Secondary ion mass spectrometry, a powerful tool for revealing ink formulations and animal skins in medieval manuscripts

XRD diffractograms, ToF-SIMS MS and ATR-FTIR spectrometry spectra, recorded on inks on historical parchments (pigments, inked areas). ToF-SIMS and ATR-FTIR spectra from non-inked areas of the parchments. See the read-me file for complete description of the files and structure, and the main manuscript for the methodology. The PCA algorithm code is also provided. Article abstract : Book production by medieval scriptoria have gained growing interest in recent studies. In this context, identifying ink compositions and parchment animal species from illuminated manuscripts is of great importance. Here, we introduce time-of-flight secondary ion mass spectrometry (ToF-SIMS) as a non-invasive tool to identify both inks and animal skins in manuscripts, at the same time. For this purpose, both positive and negative ion spectra in inked and non-inked areas were recorded. Chemical compositions of pigments (decoration) or black inks (text) were determined by searching for characteristic ion mass peaks. Animal skins were identified by data processing of raw ToF-SIMS spectra using Principal Component Analysis (PCA). In illuminated manuscripts from 15th c. to 16th c., malachite (green), azurite (blue), cinnabar (red) inorganic pigments, as well as iron-gall black ink, were identified. Carbon black and indigo (blue) organic pigments were also identified. Animal skins were identified in modern parchments of known animal species by a two-steps PCA procedure. We believe the proposed method will find extensive application in material studies of medieval manuscripts, as it is non-invasive, highly sensitive and able to identify both inks and animal skins at the same time, even from traces of pigments and tiny scanned areas.In-house PCA algorithm requires python. ToF-SIMS raw data require SurfaceLab software. ATR-FTIR raw data (.0) can be read with free-licence software (Fityk). XRD diffractograms are directly exported in .txt from .xyz files. Funding provided by: Namur Institute of Structured Matter, University of NamurCrossref Funder Registry ID: http://dx.doi.org/10.13039/501100023393Award Number:Analytical and data processing methods can be found in the manuscript

Novel Insights into the Bovine Polled Phenotype and Horn Ontogenesis in Bovidae

Despite massive research efforts, the molecular etiology of bovine polledness and the developmental pathways involved in horn ontogenesis are still poorly understood. In a recent article, we provided evidence for the existence of at least two different alleles at the Polled locus and identified candidate mutations for each of them. None of these mutations was located in known coding or regulatory regions, thus adding to the complexity of understanding the molecular basis of polledness. We confirm previous results here and exhaustively identify the causative mutation for the Celtic allele (PC) and four candidate mutations for the Friesian allele (PF). We describe a previously unreported eyelash-and-eyelid phenotype associated with regular polledness, and present unique histological and gene expression data on bovine horn bud differentiation in fetuses affected by three different horn defect syndromes, as well as in wild-type controls. We propose the ectopic expression of a lincRNA in PC/p horn buds as a probable cause of horn bud agenesis. In addition, we provide evidence for an involvement of OLIG2, FOXL2 and RXFP2 in horn bud differentiation, and draw a first link between bovine, ovine and caprine Polled loci. Our results represent a first and important step in understanding the genetic pathways and key process involved in horn bud differentiation in Bovidae

LC‐IMPACT: A regionalized life cycle damage assessment method

Life cycle impact assessment (LCIA) is a lively field of research, and data and models are continuously improved in terms of impact pathways covered, reliability, and spatial detail. However, many of these advancements are scattered throughout the scientific literature, making it difficult for practitioners to apply the new models. Here, we present the LC‐IMPACT method that provides characterization factors at the damage level for 11 impact categories related to three areas of protection (human health, ecosystem quality, natural resources). Human health damage is quantified as disability adjusted life years, damage to ecosystem quality as global species extinction equivalents (based on potentially disappeared fraction of species), and damage to mineral resources as kilogram of extra ore extracted. Seven of the impact categories include spatial differentiation at various levels of spatial scale. The influence of value choices related to the time horizon and the level of scientific evidence of the impacts considered is quantified with four distinct sets of characterization factors. We demonstrate the applicability of the proposed method with an illustrative life cycle assessment example of different fuel options in Europe (petrol or biofuel). Differences between generic and regionalized impacts vary up to two orders of magnitude for some of the selected impact categories, highlighting the importance of spatial detail in LCIA. This article met the requirements for a gold – gold JIE data openness badge described at http://jie.click/badges.info:eu-repo/semantics/publishedVersio

