117 research outputs found
Characterization of Dome Processes at Soufrière Hills Volcano, Montserrat: Synthesis of Infrared Remote Sensing Data with a Multi-parameter Database
The Advanced Spaceborne Thermal Emission Reflectance Radiometer (ASTER) is a high resolution multispectral imager ideal for discerning physical variations on the active Soufrière Hills volcanic dome. Five band thermal infrared data at 90 meter spatial resolution can produce accurate temperature and emissivity data. These data can potentially provide information of glass and vesicle distribution across the changing dome, and therefore on internal processes. One cloud-free image is captured every three months on average, with increased frequency in 2002, where the volcano was a high priority target. Six nighttime ASTER scenes of the dome have been chosen based on coverage of the entire dome, the presence of thermal infrared anomalies, and pyroclastic flow activity, as well as a relative lack of cloud cover over the active dome. Montserrat Volcano Observatory (MVO) weekly reports from 1999 to present (available online) were also ingested into a multi-parameter, searchable database. These data, which detail specific volcanic activity, were compared against the ASTER data. The database fields include SO2 flux, high temporal resolution weather satellite-derived radiance measurements, description of dome growth and collapse, and intensities of pyroclastic flows, rockfalls, fumarolic activity, and seismic activity. This database provides a unique cross-reference for the interpretation of the spaceborne data, as well as highlighting observable trends in each of the volcanic activity types. Results from this study will provide a better understanding of the capabilities of the ASTER instrument to accurately describe active dome processes and to characterize these and other processes statistically. This knowledge can be applied to other active areas to study potential indicators of volcanic activity, dome collapse, the generation of hazardous pyroclastic activity, as well as the transition from effusive dome growth to explosivity
A Nonpolar Blueberry Fraction Blunts NADPH Oxidase Activation in Neuronal Cells Exposed to Tumor Necrosis Factor-α
Inflammation and oxidative stress are key to the progressive neuronal degeneration common to chronic pathologies, traumatic injuries, and aging processes in the CNS. The proinflammatory cytokine tumor necrosis factor-alpha (TNF-α) orchestrates cellular stress by stimulating the production and release of neurotoxic mediators including reactive oxygen species (ROS). NADPH oxidases (NOX), ubiquitously expressed in all cells, have recently emerged as pivotal ROS sources in aging and disease. We demonstrated the presence of potent NOX inhibitors in wild Alaska bog blueberries partitioning discretely into a nonpolar fraction with minimal antioxidant capacity and largely devoid of polyphenols. Incubation of SH-SY5Y human neuroblastoma cells with nonpolar blueberry fractions obstructed the coalescing of lipid rafts into large domains disrupting NOX assembly therein and abolishing ROS production characteristic for TNF-α exposure. These findings illuminate nutrition-derived lipid raft modulation as a novel therapeutic approach to blunt inflammatory and oxidative stress in the aging or diseased CNS
Borrelia recurrentis employs a novel multifunctional surface protein with anti-complement, anti-opsonic and invasive potential to escape innate immunity
Borrelia recurrentis, the etiologic agent of louse-borne relapsing fever in humans, has evolved strategies, including antigenic variation, to evade immune defence, thereby causing severe diseases with high mortality rates. Here we identify for the first time a multifunctional surface lipoprotein of B. recurrentis, termed HcpA, and demonstrate that it binds human complement regulators, Factor H, CFHR-1, and simultaneously, the host protease plasminogen. Cell surface bound factor H was found to retain its activity and to confer resistance to complement attack. Moreover, ectopic expression of HcpA in a B. burgdorferi B313 strain, deficient in Factor H binding proteins, protected the transformed spirochetes from complement-mediated killing. Furthermore, HcpA-bound plasminogen/plasmin endows B. recurrentis with the potential to resist opsonization and to degrade extracellular matrix components. Together, the present study underscores the high virulence potential of B. recurrentis. The elucidation of the molecular basis underlying the versatile strategies of B. recurrentis to escape innate immunity and to persist in human tissues, including the brain, may help to understand the pathological processes underlying louse-borne relapsing fever
GlobTherm, a global database on thermal tolerances for aquatic and terrestrial organisms
CITATION: Bennett, J. M., et al. 2018. GlobTherm, a global database on thermal tolerances for aquatic and terrestrial organisms. Scientific Data, 5:180022, doi:10.1038/sdata.2018.22.The original publication is available at https://www.nature.comHow climate affects species distributions is a longstanding question receiving renewed interest owing to the need to predict the impacts of global warming on biodiversity. Is climate change forcing species to live near their critical thermal limits? Are these limits likely to change through natural selection? These and other important questions can be addressed with models relating geographical distributions of species with climate data, but inferences made with these models are highly contingent on non-climatic factors such as biotic interactions. Improved understanding of climate change effects on species will require extensive analysis of thermal physiological traits, but such data are both scarce and scattered. To overcome current limitations, we created the GlobTherm database. The database contains experimentally derived species’ thermal tolerance data currently comprising over 2,000 species of terrestrial, freshwater, intertidal and marine multicellular algae, plants, fungi, and animals. The GlobTherm database will be maintained and curated by iDiv with the aim to keep expanding it, and enable further investigations on the effects of climate on the distribution of life on Earth.https://www.nature.com/articles/sdata201822Publisher's versio
