Detection of coccolithophore blooms with biogeochemical‐argo floats

Coccolithophores (calcifying phytoplankton) form extensive blooms in temperate and subpolar oceans as evidenced from ocean-color satellites. This study examines the potential to detect coccolithophore blooms with BioGeoChemical-Argo (BGC-Argo) floats, autonomous ocean profilers equipped with bio-optical and physicochemical sensors. We first matched float data to ocean-color satellite data of calcite concentration to select floats that sampled coccolithophore blooms. We identified two floats in the Southern Ocean, which measured the particulate beam attenuation coefficient (c(p)) in addition to two core BGC-Argo variables, Chlorophyll-a concentration ([Chl-a]) and the particle backscattering coefficient (b(bp)). We show that coccolithophore blooms can be identified from floats by distinctively high values of (1) the b(bp)/c(p) ratio, a proxy for the refractive index of suspended particles, and (2) the b(bp)/[Chl-a] ratio, measurable by any BGC-Argo float. The latter thus paves the way to global investigations of environmental control of coccolithophore blooms and their role in carbon export. Plain Language Summary Coccolithophores are a group of phytoplankton that form an armor of calcite plates. Coccolithophores may form intense blooms which can be identified from space by so-called ocean-color satellites, providing global images of the color of the surface ocean. BioGeoChemical-Argo (BGC-Argo) floats, robots profiling down to 2,000 m with a variety of physicochemical and bio-optical sensors, present an increasingly attractive and cost-effective platform to study phytoplankton blooms and their impact on oceanic biogeochemical cycles. We show that coccolithophore blooms can be detected by BGC-Argo floats with high confidence, hence providing a new way to study them at the global scale as well as their role in sinking carbon. Key Points We matched profiling float trajectories with ocean-color satellite observations of coccolithophore blooms Two simple bio-optical indices permitted successful identification of coccolithophore blooms from floats in the Southern Ocean A method for identifying coccolithophore blooms at the global scale is proposed using regional thresholds of bio-optical float measurement

Multitargeted Imidazoles: Potential Therapeutic Leads for Alzheimer's and Other Neurodegenerative Diseases

Alzheimer’s disease (AD) is a complex, multifactorial disease in which different neuropathological mechanisms are likely involved, including those associated with pathological tau and Aβ species as well as neuroinflammation. In this context, the development of single multitargeted therapeutics directed against two or more disease mechanisms could be advantageous. Starting from a series of 1,5-diarylimidazoles with microtubule (MT)-stabilizing activity and structural similarities with known NSAIDs, we conducted structure−activity relationship studies that led to the identification of multitargeted prototypes with activities as MT-stabilizing agents and/or inhibitors of the cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) pathways. Several examples are brain-penetrant and exhibit balanced multitargeted in vitro activity in the low μM range. As brain-penetrant MT-stabilizing agents have proven effective against tau-mediated neurodegeneration in animal models, and because COX- and 5-LOX-derived eicosanoids are thought to contribute to Aβ plaque deposition, these 1,5-diarylimidazoles provide tools to explore novel multitargeted strategies for AD and other neurodegenerative diseases

The relative importance of phytoplankton aggregates and zooplankton fecal pellets to carbon export: insights from free-drifting sediment trap deployments in naturally iron-fertilised waters near the Kerguelen Plateau

The first KErguelen Ocean and Plateau compared Study (KEOPS1), conducted in the naturally iron-fertilised Kerguelen bloom, demonstrated that fecal material was the main pathway for exporting carbon to the deep ocean during summer (January–February 2005), suggesting a limited role of direct export via phytodetrital aggregates. The KEOPS2 project reinvestigated this issue during the spring bloom initiation (October–November 2011), when zooplankton communities may exert limited grazing pressure, and further explored the link between carbon flux, export efficiency and dominant sinking particles depending upon surface plankton community structure. Sinking particles were collected in polyacrylamide gel-filled and standard free-drifting sediment traps (PPS3/3), deployed at six stations between 100 and 400 m, to examine flux composition, particle origin and their size distributions. Results revealed an important contribution of phytodetrital aggregates (49 ± 10 and 45 ± 22% of the total number and volume of particles respectively, all stations and depths averaged). This high contribution dropped when converted to carbon content (30 ± 16% of total carbon, all stations and depths averaged), with cylindrical fecal pellets then representing the dominant fraction (56 ± 19%).At 100 and 200 m depth, iron- and biomass-enriched sites exhibited the highest carbon fluxes (maxima of 180 and 84 ± 27 mg C m-2 d-1, based on gel and PPS3/3 trap collection respectively), especially where large fecal pellets dominated over phytodetrital aggregates. Below these depths, carbon fluxes decreased (48 ± 21% decrease on average between 200 and 400 m), and mixed aggregates composed of phytodetritus and fecal matter dominated, suggesting an important role played by physical aggregation in deep carbon export.Export efficiencies determined from gels, PPS3/3 traps and 234Th disequilibria (200 m carbon flux/net primary productivity) were negatively correlated to net primary productivity with observed decreases from ~ 0.2 at low-iron sites to ~ 0.02 at high-iron sites. Varying phytoplankton communities and grazing pressure appear to explain this negative relationship. Our work emphasises the need to consider detailed plankton communities to accurately identify the controls on carbon export efficiency, which appear to include small spatio-temporal variations in ecosystem structure

