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Drosophila melanogaster is an important model for antiviral immunity in arthropods, but very few DNA viruses have been described from the family Drosophilidae. This deficiency limits our opportunity to use natural host-pathogen combinations in experimental studies, and may bias our understanding of the Drosophila virome. Here, we report fourteen DNA viruses detected in a metagenomic analysis of 6668 pool-sequenced Drosophila, sampled from forty-seven European locations between 2014 and 2016. These include three new nudiviruses, a new and divergent entomopoxvirus, a virus related to Leptopilina boulardi filamentous virus, and a virus related to Musca domestica salivary gland hypertrophy virus. We also find an endogenous genomic copy of galbut virus, a double-stranded RNA partitivirus, segregating at very low frequency. Remarkably, we find that Drosophila Vesanto virus, a small DNA virus previously described as a bidnavirus, may be composed of up to twelve segments and thus represent a new lineage of segmented DNA viruses. Two of the DNA viruses, Drosophila Kallithea nudivirus and Drosophila Vesanto virus are relatively common, found in 2 per cent or more of wild flies. The others are rare, with many likely to be represented by a single infected fly. We find that virus prevalence in Europe reflects the prevalence seen in publicly available datasets, with Drosophila Kallithea nudivirus and Drosophila Vesanto virus the only ones commonly detectable in public data from wild-caught flies and large population cages, and the other viruses being rare or absent. These analyses suggest that DNA viruses are at lower prevalence than RNA viruses in D.melanogaster, and may be less likely to persist in laboratory cultures. Our findings go some way to redressing an earlier bias toward RNA virus studies in Drosophila, and lay the foundation needed to harness the power of Drosophila as a model system for the study of DNA viruses., M.W. was supported by the UK Natural Environmental Research Council through the E3 doctoral training programme (NE/L002558/1), and S.R. was supported by Wellcome Trust PhD programme (108905/Z/15/Z). A.B. received funding from BBSRC (grant number BB/P00685X/1). T.F. received funding from Swiss National Science Foundation (grant numbers 31003A-182262, PP00P3_165836, and PP00P3_133641/1). C.G. received funding from Agence Nationale de la Recherche (grant number ANR-15-CE32-0011-01). J.G. received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (H2020-ERC-2014-CoG-647900) and from the Fundación Española para la Ciencia y la Tecnologia-Ministerio de Economía y Competitividad (FCT-15-10187). S.G. received funding from Deutsche Forschungsgemeinschaft (grant number GR 4495/2). M.K. received funding from Academy of Finland projects (268214 and 322980). M.K. received funding from Austrian Science Fund (FWF; grant number P32275). V.L. received funding from Danish Research council for natural Sciences (FNU; grant number 4002-00113B). B.S.O. received funding from the Scientific and Technological Research Council of Turkey (TUBITAK; grant number 214Z238). J.P. received funding from Deutsche Forschungsgemeinschaft (grant number PA 903/8). M.S.-R., M.S.V., and M.J. received funding from the Ministry of Education, Science and Technological Development of the Republic of Serbia (grant number 451-03-68/2020-14/200178). F.S. received funding from Deutsche Forschungsgemeinschaft (grant number STA1154/4-1; Projektnummer 408908608). M.T., A.P., and K.E. received funding from the Ministry of Education, Science and Technological Development of the Republic of Serbia (grant number 451-03-68/2020-14/200007). The DrosEU consortium has been funded by a Special Topics Network (STN) grant by the European Society of Evolutionary Biology (ESEB).

International audience; Silicon-mediated fluoride abstraction is demonstrated as a means of generating the first fluorido-cyanido transition metal complexes. This new synthetic approach is exemplified by the synthesis and characterization of the heteroleptic complexes, trans-[M IV F 4 (CN) 2 ] 2À (M = Re, Os), obtained from their homoleptic [M IV F 6 ] 2À parents. As shown by combined high-field electron paramagnetic resonance spectroscopy and magnetization measurements, the partial substitution of fluoride by cyanide ligands leads to a marked increase in the magnetic anisotropy of trans-[ReF 4 (CN) 2 ] 2À as compared to [ReF 6 ] 2À , reflecting the severe departure from an ideal octahedral (O h point group) ligand field. This methodology paves the way toward the realization of new heteroleptic transition metal complexes that may be used as highly anisotropic building-blocks for the design of high-performance molecule-based magnetic materials.

International audience; Following our recent work on the first crystallographically characterized coordination polymers based on tricobalt extended metal atom chains (EMACs), namely, [Co3(dpa)4MF6]·2DMF [M = ZrIV (1), SnIV (2), and ReIV (3); Hdpa = 2,2′-dipyridylamine; DMF = N,N′-dimethylformamide], we have generalized our synthetic approach based on robust fluoride complexes to prepare new self-assembled one-dimensional (1D) polymers formed by [Co3(dpa)4]2+ and 5d [MF6]2– [M = IrIV (4) and OsIV (5)] building blocks. These 1D complexes are isostructural and crystallize in the P4/ncc space group such that the fourfold axis is coincident with the metal axes of the rigorously linear chains. Magnetic studies reveal ferromagnetic coupling between the S = 1/2 {Co3} and [MF6]2– units in 3 and 4, whereas the nonmagnetic [MF6]2– linkers of 1 and 5 mediate antiferromagnetic coupling between the {Co3} spins. For 2, no significant exchange coupling was observed. Spin-crossover behavior, which was observed for the parent [Co3(dpa)4Cl2] complex, was not detected for 1–5 up to 300 K. This work demonstrates that EMACs and [MF6]2– complexes can be considered as appealing building blocks for the design of new functional coordination networks.

