The dietary requirement for selenium is based on its incorporation into selenoproteins, which contain the amino acid selenocysteine (Sec). The Sec insertion sequence (SECIS) is an RNA structure found in the 3′ UTR of all selenoprotein mRNAs, and it is required to convert in-frame UGA codons from termination to Sec-incorporating codons. SECIS-binding protein 2 (Sbp2) is required for Sec incorporation, but its paralogue, SECIS-binding protein 2–like (Secisbp2l), while conserved, has no known function. Here we determined the relative roles of Sbp2 and Secisbp2l by introducing CRISPR mutations in both genes in zebrafish. By monitoring selenoprotein synthesis with 75Se labeling during embryogenesis, we found that sbp2−/− embryos still make a select subset of selenoproteins but secisbp2l−/− embryos retain the full complement. Abrogation of both genes completely prevents selenoprotein synthesis and juveniles die at 14 days post fertilization. Embryos lacking Sbp2 are sensitive to oxidative stress and express the stress marker Vtg1. We propose a model where Secisbp2l is required to promote essential selenoprotein synthesis when Sbp2 activity is compromised.

The dietary requirement for selenium is based on its incorporation into selenoproteins, which contain the amino acid selenocysteine (Sec). The Sec insertion sequence (SECIS) is an RNA structure found in the 3’ UTR of all selenoprotein mRNAs, and it is required to convert in-frame UGA codons from termination to Sec-incorporating codons. There are two proteins that bind to SECIS elements, but only one, SECIS binding protein 2 (Sbp2), has been shown to be required for Sec incorporation. The Sbp2 paralogue, SECIS binding protein 2-like (Secisbp2l) is conserved in all vertebrates and shares many features with Sbp2, but its function is unknown. Here we set out to determine the relative roles of Sbp2 and Secisbp2l by introducing CRISPR mutations in both genes in zebrafish. By monitoring selenoprotein synthesis with 75Se labeling during embryogenesis, we found that sbp2-/- embryos still make a select subset of selenoproteins but secisbp2l-/- embryos retain the full complement. Abrogation of both genes completely prevents selenoprotein synthesis and juveniles die at 14 days post fertilization. Embryos lacking Sbp2 are sensitive to oxidative stress and express the stress marker vtg1. We propose a model where Secisbp2l is required to promote essential selenoprotein synthesis during stress.

Chronic musculoskeletal pains are multifaceted, and Central sensitization is a potential pathophysiological mechanism underlying a group of chronic musculoskeletal pain disorders. Neurophysiology of pain education knowledge and patient satisfaction levels of chronic musculoskeletal pain subjects may contribute to central nervous system sensitization. Hence, the aim of the study was to evaluate the impact of neurophysiology of pain education knowledge and patient satisfaction levels on central sensitization in large population of patient with chronic musculoskeletal pain. The study included 200 chronic musculoskeletal pain subjects that persisted more than 3 months with average age of 43.93±13.62. A cross-sectional study used non probability sampling. Neurophysiology of pain Questionnaire (NPQ) to know the conceptualization of pain, mood rating scale(MRS) to measure patient’s mood fluctuation because of pain, pain disability scale (PDS) for evaluating patients ability to perform certain activity, central sensitization inventory(CSI) to measure nervous system sensitization and patients satisfaction scale(PSS) to understand patient’s satisfaction towards the treatment and health care provider were used. Descriptive and correlation analyses were used for analysis. The correlation analyses showed that patient disability scale negatively correlated with mood scale and positively correlated with the age, duration of the condition, impact of pain on ADL and central sensitization. And there was a positive correlation between patient satisfaction and impact of pain on ADL. The age, mood, duration of the condition and pain disability were the factors behind central sensitization in patients with chronic musculoskeletal pain. And the neuro physiology of pain knowledge had impact on pain disability and patient satisfaction.