Prostaglandin signalling regulates ciliogenesis by modulating intraflagellar transport

Cilia are microtubule-based organelles that mediate signal transduction in a variety of tissues. Despite their importance, the signalling cascades that regulate cilium formation remain incompletely understood. Here we report that prostaglandin signalling affects ciliogenesis by regulating anterograde intraflagellar transport (IFT). Zebrafish leakytail (lkt) mutants show ciliogenesis defects, and the lkt locus encodes an ATP-binding cassette transporter (ABCC4). We show that Lkt/ABCC4 localizes to the cell membrane and exports prostaglandin E2 (PGE2), a function that is abrogated by the Lkt/ABCC4T804M mutant. PGE2 synthesis enzyme cyclooxygenase-1 and its receptor, EP4, which localizes to the cilium and activates the cyclic-AMP-mediated signalling cascade, are required for cilium formation and elongation. Importantly, PGE2 signalling increases anterograde but not retrograde velocity of IFT and promotes ciliogenesis in mammalian cells. These findings lead us to propose that Lkt/ABCC4-mediated PGE2 signalling acts through a ciliary G-protein-coupled receptor, EP4, to upregulate cAMP synthesis and increase anterograde IFT, thereby promoting ciliogenesis

Simultaneous inference on treatment effects in survival studies with factorial designs

A clinical trial with a 2 × 2 factorial design involves randomization of subjects to treatment A or [Formula: see text] and, within each group, further randomization to treatment B or [Formula: see text]. Under this design, one can assess the effects of treatments A and B on a clinical endpoint using all patients. One may additionally compare treatment A, treatment B, or combination therapy AB to [Formula: see text]. With multiple comparisons, however, it may be desirable to control the overall type I error, especially for regulatory purposes. Because the subjects overlap in the comparisons, the test statistics are generally correlated. By accounting for the correlations, one can achieve higher statistical power compared to the conventional Bonferroni correction. Herein, we derive the correlation between any two (stratified or unstratified) log-rank statistics for a 2 × 2 factorial design with a survival time endpoint, such that the overall type I error for multiple treatment comparisons can be properly controlled. In addition, we allow for adjustment of prognostic factors in the treatment comparisons and conduct simultaneous inference on the effect sizes. We use simulation studies to show that the proposed methods perform well in realistic situations. We then provide an application to a recently completed randomized controlled clinical trial on alcohol dependence. Finally, we discuss extensions of our approach to other factorial designs and multiple endpoints

Structure and electronic properties of transition metal dichalcogenide MX2 (M = Mo, W, Nb; X = S, Se) monolayers with grain boundaries

Layered transition metal dichalcogenides with unique mechanical, electronic, optical, and chemical properties can be used for novel nanoelectronic and optoelectronic devices. Large-area monolayers synthesized using chemical vapor deposition are often polycrystals with many dislocations and grain boundaries (GBs). In the present paper, atomic structure and electronic properties of MX2 (M = Mo, W, Nb; X = S, Se) with the GBs were investigated using first principles based on density functional theory. Simulation results revealed that the zigzag-oriented GBs (which consist of pentagon/heptagons (5-7) pairs) were more stable than the armchair-oriented GBs (which consist of pentagon/heptagons (5-7-5-7) pairs). The GBs induced defect levels are located within the band gap for the semiconductor materials of MX2 (M = Mo, W; X = S, Se) monolayers, and the NbS2 and NbSe2 remained as metallic materials with GBs. Results provided a possible pathway to build these nano-layered materials into nanoelectronic devices

Iron phosphide anchored nanoporous carbon as an efficient electrode for supercapacitors and the oxygen reduction reaction

Inspired by their distinctive properties, transition metal phosphides have gained immense attention as promising electrode materials for energy storage and conversion applications. The introduction of a safe and large-scale method of synthesizing a composite of these materials with carbon is of great significance in the fields of electrochemical and materials sciences. In the current effort, we successfully synthesize an iron phosphide/carbon (FeP/C) with a high specific surface area by the pyrolysis of the gel resulting from the hydrothermal treatment of an iron nitrate-phytic acid mixed solution. In comparison with the blank (P/C), the as-synthesized FeP/C appears to be an efficient electrode material for supercapacitor as well as oxygen reduction reaction (ORR) applications in an alkaline medium in a three-electrode system. In the study of supercapacitors, FeP/C shows areal capacitance of 313 mF cm at 1.2 mA cm while retaining 95% of its initial capacitance value after 10000 cycles, while in the ORR, the synthesized material exhibits high electrocatalytic activity with an onset potential of ca. 0.86 V vs. RHE through the preferred four-electron pathway and less than 6% HO production calculated in the potential range of 0.0-0.7 V vs. RHE. The stability is found to be better than those of the benchmark Pt/C (20 wt%) catalyst