C : N : P stoichiometry at the Bermuda Atlantic Time-series Study station in the North Atlantic Ocean

Nitrogen (N) and phosphorus (P) availability, in addition to other macro- and micronutrients, determine the strength of the ocean's carbon (C) uptake, and variation in the N : P ratio of inorganic nutrient pools is key to phytoplankton growth. A similarity between C : N : P ratios in the plankton biomass and deep-water nutrients was observed by Alfred C. Redfield around 80 years ago and suggested that biological processes in the surface ocean controlled deep-ocean chemistry. Recent studies have emphasized the role of inorganic N : P ratios in governing biogeochemical processes, particularly the C : N : P ratio in suspended particulate organic matter (POM), with somewhat less attention given to exported POM and dissolved organic matter (DOM). Herein, we extend the discussion on ecosystem C : N : P stoichiometry but also examine temporal variation in stoichiometric relationships. We have analyzed elemental stoichiometry in the suspended POM and total (POM + DOM) organic-matter (TOM) pools in the upper 100 m and in the exported POM and subeuphotic zone (100–500 m) inorganic nutrient pools from the monthly data collected at the Bermuda Atlantic Time-series Study (BATS) site located in the western part of the North Atlantic Ocean. C : N and N : P ratios in TOM were at least twice those in the POM, while C : P ratios were up to 5 times higher in TOM compared to those in the POM. Observed C : N ratios in suspended POM were approximately equal to the canonical Redfield ratio (C : N : P = 106 : 16 : 1), while N : P and C : P ratios in the same pool were more than twice the Redfield ratio. Average N : P ratios in the subsurface inorganic nutrient pool were ~ 26 : 1, squarely between the suspended POM ratio and the Redfield ratio. We have further linked variation in elemental stoichiometry to that of phytoplankton cell abundance observed at the BATS site. Findings from this study suggest that elemental ratios vary with depth in the euphotic zone, mainly due to different growth rates of cyanobacterial cells. We have also examined the role of the Arctic Oscillation on temporal patterns in C : N : P stoichiometry. This study strengthens our understanding of the variability in elemental stoichiometry in different organic-matter pools and should improve biogeochemical models by constraining the range of non-Redfield stoichiometry and the net relative flow of elements between pools

Resource allocation by the marine cyanobacterium Synechococcus WH8102 in response to different nutrient supply ratios

Differences in relative availability of nitrate vs. phosphate may contribute to regional variations in plankton elemental stoichiometry. As a representative of the globally abundant marine Synechococcus, strain WH8102 was grown in 16 chemostats up to 52  d at a fixed growth rate with nitrogen–phosphorus ratios (N : Psupply) of 1–50. Initially, the phosphate and nitrate concentrations in the vessel decreased when the respective nutrient was limiting. Cell growth generally stabilized, although several chemostats had apparent oscillations in biomass. We observed extensive plasticity in the elemental content and ratios. N : Pcell matched the supply values between N : Psupply 5 and 20. The C : Pcell followed a similar trend. In contrast, the mean C : Ncell was 6.8 and did not vary as a function of supply ratios. We also observed that induction of alkaline phosphatase, the fraction of P allocated to nucleic acids, and the lipid sulfoquinovosyldiacylglycerol : phosphatidyglycerol ratio inversely correlated with P availability. Our results suggest that this extensive plasticity in the elemental content and ratios depends both on the external nutrient availability as well as past growth history. Thus, our study provides a quantitative understanding of the regulation of the elemental stoichiometry of an abundant ocean phytoplankton lineage

Phosphate supply explains variation in nucleic acid allocation but not C : P stoichiometry in the western North Atlantic

