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

A case report of a family with developmental arrest of human prokaryotic stage zygote

To study the genetic variation leading to the arrest phenotype of pronuclear (PN) zygotes. We recruited a family characterized by recurrent PN arrest during in vitro fertilization (IVF) and intracytoplasmic sperm injection cycles (ICSI) and performed whole-exome sequencing for 2 individuals. The transcriptome profiles of PN-arrest zygotes were assessed by single-cell RNA sequencing analysis. The variants were then validated by PCR amplification and Sanger sequencing in the affected individuals and other family members. A family characterized by recurrent PN arrest during IVF and ICSI cycles were enrolled after giving written informed consent. Peripheral blood samples were taken for DNA extraction. Three PN-arrest zygotes from patient III-3 were used for single-cell RNA-seq as described. This phenotype was reproduced after multiple cycles of egg retrieval and after trying different fertilization methods and multiple ovulation regimens. The mutant genes of whole exon sequencing were screened and verified. The missense variant c. C1630T (p.R544W) in RGS12 was responsible for a phenotype characterized by paternal transmission. RGS12 controls Ca2+ oscillation, which is required for oocyte activation after fertilization. Single-cell transcriptome profiling of PN-arrest zygotes revealed defective established translation, RNA processing and cell cycle, which explained the failure of complete oocyte activation. Furthermore, we identified proximal genes involved in Ca2+ oscillation–cytostatic factor–anaphase-promoting complex (Ca2+ oscillation–CSF–APC) signaling, including upregulated CaMKII, ORAI1, CDC20, and CDH1 and downregulated EMI1 and BUB3. The findings indicate abnormal spontaneous Ca2+ oscillations leading to oocytes with prolonged low CSF level and high APC level, which resulted in defective nuclear envelope breakdown and DNA replication. We have identified an RGS12 variant as the potential cause of female infertility characterized by arrest at the PN stage during multiple IVF and ICSI

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