Reusable oxidation catalysis using metal-monocatecholato species in a robust metal-organic framework.

An isolated metal-monocatecholato moiety has been achieved in a highly robust metal-organic framework (MOF) by two fundamentally different postsynthetic strategies: postsynthetic deprotection (PSD) and postsynthetic exchange (PSE). Compared with PSD, PSE proved to be a more facile and efficient functionalization approach to access MOFs that could not be directly synthesized under solvothermal conditions. Metalation of the catechol functionality residing in the MOFs resulted in unprecedented Fe-monocatecholato and Cr-monocatecholato species, which were characterized by X-ray absorption spectroscopy, X-band electron paramagnetic resonance spectroscopy, and (57)Fe Mössbauer spectroscopy. The resulting materials are among the first examples of Zr(IV)-based UiO MOFs (UiO = University of Oslo) with coordinatively unsaturated active metal centers. Importantly, the Cr-metalated MOFs are active and efficient catalysts for the oxidation of alcohols to ketones using a wide range of substrates. Catalysis could be achieved with very low metal loadings (0.5-1 mol %). Unlike zeolite-supported, Cr-exchange oxidation catalysts, the MOF-based catalysts reported here are completely recyclable and reusable, which may make them attractive catalysts for 'green' chemistry processes

Reductive cleavage of P-4 by iron(I) centres: synthesis and structural characterisation of Fe-2(P-2)(2) complexes with two bridging P-2(2-) ligands

The selective transformation of white phosphorus with a beta-diketiminato iron(I) toluene complex under mild reaction conditions is reported which furnishes a new dinuclear iron(III) Fe-2(P-2)(2) complex with two bridging P-2(2-) ligands. Its reduction with potassium results in the formation of the first delocalised mixed-valent bis-diphosphido iron(II,III) complex which is isostructural with the neutral Fe2P4 precursor

Int J Mol Sci

The placenta is a key organ for fetal and brain development. Its epigenome can be regarded as a biochemical record of the prenatal environment and a potential mechanism of its association with the future health of the fetus. We investigated associations between placental DNA methylation levels and child behavioral and emotional difficulties, assessed at 3 years of age using the Strengths and Difficulties Questionnaire (SDQ) in 441 mother-child dyads from the EDEN cohort. Hypothesis-driven and exploratory analyses (on differentially methylated probes (EWAS) and regions (DMR)) were adjusted for confounders, technical factors, and cell composition estimates, corrected for multiple comparisons, and stratified by child sex. Hypothesis-driven analyses showed an association of cg26703534 () with emotional symptoms, and exploratory analyses identified two probes, cg09126090 (intergenic region) and cg10305789 (), as negatively associated with peer relationship problems, as well as 33 DMRs, mostly positively associated with at least one of the SDQ subscales. Among girls, most associations were seen with emotional difficulties, whereas in boys, DMRs were as much associated with emotional than behavioral difficulties. This study provides the first evidence of associations between placental DNA methylation and child behavioral and emotional difficulties. Our results suggest sex-specific associations and might provide new insights into the mechanisms of neurodevelopment.Exposition prénatale au tabac et à la pollution atmosphérique et effets sur la santé respiratoire et le neurodévelopment de l'enfant: rôle de la méthylation placentaireHorizon 2020 research and innovation programm

Ferritin-Mediated Iron Sequestration Stabilizes Hypoxia-Inducible Factor-1α upon LPS Activation in the Presence of Ample Oxygen

SummaryBoth hypoxic and inflammatory conditions activate transcription factors such as hypoxia-inducible factor (HIF)-1α and nuclear factor (NF)-κB, which play a crucial role in adaptive responses to these challenges. In dendritic cells (DC), lipopolysaccharide (LPS)-induced HIF1α accumulation requires NF-κB signaling and promotes inflammatory DC function. The mechanisms that drive LPS-induced HIF1α accumulation under normoxia are unclear. Here, we demonstrate that LPS inhibits prolyl hydroxylase domain enzyme (PHD) activity and thereby blocks HIF1α degradation. Of note, LPS-induced PHD inhibition was neither due to cosubstrate depletion (oxygen or α-ketoglutarate) nor due to increased levels of reactive oxygen species, fumarate, and succinate. Instead, LPS inhibited PHD activity through NF-κB-mediated induction of the iron storage protein ferritin and subsequent decrease of intracellular available iron, a critical cofactor of PHD. Thus, hypoxia and LPS both induce HIF1α accumulation via PHD inhibition but deploy distinct molecular mechanisms (lack of cosubstrate oxygen versus deprivation of co-factor iron)