Marine microbial communities mediate many biogeochemical transformations in the ocean. Consequently, processes such as primary production and carbon (C) export are linked to nutrient regeneration and are influenced by the resource demand and elemental composition of marine microbial biomass. Laboratory studies have demonstrated that differential partitioning of element resources to various cellular components can directly influence overall cellular elemental ratios, especially with respect to growth machinery (i.e., ribosomal RNA) and phosphorus (P) allocation. To investigate whether allocation to RNA is related to biomass P content and overall C : P biomass composition in the open ocean, we characterized patterns of P allocation and C : P elemental ratios along an environmental gradient of phosphate supply in the North Atlantic subtropical gyre (NASG) from 35.67° N, 64.17° W to 22.676° N, 65.526° W. Because the NASG is characterized as a P-stressed ecosystem, we hypothesized that biochemical allocation would reflect sensitivity to bioavailable phosphate, such that greater phosphate supply would result in increased allocation toward P-rich RNA for growth. We predicted these changes in allocation would also result in lower C : P ratios with increased phosphate supply. However, bulk C : P ratios were decoupled from allocation to nucleic acids and did not appear to vary systematically across a phosphate supply gradient of 2.2–14.7 μmol m−2 d−1. Overall, we found that C : P ratios ranged from 188 to 306 along the transect, and RNA represented only 6–12% of total particulate P, whereas DNA represented 11–19%. We did find that allocation to RNA was positively correlated with phosphate supply rate, suggesting a consistent physiological response in biochemical allocation to resource supply within the whole community. These results suggest that community composition and/or nonnucleic acid P pools may influence ecosystem-scale variation in C : P stoichiometry more than nucleic acid allocation or P supply in diverse marine microbial communities

Efficacy of five ‘sporicidal’ surface disinfectants against Clostridioides difficile spores in suspension tests and 4-field tests

Background: A sporicidal surface disinfection is recommended both for the outbreak and the endemic setting but a comparative evaluation on the efficacy of ‘sporicidal’ surface disinfectants using suspension tests and 4-field tests has not been performed. Aim: To determine the efficacy of five ‘sporicidal’ surface disinfectants (three ready-to-use wipes (A, B, E), two concentrates (C, D) based on peroxides or aldehydes against C. difficile spores. Methods: The efficacy was determined under clean conditions using a suspension test and the 4-field test. Each test was performed in duplicate in two separate laboratories. Wipes were wrung to collect the solution for the suspension tests. Results: Product A (peracetic acid; 5 min), product C (peracetic acid; 2% solution in 15 min or 1% solution in 30 min) and product D (peracetic acid; only 2% solution in 15 min) were effective with at least a 4 log10-reduction of C. difficile spores in suspension and on surfaces. Product B (hydrogen peroxide) was not effective in suspension (0.9 log10 after 15 min; 3.2 log10 after 1 h) and on surfaces (2.8 log10 after 15 and 60 min). Product E based on glutaraldehyde, (ethylendioxy)dimethanol and DDAC demonstrated 0.9 log10 after 4 h in suspension and 4.5 log10 after 4 h on surfaces. Conclusions: Not all surface disinfectants with a sporicidal claim were effective against C. difficile spores in standardized suspension tests and in the 4-field test. In clinical practice preference should be given to products that reliably pass the efficacy criteria of both types of tests.Peer Reviewe

The anti-invasive activity of synthetic alkaloid ethoxyfagaronine on L1210 leukemia cells is mediated by down-regulation of plasminogen activators and MT1-MMP expression and activity

Quaternary benzo[c]phenanthridines such as fagaronine are natural substances which have been reported to exhibit anticancer and anti-leukemic properties. However, the therapeutic use of these molecules is limited due to the high dose required to exhibit anti-tumor activity and subsequent toxicity. In this study, we describe the therapeutic potential of a new derivative of fagaronine, Ethoxyfagaronine (N-methyl-12-ethoxy-2hydroxy-3, 8, 9-trimethoxybenzo[c]-phenanthridiniumchlorhydrate) as an anti-leukemic agent. Cytotoxic activity and cell growth inhibition of Ethoxyfagaronine (Etxfag) was tested on murine L1210 leukemia cells using trypan blue assay and MTT assay. At the concentration of 10−7 M, Etxfag induced less than 10% of cell death. Etxfag (10−7 M) was tested on L1210 cell invasiveness using matrigel™ precoated transwell chambers and efficiently reduces the invasive potential of L1210 cells by more than 50% as compared with untreated cells. Western blot and immunofluorescence experiments showed that Etxfag decreased both MT1-MMP expression and activation at the cell surface, decreased plasmin activity by down-regulating u-PAR and uPA expression at the cell surface and increasing PAI-1 secretion in conditioned media. The set of our findings underscore the therapeutic potential of ethoxyfagaronine as a new potential anticancer agent able to prevent leukemic cell dissemination

