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91.
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92.
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
93.
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
94.
95.
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
96.
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
97.
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
98.
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
99.
Joseph T. Costello Ciarán D. McInerney Chris M. Bleakley James Selfe Alan E. Donnelly 《Journal of thermal biology》2012
Background
Cryotherapy is used in various clinical and sporting settings to reduce odema, decrease nerve conduction velocity, decrease tissue metabolism and to facilitate recovery after exercise induced muscle damage. The basic premise of cryotherapy is to cool tissue temperature and various modalities of cryotherapy such as whole body cryotherapy, cold spray, cryotherapy cuffs, frozen peas, cold water immersion, ice, and cold packs are currently being used to achieve this. However, despite its widespread use, little is known regarding the effectiveness of different cryotherapy modalities to reduce skin temperature.Objectives
To provide a synopsis of the use of thermal imaging as a method of assessing skin temperature following cryotherapy and to report the magnitude of skin temperature reductions associated with various modalities of cooling.Design
Structured narrative review.Methods
Three electronic databases were searched using keywords and MESH headings related to the use of thermal imaging in the assessment of skin temperature following cryotherapy. A hand-search of reference lists and relevant journals and text books complemented the electronic search.Summary
Nineteen studies met the inclusion criteria. A skin temperature reduction of 5–15 °C, in accordance with the recent PRICE (Protection, Rest, Ice, Compression and Elevation) guidelines, were achieved using cold air, ice massage, crushed ice, cryotherapy cuffs, ice pack, and cold water immersion. There is evidence supporting the use and effectiveness of thermal imaging in order to access skin temperature following the application of cryotherapy.Conclusions
Thermal imaging is a safe and non-invasive method of collecting skin temperature. Although further research is required, in terms of structuring specific guidelines and protocols, thermal imaging appears to be an accurate and reliable method of collecting skin temperature data following cryotherapy. Currently there is ambiguity regarding the optimal skin temperature reductions in a medical or sporting setting. However, this review highlights the ability of several different modalities of cryotherapy to reduce skin temperature. 相似文献100.
Yin W Carballo-Jane E McLaren DG Mendoza VH Gagen K Geoghagen NS McNamara LA Gorski JN Eiermann GJ Petrov A Wolff M Tong X Wilsie LC Akiyama TE Chen J Thankappan A Xue J Ping X Andrews G Wickham LA Gai CL Trinh T Kulick AA Donnelly MJ Voronin GO Rosa R Cumiskey AM Bekkari K Mitnaul LJ Puig O Chen F Raubertas R Wong PH Hansen BC Koblan KS Roddy TP Hubbard BK Strack AM 《Journal of lipid research》2012,53(1):51-65
In an attempt to understand the applicability of various animal models to dyslipidemia in humans and to identify improved preclinical models for target discovery and validation for dyslipidemia, we measured comprehensive plasma lipid profiles in 24 models. These included five mouse strains, six other nonprimate species, and four nonhuman primate (NHP) species, and both healthy animals and animals with metabolic disorders. Dyslipidemic humans were assessed by the same measures. Plasma lipoprotein profiles, eight major plasma lipid fractions, and FA compositions within these lipid fractions were compared both qualitatively and quantitatively across the species. Given the importance of statins in decreasing plasma low-density lipoprotein cholesterol for treatment of dyslipidemia in humans, the responses of these measures to simvastatin treatment were also assessed for each species and compared with dyslipidemic humans. NHPs, followed by dog, were the models that demonstrated closest overall match to dyslipidemic humans. For the subset of the dyslipidemic population with high plasma triglyceride levels, the data also pointed to hamster and db/db mouse as representative models for practical use in target validation. Most traditional models, including rabbit, Zucker diabetic fatty rat, and the majority of mouse models, did not demonstrate overall similarity to dyslipidemic humans in this study. 相似文献