Modelling size-fractionated primary production in the Atlantic Ocean from remote sensing

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordMarine primary production influences the transfer of carbon dioxide between the ocean and atmosphere, and the availability of energy for the pelagic food web. Both the rate and the fate of organic carbon from primary production are dependent on phytoplankton size. A key aim of the Atlantic Meridional Transect (AMT) programme has been to quantify biological carbon cycling in the Atlantic Ocean and measurements of total primary production have been routinely made on AMT cruises, as well as additional measurements of size-fractionated primary production on some cruises. Measurements of total primary production collected on the AMT have been used to evaluate remote-sensing techniques capable of producing basin-scale estimates of primary production. Though models exist to estimate size-fractionated primary production from satellite data, these have not been well validated in the Atlantic Ocean, and have been parameterised using measurements of phytoplankton pigments rather than direct measurements of phytoplankton size structure. Here, we re-tune a remote-sensing primary production model to estimate production in three size fractions of phytoplankton (10 μm) in the Atlantic Ocean, using measurements of size-fractionated chlorophyll and size-fractionated photosynthesis-irradiance experiments conducted on AMT 22 and 23 using sequential filtration-based methods. The performance of the remote-sensing technique was evaluated using: (i) independent estimates of size-fractionated primary production collected on a number of AMT cruises using 14C on-deck incubation experiments and (ii) Monte Carlo simulations. Considering uncertainty in the satellite inputs and model parameters, we estimate an average model error of between 0.27 and 0.63 for log10-transformed size-fractionated production, with lower errors for the small size class (10 μm), and errors generally higher in oligotrophic waters. Application to satellite data in 2007 suggests the contribution of cells 2 μm to total primary production is approximately equal in the Atlantic Ocean.UK National Centre for Earth ObservationNatural Environment Research Council (NERC)Plymouth Marine Laborator

Control of Emi2 activity and stability through Mos-mediated recruitment of PP2A.

Before fertilization, vertebrate eggs are arrested in meiosis II by cytostatic factor (CSF), which holds the anaphase-promoting complex (APC) in an inactive state. It was recently reported that Mos, an integral component of CSF, acts in part by promoting the Rsk-mediated phosphorylation of the APC inhibitor Emi2/Erp1. We report here that Rsk phosphorylation of Emi2 promotes its interaction with the protein phosphatase PP2A. Emi2 residues adjacent to the Rsk phosphorylation site were important for PP2A binding. An Emi2 mutant that retained Rsk phosphorylation but lacked PP2A binding could not be modulated by Mos. PP2A bound to Emi2 acted on two distinct clusters of sites phosphorylated by Cdc2, one responsible for modulating its stability during CSF arrest and one that controls binding to the APC. These findings provide a molecular mechanism for Mos action in promoting CSF arrest and also define an unusual mechanism, whereby protein phosphorylation recruits a phosphatase for dephosphorylation of distinct sites phosphorylated by another kinase

Cysteine oxidation targets peroxiredoxins 1 and 2 for exosomal release through a novel mechanism of redox-dependent secretion

Non-classical protein secretion is of major importance as a number of cytokines and inflammatory mediators are secreted via this route. Current evidence indicates that there are several mechanistically distinct methods of non-classical secretion. We have recently shown that peroxiredoxin (Prdx) 1 and Prdx2 are released by various cells upon exposure to inflammatory stimuli such as LPS or TNF-α. The released Prdx then acts to induce production of inflammatory cytokines. However, Prdx1 and 2 do not have signal peptides and therefore must be secreted by alternative mechanisms as has been postulated for the inflammatory mediators IL-1β and HMGB1. We show here that circulating Prdx1 and 2 are present exclusively as disulphide-linked homodimers. Inflammatory stimuli also induce in vitro release of Prdx1 and 2 as disulfide-linked homodimers. Mutation of cysteines Cys51 or Cys172 (but not Cys70) in Prdx2, and Cys52 or Cys173 (but not Cys71 or Cys83) in Prdx1 prevented dimer formation and this was associated with inhibition of their TNF-α-induced release. Thus, the presence and oxidation of key cysteine residues in these proteins are a prerequisite for their secretion in response to TNF-α and this release can be induced with an oxidant. In contrast, the secretion of the nuclear-associated danger signal HMGB1 is independent of cysteine oxidation, as shown by experiments with a cysteine-free HMGB1 mutant. Release of Prdx1 and 2 is not prevented by inhibitors of the classical secretory pathway; instead, both Prdx1 and 2 are released in exosomes from both HEK cells and monocytic cells. Serum Prdx1 and 2 are also associated with the exosomes. These results describe a novel pathway of protein secretion mediated by cysteine oxidation that underlines the importance of redox-dependent signalling mechanisms in inflammation

An international randomised placebo-controlled trial of a four-component combination pill ("polypill") in people with raised cardiovascular risk.

