Biomarker assemblages associated with the Eocene-Oligocene transition in lacustrine deposits of the Rennes Basin (France)

International audienceThe Eocene/Oligocene transition is one of the main climatic events to which more recent climate changes are often compared. Dated back to 34 Ma, it is remarkable because the Earth evolved from a greenhouse to icehouse state, permanent ice sheets appearing during the Late Eocene. In marine setting, it is marked by an increase in detrital input associated with an increase of primary productivity that resulted from well mixing of water masses (Peihzen et al., 2001). In terrestrial setting, this cooling led to major changes in animal and plant communities. For instance, palynology data show a vegetation shift from wet to dry taxa (Gregory and Chase, 1992) coincident with a large mammal turnover, the well-known "Grande coupure" (Stelhin, 1909). Although this transition is well documented in marine settings, the lack of data on lands - due to limited available outcrops - does not allow appreciating precisely its impacts on terrestrial ecosystems. Here, we have analysed the sediment infill of the Rennes Basin that consists of 300 m of organic-rich lacustrine deposits (laminated and massive) that encompass the Middle Eocene to Oligocene series, including the Eocene-Oligocene transition, the whole fully cored (CINERGY project, BRGM). About 100 samples were collected through the core enabling us to precisely decipher environmental changes that occurred during the studied interval and to focus on the Eocene/Oligocene transition. All samples were subjected to Rock-Eval and EA-irMS to measure bulk δ13C. Four over the 100 samples were analysed for their molecular content so far. For a preliminary test, we have chosen representative facies (a laminated and a massive Upper Eocene sample and a laminated and a massive Lower Oligocene sample). Lipids were extracted with an Automated Solvant Extractor (ASE200®, Dionex) using DCM:MeOH (9:1). The total extract was later separated into neutrals, acidic and polar compounds. The neutral compounds were further separated into aliphatic, aromatic, ethers and esters, ketones and alcohols. After addition of 5α-cholestane, each fraction was then analysed by Gas Chromatography-Mass spectrometry on a Trace GC Ultra gas chromatograph coupled to a TSQ Quantum XLS mass spectrometer equipped with an AS 3000 autosampler. The analysis of the different fractions of each sample revealed a high diversity of compounds that could partly be related to their source organisms or inform on the depositional environment. Hydrocarbon fraction is dominated by a series of n-alkanes that display a strong odd-over-even predominance, indicative of a good preservation. The dominance of long-chain homologues shows a strong higher plants contribution. This is confirmed by the presence of abundant and diversified higher plant pentacyclic triterpenes. These comprise angiosperms biomarkers such as oleanane, ursane and lupane, friedelin, onocerane I and diagenetic by-products (des-A-tritrepenes and aromatic derivatives). Fernene-type compounds could reveal an input from pteridophyts whereas tricyclic diterpenes indicate the presence of conifers. An algal influence is evidenced, for example, by the presence of 4-methylsteranes in the four samples. C27 to C32 hopanoids with α,β, β,β and β,α configurations show a substantial bacterial contribution. This is confirmed by high levels of hopane ketones in some beds. The comparison of angiosperm-derived biomarkers with gymnosperm-derived biomarkers indicates a stronger contribution of angiosperms in Upper Eocene samples than in Lower Oligocene samples (triterpenoids, aromatic, and rearranged-triterpenoids). This result is in agreement with palynological data (Bourdillon et al., 2012) and with the well-known cooling that is coeval with the Eocene/Oligocene transition. Reversely, the comparison between the two facies (massive and laminated) does not exhibit significant differences in the molecular assemblage. Based on this preliminary inventory of biomarkers and the richness in various biomarkers, we will proceed with the identification and quantitation on the remaining samples that cover the whole section. These preliminary results are also encouraging in the perspective of performing compound-specific isotopic analyses in order to depict, at high temporal resolution, the climatic evolution and the associated changes in plant communities during the Late Eocene and Early Oligocene and, more specifically, at the Eocene/Oligocene transition

