Vein-type graphite deposits in Sri Lanka: the ultimate fate of granulite fluids

The world-best vein graphite deposits in Sri-Lanka occur scattered through the high-grade terrain of the Wanni and Highland Complexes of Sri-Lanka. The Wanni Complex (amphibolite to granulite grade) consists of ~770-1100 Ma metagranitoids, metagabbro, charnockite, enderbitic gneisses, migmatites, clastic metasediments, including garnet-cordierite gneisses, rare to minor calc-silicate rocks as well as late to post-tectonic granites (Kröner et al., 2013). Higher metamorphic grade, reaching in places UHT-conditions (T>1000 °C) characterizes the Highland Complex. Peak metamorphism occurred during the Neoproterozoic Pan-African orogeny (~620-535 Ma), which led to the accretion of terrains in Sri Lanka and played a key role for the amalgamation of the Gondwana supercontinent (Tsunogae and Santosh, 2010). Structurally disposed in extensional fractures post-dating the Pan-African ductile structures (Kehelpannala, 1999), the graphite veins equilibrated at relatively low temperature (500-600 °C). However, the presence of mesoperthites indicate that graphite precipitation may have started at higher temperature. Samples from khondalite host rocks and quartz co-precipitated with graphite from the Bogala and Kahatagana graphite mines in the Wanni Complex were studied. Host-rocks show spectacular decompression reaction aureoles around feldspars and garnet. They contain small CO2 inclusions in garnet cores or quartz in decompression reaction aureoles. Larger, highly transposed brine inclusions are more abundant and are responsible for metasomatic features (feldspar leaching and deposition) observed in the aureoles. Fluid inclusions in vein minerals are dominantly aqueous, rarely mixed H2O+CO2. Fluid inclusions and petrographic data suggest that graphite has been deposited from fluids at decreasing pressure and temperature at relatively reduced redox conditions. Carbon isotope data indicate a dominant mantle source, mixed with small quantities of light C-bearing fluids. It has been proposed that large quantities of mantle-derived CO2 fluid have infiltrated the lower crust during the final stage of Gondwana supercontinent amalgamation (Touret et al., 2016). Formed during strong decompression at the end of a long (up to a few 10 Ma) period of isobaric cooling, the graphite veins in Sri-Lanka (and elsewhere in the former Gondwana) reflects the escape of these granulite fluids to higher crustal levels. In this respect, they are comparable to the quartz-carbonates mega-shear zones found in other granulite terranes (Newton and Manning, 2002). Depending on the redox conditions, former lower crustal fluids (mantle-derived CO2 and/or brines) may either result in mid to upper-crustal quartz-carbonate or graphite veins

State of organic seeds in France

A comprehensive range of investigations carried out between 2010 and 2012 provided information on the state of organic seeds in France. Results fit with the hypothesis that the market is a significant factor influencing the choice of seeds and cultivars (local cultivars, landraces, modern cultivars). Expectations and practices of producers selling on a local market (i.e., direct sale) differ radically from those of producers selling to long food supply chains. This study showed that the availability and use of organic seeds have significantly improved over the last three years. A vast majority of organic producers willingly use organic seeds, with, on average, 45-70 % (cereals), and 75%-100 % (vegetables) of organic seeds being planted on farms. However, the total number of derogations remained quite high: there is still space for improvement in organic seed use and supply in France. Several limiting factors and levers were identified during the study, as well as farmers’ expectations for the future on cereals, forage crops and vegetables. This study described an action plan, which must be carefully implemented. The organic sector depends on the development of a wide and adapted range of organic seeds

Validation of a Piles Dynamic Analysis Computer Code Through In Situ Tests

In order to qualify the CLAPIFOU code, which computes the dynamic response of a pile foundation subjected to earthquake or harmonic forces, a test campaign was carried out on piles, to full scale, on pile groups of 2 x 1 piles and 2 x 3 piles on the Plancoet site. The purpose of the study is to compare the results of the experiments and the digital simulations with the computer code. The comparison is good but confirms the need for a good knowledge of the soil\u27s characteristics

