A Notch Above Bowl: Specification of Niche Cells in the Drosophila Testis

Niche cells exercise elaborate control over the behavior of many tissue-specific stem cells. However, in no system do we fully understand how niche cells are specified, develop and then begin producing the signals necessary to properly regulate stem cells. Here, we take advantage of the paradigmatic stem cell-niche system of the Drosophila testis to address these fundamental questions. We first find that the Notch signaling pathway is necessary for niche cell specification and that its activity in precursor cells prevents those cells from adopting the alternative somatic cyst cell fate. We also discover that the Notch-activating ligand, Delta, is presented from the neighboring endoderm, rather than from within the gonad “proper.” Moreover, we show that niche specification occurs very early during gonadogenesis, before the expression of extant niche cell markers. We also uncover a role for the bowl pathway in influencing niche cell specification, where bowl promotes niche cell fate, while its antagonist, lines, promotes cyst cell fate. Additionally, we present data suggesting that bowl functions as a transcriptional repressor to restrict cyst cell gene expression in precursor cells, thereby inducing niche cell specification. Ultimately since niche cells influence stem cell behavior, understanding how niche cells develop and dissecting the interactions between niches and their resident stem cells is paramount if we seek to use stem cells as tools in regenerative medicine

A Landscape Analysis of Prevention of Vertical Transmission Program Data and Interventions from Fiscal Years 2019 to 2021

INTRODUCTION: In 2020, an estimated 150,000 infants acquired HIV infection through vertical transmission. With pregnant and breastfeeding women facing numerous social and health system barriers, continuity of care for mother-infant pairs (MIPs) requires prioritized engagement for timely infant HIV testing and linkage to treatment. METHODS: PEPFAR Monitoring, Evaluation and Reporting indicators were analyzed from across 14 USAID-supported countries across three fiscal years (FYs) (October 2018 - September 2021): number of HIV-exposed infants (HEI) with a sample collected for an HIV test by two months of age; percentage of HEI who received an HIV test by two months of age (EID 2mo coverage); and final outcome status of HEIs. Qualitative information on implementation of PVT interventions was gathered via a survey disseminated to USAID/PEPFAR country teams. RESULTS: From October 2018 to September 2021, 716,383 samples were collected for infant HIV tests. EID 2mo coverage increased across the FYs from 77.3% in FY19 to 83.5% in FY21. Eswatini, Lesotho, and South Africa demonstrated the highest EID 2mo coverage across all three FYs. Burundi (93.6%), DRC (92%) and Nigeria (90%) had the highest percentage of infants with a known final HIV outcome. Qualitative survey data showed that the most implemented interventions used by the countries were mentor mothers, appointment reminders, cohort registers and joint provision of MIP services. CONCLUSIONS: Achieving eVT requires a client-centered and multi-pronged approach, typically combining several PVT interventions. Country and program implementers should utilize person-centered solutions to best target MIPs to be retained in the continuum of care