Phytoplankton responses to changing temperature and nutrient availability are consistent across the tropical and subtropical Atlantic

Temperature and nutrient supply interactively control phytoplankton growth and productivity, yet the role of these drivers together still has not been determined experimentally over large spatial scales in the oligotrophic ocean. We conducted four microcosm experiments in the tropical and subtropical Atlantic (29°N-27°S) in which surface plankton assemblages were exposed to all combinations of three temperatures (in situ, 3 °C warming and 3 °C cooling) and two nutrient treatments (unamended and enrichment with nitrogen and phosphorus). We found that chlorophyll a concentration and the biomass of picophytoplankton consistently increase in response to nutrient addition, whereas changes in temperature have a smaller and more variable effect. Nutrient enrichment leads to increased picoeukaryote abundance, depressed Prochlorococcus abundance, and increased contribution of small nanophytoplankton to total biomass. Warming and nutrient addition synergistically stimulate light-harvesting capacity, and accordingly the largest biomass response is observed in the warmed, nutrient-enriched treatment at the warmest and least oligotrophic location (12.7°N). While moderate nutrient increases have a much larger impact than varying temperature upon the growth and community structure of tropical phytoplankton, ocean warming may increase their ability to exploit events of enhanced nutrient availabilit

Volume 35, AMT-1 Cruise Report and Preliminary Results

This report documents the scientific activities on board the Royal Research Ship (RRS) 'James Clark Ross' during the irst Atlantic Meridional Transect (AMT-1), 21 September to 24 October 1995. The ship sailed from Grimsby (England) for Montevideo (Uruguay) and then continued on to Stanley (Falkland Islands). The primary objective of the AMT program is to investigate basic biological processes in the open Atlantic Ocean over very broad spatial scales. For AMT-1, the meridional range covered was approximately 50 deg N to 50 deg S or nearly 8,000 nmi. The measurements to be taken during the AMT cruises are fundamental for the calibration, validation, and continuing understanding of remotely sensed observations of biological oceanography. They are also important for understanding plankton community structure over latitudinal scales and the role of the world ocean in global carbon cycles. During AMT-1 a variety of instruments were used to map the physical, chemical, and biological structure of the upper 200 m of the water column. Ocean color measurements were made using state-of-the-art sensors, whose calibration was traceable to the highest international standards. New advances in fluorometry were used to measure photosynthetic activity, which was then used to further interpret primary productivity. A unique set of samples and data were collected for the planktonic assemblages that vary throughout the range of the transect. These data will yield new interpretations on community composition and their role in carbon cycling. While the various provinces of the Atlantic Ocean were being crossed, the partial pressure of CO2 was related to biological productivity. This comparison revealed the areas of drawdown of atmospheric CO2 and how these areas relate to the surrounding biological productivity. These data, plus the measurements of light attenuation and phytoplankton optical properties, will be used as a primary input for basin-scale biological productivity models to help develop ecosystem dynamics models which will be important for improving the forecasting abilities of modelers. The AMT program is also attempting to meet the needs of international agencies in their implementation of Sensor Intercomparison and Merger for Biological and Interdisciplinary Ocean Studies (SIMBIOS), a program to develop a methodology and operational capability to combine data products from the various ocean color satellite missions

Reconciling models of primary production and photoacclimation

This is the final version. Available on open access from the Optical Society of America via the DOI in this recordPrimary production and photoacclimation models are two important classes of physiological models that find applications in remote sensing of pools and fluxes of carbon associated with phytoplankton in the ocean. They are also key components of ecosystem models designed to study biogeochemical cycles in the ocean. So far, these two classes of models have evolved in parallel, somewhat independently of each other. Here we examine how they are coupled to each other through the intermediary of the photosynthesis–irradiance parameters. We extend the photoacclimation model to accommodate the spectral effects of light penetration in the ocean and the spectral sensitivity of the initial slope of the photosynthesis–irradiance curve, making the photoacclimation model fully compatible with spectrally resolved models of photosynthesis in the ocean. The photoacclimation model contains a parameter , which is the maximum chlorophyll-to-carbon ratio that phytoplankton can attain when available light tends to zero. We explore how size-class-dependent values of could be inferred from field data on chlorophyll and carbon content in phytoplankton, and show that the results are generally consistent with lower bounds estimated from satellite-based primary production calculations. This was accomplished using empirical models linking phytoplankton carbon and chlorophyll concentration, and the range of values obtained in culture measurements. We study the equivalence between different classes of primary production models at the functional level, and show that the availability of a chlorophyll-to-carbon ratio facilitates the translation between these classes. We discuss the importance of the better assignment of parameters in primary production models as an important avenue to reduce model uncertainties and to improve the usefulness of satellite-based primary production calculations in climate research.Simons FoundationEuropean Space AgencyNational Centre for Earth ObservationNational Science Foundatio

