Does Bacillus thuringiensis have adverse effects on the host egg location by parasitoid wasps?

This study investigated the interaction between two pest biological control agents, the parasitoid wasp Trichogramma pretiosum (Hymenoptera: Trichogrammatidae) and the entomopathogen Bacillus thuringiensis (Bacillales: Bacillacea) (Bt). The aim of this study was to evaluate if the presence of Bt (formulated products Agree^®, Dipel^® and HD1 and HD11 strains) interferes in the oviposition preference of T. pretiosum to eggs of Helicoverpa zea (Lepidoptera: Noctuidae). Using an olfactometry test, the eggs of H. zea were bathed with the commercial formulations, with the Bt suspensions or distilled water, and offered to the parasitoid wasps in order to evaluate parasitism. The results showed that H. zea eggs sprayed with commercial formulations and Bt strains did not interfere in the choice made by the parasitoid. The parasitoid wasp is not able to distinguish between eggs with or without B. thuringiensis treatment, independently of strains suspension or commercial formulations. Therefore, these two control agents may be used together without negative interaction.     

Effect of temperature on reproduction and parasitism of the egg parasitoid,Anastatus orientalis (Hymenoptera: Eupelmidae)

Anastatus orientalis is a solitary endoparasitoid of Lycorma delicatula (Hemiptera: Fulgoridae) eggs. We investigated the development, longevity, fecundity, and sex ratio of A. orientalis on different temperatures to establish the optimal temperature condition for laboratory mass rearing. There were significant differences in its development and longevity between 15 °C and the rest of temperature conditions (20, 25, and 30 °C), among which were no significant differences. The average number of eggs laid by A. orientalis was higher at 20 and 25 °C, but there was no statistically significant difference in its fecundity between the two temperatures. More females emerged at 15 and 20 °C than higher temperatures.Parasitisms of A. orientalis varied with host egg ages and densities. Even in 14 day old eggs of L. delicatula, parasitoids successfully emerged from 92.3% of the parasitized eggs. On the other hand, parasitism was lowest (13.8%) on just before hatching eggs. Parasitism was negatively dependent on host density.Oviposition behavior for A. orientalis primarily occurred at 1400–1600 h, not at 2400–0800 h. The majority of this parasitoid's emergence occurred at 0800–1000 h, largely before noon. These results may be useful for controlling the adequate time for supplying host eggs and release density of this parasitoid as well as for potentially predicting the accurate time for securing parasitoid adults in laboratory mass rearing of A. orientalis.     

Insectary production and synopsis of Fopius caudatus (Hymenoptera: Braconidae), parasitoid of tephritid fruit flies indigenous to Africa

Fopius caudatus (Szépligeti) is an endophagous koinobiont egg-larval parasitoid native to Africa. It has recently been noted as a candidate for augmentative biological control of several Dacinae fruit fly pests (Diptera: Tephritidae), due to its ability to parasitize the egg stage. Previous attempts to establish this parasitoid in Hawaii, Guatemala, and Costa Rica were unsuccessful due to inability to maintain parasitoid colonies under laboratory conditions. A cohort of F. caudatus collected from Kenyan fruit flies infesting Coffea arabica was successfully colonized in Hawaii at 28 °C and 60–80% RH, resulting in the development of a laboratory-adapted colony amenable for mass production. The parasitoid was successfully developed from eggs of Ceratitis capitata and Bactrocera latifrons as a factitious host. The wasps were propagated for 15 weeks until the rearing stabilized, at which point >10,500 adults were produced with an overall sex ratio of 0.52 females and a mean host parasitism rate of 17.3%. It could parasitize Medfly eggs in fruits other than coffee, including papaya, mango, pear, squash, and sweet pepper. Female F. caudatus oviposited mainly in 24–48 h old Medfly eggs, although occasionally a few individuals eclosed when first instar fly larvae were exposed. Mean developmental time from egg to adult was 19.8 d for males and 21.5 d for females. Mean longevity was 5.2 d for males and 14.2 d for host-deprived females. This study enabled us to maintain a colony of F. caudatus for research and redistribution to other countries for biocontrol programs against Medfly.     

Biodiversity analysis of natural arthropods enemies in vineyard agroecosystems in La Rioja,Spain

Major knowledge gaps exist regarding effects of landscape-level agroecosystem composition on the presence of natural enemies of agricultural pests. The objective of this study was to evaluate the influence of landscape mosaic characteristics on the diversity of predators and parasitoids of a viticultural landscape in La Rioja, Spain. Five habitats were evaluated: Mediterranean forest, Mediterranean scrub, olive groves, natural grassland, and vineyards. In all, we collected 28,640 arthropods, representing 10 orders: Araneae, Coleoptera, Dermaptera, Diptera, Hemiptera, Hymenoptera, Mantodea, Neuroptera, Solifugae, and Thysanoptera. The grassland habitat presented the highest arthropod abundances. Carabid beetles showed preferences for Mediterranean forest and scrub, whereas reduviid bugs showed preferences for natural grassland. Landscape heterogeneity and connectivity with natural elements in the study area turn out to be effective in conservation of diversity of natural enemies of viticulture.     

