The Importance of Time Congruity in the Organisation.

In 1991 Kaufman, Lane, and Lindquist proposed that time congruity in terms of an individual's time preferences and the time use methods of an organisation would lead to satisfactory performance and enhancement of quality of work and general life. The research reported here presents a study which uses commensurate person and job measures of time personality in an organisational setting to assess the effects of time congruity on one aspect of work life, job-related affective well-being. Results show that time personality and time congruity were found to have direct effects on well-being and the influence of time congruity was found to be mediated through time personality, thus contributing to the person–job (P–J) fit literature which suggests that direct effects are often more important than indirect effects. The study also provides some practical examples of ways to address some of the previously cited methodological issues in P–J fit research

VEGAS as a Platform for Facile Directed Evolution in Mammalian Cells

Directed evolution, artificial selection toward designed objectives, is routinely used to develop new molecular tools and therapeutics. Successful directed molecular evolution campaigns repeatedly test diverse sequences with a designed selective pressure. Unicellular organisms and their viral pathogens are exceptional for this purpose and have been used for decades. However, many desirable targets of directed evolution perform poorly or unnaturally in unicellular backgrounds. Here, we present a system for facile directed evolution in mammalian cells. Using the RNA alphavirus Sindbis as a vector for heredity and diversity, we achieved 24-h selection cycles surpassing 10−3 mutations per base. Selection is achieved through genetically actuated sequences internal to the host cell, thus the system's name: viral evolution of genetically actuating sequences, or “VEGAS.” Using VEGAS, we evolve transcription factors, GPCRs, and allosteric nanobodies toward functional signaling endpoints each in less than 1 weeks’ time. © 2019 Elsevier Inc.The VEGAS system is a platform for directed evolution, a method for engineering DNA sequences, in mammalian cells. The system is highly mutagenic, facile, and self-contained, requiring no in vitro handling during evolution cycles. As a result, robust evolution campaigns can be run within the context of a mammalian cell signaling environment. We perform three such campaigns as a proof-of-concept: evolving a transcription factor, a G-protein coupled receptor, and llama-derived nanobodies toward specific in vivo activities. © 2019 Elsevier Inc

Erratum: VEGAS as a Platform for Facile Directed Evolution in Mammalian Cells (Cell (2019) 178(3) (748–761.e17), (S0092867419306221), (10.1016/j.cell.2019.05.051))

(Cell 178, 748–761.e1–e17; July 25, 2019) In our recent article reporting a platform for directed evolution in mammalian cells, we inadvertently failed to cite a paper that also reports a method for evolving biomolecules in mammalian cells (Berman et al., 2018). We have corrected the online version of our paper to cite this work, and we apologize for the omission. © 2019 Elsevier Inc

RUN and FYVE domain-containing protein 4 enhances autophagy and lysosome tethering in response to Interleukin-4

Autophagy is a key degradative pathway coordinated by external cues, including starvation, oxidative stress, or pathogen detection. Rare are the molecules known to contribute mechanistically to the regulation of autophagy and expressed specifically in particular environmental contexts or in distinct cell types. Here, we unravel the role of RUN and FYVE domain–containing protein 4 (RUFY4) as a positive molecular regulator of macroautophagy in primary dendritic cells (DCs). We show that exposure to interleukin-4 (IL-4) during DC differentiation enhances autophagy flux through mTORC1 regulation and RUFY4 induction, which in turn actively promote LC3 degradation, Syntaxin 17– positive autophagosome formation, and lysosome tethering. Enhanced autophagy boosts endogenous antigen presentation by MHC II and allows host control of Brucella abortus replication in IL-4–treated DCs and in RUFY4-expressing cells. RUFY4 is therefore the first molecule characterized to date that promotes autophagy and influences endosome dynamics in a subset of immune cells

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries