2,4-Dihydroxyphenylacetyl-L-asparagine

Induction of Broadly Cross-Reactive Stalk-Specific Antibody Responses to Influenza Group 1 and Group 2 Hemagglutinins by Natural H7N9 Virus Infection in Humans.[Pubmed:28380622]

J Infect Dis. 2017 Feb 15;215(4):518-528.

Background: The outbreak of novel avian H7N9 influenza virus infections in China in 2013 has demonstrated the continuing threat posed by zoonotic pathogens. Deciphering the immune response during natural infection will guide future vaccine development. Methods: We assessed the induction of heterosubtypic cross-reactive antibodies induced by H7N9 infection against a large panel of recombinant hemagglutinins and neuraminidases by quantitative enzyme-linked immunosorbent assay, and novel chimeric hemagglutinin constructs were used to dissect the anti-stalk or -head humoral immune response. Results: H7N9 infection induced strong antibody responses against divergent H7 hemagglutinins. Interestingly, we also found induction of antibodies against heterosubtypic hemagglutinins from both group 1 and group 2 and a boost in heterosubtypic neutralizing activity in the absence of hemagglutination inhibitory activity. Kinetic monitoring revealed that heterosubtypic binding/neutralizing antibody responses typically appeared and peaked earlier than intrasubtypic responses, likely mediated by memory recall responses. Conclusions: Our results indicate that cross-group binding and neutralizing antibody responses primarily targeting the stalk region can be elicited after natural influenza virus infection. These data support our understanding of the breadth of the postinfection immune response that could inform the design of future, broadly protective influenza virus vaccines.

Ficolin-A/2, acting as a new regulator of macrophage polarization, mediates the inflammatory response in experimental mouse colitis.[Pubmed:28380665]

Immunology. 2017 Aug;151(4):433-450.

Human ficolin-2 (FCN-2) and mouse ficolin-A (FCN-A, a ficolin-2-like molecule in mouse) are activators of the lectin complement pathway, present in normal plasma and usually associated with infectious diseases, but little is known about the role of FCN-A/2 in inflammatory bowel disease (IBD). In our present study, we found that patients with IBD exhibited much higher serum FCN-2 levels than healthy controls. In the dextran sulphate sodium-induced acute colitis mouse model, FCN-A knockout mice showed much milder disease symptoms with less histological damage, lower expression levels of pro-inflammatory cytokines [interleukin-6 (IL-6), IL-1beta and tumour necrosis factor-alpha (TNF-alpha)], chemokines (CXCL1/2/10 and CCL4) and higher levels of the anti-inflammatory cytokine IL-10 compared with wild-type mice. We demonstrated that FCN-A/2 exacerbated the inflammatory pathogenesis of IBD by stimulating M1 polarization through the TLR4/MyD88/MAPK/NF-kappaB signalling pathway in macrophages. Hence, our data suggest that FCN-A/2 may be used as a novel therapeutic target for IBD.

Bicomponent fibrous scaffolds made through dual-source dual-power electrospinning: Dual delivery of rhBMP-2 and Ca-P nanoparticles and enhanced biological performances.[Pubmed:28380671]

J Biomed Mater Res A. 2017 Aug;105(8):2199-2209.

Electrospun scaffolds incorporated with both calcium phosphates (Ca-P) and bone morphogenetic protein-2 (BMP-2) have been used for bone tissue regeneration. However, in most cases BMP-2 and Ca-P were simply mixed and loaded in a monolithic structure, risking low BMP-2 loading level, reduced BMP-2 biological activity, uncontrolled BMP-2 release and inhomogeneous Ca-P distribution. In this investigation, novel bicomponent scaffolds having evenly distributed rhBMP-2-containing fibers and Ca-P nanoparticle-containing fibers were made using an established dual-source dual-power electrospinning technique with the assistance of emulsion electrospinning and blend electrospinning. The release behavior of rhBMP-2 and Ca(2+) ions could be separately tuned and the released rhBMP-2 retained a 68% level for biological activity. MC3T3-E1 cells showed high viability and normal morphology on scaffolds. Compared to monocomponent scaffolds, enhanced cell proliferation, alkaline phosphatase activity, cell mineralization, and gene expression of osteogenic markers were achieved for bicomponent scaffolds due to the synergistic effect of rhBMP-2 and Ca-P nanoparticles. Bicomponent scaffolds with a double mass elicited further enhanced cell adhesion, spreading, proliferation, and osteogenic differentiation. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2199-2209, 2017.