The life cycle of Hymenoscyphus fraxineus on Manchurian ash,Fraxinus mandshurica,in Japan

Hymenoscyphus fraxineus causes a lethal disease known as “ash dieback” in the common ash, Fraxinus excelsior, in Europe. It is hypothesized that the fungus originated from East Asia. This fungus is found on the leaf litter of the Manchurian ash, Fraxinus mandshurica, in Japan and is reported to produce apothecia on pseudosclerotial plates formed mainly on decomposing rachises. However, dieback disease has not been reported in Japan, and little is known about the life cycle of H. fraxineus. This study was conducted to explore the behavior and life cycle of this fungus. It was revealed that, after infection by ascospores, H. fraxineus endophytically inhabits the living leaves of F. mandshurica. On fallen leaves, the fungus behaves saprophytically, producing apothecia on pseudosclerotial plates formed mainly on the decomposing rachises. Analysis by real-time quantitative polymerase chain reaction (qPCR) revealed that the amount of H. fraxineus DNA sharply increased in rachises, while such sharp increase of DNA was not found in leaflets.     

Discovery of novel leucyladenylate sulfamate surrogates as leucyl-tRNA synthetase (LRS)-targeted mammalian target of rapamycin complex 1 (mTORC1) inhibitors

According to recent studies, leucyl-tRNA synthetase (LRS) acts as a leucine sensor and modulates the activation of the mammalian target of rapamycin complex 1 (mTORC1) activation. Because overactive mTORC1 is associated with several diseases, including colon cancer, LRS-targeted mTORC1 inhibitors represent a potential option for anti-cancer therapy. In this work, we developed a series of simplified leucyladenylate sulfamate analogues that contain the N-(3-chloro-4-fluorophenyl)quinazolin-4-amine moiety to replace the adenine group. We identified several compounds with comparable activity to previously reported inhibitors and exhibited selective mTORC1 inhibition and anti-cancer activity. This study further supports the hypothesis that LRS is a promising target to modulate the mTORC1 pathway.     

Validation of the diagnostic potential of mtDNA copy number derived from whole genome sequencing

正Diagnosis of mitochondrial DNA(mt DNA)disorders has traditionally been focused on the presence of point mutations and large deletions.However,deviations in mitochondrial abundance or mt DNA copy number can also be associated with many physiological and pathological conditions(Bai and Wong,2005).For example,reduced mt DNA copy number could be a result of defective mt DNA biosynthesis or mt DNA replication and is associated     

Macrocyclic α helical peptide therapeutic modality: A perspective of learnings and challenges

Macrocyclic α-helical peptides have emerged as a compelling new therapeutic modality to tackle targets confined to the intracellular compartment. Within the scope of hydrocarbon-stapling there has been significant progress to date, including the first stapled α-helical peptide to enter into clinical trials. The principal design concept of stapled α-helical peptides is to mimic a cognate (protein) ligand relative to binding its target via an α-helical interface. However, it was the proclivity of such stapled α-helical peptides to exhibit cell permeability and proteolytic stability that underscored their promise as unique macrocyclic peptide drugs for intracellular targets. This perspective highlights key learnings as well as challenges in basic research with respect to structure-based design, innovative chemistry, cell permeability and proteolytic stability that are essential to fulfill the promise of stapled α-helical peptide drug development.     

Functional validation of miRNAs targeting genes of DNA double-strand break repair to radiosensitize non-small lung cancer cells

DNA-Double strand breaks (DSBs) generated by radiation therapy represent the most efficient lesions to kill tumor cells, however, the inherent DSB repair efficiency of tumor cells can cause cellular radioresistance and impact on therapeutic outcome. Genes of DSB repair represent a target for cancer therapy since their down-regulation can impair the repair process making the cells more sensitive to radiation. In this study, we analyzed the combination of ionizing radiation (IR) along with microRNA-mediated targeting of genes involved in DSB repair to sensitize human non-small cell lung cancer (NSCLC) cells. MicroRNAs are natural occurring modulators of gene expression and therefore represent an attractive strategy to affect the expression of DSB repair genes. As possible IR-sensitizing targets genes we selected genes of homologous recombination (HR) and non-homologous end joining (NHEJ) pathway (i.e. RAD51, BRCA2, PRKDC, XRCC5, LIG1). We examined these genes to determine whether they may be real targets of selected miRNAs by functional and biological validation. The in vivo effectiveness of miRNA treatments has been examined in cells over-expressing miRNAs and treated with IR. Taken together, our results show that hsa-miR-96-5p and hsa-miR-874-3p can directly regulate the expression of target genes. When these miRNAs are combined with IR can decrease the survival of NSCLC cells to a higher extent than that exerted by radiation alone, and similarly to radiation combined with specific chemical inhibitors of HR and NHEJ repair pathway.     

Structure-activity relationship investigation of Phe-Arg mimetic region of human glutaminyl cyclase inhibitors

Glutamyl cyclase (QC) is a promising therapeutic target because of its involvement in the pathogenesis of Alzheimer’s disease. In this study, we developed novel QC inhibitors that contain 3-aminoalkyloxy-4-methoxyphenyl and 4-aminoalkyloxyphenyl groups to replace the previously developed pharmacophore. Several potent inhibitors were identified, showing IC₅₀ values in a low nanomolar range, and were further studied for in vitro toxicity and in vivo activity. Among these, inhibitors 51 and 53 displayed the most potent Aβ_N3pE?40-lowering effects in in vivo acute model with reasonable BBB penetration, without showing cytotoxicity and hERG inhibition. The molecular modeling analysis of 53 indicated that the salt bridge interaction and the hydrogen bonding in the active site provided a high potency. Given the potent activity and favorable BBB penetration with low cytotoxicity, we believe that compound 53 may serve as a potential candidate for anti-Alzheimer’s agents.