Impacts of global change on Mediterranean forests and their services

The increase in aridity, mainly by decreases in precipitation but also by higher temperatures, is likely the main threat to the diversity and survival of Mediterranean forests. Changes in land use, including the abandonment of extensive crop activities, mainly in mountains and remote areas, and the increases in human settlements and demand for more resources with the resulting fragmentation of the landscape, hinder the establishment of appropriate management tools to protect Mediterranean forests and their provision of services and biodiversity. Experiments and observations indicate that if changes in climate, land use and other components of global change, such as pollution and overexploitation of resources, continue, the resilience of many forests will likely be exceeded, altering their structure and function and changing, mostly decreasing, their capacity to continue to provide their current services. A consistent assessment of the impacts of the changes, however, remains elusive due to the difficulty of obtaining simultaneous and complete data for all scales of the impacts in the same forests, areas and regions. We review the impacts of climate change and other components of global change and their interactions on the terrestrial forests of Mediterranean regions, with special attention to their impacts on ecosystem services. Management tools for counteracting the negative effects of global change on Mediterranean ecosystem- services are finally discussed

Short-term follow-up of chagasic patients after benznidazole treatment using multiple serological markers

<p>Abstract</p> <p>Background</p> <p>Conventional serological tests, using total soluble proteins or a cocktail of recombinant proteins from <it>T. cruzi </it>as antigens, are highly sensitive for Chagas disease diagnosis. This type of tests, however, does not seem to be reliable tools for short- and medium-term monitoring of the evolution of patients after antiparasitic treatment. The aim of the present study was to search for immunological markers that could be altered in the sera from Chagas disease patients after benznidazole treatment, and therefore have a potential predictive diagnostic value.</p> <p>Methods</p> <p>We analyzed the reactivity of sera from chagasic patients during different clinical phases of the disease against a series of immunodominant antigens, known as KMP11, PFR2, HSP70 and Tgp63. The reactivity of the sera from 46 adult Chronic Chagas disease patients living in a non-endemic country without vector transmission of <it>T. cruzi </it>(15 patients in the indeterminate stage, 16 in the cardiomiopathy stage and 16 in the digestive stage) and 22 control sera from non-infected subjects was analyzed. We also analyzed the response dynamics of sera from those patients who had been treated with benznidazole.</p> <p>Results</p> <p>Regardless of the stage of the sickness, the sera from chagasic patients reacted against KMP11, HSP70, PFR2 and Tgp63 recombinant proteins with statistical significance relative to the reactivity against the same antigens by the sera from healthy donors, patients with autoimmune diseases or patients suffering from tuberculosis, leprosy or malaria. Shortly after benznidazole treatment, a statistically significant decrease in reactivity against KMP11, HSP70 and PFR2 was observed (six or nine month). It was also observed that, following benznidazole treatment, the differential reactivity against these antigens co-relates with the clinical status of the patients.</p> <p>Conclusions</p> <p>The recombinant antigens KMP11, PFR2, Tgp63 and HSP70 are recognized by Chagas disease patients' sera at any clinical stage of the disease. Shortly after benznidazole treatment, a drop in reactivity against three of these antigens is produced in an antigen-specific manner. Most likely, analysis of the reactivity against these recombinant antigens may be useful for monitoring the effectiveness of benznidazole treatment.</p

