SUMMARY
Aberrant stress and inflammatory responses are key factors in the pathogenesis of obesity and metabolic dysfunction, and the double-stranded RNA-dependent kinase (PKR) has been proposed to play an important role in integrating these pathways. Here, we report the formation of a complex between PKR and TAR RNA-binding protein (TRBP) during metabolic and obesity-induced stress, which is critical for the regulation of eukaryotic translation initiation factor 2 alpha (eIF2α) phosphorylation and c-Jun N-terminal kinase (JNK) activation. We show that TRBP phosphorylation is induced in the setting of metabolic stress, leading to PKR activation. Suppression of hepatic TRBP reduced inflammation, JNK activity, and eIF2α phosphorylation and improved systemic insulin resistance and glucose metabolism, while TRBP overexpression exacerbated the impairment in glucose homeostasis in obese mice. These data indicate that the association between PKR and TRBP integrates metabolism with translational control and inflammatory signaling, and plays important roles in metabolic homeostasis and disease.
Bulk mineral assemblages of sediments and igneous basement rocks on the incoming CocosPlate at the Costa Rica subduction zone are examined by X-ray diffraction analyses on core samples. These samples are from Integrated Ocean Drilling Program Expedition 334 reference Site U1381, 5 km seaward of the trench. Drilling recovered approximately 100 m of sediment and 70 m of igneous oceanic basement. The sediment includes two lithologic units: hemipelagic clayey mud and siliceous to calcareous pelagic ooze. The hemipelagic unit is composed of clay minerals (50 wt.%), quartz (5 wt.%), plagioclase (5 wt.%), calcite (15 wt.%) and 30 wt.% of amorphous materials, while the pelagic unit is mostly made up of biogenic amorphous silica (50 wt.%) and calcite (50 wt.%). The igneous basement rock consists of plagioclase (50-60 wt.%), clinopyroxene (>25 wt.%), and saponite (15-40 wt.%). Saponite is more abundant in pillow basalt than in the massive section, reflecting the variable intensity of alteration. We estimate the total water influx of the sedimentary package is 6.9 m 3 /yr per m of trench length. Fluid expulsion models indicate that sediment compaction during shallow subduction causes the release of pore water while peak mineral dehydration occurs at temperatures of approximately 1008C, 40-30 km landward of the trench. This region is landward of the observed updip extent of seismicity. We posit that in this region the presence of subducting bathymetric relief capped by velocity weakening nannofossil chalk is more important in influencing the updip extent of seismicity than the thermal regime.
We examined the frictional properties of sediments on the Cocos plate offshore the Osa Peninsula, Costa Rica, and explored variations in the intrinsic frictional properties of the sediment inputs to the Costa Rica subduction zone. Sediment samples were collected at Site U1381A during the Integrated Ocean Drilling Program Expedition 334, and include hemipelagic clay to silty clay material (Unit I) and pelagic silicic to calcareous ooze (Unit II). The frictional properties of the samples were tested at a normal stress of 5 MPa under water-saturated conditions and with slip velocities ranging from 0.0028 to 2.8 mm/s for up to 340 mm of displacement. The experimental results reveal that the steady-state friction coefficient values of clay to silty clay samples are as low as~0.2, whereas those of silicic to calcareous ooze samples are as high as 0.6 to 0.8. The clay to silty clay samples show a positive dependence of friction on velocity for all tested slip velocities. In contrast, the silicic to calcareous ooze samples show a negative dependence of friction on velocity at velocities of 0.0028 to 0.28 mm/s and either neutral or positive dependence at velocities higher than 0.28 mm/s. Given the low frictional coefficient values observed for the clay to silty clay samples of Unit I, the décollement at the Costa Rica Seismogenesis Project transect offshore the Osa Peninsula likely initiates in Unit I and is initially very weak. In addition, the velocity-strengthening behavior of the clay to silty clay suggests that faults in the very shallow portion of the Costa Rica subduction zone are stable and thus behave as creeping segments. In contrast, the velocity-weakening behavior of the silicic to calcareous ooze favors unstable slip along faults. The shallow seismicity occurred at a depth as shallow as~9 km along the Costa Rica margin offshore the Osa Peninsula (M w 6.4, June 2002), indicating that materials characterized by velocity-weakening behavior constitute the fault zone at the depth of the seismicity. Fault slip nucleating along a fault in Unit II would be a likely candidate for the source of the shallow earthquake event.
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