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排序方式: 共有390条查询结果,搜索用时 109 毫秒
21.
Sayer JA Otto EA O'Toole JF Nurnberg G Kennedy MA Becker C Hennies HC Helou J Attanasio M Fausett BV Utsch B Khanna H Liu Y Drummond I Kawakami I Kusakabe T Tsuda M Ma L Lee H Larson RG Allen SJ Wilkinson CJ Nigg EA Shou C Lillo C Williams DS Hoppe B Kemper MJ Neuhaus T Parisi MA Glass IA Petry M Kispert A Gloy J Ganner A Walz G Zhu X Goldman D Nurnberg P Swaroop A Leroux MR Hildebrandt F 《Nature genetics》2006,38(6):674-681
22.
Consonni C Humphry ME Hartmann HA Livaja M Durner J Westphal L Vogel J Lipka V Kemmerling B Schulze-Lefert P Somerville SC Panstruga R 《Nature genetics》2006,38(6):716-720
In the fungal phylum Ascomycota, the ability to cause disease in plants and animals has been gained and lost repeatedly during phylogenesis. In monocotyledonous barley, loss-of-function mlo alleles result in effective immunity against the Ascomycete Blumeria graminis f. sp. hordei, the causal agent of powdery mildew disease. However, mlo-based disease resistance has been considered a barley-specific phenomenon to date. Here, we demonstrate a conserved requirement for MLO proteins in powdery mildew pathogenesis in the dicotyledonous plant species Arabidopsis thaliana. Epistasis analysis showed that mlo resistance in A. thaliana does not involve the signaling molecules ethylene, jasmonic acid or salicylic acid, but requires a syntaxin, glycosyl hydrolase and ABC transporter. These findings imply that a common host cell entry mechanism of powdery mildew fungi evolved once and at least 200 million years ago, suggesting that within the Erysiphales (powdery mildews) the ability to cause disease has been a stable trait throughout phylogenesis. 相似文献
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Colleen McBride and colleagues argue that progress on a multifaceted research agenda is necessary to reap the full benefits and avoid the potential pitfalls of the emerging area of personalized genomics. They also outline one element of this agenda, the Multiplex Initiative, which has been underway since 2006. 相似文献
25.
Kozyrev SV Abelson AK Wojcik J Zaghlool A Linga Reddy MV Sanchez E Gunnarsson I Svenungsson E Sturfelt G Jönsen A Truedsson L Pons-Estel BA Witte T D'Alfonso S Barizzone N Barrizzone N Danieli MG Gutierrez C Suarez A Junker P Laustrup H González-Escribano MF Martin J Abderrahim H Alarcón-Riquelme ME 《Nature genetics》2008,40(2):211-216
26.
Jiraporn Ousingsawat Inês Cabrita Podchanart Wanitchakool Lalida Sirianant Stefan Krautwald Andreas Linkermann Rainer Schreiber Karl Kunzelmann 《Cellular and molecular life sciences : CMLS》2017,74(1):173-181
Activated receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain like (MLKL) are essential components of the necroptotic pathway. Phosphorylated MLKL (pMLKL) is thought to induce membrane leakage, leading to cell swelling and disintegration of the cell membrane. However, the molecular identity of the necroptotic membrane pore remains unclear, and the role of pMLKL for membrane permeabilization is currently disputed. We observed earlier that the phospholipid scramblase and ion channel TMEM16F/anoctamin 6 cause large membrane currents, cell swelling, and cell death when activated by a strong increase in intracellular Ca2+. We, therefore, asked whether TMEM16F is also central to necroptotic cell death and other cellular events during necroptosis. Necroptosis was induced by TNFα, smac mimetic, and Z-VAD (TSZ) in NIH3T3 fibroblasts and the four additional cell lines HT29, 16HBE, H441, and L929. Time-dependent changes in intracellular Ca2+, cell morphology, and membrane currents were recorded. TSZ induced a small and only transient oscillatory rise in intracellular Ca2+, which was paralleled by the activation of outwardly rectifying Cl? currents, which were typical for TMEM16F/ANO6. Ca2+ oscillations were due to Ca2+ release from endoplasmic reticulum, and were independent of extracellular Ca2+. The initial TSZ-induced cell swelling was followed by cell shrinkage. Using typical channel blockers and siRNA-knockdown, the Cl? currents were shown to be due to the activation of ANO6. However, the knockdown of ANO6 or inhibitors of ANO6 did not inhibit necroptotic cell death. The present data demonstrate the activation of ANO6 during necroptosis, which, however, is not essential for cell death. 相似文献
27.
Nicole Schwarz Jessica Pruessmeyer Franz M. Hess Daniela Dreymueller Elena Pantaler Anne Koelsch Reinhard Windoffer Matthias Voss Alisina Sarabi Christian Weber Antonio S. Sechi Stefan Uhlig Andreas Ludwig 《Cellular and molecular life sciences : CMLS》2010,67(24):4233-4248
The surface-expressed transmembrane CX3C chemokine ligand 1 (CX3CL1/fractalkine) induces firm adhesion of leukocytes expressing its receptor CX3CR1. After shedding by the disintegrins and metalloproteinases (ADAM) 10 and 17, CX3CL1 also acts as soluble leukocyte chemoattractant. Here, we demonstrate that transmembrane CX3CL1 expressed on both endothelial and epithelial cells induces leukocyte transmigration. To investigate the underlying mechanism, we generated CX3CR1 variants lacking the intracellular aspartate-arginine-tyrosine (DRY) motif or the intracellular C-terminus which led to a defect in intracellular calcium response and impaired ligand uptake, respectively. While both variants effectively mediated firm cell adhesion, they failed to induce transmigration and rather mediated retention of leukocytes on the CX3CL1-expressing cell layer. Targeting of ADAM10 led to increased adhesion but reduced transmigration in response to transmembrane CX3CL1, while transmigration towards soluble CX3CL1 was not affected. Thus, transmembrane CX3CL1 mediates leukocyte transmigration via the DRY motif and C-terminus of CX3CR1 and the activity of ADAM10. 相似文献
28.
Tran Cong Tuoc Evangelos Pavlakis Marco Andreas Tylkowski Anastassia Stoykova 《Cellular and molecular life sciences : CMLS》2014,71(17):3199-3218
The mammalian neocortex is a sheet of cells covering the cerebrum that provides the structural basis for the perception of sensory inputs, motor output responses, cognitive function, and mental capacity of primates. Recent discoveries promote the concept that increased cortical surface size and thickness in phylogenetically advanced species is a result of an increased generation of neurons, a process that underlies higher cognitive and intellectual performance in higher primates and humans. Here, we review some of the advances in the field, focusing on the diversity of neocortical progenitors in different species and the cellular mechanisms of neurogenesis. We discuss recent views on intrinsic and extrinsic molecular determinants, including the role of epigenetic chromatin modifiers and microRNA, in the control of neuronal output in developing cortex and in the establishment of normal cortical architecture. 相似文献
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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