MAVS expressed by hematopoietic cells is critical for control of West Nile virus infection and pathogenesis

West Nile virus (WNV) is the most important cause of epidemic encephalitis in North America. Innate immune responses, which are critical for control of WNV infection, are initiated by signaling through pathogen recognition receptors, RIG-I and MDA5, and their downstream adaptor molecule, MAVS. Here, we show that a deficiency of MAVS in hematopoietic cells resulted in increased mortality and delayed WNV clearance from the brain. In Mavs(−/−) mice, a dysregulated immune response was detected, characterized by a massive influx of macrophages and virus-specific T cells into the infected brain. These T cells were polyfunctional and lysed peptide-pulsed target cells in vitro. However, virus-specific T cells in the brains of infected Mavs(−/−) mice exhibited lower functional avidity than those in wild-type animals, and even virus-specific memory T cells generated by prior immunization could not protect Mavs(−/−) mice from WNV-induced lethal disease. Concomitant with ineffective virus clearance, macrophage numbers were increased in the Mavs(−/−) brain, and both macrophages and microglia exhibited an activated phenotype. Microarray analyses of leukocytes in the infected Mavs(−/−) brain showed a preferential expression of genes associated with activation and inflammation. Together, these results demonstrate a critical role for MAVS in hematopoietic cells in augmenting the kinetics of WNV clearance and thereby preventing a dysregulated and pathogenic immune response. IMPORTANCE West Nile virus (WNV) is the most important cause of mosquito-transmitted encephalitis in the United States. The innate immune response is known to be critical for protection in infected mice. Here, we show that expression of MAVS, a key adaptor molecule in the RIG-I-like receptor RNA-sensing pathway, in hematopoietic cells is critical for protection from lethal WNV infection. In the absence of MAVS, there is a massive infiltration of myeloid cells and virus-specific T cells into the brain and overexuberant production of proinflammatory cytokines. These results demonstrate the important role that MAVS expression in hematopoietic cells has in regulating the inflammatory response in the WNV-infected brain

Studies of Layered Double Hydroxides

This work concerns some synthetic processes and basic properties of layered double hydroxides (LDHs). A series of LDHs, a family of newly developed materials found to have many potential uses in industry, were investigated in relating to the origin of life on early Earth. In this work, I successfully intercalated some inorganic as well as organic species. Ammonium, accompanied with ferrocyanide ion, can enter the layered space. It was found there were two kin go f intercalated ferrocyanide species: one is that exchanged with anions and became a part of layered double hydroxide, while the other is suggested to be related to ammonium ferrocyanide neutral species. Formaldehyde, ethanolamine and formate can also be involved into LDHs. To improve the crystallinity, homogeneous precipitation method, which used Urea and Hexamine, was employed. The results reveal the success in the case by Urea but not in that by Hexamine. Annealing could also be used for this purpose. However, it needs to be preocessed in its mother liquor; no improvement on the crystallinity if the material has been washed before annealing

Perceived Teacher Autonomy Support and Students' Deep Learning: The Mediating Role of Self-Efficacy and the Moderating Role of Perceived Peer Support

The purpose of this research is to test the mediation effect of self-efficacy on college student's perception of teacher autonomy support and students' deep learning, and whether the peer support perceived by students can moderate the relationship between perceived teacher autonomy support and deep learning. A survey of 1,800 college students from a provincial undergraduate normal university in Guizhou Province in China was conducted through the revised Perceived Teacher Autonomy Support Scale, Deep Learning Scale, Self-Efficacy Scale, and Perceived Peer Support Scale (Mean age = 21 years old, SD = 1.34). Data use SPSS23.0, AMOS22.0 for descriptive analysis and correlation analysis, exploratory factor analysis (EFA) and confirmatory factor analysis (CFA), moderation effect, and mediation effect analysis. The research results show that after controlling for gender, major, and grade, self-efficacy partially moderates the connection between perceived teacher autonomy support and deep learning of college students. Moreover, perceived peer support mediates the relationship between perceived teacher autonomy support and students' self-efficacy

