Plasmid rescue was performed on an oncogenically transformed cell line established by transfection of NIH/3T3 cells with normal mouse DNA and plasmids containing a murine leukemia virus long terminal repeat, and a selectable marker. One of the rescued plasmids contained newly acquired DNA 3,500 basepairs in length. This sequence was present in several extra copies in the parental cell line. It was also found to be transcribed. NIH/3T3 cells transfected with the rescued plasmid proved to be oncogenic in nude mice. The acquired sequence appeared to contain (part of) the long terminal repeat of mouse mammary tumor virus.
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In vivo self-assembled siRNAs within small extracellular vesicles attenuate LRRK2-induced neurodegeneration in Parkinson's disease models.
J Control Release
December 2024
Nanjing Drum Tower Hospital Center of Molecular Diagnostic and Therapy, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210023, China; The Second People's Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu 213003, China. Electronic address:
Rationale: Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene play an important role in Parkinson's disease (PD) pathogenesis, and downregulation of LRRK2 has become a promising therapy for PD. Here, we developed a synthetic biology strategy for the self-assembly and delivery of small interfering RNAs (siRNAs) of LRRK2 into the substantia nigra via small extracellular vesicles (sEVs) using a genetic circuit (in the form of naked DNA plasmid) to attenuate PD-like phenotypes in mouse model.
Methods: We generated the genetic circuit encoding both a neuron-targeting rabies virus glycoprotein (RVG) tag and a LRRK2 siRNA under the control of a cytomegalovirus (CMV) promoter, and assessed its therapeutic effects using LRRK2 mouse models of PD.
Dosage suppressors of gpn2ts mutants and functional insights into the role of Gpn2 in budding yeast.
PLoS One
December 2024
College of Life Sciences, Hebei Agricultural University, Baoding, Hebei, China.
Gpn2 is a highly conserved protein essential for the assembly of RNA polymerase II (RNAPII) in eukaryotic cells. Mutations in Gpn2, specifically Phe105Tyr and Leu164Pro, confer temperature sensitivity and significantly impair RNAPII assembly. Despite its crucial role, the complete range of Gpn2 functions remains to be elucidated.
View Article and Find Full Text PDFAndrographolide attenuates SARS-CoV-2 infection via an up-regulation of glutamate-cysteine ligase catalytic subunit (GCLC).
Phytomedicine
November 2024
Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand; Center for Neuroscience, Faculty of Science, Mahidol University, Bangkok 10400, Thailand. Electronic address:
Article Synopsis
- Andrographolide, a medicinal compound, shows potential anti-SARS-CoV-2 activity by targeting cellular pathways, particularly involving the NRF2 transcription factor in lung epithelial cells.
- The study used various methods like immunofluorescence staining and proteomic analysis to investigate the effects of andrographolide on infected lung cells, focusing on gene expression and cellular glutathione levels.
- Results revealed that andrographolide enhances NRF2 expression and promotes glutathione production, which could help counteract SARS-CoV-2 infection effects in lung cells.
Efficacy of colistin-based combinations against pandrug-resistant whole-genome-sequenced Klebsiella pneumoniae isolated from hospitalized patients in Egypt: an in vitro/vivo comparative study.
Gut Pathog
December 2024
Microbiology and Immunology Department, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
Background: Colistin resistance significantly constrains available treatment options and results in the emergence of pandrug-resistant (PDR) strains. Treating PDR infections is a major public health issue. A promising solution lies in using colistin-based combinations.
View Article and Find Full Text PDFEstablishment of a Reverse Genetics System for Rotavirus Vaccine Strain LLR and Developing Vaccine Candidates Carrying VP7 Gene Cloned From Human Strains Circulating in China.
J Med Virol
December 2024
National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), NHC Key Laboratory for Medical Virology and Viral Diseases, National Institute for Viral Diseases Control and Prevention, Beijing, China.
Human rotavirus A (RVA) causes acute gastroenteritis in infants and young children. The LLR RVA vaccine, which licensed in 2000 and widely used in China, significantly reduced rotavirus disease burden in China. With the changing of RV circulating strains and the emergence of new genotypes, the LLR vaccine against RVGE needed to be upgraded.
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