Ruthenium(II) Polypyridyl Complexes as FRET Donors: Structure- and Sequence-Selective DNA-Binding and Anticancer Properties

Ruthenium(II) polypyridyl complexes (RPCs) that emit from metal-to-ligand charge transfer (MLCT) states have been developed as DNA probes and are being examined as potential anticancer agents. Here, we report that MLCT-emissive RPCs that bind DNA undergo Förster resonance energy transfer (FRET) with Cy5.5-labeled DNA, forming mega-Stokes shift FRET pairs. Based on this discovery, we developed a simple and rapid FRET binding assay to examine DNA-binding interactions of RPCs with diverse photophysical properties, including non-“light switch” complexes [Ru(dppz)2(5,5′dmb)]2+ and [Ru(PIP)2(5,5′dmb)]2+ (dppz = dipyridophenazine, 5,5′dmb = 5,5′-dimethyl-2,2′-bipyridine, PIP = 2-phenyl-imidazo[4,5-f][1,10]phenanthroline). Binding affinities toward duplex, G-quadruplex, three-way junction, and mismatch DNA were determined, and derived FRET donor–acceptor proximities provide information on potential binding sites. Molecules characterized by this method demonstrate encouraging anticancer properties, including synergy with the PARP inhibitor Olaparib, and mechanistic studies indicate that [Ru(PIP)2(5,5′dmb)]2+ acts to block DNA replication fork progression

In situ recordings of large gelatinous spheres from NE Atlantic, and the first genetic confirmation of egg mass of Illex coindetii (Vérany, 1839) (Cephalopoda, Mollusca)

In total, 90 gelatinous spheres, averaging one meter in diameter, have been recorded from ~ 1985 to 2019 from the NE Atlantic Ocean, including the Mediterranean Sea, using citizen science. More than 50% had a dark streak through center. They were recorded from the surface to ~ 60–70 m depth, mainly neutrally buoyant, in temperatures between 8 and 24°C. Lack of tissue samples has until now, prohibited confirmation of species. However, in 2019 scuba divers secured four tissue samples from the Norwegian coast. In the present study, DNA analysis using COI confirms species identity as the ommastrephid broadtail shortfin squid Illex coindetii (Vérany, 1839); these are the first confirmed records from the wild. Squid embryos at different stages were found in different egg masses: (1) recently fertilized eggs (stage ~ 3), (2) organogenesis (stages ~ 17–19 and ~ 23), and (3) developed embryo (stage ~ 30). Without tissue samples from each and every record for DNA corroboration we cannot be certain that all spherical egg masses are conspecific, or that the remaining 86 observed spheres belong to Illex coindetii. However, due to similar morphology and size of these spheres, relative to the four spheres with DNA analysis, we suspect that many of them were made by I. coindetii

Direct observation of ion dynamics in supercapacitor electrodes using in situ diffusion NMR spectroscopy

Ionic transport inside porous carbon electrodes underpins the storage of energy in supercapacitors and the rate at which they can charge and discharge, yet few studies have elucidated the materials properties that influence ion dynamics. Here we use in situ pulsed field gradient NMR spectroscopy to measure ionic diffusion in supercapacitors directly. We find that confinement in the nanoporous electrode structures decreases the effective self-diffusion coefficients of ions by over two orders of magnitude compared with neat electrolyte, and in-pore diffusion is modulated by changes in ion populations at the electrode/electrolyte interface during charging. Electrolyte concentration and carbon pore size distributions also affect in-pore diffusion and the movement of ions in and out of the nanopores. In light of our findings we propose that controlling the charging mechanism may allow the tuning of the energy and power performances of supercapacitors for a range of different applications

Management and outcome of bloodstream infections: a prospective survey in 121 French hospitals (SPA-BACT survey)

