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".

Paragraph: BACKGROUND-HIV-1-infected mononuclear phagocytes release soluble factors that affect the homeostasis in tissue. HIV-1 can prompt metabolic encephalopathy with the addition of neuronal dysfunction and apoptosis. Recently, we reported that HIV-1 enhances the expression and secretion of bioactive cathepsin B in monocyte-derived macrophages, ultimately contributing to neuronal apoptosis. In this research, we request if microglia respond to HIV infection similarly by modifying the expression, secretion, neurotoxic potential of cathepsin B and the in vivo relevance of these findings. METHODS-HIV-ADA infected human primary microglia and CHME-5 were assessed for expression and activity of cathepsin B, its inhibitors, cystatins B and C, and neurotoxicity associated with these changes. Human primary neurons were exposed to supernatants from HIVinfected and uninfected microglia in the presence of cathepsin B inhibitors and apoptosis was assessed by TUNEL. Microglial expression of cathepsin B was validated in brain tissue from HIVE patients. microglia secreted significantly greater levels of cathepsin B, cystatin B, and cystatin C compared to uninfected cells. Increased apoptosis was observed in neurons exposed to supernatants from HIV-1 infected microglia at days 12 post-infection. The cathepsin B inhibitor CA-074 and cathepsin B antibody prevented neuronal apoptosis. Increased microgliaderived cathepsin B, cystatin B, and cystatin C and caspase-3+ neurons were detected in HIVE brains compared to controls. CONCLUSIONS-Our results suggest that HIV-1-induced cathepsin B production in microglia contributes to neuronal apoptosis and may be an important factor in neuronal death associated with HIVE. Human primary neuron and microglia isolation and culture-Human primary neurons and microglia were provided by Temple University's Comprehensive NeuroAIDS Center. Fetal brain tissue (gestational age 16-18 weeks) was obtained from elective abortion procedures performed in full compliance with National Institutes of Health and Temple University ethical guidelines. The tissue was washed with cold Hanks balanced salt solution (HBSS) and meninges and blood vessels were removed as previously described [Huang et al, 2011; Ghorpade et al, 1998].. For microglia, brain tissue was supplemented with Ca 2+ and Mg 2+ and then digested with 0.25% trypsin (Sigma) for 30 min at 37C. Trypsin was neutralized with fetal bovine serum (FBS), and the tissue was further dissociated to obtain single-cell suspensions. The cells were cultured in DMEM (Sigma), supplemented with a mixture containing 10% heat-inactivated FBS, 1,000 U of purified recombinant human macrophage colony stimulating factor (MCSF) per ml, penicillin and streptomycin (50 mg/ ml), and 100 mg/ml of neomycin. The mixed culture was maintained under 5% CO 2 for 7 days, and the medium was fully replaced to remove any cell debris. The microglia cells released with further incubation were collected and purified by preferential adhesion. Microglia were seeded as an adherent monolayer at a density of 3 10 6 cells/well in a 6well plate and floating cells were removed after 4h. For neurons, tissue in HBSS was digested with papain (Sigma-Aldrich, St. Louis, MO) for 30 min at 37C. Tissue was then dissociated to obtain single-cell suspensions by repeated pipetting with small bore fire polished glass Pasteur pipettes. Cells were plated in poly-D lysine-coated dishes at a density of ~ 1.8 10 6 cells/60mm dish in neurobasal media with B27 supplement, horse serum, and gentamicin (Invitrogen). After 2hr of attachment, media was replaced with fresh complete neurobasal media. Twenty-four hours later, cultures were replaced with neurobasal media without horse serum. Four days later, one fourth of the media was removed and replaced with neurobasal media supplemented with fluorodeoxyuridine (FDU) and uridine. Following FDU treatment, neurons were cultured in neurobasal medium with Glutamax and B27 supplement. One half volume of media was replaced every 48h. Purity of cell type specific cultures was assessed by immunolabeling for cell-type specific markers, including Iba-1 for microglia, GFAP for astrocyte and MAP2, neurofilament, and synaptophysin for neurons. CHME-5 microglia-The microglia cell line CHME-5 was kindly provided by Dr. Randal Davis from Oklahoma State University. It was originally obtained from human fetal microglia (Peudenier et al. 1991) transfected with the T-antigen of SV-40 virus (Janabi et al. 1995). Cells were cultured to 70% confluence in Dulbecco's modified Eagle's medium (DMEM) (Sigma Chemical Company, St. Louis, MO) supplemented with 5% inactivated Zenon et al.
Title: HIV-infected microglia mediate cathepsin B induced neurotoxicity
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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/)
True

Paragraph: Background: Epidemiological interventions aim to control the spread of infectious disease through various mechanisms, each carrying a different associated cost. Methodology: We describe a flexible statistical framework for generating optimal epidemiological interventions that are designed to minimize the total expected cost of an emerging epidemic while simultaneously propagating uncertainty regarding the underlying disease model parameters through to the decision process. The strategies produced through this framework are adaptive: vaccination schedules are iteratively adjusted to reflect the anticipated trajectory of the epidemic given the current population state and updated parameter estimates. Conclusions: Using simulation studies based on a classic influenza outbreak, we demonstrate the advantages of adaptive interventions over non-adaptive ones, in terms of cost and resource efficiency, and robustness to model misspecification.
Title: A Statistical Framework for the Adaptive Management of Epidemiological Interventions
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