In this task, you're given a paragraph and title from the research paper. Your task is to classify whether the given title is suitable or not for the research paper based on the given paragraph. Return "True" if title is proper according to paragraph else "False".

Input: Consider Input: Paragraph: Apelin is an inotropic and cardioprotective peptide that exhibits beneficial effects through activation of the APJ receptor in the pathology of cardiovascular diseases. Apelin induces the expression of angiotensin-converting enzyme 2 (ACE2) in failing hearts, thereby improving heart function in an angiotensin 1-7-dependent manner. Whether apelin antagonizes the over-activation of the renin-angiotensin system in the heart remains elusive. In this study we show that the detrimental effects of angiotensin II (Ang II) were exacerbated in the hearts of aged apelin-gene-deficient mice. Ang II-mediated cardiac dysfunction and hypertrophy were augmented in apelin knockout mice. The loss of apelin increased the ratio of angiotensin-converting enzyme (ACE) to ACE2 expression in the Ang II-stressed hearts, and Ang II-induced cardiac fibrosis was markedly enhanced in apelin knockout mice. mRNA expression of pro-fibrotic genes, such as transforming growth-factor beta (TGF-β) signaling, were significantly upregulated in apelin knockout hearts. Consistently, treatment with the ACE-inhibitor Captopril decreased cardiac contractility in apelin knockout mice. In vitro, apelin ameliorated Ang II-induced TGF-β expression in primary cardiomyocytes, accompanied with reduced hypertrophy. These results provide direct evidence that endogenous apelin plays a crucial role in suppressing Ang II-induced cardiac dysfunction and pathological remodeling. Int. J. Mol. Sci. 2019, 20, 239 2 of 12 dysfunctions [8, 10, 11] . By contrast, APJ was identified as a dual receptor to mediate cardiac hypertrophy [12, 13] via β-arrestin signaling [14, 15] . Thus, the precise role of endogenous apelin signaling in heart function remains elusive. Cardiac hypertrophy is an adaptive response to maintain cardiac function in the event of an increased workload, although prolonged cardiac hypertrophy can lead to heart failure via the ischemia of cardiomyocytes [16, 17] . In addition, cardiac fibrosis adversely increases tissue stiffness and impairs ventricular function. Consistently, cardiac hypertrophy and the development of fibrosis correlate with the deterioration of myocardial function in heart failure [18] [19] [20] . Thus, cardiac hypertrophy and fibrosis are key features of heart failure, and apelin's inotropic and protective roles in the heart are attractive as a potential therapeutic candidate for treating heart failure. Apelin has also been identified as a substrate for angiotensin-converting enzyme 2 (ACE2), which cleaves apelin with similar efficiency as its primary substrate angiotensin II (Ang II) [21] [22] [23] . ACE2 is a negative regulator of the renin-angiotensin system (RAS) that inactivates Ang II by converting it to angiotensin 1-7 (Ang 1-7) [21] [22] [23] , whereas angiotensin-converting enzyme 1 (or ACE1) activates RAS by converting Ang I to Ang II. ACE2 was also identified as a regulator of heart failure [24-26], diabetic nephropathy [27, 28] , acute lung failure [29, 30] , and the SARS (severe acute respiratory syndrome) coronavirus receptor [31, 32] . Apelin-APJ signaling has been shown to counteract the effects of Ang II on AT1R in defined physiological and pathophysiological settings. For instance, in hypertensive rat models, the continuous infusion of Ang II downregulates apelin and APJ expression [33] . We have shown that Apelin upregulates ACE2 expression. Apelin-induced ACE2 downregulates Ang II signaling while enhancing Ang 1-7-Mas receptor signaling in aged or failing hearts [34] . On the other hand, it has been suggested that the counter-balancing effects of the apelin-APJ axis on Ang II-AT1R signaling are mediated by receptor dimerization. The APJ receptor physically interacts with AT1 receptors, and exogenous apelin negatively regulates Ang II-AT1R signaling in in vitro cell culture systems and in an in vivo atherosclerosis model [35] . However, whether endogenous apelin counteracts the over-activation of RAS in the heart remains unexplored. In this study, we aimed to determine the effects of endogenous apelin on Ang II-induced pathology in the heart. We showed that Ang II-mediated cardiac dysfunction, hypertrophy, and fibrosis were augmented in apelin knockout (Apelin KO) mice. 
 Title: Loss of Apelin Augments Angiotensin II-Induced Cardiac Dysfunction and Pathological Remodeling

Output: True


Input: Consider Input: Paragraph: To date, an effective therapeutic treatment that confers strong attenuation toward coronaviruses (CoVs) remains elusive. Of all the potential drug targets, the helicase of CoVs is considered to be one of the most important. Here, we first present the structure of the full-length Nsp13 helicase of SARS-CoV (SARS-Nsp13) and investigate the structural coordination of its five domains and how these contribute to its translocation and unwinding activity. A translocation model is proposed for the Upf1like helicase members according to three different structural conditions in solution characterized through H/D exchange assay, including substrate state (SARS-Nsp13-dsDNA bound with AMPPNP), transition state (bound with ADP-AlF 4 − ) and product state (bound with ADP). We observed that the ␤19-␤20 loop on the 1A domain is involved in unwinding process directly. Furthermore, we have shown that the RNA dependent RNA polymerase (RdRp), SARS-Nsp12, can enhance the helicase activity of SARS-Nsp13 through interacting with it directly. The interacting regions were identified and can be considered common across CoVs, which provides new insights into the Replication and Transcription Complex (RTC) of CoVs. 
 Title: Delicate structural coordination of the Severe Acute Respiratory Syndrome coronavirus Nsp13 upon ATP hydrolysis

Output: True


Input: Consider Input: Paragraph: We have developed a reverse genetics system for the avian coronavirus infectious bronchitis virus (IBV) in which a full-length cDNA corresponding to the IBV genome is inserted into the vaccinia virus genome under the control of a T7 promoter sequence. Vaccinia virus as a vector for the full-length IBV cDNA has the advantage that modifications can be introduced into the IBV cDNA using homologous recombination, a method frequently used to insert and delete sequences from the vaccinia virus genome. Here we describe the use of transient dominant selection as a method for introducing modifications into the IBV cDNA. We have used it successfully for the substitution of specific nucleotides, deletion of genomic regions, and the exchange of complete genes. Infectious recombinant IBVs are generated in situ following the transfection of vaccinia virus DNA containing the modified IBV cDNA into cells infected with a recombinant fowlpox virus expressing T7 DNA-dependent RNA polymerase. 
 Title: Transient Dominant Selection for the Modification and Generation of Recombinant Infectious Bronchitis Coronaviruses


Output: True