166 research outputs found

    TACI, unlike BAFF-R, is solely activated by oligomeric BAFF and APRIL to support survival of activated B cells and plasmablasts.

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    The cytokine BAFF binds to the receptors TACI, BCMA, and BAFF-R on B cells, whereas APRIL binds to TACI and BCMA only. The signaling properties of soluble trimeric BAFF (BAFF 3-mer) were compared with those of higher-order BAFF oligomers. All forms of BAFF bound BAFF-R and TACI, and elicited BAFF-R-dependent signals in primary B cells. In contrast, signaling through TACI in mature B cells or plasmablasts was only achieved by higher-order BAFF and APRIL oligomers, all of which were also po-tent activators of a multimerization-dependent reporter signaling pathway. These results indicate that, although BAFF-R and TACI can provide B cells with similar signals, only BAFF-R, but not TACI, can respond to soluble BAFF 3-mer, which is the main form of BAFF found in circulation. BAFF 60-mer, an efficient TACI agonist, was also detected in plasma of BAFF transgenic and nontransgenic mice and was more than 100-fold more active than BAFF 3-mer for the activation of multimerization-dependent signals. TACI supported survival of activated B cells and plasmablasts in vitro, providing a rational basis to explain the immunoglobulin deficiency reported in TACI-deficient persons

    Conditions of emergence of the Sooty Bark Disease and aerobiology of Cryptostroma corticale in Europe

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    The sooty bark disease (SBD) is an emerging disease affecting sycamore maple trees (Acer pseudoplatanus) in Europe. Cryptostroma corticale, the causal agent, putatively native to eastern North America, can be also pathogenic for humans causing pneumonitis. It was first detected in 1945 in Europe, with markedly increasing reports since 2000. Pathogen development appears to be linked to heat waves and drought episodes. Here, we analyse the conditions of the SBD emergence in Europe based on a three-decadal time -series data set. We also assess the suitability of aerobiological samples using a species-specific quantitative PCR assay to inform the epidemiology of C. corticale, through a regional study in France comparing two-year aerobiological and epidemiological data, and a continental study including 12 air samplers from six countries (Czechia, France, Italy, Portugal, Sweden and Switzerland). We found that an accumulated water deficit in spring and summer lower than-132 mm correlates with SBD outbreaks. Our results suggest that C. corticale is an efficient airborne pathogen which can dis-perse its conidia as far as 310 km from the site of the closest disease outbreak. Aerobiology of C. corticale followed the SBD distribution in Europe. Pathogen detection was high in countries within the host native area and with longer disease presence, such as France, Switzerland and Czech Republic, and sporadic in Italy, where the pathogen was reported just once. The pathogen was absent in samples from Portugal and Sweden, where the disease has not been reported yet. We conclude that aerobiological surveillance can inform the spatial distribution of the SBD, and contribute to early detection in pathogen-free countries

    Conditions of emergence of the Sooty Bark Disease and aerobiology of Cryptostroma corticale in Europe

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    The sooty bark disease (SBD) is an emerging disease affecting sycamore maple trees (Acer pseudoplatanus) in Europe. Cryptostroma corticale, the causal agent, putatively native to eastern North America, can be also pathogenic for humans causing pneumonitis. It was first detected in 1945 in Europe, with markedly increasing reports since 2000. Pathogen development appears to be linked to heat waves and drought episodes. Here, we analyse the conditions of the SBD emergence in Europe based on a three-decadal time- series data set. We also assess the suitability of aerobiological samples using a species-specific quantitative PCR assay to inform the epidemiology of C. corticale, through a regional study in France comparing two- year aerobiological and epidemiological data, and a continental study including 12 air samplers from six countries (Czechia, France, Italy, Portugal, Sweden and Switzerland). We found that an accumulated water deficit in spring and summer lower than -132 mm correlates with SBD outbreaks. Our results suggest that C. corticale is an efficient airborne pathogen which can dis- perse its conidia as far as 310 km from the site of the closest disease outbreak. Aerobiology of C. corticale followed the SBD distribution in Europe. Pathogen detection was high in countries within the host native area and with longer disease presence, such as France, Switzerland and Czech Republic, and sporadic in Italy, where the pathogen was reported just once. The pathogen was absent in samples from Portugal and Sweden, where the disease has not been reported yet. We conclude that aerobiological surveillance can inform the spatial distribution of the SBD, and contribute to early detection in pathogen-free countriesinfo:eu-repo/semantics/publishedVersio

