Realistic and Theoretical 3D Modelling of the Sedimentation, Burial, Thermal and Tectonic History of the Gippsland Rift Basin

The project investigated the sedimentary, burial, thermal and tectonic history of the Gippsland rift basin, using a realistic 3D structural and stratigraphic model of the basin to constrain theoretical deterministic models, including 3D forward palaeo-landscape models and 3D burial and thermal models of the entire Gippsland Basin. An efficient Experimental Design approach was used to guide the scenario set-up for the numerical simulation software, process the palaeo-landscape results, and identify the important controlling variables

HEN1 recognizes 21-24 nt small RNA duplexes and deposits a methyl group onto the 2' OH of the 3' terminal nucleotide.

microRNAs (miRNAs) and small interfering RNAs (siRNAs) in plants bear a methyl group on the ribose of the 3' terminal nucleotide. We showed previously that the methylation of miRNAs and siRNAs requires the protein HEN1 in vivo and that purified HEN1 protein methylates miRNA/miRNA* duplexes in vitro. In this study, we show that HEN1 methylates both miRNA/miRNA* and siRNA/siRNA* duplexes in vitro with a preference for 21-24 nt RNA duplexes with 2 nt overhangs. We also demonstrate that HEN1 deposits the methyl group on to the 2' OH of the 3' terminal nucleotide. Among various modifications that can occur on the ribose of the terminal nucleotide, such as 2'-deoxy, 3'-deoxy, 2'-O-methyl and 3'-O-methyl, only 2'-O-methyl on a small RNA inhibits the activity of yeast poly(A) polymerase (PAP). These findings indicate that HEN1 specifically methylates miRNAs and siRNAs and implicate the importance of the 2'-O-methyl group in the biology of RNA silencing

CAS9 is a genome mutator by directly disrupting DNA-PK dependent DNA repair pathway.

With its high efficiency for site-specific genome editing and easy manipulation, the clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR associated protein 9 (CAS9) system has become the most widely used gene editing technology in biomedical research. In addition, significant progress has been made for the clinical development of CRISPR/CAS9 based gene therapies of human diseases, several of which are entering clinical trials. Here we report that CAS9 protein can function as a genome mutator independent of any exogenous guide RNA (gRNA) in human cells, promoting genomic DNA double-stranded break (DSB) damage and genomic instability. CAS9 interacts with the KU86 subunit of the DNA-dependent protein kinase (DNA-PK) complex and disrupts the interaction between KU86 and its kinase subunit, leading to defective DNA-PK-dependent repair of DNA DSB damage via non-homologous end-joining (NHEJ) pathway. XCAS9 is a CAS9 variant with potentially higher fidelity and broader compatibility, and dCAS9 is a CAS9 variant without nuclease activity. We show that XCAS9 and dCAS9 also interact with KU86 and disrupt DNA DSB repair. Considering the critical roles of DNA-PK in maintaining genomic stability and the pleiotropic impact of DNA DSB damage responses on cellular proliferation and survival, our findings caution the interpretation of data involving CRISPR/CAS9-based gene editing and raise serious safety concerns of CRISPR/CAS9 system in clinical application

Response of Freshwater Biofilm to pollution and ecosystem in Baiyangdian Lake of China

AbstractAn experimental study was undertaken to highlight the potential applicability of biofilms as biomonitors forming simultaneously on natural and artificial substrata in Baiyngdian Lake(China).We investigated the responses of freshwater biofilm in 8 site of Baiyngdian Lake and compared with control site (a reservoir) to assess the relative health of water. Exposure to pollution and its impact on biofilms were assessed by measuring the biomass production, Chlorophyll concentration, the algal composition, extracellular enzyme activity of bacterial communities and Polysaccharide content. This relation between the biological characters of biofilms and water quality were discussed, and the relative health of regions were demonstrated by the degree of deviation based on bioflim indicator in the following order: Fu river (S4) < Duan cun (S8) < Nan Liuzhuang (S5) < Wang jiazai (S1) < Cai putai (S7) < Zao lingzhuang (S2)< Shao Chedian (S3).. The result indicated that biofilm can provide information for pollution detection and ecological health assessment of water, and biofilm on aritificial substrata was recommended for biomonitoring in the Baiyangdian Lake

MTR4 drives liver tumorigenesis by promoting cancer metabolic switch through alternative splicing.

The metabolic switch from oxidative phosphorylation to glycolysis is required for tumorigenesis in order to provide cancer cells with energy and substrates of biosynthesis. Therefore, it is important to elucidate mechanisms controlling the cancer metabolic switch. MTR4 is a RNA helicase associated with a nuclear exosome that plays key roles in RNA processing and surveillance. We demonstrate that MTR4 is frequently overexpressed in hepatocellular carcinoma (HCC) and is an independent diagnostic marker predicting the poor prognosis of HCC patients. MTR4 drives cancer metabolism by ensuring correct alternative splicing of pre-mRNAs of critical glycolytic genes such as GLUT1 and PKM2. c-Myc binds to the promoter of the MTR4 gene and is important for MTR4 expression in HCC cells, indicating that MTR4 is a mediator of the functions of c-Myc in cancer metabolism. These findings reveal important roles of MTR4 in the cancer metabolic switch and present MTR4 as a promising therapeutic target for treating HCC