A Human Anti-Toll Like Receptor 4 Fab Fragment Inhibits Lipopolysaccharide-Induced Pro-Inflammatory Cytokines Production in Macrophages

The results of clinical and experimental studies suggest that endotoxin/toll-like receptor 4 (TLR4)-mediated proinflammatory and profibrotic signaling activation is critical in the development of hepatic fibrosis. However, studies examining the role of specific TLR4 inhibitor are still lacking. The present study was aimed to prepare a human anti-TLR4 Fab fragment, named hTLR4-Fab01, and to explore its immune activity. We screened the positive clone of anti-human TLR4 phagemid from a human phage-display antibody library using recombinant TLR4 protein, which was used as template cDNA for the amplification of variable regions of the heavy (V_H) chain and light chain (V_L), then coupled with highly conserved regions of the heavy chain domain 1 (C_H1) and the light chain (C_L), respectively. Thus, the prokaryotic expression vector pETDuet-1 of hTLR4-Fab01 was constructed and transformed into Escherichia coli (E. coli) BL21. The characteristic of hTLR4-Fab01 was examined by SDS-PAGE, Western blotting, ELISA, affinity and kinetics assay. Further, our data demonstrate that hTLR4-Fab01 could specifically bind to TLR4, and its treatment obviously attenuated the proinflammatory effect, characterized by less LPS-induced TNF-α, IL-1, IL-6 and IL-8 production in human macrophages. In conclusion, we have successfully prepared the hTLR4-Fab01 with efficient activity for blocking LPS-induced proinflammatory cytokines production, suggesting that the hTLR4-Fab01 may be a potential candidate for the treatment of hepatic fibrosis.     

Evaluation of different nitrous oxide production models with four continuous long-term wastewater treatment process data series

Five activated sludge models describing N₂O production by ammonium oxidising bacteria (AOB) were compared to four different long-term process data sets. Each model considers one of the two known N₂O production pathways by AOB, namely the AOB denitrification pathway and the hydroxylamine oxidation pathway, with specific kinetic expressions. Satisfactory calibration could be obtained in most cases, but none of the models was able to describe all the N₂O data obtained in the different systems with a similar parameter set. Variability of the parameters can be related to difficulties related to undescribed local concentration heterogeneities, physiological adaptation of micro-organisms, a microbial population switch, or regulation between multiple AOB pathways. This variability could be due to a dependence of the N₂O production pathways on the nitrite (or free nitrous acid—FNA) concentrations and other operational conditions in different systems. This work gives an overview of the potentialities and limits of single AOB pathway models. Indicating in which condition each single pathway model is likely to explain the experimental observations, this work will also facilitate future work on models in which the two main N₂O pathways active in AOB are represented together.     

Stereospecificity of peptide synthesis by means of phosphorus derivatives: a model of peptide synthesis in molecular evolution

A hypothesis is presented to explain the prebiotic formation of optically pure oligo- and polypeptides from racemic amino acids. Stereospecific condensation reactions favouring the formation of isotactic stereosequences (l-l and d-d blocks) are a basic requirement of this hypothesis. Since phosphorus derivatives such as polyphosphates or nucleic acid imidazolides were postulated to be prebiotic condensing reagents, a variety of peptide syntheses by means of phosphorus derivatives was investigated. Dipeptides and tripeptides were prepared from N-protected d,l-amino acids or d,l-amino acid esters, and d,l-leucine and d,l-valine were subjected to condensation polymerizations. The stereosequences were analysed by means of ¹³C n.m.r. spectroscopy. More than 80% of all condensations were more or less stereospecific and in all cases isotactic sequences were predominant. In the case of poly(d,l-leucines), ¹³C n.m.r. cross-polarization/magic angle spinning (CP/MAS) spectra revealed the formation of α-helical blocks.     

野生植物苦皮藤种油对几种主要害虫防治研究报告

室内测定表明:苦皮藤种油对菜青虫、黄守瓜、猿叶虫、28星瓢虫,丝绵木金星■蠖、缀叶丛螟等六种害虫有明显的拒食作用;田间试验效果:防治菜青虫,用2%、0.66%、0.5%的苦皮藤种油防效分别为86.5%、91.16%、85.37%,10%氯氰菊酯5000倍液为89.6%,苦皮藤根皮粉为79.81%,所以,苦皮藤种油与氯氰菊酯的效果相近,但优于苦皮藤根皮粉;防治黄守瓜,其防效与增产均优于DDVp。苦皮藤资源丰富,其种油将有可能成为一种很有发展前途的植物性天然产物杀虫剂或拒食剂。     

Selection for commercial forestry determines global patterns of alien conifer invasions

