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41.
Thiophene substituted acylguanidines as BACE1 inhibitors 总被引:1,自引:0,他引:1
Fobare WF Solvibile WR Robichaud AJ Malamas MS Manas E Turner J Hu Y Wagner E Chopra R Cowling R Jin G Bard J 《Bioorganic & medicinal chemistry letters》2007,17(19):5353-5356
A series of thiophene-substituted acylguanidines were designed from a pyrrole substituted acylguanidine HTS lead. This template allowed a greater flexibility, through differential Suzuki couplings, to explore the binding site of BACE1 and to enhance the inhibitory potencies. This exploration provided a 25-fold enhancement in potency to yield compound 10a, which was 150 nM in a BACE1 FRET assay. 相似文献
42.
Jeanne L. Nel Dirk J. Roux Gillian Maree Cornelius J. Kleynhans Juanita Moolman Belinda Reyers Mathieu Rouget Richard M. Cowling 《Diversity & distributions》2007,13(3):341-352
This paper establishes a framework within which a rapid and pragmatic assessment of river ecosystems can be undertaken at a broad, subcontinental scale, highlighting some implications for achieving conservation of river biodiversity in water‐limited countries. The status of river ecosystems associated with main rivers in South Africa was assessed based on the extent to which each ecosystem had been altered from its natural condition. This requires consistent data on river integrity for the entire country, which was only available for main rivers; tributaries were thus excluded from the analyses. The state of main river ecosystems in South Africa is dire: 84% of the ecosystems are threatened, with a disturbing 54% critically endangered, 18% endangered, and 12% vulnerable. Protection levels were measured as the proportion of conservation target achieved within protected areas, where the conservation target was set as 20% of the total length of each river ecosystem. Sixteen of the 112 main river ecosystems are moderately to well represented within protected areas; the majority of the ecosystems have very low levels of representation, or are not represented at all within protected areas. Only 50% of rivers within protected areas are intact, but this is a higher proportion compared to rivers outside (28%), providing some of the first quantitative data on the positive role protected areas can play in conserving river ecosystems. This is also the first assessment of river ecosystems in South Africa to apply a similar approach to parallel assessments of terrestrial, marine, and estuarine ecosystems, and it revealed that main river ecosystems are in a critical state, far worse than terrestrial ecosystems. Ecosystem status is likely to differ with the inclusion of tributaries, since options may well exist for conserving critically endangered ecosystems in intact tributaries, which are generally less regulated than main rivers. This study highlights the importance of healthy tributaries for achieving river conservation targets, and the need for managing main rivers as conduits across the landscape to support ecological processes that depend on connectivity. We also highlight the need for a paradigm shift in the way protected areas are designated, as well as the need for integrated river basin management plans to include explicit conservation visions, targets, and strategies to ensure the conservation of freshwater ecosystems and the services they provide. 相似文献
43.
Single cell tuning of Myc expression by antigen receptor signal strength and interleukin‐2 in T lymphocytes 下载免费PDF全文
44.
目的 探讨鼠李糖乳杆菌LV108及其发酵乳对免疫抑制小鼠免疫功能的调节作用。 方法 将BALB/c小鼠随机分为5组,每组10只,即空白组(正常小鼠)、模型组(免疫抑制小鼠)、药物组(免疫抑制小鼠食物中添加左旋咪唑)、LV108菌悬液组(免疫抑制小鼠食物中添加LV108菌悬液)和LV108发酵乳组(免疫抑制小鼠食物中添加LV108发酵乳),除空白组外其余组构建免疫抑制小鼠模型。干预4周后,分别测定各组小鼠体质量和脏器指数,血清中白细胞介素2(IL2)、肿瘤坏死因子α(TNFα)和免疫球蛋白G(IgG)含量,血清溶血素含量、耳肿胀度和肝、脾巨噬细胞吞噬能力。 结果 相比模型组,LV108菌悬液组和LV108发酵乳组小鼠体质量增长速度、脏器指数、血清IL2与IgG水平、血清溶血值、耳肿胀度和巨噬细胞吞噬能力显著升高(均P结论 LV108菌体及发酵乳对免疫抑制小鼠具备较全面的免疫调节作用,均可提高小鼠的自身免疫力;LV108发酵乳对小鼠的免疫调节作用强于LV108菌体。 相似文献
45.