High-temperature granulites and supercontinents

The formation of continents involves a combination of magmatic and metamorphic processes. These processes become indistinguishable at the crust-mantle interface, where the pressure-temperature (P-T) conditions of (ultra) high-temperature granulites and magmatic rocks are similar. Continents grow laterally, bymagmatic activity above oceanic subduction zones (high-pressure metamorphic setting), and vertically by accumulation of mantle-derived magmas at the base of the crust (high-temperature metamorphic setting). Both events are separated from each other in time; the vertical accretion postdating lateral growth by several tens of millions of years. Fluid inclusion data indicate that during the high-temperature metamorphic episode the granulite lower crust is invaded by large amounts of low H2O-activity fluids including high-density CO₂ and concentrated saline solutions (brines). These fluids are expelled from the lower crust to higher crustal levels at the end of the high-grade metamorphic event. The final amalgamation of supercontinents corresponds to episodes of ultra-high temperature metamorphism involving large-scale accumulation of these low-water activity fluids in the lower crust. This accumulation causes tectonic instability, which together with the heat input from the subcontinental lithospheric mantle, leads to the disruption of supercontinents. Thus, the fragmentation of a supercontinent is already programmed at the time of its amalgamation.J.L.R. Touret, M. Santosh, J.M. Huizeng

A Mouse Model for Chikungunya: Young Age and Inefficient Type-I Interferon Signaling Are Risk Factors for Severe Disease

Chikungunya virus (CHIKV) is a re-emerging arbovirus responsible for a massive outbreak currently afflicting the Indian Ocean region and India. Infection from CHIKV typically induces a mild disease in humans, characterized by fever, myalgia, arthralgia, and rash. Cases of severe CHIKV infection involving the central nervous system (CNS) have recently been described in neonates as well as in adults with underlying conditions. The pathophysiology of CHIKV infection and the basis for disease severity are unknown. To address these critical issues, we have developed an animal model of CHIKV infection. We show here that whereas wild type (WT) adult mice are resistant to CHIKV infection, WT mouse neonates are susceptible and neonatal disease severity is age-dependent. Adult mice with a partially (IFN-α/βR+/−) or totally (IFN-α/βR−/−) abrogated type-I IFN pathway develop a mild or severe infection, respectively. In mice with a mild infection, after a burst of viral replication in the liver, CHIKV primarily targets muscle, joint, and skin fibroblasts, a cell and tissue tropism similar to that observed in biopsy samples of CHIKV-infected humans. In case of severe infections, CHIKV also disseminates to other tissues including the CNS, where it specifically targets the choroid plexuses and the leptomeninges. Together, these data indicate that CHIKV-associated symptoms match viral tissue and cell tropisms, and demonstrate that the fibroblast is a predominant target cell of CHIKV. These data also identify the neonatal phase and inefficient type-I IFN signaling as risk factors for severe CHIKV-associated disease. The development of a permissive small animal model will expedite the testing of future vaccines and therapeutic candidates

Quantitative and Dynamic Assessment of the Contribution of the ER to Phagosome Formation

SummaryPhagosomes were traditionally thought to originate from an invagination and scission of the plasma membrane to form a distinct intracellular vacuole. An alternative model implicating the endoplasmic reticulum (ER) as a major component of nascent and maturing phagosomes was recently proposed (Gagnon et al., 2002). To reconcile these seemingly disparate hypotheses, we used a combination of biochemical, fluorescence imaging, and electron microscopy techniques to quantitatively and dynamically assess the contribution of the plasmalemma and of the ER to phagosome formation and maturation. We could not verify even a transient physical continuity between the ER and the plasma membrane, nor were we able to detect a significant contribution of the ER to forming or maturing phagosomes in either macrophages or dendritic cells. Instead, our data indicate that the plasma membrane is the main constituent of nascent and newly formed phagosomes, which are progressively remodeled by fusion with endosomal and eventually lysosomal compartments as phagosomes mature into acidic, degradative organelles

Oral dosing of rodents using a palatable tablet

Rationale: Delivering orally bioavailable drugs to rodents is an important component to investigating that route of administration in novel treatments for humans. However, the traditional method of oral gavage requires training, is stressful, and can induce oesophageal damage in rodents. Objectives: To demonstrate a novel administrative technique – palatable gelatine tablets – as a stress-free route of oral delivery. Methods: 24 male Lister hooded rats were sacrificed for brain tissue analysis at varying time-points after jelly administration of 30 mg/kg of the wake-promoting drug modafinil. A second group of 22 female rats were tested on locomotor activity after 30 mg/kg modafinil, or after vehicle jellies, with the locomotor data compared to the brain tissue concentrations at the corresponding times. Results: Modafinil was present in the brain tissue at all time-points, reducing in concentration over time. The pattern of brain tissue modafinil concentration is comparable to previously reported results following oral gavage. Modafinil-treated rats were more active than control rats, with greater activity during the later time-periods – similar to that previously reported following intraperitoneal injection of 40 mg/kg modafinil. Conclusions: Palatable jelly tablets are an effective route of administration of thermally-stable orally-bioavailable compounds, eliminating the stress/discomfort and health risk of oral gavage and presenting as an alternative to previously reported palatable routes of administration where high protein and fat levels may adversely affect appetite for food reward, and uptake rate in the gastrointestinal tract.Publisher PDFPeer reviewe

