Focusing of upward fluid migration beneath volcanic arcs : effect of mineral grain size variation in the mantle wedge

Author Posting. © American Geophysical Union, 2015. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry, Geophysics, Geosystems 16 (2015): 3905–3923, doi:10.1002/2015GC005950.We use numerical models to investigate the effects of mineral grain size variation on fluid migration in the mantle wedge at subduction zones and on the location of the volcanic arc. Previous coupled thermal-grain size evolution (T-GSE) models predict small grain size (<1 mm) in the corner flow of the mantle wedge, a downdip grain size increase by ∼2 orders of magnitude along the base of the mantle wedge, and finer grain size in the mantle wedge for colder-slab subduction zones. We integrate these T-GSE modeling results with a fluid migration model, in which permeability depends on grain size, and fluid flow through a moving mantle matrix is driven by fluid buoyancy and dynamic pressure gradients induced by mantle flow. Our modeling results indicate that fluids introduced along the base of the mantle wedge beneath the fore arc are initially dragged downdip by corner flow due to the small grain size and low permeability immediately above the slab. As grain size increases with depth, permeability increases, resulting in upward fluid migration. Fluids released beneath the arc and the back arc are also initially dragged downdip, but typically are not transported as far laterally before they begin to travel upward. As the fluids rise through the back-arc mantle wedge, they become deflected toward the trench due to the effect of mantle inflow. The combination of downdip migration in the fore arc and trench-ward migration in the back arc results in pathways that focus fluids beneath the arc.International Research Institute of Disaster Science, Tohoku University; NSF; MARGINS Postdoctoral Fellowship . Grant Number: NSF OCE-08408002016-05-1

Dopaminergic neuroprotective effects of rotigotine via 5-HT1A receptors: Possibly involvement of metallothionein expression in astrocytes

Astrocytes exert neuroprotective effects through production of antioxidant molecules and neurotrophic factors. A recent study showed that stimulation of astrocyte serotonin 1A (5-HT1A) receptors promotes astrocyte proliferation and upregulation of the antioxidant molecules metallothionein (MT)-1,2, which protect dopaminergic neurons against oxidative stress. Rotigotine, an anti-parkinsonian drug, can bind to dopamine and 5-HT1A receptors. In this study, we examined neuroprotective effects of rotigotine in models of Parkinson's disease and involvement of astrocyte 5-HT1A receptors in neuroprotective effects of rotigotine against dopaminergic neurodegeneration. Rotigotine increased the number of astrocytes and MT-1,2 expression in cultured astrocytes. Pretreatment with conditioned media from rotigotine-treated astrocytes significantly inhibited 6-hydroxydopamine (6-OHDA)-induced dopaminergic neurotoxicity. These effects were completely blocked by a 5-HT1A antagonist or MT-1,2 specific antibody. Subcutaneous administration of rotigotine increased MT-1,2 expression in striatal astrocytes and prevented reduction of dopaminergic neurons in the substantia nigra of a 6-OHDA-lesioned mouse model of Parkinson's disease. These effects were blocked by co-administration with a 5-HT1A antagonist. These results suggest that rotigotine exerts neuroprotective effects through upregulation of MT expression in astrocytes by targeting 5-HT1A receptors. Our findings provide a possible therapeutic application of rotigotine to prevent dopaminergic neurodegeneration in Parkinson's disease

Sharp thermal transition in the forearc mantle wedge as a consequence of nonlinear mantle wedge flow

Author Posting. © American Geophysical Union, 2011. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 38 (2011): L13308, doi:10.1029/2011GL047705.In the forearc mantle wedge, the thermal field depends strongly on slab-driven mantle wedge flow. The flow is in turn affected by the thermal field via the temperature dependence of mantle rheology. Using thermal modeling, we show that the nonlinear feedback between the thermal and flow fields always leads to complete stagnation of the mantle wedge over a shallow, weakened part of the slab-mantle interface and an abrupt onset of mantle flow further down-dip. The abrupt increase in flow velocity leads to a sharp thermal transition from a cold stagnant to a hot flowing part of the wedge. This sharp thermal transition is inherent to all subduction zones, explaining a commonly observed sharp arc-ward increase in seismic attenuation.This research was partially supported by National Science Foundation through a MARGINS postdoctoral fellowship (NSF OCE‐0840800) and by Natural Environment Research Council

High Glucose Increases Metallothionein Expression in Renal Proximal Tubular Epithelial Cells

Metallothionein (MT) is an intracellular metal-binding, cysteine-rich protein, and is a potent antioxidant that protects cells and tissues from oxidative stress. Although the major isoforms MT-1 and -2 (MT-1/-2) are highly inducible in many tissues, the distribution and role of MT-1/-2 in diabetic nephropathy are poorly understood. In this study, diabetes was induced in adult male rats by streptozotocin, and renal tissues were stained with antibodies for MT-1/-2. MT-1/-2 expression was also evaluated in mProx24 cells, a mouse renal proximal tubular epithelial cell line, stimulated with high glucose medium and pretreated with the antioxidant vitamin E. MT-1/-2 expression was gradually and dramatically increased, mainly in the proximal tubular epithelial cells and to a lesser extent in the podocytes in diabetic rats, but was hardly observed in control rats. MT-1/-2 expression was also increased by high glucose stimulation in mProx24 cells. Because the induction of MT was suppressed by pretreatment with vitamin E, the expression of MT-1/-2 is induced, at least in part, by high glucose-induced oxidative stress. These observations suggest that MT-1/-2 is induced in renal proximal tubular epithelial cells as an antioxidant to protect the kidney from oxidative stress, and may offer a novel therapeutic target against diabetic nephropathy

