APOBEC3A is a cytidine deaminase driving mutagenesis, DNA replication stress and DNA damage in cancer cells. While the APOBEC3A-induced vulnerability of cancers offers an opportunity for therapy, APOBEC3A protein and mRNA are difficult to quantify in tumors due to their low abundance. Here, we describe a quantitative and sensitive assay to measure the ongoing activity of APOBEC3A in tumors. Using hotspot RNA mutations identified from APOBEC3A-positive tumors and droplet digital PCR, we develop an assay to quantify the RNA-editing activity of APOBEC3A. This assay is superior to APOBEC3A protein-and mRNA-based assays in predicting the activity of APOBEC3A on DNA. Importantly, we demonstrate that the RNA mutation-based APOBEC3A assay is applicable to clinical samples from cancer patients. Our study presents a strategy to follow the dysregulation of APOBEC3A in tumors, providing opportunities to investigate the role of APOBEC3A in tumor evolution and to target the APOBEC3A-induced vulnerability in therapy.
Change in the translucency of squid mantle muscle during its storage at 0 ∞ C was studied by monitoring L* value and turbidity. Two indicators showed that squid mantle muscle lost its translucency and reached maximal turbidity within 24 h of storage. Thickness of mantle muscle also increased by 15% in 12 h, earlier than the loss of translucency. ATP content decreased with storage time and was completely lost in almost 24 h, a similar period to translucency loss, but later than rigor contraction. Development of black color on skin surface by chromatophores was fully achieved in 24 h. It was thus concluded that ATP content was well correlated with a loss of translucency or increase in the turbidity of mantle muscle and development of dark color on the surface skin of mantle.
Objective Youth with early-onset mood or psychotic disorders are occasionally prescribed metformin to manage cardiometabolic risk. This retrospective study explores the demographic, clinical and metabolic factors associated with metformin prescription youth with mood or psychotic disorders. Method Participants included 72 youth with mood or psychotic disorders from a young adult mental health inpatient unit, of which 18 (33%) were newly prescribed metformin, and 54 (66%) were not prescribed metformin. Demographic and clinical information were extracted from the patients’ medical files along with body mass index (BMI), fasting serum bloods and calculated updated homeostatic model of insulin resistance assessment (HOMA2-IR) scores to compare profiles between groups. Results Of those prescribed metformin, 83% were overweight or obese and 72% had elevated HOMA2-IR scores. Of those not receiving metformin treatment, 41% were overweight or obese and 22% had elevated HOMA2-IR scores. Youth prescribed metformin had significantly higher BMI, and elevated markers of insulin resistance, but did not differ to those not prescribed metformin on other demographic, clinical or metabolic factors. Conclusions While metformin is prescribed to some youth with mood or psychotic disorders displaying markers of cardiometabolic disturbance, there is a need to develop clearer treatment guidelines for metformin in these youth.
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