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: Rift Valley fever virus (RVFV) (genus Phlebovirus, family Bunyaviridae) is a negative-stranded RNA virus with a tripartite genome. RVFV is transmitted by mosquitoes and causes fever and severe hemorrhagic illness among humans, and fever and high rates of abortions in livestock. A nonstructural RVFV NSs protein inhibits the transcription of host mRNAs, including interferon-b mRNA, and is a major virulence factor. The present study explored a novel function of the RVFV NSs protein by testing the replication of RVFV lacking the NSs gene in the presence of actinomycin D (ActD) or a-amanitin, both of which served as a surrogate of the host mRNA synthesis suppression function of the NSs. In the presence of the hosttranscriptional inhibitors, the replication of RVFV lacking the NSs protein, but not that carrying NSs, induced doublestranded RNA-dependent protein kinase (PKR)-mediated eukaryotic initiation factor (eIF)2a phosphorylation, leading to the suppression of host and viral protein translation. RVFV NSs promoted post-transcriptional downregulation of PKR early in the course of the infection and suppressed the phosphorylated eIF2a accumulation. These data suggested that a combination of RVFV replication and NSs-induced host transcriptional suppression induces PKR-mediated eIF2a phosphorylation, while the NSs facilitates efficient viral translation by downregulating PKR and inhibiting PKR-mediated eIF2a phosphorylation. Thus, the two distinct functions of the NSs, i.e., the suppression of host transcription, including that of type I interferon mRNAs, and the downregulation of PKR, work together to prevent host innate antiviral functions, allowing efficient replication and survival of RVFV in infected mammalian hosts.

Output: Rift Valley Fever Virus NSs Protein Promotes Post-Transcriptional Downregulation of Protein Kinase PKR and Inhibits eIF2a Phosphorylation


Input: Consider Input: Graphical Abstract Highlights d Binding to all influenza A subtypes neutralizing seasonal and pandemic strains d Utilizes a rare VH (VH6-1) and carries a low level of somatic mutations d Highly conserved epitope encompassing fusion peptide and hydrophobic groove d Superior therapeutic window compared to oseltamivir in animals Correspondence zhuq@medimmune.com (Q.Z.), john.skehel@crick.ac.uk (J.J.S.) In Brief Identification of a human monoclonal antibody that reacts effectively with all influenza A hemagglutinin subtypes paves the way for developing immunotherapy for people infected with the flu virus. Accession Numbers 5JW5 5JW4 5JW3 KX398429 KX398468 SUMMARY Influenza virus remains a threat because of its ability to evade vaccine-induced immune responses due to antigenic drift. Here, we describe the isolation, evolution, and structure of a broad-spectrum human monoclonal antibody (mAb), MEDI8852, effectively reacting with all influenza A hemagglutinin (HA) subtypes. MEDI8852 uses the heavy-chain VH6-1 gene and has higher potency and breadth when compared to other anti-stem antibodies. MEDI8852 is effective in mice and ferrets with a therapeutic window superior to that of oseltamivir. Crystallographic analysis of Fab alone or in complex with H5 or H7 HA proteins reveals that MEDI8852 binds through a coordinated movement of CDRs to a highly conserved epitope encompassing a hydrophobic groove in the fusion domain and a large portion of the fusion peptide, distinguishing it from other structurally characterized cross-reactive antibodies. The unprecedented breadth and potency of neutralization by MEDI8852 support its development as immunotherapy for influenza virus-infected humans.

Output: Structure and Function Analysis of an Antibody Recognizing All Influenza A Subtypes Article Structure and Function Analysis of an Antibody Recognizing All Influenza A Subtypes