    Rio1 mediates ATP-dependent final maturation of 40S ribosomal subunits

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    During the last step in 40S ribosome subunit biogen-esis, the PIN-domain endonuclease Nob1 cleaves the 20S pre-rRNA at site D, to form the mature 18S rRNAs. Here we report that cleavage occurs in particles that have largely been stripped of previously character-ized pre-40S components, but retain the endonu-clease Nob1, its binding partner Pno1 (Dim2) and the atypical ATPase Rio1. Within the Rio1-associated pre-40S particles, in vitro pre-rRNA cleavage was strongly stimulated by ATP and required nucleotide binding by Rio1. In vivo binding sites for Rio1, Pno1 and Nob1 were mapped by UV cross-linking in ac-tively growing cells. Nob1 and Pno1 bind overlap-ping regions within the internal transcribed spacer 1, and both bind directly over cleavage site D. Bind-ing sites for Rio1 were within the core of the 18S rRNA, overlapping tRNA interaction sites and distinct from the related kinase Rio2. Site D cleavage occurs within pre-40S-60S complexes and Rio1-associated particles efficiently assemble into these complexes, whereas Pno1 appeared to be depleted relative to Nob1. We speculate that Rio1-mediated dissociation of Pno1 from cleavage site D is the trigger for final 18S rRNA maturation

    The JWST Early Release Science Program for the Direct Imaging and Spectroscopy of Exoplanetary Systems

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    The direct characterization of exoplanetary systems with high-contrast imaging is among the highest priorities for the broader exoplanet community. As large space missions will be necessary for detecting and characterizing exo-Earth twins, developing the techniques and technology for direct imaging of exoplanets is a driving focus for the community. For the first time, JWST will directly observe extrasolar planets at mid-infrared wavelengths beyond 5 μm, deliver detailed spectroscopy revealing much more precise chemical abundances and atmospheric conditions, and provide sensitivity to analogs of our solar system ice-giant planets at wide orbital separations, an entirely new class of exoplanet. However, in order to maximize the scientific output over the lifetime of the mission, an exquisite understanding of the instrumental performance of JWST is needed as early in the mission as possible. In this paper, we describe our 55 hr Early Release Science Program that will utilize all four JWST instruments to extend the characterization of planetary-mass companions to ∼15 μm as well as image a circumstellar disk in the mid-infrared with unprecedented sensitivity. Our program will also assess the performance of the observatory in the key modes expected to be commonly used for exoplanet direct imaging and spectroscopy, optimize data calibration and processing, and generate representative data sets that will enable a broad user base to effectively plan for general observing programs in future Cycles

    Phenological changes of oceanic phytoplankton in the 1980s and 2000s as revealed by remotely sensed ocean-color observations

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    We investigated the phenology of oceanic phytoplankton at large scales over two 5-year time periods: 1979–1983 and 1998–2002. Two ocean-color satellite data archives (Coastal Zone Color Scanner (CZCS) and Sea-viewing Wide Field-of-view Sensor (SeaWiFS)) were used to investigate changes in seasonal patterns of concentration-normalized chlorophyll. The geographic coverage was constrained by the CZCS data distribution. It was best for the Northern Hemisphere and also encompassed large areas of the Indian, South Pacific, and Equatorial Atlantic regions. For each 2° pixel, monthly climatologies were developed for satellite-derived chlorophyll, and the resulting seasonal cycles were statistically grouped using cluster analysis. Five distinct groups of mean seasonal cycles were identified for each half-decade period. Four types were common to both time periods and correspond to previously identified phytoplankton regimes: Bloom, Tropical, Subtropical North, and Subtropical South. Two other mean seasonal cycles, one in each of the two compared 5-year periods, were related to transitional or intermediate states (Transitional Tropical and Transitional Bloom). Five mean seasonal cycles (Bloom, Tropical, Subtropical North, and Subtropical South, Transitional Bloom) were further confirmed when the whole SeaWiFS data set (1998–2010) was analyzed. For ~35% of the pixels analyzed, characteristic seasonal cycles of the 1979–1983 years differed little from those of the 1998–2002 period. For ~65% of the pixels, however, phytoplankton seasonality patterns changed markedly, especially in the Northern Hemisphere. Subtropical regions of the North Pacific and Atlantic experienced a widespread expansion of the Transitional Bloom regime, which appeared further enhanced in the climatology based on the full SeaWiFS record (1998–2010), and, as showed by a more detailed analysis, is associated to La Niña years. This spatial pattern of Transitional Bloom regime reflects a general smoothing of seasonality at macroscale, coming into an apparent greater temporal synchrony of the Northern Hemisphere. The Transitional Bloom regime is also the result of a higher variability, both in space and time. The observed change in phytoplankton dynamics may be related not only to biological interactions but also to large-scale changes in the coupled atmosphere–ocean system. Some connections are indeed found with climate indices. Changes were observed among years belonging to opposite phases of ENSO, though discernible from the change among the two periods and within the SeaWiFS era (1998–2010). These linkages are considered preliminary at present and are worthy of further investigation