Question Are the patterns of alien conifer (Pinaceae, Cupressaceae) invasions different between continents, and how is invasion success influenced by commercial forestry practices? Location Temperate and subtropical countries and regions (n = 60) from five continents spanning both hemispheres. Methods We used generalized linear mixed models to test how continent identity, region area and use in commercial forestry affect probabilities of Pinaceae and Cupressaceae species to escape following introduction and cumulative logit regression models to assess how these predictors affect the likelihood that a species becomes naturalized or invasive. Results Sixty Pinaceae of a global total of 232 and 26 Cupressaceae of a total of 142 species have escaped from cultivation across the study regions examined. Average numbers of both alien Pinaceae and Cupressaceae species per region were highest in Oceania, followed by Africa. Moreover, the probability of alien Cupressaceae and Pinaceae becoming naturalized or invasive was particularly high in these two continents. For both families, species used in commercial forestry have a significantly higher probability of escape than those which are only introduced for ornamental or other purposes. In the case of Pinaceae, forestry species also become naturalized or invasive more frequently than non‐forestry species, while no such effect was detectable for Cupressaceae. Conclusions We found that non‐native conifers are more likely to escape from cultivation, naturalize and turn into invasive weeds on the continents of the Southern Hemisphere. In addition to this biogeographic signal, introduction effort strongly determines the behaviour of introduced Pinaceae, and less so, Cupressaceae. A clear conflict exists between the economic benefits of conifer forestry and the risks to the environment from invasions. Future expansion of commercial forestry should address spatial planning to ecosystems vulnerable to invasion and adopt comprehensive risk assessment procedures.     

EBNA3C Augments Pim-1 Mediated Phosphorylation and Degradation of p21 to Promote B-Cell Proliferation

Epstein–Barr virus (EBV), a ubiquitous human herpesvirus, can latently infect the human population. EBV is associated with several types of malignancies originating from lymphoid and epithelial cell types. EBV latent antigen 3C (EBNA3C) is essential for EBV-induced immortalization of B-cells. The Moloney murine leukemia provirus integration site (PIM-1), which encodes an oncogenic serine/threonine kinase, is linked to several cellular functions involving cell survival, proliferation, differentiation, and apoptosis. Notably, enhanced expression of Pim-1 kinase is associated with numerous hematological and non-hematological malignancies. A higher expression level of Pim-1 kinase is associated with EBV infection, suggesting a crucial role for Pim-1 in EBV-induced tumorigenesis. We now demonstrate a molecular mechanism which reveals a direct role for EBNA3C in enhancing Pim-1 expression in EBV-infected primary B-cells. We also showed that EBNA3C is physically associated with Pim-1 through its amino-terminal domain, and also forms a molecular complex in B-cells. EBNA3C can stabilize Pim-1 through abrogation of the proteasome/Ubiquitin pathway. Our results demonstrate that EBNA3C enhances Pim-1 mediated phosphorylation of p21 at the Thr¹⁴⁵ residue. EBNA3C also facilitated the nuclear localization of Pim-1, and promoted EBV transformed cell proliferation by altering Pim-1 mediated regulation of the activity of the cell-cycle inhibitor p21/WAF1. Our study demonstrated that EBNA3C significantly induces Pim-1 mediated proteosomal degradation of p21. A significant reduction in cell proliferation of EBV-transformed LCLs was observed upon stable knockdown of Pim-1. This study describes a critical role for the oncoprotein Pim-1 in EBV-mediated oncogenesis, as well as provides novel insights into oncogenic kinase-targeted therapeutic intervention of EBV-associated cancers.     

Electrochemical Identification of <i>Yulania</i> spp. by Fingerprinting of Leaves Using Glassy Carbon Electrode

In this communication, we used electrochemical sensor for recording the electrochemical profiles of eleven species of Yulania spp. from leaf extract. Two solvents and two buffer conditions were used for electrochemical fingerprints collection. Their electrochemical fingerprints can be converted to different patterns and consequently for species recognition. The results indicate the pattern recognition is much convenient than that of the recognition of species directly using voltammetric signal. The current information in electrochemical fingerprinting represents the type and amount of electrochemically active molecules, which linked to the genetic differences among the plants. Therefore, the electrochemical fingerprints were applied for further phylogenetic study. The phylogenetic tree deduced from voltametric curves is divided into three main groups. The first clade contains Y. denudate, Liriodendron chinense, Y. cylindrica, Y. biondii, Y. sprengeri. The second clade contains Y. zenii, Y. liliiflora, Y. kobus, and Y. amoena. The third clade contains Y. × soulangeana, Manglietia fordiana and Y. sinostellata. In addition, Y. salicifolia is not in these main clades. The results demonstrate that electrochemical fingerprinting can be used as a com-plementary tool in the study of phylogenetics.     

Long-term,multidomain analyses to identify the breed and allelic effects in MSTN-edited pigs to overcome lameness and sustainably improve nutritional meat production

Science China Life Sciences - Beef and mutton production has been aided by breeding to integrate allelic diversity for myostatin (MSTN), but a lack of diversity in the MSTN germplasm has limited...