Research priorities for European paediatric emergency medicine

Objective Research in European Paediatric Emergency Medicine (REPEM) network is a collaborative group of 69 paediatric emergency medicine (PEM) physicians from 20 countries in Europe, initiated in 2006. To further improve paediatric emergency care in Europe, the aim of this study was to define research priorities for PEM in Europe to guide the development of future research projects. Design and Setting We carried out an online survey in a modified three-stage Delphi study. Eligible participants were members of the REPEM network. In stage 1, the REPEM steering committee prepared a list of research topics. In stage 2, REPEM members rated on a 6-point scale research topics and they could add research topics and comment on the list for further refinement. Stage 3 included further prioritisation using the Hanlon Process of Prioritisation (HPP) to give more emphasis to the feasibility of a research topic. Results Based on 52 respondents (response rates per stage varying from 41% to 57%), we identified the conditions 'fever', 'sepsis' and 'respiratory infections', and the processes/interventions 'biomarkers', 'risk stratification' and 'practice variation' as common themes of research interest. The HPP identified highest priority for 4 of the 5 highest prioritised items by the Delphi process, incorporating prevalence and severity of each condition and feasibility of undertaking such research. Conclusions While the high diversity in emergency department (ED) populations, cultures, healthcare systems and healthcare delivery in European PEM prompts to focus on practice variation of ED conditions, our defined research priority list will help guide further collaborative research efforts within the REPEM network to improve PEM care in Europe.publishersversionPeer reviewe

Dendritic Cells Crosspresent Antigens from Live B16 Cells More Efficiently than from Apoptotic Cells and Protect from Melanoma in a Therapeutic Model

Dendritic cells (DC) are able to elicit anti-tumoral CD8+ T cell responses by cross-presenting exogenous antigens in association with major histocompatibility complex (MHC) class I molecules. Therefore they are crucial actors in cell-based cancer immunotherapy. Although apoptotic cells are usually considered to be the best source of antigens, live cells are also able to provide antigens for cross-presentation by DC. We have recently shown that prophylactic immunotherapy by DC after capture of antigens from live B16 melanoma cells induced strong CD8+ T-cell responses and protection against a lethal tumor challenge in vivo in C57Bl/6 mice. Here, we showed that DC cross-presenting antigens from live B16 cells can also inhibit melanoma lung dissemination in a therapeutic protocol in mice. DC were first incubated with live tumor cells for antigen uptake and processing, then purified and irradiated for safety prior to injection. This treatment induced stronger tumor-specific CD8+ T-cell responses than treatment by DC cross-presenting antigens from apoptotic cells. Apoptotic B16 cells induced more IL-10 secretion by DC than live B16 cells. They underwent strong native antigen degradation and led to the expression of fewer MHC class I/epitope complexes on the surface of DC than live cells. Therefore, the possibility to use live cells as sources of tumor antigens must be taken into account to improve the efficiency of cancer immunotherapy

Cholesteryl ester transfer protein (CETP) as a drug target for cardiovascular disease

