基于NGS的染色质测序在肿瘤研究中的应用

染色质是真核生物细胞核内由核酸和蛋白质组成的复合结构,有着精密且复杂的三维结构。染色质除基本的DNA序列外,内部还存在着不同化学修饰,DNA-蛋白质相互作用,DNA-DNA相互作用和DNA-RNA相互作用,以上这些若发生改变都可能在肿瘤发生发展过程中起到至关重要的作用。通过不同的染色质测序方法,可以解析出这些改变,并进一步加深研究者对肿瘤形成机制的理解,最终应用于肿瘤的治疗。本文对常见的染色质测序技术部分原理和应用进行综述。     

Molecular Evolution of Visual Opsin Genes during the Behavioral Shifts between Different Photic Environments in Geckos

Reptiles are the most morphologically and physiologically diverse tetrapods, with the squamates having the most diverse habitats. Lizard is an important model system for understanding the role of visual ecology,phylogeny and behavior on the structure of visual systems.In this study, we compared three opsin genes(RH2, LWS and SWS1) among 49 reptile species to detect positively selected genes as well as amino acid sites. Our results indicated that visual opsin genes have undergone divergent selection pressures in all lizards and RH2 and LWS suffered stronger positive selection than SWS1. Twelve positively selected sites were picked out for RH2 and LWS. Moreover,many diagnostic sites were found between geckos and non-gecko lizards, most of which were located near the positively selected sites and some of them have already been reported to be responsible for significant shifts of the wavelength of maximum absorption(λ_(max)). The results indicated that the gecko lineage accelerated the evolution of these genes to adapt to the dim-light environment or nocturnality as well as the switch between nocturnality and diurnality.     

Piezoelectric Pump Used in Bionic Underwater Propulsion Unit

A new piezoelectric pump can pump liquid either forward or backward and adjust the flow rate. Thus an object can be driven forward or backward at different speeds. The driver of the pump, a circular piezoelectric plate, is modelled by Finite Element Method （FEM） in ANSYS and its performance is simulated and analyzed. The pump gives the best performance when the driving signals of the inlet and outlet valves have a bigger duty cycle and the plate has a higher voltage applied.     

Characterizing mobile element insertions in 5675 genomes

Mobile element insertions (MEIs) are a major class of structural variants (SVs) and have been linked to many human genetic disorders, including hemophilia, neurofibromatosis, and various cancers. However, human MEI resources from large-scale genome sequencing are still lacking compared to those for SNPs and SVs. Here, we report a comprehensive map of 36 699 non-reference MEIs constructed from 5675 genomes, comprising 2998 Chinese samples (∼26.2×, NyuWa) and 2677 samples from the 1000 Genomes Project (∼7.4×, 1KGP). We discovered that LINE-1 insertions were highly enriched in centromere regions, implying the role of chromosome context in retroelement insertion. After functional annotation, we estimated that MEIs are responsible for about 9.3% of all protein-truncating events per genome. Finally, we built a companion database named HMEID for public use. This resource represents the latest and largest genomewide study on MEIs and will have broad utility for exploration of human MEI findings.     

HMGB3 promotes PARP inhibitor resistance through interacting with PARP1 in ovarian cancer

Poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) resistance remains a therapeutic challenge in ovarian cancer. High-mobility group box 3 (HMGB3) plays significant roles in the development of drug resistance of many cancers. However, the function of HMGB3 in PARPi resistance is poorly understood. In the current study, we clarified that HMGB3 was aberrantly overexpressed in high-grade serous ovarian carcinoma (HGSOC) tissues, and high HMGB3 levels indicated shorter overall survival and drug resistance in HGSOC. The overexpression of HMGB3 increased the insensitivity of ovarian cancer to PARPi, whereas HMGB3 knockdown reduced PARPi resistance. Mechanistically, PARP1 was identified as a novel interaction partner of HMGB3, which could be blocked using olaparib and was enhanced upon DNA damage conditions. We further showed that loss of HMGB3 induced PARP1 trapping at DNA lesions and inhibited the PARylation activity of PARP1, resulting in an increased DNA damage response and cell apoptosis. The PARPi-resistant role of HMGB3 was also verified in a xenograft mouse model. In conclusion, HMGB3 promoted PARPi resistance via interacting with PARP1, and the targeted inhibition of HMGB3 might overcome PARPi resistance in ovarian cancer therapy.Subject terms: Chemotherapy, Ovarian cancer, Ovarian cancer, Cancer therapeutic resistance     

Enhanced retroviral transduction of 293 cells cultured on liquid-liquid interfaces

In clinical research, retrovirus-mediated gene therapy is one of the most commonly used methods to deliver and express the gene of interest due its ability to allow for stable gene integration into the chromosomes of target cells. To elevate the efficiency of viral transduction, several restrictions, such as low virus-cell encounters and the necessity for cell division, must be improved. In this study, we focused on the possibility of accelerating cell division and the ensuing increment of viral transduction on flexible substrata. Perfluorocarbon FC-40 was harnessed to form a liquid-liquid interface with culture medium. Enhanced green fluorescence protein (EGFP) was employed as the marker gene to quickly illustrate the percentage of viral infection. The results indicate that the gene transfer efficiency to 293 cells cultured on protein-precoated liquid-liquid interfaces was higher than in cells cultured on rigid polystyrene surfaces. This increased transduction rate on the liquid-liquid interface is consistent with the acceleration of division of 293 cells on a flexible interface, which exhibited less adhesiveness. The effect of cell-cell contact inhibition on the rate of gene transduction is also addressed in this study.