Invasion-Block and S-MARVEL: A high-content screening and image analysis platform identifies ATM kinase as a modulator of melanoma invasion and metastasis.

Robust high-throughput assays are crucial for the effective functioning of a drug discovery pipeline. Herein, we report the development of Invasion-Block, an automated high-content screening platform for measuring invadopodia-mediated matrix degradation as a readout for the invasive capacity of cancer cells. Combined with Smoothen-Mask and Reveal, a custom-designed, automated image analysis pipeline, this platform allowed us to evaluate melanoma cell invasion capacity posttreatment with two libraries of compounds comprising 3840 U.S. Food and Drug Administration (FDA)-approved drugs with well-characterized safety and bioavailability profiles in humans as well as a kinase inhibitor library comprising 210 biologically active compounds. We found that Abl/Src, PKC, PI3K, and Ataxia-telangiectasia mutated (ATM) kinase inhibitors significantly reduced melanoma cell invadopodia formation and cell invasion. Abrogation of ATM expression in melanoma cells via CRISPR-mediated gene knockout reduced 3D invasion in vitro as well as spontaneous lymph node metastasis in vivo. Together, this study established a rapid screening assay coupled with a customized image-analysis pipeline for the identification of antimetastatic drugs. Our study implicates that ATM may serve as a potent therapeutic target for the treatment of melanoma cell spread in patients.

Measuring the 2D baryon acoustic oscillation signal of galaxies in WiggleZ: cosmological constraints.

We present results from the 2D anisotropic baryon acoustic oscillation (BAO) signal present in the final data set from the WiggleZ Dark Energy Survey. We analyse the WiggleZ data in two ways: first using the full shape of the 2D correlation function and secondly focusing only on the position of the BAO peak in the reconstructed data set. When fitting for the full shape of the 2D correlation function we use a multipole expansion to compare with theory. When we use the reconstructed data we marginalize over the shape and just measure the position of the BAO peak, analysing the data in wedges separating the signal along the line of sight from that parallel to the line of sight. We verify our method with mock data and find the results to be free of bias or systematic offsets. We also redo the pre-reconstruction angle-averaged (1D) WiggleZ BAO analysis with an improved covariance and present an updated result. The final results are presented in the form of Ω c h2, H(z), and DA (z) for three redshift bins with effective redshifts z = 0.44, 0.60, and 0.73. Within these bins and methodologies, we recover constraints between 5 and 22 per cent error. Our cosmological constraints are consistent with flat ΛCDM cosmology and agree with results from the Baryon Oscillation Spectroscopic Survey.