Collagen adhesion gene is associated with blood stream infections caused by methicillin-resistant Staphylococcus aureus

Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) causes hospital- and community-acquired infections. It is not clear whether genetic characteristics of the bacteria contribute to disease pathogenesis in MRSA infection. We hypothesized that whole genome analysis of MRSA strains could reveal the key gene loci and/or the gene mutations that affect clinical manifestations of MRSA infection. Methods: Whole genome sequences (WGS) of MRSA of 154 strains were analyzed with respect to clinical manifestations and data. Further, we evaluated the association between clinical manifestations in MRSA infection and genomic information. Results: WGS revealed gene mutations that correlated with clinical manifestations of MRSA infection. Moreover, 12 mutations were selected as important mutations by Random Forest analysis. Cluster analysis revealed strains associated with a high frequency of bloodstream infection (BSI). Twenty seven out of 34 strains in this cluster caused BSI. These strains were all positive for collagen adhesion gene (cna) and have mutations in the locus, those were selected by Random Forest analysis. Univariate and multivariate analysis revealed that these gene mutations were the predictor for the incidence of BSI. Interestingly, mutant CNA protein showed lower attachment ability to collagen, suggesting that the mutant protein might contribute to the dissemination of bacteria. Conclusions: These findings suggest that the bacterial genotype affects the clinical characteristics of MRSA infection. (c) 2019 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases

Grain-size distribution in the mantle wedge of subduction zones

Author Posting. © American Geophysical Union, 2011. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 116 (2011): B10203, doi:10.1029/2011JB008294.Mineral grain size plays an important role in controlling many processes in the mantle wedge of subduction zones, including mantle flow and fluid migration. To investigate the grain-size distribution in the mantle wedge, we coupled a two-dimensional (2-D) steady state finite element thermal and mantle-flow model with a laboratory-derived grain-size evolution model. In our coupled model, the mantle wedge has a composite olivine rheology that incorporates grain-size-dependent diffusion creep and grain-size-independent dislocation creep. Our results show that all subduction settings lead to a characteristic grain-size distribution, in which grain size increases from 10 to 100 μm at the most trenchward part of the creeping region to a few centimeters in the subarc mantle. Despite the large variation in grain size, its effect on the mantle rheology and flow is very small, as >90% of the deformation in the flowing part of the creeping region is accommodated by grain-size-independent dislocation creep. The predicted grain-size distribution leads to a downdip increase in permeability by ∼5 orders of magnitude. This increase is likely to promote greater upward migration of aqueous fluids and melts where the slab reaches ∼100 km depth compared with shallower depths, potentially providing an explanation for the relatively uniform subarc slab depth. Seismic attenuation derived from the predicted grain-size distribution and thermal field is consistent with the observed seismic structure in the mantle wedge at many subduction zones, without requiring a significant contribution by the presence of melt.Funding for this research was provided by the National Science Foundation through a MARGINS Postdoctoral Fellowship (NSF OCE‐0840800) and NSF grant EAR‐0854673

Systematic analysis of mitochondrial genes associated with hearing loss in the Japanese population: dHPLC reveals a new candidate mutation

<p>Abstract</p> <p>Background</p> <p>Variants of mitochondrial DNA (mtDNA) have been evaluated for their association with hearing loss. Although ethnic background affects the spectrum of mtDNA variants, systematic mutational analysis of mtDNA in Japanese patients with hearing loss has not been reported.</p> <p>Methods</p> <p>Using denaturing high-performance liquid chromatography combined with direct sequencing and cloning-sequencing, Japanese patients with prelingual (N = 54) or postlingual (N = 80) sensorineural hearing loss not having pathogenic mutations of m.1555A > G and m.3243A > G nor <it>GJB2 </it>were subjected to mutational analysis of mtDNA genes (<it>12S rRNA</it>, <it>tRNA</it>^{<it>Leu(UUR)</it>}, <it>tRNA</it>^{<it>Ser(UCN)</it>}, <it>tRNA</it>^<it>Lys</it>, <it>tRNA</it>^<it>His</it>, <it>tRNA</it>^{<it>Ser(AGY)</it>}, and <it>tRNA</it>^<it>Glu</it>).</p> <p>Results</p> <p>We discovered 15 variants in <it>12S rRNA </it>and one homoplasmic m.7501A > G variant in <it>tRNA</it>^{<it>Ser(UCN)</it>}; no variants were detected in the other genes. Two criteria, namely the low frequency in the controls and the high conservation among animals, selected the m.904C > T and the m.1105T > C variants in <it>12S rRNA </it>as candidate pathogenic mutations. Alterations in the secondary structures of the two variant transcripts as well as that of m.7501A > G in <it>tRNA</it>^{<it>Ser(UCN) </it>}were predicted.</p> <p>Conclusions</p> <p>The m.904C > T variant was found to be a new candidate mutation associated with hearing loss. The m.1105T > C variant is unlikely to be pathogenic. The pathogenicity of the homoplasmic m.7501T > A variant awaits further study.</p