Syntheses, characterization, and DNA binding studies of a series of copper(II), nickel(II), platinum(II) and zinc(II) complexes derived from Schiff base ligand

Three seriesof metalsalophencomplexesderivedfromZn2+,Cu2+, Pt2+and Ni2+havebeensynthesizedand their interaction with quadruplex DNA has been evaluated. The compounds differ on the number of ethylpiperidinesubstituents.They have been characterized by 1H NMR, IR and UV-visible spectroscopies and by HR-masss pectrometry.Their luminescent properties have been also evaluated and we can observe that, as expected,Zn2+and Pt2+complexesare those displaying more interesting luminescence with an emission band red-shifted with respect to the corresponding uncoordinated ligand. DNAinteractionswithG4 and duplex DNA were evaluated by FRET melting assays(for the Zn2+, Cu2+and Ni2+complexes)and by emission titrations(for one Pt2+complex)which indicated that the disubstitutedcompounds2-Niand2-Ptare the only onesthat display good affinityfor G4 DNAstructure

Erratum to: Cross section measurements of 155,157Gd(n, γ) induced by thermal and epithermal neutrons

After publication of the paper, the authors noticed some errors in the list of authors and in the list of affiliations. Their correct version is given in this erratum

Radiative Neutron Capture Cross-Section Measurement of Ge Isotopes at n_TOF CERN Facility and Its Importance for Stellar Nucleosynthesis

This work was supported by the Austrian Science Fund FWF (J3503), the Adolf Messer Foundation (Germany), the UK Science and Facilities Council (ST/M006085/1), and the European Research Council ERC-2015-StG No. 677497. We also acknowledge the support of the National Science Centre, Poland, under the grant UMO-2016/22/M/ST2/00183, the MSMT of the Czech Republic and the Croatian Science Foundation under the project IP-2018-01-8570.This manuscript summarizes the results of radiative neutron capture cross-section measurements on two stable germanium isotopes, Ge-70 and Ge-73. Experiments were performed at the n_TOF facility at CERN via the time-of-flight technique, over a wide neutron energy range, for all stable germanium isotopes (70,72,73,74, and 76). Results for Ge-70 [Phys. Rev. C 100, 045804 (2019)] and Ge-73 [Phys. Lett. B 790, 458 (2019)] are already published. In the field of nuclear structure, such measurements allow to study excited levels close to the neutron binding energy and to obtain information on nuclear properties. In stellar nucleosynthesis research, neutron induced reactions on germanium are of importance for nucleosynthesis in the weak component of the slow neutron capture processes.Austrian Science Fund (FWF) J3503Adolf Messer Foundation (Germany)UK Science and Facilities Council ST/M006085/1European Research Council (ERC)European Commission 677497National Science Centre, Poland UMO-2016/22/M/ST2/00183Ministry of Education, Youth & Sports - Czech RepublicCroatian Science Foundation IP-2018-01-857

Individual and combined effects of chemical and mechanical power on postoperative pulmonary complications: a secondary analysis of the REPEAT study

Introduction: Intra-operative supplemental oxygen and mechanical ventilation expose the lungs to potentially injurious energy. This can be quantified as 'chemical power' and 'mechanical power', respectively. In this study, we sought to determine if intra-operative chemical and mechanical power, individually and/or in combination, are associated with postoperative pulmonary complications. Methods: Using an individual patient data analysis of three randomised clinical trials of intra-operative ventilation, we summarised intra-operative chemical and mechanical power using time-weighted averages. We evaluated the association between intra-operative chemical and mechanical power and a collapsed composite of postoperative pulmonary complications using multivariable logistic regression to estimate the odds ratios related to the effect of 1 J.min-1 increase in chemical or mechanical power with adjustment for demographic and intra-operative characteristics. We also included an interaction term to assess for potential synergistic effects of chemical and mechanical power on postoperative pulmonary complications. Results: Of 3837 patients recruited to three individual trials, 2492 with full datasets were included in the analysis. Intra-operative time-weighted average (SD) chemical power was 10.2 (3.9) J.min-1 and mechanical power was 10.5 (4.4) J.min-1. An increase of 1 J.min-1 in chemical power was associated with 8% higher odds of postoperative pulmonary complications (OR 1.08, 95%CI 1.05-1.10, p < 0.001), while the same increase in mechanical power raised odds by 5% (OR 1.05, 95%CI 1.02-1.08, p = 0.003). We did not find evidence of a significant interaction between chemical and mechanical power (p = 0.40), suggestive of an additive rather than synergistic effect on postoperative pulmonary complications. Discussion: Both chemical and mechanical power are independently associated with postoperative pulmonary complications. Further work is required to determine causality