International audience; Microarrays are powerful tools for high throughput analysis, and hundreds or thousands of molecular interactions can be assessed simultaneously using very small amounts of analytes. Nucleotide microarrays are well established in plant research, but carbohydrate microarrays are much less established, and one reason for this is a lack of suitable glycans with which to populate arrays. Polysaccharide microarrays are relatively easy to produce because of the ease of immobilizing large polymers noncovalently onto a variety of microarray surfaces, but they lack analytical resolution because polysaccharides often contain multiple distinct carbohydrate substructures. Microarrays of defined oligosaccharides potentially overcome this problem but are harder to produce because oligosaccharides usually require coupling prior to immobilization. We have assembled a library of well characterized plant oligosaccharides produced either by partial hydrolysis from polysaccharides or by de novo chemical synthesis. Once coupled to protein, these neoglycoconjugates are versatile reagents that can be printed as microarrays onto a variety of slide types and membranes. We show that these microarrays are suitable for the high throughput characterization of the recognition capabilities of monoclonal antibodies, carbohydrate-binding modules, and other oligosaccharide-binding proteins of biological significance and also that they have potential for the characterization of carbohydrate-active enzymes.

Information about the effects of phthalates and non-phthalate substitute cyclohexane-1,2-dicarboxylic acid diisononyl ester (HEXAMOLL (R) DINCH) on children's neurodevelopment is limited. The aim of the present research is to evaluate the association between phthalate /HEXAMOLL (R) DINCH exposure and child neurodevelopment in three European cohorts involved in HBM4EU Aligned Studies. Participating subjects were school-aged children belonging to the Northern Adriatic cohort II (NAC-II), Italy, Odense Child Cohort (OCC), Denmark, and PCB cohort, Slovakia. In each cohort, children's neurodevelopment was assessed through the Full-Scale Intelligence Quotient score (FSIQ) of the Wechsler Intelligence Scale of Children test using three different editions. The children's urine samples, collected for one point in time concurrently with the neurodevelopmental evaluation, were analyzed for several phthalates/HEXAMOLL (R) DINCH biomarkers. The relation between phthalates/HEXAMOLL (R) DINCH and FSIQ was explored by applying separate multiple linear regressions in each cohort. The means and standard deviations of FSIQ were 109 +/- 11 (NAC-II), 98 +/- 12 (OCC), and 81 +/- 15 (PCB cohort). In NAC-II, direct associations between FSIQ and DEHP's biomarkers were found: 50H-MEHP+5oxo-MEHP ((3 = 2.56; 95% CI 0.58-4.55; N = 270), 50H-MEHP+5cx-MEPP (beta = 2.48; 95% CI 0.47-4.49; N = 270) and 5OH-MEHP (beta = 2.58; 95% CI 0.65-4.51; N = 270). On the contrary, in the OCC the relation between DEHP's biomarkers and FSIQ tended to be inverse but imprecise (p-value >= 0.10). No associations were found in the PCB cohort. FSIQ was not associated with HEXAMOLL (R) DINCH in any cohort. In conclusion, these results do not provide evidence of an association between concurrent phthalate/DINCHHEXAMOLLR DINCH exposure and IQ in children., European Commission 733032 European Union through its Sixth Framework Program for RTD FOOD-CT-2006-016253, Institute for Maternal and Child Health IRCCS "Burlo Garofolo", Trieste, Italy (Ministry of Health-Italy) RC 12/12, CROME LIFE Project "Cross-Mediterranean Environment and Health Network" LIFE12 ENV/GR/001040, Odense University Hospital, Denmark, University of Southern Denmark Mental Health Service of the Region of Southern Denmark Odense Patient data Exploratory Network (OPEN), Denmark Danish Center for Hormone Disrupting Chemicals MST-611-00012, Det Frie Forskningsrad (DFF) 4004-00352B_FSS, Novo Nordisk Foundation NNF19OC0058266 NNF17OC0029404, Sygeforsikring Danmark 2021-0173, Odense University Hospital, Helsefonden Beckettfonden, Danish Mental Health Fund, Health Insurance Denmark, Velux Fonden, Slovak Research and Development Agency APVV-0571-12, Ministry of Health of the Slovak Republic 2014/47-SZU-11, Region of Southern Denmark, The Municipality of Odense, Denmark, Rigshospitalet

The Ca2+-sensor protein calmodulin (CaM) is a major regulator of multiple cell functions. A unique and puzzling feature of human, and all so far investigated mammals, is the presence of three distinct CaM genes on different chromosomes, which code for identical proteins. How this case of apparent genetic redundancy evolved and why it could be to the advantage of the mammalian organisms is not well established. With a main focus on humans, this article aims to review existing literature addressing how the genes nonetheless differ in function. Clearly, the three CaM genes are differentially expressed in different tissues, during development, in response to different stimuli, and other factors including environmental conditions. As shown in hippocampal neurons, different mRNAs from the CAM genes may even localize differently within the same cell. Regulation of CaM gene expression is achieved by a variety of regulatory elements present in the three genes, including different promotor/insulator elements and 3′- and 5′-noncoding regions differing in length and sequence, as well as regulation by epigenetic factors and miRNAs. Here, we hypothesize that predicted differences in mRNA stability and translational efficiency due to divergent codon usage could play an additional regulatory role as the three genes differ markedly in their use of synonymous codons. CALM3, predicted to produce a relatively stable mRNA may be important where the transcription level is low or transiently absent, e.g. during spermatogenesis. In contrast, CALM2 with a predicted much shorter mRNA half-life, may provide better temporal control of CaM levels. Deciphering the underlying mechanisms responsible for all this complexity may help to understand why this unique multigenic arrangement may be an advantage for the optimal spatio-temporal expression of CaM in higher eukaryotes. Finally, we discuss the expression of the CaM genes in selected human pathologies, and how mutations in these genes are responsible for the appearance of serious congenital syndromes, mainly affecting the heart, and although less known, possibly also affecting the functionality of the central nervous system and other organs. Danish Research Council DFF-4004-00560 Ministerio de Ciencia e Innovación PID2019-103850GB-I00