Palaeoenvironments and palaeoclimate records in lacustrine deposits at the Eocene-Oligocene Transition. New insight from de CDB1 borehole (Rennes Basin, France)

On behalf the CINERGY project, a 675m-long borehole was cored through the sedimentary column (405 m) and the basement (270 m). The studied interval encompasses 3 lithostratigraphic units, from 66m to 405m depth. The chronostratigraphic framework of the sedimentary series relies on benthic foraminifera and palynology. Palaeoenvironmental reconstruction is based on sedimentology, pollen analysis and clay mineralogy. 95% of the series deposited continuously from the Early-Middle Bartonian to the Rupelian, including 290 m-thick lacustrine shaly organic deposits, alternating open and closed system depending on the floatting vegetal mats extension. Climate evolution is illustrated by palynological content. The Eocene climate evolves from a from warm and humid condition to a more contrasted seasons. the EOT is marked by a short drier and fresher period, the Rupelian is characterized by disappearance of megathermic taxa but back to more humid condition. Clay mineralogy changes more abruptly at the E/O boundary (~200 m depth), from an almost pure kaolinitic content to a kaolinite-smectite dominated assemblage. Whether the sudden mineralogical change across de E/O boundary is related to a change in source material or to a change in the hydrolysis in soil clay production, a climatic origin is very likely

Paléoenvironnements et paléoclimats enregistrés dans le bassin éo-oligocène de Rennes. Apports du forage CDB1 (projet CINERGY).

Dans le cadre du projet CINERGY, un forage carotté de 675 m a recoupé l'ensemble de la série sédimentaire remplissant ce bassin, puis la partie altérée du socle sur plus de 100 m et le socle sain sur 150 m. La série sédimentaire carottée a fait l'objet d'une première étude intégrant biostratigraphie, minéralogie, sédimentologie de faciès et analyse séquentielle, visant à établir le cadre chronostratigraphique, l'évolution des paléoenvironnements et du climat. L'intervalle étudié (66-405 m) comprend 4 unités lithostratigraphiques : - les Marnes à Natica (66-85 m) correspondent à des dépôts laguno-marins argilo-calcaires. La malacofaune et les associations de dinokystes sont typiquement rupéliennes ; - les Sapropèles inférieurs (85-206 m) sont caractérisés par des alternances d'argiles laminées et massives à traces de racines. Le Rupélien inférieur est attesté par la présence du pollen B. hohli. La limite E/O est localisée dans l'intervalle 189-206 m ; - les Argiles à Mohria (206-375 m) ont des faciès similaires, mais particulièrement riches en matière organique. Ces deux formations témoignent d'un environnement lacustre à palustre. Les associations polliniques sont d'âge Priabonien ; - la Formation basale argilo-sableuse (375-405 m) correspond à l'apparition des premiers sables. Les environnements de dépôts fluctuent entre fluvio-lacustre et fluvio-marin. Ces dépôts ont pu être datés par les pollens et les foraminifères du Lutétien supérieur au Bartonien. L'analyse séquentielle de cette succession montre deux MFS majeures, l'une dans les dépôts côtiers vers 380 m, l'autre dans les dépôts très organiques lacustres vers 240 m. A l'échelle de la séquence élémentaire, deux types d'unités génétiques sont définies selon l'environnement lacustre ou lagunaire. La comparaison du bassin de Rennes avec celui de Saffré indique une subsidence nettement plus importante pendant le Priabonien à Rennes. La comparaison avec d'autres bassins ouest-européens place les bassins de Rennes et Saffré dans une dynamique intermédiaire entre les bassins d'effondrement très subsidents comme le fossé rhénan et les bassins intracratoniques parisien, belge ou anglais. L'étude palynologique montre un changement important de la végétation à la fin de l'Eocène avec l'augmentation des Pinacées, puis un changement plus profond du climat à l'Oligocène avec le développement des Herbacées, attestant d'une saison sèche plus marquée, et l'apparition de la chlorite-smectite. A l'échelle ouest-européenne, on constate la simultanéité de ce refroidissement fini-éocène. Une étude à plus haute résolution de cet intervalle clé, particulièrement bien enregistré à Rennes, fournira des réponses sur ce changement global

