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91.
Wagner SJ Skripchenko A Donnelly DJ Ramaswamy K Detty MR 《Bioorganic & medicinal chemistry》2005,13(21):5927-5935
Thio- and selenoxanthylium dyes were prepared by the addition of 2-lithiothiophene, 4-N,N-dimethylaminophenylmagnesium bromide, and 1-naphthylmagnesium bromide to the appropriate 2,7-bis-N,N-dimethylaminochalcogenoxanthen-9-one, followed by dehydration and ion exchange to the chloride salts. The corresponding chalcogenoxanthylium dyes were evaluated as photosensitizers for the inactivation of intracellular and extracellular virus in red blood cell suspensions and for the inactivation of selected strains of gram (+) and gram (-) bacteria in red blood cell suspensions. Selected combinations of photosensitizer and light gave >6 log10 inactivation of intracellular and extracellular virus, and >4 log10 inactivation of extracellular bacteria with varying levels of hemolyis, following a 42-day storage of red blood cell suspensions. Photocleavage experiments with plasmid DNA and the chalcogenoxanthylium dyes suggested the genomic material contained in the virus and in the bacteria as one possible target for the photodynamic action of some of these dyes. 相似文献
92.
Donnelly MJ McCall PJ Lengeler C Bates I D'Alessandro U Barnish G Konradsen F Klinkenberg E Townson H Trape JF Hastings IM Mutero C 《Malaria journal》2005,4(1):12-5
There are already 40 cities in Africa with over 1 million inhabitants and the United Nations Environmental Programme estimates that by 2025 over 800 million people will live in urban areas. Recognizing that malaria control can improve the health of the vulnerable and remove a major obstacle to their economic development, the Malaria Knowledge Programme of the Liverpool School of Tropical Medicine and the Systemwide Initiative on Malaria and Agriculture convened a multi-sectoral technical consultation on urban malaria in Pretoria, South Africa from 2nd to 4th December, 2004. The aim of the meeting was to identify strategies for the assessment and control of urban malaria. This commentary reflects the discussions held during the meeting and aims to inform researchers and policy makers of the potential for containing and reversing the emerging problem of urban malaria. 相似文献
93.
Background
A single base pair mutation in the sodium channel confers knock-down resistance to pyrethroids in many insect species. Its occurrence in Anopheles mosquitoes may have important implications for malaria vector control especially considering the current trend for large scale pyrethroid-treated bednet programmes. Screening Anopheles gambiae populations for the kdr mutation has become one of the mainstays of programmes that monitor the development of insecticide resistance. The screening is commonly performed using a multiplex Polymerase Chain Reaction (PCR) which, since it is reliant on a single nucleotide polymorphism, can be unreliable. Here we present a reliable and potentially high throughput method for screening An. gambiae for the kdr mutation.Methods
A Hot Ligation Oligonucleotide Assay (HOLA) was developed to detect both the East and West African kdr alleles in the homozygous and heterozygous states, and was optimized for use in low-tech developing world laboratories. Results from the HOLA were compared to results from the multiplex PCR for field and laboratory mosquito specimens to provide verification of the robustness and sensitivity of the technique.Results and Discussion
The HOLA assay, developed for detection of the kdr mutation, gives a bright blue colouration for a positive result whilst negative reactions remain colourless. The results are apparent within a few minutes of adding the final substrate and can be scored by eye. Heterozygotes are scored when a sample gives a positive reaction to the susceptible probe and the kdr probe. The technique uses only basic laboratory equipment and skills and can be carried out by anyone familiar with the Enzyme-linked immunosorbent assay (ELISA) technique. A comparison to the multiplex PCR method showed that the HOLA assay was more reliable, and scoring of the plates was less ambiguous.Conclusion
The method is capable of detecting both the East and West African kdr alleles in the homozygous and heterozygous states from fresh or dried material using several DNA extraction methods. It is more reliable than the traditional PCR method and may be more sensitive for the detection of heterozygotes. It is inexpensive, simple and relatively safe making it suitable for use in resource-poor countries. 相似文献94.
Weiss MD Donnelly WH Rossignol C Varoqui H Erickson JD Anderson KJ 《Journal of molecular histology》2005,36(4):301-309
Summary System A is a highly regulated, Na+-dependent transporter that accepts neutral amino acids containing short, polar side chains. System A plays an important role
during rat development as decreased pup weights are observed in dams infused during gestation with a non-metabolizable System
A substrate. Given the potential importance of SNAT1 during development in the rat brain, we examined whether SNAT1 would
be present at an earlier gestation during organogenesis in multiple organs by immunohistochemistry and immunoblotting. SNAT1
protein was observed in the developing lungs, intestines, kidneys, heart, pancreas, and skeletal muscle of rats at prenatal
days 14, 17, 19, 21, and postnatal day 2 rats. SNAT1 protein expression decreased in the liver and intestine shortly after
birth and as the rat matured. SNAT1 expression was constant throughout development in the lungs and kidney and increased in
the heart from prenatal day 19 to postnatal day 2. Highest levels of expression in older animals were seen in organs undergoing
rapid cell division. 相似文献
95.
Herd-level risk factors associated with tuberculosis breakdowns among cattle herds in England before the 2001 foot-and-mouth disease epidemic 总被引:2,自引:0,他引:2
Johnston WT Gettinby G Cox DR Donnelly CA Bourne J Clifton-Hadley R Le Fevre AM McInerney JP Mitchell A Morrison WI Woodroffe R 《Biology letters》2005,1(1):53-56
A case-control study of the factors associated with the risk of a bovine tuberculosis (TB) breakdown in cattle herds was undertaken within the randomized badger culling trial (RBCT). TB breakdowns occurring prior to the 2001 foot-and-mouth disease epidemic in three RBCT triplets were eligible to be cases; controls were selected from the same RBCT area. Data from 151 case farms and 117 control farms were analysed using logistic regression. The strongest factors associated with an increased TB risk were movement of cattle onto the farm from markets or farm sales, operating a farm over multiple premises and the use of either covered yard or 'other' housing types. Spreading artificial fertilizers or farmyard manure on grazing land were both associated with decreased risk. These first case-control results from the RBCT will be followed by similar analyses as more data become available. 相似文献
96.
