.118 Da adduct on S57 and/or C58, and treatment with deuterated tachypleginA-2 confirmed that the adduct was derived from the compound itself. Recombinant TgMLC1 containing a C58S mutation (but not S57A) was refractory to click labelling and no longer exhibited a mobility shift in response to compound treatment, identifying C58 as the site of compound binding on TgMLC1. Finally, a knock-in parasite line expressing the C58S mutation showed decreased sensitivity to compound treatment in a quantitative 3D motility assay. These data strongly support a model in which tachypleginA and its analogues inhibit the motility of T. gondii by binding directly and covalently to C58 of TgMLC1, thereby causing a decrease in the activity of the parasite's myosin motor. Publisher PDFPeer reviewe

Microbial oxidation of arsenite in a subarctic environment: diversity of arsenite oxidase genes and identification of a psychrotolerant arsenite oxidiser

Background: Arsenic is toxic to most living cells. The two soluble inorganic forms of arsenic are arsenite (+3) and arsenate (+5), with arsenite the more toxic. Prokaryotic metabolism of arsenic has been reported in both thermal and moderate environments and has been shown to be involved in the redox cycling of arsenic. No arsenic metabolism (either dissimilatory arsenate reduction or arsenite oxidation) has ever been reported in cold environments (i.e. < 10°C). Results: Our study site is located 512 kilometres south of the Arctic Circle in the Northwest Territories, Canada in an inactive gold mine which contains mine waste water in excess of 50 mM arsenic. Several thousand tonnes of arsenic trioxide dust are stored in underground chambers and microbial biofilms grow on the chamber walls below seepage points rich in arsenite-containing solutions. We compared the arsenite oxidisers in two subsamples (which differed in arsenite concentration) collected from one biofilm. 'Species' (sequence) richness did not differ between subsamples, but the relative importance of the three identifiable clades did. An arsenite-oxidising bacterium (designated GM1) was isolated, and was shown to oxidise arsenite in the early exponential growth phase and to grow at a broad range of temperatures (4-25°C). Its arsenite oxidase was constitutively expressed and functioned over a broad temperature range. Conclusions: The diversity of arsenite oxidisers does not significantly differ from two subsamples of a microbial biofilm that vary in arsenite concentrations. GM1 is the first psychrotolerant arsenite oxidiser to be isolated with the ability to grow below 10°C. This ability to grow at low temperatures could be harnessed for arsenic bioremediation in moderate to cold climates

110GHz fT Silicon Bipolar Transistors Implemented using Fluorine Implantation for Boron Diffusion Suppression

This paper investigates how fluorine implantation can be used to suppress boron diffusion in the base of a double polysilicon silicon bipolar transistor and hence deliver a record fT of 110 GHz. Secondary Ion Mass Spectroscopy (SIMS) and transmission electron microscopy are used to characterize the effect of the fluorine implantation energy and dose, the anneal temperature and ambient and the germanium pre-amorphisation implant on the fluorine profiles. These results show that retention of fluorine in the silicon is maximised when a high-energy fluorine implant is combined with a low thermal budget inert anneal. TEM images show that a high-energy fluorine implant into germanium pre-amorphised silicon eliminates the end of range defects from the germanium implant and produces a band of dislocation loops deeper in the silicon at the range of the fluorine implant. Boron SIMS profiles show a suppression of boron diffusion for fluorine doses at and above 5?1014cm-2, but no suppression at lower fluorine doses. This suppression of boron diffusion correlates with the appearance on the SIMS profiles of a fluorine peak at a depth of approximately Rp/2, which is attributed to fluorine trapped in vacancy-fluorine clusters. The introduction of a fluorine implant at this critical fluorine dose into a bipolar transistor process flow leads to an increase in cut-off frequency from 46 to 60GHz. Further optimisation of the base-width and the collector profile leads to a further increase in cut-off frequency to 110GHz. Two factors are postulated to contribute to the suppression of boron diffusion by the fluorine implant. First, the elimination of the germanium end of range defects, and the associated interstitial population, by the fluorine implant, removes a source of transient enhanced diffusion. Second, any interstitials released by the dislocation loops at the range of the fluorine implant would be expected to recombine at the vacancy-fluorine clusters before reaching the boron profile

Opportunities, Advances and Challenges of Hydrogen micro Gas Turbines

When green hydrogen becomes more prevalent for the buffering of renewable energy, one way to utilize this hydrogen is to use it is a small gas turbine. The units proposed in this article would be part of a flexible, modular, scalable, robust, easily maintainable and economically viable solution for large-scale grid balancing, small scale combined heat and power and ultra-low emission transportation

The UoSAT-C,D & E Technology Demonstration Satellites

The University of Surrey (UK) planned a small, inexpensive spacecraft (UoSAT-C) to be launched by NASA on a DELTA launch vehicle as a secondary payload into low-Earth orbit in 1989. This launch has been postponed, but the University has obtained two launch slots on ARIANE. Two spacecraft, UoSATs D & E are currently under construction at The UoSAT Spacecraft Engineering Research Unit at Surrey and they involve collaboration with international experimenters. The spacecraft will carry the majority of the payloads from the postponed UoSAT-C mission. UoSAT-D & E will established by the spacecraft launched NASA, develop further the objectives preceding UoSAT-1 and UoSAT-2 into low Earth, polar orbit by The paper describes the architecture and experiments of the satellite including: Satellite Communications using digital store-&-forward techniques serving remote and under-developed areas and the amateur radio community. Space Technology providing an in-orbit demonstration and operational evaluation of novel technologies and techniques such as transputers and solar cell evaluation. Space Science supporting sophisticated, yet inexpensive space science objectives studying the radiation environment in low Earth orbit such as Cosmic Particle Detection and Radiation Total Dose Measurement