Beneficial microorganisms for corals (BMCs) ameliorate environmental stress, but whether they can prevent mortality and the underlying host response mechanisms remains elusive. Here, we conducted omics analyses on the coral Mussismilia hispida exposed to bleaching conditions in a long-term mesocosm experiment and inoculated with a selected BMC consortium or a saline solution placebo. All corals were affected by heat stress, but the observed "post-heat stress disorder" was mitigated by BMCs, signified by patterns of dimethylsulfoniopropionate degradation, lipid maintenance, and coral host transcriptional reprogramming of cellular restructuration, repair, stress protection, and immune genes, concomitant with a 40% survival rate increase and stable photosynthetic performance by the endosymbiotic algae. This study provides insights into the responses that underlie probiotic host manipulation. We demonstrate that BMCs trigger a dynamic microbiome restructuring process that instigates genetic and metabolic alterations in the coral host that eventually mitigate coral bleaching and mortality. ; This research project won the Great Barrier Reef Foundation's Out of the Blue Box Reef Innovation Challenge People's Choice Award supported by The Tiffany & Co.Foundation. C.R.V. was supported through the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation) Project Numbers 433042944 and 458901010. R.S.P. was supported through KAUST grant number BAS/1/1095-01-01 and the Rio de Janeiro Marine Aquarium Research Center. E.P.S. received support from the Graduate Programs of Science (Microbiology) and Plant Biotechnology and Bioprocess Engineering (PBV)/Federal University of Rio de Janeiro, the Brazilian Government Research Agency CAPES, and the CAPES PRINT international mobility grant.
Clear role descriptions promote the quality of interprofessional collaboration. Currently, it is unclear to what extent healthcare professionals consider pharmaceutical care (PC) activities to be nurses' responsibility in order to obtain best care quality. This study aimed to create and evaluate a framework describing potential nursing tasks in PC and to investigate nurses' level of responsibility. A framework of PC tasks and contextual factors was developed based on literature review and previous DeMoPhaC project results. Tasks and context were cross-sectionally evaluated using an online survey in 14 European countries. A total of 923 nurses, 240 physicians and 199 pharmacists responded. The majority would consider nurses responsible for tasks within: medication self-management (86–97%), patient education (85–96%), medication safety (83–95%), monitoring adherence (82–97%), care coordination (82–95%), and drug monitoring (78–96%). The most prevalent level of responsibility was 'with shared responsibility'. Prescription management tasks were considered to be nurses' responsibility by 48–81% of the professionals. All contextual factors were indicated as being relevant for nurses' role in PC by at least 74% of the participants. No task nor contextual factor was removed from the framework after evaluation. This framework can be used to enable healthcare professionals to openly discuss allocation of specific (shared) responsibilities and tasks. ; This research was supported by the Erasmus+ Programme of the European Union [grant number 2018-1-BE02-KA203-046861] and MDMJ accountants, Belgium.
The composition of local mammalian carnivore communities has far-reaching effects on terrestrial ecosystems worldwide. To better understand how carnivore communities are structured, we analysed camera trap data for 108087 trap days across 12 countries spanning five continents. We estimate local probabilities of co-occurrence among 768 species pairs from the order Carnivora and evaluate how shared ecological traits correlate with probabilities of co-occurrence. Within individual study areas, species pairs co-occurred more frequently than expected at random. Co-occurrence probabilities were greatest for species pairs that shared ecological traits including similar body size, temporal activity pattern and diet. However, co-occurrence decreased as compared to other species pairs when the pair included a large-bodied carnivore. Our results suggest that a combination of shared traits and top-down regulation by large carnivores shape local carnivore communities globally. ; Ministry of Environment, Water, Forest and Tourism and Wildlife Conservation Society in Madagascar; Department of National Parks and United States Agency for International Development/Wula Nafaa Project in SenegalUnited States Agency for International Development (USAID); Cederberg Conservancy and Cape-Nature in South Africa; US Forest ServiceUnited States Department of Agriculture (USDA)United States Forest Service; Belize Forest Department; Belize Audubon Society; Programme for Belize; Las Cuevas Research Station; Bull Run Farm; Gallon Jug Estate; Yalbac Ranch and Cattle Company; NSF LTREB Grant [1556248]; Ministry of Ecology and Natural Resources of Misiones; National Park Administration of Argentina; Ledesma S.A.; Arauco SA; Department of National conduct surveys in Chitwan National Park; WWF Networks; US Fish & Wildlife ServiceUS Fish & Wildlife Service; Hurvis Family; WWF Team; Directorate for Nature Management; Norwegian Research CouncilResearch Council of Norway; Department of National conduct surveys in Indonesia ; We thank the Ministry of the Environment, Wildlife and Tourism, the Department of Wildlife and National Parks, and the Botswana Predator Conservation Trust for permission to conduct the study in Botswana; the Ministry of Environment, Water, Forest and Tourism and Wildlife Conservation Society in Madagascar; the Department of National Parks and United States