Toxicity of mycotoxins to insects and underlying molecular and biochemical mechanisms

Mycotoxins are synthesized by fungi and released as secondary metabolites toxic to many animal species. The structurally diverse mycotoxins can be carcinogenic, mutagenic, teratogenic, estrogenic, hemorrhagic, immunotoxic, nephrotoxic, hepatotoxic, dermotoxic, and neurotoxic to humans and other mammals. To minimize the harmful effects of mycotoxins on humans, strict regulations have been established worldwide. Economic losses due to mycotoxin contamination are enormous and estimated at millions of dollars annually in the United States alone Insects inevitably encounter mycotoxins in nature when they feed on unharvested (mummy) fruits in orchard situations. Insects can be vectors of fungal spores and also facilitate fungal access to their host plants. Insects in turn may take advantage of fungi for protection against their natural enemies and for processing refractory plant constituents to increase their digestibility. This interaction is manifested in many crops as an association between insect damage and increase in mycotoxin contamination. Control of insects can thus reduce fungal toxin levels in crops. Understanding how insects deal with mycotoxins is critical in control of both insect pests and mycotoxin contamination. In this study, three insects, including Helicoverpa zea (corn earworm), Amyelois transitella (navel orangeworm) and Apis mellifera (honey bee) varying in their exposure to mycotoxins were selected to study toxicity of mycotoxins to insects and to elucidate their underlying mechanisms of toxicity. To compare toxicity of mycotoxins to H. zea with that to A. transitella, I measured the developmental delay caused by aflatoxin B1 (AFB1), and found that the LC50 (defined as the concentration preventing 50% of newly hatched larvae from entering the second instar within 48 hr) for AFB1 is 100 times greater for A. transitella than that for H. zea. Similarly, A. transitella first instars display substantially higher tolerance of ochratoxin A (OTA) than do H. zea. Honey bees and their resource-rich nests are hosts to a wide range of saprophytic fungi, including species that produce mycotoxins. Bioassays showed that the honey bee workers can tolerate relatively high levels of aflatoxins (1-2.5μg/g AFB1) and ochratoxins (1μg/g OTA). Cytochrome P450 monooxygenases (P450s) are critical in detoxification and activation of mycotoxins. In this study, I found that midgut homogenates isolated from H. zea larvae consuming diets supplemented with phytochemicals (coumarin and xanthotoxin) showed significant AFB1 disappearance and generated two metabolites, with the primary one identified as aflatoxin P1 (AFP1), an O-demethylated less toxic product of AFB1.Three P450 proteins from H. zea including CYP6B8, CYP6B27 and CYP321A1 were co-expressed with house fly reductase in insect cells and only the expressed CYP321A1 can metabolize AFB1, producing the same two metabolites as the midgut homogenates. RT-PCR gel blots indicated that the magnitude of CYP321A1 transcript induction by these chemicals is associated with the magnitude of increase in the metabolic activities of induced midgut enzymes (coumarin>xanthotoxin>indole 3-carbinol). These results indicate that induction of P450s, such as CYP321A1, plays an important role in reducing AFB1 toxicity to H. zea. Docking of AFB1 in the molecular models of CYP321A1 and CYP6B8 highlights differences in their proximal catalytic site volumes that allow only CYP321A1 to generate the AFP1 metabolite. Enhancement of the toxicity of AFB1 by piperonyl butoxide, a P450 inhibitor, indicates a role for P450s in AFB1 detoxification in honey bees. Extracts of propolis, a complex mixture of plant-derived chemicals that contains many flavonoids and other phenolic compounds, similarly ameliorated aflatoxin toxicity and delayed the onset of mortality. Collectively, these results suggest that tolerance of AB1 by honey bees may be due to P450-mediated metabolic detoxification. To understand molecular mechanisms underlying detoxification of mycotoxins by navel orangeworms, three full-length P450 cDNAs, including CYP6AB11, CYP321C1 and CYP6B44, were isolated from larval midguts using Rapid Amplification of cDNA Ends PCR. These P450s were co-expressed with house fly reductase and fruit fly cytochrome b5 in Sf9 insect cells infected with recombinant baculoviruses. Assays conducted with 16 compounds, including AFB1, showed that CYP6AB11 can efficiently metabolize imperatorin (0.88pmol/min/pmol) and slowly metabolize PBO (0.11 pmol/min/pmol). In view of all of results, it is clear that similar metabolic pathways of detoxification of mycotoxins similar to those found in mammals exist in insects. However, some insects, such as navel orangeworm, may have evolved in response to specializing on food containing mycotoxin-releasing fungi such as navel orangeworm. A potentially safe and sustainable approach for managing this serious fungus vector in orchards may be to use natural essential oil synergists. My results show that myristicin, a natural essential oil compound, synergized the toxicity of α-cypermethrin, a pyrethroid insecticide, over time and slightly increased toxicity of a plant toxin, xanthotoxin, after seven days. Myristicin should be explored further as a field treatment to reduce survival of this pest species and to prevent aflatoxin contamination in orchard situations

Sterigmatocystin limits plasmodium falciparum proliferation and transmission

As part of our drug discovery program against malaria, the Penicillium janthinellum ex-tract was discovered to inhibit P. falciparum proliferation in blood and transmission to mosquitoes. Bioactivity-guided fractionation of P. janthinellum extraction was carried out using chromatographic techniques. We determined the activities of fractions against Plasmodium falciparum asexual stage parasite proliferation in culture and sexual stage parasite transmission to mosquitoes using standard membrane feeding assays (SMFA). One active compound was isolated. Based on mass spectrom-etry and nuclear magnetic resonance profiles, the compound was structurally determined to be sterigmatocystin. Sterigmatocystin inhibited P. falciparum proliferation in the blood with an IC50 of 34 µM and limited the sexual parasites to infect mosquitoes with an IC50 of 48 µM. Meanwhile, sterigmatocystin did not show any acute toxicity to human kidney cells at a concentration of 64 µM or lower. Sterigmatocystin can be used as a drug lead for malaria control and as a probe to understand molecular mechanisms of malaria transmission

Tris(diphenyl­propyl­phosphine-κP)-μ2-iodido-tri-μ3-sulfido-sulfidotricopper(I)tungsten(VI)

A neutral W/S/Cu cluster, [Cu3WIS4(C15H17P)3], was formed by the reaction of tetra­thio­tungstate(VI), CuI and diphenyl­propyl­phosphine (dpp) in dimethyl­formamide. The title compound exhibits a neutral half-open cubane-like skeleton, with Cu—I bonds of 2.8056 (8) and 2.9008 (8) Å, and one Cu⋯I short contact of 3.1722 (6) Å. The W atom exhibits a tetra­hedral coordination geometry through bonding to three μ3-S and one terminal S atom. The three CuI atoms are in two different coordination environments: one Cu atom exhibits a triangular coordination geometry being coordinated by one P atom from dpp and two μ3-S atoms, whereas the remaining two Cu centers are tetra­hedrally coordinated, forming the CuPIS2 core

A Tale of Two Counties: How Two School Libraries in Rural Western China Serve Local Needs

This report presents a case study of school library programs in two rural counties in Western China. Since 2002, the libraries of Tianzhu and Tongwei high schools have undertaken a series of outreach initiatives to improve local residents’ access to information and to address their cultural and educational needs. Over the past decade, both school libraries have played a leading role in improving the quality of life and enhancing the information literacy of local residents. Tianzhu No. 1 High School Library 天祝一中图书馆—which serves a large Tibetan and other minority populations—has gained a reputation for its oral history of local culture program. This program trains students to conduct interviews with folk artists and scholars and then post their audiovisual recordings on websites. Tongwei No. 1 High School Library 通渭一中图书馆 is known for providing health care information through both in-person workshops and online. Recently, it implemented a tutoring service aimed at teaching residents to use online resources. These programs have been successful and sustainable in part because of the sponsorship and funding of the U.S.-based Evergreen Education Foundation (EEF) 美国青树教育基 金会. This report analyzes the results of these major initiatives, both of which do a great deal to reach out to rural residents, particularly farmers and the elderly

A Tale of Two Counties: How Two School Libraries in Rural Western China Serve Local Needs

This report presents a case study of school library programs in two rural counties in Western China. Since 2002, the libraries of Tianzhu and Tongwei high schools have undertaken a series of outreach initiatives to improve local residents’ access to information and to address their cultural and educational needs. Over the past decade, both school libraries have played a leading role in improving the quality of life and enhancing the information literacy of local residents. Tianzhu No. 1 High School Library 天祝一中图书馆—which serves a large Tibetan and other minority populations—has gained a reputation for its oral history of local culture program. This program trains students to conduct interviews with folk artists and scholars and then post their audiovisual recordings on websites. Tongwei No. 1 High School Library 通渭一中图书馆 is known for providing health care information through both in-person workshops and online. Recently, it implemented a tutoring service aimed at teaching residents to use online resources. These programs have been successful and sustainable in part because of the sponsorship and funding of the U.S.-based Evergreen Education Foundation (EEF) 美国青树教育基 金会. This report analyzes the results of these major initiatives, both of which do a great deal to reach out to rural residents, particularly farmers and the elderly

