Mumps, a common childhood disease in the pre-vaccine era that causes swelling of the parotid salivary glands, can lead to orchitis, viral meningitis, and sensorineural deafness. While the incidence of disease decreased dramatically after the vaccine was added to standard vaccination schedules, the disease has made a substantial resurgence in recent years. As a result, it becomes critical to examine the factors involved in recurring outbreaks. Although low and incomplete vaccination coverage may be a key reason, it does not fully explain the issue due to the high rate of occurrence in populations with high vaccination coverage rates. Multiple studies suggest that waning immunity and secondary vaccine failure play a large role, the effects of which were previously masked by subclinical boosting. Significant knowledge gaps persist around the exact role and mechanism of waning immunity and demonstrate the need for more research in this area, as well as a reevaluation of mumps vaccine policy.

Combined pre−/postcapillary pulmonary hypertension (Cpc‐PH), a complication of left heart failure, is associated with higher mortality rates than isolated postcapillary pulmonary hypertension alone. Currently, knowledge gaps persist on the mechanisms responsible for the progression of isolated postcapillary pulmonary hypertension (Ipc‐PH) to Cpc‐PH. Here, we review the biomechanical and mechanobiological impact of left heart failure on pulmonary circulation, including mechanotransduction of these pathological forces, which lead to altered biological signaling and detrimental remodeling, driving the progression to Cpc‐PH. We focus on pathologically increased cyclic stretch and decreased wall shear stress; mechanotransduction by endothelial cells, smooth muscle cells, and pulmonary arterial fibroblasts; and signaling‐stimulated remodeling of the pulmonary veins, capillaries, and arteries that propel the transition from Ipc‐PH to Cpc‐PH. Identifying biomechanical and mechanobiological mechanisms of Cpc‐PH progression may highlight potential pharmacologic avenues to prevent right heart failure and subsequent mortality.

Expressing antibodies as fusions to the non‐self‐cleaving Mxe GyrA intein allows for site‐specific chemical functionalization via expressed protein ligation. It is highly desirable to maximize the yield of functionalizable protein; and previously an evolved intein, 202‐08, was identified that could increase protein fusion production in yeast. Given that the −1 amino acid residue upstream of inteins can affect cleavage efficiency, we examined the effects of amino acid variability at this position on 202‐08 intein cleavage efficiency and secretion yield. Varying the −1 residue resulted in a wide range of cleavage behaviors with some amino acids yielding substantial autocleaved product that could not be functionalized. Autocleavage was noticeably higher with the 202‐08 intein compared with the wild‐type Mxe GyrA intein and resulted directly from the catalytic activity of the intein. Refeeding of production cultures with nitrogen base and casamino acids reduced, but did not eliminate autocleavage, while increasing protein‐intein production up to seven‐fold. Importantly, two amino acids, Gly and Ala, at the −1 position resulted in good cleavage efficiency with no undesirable autocleavage, and can be used in concert with refeeding strategies to increase total functionalizable protein yield for multiple protein fusion partners. Taken together, we describe an optimized yeast expression platform for protein‐intein fusions. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2736, 2019

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