Avelumab in patients with previously treated metastatic melanoma: phase 1b results from the JAVELIN Solid Tumor trial

Background We report phase 1b data from patients enrolled in the JAVELIN Solid Tumor clinical trial (NCT01772004) with unresectable stage IIIC or IV melanoma that had progressed after ≥1 line of therapy for metastatic disease. Patients and methods Patients received avelumab (10 mg/kg)—a human anti–PD-L1 antibody. Assessments included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Results As of December 31, 2016, 51 patients were treated and followed for a median of 24.2 months (range, 16.1–31.5). Most patients had cutaneous (n = 28 [54.9%]) or ocular (n = 16 [31.4%]) melanoma and had received a median of 2 prior lines of therapy (range, 0–4), including ipilimumab (n = 26 [51.0%]). The confirmed ORR was 21.6% (95% CI, 11.3–35.3; complete response, 7.8%; partial response, 13.7%). The median duration of response was not estimable (95% CI, 2.6 months-not estimable). Median PFS and OS were 3.1 months (95% CI, 1.4–6.3) and 17.2 months (95% CI, 6.6-not estimable), respectively. Subgroup analyses suggested meaningful clinical activity (ORR [95% CI]) in patients with non-ocular melanoma (31.4% [16.9–49.3]), PD-L1–positive tumors (42.1% [20.3–66.5]), or prior ipilimumab therapy (30.8% [14.3–51.8]). Thirty-nine patients (76.5%) had a treatment-related adverse event (TRAE), most commonly infusion-related reaction (29.4%), fatigue (17.6%), and chills (11.8%); 4 patients (7.8%) had a grade 3 TRAE. Five patients (9.8%) had an immune-related TRAE (all were grade 1/2). No grade 4 TRAEs or treatment-related deaths were reported. Conclusion Avelumab showed durable responses, promising survival outcomes, and an acceptable safety profile in patients with previously treated metastatic melanoma. Trial registration ClinicalTrials.gov identifier: NCT01772004This trial was sponsored by Merck KGaA, Darmstadt, Germany, and is part of an alliance between Merck KGaA and Pfizer, Inc., New York, NY, USA. Medical writing support was provided by ClinicalThinking, Inc., Hamilton, NJ, USA, and funded by Merck KGaA, and Pfizer, Inc

Knocking at the brain’s door: intravital two-photon imaging of autoreactive T cell interactions with CNS structures

Since the first applications of two-photon microscopy in immunology 10 years ago, the number of studies using this advanced technology has increased dramatically. The two-photon microscope allows long-term visualization of cell motility in the living tissue with minimal phototoxicity. Using this technique, we examined brain autoantigen-specific T cell behavior in experimental autoimmune encephalitomyelitis, the animal model of human multiple sclerosis. Even before disease symptoms appear, the autoreactive T cells arrive at their target organ. There they crawl along the intraluminal surface of central nervous system (CNS) blood vessels before they extravasate. In the perivascular environment, the T cells meet phagocytes that present autoantigens. This contact activates the T cells to penetrate deep into the CNS parenchyma, where the infiltrated T cells again can find antigen, be further activated, and produce cytokines, resulting in massive immune cell recruitment and clinical disease

The Cell Adhesion Molecule “CAR” and Sialic Acid on Human Erythrocytes Influence Adenovirus In Vivo Biodistribution

