Les toxines des cyanobactéries : revue de synthèse

La toxicité du phytoplancton est un problème dont l'importance est grandissante en France comme en Europe. Cette toxicité se manifeste surtout lors de l'ingestion de cyanobactéries formant des fleurs d'eau superficielles liées à l'eutrophisation. Microcystis aeruginosa est l'espèce la plus fréquemment incriminée, mais 75 % des souches de cyanobactéries d'eau douce seraient des toxiques potentielles. Lorsque des clones sont isolés d'un plan d'eau dans lequel des manifestations de toxicité ont été observées, des souches toxiques et non toxiques sont obtenues. La connaissance des conditions d'expression de la toxicité représente un sujet important actuellement peu étudié. Un mammifère peut mourir s'il passe dans son sang 0,07 mg de toxine de Microcystis par kg de son poids. En pratique, de nombreux cas de morts de bétail ont été recensés. Les toxines qui causent des accidents sont des endotoxines non rejetées par les cellules vivantes, mais libéré au cours de leur lyse. Ceci explique que des cas d'intoxication humaine par l'intermédiaire de l'eau de boisson ont pu être observés. On distingue principalement : des microcystines, hépatotoxines produites par diverses cyanobactéries dont Microcystis et Oscillatoria, et des anatoxines, neurotoxines produites par des Anabaena. Certaines cyanobactéries produiraient un mélange des deux formes. En sus du test de toxicité classique sur la souris, plusieurs autres tests existent. L'analyse est généralement réalisée par chromatographie liquide à haute pression. Des produits actifs synthétisés par des cyanobactéries possèdent une fonction antibiotique et sont susceptibles de jouer un rôle dans le comportement des espèces et leur dominance ou de les protéger contre le broutage. Ces produits seraient des exotoxines différentes des précédentes.The aim of the paper is to present in the French language the international knowledge related to freshwater cyanobacterial toxins, a problem of great significance in our European countries but largely unknown by people in France. An analytical review of a selection of works chosen from the extensive existing literature is presented. At the present time, the mains works come from : U.S.A., with CARMICHAEL and coworkers, continuing the researchs from CORHAM; Scotland, with CODD; Scandinavia with ERIKSSON, LINDHOLM; and Japan with WATANABE, HARADA, but also many others scientists.In freshwater, poisoning is typically associated with the ingestion of the cyanobacteria appearing in large amount, at the surface of some water bodies, and called water blooms. Many cases of livestock death (concerning sheeps, calves but also adult oxen and horses), associated with the consumption of such water blooms are reported, also, deaths of wild mammals (muskrats, and hogs), birds (ducks, geese), fishes, invertebrate, and human illness following bathing are known. But, because toxins are not destroyed by conventional sand filtration treatment, human illness may also arise from drinking water taken out from an impoundment with a cyanobacterial bloom. Cases are known from United States, Scandinavia and Sardinia. This tap water problem is serious because probabilities of long term diseases, such as tumors promotion, are now considered high.Seventy-five percent of fresh water cyanobacterial strains are potentially toxic, but, on the whole, only some clones from a single species, simultaneously isolated out of an unique body of water, are toxic. However, there are no evidence that the nontoxic strains could never become toxic.Cyanobacteria are also known as blue-green algae, Myxophyceae or Cyanophyta, and are typically microscopic prokaryotes, but with chlorophyll a. Toxic clones belong to : a) the Chroococcales, single coccoid cells embedded in a gelatinous matrix, represented by species of the genera Coelosphaerium, Gomphosphaeria, and Microcystis whose the species M. aeruginosa is the most frequently quotted toxic Cyanobacteria. b) the Nostocales, filamentous forms, some of them with exocellular sheath. Many are nitrogen fixing species belonging to the genera Nodularia, Anabaena, Aphanizomenon and Nostoc, others belong to the genera Oscillatoria, and are sot known as nitrogen fixers.Most often the mice toxicity test is used to identify toxic water blooms, it allows to define the lethal doses of the toxins or of the toxic organisms. But