C–O–H–S fluids and granitic magma : how S partitions and modifies CO2 concentrations of fluid-saturated felsic melt at 200 MPa

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Contributions to Mineralogy and Petrology 162 (2011): 849-865, doi:10.1007/s00410-011-0628-1.Hydrothermal volatile-solubility and partitioning experiments were conducted with fluid-saturated haplogranitic melt, H2O, CO2, and S in an internally heated pressure vessel at 900°C and 200 MPa; three additional experiments were conducted with iron-bearing melt. The run-product glasses were analyzed by electron microprobe, FTIR, and SIMS; and they contain ≤ 0.12 wt% S, ≤ 0.097 wt.% CO2, and ≤ 6.4 wt.% H2O. Apparent values of log ƒO2 for the experiments at run conditions were computed from the [(S6+)/(S6++S2-)] ratio of the glasses, and they range from NNO-0.4 to NNO+1.4. The C-O-H-S fluid compositions at run conditions were computed by mass balance, and they contained 22-99 mol% H2O, 0-78 mol% CO2, 0-12 mol% S, and < 3 wt% alkalis. Eight S-free experiments were conducted to determine the H2O and CO2 concentrations of melt and fluid compositions and to compare them with prior experimental results for C-O-H fluid-saturated rhyolite melt, and the agreement is excellent. Sulfur partitions very strongly in favor of fluid in all experiments, and the presence of S modifies the fluid compositions, and hence, the CO2 solubilities in coexisting felsic melt. The square of the mole fraction of H2O in melt increases in a linear fashion, from 0.05-0.25, with the H2O concentration of the fluid. The mole fraction of CO2 in melt increases linearly, from 0.0003-0.0045, with the CO2 concentration of C-O-H-S fluids. Interestingly, the CO2 concentration in melts, involving relatively reduced runs (log ƒO2 ≤ NNO+0.3) that contain 2.5-7 mol% S in the fluid, decreases significantly with increasing S in the system. This response to the changing fluid composition causes the H2O and CO2 solubility curve for C-O-H-S fluid-saturated haplogranitic melts at 200 MPa to shift to values near that modeled for C-O-H fluid-saturated, S-free rhyolite melt at 150 MPa. The concentration of S in haplogranitic melt increases in a linear fashion with increasing S in C-O-H-S fluids, but these data show significant dispersion that likely reflects the strong influence of ƒO2 on S speciation in melt and fluid. Importantly, the partitioning of S between fluid and melt does not vary with the (H2O/H2O+CO2) ratio of the fluid. The fluid-melt partition coefficients for H2O, CO2, and S and the atomic (C/S) ratios of the run-product fluids are virtually identical to thermodynamic constraints on volatile partitioning and the H, S, and C contents of pre-eruptive magmatic fluids and volcanic gases for subduction-related magmatic systems thus confirming our experiments are relevant to natural eruptive systems.This research was supported in part by National Science Foundation awards EAR 0308866 and EAR-0836741 to J.D.W

Somatic PIK3R1 Variation as a Cause of Vascular Malformations and Overgrowth

PurposeSomatic activating variants in the PI3K-AKT pathway cause vascular malformations with and without overgrowth. We previously reported an individual with capillary and lymphatic malformation harboring a pathogenic somatic variant in PIK3R1, which encodes three PI3K complex regulatory subunits. Here, we investigate PIK3R1 in a large cohort with vascular anomalies and identify an additional 16 individuals with somatic mosaic variants in PIK3R1.MethodsAffected tissue from individuals with vascular lesions and overgrowth recruited from a multisite collaborative network was studied. Next-generation sequencing targeting coding regions of cell-signaling and cancer-associated genes was performed followed by assessment of variant pathogenicity.ResultsThe phenotypic and variant spectrum associated with somatic variation in PIK3R1 is reported herein. Variants occurred in the inter-SH2 or N-terminal SH2 domains of all three PIK3R1 protein products. Phenotypic features overlapped those of the PIK3CA-related overgrowth spectrum (PROS). These overlapping features included mixed vascular malformations, sandal toe gap deformity with macrodactyly, lymphatic malformations, venous ectasias, and overgrowth of soft tissue or bone.ConclusionSomatic PIK3R1 variants sharing attributes with cancer-associated variants cause complex vascular malformations and overgrowth. The PIK3R1-associated phenotypic spectrum overlaps with PROS. These data extend understanding of the diverse phenotypic spectrum attributable to genetic variation in the PI3K-AKT pathway

Relief of Preintegration Inhibition and Characterization of Additional Blocks for HIV Replication in Primary Mouse T Cells