The European Human Biomonitoring Initiative (HBM4EU) assessed human biomonitoring data on phthalates in children and adolescents, that were sampled between 2014 and 2021, in a harmonised way. These so-called “HBM4EU Aligned Studies” revealed that almost all children and adolescents were exposed to multiple phthalates concurrently. Some phthalates have been shown to act in a dose-additive manner, thus, a mixture risk assessment is warranted. In our study, we determine the risk from combined exposure to five anti-androgenic phthalates, namely DEHP, DiBP, DnBP, BBzP and DiNP by making use of the hazard index (HI) approach. Toxicologically-based human biomonitoring guidance values (HBM-GVs) derived within the framework of HBM4EU served as basis. Our results show that exposures of 17% of children and adolescents from twelve European countries resulted in hazard indices (HI) > 1 with an HI of 1.77 at the 95th percentile (geometric mean, GM = 0.44). Main drivers for the mixture risk are DnBP and DiBP. Generalized Linear Model (GLM) analysis including four major exposure determinants (age, sex, European region, sampling year) simultaneously reveal differences for the European regions and between sampling years. Children and adolescents living in the Eastern region of Europe have on average, higher HIs (GM=0.58) than in the Southern region (GM = 0.36) and Western region (GM = 0.42). Moreover, participants from which urine samples were taken in the earlier years (2014–2016) seem to have higher average HI levels than participants from studies with later sampling periods. Strikingly, the majority (63%) of participants with HIs > 1 would have gone unnoticed in single substance risk assessments as individual phthalates levels were below corresponding HBM-GVs. Thus, our results underline the importance of mixture risk assessment approaches to adequately address risks from concurrent chemical exposure. The HBM4EU project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 733032 and received co-funding from the author’s organizations. GerES V received funding by the German Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection. The Norwegian Institute of Public Health (NIPH) has contributed to funding of the NEB II. The laboratory measurements have partly been funded by the Research Council of Norway through research projects (275903 and 268465). The Slovenian SLO-CRP study was cofinanced by the Jozef Stefan Institute program P1-0143, and a national project “Exposure of children and adolescents to selected chemicals through their habitat environment” (grant agreement No. C2715-16-634802). BEA study was co-funded by the Spanish Ministry of Agriculture, Fisheries and Food and the Insituto de Salud Carlos III (SEG 1321/15). CROME study is co-funded by the European Commission research funds of Horizon 2020 (LIFE12 ENV/GR/001040). InAirQ is cofunded by Interreg CENTRAL EUROPE and the National Public Health Center, Hungary. ESTEBAN received funding by the Santé Public France and the French ministries of Health and the Environment. PCB cohort follow-up was funded by the Slovak Ministry of Health and the Slovak Research and Development Agency (project no PVV-0571-1). SPECIMEn-NL study was funded under the HBM4EU project. 3xG received cofunding from NIRAS, STORA and MONA. FLEHS IV was co-financed dby the Government of Flanders, Department of Environment & Spatial development. The CELSPAC studies are supported by the MEYS (LM2018121, CZ.02.1.01/0.0/0.0/17_043/0009632 and CZ.02.1.01/0.0/0.0/15_003/0000469) and from the European Union’s Horizon 2020 research and innovation programme under grant agreement (857560). The OCC studies was supported by Odense University Hospital, Denmark, the Region of Southern Denmark, The Municipality of Odense, Denmark, The University of Southern Denmark, Odense Patient data Exploratory Network (OPEN), Denmark, The Danish Center for Hormone Disrupting Chemicals (MST-611-00012), The Danish Research Council (4004-00352B_FSS), Novo Nordisk Foundation, Denmark (grant no. NNF19OC0058266 and NNF17OC0029404), HBM4EU, EU Horizon 2020 (grant no. 733032). Sí

17 pags., 4 figs., 2 tabs., Sea ice plays a pivotal role in Earth's climate and its past reconstruction is crucial to investigate the connections and feedbacks with the other components of the climate system. Among the available archives that store information of past sea ice are marine and ice cores. Recent studies on the IP biomarker extracted from marine sediments has shown great skill to infer past changes of Arctic sea ice. In ice matrixes, sodium, bromine and iodine have shown potential to store the fingerprint of sea ice presence. The development of an unambiguous sea ice proxy from ice cores, however, has proven to be a challenging task especially in the Arctic realm. In this work we analyze the sodium, bromine and iodine records in the RECAP ice core, coastal eastern Greenland, to investigate the sea ice variability in the northern North Atlantic Ocean through the last 11,000 years of the current interglacial, i.e. the Holocene. We compare the RECAP records with marine sea ice proxy records available from the northern North Atlantic. We suggest that RECAP sodium concentrations can be associated with variability of sea ice extent, while the bromine-to-sodium ratios and iodine are associated respectively with seasonal sea ice and bioproductivity from open ocean and fresh sea ice surfaces. According to our interpretation, we find that sea ice was at its lowest extent and seasonal in nature during the early Holocene in all regions of the North Atlantic. Increasing sea ice signals are seen from ca. 8–9 ka b2k, in line with long-term Holocene cooling. The increasing sea ice trend appears uninterrupted in the Fram Strait and North Iceland while reaching a maximum ca. 5 ka b2k in the East Greenland region. Sea ice modifications during the last 5000 years display great variability in East Greenland with intermediate conditions between the early and mid Holocene, possibly associated with local fjord dynamics. The last sea ice maximum was reached across all regions 1000 years b2k., The RECAP ice coring effort was financed by the Danish Research Council through a Sapere Aude grant, the NSF through the Division of Polar Programs, the Alfred Wegener Institute, and the European Research Council under the European Community's Seventh Framework Programme (FP7/2007e2013)/ERC grant agreement The RECAP ice coring effort was financed by the Danish Research Council through a Sapere Aude grant, the NSF through the Division of Polar Programs, the Alfred Wegener Institute, and the European Research Council under the European Community's Seventh Framework Programme (FP7/2007e2013)/ERC grant agreement 610055 through the Ice2Ice project. Additional funding support for the paper has been provided by the Centre for Climate Dynamics at the Bjerknes Centre. through the Ice2Ice project. Additional funding support for the paper has been provided by the Centre for Climate Dynamics at the Bjerknes Centre.

