In vivo production of psilocybin in E. coli.

Psilocybin, the prodrug of the psychoactive molecule psilocin, has demonstrated promising results in clinical trials for the treatment of addiction, depression, and post-traumatic stress disorder. The development of a psilocybin production platform in a highly engineerable microbe could lead to rapid advances towards the bioproduction of psilocybin for use in ongoing clinical trials. Here, we present the development of a modular biosynthetic production platform in the model microbe, Escherichia coli. Efforts to optimize and improve pathway performance using multiple genetic optimization techniques were evaluated, resulting in a 32-fold improvement in psilocybin titer. Further enhancements to this genetically superior strain were achieved through fermentation optimization, ultimately resulting in a fed-batch fermentation study, with a production titer of 1.16 g/L of psilocybin. This is the highest psilocybin titer achieved to date from a recombinant organism and a significant step towards demonstrating the feasibility of industrial production of biologically-derived psilocybin.

Perceptions of Weight Loss in Older Adults Following a 6-Month Weight Loss Program: A Qualitative Research Study.

BACKGROUND: Obesity in older adults contributes to increasing comorbidities and decreased quality of life. There is limited research that includes older adults' perspectives on weight loss. OBJECTIVE: The purpose of this qualitative study was to gain a better understanding of older adults' perceptions and experiences related to weight loss immediately after a 6-month weight loss intervention. DESIGN: A qualitative research design using semi-structured interviews conducted as part of a larger research study exploring weight loss and/or aerobic exercise on muscle inflammation. PARTICIPANTS/SETTING: A sample of community-based older adults (n = 11) in Southwestern Ohio were recruited from September 2018 through August 2019 after completion of a 6-month weight loss intervention. Eligible participants were older than 58 years, with a body mass index (calculated as kg/m2) >27, and sedentary with no cognitive deficits. Exclusions included cancer, heart disease, diabetes, and tobacco use. ANALYSIS: Interviews were recorded, transcribed verbatim, and analyzed using thematic analysis. Descriptive statistics were used for demographic data. RESULTS: Three emergent themes included barriers and challenges to weight loss, which included caregiving roles, challenges with increasing protein intake, and ambivalence to change; personal strategies for success (eg, portion control and meal flexibility); and external strategies for success (eg, visual graphs as feedback measures, alternate measures of success, and social support). CONCLUSIONS: The results of this qualitative study provide insight into older adults' experiences with weight loss, which may be considered when designing weight management interventions. However, more research is needed to examine strategies to address the challenges identified by participants in this research study. Future qualitative research should also focus on weight loss perspectives of older adults in other racial and ethnic groups.

Hyperstructures, genome analysis and I-cells.

New concepts may prove necessary to profit from the avalanche of sequence data on the genome, transcriptome, proteome and interactome and to relate this information to cell physiology. Here, we focus on the concept of large activity-based structures, or hyperstructures, in which a variety of types of molecules are brought together to perform a function. We review the evidence for the existence of hyperstructures responsible for the initiation of DNA replication, the sequestration of newly replicated origins of replication, cell division and for metabolism. The processes responsible for hyperstructure formation include changes in enzyme affinities due to metabolite-induction, lipid-protein affinities, elevated local concentrations of proteins and their binding sites on DNA and RNA, and transertion. Experimental techniques exist that can be used to study hyperstructures and we review some of the ones less familiar to biologists. Finally, we speculate on how a variety of in silico approaches involving cellular automata and multi-agent systems could be combined to develop new concepts in the form of an Integrated cell (I-cell) which would undergo selection for growth and survival in a world of artificial microbiology.