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Abstract G protein-coupled receptors (GPCRs), which regulate numerous intracellular signaling cascades that mediate many essential physiological processes, are attractive yet underexploited insecticide targets. RNA interference (RNAi) technology could facilitate the custom design of environmentally safe pesticides that target GPCRs in select target pests yet are not toxic to non-target species. This study investigates the hypothesis that an RNAi yeast insecticide designed to silence mosquito serotonin receptor 1 (5-HTR1) genes can kill mosquitoes without harming non-target arthropods. 5-HTR.426, a Saccharomyces cerevisiae strain that expresses an shRNA targeting a site specifically conserved in mosquito 5-HTR1 genes, was generated. The yeast can be heat-inactivated and delivered to mosquito larvae as ready-to-use tablets or to adult mosquitoes using attractive targeted sugar baits (ATSBs). The results of laboratory and outdoor semi-field trials demonstrated that consumption of 5-HTR.426 yeast results in highly significant mortality rates in Aedes, Anopheles, and Culex mosquito larvae and adults. Yeast consumption resulted in significant 5-HTR1 silencing and severe neural defects in the mosquito brain but was not found to be toxic to non-target arthropods. These results indicate that RNAi insecticide technology can facilitate selective targeting of GPCRs in intended pests without impacting GPCR activity in non-targeted organisms. In future studies, scaled production of yeast expressing the 5-HTR.426 RNAi insecticide could facilitate field trials to further evaluate this promising new mosquito control intervention.

At Kansas City University, anatomy laboratories were delivered via remote (REM) or on-campus (OC) formats due to COVID-19, creating an opportunity to evaluate student perceptions of differences in laboratory delivery format. A six-item survey of Likert scale and open-ended questions explored the utility of anatomy software, prelab instruction handouts, and prosection reviews. Likert scale validity was analyzed using Cronbach's a; responses were compared among REM and OC formats using Chi-square. Descriptive codes were applied to summarize responses, which were grouped and converted into percentages. Statistically significant differences in REM versus OC formats were determined for the helpfulness of the prelab handouts ([chi-squared], 28.00; df, 4; p < 0.001) and effectiveness of cadavers in learning anatomy ([chi-squared], 20.58; df, 4; p < 0.0004). Trends in responses noted disagreement in the effectiveness of anatomy software (REM, 69.8%; OC, 51.08%), but agreement with the helpfulness of prosection reviews (REM, 85.9%; OC, 61.6%) (Cronbach a: REM, 0.648; OC, 0.646). Themes from narrative REM comments (n = 496) noted anatomy software was difficult to use (33.1%) and had issues with orientation (15.5%), as well as a student preference for OC laboratories (12.5%). The OC format responses (n = 456) noted poor software design (47.9%), unnecessary for studying (35.4%), and preference for in-person laboratories (7.4%). Qualitative analysis of narrative comments detailed other resources used, including Complete Anatomy™ and YouTube™. Trends highlighted the prelab handouts and prosection reviews for learning, the ineffectiveness of anatomy software, and a preference for OC laboratories. We highlight student perspectives of REM versus OC laboratory formats in response to COVID-19.

ObjectivesThe purpose of this systematic review was to examine how the scientific community in Europe that is involved with research with animals perceives and experiences the implementation of 3R (Replace, Reduce, Refine).MethodsA systematic search of the literature published in the past ten years was performed in PubMed, Web of Science and Scopus. Publications were screened for eligibility using a priori inclusion criteria, and only empirical evidence (quantitative, qualitative, or mixed methodologies) was retained. Quantitative survey items were investigated by conducting a meta-analysis, and the qualitative data was summarized using an inductive meta-synthetic approach. Included publications were assessed using the Quality Assessment for Diverse Studies tool.Results17 publications were included (eight quantitative, seven qualitative, two mixed-methods). The meta-analysis revealed that scientists are skeptical about achieving replacement, even if they believe that 3R improve the quality of experimental results. They are optimistic concerning the impact of 3R on research costs and innovation, and see education as highly valuable for the implementation of 3R. The meta-synthesis revealed four barriers (systemic dynamics, reification process, practical issues, insufficient knowledge) and four facilitators (efficient use of animals, caring for animals, regulatory uptake, supportive workplace environment).ConclusionThese findings show actionable levers at the local and systemic levels, and may inform regulators and institutions in their 3R policies.Trial registrationThe protocol was registered into the PROSPERO database under the number CRD42023395769.

