SINEUPs are a novel class of natural and synthetic non-coding antisense RNA molecules able to increase the translation of a target mRNA. They present a modular organization comprising an unstructured antisense target-specific domain, which sets the specificity of each individual SINEUP, and a structured effector domain, which is responsible for the translation enhancement. In order to design a fully functional in vitro transcribed SINEUP for therapeutics applications, SINEUP RNAs were synthesized in vitro with a variety of chemical modifications and screened for their activity on endogenous target mRNA upon transfection. Three combinations of modified ribonucleotides-2'O methyl-ATP (Am), N6 methyl-ATP (m6A), and pseudo-UTP (ψ)-conferred SINEUP activity to naked RNA. The best combination tested in this study was fully modified with m6A and ψ. Aside from functionality, this combination conferred improved stability upon transfection and higher thermal stability. Common structural determinants of activity were identified by circular dichroisms, defining a core functional structure that is achieved with different combinations of modifications.
Purpose: Disaster management agencies are mandated to reduce risk for the populations that they serve. Yet, inequities in how they function may result in their activities creating disaster risk, particularly for already vulnerable and marginalized populations. In this article, how disaster management agencies create disaster risk for vulnerable and marginalized groups is examined, seeking to show the ways existing policies affect communities, and provide recommendations on policy and future research.
Design/methodology/approach: The authors undertook a systematic review of the US disaster management agency, Federal Emergency Management Agency (FEMA), examining its programs through a lens of equity to understand how they shape disaster risk.
Findings: Despite a growing commitment to equity within FEMA, procedural, distributive, and contextual inequities result in interventions that perpetuate and amplify disaster risk for vulnerable and marginalized populations. Some of these inequities could be remediated by shifting toward a more bottom-up approach to disaster management, such as community-based disaster risk reduction approaches.
Practical implications: Disaster management agencies and other organizations can use the results of this study to better understand how to devise interventions in ways that limit risk creation for vulnerable populations, including through community-based approaches.
Originality/value: This study is the first to examine disaster risk creation from an organizational perspective, and the first to focus explicitly on how disaster management agencies can shape risk creation. This helps understand the linkages between disaster risk creation, equity and organizations.