Comprehensive Network Analysis Reveals Alternative Splicing-Related lncRNAs in Hepatocellular Carcinoma

© Copyright © 2020 Wang, Wang, Bhat, Chen, Xu, Mo, Yi and Zhou. It is increasingly appreciated that long non-coding RNAs (lncRNAs) associated with alternative splicing (AS) could be involved in aggressive hepatocellular carcinoma. Although many recent studies show the alteration of RNA alternative splicing by deregulated lncRNAs in cancer, the extent to which and how lncRNAs impact alternative splicing at the genome scale remains largely elusive. We analyzed RNA-seq data obtained from 369 hepatocellular carcinomas (HCCs) and 160 normal liver tissues, quantified 198,619 isoform transcripts, and identified a total of 1,375 significant AS events in liver cancer. In order to predict novel AS-associated lncRNAs, we performed an integration of co-expression, protein-protein interaction (PPI) and epigenetic interaction networks that links lncRNA modulators (such as splicing factors, transcript factors, and miRNAs) along with their targeted AS genes in HCC. We developed a random walk-based multi-graphic (RWMG) model algorithm that prioritizes functional lncRNAs with their associated AS targets to computationally model the heterogeneous networks in HCC. RWMG shows a good performance evaluated by the ROC curve based on cross-validation and bootstrapping strategies. As a conclusion, our robust network-based framework has derived 31 AS-related lncRNAs that not only validates known cancer-associated cases MALAT1 and HOXA11-AS, but also reveals new players such as DNM1P35 and DLX6-AS1with potential functional implications. Survival analysis further provides insights into the clinical significance of identified lncRNAs

Exploratory spatial data analysis for the identification of risk factors to birth defects

BACKGROUND: Birth defects, which are the major cause of infant mortality and a leading cause of disability, refer to "Any anomaly, functional or structural, that presents in infancy or later in life and is caused by events preceding birth, whether inherited, or acquired (ICBDMS)". However, the risk factors associated with heredity and/or environment are very difficult to filter out accurately. This study selected an area with the highest ratio of neural-tube birth defect (NTBD) occurrences worldwide to identify the scale of environmental risk factors for birth defects using exploratory spatial data analysis methods. METHODS: By birth defect registers based on hospital records and investigation in villages, the number of birth defects cases within a four-year period was acquired and classified by organ system. The neural-tube birth defect ratio was calculated according to the number of births planned for each village in the study area, as the family planning policy is strictly adhered to in China. The Bayesian modeling method was used to estimate the ratio in order to remove the dependence of variance caused by different populations in each village. A recently developed statistical spatial method for detecting hotspots, Getis's [Image: see text] [7], was used to detect the high-risk regions for neural-tube birth defects in the study area. RESULTS: After the Bayesian modeling method was used to calculate the ratio of neural-tube birth defects occurrences, Getis's [Image: see text] statistics method was used in different distance scales. Two typical clustering phenomena were present in the study area. One was related to socioeconomic activities, and the other was related to soil type distributions. CONCLUSION: The fact that there were two typical hotspot clustering phenomena provides evidence that the risk for neural-tube birth defect exists on two different scales (a socioeconomic scale at 6.84 km and a soil type scale at 22.8 km) for the area studied. Although our study has limited spatial exploratory data for the analysis of the neural-tube birth defect occurrence ratio and for finding clues to risk factors, this result provides effective clues for further physical, chemical and even more molecular laboratory testing according to these two spatial scales

Precise Measurements of Branching Fractions for Ds+D_s^+ Meson Decays to Two Pseudoscalar Mesons

We measure the branching fractions for seven $D_{s}^{+}$ two-body decays to pseudo-scalar mesons, by analyzing data collected at $\sqrt{s}=4.178\sim4.226$ GeV with the BESIII detector at the BEPCII collider. The branching fractions are determined to be $\mathcal{B}(D_s^+\to K^+\eta^{\prime})=(2.68\pm0.17\pm0.17\pm0.08)\times10^{-3}$, $\mathcal{B}(D_s^+\to\eta^{\prime}\pi^+)=(37.8\pm0.4\pm2.1\pm1.2)\times10^{-3}$, $\mathcal{B}(D_s^+\to K^+\eta)=(1.62\pm0.10\pm0.03\pm0.05)\times10^{-3}$, $\mathcal{B}(D_s^+\to\eta\pi^+)=(17.41\pm0.18\pm0.27\pm0.54)\times10^{-3}$, $\mathcal{B}(D_s^+\to K^+K_S^0)=(15.02\pm0.10\pm0.27\pm0.47)\times10^{-3}$, $\mathcal{B}(D_s^+\to K_S^0\pi^+)=(1.109\pm0.034\pm0.023\pm0.035)\times10^{-3}$, $\mathcal{B}(D_s^+\to K^+\pi^0)=(0.748\pm0.049\pm0.018\pm0.023)\times10^{-3}$, where the first uncertainties are statistical, the second are systematic, and the third are from external input branching fraction of the normalization mode $D_s^+\to K^+K^-\pi^+$. Precision of our measurements is significantly improved compared with that of the current world average values

