A Novel Citrullinated Modification of Histone 3 and Its Regulatory Mechanisms Related to IPO-38 Antibody-Labeled Protein

IPO-38 is a potential biomarker for early diagnosis of gastric cancer that we recently identified. Although we characterized its chemical nature as a nucleosome histone, we suspected the existence of histone modification for the IPO-38 antibody-labeled protein. Here, we used a commercially available modified histone peptide array to identify the type and site of histone modification labeled by the IPO-38 monoclonal antibody. In protein array analysis, the citrulline modification of histone 3 on arginine 26 (H3R26Cit) yielded the strongest signal. Although peptidyl arginine deiminase-2 and -4 (PADI2 and PADI4, respectively) can catalyze the conversion of arginine to citrulline, we observed that only PADI4 expression correlated with the citrulline histone modification of H3R26Cit. Overexpression of PADI4, via transfection of a eukaryotic expression vector, and knockdown of PADI4 gene expression, by a PADI4 CRISPR/Cas9 vector, confirmed the crucial function of PADI4 on the increased level of H3R26Cit in gastric cancer cell lines. By immunoprecipitation and immunoblotting, we found an interaction between H3R26Cit and H3K27me3. Our study established the first link between the IPO-38 antigen and citrullinated histone 3, and clarified the upstream regulatory enzyme PADI4. The new findings suggest an important role for the citrullination modification of histone in gastric cancer biology, and should help us optimize the development of a sensitive and specific diagnostic reagent

LncRNAs GIHCG and SPINT1-AS1 Are Crucial Factors for Pan-Cancer Cells Sensitivity to Lapatinib

Lapatinib is a small molecule inhibitor of EGFR (HER1) and ERBB2 (HER2) receptors, which is used for treatment of advanced or metastatic breast cancer. To find the drug resistance mechanisms of treatment for EGFR/ERBB2 positive tumors, we analyzed the possible effects of lncRNAs. In this study, using CCLE (Cancer Cell Line Encyclopedia) database, we explored the relationship between the lncRNAs and Lapatinib sensitivity/resistance, and then validated those findings through in vitro experiments. We found that the expression of EGFR/ERBB2 and activation of ERBB pathway was significantly related to Lapatinib sensitivity. GO (Gene Oncology) analysis of top 10 pathways showed that the sensitivity of Lapatinib was positively correlated with cell keratin, epithelial differentiation, and cell-cell junction, while negatively correlated with signatures of extracellular matrix. Forty-four differentially expressed lncRNAs were found between the Lapatinib sensitive and resistant groups (fold-change > 1.5, P < 0.01). Gene set variation analysis (GSVA) was performed based on 44 lncRNAs and genes in the top 10 pathways. Five lncRNAs were identified as hub molecules. Co-expression network was constructed by more than five lncRNAs and 199 genes in the top 10 pathways, and three lncRNAs (GIHCG, SPINT1-AS1, and MAGI2-AS3) and 47 genes were identified as close-related molecules. The three lncRNAs in epithelium-derived cancers were differentially expressed between sensitive and resistant groups, but no significance was found in non-epithelium-derived cancer cells. Correlation analysis showed that SPINT1-AS1 (R = −0.715, P < 0.001) and GIHCG (R = 0.557, P = 0.013) were correlated with the IC50 of epithelium-derived cancer cells. In further experiments, GIHCG knockdown enhanced cancer cell susceptibility to Lapatinib, while high level of SPINT1-AS1 was a sensitive biomarker of NCI-N87 and MCF7 cancer cells to Lapatinib. In conclusions, lncRNAs GIHCG and SPINT1-AS1 were involved in regulating Lapatinib sensitivity. Up-regulation of GIHCG was a drug-resistant biomarker, while up-regulation of SPINT1-AS1 was a sensitive indicator

Further comprehension of natural gas accumulation, distribution, and prediction prospects in China

In-depth research reveals that the natural gas accumulation and distribution are characterized by cycle, sequence, equilibrium, traceability, and multi-stage. To be specific, every geotectonic cycle represents a gas reservoir forming system where natural gas is generated, migrated, accumulated, and formed into a reservoir in a certain play. Essentially, hydrocarbon accumulation occurs when migration force and resistance reach an equilibrium. In this situation, the closer to the source rock, the higher the accumulation efficiency is. Historically, reservoirs were formed in multiple phases. Moreover, zones in source rocks and adjacent to source rocks, unconformity belts, and faulted anticline belts are favorable areas to finding large gas fields. Apart from the common unconformity belts and faulted anticline belts, in-source and near-source zones should be considered as critical targets for future exploration. Subsequent exploration should focus on Upper Palaeozoic in the southeastern Ordos Basin, Triassic in southwestern Sichuan Basin, Jurassic in the northern section of the Kuqa Depression and other zones where no great breakthroughs have been made. Keywords: Large gas field, Distribution characteristics, Potential zone, Prospec

