A chemosensor for dihydrogenphosphate based on an oxoazamacrocycle possessing three thiourea arms

We report a new H-bond macrocyclic chromogenic chemosensor in organic media, H3L, which displayed drastic changes in its UV–vis spectra revealing selectivity for dihydrogenphosphate over other inorganic anions, such as acetate or fluoride. The X-ray crystal structures of the [H4L⋯NO3]·(CH3CN)4 and [H4L⋯CF3CO2]·(CH3CN)2 salt complexes are also reportedR. B. thanks the Xunta de Galicia (Spain), Projects PGIDI10PXIB209028PR and INCITE09E1R209058ES. M. V. L. thanks the Directorate-General for Research and Development of the Xunta of Galicia (INCITE09 209 084 PR) and the Ministry for Science and Innovation of Spain (CTQ2009-14431/BQU) for financial supportS

Stereoselective Formation of Chiral Metallopeptides

This is the peer reviewed version of the following article: Rama, G., Ardá, A., Maréchal, J., Gamba, I., Ishida, H., Jiménez‐Barbero, J., Vázquez, M. E. and Vázquez López, M. (2012), Stereoselective Formation of Chiral Metallopeptides. Chem. Eur. J., 18: 7030-7035, which has been published in final form at https://doi.org/10.1002/chem.201201036. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsPlaying into our hands: The achiral bipyridine amino acid fluorenylmethyloxycarbonyl 5‐amino‐3‐oxapentanoic acid (Fmoc‐O1PenBpy‐OH) has been used for the solid‐phase synthesis of metallopeptides. Circular dichroism, molecular modeling, and NMR spectroscopic studies show that the chirality of the resulting metal complexes in aqueous solution is determined, and can thus be controlled, by the stereochemistry of one proline residue in the loop between the two coordinating O1PenBpy residuesConsolider Ingenio. Grant Number: CSD2007‐00006 Xunta de Galicia. Grant Numbers: INCITE09 209 084PR, GRC2010/12, PGIDIT08CSA‐047209PR PRESTO Program of JST Grant‐in‐Aid for Scientific Research (C) from the Ministry of Education, Culture, Sports, Science, and Technology. Grant Number: 21550163 International Iberian Nanotechnology Laboratory (INL)S

Programmed stereoselective assembly of DNA-binding helical metallopeptides

A flexible and versatile synthetic approach for the construction of water-stable DNA-binding chiral peptide helicates based on the solid phase peptide synthesis (SPPS) methodology is reportedWe are thankful for the support given by the Spanish grants SAF2010-20822-C02, CTQ2012-31341, CTQ2011-23336, CCTQ2010-16959 Consolider Ingenio 2010 CSD2007-00006, the Xunta de Galicia, GRC2010/12, GRC2013-041, PGIDIT08CSA-047209PR, and the Generalitat de Catalunya, 2009SGR68. Support of COST Action CM1105 is kindly acknowledged. G.R. thanks the INL for his PhD fellowship and E. O. the UAB for her PhD grantS

The folding of a metallopeptide

We have applied solid-phase synthesis methods for the construction of tris(bipyridyl) peptidic ligands that coordinate Fe(II) ions with high affinity and fold into stable mononuclear metallopeptides. The main factors influencing the folding pathway and chiral control of the peptidic ligands around the metal ions have been studied both by experimental techniques (CD, UV-vis and NMR) and molecular modeling tools. Amongst the numerous molecular variables that have been studied, this study clearly illustrates how the chirality of a given set of aminoacids (proline in this case) of the peptide dictates the chirality of the metal center of the resulting metallopeptide. Moreover, the relatively hydrophobic peptidic models used in this work show that the most stable structures present reduced solvent contacts and, in counterpart, stabilize the cis configuration of the proline residuesWe are thankful for the support given by the Spanish grants SAF2013-41943-R, CTQ2012-31341, CTQ2011-23336 and CTQ2013-49317-EXP; the ERDF and the European Research Council (Advanced Grant 340055); the Xunta de Galicia grants GRC2013-041 and PGIDIT08CSA-047209PR and the Generalitat de Catalunya grant 2009SGR68. Support of COST Action CM1105 is kindly acknowledged. G.R. thanks the INL for his PhD fellowshipS

Selective G-quadruplex binding by oligoarginine-Ru(dppz) metallopeptides

A set of Ru(II) metallopeptides containing the dppz ligand has been synthesized using SPPS methods. Fluorescence titration studies show that those metallopeptides featuring an octaarginine tail display a large binding preference for DNA G-quadruplex structures over those lacking it, and also that the interplay between the octoarginine functionalization and the ancillary ligand in the complex has an essential role in the recognition process. Furthermore, the oligoarginine metallopeptides are also efficiently internalized, causing cell death with signs of apoptosisFinancial support from the Spanish grants CTQ2015-70698-R, BFU2013-43513-R and SAF2014-56763-R, the Xunta de Galicia Centro Singular de Investigacion de Galicia accreditation 2016–2019.CICECO – Aveiro Institute of Materials, POCI-01-0145-FEDER007679 (UID/CTM/50011/2013), the UE ERDF and the Fundación AECC (IDEAS197VAZQ-Singulares 2014), are acknowledgedS

Canonical DNA minor groove insertion of bisbenzamidine-Ru(ii) complexes with chiral selectivity

We report the first Ru(ii) coordination compounds that interact with DNA through a canonical minor groove insertion mode and with selectivity for A/T rich sites. This was made possible by integrating a bis-benzamidine minor groove DNA-binding agent with a ruthenium(ii) complex. Importantly, one of the enantiomers (Δ-[Ru(bpy)2b4bpy]2+, Δ-4Ru) shows a considerably higher DNA affinity than the parent organic ligand and the other enantiomer, particularly for the AATT sequence, while the other enantiomer preferentially targets long AAATTT sites with overall lower affinity. Finally, we demonstrate that the photophysical properties of these new binders can be exploited for DNA cleavage using visible light

An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. RESULTS: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. CONCLUSIONS: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups

Production of He-4 and (4) in Pb-Pb collisions at root(NN)-N-S=2.76 TeV at the LHC

Results on the production of He-4 and (4) nuclei in Pb-Pb collisions at root(NN)-N-S = 2.76 TeV in the rapidity range vertical bar y vertical bar <1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0-10% central events are found to be dN/dy4(He) = (0.8 +/- 0.4 (stat) +/- 0.3 (syst)) x 10(-6) and dN/dy4 = (1.1 +/- 0.4 (stat) +/- 0.2 (syst)) x 10(-6), respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (T-chem = 156 MeV) as for light hadrons. The measured ratio of (4)/He-4 is 1.4 +/- 0.8 (stat) +/- 0.5 (syst). (C) 2018 Published by Elsevier B.V.Peer reviewe

Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires

The production of tt‾ , W+bb‾ and W+cc‾ is studied in the forward region of proton–proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fb−1 . The W bosons are reconstructed in the decays W→ℓν , where ℓ denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of $t\overline{t}$, $W+b\overline{b}$ and $W+c\overline{c}$ is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 $\pm$ 0.02 \mbox{fb}^{-1}. The $W$ bosons are reconstructed in the decays $W\rightarrow\ell\nu$, where $\ell$ denotes muon or electron, while the $b$ and $c$ quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions