Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) promotes angiogenesis and ischemia-induced neovascularization via NADPH oxidase 4 (NOX4) and nitric oxide-dependent mechanisms

Background: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has the ability to inhibit angiogenesis by inducing endothelial cell death, as well as being able to promote pro-angiogenic activity in vitro. These seemingly opposite effects make its role in ischemic disease unclear. Using Trail(-/-) and wildtype mice, we sought to determine the role of TRAIL in angiogenesis and neovascularization following hindlimb ischemia. Methods and Results: Reduced vascularization assessed by real-time 3-dimensional Vevo ultrasound imaging and CD31 staining was evident in Trail(-/-) mice after ischemia, and associated with reduced capillary formation and increased apoptosis. Notably, adenoviral TRAIL administration significantly improved limb perfusion, capillary density, and vascular smooth-muscle cell content in both Trail(-/-) and wildtype mice. Fibroblast growth factor-2, a potent angiogenic factor, increased TRAIL expression in human microvascular endothelial cell-1, with fibroblast growth factor-2-mediated proliferation, migration, and tubule formation inhibited with TRAIL siRNA. Both fibroblast growth factor-2 and TRAIL significantly increased NADPH oxidase 4 (NOX4) expression. TRAIL-inducible angiogenic activity in vitro was inhibited with siRNAs targeting NOX4, and consistent with this, NOX4 mRNA was reduced in 3-day ischemic hindlimbs of Trail(-/-) mice. Furthermore, TRAIL-induced proliferation, migration, and tubule formation was blocked by scavenging H2O2, or by inhibiting nitric oxide synthase activity. Importantly, TRAIL-inducible endothelial nitric oxide synthase phosphorylation at Ser-1177 and intracellular human microvascular endothelial cell-1 cell nitric oxide levels were NOX4 dependent. Conclusions: This is the first report demonstrating that TRAIL can promote angiogenesis following hindlimb ischemia in vivo. The angiogenic effect of TRAIL on human microvascular endothelial cell-1 cells is downstream of fibroblast growth factor-2, involving NOX4 and nitric oxide signaling. These data have significant therapeutic implications, such that TRAIL may improve the angiogenic response to ischemia and increase perfusion recovery in patients with cardiovascular disease and diabetes.Belinda Ann Di Bartolo, Siân Peta Cartland, Leonel Prado-Lourenco, Thomas Scott Griffith, Carmine Gentile, Jayant Ravindran, Nor Saadah Muhammad Azahri, Thuan Thai, Amanda Wing Shee Yeung, Shane Ross Thomas, Mary Meltem Kavurm

For the Progress of “Faustus and Helen”: Crane, Whitman, and the Metropolitan Progress Poem

This essay is meant to invigorate a critical discussion of the progress poem—a genre that, while prevalent in American literature, has been virtually ignored by critics and scholars. In lieu of tackling the genre in its entirety, a project too large for just one article, the author focuses the argument through the well-known alignment between Walt Whitman and Hart Crane on the subject of the modern city. It is through the progress poem genre that Crane and Whitman’s peculiar place in metropolitan poetics can best be understood, and it is through their poetry that scholars can begin to approach the broader issue of the progress poem’s place in American literature. Cet article vise à soulever un débat critique au sujet de la poésie du progrès, un genre courant dans la littérature étatsunienne, mais pratiquement ignoré par les critiques et les commentateurs. Plutôt que d’aborder le genre dans son entièreté – un projet qui déborde du cadre d’un article –, l’auteur resserre l’argumentation autour du parallèle bien connu entre Walt Whitman et Hart Crane concernant le traitement de la ville moderne. C’est la poésie du progrès en tant que genre qui permet le mieux de comprendre la place particulière qu’occupent ces deux auteurs dans la poésie métropolitaine, et c’est par leurs poèmes que les chercheurs peuvent aborder la question plus vaste de la place du poème sur le progrès dans la littérature étatsunienne

Open data from the third observing run of LIGO, Virgo, KAGRA, and GEO

The global network of gravitational-wave observatories now includes five detectors, namely LIGO Hanford, LIGO Livingston, Virgo, KAGRA, and GEO 600. These detectors collected data during their third observing run, O3, composed of three phases: O3a starting in 2019 April and lasting six months, O3b starting in 2019 November and lasting five months, and O3GK starting in 2020 April and lasting two weeks. In this paper we describe these data and various other science products that can be freely accessed through the Gravitational Wave Open Science Center at https://gwosc.org. The main data set, consisting of the gravitational-wave strain time series that contains the astrophysical signals, is released together with supporting data useful for their analysis and documentation, tutorials, as well as analysis software packages