Project description:Experimental V4020 is derived from VEEV TC-83, a vaccine with a long track record of use in lab and military personnel at risk. V4020 was generated from an infectious DNA clone, secured genetic stability by employing stabilizing mutation at position 120 in the E2 protein, and by rearrangement of structural genes. In this study, serial passages in brain tissues of mice were performed to compare safety and genetic stability of V4020 and TC-83 experimental vaccines. During five serial passages in brain, less severe clinical manifestations and lower viral load were observed in V4020 mice and all animals survived. In contrast, 13.3% of mice met euthanasia criteria during the passages in TC-83 group. At 2 DPI, RNA-Seq analysis of brain tissues revealed that V4020 mice had lower rates of mutations throughout five passages. Higher synonymous mutation ratio was observed in the nsP4 (RdRP) gene of TC-83 compared to V4020 mice. At 2 DPI, both viruses induced different expression profiles of host genes involved into neuro-regeneration. Taken together, these results provide evidence for the improved safety and genetic stability of the experimental V4020 VEEV vaccine in a murine model. While no single nucleotide polymorphisms that have been previously linked to virulence were identified, more neuro-virulence markers were observed in serial passaged TC-83 compared to V4020. This study suggests a complex polygenic basis for neuro-virulent reversion in VEEV live attenuated vaccines and provides evidence for the advanced safety and genetic stability of V4020.
Project description:We carried out the analysis using human skin fibrobllast HCA2 (MJ90) cells. Cells were indcued to be senescent cells by treatment with doxorubicin for 24 hrs, tert-butyl-hydroperoxide for 24 hrs, or serial passages as well as nultin3a + RO3306. As a result, we found simailar transcriptome signatures among senescent cells induced by various stimuli
2019-10-08 | GSE138508 | GEO
Project description:Generation and Characterization of Lung Cancer PDX Models from Human Specimens Across Serial Passages
Project description:Comparison of DNA copy number changes between human sarcomas and corresponding xenografts, as well as between xenograft serial passages. Array CGH was performed using a homemade 1 Mb BAC/PAC microarray on 15 cases with a total of 36 samples.
Project description:We established a large panel of preclinical models of human RCC directly from patients, faithfully reproducing the biological features of the original tumor. RCC tissues were collected for 8 years from 336 patients undergoing surgery, xenografted subcutaneously in nude mice, and serially passaged into new mice up to 13 passages. Tissue samples from the primary tumor and tumors grown in mice through passages were analyzed at the histology, genetic and for of them at the molecular levels for biological tissue stability. We established a large panel of 30 RCC models and 5 them of the clear cell type (clear cell renal cell carcinoma, CCC) were characterized at the mRNA expression level. We used Affymetrix whole genome microarrays to analyze the stability of the PDX models comparing the primary tumor (P0) with the subsequent passages in mice (P1 â¦).
Project description:This paper presents a teleoperation system of robot grasping for undefined objects based on a real-time EEG (Electroencephalography) measurement and shared autonomy. When grasping an undefined object in an unstructured environment, real-time human decision is necessary since fully autonomous grasping may not handle uncertain situations. The proposed system allows involvement of a wide range of human decisions throughout the entire grasping procedure, including 3D movement of the gripper, selecting proper grasping posture, and adjusting the amount of grip force. These multiple decision-making procedures of the human operator have been implemented with six flickering blocks for steady-state visually evoked potentials (SSVEP) by dividing the grasping task into predefined substeps. Each substep consists of approaching the object, selecting posture and grip force, grasping, transporting to the desired position, and releasing. The graphical user interface (GUI) displays the current substep and simple symbols beside each flickering block for quick understanding. The tele-grasping of various objects by using real-time human decisions of selecting among four possible postures and three levels of grip force has been demonstrated. This system can be adapted to other sequential EEG-controlled teleoperation tasks that require complex human decisions.