DNA-based vaccination against carcinoembryonic antigen

DNA vaccination is based on in vivo delivery of plasmids encoding an antigen, leading to antigen synthesis and specific immunity. This technology is still in its infancy but has advantages over conventional vaccination, such as the stimulation of all arms of the immune response, i.e., humoral immunity, T-helper (17h) cells and cytotoxic T lymphocytes (CTLs). We studied DNA vaccination against human carcinoembryonic antigen (CEA) in mice. Our hypothesis was that codelivery of cytokine- and CEA-encoding plasmids could regulate responses, and allow polarization of Th responses to either type 1 (Th1) or type 2 (Th2). We found that intramuscular injection of the CEA plasmid alone induced antibodies, Th1 cells and CTLs reactive to CEA. These mice had increased immunity against transplanted syngeneic CEA+ stably transfected tumor cell lines, but always developed lethal tumors. Coinjection of the CEA plasmid with a vector encoding either IL-12 or interferon gamma (IFNgamma) markedly enhanced IgG2a production (IFNgamma-dependent), IFNgamma secretion by spleen cells (a Th1 cytokine) and CTL-mediated tumor cell lysis, in a CEA-specific way. Moreover, resistance to a tumor challenge was greatly improved, such that up to 80% of mice survived tumor free. In contrast, coinjection of CEA and IL-4 genes increased CEA-specific IgG1 levels (IL-4-dependent) and IL-4 secretion by lymphocytes (a Th2 cytokine), but decreased both CTL activity and tumor resistance. Thus, we could readily enhance or polarize immunity. The IL-12 cDNA had the strongest adjuvant effect, which was only observed when it was injected at the same site as the CEA gene. To analyze effector components, we studied IL-12-plasmid-enhanced DNA vaccination in gene knockout mice, lacking either CD3, CD4, CD8. IFNgamma, perforin or Fas ligand (FasL). Only mice expressing all of CD3, CD4, IFNgamma, CD8 and perforin, and inoculated with both the CEA and IL-12 genes, could fully resist a tumor challenge. The Fas/FasL lyti

Palladium-Catalyzed Cascade Cyclization-Oxidative Olefination of tert-Butyl 2-Alkynylbenozates

Palladium(II) can catalyze the oxidative coupling of tert-butyl 2-alkynylbenzoates with olefins such as acrylates and styrenes, leading to isocoumarines. The reaction was carried out under simple aerobic conditions, and in most cases, high selectivity has been attained

rationaldesignofavisiblelightphotochromicdiaryletheneasimplestrategybyextendingconjugationwithelectrondonatinggroups

Photochromic diarylethenes have been widely used in many fields. however, their cyclization process must be induced by uv light. in this article, a simple strategy is developed by extending pi-conjugation with electron donating groups. the modified dirylethene derivative can photocyclolize under 405-nm light with a good photochromic efficiency. meanwhile, its absorption and moderate fluorescence can be switched effectively in both directions by visible lights (405 and 520 nm, respectively) in different solutions and in living cells. we believe that this simple method will become a versatile strategy for developing various dirylethylenes with visible-light photochromism

thesemirigidvibratingrotortargetmodelforatompolyatomresationapplicationtofch2d2ch2dchd2dfhf

由于含时波包方法具有经典的直观又不乏量子力学的准确，选择含时波包方法来处理F+CH2D2→CH2D／CHD2+DF／HF反应．把半刚性振转子(SVRT)模型应用到该反应体系中，研究了两个通道中该反应从基态反应物开始在修正过的J1(MJ1)势能面上计算出来了反应几率、积分截面、速率常数．反应几率随能量变化的图的数值结果给出了振荡结构，这些振荡结构是可以和动力学振荡联系起来的．而这些振荡结构在积分截面随着能量变化的图中就被反应几率求和后的平均结果所掩盖了．速率常数和实验结果的比较也得到了较好的结果

thesemirigidvibratingrotortargetmodelforatompolyatomresationapplicationtofch2d2ch2dchd2dfhf

由于含时波包方法具有经典的直观又不乏量子力学的准确，选择含时波包方法来处理F+CH2D2→CH2D／CHD2+DF／HF反应．把半刚性振转子(SVRT)模型应用到该反应体系中，研究了两个通道中该反应从基态反应物开始在修正过的J1(MJ1)势能面上计算出来了反应几率、积分截面、速率常数．反应几率随能量变化的图的数值结果给出了振荡结构，这些振荡结构是可以和动力学振荡联系起来的．而这些振荡结构在积分截面随着能量变化的图中就被反应几率求和后的平均结果所掩盖了．速率常数和实验结果的比较也得到了较好的结果