A digraph is eulerian if it is connected and every vertex has its in-degree equal to its outdegree. Having a spanning eulerian subdigraph is thus a weakening of having a hamiltonian cycle. In this paper, we first characterize the pairs (D, a) of a semicomplete digraph D and an arc a such that D has a spanning eulerian subdigraph containing a. In particular, we show that if D is 2-arc-strong, then every arc is contained in a spanning eulerian subdigraph. We then characterize the pairs (D, a) of a semicomplete digraph D and an arc a such that D has a spanning eulerian subdigraph avoiding a. In particular, we prove that every 2-arc-strong semicomplete digraph has a spanning eulerian subdigraph avoiding any prescribed arc. We also prove the existence of a (minimum) function f (k) such that every f (k)-arc-strong semicomplete digraph contains a spanning eulerian subdigraph avoiding any prescribed set of k arcs. We conjecture that f (k) = k + 1 and establish this conjecture for k ≤ 3 and when the k arcs that we delete form a forest of stars. A digraph D is eulerian-connected if for any two distinct vertices x, y, the digraph D has a spanning (x, y)-trail. We prove that every 2-arc-strong semicomplete digraph is eulerianconnected. All our results may be seen as arc analogues of well-known results on hamiltonian paths and cycles in semicomplete digraphs.

Tumor vessel co-option is poorly understood, yet it is a resistance mechanism against anti-angiogenic therapy (AAT). The heterogeneity of co-opted endothelial cells (ECs) and pericytes, co-opting cancer and myeloid cells in tumors growing via vessel co-option, has not been investigated at the single-cell level. Here, we use a murine AAT-resistant lung tumor model, in which VEGF-targeting induces vessel co-option for continued growth. Single-cell RNA sequencing (scRNA-seq) of 31,964 cells reveals, unexpectedly, a largely similar transcriptome of co-opted tumor ECs (TECs) and pericytes as their healthy counterparts. Notably, we identify cell types that might contribute to vessel co-option, i.e., an invasive cancer-cell subtype, possibly assisted by a matrix-remodeling macrophage population, and another M1-like macrophage subtype, possibly involved in keeping or rendering vascular cells quiescent. ispartof: CELL REPORTS vol:35 issue:11 ispartof: location:United States status: published

Targeting the protein–protein interaction (PPI) between nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) is a potential therapeutic strategy to control diseases involving oxidative stress. Here, six classes of known small-molecule Keap1–Nrf2 PPI inhibitors were dissected into 77 fragments in a fragment-based deconstruction reconstruction (FBDR) study and tested in four orthogonal assays. This gave 17 fragment hits of which six were shown by X-ray crystallography to bind in the Keap1 Kelch binding pocket. Two hits were merged into compound 8 with a 220–380-fold stronger affinity (Ki = 16 μM) relative to the parent fragments. Systematic optimization resulted in several novel analogues with Ki values of 0.04–0.5 μM, binding modes determined by X-ray crystallography, and enhanced microsomal stability. This demonstrates how FBDR can be used to find new fragment hits, elucidate important ligand–protein interactions, and identify new potent inhibitors of the Keap1–Nrf2 PPI. Targeting the protein-protein interaction (PPI) between nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) is a potential therapeutic strategy to control diseases involving oxidative stress. Here, six classes of known small-molecule Keap1-Nrf2 PPI inhibitors were dissected into 77 fragments in a fragment-based deconstruction reconstruction (FBDR) study and tested in four orthogonal assays. This gave 17 fragment hits of which six were shown by X-ray crystallography to bind in the Keap1 Kelch binding pocket. Two hits were merged into compound 8 with a 220-380-fold stronger affinity (Ki = 16 μM) relative to the parent fragments. Systematic optimization resulted in several novel analogues with Ki values of 0.04-0.5 μM, binding modes determined by X-ray crystallography, and enhanced microsomal stability. This demonstrates how FBDR can be used to find new fragment hits, elucidate important ligand-protein interactions, and identify new potent inhibitors of the Keap1-Nrf2 PPI.