Eco-friendly new mosquito control innovations are critical for the ongoing success of global mosquito control programs. In this study, Sh.463_56.10R, a robust RNA interference (RNAi) yeast insecticide strain that is suitable for scaled fermentation, was evaluated under semi-field conditions. Inactivated and dried Sh.463_56.10R yeast induced significant mortality of field strain Aedes aegypti, Aedes albopictus, and Culex quinquefasciatus larvae in semi-field larvicide trials conducted outdoors in St. Augustine, Trinidad, where 100% of the larvae were dead within 24 h. The yeast was also stably suspended in commercial bait and deployed as an active ingredient in miniature attractive targeted sugar bait (ATSB) station sachets. The yeast ATSB induced high levels of Aedes and Culex mosquito morbidity in semi-field trials conducted in Trinidad, West Indies, as well as in Bangkok, Thailand, in which the consumption of the yeast resulted in adult female mosquito death within 48 h, faster than what was observed in laboratory trials. These findings support the pursuit of large-scale field trials to further evaluate the Sh.463_56.10R insecticide, a member of a promising new class of species-specific RNAi insecticides that could help combat insecticide resistance and support effective mosquito control programs worldwide.

Abstract The use of lure-and-kill, large-volume ovitraps to control Aedes aegypti and Aedes albopictus populations has shown promise across multiple designs that target gravid females (adulticidal) or larvae post-oviposition (larvicidal). Here we report on a pilot trial to deploy 10 L yeast-baited ovitraps at select sites in Curepe, Trinidad, West Indies during July to December, 2019. Oviposition rates among ovitraps placed in three Treatment sites were compared to a limited number of traps placed in three Control areas (no Aedes management performed), and three Vector areas (subjected to standard Ministry of Health, Insect Vector Control efforts). Our goal was to gain baseline information on efforts to saturate the Treatment sites with ovitraps within 20–25 m of each other and compare oviposition rates at these sites with background oviposition rates in Control and Vector Areas. Although yeast-baited ovitraps were highly attractive to gravid Aedes females, a primary limitation encountered within the Treatment sites was the inability to gain access to residential compounds for trap placement, primarily due to residents being absent during the day. This severely limited our intent to saturate these areas with ovitraps, indicating that future studies must include plans to account for these inaccessible zones during trap placement.

Inclusion and diversity in precision oncology are essential in reducing cancer disparities among racial and ethnic groups. However, present studies have favored the recruitment and participation of Whites, with limited applicability of their results to minority groups. Many reasons for their underrepresentation are downstream manifestations of structural racism. Therefore, this scoping review provides a precise mapping of recruitment and participation barriers for minorities in precision oncology that are associated with structural racism, including a critical appraisal of how disciplinary norms, paradigms, and tools used therein could inadvertently contribute to unforeseen inclusion and diversity challenges. Empirical and theoretical publications from Web of Science and PubMed were searched and analyzed to identify recruitment and participation barriers for minorities in precision oncology. In addition, using the public health critical race praxis (PHCRP) as guiding analytical framework, empirical studies were analyzed to identify unforeseen barriers resulting from simplification processes, assumptions, norms, paradigms, and tools used during the research process. One-hundred thirty-five barriers to recruitment and participation were identified or reported in included publications. They were subsequently categorized as being a manifestation of one of the following forms of racism, namely internalized, interpersonal, institutional, and structural racism. The PCHRP analysis revealed four additional factors to be considered in precision oncology studies in ensuring appropriate representation of their study populations. Future interventions aimed at reducing health disparities should focus predominantly on barriers associated with structural and institutional racism, which should then have ripple effects on other forms of racism. Importantly, the four factors identified through the PHCRP framework could further explain the lower participation rates of minorities in precision oncology and related activities. Therefore, they should be given due consideration by all stakeholders involved in the precision oncology ecosystem, from researchers and healthcare professionals to policy-makers, research ethics committees, and funders.