Cerebrospinal Fluid Dendritic Cells Infiltrate the Brain Parenchyma and Target the Cervical Lymph Nodes under Neuroinflammatory Conditions

BACKGROUND: In many neuroinflammatory diseases, dendritic cells (DCs) accumulate in several compartments of the central nervous system (CNS), including the cerebrospinal fluid (CSF). Myeloid DCs invading the inflamed CNS are thus thought to play a major role in the initiation and perpetuation of CNS-targeted autoimmune responses. We previously reported that, in normal rats, DCs injected intra-CSF migrated outside the CNS and reached the B-cell zone of cervical lymph nodes. However, there is yet no information on the migratory behavior of CSF-circulating DCs under neuroinflammatory conditions. METHODOLOGY/PRINCIPAL FINDINGS: To address this issue, we performed in vivo transfer experiments in rats suffering from experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. EAE or control rats were injected intra-CSF with bone marrow-derived myeloid DCs labeled with the fluorescent marker carboxyfluorescein diacetate succinimidyl ester (CFSE). In parallel experiments, fluorescent microspheres were injected intra-CSF to EAE rats in order to track endogenous antigen-presenting cells (APCs). Animals were then sacrificed on day 1 or 8 post-injection and their brain and peripheral lymph nodes were assessed for the presence of microspheres(+) APCs or CFSE(+) DCs by immunohistology and/or FACS analysis. Data showed that in EAE rats, DCs injected intra-CSF substantially infiltrated several compartments of the inflamed CNS, including the periventricular demyelinating lesions. We also found that in EAE rats, as compared to controls, a larger number of intra-CSF injected DCs reached the cervical lymph nodes. This migratory behavior was accompanied by an accentuation of EAE clinical signs and an increased systemic antibody response against myelin oligodendrocyte glycoprotein, a major immunogenic myelin antigen. CONCLUSIONS/SIGNIFICANCE: Altogether, these results indicate that CSF-circulating DCs are able to both survey the inflamed brain and to reach the cervical lymph nodes. In EAE and maybe multiple sclerosis, CSF-circulating DCs may thus support the immune responses that develop within and outside the inflamed CNS

Prioritisation of Anti-SARS-Cov-2 Drug Repurposing Opportunities Based on Plasma and Target Site Concentrations Derived from their Established Human Pharmacokinetics.

There is a rapidly expanding literature on the in vitro antiviral activity of drugs that may be repurposed for therapy or chemoprophylaxis against SARS-CoV-2. However, this has not been accompanied by a comprehensive evaluation of the target plasma and lung concentrations of these drugs following approved dosing in humans. Accordingly, EC90 values recalculated from in vitro anti-SARS-CoV-2 activity data was expressed as a ratio to the achievable maximum plasma concentrations (Cmax) at an approved dose in humans (Cmax/EC90 ratio). Only 14 of the 56 analysed drugs achieved a Cmax/EC90 ratio above 1. A more in-depth assessment demonstrated that only nitazoxanide, nelfinavir, tipranavir (ritonavir-boosted) and sulfadoxine achieved plasma concentrations above their reported anti-SARS-CoV-2 activity across their entire approved dosing interval. An unbound lung to plasma tissue partition coefficient (Kp Ulung ) was also simulated to derive a lung Cmax/EC50 as a better indicator of potential human efficacy. Hydroxychloroquine, chloroquine, mefloquine, atazanavir (ritonavir-boosted), tipranavir (ritonavir-boosted), ivermectin, azithromycin and lopinavir (ritonavir-boosted) were all predicted to achieve lung concentrations over 10-fold higher than their reported EC50 . Nitazoxanide and sulfadoxine also exceeded their reported EC50 by 7.8- and 1.5-fold in lung, respectively. This analysis may be used to select potential candidates for further clinical testing, while deprioritising compounds unlikely to attain target concentrations for antiviral activity. Future studies should focus on EC90 values and discuss findings in the context of achievable exposures in humans, especially within target compartments such as the lung, in order to maximise the potential for success of proposed human clinical trials