μ3-Iodo-tri-μ3-sulfido-sulfidotris[tris­(4-methoxy­phen­yl)phosphine-κP]tri­copper(I)tungsten(VI) N,N-dimethyl­formide solvate

A new W/S/Cu cluster, [Cu3WIS4(C21H21O3P)3]·C3H7NO, was formed by the reaction of ammonium tetra­thio­tungstate(VI), cuprous iodide and tris­(4-methoxy­phen­yl)phosphine in N,N-dimethyl­formamide. The title compound exhibits a heavily distorted cubane-like skeleton in which the average Cu—I, Cu—S and W—μ3-S distances are 2.934, 2.302 and 2.249 Å, respectively. The W atom exhibits tetrahedral geometry, formed by three μ3-S and one terminal S atom; the W—S(terminal) bond length is 2.1426 (13) Å. Each Cu atom is coordinated by one P atom from a tris­(4-methoxy­phen­yl)phosphine (mop), two μ3-S and one μ3-I atom, forming a distorted tetra­hedral coordination geometry. Some of the mop ligand methyl groups have large librations. Together with the three neutral mop ligands, the title compound is neutral; this contrasts with the all-halogen-coordinated Mo/S/Ag clusters with the same structure, which carry negative charge

Community structure of tenebrionid beetles in the Ulan Buh Desert (Inner Mongolia, China) (Coleoptera: Tenebrionidae)

Tenebrionids are a conspicuous faunal component of Central Asian deserts, but little is known about their community ecology. We investigated how tenebrionid community structure varied along a vegetational gradient in the Ulan Buh Desert (Gobi Desert). Sampling was done with pitfall traps in three sites with different vegetation cover. Species abundance distributions were fitted by the geometric series model, which expresses the "niche pre-emption" hypothesis. Community structure was investigated using different measures of diversity (number of species, Margaleff richness and Shannon-Weaner index), dominance (Simpson and Berger-Parker indexes) and evenness (Pielou's index). The observed tenebrionid species richness was similar to that known from other Gobi Desert sites. The three investigated sites have similar species-abundance patterns, but the most dominant species varied among them. This suggests that the local environment operates a filtering action on the same basic fauna, allowing different species to dominate under different conditions. Overall, the highest total abundance was observed in the true desert site, however this site had a community structure similar to that observed in the site with more vegetation. By contrast, the investigated site with intermediate conditions showed a higher diversity and evenness, and a lower dominance. Thus, intermediate conditions of plant cover favour tenebrionid diversity, whereas a dense cover or a very sparse cover increases the dominance

Uloma (Uloma) intricornicula Liu, Ren & Wang, 2007 (Coleoptera, Tenebrionidae, Ulomini): Descriptions of the larva and pupa and new distributional records

The genus Uloma Dejean, 1821 (Coleoptera, Tenebrionidae, Ulomini) comprises more than 200 species and subspecies worldwide, 37 of which are recorded from China. However, the morphology of the immature stages of Chinese Uloma have been poorly documented. Up to now, larva and pupa descriptions are available for only one species, Uloma (Uloma) metogana Ren, 2004.The larva and pupa of Uloma (Uloma) intricornicula Liu, Ren & Wang, 2007, from southern China, are described and illustrated for the first time and are compared with those of U. (U.) metogana Ren, 2004. Differences between male and female pupae of this species are highlighted. New distributional data for U. (U.) intricornicula are also provided. Finally, 13 Uloma species from China are formally assigned to the nominated subgenus

A diverse global fungal library for drug discovery

Background: Secondary fungal metabolites are important sources for new drugs against infectious diseases and cancers. Methods: To obtain a library with enough diversity, we collected about 2,395 soil samples and 2,324 plant samples from 36 regions in Africa, Asia, and North America. The collection areas covered various climate zones in the world. We examined the usability of the global fungal extract library (GFEL) against parasitic malaria transmission, Gram-positive and negative bacterial pathogens, and leukemia cells. Results: Nearly ten thousand fungal strains were isolated. Sequences of nuclear ribosomal internal transcribed spacer (ITS) from 40 randomly selected strains showed that over 80% were unique. Screening GFEL, we found that the fungal extract from was able to block transmission to , and the fungal extract from was able to kill myelogenous leukemia cell line K562. We also identified a set of candidate fungal extracts against bacterial pathogens