Mass Spectrometry-Based Metabolomics to Elucidate Functions in Marine Organisms and Ecosystems

Marine systems are very diverse and recognized as being sources of a wide range of biomolecules. This review provides an overview of metabolite profiling based on mass spectrometry (MS) approaches in marine organisms and their environments, focusing on recent advances in the field. We also point out some of the technical challenges that need to be overcome in order to increase applications of metabolomics in marine systems, including extraction of chemical compounds from different matrices and data management. Metabolites being important links between genotype and phenotype, we describe added value provided by integration of data from metabolite profiling with other layers of omics, as well as their importance for the development of systems biology approaches in marine systems to study several biological processes, and to analyze interactions between organisms within communities. The growing importance of MS-based metabolomics in chemical ecology studies in marine ecosystems is also illustrated

Biochemical Trade-Offs: Evidence for Ecologically Linked Secondary Metabolism of the Sponge Oscarella balibaloi

Secondary metabolite production is assumed to be costly and therefore the resource allocation to their production should be optimized with respect to primary biological functions such as growth or reproduction. Sponges are known to produce a great diversity of secondary metabolites with powerful biological activities that may explain their domination in some hard substrate communities both in terms of diversity and biomass. Oscarella balibaloi (Homoscleromorpha) is a recently described, highly dynamic species, which often overgrows other sessile marine invertebrates. Bioactivity measurements (standardized Microtox assay) and metabolic fingerprints were used as indicators of the baseline variations of the O. balibaloi secondary metabolism, and related to the sponge reproductive effort over two years. The bioactivity showed a significant seasonal variation with the lowest values at the end of spring and in early summer followed by the highest bioactivity in the late summer and autumn. An effect of the seawater temperature was detected, with a significantly higher bioactivity in warm conditions. There was also a tendency of a higher bioactivity when O. balibaloi was found overgrowing other sponge species. Metabolic fingerprints revealed the existence of three principal metabolic phenotypes: phenotype 1 exhibited by a majority of low bioactive, female individuals, whereas phenotypes 2 and 3 correspond to a majority of highly bioactive, non-reproductive individuals. The bioactivity was negatively correlated to the reproductive effort, minimal bioactivities coinciding with the period of embryogenesis and larval development. Our results fit the Optimal Defense Theory with an investment in the reproduction mainly shaping the secondary metabolism variability, and a less pronounced influence of other biotic (species interaction) and abiotic (temperature) factors

Measurement of isotopic separation of argon with the prototype of the cryogenic distillation plant Aria for dark matter searches

The Aria cryogenic distillation plant, located in Sardinia, Italy, is a key component of the DarkSide-20k experimental program for WIMP dark matter searches at the INFN Laboratori Nazionali del Gran Sasso, Italy. Aria is designed to purify the argon, extracted from underground wells in Colorado, USA, and used as the DarkSide-20k target material, to detector-grade quality. In this paper, we report the first measurement of argon isotopic separation by distillation with the 26 m tall Aria prototype. We discuss the measurement of the operating parameters of the column and the observation of the simultaneous separation of the three stable argon isotopes: 36Ar , 38Ar , and 40Ar . We also provide a detailed comparison of the experimental results with commercial process simulation software. This measurement of isotopic separation of argon is a significant achievement for the project, building on the success of the initial demonstration of isotopic separation of nitrogen using the same equipment in 2019.ISSN:1434-6044ISSN:1434-605

Separating 39Ar from 40Ar by cryogenic distillation with Aria for dark-matter searches

Aria is a plant hosting a 350m cryogenic isotopic distillation column, the tallest ever built, which is being installed in a mine shaft at Carbosulcis S.p.A., Nuraxi-Figus (SU), Italy. Aria is one of the pillars of the argon dark-matter search experimental program, lead by the Global Argon Dark Matter Collaboration. It was designed to reduce the isotopic abundance of 39Ar in argon extracted from underground sources, called Underground Argon (UAr), which is used for dark-matter searches. Indeed, 39Ar is a ��-emitter of cosmogenic origin, whose activity poses background and pile-up concerns in the detectors. In this paper, we discuss the requirements, design, construction, tests, and projected performance of the plant for the isotopic cryogenic distillation of argon. We also present the successful results of the isotopic cryogenic distillation of nitrogen with a prototype plant.ISSN:1434-6044ISSN:1434-605

SiPM-matrix readout of two-phase argon detectors using electroluminescence in the visible and near infrared range

Proportional electroluminescence (EL) in noble gases is used in two-phase detectors for dark matter searches to record (in the gas phase) the ionization signal induced by particle scattering in the liquid phase. The “standard” EL mechanism is considered to be due to noble gas excimer emission in the vacuum ultraviolet (VUV). In addition, there are two alternative mechanisms, producing light in the visible and near infrared (NIR) ranges. The first is due to bremsstrahlung of electrons scattered on neutral atoms (“neutral bremsstrahlung”, NBrS). The second, responsible for electron avalanche scintillation in the NIR at higher electric fields, is due to transitions between excited atomic states. In this work, we have for the first time demonstrated two alternative techniques of the optical readout of two-phase argon detectors, in the visible and NIR range, using a silicon photomultiplier matrix and electroluminescence due to either neutral bremsstrahlung or avalanche scintillation. The amplitude yield and position resolution were measured for these readout techniques, which allowed to assess the detection threshold for electron and nuclear recoils in two-phase argon detectors for dark matter searches. To the best of our knowledge, this is the first practical application of the NBrS effect in detection science.ISSN:1434-6044ISSN:1434-605

