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.

Input: Consider Input: The presence of immunoglobulin oligoclonal bands in the cerebrospinal fluid of Multiple Sclerosis (MS) patients supports the hypothesis of an infectious etiology, although the antigenic targets remain elusive. Neurotropic mouse hepatitis virus (MHV) infection in mice provides a useful tool for studying mechanisms of demyelination in a virus-induced experimental model of MS. This study uses Affymetrix microarray analysis to compare differential spinal cord mRNA levels between mice infected with demyelinating and non-demyelinating strains of MHV to identify host immune genes expressed in this demyelinating disease model. The study reveals that during the acute stage of infection, both strains induce inflammatory innate immune response genes, whereas upregulation of several immunoglobulin genes during chronic stage infection is unique to infection with the demyelinating strain. Results suggest that the demyelinating strain induced an innate-immune response during acute infection that may promote switching of Ig isotype genes during chronic infection, potentially playing a role in antibody-mediated progressive demyelination even after viral clearance.

Output: Demyelinating strain of mouse hepatitis virus infection bridging innate and adaptive immune response in the induction of demyelination


Input: Consider Input: Infectious bronchitis virus (IBV), the first coronavirus described, was initially associated with severe respiratory disease. However, outbreaks have more recently also been associated with nephropathogenesis. Topographically interrelated antigenic determinants of the nephropathogenic Gray strain of IBV were characterized using eleven monoclonal antibodies (MAbs). Four MAbs (IgG 2a~c) defined epitopes that were both conformation-independent and group specific, reacting with Gray, Arkansas (Ark), and Massachusetts41 (Mass41) strains. Seven MAbs (IgG 1~:) defined conformation-dependent epitopes that could differentiate the Gray from the Ark and Mass strains. The spike protein specificity of the MAbs was determined with the conformation-independent MAbs and one MAb that reacted only in "non-denaturing" western blot assays. Competitive binding studies using these MAbs suggested a high degree of functional dependency among the associated epitopes as might be expected with a protein of complex secondary and tertiary structure. At least two regions associated with complete protection of infected embryos were identified that consisted of both conformation-dependent and independent epitopes. However, a "non-neutralizing" MAb, which did not protect the embryo from gross lesions, did inhibit virus-induced lesions and replication in the kidneys. These MAbs should be valuable tools in studying IBV pathogenesis.

Output: Epitopes on the spike protein of a nephropathogenic strain of infectious bronchitis virus


Input: Consider Input: Cystathionine-β-synthase (CBS) has been recently identified as a drug target for several forms of cancer. Currently no potent and selective CBS inhibitors are available. Using a composite collection of 8871 clinically used drugs and well-annotated pharmacological compounds (including the LOPAC library, the FDA Approved Drug Library, the NIH Clinical Collection, the New Prestwick Chemical Library, the US Drug Collection, the International Drug Collection, the `Killer Plates' collection and a small custom collection of PLP-dependent enzyme inhibitors), we conducted an in vitro screen in order to identify inhibitors for CBS using a primary 7-azido-4methylcoumarin (AzMc) screen to detect CBS-derived hydrogen sulfide (H 2 S) production. Initial hits were subjected to counterscreens using the methylene blue assay (a secondary assay to measure H 2 S production) and were assessed for their ability to quench the H 2 S signal produced by the H 2 S donor compound GYY4137. Four compounds, hexachlorophene, tannic acid, aurintricarboxylic acid and benserazide showed concentration-dependent CBS inhibitory actions without scavenging H 2 S released from GYY4137, identifying them as direct CBS inhibitors. Hexachlorophene (IC 50 : ~60 μM), tannic acid (IC 50 : ~40 μM) and benserazide (IC 50 : ~30 μM) were less potent CBS inhibitors than the two reference compounds AOAA (IC 50 : ~3 μM) and NSC67078 (IC 50 : ~1 μM), while aurintricarboxylic acid (IC 50 : ~3 μM) was equipotent with AOAA. The second reference compound NSC67078 not only inhibited the CBS-induced AzMC fluorescence signal (IC 50 : ~1 μM), but also inhibited with the GYY4137-induced AzMC fluorescence signal with (IC 50 of ~6 μM) indicative of scavenging/non-specific effects. Hexachlorophene (IC 50 : ~6 μM), tannic acid (IC 50 : ~20 μM), benserazide (IC 50 : ~20 μM), and NSC67078 (IC 50 : ~0.3 μM) inhibited HCT116 colon cancer cells proliferation with greater potency than AOAA (IC 50 : ~300 μM). In contrast, although a CBS inhibitor in the cell-free assay, aurintricarboxylic acid failed to inhibit HCT116 proliferation at lower concentrations, and stimulated cell proliferation at 300 μM. Copper-containing compounds present in the libraries, were also found to be potent inhibitors of recombinant CBS; however this activity was due to the CBS inhibitory effect of copper ions themselves. However, copper ions, up to 300 μM, did not inhibit HCT116 cell proliferation. Benserazide was only a weak inhibitor of the activity of the other H 2 S-generating enzymes CSE and 3-MST activity (16% and 35% inhibition at 100 μM, respectively) in vitro. Benserazide suppressed HCT116 mitochondrial function and inhibited proliferation of the high CBS-expressing colon cancer cell line HT29, but not the low CBSexpressing line, LoVo. The major benserazide metabolite 2,3,4-trihydroxybenzylhydrazine also inhibited CBS activity and suppressed HCT116 cell proliferation in vitro. In an in vivo study of nude mice bearing human colon cancer cell xenografts, benserazide (50 mg/kg/day s.q.) prevented tumor growth. In silico docking simulations showed that benserazide binds in the active site of the enzyme and reacts with the PLP cofactor by forming reversible but kinetically stable Schiff baselike adducts with the formyl moiety of pyridoxal. We conclude that benserazide inhibits CBS activity and suppresses colon cancer cell proliferation and bioenergetics in vitro, and tumor growth in vivo. Further pharmacokinetic, pharmacodynamic and preclinical animal studies are necessary to evaluate the potential of repurposing benserazide for the treatment of colorectal cancers.


Output: Screening of a composite library of clinically used drugs and well-characterized pharmacological compounds for cystathionine β-synthase inhibition identifies benserazide as a drug potentially suitable for repurposing for the experimental therapy of colon cancer HHS Public Access