We identified clinically relevant biomarkers of AD, including novel markers, easily sampled and typed in infants. These markers may provide objective assessment of disease severity and suggest new therapeutic targets, or response measurement targets for AD. Future studies will be required to determine whether these biomarkers, seen in very early AD, can predict disease outcomes or comorbidities.
The effect of gene expression burden on engineered cells has motivated the use of “whole-cell models” (WCMs) that use shared cellular resources to predict how unnatural gene expression affects cell growth. A common problem with many WCMs is their inability to capture translation in sufficient detail to consider the impact of ribosomal queue formation on mRNA transcripts. To address this, we have built a “stochastic cell calculator” (StoCellAtor) that combines a modified TASEP with a stochastic implementation of an existing WCM. We show how our framework can be used to link a synthetic construct’s modular design (promoter, ribosome binding site (RBS) and codon composition) to protein yield during continuous culture, with a particular focus on the effects of low-efficiency codons and their impact on ribosomal queues. Through our analysis, we recover design principles previously established in our work on burden-sensing strategies, namely that changing promoter strength is often a more efficient way to increase protein yield than RBS strength. Importantly, however, we show how these design implications can change depending on both the duration of protein expression, and on the presence of ribosomal queues.
Summary Atopic Dematitis (AD), also known as eczema, is a common inflammatory skin disease which usually appears during the early stages of life. It is estimated that approximately 15 million people in the UK are currently living with AD, affecting up to 20% of children. Indicators, such as a specific protein level in the body which is related to the presence or seriousness of a disease in a patient, may be important in ensuring proper treatment. Indicators of the seriousness of AD have been described for adults, however there is a need for similar indicators which could be used to define the seriousness of AD in infants, as this is usually when onset of the condition occurs. This study aimed to identify easily obtainable indicators from the skin of infants which could be used to predict AD. 100 children who had just developed moderate to severe AD which had not yet been treated and 20 children without AD were sampled as part of this study. The level of seriousness of AD in the affected children was graded at the start of the study and samples of the outer‐most layer of skin were taken from all participants. In total, 31 out of 66 indicators measured showed different levels in infants with AD than infants without AD. These indicators are known to be involved in various processes including the body's natural defence and the formation of new blood vessels. The authors of this study concluded that these results demonstrate easily obtainable indicators can be used to predict AD in infants, and that natural defence responses in the outer layer of skin are essential in preventing development of AD in infants.
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