Targeted inhibition of interleukin-6 with CNTO 328 sensitizes pre-clinical models of multiple myeloma to dexamethasone-mediated cell death
Interleukin (IL)-6-mediated signaling attenuates the anti-myeloma activity of glucocorticoids (GCs). We therefore sought to evaluate whether CNTO 328, an anti-IL-6 monoclonal antibody in clinical development, could enhance the apoptotic activity of dexamethasone (dex) in pre-clinical models of myeloma. CNTO 328 potently increased the cytotoxicity of dex in IL-6-dependent and –independent human myeloma cell lines (HMCLs), including a bortezomib-resistant HMCL. Isobologram analysis revealed that the CNTO 328/dex combination was highly synergistic. Addition of bortezomib to CNTO 328/dex further enhanced the cytotoxicity of the combination. Experiments with pharmacologic inhibitors revealed a role for the p44/42 mitogen-activated protein kinase pathway in IL-6-mediated GC resistance. Although CNTO 328 alone induced minimal cell death, it potentiated dex-mediated apoptosis, as evidenced by increased activation of caspases-8, -9, and -3, Annexin-V staining, and DNA fragmentation. The ability of CNTO 328 to sensitize HMCLs to dex-mediated apoptosis was preserved in the presence of human bone marrow stromal cells. Importantly, the increased activity of the combination was also seen in plasma cells from patients with GC-resistant myeloma. Taken together, our data provide a strong rationale for the clinical development of the CNTO 328/dex regimen for patients with myeloma
Has Instagram Fundamentally Altered the 'Family Snapshot'?
This paper considers how parents use the social media platform Instagram to facilitate the capture, curation and sharing of ‘family snapshots’. Our work draws upon established cross-disciplinary literature relating to film photography and the composition of family albums in order to establish whether social media has changed the way parents visually present their families. We conducted a qualitative visual analysis of a sample of 4,000 photographs collected from Instagram using hashtags relating to children and parenting. We show that the style and composition of snapshots featuring children remains fundamentally unchanged and continues to be dominated by rather bland and idealised images of the happy family and the cute child. In addition, we find that the frequent taking and sharing of photographs via Instagram has inevitably resulted in a more mundane visual catalogue of daily life. We note a tension in the desire to use social media as a means to evidence good parenting, while trying to effectively manage the social identity of the child and finally, we note the reluctance of parents to use their own snapshots to portray family tension or disharmony, but their willingness to use externally generated content for this purpose
Blockade of interleukin-6 signalling with siltuximab enhances melphalan cytotoxicity in preclinical models of multiple myeloma
Signalling through the interleukin (IL)-6 pathway induces proliferation and drug resistance of multiple myeloma cells. We therefore sought to determine whether the IL-6-neutralizing monoclonal antibody siltuximab, formerly CNTO 328, could enhance the activity of melphalan, and to examine some of the mechanisms underlying this interaction. Siltuximab increased the cytotoxicity of melphalan in KAS-6/1, INA-6, ANBL-6, and RPMI 8226 human myeloma cell lines (HMCLs) in an additive-to-synergistic manner, and sensitized resistant RPMI 8226.LR5 cells to melphalan. These anti-proliferative effects were accompanied by enhanced activation of drug-specific apoptosis in HMCLs grown in suspension, and in HMCLs co-cultured with a human-derived stromal cell line. Siltuximab with melphalan enhanced activation of caspase-8, caspase-9, and the downstream effector caspase-3 compared with either of the single agents. This increased induction of cell death occurred in association with enhanced Bak activation. Neutralization of IL-6 also suppressed signalling through the phosphoinositide 3-kinase/Akt pathway, as evidenced by decreased phosphorylation of Akt, p70 S6 kinase and 4E-BP1. Importantly, the siltuximab/melphalan regimen demonstrated enhanced anti-proliferative effects against primary plasma cells derived from patients with myeloma, monoclonal gammopathy of undetermined significance, and amyloidosis. These studies provide a rationale for translation of siltuximab into the clinic in combination with melphalan-based therapies
Human Complement Regulators C4b-Binding Protein and C1 Esterase Inhibitor Interact with a Novel Outer Surface Protein of Borrelia recurrentis
The spirochete Borrelia recurrentis is the causal agent of louse-borne relapsing fever and is transmitted to humans by the infected body louse Pediculus humanus. We have recently demonstrated that the B. recurrentis surface receptor, HcpA, specifically binds factor H, the regulator of the alternative pathway of complement activation, thereby inhibiting complement mediated bacteriolysis. Here, we show that B. recurrentis spirochetes express another potential outer membrane lipoprotein, termed CihC, and acquire C4b-binding protein (C4bp) and human C1 esterase inhibitor (C1-Inh), the major inhibitors of the classical and lectin pathway of complement activation. A highly homologous receptor for C4bp was also found in the African tick-borne relapsing fever spirochete B. duttonii. Upon its binding to B. recurrentis or recombinant CihC, C4bp retains its functional potential, i.e. facilitating the factor I-mediated degradation of C4b. The additional finding that ectopic expression of CihC in serum sensitive B. burgdorferi significantly increased spirochetal resistance against human complement suggests this receptor to substantially contribute, together with other known strategies, to immune evasion of B. recurrentis
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