Identification et ciblage thérapeutique d'ARNs non-codants et leurs interacteurs protéiques

L'importance des interactions ARN-protéines dans la biologie du cancer a été de plus en plus reconnue au cours des dernières années. Les protéines de liaison à l'ARN (RBP) régulent la maturation, la stabilité et la localisation subcellulaire des transcrits d'ARN, et sont également les moteurs de la fonction des ARN non codants impliqués dans de multiples processus biologiques. En outre, les interactions ARN-RBP sont apparues comme des régulateurs de l'oncogenèse et donc comme des cibles thérapeutiques potentielles.Le long ARN non codant (lncRNA) humain CASC15 a été signalé comme étant dérégulé dans le mélanome métastatique humain. Notre laboratoire a récemment identifié son orthologue chez le poisson zèbre, dont la séquence primaire est peu conservée au cours de l'évolution. À l'aide d'un modèle inductible de cancer de la peau chez le poisson zèbre, qui correspond étroitement au processus humain, nous avons démontré que CASC15 chez le poisson zèbre atténue l'initiation et la progression du mélanome. Ainsi, l'expression de CASC15 humain chez le poisson zèbre mutant pour ce lncRNA permet le sauvetage du phénotype de progression du mélanome. Nous supposons que chez les deux orthologues, les mêmes interactions ARN-RBPs expliquent leur conservation fonctionnelle. Dans mon premier projet, j'ai étudié le mécanisme d'action moléculaire de CASC15 dans une lignée cellulaire humaine. Comme pour le poisson zèbre, la délétion de CASC15 dans les cellules de mélanome humain accélère leur migration. De plus, en combinant différentes approches moléculaires et biochimiques, j'ai identifié un ensemble d'interacteurs protéiques commun chez les orthologues de CASC15 qui conduisent à leur conservation fonctionnelle. Ces résultats mettent en lumière la relation entre le mécanisme d'action et la compatibilité fonctionnelle entre les lncRNA de différentes espèces animales divergentes au niveau de leur séquence.En parallèle, j'ai également étudié YTHDF2, une RBP impliquée dans de multiples cancers humains. Cette protéine reconnaît une marque de méthylation présente dans des transcrits d'ARN spécifiques qui régule leur stabilité. La délétion de YTHDF2 empêche l’apparition et le développement de la leucémie aiguë myéloïde tout en préservant l'hématopoïèse normale in vivo. En raison de cette spécificité cancéreuse, YTHDF2 est apparu comme une cible thérapeutique unique. Cependant, l'identification de petites molécules qui ciblent les interactions ARN-RBPs dans les cellules est actuellement limitée par l'absence de méthodes de criblage non biaisées. Dans mon deuxième projet, j'ai adapté notre technologie d'interaction ARN-RBPs à une plateforme de criblage de médicaments. J'ai identifié plusieurs composés approuvés par la FDA qui inhibent spécifiquement la liaison de YTHDF2 à ses ARN cibles et j'ai établi la procédure pour contrôler la spécificité des résultats identifiés. Afin de trouver de nouvelles molécules, j'ai appliqué un crible computationnel basé sur les ligands identifiés ainsi que des fragments de ces derniers. L’ensemble de ce travail démontre que la protéine YTHDF2 peut être traitée par des médicaments et corrobore la fiabilité de notre méthode pour l'identification d'inhibiteurs ciblant des interactions ARN-RBPs spécifiques.En conclusion, j'ai établi des modèles in vivo, des systèmes cellulaires et des outils moléculaires robustes, menant à l'identification et au ciblage d'interactions fonctionnelles ARN-RBPs ayant des rôles cruciaux dans les cancers humains.The importance of RNA-protein interactions in cancer biology has been increasingly acknowledged in the past years. RNA-binding proteins (RBPs) regulate the maturation, stability, and subcellular localization of RNA transcripts. RBPs are also the drivers of the function of long non-coding RNAs implicated in multiple biological processes. In addition, RNA-RBP interactions have arisen as regulators of tumorigenesis and therefore as potential therapeutic targets.The human long non-coding RNA (lncRNA) CASC15 has been reported to be dysregulated in human metastatic melanoma. Our laboratory recently identified its zebrafish ortholog, whose primary sequence is poorly conserved throughout evolution. Using an inducible zebrafish skin cancer model that closely parallels the human process, we demonstrated that the zebrafish casc15 attenuates melanoma initiation and progression. Importantly, the expression of human CASC15 in the zebrafish lncRNA mutant rescued the melanoma progression phenotype. We hypothesized that the same RBP interactions in both orthologous transcripts underlie their functional conservation. In my first project, I investigated the molecular mechanism of action of CASC15 in a human cell line. Similar to zebrafish, the depletion of CASC15 in human melanoma cells mutant increases their migration behavior. In addition, by combining different molecular and biochemical approaches, I identified a common set of functional protein interactors that drive the functional conservation of CASC15 orthologs. These findings shed light on the relationship between mechanism of action and functional compatibility between lncRNA from different animal species divergent in sequence.In parallel, I also studied YTHDF2, an important RBP implicated in multiple human cancers. This protein recognizes an abundant methylation mark present in specific RNA transcripts and regulates their stability. YTHDF2 knockout compromises leukemic stem cells while preserving normal hematopoiesis in vivo. Because of this cancer-specificity property, YTHDF2 has emerged as a unique therapeutic target. However, the identification of small molecules that target RNA-protein interactions in cell is currently limited by the absence of unbiased scalable screening methods. In my second project, I have adapted our RNA-protein interaction technology to a drug screening platform. I identified several FDA-approved compounds that specifically inhibit YTHDF2 binding to its target RNAs and established the pipeline to control for the specificity of the identified hits. In order to find novel small molecule inhibitors, I expanded the collection of tested drugs by following a ligand-based computational screen as well as including fragments of the hit compounds. In conclusion, this work demonstrates that YTHDF2 protein is druggable and corroborates the reliability of our method to be used for the identification of inhibitors targeting specific RNA-protein interactions.Together, I have established in vivo models, cellular systems, and robust molecular tools, leading to the identification and targeting of functional RNA-RBP interactions with crucial roles in human cancers

