Sensorineural hearing loss is a common and currently irreversible disorder, because mammalian hair cells (HCs) do not regenerate and current stem cell and gene delivery protocols result only in immature HC-like cells. Importantly, although the transcriptional regulators of embryonic HC development have been described, little is known about the postnatal regulators of maturating HCs. Here we apply a cell type-specific functional genomic analysis to the transcriptomes of auditory and vestibular sensory epithelia from early postnatal mice. We identify RFX transcription factors as essential and evolutionarily conserved regulators of the HC-specific transcriptomes, and detect Rfx1,2,3,5 and 7 in the developing HCs. To understand the role of RFX in hearing, we generate Rfx1/3 conditional knockout mice. We show that these mice are deaf secondary to rapid loss of initially well-formed outer HCs. These data identify an essential role for RFX in hearing and survival of the terminally differentiating outer HCs.

Accurate disease models are essential for understanding disease pathogenesis and for developing new therapeutics. As stem cells are capable of self-renewal and differentiation, they are ideally suited both for generating these models and for obtaining the large quantities of cells required for drug development and transplantation therapies. Jellyfish collagen is showing great promise as a next generation matrix enabling improved outcomes in 2D and 3D cell culture and regenerative medicine. Here, we report the potential of jellyfish collagen for culturing induced pluripotent stem cell derived cell lines (iPSCs) for modeling human diseases. Jellyfish collagen from Rhizostoma pulmo (Jellagen R) was evaluated for the growth and viability of iPSC-derived microgliallike cells (iMGL) comparing to cells cultured on rat tail collagen 1, laminin-511 and tissue culture plastic. Viability was measured using MTT, XTT, Alamar Blue and Annexin V, since this last assay has the aim of evaluating the onset of apoptosis. Cell ramification was measured using Neurotracker software and ramification measured on the InCucyte S3 TM. Cell surface receptor expression was quantified using flow cytometry. Microglia markers used for immunocytochemistry were IBA1, CD11b, TREM2, TMEM119, and P2RY12. We report that iPSC-derived microglia can be successfully cultured on Jellagen R jellyfish collagen demonstrating a more ramified cell morphology compared to cells cultured on mammalian rat tail collagen I and comparable to Laminin-511.

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The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic has led to an unprecedented public health crisis. The collective global response has led to production of multiple safe and effective vaccines utilizing novel platforms to combat the virus that have propelled the field of vaccinology forward. Significant challenges to universal vaccine effectiveness remain, including immune evasion by SARS-CoV-2 variants, waning of immune response, inadequate knowledge of correlates of protection, and dosing in special populations. This review serves as a detailed evaluation of the development of the current SARS-CoV-2 vaccines, their effectiveness, and challenges to their deployment as a preventive tool.

While oscillometry identified more veterans as obstructed, obstruction was not uranium-related. However, the added sensitivity of this method implies a benefit in wider surveillance of exposed cohorts and holds promise in identifying abnormalities in areas of the lung historically described as silent.