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1.
Zhang Z Lee JC Lin L Olivas V Au V LaFramboise T Abdel-Rahman M Wang X Levine AD Rho JK Choi YJ Choi CM Kim SW Jang SJ Park YS Kim WS Lee DH Lee JS Miller VA Arcila M Ladanyi M Moonsamy P Sawyers C Boggon TJ Ma PC Costa C Taron M Rosell R Halmos B Bivona TG 《Nature genetics》2012,44(8):852-860
Human non-small cell lung cancers (NSCLCs) with activating mutations in EGFR frequently respond to treatment with EGFR-targeted tyrosine kinase inhibitors (TKIs), such as erlotinib, but responses are not durable, as tumors acquire resistance. Secondary mutations in EGFR (such as T790M) or upregulation of the MET kinase are found in over 50% of resistant tumors. Here, we report increased activation of AXL and evidence for epithelial-to-mesenchymal transition (EMT) in multiple in vitro and in vivo EGFR-mutant lung cancer models with acquired resistance to erlotinib in the absence of the EGFR p.Thr790Met alteration or MET activation. Genetic or pharmacological inhibition of AXL restored sensitivity to erlotinib in these tumor models. Increased expression of AXL and, in some cases, of its ligand GAS6 was found in EGFR-mutant lung cancers obtained from individuals with acquired resistance to TKIs. These data identify AXL as a promising therapeutic target whose inhibition could prevent or overcome acquired resistance to EGFR TKIs in individuals with EGFR-mutant lung cancer. 相似文献
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Omer R. Larson Steven G. Platt Zannita Fast Horse Thomas R. Rainwater Stanlee M. Miller 《西北部美国博物学家》2011,71(2)
From October 2003 through April 2006, we collected 565 fleas incidental to a distribution survey of mammals in southwestern South Dakota. Sixty-one specimens, representing 18 species of mammals, possessed 20 species of fleas. The geographic distributions of these flea species revealed 8 new records for the Black Hills and its adjacent grasslands. Four species— Megarthroglossus divisus, Stenoponia americana, Odontopsyllus dentatus, and Amaradix euphorbi —constitute new records for South Dakota, thus increasing the state’s known flea fauna to 42 species. Hunters, trappers, and field biologists should be aware that serosurveillance during the 1990s revealed the presence of sylvatic plague and tularemia in the Black Hills area. Desde octubre de 2003 hasta abril de 2006, colectamos 565 pulgas de manera incidental durante un estudio de la distribución de mamíferos en el suroeste del estado de Dakota del Sur. Los 61 especímenes, que representaban 18 especies de mamíferos, albergaban 20 especies de pulgas. Sus distribuciones geográficas revelaron 8 nuevos registros para las Colinas Negras (Black Hills) y las praderas adyacentes. Cuatro de estas especies ( Megarthroglossus divisus, Stenoponia americana, Odontopsyllus dentatus y Amaradix euphorbi ) constituyen nuevos registros para Dakota del Sur. Esto aumenta el número de especies de pulgas conocidas del estado a 42 especies. Los cazadores, tramperos y biólogos de campo deben estar conscientes de que la vigilancia serológica durante la década de los 1990 reveló la presencia de la plaga silvática y la tularemia en el área de las Colinas Negras. 相似文献
4.