The relative importance of phytoplankton aggregates and zooplankton fecal pellets to carbon export: insights from free-drifting sediment trap deployments in naturally iron-fertilised waters near the Kerguelen Plateau

The first KErguelen Ocean and Plateau compared Study (KEOPS1), conducted in the naturally iron-fertilised Kerguelen bloom, demonstrated that fecal material was the main pathway for exporting carbon to the deep ocean during summer (January–February 2005), suggesting a limited role of direct export via phytodetrital aggregates. The KEOPS2 project reinvestigated this issue during the spring bloom initiation (October–November 2011), when zooplankton communities may exert limited grazing pressure, and further explored the link between carbon flux, export efficiency and dominant sinking particles depending upon surface plankton community structure. Sinking particles were collected in polyacrylamide gel-filled and standard free-drifting sediment traps (PPS3/3), deployed at six stations between 100 and 400 m, to examine flux composition, particle origin and their size distributions. Results revealed an important contribution of phytodetrital aggregates (49+/-10 and 45+/-22% of the total number and volume of particles respectively, all stations and depths averaged). This high contribution dropped when converted to carbon content (30+/-16% of total carbon, all stations and depths averaged), with cylindrical fecal pellets then representing the dominant fraction (56+/-19 %). At 100 and 200m depth, iron- and biomass-enriched sites exhibited the highest carbon fluxes (maxima of 180 and 84+/- 27 mgCm-2 d-1, based on gel and PPS3/3 trap collection respectively), especially where large fecal pellets dominated over phytodetrital aggregates. Below these depths, carbon fluxes decreased (48+/-21%decrease on average between 200 and 400 m), and mixed aggregates composed of phytodetritus and fecal matter dominated, suggesting an important role played by physical aggregation in deep carbon export. Export efficiencies determined from gels, PPS3/3 traps and 234Th disequilibria (200m carbon flux/net primary productivity) were negatively correlated to net primary productivity with observed decreases from ~0.2 at low-iron sites to ~0.02 at high-iron sites. Varying phytoplankton communities and grazing pressure appear to explain this negative relationship. Our work emphasises the need to consider detailed plankton communities to accurately identify the controls on carbon export efficiency, which appear to include small spatio-temporal variations in ecosystem structure

Chemometric perspectives on plankton community responses to natural iron fertilisation over and downstream of the Kerguelen Plateau in the Southern Ocean

International audienceWe examined phytoplankton community responses to natural iron fertilisation at 32 sites over and downstream from the Kerguelen Plateau in the Southern Ocean during the austral spring bloom in October–November 2011. The community structure was estimated from chemical and isotopic measurements (particulate organic carbon – POC; 13C-POC; particulate nitrogen – PN; 15N-PN; and biogenic silica – BSi) on size-fractionated samples from surface waters (300, 210, 50, 20, 5, and 1 μm fractions). Higher values of 13C-POC (vs. co-located 13C values for dissolved inorganic carbon – DIC) were taken as indicative of faster growth rates and higher values of 15N-PN (vs. co-located 15N-NO3 source values) as indicative of greater nitrate use (rather than ammonium use, i.e. higher f ratios).Community responses varied in relation to both regional circulation and the advance of the bloom. Iron-fertilised waters over the plateau developed dominance by very large diatoms (50–210 μm) with high BSi / POC ratios, high growth rates, and significant ammonium recycling (lower f ratios) as biomass built up. In contrast, downstream polar frontal waters with a similar or higher iron supply were dominated by smaller diatoms (20–50 μm) and exhibited greater ammonium recycling. Stations in a deep-water bathymetrically trapped recirculation south of the polar front with lower iron levels showed the large-cell dominance observed on the plateau but much less biomass. Comparison of these communities to surface water nitrate (and silicate) depletions as a proxy for export shows that the low-biomass recirculation feature had exported similar amounts of nitrogen to the high-biomass blooms over the plateau and north of the polar front. This suggests that early spring trophodynamic and export responses differed between regions with persistent low levels vs. intermittent high levels of iron fertilisation