Integrated analysis of non-coding RNA and mRNA expression profiles of 2 pig breeds differing in muscle traits.[Pubmed:28380516]

J Anim Sci. 2017 Mar;95(3):1092-1103.

Production of high-quality meat is important to satisfy the consumer and allow the pork industry to be competitive. It is evident that different muscle fiber types in different breeds greatly influence the pork quality, but the underlying molecular mechanism remains unclear. We used Ribo-Zero RNA-Seq and miRNA-Seq to examine global expressions of protein-coding transcripts and non-coding RNAs including miRNA, lncRNA, and circRNA in the longissimus dorsi of Landrace and Lantang pigs. Of the 22,469 identified coding transcripts, only 547 candidates were differentially expressed, including 461 upregulated and 86 downregulated transcripts in the Lantang pigs compared with Landrace. Gene ontology analysis of these differentially-expressed transcripts further revealed 17 genes involved in myogenesis. In addition, 5,566 lncRNA and 4,360 circRNA candidates were found to be differentially expressed. Of these, 3,976 lncRNAs and 1,401 circRNAs were upregulated in the Lantang library, while 1,590 lncRNAs and 2,959 circRNAs were downregulated. Of the differentially expressed circRNAs, 236 candidates were edited from 93 functional hosting-genes related to myogenesis. We found 96 showed upregulation and 140 showed downregulation. By analyzing Ribo-Zero RNA-Seq data in combination with matched miRNA profiles, we identified 68 sponge modulators participating in 26 miRNA-mediated ceRNA interactions, including 19 lncRNAs, 40 circRNAs, and 9 mRNAs. Our study uncovered a novel post-transcriptional regulation layer which could help in the understanding of the mechanisms that underlie porcine myofiber development in different breeds.

A spider toxin (JSTX) inhibits L-glutamate uptake by rat brain synaptosomes.[Pubmed:2564797]

Brain Res. 1989 Jan 9;476(2):354-7.

Joro spider toxin (JSTX), a specific blocker of glutamate receptors, was found to exert a prominent suppressive action on the Na+-dependent binding of L-glutamate to synaptic membranes and on glutamate uptake by synaptosomes in a dose-dependent manner. In contrast, the synthesized 2,4-dihydroxyphenylacetylasparagine (2,4-DHPA-ASN), a common moiety of spider toxins, which has been shown to exhibit almost the same activity as intact JSTX with respect to the inhibition of Na+-independent glutamate binding to its synaptic membrane receptors, shows lower potency in inhibiting Na+-dependent binding and uptake of L-glutamate. From these findings, it is clear that JSTX has the ability to inhibit not only L-glutamate binding to its synaptic membrane receptors but also L-glutamate uptake by synaptosomes, and that polyamines linked to 2,4-DHPA-ASN in the molecule of spider toxins may participate in the inhibition of L-glutamate uptake.

Inhibitory effect of 2,4-dihydroxyphenylacetylasparagine, a common moiety of spider toxin, on glutamate binding to rat brain synaptic membranes.[Pubmed:2827066]

Neurosci Lett. 1987 Oct 16;81(1-2):199-203.

2,4-Dihydroxyphenylacetylasparagine (2,4-DHPA-ASN), a common moiety of molecules of spider toxins, was shown to inhibit L-[3H]glutamic acid binding to rat brain synaptic membranes in a dose-dependent manner. The inhibitory effect of 2,4-DHPA-ASN was almost the same as that of intact spider toxin isolated from Nephila clavata, but significantly higher than that of 2,4-dihydroxyphenylacetic acid (2,4-DHPA). In addition, neither 2,4-dihydroxybenzoic acid nor the isomers of 2,4-DHPA suppressed the glutamate binding. These results suggested that 2,4-DHPA might be the functional part and asparagine in the molecules of spider toxins seemed to cause increasing affinity toward the recognition site of glutamate binding.