Distributions of phytoplankton carbohydrate, protein and lipid in the world oceans from satellite ocean colour

Energy value of phytoplankton regulates the growth of higher trophic species, affecting the tropic balance and sustainability of marine food webs. Therefore, developing our capability to estimate and monitor, on a global scale, the concentrations of macromolecules that determine phytoplankton energy value, would be invaluable. Reported here are the first estimates of carbohydrate, protein, lipid, and overall energy value of phytoplankton in the world oceans, using ocean-colour data from satellites. The estimates are based on a novel bio-optical method that utilises satellite-derived bio-optical fingerprints of living phytoplankton combined with allometric relationships between phytoplankton cells and cellular macromolecular contents. The annually-averaged phytoplankton energy value, per cubic meter of sub-surface ocean, varied from less than 0.1 kJ in subtropical gyres, to 0.5–1.0 kJ in parts of the equatorial, northern and southern latitudes, and rising to more than 10 kJ in certain coastal and optically complex waters. The annually-averaged global stocks of carbohydrate, protein and lipid were 0.044, 0.17 and 0.108 gigatonnes, respectively, with monthly stocks highest in September and lowest in June, over 1997-2013. The fractional contributions of phytoplankton size classes e.g., picoplankton, nanoplankton and microplankton to surface concentrations and global stocks of macromolecules varied considerably across marine biomes classified as Longhurst provinces. Among these provinces, the highest annually-averaged surface concentrations of carbohydrate, protein, and lipid were in North-East Atlantic Coastal Shelves, whereas, the lowest concentration of carbohydrate or lipid were in North Atlantic Tropical Gyral, and that of protein was in North Pacific Subtropical Gyre West. The regional accuracy of the estimates and their sensitivity to satellite inputs are quantified from the bio-optical model, which show promise for possible operational monitoring of phytoplankton energy value from satellite ocean colour. Adequate in situ measurements of macromolecules and improved retrievals of inherent optical properties from high-resolution satellite images, would be required to validate these estimates at local sites, and to further improve their accuracy in the world oceans

Predicting Prokaryotic Ecological Niches Using Genome Sequence Analysis

Automated DNA sequencing technology is so rapid that analysis has become the rate-limiting step. Hundreds of prokaryotic genome sequences are publicly available, with new genomes uploaded at the rate of approximately 20 per month. As a result, this growing body of genome sequences will include microorganisms not previously identified, isolated, or observed. We hypothesize that evolutionary pressure exerted by an ecological niche selects for a similar genetic repertoire in those prokaryotes that occupy the same niche, and that this is due to both vertical and horizontal transmission. To test this, we have developed a novel method to classify prokaryotes, by calculating their Pfam protein domain distributions and clustering them with all other sequenced prokaryotic species. Clusters of organisms are visualized in two dimensions as ‘mountains’ on a topological map. When compared to a phylogenetic map constructed using 16S rRNA, this map more accurately clusters prokaryotes according to functional and environmental attributes. We demonstrate the ability of this map, which we term a “niche map”, to cluster according to ecological niche both quantitatively and qualitatively, and propose that this method be used to associate uncharacterized prokaryotes with their ecological niche as a means of predicting their functional role directly from their genome sequence

Independent evolution of shape and motility allows evolutionary flexibility in Firmicutes bacteria

