Lava flow morphology at an erupting andesitic stratovolcano: a satellite perspective on El Reventador, Ecuador

Lava flows pose a significant hazard to infrastructure and property located close to volcanoes, and understanding how flows advance is necessary to manage volcanic hazard during eruptions. Compared to low-silica basaltic flows, flows of andesite composition are infrequently erupted and so relatively few studies of their characteristics and behaviour exist. We use El Reventador, Ecuador as a target to investigate andesitic lava flow properties during a 4.5 year period of extrusive eruption between February 2012 and August 2016. We use satellite radar to map the dimensions of 43 lava flows and look at variations in their emplacement behaviour over time. We find that flows descend the north and south flanks of El Reventador, and were mostly emplaced during durations shorter than the satellite repeat interval of 24 days.Flows ranged in length from 0.3 to 1.7 km, and the length of these flows decreased over the observation period. We measure a decrease in flow volume with time that is correlated with a long-term exponential decrease in eruption rate, and propose that this behaviour is caused by temporary magma storage in the conduit acting as a melt capacitor between the magma reservoir and the surface. We use the dimensions of the flow levees and widths to estimate the flow yield strengths, which were of the order of 10-100 kPa. We observe that some flows were diverted by topographic obstacles, and compare measurements of decreased channel width and increased flow thickness at the obstacles with observations from laboratory experiments. Radar observations, such as those presented here, could be used to map and measure properties of evolving lava flow fields at other remote or difficult to monitor volcanoes

Ca2+ and synaptotagmin VII–dependent delivery of lysosomal membrane to nascent phagosomes

Synaptotagmin (Syt) VII is a ubiquitously expressed member of the Syt family of Ca2+ sensors. It is present on lysosomes in several cell types, where it regulates Ca2+-dependent exocytosis. Because [Ca2+]i and exocytosis have been associated with phagocytosis, we investigated the phagocytic ability of macrophages from Syt VII−/− mice. Syt VII−/− macrophages phagocytose normally at low particle/cell ratios but show a progressive inhibition in particle uptake under high load conditions. Complementation with Syt VII rescues this phenotype, but only when functional Ca2+-binding sites are retained. Reinforcing a role for Syt VII in Ca2+-dependent phagocytosis, particle uptake in Syt VII−/− macrophages is significantly less dependent on [Ca2+]i. Syt VII is concentrated on peripheral domains of lysosomal compartments, from where it is recruited to nascent phagosomes. Syt VII recruitment is rapidly followed by the delivery of Lamp1 to phagosomes, a process that is inhibited in Syt VII−/− macrophages. Thus, Syt VII regulates the Ca2+-dependent mobilization of lysosomes as a supplemental source of membrane during phagocytosis

Using satellite radar amplitude imaging for monitoring syn-eruptive changes in surface morphology at an ice-capped stratovolcano

Satellite-based measurements of synthetic aperture radar amplitude provide a method for monitoring volcanoes during unrest and eruptions even when visual observations are not possible, for example due to poor weather or at night, and when radar phase measurements are noisy or decorrelated. Here, we use high resolution radar amplitude images from the TerraSAR-X and COSMO SkyMed satellites to investigate surface changes associated with explosive eruptions of Cotopaxi volcano, Ecuador in August 2015. We generate change difference and amplitude ratio maps spanning the start of explosive activity at Cotopaxi, which show complex spatial variations in radar amplitude both on and around the summit ice-cap that we attribute to a number of processes related to the eruption. Observed amplitude decreases are caused by crater deepening, ashfall onto ice and surface smoothing by ashfall onto slopes facing away from the satellite, while amplitude increases are due to deposition of coarse lapilli and wet tephra, increased soil saturation due to geothermally driven glacier melting, and smoothing of slopes facing towards the satellite. We discuss the potential applications of radar amplitude images for monitoring and hazard evaluation at active volcanoes

A protective role for the Lectin CD169/Siglec-1 against a pathogenic murine retrovirus

