Developmental switch of intestinal antimicrobial peptide expression

Paneth cell–derived enteric antimicrobial peptides provide protection from intestinal infection and maintenance of enteric homeostasis. Paneth cells, however, evolve only after the neonatal period, and the antimicrobial mechanisms that protect the newborn intestine are ill defined. Using quantitative reverse transcription–polymerase chain reaction, immunohistology, reverse-phase high-performance liquid chromatography, and mass spectrometry, we analyzed the antimicrobial repertoire in intestinal epithelial cells during postnatal development. Surprisingly, constitutive expression of the cathelin-related antimicrobial peptide (CRAMP) was observed, and the processed, antimicrobially active form was identified in neonatal epithelium. Peptide synthesis was limited to the first two weeks after birth and gradually disappeared with the onset of increased stem cell proliferation and epithelial cell migration along the crypt–villus axis. CRAMP conferred significant protection from intestinal bacterial growth of the newborn enteric pathogen Listeria monocytogenes. Thus, we describe the first example of a complete developmental switch in innate immune effector expression and anatomical distribution. Epithelial CRAMP expression might contribute to bacterial colonization and the establishment of gut homeostasis, and provide protection from enteric infection during the postnatal period

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Differences in dietary intakes, food sources and determinants of total flavonoids between Mediterranean and non-Mediterranean countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

A greater adherence to the traditional Mediterranean (MED) diet is associated with a reduced risk of developing chronic diseases. This dietary pattern is based on higher consumption of plant products that are rich in flavonoids. We compared the total flavonoid dietary intakes, their food sources and various lifestyle factors between MED and non-MED countries participating in the EPIC study. Flavonoid intakes and their food sources for 35,628 subjects, aged 35-74 years and recruited between 1992 and 2000, in twenty-six study centres were estimated using standardised 24 h dietary recall software (EPIC-Soft®). An ad hoc food composition database on flavonoids was compiled using analytical data from the United States Department of Agriculture and Phenol-Explorer databases. Moreover, it was expanded to include using recipes, estimations of missing values and flavonoid retention factors. No significant differences in total flavonoid mean intake between non-MED countries (373·7 mg/d) and MED countries (370·2 mg/d) were observed. In the non-MED region, the main contributors were proanthocyanidins (48·2%) and flavan-3-ol monomers (24·9%) and the principal food sources were tea (25·7%) and fruits (32·8%). In the MED region, proanthocyanidins (59·0%) were by far the most abundant contributor and fruits (55·1%), wines (16·7%) and tea (6·8%) were the main food sources. The present study shows similar results for total dietary flavonoid intakes, but significant differences in flavonoid class intakes, food sources and some characteristics between MED and non-MED countries. These differences should be considered in studies about the relationships between flavonoid intake and chronic diseases

Resilience Management Guidelines for Critical Infrastructures, Practical Solutions Addressing Expected and Unexpected Events

Crises and disasters (Eyjafjallajökull and Deepwater Horizon 2010, Fukushima Daiichi 2011, and more recently the wildfire in Sweden 2018) have made it obvious that a more resilient approach to preparing for and dealing with such events is needed. This paper presents the results of the H2020 DARWIN project, which contributes to improving responses to expected and unexpected crises affecting critical infrastructures and social structures, whether man-made events (e.g. cyber-attacks) or natural events (e.g. earthquakes). The main result of the Darwin project is the creation of the DARWIN Resilience Management Guidelines (DRMG). The DRMG are evolving guidelines, designed to improve the ability of stakeholders to monitor, anticipate and learn from crises, and thereby allow them to adapt and respond more effectively and operate more efficiently during disasters. These guidelines are not prescriptive. Instead, they enable organizations to have a critical view of their own crisis management activities. The target beneficiaries of DARWIN are crisis management managers and practitioners responsible for public safety, such as critical infrastructures and service providers, which might be affected by a crisis, as well as the public and media. The DRMG are not meant to be dust-collectors on a shelf. To this end, they have been made into a variety of formats to support their evolution, ease of use and maintenance. Within this paper, the reader is introduced to the DRMG in its different formats, as well as a host of innovative tools (e.g. DRMG Wiki, serious gaming, training packages) developed by the project to support resilience management learning and the uptake of the guidelines. A multidisciplinary approach is applied, involving experts in the field of resilience, crisis and risk management, social media, and service providers in the air traffic management and healthcare domains. To ensure transnational, cross-sector applicability, long-term relevance and uptake of project results, the DARWIN Community of Practitioners (DCoP) has been established, with membership including experts and end users from different fields of expertise and from across multiple critical infrastructure domains. The DCoP has been involved in an iterative development and evaluation process to provide feedback on the results. The evaluation in pilot exercises and other activities involved 247 practitioners from 22 countries. The DCoP members contributed with knowledge and experience ensuring the feasibility of adapting them to other critical infrastructure domains. Our achievement is the current version of guidelines and associated innovative tools proposing practical interventions that end-users find useful. This paper includes testimonials of end-users within and outside the consortium. This document represents an invitation to explore the content of the guidelines, to encourage its use and further developments of the resilience management. Concluding Paper of the H2020 DARWIN Project as published 25 March 2019 on www.h2020darwin.e

