排序方式: 共有34条查询结果,搜索用时 15 毫秒
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Levin Y 《Proteomics》2011,11(12):2565-2567
Designing an experiment for quantitative proteomic analysis is not a trivial task. One of the key factors influencing the success of such studies is the number of biological replicates included in the analysis. This, along with the measured variation will determine the statistical power of the analysis. Presented is a simple yet powerful analysis to determine the appropriate sample size required for reliable and reproducible results, based on the total variation (technical and biological). This approach can also be applied retrospectively for the interpretation of results as it takes into account both significance (p value) and quantitative difference (fold change) of the results. 相似文献
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Hu J Nudelman G Shimoni Y Kumar M Ding Y López C Hayot F Wetmur JG Sealfon SC 《PloS one》2011,6(2):e16614
In the first few hours following Newcastle disease viral infection of human monocyte-derived dendritic cells, the induction of IFNB1 is extremely low and the secreted type I interferon response is below the limits of ELISA assay. However, many interferon-induced genes are activated at this time, for example DDX58 (RIGI), which in response to viral RNA induces IFNB1. We investigated whether the early induction of IFNBI in only a small percentage of infected cells leads to low level IFN secretion that then induces IFN-responsive genes in all cells. We developed an agent-based mathematical model to explore the IFNBI and DDX58 temporal dynamics. Simulations showed that a small number of early responder cells provide a mechanism for efficient and controlled activation of the DDX58-IFNBI positive feedback loop. The model predicted distributions of single cell responses that were confirmed by single cell mRNA measurements. The results suggest that large cell-to-cell variation plays an important role in the early innate immune response, and that the variability is essential for the efficient activation of the IFNB1 based feedback loop. 相似文献
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Viktoria Stelzhammer Bob Amess Daniel Martins‐de‐Souza Yishai Levin Susan E. Ozanne Malgorzata S. Martin‐Gronert Sebastian Urday Sabine Bahn Paul C. Guest 《Proteomics》2012,12(22):3386-3392
Studies of neuronal, endocrine, and metabolic disorders would be facilitated by characterization of the hypothalamus proteome. Protein extracts prepared from 16 whole rat hypothalami were measured by data‐independent label‐free nano LC‐MS/MS. Peptide features were detected, aligned, and searched against a rat Swiss‐Prot database using ProteinLynx Global Server v.2.5. The final combined dataset comprised 21 455 peptides, corresponding to 622 unique proteins, each identified by a minimum of two distinct peptides. The majority of the proteins (69%) were cytosolic, and 16% were membrane proteins. Important proteins involved in neurological and synaptic function were identified including several members of the Ras‐related protein family and proteins involved in glutamate biosynthesis. 相似文献
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Elez D. Vainer Juliane Kania-Almog Ghadeer Zatara Yishai Levin Gilad W. Vainer 《Molecular & cellular proteomics : MCP》2020,19(10):1619-1631
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- •TOP: robust, bio-friendly FFPE proteome extraction method with less fixation bias.
- •Proteome of MSI-H colorectal cancer identifies immunobiology key elements.
- •MSI-H tumor displays an “INFg-STAT1 centric signature”.
- •Long-term IFNg induction In-vitro mimicks MSI-H signature.
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Sofia Johansson Mali Salmon-Divon Maria H. Johansson Yishai Pickman Petter Brodin Klas K?rre Ramit Mehr Petter H?glund 《PloS one》2009,4(6)
Murine natural killer (NK) cells express inhibitory Ly49 receptors for MHC class I molecules, which allows for “missing self” recognition of cells that downregulate MHC class I expression. During murine NK cell development, host MHC class I molecules impose an “educating impact” on the NK cell pool. As a result, mice with different MHC class I expression display different frequency distributions of Ly49 receptor combinations on NK cells. Two models have been put forward to explain this impact. The two-step selection model proposes a stochastic Ly49 receptor expression followed by selection for NK cells expressing appropriate receptor combinations. The sequential model, on the other hand, proposes that each NK cell sequentially expresses Ly49 receptors until an interaction of sufficient magnitude with self-class I MHC is reached for the NK cell to mature. With the aim to clarify which one of these models is most likely to reflect the actual biological process, we simulated the two educational schemes by mathematical modelling, and fitted the results to Ly49 expression patterns, which were analyzed in mice expressing single MHC class I molecules. Our results favour the two-step selection model over the sequential model. Furthermore, the MHC class I environment favoured maturation of NK cells expressing one or a few self receptors, suggesting a possible step of positive selection in NK cell education. Based on the predicted Ly49 binding preferences revealed by the model, we also propose, that Ly49 receptors are more promiscuous than previously thought in their interactions with MHC class I molecules, which was supported by functional studies of NK cell subsets expressing individual Ly49 receptors. 相似文献
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Hila Zigdon Alon Savidor Yishai Levin Anna Meshcheriakova Raphael Schiffmann Anthony H. Futerman 《PloS one》2015,10(3)
Gaucher disease, a recessive inherited metabolic disorder caused by defects in the gene encoding glucosylceramidase (GlcCerase), can be divided into three subtypes according to the appearance of symptoms associated with central nervous system involvement. We now identify a protein, glycoprotein non-metastatic B (GPNMB), that acts as an authentic marker of brain pathology in neurological forms of Gaucher disease. Using three independent techniques, including quantitative global proteomic analysis of cerebrospinal fluid (CSF) in samples from Gaucher disease patients that display neurological symptoms, we demonstrate a correlation between the severity of symptoms and GPNMB levels. Moreover, GPNMB levels in the CSF correlate with disease severity in a mouse model of Gaucher disease. GPNMB was also elevated in brain samples from patients with type 2 and 3 Gaucher disease. Our data suggest that GPNMB can be used as a marker to quantify neuropathology in Gaucher disease patients and as a marker of treatment efficacy once suitable treatments towards the neurological symptoms of Gaucher disease become available. 相似文献
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Dysregulated miRNA biogenesis downstream of cellular stress and ALS‐causing mutations: a new mechanism for ALS
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Anna Emde Chen Eitan Lee‐Loung Liou Ryan T Libby Natali Rivkin Iddo Magen Irit Reichenstein Hagar Oppenheim Raya Eilam Aurelio Silvestroni Betty Alajajian Iddo Z Ben‐Dov Julianne Aebischer Alon Savidor Yishai Levin Robert Sons Scott M Hammond John M Ravits Eran Hornstein 《The EMBO journal》2015,34(21):2633-2651
Interest in RNA dysfunction in amyotrophic lateral sclerosis (ALS) recently aroused upon discovering causative mutations in RNA‐binding protein genes. Here, we show that extensive down‐regulation of miRNA levels is a common molecular denominator for multiple forms of human ALS. We further demonstrate that pathogenic ALS‐causing mutations are sufficient to inhibit miRNA biogenesis at the Dicing step. Abnormalities of the stress response are involved in the pathogenesis of neurodegeneration, including ALS. Accordingly, we describe a novel mechanism for modulating microRNA biogenesis under stress, involving stress granule formation and re‐organization of DICER and AGO2 protein interactions with their partners. In line with this observation, enhancing DICER activity by a small molecule, enoxacin, is beneficial for neuromuscular function in two independent ALS mouse models. Characterizing miRNA biogenesis downstream of the stress response ties seemingly disparate pathways in neurodegeneration and further suggests that DICER and miRNAs affect neuronal integrity and are possible therapeutic targets. 相似文献