International audience; Background:Pseudomonas syringae are ubiquitous epiphytic plant pathogens infecting a wide range of important agricultural plant species. Bacteriophages has been proposed as biocontrol agents against plant pathogens, however, in order to utilize this approach, a deeper understanding of phage diversity and phage-host interactions is required.Materials and Methods: Phages targeting P. syringae GAW0113 were isolated from organic waste samples. Three distinct phage isolates were purified and subjected to whole-genome sequencing, comparative genomics, transmission electron microscopy and host-range assay using a wide selection of diverse P. syringae isolates.Results: The three phage isolates, Pseudomonas phage Bertil, Misse, and Strit, were shown to have podovirus morphology with a short tail stub and isometric head. They had double-stranded DNA ranging from 41,342 to 41,374 bp in size comprising 50–51 open reading frames. The three phage genomes were highly similar and genomic comparison analyses showed that they all belong to the Autographiviridae family of the order Caudovirales. All three phages were shown to have a narrow host-range.Conclusions: The three phages were shown to share morphological and genomic features with other phages in the Autographiviridae family, however, based on the limited nucleotide similarity we propose that the phages constitute a novel genus. All three phages were found to infect multiple strains of P. syringae covering several phylogroups.

[EN] Several M-type SrFeO nanoparticle samples with different morphologies have been synthesized by different hydrothermal and sol-gel synthesis methods. Combined Rietveld refinements of neutron and X-ray powder diffraction data with a constrained structural model reveal a clear correlation between crystallite size and long-range magnetic order, which influences the macroscopic magnetic properties of the sample. The tailor-made powder samples were compacted into dense bulk magnets (>90% of the theoretical density) by spark plasma sintering (SPS). Powder diffraction as well as X-ray and neutron pole figure measurements and analyses have been carried out on the compacted specimens in order to characterize the nuclear (structural) and magnetic alignment of the crystallites within the dense magnets. The obtained results, combined with macroscopic magnetic measurements, reveal a direct influence of the nanoparticle morphology on the self-induced texture, crystallite growth during compaction and macroscopic magnetic performance. An increasing diameter-to-thickness aspect ratio of the platelet-like nanoparticles leads to increasing degree of crystallite alignment achieved by SPS. Consequently, magnetically aligned, highly dense magnets with excellent magnetic performance (30(3) kJ m) are obtained solely by nanostructuring means, without application of an external magnetic field before or during compaction. The demonstrated control over nanoparticle morphology and, in turn, crystal and magnetic texture is a key step on the way to designing nanostructured hexaferrite magnets with optimized performance., This work was financially supported by the Danish Research Council for Technology and Production Sciences through a Sapere Aude grant (Improved Permanent Magnets through Nanostructuring), the Danish National Research Foundation (Center for Materials Crystallography, DNRF93), Innovation Fund Denmark (Green Chemistry for Advanced Materials, GCAM-4107-000008B), Innovation Fund Denmark (MAGFLY- 7046-00015A) and the Danish Center for Synchrotron and Neutron Science (DanScatt). Cecilia Granados-Miralles acknowledges financial support from MICINN through the “Juan de la Cierva” Program (FJC2018-035532-I). The authors gratefully acknowledge the beamtime granted by the European Synchrotron Radiation Facility (ESRF), to collect the high-resolution powder X-ray diffraction data, as well as the Australian Centre for Neutron Scattering, Australian Nuclear Science and Technology Organisation, for providing the neutron research facilities to perform the studies used in this work. Matilde Saura-Múzquiz is grateful for the financial support received from Oticon Fonden and Augustinus Fonden. Affiliation with the Center for Integrated Materials Research (iMAT) at Aarhus University is gratefully acknowledged. Jakob Voldum Ahlburg and Frederik Holm Gjørup are thanked for their assistance with the VSM data extraction.

International audience; In this article, we develop novel theory on the differentiated impact of verbal and visual texts on the emergence, rise, establishment, and consolidation of institutions. Integrating key insights from social semiotics into a discursive model of institutionalization, we identify distinct affordances of verbal and visual text based on the constitutive features of the respective semiotic modes. In an effort to extend scholarly inquiry into the relationship of text and institutions, we develop a set of propositions on how and under which conditions verbal and visual text, respectively, facilitate the institutionalization of novel ideas in each stage of the process. Our theory development has implications for research on institutions as communicative accomplishments, contributes to the nascent line of multimodal research, and provides novel insights into institutional emergence.

Seagrass meadows play a significant role in the formation of carbonate sediments, serving as a substrate for carbonate-producing epiphyte communities. The magnitude of the epiphyte load depends on plant structural and physiological parameters, related to the time available for epiphyte colonization. Yet, the carbonate accumulation is likely to also depend on the carbonate saturation state of seawater (Ω) that tends to decrease as latitude increases due to decreasing temperature and salinity. A decrease in carbonate accumulation with increasing latitude has already been demonstrated for other carbonate producing communities. The aim of this study was to assess whether there was any correlation between latitude and the epiphyte carbonate load and net carbonate production rate on seagrass leaves. Shoots from 8 different meadows of the Zostera genus distributed across a broad latitudinal range (27 °S to up to 64 °N) were sampled along with measurements of temperature and Ω. The Ω within meadows significantly decreased as latitude increased and temperature decreased. The mean carbonate content and load on seagrass leaves ranged from 17% DW to 36% DW and 0.4–2.3 mg CO cm, respectively, and the associated mean carbonate net production rate varied from 0.007 to 0.9 mg CO cm d. Mean carbonate load and net production rates decreased from subtropical and tropical, warmer regions towards subpolar latitudes, consistent with the decrease in Ω. These results point to a latitudinal variation in the contribution of seagrass to the accumulation of carbonates in their sediments which affect important processes occurring in seagrass meadows, such as nutrient cycling, carbon sequestration and sediment accretion., I.M. was supported by a Pre-Doctoral fellowship by the Government of the Balearic Islands, D.K.-J. was supported by the COCOA project under the BONUS program funded by the EU 7th framework program and the Danish Research Council. The study is also a contribution to the Greenland Ecosystem Monitoring programme (www.G-E-M.dk), the Arctic Science Partnership (ASP, asp-net.org) and the project PTDC/MAR-EST/3223/2014 of Foundation of Science and Technology of Portugal (FCT).