Inroads to Predict in Vivo Toxicology—An Introduction to the eTOX Project

There is a widespread awareness that the wealth of preclinical toxicity data that the pharmaceutical industry has generated in recent decades is not exploited as efficiently as it could be. Enhanced data availability for compound comparison (“read-across”), or for data mining to build predictive tools, should lead to a more efficient drug development process and contribute to the reduction of animal use (3Rs principle). In order to achieve these goals, a consortium approach, grouping numbers of relevant partners, is required. The eTOX (“electronic toxicity”) consortium represents such a project and is a public-private partnership within the framework of the European Innovative Medicines Initiative (IMI). The project aims at the development of in silico prediction systems for organ and in vivo toxicity. The backbone of the project will be a database consisting of preclinical toxicity data for drug compounds or candidates extracted from previously unpublished, legacy reports from thirteen European and European operation-based pharmaceutical companies. The database will be enhanced by incorporation of publically available, high quality toxicology data. Seven academic institutes and five small-to-medium size enterprises (SMEs) contribute with their expertise in data gathering, database curation, data mining, chemoinformatics and predictive systems development. The outcome of the project will be a predictive system contributing to early potential hazard identification and risk assessment during the drug development process. The concept and strategy of the eTOX project is described here, together with current achievements and future deliverables

DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

Peer reviewe

Distal Femoral Cortical Irregularity at Knee MRI: Increased Prevalence in Youth Competitive Alpine Skiers

Background Tumor-like cortical irregularities at the posterior distal femur are common incidental findings in adolescents, but the origin of these irregularities is debated. Purpose To compare the prevalence of distal femoral cortical irregularities (DFCIs) at different tendon attachment sites in youth competitive alpine skiers with that in young adults. Materials and Methods In this secondary analysis of a prospective trial, unenhanced 3-T knee MRI scans obtained in youth competitive alpine skiers were compared with images in control participants of the same age from 2014 to 2019 (Cantonal Ethics Committee Zurich registry number: KEK-ZH-2017-01395) for presence of DFCIs at the femoral attachment of the medial head of the gastrocnemius muscle (MHG) and/or lateral head of the gastrocnemius muscle (LHG) and adductor magnus tendon by two radiologists. DFCI size and tendon attachment position were measured. Tendon attachment position and associated MRI findings (meniscus, cartilage, bone marrow edema, joint effusion, ligaments, tendons) were examined for an association with DFCI. Pearson χ$^{2}$, Student t test, logistic regression, and κ statistics were applied. Results Unilateral knee MRI scans obtained in 105 skiers (mean age, 14.8 years ± 0.6 [standard deviation]; 66 boys) and in 105 control participants (mean age, 14.6 years ± 0.5; 59 boys) were evaluated. DFCIs were found in 61 of 105 skiers (58%; 95% confidence interval [CI]: 48.5%, 67.2%) compared with 28 of 105 control participants (27%; 95% CI: 18.9%, 35.7%) (P < .001). Two skiers had more than one DFCI. Distribution of DFCIs for skiers and control participants was 60 of 63 (95.2%) and 26 of 28 (92.8%) at the MHG, three of 63 (4.8%) and one of 28 (3.6%) at the LHG, and zero of 63 (0%) and one of 28 (3.6%) at the adductor magnus attachment site, respectively. Interreader agreement was almost perfect (κ = 0.87; 95% CI: 0.80, 0.93). The mean size of MHG-related DFCIs in skiers (3.7 mm) was not different compared to the size of those in control participants (3.4 mm) (P = .32), nor was a difference found for the MHG tendon attachment position in knees with DFCI (63.9 mm vs 63.0 mm, P = .83) or without DFCI (63.6 mm vs 62.8 mm, P = .86). Regarding associated MRI findings, increased signal intensity of the MHG tendon showed a significant association with MHG-related DFCI in both groups (P = .01 for both). Conclusion A distal femoral cortical irregularity at the attachment sites of tendons was a frequent incidental finding on knee MRI scans, with an increased prevalence in youth competitive alpine skiers. © RSNA, 2020 Online supplemental material is available for this article