The metabolic checkpoint kinase mTOR is essential for IL-15 signaling during the development and activation of NK cells

International audienceInterleukin 15 (IL-15) controls both the homeostasis and the peripheral activation of natural killer (NK) cells. The molecular basis for this duality of action remains unknown. Here we found that the metabolic checkpoint kinase mTOR was activated and boosted bioenergetic metabolism after exposure of NK cells to high concentrations of IL-15, whereas low doses of IL-15 triggered only phosphorylation of the transcription factor STAT5. mTOR stimulated the growth and nutrient uptake of NK cells and positively fed back on the receptor for IL-15. This process was essential for sustaining NK cell proliferation during development and the acquisition of cytolytic potential during inflammation or viral infection. The mTORC1 inhibitor rapamycin inhibited NK cell cytotoxicity both in mice and humans; this probably contributes to the immunosuppressive activity of this drug in different clinical settings

Transforming growth factor-beta and Notch ligands act as opposing environmental cues in regulating the plasticity of type 3 innate lymphoid cells

International audienceGroup 3 innate lymphoid cells (ILC3s) are composed of subsets that are either positive or negative for the natural cytotoxicity receptor (NCR) NKp46 (encoded by Ncr1). ILC3s are located at mucosal sites, such as in the intestine and lung, where they are exposed to billions of commensal microbes and potentially harmful pathogens. Together with T cells, the various ILC3 subsets maintain the balance between homeostasis and immune activation. Through genetic mapping, we identified a previously uncharacterized subset of NCR- ILC3s in mice that transiently express Ncr1, demonstrating previously undescribed heterogeneity within the ILC3 population. In addition, we showed that sustained Notch signaling was required for the maintenance of the NCR+ phenotype and that the cytokine transforming growth factor-beta (TGF-beta) impaired the development of NCR+ ILC3s. Thus, the plasticity of ILC3s is regulated by the balance between the opposing effects of Notch and TGF-beta signaling, maintaining homeostasis in the face of continual challenges

The DarkSide experiment

DarkSide is a dark matter direct search experiment at Laboratori Nazionali del Gran Sasso (LNGS). DarkSide is based on the detection of rare nuclear recoils possibly induced by hypothetical dark matter particles, which are supposed to be neutral, massive (m > 10 GeV) and weakly interactive (WIMP). The dark matter detector is a two-phase time projection chamber (TPC) filled with ultra-pure liquid argon. The TPC is placed inside a muon and a neutron active vetoes to suppress the background. Using argon as active target has many advantages, the key features are the strong discriminant power between nuclear and electron recoils, the spatial reconstruction and easy scalability to multi-tons size. At the moment DarkSide-50 is filled with ultra-pure argon, extracted from underground sources, and from April 2015 it is taking data in its final configuration. When combined with the preceding search with an atmospheric argon target, it is possible to set a 90% CL upper limit on the WIMP-nucleon spin-independent cross section of 2.0×10 -44 cm2 for a WIMP mass of 100 GeV/c2. The next phase of the experiment, DarkSide-20k, will be the construction of a new detector with an active mass of ∼ 20 tons.ISSN:1124-1896ISSN:1826-9885ISSN:2037-490

Study of scintillation light collection, production and propagation in a 4 tonne dual-phase LArTPC

The 3×1×1 m3 demonstrator is a dual phase liquid argon time projection chamber that has recorded cosmic rays events in 2017 at CERN. The light signal in these detectors is crucial to provide precise timing capabilities. The performance of the photon detection system, composed of five PMTs, are discussed. The collected scintillation and electroluminescence light created by passing particles has been studied in various detector conditions. In particular, the scintillation light production and propagation processes have been analyzed and compared to simulations, improving the understanding of some liquid argon properties.ISSN:1748-022

A 4 tonne demonstrator for large-scale dual-phase liquid argon time projection chambers

A 10 kilo-tonne dual-phase liquid argon TPC is one of the detector options considered for the Deep Underground Neutrino Experiment (DUNE). The detector technology relies on amplification of the ionisation charge in ultra-pure argon vapour and offers several advantages compared to the traditional single-phase liquid argon TPCs. A 4.2 tonne dual-phase liquid argon TPC prototype, the largest of its kind, with an active volume of \three has been constructed and operated at CERN. In this paper we describe in detail the experimental setup and detector components as well as report on the operation experience. We also present the first results on the achieved charge amplification, prompt scintillation and electroluminescence detection, and purity of the liquid argon from analyses of a collected sample of cosmic ray muons.ISSN:1748-022