Missing ophiolitic rocks along the Mae Yuam Fault as the Gondwana-Tethys divide in north-west Thailand

Thailand comprises two continental blocks: Sibumasu and Indochina. The clastic rocks of the Triassic Mae Sariang Group are distributed in the Mae Hong Son-Mae Sariang area, north-west Thailand, which corresponds to the central part of Sibumasu. The clastic rocks yield abundant detrital chromian spinels, indicating a source of ultramafic/mafic rocks. The chemistry of the detrital chromian spinels suggests that they were derived from three different rock types: ocean-floor peridotite, chromitite and intraplate basalt, and that ophiolitic rocks were exposed in the area, where there are no outcrops of them at present. Exposition of an ophiolitic complex denotes a suture zone or other tectonic boundary. The discovery of chromian spinels suggests that the Gondwana-Tethys divide is located along the Mae Yuam Fault zone. Both paleontological and tectonic aspects support this conclusion. © 2004 Blackwell Publishing Asia Pty Ltd

Regulation of hepatitis C virus secretion by the Hrs-dependent exosomal pathway

AbstractThe molecular mechanisms of assembly and budding of hepatitis C virus (HCV) remain poorly understood. The budding of several enveloped viruses requires an endosomal sorting complex required for transport (ESCRT), which is part of the cellular machinery used to form multivesicular bodies (MVBs). Here, we demonstrated that Hrs, an ESCRT-0 component, is critical for the budding of HCV through the exosomal secretion pathway. Hrs depletion caused reduced exosome production, which paralleled with the decrease of HCV replication in the host cell, and that in the culture supernatant. Sucrose-density gradient separation of the culture supernatant of HCV-infected cells revealed the co-existence of HCV core proteins and the exosome marker. Furthermore, both the core protein and an envelope protein of HCV were detected in the intraluminal vesicles of MVBs. These results suggested that HCV secretion from host cells requires Hrs-dependent exosomal pathway in which the viral assembly is also involved

Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice

Autophagy is a membrane-trafficking mechanism that delivers cytoplasmic constituents into the lysosome/vacuole for bulk protein degradation. This mechanism is involved in the preservation of nutrients under starvation condition as well as the normal turnover of cytoplasmic component. Aberrant autophagy has been reported in several neurodegenerative disorders, hepatitis, and myopathies. Here, we generated conditional knockout mice of Atg7, an essential gene for autophagy in yeast. Atg7 was essential for ATG conjugation systems and autophagosome formation, amino acid supply in neonates, and starvation-induced bulk degradation of proteins and organelles in mice. Furthermore, Atg7 deficiency led to multiple cellular abnormalities, such as appearance of concentric membranous structure and deformed mitochondria, and accumulation of ubiquitin-positive aggregates. Our results indicate the important role of autophagy in starvation response and the quality control of proteins and organelles in quiescent cells

Optimized protocol for the extraction of RNA and DNA from frozen whole blood sample stored in a single EDTA tube

Cryopreservation of whole blood is useful for DNA collection, and clinical and basic research. Blood samples in ethylenediaminetetraacetic acid disodium salt (EDTA) tubes stored at − 80 °C are suitable for DNA extraction, but not for high-quality RNA extraction. Herein, a new methodology for high-quality RNA extraction from human blood samples is described. Quickly thawing frozen whole blood on aluminum blocks at room temperature could minimize RNA degradation, and improve RNA yield and quality compared with thawing the samples in a 37 °C water bath. Furthermore, the use of the NucleoSpin RNA kit increased RNA yield by fivefold compared with the PAXgene Blood RNA Kit. Thawing blood samples on aluminum blocks significantly increased the DNA yield by ~ 20% compared with thawing in a 37 °C water bath or on ice. Moreover, by thawing on aluminum blocks and using the NucleoSpin RNA and QIAamp DNA Blood kits, the extraction of RNA and DNA of sufficient quality and quantity was achieved from frozen EDTA whole blood samples that were stored for up to 8.5 years. Thus, extracting RNA from frozen whole blood in EDTA tubes after long-term storage is feasible. These findings may help advance gene expression analysis, as well as biomarker research for various diseases

p62/SQSTM1-droplet serves as a platform for autophagosome formation and anti-oxidative stress response