Functional morphological adaptation is an implicit assumption across many ecological studies. However, despite a few pioneering attempts to link bacterial form and function, functional morphology is largely unstudied in prokaryotes. One intriguing candidate for analysis is bacterial shape, as multiple lines of theory indicate that cell shape and motility should be strongly correlated. Here we present a large-scale use of modern phylogenetic comparative methods to explore this relationship across 325 species of the phylum Firmicutes. In contrast to clear predictions from theory, we show that cell shape and motility are not coupled, and that transitions to and from flagellar motility are common and strongly associated with lifestyle (free-living or host-associated). We find no association between shape and lifestyle, and contrary to recent evidence, no indication that shape is associated with pathogenicity. Our results suggest that the independent evolution of shape and motility in this group might allow a greater evolutionary flexibility

The SOFIA Pilot Trial:A cluster-randomized trial of coordinated, co-produced care to reduce mortality and improve quality of life in people with severe mental illness in the general practice setting

Abstract Background People with severe mental illness (SMI) have an increased risk of premature mortality, predominantly due to somatic health conditions. Evidence indicates that primary and tertiary prevention and improved treatment of somatic conditions in patients with SMI could reduce this excess mortality. This paper reports a protocol designed to evaluate the feasibility of a coordinated co-produced care program (SOFIA model, a Danish acronym for Severe Mental Illness and Physical Health in General Practice) in the general practice setting to reduce mortality and improve quality of life in patients with severe mental illness. Methods The SOFIA pilot trial is designed as a cluster randomized controlled trial targeting general practices in two regions in Denmark. We aim to include 12 practices, each of which is instructed to recruit up to 15 community-dwelling patients aged 18 and older with SMI. Practices will be randomized by a computer in a ratio of 2:1 to deliver a coordinated care program or usual care during a 6-month study period. A randomized algorithm is used to perform randomization. The coordinated care program includes educational training of general practitioners and their clinical staff educational training of general practitioners and their clinical staff, which covers clinical and diagnostic management and focus on patient-centered care of this patient group, after which general practitioners will provide a prolonged consultation focusing on individual needs and preferences of the patient with SMI and a follow-up plan if indicated. The outcomes will be parameters of the feasibility of the intervention and trial methods and will be assessed quantitatively and qualitatively. Assessments of the outcome parameters will be administered at baseline, throughout, and at end of the study period. Discussion If necessary the intervention will be revised based on results from this study. If delivery of the intervention, either in its current form or after revision, is considered feasible, a future, definitive trial to determine the effectiveness of the intervention in reducing mortality and improving quality of life in patients with SMI can take place. Successful implementation of the intervention would imply preliminary promise for addressing health inequities in patients with SMI. Trial registration The trial was registered in Clinical Trials as of November 5, 2020, with registration number NCT04618250 . Protocol version: January 22, 2021; original versio

Targeting focal adhesion assembly by ethoxyfagaronine prevents lymphoblastic cell adhesion to fibronectin

Background: Leukemic cell adhesion to proteins of the bone marrow microenvironment provides signals which control morphology, motility and cell survival. We described herein the ability of ethoxyfagaronine (etxfag), a soluble synthetic derivative of fagaronine, to prevent leukemic cell adhesion to fibronectin peptide (FN/V). Methods: Phosphorylation of fak and pyk2 were evaluated by immunoblotting. Labelled proteins were localized by confocal microscopy. PI 3-kinase activity was evaluated by in vitro kinase assay. Results: Subtoxic concentration of etxfag reduced L1210 cell adhesion to FN/V dependently of β1 integrin engagement. Etxfag impaired FN-dependent formation of β1 clustering without modifying β1 expression at the cell membrane. This was accompanied by a decrease of focal adhesion number, a diminution of fak and pyk2 phosphorylation at Tyr-576, Tyr-861 and Tyr-579, respectively leading to their dissociations from β1 integrin and inhibition of PI 3-kinase activity. Etxfag also induced a cell retraction accompanied by a redistribution of phosphorylated fak and pyk2 in the perinuclear region and lipid raft relocalization. Conclusion: Through its anti-adhesive potential, etxfag, combined with conventional cytotoxic drugs could be potentially designed as a new anti-leukemic drug