Reply to Smolensky and Hermida: The potential role of internal circadian time in tailored anti-hypertensive medication dosing

2021 ◽  
pp. 101539
Author(s):  
Nicole P. Bowles ◽  
Steven A. Shea
Keyword(s):  
Potential Role ◽  
Circadian Time

scholarly journals Chronoefficacy of the herbal medicines Puerariae radix and Coptidis rhizoma in mice: A potential role of REV-ERBα

2021 ◽  
Author(s):  
Jinming Liu ◽  
Haiman Xu ◽  
Li Zhang ◽  
Shuai Wang ◽  
Danyi Lu ◽  
...  
Keyword(s):  
Drug Target ◽  
Potential Role ◽  
Target Genes ◽  
Herbal Medicines ◽  
Chronic Colitis ◽  
Active Constituent ◽  
Circadian Time ◽  
Coptidis Rhizoma ◽  
Underlying Mechanisms

Abstract Background Identifying drugs with circadian time-dependent efficacy (chronoefficacy) and understanding the underlying mechanisms would help to improve drug treatment outcome. Here, we aimed to determine chronoefficacy of the herbal medicines Puerariae radix (PR) and Coptidis rhizoma (CR), and investigate a potential role of REV-ERBα as a drug target in generating chronoefficacy. Materials and methods PR and CR efficacy were assessed based on the diseases hyperhomocysteinemia and chronic colitis, respectively. The efficacy of PR against hyperhomocysteinemia in mice was evaluated by measuring total homocysteine, triglyceride levels and lipid accumulation. The efficacy of CR against chronic colitis in mice was evaluated by measuring disease activity index, colon length, malondialdehyde/myeloperoxidase activities and IL-1β/IL-6 levels. The underlying mechanisms related to REV-ERBα target genes were analyzed by qPCR. Puerarin in PR and berberine in CR were analyzed by UPLC-QTOF/MS. Results PR dosed at ZT10 generated a better efficacy against hyperhomocysteinemia than drug dosed at ZT2. Furthermore, PR increased the expressions of REV-ERBα target genes Bhmt, Cbs and Cth (encoding three key enzymes responsible for homocysteine catabolism), thereby alleviating hyperhomocysteinemia in mice. Moreover, CR attenuated chronic colitis in mice in a circadian time-dependent manner. ZT10 dosing generated a better anti-colitis efficacy as compared to ZT2 dosing. This was accompanied by lower production of colonic inflammatory cytokines (i.e, Nlrp3, IL-1β, IL-6, Tnf-α and Ccl2, REV-ERBα target genes) in colitis mice at ZT10 dosing. The circadian patterns of PR and CR effects were respectively consistent with those of puerarin (a main active constituent of PR, a REV-ERBα antagonist) and berberine (a main active constituent of CR, a REV-ERBα agonist). Conclusion The therapeutic effects of PR and CR depend on dosing time in mice, which are probably attributed to circadian expression of REV-ERBα as the drug target. Our findings have implications for improving therapeutic outcomes of herbal medicines with a chronotherapeutics approach.

POPDC proteins and cardiac function

2019 ◽  
Vol 47 (5) ◽  
pp. 1393-1404 ◽  
Author(s):  
Thomas Brand
Keyword(s):  
Potential Role ◽  
Striated Muscle ◽  
Short Review ◽  
Effector Proteins ◽  
Muscle Disease ◽  
Disease Genes ◽  
Protein Protein Interaction ◽  
Interaction Partners ◽  
And Function

Abstract The Popeye domain-containing gene family encodes a novel class of cAMP effector proteins in striated muscle tissue. In this short review, we first introduce the protein family and discuss their structure and function with an emphasis on their role in cyclic AMP signalling. Another focus of this review is the recently discovered role of POPDC genes as striated muscle disease genes, which have been associated with cardiac arrhythmia and muscular dystrophy. The pathological phenotypes observed in patients will be compared with phenotypes present in null and knockin mutations in zebrafish and mouse. A number of protein–protein interaction partners have been discovered and the potential role of POPDC proteins to control the subcellular localization and function of these interacting proteins will be discussed. Finally, we outline several areas, where research is urgently needed.

The Effect of Path Length and Display Size on Memory for Spatial Information

2012 ◽  
Vol 59 (3) ◽  
pp. 147-152 ◽  
Author(s):  
Katherine Guérard ◽  
Sébastien Tremblay
Keyword(s):  
Path Length ◽  
Potential Role ◽  
Spatial Information ◽  
Recall Performance ◽  
Minor Role ◽  
Length Effect ◽  
Serial Memory ◽  
Fixed Reference ◽  
A Minor

In serial memory for spatial information, some studies showed that recall performance suffers when the distance between successive locations increases relatively to the size of the display in which they are presented (the path length effect; e.g., Parmentier et al., 2005) but not when distance is increased by enlarging the size of the display (e.g., Smyth & Scholey, 1994). In the present study, we examined the effect of varying the absolute and relative distance between to-be-remembered items on memory for spatial information. We manipulated path length using small (15″) and large (64″) screens within the same design. In two experiments, we showed that distance was disruptive mainly when it is varied relatively to a fixed reference frame, though increasing the size of the display also had a small deleterious effect on recall. The insertion of a retention interval did not influence these effects, suggesting that rehearsal plays a minor role in mediating the effects of distance on serial spatial memory. We discuss the potential role of perceptual organization in light of the pattern of results.

Business Model Literature Overview

2014 ◽  
pp. 79-130 ◽  
Author(s):  
Ales Novak
Keyword(s):  
Business Model ◽  
Financial Reporting ◽  
Business Models ◽  
Potential Role ◽  
Financial Instruments ◽  
Business Logic ◽  
Literature Overview ◽  
Ifrs 9 ◽  
Definition Of

The term ?business model' has recently attracted increased attention in the context of financial reporting and was formally introduced into the IFRS literature when IFRS 9 Financial Instruments was published in November 2009. However, IFRS 9 did not fully define the term ‘business model'. Furthermore, the literature on business models is quite diverse. It has been conducted in largely isolated fashion; therefore, no generally accepted definition of ?business model' has emerged. Therefore, a better understanding of the notion itself should be developed before further investigating its potential role within financial reporting. The aim of this paper is to highlight some of the perceived key themes and to identify other bases for grouping/organizing the literature based on business models. The contributions this paper makes to the literature are twofold: first, it complements previous review papers on business models; second, it contains a clear position on the distinction between the notions of the business model and strategy, which many authors identify as a key element in better explaining and communicating the notion of the business model. In this author's opinion, the term ‘strategy' is a dynamic and forward-looking notion, a sort of directional roadmap for future courses of action, whereas, ‘business model' is a more static notion, reflecting the conceptualisation of the company's underlying core business logic. The conclusion contains the author's thoughts on the role of the business model in financial reporting.

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