排序方式: 共有67条查询结果,搜索用时 31 毫秒
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Furuhashi M Tuncman G Görgün CZ Makowski L Atsumi G Vaillancourt E Kono K Babaev VR Fazio S Linton MF Sulsky R Robl JA Parker RA Hotamisligil GS 《Nature》2007,447(7147):959-965
Adipocyte fatty-acid-binding protein, aP2 (FABP4) is expressed in adipocytes and macrophages, and integrates inflammatory and metabolic responses. Studies in aP2-deficient mice have shown that this lipid chaperone has a significant role in several aspects of metabolic syndrome, including type 2 diabetes and atherosclerosis. Here we demonstrate that an orally active small-molecule inhibitor of aP2 is an effective therapeutic agent against severe atherosclerosis and type 2 diabetes in mouse models. In macrophage and adipocyte cell lines with or without aP2, we also show the target specificity of this chemical intervention and its mechanisms of action on metabolic and inflammatory pathways. Our findings demonstrate that targeting aP2 with small-molecule inhibitors is possible and can lead to a new class of powerful therapeutic agents to prevent and treat metabolic diseases such as type 2 diabetes and atherosclerosis. 相似文献
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P Wei WW Wong JS Park EE Corcoran SG Peisajovich JJ Onuffer A Weiss WA Lim 《Nature》2012,488(7411):384-388
Bacterial pathogens have evolved specific effector proteins that, by interfacing with host kinase signalling pathways, provide a mechanism to evade immune responses during infection. Although these effectors contribute to pathogen virulence, we realized that they might also serve as valuable synthetic biology reagents for engineering cellular behaviour. Here we exploit two effector proteins, the Shigella flexneri OspF protein and Yersinia pestis YopH protein, to rewire kinase-mediated responses systematically both in yeast and mammalian immune cells. Bacterial effector proteins can be directed to inhibit specific mitogen-activated protein kinase pathways selectively in yeast by artificially targeting them to pathway-specific complexes. Moreover, we show that unique properties of the effectors generate new pathway behaviours: OspF, which irreversibly inactivates mitogen-activated protein kinases, was used to construct a synthetic feedback circuit that shows novel frequency-dependent input filtering. Finally, we show that effectors can be used in T cells, either as feedback modulators to tune the T-cell response amplitude precisely, or as an inducible pause switch that can temporarily disable T-cell activation. These studies demonstrate how pathogens could provide a rich toolkit of parts to engineer cells for therapeutic or biotechnological applications. 相似文献
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The Atlantic Forest is one of the most threatened ecosystems in Brazil, with only 22% of its original coverage remaining. Despite around 900 species of Polistinae being described worldwide and their being widely distributed in the Neotropical region, they are still poorly known in northeastern Brazil, especially in Atlantic Forest. The aim of this work was a survey of social wasps in three fragments of Atlantic Forest with differences in the level of regeneration and in the physiognomy, performed at Michelin Ecological Reserve (located in Igrapiúna, southern Bahia State, Brazil) and employing three methodologies – attractive solution, Malaise trap and light trap ‘Luiz de Queiroz’ – for 12 months in transects. A total of 1066 specimens, belonging to 29 species from nine genera, were collected in the reserve. Epiponini was the richest tribe (23 species) followed by Mischocyttarini (five species) and Polistini (one species). The Malaise trap was not efficient during the night, having a deficit of 5110 hours; the only nocturnal genus, Apoica, was collected with a light trap – an attractive solution that was more efficient. Once it was left for 12 discontinuous days (72 hours), showing that more than one methodology is desirable for wasp surveys. Latitudinal analysis comparing the study area with other areas grouped the Michelin Ecological Reserve with areas in southeastern Brazil, which may be related to a lack of standardization in collecting methods. This study presented the highest richness in this region. 相似文献
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CAD and CAE Integration Through Scientific Visualization Techniques for Illumination Design 总被引:1,自引:0,他引:1
Engineers tend to use different software to perform tasks such as geometry modeling, database management, numerical analysis, and visualization. This may cause decrease of productivity and loss of information during the conversion process between different data file formats. This paper presents a computer aided design (CAD) and computer aided engineering (CAE) system integration using scientific visualization tools and techniques. It deals with the development of a 3D CAD add-in for lighting analysis which uses the CAD model as 3D interface for creating a lighting scheme, processing, and visualizing 2D or 3D illuminance fields. Visualization features as color and contour mapping were developed using the visualization toolkit (VTK) toolkit. The application integrates all functionalities of the 3D CAD with tools for light sources database management, pre-processing, processing, and post-processing of illuminance fields in a single environment. This approach increases productivity and eliminates the need for different software. 相似文献
