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421.
Florian Hoss Juan F. Rodriguez-Alcazar Eicke Latz 《Cellular and molecular life sciences : CMLS》2017,74(7):1211-1229
The inflammasome adapter ASC links activated inflammasome sensors to the effector molecule pro-caspase-1. Recruitment of pro-caspase-1 to ASC promotes the autocatalytic activation of caspase-1, which leads to the release of pro-inflammatory cytokines, such as IL-1β. Upon triggering of inflammasome sensors, ASC assembles into large helical fibrils that interact with each other serving as a supramolecular signaling platform termed the ASC speck. Alternative splicing, post-translational modifications of ASC, as well as interaction with other proteins can perturb ASC function. In several inflammatory diseases, ASC specks can be found in the extracellular space and its presence correlates with poor prognosis. Here, we review the role of ASC in inflammation, and focus on the structural mechanisms that lead to ASC speck formation, the regulation of ASC function during inflammasome assembly, and the importance of ASC specks in disease. 相似文献
422.
Micro panels characterized by large numbers of individuals observed over a short time period provide a rich source of information, but as yet there is only limited experience in using such data for forecasting. Existing simulation evidence supports the use of a fixed‐effects approach when forecasting but it is not based on a truly micro panel set‐up. In this study, we exploit the linkage of a representative survey of more than 250,000 Australians aged 45 and over to 4 years of hospital, medical and pharmaceutical records. The availability of panel health cost data allows the use of predictors based on fixed‐effects estimates designed to guard against possible omitted variable biases associated with unobservable individual specific effects. We demonstrate the preference towards fixed‐effects‐based predictors is unlikely to hold in many practical situations, including our models of health care costs. Simulation evidence with a micro panel set‐up adds support and additional insights to the results obtained in the application. These results are supportive of the use of the ordinary least squares predictor in a wide range of circumstances. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献
423.
The composition of the gut microbiota is in constant flow under the influence of factors such as the diet, ingested drugs, the intestinal mucosa, the immune system, and the microbiota itself. Natural variations in the gut microbiota can deteriorate to a state of dysbiosis when stress conditions rapidly decrease microbial diversity and promote the expansion of specific bacterial taxa. The mechanisms underlying intestinal dysbiosis often remain unclear given that combinations of natural variations and stress factors mediate cascades of destabilizing events. Oxidative stress, bacteriophages induction and the secretion of bacterial toxins can trigger rapid shifts among intestinal microbial groups thereby yielding dysbiosis. A multitude of diseases including inflammatory bowel diseases but also metabolic disorders such as obesity and diabetes type II are associated with intestinal dysbiosis. The characterization of the changes leading to intestinal dysbiosis and the identification of the microbial taxa contributing to pathological effects are essential prerequisites to better understand the impact of the microbiota on health and disease. 相似文献
424.
Dalila de Fátima Ferreira Leonardo Esteves Lopes 《Journal of Natural History》2017,51(23-24):1425-1435
The Lined Seedeater (Sporophila lineola) is a migratory species that inhabits a variety of open habitats in South America. We studied the breeding biology and territorial behaviour of a colour-banded population of the species in the Universidade Federal de Viçosa, Campus Florestal (1–19,8808ºS, –44,4136ºW), during two breeding seasons (2014/2015 and 2015/2016), which spans from December to April. We monitored 74 nests of this species. The nest is a low cup supported between a fork. Nests are mainly built with grass stems and rootlets, with spider-web used to hold the material together and to bind the nest to its supporting plant. Females are solely responsible for nest building and incubation, which is synchronic, and also for feeding nestlings to a large extent. Males are responsible for defending the territory, which corresponds to a small portion of the home range restricted to the nest environs, and also feed the nestlings. Mean clutch size is two eggs (78% of nests monitored), with clutches of three (20.3%) and four (1.7%) eggs also observed. Eggs are whitish, covered with dark brown blotches and spots to a variable extent. Mean incubation period, considered as the period between the onset of incubation and hatching of the first egg, is 11 days. Nestling period, considered as the period between hatching of the first egg and fledging of the last young, is 10 days. During the first breeding season, the simple percentage of successful nests was 34.1%, while the Mayfield success was 29.8%, with slightly higher values observed during the second breeding season, with 39.4% and 35.7%, respectively. We recorded, for the first time, three cases of polygamy in the species. We also recorded breeding site fidelity for the first time in the species, with males returning to the same territory owned in a previous breeding season. 相似文献
425.