Oliver Robineau,1 Jérome Robert,2 Christian Rabaud,3 Jean-Pierre Bedos,4 Emmanuelle Varon,5 Yves Péan,6 Rémy Gauzit,7 Serge Alfandari8 On behalf of the Société de Pathologie Infectieuse de Langue Française (SPILF), the Observatoire National de l’Épidémiologie de la Résistance Bactérienne aux Antibiotiques (ONERBA), and the Surveillance de la Prescription des Antibiotiques (SPA) Group 1Infectious Disease Department, Dron Hospital, Univ Lille, Tourcoing, 2Sorbonne University, UPMC Univ Paris 06, CR7, CIMI, Team E13 (Bacteriology), Paris, 3Infectious Disease Department, Nancy University Hospital, Nancy, 4Intensive Care Unit, Henri Mignot Hospital, Le Chesnay, 5Bacteriology Laboratory, HEGP, 6Observatoire National de L’epidémiologie de la Résistance Bactérienne aux Antibiotiques (OneRBa), 7Intensive Care Unit, Cochin Hospital, APHP, Paris, 8Intensive Care Unit, Dron Hospital, Tourcoing, France Background: Bloodstream infections (BSIs) are severe infections that can be community or hospital acquired. Effects of time to appropriate treatment and impact of antimicrobial management team are discussed in terms of outcome of BSI. We sought to evaluate the impact of initial BSI management on short-term mortality. Patients and methods: A prospective, multicenter survey was conducted in 121 French hospitals. Participants declaring BSI during a 1-month period were included consecutively. Data on patient comorbidities, illness severity, BSI management, and resistance profile of bacterial strains were collected. Predictors of 10-day mortality were identified by multivariate regression for overall BSI, health care-related and hospital-acquired BSI. Results: We included 1,952 BSIs. More than a third of them were hospital acquired (39%). Multidrug resistance was identified in 10% of cases, mainly in health care-related BSI. Empirical therapy and targeted therapy were appropriate for 61% and 94% of cases, respectively. Increased 10-day mortality was associated with severe sepsis, septic shock, increasing age, and any focus other than the urinary tract. Decreased mortality was associated with receiving at least one active antibiotic within the first 48 hours. Intervention of antimicrobial management team during the acute phase of BSI was associated with a decreased mortality at day 10 in the overall population and in health care-related BSI. Conclusion: Optimizing BSI management by increasing rapidity of appropriate treatment initiation may decrease short-term mortality, even in countries with low rate of multidrug-resistant organisms. Early intervention of antimicrobial management team is crucial in terms of mortality. Keywords: mortality, bloodstream infections, antimicrobial management team, community-acquired infection, health care-related infectio

Charcoal scarcity in Epigravettian settlements with mammoth bone dwellings: the taphonomic evidence from Mezhyrich (Ukraine)

International audienc

Enquête SPA2 de prévalence et de bon usage des anti-infectieux dans 314 hôpitaux français en 2010

International audienceObjectivesWe aimed to assess antibiotic prescriptions to identify potential targets for improvement.MethodsWe conducted a point prevalence survey (November 2010) of antibiotic use in 314 voluntary hospitals recruited by the French Infectious Diseases Society (SPILF) and the National Observatory for Epidemiology of Bacterial Resistance to Antimicrobials (ONERBA). Data were entered online, immediately analyzed and exported.ResultsThe prevalence of antibiotic use was 19.5% (9059/46,446patients). A higher prevalence was observed in the infectious disease (58.4%), hematology (58%), and intensive care (48.7%) units. The three most frequently used antibiotic classes were aminopenicillins (23.8%), fluoroquinolones (17.9%), and 3rd-generation cephalosporins (16.7%). A monotherapy was prescribed to 64% of patients. The reasons for the antibiotic prescription were written in the medical records of 74% of patients and 62% were consistent with the local guidelines.ConclusionOur results are similar to that of other studies. Various local targets for improvement have been identified to help hospitals define a better antibiotic stewardship.ObjectifsÉvaluer les prescriptions antibiotiques afin de proposer des pistes d’amélioration.MéthodesNous avons réalisé une enquête de prévalence de l’antibiothérapie, en novembre 2010, dans 314 hôpitaux volontaires recrutés par les réseaux de la SPILF et de l’ONERBA. Les données étaient saisies en ligne avec une analyse instantanée et un export des données.RésultatsLa prévalence de l’antibiothérapie était de 19,5 % (9059/46 446patients). Elle était plus élevée en maladies infectieuses (58,4 %), hématologie (58 %) et réanimation (48,7 %). Les trois classes les plus fréquentes étaient les aminopénicillines (23,8 %), les fluoroquinolones (17,9 %) et les céphalosporines de 3e génération (16,7 %). Une monothérapie était utilisée dans 64 % des cas. Le motif de la prescription était noté dans le dossier médical dans 74 % des cas et était conforme aux recommandations locales dans 62 %.ConclusionsCes résultats sont similaires à ceux d’autres enquêtes. Des possibilités d’amélioration sur des critères locaux permettent aux établissements d’orienter leurs politiques d’amélioration de la prescription