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Introduction: Alterations in multiple subregions of the human prefrontal cortex (PFC) have been heavily implicated in psychiatric diseases. Moreover, emerging evidence suggests that circadian rhythms in gene expression are present across the brain, including in the PFC, and that these rhythms are altered in disease. However, investigation into the potential circadian mechanisms underlying these diseases in animal models must contend with the fact that the human PFC is highly evolved and specialized relative to that of rodents.

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Challenges and opportunities for statistical power and biomarker identification arising from rhythmic variation in proteomics.

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January 2025

Section of Chronobiology, School of Biosciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH UK.

Time-of-day variation in the molecular profile of biofluids and tissues is a well-described phenomenon, but-especially for proteomics-is rarely considered in terms of the challenges this presents to reproducible biomarker identification. We provide a case study analysis of human circadian and ultradian rhythmicity in proteins, including in the complement and coagulation cascades and apolipoproteins, with PLG, CFAH, ZA2G and ITIH2 demonstrated as rhythmic for the first time. We also show that rhythmicity increases the risk of Type II errors due to the reduction in statistical power from increased variance, and that controlling for rhythmic time-of-day variation improves statistical power and reduces the chances of Type II errors.

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Circadian metabolism regulates the macrophage inflammatory response.

Life Metab

December 2022

School of Life Sciences and Technology, ShanghaiTech University, Shanghai 201210, China.

Macrophages are an integral part of the innate immune system and coordinate host defense to microbial infections, as well as shaping the remodeling response after tissue injury. Metabolism is now appreciated to be a powerful and pervasive regulator of the identity and function of macrophages. Upon exposure to microbial ligands, macrophage inflammatory activation and the associated induction of phagocytosis, inflammatory responses, and other host defense activities are supported by dynamic changes to cellular metabolism.

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Background: Circadian rhythm disruption (CRD) affects the expression levels of a range of biological clock genes, such as brain and muscle ARNT-Like-1 (BMAL1), which is considered to be an important factor in triggering or exacerbating inflammatory response. However, the underlying effect of CRD on the pathogenesis of apical periodontitis, a common oral inflammatory disease, currently remains unknown. Exploring the effects and pathogenic mechanisms of CRD on apical periodontitis will be beneficial in providing new ideas for the prevention and treatment of apical periodontitis.

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