TASK DEFINITION: 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".
PROBLEM: Paragraph: We aimed to test the hypothesis that gene silencing of tumor necrosis factor alpha converting enzyme (TACE) may attenuate lesion inflammation and positive vascular remodeling and enhance plaque stability in a rabbit model of atherosclerosis. Lentivirus-mediated TACE shRNA was injected into the abdominal aortic plaques of rabbits which effectively down-regulated TACE expression and activities from week 8 to week 16. TACE gene silencing reduced remodeling index and plaque burden, and diminished the content of macrophages and lipids while increased that of smooth muscle cells and collagen in the aortic plaques. In addition, TACE gene silencing attenuated the local expression of P65, iNOS, ICAM-1, VEGF and Flt-1 and activities of MMP9 and MMP2 while increased the local expression of TGF-1 together with reduced number of neovessels in the aorta. TACE shRNA treatment resulted in down-regulated expression of TACE in macrophages and blunted ERK-P38 phosphorylation and tube formation of co-cultured mouse vascular smooth muscle cells or human umbilical vein endothelial cells. In conclusion, gene silencing of TACE enhanced plaque stability and improved vascular positive remodeling. The mechanisms may involve attenuated local inflammation, neovascularization and MMP activation, as well as enhanced collagen production probably via down-regulated ERK-NF-B and upregulated TGF-1 signaling pathways. Tumor necrosis factor alpha converting enzyme (TACE), also known as ADAM17 (A disintegrin and A metalloproteinase 17), was initially discovered as a protease that cleaves the 26-kDa precursor of TNF- and sheds transmembrane TNF- to generate a soluble form of TNF- that can bind to TNF- receptors to induce inflammatory response 1 . Recently it has been recognized that TACE is a type I transmembrane protein and a member of a superfamily of Zn dependent metalloproteases. The major physiological role of TACE is to regulate the proteolytic release of a number of growth factors, cytokines, adhesion molecules and cleavage enzymes from cellular membrane 2,3 . The major pro-inflammatory cytokine processed by TACE is TNF- which is produced by macrophages, monocytes and T-cells, and acts as a major player in the pathogenesis of inflammation. It has been increasingly recognized that TACE-mediated shedding is involved in a variety of diseases such as ischemia, heart failure, arthritis, atherosclerosis, diabetes, cancer, neurological and immune diseases 3-5 . Ashley EA et al. provided functional evidence for TACE as a candidate gene of atherosclerosis susceptibility and found that polymorphisms of the TACE genes had relation to cardiovascular mortality in humans 6 . Canault M et al. found that TACE expression was associated with lesion formation in atherosclerosis-prone sites of apolipoprotein E-knockout (ApoE -/-) mice 7 . Oksala N demonstrated that TACE was upregulated in advanced human atherosclerotic lesions in samples from carotid, aortic, and femoral arteries compared to samples from internal thoracic artery free of atherosclerotic plaques 8 . In addition, Stoehr R et al. showed that loss of TIMP3, an endogenous inhibitor of TACE, exacerbated atherosclerosis 1
Title: Gene silencing of TACE enhances plaque stability and improves vascular remodeling in a rabbit model of atherosclerosis

SOLUTION: False

PROBLEM: Paragraph: Bluetongue virus (BTV) encodes a single capping protein, VP4, which catalyzes all reactions required to generate cap1 structures on nascent viral transcripts. Further, structural analysis by X-ray crystallography indicated each catalytic reaction is arranged as a discrete domain, including a nucleoside-2 0 -O-methyltransferase (2 0 -O MTase). In this study, we have exploited the structural information to identify the residues that are important for the catalytic activity of 2 0 -O MTase of VP4 and their influence on BTV replication. The effect of these mutations on GMP binding, guanylyltransferase (GTase) and methylase activities were analysed by a series of in vitro biochemical assays using recombinant mutant proteins; subsequently their effects on virus replication were assessed by introducing the same mutations in replicating viral genome using a reverse genetics system. Our data showed that single substitution mutations in the catalytic tetrad K-D-K-E were sufficient to abolish 2 0 -O MTase activity in vitro and to completely abrogate BTV replication in cells; although these mutants retained the upstream GMP binding, GTase and guanine-N7-methyltransferase activities. Mutations of the surrounding substrate-binding pocket (predicted to recruit cap0) had variable effects on in vitro VP4 capping activity. Only triple but not single substitution mutations of these residues in genome resulted in reduced virus replication kinetics. This is the first report investigating the importance of 2 0 -O MTase function for any member of the Reoviridae and highlights the significance of K-D-K-E tetrad and surrounding residues for the efficiency of 2 0 -O MTase activity and in turn, for virus fitness.
Title: Structure-based identification of functional residues in the nucleoside- 2 0 -O-methylase domain of Bluetongue virus VP4 capping enzyme-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

SOLUTION: True

PROBLEM: Paragraph: Molecular beacons are dual-labelled probes that are typically used in real-time PCR assays, but have also been conjugated with solid matrices for use in microarrays or biosensors. We have developed a fluid array system using microsphere-conjugated molecular beacons and the flow cytometer for the specific, multiplexed detection of unlabelled nucleic acids in solution. For this array system, molecular beacons were conjugated with microspheres using a biotin-streptavidin linkage. A bridged conjugation method using streptavidin increased the signal-tonoise ratio, allowing for further discrimination of target quantitation. Using beads of different sizes and molecular beacons in two fluorophore colours, synthetic nucleic acid control sequences were specifically detected for three respiratory pathogens, including the SARS coronavirus in proof-of-concept experiments. Considering that routine flow cytometers are able to detect up to four fluorescent channels, this novel assay may allow for the specific multiplex detection of a nucleic acid panel in a single tube.
Title: A molecular beacon, bead-based assay for the detection of nucleic acids by flow cytometry

SOLUTION:
True