97.
Dominique F. Bonafoux Sheri L. Bonar Michael Clare Ann M. Donnelly Jeanette L. Glaenzer Julia A. Guzova He Huang Nandidni N. Kishore Francis J. Koszyk Patrick J. Lennon Adam Libby Sumathy Mathialagan David S. Oburn Sharon A Rouw Cynthia D. Sommers Catherine S. Tripp Lori J. Vanella Richard Weier Serge G. Wolfson Horng-Chih Huang 《Bioorganic & medicinal chemistry》2010,18(1):403-414
Series of aminopyridinecarboxamide-based inhibitors were synthesized and tested against human recombinant IKK-2 and in IL-1β stimulated synovial fibroblasts. The 2-amino-5-chloropyridine-4-carboxamides were identified as the most potent inhibitors with improved cellular activity. 相似文献
98.
Melanocortin-4 receptor (MC4R) has an important regulatory role in energy homeostasis and food intake. Peptide agonists of the MC4R are characterized by the conserved sequence His6-Phe7-Arg8-Trp9, which is crucial for their interaction with the receptor. This investigation utilized the covalent attachment approach to identify receptor residues in close proximity to the bound ligand [Nle4,d-Phe7]melanocyte-stimulating hormone (NDP-MSH), thereby differentiating between residues directly involved in ligand binding and those mutations that compromise ligand binding by inducing conformational changes in the receptor. Also, recent X-ray structures of G-protein-coupled receptors were utilized to refine a model of human MC4R in the active state (R?), which was used to generate a better understanding of the binding mode of the ligand NDP-MSH at the atomic level.The mutation of residues in the human MC4R—such as Leu106 of extracellular loop 1, and Asp122, Ile125, and Asp126 of transmembrane (TM) helix 3, His264 (TM6), and Met292 (TM7)—to Cys residues produced definitive indications of proximity to the side chains of residues in the core region of the peptide ligand. Of particular interest was the contact between d-Phe7 on the ligand and Ile125 of TM3 on the MC4R. Additionally, Met292 (TM7) equivalent to Lys(7.45) (Ballesteros numbering scheme) involved in covalently attaching retinal in rhodopsin is shown to be in close proximity to Trp9.For the first time, the interactions between the terminal regions of NDP-MSH and the receptor are described. The amino-terminus appears to be adjacent to a series of hydrophilic residues with novel interactions at Cys196 (TM5) and Asp189 (extracellular loop 2). These interactions are reminiscent of sequential ligand binding exhibited by the β2-adrenergic receptor, with the former interaction being equivalent to the known interaction involving Ser204 of the β2-adrenergic receptor. 相似文献
99.
Investigations were conducted into the biochemical and mechanical states of cross-bridges during isometric muscle contraction. Rapid length steps (3 or 6 nm hs(-1)) were applied to rabbit psoas fibers, permeabilized and isometric, at either 12 degrees C or 20 degrees C. Fibers were activated by photolysis of P(3)-1-(2-nitrophenyl)-ethyl ester of ATP infused into rigor fibers at saturating Ca(2+). Sarcomere length, tension, and phosphate release were recorded-the latter using the MDCC-PBP fluorescent probe. A reduction in strain, induced by a rapid release step, produced a short-lived acceleration of phosphate release. Rates of the phosphate transient and that of phases 3 and 4 of tension recovery were unaffected by step size but were elevated at higher temperatures. In contrast the amplitude of the phosphate transient was smaller at 20 degrees C than 12 degrees C. The presence of 0.5 or 1.0 mM added ADP during a release step reduced both the rate of tension recovery and the poststep isometric tension. A kinetic scheme is presented to simulate the observed data and to precisely determine the rate constants for the elementary steps of the ATPase cycle. 相似文献
100.
Sekiya M Mulcahy G Irwin JA Stack CM Donnelly SM Xu W Collins P Dalton JP 《FEBS letters》2006,580(21):5016-5022
The parasitic helminth Fasciola hepatica secretes a 2-Cys peroxiredoxin (Prx) that may play important functions in host-parasite interaction. Recombinant peroxiredoxin (FhePrx) prevented metal-catalyzed oxidative nicking of plasmid DNA and detoxified hydrogen peroxide when coupled with Escherichia coli thioredoxin and thioredoxin reductase (k(cat)/K(m)=5.2 x 10(5)M(-1)s(-1)). Enzyme kinetic analysis revealed that the catalytic efficiency of FhePrx is similar to other 2-Cys peroxiredoxins; the enzyme displayed saturable enzyme Michaelis-Menten type kinetics with hydrogen peroxide, cumene hydroperoxide and t-butyl hydroperoxide, and is sensitive to concentrations of hydrogen peroxide above 0.5 mM. Like the 2-Cys peroxiredoxins from a related helminth, Schistosoma mansoni, steady-state kinetics indicate that FhePrx exhibits a saturable, single displacement-like reaction mechanism rather than non-saturable double displacement (ping-pong) enzyme substitution mechanism common to other peroxiredoxins. However, unlike the schistosome Prxs, FhePrx could not utilise reducing equivalents supplied by glutathione or glutathione reductase. 相似文献