Adjoint-based uncertainty quantification for inhomogeneous friction on a slow-slipping fault

Long-term slow-slip events (LSSEs) usually occur on the deep, shallow parts of subducting plates and have substantial relation with adjacent megathrust fault motion. Conventional techniques of quantifying slow earthquake frictional features show that these features may be indicative of predictive seismic motion; however, quantifying high-accuracy uncertainty of the frictional fields has not yet been achieved. We therefore propose a method of uncertainty quantification for spatially inhomogeneous frictional features from slip motion on an LSSE fault--megathrust fault complex in southwestern Japan. By combining a fault motion model that mimics slow-slip motion and a variational data assimilation (DA) technique using a second-order adjoint method, we have succeeded in quantifying the spatial distribution of the uncertainty of the frictional features. Further, evaluation of the spatial distribution in high-resolution reveals the correlation between the dynamics of the slow-slip motion and the important components of the frictional features, which is valuable information for observational DA design. Findings from this study are expected to advance the theoretical foundation of applied seismic motion prediction techniques using slow-slip frictional features as stress meters for megaquakes, as well as improve understanding of the relationship between the slow-slip motion and frictional parameters of a fault

Expression of the peroxisome proliferator activated receptor γ gene is repressed by DNA methylation in visceral adipose tissue of mouse models of diabetes

<p>Abstract</p> <p>Background</p> <p>Adipose tissues serve not only as a store for energy in the form of lipid, but also as endocrine tissues that regulates metabolic activities of the organism by secreting various kinds of hormones. Peroxisome proliferator activated receptor γ (PPARγ) is a key regulator of adipocyte differentiation that induces the expression of adipocyte-specific genes in preadipocytes and mediates their differentiation into adipocytes. Furthermore, PPARγ has an important role to maintain the physiological function of mature adipocyte by controlling expressions of various genes properly. Therefore, any reduction in amount and activity of PPARγ is linked to the pathogenesis of metabolic syndrome.</p> <p>Results</p> <p>In this study, we investigated the contribution of epigenetic transcriptional regulatory mechanisms, such as DNA methylation, to the expression of the PPARγ gene, and further evaluated the contribution of such epigenetic regulatory mechanisms to the pathogenesis of metabolic syndrome. In 3T3-L1 preadipocytes, the promoter of the PPARγ2 gene was hypermethylated, but was progressively demethylated upon induction of differentiation, which was accompanied by an increase of mRNA expression. Moreover, treatment of cells with 5'-aza-cytideine, an inhibitor of DNA methylation, increased expression of the PPARγ gene in a dose-dependent manner. Methylation <it>in vitro </it>of a PPARγ promoter-driven reporter construct also repressed the transcription of a downstream reporter gene. These results suggest that the expression of the PPARγ gene is inhibited by methylation of its promoter. We next compared the methylation status of the PPARγ promoters in adipocytes from wild-type (WT) mice with those from two diabetic mouse models: <it>+Lepr</it>^<it>db</it><it>/+Lepr</it>^{<it>db </it>}and diet-induced obesity mice. Interestingly, we found increased methylation of the PPARγ promoter in visceral adipose tissues (VAT) of the mouse models of diabetes, compared to that observed in wild-type mice. We observed a concomitant decrease in the level of PPARγ mRNA in the diabetic mice compared to the WT mice.</p> <p>Conclusion</p> <p>We conclude that the expression of PPARγ gene is regulated by DNA methylation of its promoter region and propose that reduced expression of PPARγ owing to DNA methylation in adipocytes of the VAT may contribute to the pathogenesis of metabolic syndrome.</p

Microscopic dissection of the process of stress granule assembly

AbstractStress granules (SGs) are mRNA triage sites that are formed in response to a variety of cellular stress. To study how SGs bring about the massive spatial compartmentalization, we monitored the localization of various RNA-binding proteins (RBPs) targeted to SGs upon exposure to stress. We discovered that concomitant with the onset of eIF2α phosphorylation, RBPs accumulate locally in the cytoplasm, which leads to increased inter-molecular interactions and the formation of robustly detergent-resistant foci. Subsequently, microtubules (MTs) mediate 1) the ordered spatial organization of SGs and 2) the recruitment of a set of nuclear-localized SG components to the cytoplasm. Meanwhile, MTs did not appear to be required for the maintenance of SG distribution after its assembly. Our data suggest that the process of SG formation is composed of MT-independent and -dependent pathways, which take place sequentially during stress response