scholarly journals Inhibition of Human Ether-A-Go-Go-Related Gene (hERG) Potassium Current by the Novel Sotalol Analogue, Soestalol

2020 ◽  
Vol 6 (7) ◽  
pp. 756-759
Author(s):  
Tyler Shugg ◽  
John C. Somberg ◽  
Janos Molnar ◽  
Brian R. Overholser
2015 ◽  
Vol 114 (2) ◽  
pp. 1272-1285
Author(s):  
Yan Gai ◽  
Janet L. Ruhland ◽  
Tom C. T. Yin

The precedence effect (PE) is an auditory illusion that occurs when listeners localize nearly coincident and similar sounds from different spatial locations, such as a direct sound and its echo. It has mostly been studied in humans and animals with immobile heads in the horizontal plane; speaker pairs were often symmetrically located in the frontal hemifield. The present study examined the PE in head-unrestrained cats for a variety of paired-sound conditions along the horizontal, vertical, and diagonal axes. Cats were trained with operant conditioning to direct their gaze to the perceived sound location. Stereotypical PE-like behaviors were observed for speaker pairs placed in azimuth or diagonally in the frontal hemifield as the interstimulus delay was varied. For speaker pairs in the median sagittal plane, no clear PE-like behavior occurred. Interestingly, when speakers were placed diagonally in front of the cat, certain PE-like behavior emerged along the vertical dimension. However, PE-like behavior was not observed when both speakers were located in the left hemifield. A Hodgkin-Huxley model was used to simulate responses of neurons in the medial superior olive (MSO) to sound pairs in azimuth. The novel simulation incorporated a low-threshold potassium current and frequency mismatches to generate internal delays. The model exhibited distinct PE-like behavior, such as summing localization and localization dominance. The simulation indicated that certain encoding of the PE could have occurred before information reaches the inferior colliculus, and MSO neurons with binaural inputs having mismatched characteristic frequencies may play an important role.


2001 ◽  
Vol 165 (1) ◽  
pp. 71-79 ◽  
Author(s):  
Inko Nimmrich ◽  
Silke Erdmann ◽  
Ute Melchers ◽  
Slava Chtarbova ◽  
Ulrich Finke ◽  
...  

2021 ◽  
pp. 153537022110117
Author(s):  
Yuting Zhang ◽  
Peifang Qin ◽  
Linlin Tian ◽  
Jianguo Yan ◽  
Yali Zhou

Mediator is an evolutionarily conserved multi-protein complex that mediates the interaction between different proteins as a basic linker in the transcription mechanism of eukaryotes. It interacts with RNA polymerase II and participates in the process of gene expression. Mediator complex subunit 19 or regulation by oxygen 3, or lung cancer metastasis-related protein 1 is located at the head of the mediator complex; it is a multi-protein co-activator that induces the transcription of RNA polymerase II by DNA transcription factors. It is a tumor-related gene that plays an important role in transcriptional regulation, cell proliferation, and apoptosis and is closely related to the occurrence and development of the cancers of the lung, bladder, skin, etc. Here, we used the structure of mediator complex subunit 19 to review its role in tumor progression, fat metabolism, drug therapy, as well as the novel coronavirus, which has attracted much attention at present, suggesting that mediator complex subunit 19 has broad application in the occurrence and development of clinical diseases. As a tumor-related gene, the role and mechanism of mediator complex subunit 19 in the regulation of tumor growth could be of great significance for the diagnosis, prognosis, and treatment of mediator complex subunit 19 -related tumors.


FEBS Letters ◽  
1993 ◽  
Vol 336 (1) ◽  
pp. 79-82 ◽  
Author(s):  
A.B. Shevelev ◽  
M.A. Svarinsky ◽  
A.I. Karasin ◽  
Ya.N. Kogan ◽  
G.G. Chestukhina ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Chenchen Mao ◽  
Liangliang Ma ◽  
Yingpeng Huang ◽  
Xinxin Yang ◽  
He Huang ◽  
...  

BackgroundAsians have the highest incidence of gastric cancer (GC), and the prognosis of Asian GC is poor. Furthermore, the therapeutics for Asian GC is limited because of genetic heterogeneity and screening difficulty at the early stage. This study aimed to develop an immune-related gene (IRG)-based prognostic signature and to explore prognosis-related regulatory mechanism and therapeutic target for Asian GC.MethodsTo elucidate the prognostic value of IRGs in Asian GC, a comprehensive analysis of IRG expression profiles and overall survival times in 364 Asian GC patients from the Asian Cancer Research Group (ACRG) and The Cancer Genome Atlas (TCGA) databases was performed, and a novel prognostic index was established. To further explore regulatory prognosis mechanisms and therapeutic targets, a tumor immunogenomic landscape analysis, including stromal and immune subcomponents, cell types, panimmune gene sets, and immunomodulatory genes, was performed.ResultOur analysis allowed the creation of an optimal risk assessment model, the Asian-specific IRG-based prognostic index (ASIRGPI), which showed a high accuracy in predicting survival in Asian GC. We also developed an ASIRGPI-based nomogram to predict the 3- and 5-year overall survival (OS) of Asian GC patients. The impact of the ASIRGPI on the worse prognosis of Asian GC was possibly related to the stromal component remodeling. Specifically, TGFβ gene sets were significantly associated with the ASIRGPI and worse prognosis. Immunomodulatory gene analysis further revealed that TGFβ1 and EDNRB may be the novel potential therapeutic targets for Asian GC.ConclusionsAs a tumor microenvironment-relevant gene set-based prognostic signature, the ASIRGPI model provides an effective approach for evaluating the prognosis of Asian GC and may even prolong OS by enabling the selection of individualized therapy with the novel targets.


2011 ◽  
Vol 51 (6) ◽  
pp. 442-453 ◽  
Author(s):  
Haodan Zhu ◽  
Dongyan Huang ◽  
Wei Zhang ◽  
Zongfu Wu ◽  
Yan Lu ◽  
...  

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