Photoactive assemblies of organic compounds and biomolecules: drug-protein supramolecular systems

[EN] The properties of singlet and triplet excited states are strongly medium-dependent. Hence, these species constitute valuable tools as reporters to probe compartmentalised microenvironments, including drug@protein supramolecular systems. In the present review, the attention is focused on the photophysical properties of the probe drugs (rather than those of the protein chromophores) using transport proteins (serum albumins and 1-acid glycoproteins) as hosts. Specifically, fluorescence measurements allow investigating the structural and dynamic properties of biomolecules or their complexes. Thus, the emission quantum yields and the decay kinetics of the drug singlet excited states provide key information to determine important parameters such as the stoichiometry of the complex, the binding constant, the relative degrees of occupancy of the different compartments, etc. Application of the FRET concept allows determining donor-acceptor interchromophoric distances. In addition, anisotropy measurements can be related to the orientation of the drug within the binding sites, where the degrees of freedom for conformational relaxation are restricted. Transient absorption spectroscopy is also a potentially powerful tool to investigate the binding of drugs to proteins, where formation of encapsulated triplet excited states is favoured over other possible processes leading to ionic species (i. e. radical ions), and their photophysical properties are markedly sensitive to the microenvironment experienced within the protein binding sites. Even under aerobic conditions, the triplet lifetimes of protein-complexed drugs are remarkably long, which provides a broad dynamic range for identification of distinct triplet populations or for chiral discrimination. Specific applications of the laser flash photolysis technique include the determination of drug distribution among the bulk solution and the protein binding sites, competition of two types of proteins to bind a 3 drug, occurrence of drug-drug interactions within protein binding sites, enzymatic-like activity of the protein or determination of enantiomeric compositions. The use of proteins as supramolecular hosts modifies the photoreactivity of encapsulated substrates by providing protection against oxygen or other external reagents, by imposing conformational restrictions in the binding pockets, or by influencing the stereochemical outcome. In this review, a selected group of examples is presented including decarboxylation, dehalogenation, nucleophilic addition, dimerisation, oxidation, Norrish type II reaction, photo-Fries rearrangement and 6 electrocyclisationFinancial support from the Spanish Government (CTQ2010-14882, JCI-2011-09926, RyC-2007-00476), from the EU (PCIG12-GA-2012-334257), from the Universitat Politènica de València (SP20120757) and from the Consellería de Educació, Cultura i Esport (PROMETEOII/2013/005, GV/2013/051) is gratefully acknowledged.Vayá Pérez, I.; Lhiaubet-Vallet, VL.; Jiménez Molero, MC.; Miranda Alonso, MÁ. (2014). Photoactive assemblies of organic compounds and biomolecules: drug-protein supramolecular systems. Chemical Society Reviews. 43:4102-4122. https://doi.org/10.1039/C3CS60413FS410241224

Characterization of the Tomato ARF Gene Family Uncovers a Multi-Levels Post-Transcriptional Regulation Including Alternative Splicing

Background: The phytohormone auxin is involved in a wide range of developmental processes and auxin signaling is known to modulate the expression of target genes via two types of transcriptional regulators, namely, Aux/IAA and Auxin Response Factors (ARF). ARFs play a major role in transcriptional activation or repression through direct binding to the promoter of auxin-responsive genes. The present study aims at gaining better insight on distinctive structural and functional features among ARF proteins. Results: Building on the most updated tomato (Solanum lycopersicon) reference genome sequence, a comprehensive set of ARF genes was identified, extending the total number of family members to 22. Upon correction of structural annotation inconsistencies, renaming the tomato ARF family members provided a consensus nomenclature for all ARF genes across plant species. In silico search predicted the presence of putative target site for small interfering RNAs within twelve Sl-ARFs while sequence analysis of the 59-leader sequences revealed the presence of potential small uORF regulatory elements. Functional characterization carried out by transactivation assay partitioned tomato ARFs into repressors and activators of auxin-dependent gene transcription. Expression studies identified tomato ARFs potentially involved in the fruit set process. Genome-wide expression profiling using RNA-seq revealed that at least one third of the gene family members display alternative splicing mode of regulation during the flower to fruit transition. Moreover, the regulation of several tomato ARF genes by both ethylene and auxin, suggests their potential contribution to the convergence mechanism between the signaling pathways of these two hormones. Conclusion: All together, the data bring new insight on the complexity of the expression control of Sl-ARF genes at the transcriptional and post-transcriptional levels supporting the hypothesis that these transcriptional mediators might represent one of the main components that enable auxin to regulate a wide range of physiological processes in a highly specific and coordinated manner

Crowdsourced assessment of common genetic contribution to predicting anti-TNF treatment response in rheumatoid arthritis

Correction: vol 7, 13205, 2016, doi:10.1038/ncomms13205Rheumatoid arthritis (RA) affects millions world-wide. While anti-TNF treatment is widely used to reduce disease progression, treatment fails in Bone-third of patients. No biomarker currently exists that identifies non-responders before treatment. A rigorous community-based assessment of the utility of SNP data for predicting anti-TNF treatment efficacy in RA patients was performed in the context of a DREAM Challenge (http://www.synapse.org/RA_Challenge). An open challenge framework enabled the comparative evaluation of predictions developed by 73 research groups using the most comprehensive available data and covering a wide range of state-of-the-art modelling methodologies. Despite a significant genetic heritability estimate of treatment non-response trait (h(2) = 0.18, P value = 0.02), no significant genetic contribution to prediction accuracy is observed. Results formally confirm the expectations of the rheumatology community that SNP information does not significantly improve predictive performance relative to standard clinical traits, thereby justifying a refocusing of future efforts on collection of other data.Peer reviewe

Le respirateur en néonatologie

Issue d’une longue histoire à la fois scientifique et technologique, la réanimation, mot introduit dans la langue française dans les années 1950, a pris son plein essor dans la seconde moitié du XXe siècle. Grâce au respirateur, la réanimation respiratoire y tient une place majeure. Cette machine fut introduite dans l’arsenal thérapeutique du nourrisson et du nouveau-né vers 1962 en même temps qu’était proposé le terme de néonatologie pour les soins apportés aux enfants dans les premières sem..

INFECTIONS MATERNO-FOETALES A CANDIDA ALBICANS (REVUE DE LA LITTERATURE A PROPOS DE 8 CAS)

NANCY1-SCD Medecine (545472101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Réseaux et périnatalité (à travers l'édification du réseau périnatal lorrain)

Le Réseau Périnatal Lorrain est né officiellement le 25 juin 2001. Ce travail de présentation retrace les étapes nationales et régionales de cette naissance. L organisation sanitaire en réseau, dans ses enjeux, son cadre d application pratique et législatif, est initialement présentée dans une démarche de Santé Publique. Un historique de la Périnatalité en France permet ensuite de dégager les différentes politiques finalisées de périnatalité au cours des soixante dernières années. Ce travail aboutit à la constitution et la présentation des réseaux de soins et de santé en périnatalité, dans le cadre législatif actuel, mais aussi avec les interrogations qui les accompagnent. Le Réseau Périnatal Lorrain s est construit à partir d orientations nationales et sur les données épidémiologiques propres à la Région Lorraine. Il est fait état de l organisation et du mode de fonctionnement actuel du Réseau Périnatal Lorrain, mais aussi des perspectives et des projets à venirNANCY1-SCD Medecine (545472101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Retour à domicile du prématuré (rôle du médecin généraliste)

NANCY1-SCD Medecine (545472101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF