Plasticity is a hallmark of the respiratory neural control system. Phrenic long-term facilitation (pLTF) is one form of respiratory plasticity characterized by persistent increases in phrenic nerve activity following acute intermittent hypoxia (AIH). Although there is evidence that key steps in the cellular pathway giving rise to pLTF are localized within phrenic motor neurons (PMNs), the impact of AIH on the strength of breathing-related synaptic inputs to PMNs remains unclear. Further, the functional impact of AIH is enhanced by repeated/daily exposure to AIH (dAIH). Here, we explored the effects of AIH vs. 2 weeks of dAIH preconditioning on spontaneous and evoked responses recorded in anesthetized, paralyzed (with pancuronium bromide) and mechanically ventilated rats. Evoked phrenic potentials were elicited by respiratory cycle-triggered lateral funiculus stimulation at C2 delivered prior to- and 60 min post-AIH (or an equivalent time in controls). Charge-balanced biphasic pulses (100 µs/phase) of progressively increasing intensity (100 to 700 µA) were delivered during the inspiratory and expiratory phases of the respiratory cycle. Although robust pLTF (~60% from baseline) was observed after a single exposure to moderate AIH (3 x 5 min; 5 min intervals), there was no effect on evoked phrenic responses, contrary to our initial hypothesis. However, in rats preconditioned with dAIH, baseline phrenic nerve activity and evoked responses were increased, suggesting that repeated exposure to AIH enhances functional synaptic strength when assessed using this technique. The impact of daily AIH preconditioning on synaptic inputs to PMNs raises interesting questions that require further exploration.Multiciliated cells play critical roles in the airway, reproductive organs and brain. Generation of multiple cilia requires both activation of a specialized transcriptional program and subsequent massive amplification of centrioles within the cytoplasm. The E2F4 transcription factor is required for both roles, and consequently for multiciliogenesis. Here, we establish that E2F4 associates with two distinct components of the centriole replication machinery, Deup1 and SAS6, targeting non-homologous domains in these proteins. We map Deup1 and SAS6 binding to E2F4's N-terminus, and show that this domain is sufficient to mediate E2F4's cytoplasmic role in multiciliogenesis. This sequence is highly conserved across the E2F family, but the ability to bind Deup1 and SAS6 is specific to E2F4 and E2F5, consistent with their shared roles in multiciliogenesis. By generating E2F4/E2F1 chimeras, we identify a six-residue motif that is critical for Deup1 and SAS6 binding. We propose that the ability of E2F4 and E2F5 to recruit Deup1 and/or SAS6, and enable centriole replication, contributes to their cytoplasmic roles in multiciliogenesis.Vaccinia virus produces two types of virions known as single-membraned intracellular mature virus (MV) and double-membraned extracellular enveloped virus (EV). EV production peaks earlier when initial MV are further wrapped and secreted to spread infection within the host. However, late during infection MV accumulate intracellularly and become important for host-to-host transmission. The process that regulates this switch remains elusive and is thought to be influenced by host factors. Here we examined the hypothesis that EV and MV production are regulated by the virus through expression of F13 and the MV-specific protein A26.  https://www.selleckchem.com/products/acy-775.html  By switching the promoters and altering the expression kinetics of F13 and A26, we demonstrate that A26 expression downregulates EV production and plaque size, thus limiting viral spread. This process correlates with A26 association with the MV surface protein A27 and exclusion of F13, thus reducing EV titres. Thus, MV maturation is controlled by the abundance of the viral A26 protein, to balance intra-host dissemination and inter-host transmission, so virus maturation pathways must be tightly controlled. Here we provide evidence that the abundance and kinetics of expression of the viral protein A26 regulates this process by preventing formation of the first form and shifting maturation towards the second form. A26 is expressed late after the initial wave of progeny virions is produced, so sufficient viral dissemination is ensured, and provides virions with enhanced environmental stability. Conservation of A26 in all vertebrate poxviruses but those transmitted exclusively via biting arthropods reveals the importance of A26-controlled virus maturation for transmission routes involving environmental exposure.Peroxiredoxin 1 (PRDX1) is a cellular antioxidant enzyme crucial for diverse fundamental biological processes, such as autophagy, inflammation and carcinogenesis. However, molecular mechanisms underpinning its diverse roles are not well understood. Here, we report that PRDX1 positively regulates interferon induction and that pseudorabies virus (PRV) targets PRDX1 to evade interferon (IFN) induction. PRV UL13 encodes a serine/threonine kinase important for PRV infection, although its biological function remains obscure. We identified PRDX1 as a UL13-interacting protein. Virological and biochemical assays demonstrate that PRDX1 promotes IFN induction via interacting with TANK-binding kinase 1 (TBK1) and inhibitor-κb kinase ε (IKKε). Conversely, UL13 accelerates PRDX1 degradation via the ubiquitin-proteosome pathway in a kinase-dependent manner. In doing so, PRV inhibits IFN induction during productive infection, which requires PRDX1 expression. This study uncovers an essential role of PRDX1 in innate immune response and reveals a new viral immune evasion strategy to counteract cellular defense. Importance Pseudorabies virus (PRV) interacts with numerous cellular proteins during a productive infection. Here, we demonstrated the interaction of viral protein UL13 with the antioxidant enzyme PRDX1, which functions in multiple signal transduction pathways. We found that PRDX1 participates in the type I interferon pathway by interacting with TBK1 and IKKε, thereby negatively regulating PRV propagation. However, UL13 ubiquitinates PRDX1, which routes PRDX1 into proteasomes for degradation and effectively reduces its expression. These results illuminate the fundamental role that PRDX1 plays in the interferon pathway, and identify a potential target for the control of PRV infection.