some others tests have been applied or suggested, they use others animals : fishes, zooplankton or microorganisms, and isolated organs or cells cultures, many are not specific. Currently the modern immunological tests are not yet adapted to identify fresh-water cyanobacterial toxins.The main toxins that can be distinguished are the microcystins and the anatoxins. The microcystins are hepatotoxins from various cyanobacteria belonging principally to the genera Microcystis and Oscilatoria; they promote liver haemorrhages. The anatoxins are neurotoxins from Anabaena and death occur by breath arrest. Some cyanobacteria simultaneously produce the two forms. A mammal may be killed by a blood level content of 0.07 mg of Microcystis toxin per kg of body weight. Cyanobacterial toxins are endotoxins which diffuse during cell lysis. This explain why toxins can be found in water from impoundments with cyanobacterial blooms. In this case, the toxins can possibly originate in a thick metalimnic plankton layer, not seen from surface.Toxin analysis is usually performed using high pressure liquid chromatography but also thin layer chromatography, and particularly the high performance modem technique. Molecular structures are eluciated using, fast atoms bombardment spectrometry, mass spectrometry and nuclear magnetic resonance. The microcystins are cyclic heptapeptides of low molecular weight, they differed in amino-acids composition; a characteristic one, built up with 20 carbons, is called ADDA. Microcystins toxicity ensue as they act as strong inhibitors upon phosphatase activities. The anatoxins-a are alkaloids, others anatoxins are peptides or currently unknown.The causes of the expression of the toxicity remain to be elucidated. In the years to come, much progress can be achieved by using new genetic tools. Nevertheless, as the largest problems occur always associated with water-blooms, and rise under high sunlight in hot periods, toxicity appears in the whole, associated with eutrophication, and as many toxic species are nitrogen fixers which do not need inorganic nitrogen to grow, problems follow generally a plentiful phosphorous load of water bodies due to human operations. As toxins accumulate in the cells, they could be actives either only after cells consumption, or after toxins discharge during cell lysis. Cyanobacterial toxicity is not due to bacteria associated with the cyanobacteria and can appear in pure axeniccultures. Toxicity is not associated with the presence of cell plasmids. It was shows that optimal conditions for growth did sot coincide with those for toxin production and vary with the growth phase. On the whole, the optimum temperatures, for toxin maximum production, were at about 25 °C for different cultures. Light intensity would be the primary important factor for the production of the toxin, but, in cyanobacteria cultures, this production can occur at relatively low light intensity.Some related cyanobacterial products are not true toxins but are exotoxins acting as antibiotics and can affect species behaviour or dominance and help deter grazers. Since LEFEVRE and coworkers studies, and after a long quiescent period, ecologists take these products anew into account when studying plankton ecology and successions. Only some phytoplankton responds to cyanobacterial extracellular products. Among zooplankton there are species avoiding actively the cyanobacteria and insensitive ones. Chemists have already started search for antitoxins chemicals and found promising curative results. On the other band, biotechnology could take advantage of all these various cyanobacterial products to obtain new drags having pharmacological or agronomical uses. Some true toxins could be used as anti-neoplastics, and products, involved in allelopathic reactions, have antibiotic and antivirus activities. The use of toxins as commercial algicide for chlorophycean waterbloom control had been suggested, but the action spectra of the toxins must be precisely known before extensive implementation. From another point of view, « microalgal » by-products, used as food additives have to be carefully checked for possible toxins.As SKULBERG et al. could rite in 1984, toxic blue-green algal blooms is a growing problem in Europe. Scientists involved in health supervision had to be watchful to it in a way to prevent people from possible major accidents