    Monitoring of French Polynesia coral reefs and their recent development

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    French Polynesia, consisting of 118 islands in the centre of the Pacific Ocean, has more than 15000 km2 of reefs and lagoons managed by the local government. Tourism and pearl culture are the two main economic resources of the country. Polynesian coral reefs are extremely diverse and are among those for which we have thorough knowledge. The exploitation of local resources has been recorded for multiple decades and includes : coral materials, fishing, harvest and export of mother-of-pearl molluscs, pearl production, and ornamental fish. All over the country, many monitoring programmes have been launched to measure the health of reefs and the natural and anthropogenic perturbations that they suffer : hurricanes and seismic events, water quality, health of benthic and fish communities, pearl oyster pathology and radiobiology. These data, collected over the last few decades, allowed to defi ne the relative importance of natural and anthropogenic degradation on reefs and lagoons, and to explain the present status of reefs at different spatial scales. Devastating hurricanes are rare (1903-1906, 1982-1983 and occasionally at other times), but they may annihilate outer slope coral communities on some islands. Bleaching events with considerable coral mortality at different geographical scales occurred mainly in 1991, 1994 and 2003. Outbreaks of Acanthaster destroyed numerous reefs (lagoons and outer slopes) from 1978-1982 and a new demographic wave began in 2006 at many Society islands. Eutrophication events only occurred occasionally and only in some lagoons. Whereas natural catastrophic events degrade the coral reef ecosystem across many islands, at the archipelago or even regional scale, anthropogenic degradation is limited to a few Society Islands, occurring rarely on atolls and not at all on those (one third) which are uninhabited. The main causes of reef degradation in some areas of Tahiti and Moorea include the embankment of fringing zones, coral mining, overfishing, absence of urban sewage treatment and the development of leisure and tourism activities. Because of its large geographical extent, one may conclude that major reef degradation in French Polynesia is caused by catastrophic natural events. On the other hand, anthropogenic degradation is more localized. Unfortunately, the synergistic effects of these causes of degradation prevent reefs from recovering. Optimum coral cover on French Polynesian outer reef slopes is between 50-60 %. After a major destructive impact (hurricane, bleaching, Acanthaster) a reef is reduced to less than 10 % coral cover, however if no more major disturbance events occur a reef will recover in about 12 years. Most of the 15000 km2 of reefs and lagoons in French Polynesia are in good health, and along with their neighbouring reefs in East and Central Pacific they are considered as the least degraded reefs worldwide and at a low risk of becoming degraded in the few next decades. However, we are more and more anxious about the future of reefs in the world particularly because present simulations predict that major impacts of climate change would include : elevation of sea surface temperatures, increase in the strength of hurricanes and acidification of seawater which will affect the formation of coral structuresLa Polynésie française, 118 îles au coeur du Pacifique, possède une surface de plus de 15000 km2 de récifs et lagons gérés par le gouvernement polynésien. Le tourisme et la perliculture représentent les deux ressources économiques majeures du Pays. Les formations récifales très diversifiées sont parmi les mieux connues. Plusieurs suivis d'exploitation des ressources sont opérationnels depuis des décennies : granulats coralliens, pêche pour l'alimentation, collecte et exportation de mollusques nacriers, production de perles, poissons d'ornement. À l'échelle du Pays de très nombreux programmes de surveillance de l'état des récifs et des perturbations qu'ils subissent, naturelles et anthropiques, ont été mis en place: perturbations cycloniques et sismiques, qualité des eaux, état de santé des peuplements benthiques et ichtyologiques, pathologie des nacres, radiobiologie. Toutes ces données recueillies au fil des décennies ont permis d'établir l'importance relative des dégradations naturelles et anthropiques sur les récifs et lagons polynésiens et d'expliquer leur état de santé actuel en considérant différentes échelles spatiales. Les périodes cycloniques dévastatrices pour les récifs sont rares (1903-1906, 1982-1983 et épisodiquement) mais les cyclones ont parfois anéanti les communautés coralliennes de pentes externes dans certaines îles. Les blanchissements suivis de mortalités importantes à des échelles spatiales diverses, ont été surtout ceux de 1991, 1994 et 2003. Les explosions démographiques d'Acanthaster ont détruit de nombreux récifs (lagons et pentes externes) en 1978-1982 et une nouvelle pullulation s'amplifie depuis 2006 dans plusieurs îles de la Société. Les crises dystrophiques n'ont perturbé qu'épisodiquement certains lagons. Si les événements naturels précédents dégradent les récifs à l'échelle de plusieurs îles, d'archipel ou du Pays, les dégradations anthropiques sont limitées à quelques îles peuplées de la Société, plus exceptionnellement dans les atolls et encore moins dans un tiers d'entre eux qui sont inhabités. Les remblais en zone frangeante, les extractions de matériaux coralliens, la surpêche, l'absence de réseaux d'assainissement des eaux usées urbaines et le développement d'activités de loisir et du tourisme sont les causes essentielles de la dégradation des communautés coralliennes du lagon dans certains secteurs de Tahiti et de Moorea. Ainsi apparaît-il clairement que les dégradations majeures des récifs en Polynésie sont occasionnées par des phénomènes naturels compte tenu de leur étendue géographique. En revanche les dégradations anthropiques sont géographiquement plus localisées. Malheureusement la synergie des deux causes de dégradation ne facilite pas la récupération des récifs. Il est établi qu'une pente externe avec un recouvrement corallien de 50-60 % est à son optimum. Une dégradation majeure (cyclone, blanchissement, Acanthaster) réduit ce recouvrement à moins de 10 %. La communauté met une douzaine d'années pour revenir au recouvrement optimum si aucune autre perturbation importante ne survient. La très large majorité des 15000 km2 de récifs et lagons de Polynésie française sont en bonne santé. Avec leurs voisins du Pacifique Est et Central, ces formations coralliennes sont considérées comme les moins dégradées au monde et à faible risque de dégradation dans les prochaines décennies

