RESUMEN
In addition to functioning as an antioxidant, anti-inflammatory and age-defying cellular component, DHA impacts the immune system by facilitating the pathogen invasion. The mechanism through which DHA regulates immune suppression remains obscure. In our study, we postulated that DHA might interact with GPR120 to shape the dendritic cell (DC) differentiation and subsequently drive T cell proliferation during the virus infection. In vitro, the proportion of costimulatory molecules and HLA-DR on DC that generated from exogenous and endogenous (fad3b expression) DHA supplemented mice were significantly lower than wild-type mice. Given the importance of FAs, DHA is not only a critical cellular constituent but also a cell signaling molecule and FA deficiency reduces DC generation; we used GPR120-/- mice to determine whether DHA receptor deficiency disorders DC maturation processing. Novelty, the expression of GPR120 on DC from wild-type (WT) mice was inversely related to DC activation and DC from the GPR120-/- mice maintained a spontaneous maturation status. In vivo, both the excessive activation of GPR120 by DHA and the deletion of GPR120 effectively skewed the balance of Th17/Tregs and reduced the production of VNA and protection of vaccination. Overall, our results revealed a mechanism that the GPR120 self-regulation plays a crucial role in sensing DHA variation, which provides a new prospect for therapeutic manipulation in autoimmune diseases and the design of a vaccine adjuvant.
Asunto(s)
Células Dendríticas/metabolismo , Fagocitosis/fisiología , Receptores Acoplados a Proteínas G/metabolismo , Linfocitos T Reguladores/metabolismo , Células Th17/metabolismo , Animales , Compuestos de Boro , Proliferación Celular/genética , Proliferación Celular/fisiología , Supervivencia Celular/genética , Supervivencia Celular/fisiología , Virus de la Encefalitis Japonesa (Especie)/genética , Femenino , Citometría de Flujo , Cromatografía de Gases y Espectrometría de Masas , Ratones , Ratones Endogámicos C57BL , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , Fagocitosis/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores Acoplados a Proteínas G/genética , Análisis de Secuencia de ARN/métodosRESUMEN
The reduced amino acids perform powerful ability for both simplifying protein complexity and identifying functional conserved regions. However, dealing with different protein problems may need different kinds of cluster methods. Encouraged by the success of pseudo-amino acid composition algorithm, we developed a freely available web server, called PseKRAAC (the pseudo K-tuple reduced amino acids composition). By implementing reduced amino acid alphabets, the protein complexity can be significantly simplified, which leads to decrease chance of overfitting, lower computational handicap and reduce information redundancy. PseKRAAC delivers more capability for protein research by incorporating three crucial parameters that describes protein composition. Users can easily generate many different modes of PseKRAAC tailored to their needs by selecting various reduced amino acids alphabets and other characteristic parameters. It is anticipated that the PseKRAAC web server will become a very useful tool in computational proteomics and protein sequence analysis. AVAILABILITY AND IMPLEMENTATION: Freely available on the web at http://bigdata.imu.edu.cn/psekraac CONTACTS: yczuo@imu.edu.cn or imu.hema@foxmail.com or yanglei_hmu@163.comSupplementary information: Supplementary data are available at Bioinformatics online.
Asunto(s)
Proteínas/química , Análisis de Secuencia de Proteína/métodos , Programas Informáticos , Algoritmos , Internet , Proteómica/métodosRESUMEN
Membrane transporters play crucial roles in the fundamental cellular processes of living organisms. Computational techniques are very necessary to annotate the transporter functions. In this study, a multi-class K nearest neighbor classifier based on the increment of diversity (KNN-ID) was developed to discriminate the membrane transporter types when the increment of diversity (ID) was introduced as one of the novel similarity distances. Comparisons with multiple recently published methods showed that the proposed KNN-ID method outperformed the other methods, obtaining more than 20% improvement for overall accuracy. The overall prediction accuracy reached was 83.1%, when the K was selected as 2. The prediction sensitivity achieved 76.7%, 89.1%, 80.1% for channels/pores, electrochemical potential-driven transporters, primary active transporters, respectively. Discrimination and comparison between any two different classes of transporters further demonstrated that the proposed method is a potential classifier and will play a complementary role for facilitating the functional assignment of transporters.
Asunto(s)
Biología Computacional/métodos , Proteínas de Transporte de Membrana/química , Algoritmos , Aminoácidos/química , Bases de Datos de Proteínas , Proteínas de Transporte de Membrana/clasificación , Reproducibilidad de los ResultadosRESUMEN
Hedgehog (Hh) pathway has been studied in various animal body life procedures and is suggested to be important for the development of multiple organs. The genes involved in the Hh signaling pathway were expressed in the ovary of mice, pigs and cattle. However, the function of Hh signaling pathway on oocyte maturation and early embryonic development is still controversial. We detected the effect of sonic hedgehog (Shh) and cyclopamine on the in vitro maturation of mouse oocytes and embryo development. The results showed that the presence of Shh or cyclopamine resulted in similar oocyte maturation to control groups. Shh did not improve early embryonic development. However, the supplement of cyclopamine depressed early embryo development. The mRNA of shh, ptch1, smo and gli1 were less detected in the denuded oocytes. The expression levels of ptch1 ascended from the uncleaved zygote to blastocyst stage. Smo or gli1 were expressed on a higher level at the two-cell or four-cell stage in early embryonic development separately. Therefore, Shh did not affect mouse oocyte maturation and early embryo development, but cyclopamine led to inhibited development of mouse early embryo. The effects of Hh signaling on the oocyte maturation and early embryo development might be species-specific.