Synthesis and analysis of the anticancer activity of platinum(ii) complexes incorporating dipyridoquinoxaline variants

Eight platinum(ii) complexes with anticancer potential have been synthesised and characterised. These complexes are of the type [Pt(I)(A)], where I is either dipyrido[3,2-f:2′,3′-h]quinoxaline (dpq) or 2,3-dimethyl-dpq (23Medpq) and A is one of the R,R or S,S isomers of either 1,2-diaminocyclohexane (SS-dach or RR-dach) or 1,2-diaminocyclopentane (SS-dacp or RR-dacp). The CT-DNA binding of these complexes and a series of other complexes were assessed using fluorescent intercalator displacement assays, resulting in unexpected trends in DNA binding affinity. The cytotoxicity of the eight synthesised compounds was determined in the L1210 cell line; the most cytotoxic of these were [Pt(dpq)(SS-dach)]Cl and [Pt(dpq)(RR-dach)]Cl, with IC values of 0.19 and 0.80 μM, respectively. The X-ray crystal structure of the complex [Pt(dpq)(SS-dach)](ClO)·1.75HO is also reported. This journal i

Prion infection impairs cholesterol metabolism in neuronal cells

Conversion of prion protein (PrPC) into a pathological isoform (PrPSc) during prion infection occurs in lipid rafts and is dependent on cholesterol. Here, we show that prion infection increases the abundance of cholesterol transporter, ATP-binding cassette transporter type A1 (ATP-binding cassette transporter type A1), but reduces cholesterol efflux from neuronal cells leading to the accumulation of cellular cholesterol. Increased abundance of ABCA1 in prion disease was confirmed in prion-infected mice. Mechanistically, conversion of PrPC to the pathological isoform led to PrPSc accumulation in rafts, displacement of ABCA1 from rafts and the cell surface, and enhanced internalization of ABCA1. These effects were abolished with reversal of prion infection or by loading cells with cholesterol. Stimulation of ABCA1 expression with liver X receptor agonist or overexpression of heterologous ABCA1 reduced the conversion of prion protein into the pathological form upon infection. These findings demonstrate a reciprocal connection between prion infection and cellular cholesterol metabolism, which plays an important role in the pathogenesis of prion infection in neuronal cells

Contrasting frustrated Lewis pair reactivity with selenium- and boron-based Lewis acids

The activation of π‐bonds in diynyl esters has been investigated by using soft and hard Lewis acids. In the case of the soft selenium Lewis acid PhSeCl, sequential activation of the alkyne bonds leads initially to an isocoumarin (1 equiv PhSeCl) and then to a tetracyclic conjugated structure with the isocoumarin subunit fused to a benzoselenopyran (3 equiv PhSeCl). Conversely, the reaction with the hard Lewis acidic borane B(C6F5)3 initiates a cascade reaction to yield a complex π‐conjugated system containing phthalide and indene subunits

Radial Velocity Discovery of an Eccentric Jovian World Orbiting at 18 au

Based on two decades of radial velocity (RV) observations using Keck/High Resolution Echelle Spectrometer (HIRES) and McDonald/Tull, and more recent observations using the Automated Planet Finder, we found that the nearby star HR 5183 (HD 120066) hosts a 3 minimum mass planet with an orbital period of yr. The orbit is highly eccentric (e ≃ 0.84), shuttling the planet from within the orbit of Jupiter to beyond the orbit of Neptune. Our careful survey design enabled high cadence observations before, during, and after the planet\u27s periastron passage, yielding precise orbital parameter constraints. We searched for stellar or planetary companions that could have excited the planet\u27s eccentricity, but found no candidates, potentially implying that the perturber was ejected from the system. We did identify a bound stellar companion more than 15,000 au from the primary, but reasoned that it is currently too widely separated to have an appreciable effect on HR 5183 b. Because HR 5183 b\u27s wide orbit takes it more than 30 au (1\u27\u27) from its star, we also explored the potential of complimentary studies with direct imaging or stellar astrometry. We found that a Gaia detection is very likely, and that imaging at 10 μm is a promising avenue. This discovery highlights the value of long-baseline RV surveys for discovering and characterizing long-period, eccentric Jovian planets. This population may offer important insights into the dynamical evolution of planetary systems containing multiple massive planets

Comparison of aircraft-derived observations with in situ research aircraft measurements

Mode Selective Enhanced Surveillance (Mode-S EHS) reports are aircraft-based observations that have value in numerical weather prediction (NWP). These reports contain the aircraft's state vector in terms of its speed, direction, altitude and Mach number. Using the state vector, meteorological observations of temperature and horizontal wind can be derived. However, Mode-S EHS processing reduces the precision of the state vector from 16-bit to 10-bit binary representation. We use full precision data from research grade instruments, on-board the United Kingdom's Facility for Atmospheric Airborne Measurements, to emulate Mode-S EHS reports and to compare with derived observations. We aim to understand the observation errors due to the reduced precision of Mode-S EHS reports. We derive error models to estimate these observation errors. The temperature error increases from 1.25 K to 2.5 K between an altitude of 10 km and the surface due to its dependency on Mach number and also Mode-S EHS precision. For the cases studied, the zonal wind error is around 0.50 ms− 1 and the meridional wind error is 0.25 ms− 1. The wind is also subject to systematic errors that are directionally dependent. We conclude that Mode-S EHS derived horizontal winds are suitable for data assimilation in high-resolution NWP. Temperature reports may be usable when aggregated from multiple aircraft. While these reduced precision, high frequency data provide useful, albeit noisy, observations; direct reports of the higher precision data would be preferable

Foundations of Translational Ecology

Ecologists who specialize in translational ecology (TE) seek to link ecological knowledge to decision making by integrating ecological science with the full complement of social dimensions that underlie today\u27s complex environmental issues. TE is motivated by a search for outcomes that directly serve the needs of natural resource managers and decision makers. This objective distinguishes it from both basic and applied ecological research and, as a practice, it deliberately extends research beyond theory or opportunistic applications. TE is uniquely positioned to address complex issues through interdisciplinary team approaches and integrated scientist–practitioner partnerships. The creativity and context-specific knowledge of resource managers, practitioners, and decision makers inform and enrich the scientific process and help shape use-driven, actionable science. Moreover, addressing research questions that arise from on-the-ground management issues – as opposed to the top-down or expert-oriented perspectives of traditional science – can foster the high levels of trust and commitment that are critical for long-term, sustained engagement between partners