Autoimmune blistering diseases treated with glucocorticoids: An international study of steroid‐induced myopathy

BACKGROUND: Patients with autoimmune blistering diseases (AIBDs) are often exposed to chronic glucocorticoid (GC) treatment with many side effects. Glucocorticoid-induced myopathy (GIM) is a well-established side effect, which particularly affects the proximal muscles. The Glucocorticoid Toxicity Index (GTI) is a validated global assessment tool which quantifies GC toxicity over time. OBJECTIVES: This study marks the first study which analyses GIM in patients with AIBDs. The objectives of this study were to utilize the GTI to investigate the nature and prevalence of GIM in AIBD patients and explore potential risk factors. METHODS: This international cohort study was conducted in blistering disease clinics across Australia, China, Greece, Iran, Japan, the Philippines, Turkey and the United States of America between February 2019 and July 2023. The GTI tool was completed by a medical practitioner at each patient visit. Data related to glucocorticoid toxicity were entered into the Steritas GTI 2.0 to generate an aggregate improvement and cumulative worsening score at each visit. RESULTS: The study included 139 patients. There were 132 episodes of myopathy, and 47.5% of patients developed muscle weakness at some point during the study period. Cumulative GC dose correlated positively with myopathy risk, while average dose and treatment duration were not significant. Older age, male gender and obesity more than doubled the likelihood of developing GIM. CONCLUSIONS: GIM is a common side effect experienced by AIBD patients on GC treatment. Muscle weakness is less likely to occur if cumulative GC dose is less than 0.75 mg/kg/day. Studies of exercise programs to mitigate myopathy and newer alternative treatments to reduce cumulative GC dose should be considered

Dissection of QTL effects for root traits using a chromosome arm-specific mapping population in bread wheat

A high-resolution chromosome arm-specific mapping population was used in an attempt to locate/detect gene(s)/QTL for different root traits on the short arm of rye chromosome 1 (1RS) in bread wheat. This population consisted of induced homoeologous recombinants of 1RS with 1BS, each originating from a different crossover event and distinct from all other recombinants in the proportions of rye and wheat chromatin present. It provides a simple and powerful approach to detect even small QTL effects using fewer progeny. A promising empirical Bayes method was applied to estimate additive and epistatic effects for all possible marker pairs simultaneously in a single model. This method has an advantage for QTL analysis in minimizing the error variance and detecting interaction effects between loci with no main effect. A total of 15 QTL effects, 6 additive and 9 epistatic, were detected for different traits of root length and root weight in 1RS wheat. Epistatic interactions were further partitioned into inter-genomic (wheat and rye alleles) and intra-genomic (rye–rye or wheat–wheat alleles) interactions affecting various root traits. Four common regions were identified involving all the QTL for root traits. Two regions carried QTL for almost all the root traits and were responsible for all the epistatic interactions. Evidence for inter-genomic interactions is provided. Comparison of mean values supported the QTL detection

Agonist-induced membrane nanodomain clustering drives GLP-1 receptor responses in pancreatic beta cells

The glucagon-like peptide-1 receptor (GLP-1R), a key pharmacological target in type 2 diabetes (T2D) and obesity, undergoes rapid endocytosis after stimulation by endogenous and therapeutic agonists. We have previously highlighted the relevance of this process in fine-tuning GLP-1R responses in pancreatic beta cells to control insulin secretion. In the present study, we demonstrate an important role for the translocation of active GLP-1Rs into liquid-ordered plasma membrane nanodomains, which act as hotspots for optimal coordination of intracellular signaling and clathrin-mediated endocytosis. This process is dynamically regulated by agonist binding through palmitoylation of the GLP-1R at its carboxyl-terminal tail. Biased GLP-1R agonists and small molecule allosteric modulation both influence GLP-1R palmitoylation, clustering, nanodomain signaling, and internalization. Downstream effects on insulin secretion from pancreatic beta cells indicate that these processes are relevant to GLP-1R physiological actions and might be therapeutically targetable

Author Correction: Super-resolution microscopy compatible fluorescent probes reveal endogenous glucagon-like peptide-1 receptor distribution and dynamics.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Capital income taxation and risk taking under prospect theory

Abstract: This research examines capital income taxation for a loss averse investor under some acceptable in the literature reference levels relative to which are the changes in the level of wealth valued. Depending on the reference level, some results indicate that it could be possible for a capital income tax increase not to stimulate risk taking even if the tax code provides the attractive full loss offset provisions. However, risk taking can be stimulated if the investor interprets part of the tax as a loss instead as a reduced gain. Then investor becomes risk seeking and moves away from the discomfort zone of relative losses. This later response to taxation causes private risk taking to increase which is contrary to what evolves from assuming an expected utility model. Finally, a number of other reference standards are examined as well.