Indication of activated senescence pathways in the temporal arteries of patients with giant cell arteritis

OBJECTIVES: Giant cell arteritis (GCA) affects almost exclusively individuals above 50 years old, suggesting a role of aging-related changes such as cellular senescence in its pathobiology. p21 WAF1/CIP1 and p16/INK4A play key roles in two distinct pathways leading to senescence. The proinflammatory molecules Interleukin (IL)-6 and Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), which are key components of the senescence-associated secretory phenotype (SASP), are effective targets of treatment in GCA. Here, we aim to investigate the presence of p21 and p16 positive cells producing these SASP cytokines in temporal artery biopsies (TABs) of patients with GCA.METHODS: Eight patients with GCA and 14 age-matched, non-GCA individuals who underwent a TAB were included. Immunohistochemical staining of p21, p16, IL-6 and GM-CSF was performed. Multiplex immunofluorescent staining was performed to investigate the colocalization of p21 and p16 with IL-6, GM-CSF, and immune cell markers (CD68, CD3, CD20).RESULTS: p16, p21, IL-6 and GM-CSF were elevated in the TABs of patients with GCA. Both p16 and p21 expressing cells were mainly found near the internal lamina elastica, especially among giant cells and macrophages, although p21 and p16 expression could be found in all three layers of the vessels. Expression of p16 and p21 was occasionally found in T cells but not B cells. p16+ and p21+ cells expressing GM-CSF/IL-6 were detected throughout the TABs.CONCLUSION: Our data suggests the presence of activated senescence pathways at the site of vascular inflammation in GCA and support further research into the role of senescence in the pathophysiology of GCA. This article is protected by copyright. All rights reserved.</p

OP0137 GENOME-WIDE WHOLE-BLOOD TRANSCRIPTOME PROFILING IN A LARGE EUROPEAN COHORT OF SYSTEMIC SCLEROSIS PATIENTS

Background:The analysis of annotated transcripts from genome-wide expression studies data is of paramount importance to understand the molecular phenomena underlying the occurrence of complex diseases, such as systemic sclerosis (SSc).Objectives:To perform whole-blood transcriptome and pathway analysis on whole-blood (WB) RNA collected in two cohorts of European SSc patients. Via a discovery and validation strategy we aimed at characterizing the molecular pathways that differentiate SSc from controls and that are reproducible in geographically diverse populations.Methods:WB samples from 252 controls and 162 SSc patients were collected in RNA stabilizers. Patients were divided into a discovery (n=79; Southern Europe) and validation cohort (n=83; Central-Western Europe). RNA sequencing was performed by an Illumina assay. Functional annotations of Reactome pathways were performed with the FAIME algorithm. In parallel, a immunophenotyping analysis on 28 circulating cell populations was assessed. We then tested: the presence of differentially expressed genes or pathways and the correlation between absolute cell counts and RNA transcripts/FAIME scores in regression models. Results significant in both populations were considered as replicated.Results:A total of 15224 genes and 1277 related functional pathways were available for analysis. Among these, 99 genes and 225 pathways were significant in both sets. The heatmap in figure shows the relative expression of replicated pathways and the distribution of cases and controls (red and green bars). Among the significant pathways we found a deregulation in: type-I IFN, TLR-cascade and signalling, function of the tumor suppressor p53 protein, platelet degranulation and activation. Correlation analysis showed that the count of several cell subtypes is jointly associated with RNA transcripts or FAIME scores with strong differences in relation to the geographical origin of samples; neutrophils emerged as the major determinant of gene expression in SSc-whole-blood samples.Conclusion:We discovered a set of differentially expressed genes and pathways that could be validated in two independent sets of SSc patients highlighting a number of deregulated molecular processes that have relevance for the pathogenesis of autoimmunity and SSc.Acknowledgments:This work was supported by EU/EFPIA/Innovative Medicines Initiative Joint Undertaking PRECISESADS grant No. 115565.Disclosure of Interests:Lorenzo Beretta Grant/research support from: Pfizer, Guillermo Barturen: None declared, Barbara Vigone: None declared, Chiara Bellocchi: None declared, Nicolas Hunzelmann: None declared, Ellen Delanghe: None declared, László Kovács: None declared, Ricard Cervera: None declared, Maria Gerosa: None declared, Rafaela Ortega Castro: None declared, Isabel Almeida: None declared, Divi Cornec: None declared, Carlo Chizzolini Consultant of: Boehringer Ingelheim, Roche, Jacques-Olivier Pers: None declared, Zuzanna Makowska Employee of: Bayer AG, Anne buttgereit Employee of: Bayer AG, Ralf Lesche Employee of: Bayer, Martin Kerick: None declared, Marta Alarcon-Riquelme: None declared, Javier Martin Ibanez: None declare

