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General Introductory Topics
Published in Vadim Backman, Adam Wax, Hao F. Zhang, A Laboratory Manual in Biophotonics, 2018
Vadim Backman, Adam Wax, Hao F. Zhang
Transcription factors are DNA-binding proteins. Some DNA-binding proteins are activators, while others are repressors. Their names tell it all: Activators increase the rate of gene transcription, while repressors do the opposite. These factors are critically important in transcription, as without their help, only a very low level of transcriptional activity would be possible. Other modulator molecules include coactivators—proteins that assist transcription factors to increase the rate of gene transcription—and corepressors—proteins that work with transcription factors to decrease the rate of transcription.
The roadmap towards cure of chronic hepatitis B virus infection
Published in Journal of the Royal Society of New Zealand, 2022
In contrast, HBx binds the HBV minichromosome and modifies the epigenetic regulation of cccDNA function. HBV X-inhibitors may be a potential approach to silence cccDNA without off-target effects. Direct gene editing approaches include cccDNA degradation through IFN-α/Lymphotoxin-β receptor agonist (via APOBEC3A/B), or cccDNA cleavage via nucleases including Zinc-finger nucleases (ZFNs), transcription-activator like effector nucleases (TALENS) and CRISPR/Cas9 approach. In in vitro experiments, combining Cas9 with guide RNAs which target conserved regions within HBV cccDNA, achieves profound reductions in cccDNA and all HBV proteins (Wang et al. 2017). In addition to destroying cccDNA, CRISPR/Cas9 will also remove HBV integrins from the host genome, thereby reducing any long-term risk of hepatocarcinogenesis. The important challenges facing the successful use of gene editing approaches in patients include how to measure efficacy (no standardised cccDNA quantification assay), how to deliver the drug efficiently to the nucleus of every infected hepatocyte and finally, how to mitigate the long-term risks of chromosomal translocation in otherwise healthy young people (Table 1).
In vivo immune activation of splenocytes following exposure to tar from Asian sand dust
Published in Journal of Toxicology and Environmental Health, Part A, 2020
Mengyue Shen, Yuan Song, Takamichi Ichinose, Kentaro Morita, Duo Wang, Keiichi Arashidani, Yasuhiro Yoshida
Redox-active organic chemicals on the particle surface play important roles in PM-induced inflammation (Kepley et al. 2003; Li et al. 2009; Nalepa, Siemianowska, and Skibniewska 2012; Ng et al. 1998). In this study, it is possible that the oxidative stress induced by the combination of heated-ASD and PAHs in tar was involved in splenic inflammation. Ng et al. (1998) demon strated that PAHs activated the transcription factor, activator protein-1 (AP-1), through mitogen-activated protein kinase (MAPK). Li et al. (2009) showed that high levels of PAH-associated oxidative stress activated MAPK and NF-κB and induced several inflammatory responses. However, our data noted that NF-κB activation was not observed in response to tar administration. This is consistent with non-enhancement of LPS-induced IL-6 and TNF-α production in splenocytes. However, NFAT was significantly activated by tar administration, indicating that T cell activation might be the main cause of this inflammation.
Gene doping: Present and future
Published in European Journal of Sport Science, 2020
Rebeca Araujo Cantelmo, Alessandra Pereira da Silva, Celso Teixeira Mendes-Junior, Daniel Junqueira Dorta
Some techniques have been helpful to leverage research in the field of gene editing, increasingly contributing to gene editing development and improvement. Among these techniques, zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and particularly the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR associated protein 9 (CRISPR-Cas9) are noteworthy. These tools are applied in genetic manipulation and have diverse functions including gene introduction or replacement, precise DNA insertion or deletions of various lengths, and production of knock-in and knockout animals and plants. However, all these genome-editing techniques require several processes to evaluate and to regularize their practice so that the underlying risks are known and their misuse can be avoided in the future (Fears & Meulen, 2017; Mashimo, 2014).