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81.
The Golgi apparatus is composed of biochemically distinct early (cis, medial) and late (trans, TGN) cisternae. There is debate about the nature of these cisternae. The stable compartments model predicts that each cisterna is a long-lived structure that retains a characteristic set of Golgi-resident proteins. In this view, secretory cargo proteins are transported by vesicles from one cisterna to the next. The cisternal maturation model predicts that each cisterna is a transient structure that matures from early to late by acquiring and then losing specific Golgi-resident proteins. In this view, secretory cargo proteins traverse the Golgi by remaining within the maturing cisternae. Various observations have been interpreted as supporting one or the other mechanism. Here we provide a direct test of the two models using three-dimensional time-lapse fluorescence microscopy of the yeast Saccharomyces cerevisiae. This approach reveals that individual cisternae mature, and do so at a consistent rate. In parallel, we used pulse-chase analysis to measure the transport of two secretory cargo proteins. The rate of cisternal maturation matches the rate of protein transport through the secretory pathway, suggesting that cisternal maturation can account for the kinetics of secretory traffic. 相似文献
82.
Neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease trigger neuronal cell death through endogenous suicide pathways. Surprisingly, although the cell death itself may occur relatively late in the course of the degenerative process, the mediators of the underlying cell-death pathways have shown promise as potential therapeutic targets. 相似文献
83.
Field GD Gauthier JL Sher A Greschner M Machado TA Jepson LH Shlens J Gunning DE Mathieson K Dabrowski W Paninski L Litke AM Chichilnisky EJ 《Nature》2010,467(7316):673-677
To understand a neural circuit requires knowledge of its connectivity. Here we report measurements of functional connectivity between the input and ouput layers of the macaque retina at single-cell resolution and the implications of these for colour vision. Multi-electrode technology was used to record simultaneously from complete populations of the retinal ganglion cell types (midget, parasol and small bistratified) that transmit high-resolution visual signals to the brain. Fine-grained visual stimulation was used to identify the location, type and strength of the functional input of each cone photoreceptor to each ganglion cell. The populations of ON and OFF midget and parasol cells each sampled the complete population of long- and middle-wavelength-sensitive cones. However, only OFF midget cells frequently received strong input from short-wavelength-sensitive cones. ON and OFF midget cells showed a small non-random tendency to selectively sample from either long- or middle-wavelength-sensitive cones to a degree not explained by clumping in the cone mosaic. These measurements reveal computations in a neural circuit at the elementary resolution of individual neurons. 相似文献
84.
A hierarchical multiple criteria model for eliciting relative preferences in conflict situations 总被引:1,自引:1,他引:0
A multiple criteria decision analysis(MCDA) approach is designed for capturing the relative preference information of a decision maker involved in a conflict.More specifically,an MCDA approach based on the outranking method,ELECTRE III,is employed for ranking states or possible scenarios in the conflict from most to least preferred,where ties are allowed,for a decision maker according to his or her value system.To demonstrate how this preference elicitation methodology can be conveniently implemented in practice within the framework of the Graph Model for Conflict Resolution,it is applied to a real world water supply crisis which occurred in the town of North Battleford,located in the Canadian province of Saskatchewan. 相似文献
85.
Lim J Crespo-Barreto J Jafar-Nejad P Bowman AB Richman R Hill DE Orr HT Zoghbi HY 《Nature》2008,452(7188):713-718
Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disease caused by expansion of a glutamine-encoding repeat in ataxin 1 (ATXN1). In all known polyglutamine diseases, the glutamine expansion confers toxic functions onto the protein; however, the mechanism by which this occurs remains enigmatic, in light of the fact that the mutant protein apparently maintains interactions with its usual partners. Here we show that the expanded polyglutamine tract differentially affects the function of the host protein in the context of different endogenous protein complexes. Polyglutamine expansion in ATXN1 favours the formation of a particular protein complex containing RBM17, contributing to SCA1 neuropathology by means of a gain-of-function mechanism. Concomitantly, polyglutamine expansion attenuates the formation and function of another protein complex containing ATXN1 and capicua, contributing to SCA1 through a partial loss-of-function mechanism. This model provides mechanistic insight into the molecular pathogenesis of SCA1 as well as other polyglutamine diseases. 相似文献
86.
The amphioxus genome and the evolution of the chordate karyotype 总被引:2,自引:0,他引:2
Putnam NH Butts T Ferrier DE Furlong RF Hellsten U Kawashima T Robinson-Rechavi M Shoguchi E Terry A Yu JK Benito-Gutiérrez EL Dubchak I Garcia-Fernàndez J Gibson-Brown JJ Grigoriev IV Horton AC de Jong PJ Jurka J Kapitonov VV Kohara Y Kuroki Y Lindquist E Lucas S Osoegawa K Pennacchio LA Salamov AA Satou Y Sauka-Spengler T Schmutz J Shin-I T Toyoda A Bronner-Fraser M Fujiyama A Holland LZ Holland PW Satoh N Rokhsar DS 《Nature》2008,453(7198):1064-1071
87.
Yang L Anderson DE Baecher-Allan C Hastings WD Bettelli E Oukka M Kuchroo VK Hafler DA 《Nature》2008,454(7202):350-352
88.
丁兆运 《烟台师范学院学报(自然科学版)》2001,17(2):134-137
随着中国城市中增长及居民生活水平的提高,中国城市生活垃圾的排放量越来越大,已严重影响了中国城市化的进程。对其治理问题已成为困扰中国各级政府的一大难题。资源化是解决垃圾问题的有效途径。根据中国国情,提出了城市生活垃圾资源化的具体措施。 相似文献
89.
90.
PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression
Day CL Kaufmann DE Kiepiela P Brown JA Moodley ES Reddy S Mackey EW Miller JD Leslie AJ DePierres C Mncube Z Duraiswamy J Zhu B Eichbaum Q Altfeld M Wherry EJ Coovadia HM Goulder PJ Klenerman P Ahmed R Freeman GJ Walker BD 《Nature》2006,443(7109):350-354
Functional impairment of T cells is characteristic of many chronic mouse and human viral infections. The inhibitory receptor programmed death 1 (PD-1; also known as PDCD1), a negative regulator of activated T cells, is markedly upregulated on the surface of exhausted virus-specific CD8 T cells in mice. Blockade of this pathway using antibodies against the PD ligand 1 (PD-L1, also known as CD274) restores CD8 T-cell function and reduces viral load. To investigate the role of PD-1 in a chronic human viral infection, we examined PD-1 expression on human immunodeficiency virus (HIV)-specific CD8 T cells in 71 clade-C-infected people who were naive to anti-HIV treatments, using ten major histocompatibility complex (MHC) class I tetramers specific for frequently targeted epitopes. Here we report that PD-1 is significantly upregulated on these cells, and expression correlates with impaired HIV-specific CD8 T-cell function as well as predictors of disease progression: positively with plasma viral load and inversely with CD4 T-cell count. PD-1 expression on CD4 T cells likewise showed a positive correlation with viral load and an inverse correlation with CD4 T-cell count, and blockade of the pathway augmented HIV-specific CD4 and CD8 T-cell function. These data indicate that the immunoregulatory PD-1/PD-L1 pathway is operative during a persistent viral infection in humans, and define a reversible defect in HIV-specific T-cell function. Moreover, this pathway of reversible T-cell impairment provides a potential target for enhancing the function of exhausted T cells in chronic HIV infection. 相似文献