Western juniper ( Juniperus occidentalis spp. occidentalis ) has rapidly expanded into shrub steppe communities in the intermountain Northwest during the past 120 yr. Cutting juniper is a management tool used to restore shrub steppe communities. Response of the understory after cutting is strongly influenced by plant species composition existing prior to treatment. This study assessed distribution patterns of understory plants over 2 growing seasons after tree cutting in a western juniper woodland. Cover, density, and diversity of understory species were compared among 3 locations: interspaces, duff zones (previously under tree canopies), and debris zones (beneath cut trees). Plant cover density increased in all zones following tree cutting. Understory vegetation in cut woodlands exhibited strong zonal distribution. Cover and density of Poa sandbergii and Sitanion hystrix and canopy cover of annual forbs were greatest in duff zones ( P P < 0.05). Debris zones tended to have the lowest overall understory cover and plant density values. Under juniper debris many species common to interspaces were reduced in density, although plants that survived or established beneath debris grew larger than their counterparts in interspaces. Species increased in density and cover under debris were plants characteristic of duff zones and whose seeds are typically wind dispersed. 相似文献
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Behavior of migrant birds in relation to temperature was studied and compared to that of resident species in the northern Mojave Desert. Migrants reduced foraging intensity above 30 C, but resident species showed no striking decrease in intensity of foraging at temperatures up to 35 C. Migrant species shifted activities to shaded microhabitats at temperatures between 20 and 30 C; the resident Verdin showed a similar shift at 35 C. Most migrants decreased the amount of time spent foraging at temperatures above 30; Verdins showed a similar but stronger response to temperatures about 30 C. Significant reductions in the use of hovering and hawking maneuvers were found among migrants at temperatures above 30 C. Migrants showed similar types of behavioral adjustments to temperatures as did resident desert species, but they responded earlier in the daily temperature cycle. Desert birds appear to correlate their daily activity strongly with temperature, but nondesert species may respond either to temperature or time of day. 相似文献
6.
Hormonal pregnancy tests and neural tube malformations 总被引:2,自引:0,他引:2
7.
A radiation hybrid map of the rat genome containing 5,255 markers. 总被引:17,自引:0,他引:17
T K Watanabe M T Bihoreau L C McCarthy S L Kiguwa H Hishigaki A Tsuji J Browne Y Yamasaki A Mizoguchi-Miyakita K Oga T Ono S Okuno N Kanemoto E Takahashi K Tomita H Hayashi M Adachi C Webber M Davis S Kiel C Knights A Smith R Critcher J Miller T Thangarajah P J Day J R Hudson Y Irie T Takagi Y Nakamura P N Goodfellow G M Lathrop A Tanigami M R James 《Nature genetics》1999,22(1):27-36
A whole-genome radiation hybrid (RH) panel was used to construct a high-resolution map of the rat genome based on microsatellite and gene markers. These include 3,019 new microsatellite markers described here for the first time and 1,714 microsatellite markers with known genetic locations, allowing comparison and integration of maps from different sources. A robust RH framework map containing 1,030 positions ordered with odds of at least 1,000:1 has been defined as a tool for mapping these markers, and for future RH mapping in the rat. More than 500 genes which have been mapped in mouse and/or human were localized with respect to the rat RH framework, allowing the construction of detailed rat-mouse and rat-human comparative maps and illustrating the power of the RH approach for comparative mapping. 相似文献
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Summary Using computer simulations and behavioral experiments with the American cockroach, we found that active vs passive (barrier-directed) wall-following can be readily distinguished and quantified by incorporating a range of convex curves into test arenas. Although previously considered strongly thigmotactic, more than 50% of running American cockroaches depart convex curves with diameters, less than 1 m. A new framework for evaluating wall-following behaviors is presented. 相似文献
10.
Charybdotoxin, a protein inhibitor of single Ca2+-activated K+ channels from mammalian skeletal muscle 总被引:1,自引:0,他引:1
The recent development of techniques for recording currents through single ionic channels has led to the identification of a K+-specific channel that is activated by cytoplasmic Ca2+. The channel has complex properties, being activated by depolarizing voltages and having a voltage-sensitivity that is modulated by cytoplasmic Ca2+ levels. The conduction behaviour of the channel is also unusual, its high ionic selectivity being displayed simultaneously with a very high unitary conductance. Very little is known about the biochemistry of this channel, largely due to the lack of a suitable ligand for use as a biochemical probe for the channel. We describe here a protein inhibitor of single Ca2+-activated K+ channels of mammalian skeletal muscle. This inhibitor, a minor component of the venom of the Israeli scorpion, Leiurus quinquestriatus, reversibly blocks the large Ca2+-activated K+ channel in a simple biomolecular reaction. We have partially purified the active component, a basic protein of relative molecular mass (Mr) approximately 7,000. 相似文献