Animated Edge Textures in Node-Link Diagrams: a Design Space and Initial Evaluation

International audienceNetwork edge data attributes are usually encoded using color, opacity, stroke thickness and stroke pattern, or some combination thereof. In addition to these static variables, it is also possible to animate dynamic particles flowing along the edges. This opens a larger design space of animated edge textures, featuring additional visual encodings that have potential not only in terms of visual mapping capacity but also playfulness and aesthetics. Such animated edge textures have been used in several commercial and design-oriented visualizations, but to our knowledge almost always in a relatively ad hoc manner. We introduce a design space and Web-based framework for generating animated edge textures, and report on an initial evaluation of particle properties – particle speed, pattern and frequency – in terms of visual perception

Circulating autoreactive proteinase 3(+) B cells and tolerance checkpoints in ANCA-associated vasculitis

BACKGROUND: Little is known about the autoreactive B cells in antineutrophil cytoplasmic antibody–associated (ANCA-associated) vasculitis (AAV). We aimed to investigate tolerance checkpoints of circulating antigen-specific proteinase 3–reactive (PR3(+)) B cells. METHODS: Multicolor flow cytometry in combination with bioinformatics and functional in vitro studies were performed on baseline samples of PBMCs from 154 well-characterized participants of the RAVE trial (NCT00104299) with severely active PR3-AAV and myeloperoxidase-AAV (MPO-AAV) and 27 healthy controls (HCs). Clinical data and outcomes from the trial were correlated with PR3(+) B cells (total and subsets). RESULTS: The frequency of PR3(+) B cells among circulating B cells was higher in participants with PR3-AAV (4.77% median [IQR, 3.98%–6.01%]) than in participants with MPO-AAV (3.16% median [IQR, 2.51%–5.22%]) and participants with AAV compared with HCs (1.67% median [IQR, 1.27%–2.16%], P < 0.001 for all comparisons), implying a defective central tolerance checkpoint in patients with AAV. Only PBMCs from participants with PR3-AAV contained PR3(+) B cells capable of secreting PR3-ANCA IgG in vitro, proving they were functionally distinct from those of participants with MPO-AAV and HCs. Unsupervised clustering identified subtle subsets of atypical autoreactive PR3(+) memory B cells accumulating through the maturation process in patients with PR3-AAV. PR3(+) B cells were enriched in the memory B cell compartment of participants with PR3-AAV and were associated with higher serum CXCL13 levels, suggesting an increased germinal center activity. PR3(+) B cells correlated with systemic inflammation (C-reactive protein and erythrocyte sedimentation rate, P < 0.05) and complete remission (P < 0.001). CONCLUSION: This study suggests the presence of defective central antigen-independent and peripheral antigen-dependent checkpoints in patients with PR3-AAV, elucidating the selection process of autoreactive B cells. TRIAL REGISTRATION: ClinicalTrials.gov NCT00104299. FUNDING: The Vasculitis Foundation, the National Institute of Allergy and Infectious Diseases of the NIH, and the Mayo Foundation for Education and Research

An update on the use of tolvaptan for autosomal dominant polycystic kidney disease: consensus statement on behalf of the ERA Working Group on Inherited Kidney Disorders, the European Rare Kidney Disease Reference Network and Polycystic Kidney Disease International

Approval of the vasopressin V2 receptor antagonist tolvaptan-based on the landmark TEMPO 3:4 trial-marked a transformation in the management of autosomal dominant polycystic kidney disease (ADPKD). This development has advanced patient care in ADPKD from general measures to prevent progression of chronic kidney disease to targeting disease-specific mechanisms. However, considering the long-term nature of this treatment, as well as potential side effects, evidence-based approaches to initiate treatment only in patients with rapidly progressing disease are crucial. In 2016, the position statement issued by the European Renal Association (ERA) was the first society-based recommendation on the use of tolvaptan and has served as a widely used decision-making tool for nephrologists. Since then, considerable practical experience regarding the use of tolvaptan in ADPKD has accumulated. More importantly, additional data from REPRISE, a second randomized clinical trial (RCT) examining the use of tolvaptan in later-stage disease, have added important evidence to the field, as have post hoc studies of these RCTs. To incorporate this new knowledge, we provide an updated algorithm to guide patient selection for treatment with tolvaptan and add practical advice for its use