Silencing of two insulin receptor genes disrupts nymph-adult transition of alate brown citrus aphid

Insulin receptors play key roles in growth, development, and polymorphism in insects. Here, we report two insulin receptor genes (AcInR1 and AcInR2) from the brown citrus aphid, Aphis (Toxoptera) citricidus. Transcriptional analyses showed that AcInR1 increased during the nymph-adult transition in alate aphids, while AcInR2 had the highest expression level in second instar nymphs. AcInR1 is important in aphid development from fourth instar nymphs to adults as verified by dsRNA feeding mediated RNAi. The silencing of AcInR1 or/and AcInR2 produced a variety of phenotypes including adults with normal wings, malformed wings, under-developed wings, and aphids failing to develop beyond the nymphal stages. Silencing of AcInR1 or AcInR2 alone, and co-silencing of both genes, resulted in 73% or 60%, and 87% of aphids with problems in the transition from nymph to normal adult. The co-silencing of AcInR1 and AcInR2 resulted in 62% dead nymphs, but no mortality occurred by silencing of AcInR1 or AcInR2 alone. Phenotypes of adults in the dsInR1 and dsInR2 were similar. The results demonstrate that AcInR1 and AcInR2 are essential for successful nymph-adult transition in alate aphids and show that RNAi methods may be useful for the management of this pest

Patterns of exon-intron architecture variation of genes in eukaryotic genomes

<p>Abstract</p> <p>Background</p> <p>The origin and importance of exon-intron architecture comprises one of the remaining mysteries of gene evolution. Several studies have investigated the variations of intron length, GC content, ordinal position in a gene and divergence. However, there is little study about the structural variation of exons and introns.</p> <p>Results</p> <p>We investigated the length, GC content, ordinal position and divergence in both exons and introns of 13 eukaryotic genomes, representing plant and animal. Our analyses revealed that three basic patterns of exon-intron variation were present in nearly all analyzed genomes (<it>P </it>< 0.001 in most cases): an ordinal reduction of length and divergence in both exon and intron, a co-variation between exon and its flanking introns in their length, GC content and divergence, and a decrease of average exon (or intron) length, GC content and divergence as the total exon numbers of a gene increased. In addition, we observed that the shorter introns had either low or high GC content, and the GC content of long introns was intermediate.</p> <p>Conclusion</p> <p>Although the factors contributing to these patterns have not been identified, our results provide three important clues: common factor(s) exist and may shape both exons and introns; the ordinal reduction patterns may reflect a time-orderly evolution; and the larger first and last exons may be splicing-required. These clues provide a framework for elucidating mechanisms involved in the organization of eukaryotic genomes and particularly in building exon-intron structures.</p

Enterovirus 71 viral capsid protein linear epitopes: Identification and characterization

Background: To characterize the human humoral immune response against enterovirus 71 (EV71) infection and map human epitopes on the viral capsid proteins. Methods: A series of 256 peptides spanning the capsid proteins (VP1, VP2, VP3) of BJ08 strain (genomic C4) were synthesized. An indirect enzyme-linked immunosorbent assay (ELISA) was carried out to detect anti-EV71 IgM and IgG in sera of infected children in acute or recovery phase. The partially overlapped peptides contained 12 amino acids and were coated in the plate as antigen (0.1 μg/μl). Sera from rabbits immunized with inactivated BJ08 virus were also used to screen the peptide panel. Results: A total of 10 human anti-EV71 IgM epitopes (vp1-14 in VP1; vp2-6, 21, 40 and 50 in VP2 and vp3-10, 12, 15, 24 and 75 in VP3) were identified in acute phase sera. In contrast, only one anti-EV71 IgG epitope in VP1 (vp1-15) was identified in sera of recovery stage. Four rabbit anti-EV71 IgG epitopes (vp1-14, 31, 54 and 71) were identified and mapped to VP1. Conclusion: These data suggested that human IgM epitopes were mainly mapped to VP2 and VP3 with multiepitope responses occurred at acute infection, while the only IgG epitope located on protein VP1 was activated in recovery phase sera. The dynamic changes of humoral immune response at different stages of infection may have public health significance in evaluation of EV71 vaccine immunogenicity and the clinical application of diagnostic reagents

Antithrombin III Alleviates Myocardial Ischemia/Reperfusion Injury by Inhibiting Excessive Autophagy in a Phosphoinositide 3-Kinase/Akt-Dependent Manner

Autophagy is fundamental to myocardial ischemia/reperfusion (I/R) injury. Antithrombin III (AT) has been shown to protect cardiomyocytes against I/R injury; however, it is unknown whether it modulates autophagy. The objective of this study was to investigate whether AT regulates autophagy during I/R injury and, if so, to identify the potential mechanism involved. Our study showed that AT attenuated I/R injury in vivo and hypoxia/reoxygenation (H/R) injury in vitro. Autophagy was increased both in H9C2 cardiomyocytes during H/R injury and in mouse hearts following I/R injury. The stimulation of autophagy by rapamycin attenuated the protective effect of AT against H9C2 cell injury, indicating that autophagy is involved in the protective role of AT. Furthermore, the cardioprotective effects of AT were abolished by A6730, a specific Akt inhibitor. This study shows that AT exhibits cardioprotective effects by modulating autophagy during I/R injury in a phosphoinositide 3-kinase/Akt-dependent manner

Synthesis of novel spin-labeled podophyllotoxin derivatives as potential antineoplastic agents: Part XXV

A series of novel spin-labeled 4β-[(4-substituted)-1,2,3-triazol-1-yl]podophyllotoxin derivatives (17a–h) were firstly designed and synthesized with significant regioselectivity by employing Cu(I) catalyzed click approach, and evaluated for cytotoxicity against four human tumor cell lines (A-549, DU145, KB, and KBvin). Among them, compound 17h displayed the highest cytotoxic activity against the tumor cell lines tested. Significantly, compound 17h showed superior cytotoxic activity compared with etoposide (IC50 6.30 to>10 μM), a clinically available anticancer drug. Significant activity toward the drug resistant KBvin cell line revealed promising future for compound 17h as a new generation of epipodophyllotoxin-derived antitumor clinical trial candidate