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Secretory proteins are transported to the Golgi complex in vesicles that bud from the endoplasmic reticulum. The cytoplasmic coat protein complex II (COPII) is responsible for cargo sorting and vesicle morphogenesis. COPII was first described in Saccharomyces cerevisiae, but its basic function is conserved throughout all eukaryotes. Nevertheless, the COPII coat has adapted to the higher complexity of mammalian physiology, achieving more sophisticated levels of secretory regulation. In this review we cover aspects of mammalian COPII-mediated regulation of secretion, in particular related to the function of COPII paralogues, the spatial organization of cargo export and the role of accessory proteins.

Pulmonary arterial hypertension (PAH) is a rare, debilitating and rapidly progressive disease. Although there have been important medical advances in PAH management, the search for a cure continues. Despite an increased understanding of the disease, data on the wider effect of PAH on patients and carers, beyond the clinical symptoms, are still limited. In order to explore this, a large-scale international survey investigated four key areas affected by PAH (physical and practical, emotional, social, and information needs) and provides new insight into patients' and carers' experiences of living with the disease. The results from the survey highlight not only the limited ability of patients to carry out everyday tasks, but also the financial impact and social isolation experienced by both patients and carers. The study confirmed that a decline in a patient's World Health Organization functional class, which indicates an increase in clinical severity of the disease, is associated with greater limitations. Results from the survey demonstrate the need for multidisciplinary PAH management and a comprehensive standard of care to assess and improve all aspects of well-being for both patients and carers. In addition, they underline the need for updated PAH guidelines that address these needs. @ERSpublications PAH has a profound impact on numerous aspects of patients' and carers' lives http://ow.ly/pWWYf This article has supplementary material available from err.ersjournals.comFull survey results, along with a call to action, are available at www.phaeurope.org/projects-activities/pah-patient-andcarer-survey

Translation initiation is a key step for regulating the level of numerous proteins within the cell. In bacteria, the 30S initiation complex directly binds to the translation initiation region (TIR) of the mRNA. How the ribosomal 30S subunit assembles on highly structured TIR is not known. Using fluorescence-based experiments, we assayed 12 different mRNAs that form secondary structures with various stabilities and contain Shine-Dalgarno (SD) sequences of different strengths. A strong correlation was observed between the stability of the mRNA structure and the association and dissociation rate constants. Interestingly, in the presence of initiation factors and initiator tRNA, the association kinetics of structured mRNAs showed two distinct phases. The second phase was found to be important for unfolding structured mRNAs to form a stable 30S initiation complex. We show that unfolding of structured mRNAs requires a SD sequence, the start codon, fMet-tRNA(fMet), and the GTP bound form of initiation factor 2 bound to the 30S subunit.