Whole-animal multiplexed single-cell RNA-seq reveals transcriptional shifts across Clytia medusa cell types.

We present an organism-wide, transcriptomic cell atlas of the hydrozoan medusa Clytia hemisphaerica and describe how its component cell types respond to perturbation. Using multiplexed single-cell RNA sequencing, in which individual animals were indexed and pooled from control and perturbation conditions into a single sequencing run, we avoid artifacts from batch effects and are able to discern shifts in cell state in response to organismal perturbations. This work serves as a foundation for future studies of development, function, and regeneration in a genetically tractable jellyfish species. Moreover, we introduce a powerful workflow for high-resolution, whole-animal, multiplexed single-cell genomics that is readily adaptable to other traditional or nontraditional model organisms.

Onecut Regulates Core Components of the Molecular Machinery for Neurotransmission in Photoreceptor Differentiation.

Photoreceptor cells (PRC) are neurons highly specialized for sensing light stimuli and have considerably diversified during evolution. The genetic mechanisms that underlie photoreceptor differentiation and accompanied the progressive increase in complexity and diversification of this sensory cell type are a matter of great interest in the field. A role of the homeodomain transcription factor Onecut (Oc) in photoreceptor cell formation is proposed throughout multicellular organisms. However, knowledge of the identity of the Oc downstream-acting factors that mediate specific tasks in the differentiation of the PRC remains limited. Here, we used transgenic perturbation of the Ciona robusta Oc protein to show its requirement for ciliary PRC differentiation. Then, transcriptome profiling between the trans-activation and trans-repression Oc phenotypes identified differentially expressed genes that are enriched in exocytosis, calcium homeostasis, and neurotransmission. Finally, comparison of RNA-Seq datasets in Ciona and mouse identifies a set of Oc downstream genes conserved between tunicates and vertebrates. The transcription factor Oc emerges as a key regulator of neurotransmission in retinal cell types.

Integrating Financial Incentives for Viral Load Suppression into HIV Care Coordination Programs: Considerations for Development and Implementation.

CONTEXT: Interventions that support durable viral load suppression (VLS) among people living with HIV (PLWH) who face barriers to treatment adherence are needed to maintain optimal individual health, prevent new HIV infections, and advance health equity. Efficacy trials indicate that financial incentives (FIs) are a promising strategy for promoting VLS, although less is known about their implementation in "real-world" settings. This article describes considerations for the development and implementation of FI interventions identified in existing literature, and how they informed the scale-up of a multilevel treatment adherence support program designed to increase VLS among PLWH in New York City. PROGRAM: The Undetectables VLS Program comprises a social marketing campaign and a "tool kit" of evidence-based HIV treatment adherence strategies, including quarterly FIs ($100) that patients receive for achieving or maintaining an undetectable viral load (<200 copies/mL; also referred to as VLS). The intervention was developed and pilot tested by Housing Works Community Healthcare and the University of Pennsylvania from 2014 to 2016. Initial findings from the pilot evaluation showed a statistically significant positive effect on VLS. IMPLEMENTATION: The New York City Department of Health and Mental Hygiene contracted with 7 agencies across New York City to scale up The Undetectables Program over a 3-year period (2016-2019) by integrating the program into existing services for PLWH. EVALUATION PLANS: Quality indicators (eg, percentage of clients who received an FI each quarter; percentage of clients who were virally suppressed at 90 days postenrollment) will be used to measure program performance and impact over time. DISCUSSION: Recommendations for implementing FIs for PLWH include packaging FIs with client-centered, evidence-based adherence strategies, incorporating FIs into existing service delivery systems, and obtaining organization-wide buy-in to facilitate their implementation. Implementation science research is needed to identify strategies to effectively implement and sustain evidence-based FI interventions.