Lymph- and blood-borne retroviruses exploit CD169/Siglec-1-mediated capture by subcapsular sinus and marginal zone metallophilic macrophages for trans-infection of permissive lymphocytes. However, the impact of CD169-mediated virus capture on retrovirus dissemination and pathogenesis in vivo is unknown. In a murine model of the splenomegaly-inducing retrovirus Friend virus complex (FVC) infection, we find that while CD169 promoted draining lymph node infection, it limited systemic spread to the spleen. At the spleen, CD169-expressing macrophages captured incoming blood-borne retroviruses and limited their spread to the erythroblasts in the red pulp where FVC manifests its pathogenesis. CD169-mediated retroviral capture activated conventional dendritic cells 1 (cDC1s) and promoted cytotoxic CD8+ T cell responses, resulting in efficient clearing of FVC-infected cells. Accordingly, CD169 blockade led to higher viral loads and accelerated death in susceptible mouse strains. Thus, CD169 plays a protective role during FVC pathogenesis by reducing viral dissemination to erythroblasts and eliciting an effective cytotoxic T lymphocyte response via cDC1s

Semen-Derived Amyloid Fibrils Drastically Enhance HIV Infection

SummarySexual intercourse is the major route of HIV transmission. To identify endogenous factors that affect the efficiency of sexual viral transmission, we screened a complex peptide/protein library derived from human semen. We show that naturally occurring fragments of the abundant semen marker prostatic acidic phosphatase (PAP) form amyloid fibrils. These fibrils, termed Semen-derived Enhancer of Virus Infection (SEVI), capture HIV virions and promote their attachment to target cells, thereby enhancing the infectious virus titer by several orders of magnitude. Physiological concentrations of SEVI amplified HIV infection of T cells, macrophages, ex vivo human tonsillar tissues, and transgenic rats in vivo, as well as trans-HIV infection of T cells by dendritic or epithelial cells. Amyloidogenic PAP fragments are abundant in seminal fluid and boost semen-mediated enhancement of HIV infection. Thus, they may play an important role in sexual transmission of HIV and could represent new targets for its prevention

Understanding cyclic seismicity and ground deformation patterns at volcanoes: intriguing lessons from Tungurahua volcano, Ecuador

Cyclic seismicity and ground deformation patterns are observed on many volcanoes worldwide where seismic swarms and the tilt of the volcanic flanks provide sensitive tools to assess the state of volcanic activity. Ground deformation at active volcanoes is often interpreted as pressure changes in a magmatic reservoir, and tilt is simply translated accordingly into inflation and deflation of such a reservoir. Tilt data recorded by an instrument in the summit area of Tungurahua volcano in Ecuador, however, show an intriguing and unexpected behaviour on several occasions: prior to a Vulcanian explosion when a pressurisation of the system would be expected, the tilt signal declines significantly, hence indicating depressurisation. At the same time, seismicity increases drastically. Envisaging that such a pattern could carry the potential to forecast Vulcanian explosions on Tungurahua, we use numerical modelling and reproduce the observed tilt patterns in both space and time. We demonstrate that the tilt signal can be more easily explained as caused by shear stress due to viscous flow resistance, rather than by pressurization of the magmatic plumbing system. In general, our numerical models prove that if magma shear viscosity and ascent rate are high enough, the resulting shear stress is sufficient to generate a tilt signal as observed on Tungurahua. Furthermore, we address the interdependence of tilt and seismicity through shear stress partitioning and suggest that a joint interpretation of tilt and seismicity can shed new light on the eruption potential of silicic volcanoes

Murine Leukemia Virus Spreading in Mice Impaired in the Biogenesis of Secretory Lysosomes and Ca2+-Regulated Exocytosis

