Experimental infection of European red deer (Cervus elaphus) with bluetongue virus serotypes 1 and 8

Short communication.-- et al.Bluetongue (BT) is a climate change-related emerging infectious disease in Europe. Outbreaks of serotypes 1, 2, 4, 6, 8, 9, 11, and 16 are challenging Central and Western Europe since 1998. Measures to control or eradicate bluetongue virus (BTV) from Europe have been implemented, including movement restrictions and vaccination of domestic BTV-susceptible ruminants. However, these measures are difficult to apply in wild free-ranging hosts of the virus, like red deer (Cervus elaphus), which could play a role in the still unclear epidemiology of BT in Europe. We show for the first time that BTV RNA can be detected in European red deer blood for long periods, comparable to those of domestic ruminants, after experimental infection with BTV-1 and BTV-8. BTV RNA was detected in experimentally infected red deer blood up to the end of the study (98¿112 dpi). BTV-specific antibodies were found in serum both by enzyme-linked immunosorbent assay (ELISA) and virus neutralization (VNT) from 8 to 12 dpi to the end of the study, peaking at 17¿28 dpi. Our results indicate that red deer can be infected with BTV and maintain BTV RNA for long periods, remaining essentially asymptomatic. Thus, unvaccinated red deer populations have the potential to be a BT reservoir in Europe, and could threaten the success of the European BTV control strategy. Therefore, wild and farmed red deer should be taken into account for BTV surveillance, and movement restrictions and vaccination schemes applied to domestic animals should be adapted to include farmed or translocated red deer.We acknowledge the funding from JCCM PAI08-0287-8502, the Government of Scotland, and INIA-MARM CC08-020 (additional support to CISA). Caterina Falconi had a grant from the Government of Sardinia.Peer Reviewe

Simplified immunosuppressive and neuroprotective agents based on gracilin A

The architecture and bioactivity of natural products frequently serve as embarkation points for the exploration of biologically relevant chemical space. Total synthesis followed by derivative synthesis has historically enabled a deeper understanding of structure–activity relationships. However, synthetic strategies towards a natural product are not always guided by hypotheses regarding the structural features required for bioactivity. Here, we report an approach to natural product total synthesis that we term ‘pharmacophore-directed retrosynthesis’. A hypothesized, pharmacophore of a natural product is selected as an early synthetic target and this dictates the retrosynthetic analysis. In an ideal application, sequential increases in the structural complexity of this minimal structure enable development of a structure–activity relationship profile throughout the course of the total synthesis effort. This approach enables the identification of simpler congeners retaining bioactivity at a much earlier stage of a synthetic effort, as demonstrated here for the spongiane diterpenoid, gracilin A, leading to simplified derivatives with potent neuroprotective and immunosuppressive activityThe authors acknowledge support from the NIH (R37 GM052964 to D.R.), NSF (CHE1800411, to D.R.) the Robert A. Welch Foundation (AA-1280 to D.R.), FEDER co-funded grants from CONSELLERIA DE Cultura, EDUCACION e ordenación Universitaria Xunta de Galicia (2017 GRC GI-1682, ED431C 2017/01), CDTI and Technological Funds, supported by Ministerio de Economía, Industria y Competitividad (AGL2014- 58210-R, AGL2016-78728-R, AEI/FEDER, UE) (to L.M.B.), ISCIII/PI1/01830 (to A.A.) and RTC-2016-5507-2 and ITC-20161072, from EU POCTEP 0161-Nanoeaters-1-E-1, Interreg AlertoxNet EAPA-317-2016 and H2020 778069-EMERTOX (to L.M.B.) and from the European Union’s Seventh Framework Programme managed by the Research Executive Agency (FP7/2007-2013 under grant agreement 312184 PHARMASEA to L.M.B. and M.J.). N. Bhuvanesh and J. Reibenspies (Center for X-ray Analysis, TAMU) secured X-ray data and W. Russell (Laboratory for Biological Mass Spectrometry, TAMU) provided mass data. Correspondence and requests for materials should be directed to D. Romo (chemistry) and L. Botana (biology).S

