No abstract

While effective for slowing the transmission of SARS-CoV-2, public health measures, such as physical distancing and stay-at-home orders, have significantly shifted the way people interact and maintain social connections. To better understand how people sought social and psychological support amid the pandemic, we conducted a longitudinal qualitative evaluation of participants enrolled in a COVID-19 treatment trial (N = 30). All participants from the parent trial who consented to being contacted for future research studies were recruited electronically via email, and first-round virtual interviews were conducted between December 2020 and March 2021. Participants who participated in first-round interviews were contacted again, and follow-up interviews were conducted in January–February 2022. The results reported significant shifts in how participants connected to social support, including changes from physical to virtual modalities, and using different social networks for distinct purposes (i.e., Reddit/Facebook for information, WhatsApp for community connection). While having COVID-19, profound loneliness during isolation was described; yet, to mitigate effects, virtual support (i.e., emotional, knowledge-seeking) as well as in-person material support (e.g., groceries, snow-shoveling), were key. Public health efforts are needed to develop interventions that will improve the narratives about mental health challenges related to COVID-19 isolation, and to provide opportunities to share challenges in a supportive manner among social networks. Supporting social cohesion, despite the everchanging nature of COVID-19, will necessitate innovative multimodal strategies that learn from lived experiences across various stages of the pandemic.

We previously described the design of triacetic acid lactone (TAL) biosensor ‘AraC-TAL1’, based on the AraC regulatory protein. Although useful as a tool to screen for enhanced TAL biosynthesis, this variant shows elevated background (leaky) expression, poor sensitivity and relaxed inducer specificity, including responsiveness to orsellinic acid (OA). More sensitive biosensors specific to either TAL or OA can aid in the study and engineering of polyketide synthases that produce these and similar compounds. In this work, we employed a TetA-based dual-selection to isolate new TAL-responsive AraC variants showing reduced background expression and improved TAL sensitivity. To improve TAL specificity, OA was included as a ‘decoy’ ligand during negative selection, resulting in the isolation of a TAL biosensor that is inhibited by OA. Finally, to engineer OA-specific AraC variants, the iterative protein redesign and optimization computational framework was employed, followed by 2 rounds of directed evolution, resulting in a biosensor with 24-fold improved OA/TAL specificity, relative to AraC-TAL1.

No abstract

We previously described the design of triacetic acid lactone (TAL) biosensor “AraC-TAL1”, based on the AraC regulatory protein. While useful as a tool to screen for enhanced TAL biosynthesis, this variant shows elevated background (leaky) expression, poor sensitivity, and relaxed inducer specificity, including responsiveness to orsellinic acid (OA). More sensitive biosensors specific to either TAL or OA can aid in the study and engineering of polyketide synthases that produce these and similar compounds. In this work, we employed a TetA-based dual-selection to isolate new TAL-responsive AraC variants showing reduced background expression and improved TAL sensitivity. To improve TAL specificity, OA was included as a “decoy” ligand during negative selection, resulting in isolation of a TAL biosensor that is inhibited by OA. Finally, to engineer OA-specific AraC variants, the IPRO computational framework was employed, followed by two rounds of directed evolution, resulting in a biosensor with 24-fold improved OA/TAL specificity, relative to AraC-TAL1.