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Rasmann S Köllner TG Degenhardt J Hiltpold I Toepfer S Kuhlmann U Gershenzon J Turlings TC 《Nature》2005,434(7034):732-737
Plants under attack by arthropod herbivores often emit volatile compounds from their leaves that attract natural enemies of the herbivores. Here we report the first identification of an insect-induced belowground plant signal, (E)-beta-caryophyllene, which strongly attracts an entomopathogenic nematode. Maize roots release this sesquiterpene in response to feeding by larvae of the beetle Diabrotica virgifera virgifera, a maize pest that is currently invading Europe. Most North American maize lines do not release (E)-beta-caryophyllene, whereas European lines and the wild maize ancestor, teosinte, readily do so in response to D. v. virgifera attack. This difference was consistent with striking differences in the attractiveness of representative lines in the laboratory. Field experiments showed a fivefold higher nematode infection rate of D. v. virgifera larvae on a maize variety that produces the signal than on a variety that does not, whereas spiking the soil near the latter variety with authentic (E)-beta-caryophyllene decreased the emergence of adult D. v. virgifera to less than half. North American maize lines must have lost the signal during the breeding process. Development of new varieties that release the attractant in adequate amounts should help enhance the efficacy of nematodes as biological control agents against root pests like D. v. virgifera. 相似文献
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Francisco E. de L. Nascimento Juan Pablo Botero Marcos Aragão Sergio Ricardo Andena 《Journal of Natural History》2017,51(41-42):2429-2441
The Atlantic Forest is considered a hotspot biome, one of the most diverse in the world. Currently, due to deforestation, only 22% of the original cover remains, and only 7.5% well preserved. Despite the global importance of this biome, it still lacks basic studies, e.g. primary inventories. Cerambycidae is one of the most diverse groups of beetles, with high ecological and economic importance. The aim of this work was to survey the longhorn beetles (Cerambycidae) in three fragments (Pacangê, Vila 5 and Pancada Grande) of Atlantic Forest within Reserva Ecológica da Michelin (southern Bahia State, Brazil). A total of 166 individuals belonging to 53 species were recorded, 15 of them new geographical records for the state, and one for Brazil. The Shannon index (H) shows Pacangê (H = 2.665) as the most diverse fragment, followed by Pancada Grande (H = 2.658) and Vila 5 (H = 2.565). The most abundant species were Nyssodrysina lignaria (38 specimens collected), followed by Compsibidion vanum (31 specimens). One hundred and ten specimens were captured in Malaise traps, while in light traps only 56 specimens were caught; however, the richness and consequently the diversity in light traps was higher. This is one of the few studies carried out in Atlantic Forest surveying longhorn beetles, and provides primary data on these taxa, to help develop conservation policies for this threatened biome. 相似文献
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Paulo R. Melo-Sampaio Ivan Prates Pedro L. V. Peloso Renato Recoder Francisco Dal Vechio Sergio Marques-Souza 《Journal of Natural History》2020,54(1-4):43-62
ABSTRACT Few studies have focused on the diverse fauna of southwestern Brazilian Amazonia. This region, spared from large-scale human occupation until the second half of the twentieth century, has been threatened by expanding agriculture, logging, and mining. Here, we describe a new nurse frog (Allobates, Aromobatidae) from the open highland habitats of Serra dos Pacaás Novos, one of the few large remnants of relatively intact native vegetation in the Brazilian state of Rondônia. The new species is diagnosed by its metallic orange dorsal colouration, weakly expanded discs on hands, and presence of two subarticular tubercles on Finger IV. A phylogenetic analysis based on DNA sequence data recovered the new species as more closely related to nurse frogs from the Madeira and Tapajós River basins; this pattern may reflect a history of dispersal uphill from a lowland ancestor. Our results also indicate that the generic assignment of Allobates alessandroi (Grant and Rodriguez, 2001), a high-elevation species from the Andes of Peru, needs to be reassessed; we discuss the phylogenetic affinities of this species based on morphological attributes. http://www.zoobank.org/urn:lsid:zoobank.org:act:79131D82-B1B6-455D-AD9A-676D7E0783BC 相似文献
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