Auditory P50 suppression, which is assessed using a paired auditory stimuli (S1 and S2) paradigm to record the P50 mid-latency evoked potential, is assumed to reflect sensory gating. Recently, P50 suppression deficits were observed in patients with anxiety disorders, including panic disorder, post-traumatic stress disorder and obsessive-compulsive disorder, as we previously reported. The processes of fear conditioning are thought to play a role in the pathophysiology of anxiety disorders. In addition, we found that the P50 sensory gating mechanism might be physiologically associated with fear conditioning and extinction in a simple human fear-conditioning paradigm that involved a light signal as a conditioned stimulus (CS+). Our objective was to investigate the different patterns of P50 suppression in a discrimination fear-conditioning paradigm with both a CS+ (danger signal) and a CS- (safety signal). Twenty healthy volunteers were recruited. We measured the auditory P50 suppression in the control (baseline) phase, in the fear-acquisition phase, and in the fear-extinction phase using a discrimination fear-conditioning paradigm. Two-way (CSs vs. phase) Analysis of variance with repeated measures demonstrated a significant interaction between the two factors. Post-hoc LSD analysis indicated that the P50 S2/S1 ratio in the CS+ acquisition phase was significantly higher than that in the CS- acquisition phase. These results suggest that the auditory P50 sensory gating might differ according to the cognition of the properties (potentially dangerous or safe) of the perceived signal.
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http://dx.doi.org/10.1016/j.ijpsycho.2012.01.004 | DOI Listing |
Elife
January 2025
Department of Neurology, Baylor College of Medicine, Houston, United States.
Biochem Biophys Res Commun
January 2025
The Rappaport Faculty of Medicine and Research Institute, and the Rappaport Technion Integrated Cancer Center (R-TICC), Technion-Israel Institute of Technology, Haifa, 3109601, Israel. Electronic address:
The ubiquitin proteasome system (UPS), driven by ubiquitin as a degradation signal, eliminates, in a highly specific manner, 'abnormal' proteins and proteins that completed their function. This process involves a hierarchical cascade of E1, E2, and E3 enzymes. The E3 ubiquitin ligases, act as specific receptors that bind their cognate substrates.
View Article and Find Full Text PDFAnnu Rev Public Health
December 2024
3Dissemination and Implementation Science Program, Adult and Child Center for Outcomes Research and Delivery Science, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
When complex public health and health services interventions are implemented in real-world settings, adaptations should be expected, embraced, and studied rather than suppressed and ignored. A substantial amount of recent research has been conducted on the assessment of some types of adaptations, and interest in guiding adaptations to both interventions and implementation strategies is growing. However, there is still a need to investigate the optimal ways to systematically and pragmatically document, analyze, and iteratively guide adaptations as well as to measure the impact of those adaptations on implementation and effectiveness outcomes.
View Article and Find Full Text PDFNat Commun
December 2024
Department of Urology, Weill Cornell Medicine, New York, NY, USA.
The androgen receptor (AR) is central in prostate tissue identity and differentiation, and controls normal growth-suppressive, prostate-specific gene expression. It also drives prostate tumorigenesis when hijacked for oncogenic transcription. The execution of growth-suppressive AR transcriptional programs in prostate cancer (PCa) and the potential for reactivation remain unclear.
View Article and Find Full Text PDFSci Adv
December 2024
Department of Surgery, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Direct targeting of the -mutant protein using covalent inhibitors (G12Ci) acts on human non-small cell lung cancer (NSCLC). However, drug resistance is an emerging concern in this approach. Here, we show that MRTX849, a covalent inhibitor targeting the mutation, leads to the reactivation of the mitogen-activated protein kinase signaling pathway in MRTX849-resistant NSCLC and pancreatic ductal adenocarcinoma.
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