Treatment with a BH3 mimetic overcomes the resistance of latency III EBV (+) cells to p53-mediated apoptosis

P53 inactivation is often observed in Burkitt's lymphoma (BL) cells due to mutations in the p53 gene or overexpression of its negative regulator, murine double minute-2 (MDM2). This event is now considered an essential part of the oncogenic process. Epstein–Barr virus (EBV) is strongly associated with BL and is a cofactor in its development. We previously showed that nutlin-3, an antagonist of MDM2, activates the p53 pathway in BL cell lines harboring wild-type p53. However, nutlin-3 strongly induced apoptosis in EBV (−) or latency I EBV (+) cells, whereas latency III EBV (+) cells were much more resistant. We show here that this resistance to apoptosis is also observed in latency III EBV (+) lymphoblastoid cell lines. We also show that, in latency III EBV (+) cells, B-cell lymphona 2 (Bcl-2) is selectively overproduced and interacts with Bcl-2-associated X protein (Bax), preventing its activation. The treatment of these cells with the Bcl-2-homology domain 3 mimetic ABT-737 disrupts Bax/Bcl-2 interaction and allows Bax activation by nutlin-3. Furthermore, treatment with these two compounds strongly induces apoptosis. Thus, a combination of Mdm2 and Bcl-2 inhibitors might be a useful anti-cancer strategy for diseases linked to EBV infection

30 years in the life of an active submarine volcano: A time-lapse bathymetry study of the Kick-‘em-Jenny Volcano, Lesser Antilles

Effective monitoring is an essential part of identifying and mitigating volcanic hazards. In the submarine environment this is more difficult than onshore because observations are typically limited to land-based seismic networks and infrequent shipboard surveys. Since the first recorded eruption in 1939, the Kick-‘em-Jenny (KeJ) volcano, located 8km off northern Grenada, has been the source of 13 episodes of T-phase signals. These distinctive seismic signals, often coincident with heightened body-wave seismicity, are interpreted as extrusive eruptions. They have occurred with a recurrence interval of around a decade, yet direct confirmation of volcanism has been rare. By conducting new bathymetric surveys in 2016 and 2017 and reprocessing 4 legacy datasets spanning 30 years we present a clearer picture of the development of KeJ through time. Processed grids with a cell size of 5m and vertical precision on the order of 1-4m allow us to correlate T-phase episodes with morphological changes at the volcano's edifice. In the time-period of observation 7.09x106 m3 of material has been added through constructive volcanism – yet 5 times this amount has been lost through landslides. Limited recent magma production suggests that KeJ may be susceptible to larger eruptions with longer repeat times than have occurred during the study interval, behavior more similar to sub-aerial volcanism in the arc than previously thought. T-phase signals at KeJ have a varied origin and are unlikely to be solely the result of extrusive submarine eruptions. Our results confirm the value of repeat swath bathymetry surveys in assessing submarine volcanic hazards

c-Rel Deficiency Increases Caspase-4 Expression and Leads to ER Stress and Necrosis in EBV-Transformed Cells

LMP1-mediated activation of nuclear factor of kappaB (NF-κB) is critical for the ligand independent proliferation and cell survival of in vitro EBV-transformed lymphoblastoid cell lines (LCLs). Previous experiments revealed that a majority of LMP1-dependent responses are regulated by NF-κB. However, the extent that individual NF-κB family members are required for these responses, in particular, c-Rel, whose expression is restricted to mature hematopoietic cells, remains unclear. Here we report that low c-Rel expression in LCLs derived from a patient with hyper-IgM syndrome (Pt1), resulted in defects in proliferation and cell survival. In contrast to studies that associated loss of NF-κB with increased apoptosis, Pt1 LCLs failed to initiate apoptosis and alternatively underwent autophagy and necrotic cell death. Whereas the proliferation defect appeared linked to a c-Rel-associated decrease in c-myc expression, identified pro-survival and pro-apoptotic targets were expressed at or near control levels consistent with the absence of apoptosis. Ultrastructural examination of Pt1 LCLs revealed a high level of cellular and ER stress that was further supported by gene expression profiling showing the upregulation of several genes involved in stress and inflammation. Apoptosis-independent cell death was accompanied by increased expression of the inflammatory marker, caspase-4. Using gene overexpression and siRNA knockdown we demonstrated that levels of c-Rel directly modulated expression of caspase-4 as well as other ER stress genes. Overall, these findings reveal the importance of c-Rel in maintaining LCL viability and that decreased expression results in ER stress and a default response leading to necrotic cell death

