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排序方式: 共有9625条查询结果,搜索用时 78 毫秒
931.
Ming‐Dong Zhang Amit Zeisel André Calas Marc Landry Matthew Fuszard Sally L Shirran Robert Schnell Árpád Dobolyi Márk Oláh Lauren Spence Jan Mulder Henrik Martens Miklós Palkovits Mathias Uhlen Harald H Sitte Catherine H Botting Ludwig Wagner Sten Linnarsson Tibor Harkany 《The EMBO journal》2015,34(1):36-54
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933.
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935.
Clarissa Liesche Kristin?S. Gru?mayer Michael Ludwig Stefan W?rz Karl Rohr Dirk-Peter Herten Jo?l Beaudouin Roland Eils 《Biophysical journal》2015,109(11):2352-2362
The number of fluorophores within a molecule complex can be revealed by single-molecule photobleaching imaging. A widely applied strategy to analyze intensity traces over time is the quantification of photobleaching step counts. However, several factors can limit and bias the detection of photobleaching steps, including noise, high numbers of fluorophores, and the possibility that several photobleaching events occur almost simultaneously. In this study, we propose a new approach, to our knowledge, to determine the fluorophore number that correlates the intensity decay of a population of molecule complexes with the decay of the number of visible complexes. We validated our approach using single and fourfold Atto-labeled DNA strands. As an example we estimated the subunit stoichiometry of soluble CD95L using GFP fusion proteins. To assess the precision of our method we performed in silico experiments showing that the estimates are not biased for experimentally observed intensity fluctuations and that the relative precision remains constant with increasing number of fluorophores. In case of fractional fluorescent labeling, our simulations predicted that the fluorophore number estimate corresponds to the product of the true fluorophore number with the labeling fraction. Our method, denoted by spot number and intensity correlation (SONIC), is fully automated, robust to noise, and does not require the counting of photobleaching events. 相似文献
936.
Serena C. Hedgepeth M. Iveth Garcia Larry E. Wagner II Ana M. Rodriguez Sree V. Chintapalli Russell R. Snyder Gary D. V. Hankins Beric R. Henderson Kirsty M. Brodie David I. Yule Damian B. van Rossum Darren Boehning 《The Journal of biological chemistry》2015,290(11):7304-7313
The inositol 1,4,5-trisphosphate receptor (IP3R) is a ubiquitously expressed endoplasmic reticulum (ER)-resident calcium channel. Calcium release mediated by IP3Rs influences many signaling pathways, including those regulating apoptosis. IP3R activity is regulated by protein-protein interactions, including binding to proto-oncogenes and tumor suppressors to regulate cell death. Here we show that the IP3R binds to the tumor suppressor BRCA1. BRCA1 binding directly sensitizes the IP3R to its ligand, IP3. BRCA1 is recruited to the ER during apoptosis in an IP3R-dependent manner, and, in addition, a pool of BRCA1 protein is constitutively associated with the ER under non-apoptotic conditions. This is likely mediated by a novel lipid binding activity of the first BRCA1 C terminus domain of BRCA1. These findings provide a mechanistic explanation by which BRCA1 can act as a proapoptotic protein. 相似文献
937.
Christina Brennenstuhl Naoyuki Tanimoto Markus Burkard Rebecca Wagner Sylvia Bolz Dragana Trifunovic Clement Kabagema-Bilan Francois Paquet-Durand Susanne C. Beck Gesine Huber Mathias W. Seeliger Peter Ruth Bernd Wissinger Robert Lukowski 《The Journal of biological chemistry》2015,290(16):10242-10255
Phosphodiesterase-6 (PDE6) is a multisubunit enzyme that plays a key role in the visual transduction cascade in rod and cone photoreceptors. Each type of photoreceptor utilizes discrete catalytic and inhibitory PDE6 subunits to fulfill its physiological tasks, i.e. the degradation of cyclic guanosine-3′,5′-monophosphate at specifically tuned rates and kinetics. Recently, the human PDE6H gene was identified as a novel locus for autosomal recessive (incomplete) color blindness. However, the three different classes of cones were not affected to the same extent. Short wave cone function was more preserved than middle and long wave cone function indicating that some basic regulation of the PDE6 multisubunit enzyme was maintained albeit by a unknown mechanism. To study normal and disease-related functions of cone Pde6h in vivo, we generated Pde6h knock-out (Pde6h−/−) mice. Expression of PDE6H in murine eyes was restricted to both outer segments and synaptic terminals of short and long/middle cone photoreceptors, whereas Pde6h−/− retinae remained PDE6H-negative. Combined in vivo assessment of retinal morphology with histomorphological analyses revealed a normal overall integrity of the retinal organization and an unaltered distribution of the different cone photoreceptor subtypes upon Pde6h ablation. In contrast to human patients, our electroretinographic examinations of Pde6h−/− mice suggest no defects in cone/rod-driven retinal signaling and therefore preserved visual functions. To this end, we were able to demonstrate the presence of rod PDE6G in cones indicating functional substitution of PDE6. The disparities between human and murine phenotypes caused by mutant Pde6h/PDE6H suggest species-to-species differences in the vulnerability of biochemical and neurosensory pathways of the visual signal transduction system. 相似文献
938.
