instruction:
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".
question:
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
answer:
True


question:
Paragraph: Experimental coronavirus retinopathy (ECOR) is a virally triggered model of retinal degeneration composed of both genetic and autoimmune components. Since TNF-a plays a role in immune-mediated processes we evaluated the levels of TNF-a/TNF-a receptors and the downstream signaling molecule nitric oxide (NO) during disease in both retinal degeneration susceptible BALB/c and degeneration resistant CD-1 mice. Following coronavirus injection, TNF-a mRNA was detected at higher levels within the retinas, and concentrations of TNF-a ( p < 0.005) and sTNFR1 ( p < 0.0005) proteins were increased within the sera of BALB/c but not CD-1 mice. While concentrations of sTNFR2 proteins were elevated in both BALB/c ( p < 0.00005) and CD-1 ( p < 0.005) mice compared to controls, concentrations were higher in BALB/c mice ( p < 0.0005). Gene expression of iNOS while initially high in BALB/c mice decreased during the acute phase of infection, while it increased in CD-1 mice. These trends are attributable to differences in monocyte TNFR2 release ( p < 0.0005) between the strains since sTNFR2 decreased ( p < 0.01) levels of NO production. These studies demonstrate that retinal degeneration following viral infection is associated with increased release of TNF-a/TNF receptors combined with a down-regulation of NO. Furthermore they suggest that these molecules are involved in alterations in immune response leading to autoimmune reactivity. Published by Elsevier B.V. 
 Title: Retinal degeneration in experimental coronavirus retinopathy (ECOR) is associated with increased TNF-a, soluble TNFR2 and altered TNF-a signaling
answer:
False


question:
Paragraph: Viral envelope glycoproteins are oligomeric and the quaternary structure is critical for their membrane fusion activity. Typically the transmembrane glycoproteins of class I fusion proteins contain the oligomerization domains and the surface glycoproteins (SU) are monomeric. However, it has been previously demonstrated [J. Biol. Chem. 277 (2002) 19727] that the SU of a murine hepatitis coronavirus (MHV) forms dimers, the dimerization domain overlaps the receptor-binding domain (RBD) and that this dimeric state is important for binding to receptor molecules that initiates entry into cells. We have previously expressed various soluble fragments of the SARS-CoV SU and identified stably folded fragments (residues 272-537) that contain the RBD [Biochem. Biophys. Res. Commun. 312 (2003) 1159]. Here, we further characterize these and other fragments in an attempt to identify possible dimerization domains and their role for membrane fusion. We demonstrate that the SU and a shorter 260-amino acid N-terminal fragment (residues 17-276), which folds independently, form dimers. In contrast to the previously characterized MHV SU dimerization, this fragment is upstream and distinct from the RBD. Its deletion abolished S-mediated cell membrane fusion but retained the SUreceptor-binding function indicating the possibility for a role in post-receptor binding steps of the virus entry mechanism. Interestingly, the whole soluble S ectodomain (Se) that contains the dimerization domain but not the transmembrane domain and the cytoplasmic tail forms trimers suggesting the existence of a trimerization domain in the TM subunit in its prefusion state that may lead to a conformation unfavorable for formation of higher-order multimeric structures. These results demonstrate the existence of SU dimers and Se trimers, and indicate the possibility for an unknown mechanism of their role in entry. They also further characterize the S-mediated membrane fusion and could be important for understanding the mechanisms of virus entry, and in the development of therapeutics and vaccines. 
 Title: Oligomerization of the SARS-CoV S glycoprotein: dimerization of the N-terminus and trimerization of the ectodomain
answer:

True