Development of a small animal model to study HIV replication and pathogenesis has been hampered by the failure of the virus to replicate in non-primate cells. Most studies aimed at achieving replication in murine cells have been limited to fibroblast cell lines, but generating an appropriate model requires overcoming blocks to viral replication in primary T cells. We have studied HIV-1 replication in CD4+ T cells from human CD4/ CCR5/Cyclin T1 transgenic mice. Expression of hCD4 and hCCR5 in mouse CD4+ T cells enabled efficient entry of R5 strain HIV-1. In mouse T cells, HIV-1 underwent reverse transcription and nuclear import as efficiently as in human T cells. In contrast, chromosomal integration of HIV-1 proviral DNA was inefficient in activated mouse T cells. This process was greatly enhanced by providing a secondary T cell receptor (TCR) signal after HIV-1 infection, especially between 12 to 24 h post infection. This effect was specific for primary mouse T cells. The pathways involved in HIV replication appear to be PKCθ−, CARMA1-, and WASp-independent. Treatment with Cyclosporin A (CsA) further relieved the pre-integration block. However, transcription of HIV-1 RNA was still reduced in mouse CD4+ T cells despite expression of the hCyclin T1 transgene. Additional post-transcriptional defects were observed at the levels of Gag expression, Gag processing, Gag release and virus infectivity. Together, these post-integration defects resulted in a dramatically reduced yield of infectious virus (300–500 fold) after a single cycle of HIV-1 replication. This study implies the existence of host factors, in addition to those already identified, that are critical for HIV-1 replication in mouse cells. This study also highlights the differences between primary T cells and cell lines regarding pre-integration steps in the HIV-1 replication cycle

Phosphofructo-1-Kinase Deficiency Leads to a Severe Cardiac and Hematological Disorder in Addition to Skeletal Muscle Glycogenosis

Mutations in the gene for muscle phosphofructo-1-kinase (PFKM), a key regulatory enzyme of glycolysis, cause Type VII glycogen storage disease (GSDVII). Clinical manifestations of the disease span from the severe infantile form, leading to death during childhood, to the classical form, which presents mainly with exercise intolerance. PFKM deficiency is considered as a skeletal muscle glycogenosis, but the relative contribution of altered glucose metabolism in other tissues to the pathogenesis of the disease is not fully understood. To elucidate this issue, we have generated mice deficient for PFKM (Pfkm−/−). Here, we show that Pfkm−/− mice had high lethality around weaning and reduced lifespan, because of the metabolic alterations. In skeletal muscle, including respiratory muscles, the lack of PFK activity blocked glycolysis and resulted in considerable glycogen storage and low ATP content. Although erythrocytes of Pfkm−/− mice preserved 50% of PFK activity, they showed strong reduction of 2,3-biphosphoglycerate concentrations and hemolysis, which was associated with compensatory reticulocytosis and splenomegaly. As a consequence of these haematological alterations, and of reduced PFK activity in the heart, Pfkm−/− mice developed cardiac hypertrophy with age. Taken together, these alterations resulted in muscle hypoxia and hypervascularization, impaired oxidative metabolism, fiber necrosis, and exercise intolerance. These results indicate that, in GSDVII, marked alterations in muscle bioenergetics and erythrocyte metabolism interact to produce a complex systemic disorder. Therefore, GSDVII is not simply a muscle glycogenosis, and Pfkm−/− mice constitute a unique model of GSDVII which may be useful for the design and assessment of new therapies

ALIX Regulates Tumor-Mediated Immunosuppression by Controlling EGFR Activity and PD-L1 Presentation

This work was supported by Cancer Research UK (grants C1519/A6906 and C5255/A15935); by the King’s College London-UCL Comprehensive Cancer Imaging Centre (CRUK and EPSRC, grants C1519/A10331 and C1519/A16463), in association with the MRC and DoH (grant C1519/A10331); by the EU FP7 grants IMAGINT (EC grant: 259881); and by KCL Breast Cancer Now Unit funding (for F.F.-B.; grant KCL-Q2-Y5). J.G.C. is a Wellcome Trust Senior Research fellow (206346/Z/17/Z). The purchase of the siRNA library was possible thanks to a generous gift from Ms. Marianne B. Blake, who raised funds during the 2010 London Marathon through Dimbleby Cancer Care

Prevalence of pfmdr1, pfcrt, pfdhfr and pfdhps mutations associated with drug resistance, in Luanda, Angola