CEPC Conceptual Design Report: Volume 2 - Physics & Detector

The Circular Electron Positron Collider (CEPC) is a large international scientific facility proposed by the Chinese particle physics community to explore the Higgs boson and provide critical tests of the underlying fundamental physics principles of the Standard Model that might reveal new physics. The CEPC, to be hosted in China in a circular underground tunnel of approximately 100 km in circumference, is designed to operate as a Higgs factory producing electron-positron collisions with a center-of-mass energy of 240 GeV. The collider will also operate at around 91.2 GeV, as a Z factory, and at the WW production threshold (around 160 GeV). The CEPC will produce close to one trillion Z bosons, 100 million W bosons and over one million Higgs bosons. The vast amount of bottom quarks, charm quarks and tau-leptons produced in the decays of the Z bosons also makes the CEPC an effective B-factory and tau-charm factory. The CEPC will have two interaction points where two large detectors will be located. This document is the second volume of the CEPC Conceptual Design Report (CDR). It presents the physics case for the CEPC, describes conceptual designs of possible detectors and their technological options, highlights the expected detector and physics performance, and discusses future plans for detector R&D and physics investigations. The final CEPC detectors will be proposed and built by international collaborations but they are likely to be composed of the detector technologies included in the conceptual designs described in this document. A separate volume, Volume I, recently released, describes the design of the CEPC accelerator complex, its associated civil engineering, and strategic alternative scenarios

CEPC Conceptual Design Report: Volume 2 - Physics & Detector

The Circular Electron Positron Collider (CEPC) is a large international scientific facility proposed by the Chinese particle physics community to explore the Higgs boson and provide critical tests of the underlying fundamental physics principles of the Standard Model that might reveal new physics. The CEPC, to be hosted in China in a circular underground tunnel of approximately 100 km in circumference, is designed to operate as a Higgs factory producing electron-positron collisions with a center-of-mass energy of 240 GeV. The collider will also operate at around 91.2 GeV, as a Z factory, and at the WW production threshold (around 160 GeV). The CEPC will produce close to one trillion Z bosons, 100 million W bosons and over one million Higgs bosons. The vast amount of bottom quarks, charm quarks and tau-leptons produced in the decays of the Z bosons also makes the CEPC an effective B-factory and tau-charm factory. The CEPC will have two interaction points where two large detectors will be located. This document is the second volume of the CEPC Conceptual Design Report (CDR). It presents the physics case for the CEPC, describes conceptual designs of possible detectors and their technological options, highlights the expected detector and physics performance, and discusses future plans for detector R&D and physics investigations. The final CEPC detectors will be proposed and built by international collaborations but they are likely to be composed of the detector technologies included in the conceptual designs described in this document. A separate volume, Volume I, recently released, describes the design of the CEPC accelerator complex, its associated civil engineering, and strategic alternative scenarios

CEPC Conceptual Design Report: Volume 2 - Physics & Detector

The Circular Electron Positron Collider (CEPC) is a large international scientific facility proposed by the Chinese particle physics community to explore the Higgs boson and provide critical tests of the underlying fundamental physics principles of the Standard Model that might reveal new physics. The CEPC, to be hosted in China in a circular underground tunnel of approximately 100 km in circumference, is designed to operate as a Higgs factory producing electron-positron collisions with a center-of-mass energy of 240 GeV. The collider will also operate at around 91.2 GeV, as a Z factory, and at the WW production threshold (around 160 GeV). The CEPC will produce close to one trillion Z bosons, 100 million W bosons and over one million Higgs bosons. The vast amount of bottom quarks, charm quarks and tau-leptons produced in the decays of the Z bosons also makes the CEPC an effective B-factory and tau-charm factory. The CEPC will have two interaction points where two large detectors will be located. This document is the second volume of the CEPC Conceptual Design Report (CDR). It presents the physics case for the CEPC, describes conceptual designs of possible detectors and their technological options, highlights the expected detector and physics performance, and discusses future plans for detector R&D and physics investigations. The final CEPC detectors will be proposed and built by international collaborations but they are likely to be composed of the detector technologies included in the conceptual designs described in this document. A separate volume, Volume I, recently released, describes the design of the CEPC accelerator complex, its associated civil engineering, and strategic alternative scenarios