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Reconsolidation is a putative neuronal process in which the retrieval of a previously consolidated memory returns it to a labile state that is once again subject to stabilization. This study explored the idea that reconsolidation occurs in spatial memory when animals retrieve memory under circumstances in which new memory encoding is likely to occur. Control studies confirmed that intrahippocampal infusions of anisomycin inhibited protein synthesis locally and that the spatial training protocols we used are subject to overnight protein synthesis-dependent consolidation. We then compared the impact of anisomycin in two conditions: when memory retrieval occurred in a reference memory task after performance had reached asymptote over several days; and after a comparable extent of training of a delayed matching-to-place task in which new memory encoding was required each day. Sensitivity to intrahippocampal anisomycin was observed only in the protocol involving new memory encoding at the time of retrieval. 相似文献
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Nowicki MW Tulloch LB Worralll L McNae IW Hannaert V Michels PA Fothergill-Gilmore LA Walkinshaw MD Turner NJ 《Bioorganic & medicinal chemistry》2008,16(9):5050-5061
The glycolytic pathway has been considered a potential drug target against the parasitic protozoan species of Trypanosoma and Leishmania. We report the design and the synthesis of inhibitors targeted against Trypanosoma brucei phosphofructokinase (PFK) and Leishmania mexicana pyruvate kinase (PyK). Stepwise library synthesis and inhibitor design from a rational starting point identified furanose sugar amino amides as a novel class of inhibitors for both enzymes with IC50 values of 23 μM and 26 μM against PFK and PyK, respectively. Trypanocidal activity also showed potency in the low micromolar range and confirms these inhibitors as promising candidates for the development towards the design of anti-trypanosomal drugs. 相似文献
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Animals that specialize on nectar can be expected to face shortages of energy at times or in places where floral resources fade. Using a nectar-feeding marsupial, the eastern pygmy-possum Cercartetus nanus as a model, we predicted that animals would respond rapidly to an artificial energy supplement by showing improved body condition and increased local abundance. We also tested the hypothesis that responses would be more pronounced in burnt than in unburnt habitats due to the expectation that food would be limiting after fire. Energy was added in the form of sugar solution to two burnt and two unburnt woodland sites on the New South Wales coast, but not to two sets of equivalent control sites. The responses of pygmy-possums were compared between sites a month before and a month after supplementation during early autumn when flowers were diminishing. The energy supplement increased on-site immigration and a tail-fat index of body condition, but had no overall effect on the abundance or mean body mass of pygmy-possums. There was no effect of habitat; floral abundance was equal across sites. The results show that C. nanus responded rapidly to the energy supplement, and indicate that animals monitor shifts in the resource base continuously. Similar resource tracking abilities have been demonstrated previously in more mobile nectar-feeders, such as honeyeaters and bats. We suggest that such abilities should be generally advantageous in any species that depend on ephemeral resources. 相似文献
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Shu X Luhmann UF Aleman TS Barker SE Lennon A Tulloch B Chen M Xu H Jacobson SG Ali R Wright AF 《PloS one》2011,6(11):e27433
A single founder mutation resulting in a Ser163Arg substitution in the C1QTNF5 gene product causes autosomal dominant late-onset retinal macular degeneration (L-ORMD) in humans, which has clinical and pathological features resembling age-related macular degeneration. We generated and characterised a mouse "knock-in" model carrying the Ser163Arg mutation in the orthologous murine C1qtnf5 gene by site-directed mutagenesis and homologous recombination into mouse embryonic stem cells. Biochemical, immunological, electron microscopic, fundus autofluorescence, electroretinography and laser photocoagulation analyses were used to characterise the mouse model. Heterozygous and homozygous knock-in mice showed no significant abnormality in any of the above measures at time points up to 2 years. This result contrasts with another C1qtnf5 Ser163Arg knock-in mouse which showed most of the features of L-ORMD but differed in genetic background and targeting construct. 相似文献