On self-nonself discrimination in pattern recognition

<正>Wide distribution and broad reactivity are cardinal features of pattern recognition receptors that allow rapid mobiliza-tion of large numbers of effectors to deal with pathogens.However, these features come with significant baggage as the receptors have been shown to interact with many intra-cellular components, collectively called danger-associated     

Coupling of Graphene Plasmonics Modes Induced by Near-Field Perturbation at Terahertz Frequencies

Plasmonics - The coupling between graphene surface plasmonic (GSP) modes and evanescent wave modes induced by near-field perturbation is investigated systematically in the grating-spacer-graphene...     

Identification of 14-3-3 Proteins Phosphopeptide-Binding Specificity Using an Affinity-Based Computational Approach

The 14-3-3 proteins are a highly conserved family of homodimeric and heterodimeric molecules, expressed in all eukaryotic cells. In human cells, this family consists of seven distinct but highly homologous 14-3-3 isoforms. 14-3-3σ is the only isoform directly linked to cancer in epithelial cells, which is regulated by major tumor suppressor genes. For each 14-3-3 isoform, we have 1,000 peptide motifs with experimental binding affinity values. In this paper, we present a novel method for identifying peptide motifs binding to 14-3-3σ isoform. First, we propose a sampling criteria to build a predictor for each new peptide sequence. Then, we select nine physicochemical properties of amino acids to describe each peptide motif. We also use auto-cross covariance to extract correlative properties of amino acids in any two positions. Finally, we consider elastic net to predict affinity values of peptide motifs, based on ridge regression and least absolute shrinkage and selection operator (LASSO). Our method tests on the 1,000 known peptide motifs binding to seven 14-3-3 isoforms. On the 14-3-3σ isoform, our method has overall pearson-product-moment correlation coefficient (PCC) and root mean squared error (RMSE) values of 0.84 and 252.31 for N–terminal sublibrary, and 0.77 and 269.13 for C–terminal sublibrary. We predict affinity values of 16,000 peptide sequences and relative binding ability across six permutated positions similar with experimental values. We identify phosphopeptides that preferentially bind to 14-3-3σ over other isoforms. Several positions on peptide motifs are in the same amino acid category with experimental substrate specificity of phosphopeptides binding to 14-3-3σ. Our method is fast and reliable and is a general computational method that can be used in peptide-protein binding identification in proteomics research.     

Linking membrane dynamics and trafficking to autophagy and the unfolded protein response

Cellular stressors typically induce two protective counter‐responses—autophagy and the unfolded protein response (UPR). It is conceivable that these two endoplasmic reticulum (ER) membrane‐based processes would intersect/interact somehow with the constitutive housekeeping process of exocytic membrane traffic from the ER. How exactly might this occur? Recent evidence indicates that a conserved Rab protein, Rab1/Ypt1p, has functional roles in UPR and autophagy. This molecular switch and its associated effectors may therefore serve to link up a network of cellular responses to stress through changes in membrane dynamics and protein turnover. The notion provides further explanations as to why elevation of Rab1/Ypt1p levels could counter the cytotoxicity of α‐synuclein, and a similar mode of protection may well be at work against other stresses. J. Cell. Physiol. 228: 1638–1640, 2013. © 2013 Wiley Periodicals, Inc.     

LncRNA Bmp1 promotes the healing of intestinal mucosal lesions via the miR-128-3p/PHF6/PI3K/AKT pathway

Intestinal mucosal injuries are directly or indirectly related to many common acute and chronic diseases. Long non-coding RNAs (lncRNAs) are expressed in many diseases, including intestinal mucosal injury. However, the relationship between lncRNAs and intestinal mucosal injury has not been determined. Here, we investigated the functions and mechanisms of action of lncRNA Bmp1 on damaged intestinal mucosa. We found that Bmp1 was increased in damaged intestinal mucosal tissue and Bmp1 overexpression was able to alleviate intestinal mucosal injury. Bmp1 overexpression was found to influence cell proliferation, colony formation, and migration in IEC-6 or HIEC-6 cells. Moreover, miR-128-3p was downregulated after Bmp1 overexpression, and upregulation of miR-128-3p reversed the effects of Bmp1 overexpression in IEC-6 cells. Phf6 was observed to be a target of miR-128-3p. Furthermore, PHF6 overexpression affected IEC-6 cells by activating PI3K/AKT signaling which was mediated by the miR-128-3p/PHF6 axis. In conclusion, Bmp1 was found to promote the expression of PHF6 through the sponge miR-128-3p, activating the PI3K/AKT signaling pathway to promote cell migration and proliferation.Subject terms: Cell growth, Cell migration