Análisis de la convivencia escolar en las aulas multiculturales de Educación Secundaria

This research study analyzes teacher training in order to promote and manage coexistence at secondary education schools by means of a description of students’ behaviors and by providing some proposals for improvement. We used a documentary analysis of university teacher training programs and a descriptive and assessment questionnaire of students’ behaviors towards coexistence and teachers´ reactions at five schools with a high immigration rate. Also, we developed a teacher focus group in order to put forwards some suggestions for improving these contexts. Results show a lack of training of teachers on these issues, significant differences in the assessment of certain behaviors measured by gender and teaching experience, disapproving responses by both males and females teachers, and a limited use of educational strategies that might improve coexistence at schools.Esta investigación pretende analizar la formación del profesorado para promover y gestionar la convivencia en las aulas en los Centros de Educación Secundaria, describir las conductas del alumnado que la alteran y ofrecer opciones de mejora.Se realiza un análisis documental de los programas de formación inicial de las universidades; se elabora un cuestionario descriptivo y valorativo de conductas del alumnado contrarias a la convivencia y respuestas del profesorado, en cinco centros con elevado número de alumnado inmigrante; y realiza un grupo de discusión de profesorado para ofrecer opciones de mejora de estos contextos. Y constata la escasa formación inicial del profesorado en estos aspectos, comprobado la existencia de diferencias significativas en la valoración de algunas conductas en función del género, de la experiencia docente y el uso por ambos géneros de respuestas usualmente sancionadoras, y el escaso empleo de estrategias educativas/formativas que permitan aumentar la convivencia en el Centro

Ground-based detection of an extended helium atmosphere in the Saturn-mass exoplanet WASP-69b

Hot gas giant exoplanets can lose part of their atmosphere due to strong stellar irradiation, affecting their physical and chemical evolution. Studies of atmospheric escape from exoplanets have mostly relied on space-based observations of the hydrogen Lyman-{\alpha} line in the far ultraviolet which is strongly affected by interstellar absorption. Using ground-based high-resolution spectroscopy we detect excess absorption in the helium triplet at 1083 nm during the transit of the Saturn-mass exoplanet WASP-69b, at a signal-to-noise ratio of 18. We measure line blue shifts of several km/s and post transit absorption, which we interpret as the escape of part of the atmosphere trailing behind the planet in comet-like form. [Additional notes by authors: Furthermore, we provide upper limits for helium signals in the atmospheres of the exoplanets HD 209458b, KELT-9b, and GJ 436b. We investigate the host stars of all planets with detected helium signals and those of the three planets we derive upper limits for. In each case we calculate the X-ray and extreme ultraviolet flux received by these planets. We find that helium is detected in the atmospheres of planets (orbiting the more active stars and) receiving the larger amount of irradiation from their host stars.]Comment: Submitted to Science on 14 March 2018; Accepted by Science on 16 November 2018; Published by Science on 6 December 2018. This is the author's version of the work. It is posted here by permission of the AAAS for personal use. The definitive version was published in Science, on 6 December 2018 - Report: pages 21 (preprint), 4 figures - Supplementary materials: 22 pages, 10 figures, 3 table

A multiproxy study distinguishes environmental change from diagenetic alteration in the recent sedimentary record of the inner Cadiz Bay (SW Spain)