Agency for International Development/Wula Nafaa Project in Senegal; and The Cederberg Conservancy and Cape-Nature in South Africa for permission and/or supporting the research in Africa. We thank Parks Canada staff and volunteers for collecting data in Canada, the US Forest Service for financing and collecting data in the USA along with volunteers from the Student Conservation Association, and the Belize Forest Department, Belize Audubon Society, Programme for Belize, Las Cuevas Research Station, Bull Run Farm, Gallon Jug Estate, and Yalbac Ranch and Cattle Company for permission and support in conducting research in Belize. Funding for camera trap surveys in Canada was provided in part by NSF LTREB Grant 1556248. We thank the Ministry of Ecology and Natural Resources of Misiones, the National Park Administration of Argentina, Ledesma S.A. and Arauco SA for permissions and support to conduct camera trap surveys. We thank the Iran Department of Environment for permission to work within the reserves in Iran, Department of National conduct surveys in Chitwan National Park, and in Indonesia, WWF Networks, US Fish & Wildlife Service and the Hurvis Family for financially supporting the research, the Indonesian Ministry of Forestry for permission to conduct the study, and the WWF Team for their support. We also thank the Directorate for Nature Management and The Norwegian Research Council for financing camera trap surveys in Norway. ; Public domain authored by a U.S. government employee
The costimulation of immune cells using first-generation anti-4-1BB monoclonal antibodies (mAbs) has demonstrated anti-tumor activity in human trials. Further clinical development, however, is restricted by significant off-tumor toxicities associated with FcγR interactions. Here, we have designed an Fc-free tumor-targeted 4-1BB-agonistic trimerbody, 1D8N/CEGa1, consisting of three anti-4-1BB single-chain variable fragments and three anti-EGFR single-domain antibodies positioned in an extended hexagonal conformation around the collagen XVIII homotrimerization domain. The1D8N/CEGa1 trimerbody demonstrated high-avidity binding to 4-1BB and EGFR and a potent in vitro costimulatory capacity in the presence of EGFR. The trimerbody rapidly accumulates in EGFR-positive tumors and exhibits anti-tumor activity similar to IgG-based 4-1BB-agonistic mAbs. Importantly, treatment with 1D8N/CEGa1 does not induce systemic inflammatory cytokine production or hepatotoxicity associated with IgG-based 4-1BB agonists. These results implicate FcγR interactions in the 4-1BB-agonist-associated immune abnormalities, and promote the use of the non-canonical antibody presented in this work for safe and effective costimulatory strategies in cancer immunotherapy. ; We thank M. Jure-Kunkel, M. Rescigno and A. Villalobo for reagents, M.G. Gonzalez Bueno and B. Acosta (IIBm) for technical support, and the staff of beamline B21at Diamond Light Source (Didcot, UK) for their excellent technical assistance. This study was supported by grants from the European Union [IACT Project (602262), iNEXT Project (1676) and a Marie Curie Career Integration Grant (PCIG13-GA-2013-618914)], the Ministerio de Economía y Competitividad (CTQ2017-83810-R, RTC-2016-5118-1, SAF2017-83267-C2-1-R, SAF2017-89437-P, and PTQ-16-08340), the Fondo de Investigación Sanitaria/Instituto de Salud Carlos III (PI16/00357 and PI16/00895), the UK Research and Innovation (18130023), and the Danish Council for Independent Research (DFF-6110-0053). The CIC bioGUNE is a Severo Ochoa Center of Excellence (Ministerio de Economia y Competitividad award SEV-2016-0644). This study was also funded by FEDER. ; Sí
NOMAD is a suite of three spectrometers that will be launched in 2016 as part of the joint ESA-Roscosmos ExoMars Trace Gas Orbiter mission. The instrument contains three channels that cover the IR and UV spectral ranges and can perform solar occultation, nadir and limb observations, to detect and map a wide variety of Martian atmospheric gases and trace species. Part I of this work described the models of the UVIS channel; in this second part, we present the optical models representing the two IR channels, SO (Solar Occultation) and LNO (Limb, Nadir and Occultation), and use them to determine signal to noise ratios (SNRs) for many expected observational cases. In solar occultation mode, both the SO and LNO channel exhibit very high SNRs >5000. SNRs of around 100 were found for the LNO channel in nadir mode, depending on the atmospheric conditions, Martian surface properties, and observation geometry. ; NOMAD has been made possible thanks to funding by the Belgian Science Policy Office (BELSPO) and financial and contractual coordination by the ESA Prodex Office. The research was performed as part of the "Inter university Attraction Poles" programme financed by the Belgian government (Planet TOPERS). UK funding is acknowledged under the UK Space Agency grant ST/I003061/1. ; https://www.osapublishing.org/oe/abstract.cfm?uri=oe-24-4-3790
