Conductance statistics from a large array of sub-10 nm molecular junctions

Devices made of few molecules constitute the miniaturization limit that both inorganic and organic-based electronics aspire to reach. However, integration of millions of molecular junctions with less than 100 molecules each has been a long technological challenge requiring well controlled nanometric electrodes. Here we report molecular junctions fabricated on a large array of sub-10 nm single crystal Au nanodots electrodes, a new approach that allows us to measure the conductance of up to a million of junctions in a single conducting Atomic Force Microscope (C-AFM) image. We observe two peaks of conductance for alkylthiol molecules. Tunneling decay constant (beta) for alkanethiols, is in the same range as previous studies. Energy position of molecular orbitals, obtained by transient voltage spectroscopy, varies from peak to peak, in correlation with conductance values.Comment: ACS Nano (in press

The G-Quadruplex Ligand Telomestatin Impairs Binding of Topoisomerase IIIα to G-Quadruplex-Forming Oligonucleotides and Uncaps Telomeres in ALT Cells

In Alternative Lengthening of Telomeres (ALT) cell lines, specific nuclear bodies called APBs (ALT-associated PML bodies) concentrate telomeric DNA, shelterin components and recombination factors associated with telomere recombination. Topoisomerase IIIα (Topo III) is an essential telomeric-associated factor in ALT cells. We show here that the binding of Topo III to telomeric G-overhang is modulated by G-quadruplex formation. Topo III binding to G-quadruplex-forming oligonucleotides was strongly inhibited by telomestatin, a potent and specific G-quadruplex ligand. In ALT cells, telomestatin treatment resulted in the depletion of the Topo III/BLM/TRF2 complex and the disruption of APBs and led to the segregation of PML, shelterin components and Topo III. Interestingly, a DNA damage response was observed at telomeres in telomestatin-treated cells. These data indicate the importance of G-quadruplex stabilization during telomere maintenance in ALT cells. The function of TRF2/Topo III/BLM in the resolution of replication intermediates at telomeres is discussed

Estimation of π-π Electronic Couplings from Current Measurements

The - interactions between organic molecules are among the most important parameters for optimizing the transport and optical properties of organic transistors, light-emitting diodes, and (bio-)molecular devices. Despite substantial theoretical progress, direct experimental measurement of the - electronic coupling energy parameter t has remained an old challenge due to molecular structural variability and the large number of parameters that affect charge transport. Here, we propose a study of - interactions from electrochemical and current measurements on a large array of ferrocene-thiolated gold nanocrystals. We confirm the theoretical prediction that t can be assessed from a statistical analysis of current histograms. The extracted value of t ≈ 35 meV is in the expected range based on our density functional theory analysis. Furthermore, the t distribution is not necessarily Gaussian and could be used as an ultrasensitive technique to assess intermolecular distance fluctuation at the sub-angstrom level. The present work establishes a direct bridge between quantum chemistry, electrochemistry, organic electronics, and mesoscopic physics, all of which were used to discuss results and perspectives in a quantitative manner

Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma.

We collated data from 157 unpublished cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma and 20 publicly available datasets in an integrated analysis of >1,000 cases. We identified co-segregating mutations in histone-mutant subgroups including loss of FBXW7 in H3.3G34R/V, TOP3A rearrangements in H3.3K27M, and BCOR mutations in H3.1K27M. Histone wild-type subgroups are refined by the presence of key oncogenic events or methylation profiles more closely resembling lower-grade tumors. Genomic aberrations increase with age, highlighting the infant population as biologically and clinically distinct. Uncommon pathway dysregulation is seen in small subsets of tumors, further defining the molecular diversity of the disease, opening up avenues for biological study and providing a basis for functionally defined future treatment stratification

Polyphenols bioaccessibility and bioavailability assessment in ipecac infusion using a combined assay of simulated in vitro digestion and Caco-2 cell model

In this report, we investigated for the first time the total polyphenols content (TPC) and antioxidant activity before and after digestion of Carapichea ipecacuanha root infusion, better known as ipecac, prepared at different concentrations. An in vitro digestion system coupled to a Caco-2 cell model was applied to study the bioavailability of antioxidant compounds. The ability of ipecac bioaccessible fractions to inhibit reactive oxygen species (ROS) generation at cellular level was also evaluated. The findings revealed that water volume of 50 mL g-1 of sample provided the maximum yield of extraction of TPC and antioxidant activity. Polyphenols increased in content and activity after digestion and they were highly bioavailable (75% of intestinal absorption). Polyphenols were also present in the residual parts which indicate a possible local activity. Results also suggest that ipecac infusion could represent a promising source of effective bioavailable antioxidants to be exploited in functional foods field.This study was supported by the financial project of LIP‐MB laboratory LR11ES24 of INSAT, University of Carthage and by the University of Tunis El Manar, Ministry of Higher Education and Scientific Research of Tunisia through the scholarship support provided to the first author. We are grateful to Dr. Chokri Messaoud for the identification of the plant.Peer Reviewe

Evaluation of antileishmanial, cytotoxic and antioxidant activities of essential oils extracted from plants issued from the leishmaniasis-endemic region of Sned (Tunisia)

International audienceIn this study, we tested 10 essential oils (EOs) extracted from 10 plants issued from Sned region (Tunisia) to evaluate both their leishmanicidal effects against Leishmania major and L. infantum, and their cytotoxicity against murine macrophage cell line RAW 264.7 (ATCC, TIB-71). The antioxidant activity was also monitored by the DDPH method, while the chemical composition of active EO was assessed by GC-MS analysis. The results showed that the EOs obtained from Thymus hirtus sp. algeriensis (rich on monoterpenoids, especially linalool at 17.62% and camphor at 13.82%) is significantly active against both L. major and L. infantum, whereas Ruta chalepensis EO (rich on 2-undecanone at 84.28%) is only active against L. infantum. Both oil extracts showed low cytotoxicity towards murine macrophages. The characteristic ratios (IC80 Raw264.7 cells/IC50 L. infantum and IC80 Raw264.7 cells/IC50 L. major) were, respectively, 2.7 and 1.57 for T. hirtus sp. algeriensis, and 1.34 and 0.19 for R. chalepensis. However, when measuring the antioxidant effects (DDPH method), the two latter EOs presented a moderate 2,2-diphenyl-2-picrylhydrazyl hydrate scavenging effects compared to EOs from Eucaliptus globulus, Pinus halepensis, Pituranthos tortuosus, Rosmarinus officinalis, Tetraclinis articulata or to BHT