AN INTERNATIONAL APPROACH TO ASSESSMENT ANDFEEDBACK WITHIN COLLABORATIVE DIGITAL MEDIA PROJECTS

BackgroundThe Intercultural Design Camp (ICDC) is a collaboration between the Schools of Creative Practice offour European higher education institutions: Linköping University, Sweden; The University of the Westof Scotland; Stuttgart Media University, Germany and Artevelde University College Ghent, Belgium.Emerging from the development of a joint post-graduate proposal, the ICDC project has grown. Pilotedin 2009 in Muensingen, Germany as a one-week summer school, the focus of the project wasintended to strengthen internalization between the students and staff of the partner Universities.Working to a given theme, and collaborative creative briefs, student participants developed andproduced multimedia solutions and artefacts [1].This pilot was very successful and acted as a catalyst to staff and student Erasmus exchange and thesharing of best practice in Learning, Teaching and Assessment between the partners. A second selffunded‘pilot’ camp was planned and undertaken in Dumfries, Scotland in 2010. Discussions continuedregarding the extension of the ICDC project to become a two-week event in order to allow studentparticipants the time to develop and produce an extended piece of cross-media product [1].The cost for realizing an extended concept would be high. An application for funding within the EULife-Long-Learning-Programme was successfully made. A third, this time EU funded Design Camptook place in Grebbestad (Sweden) in August 2011 [2]. Further EU funding allowed realizing a fourthICDC in Kemmel, Belgium, August 2012.Learning Teaching, Assessment and FeedbackThe content of the ICDC is designed to extend and further the student’s abilities and participation incontemporary methods and practices associated with creative media practice and convergentproduction. At the camp, and in response to given thematic briefs, an International group of studentswith divergent backgrounds and skill-sets, come together in small creative teams to develop andproduce a collaborative project in which a range of ideas, experience and technologies converge.These Collaborative Projects often have an on-line output, whether through products devised forstreaming, pod-casting or interactive broadcast. An innovative variety of projects are encouraged.These could include digital photography and the moving image, interactive design and performance,site-specific installations and exhibitions.Students are also encouraged to experience contemporary creative context within the areas ofpractice while at the camp. This is delivered via lectures given by the visiting and host staff. Studentsare also encouraged to evaluate the benefits of a variety of production approaches and techniques.The project addresses the interface between research and practice in creative media practice andencourages participants to gain solid experience of working in interdisciplinary creative teams.With every run of the Intercultural Design Camp the objectives and expectations have been raised. Inthe first run, as already mentioned, the main intention was to bring together students and teachersfrom different European Countries to work and live together in order to foster the internationalization.The second run had mainly the same approach but the intensiveness of the experience has beenincreased by strengthen the aspect of cooperative international work. The focus of the third camp wason the one hand to switch from solely conceptual work to additional productive activities and on theother hand to incorporate internet-based international cooperation prior to the camp. Therefore theVirtual Learning Environment (VLE) Moodle has been chosen as base tool and first experiences havebeen gained through the Grebbestad camp [2]. Generally the intensification of the digital cooperation in the preliminary stage of the camp and particularly the integration of the camp into the studentrecords have been the main aspects of this years’ Intercultural Design Camp. To give frequent andhelpful feedback to the students and to assess their work at the end of the camp are the crucialaspects in this respect, but doing this with international groups from quite different educational andcultural systems and also different grading systems is a quite challenging task.Intercultural Designcamp (ICDC