IMPACT World+: a globally regionalized life cycle impact assessment method

Purpose This paper addresses the need for a globally regionalized method for life cycle impact assessment (LCIA), integrating multiple state-of-the-art developments as well as damages on water and carbon areas of concern within a consistent LCIA framework. This method, named IMPACT World+, is the update of the IMPACT 2002+, LUCAS, and EDIP methods. This paper first presents the IMPACT World+ novelties and results and then analyzes the spatial variability for each regionalized impact category. Methods With IMPACT World+, we propose a midpoint-damage framework with four distinct complementary viewpoints to present an LCIA profile: (1) midpoint impacts, (2) damage impacts, (3) damages on human health, ecosystem quality, and resources & ecosystem service areas of protection, and (4) damages on water and carbon areas of concerns. Most of the regional impact categories have been spatially resolved and all the long-term impact categories have been subdivided between shorterterm damages (over the 100 years after the emission) and long-term damages. The IMPACT World+ method integrates developments in the following categories, all structured according to fate (or competition/scarcity), exposure, exposure response, and severity: (a) Complementary to the global warming potential (GWP100), the IPCC Global Temperature Potentials (GTP100) are used as a proxy for climate change long-term impacts at midpoint. At damage level, shorter-term damages (over the first 100 years after emission) are also differentiated from long-term damages. (b) Marine acidification impact is based on the same fate model as climate change, combined with the H+ concentration affecting 50% of the exposed species. (c) For mineral resources depletion impact, the material competition scarcity index is applied as a midpoint indicator. (d) Terrestrial and freshwater acidification impact assessment combines, at a resolution of 2° × 2.5° (latitude × longitude), global atmospheric source-deposition relationships with soil and water ecosystems’sensitivity. (e) Freshwater eutrophication impact is spatially assessed at a resolution grid of 0.5° × 0.5°, based on a global hydrological dataset. (f) Ecotoxicity and human toxicity impact are based on the parameterized version of USEtox for continents. We consider indoor emissions and differentiate the impacts of metals and persistent organic pollutants for the first 100 years from longer-term impacts. (g) Impacts on human health related to particulate matter formation are modeled using the USEtox regional archetypes to calculate intake fractions and epidemiologically derived exposure response factors. (h) Water consumption impacts are modeled using the consensus-based scarcity indicator AWARE as a proxy midpoint, whereas damages account for competition and adaptation capacity. (i) Impacts on ecosystem quality from land transformation and occupation are empirically characterized at the biome level. Results and discussion We analyze the magnitude of global potential damages for each impact indicator, based on an estimation of the total annual anthropogenic emissions and extractions at the global scale (i.e., Bdoing the LCA of the world^). Similarly with ReCiPe and IMPACT 2002+, IMPACT World+ finds that (a) climate change and impacts of particulate matter formation have a dominant contribution to global human health impacts whereas ionizing radiation, ozone layer depletion, and photochemical oxidant formation have a low contribution and (b) climate change and land use have a dominant contribution to global ecosystem quality impact. (c) New impact indicators introduced in IMPACT World+ and not considered in ReCiPe or IMPACT 2002+, in particular water consumption impacts on human health and the long-term impacts of marine acidification on ecosystem quality, are significant contributors to the overall global potential damage. According to the areas of concern version of IMPACT World+ applied to the total annual world emissions and extractions, damages on the water area of concern, carbon area of concern, and the remaining damages (not considered in those two areas of concern) are of the same order of magnitude, highlighting the need to consider all the impact categories. The spatial variability of human health impacts related to exposure to toxic substances and particulate matter is well reflected by using outdoor rural, outdoor urban, and indoor environment archetypes. For Bhuman toxicity cancer^ impact of substances emitted to continental air, the variability between continents is of two orders of magnitude, which is substantially lower than the 13 orders of magnitude total variability across substances. For impacts of water consumption on human health, the spatial variability across extraction locations is substantially higher than the variations between different water qualities. For regionalized impact categories affecting ecosystem quality (acidification, eutrophication, and land use), the characterization factors of half of the regions (25th to 75th percentiles) are within one to two orders of magnitude and the 95th percentile within three to four orders of magnitude, which is higher than the variability between substances, highlighting the relevance of regionalizing. Conclusions IMPACT World+ provides characterization factors within a consistent impact assessment framework for all regionalized impacts at four complementary resolutions: global default, continental, country, and native (i.e., original and non-aggregated) resolutions. IMPACT World+ enables the practitioner to parsimoniously account for spatial variability and to identify the elementary flows to be regionalized in priority to increase the discriminating power of LCA