Although it has been known for 50 years that adenoviruses (Ads) interact with erythrocytes ex vivo, the molecular and structural basis for this interaction, which has been serendipitously exploited for diagnostic tests, is unknown. In this study, we characterized the interaction between erythrocytes and unrelated Ad serotypes, human 5 (HAd5) and 37 (HAd37), and canine 2 (CAV-2). While these serotypes agglutinate human erythrocytes, they use different receptors, have different tropisms and/or infect different species. Using molecular, biochemical, structural and transgenic animal-based analyses, we found that the primary erythrocyte interaction domain for HAd37 is its sialic acid binding site, while CAV-2 binding depends on at least three factors: electrostatic interactions, sialic acid binding and, unexpectedly, binding to the coxsackievirus and adenovirus receptor (CAR) on human erythrocytes. We show that the presence of CAR on erythrocytes leads to prolonged in vivo blood half-life and significantly reduced liver infection when a CAR-tropic Ad is injected intravenously. This study provides i) a molecular and structural rationale for Ad–erythrocyte interactions, ii) a basis to improve vector-mediated gene transfer and iii) a mechanism that may explain the biodistribution and pathogenic inconsistencies found between human and animal models

Context-Dependent Encoding of Fear and Extinction Memories in a Large-Scale Network Model of the Basal Amygdala

The basal nucleus of the amygdala (BA) is involved in the formation of context-dependent conditioned fear and extinction memories. To understand the underlying neural mechanisms we developed a large-scale neuron network model of the BA, composed of excitatory and inhibitory leaky-integrate-and-fire neurons. Excitatory BA neurons received conditioned stimulus (CS)-related input from the adjacent lateral nucleus (LA) and contextual input from the hippocampus or medial prefrontal cortex (mPFC). We implemented a plasticity mechanism according to which CS and contextual synapses were potentiated if CS and contextual inputs temporally coincided on the afferents of the excitatory neurons. Our simulations revealed a differential recruitment of two distinct subpopulations of BA neurons during conditioning and extinction, mimicking the activation of experimentally observed cell populations. We propose that these two subgroups encode contextual specificity of fear and extinction memories, respectively. Mutual competition between them, mediated by feedback inhibition and driven by contextual inputs, regulates the activity in the central amygdala (CEA) thereby controlling amygdala output and fear behavior. The model makes multiple testable predictions that may advance our understanding of fear and extinction memories

Mathematical models for immunology:current state of the art and future research directions

The advances in genetics and biochemistry that have taken place over the last 10 years led to significant advances in experimental and clinical immunology. In turn, this has led to the development of new mathematical models to investigate qualitatively and quantitatively various open questions in immunology. In this study we present a review of some research areas in mathematical immunology that evolved over the last 10 years. To this end, we take a step-by-step approach in discussing a range of models derived to study the dynamics of both the innate and immune responses at the molecular, cellular and tissue scales. To emphasise the use of mathematics in modelling in this area, we also review some of the mathematical tools used to investigate these models. Finally, we discuss some future trends in both experimental immunology and mathematical immunology for the upcoming years

A search for resonances decaying into a Higgs boson and a new particle X in the XH→qqbb final state with the ATLAS detector

A search for heavy resonances decaying into a Higgs boson ($H$) and a new particle ($X$) is reported, utilizing 36.1 fb$^{-1}$ of proton-proton collision data at $\sqrt{s} =$ 13 TeV collected during 2015 and 2016 with the ATLAS detector at the CERN Large Hadron Collider. The particle $X$ is assumed to decay to a pair of light quarks, and the fully hadronic final state $XH \rightarrow q\bar q'b\bar b$ is analysed. The search considers the regime of high $XH$ resonance masses, where the $X$ and $H$ bosons are both highly Lorentz-boosted and are each reconstructed using a single jet with large radius parameter. A two-dimensional phase space of $XH$ mass versus $X$ mass is scanned for evidence of a signal, over a range of $XH$ resonance mass values between 1 TeV and 4 TeV, and for $X$ particles with masses from 50 GeV to 1000 GeV. All search results are consistent with the expectations for the background due to Standard Model processes, and 95% CL upper limits are set, as a function of $XH$ and $X$ masses, on the production cross-section of the $XH\rightarrow q\bar q'b\bar b$ resonance