A Hybrid Model Based on Support Vector Machine for Bus Travel-Time Prediction

Effective bus travel time prediction is essential in transit operation system. An improved support vector machine (SVM) is applied in this paper to predict bus travel time and then the efficiency of the improved SVM is checked. The improved SVM is the combination of traditional SVM, Grubbs’ test method and an adaptive algorithm for bus travel-time prediction. Since error data exists in the collected data, Grubbs’ test method is used for removing outliers from input data before applying the traditional SVM model. Besides, to decrease the influence of the historical data in different stages on the forecast result of the traditional SVM, an adaptive algorithm is adopted to dynamically decrease the forecast error. Finally, the proposed approach is tested with the data of No. 232 bus route in Shenyang. The results show that the improved SVM has good prediction accuracy and practicality

Modeling Travel Mode Choices in Connection to Metro Stations by Mixed Logit Models: A Case Study in Nanjing, China

Urban rail transit trips usually involve multiple stages, which can be differentiated in terms of transfers that may involve distinct access and egress modes. Most studies on access and egress mode choices of urban rail transit have separately examined the two mode choices. However, in reality, the two choices are temporally correlated. This study, therefore, has sequentially applied the mixed logit to examine the contributors of access and egress mode choices of urban metro commuters using the data from a recent survey conducted in Nanjing, China. 9 typical multimodal combinations constituted by 5 main access modes (walk, bike, electric bike, bus, and car) and 2 main egress modes (walk and bus) are included in the study. The result proves that the model is reliable and reproductive in analyzing access/egress mode choices of metro commuters. Estimation results prove the existence of time constraint and service satisfaction effect of access trip on commuters’ egress mode choice and reveal the importance of transfer infrastructure and environments that serve for biking, walking, bus riding, and car parking in commuter’s connection choice. Also, policy implications are segmentally concluded for the transfer needs of commuters in different groups to encourage the use of metro multimodal trips

Airway Memory CD4 + T Cells Mediate Protective Immunity against Emerging Respiratory Coronaviruses

Two zoonotic coronaviruses (CoV), SARS-CoV and MERS-CoV have crossed species to cause severe human respiratory disease. Here, we showed that induction of airway memory CD4+ T cells specific for a conserved epitope shared by SARS-CoV and MERS-CoV is a potential strategy for developing pan-coronavirus vaccines. Airway memory CD4+ T cells differed phenotypically and functionally from lung-derived cells and were crucial for protection against both CoVs in mice. Protection was interferon-γ-dependent and required early induction of robust innate and virus-specific CD8+ T cell responses. The conserved epitope was also recognized in SARS-CoV and MERS-CoV-infected human leukocyte antigen DR2 and DR3 transgenic mice, indicating potential relevance in human populations. Additionally, this epitope was cross-protective between human and bat CoVs, the progenitors for many human CoVs. Vaccine strategies that induce airway memory CD4+ T cells targeting conserved epitopes may have broad applicability in the context of new CoV and other respiratory virus outbreaks

Genome wide exploration of the origin and evolution of amino acids

Background: Even after years of exploration, the terrestrial origin of bio-molecules remains unsolved and controversial. Today, observation of amino acid composition in proteins has become an alternative way for a global understanding of the mystery encoded in whole genomes and seeking clues for the origin of amino acids. Results: In this study, we statistically monitored the frequencies of 20 alpha-amino acids in 549 taxa from three kingdoms of life: archaebacteria, eubacteria, and eukaryotes. We found that the amino acids evolved independently in these three kingdoms; but, conserved linkages were observed in two groups of amino acids, (A, G, H, L, P, Q, R, and W) and (F, I, K, N, S, and Y). Moreover, the amino acids encoded by GC-poor codons (F, Y, N, K, I, and M) were found to "lose" their usage in the development from single cell eukaryotic organisms like S. cerevisiae to H. sapiens, while the amino acids encoded by GC-rich codons (P, A, G, and W) were found to gain usage. These findings further support the co-evolution hypothesis of amino acids and genetic codes. Conclusion: We proposed a new chronological order of the appearance of amino acids (L, A, V/E/G, S, I, K, T, R/D, P, N, F, Q, Y, M, H, W, C). Two conserved evolutionary paths of amino acids were also suggested: A -> G -> R -> P and K -> Y.National Natural Science Foundation of China [20572061, 20732004]; Program for New Century Excellent Talents in University (NCET) of MO