土壤碳(C)、氮(N)、磷(P)是参与植物光合作用和影响生态系统初级生产力的主要元素。甘南高原是黄河流域重要的生态屏障,为了解该区不同林分土壤养分状况的差异,选取该区4种典型林分:云杉林、华北落叶松林、巴山冷杉林以及岷江冷杉糙皮桦混交林为研究对象,研究土壤C、N、P化学计量特征。结果表明:(1)岷江冷杉及糙皮桦混交林土壤C、N含量最高,云杉林土壤N、P含量最低。不同林分间P含量差异显著(P<0.05),不同土层间C、N含量差异均显著(P<0.05)。(2)云杉林土壤C : N值显著高于其他林分,岷江冷杉及糙皮桦混交林土壤N : P及C : P高于其他林分。(3)海拔、土壤pH、容重与土壤含水量是影响土壤养分的重要因素。土壤C含量与N、P含量均显著相关(P<0.05)。总体来说,不同林分土壤化学计量特征具有显著差异,混交林土壤养分状况较纯林好,未来森林管理和植被建设中,可以通过选择合适的树种和提高树种多样性有效改善森林土壤质量。 相似文献
46.
R. M. Cowling C. R. Cartwright J. E. Parkington J. C. Allsopp 《Journal of Biogeography》1999,26(2):367-378
Aim The aim of this paper is to analyse fossil charcoal deposits, largely identified to the species level and spanning a sequence from the late Holocene to < 40,000 BP , in order to reconstruct Late Quaternary vegetation and climatic patterns in the western (winter-rainfall) fynbos biome of South Africa. Location The charcoals were excavated from the Elands Bay Cave (32°19S, 18°20E) on the semiarid (200–250 mmyr?1), winter-rainfall coastline of the western fynbos biome. Methods Patterns in the charcoal data set over time were sought by manual sorting of the charcoal×sample matrix, as well as by subjecting the data to multivariate analysis. Palaeoclimatic reconstruction was attempted by comparing the climatic controls on contemporary vegetation communities that resembled the fossil assemblages. Charcoal diversity was modelled using sample age and number of charcoal fragments as explanatory variables. Results The fossil assemblages ranged from xeric communities (similar to those presently occurring at the site) during the Holocene, to more mesic thicket and fynbos vegetation in the terminal Pleistocene, to Afromontane forest and riverine woodland communities after about 18,000 BP . Diversity of the charcoal samples increased monotonically with increasing sample age. Main conclusions The results suggest that, unlike the eastern fynbos biome, which is under fundamentally different climatic controls, soil moisture conditions in the western part of the biome were higher in the Last Glacial than during the Holocene. This scenario may help to explain the higher regional richness and associated diversification in the western than eastern part of the biome. 相似文献
47.
We used polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) techniques to demonstrate the presence of Brassica B-genome chromosomes and putative B-genome introgressions in B. napus x B. juncea interspecific progeny. The B-genome--specific repeat sequence pBNBH35 was used to generate PCR products and FISH probes. The highest frequencies of viable progeny were obtained when B. napus was the maternal parent of the interspecific hybrid and the first backcross. B-genome--positive PCR assays were found in 34/51 fertile F2 progeny (67%), which was more than double the proportion found in fertile BC(1) progeny. Four B-genome--positive F(2)-derived families and 1 BC(1)-derived family were fixed or segregating for B. juncea morphology in the F(4) and BC(1)S(2), respectively, but in only 2 of these families did B. juncea-type plants exhibit B. juncea chromosome count (2n = 36) and typical B-genome FISH signals on 16 chromosomes. The remaining B. juncea-type plants had B. napus chromosome count (2n = 38) and no B-genome FISH signals, except for 1 exceptional F(4)-derived line that exhibited isolated and weak B-genome FISH signals on 11 chromosomes and typical A-genome FISH signals. B. juncea morphology was associated with B-genome--positive PCR signals but not necessarily with 16 intact B-genome chromosomes as detected by FISH. B-genome chromosomes tend to be eliminated during selfing or backcrossing after crossing B. juncea with B. napus, and selection of lines containing B-genome chromatin during early generations would be promoted by use of this B-genome repetitive marker. 相似文献
48.