Marcelo S. Perlin João F. Caldeira André A. P. Santos Martin Pontuschka 《Journal of forecasting》2017,36(4):454-467
We look into the interaction of Google's search queries and several aspects of international equity markets. Using a novel methodology for selecting words and a vector autoregressive modeling approach, we study whether the search queries of finance‐related words can have an impact on returns, volatility of returns and traded volume in four different English‐speaking countries. We identify several words whose search frequency is associated with changes in the dependent variables. In particular, we find that increases in search queries including the word stock predict increased volatility and decreased index returns over the next week. On top of that, we investigate the performance of a market‐timing strategy based on the search frequency of this word and benchmark it against random words from the Word‐Net database and a naive buy‐and‐hold strategy. The results of this empirical application are positive and particularly stronger during the global crisis of 2009. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献
426.
427.
428.
Antoni Camins Javier G. Pizarro Daniel Alvira Javier Gutierrez-Cuesta Aurelio Vazquez de la Torre Jaume Folch Francesc X. Sureda Ester Verdaguer Felix Junyent Joaquín Jordán Isidre Ferrer Mercè Pallàs 《Cellular and molecular life sciences : CMLS》2010,67(22):3865-3882
In the present study we demonstrated that neurotoxin MPP+-induced DNA damage is followed by ataxia telangiectasia muted (ATM) activation either in cerebellar granule cells (CGC) or in B65 cell line. In CGC, the selective ATM inhibitor KU-55933 showed neuroprotective effects against MPP+-induced neuronal cell loss and apoptosis, lending support to the key role of ATM in experimental models of Parkinson’s disease. Likewise, we showed that knockdown of ATM levels in neuroblastoma B65 cells using an ATM-specific siRNA attenuates the phosphorylation of retinoblastoma protein without affecting other cell-cycle proteins involved in the G0/G1 cell-cycle phase. Moreover, we demonstrated DNA damage, in human brain samples of PD patients. These findings support a model in which MPP+ leads to ATM activation with a subsequent DNA damage response and activation of pRb. Therefore, this study demonstrates a new link between DNA damage by MPP+ and cell-cycle re-entry through retinoblastoma protein phosphorylation. 相似文献
429.
Hüffmeier U Uebe S Ekici AB Bowes J Giardina E Korendowych E Juneblad K Apel M McManus R Ho P Bruce IN Ryan AW Behrens F Lascorz J Böhm B Traupe H Lohmann J Gieger C Wichmann HE Herold C Steffens M Klareskog L Wienker TF Fitzgerald O Alenius GM McHugh NJ Novelli G Burkhardt H Barton A Reis A 《Nature genetics》2010,42(11):996-999
Psoriatic arthritis (PsA) is an inflammatory joint disease that is distinct from other chronic arthritides and which is frequently accompanied by psoriasis vulgaris (PsV) and seronegativity for rheumatoid factor. We conducted a genome-wide association study in 609 German individuals with PsA (cases) and 990 controls with replication in 6 European cohorts including a total of 5,488 individuals. We replicated PsA associations at HLA-C and IL12B and identified a new association at TRAF3IP2 (rs13190932, P = 8.56 × 10?1?). TRAF3IP2 was also associated with PsV in a German cohort including 2,040 individuals (rs13190932, P = 1.95 × 10?3). Sequencing of the exons of TRAF3IP2 identified a coding variant (p.Asp10Asn, rs33980500) as the most significantly associated SNP (P = 1.13 × 10?2?, odds ratio = 1.95). Functional assays showed reduced binding of this TRAF3IP2 variant to TRAF6, suggesting altered modulation of immunoregulatory signals through altered TRAF interactions as a new and shared pathway for PsA and PsV. 相似文献
430.
This paper proposes the use of the bias‐corrected bootstrap for interval forecasting of an autoregressive time series with an arbitrary number of deterministic components. We use the bias‐corrected bootstrap based on two alternative bias‐correction methods: the bootstrap and an analytic formula based on asymptotic expansion. We also propose a new stationarity‐correction method, based on stable spectral factorization, as an alternative to Kilian's method exclusively used in past studies. A Monte Carlo experiment is conducted to compare small‐sample properties of prediction intervals. The results show that the bias‐corrected bootstrap prediction intervals proposed in this paper exhibit desirable small‐sample properties. It is also found that the bootstrap bias‐corrected prediction intervals based on stable spectral factorization are tighter and more stable than those based on Kilian's stationarity‐correction. The proposed methods are applied to interval forecasting for the number of tourist arrivals in Hong Kong. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献