Critical Event Processing and Its Regulatory Application

Author(s):  
Michael Fang ◽  
George Q. Huang ◽  
Y. F. Zhang ◽  
T. Qu ◽  
Q. Y. Dai
2019 ◽  
Vol 133 (20) ◽  
pp. 2045-2059 ◽  
Author(s):  
Da Zhang ◽  
Xiuli Wang ◽  
Siyao Chen ◽  
Selena Chen ◽  
Wen Yu ◽  
...  

Abstract Background: Pulmonary artery endothelial cell (PAEC) inflammation is a critical event in the development of pulmonary arterial hypertension (PAH). However, the pathogenesis of PAEC inflammation remains unclear. Methods: Purified recombinant human inhibitor of κB kinase subunit β (IKKβ) protein, human PAECs and monocrotaline-induced pulmonary hypertensive rats were employed in the study. Site-directed mutagenesis, gene knockdown or overexpression were conducted to manipulate the expression or activity of a target protein. Results: We showed that hydrogen sulfide (H2S) inhibited IKKβ activation in the cell model of human PAEC inflammation induced by monocrotaline pyrrole-stimulation or knockdown of cystathionine γ-lyase (CSE), an H2S generating enzyme. Mechanistically, H2S was proved to inhibit IKKβ activity directly via sulfhydrating IKKβ at cysteinyl residue 179 (C179) in purified recombinant IKKβ protein in vitro, whereas thiol reductant dithiothreitol (DTT) reversed H2S-induced IKKβ inactivation. Furthermore, to demonstrate the significance of IKKβ sulfhydration by H2S in the development of PAEC inflammation, we mutated C179 to serine (C179S) in IKKβ. In purified IKKβ protein, C179S mutation of IKKβ abolished H2S-induced IKKβ sulfhydration and the subsequent IKKβ inactivation. In human PAECs, C179S mutation of IKKβ blocked H2S-inhibited IKKβ activation and PAEC inflammatory response. In pulmonary hypertensive rats, C179S mutation of IKKβ abolished the inhibitory effect of H2S on IKKβ activation and pulmonary vascular inflammation and remodeling. Conclusion: Collectively, our in vivo and in vitro findings demonstrated, for the first time, that endogenous H2S directly inactivated IKKβ via sulfhydrating IKKβ at Cys179 to inhibit nuclear factor-κB (NF-κB) pathway activation and thereby control PAEC inflammation in PAH.


2014 ◽  
Vol 73 (1) ◽  
pp. 25-34 ◽  
Author(s):  
Magali Ginet ◽  
Jacques Py ◽  
Cindy Colomb

This study examines the influence of familiarity on witnesses’ memory and the individual effectiveness of each of the four cognitive interview instructions in improving witnesses’ recall of scripted events. Participants (N = 195), either familiar or unfamiliar with the hospital script, were presented with a video of a surgical operation. One week later, an interviewer used one of the four cognitive interview instructions or a control instruction to ask them about the video. Participants familiar with the surgery context recalled significantly more correct information and, in particular, more consistent and irrelevant details than those unfamiliar with the surgery context. Furthermore, the results confirmed the effectiveness of all four cognitive interview mnemonics in enhancing the amount of correct information reported, irrespective of the participants’ familiarity with the critical event. However, their efficacy differed depending on the category of details considered. The practical implications of these results are discussed.


2006 ◽  
Author(s):  
Jean M. Catanzaro ◽  
Matthew R. Risser ◽  
John W. Gwynne ◽  
Daniel I. Manes

2018 ◽  
Vol 22 (4) ◽  
pp. 247-267
Author(s):  
Rachel A. Sluis ◽  
◽  
Mark J. Boschen ◽  
David L. Neumann ◽  
Karen Murphy ◽  
...  

2012 ◽  
Vol 35 (3) ◽  
pp. 540-554 ◽  
Author(s):  
Shang-Lian PENG ◽  
Zhan-Huai LI ◽  
Qun CHEN ◽  
Qiang LI

2020 ◽  
Vol 30 (10) ◽  
pp. 5544-5559 ◽  
Author(s):  
Jonathan D Power ◽  
Charles J Lynch ◽  
Babatunde Adeyemo ◽  
Steven E Petersen

Abstract This article advances two parallel lines of argument about resting-state functional magnetic resonance imaging (fMRI) signals, one empirical and one conceptual. The empirical line creates a four-part organization of the text: (1) head motion and respiration commonly cause distinct, major, unwanted influences (artifacts) in fMRI signals; (2) head motion and respiratory changes are, confoundingly, both related to psychological and clinical and biological variables of interest; (3) many fMRI denoising strategies fail to identify and remove one or the other kind of artifact; and (4) unremoved artifact, due to correlations of artifacts with variables of interest, renders studies susceptible to identifying variance of noninterest as variance of interest. Arising from these empirical observations is a conceptual argument: that an event-related approach to task-free scans, targeting common behaviors during scanning, enables fundamental distinctions among the kinds of signals present in the data, information which is vital to understanding the effects of denoising procedures. This event-related perspective permits statements like “Event X is associated with signals A, B, and C, each with particular spatial, temporal, and signal decay properties”. Denoising approaches can then be tailored, via performance in known events, to permit or suppress certain kinds of signals based on their desirability.


Sign in / Sign up

Export Citation Format

Share Document