In this study, we reconstruct the recent environmental evolution of the inner Cadiz Bay using sedimentary records reaching back as far as AD 1700. We report lithological descriptions of the sediments and extensive mineralogical and geochemical analyses. An extraction technique that identifies different Fe phases provides an assessment of diagenetic alteration, which allows an estimation of the original organic matter inputs to the inner Cadiz Bay. Downcore variations in Corg/N ratios, δ13Corg and δ15N are related to changes in organic matter sources and the trophic state of the water column. The downcore records of selected trace metals (e.g. Pb, Zn and Cu) are interpreted to reflect changes in heavy metal pollution in the bay, while records of other elements (e.g. Mn and P) are likely overprinted by diagenetic alteration. Major environmental shifts took place during the 20th century, when the population around Cadiz Bay increased exponentially. Increases in sediment accumulation rates, organic matter inputs and heavy metal contents, in parallel with increases in δ13Corg and δ15N over this period, are interpreted as direct effects of the increasing anthropogenic influence in the area. The results of this study suggest that multiproxy approaches and detailed consideration of diagenetic overprinting are required to reconstruct past environmental conditions from coastal sediments

Energy substrate metabolism, mitochondrial structure and oxidative stress after cardiac ischemia-reperfusion in mice lacking UCP3.

Myocardial ischemia-reperfusion (IR) injury may result in cardiomyocyte dysfunction. Mitochondria play a critical role in cardiomyocyte recovery after IR injury. The mitochondrial uncoupling protein 3 (UCP3) has been proposed to reduce mitochondrial reactive oxygen species (ROS) production and to facilitate fatty acid oxidation. As both mechanisms might be protective following IR injury, we investigated functional, mitochondrial structural, and metabolic cardiac remodeling in wild-type mice and in mice lacking UCP3 (UCP3-KO) after IR. Results showed that infarct size in isolated perfused hearts subjected to IR ex vivo was larger in adult and old UCP3-KO mice than in equivalent wild-type mice, and was accompanied by higher levels of creatine kinase in the effluent and by more pronounced mitochondrial structural changes. The greater myocardial damage in UCP3-KO hearts was confirmed in vivo after coronary artery occlusion followed by reperfusion. S1QEL, a suppressor of superoxide generation from site IQ in complex I, limited infarct size in UCP3-KO hearts, pointing to exacerbated superoxide production as a possible cause of the damage. Metabolomics analysis of isolated perfused hearts confirmed the reported accumulation of succinate, xanthine and hypoxanthine during ischemia, and a shift to anaerobic glucose utilization, which all recovered upon reoxygenation. The metabolic response to ischemia and IR was similar in UCP3-KO and wild-type hearts, being lipid and energy metabolism the most affected pathways. Fatty acid oxidation and complex I (but not complex II) activity were equally impaired after IR. Overall, our results indicate that UCP3 deficiency promotes enhanced superoxide generation and mitochondrial structural changes that increase the vulnerability of the myocardium to IR injury.We are grateful to F. S´ anchez-Madrid, B. Iba´nez ˜ and E. Lara for facilitating experiments at CNIC (Madrid, Spain) and to W.E. Louch for facilitating experiments at the University of Oslo (Oslo, Norway). We thank B. Littlejohns, I. Khaliulin and H. Lin from M.S. Suleiman’s group (University of Bristol, Bristol, UK) for their valuable help with Langendorff perfusion experiments. We also thank E.T. Chouchani from M.P. Murphy’s group (Cambridge, UK) for help with metabolomics analysis, M. Guerra of the Electron Microscopy Unit at CBMSO (Madrid, Spain) for processing the samples for electron microscopy analysis, and A.V. Alonso (CNIC) for echocardiography analyses. The work in our laboratory is funded the Instituto de Salud Carlos III (FIS PI19/01030) to SC. Institutional grants from the Fundacion ´ Ramon ´ Areces and Banco de Santander to the CBMSO are also acknowledged.S

Limits to dark matter annihilation cross-section from a combined analysis of MAGIC and Fermi-LAT observations of dwarf satellite galaxies