et al. ; A new set of measurements of the top quark mass are presented, based on the proton-proton data recorded by the CMS experiment at the LHC at √s=8 TeV corresponding to a luminosity of 19.7 fb-1. The top quark mass is measured using the lepton+jets, all-jets and dilepton decay channels, giving values of 172.35±0.16(stat)±0.48(syst) GeV, 172.32±0.25(stat)±0.59(syst) GeV, and 172.82±0.19(stat)±1.22(syst) GeV, respectively. When combined with the published CMS results at √s=7 TeV, they provide a top quark mass measurement of 172.44±0.13(stat)±0.47(syst) GeV. The top quark mass is also studied as a function of the event kinematical properties in the lepton+jets decay channel. No indications of a kinematic bias are observed and the collision data are consistent with a range of predictions from current theoretical models of tt production. ; Individuals have received support from the Marie-Curie program and the European Research Council and EPLANET (European Union); the Leventis Foundation; the A. P. Sloan Foundation; the Alexander von Humboldt Foundation; the Belgian Federal Science Policy Office; the Fonds pour la Formation à la Recherche dans l'Industrie et dans l'Agriculture (FRIA-Belgium); the Agentschap voor Innovatie door Wetenschap en Technologie (IWT-Belgium); the Ministry of Education, Youth and Sports (MEYS) of the Czech Republic; the Council of Science and Industrial Research, India; the HOMING PLUS program of the Foundation for Polish Science, cofinanced from European Union, Regional Development Fund; the OPUS program of the National Science Center (Poland); the Compagnia di San Paolo (Torino); the Consorzio per la Fisica (Trieste); MIUR project 20108T4XTM (Italy); the Thalis and Aristeia programs cofinanced by EU-ESF and the Greek NSRF; the National Priorities Research Program by Qatar National Research Fund; the Rachadapisek SomWetenschappelijk Onderzopot Fund for Postdoctoral Fellowship, Chulalongkorn University (Thailand); and the Welch Foundation, Contract No. C-1845. ; Peer Reviewed
The authors would like to thank the leadership of the Deep Ocean Stewardship Initiative (DOSI), including Lisa Levin, Maria Baker, and Kristina Gjerde, for their support in developing this review. This work evolved from a meeting of the DOSI Oil and Gas working group supported by the J.M. Kaplan Fund, and associated with the Deep-Sea Biology Symposium in Aveiro, Portugal in September 2015. The members of the Oil and Gas working group that contributed to our discussions at that meeting or through the listserve are acknowledged for their contributions to this work. We would also like to thank the three reviewers and the editor who provided valuable comments and insight into the work presented here. DJ and AD were supported by funding from the European Union's Horizon 2020 research and innovation programme under the MERCES (Marine Ecosystem Restoration in Changing European Seas) project, grant agreement No 689518. AB was supported by CNPq grants 301412/2013-8 and 200504/2015-0. LH acknowledges funding provided by a Natural Environment Research Council grant (NE/L008181/1). This output reflects only the authors' views and the funders cannot be held responsible for any use that may be made of the information contained therein. ; Peer reviewed ; Publisher PDF
International audience; High content omic techniques in combination with stable human in vitro cell culture systems have the potential to improve on current pre-clinical safety regimes by providing detailed mechanistic information of altered cellular processes. Here we investigated the added benefit of integrating transcriptomics, proteomics and metabolomics together with pharmacokinetics for drug testing regimes. Cultured human renal epithelial cells (RPTEC/TERT1) were exposed to the nephrotoxin Cyclosporine A (CsA) at therapeutic and supratherapeutic concentrations for 14 days. CsA was quantified in supernatants and cellular lysates by LC-MS/MS for kinetic modeling. There was a rapid cellular uptake and accumulation of CsA, with a non-linear relationship between intracellular and applied concentrations. CsA at 15 µM induced mitochondrial disturbances and activation of the Nrf2-oxidative-damage and the unfolded protein-response pathways. All three omic streams provided complementary information, especially pertaining to Nrf2 and ATF4 activation. No stress induction was detected with 5 µM CsA; however, both concentrations resulted in a maximal secretion of cyclophilin B. The study demonstrates for the first time that CsA-induced stress is not directly linked to its primary pharmacology. In addition we demonstrate the power of integrated omics for the elucidation of signaling cascades brought about by compound induced cell stress.
Climate change is predicted to result in changes in the geographic ranges and local prevalence of infectious diseases, either through direct effects on the pathogen, or indirectly through range shifts in vector and reservoir species. To better understand the occurrence of monkeypox virus (MPXV), an emerging Orthopoxvirus in humans, under contemporary and future climate conditions, we used ecological niche modeling techniques in conjunction with climate and remote-sensing variables. We first created spatially explicit probability distributions of its candidate reservoir species in Africa's Congo Basin. Reservoir species distributions were subsequently used to model current and projected future distributions of human monkeypox (MPX). Results indicate that forest clearing and climate are significant driving factors of the transmission of MPX from wildlife to humans under current climate conditions. Models under contemporary climate conditions performed well, as indicated by high values for the area under the receiver operator curve (AUC), and tests on spatially randomly and non-randomly omitted test data. Future projections were made on IPCC 4th Assessment climate change scenarios for 2050 and 2080, ranging from more conservative to more aggressive, and representing the potential variation within which range shifts can be expected to occur. Future projections showed range shifts into regions where MPX has not been recorded previously. Increased suitability for MPX was predicted in eastern Democratic Republic of Congo. Models developed here are useful for identifying areas where environmental conditions may become more suitable for human MPX; targeting candidate reservoir species for future screening efforts; and prioritizing regions for future MPX surveillance efforts.
