MAVS Is essential for primary CD4 + T cell immunity but not for recall T cell responses following an attenuated West Nile virus infection

ABSTRACT The use of pathogen recognition receptor (PRR) agonists and the molecular mechanisms involved have been the major focus of research in individual vaccine development. West Nile virus (WNV) nonstructural (NS) 4B-P38G mutant has several features for an ideal vaccine candidate, including significantly reduced neuroinvasiveness, induction of strong adaptive immunity, and protection of mice from wild-type (WT) WNV infection. Here, we determined the role of mitochondrial antiviral signaling protein (MAVS), the adaptor protein for RIG-I-like receptor in regulating host immunity against the NS4B-P38G vaccine. We found that Mavs −/− mice were more susceptible to NS4B-P38G priming than WT mice. Mavs −/− mice had a transiently reduced production of antiviral cytokines and an impaired CD4 + T cell response in peripheral organs. However, antibody and CD8 + T cell responses were minimally affected. NS4B-P38G induced lower type I interferon (IFN), IFN-stimulating gene, and proinflammatory cytokine responses in Mavs −/− dendritic cells and subsequently compromised the antigen-presenting capacity for CD4 + T cells. Interestingly, Mavs −/− mice surviving NS4B-P38G priming were all protected from a lethal WT WNV challenge. NS4B-P38G-primed Mavs −/− mice exhibited equivalent levels of protective CD4 + T cell recall response, a modestly reduced WNV-specific IgM production, but more robust CD8 + T cell recall response. Taken together, our results suggest that MAVS is essential for boosting optimal primary CD4 + T cell responses upon NS4B-P38G vaccination and yet is dispensable for host protection and recall T cell responses during secondary WT WNV infection. IMPORTANCE The production of innate cytokines induced by the recognition of pathogen recognition receptors (PRRs) via their cognate ligands are critical for enhancing antigen-presenting cell functions and influencing T cell responses during microbial infection. The use of PRR agonists and the underlying molecular mechanisms have been the major focus in individual vaccine development. Here, we determined the role of mitochondrial antiviral-signaling protein (MAVS), the adaptor protein for RIG-I like receptor in regulating host immunity against the live attenuated West Nile virus (WNV) vaccine strain, the nonstructural (NS) 4B-P38G mutant. We found that MAVS is important for boosting optimal primary CD4 + T cell response during NS4B-P38G vaccination. However, MAVS is dispensable for memory T cell development and host protection during secondary wild-type WNV infection. Overall, these results may be utilized as a paradigm to aid in the rational development of other efficacious live attenuated flavivirus vaccines

Smart Kids Application to Develop the Potential Interests for Children

Children today are growing up in a rapidly developing world filled with quickly evolving technologies, such as the Internet, smartphones, and smart mobile devices, etc. As a result, more applications designed with children as the targeted population, and young students have more ways to obtain educational resources online. This work will discuss an educational app for children who want to find out more about their interests or help them to explore their interests in different topics such as science and health from a youth perspective. The proposed project will be implemented as a mobile application and specifically an android application based on a web crawler system and a recommendation system. The system will collect data from specific organizations, which have educational articles aimed at children, such as extension.org. Also, we have collected requirements, designed and developed a user-friendly Android application for teenagers (i.e., based on user feedback) and students can utilize this app to access exciting topics (e.g., youth science). We aim to improve user experience in the area of STEM content access. Based on the student interaction with the application, we will refine the design of our recommendation system to analyze student interests and provide comparative data to support the targeted population in quickly finding information in their fields of interest

Signatures of Gate-Tunable Superconductivity in Trilayer Graphene/Boron Nitride Moir\'e Superlattice

Understanding the mechanism of high temperature (high Tc) superconductivity is a central problem in condensed matter physics. It is often speculated that high Tc superconductivity arises from a doped Mott insulator as described by the Hubbard model. An exact solution of the Hubbard model, however, is extremely challenging due to the strong electron-electron correlation. Therefore, it is highly desirable to experimentally study a model Hubbard system in which the unconventional superconductivity can be continuously tuned by varying the Hubbard parameters. Here we report signatures of tunable superconductivity in ABC-trilayer graphene (TLG) / boron nitride (hBN) moir\'e superlattice. Unlike "magic angle" twisted bilayer graphene, theoretical calculations show that under a vertical displacement field the ABC-TLG/hBN heterostructure features an isolated flat valence miniband associated with a Hubbard model on a triangular superlattice. Upon applying such a displacement field we find experimentally that the ABC-TLG/hBN superlattice displays Mott insulating states below 20 Kelvin at 1/4 and 1/2 fillings, corresponding to 1 and 2 holes per unit cell, respectively. Upon further cooling, signatures of superconducting domes emerge below 1 kelvin for the electron- and hole-doped sides of the 1/4 filling Mott state. The electronic behavior in the TLG/hBN superlattice is expected to depend sensitively on the interplay between the electron-electron interaction and the miniband bandwidth, which can be tuned continuously with the displacement field D. By simply varying the D field, we demonstrate transitions from the candidate superconductor to Mott insulator and metallic phases. Our study shows that TLG/hBN heterostructures offer an attractive model system to explore rich correlated behavior emerging in the tunable triangular Hubbard model.Comment: 14 pages, 4 figure