<p>Abstract</p> <p>Background</p> <p>Malaria is the infectious disease causing the highest morbidity and mortality in Angola and due to widespread chloroquine (CQ) resistance, the country has recently changed its first-line treatment recommendations for uncomplicated malaria, from CQ to artemisinin combination therapies (ACT) in adults, and sulphadoxine/pyrimethamine (S/P) in pregnant women. Loss of SP sensitivity is, however, progressing rapidly in Africa and, in this study, were investigated a number of molecular markers associated to CQ and S/P.</p> <p>Methods</p> <p>Blood samples were collected from 245 children with uncomplicated malaria, admitted at the Pediatric Hospital Dr. David Bernardino (HPDB), Angola, and the occurrence of mutations in <it>Plasmodium falciparum </it>was investigated in the <it>pfmdr1 </it>(N86Y) and <it>pfcrt </it>(K76T) genes, associated with CQ resistance, as well as in <it>pfdhfr </it>(C59R) and <it>pfdhps </it>(K540E), conferring SP resistance.</p> <p>Results</p> <p>The frequencies of <it>pfmdr1 </it>mutations in codon 86 were 28.6% N, 61.3% Y and 10.1% mixed infections (NY). The frequency of <it>pfcrt </it>mutations in codon 76 were 93.9% K, 5.7% T and 0.4% mixed infections (KT). For <it>pfdhfr </it>the results were in codon 59, 60.6% C, 20.6% R and 18.8% mixed infections (CR). Concerning <it>pfdhps</it>, 6.3% of the isolates were bearers of the mutation 540E and 5.4% mixed infections (K540E).</p> <p>Conclusion</p> <p>The results of this epidemiologic study showed high presence of CQ resistance markers while for SP a much lower prevalence was detected for the markers under study.</p

Quantifying the effectiveness of climate change mitigation through forest plantations and carbon sequestration with an integrated land-use model

<p>Abstract</p> <p>Background</p> <p>Carbon plantations are introduced in climate change policy as an option to slow the build-up of atmospheric carbon dioxide (CO₂) concentrations. Here we present a methodology to evaluate the potential effectiveness of carbon plantations. The methodology explicitly considers future long-term land-use change around the world and all relevant carbon (C) fluxes, including all natural fluxes. Both issues have generally been ignored in earlier studies.</p> <p>Results</p> <p>Two different baseline scenarios up to 2100 indicate that uncertainties in future land-use change lead to a near 100% difference in estimates of carbon sequestration potentials. Moreover, social, economic and institutional barriers preventing carbon plantations in natural vegetation areas decrease the physical potential by 75–80% or more.</p> <p>Nevertheless, carbon plantations can still considerably contribute to slowing the increase in the atmospheric CO₂concentration but only in the long term. The most conservative set of assumptions lowers the increase of the atmospheric CO₂concentration in 2100 by a 27 ppm and compensates for 5–7% of the total energy-related CO₂emissions. The net sequestration up to 2020 is limited, given the short-term increased need for agricultural land in most regions and the long period needed to compensate for emissions through the establishment of the plantations. The potential is highest in the tropics, despite projections that most of the agricultural expansion will be in these regions. Plantations in high latitudes as Northern Europe and Northern Russia should only be established if the objective to sequester carbon is combined with other activities.</p> <p>Conclusion</p> <p>Carbon sequestration in plantations can play an important role in mitigating the build-up of atmospheric CO₂. The actual magnitude depends on natural and management factors, social barriers, and the time frame considered. In addition, there are a number of ancillary benefits for local communities and the environment. Carbon plantations are, however, particularly effective in the long term. Furthermore, plantations do not offer the ultimate solution towards stabilizing CO₂concentrations but should be part of a broader package of options with clear energy emission reduction measures.</p

Quantitative Microscopy Reveals Centromeric Chromatin Stability, Size, and Cell Cycle Mechanisms to Maintain Centromere Homeostasis

The deposited item is a book chapter and is part of the series "Centromeres and Kinetochores" published by the publisher Springer Verlag. The deposited book chapter is a post-print version and has been submitted to peer reviewing. There is no public supplementary material available for this publication. This publication hasn't any creative commons license associated.Centromeres are chromatin domains specified by nucleosomes containing the histone H3 variant, CENP-A. This unique centromeric structure is at the heart of a strong self-templating epigenetic mechanism that renders centromeres heritable. We review how specific quantitative microscopy approaches have contributed to the determination of the copy number, architecture, size, and dynamics of centromeric chromatin and its associated centromere complex and kinetochore. These efforts revealed that the key to long-term centromere maintenance is the slow turnover of CENP-A nucleosomes, a critical size of the chromatin domain and its cell cycle-coupled replication. These features come together to maintain homeostasis of a chromatin locus that directs its own epigenetic inheritance and facilitates the assembly of the mitotic kinetochore.There are no funders and sponsors indicated explicitly in the document.info:eu-repo/semantics/publishedVersio