Input: Consider Input: this work presents a simple one-pot protocol to achieve core-doped shell nanohybrids comprising silver nanoparticles, curcumin and thermoresponsive polymeric shell taking advantage of the reducing properties of phenolic curcumin substance and its ability to decorate metallic surfaces. Silver nanoparticles were synthesized, via sodium citrate and silver nitrate addition into a boiling aqueous solution of curcumin, monomers and surfactant. curcumin and sodium citrate promoted silver nucleation, acting as reducing and stabilizing agents. these curcumin-capped Agnps enabled, after adding the radical polymerization initiator, the assembling of the growing polymer chains around the hydrophobic Agnp surface. the resultant core-doped shell nanohybrids exhibit plasmonic, luminescent and volume thermoresponsive properties, with improved possibilities to be used as successful therapeutic platforms. In fact, the possibility to nanoconfine the synergistic antioxidant, antiviral, antibacterial features of silver and curcumin in one bioavailable hybrid paves the way to promising applications in the biomedical field. The exciting electronic, optical, catalytic and antimicrobial properties of metal NPs can be stymied by their tendency to aggregate. To overcome this issue and provide metallic nanoparticles with additional features, the hybridization with polymeric materials is a successful strategy. In this regard, polymer micro/nanogels exhibit high colloidal stability, great versatility in their chemical and topological composition, drug loading and functionalization capabilities 1 that make them unique vehicles and reservoirs for metal nanoparticles 2,3 . Additionally, the permeability of the gel-system coating allows a controlled loading and release of bioactive molecules and drugs. Furthermore, polymer microgels are frequently used as nanoreactors for the in situ synthesis of metallic NPs 4 , and small particles decorating the microgel are successfully formed 5 . However, the control over the metallic NP structure and distribution is rather difficult. Core-shell hybrid nanogels usually face metal@polymer nanohybrid synthesis from a different point of view; and the most reported protocols are based on the polymer self-assembling around a preformed metal NP. The ligand exchange using polymers with functional groups able to attach the metal NP is a successful approach to attain thin polymer shells 6 . However to achieve polymer coating with tunable thickness, polymerization in heterogeneous media, as free radical precipitation polymerization (FRPP) is the most widely choice 7,8 . Since this technique relies on the precipitation of water insoluble growing polymer chain, a previous surface preparation of metal NP is required. Note that the organic polymer is not compatible with the anionic citrate ligand, commonly used to synthesize metal NPs, in aqueous medium 9,10 . Therefore a variety of strategies can be found in the literature, mainly for gold 7, 8, [11] [12] [13] [14] [15] , whereas works focused on achieving silver@polymer core-shell nanogels are scarce; despite the reliable properties of silver NPs in applications as ultrasensitive analysis of molecules through Surface Enhanced Raman Spectroscopy (SERS) 2,16 , catalysis 17 , cancer cell imaging 16,18 and other applications related to their antimicrobial properties 19 . Recently, we developed one-step protocol supporting core-shell hybrid nanogel synthesis, regardless of the monomer polarity. The strategy was based on the use of hydrophobic thiolated methacrylate monomer as compatible bridge between the as-synthesized Au@citrate surface and the growing polymer chains 14 . The modification of the metal surface with the hydrophobic compound led to effective polymer self-assembling around the inorganic core. Thus, we envisioned, in this work, that hydrophobic molecules as curcumin (Fig. 1A) , having a two-fold function, as reducing agent in silver NP synthesis as well as diminishing the interfacial energy between the growing polymer chain and the metallic surface, might trigger the core-shell hybrid NP assembly. Previous backgrounds evidenced the curcumin ability to reduce Ag + and Au 3+ ions to silver 20-22 and gold 23 nanoparticles, without any other additional reductant or in the presence of citrate and CTBA to modulate NP shape 24 . Thus, Kundu and Nithiyanantham 20 , in a pioneer work, were able to synthesize different shapes of AgNP (spheres, nanowires and anisotropic nanoflakes) by tuning the molar ratio of curcumin to AgNO 3 . Nevertheless, even though the reductant ability of curcumin has been already reported, it should be noted that, as far as we know, none has postulated that hydrophobic curcumin presence nearby metal surface may facilitate polymer self-assembling during post-crosslinking polymerization. In addition, by considering the antioxidant properties of this natural phenolic compound, our curcumin-promoted Ag@nanogel hybrid system will state a double benefit arising from the biomedical properties of curcumin itself, as antibacterial, self-healing 25,26 , antiviral 27 and anti-inflammatory 28 ; and from the antibacterial 19 synergistic effect and remarkable antiviral 29 activity of particles comprising silver nanoparticles and curcumin in one hybrid. Moreover, encapsulation of curcumin in the hydrophobic polymer shell will increase curcumin bioavailability protecting curcumin from hydrolytic degradation 30 , since this is the main limitation for its therapeutic applications. experimental Materials. The monomer 2-(2-methoxyethoxy)ethyl methacrylate (MEO 2 MA) (Aldrich 95%) was purified by passing through a neutral alumina column. Tetraethylene glycol dimethacrylate (TEGDMA) (≥90%), trisodium citrate dihydrate (≥98%) and silver nitrate (AgNO 3 ) (99.99%) were purchased from Aldrich. Sodium dodecyl sulfate (SDS) (≥97%) and ammonium persulfate (APS) (>98%), were purchased from Fluka. Curcumin (≥98%) was obtained from Acros Organics. All chemical reagents were employed as received. The solvents used, ethanol and water, were analytical and Milli-Q grade, respectively.


Output: curcumin to promote the Synthesis of Silver nps and their Self- Assembly with a thermoresponsive polymer in core-Shell nanohybrids