The preliminary meta-analysis of RCT data were presented at BPS 2018 by NH. The preprint version of this paper has been deposited on medrxiv: https://doi.org/10.1101/2020.09.07.20189571.Copyright © 2021 The Author(s). Development of cholesteryl ester transfer protein (CETP) inhibitors for coronary heart disease (CHD) has yet to deliver licensed medicines. To distinguish compound from drug target failure, we compared evidence from clinical trials and drug target Mendelian randomization of CETP protein concentration, comparing this to Mendelian randomization of proprotein convertase subtilisin/kexin type 9 (PCSK9). We show that previous failures of CETP inhibitors are likely compound related, as illustrated by significant degrees of between-compound heterogeneity in effects on lipids, blood pressure, and clinical outcomes observed in trials. On-target CETP inhibition, assessed through Mendelian randomization, is expected to reduce the risk of CHD, heart failure, diabetes, and chronic kidney disease, while increasing the risk of age-related macular degeneration. In contrast, lower PCSK9 concentration is anticipated to decrease the risk of CHD, heart failure, atrial fibrillation, chronic kidney disease, multiple sclerosis, and stroke, while potentially increasing the risk of Alzheimer’s disease and asthma. Due to distinct effects on lipoprotein metabolite profiles, joint inhibition of CETP and PCSK9 may provide added benefit. In conclusion, we provide genetic evidence that CETP is an effective target for CHD prevention but with a potential on-target adverse effect on age-related macular degeneration.This research has been conducted using the UK Biobank Resource under Application Number 12113. The authors are grateful to UK Biobank participants. We gratefully acknowledge the support of UCLEB and CHARGE. Funding and role of funding sources: A.F.S. is supported by BHF grant PG/18/5033837 and the UCL BHF Research Accelerator AA/18/6/34223. C.F. and A.F.S. received additional support from the National Institute for Health Research University College London Hospitals Biomedical Research Centre. M.G.M. is supported by a BHF Fellowship FS/17/70/33482. A.D.H. is an NIHR Senior Investigator. This work was supported by the UKRI/NIHR Strategic Priorities Award in Multimorbidity Research (MR/V033867/1). This work was additionally supported by a grant [R01 LM010098] from the National Institutes of Health (USA). We further acknowledge support from the Rosetrees and Stoneygate Trust. The UCLEB Consortium is supported by a British Heart Foundation Program Grant (RG/10/12/28456). T.R.G. receives support from the UK Medical Research Council (MC_UU_00011/4). D.O.M.K. is supported by the Dutch Science Organization (ZonMW-VENI Grant 916.14.023). A D.H. receives support from the UK Medical Research (MC_UU_12019/1). M.K. is supported by the Wellcome Trust (221854/Z/20/Z), the UK Medical Research Council (MR/S011676/1, MR/R024227/1), National Institute on Aging (NIH), US (R01AG062553), and the Academy of Finland (311492). D.A.L. is supported by a Bristol BHF Accelerator Award (AA/18/7/34219) and BHF Chair (CH/F/20/90003) and works in a unit that receives support from the University of Bristol and the UK Medical Research Council (MC_UU_00011/6). D.A.L. is a National Institute of Health Research Senior Investigator (NF-0616-10102). N.F. is supported by the National Institutes of Health (R01-MD012765, R01-DK117445, R21- HL140385). P.C. is supported by the Thailand Research Fund (MRG6280088. UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council, Department of Health, Scottish Government, and the Northwest Regional Development Agency. It has also had funding from the Welsh Assembly Government and the British Heart Foundation. Infrastructure for the CHARGE Consortium is supported in part by the National Heart, Lung, and Blood Institute grant R01HL105756

Accommodating a Non-Conservative Internal Mutation by WaterMediated Hydrogen-Bonding Between β-Sheet Strands: A Comparison of Human and Rat Type B (Mitochondrial) Cytochrome b5

Mammalian type B (mitochondrial) cytochromes b5 exhibit greater amino acid sequence diversity than their type A (microsomal) counterparts, as exemplified by the type B proteins from human (hCYB5B) and rat (rCYB5B). The comparison of X-ray crystal structures of hCYB5B and rCYB5B reported herein reveals a striking difference in packing involving the five-stranded β-sheet, attributable to fully buried residue 21 in strand β4. The greater bulk of Leu21 in hCYB5B in comparison to Thr21 in rCYB5B results in a substantial displacement of the first two residues in β5, and consequent loss of two of the three hydrogen bonds between β5 and β4. Hydrogen-bonding between the residues is instead mediated by two well-ordered, fully buried water molecules. In a 10 ns molecular dynamics simulation, one of the buried water molecules in the hCYB5B structure exchanged readily with solvent via intermediates having three water molecules sandwiched between β4 and β5. When the buried water molecules were removed prior to a second 10 ns simulation, β4 and β5 formed persistent hydrogen bonds identical to those in rCYB5B, but the Leu21 side chain was forced to adopt a rarely observed conformation. Despite the apparently greater ease of water access to the interior of hCYB5B than of rCYB5B suggested by these observations, the two proteins exhibit virtually identical stability, dynamic and redox properties. The results provide new insight into the factors stabilizing the cytochrome b5 fold