A split ß-lactamase sensor for the detection of DNA modification by cisplatin and ruthenium-based chemotherapeutic drugs.

Here we present a split-enzyme sensor approach for the sequence-specific detection of metal-based drug adducts of DNA. Split ß-lactamase reporters were constructed using domain A of the High Mobility Group Box 1 protein (HMGB1a) in conjunction with zinc finger DNA-binding domains. As a proof of concept, the sensors were characterized with the well-known drug cisplatin, which forms 1,2-intrastrand crosslinks with DNA that are recognized by HMGB1a. After promising results with cisplatin, five ruthenium-based drugs were studied, four of which produced significant signal over background. These results highlight the utility of our approach for rapid screening of novel metal-based chemotherapeutic drug candidates and provide evidence that HMGB1a likely binds to DNA adducts formed by NAMI-A (imidazolium trans-tetrachlorodimethylsulfoxideimidazoleruthenate(III)), KP1019 (indazolium trans-tetrachlorodiindazoleruthenate(III)), KP418 (imidazolium trans-tetrachlorodiimidazoleruthenate(III)), and RAPTA-C (dichloro(η6-p-cymene)(1,3,5-triaza-7-phosphaadamantane)ruthenium(II)). These results thus imply a potential biologically relevant mode of action for the ruthenium-based drugs investigated herein.

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.