共查询到20条相似文献,搜索用时 13 毫秒
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Recent aggressive attacks on innocent citizens have resulted in governments increasing security. However, there is a good case for prevention rather than reaction. Bioweapons, mycotoxins, fungal biocontrol agents (FBCA), and even pharmaceuticals contain, or are, toxins and need to be considered in the context of the new paradigm. Is it desirable to discuss such issues? None of the fungi are (a) as toxic as botulinum toxin from Clostridium botulinum, and (b) as dangerous as nuclear weapons. One toxin may be defined as a pharmaceutical and vice versa simply by a small change in concentration or a moiety. Mycotoxins are defined as naturally occurring toxic compounds obtained from fungi. They are the biggest chronic health risk when incorporated into the diet. The current list of fungal toxins as biochemical weapons is small, although awareness is growing of the threats they may pose. T-2 toxin is perhaps the biggest concern. A clear distinction is required between the biological (fungus) and chemical (toxin) aspects of the issue. There is an obvious requirement to be able to trace these fungi and compounds in the environment and to know when concentrations are abnormal. Many FBCA, produce toxins. This paper indicates how to treat mycotoxicosis and decontaminate mycotoxins. There is considerable confusion and inconsistency surrounding this topic which requires assessment in an impartial and scientific manner. 相似文献
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Mice with severe combined immunodeficiency (SCID mice) have become a favored model system for the study of many parasitic diseases. In this review, Samuel Stanley Jr and Herbert Virgin IV provide a brief overview of the biology of the SCID mouse, and review some examples of how the SCID mouse model has been applied to the study of the immunology of a number of different parasitic diseases. 相似文献
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Z S Pawlowski 《Parassitologia》1983,25(2-3):141-150
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Analysis of the evolution, localization and biologic function of papain family cysteine proteases in metazoan and protozoan parasites has provided important and often surprising insights into the biochemistry and cellular function of this diverse enzyme family. Furthermore, the relative lack of redundancy of cysteine proteases in parasites compared to their mammalian hosts makes them attractive targets for the development of new antiparasitic chemotherapy. The treatment of experimental models of parasitic diseases with cysteine protease inhibitors has provided an important 'proof of concept' for the use of cysteine protease inhibitors in vivo. Evidence has now accumulated that cysteine protease inhibitors can selectively arrest replication of a microbial pathogen without untoward toxicity to the host. Furthermore, this can be achieved with reasonable dosing schedules and oral administration of the drug. Initial studies have confirmed the efficacy of cysteine protease inhibitors in treatment of Trypanosoma cruzi, Plasmodium falciparum and Leishmania major. Work on Trypanosoma brucei, the agent of African trypanosomiasis, is preliminary but also promising. Target validation studies have shown that biotinylated or radiolabeled irreversible inhibitors specifically bind to the cysteine protease targets thought to represent the major activity within the parasite. In the case of T. cruzi, the effect of inhibitors appears to be predominantly in blocking protease processing. Transfection studies using variant constructs have supported this model. Finally, the generation of null mutants for the multiple protease genes in Leishmania mexicana has provided the first genetic support for the key role of this enzyme family in parasite virulence. Safety studies in rodents and analysis of uptake of inhibitors by parasites and host cells suggest that the selectivity of inhibitors for the parasite targets may reside in the lack of redundancy of parasite proteases, the higher concentration of host proteases in intracellular compartments, and differential uptake of inhibitors by parasites. Attempts to elicit resistance to cysteine protease inhibitors in parasite cultures suggest that mechanisms of induced resistance are independent of resistance to the traditional antiparasitic agents. This suggests that cysteine protease inhibitors may provide an alternative to traditional therapy in drug-resistant organisms. 相似文献
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The close quantitative interrelation between the reaction of birch to abiotic stress (spring–summer droughts) (the degree to which the yearly radial increment of trees decreases) and entomoresistance has been established. Tree stands that were heavily defoliated by gypsy moth showed a much stronger reaction to the droughts which preceded the outbreaks by the decrease in their radial increment than those weakly defoliated by this phytophagous insect. The reaction of trees to the abiotic stress is regarded as the key factor that controls the drop in their entomoresistance during outbreaks of gypsy moth in woods damaged by anthropogenic effects. 相似文献