In July 2015 the well-known affairs Web site, Ashley Madison, was hacked and both customer details and internal company correspondence were stolen, and later dumped online for public access. In the analysis of the data, it became clear that the site had extensively used bots to attract customers. This paper brings together these bots with a short story by Candas Jane Dorsey about the discomfiting potential of human-machine intimacies. I use the two to help me explore what I argue is an inbuilt and little discussed expectation/requirement of “authentic” intimacy: humanness.

21 pags, 10 figs., 1 tab., 4 apps.-- Open Access funded by Creative Commons Atribution Licence 4.0, Although it has been demonstrated that the speed and magnitude of the recent Arctic sea ice decline is unprecedented for the past 1450 years, few records are available to provide a paleoclimate context for Arctic sea ice extent. Bromine enrichment in ice cores has been suggested to indicate the extent of newly formed sea ice areas. Despite the similarities among sea ice indicators and ice core bromine enrichment records, uncertainties still exist regarding the quantitative linkages between bromine reactive chemistry and the first-year sea ice surfaces. Here we present a 120 000-year record of bromine enrichment from the RECAP (REnland ice CAP) ice core, coastal east Greenland, and interpret it as a record of first-year sea ice. We compare it to existing sea ice records from marine cores and tentatively reconstruct past sea ice conditions in the North Atlantic as far north as the Fram Strait (50-85° N). Our interpretation implies that during the last deglaciation, the transition from multi-year to first-year sea ice started at ~17.5 ka, synchronously with sea ice reductions observed in the eastern Nordic Seas and with the increase in North Atlantic ocean temperature. First-year sea ice reached its maximum at 12.4-11.8 ka during the Younger Dryas, after which open-water conditions started to dominate, consistent with sea ice records from the eastern Nordic Seas and the North Icelandic shelf. Our results show that over the last 120 000 years, multi-year sea ice extent was greatest during Marine Isotope Stage (MIS) 2 and possibly during MIS 4, with more extended first-year sea ice during MIS 3 and MIS 5. Sea ice extent during the Holocene (MIS 1) has been less than at any time in the last 120 000 years., The RECAP ice coring effort was financed by the Danish Research Council through a Sapere Aude Grant, the NSF through the Division of Polar Programs, the Alfred Wegener Institute, and the European Research Council under the European Community’s Seventh Framework Programme (FP7/2007- 2013)/ERC grant agreement 610055 through the Ice2Ice project and the Early Human Impact project (grant agreement 267696). This study has also received funding from the European Research Council Executive Agency under the European Union’s Horizon 2020 Research and Innovation programme (Project ERC-2016- COG 726349 CLIMAHAL).

We report on the emergence of bulk, valley-polarized currents in graphene-based devices, driven by spatially varying regions of broken sublattice symmetry, and revealed by nonlocal resistance (RNL) fingerprints. By using a combination of quantum transport formalisms, giving access to bulk properties as well as multiterminal device responses, the presence of a nonuniform local band gap is shown to give rise to valley-dependent scattering and a finite Fermi-surface contribution to the valley Hall conductivity, related to characteristics of RNL. These features are robust against disorder and provide a plausible interpretation of controversial experiments in graphene/hexagonal boron nitride superlattices. Our findings suggest both an alternative mechanism for the generation of valley Hall effect in graphene and a route towards valley-dependent electron optics, by materials and device engineering., S.R.P. acknowledges funding from the Irish Research Council under the Laureate awards program. J.H.G. and S.R. acknowledge funding from the European Union Seventh Framework Programme under Grant No. 881603 (Graphene Flagship). ICN2 is funded by the CERCA Programme/Generalitat de Catalunya and supported by the Severo Ochoa programme (MINECO Grant. No. SEV-2017-0706). The Center for Nanostructured Graphene is sponsored by the Danish National Research Foundation, Project No. DNRF103.

12 pags., 3 figs., 1 tab. -- Open Access funded by Creative Commons Atribution Licence 4.0, Atmospheric iodine chemistry has a large influence on the oxidizing capacity and associated radiative impacts in the troposphere. However, information on the evolution of past atmospheric iodine levels is restricted to the industrial period while its long-term natural variability remains unknown. The current levels of iodine in the atmosphere are controlled by anthropogenic ozone deposition to the ocean surface. Here, using high-resolution geochemical measurements from coastal eastern Greenland ReCAP (REnland ice CAP project) ice core, we report the first record of atmospheric iodine variability in the North Atlantic during the Holocene (i.e., the last 11 700 years). Surprisingly, our results reveal that the highest iodine concentrations in the record were found during the Holocene Thermal Maximum (HTM; ∼ 11 500-5500 years before-present). These high iodine levels could be driven by marine primary productivity resulting in an Early Holocene >biological iodine explosion>. The high and stable iodine levels during this past warm period are a useful observational constraint on projections of future changes in Arctic atmospheric composition and climate resulting from global warming., This work was supported by CSIC. The RECAP ice coring effort was financed by the Danish Research Council through a Sapere Aude grant, the NSF through the Division of Polar Programs, the Alfred Wegener Institute, and the European Research Council under the European Community’s Seventh Framework Programme (FP7/2007-2013), and an ERC grant agreement 610055 through the Ice2Ice project and the Early Human Impact project (267696). Juan Pablo Corella had a Juan de la Cierva – Incorporación postdoctoral contract (ref. IJCI-2015-23839). Juliane Müller received funding through a Helmholtz Research grant VH-NG-1101. This study has received funding from the European Research Council Executive Agency under the European Union’s Horizon 2020 Research and Innovation program (Project ERC-2016-COG 726349 CLIMAHAL).

