Precise spatiotemporal control of mRNA translation machinery is essential to the development of highly complex systems like the neocortex. However, spatiotemporal regulation of translation machinery in the developing neocortex remains poorly understood. Here, we show that an RNA-binding protein, Hu antigen R (HuR), regulates both neocorticogenesis and specificity of neocortical translation machinery in a developmental stage-dependent manner in mice. Neocortical absence of HuR alters the phosphorylation states of initiation and elongation factors in the core translation machinery. In addition, HuR regulates the temporally specific positioning of functionally related mRNAs into the active translation sites, the polysomes. HuR also determines the specificity of neocortical polysomes by defining their combinatorial composition of ribosomal proteins and initiation and elongation factors. For some HuR-dependent proteins, the association with polysomes likewise depends on the eukaryotic initiation factor 2 alpha kinase 4, which associates with HuR in prenatal developing neocortices. Finally, we found that deletion of HuR before embryonic day 10 disrupts both neocortical lamination and formation of the main neocortical commissure, the corpus callosum. Our study identifies a crucial role for HuR in neocortical development as a translational gatekeeper for functionally related mRNA subgroups and polysomal protein specificity.

Rosacea is a chronic inflammatory disorder of the central face with multiple overlapping presentations. Recent advancements are reshaping our understanding of rosacea from both a pathophysiologic perspective and clinical approach to therapy, introducing novel agents that have improved patient outcomes and reduced morbidity. In this article, we aim to outline the advancements in understanding, diagnosing, and managing rosacea and to familiarize physicians with the literature, thereby allowing us to better practice safe and effective medicine.

5. Guilpain P, Le Bihan C, Foulongne V, et al. Response to: 'Severe COVID-19 associated pneumonia in 3 patients with systemic sclerosis treated with rituximab' by Avouac et al. Ann Rheum Dis. 2020.

Background Isotretinoin has been reported to elevate creatine kinase, which may lead to fatal rhabdomyolysis.Objective To review the literature and propose practice guidelines for management of elevated creatine kinase during isotretinoin therapy.Findings Patients have intrinsic and extrinsic qualities that may synergistically work with isotretinoin to elevate serum creatine kinase. Darker skin types and males on isotretinoin are more likely to have elevated creatine kinase. Isotretinoin may induce oxidative stress within muscle tissue, thereby leading to elevations in serum creatine kinase.Conclusion Evidence supports a tenuous correlation between isotretinoin, elevated creatine kinase, and exercise. Physicians should consider obtaining baseline creatine kinase on elite athletes and counseling patients on risk factors that may elevate creatine kinase. However, the potential for elevated CK is not a contraindication for isotretinoin therapy. Capsule Summary• Since 1982 there have been multiple reports of patients who had elevated creatine kinase levels during their course of isotretinoin, mostly with concurrent exercise.• Physicians should consider obtaining baseline creatine kinase in elite athletes and counseling patients that vigorous exercise and male gender are associated with elevated creatine kinase.

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