Composition and evolution of the continental crust: Retrospect and prospect

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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

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

Amiloride inhibits macropinocytosis by lowering submembranous pH and preventing Rac1 and Cdc42 signaling

Inhibitors of Na+/H+ exchange proteins block macropinocytosis by lowering the pH near the plasma membrane, which in turn inhibits actin remodeling by Rho family GTPases

Galectin-1-Binding Glycoforms of Haptoglobin with Altered Intracellular Trafficking, and Increase in Metastatic Breast Cancer Patients

Sera from 25 metastatic breast cancer patients and 25 healthy controls were subjected to affinity chromatography using immobilized galectin-1. Serum from the healthy subjects contained on average 1.2 mg per ml (range 0.7–2.2) galectin-1 binding glycoproteins, whereas serum from the breast cancer patients contained on average 2.2 mg/ml (range 0.8–3.9), with a higher average for large primary tumours. The major bound glycoproteins were α-2-macroglobulin, IgM and haptoglobin. Both the IgM and haptoglobin concentrations were similar in cancer compared to control sera, but the percentage bound to galectin-1 was lower for IgM and higher for haptoglobin: about 50% (range 20–80) in cancer sera and about 30% (range 25–50) in healthy sera. Galectin-1 binding and non-binding fractions were separated by affinity chromatography from pooled haptoglobin from healthy sera. The N-glycans of each fraction were analyzed by mass spectrometry, and the structural differences and galectin-1 mutants were used to identify possible galectin-1 binding sites. Galectin-1 binding and non-binding fractions were also analyzed regarding their haptoglobin function. Both were similar in forming complex with haemoglobin and mediate its uptake into alternatively activated macrophages. However, after uptake there was a dramatic difference in intracellular targeting, with the galectin-1 non-binding fraction going to a LAMP-2 positive compartment (lysosomes), while the galectin-1 binding fraction went to larger galectin-1 positive granules. In conclusion, galectin-1 detects a new type of functional biomarker for cancer: a specific type of glycoform of haptoglobin, and possibly other serum glycoproteins, with a different function after uptake into tissue cells

Recycling of the Membrane-anchored Chemokine, CX 3 CL1

CX(3)CL1 (fractalkine) plays an important role in inflammation by acting as both chemoattractant and as an adhesion molecule. As for other chemokines, expression of CX(3)CL1 is known to be regulated at the level of transcription and translation. The unique transmembrane structure of CX(3)CL1 raises the possibility of additional functional regulation by altering its abundance at the cell surface. This could be accomplished in principle by changes in traffic between subcellular compartments. To analyze this possibility we examined the subcellular distribution of CX(3)CL1 in human ECV-304 cells stably expressing untagged or green fluorescent protein-tagged forms of the chemokine. CX(3)CL1 was present in two distinct compartments, diffusely on the plasma membrane and in a punctate juxtanuclear compartment. The latter shared some features with, yet was distinct from the conventional endocytic pathway and may represent a specialized recycling subcompartment. Accordingly, surface CX(3)CL1 was found to be in dynamic equilibrium with the juxtanuclear vesicular compartment. Intracellular CX(3)CL1 co-localized with the SNARE (soluble N-ethylmaleimide factor attachment protein receptor) proteins syntaxin-13 and VAMP-3. Cleavage of VAMP-3 by tetanus toxin or impairment of syntaxin-13 function by expression of a dominant-negative allele inhibited the ability of internalized CX(3)CL1 to traffic back to the plasma membrane. These data demonstrate the existence of a dynamic, SNARE-mediated recycling of CX(3)CL1 from the cell surface to and from an endomembrane storage compartment. The intracellular storage depot may serve as a source of the chemokine that could be rapidly mobilized by stimuli

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

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

MHC Class I Endosomal and Lysosomal Trafficking Coincides with Exogenous Antigen Loading in Dendritic Cells

BACKGROUND: Cross-presentation by dendritic cells (DCs) is a crucial prerequisite for effective priming of cytotoxic T-cell responses against bacterial, viral and tumor antigens; however, this antigen presentation pathway remains poorly defined. METHODOLOGY/PRINCIPAL FINDINGS: In order to develop a comprehensive understanding of this process, we tested the hypothesis that the internalization of MHC class I molecules (MHC-I) from the cell surface is directly involved in cross-presentation pathway and the loading of antigenic peptides. Here we provide the first examination of the internalization of MHC-I in DCs and we demonstrate that the cytoplasmic domain of MHC-I appears to act as an addressin domain to route MHC-I to both endosomal and lysosomal compartments of DCs, where it is demonstrated that loading of peptides derived from exogenously-derived proteins occurs. Furthermore, by chasing MHC-I from the cell surface of normal and transgenic DCs expressing mutant forms of MHC-I, we observe that a tyrosine-based endocytic trafficking motif is required for the constitutive internalization of MHC-I molecules from the cell surface into early endosomes and subsequently deep into lysosomal peptide-loading compartments. Finally, our data support the concept that multiple pathways of peptide loading of cross-presented antigens may exist depending on the chemical nature and size of the antigen requiring processing. CONCLUSIONS/SIGNIFICANCE: We conclude that DCs have 'hijacked' and adapted a common vacuolar/endocytic intracellular trafficking pathway to facilitate MHC I access to the endosomal and lysosomal compartments where antigen processing and loading and antigen cross-presentation takes place