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Invasive fungal infections have become a major cause of mortality in immunocompromised individuals. Despite the current availability of number of highly active antifungal agents, overall mortality remains around 40%. Importantly, it is clear that a failure to restore host immunity leads to worse outcomes. These observations provide clear rationale for the development of novel immunotherapies to improve outcomes in immunocompromised individuals with invasive fungal infections. In this article we summarise the key advances that have been made in the field of immunotherapy for fungal infections in recent years, with a particular focus on clinical studies of interferon-γ therapy, adoptive T cell therapy, and gene therapy for chronic granulomatous disorder. In addition a number of pre-clinical approaches are reviewed. 相似文献
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Cholesterol as a target for toxins 总被引:2,自引:0,他引:2
B. de Kruijff 《Bioscience reports》1990,10(2):127-130
A mechanism is proposed for the way in which cholesterol facilitates channel formation by polyene antibiotics and bacterial protein toxins. Central elements of the model are: (i) interactions between the ring system of the sterol and rigid elements of the polyene or toxin molecule, and (ii) the specific orientation of cholesterol within the membrane. 相似文献
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Jin Woo Bok Rosa Ye Kenneth D Clevenger David Mead Megan Wagner Amanda Krerowicz Jessica C Albright Anthony W Goering Paul M Thomas Neil L Kelleher Nancy P Keller Chengcang C Wu 《BMC genomics》2015,16(1)
Background
With thousands of fungal genomes being sequenced, each genome containing up to 70 secondary metabolite (SM) clusters 30–80 kb in size, breakthrough techniques are needed to characterize this SM wealth.Results
Here we describe a novel system-level methodology for unbiased cloning of intact large SM clusters from a single fungal genome for one-step transformation and expression in a model host. All 56 intact SM clusters from Aspergillus terreus were individually captured in self-replicating fungal artificial chromosomes (FACs) containing both the E. coli F replicon and an Aspergillus autonomously replicating sequence (AMA1). Candidate FACs were successfully shuttled between E. coli and the heterologous expression host A. nidulans. As proof-of-concept, an A. nidulans FAC strain was characterized in a novel liquid chromatography-high resolution mass spectrometry (LC-HRMS) and data analysis pipeline, leading to the discovery of the A. terreus astechrome biosynthetic machinery.Conclusion
The method we present can be used to capture the entire set of intact SM gene clusters and/or pathways from fungal species for heterologous expression in A. nidulans and natural product discovery.Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1561-x) contains supplementary material, which is available to authorized users. 相似文献16.
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Steinbach WJ Reedy JL Cramer RA Perfect JR Heitman J 《Nature reviews. Microbiology》2007,5(6):418-430
The number of immunocompromised patients with invasive fungal infections continues to increase and new antifungal therapies are not keeping pace with the growing incidence of these infections and their associated mortality. Calcineurin inhibition is currently used to exert effective immunosuppression following organ transplantation and in treating various other conditions. However, the calcineurin pathway is also intricately involved in the growth and pathogenesis of the three major fungal pathogens of humans, Cryptococcus neoformans, Candida albicans and Aspergillus fumigatus, and the exploitation of fungal calcineurin pathways holds great promise for the future development of novel antifungal agents. This Review summarizes our current understanding of calcineurin biology in these fungal species, and its exciting potential role in treating invasive fungal infections. 相似文献
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Secretion of a potential virulence factor, a fungal ribonucleotoxin, during human aspergillosis infections 总被引:10,自引:1,他引:9
We show by cloning and nucleotide sequence analysis that the 18kDa antigen found in the urine of patients suffering from aspergillosis is related to the fungal protein toxins restrictocin and mitogillin. These are inhibitors of translation which act by catalytic inactivation of eukaryotic ribosomes; they may be implicated in the pathogenesis of the disease. 相似文献