    The Cellular Prion Protein Interacts with the Tissue Non-Specific Alkaline Phosphatase in Membrane Microdomains of Bioaminergic Neuronal Cells

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    BACKGROUND: The cellular prion protein, PrP(C), is GPI anchored and abundant in lipid rafts. The absolute requirement of PrP(C) in neurodegeneration associated to prion diseases is well established. However, the function of this ubiquitous protein is still puzzling. Our previous work using the 1C11 neuronal model, provided evidence that PrP(C) acts as a cell surface receptor. Besides a ubiquitous signaling function of PrP(C), we have described a neuronal specificity pointing to a role of PrP(C) in neuronal homeostasis. 1C11 cells, upon appropriate induction, engage into neuronal differentiation programs, giving rise either to serotonergic (1C11(5-HT)) or noradrenergic (1C11(NE)) derivatives. METHODOLOGY/PRINCIPAL FINDINGS: The neuronal specificity of PrP(C) signaling prompted us to search for PrP(C) partners in 1C11-derived bioaminergic neuronal cells. We show here by immunoprecipitation an association of PrP(C) with an 80 kDa protein identified by mass spectrometry as the tissue non-specific alkaline phosphatase (TNAP). This interaction occurs in lipid rafts and is restricted to 1C11-derived neuronal progenies. Our data indicate that TNAP is implemented during the differentiation programs of 1C11(5-HT) and 1C11(NE) cells and is active at their cell surface. Noteworthy, TNAP may contribute to the regulation of serotonin or catecholamine synthesis in 1C11(5-HT) and 1C11(NE) bioaminergic cells by controlling pyridoxal phosphate levels. Finally, TNAP activity is shown to modulate the phosphorylation status of laminin and thereby its interaction with PrP. CONCLUSION/SIGNIFICANCE: The identification of a novel PrP(C) partner in lipid rafts of neuronal cells favors the idea of a role of PrP in multiple functions. Because PrP(C) and laminin functionally interact to support neuronal differentiation and memory consolidation, our findings introduce TNAP as a functional protagonist in the PrP(C)-laminin interplay. The partnership between TNAP and PrP(C) in neuronal cells may provide new clues as to the neurospecificity of PrP(C) function

    Global mapping of binding sites for Nrf2 identifies novel targets in cell survival response through ChIP-Seq profiling and network analysis

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    The Nrf2 (nuclear factor E2 p45-related factor 2) transcription factor responds to diverse oxidative and electrophilic environmental stresses by circumventing repression by Keap1, translocating to the nucleus, and activating cytoprotective genes. Nrf2 responses provide protection against chemical carcinogenesis, chronic inflammation, neurodegeneration, emphysema, asthma and sepsis in murine models. Nrf2 regulates the expression of a plethora of genes that detoxify oxidants and electrophiles and repair or remove damaged macromolecules, such as through proteasomal processing. However, many direct targets of Nrf2 remain undefined. Here, mouse embryonic fibroblasts (MEF) with either constitutive nuclear accumulation (Keap1−/−) or depletion (Nrf2−/−) of Nrf2 were utilized to perform chromatin-immunoprecipitation with parallel sequencing (ChIP-Seq) and global transcription profiling. This unique Nrf2 ChIP-Seq dataset is highly enriched for Nrf2-binding motifs. Integrating ChIP-Seq and microarray analyses, we identified 645 basal and 654 inducible direct targets of Nrf2, with 244 genes at the intersection. Modulated pathways in stress response and cell proliferation distinguish the inducible and basal programs. Results were confirmed in an in vivo stress model of cigarette smoke-exposed mice. This study reveals global circuitry of the Nrf2 stress response emphasizing Nrf2 as a central node in cell survival response
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