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045) in the supine position versus 80°. Moreover, the relative volume contributions of the rib cage and abdominal compartments to tidal volume modified significantly with posture. The electromyographic activity during inspiratory and expiratory cough phases was lower in subjects with DMD compared to healthy subjects for all evaluated muscles (P less then .05), but no significant differences were observed with posture change. Conclusions In subjects with DMD, posture influenced CPF and the relative contribution of the rib cage and abdominal compartments to tidal volume. However, muscular electromyographic activation was not influenced by posture in subjects with DMD and healthy subjects.Background High-frequency jet ventilation (HFJV) has been used in conjunction with conventional ventilation for premature infants with respiratory failure. We sought to identify parameters that were associated with mortality in subjects who underwent HFJV. Tanshinone C Methods Subjects were enrolled if birthweight was ≤ 2,000 g and they were ≤ 34 weeks gestational age. Subjects were excluded if they received HFJV at the time of admission because we aimed to study subjects who failed conventional ventilation. Subject demographics, ventilator parameters, and laboratory data were extracted and analyzed. The Mann-Whitney U-test was used to assess differences in continuous variables, and the chi-square and Fisher exact tests were used for categorical variables between the groups. To assess variables that were predictive of mortality, we used both univariate and multivariate logistic regression analysis. Independent predictors of mortality were identified and used to create a multivariate risk score. Receiver operating characteristic curves were constructed to evaluate the predictive accuracy of the multivariate risk score. Results A total of 53 premature subjects (n = 37 male) were studied, of whom 39 (74%) survived to discharge or transfer back to referring hospital. In the univariate model, female sex, older gestational age, higher birthweight, HFJV peak inspiratory pressure at 1 h, and oxygen saturation index at 4 h were associated with mortality. In the final multivariate logistic regression model, female sex (odds ratio 4.1, 95% CI 1.2-19.8, P = .044), closed ductus arteriosus (odds ratio 7.7, 95% CI 1.3-39.5, P = .016), and oxygen saturation index > 5.5 (odds ratio 6.0, 95% CI 1.5-28.3, P = .02) were independent predictors of mortality. Conclusions We identified that oxygen saturation index > 5.5 after 4 h of HFJV, female sex, and closed ductus arteriosus were independent predictors of mortality.The role of two-pore channel type 2 (TPC2, encoded by tcpn2)-mediated Ca2+ release was recently characterized in zebrafish during establishment of the early spinal circuitry, one of the key events in the coordination of neuromuscular activity. Here, we extend our study to investigate the in vivo role of TPC2 in the regulation of caudal primary motor neuron (CaP) axon extension. We used a combination of TPC2 knockdown with a translation-blocking morpholino antisense oligonucleotide (MO), TPC2 knockout via the generation of a tpcn2 dhkz1a mutant line of zebrafish using CRISPR/Cas9 gene-editing and pharmacological inhibition of TPC2 via incubation with bafilomycin A1 (an H+-ATPase inhibitor) or trans-ned-19 (an NAADP receptor antagonist), and showed that these treatments attenuated CaP Ca2+ signaling and inhibited axon extension. We also characterized the expression of an arc1-like transcript in CaPs grown in primary culture. MO-mediated knockdown of ARC1-like in vivo led to attenuation of the Ca2+ transients in the CaP growth cones and an inhibition of axon extension. Together, our new data suggest a link between ARC1-like, TPC2 and Ca2+ signaling during axon extension in zebrafish.NFE2L2/NRF2 is a transcription factor and master regulator of cellular antioxidant response. Aberrantly high NRF2-dependent transcription is recurrent in human cancer, and conversely NRF2 activity is diminished with age and in neurodegenerative as well as metabolic disorders. Though NRF2 activating drugs are clinically beneficial, NRF2 inhibitors do not yet exist. Here we used a gain-of-function genetic screen of the kinome to identify new druggable regulators of NRF2 signaling. We found that the understudied protein kinase Brain Specific Kinase 2 (BRSK2) and the related BRSK1 kinases suppress NRF2-dependent transcription and NRF2 protein levels in an activity-dependent manner. Integrated phosphoproteomics and RNAseq studies revealed that BRSK2 drives AMPK signaling and suppresses the mTOR pathway. As a result, BRSK2 kinase activation suppressed ribosome-RNA complexes, global protein synthesis, and NRF2 protein levels. Collectively our data illuminate the BRSK2 and BRSK1 kinases, in part by functionally connecting them to NRF2 signaling and mTOR. This signaling axis may prove useful for therapeutically targeting NRF2 in human disease.Mechanical forces, growth factors and the extracellular matrix all play crucial roles in cell adhesion. To understand how epidermal growth factor receptor (EGFR) impacts the mechanics of adhesion, we employed tension gauge tether (TGT) probes displaying the integrin ligand cRGDfK and quantified integrin tension. EGF exposure significantly increased spread area, cell circularity, integrated integrin tension, mechanical rupture density, radial organization and size of focal adhesions in Cos-7 cells on TGT surfaces. These findings suggest that EGFR regulates integrin tension and the spatial organization of focal adhesions. Additionally, we found that the mechanical tension threshold for outside-in integrin activation is tunable by EGFR. Parallel genetic and pharmacologic strategies demonstrated that these phenotypes are driven by ligand-dependent EGFR signaling. Our results establish a novel mechanism whereby EGFR regulates integrin activation and cell adhesion, providing control over cellular responses to the environment.This article has an associated First Person interview with the first author of the paper.Dendritic cell (DC) aggresome-like induced structures (DALIS) are protein aggregates of polyubiquitylated proteins that form transiently during DC maturation. DALIS scatter randomly throughout the cytosol and serve as antigen storage sites synchronising DC maturation and antigen presentation. Maturation of DCs is accompanied by the induction of the ubiquitin-like modifier FAT10 that localises to aggresomes that are structures similar to DALIS. FAT10 is conjugated to substrate proteins and serves as a signal for their rapid and irreversible degradation by the 26S proteasome similar to, yet independently of ubiquitin, thereby contributing to antigen presentation. Here we have investigated whether FAT10 is involved in the formation and turnover of DALIS and whether proteins accumulating in DALIS can be FAT10ylated. We found that FAT10 localises to DALIS in maturing DCs and that this localisation occurs independently of its conjugation to substrates. Additionally, we investigated the DALIS turnover in FAT10-deficient and -proficient DCs and observed FAT10-mediated disassembly of DALIS.