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991.
Young-Wook Chin Woo-Kyung Kang Hae Won Jang Timothy L. Turner Hyo Jin Kim 《Journal of industrial microbiology & biotechnology》2016,43(11):1517-1525
Enormous advances in genome editing technology have been achieved in recent decades. Among newly born genome editing technologies, CRISPR/Cas9 is considered revolutionary because it is easy to use and highly precise for editing genes in target organisms. CRISPR/Cas9 technology has also been applied for removing unfavorable target genes. In this study, we used CRISPR/Cas9 technology to reduce ethyl carbamate (EC), a potential carcinogen, which was formed during the ethanol fermentation process by yeast. Because the yeast CAR1 gene encoding arginase is the key gene to form ethyl carbamate, we inactivated the yeast CAR1 gene by the complete deletion of the gene or the introduction of a nonsense mutation in the CAR1 locus using CRISPR/Cas9 technology. The engineered yeast strain showed a 98 % decrease in specific activity of arginase while displaying a comparable ethanol fermentation performance. In addition, the CAR1-inactivated mutants showed reduced formation of EC and urea, as compared to the parental yeast strain. Importantly, CRISPR/Cas9 technology enabled generation of a CAR1-inactivated yeast strains without leaving remnants of heterologous genes from a vector, suggesting that the engineered yeast by CRISPR/Cas9 technology might sidestep GMO regulation. 相似文献
992.
Zhezhu Han Seungha Lee Suyeon Je Chi-Yong Eom Hye Jin Choi Jae J. Song Joo-Hang Kim 《Apoptosis : an international journal on programmed cell death》2016,21(3):351-364
In this study, we demonstrated that survivin downregulation with TRAIL expression greatly enhanced the cytotoxic death of pancreatic cancer cells after gemcitabine treatment. Using real-time RT-PCR, we analyzed five survivin shRNAs to identify the best target sequence for suppression of human survivin, with the goal of treating gemcitabine-resistant pancreatic cancer cells. Survivin shRNA 5, corresponding to target 5, showed the greatest reduction in survivin mRNA levels. Furthermore, combined treatment with survivin shRNA-expressing adenovirus with gemcitabine plus TRAIL decreased uncleaved PARP and increased consequent PARP cleavage, which was correlated with the greatest levels of survivin downregulation and cell death. These results indicate that survivin functions as a common mediator of gemcitabine- and TRAIL-induced cell death. Using a nude mouse model implanted with MiaPaCa-2 pancreatic cancer cells, we observed tumor regression induced by an oncolytic adenovirus expressing survivin shRNA and TRAIL plus gemcitabine. Together, our findings provide a strong rationale for treating pancreatic cancer patients with both gemcitabine and oncolytic adenovirus armed with survivin shRNA and TRAIL. 相似文献
993.
994.
Joon Ha Park Bich Na Shin Ji Hyeon Ahn Jeong-Hwi Cho In Hye Kim Dae Won Kim Moo-Ho Won Seongkweon Hong Jun Hwi Cho Choong-Hyun Lee 《Cellular and molecular neurobiology》2016,36(5):821-828
Proline-rich Akt substrate of 40-kDa (PRAS40) is one of the important interactive linkers between Akt and mTOR signaling pathways. The increase of PRAS40 is related with the reduction of brain damage induced by cerebral ischemia. In the present study, we investigated time-dependent changes in PRAS40 and phospho-PRAS40 (p-PRAS40) immunoreactivities in the hippocampal CA1 region of the gerbil after 5 min of transient cerebral ischemia. PRAS40 immunoreactivity in the CA1 region was decreased in pyramidal neurons from 12 h after ischemic insult in a time-dependent manner, and, at 5 days post-ischemia, PRAS40 immunoreactivity was newly expressed in astrocytes. p-PRAS40 immunoreactivity in the CA1 pyramidal neurons was hardly found 12 h and apparently detected again 1 and 2 days after ischemic insult. At 5 days post-ischemia, p-PRAS40 immunoreactivity in the CA1 pyramidal neurons was not found. These results indicate that ischemia-induced changes in PRAS40 and p-PRAS40 immunoreactivities in CA1 pyramidal neurons and astrocytes may be closely associated with delayed neuronal death in the hippocampal CA1 region following transient cerebral ischemia. 相似文献
995.
996.
Mitochondrial Dysfunction and Ca2+ Overload Contributes to Hesperidin Induced Paraptosis in Hepatoblastoma Cells,HepG2 下载免费PDF全文
997.
998.
The signal peptide peptidase SppA is involved in sterol regulatory element‐binding protein cleavage and hypoxia adaptation in Aspergillus nidulans 下载免费PDF全文
Sun‐Ki Koh Mee‐Hyang Jeon Dawoon Chung Yin‐Won Lee Suhn‐Kee Chae 《Molecular microbiology》2016,100(4):635-655
Using forward genetics, we revealed that the signal peptide peptidase (SPP) SppA, an aspartyl protease involved in regulated intramembrane proteolysis (RIP), is essential for hypoxia adaptation in Aspergillus nidulans, as well as hypoxia‐sensitive mutant alleles of a sterol regulatory element‐binding protein (SREBP) srbA and the Dsc ubiquitin E3 ligase complex dscA‐E. Both null and dead activity [D337A] mutants of sppA failed to grow in hypoxia, and the growth defect of ΔsppA was complemented by nuclear SrbA‐N381 expression. Additionally, SppA interacted with SrbA in the endoplasmic reticulum, where SppA localized in normoxia and hypoxia. Expression of the truncated SrbA‐N414 covering the SrbA sequence prior to the second transmembrane region rescued the growth of ΔdscA but not of ΔsppA in hypoxia. Unlike ΔdscA and ΔdscA;ΔsppA double mutants, in which SrbA cleavage was blocked, the molecular weight of cleaved SrbA increased in ΔsppA compared to the control strain in immunoblot analyses. Overall, our data demonstrate the sequential cleavage of SrbA by Dsc‐linked proteolysis followed by SppA, proposing a new model of RIP for SREBP cleavage in fungal hypoxia adaptation. Furthermore, the function of SppA in hypoxia adaptation was consistent in Aspergillus fumigatus, suggesting the potential roles of SppA in fungal pathogenesis. 相似文献
999.
1000.
Byoung‐Hoon Min Jun‐Seop Shin Won Young Jeong Ga Eul Lee Min Sun Kim Ju Eun Kim Chung‐Gyu Park 《Journal of medical primatology》2016,45(4):206-208
Autoimmune bullous disease is very uncommon in non‐human primates. We observed a bullous skin disease in a male rhesus monkey while conducting porcine islet xenotransplantation. Fifty days after the transplantation, multiple bullous skin lesions were observed. There was no mucosal involvement. Skin biopsy results demonstrated a subepidermal blister with no necrotic keratinocytes. Immunofluorescent staining showed linear IgG deposition at the roof of the blister. These skin lesions spontaneously disappeared. Considering these results, this monkey was diagnosed with bullous pemphigoid (BP). As far as we know, this is the first report of BP in non‐human primates. 相似文献