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T J Hamblin 《BMJ (Clinical research ed.)》1982,285(6349):1136-1137
75.
Spore formation is a sophisticated mechanism by which some bacteria survive conditions of stress and starvation by producing a multilayered protective capsule enclosing their condensed DNA. Spores are highly resistant to damage by heat, radiation, and commonly employed antibacterial agents. Previously, spores have also been shown to be resistant to photodynamic inactivation using dyes and light that easily destroy the corresponding vegetative bacteria. We have discovered that Bacillus spores are susceptible to photoinactivation by phenothiazinium dyes and low doses of red light. Dimethylmethylene blue, methylene blue, new methylene blue, and toluidine blue O are all effective, while alternative photosensitizers such as Rose Bengal, polylysine chlorin(e6) conjugate, a tricationic porphyrin, and a benzoporphyrin derivative, which easily kill vegetative cells, are ineffective. Spores of Bacillus cereus and B. thuringiensis are most susceptible, B. subtilis and B. atrophaeus are also killed, and B. megaterium is resistant. Photoinactivation is most effective when excess dye is washed from the spores, showing that the dye binds to the spores and that excess dye in solution can quench light delivery. The relatively mild conditions needed for spore killing could have applications for treating wounds contaminated by anthrax spores, for which conventional sporicides would have unacceptable tissue toxicity. 相似文献
76.
Hydrobiologia - The Arrow Lakes Reservoir and Kootenay Lake are comparable large reservoirs formed by the addition of storage onto natural lakes. Both have significant storage reservoirs upstream... 相似文献
77.
M Lundervold EJ Milner-Gulland CJ O'Callaghan C Hamblin A Corteyn AP Macmillan 《Acta veterinaria Scandinavica》2004,45(4):211-224
The results of a serological survey of livestock in Kazakhstan, carried out in 1997–1998, are reported. Serum samples from
958 animals (cattle, sheep and goats) were tested for antibodies to foot and mouth disease (FMD), bluetongue (BT), epizootic
haemorrhagic disease (EHD), rinderpest (RP) and peste des petits ruminants (PPR) viruses, and to Brucella spp. We also investigated the vaccination status of livestock and related this to changes in veterinary provision since independence
in 1991. For the 2 diseases under official surveillance (FMD and brucellosis) our results were similar to official data, although
we found significantly higher brucellosis levels in 2 districts and widespread ignorance about FMD vaccination status. The
seroprevalence for BT virus was 23%, and seropositive animals were widespread suggesting endemicity, despite the disease not
having being previously reported. We found a few seropositives for EHDV and PPRV, which may suggest that these diseases are
also present in Kazakhstan. An hierarchical model showed that seroprevalence to FMD and BT viruses were clustered at the farm/village
level, rather than at a larger spatial scale. This was unexpected for FMD, which is subject to vaccination policies which
vary at the raion (county) level. 相似文献
78.
Hamblin K Standley DM Rogers MB Stechmann A Roger AJ Maytum R van der Giezen M 《Molecular microbiology》2008,68(6):1395-1405
The anaerobic lifestyle of the intestinal parasite Blastocystis raises questions about the biochemistry and function of its mitochondria-like organelles. We have characterized the Blastocystis succinyl-CoA synthetase (SCS), a tricarboxylic acid cycle enzyme that conserves energy by substrate-level phosphorylation. We show that SCS localizes to the enigmatic Blastocystis organelles, indicating that these organelles might play a similar role in energy metabolism as classic mitochondria. Although analysis of residues inside the nucleotide-binding site suggests that Blastocystis SCS is GTP-specific, we demonstrate that it is ATP-specific. Homology modelling, followed by flexible docking and molecular dynamics simulations, indicates that while both ATP and GTP fit into the Blastocystis SCS active site, GTP is destabilized by electrostatic dipole interactions with Lys 42 and Lys 110, the side-chains of which lie outside the nucleotide-binding cavity. It has been proposed that residues in direct contact with the substrate determine nucleotide specificity in SCS. However, our results indicate that, in Blastocystis , an electrostatic gatekeeper controls which ligands can enter the binding site. 相似文献
79.
Hamblin JN Angell TD Ballantine SP Cook CM Cooper AW Dawson J Delves CJ Jones PS Lindvall M Lucas FS Mitchell CJ Neu MY Ranshaw LE Solanke YE Somers DO Wiseman JO 《Bioorganic & medicinal chemistry letters》2008,18(14):4237-4241
Optimisation of a high-throughput screening hit resulted in the discovery of 4-(substituted amino)-1-alkyl-pyrazolo[3,4-b]pyridine-5-carboxamides as potent and selective inhibitors of Phosphodiesterase 4 (PDE4). Herein, we describe early SAR studies around this novel template highlighting preferred substituents and rationalization of SAR through X-ray crystal structures of analogues bound to the PDE4 active site. Pyrazolopyridine 20a was found to be a potent and selective PDE4 inhibitor which also inhibits LPS induced TNF-α production from isolated human peripheral blood mononuclear cells and has an encouraging rat PK profile suitable for oral dosing. 相似文献
80.
Shock wave-mediated molecular delivery into cells 总被引:3,自引:0,他引:3
A single shock wave generated by a shock tube is able to effectively deliver macromolecules such as fluorescein isothiocyanate-dextran into the cytoplasm of living cells without causing cytotoxicity. We report on the effect of varying the molecular weight of the dextran and the number of shock waves on the efficiency of delivery into a cancer cell line. The fraction of cells permeabilized and the total fluorescence delivered were measured by flow cytometry, and the cellular viability by a tetrazolium assay on adherent cells and these values were compared to cell permeabilization using digitonin. Shock waves can deliver molecules of up to 2000000 molecular weight into the cytoplasm of cells without toxicity and may have applications in gene therapy. 相似文献