We present the first joint analysis of gamma-ray data from the MAGIC Cherenkov telescopes and the Fermi Large Area Telescope (LAT) to search for gamma-ray signals from dark matter annihilation in dwarf satellite galaxies. We combine 158 hours of Segue 1 observations with MAGIC with 6-year observations of 15 dwarf satellite galaxies by the Fermi-LAT. We obtain limits on the annihilation cross-section for dark matter particle masses between 10 GeV and 100 TeV - the widest mass range ever explored by a single gamma-ray analysis. These limits improve on previously published Fermi-LAT and MAGIC results by up to a factor of two at certain masses. Our new inclusive analysis approach is completely generic and can be used to perform a global, sensitivity-optimized dark matter search by combining data from present and future gamma-ray and neutrino detectors.Comment: 19 pages, 3 figures. V2: Few typos corrected and references added. Matches published version JCAP 02 (2016) 03

Seafloor Morphology and Processes in the Alboran Sea

The seafloor of the Alboran Sea reflects its complex tectonic, sedimentary, and oceanography dynamics as a consequence of the geological context, involving interaction between the Eurasian and African plates, and oceanographic context, as it is where the Atlantic and Mediterranean waters meet. Their physiography has a semi-enclosed configuration characterized by two margins (the Spanish Iberian and North Africa—mostly Moroccan margins) enclosing deep basins. Tectonic activity is mainly attested by folds and faults that predominantly affect the central and eastern seafloor sectors, as well as numerous seamounts and fluid-flow features (pockmarks, mud volcanoes, and diapirs) that dot the seafloor. The sedimentary and oceanographic processes allow us to distinctly define two principal environments in the Alboran Sea: the shallow proximal margin (continental shelf); and the deep distal margin (continental slope and base of the slope) with the adjacent sub-basins. The shelf mostly comprises prodeltaic and infralittoral prograding wedges, with local bedform fields, submarine valleys, and wave-cut terraces. Coastal and fluvio-marine sedimentary processes, acting since the last glacial period, are responsible for these features. The deep marine environment is characterised by the ubiquity of contourites, whose continuity is interrupted by turbidite systems, canyons, and landslides. The alongslope action of the Mediterranean waters and their interfaces with the Atlantic water has been the main process governing transport, seafloor reworking, and sedimentation of contourites. Mass-movement processes are responsible for the formation of: (1) turbidite systems—turbidity flows and mass flows were dominant during the last glacial sea-level lowstand, evolving to dilute gravity flows during present interglacial high stand; and (2) landslides—the main triggering factors comprising over-steepening, seismicity, under consolidation due to overpressure by interstitial fluids, stratigraphy, and high sedimentation rates. Locally, still-undetermined biological activity in the Spanish and coral activity in the Moroccan margin generated fields of mounded bioconstructions. The seafloor morphology of the Alboran Sea offers interesting clues for assessing the main potential geological hazards, with tectonic seismicity and landslides (as well as their related tsunamis) being some of the most important potential hazards affecting coastal populations. In addition, the seafloor morphology in combination with assemblages of habitat-forming species enables habitat identification and mapping.En prens

Sterilization matters: Consequences of different sterilization techniques on gold nanoparticles

Nanoparticles (NPs) can offer many advantages over traditional drug design and delivery, as well as toward medical diagnostics. As with any medical device or pharmaceutical drug intended to be used for in vivo biomedical applications, NPs must be sterile. However, very little is known regarding the effect of sterilization methods on the intrinsic properties and stability of NPs. Herein a detailed analysis of physicochemical properties of two types of AuNPs upon sterilization by means of five different techniques is reported. In addition, cell viability and production of reactive oxygen species are studied. The results indicate that sterilization by ethylene oxide seems to be the most appropriate technique for both types of NPs. It is concluded that it is crucial to test several methods in order to establish the specific type of sterilization to be performed for each particular NP.The authors acknowledge financial support from the Xunta de Galicia (PGIDIT06TMT31402PR), SUDOE (IMMUNONET-SOE1/1P1/E014), and Spanish Ministry of Science and Innovation (Consolider Ingenio 2010, CSD2006-12, NANOBIOMED). Ángela França was supported with a Leonardo da Vinci Fellowship. Jesús Martinez de la Fuente thanks ARAID for financial support.Peer reviewe