Reproducibility in the absence of selective reporting: An illustration from large‐scale brain asymmetry research

The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p-hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left-right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta-analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an "ideal publishing environment," that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically-used sample sizes

Memoria 1980

El día 23 de julio de 1980 tomó posesión de su cargo el nuevo Presidente del C.S.I.C. D. Alejandro Nieto. Después de un breve acto en la Sala de Juntas del Ministerio de Universidades e Investigación -en el que, con asistencia de los altos cargos del Departamento y numerosos miembros del C.S.I.C, intervinieron el Ministro, D. Luis Gonzalez Seara, y el Presidente saliente, D. Carlos Sánchez del Reo-, se traslado el Sr. Nieto a la Sala de Juntas del Consejo, donde estaban convocados los componentes de la Junta de Gobierno y de las Comisiones Científica y Económica del C.S.I.C. Ante ellos expuso un programa de actuación, del que aquí se entresacan las líneas más relevantes.N

Searches for the ZγZ\gamma decay mode of the Higgs boson and for new high-mass resonances in pppp collisions at s=13\sqrt{s} = 13 TeV with the ATLAS detector

International audienceThis article presents searches for the Zγ decay of the Higgs boson and for narrow high-mass resonances decaying to Zγ, exploiting Z boson decays to pairs of electrons or muons. The data analysis uses 36.1 fb$^{−1}$ of pp collisions at $\sqrt{s}=13$ recorded by the ATLAS detector at the CERN Large Hadron Collider. The data are found to be consistent with the expected Standard Model background. The observed (expected — assuming Standard Model pp → H → Zγ production and decay) upper limit on the production cross section times the branching ratio for pp → H → Zγ is 6.6. (5.2) times the Standard Model prediction at the 95% confidence level for a Higgs boson mass of 125.09 GeV. In addition, upper limits are set on the production cross section times the branching ratio as a function of the mass of a narrow resonance between 250 GeV and 2.4 TeV, assuming spin-0 resonances produced via gluon-gluon fusion, and spin-2 resonances produced via gluon-gluon or quark-antiquark initial states. For high-mass spin-0 resonances, the observed (expected) limits vary between 88 fb (61 fb) and 2.8 fb (2.7 fb) for the mass range from 250 GeV to 2.4 TeV at the 95% confidence level

Search for direct top squark pair production in final states with two leptons in s=13\sqrt{s} = 13 TeV pppp collisions with the ATLAS detector

International audienceThe results of a search for direct pair production of top squarks in events with two opposite-charge leptons (electrons or muons) are reported, using $36.1~\hbox {fb}^{-1}$ of integrated luminosity from proton–proton collisions at $\sqrt{s}=13$ TeV collected by the ATLAS detector at the Large Hadron Collider. To cover a range of mass differences between the top squark $\tilde{t}$ and lighter supersymmetric particles, four possible decay modes of the top squark are targeted with dedicated selections: the decay $\tilde{t} \rightarrow b \tilde{\chi }_{1}^{\pm }$ into a b-quark and the lightest chargino with $\tilde{\chi }_{1}^{\pm } \rightarrow W \tilde{\chi }_{1}^{0}$ , the decay $\tilde{t} \rightarrow t \tilde{\chi }_{1}^{0}$ into an on-shell top quark and the lightest neutralino, the three-body decay $\tilde{t} \rightarrow b W \tilde{\chi }_{1}^{0}$ and the four-body decay $\tilde{t} \rightarrow b \ell \nu \tilde{\chi }_{1}^{0}$ . No significant excess of events is observed above the Standard Model background for any selection, and limits on top squarks are set as a function of the $\tilde{t}$ and $\tilde{\chi }_{1}^{0}$ masses. The results exclude at 95% confidence level $\tilde{t}$ masses up to about 720 GeV, extending the exclusion region of supersymmetric parameter space covered by previous searches