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.

The renin-angiotensin system plays an important role in the maintenance of blood pressure homeostasis. The angiotensin-converting enzyme (ACE) converts angiotensin I into angiotensin II. Angiotensin II, which binds the angiotensin II type-1 receptor (AT1R), is a potent vasoconstrictor. On a pathophysiological basis, both ACE I/D and AT1R A1166C polymorphism lead to an enhanced activity of the angiotensin II-AT1R axis, thereby possibly contributing to circulatory disturbances. A mutually facilitatory effect may be presumed between the two polymorphisms. We examined whether this synergistic effect is involved in the evolution of different types of ischemic stroke. Genetic and clinical data on 308 consecutive patients with acutely developing ischemic stroke were analyzed. A total of 272 stroke and neuroimaging alteration-free subjects served as a control group. Univariate and logistic regression statistical approaches were used. The ACE D allele combined with the AT1R 1166C allele did not yield a risk of ischemic stroke. However, the co-occurrence of the homozygous ACE D/D and at least one AT1R 1166C allele was more frequent in the ischemic stroke group than in the control group (22.4 vs 11%, p < 0.005, OR, 2.33; 95% CI, 1.46-3.7). After specific subgroup analysis, this synergistic association was even stronger for small-vessel ischemic stroke (OR, 3.44; 95% CI, 1.9-6.24; p < 0.0005). Multivariate logistic regression analysis of the data confirmed this association (adjusted OR, 3.54, 95% CI, 1.88-7.16; p < 0.0005). Our results demonstrate that ACE D/D and AT1R 1166C NeuroMolecular Medicine
Coexistence of Angiotensin II Type-1 Receptor A1166C and Angiotensin-Converting Enzyme D/D Polymorphism Suggests Susceptibility for Small-Vessel-Associated Ischemic Stroke

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
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)

SARS coronavirus (SARS-CoV) develops an antagonistic mechanism by which to evade the antiviral activities of interferon (IFN). Previous studies suggested that SARS-CoV papain-like protease (PLpro) inhibits activation of the IRF3 pathway, which would normally elicit a robust IFN response, but the mechanism(s) used by SARS PLpro to inhibit activation of the IRF3 pathway is not fully known. In this study, we uncovered a novel mechanism that may explain how SARS PLpro efficiently inhibits activation of the IRF3 pathway. We found that expression of the membrane-anchored PLpro domain (PLpro-TM) from SARS-CoV inhibits STING/ TBK1/IKKε-mediated activation of type I IFNs and disrupts the phosphorylation and dimerization of IRF3, which are activated by STING and TBK1. Meanwhile, we showed that PLpro-TM physically interacts with TRAF3, TBK1, IKKε, STING, and IRF3, the key components that assemble the STING-TRAF3-TBK1 complex for activation of IFN expression. However, the interaction between the components in STING-TRAF3-TBK1 complex is disrupted by PLpro-TM. Furthermore, SARS PLpro-TM reduces the levels of ubiquitinated forms of RIG-I, STING, TRAF3, TBK1, and IRF3 in the STING-TRAF3-TBK1 complex. These results collectively point to a new mechanism used by SARS-CoV through which PLpro negatively regulates IRF3 activation by interaction with STING-TRAF3-TBK1 complex, yielding a SARS-CoV countermeasure against host innate immunity.

SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3- TBK1 complex