Global ensemble projections reveal trophic amplification of ocean biomass declines with climate change

While the physical dimensions of climate change are now routinely assessed through multimodel intercomparisons, projected impacts on the global ocean ecosystem generally rely on individual models with a specific set of assumptions. To address these single-model limitations, we present standardized ensemble projections from six global marine ecosystem models forced with two Earth system models and four emission scenarios with and without fishing. We derive average biomass trends and associated uncertainties across the marine food web. Without fishing, mean global animal biomass decreased by 5% (±4% SD) under low emissions and 17% (±11% SD) under high emissions by 2100, with an average 5% decline for every 1 °C of warming. Projected biomass declines were primarily driven by increasing temperature and decreasing primary production, and were more pronounced at higher trophic levels, a process known as trophic amplification. Fishing did not substantially alter the effects of climate change. Considerable regional variation featured strong biomass increases at high latitudes and decreases at middle to low latitudes, with good model agreement on the direction of change but variable magnitude. Uncertainties due to variations in marine ecosystem and Earth system models were similar. Ensemble projections performed well compared with empirical data, emphasizing the benefits of multimodel inference to project future outcomes. Our results indicate that global ocean animal biomass consistently declines with climate change, and that these impacts are amplified at higher trophic levels. Next steps for model development include dynamic scenarios of fishing, cumulative human impacts, and the effects of management measures on future ocean biomass trends

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

An Antiviral Response Directed by PKR Phosphorylation of the RNA Helicase A

The double-stranded RNA-activated protein kinase R (PKR) is a key regulator of the innate immune response. Activation of PKR during viral infection culminates in phosphorylation of the α subunit of the eukaryotic translation initiation factor 2 (eIF2α) to inhibit protein translation. A broad range of regulatory functions has also been attributed to PKR. However, as few additional PKR substrates have been identified, the mechanisms remain unclear. Here, PKR is shown to interact with an essential RNA helicase, RHA. Moreover, RHA is identified as a substrate for PKR, with phosphorylation perturbing the association of the helicase with double-stranded RNA (dsRNA). Through this mechanism, PKR can modulate transcription, as revealed by its ability to prevent the capacity of RHA to catalyze transactivating response (TAR)–mediated type 1 human immunodeficiency virus (HIV-1) gene regulation. Consequently, HIV-1 virions packaged in cells also expressing the decoy RHA peptides subsequently had enhanced infectivity. The data demonstrate interplay between key components of dsRNA metabolism, both connecting RHA to an important component of innate immunity and delineating an unanticipated role for PKR in RNA metabolism

Islamism and the state after the Arab uprisings: Between people power and state power

The authors would like to thank the Arts and Humanities Research Council for facilitating the research for this article through their support of the research network People Power versus State Power of the Centre for the Advanced Study of the Arab World.This paper examines the trajectories of different Islamist trends in the light of the Arab uprisings. It proposes a distinction between statist and non-statist Islamism to help understand the multiplicity of interactions between Islamists and the state, particularly after 2011. It is outlined how statist Islamists (Islamist parties principally) can contribute to the stabilization and democratization of the state when their interactions with other social and political actors facilitate consensus building in national politics. By contrast when these interactions are conflictual, it has a detrimental impact on both the statist Islamists, and the possibility of democratic politics at the national level. Non statist-Islamists (from quietist salafi to armed jihadi) who prioritize the religious community over national politics are directly impacted by the interactions between statist Islamists and the state, and generally tend to benefit from the failure to build a consensus over democratic national politics. Far more than nationally-grounded statist Islamists, non-statist Islamists shape and are shaped by the regional dynamics on the Arab uprisings and the international and transnational relations between the different countries and conflict areas of the Middle East. The Arab uprisings and their aftermath reshaped pre-existing national and international dynamics of confrontation and collaboration between Islamists and the state, and between statist and non-statists Islamists, for better (Tunisia) and for worse (Egypt).PostprintPeer reviewe

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population