Viaje de los padres misioneros del convento del Cuzco a las tribus salvajes de los campas, piros, cunibos y sipibos en el año de 1874,

Mode of access: Internet

B-4 Greenhouse Emissions from Tofu Production

Background: Tofu is perceived as healthy and ecofriendly protein-rich food, but little is known about the carbon footprint generated by this soy product. Objectives: The purpose of this study was to evaluate the emissions of greenhouse gases (GHG) generated by the production of tofu. Methods: We performed a life cycle assessment (LCA) to calculate the greenhouse gases emissions (GHG) generated by tofu using SimaPro 7. Our LCA calculations include materials and energy inputs required to produce tofu: whole soybeans, water, electricity, natural gas, transportation and packaging materials. The functional unit: 1 kg of tofu. The boundary is from cradle to factory gate. Results: The total GHG emissions per one kilogram of tofu produced are 893 g of CO2eq. Monte Carlo simulations shows that the CO2eq estimation is robust. The GHG emissions are mainly generated by whole soybeans (50%), natural gas (27%), packaging (13%), transportation (6%) and electricity (4%). Conclusion: Tofu is a protein rich food that generates relatively low GHG emissions when compared to protein-rich animal foods. Tofu generates 22 to 34 times less greenhouse gas emissions than beef products. Thus, tofu is a suitable food to consume by people who intend to reduce their carbon footprint by dietary choices

Una anàlisi comparativa de la despesa militar espanyola en el molt llarg termini (1850-2009)

Military spending has been one of the main budgetary priorities in Spain throughout most of the contemporary period. In this article, the authors present, firstly, a series of Spanish military expenditure from 1850 to the present day as the basis for a long-term comparative analysis of fiscal measures of military implication used by the Spanish State; this is followed by the application of an econometric model to provide an overview of the factors that have affected military expenditure and their consequences in economic terms.RESUMEl finançament de la institució militar ha estat una de les principals prioritats pressupostàries de l’Estat espanyol durant bona part de l’etapa contemporània. En les pàgines que segueixen a continuació es presenta, en primer lloc, una sèrie de despesa militar espanyola des de 1850 fins a l’actualitat amb l’objectiu d’analitzar l’esforç fiscal de l’Estat espanyol en l’àmbit militar en el llarg termini des d’una perspectiva comparada; en segon lloc, es realitza, mitjançant l’aplicació de la metodologia economètrica, una primera aproximació als condicionants d’aquesta despesa i a les seves conseqüències a nivell econòmic.RESUMENLa financiación de la institución militar ha sido una de las principales prioridades presupuestarias del estado español durante buena parte de la etapa contemporánea. En las páginas que siguen se presenta, en primer lugar, una serie de gasto militar español desde 1850 hasta la actualidad con el objetivo de analizar el esfuerzo fiscal del estado español en el ámbito militar en el largo plazo desde una perspectiva comparada; en según lugar, se realiza, mediante la aplicación de la metodología econométrica, una primera aproximación a los condicionantesde este gasto y a sus consecuencias a nivel económico