Attitudes of both groups are generally quite positive in relation to ID and sexuality.

Multiciliated cells (MCCs) are specialized epithelia with apical bundles of motile cilia that direct fluid flow. MCC dysfunction is associated with human diseases of the respiratory, reproductive, and central nervous systems. Further, the appearance of renal MCCs has been cataloged in several kidney conditions, where their function is unknown. Despite their pivotal health importance, many aspects of MCC development remain poorly understood. Here, we utilized a chemical screen to identify molecules that affect MCC ontogeny in the zebrafish embryo kidney, and found prostaglandin signaling is essential both for renal MCC progenitor formation and terminal differentiation. Moreover, we show that prostaglandin activity is required downstream of the transcription factorets variant 5a(etv5a) during MCC fate choice, where modulating prostaglandin E2(PGE2) levels rescued MCC number. The discovery that prostaglandin signaling mediates renal MCC development has broad implications for other tissues, and could provide insight into a multitude of pathological states.

One driver skill that has been found to correlate with crash risk is hazard perception ability.The purpose of this study was to investigate how hazard perception latencies change between high and low sleepiness for a high risk group (novice drivers) and a lower risk group (experienced drivers). Thirty-two novice drivers (aged 17-24 years) and thirty experienced drivers (aged 28-36) completed a validated video-based hazard perception test, in which participants were asked to anticipate genuine traffic conflicts in footage filmed from the driver's perspective, with separate groups tested at either 10am (lower sleepiness) or at 3am (higher sleepiness). We found a significant interaction between sleepiness and experience, indicating that the hazard perception skills of the more experienced drivers were relatively unaffected by mild increases in sleepiness while the inexperienced drivers were significantly slowed. The findings suggest that the disproportionate sleepiness-related accident involvement of young, inexperienced drivers could be partly due to a slowing of their ability to anticipate traffic hazards.

Renal functional units known as nephrons undergo patterning events during development that create a segmental array of cellular compartments with discrete physiological identities. Here, from a forward genetic screen using zebrafish, we report the discovery that transcription factor AP-2 alpha (tfap2a) coordinates a gene regulatory network that activates the terminal differentiation program of distal segments in the pronephros. We found that tfap2a acts downstream of Iroquois homeobox 3b (irx3b), a distal lineage transcription factor, to operate a circuit consisting of tfap2b, irx1a and genes encoding solute transporters that dictate the specialized metabolic functions of distal nephron segments. Interestingly, this regulatory node is distinct from other checkpoints of differentiation, such as polarity establishment and ciliogenesis. Thus, our studies reveal insights into the genetic control of differentiation, where tfap2a is essential for regulating a suite of segment transporter traits at the final tier of zebrafish pronephros ontogeny. These findings have relevance for understanding renal birth defects, as well as efforts to recapitulate nephrogenesis in vivo to facilitate drug discovery and regenerative therapies.

A functional vertebrate kidney relies on structural units called nephrons, which are epithelial tubules with a sequence of segments each expressing a distinct repertoire of solute transporters. The transcriptional codes driving regional specification, solute transporter program activation, and terminal differentiation of segment populations remain poorly understood. Here, we demonstrate that the KCTD15 paralogs, kctd15a and kctd15b, function in concert to restrict distal early (DE)/thick ascending limb (TAL) segment lineage assignment in the developing zebrafish pronephros by repressing Tfap2a activity. During renal ontogeny, expression of these factors co-localized with tfap2a in distal tubule precursors. kctd15 loss primed nephron cells to adopt distal fates by driving slc12a1, kcnj1a.1, and stc1 expression. These phenotypes were resultant of Tfap2a hyperactivity, where kctd15a/b-deficient embryos exhibited increased abundance of this transcription factor. Interestingly, tfap2a reciprocally promoted kctd15 transcription, unveiling a circuit of autoregulation operating in nephron progenitors. Concomitant kctd15b knockdown with tfap2a overexpression further expanded the DE population. Our study reveals that a transcription factor-repressor feedback module employs tight regulation of Tfap2a and Kctd15 kinetics to control nephron segment fate choice and differentiation during kidney development.