BACKGROUND:There has been widespread interest in the potential of combination cardiovascular medications containing aspirin and agents to lower blood pressure and cholesterol ('polypills') to reduce cardiovascular disease. However, no reliable placebo-controlled data are available on both efficacy and tolerability. METHODS:We conducted a randomised, double-blind placebo-controlled trial of a polypill (containing aspirin 75 mg, lisinopril 10 mg, hydrochlorothiazide 12.5 mg and simvastatin 20 mg) in 378 individuals without an indication for any component of the polypill, but who had an estimated 5-year cardiovascular disease risk over 7.5%. The primary outcomes were systolic blood pressure (SBP), LDL-cholesterol and tolerability (proportion discontinued randomised therapy) at 12 weeks follow-up. FINDINGS:At baseline, mean BP was 134/81 mmHg and mean LDL-cholesterol was 3.7 mmol/L. Over 12 weeks, polypill treatment reduced SBP by 9.9 (95% CI: 7.7 to 12.1) mmHg and LDL-cholesterol by 0.8 (95% CI 0.6 to 0.9) mmol/L. The discontinuation rates in the polypill group compared to placebo were 23% vs 18% (RR 1.33, 95% CI 0.89 to 2.00, p = 0.2). There was an excess of side effects known to the component medicines (58% vs 42%, p = 0.001), which was mostly apparent within a few weeks, and usually did not warrant cessation of trial treatment. CONCLUSIONS:This polypill achieved sizeable reductions in SBP and LDL-cholesterol but caused side effects in about 1 in 6 people. The halving in predicted cardiovascular risk is moderately lower than previous estimates and the side effect rate is moderately higher. Nonetheless, substantial net benefits would be expected among patients at high risk. TRIAL REGISTRATION:Australian New Zealand Clinical Trials Registry ACTRN12607000099426

Reduced level of arousal and increased mortality in adult acute medical admissions: a systematic review and meta-analysis

Abstract Background Reduced level of arousal is commonly observed in medical admissions and may predict in-hospital mortality. Delirium and reduced level of arousal are closely related. We systematically reviewed and conducted a meta-analysis of studies in adult acute medical patients of the relationship between reduced level of arousal on admission and in-hospital mortality. Methods We conducted a systematic review (PROSPERO: CRD42016022048), searching MEDLINE and EMBASE. We included studies of adult patients admitted with acute medical illness with level of arousal assessed on admission and mortality rates reported. We performed meta-analysis using a random effects model. Results From 23,941 studies we included 21 with 14 included in the meta-analysis. Mean age range was 33.4 - 83.8 years. Studies considered unselected general medical admissions (8 studies, n=13,039) or specific medical conditions (13 studies, n=38,882). Methods of evaluating level of arousal varied. The prevalence of reduced level of arousal was 3.1%-76.9% (median 13.5%). Mortality rates were 1.7%-58% (median 15.9%). Reduced level of arousal was associated with higher in-hospital mortality (pooled OR 5.71; 95% CI 4.21-7.74; low quality evidence: high risk of bias, clinical heterogeneity and possible publication bias). Conclusions Reduced level of arousal on hospital admission may be a strong predictor of in-hospital mortality. Most evidence was of low quality. Reduced level of arousal is highly specific to delirium, better formal detection of hypoactive delirium and implementation of care pathways may improve outcomes. Future studies to assess the impact of interventions on in-hospital mortality should use validated assessments of both level of arousal and delirium

A general piecewise multi-state survival model: Application to breast cancer

Multi-state models are considered in the field of survival analysis for modelling illnesses that evolve through several stages over time. Multi-state models can be developed by applying several techniques, such as non-parametric, semi-parametric and stochastic processes, particularly Markov processes. When the development of an illness is being analysed, its progression is tracked periodically. Medical reviews take place at discrete times, and a panel data analysis can be formed. In this paper, a discrete-time piecewise non-homogeneous Markov process is constructed for modelling and analysing a multi-state illness with a general number of states. The model is built, and relevant measures, such as survival function, transition probabilities, mean total times spent in a group of states and the conditional probability of state change, are determined. A likelihood function is built to estimate the parameters and the general number of cut-points included in the model. Time-dependent covariates are introduced, the results are obtained in a matrix algebraic form and the algorithms are shown. The model is applied to analyse the behaviour of breast cancer. A study of the relapse and survival times of 300 breast cancer patients who have undergone mastectomy is developed. The results of this paper are implemented computationally with MATLAB and R.Ministerio de Economía y Competitividad FQM-307European Regional Development Fund (ERDF) MTM2017-88708-PUniversity of Milano-Bicocca 2014-ATE-022

Isolation of a wide range of minerals from a thermally treated plant: Equisetum arvense, a Mare’s tale

Silica is the second most abundant biomineral being exceeded in nature only by biogenic CaCO3. Many land plants (such as rice, cereals, cucumber, etc.) deposit silica in significant amounts to reinforce their tissues and as a systematic response to pathogen attack. One of the most ancient species of living vascular plants, Equisetum arvense is also able to take up and accumulate silica in all parts of the plant. Numerous methods have been developed for elimination of the organic material and/or metal ions present in plant material to isolate biogenic silica. However, depending on the chemical and/or physical treatment applied to branch or stem from Equisetum arvense; other mineral forms such glass-type materials (i.e. CaSiO3), salts (i.e. KCl) or luminescent materials can also be isolated from the plant material. In the current contribution, we show the chemical and/or thermal routes that lead to the formation of a number of different mineral types in addition to biogenic silica

Vaccination against trypanosomiasis: Can it be done or is the trypanosome truly the ultimate immune destroyer and escape artist?

To date, human African trypanosomiasis (HAT) still threatens millions of people throughout sub-Sahara Africa, and new approaches to disease prevention and treatment remain a priority. It is commonly accepted that HAT is fatal unless treatment is provided. However, despite the well-described general symptoms of disease progression during distinct stages of the infection, leading to encephalitic complications, coma and death, a substantial body of evidence has been reported suggesting that natural acquired immunity could occur. Hence, if under favorable conditions natural infections can lead to correct immune activation and immune protection against HAT, the development of an effective anti-HAT vaccine should remain a central goal in the fight against this disease.<br /> In this review, we will (1) discuss the vaccine candidates that have been proposed over the past years, (2) highlight the main obstacles that an efficient anti-trypanosomiasis vaccine needs to overcome and (3) critically reflect on the validity of the widely used murine model for HAT