Sharon A. Cowling 《Global Change Biology》2001,7(3):231-239
The plant fossil record was reviewed to highlight how consideration of plant carbon balance strengthens our understanding of various evolutionary innovation and extinction events. Following a brief physiological primer to carbon acquisition and allocation in C3‐plants, specific evolutionary events are discussed in connection with postulated carbon‐based mechanisms. Primary topics include: (i) the evolution of plants with the C4‐photosynthetic pathway; (ii) the surprising lack of plant extinctions during the Pleistocene (1.6 million years ago, Ma); (iii) the trend toward declining plant diversity and increasing rates of herbivory across the Palaeocene/Eocene transition (57–52 Ma); and (iv) megaherbivore extinctions at the end of the Pleistocene (10 thousand years ago, Ka). A framework is presented for testing hypotheses on the cause–effect relationships between global carbon cycling, plant carbon dynamics and the evolution of terrestrial ecosystems. 相似文献
49.
Dominique?StrasbergEmail author Mathieu?Rouget David?M.?Richardson Stephane?Baret Joel?Dupont Richard?M.?Cowling 《Biodiversity and Conservation》2005,14(12):3015-3032
Most natural habitat in the Mascarene Islands (Mauritius, La Réunion and Rodrigues) has been transformed. Although urbanisation,
agriculture and alien plant invasions have transformed large areas in La Réunion, the island has by far the greatest area
of intact habitats in the Mascarenes, but remaining natural areas are under threat. We propose a protocol for defining a system
of habitat types and for using these to provide a preliminary assessment of conservation priorities for La Réunion. The protocol
draws on existing data and expert knowledge to map habitat types, assesses the extent of habitat transformation, and quantifies
heterogeneity between habitat types based on climate, topography and geology. The pattern of habitat transformation was uneven
among the nineteen habitat types identified. While three habitats have lost > 95% of their original area, four still retain>
80% of their original extent. Habitat types could be grouped into the following categories: (i) transformed habitats with
low levels of plant endemism, (ii) habitats confined to homogenous geology with high levels of plantendemism, and (iii) species-rich
heterogeneous habitats on diverse geological types. Priority habitats were also identified using municipalities as a basis
for implementation. Urgent action is required for several habitat types where a large part of the original extent has been
transformed. Three municipalities which contain more than 10 habitat types should receive conservation priority. The analysis
provides the basis for setting conservation priorities in La Réunion at the regional and local scale. Implications of the
results are discussed with reference to requirements for finer-scale conservation planning. 相似文献
50.
Commercial forests in many parts of the world are deficient in nitrogen and phosphorus. These nutrient-deficient forests often exist in close proximity to large animal feeding operations, meat processing and other food, textile, or other biomass-processing plants, and municipal waste treatment facilities. Many of these facilities produce large surpluses of nitrogen, phosphorus, and organic matter as gaseous ammonia, urea, uric acid, phosphorus compounds, bacterial sludges, and partially treated municipal wastewaters. These co-existing and substantial nutrient deficiencies and surpluses offer ready-made opportunities for discovery, demonstration, and commercial development of science-based, technology-facilitated, environmentally sound, economically viable, and socially acceptable "win-win alliances" among these major industries based on the principles of industrial ecology and sustainable development. The major challenge is to discover practical means to capture the surplus nutrients and put them to work in forest stands from which value-added products can be produced and sold at a profit. 相似文献