In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.
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Question: From 2002 to 2003, a global pandemic of severe acute respiratory syndrome (SARS) spread to 5 continents and caused 8000 respiratory infections and 800 deaths. To ameliorate the effects of future outbreaks as well as to prepare for biodefense, a process for the production of a recombinant protein vaccine candidate is under development. Previously, we reported the 5 L scale expression and purification of a promising recombinant SARS vaccine candidate, RBD219-N1, the 218eamino acid residue receptorbinding domain (RBD) of SARS coronavirus expressed in yeastePichia pastoris X-33. When adjuvanted with aluminum hydroxide, this protein elicited high neutralizing antibody titers and high RBD-specific antibody titers. However, the yield of RBD219-N1 (60 mg RBD219-N1 per liter of fermentation supernatant; 60 mg/L FS) still required improvement to reach our target of >100 mg/L FS. In this study, we optimized the 10 L scale production process and increased the fermentation yield 6-to 7-fold to 400 mg/ L FS with purification recovery >50%. A panel of characterization tests indicated that the process is reproducible and that the purified, tag-free RBD219-N1 protein has high purity and a well-defined structure and is therefore a suitable candidate for production under current Good Manufacturing Practice and future phase-1 clinical trials.

Answer: Optimization of the Production Process and Characterization of the Yeast-Expressed SARS-CoV Recombinant Receptor-Binding Domain (RBD219-N1), a SARS Vaccine Candidate


Question: The immunostimulatory effects of oligodeoxyribonucleotides (ODN) containing unmethylated CpG dinucleotides (CpG-ODN) in certain base contexts have been extensively studied in man and mice. One major action is their ability to trigger production of massive amounts of interferon-a (IFN-a) by plasmacytoid dendritic cells (PDC), also referred to as natural IFN-a/b producing cells (NIPC). The present study using porcine PBMC activated by CpG-ODN or plasmid DNA revealed a considerable variation in the IFN-a production in response to various CpG-ODN constructs. Several phosphodiester ODNs, such as 5 0 TTTTCAATTCGAAGATGAAT 3 0 (ODN H), and the plasmid pcDNA3 all required pre-incubation with lipofectin in order to induce IFN-a. Intact unmethylated CpGs were also important, because methylation or substitution of the cytosines and CpG-inversion strongly reduced the IFN-a induction by single-or double-stranded forms of ODN H. Certain CpG-ODNs that contained flanking phosphorothioate or phosphodiester poly-G sequences were potent inducers of IFN-a without pre-incubation with lipofectin, for instance the ODN 2216 (5 0 GGGGGACGATCGTCGGGGGG 3 0 ). While poly-G sequences have been suggested to increase uptake of ODNs by cells, they did not obviate the need for lipofectin when added to the ODN H. However, they resulted in up to five-fold increases of the IFN-a levels caused by ODN H upon lipofection, indicating other enhancing effects of poly-G sequences on the induction of IFN-a. The identity of the IFN-a producing cells (IPC) stimulated by CpG-ODN or plasmid DNA was studied by means of flow cytometry using combined staining for intracellular IFN-a and surface markers. Approximately 1-3 IPC/10 3 PBMC were detected, compared to only 3 IPC/10 4 PBMC stimulated by Aujeszky's disease virus. The IPC frequencies were confirmed by detection of IFN-a mRNA positive cells by in situ hybridisation. The IPC induced by CpG-ODN or plasmid DNA had a similar phenotype, expressing CD2 and CD4 and intermediate levels of MHC class II and the myeloid marker SWC3, but not the markers of T and B cells or

Answer: Characteristics of oligodeoxyribonucleotides that induce interferon (IFN)-a in the pig and the phenotype of the IFN-a producing cells monocytes (CD3, CD21 and CD14)


Question: , the active isoform of X-box binding protein 1 (XBP-1), is a key regulator of UPR. Previously, we showed that a histone acetyltransferase (HAT), p300/CBP-associated factor (PCAF), binds to XBP-1S and functions as an activator of XBP-1S. Here, we identify general control nonderepressible 5 (GCN5), a HAT with 73% identity to PCAF, as a novel XBP-1S regulator. Both PCAF and GCN5 bind to the same domain of XBP-1S. Surprisingly, GCN5 potently blocks the XBP-1Smediated transcription, including cellular UPR genes and latent membrane protein 1 of Epstein-Barr virus. Unlike PCAF, GCN5 acetylates XBP-1S and enhances nuclear retention and protein stability of XBP-1S. However, such GCN5-mediated acetylation of XBP-1S shows no effects on XBP-1S activity. In addition, the HAT activity of GCN5 is not required for repression of XBP-1S target genes. We further demonstrate that GCN5 inhibits XBP-1S-mediated transcription by disrupting the PCAF-XBP-1S interaction and preventing the recruitment of XBP-1S to its target genes. Taken together, our results represent the first work demonstrating that GCN5 and PCAF exhibit different functions and antagonistically regulate the XBP-1S-mediated transcription. Oncotarget 272

Answer:
Oncotarget, Vol. 6, No. 1 GCN5 inhibits XBP-1S-mediated transcription by antagonizing PCAF action