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

Soil carbon loss in warmed subarctic grasslands is rapid and restricted to topsoil

Global warming may lead to carbon transfers from soils to the atmosphere, yet this positive feedback to the climate system remains highly uncertain, especially in subsoils (Ilyina and Friedlingstein, 2016; Shi et al., 2018). Using natural geothermal soil warming gradients of up to +6.4 degrees C in subarctic grasslands (Sigurdsson et al., 2016), we show that soil organic carbon (SOC) stocks decline strongly and linearly with warming (-2.8 t ha(-1) degrees C-1). Comparison of SOC stock changes following medium-term (5 and 10 years) and long-term (> 50 years) warming revealed that all SOC stock reduction occurred within the first 5 years of warming, after which continued warming no longer reduced SOC stocks. This rapid equilibration of SOC observed in Andosol suggests a critical role for ecosystem adaptations to warming and could imply short-lived soil carbon-climate feedbacks. Our data further revealed that the soil C loss occurred in all aggregate size fractions and that SOC stock reduction was only visible in topsoil (0-10 cm). SOC stocks in subsoil (10-30 cm), where plant roots were absent, showed apparent conservation after > 50 years of warming. The observed depth-dependent warming responses indicate that explicit vertical resolution is a prerequisite for global models to accurately project future SOC stocks for this soil type and should be investigated for soils with other mineralogies

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

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

Exposure to Apoptotic Activated CD4+ T Cells Induces Maturation and APOBEC3G- Mediated Inhibition of HIV-1 Infection in Dendritic Cells

Dendritic cells (DCs) are activated by signaling via pathogen-specific receptors or exposure to inflammatory mediators. Here we show that co-culturing DCs with apoptotic HIV-infected activated CD4+ T cells (ApoInf) or apoptotic uninfected activated CD4+ T cells (ApoAct) induced expression of co-stimulatory molecules and cytokine release. In addition, we measured a reduced HIV infection rate in DCs after co-culture with ApoAct. A prerequisite for reduced HIV infection in DCs was activation of CD4+ T cells before apoptosis induction. DCs exposed to ApoAct or ApoInf secreted MIP-1α, MIP-1β, MCP-1, and TNF-α; this effect was retained in the presence of exogenous HIV. The ApoAct-mediated induction of co-stimulatory CD86 molecules and reduction of HIV infection in DCs were partially abrogated after blocking TNF-α using monoclonal antibodies. APOBEC3G expression in DCs was increased in co-cultures of DCs and ApoAct but not by apoptotic resting CD4+ T cells (ApoRest). Silencing of APOBEC3G in DC abrogated the HIV inhibitory effect mediated by ApoAct. Sequence analyses of an env region revealed significant induction of G-to-A hypermutations in the context of GG or GA dinucleotides in DNA isolated from DCs exposed to HIV and ApoAct. Thus, ApoAct-mediated DC maturation resulted in induction of APOBEC3G that was important for inhibition of HIV-infection in DCs. These findings underscore the complexity of differential DC responses evoked upon interaction with resting as compared with activated dying cells during HIV infection

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

Overview of biologically digested leachate treatment using adsorption

Biological process is effective in treating most biodegradable organic matter present in leachate; however, a significant amount of ammonia, metals and refractory organic compounds may still remain in this biologically digested leachate. This effluent cannot be released to receiving bodies until the discharge limit is met. Several physical/chemical processes have been practiced as post-treatment to remove the remaining pollutants including coagulation–flocculation, oxidation and adsorption. Adsorption is often applied in leachate treatment as it enhances removal of refractory organic compounds. This chapter will focus on works related to adsorption as one of the commonly used methods to treat biologically digested leachate further down to acceptable discharge limit

Overview of biologically digested leachate treatment using adsorption

Biological process is effective in treating most biodegradable organic matter present in leachate; however, a significant amount of ammonia, metals and refractory organic compounds may still remain in this biologically digested leachate. This effluent cannot be released to receiving bodies until the discharge limit is met. Several physical/chemical processes have been practiced as post-treatment to remove the remaining pollutants including coagulation–flocculation, oxidation and adsorption. Adsorption is often applied in leachate treatment as it enhances removal of refractory organic compounds. This chapter will focus on works related to adsorption as one of the commonly used methods to treat biologically digested leachate further down to acceptable discharge limit