Enhanced production of multi-strange hadrons in high-multiplicity proton-proton collisions

At sufficiently high temperature and energy density, nuclear matter undergoes a transition to a phase in which quarks and gluons are not confined: the quark-gluon plasma (QGP)(1). Such an exotic state of strongly interacting quantum chromodynamics matter is produced in the laboratory in heavy nuclei high-energy collisions, where an enhanced production of strange hadrons is observed(2-6). Strangeness enhancement, originally proposed as a signature of QGP formation in nuclear collisions(7), is more pronounced for multi-strange baryons. Several effects typical of heavy-ion phenomenology have been observed in high-multiplicity proton-proton (pp) collisions(8,9), but the enhanced production of multi-strange particles has not been reported so far. Here we present the first observation of strangeness enhancement in high-multiplicity proton-proton collisions. We find that the integrated yields of strange and multi-strange particles, relative to pions, increases significantly with the event charged-particle multiplicity. The measurements are in remarkable agreement with the p-Pb collision results(10,11), indicating that the phenomenon is related to the final system created in the collision. In high-multiplicity events strangeness production reaches values similar to those observed in Pb-Pb collisions, where a QGP is formed.Peer reviewe

phi-Meson production at forward rapidity in p-Pb collisions at root s(NN)=5.02 TeV and in pp collisions at root s=2.76 TeV

The first study of phi-meson production in p-Pb collisions at forward and backward rapidity, at a nucleonnucleon centre-of-mass energy root s(NN)= 5.02 TeV, has been performed with the ALICE apparatus at the LHC. The phi-mesons have been identified in the dimuon decay channel in the transverse momentum (p(T)) range 1 <p(T) <7GeV/c, both in the p-going (2.03 <y <3.53) and the Pb-going (-4.46 <y <-2.96) directions - where ystands for the rapidity in the nucleon-nucleon centre-of-mass - the integrated luminosity amounting to 5.01 +/- 0.19nb(-1) and 5.81 +/- 0.20nb(-1), respectively, for the two data samples. Differential cross sections as a function of transverse momentum and rapidity are presented. The forward-backward ratio for f-meson production is measured for 2.96Peer reviewe

Measurement of the production of high-p(T) electrons from heavy-flavour hadron decays in Pb-Pb collisions at root s(NN)=2.76 TeV

CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFINANCIADORA DE ESTUDOS E PROJETOS - FINEPFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPElectrons from heavy-flavour hadron decays (charm and beauty) were measured with the ALICE detector in Pb-Pb collisions at a centre-of-mass of energy root s(NN) = 2.76 TeV. The transverse momentum (pT) differential production yields at mid-rapidity were used to calculate the nuclear modification factor R-AA in the interval 3 < p(T) < 18 GeV/c. The R-AA shows a strong suppression compared to binary scaling of pp collisions at the same energy (up to a factor of 4) in the 10% most central Pb-Pb collisions. There is a centrality trend of suppression, and a weaker suppression (down to a factor of 2) in semi-peripheral (50-80%) collisions is observed. The suppression of electrons in this broad p(T) interval indicates that both charm and beauty quarks lose energy when they traverse the hot medium formed in Pb-Pb collisions at LHC.771467481CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFINANCIADORA DE ESTUDOS E PROJETOS - FINEPFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFINANCIADORA DE ESTUDOS E PROJETOS - FINEPFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPSem informaçãoSem informaçãoSem informaçãoThe ALICE Collaboration would like to thank all its engineers and technicians for their invaluable contributions to the construction of the experiment and the CERN accelerator teams for the outstanding performance of the LHC complex. The ALICE Collaboration gratefully acknowledges the resources and support provided by all Grid centres and the Worldwide LHC Computing Grid (WLCG) collaboration. The ALICE Collaboration acknowledges the following funding agencies for their support in building and running the ALICE detector: A.I. Alikhanyan National Science Laboratory (Yerevan Physics Institute) Foundation (ANSL), State Committee of Science and World Federation of Scientists (WFS), Armenia; Austrian Academy of Sciences and Nationalstiftung für Forschung, Technologie und Entwicklung, Austria; Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Financiadora de Estudos e Projetos (Finep) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Brazil; Ministry of Education of China (MOE of China), Ministry of Science & Technology of China (MOST of China) and National Natural Science Foundation of China (NSFC), China; Ministry of Science, Education and Sports and Croatian Science Foundation, Croatia; Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Cuba; Ministry of Education, Youth and Sports of the Czech Republic, Czech Republic; Danish National Research Foundation (DNRF), The Carlsberg Foundation and The Danish Council for Independent Research–Natural Sciences, Denmark; Helsinki Institute of Physics (HIP), Finland; Commissariat à l'Energie Atomique (CEA) and Institut National de Physique Nucléaire et de Physique des Particules (IN2P3) and Centre National de la Recherche Scientifique (CNRS), France; Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie (BMBF) and GSI Helmholtzzentrum für Schwerionenforschung GmbH, Germany; Ministry of Education, Research and Religious Affairs, Greece; National Research, Development and Innovation Office, Hungary; Department of Atomic Energy, Government of India (DAE), India; Indonesian Institute of Science, Indonesia; Centro Fermi – Museo Storico della Fisica e Centro Studi e Ricerche Enrico Fermi and Istituto Nazionale di Fisica Nucleare (INFN), Italy; Institute for Innovative Science and Technology, Nagasaki Institute of Applied Science (IIST), Japan Society for the Promotion of Science (JSPS) KAKENHI and Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan; Consejo Nacional de Ciencia y Tecnología (CONACYT), through Fondo de Cooperación Internacional en Ciencia y Tecnología (FONCICYT) and Dirección General de Asuntos del Personal Academico (DGAPA), Mexico; Nationaal instituut voor subatomaire fysica (Nikhef), Netherlands; The Research Council of Norway, Norway; Commission on Science and Technology for Sustainable Development in the South (COMSATS), Pakistan; Pontificia Universidad Católica del Perú, Peru; Ministry of Science and Higher Education and National Science Centre, Poland; Ministry of Education and Scientific Research, Institute of Atomic Physics and Romanian National Agency for Science, Technology and Innovation, Romania; Joint Institute for Nuclear Research (JINR), Ministry of Education and Science of the Russian Federation and National Research Centre Kurchatov Institute, Russia; Ministry of Education, Science, Research and Sport of the Slovak Republic, Slovakia; National Research Foundation of South Africa, South Africa; Korea Institute of Science and Technology Information and National Research Foundation of Korea (NRF), South Korea; Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) and Ministerio de Ciencia e Innovacion, Spain; Knut & Alice Wallenberg Foundation (KAW) and Swedish Research Council (VR), Sweden; European Organization for Nuclear Research, Switzerland; National Science and Technology Development Agency (NSDTA), Office of the Higher Education Commission under NRU project of Thailand and Suranaree University of Technology (SUT), Thailand; Turkish Atomic Energy Agency (TAEK), Turkey; National Academy of Sciences of Ukraine, Ukraine; Science and Technology Facilities Council (STFC), United Kingdom; National Science Foundation of the United States of America (NSF) and United States Department of Energy, Office of Nuclear Physics (DOE NP), United States