Autophagy contributes to the selective degradation of liquid droplets, including the P-Granule, Ape1-complex and p62/SQSTM1-body, although the molecular mechanisms and physiological relevance of selective degradation remain unclear. In this report, we describe the properties of endogenous p62-bodies, the effect of autophagosome biogenesis on these bodies, and the in vivo significance of their turnover. p62-bodies are low-liquidity gels containing ubiquitin and core autophagy-related proteins. Multiple autophagosomes form on the p62-gels, and the interaction of autophagosome-localizing Atg8-proteins with p62 directs autophagosome formation toward the p62-gel. Keap1 also reversibly translocates to the p62-gels in a p62-binding dependent fashion to activate the transcription factor Nrf2. Mice deficient for Atg8-interaction-dependent selective autophagy show that impaired turnover of p62-gels leads to Nrf2 hyperactivation in vivo. These results indicate that p62-gels are not simple substrates for autophagy but serve as platforms for both autophagosome formation and anti-oxidative stress. Liquid-liquid phase separation of p62/SQSTM1 has been previously described, although the significance in vivo remains unclear. Here the authors show p62 droplets contain ubiquitin, autophagy-related proteins and Keap1 to serve as platform of not only autophagosome formation but also Nrf2 activation.Peer reviewe

Interferon signaling and hypercytokinemia-related gene expression in the blood of antidepressant non-responders

Only 50% of patients with depression respond to the first antidepressant drug administered. Thus, biomarkers for prediction of antidepressant responses are needed, as predicting which patients will not respond to antidepressants can optimize selection of alternative therapies. We aimed to identify biomarkers that could predict antidepressant responsiveness using a novel data-driven approach based on statistical pattern recognition. We retrospectively divided patients with major depressive disorder into antidepressant responder and non-responder groups. Comprehensive gene expression analysis was performed using peripheral blood without narrowing the genes. We designed a classifier according to our own discrete Bayes decision rule that can handle categorical data. Nineteen genes showed differential expression in the antidepressant non-responder group (n = 15) compared to the antidepressant responder group (n = 15). In the training sample of 30 individuals, eight candidate genes had significantly altered expression according to quantitative real-time polymerase chain reaction. The expression of these genes was examined in an independent test sample of antidepressant responders (n = 22) and non-responders (n = 12). Using the discrete Bayes classifier with the HERC5, IFI6, and IFI44 genes identified in the training set yielded 85% discrimination accuracy for antidepressant responsiveness in the 34 test samples. Pathway analysis of the RNA sequencing data for antidepressant responsiveness identified that hypercytokinemia- and interferon-related genes were increased in non-responders. Disease and biofunction analysis identified changes in genes related to inflammatory and infectious diseases, including coronavirus disease. These results strongly suggest an association between antidepressant responsiveness and inflammation, which may be useful for future treatment strategies for depression

Impact of Anatomical Resection for Hepatocellular Carcinoma With Microportal Invasion (vp1): A Multi-institutional Study by the Kyushu Study Group of Liver Surgery

Objective: The aim of the present study was to evaluate the value of anatomical resectionfor HCC with micro-portal vascular invasion (vp1) between 2000 and 2010. Summaryof Background: Vascular invasion has been reported as a prognostic factor of liverresection for hepatocellular carcinoma (HCC). Anatomical resection for HCC has resulted in optimum outcomes of eradicating intrahepatic micrometastases through the portal vein, but opposite results have also been reported. Methods: A clinical chart review was performed for 546 HCC patients with vp1. We retrospectively evaluated the recurrence-free survival (RFS) between anatomical (AR)and non-anatomical resection (NAR). The site of recurrence was also compared between these groups. The influence of AR on the overall survival (OS) and RFS rates was analyzed in patients selected by propensity score matching, and the prognostic factors were identified.Results: A total of 546 patients were enrolled, including 422 in the AR group and 124 in the NAR group. There was no difference in the 5-year OS and RFS rates between the two groups. Local recurrence was significantly more frequent in the NAR group than in the AR group. In a multivariate analysis, hepatitis C (HCV), PIVKAII ?380 mAU/ml, tumor diameter ?5 cm and ?70 years of age were significant predictors of a poor RFS after liverresection. There were no significant differences in the OS or RFS between the AR and NAR groups by a propensity score-matched analysis. Conclusion: Although local recurrence around the resection site was suppressed by AR, AR for HCC with vp1 did not influence the RFS or OS rates after hepatectomy in the modern era