Genome-scale reconstructions of the mammalian secretory pathway predict metabolic costs and limitations of protein secretion

In mammalian cells, >25% of synthesized proteins are exported through the secretory pathway. The pathway complexity, however, obfuscates its impact on the secretion of different proteins. Unraveling its impact on diverse proteins is particularly important for biopharmaceutical production. Here we delineate the core secretory pathway functions and integrate them with genome-scale metabolic reconstructions of human, mouse, and Chinese hamster ovary\ua0cells. The resulting reconstructions enable the computation of energetic costs and machinery demands of each secreted protein. By integrating additional omics data, we find that highly secretory cells have adapted to reduce expression and secretion of other expensive host cell proteins. Furthermore, we predict metabolic costs and maximum productivities of biotherapeutic proteins and identify protein features that most significantly impact protein secretion. Finally, the model successfully predicts the increase in secretion of a monoclonal antibody after silencing a highly expressed selection marker. This work represents a knowledgebase of the mammalian secretory pathway that serves as a novel tool for systems biotechnology

A nanoporous, ultrahydrophobic aluminum-coating process with exceptional dropwise condensation and shedding properties

Many studies have shown that dropwise condensation can enhance air-side heat transfer coefficients by at least an order of magnitude relative to filmwise condensation. However, among the hundreds of superhydrophobic surface-modification processes previously reported, there remains a lack of coating methods that enable stable dropwise condensation and can be applied to aluminum—by far the most common material for the air side of heat exchangers, e.g. in air conditioning. Here we present a bottom-up synthesis technique to grow zinc oxide-based films on to aluminum with tunable nanoporosity and strongly re-entrant surface features. These surfaces exhibit exceptional static water contact angles of up to 178° with a hysteresis less than 3° and a slide angle of 1°. We have further characterized the surfaces in the presence of six different liquids, and show that our optimal surface can repel even dipropylene glycol with a contact angle of 124°, even though its surface tension is less than half that of water. Crucially, we have also tested our films under water-condensing conditions in flowing air, characterizing the droplet-shedding behavior, and we have understood how to tune the growth process to deliver stable droplet-shedding instead of flooding. The process uses inexpensive reagents, can operate below 100 °C via immersion in an aqueous bath, and takes 1–3 h to complete, making it readily scalable to areas of many square meters and complex geometries

Urticaria and infections

Urticaria is a group of diseases that share a distinct skin reaction pattern. Triggering of urticaria by infections has been discussed for many years but the exact role and pathogenesis of mast cell activation by infectious processes is unclear. In spontaneous acute urticaria there is no doubt for a causal relationship to infections and all chronic urticaria must have started as acute. Whereas in physical or distinct urticaria subtypes the evidence for infections is sparse, remission of annoying spontaneous chronic urticaria has been reported after successful treatment of persistent infections. Current summarizing available studies that evaluated the course of the chronic urticaria after proven Helicobacter eradication demonstrate a statistically significant benefit compared to untreated patients or Helicobacter-negative controls without urticaria (p < 0.001). Since infections can be easily treated some diagnostic procedures should be included in the routine work-up, especially the search for Helicobacter pylori. This review will update the reader regarding the role of infections in different urticaria subtypes