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.
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Question: The respiratory syncytial virus (RSV) fusion (F) glycoprotein is a major target of neutralizing antibodies arising from natural infection, and antibodies that specifically bind to the prefusion conformation of RSV F generally demonstrate the greatest neutralization potency. Prefusion-stabilized RSV F variants have been engineered as vaccine antigens, but crystal structures of these variants have revealed conformational differences in a key antigenic site located at the apex of the trimer, referred to as antigenic site Ø. Currently, it is unclear if flexibility in this region is an inherent property of prefusion RSV F or if it is related to inadequate stabilization of site Ø in the engineered variants. Therefore, we set out to investigate the conformational flexibility of antigenic site Ø, as well as the ability of the human immune system to recognize alternative conformations of this site, by determining crystal structures of prefusion RSV F bound to neutralizing human-derived antibodies AM22 and RSD5. Both antibodies bound with high affinity and were specific for the prefusion conformation of RSV F. Crystal structures of the complexes revealed that the antibodies recognized distinct conformations of antigenic site Ø, each diverging at a conserved proline residue located in the middle of an α-helix. These data suggest that antigenic site Ø exists as an ensemble of conformations, with individual antibodies recognizing discrete states. Collectively, these results have implications for the refolding of pneumovirus and paramyxovirus fusion proteins and should inform development of prefusion-stabilized RSV F vaccine candidates. Respiratory syncytial virus (RSV) is a pervasive pathogen that causes severe lower respiratory tract infections, leading to~100,000 deaths globally each year and hundreds of millions of dollars in healthcare costs. However, despite its prevalence, there is no vaccine for RSV and the only available therapy is limited to high-risk infants, leaving the vast majority of people with no effective means of prevention or treatment. The RSV fusion (F) protein is a major target of neutralizing antibodies, including extremely potent antibodies that PLOS Pathogens | https://doi.recognize prefusion-specific epitopes. In this study, we determined the crystal structures of two neutralizing human antibodies bound to prefusion RSV F. Our results reveal that each antibody recognizes a different conformation of a neutralization-sensitive epitope, suggesting that this region is inherently flexible and may be important for RSV F function. These results should guide future vaccine-design efforts and help elucidate the mechanisms of RSV F triggering and fusion. Conformational flexibility of antigenic site Ø PLOS Pathogens | https://doi.

Answer: Alternative conformations of a major antigenic site on RSV F


Question: Aims: The chronic consumption of alcohol is known to result in neurodegeneration and impairment of cognitive function. Pathological and neuroimaging studies have confirmed that brain atrophy in alcoholics is mainly due to widespread white matter (WM) loss with neuronal loss restricted to specific regions, such as the prefrontal cortex. Neuroimaging studies of cigarette smokers also suggest that chronic inhalation of tobacco smoke leads to brain atrophy, although the neurotoxic component is unknown. As a high proportion of chronic alcoholics also smoke cigarettes it has been hypothesized that at least some alcohol-related brain damage is due to tobacco smoke exposure. Methods: 39 Long Evans rats were subjected to 8 weeks exposure to alcohol and/or 5 weeks coexposure to nicotine-specific nitrosamine ketone (NNK), a proxy for tobacco smoke. Their frontal WM was then assayed with transmission electron microscopy. Results: NNK and ethanol co-exposure had a synergistic effect in decreasing myelinated fibre density. Furthermore, NNK treatment led to a greater reduction in myelin sheath thickness than ethanol whereas only the ethanol-treated animals showed a decrease in unmyelinated fibre density. Conclusion: These data suggest that NNK causes WM degeneration, an effect that is exacerbated by alcohol, but unlike alcohol, it has little impact on the neuronal components of the brain.

Answer: The Differential Effects of Alcohol and Nicotine- Specific Nitrosamine Ketone on White Matter Ultrastructure


Question: Chronic infection and cancer are associated with suppressed T cell responses in the presence of cognate antigen. Recent work identified memory-like CXCR5 + TCF1 + CD8 + T cells that sustain T cell responses during persistent infection and proliferate upon anti-PD1 treatment. Approaches to expand these cells are sought. We show that blockade of interferon type 1 (IFN-I) receptor leads to CXCR5 + CD8 + T cell expansion in an IL-27-and STAT1-dependent manner. IFNAR1 blockade promoted accelerated cell division and retention of TCF1 in virus-specific CD8 + T cells. We found that CD8 + T cell-intrinsic IL-27 signaling safeguards the ability of TCF1 hi cells to maintain proliferation and avoid terminal differentiation or programmed cell death. Mechanistically, IL-27 endowed rapidly dividing cells with IRF1, a transcription factor that was required for sustained division in a cell-intrinsic manner. These findings reveal that IL-27 opposes IFN-I to uncouple effector differentiation from cell division and suggest that IL-27 signaling could be exploited to augment self-renewing T cells in chronic infections and cancer.

Answer:
IL-27 promotes the expansion of self-renewing CD8 + T cells in persistent viral infection