Magnetic materials are ubiquitous in electric devices and motors making them indispensable for modern-day society. The hexaferrites currently constitute the most widely used permanent magnets (PMs), accounting for 85% (by weight) of the global sales of PMs. This work presents a complete bottom-up nanostructuring protocol for preparation of magnetically aligned, high-performance hexaferrite PMs with a record-high (BH)max for dry-processed ferrites. The procedure includes the supercritical hydrothermal flow synthesis of anisotropic magnetic-single-domain strontium hexaferrite (SrFe12O19) nanocrystallites of various sizes, and their subsequent compaction into bulk magnets by spark plasma sintering (SPS). Interestingly, Rietveld modeling of neutron powder diffraction data reveals a significant difference between the magnetic structure of the thinnest nanoplatelets and the bulk compound, indicating the Sr-containing atomic layer to be the termination layer. Subsequently, high-density SrFe12O19 magnets (>95% of the theoretical density) are produced by SPS of the flow-synthesized nanoplatelets. Texture analysis by X-ray pole figure measurements demonstrates how the anisotropic shape of the nanoplatelets causes a self-induced alignment during SPS, without application of an external magnetic field. The self-induced texture is accompanied by crystallite growth along the magnetic easy-axis, i.e., the thickness of the platelets, resulting in high-performance PMs with square hysteresis curves and (BH)max of 30 kJ/m3. The (BH)max is further enhanced by annealing, reaching 36 kJ/m3 after 4 h at 850 °C, which exceeds the (BH)max of the highest grade of dry-processed commercial ferrites worldwide., This work was financially supported by the Danish Research Council for Technology and Production Sciences through a Sapere Aude grant (Improved Permanent Magnets through Nanostructuring), the Danish National Research Foundation (Center for Materials Crystallography, DNRF93), Innovation Fund Denmark (Green Chemistry for Advanced Materials, GCAM-4107-000008B), and the Danish Center for Synchrotron and Neutron Science (DanScatt). The authors gratefully acknowledge the beamtime granted by SPring-8 synchrotron, Harima Science Park, to perform the high-resolution powder diffraction data, as well as the Australian Centre for Neutron Scattering, Australian Nuclear Science and Technology. Organisation, for providing the neutron research facilities used in this work. Affiliation with the Center for Integrated Materials Research (iMAT) at Aarhus University is gratefullyacknowledged.

Publisher's version (útgefin grein), We present here a survey of high-ionization absorption lines in the afterglow spectra of long-duration gamma-ray bursts (GRBs) obtained with the VLT/X-shooter spectrograph. Our main goal is to investigate the circumburst medium in the natal regions of GRBs. Our primary focus is on the N Vλλ 1238, 1242 line transitions, but we also discuss other high-ionization lines such as O VI, C IV, and Si IV. We find no correlation between the column density of N V and the neutral gas properties such as metallicity, H I column density, and dust depletion; however, the relative velocity of N V, typically a blueshift with respect to the neutral gas, is found to be correlated with the column density of H I. This may be explained if the N V gas is part of an H II region hosting the GRB, where the region’s expansion is confined by dense, neutral gas in the GRB’s host galaxy. We find tentative evidence (at 2σ significance) that the X-ray derived column density, NH, X, may be correlated with the column density of N V, which would indicate that both measurements are sensitive to the column density of the gas located in the vicinity of the GRB. We investigate the scenario where N V (and also O VI) is produced by recombination after the corresponding atoms have been stripped entirely of their electrons by the initial prompt emission, in contrast to previous models where highly ionized gas is produced by photoionization from the GRB afterglow., KEH and PJ acknowledge support by a Project Grant (162948–051) from The Icelandic Research Fund. JK acknowledges financial support from the Danish Council for Independent Research (EU-FP7 under the Marie-Curie grant agreement no. 600207) with reference DFF–MOBILEX–5051–00115. JJ acknowledges support from NOVA and NWO-FAPESP grant for advanced instrumentation in astronomy. AG acknowledges the financial support from the Slovenian Research Agency (research core funding no. P1-0031 and project grant no. J1-8136). AdUP, CCT, and ZC acknowledge support from the Spanish Ministry of Economy and Competitivity under grant number AYA 2014-58381-P. AdUP and CCT acknowledge support from Ramon y Cajal fellowships (RyC-2012-09975 and RyC-2012-09984). AdUP acknowledges support from a grant from the BBVA foundation for researchers and cultural creators. ZC acknowledges support from the Juan de la Cierva Incorporación fellowship IJCI-2014-21669 and from the Spanish research project AYA 2014-58381-P. RS-R acknowledges support from ASI (Italian Space Agency) through the contract no. 2015-046-R.0 and from European Union Horizon 2020 Programme under the AHEAD project (grant agreement no. 654215).