Retroviruses have been observed to bud intracellularly into multivesicular bodies (MVB), in addition to the plasma membrane. Release from MVB is thought to occur by Ca(2+)-regulated fusion with the plasma membrane.To address the role of the MVB pathway in replication of the murine leukemia virus (MLV) we took advantage of mouse models for the Hermansky-Pudlak syndrome (HPS) and Griscelli syndrome. In humans, these disorders are characterized by hypopigmentation and immunological alterations that are caused by defects in the biogenesis and trafficking of MVBs and other lysosome related organelles. Neonatal mice for these disease models lacking functional AP-3, Rab27A and BLOC factors were infected with Moloney MLV and the spread of virus into bone marrow, spleen and thymus was monitored. We found a moderate reduction in MLV infection levels in most mutant mice, which differed by less than two-fold compared to wild-type mice. In vitro, MLV release form bone-marrow derived macrophages was slightly enhanced. Finally, we found no evidence for a Ca(2+)-regulated release pathway in vitro. Furthermore, MLV replication was only moderately affected in mice lacking Synaptotagmin VII, a Ca(2+)-sensor regulating lysosome fusion with the plasma membrane.Given that MLV spreading in mice depends on multiple rounds of replication even moderate reduction of virus release at the cellular level would accumulate and lead to a significant effect over time. Thus our in vivo and in vitro data collectively argue against an essential role for a MVB- and secretory lysosome-mediated pathway in the egress of MLV

The receptors for gibbon ape leukemia virus and amphotropic murine leukemia virus are not downregulated in productively infected cells

<p>Abstract</p> <p>Background</p> <p>Over the last several decades it has been noted, using a variety of different methods, that cells infected by a specific gammaretrovirus are resistant to infection by other retroviruses that employ the same receptor; a phenomenon termed receptor interference. Receptor masking is thought to provide an earlier means of blocking superinfection, whereas receptor down regulation is generally considered to occur in chronically infected cells.</p> <p>Results</p> <p>We used replication-competent GFP-expressing viruses containing either an amphotropic murine leukemia virus (A-MLV) or the gibbon ape leukemia virus (GALV) envelope. We also constructed similar viruses containing fluorescence-labeled Gag proteins for the detection of viral particles. Using this repertoire of reagents together with a wide range of antibodies, we were able to determine the presence and availability of viral receptors, and detect viral envelope proteins and particles presence on the cell surface of chronically infected cells.</p> <p>Conclusions</p> <p>A-MLV or GALV receptors remain on the surface of chronically infected cells and are detectable by respective antibodies, indicating that these receptors are not downregulated in these infected cells as previously proposed. We were also able to detect viral envelope proteins on the infected cell surface and infected cells are unable to bind soluble A-MLV or GALV envelopes indicating that receptor binding sites are masked by endogenously expressed A-MLV or GALV viral envelope. However, receptor masking does not completely prevent A-MLV or GALV superinfection.</p

Investigation of the key chemical structures involved in the anticancer activity of disulfiram in A549 non-small cell lung cancer cell line

© 2018 The Author(s). Background: Disulfiram (DS), an antialcoholism medicine, demonstrated strong anticancer activity in the laboratory but did not show promising results in clinical trials. The anticancer activity of DS is copper dependent. The reaction of DS and copper generates reactive oxygen species (ROS). After oral administration in the clinic, DS is enriched and quickly metabolised in the liver. The associated change of chemical structure may make the metabolites of DS lose its copper-chelating ability and disable their anticancer activity. The anticancer chemical structure of DS is still largely unknown. Elucidation of the relationship between the key chemical structure of DS and its anticancer activity will enable us to modify DS and speed its translation into cancer therapeutics. Methods: The cytotoxicity, extracellular ROS activity, apoptotic effect of DS, DDC and their analogues on cancer cells and cancer stem cells were examined in vitro by MTT assay, western blot, extracellular ROS assay and sphere-reforming assay. Results: Intact thiol groups are essential for the in vitro cytotoxicity of DS. S-methylated diethyldithiocarbamate (S-Me-DDC), one of the major metabolites of DS in liver, completely lost its in vitro anticancer activity. In vitro cytotoxicity of DS was also abolished when its thiuram structure was destroyed. In contrast, modification of the ethyl groups in DS had no significant influence on its anticancer activity. Conclusions: The thiol groups and thiuram structure are indispensable for the anticancer activity of DS. The liver enrichment and metabolism may be the major obstruction for application of DS in cancer treatment. A delivery system to protect the thiol groups and development of novel soluble copper-DDC compound may pave the path for translation of DS into cancer therapeutics.This work was supported by grant from British Lung Foundation (RG14–8) and Innovate UK (104022).Published versio