A Molecular Tool Targeting the Base-Flipping Activity of Human UHRF1

During DNA replication, ubiquitin-like, containing PHD and RING fingers domains 1 (UHRF1) plays key roles in the inheritance of methylation patterns to daughter strands by recognizing through its SET and RING-associated domain (SRA) the methylated CpGs and recruiting DNA methyltransferase 1 (DNMT1). Herein, our goal is to identify UHRF1 inhibitors targeting the 5′-methylcytosine (5mC) binding pocket of the SRA domain to prevent the recognition and flipping of 5mC and determine the molecular and cellular consequences of this inhibition. For this, we used a multidisciplinary strategy combining virtual screening and molecular modeling with biophysical assays in solution and cells. We identified an anthraquinone compound able to bind to the 5mC binding pocket and inhibit the base-flipping process in the low micromolar range. We also showed in cells that this hit impaired the UHRF1/DNMT1 interaction and decreased the overall methylation of DNA, highlighting the critical role of base flipping for DNMT1 recruitment and providing the first proof of concept of the druggability of the 5mC binding pocket. The selected anthraquinone appears thus as a key tool to investigate the role of UHRF1 in the inheritance of methylation patterns, as well as a starting point for hit-to-lead optimizations.     

Pressure‐Induced Conversion of a Paramagnetic FeCo Complex into a Molecular Magnetic Switch with Tuneable Hysteresis

A key challenge in the design of magnetic molecular switches is to obtain bistability at room temperature. Here, we show that application of moderate pressure makes it possible to convert a paramagnetic Fe^III₂Co^II₂ square complex into a molecular switch exhibiting a full dia‐ to paramagnetic transition: Fe^IICo^III ? Fe^IIICo^II. Moreover, the complex follows a rare behavior: the higher the pressure, the broader the magnetic hysteresis. Thus, the application of an adequate pressure allows inducing a magnetic bistability at room temperature with predictable hysteresis width. The structural studies at different pressures suggest that the pressure‐enhanced bistability is due to the strengthening of intermolecular interactions upon pressure increase. An original microscopic Ising‐like model including pressure effects is developed to simulate this unprecedented behavior. Overall, this study shows that FeCo complexes could be very sensitive piezo switches with potential use as sensors.     

Transparent Interconnection of Metro Access and Metro Core Networks Including Protection

We proposed and demonstrated a solution for the transparent interconnection of metro access and metro core networks enabling end-to-end wavelength provisioning including the protection.     

Reactant concentrations from fluorescence correlation spectroscopy with tailored fluorescent probes. An example of local calibration-free pH measurement

The present account is concerned with the measurement of local reactant concentrations by observing specific fluorescent probes in fluorescence correlation spectroscopy (FCS). The Theoretical Analysis section revisits the photophysical, thermodynamic, and kinetic information that is contained in the corresponding FCS correlation curves. In particular, we examine the conditions under which FCS is revealed as a superior tool to measure concentrations of reactive species. Careful molecular engineering of the specific fluorescent probes that simultaneously integrates photophysical, thermodynamic, and kinetic constraints will be required to benefit most from FCS. We illustrate the FCS titration approach with a series of fluorescent probes that we tailored to measure pH at around 4-6 by FCS after two-photon excitation. We show that an optimal design allows one to access pH without any preliminary calibrations such as the determination of the protonation constant or the photophysical properties of the fluorescent probe.     

A simple calibration procedure for volatile organic compounds sampling in air with adsorptive solid-phase microextraction fibres

Adsorptive solid-phase microextraction (SPME) fibres have proven to be a reliable means of sampling volatile organic compounds (VOCs) in air. In this work, polydimethylsiloxane/carboxen (PDMS/CAR) fibres were used to test a new approach of air sampling strategy with SPME in the lab which could lighten calibration procedure and enhance the use of this already rapid, simple, convenient and cost effective sampling technique. Indeed, only one curve can be used whatever the extraction time chosen by the analyst under constant conditions of air velocity and temperature. Ficks' law of diffusion was used to model SPME grab sampling when the fibre was totally exposed to the air sample. Experimental sampling rates were then determined by GC-FID for different sampling conditions, i.e. in a flowing air stream of known velocity ("dynamic mode") and in a stagnant air ("static mode"). These sampling rates were found to be 3.50 and 17.80 mL min(-1) for acetone, 4.06 and 21.20 mL min(-1) for 1,2-dichloroethane, 5.10 and 27.80 mL min(-1) for toluene and 5.36 and 30.80 mL min(-1) for butyl acetate, for static and dynamic sampling modes respectively. Deviation from linearity of the calibration curves, indicating that a significant fraction of the adsorption sites are occupied, were determined. They were found to be approximately equal to 0.9, 1.57, 3.82 and 4.37 nmol for acetone, dichloroethane, toluene and butyl acetate, respectively. Experimentally determined sampling rates of these isolated compounds were also valid when a complex equimolar gaseous mixture was investigated, but deviation from linearity appears earlier. Then, for a given application, sampling times should be chosen very carefully to avoid competitive adsorption and hence, bad quantitative analysis results.     

Merging metathesis and photochemical Csp3-H activation: Access to masked β-formyl hexanolides and their rearrangement to furofuranones

β-Masked formyl hexanolides were prepared by a three-step sequence including esterification of homoallylic alcohols, ring-closing metathesis and the photochemically induced addition of dioxanyl radical. When treated under oxidative conditions, the adducts underwent cleavage of the ketal group leading after rearrangement to parent furofuranones, structures found in some biological active compounds.     

Synthesis of Phosphorus Containing Polymers by Phase Transfer Catalysis (PTC). I. Comparative Study between Liquid-Liquid and Liquid-Vapor Systems

Abstract

Polyphosphonates were synthesized by interfacial alkaline polycondensation of bispheml A (BA) with phenyldichlorophosphonate (PPD) and cyclohexyl-dichlorophosphonate (CPD) in liquid-liquid[1] (1–1) and Iiquid-vapoR[2] (I-v) systems.     

On the Ma–Trudinger–Wang curvature on surfaces

We investigate the properties of the Ma–Trudinger–Wang nonlocal curvature tensor in the case of surfaces. In particular, we prove that a strict form of the Ma–Trudinger– Wang condition is stable under C ⁴ perturbation if the nonfocal domains are uniformly convex; and we present new examples of positively curved surfaces which do not satisfy the Ma–Trudinger–Wang condition. As a corollary of our results, optimal transport maps on a “sufficiently flat” ellipsoid are in general nonsmooth.