Mohamad Navab Arnab Chattopadhyay Greg Hough David Meriwether Spencer I. Fogelman Alan C. Wagner Victor Grijalva Feng Su G. M. Anantharamaiah Lin H. Hwang Kym F. Faull Srinivasa T. Reddy Alan M. Fogelman 《Journal of lipid research》2015,56(4):871-887
We previously reported that i) a Western diet increased levels of unsaturated lysophosphatidic acid (LPA) in small intestine and plasma of LDL receptor null (LDLR−/−) mice, and ii) supplementing standard mouse chow with unsaturated (but not saturated) LPA produced dyslipidemia and inflammation. Here we report that supplementing chow with unsaturated (but not saturated) LPA resulted in aortic atherosclerosis, which was ameliorated by adding transgenic 6F tomatoes. Supplementing chow with lysophosphatidylcholine (LysoPC) 18:1 (but not LysoPC 18:0) resulted in dyslipidemia similar to that seen on adding LPA 18:1 to chow. PF8380 (a specific inhibitor of autotaxin) significantly ameliorated the LysoPC 18:1-induced dyslipidemia. Supplementing chow with LysoPC 18:1 dramatically increased the levels of unsaturated LPA species in small intestine, liver, and plasma, and the increase was significantly ameliorated by PF8380 indicating that the conversion of LysoPC 18:1 to LPA 18:1 was autotaxin dependent. Adding LysoPC 18:0 to chow increased levels of LPA 18:0 in small intestine, liver, and plasma but was not altered by PF8380 indicating that conversion of LysoPC 18:0 to LPA 18:0 was autotaxin independent. We conclude that i) intestinally derived unsaturated (but not saturated) LPA can cause atherosclerosis in LDLR−/− mice, and ii) autotaxin mediates the conversion of unsaturated (but not saturated) LysoPC to LPA. 相似文献
939.
Kyle Lapham Mark N. Kvale Jue Lin Sheryl Connell Lisa A. Croen Brad P. Dispensa Lynn Fang Stephanie Hesselson Thomas J. Hoffmann Carlos Iribarren Eric Jorgenson Lawrence H. Kushi Dana Ludwig Tetsuya Matsuguchi William B. McGuire Sunita Miles Charles P. Quesenberry Jr. Sarah Rowell Marianne Sadler Lori C. Sakoda David Smethurst Carol P. Somkin Stephen K. Van Den Eeden Lawrence Walter Rachel A. Whitmer Pui-Yan Kwok Neil Risch Catherine Schaefer Elizabeth H. Blackburn 《Genetics》2015,200(4):1061-1072
The Kaiser Permanente Research Program on Genes, Environment, and Health (RPGEH) Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort includes DNA specimens extracted from saliva samples of 110,266 individuals. Because of its relationship to aging, telomere length measurement was considered an important biomarker to develop on these subjects. To assay relative telomere length (TL) on this large cohort over a short time period, we created a novel high throughput robotic system for TL analysis and informatics. Samples were run in triplicate, along with control samples, in a randomized design. As part of quality control, we determined the within-sample variability and employed thresholds for the elimination of outlying measurements. Of 106,902 samples assayed, 105,539 (98.7%) passed all quality control (QC) measures. As expected, TL in general showed a decline with age and a sex difference. While telomeres showed a negative correlation with age up to 75 years, in those older than 75 years, age positively correlated with longer telomeres, indicative of an association of longer telomeres with more years of survival in those older than 75. Furthermore, while females in general had longer telomeres than males, this difference was significant only for those older than age 50. An additional novel finding was that the variance of TL between individuals increased with age. This study establishes reliable assay and analysis methodologies for measurement of TL in large, population-based human studies. The GERA cohort represents the largest currently available such resource, linked to comprehensive electronic health and genotype data for analysis. 相似文献