Grapholita molesta is a notorious fruit borer globally, causing severe damage to fruit production. To control the pest, one commonly used mean is pheromone-mediated management. As an important sex pheromone, Z-8-dodecenyl acetate (Z8–12: Ac), is often coformulated with other active ingredients to regulate the behavior of G. molesta. To uncover its interactions with G. molesta pheromone binding protein 2 (GmolPBP2) is used to help develop insect attractants. During 200 ns molecular dynamics simulations, two representative conformations of the GmolPBP2-Z8–12: Ac complex are selected. Conformation II at the time of 14–106 ns is dominantly maintained by the hydrophobic interactions and hydrogen bond. In Conformation I, which lasts from 106 to 200 ns, the hydrophobic interactions are enhanced while the hydrogen bond is quite weakened, due to the formation of a more sophisticated hydrophobic binding pocket and the enlargement of hydrogen bond distance. Taking the two conformations as a whole, the affinity between GmolPBP2 and Z8–12: Ac is crucially determined by three hot-spots including Phe11, Trp36, and Ile51. These results would provide a basis for the discovery, optimization, and design of leading compounds potentially active to attract G. molesta.

Given the advantages of behavioral disruption application in pest control and the damage of Cydia pomonella, due progresses have not been made in searching active semiochemicals for codling moth. In this research, 31 candidate semiochemicals were ranked for their binding potential to Cydia pomonella pheromone binding protein 2 (CpomPBP2) by simulated docking, and this sorted result was confirmed by competitive binding assay. This high predicting accuracy of virtual screening led to the construction of a rapid and viable method for semiochemicals searching. By reference to binding mode analyses, hydrogen bond and hydrophobic interaction were suggested to be two key factors in determining ligand affinity, so is the length of molecule chain. So it is concluded that semiochemicals of appropriate chain length with hydroxyl group or carbonyl group at one head tended to be favored by CpomPBP2. Residues involved in binding with each ligand were pointed out as well, which were verified by computational alanine scanning mutagenesis. Progress made in the present study helps establish an efficient method for predicting potentially active compounds and prepares for the application of high-throughput virtual screening in searching semiochemicals by taking insights into binding mode analyses.

Codlemone exhibited high affinity to CpomPBP1, studying their binding mode can provide insights into the rational design of active semiochemicals. Our findings suggested that residues including Phe12, Phe36, Trp37, Ile52, Ile 94, Ala115 and Phe118 were favorable to the binding of Codlemone to CpomPBP1, whereas residues providing unfavorable contributions like Ser56 were negative to the binding. Van der waals energy and electrostatic energy, mainly derived from the sidechains of favorable residues, contributed most in the formation and stability keeping of CpomPBP1-Codlemone complex. Of the residues involved in the interaction between CpomPBP1 and Codlemone, Phe12 and Trp37, whose mutation into Ala caused significant decrease of CpomPBP1 binding ability, were two key residues in determining the binding affinity of Codlemone to CpomPBP1. This study shed lights on discovering novel active semiochemicals as well as facilitating chemical modification of lead semiochemicals.

Glutathione S-transferases (GSTs) are important detoxification enzymes involved in the development of metabolic resistance in Plutella xylostella. Uncovering the interactions between representative PxGSTs and the inhibitor S-hexyl glutathione (GTX), helps in the development of effective PxGST inhibitors for resistance management. As the PxGST most severely inhibited by GTX, PxGSTσ (sigma-class PxGST) adopts the canonical fold of insect GSTs. The formation of the PxGSTσ-GTX complex is mainly driven by H-bond and hydrophobic interactions derived from the side chains of favorable residues. Of the residues composing the active site of PxGSTσ, Lys43 and Arg99 are two hot spots, first reported in the binding of GSH derivatives to GSTs. Such differences indicate the metabolism discrimination of different insect GSTs. Unfavorable interactions between the PxGSTσ active site and GTX are depicted as well. The research guides the discovery and optimization of PxGSTσ inhibitors.

A full-length cDNA encoding Cydia pomonella pheromone binding protein 1 (CpomPBP1) was cloned and characterized. CpomPBP1, possessing the typical characteristics of lepidopteran odorant binding proteins, was detected to be specifically expressed in the antennae of male and female moths at the mRNA and protein level. Soluble recombinant CpomPBP1 was subjected to in vitro binding to analyse its binding properties and to search for potentially active semiochemicals. A competitive binding assay showed that three 12-carbon ligands, codlemone, 1-dodecanol and E,E-2,4-dodecadienal, were able to bind to CpomPBP1 in decreasing order of affinity. Moreover, unlike the wild-type CpomPBP1, the C-terminus truncated CpomPBP1 exhibited high affinity to ligands even in an acidic environment, suggesting that the C-terminus plays a role in preventing ligands from binding to CpomPBP1 in a lower pH environment.

No abstract

AML1/RUNX1 is a critical transcription factor in hematopoietic cell differentiation and proliferation. From the AML1 gene, at least three isoforms, AML1a, AML1b and AML1c, are produced through alternative splicing. AML1a interferes with the function of AML1b/1c, which are often called AML1. In the current study, we found a higher expression level of AML1a in ALL patients in comparison to the controls. Additionally, AML1a represses transcription from promotor of macrophage-colony simulating factor receptor (M-CSFR) mediated by AML1b, indicating that AML1a antagonized the effect of AML1b. In order to investigate the role of AML1a in hematopoiesis and leukemogenesis in vivo, bone marrow mononuclear cells (BMMNCs) from mice were transduced with AML1a and transplanted into lethally irradiated mice, which develop lymphoblastic leukemia after transplantation. Taken together, these results indicate that overexpression of AML1a may be an important contributing factor to leukemogenesis.

BackgroundMeloidogyne incognita is a devastating nematode that causes significant losses in cucumber production worldwide. Although numerous studies have emphasized on the susceptible response of plants after nematode infection, the exact regulation mechanism of M. incognita-resistance in cucumber remains elusive. Verification of an introgression line, ‘IL10–1’, with M. incognita-resistance provides the opportunity to unravel the resistance mechanism of cucumber against M. incognita.ResultsIn the present study, analyses of physiological responses and transcriptional events between IL10–1 (resistant line) and CC3 (susceptible line) were conducted after M. incognita infection. Physiological observations showed abnormal development of giant cells and M. incognita in IL10–1, which were the primary differences compared with CC3. Furthermore, Gene ontology (GO) analysis revealed that genes encoding cell wall proteins were up-regulated in IL10–1 and that the highly expressed lipid transfer protein gene (Csa6G410090) might be the principal regulator of this up-regulation. Simultaneously, analyses of gene expression profiles revealed more auxin-related genes were suppressed in IL10–1 than in those of CC3, which corresponded with the lower level of indole acetic acid (IAA) in the roots of IL10–1 than in those of CC3. Additionally, poor nucleus development as a clear indication of abnormal giant cells in IL10–1 was related to inhibition of the cell cycle. Of those genes related to the cell cycle, the F-box domain Skp2-like genes were down-regulated in IL10–1, whereas more of these genes were up-regulated in CC3.ConclusionsAll of these findings indicate that suppressed expression of genes related to auxin and the cell cycle and highly expressed cell wall proteins play important roles in the abnormal development of giant cells, which hinders the development of M. incognita, thereby causing resistance to M. incognita in IL10–1. Knowledge from this research will provide a useful foundation for developing effective strategies in M. incognita-resistance breeding.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-4979-0) contains supplementary material, which is available to authorized users.