Genome-wide promoter responses to CRISPR perturbations of regulators reveal regulatory networks in Escherichia coli.

Elucidating genome-scale regulatory networks requires a comprehensive collection of gene expression profiles, yet measuring gene expression responses for every transcription factor (TF)-gene pair in living prokaryotic cells remains challenging. Here, we develop pooled promoter responses to TF perturbation sequencing (PPTP-seq) via CRISPR interference to address this challenge. Using PPTP-seq, we systematically measure the activity of 1372 Escherichia coli promoters under single knockdown of 183 TF genes, illustrating more than 200,000 possible TF-gene responses in one experiment. We perform PPTP-seq for E. coli growing in three different media. The PPTP-seq data reveal robust steady-state promoter activities under most single TF knockdown conditions. PPTP-seq also enables identifications of, to the best of our knowledge, previously unknown TF autoregulatory responses and complex transcriptional control on one-carbon metabolism. We further find context-dependent promoter regulation by multiple TFs whose relative binding strengths determined promoter activities. Additionally, PPTP-seq reveals different promoter responses in different growth media, suggesting condition-specific gene regulation. Overall, PPTP-seq provides a powerful method to examine genome-wide transcriptional regulatory networks and can be potentially expanded to reveal gene expression responses to other genetic elements.

Telepresence Robot Intervention to Reduce Loneliness and Social Isolation in Older Adults Living at Home (Project DOMIROB): Protocol for a Clinical Nonrandomized Study.

BACKGROUND: There is a growing prevalence of loneliness and social isolation among older adults (OAs). These problems are often associated with depressive states, cognitive decline, sleep disorders, addictions, and increased mortality. To limit loneliness and social isolation in OAs, some authors recommend the use of new communication technologies to maintain a social link with family members as well as with health and social care professionals. Among these communication tools, telepresence robots (TRs) seem to be a promising solution. These robots offer users the possibility of making video calls with their relatives, social workers, and health care professionals, to maintain social contact and access to support services while living at home. Nevertheless, TRs have been relatively unstudied in real-life environments. OBJECTIVE: The main objective of this study is to measure the impact of a 12-week intervention using a TR on the feeling of loneliness and on social isolation of OAs living at home. Its secondary objective is to establish recommendations for the implementation of TRs in the studied context. METHODS: A nonrandomized study will be conducted among 60 OAs living at home who will participate in the study for 24 weeks. During this period, they will host a TR for 12 weeks to use it in their home. After the end of the intervention a 12-week follow-up ensues. In total, 4 evaluations will be performed over the entire experimental phase for each participant at weeks 0, 6, 12, and 24. A multidimensional assessment of the impact of the robot will be performed using a multimethod approach including standardized scales and a semistructured interview. This assessment will also help to identify the ergonomic aspects that influence the robot's usability and acceptability among OAs. RESULTS: Data collection started in September 2020 and is expected to be completed in early 2023. In August 2022, 56 participants were recruited for the study. Data analysis will take place between August 2022 and is expected to be completed in early 2023. CONCLUSIONS: The DOMIROB study will provide new knowledge on the impact of social TRs in OAs living at home. The results will make it possible to suggest technological, ethical, and organizational recommendations for the use and implementation of TRs for OAs in real-life settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT04767100; https://clinicaltrials.gov/ct2/show/NCT04767100. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/40528.