Faulting structure above the Main Himalayan Thrust as shown by relocated aftershocks of the 2015 Mw7.8 Gorkha, Nepal, earthquake

The 25 April 2015, Mw7.8 Gorkha, Nepal, earthquake ruptured a shallow section of the Indian‐Eurasian plate boundary by reverse faulting with NNE‐SSW compression, consistent with the direction of current Indian‐Eurasian continental collision. The Gorkha main shock and aftershocks were recorded by permanent global and regional arrays and by a temporary local broadband array near the China‐Nepal border deployed prior to the Gorkha main shock. We relocate 272 earthquakes with Mw>3.5 by applying a multiscale double‐difference earthquake relocation technique to arrival times of direct and depth phases recorded globally and locally. We determine a well‐constrained depth of 18.5 km for the main shock hypocenter which places it on the Main Himalayan Thrust (MHT). Many of the aftershocks at shallower depths illuminate faulting structure in the hanging wall with dip angles that are steeper than the MHT. This system of thrust faults of the Lesser Himalaya may accommodate most of the elastic strain of the Himalayan orogeny.Key PointsWe relocate the 2015 Gorkha earthquakes using teleseismic and regional waveformsThe main shock is located on the horizontal Main Himalaya Thrust (MHT) at a depth of 18.5 kmAftershocks show faulting structure in the hanging wall above the MHTPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135634/1/grl53895.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135634/2/grl53895_am.pd

Human Papillomavirus Type 18 E6 and E7 Genes Integrate into Human Hepatoma Derived Cell Line Hep G2

Background and Objectives: Human papillomaviruses have been linked causally to some human cancers such as cervical carcinoma, but there is very little research addressing the effect of HPV infection on human liver cells. We chose the human hepatoma derived cell line Hep G2 to investigate whether HPV gene integration took place in liver cells as well. Methods: We applied PCR to detect the possible integration of HPV genes in Hep G2 cells. We also investigated the expression of the integrated E6 and E7 genes by using RT-PCR and Western blotting. Then, we silenced E6 and E7 expression and checked the cell proliferation and apoptosis in Hep G2 cells. Furthermore, we analyzed the potential genes involved in cell cycle and apoptosis regulatory pathways. Finally, we used in situ hybridization to detect HPV 16/18 in hepatocellular carcinoma samples. Results: Hep G2 cell line contains integrated HPV 18 DNA, leading to the expression of the E6 and E7 oncogenic proteins. Knockdown of the E7 and E6 genes expression reduced cell proliferation, caused the cell cycle arrest at the S phase, and increased apoptosis. The human cell cycle and apoptosis real-time PCR arrays analysis demonstrated E6 and E7-mediated regulation of some genes such as Cyclin H, UBA1, E2F4, p53, p107, FASLG, NOL3 and CASP14. HPV16/18 was found in only 9% (9/100) of patients with hepatocellular carcinoma. Conclusion: Our investigations showed that HPV 18 E6 and E7 genes can be integrated into the Hep G2, and we observed a low prevalence of HPV 16/18 in hepatocellular carcinoma samples. However, the precise risk of HPV as causative agent of hepatocellular carcinoma needs further study

Genome-wide analyses identify KLF4 as an important negative regulator in T-cell acute lymphoblastic leukemia through directly inhibiting T-cell associated genes

é 2015 Li et al. Background: Kruppel-like factor 4 (KLF4) induces tumorigenesis or suppresses tumor growth in a tissue-dependent manner. However, the roles of KLF4 in hematological malignancies and the mechanisms of action are not fully understood. Methods: Inducible KLF4-overexpression Jurkat cell line combined with mouse models bearing cell-derived xenografts and primary T-cell acute lymphoblastic leukemia (T-ALL) cells from four patients were used to assess the functional role of KLF4 in T-ALL cells in vitro and in vivo. A genome-wide RNA-seq analysis was conducted to identify genes regulated by KLF4 in T-ALL cells. Chromatin immunoprecipitation (ChIP) PCR was used to determine direct binding sites of KLF4 in T-ALL cells. Results: Here we reveal that KLF4 induced apoptosis through the BCL2/BCLXL pathway in human T-ALL cell lines and primary T-ALL specimens. In consistence, mice engrafted with KLF4-overexpressing T-ALL cells exhibited prolonged survival. Interestingly, the KLF4-induced apoptosis in T-ALL cells was compromised in xenografts but the invasion capacity of KLF4-expressing T-ALL cells to hosts was dramatically dampened. We found that KLF4 overexpression inhibited T cell-associated genes including NOTCH1, BCL11B, GATA3, and TCF7. Further mechanistic studies revealed that KLF4 directly bound to the promoters of NOTCH1, BCL2, and CXCR4 and suppressed their expression. Additionally, KLF4 induced SUMOylation and degradation of BCL11B. Conclusions: These results suggest that KLF4 as a major transcription factor that suppresses the expression of T-cell associated genes, thus inhibiting T-ALL progression.Link_to_subscribed_fulltex