15 pags, 8 figs, 1 tab. -- This article contains supplementary material (Table S1, Figs. S1–S4, and Data Sets S1–S4.1), The low-density lipoprotein receptor (LDLR) and related receptors are important for the transport of diverse biomolecules across cell membranes and barriers. Their functions are especially relevant for cholesterol homeostasis and diseases, including neurodegenerative and kidney disorders. Members of the LDLR-related protein family share LDLR class A (LA) repeats providing binding properties for lipoproteins and other biomolecules. We previously demonstrated that short linker regions between these LA repeats contain conserved O-glycan sites. Moreover, we found that O-glycan modifications at these sites are selectively controlled by the GalNAc-transferase isoform, GalNAc-T11. However, the effects of GalNAc-T11–mediated O-glycosylation on LDLR and related receptor localization and function are unknown. Here, we characterized O-glycosylation of LDLR-related proteins and identified conserved O-glycosylation sites in the LA linker regions of VLDLR, LRP1, and LRP2 (Megalin) from both cell lines and rat organs. Using a panel of gene-edited isogenic cell line models, we demonstrate that GalNAc-T11–mediated LDLR and VLDLR O-glycosylation is not required for transport and cell-surface expression and stability of these receptors but markedly enhances LDL and VLDL binding and uptake. Direct ELISA-based binding assays with truncated LDLR constructs revealed that O-glycosylation increased affinity for LDL by 5-fold. The molecular basis for this observation is currently unknown, but these findings open up new avenues for exploring the roles of LDLR-related proteins in disease., This work was supported by the Læge Sofus Carl Emil Friis og hustru Olga Doris Friis’ Legat, the Kirsten og Freddy Johansen Fonden, the Lundbeck Foundation, the A.P. Møller og Hustru Chastine Mc-Kinney Møllers Fond til Almene Formaal, the Mizutani Foundation, the Novo Nordisk Foundation, the Danish Research Council Sapere Aude Research Talent Grant (to K. T. S.), and the Danish National Research Foundation (DNRF107). The authors declare that they have no conflicts of interest with the contents of this article

International audience; The Consortium for Top-Down Proteomics (CTDP) proposes a standardized notation, ProForma, for writing the sequence of fully characterized proteoforms. ProForma provides a means to communicate any proteoform by writing the amino acid sequence using standard one-letter notation and specifying modifications or unidentified mass shifts within brackets following certain amino acids. The notation is unambiguous, human-readable, and can easily be parsed and written by bioinformatic tools. This system uses seven rules and supports a wide range of possible use cases, ensuring compatibility and reproducibility of proteoform annotations. Standardizing proteoform sequences will simplify storage, comparison, and reanalysis of proteomic studies, and the Consortium welcomes input and contributions from the research community on the continued design and maintenance of this standard.

Calmodulin (CaM) is a universal regulator for a huge number of proteins in all eukaryotic cells. Best known is its function as a calcium-dependent modulator of the activity of enzymes, such as protein kinases and phosphatases, as well as other signaling proteins including membrane receptors, channels and structural proteins. However, less well known is the fact that CaM can also function as a Ca2+-dependent adaptor protein, either by bridging between different domains of the same protein or by linking two identical or different target proteins together. These activities are possible due to the fact that CaM contains two independently-folded Ca2+ binding lobes that are able to interact differentially and to some degree separately with targets proteins. In addition, CaM can interact with and regulates several proteins that function exclusively as adaptors. This review provides an overview over our present knowledge concerning the structural and functional aspects of the role of CaM as an adaptor protein and as a regulator of known adaptor/scaffold proteins., The work in the authors laboratories were funded by grant SAF2014-52048-R from the Secretaría de Estado de Investigación, Desarrollo e Innovación (to AV); the Danish Research Council DFF- 4004-00560, the AP Møller Foundation, Dagmar Marshalls Foundation, Einar Willumsen Foundation, Aase and Ejnar Danielsen Foundation, Wedell Wedellsborg Foundation, Frænkels Foundation and Danish Heart Foundation 13-04-R94-A4547-2280 (to MWB); and the National Sciences and Engineering Research Council of Canada RGPIN/05977-2015 (to HJV).

Total control over the electronic spin relaxation in molecular nanomagnets is the ultimate goal in the design of new molecules with evermore realizable applications in spin-based devices. For single-ion lanthanide systems, with strong spin-orbit coupling, the potential applications are linked to the energetic structure of the crystal field levels and quantum tunneling within the ground state. Structural engineering of the timescale of these tunneling events via appropriate design of crystal fields represents a fundamental challenge for the synthetic chemist, since tunnel splittings are expected to be suppressed by crystal field environments with sufficiently high-order symmetry. Here, we report the long missing study of the effect of a non-linear (C4) to pseudo-linear (D4d) change in crystal field symmetry in an otherwise chemically unaltered dysprosium complex. From a purely experimental study of crystal field levels and electronic spin dynamics at milliKelvin temperatures, we demonstrate the ensuing threefold reduction of the tunnel splitting., M.A.S., U.B.H., K.L., and J.Be. acknowledge financial support from the Danish Research Councils for Independent Research (12-125226). M.A.S., U.B.H., M.R, and K.L. acknowledge DANSCATT for financial support for the neutron scattering experiments. For the experiments conducted at FRM II, this project has received funding from the European Union’s 7th Framework Programme for research, technological development and demonstration under the NMI3-II Grant number 283883. M.A.S. thanks the Oticon Foundation (16-2669), and the Augustinus Foundation (16-2917) for financial support in relation to a research stay at Institut für Physikalische Chemie, Universität Stuttgart, Germany. M.P. and J.v.S. thank the DFG for funding (SL104/5-1). K.S.P. thanks the Danish Research Council for Independent Research for a DFF-Sapere Aude Research Talent grant (4090-00201). E.B., A.A, and, J.Ba. acknowledge the financial support of Spanish MINECO project MAT2017-83468-R. M.J. acknowledges the Swiss National Science Foundation.

International audience; This chapter examines how proponents of industrialization used multiple modes of communication to socially construct the rational myth of industrialization in the French construction sector after World War II. We illuminate the respective roles of visual and verbal communication in this process. Our findings suggest that actors construct rational myths according to the following step-by-step method: first, they use visuals to suggest associations between new practices and valuable purposes; then they use verbal text to establish the technical rationality of certain practices; and lastly, they employ both verbal and visual communications to convey their mythical features.