A toxin hunter in the microworld of bacteria: a project on novel inhibitors against bacterial AB5 toxins

[要旨] 病原性細菌が産生する蛋白性のAB5型トキシンは1個のAサブユニットと5個のBサブユニットから構成される外毒素である。両サブユニットはそれぞれ特徴的な役割を持ち，互いに巧妙に機能分担をして一つのトキシンを形成している。Aサブユニットは主に毒性に直接関与する特異的な酵素活性を有する。一方，Bサブユニットは標的細胞のレセプターに対する結合能を有し，AB5型トキシンを標的細胞に吸着させる。ここでは毒性が全く異なるAB5型トキシンとして，コレラ菌が産生するコレラトキシン（CT），腸管出血性大腸菌が産生する志賀様トキシン（Stx），及び志賀トキシン産生大腸菌が産生するサブチラーゼサイトトキシン（SubAB）の3種類に関して，その作用メカニズムに着目した毒性を抑制する阻害因子の探索などの研究を紹介する。これらの3種類のAB5型トキシンに着目した理由は，それぞれのトキシンを産生する病原菌による感染症が世界的に流行し，社会問題となっているからである。つまり，コレラ菌は依然として発展途上国で大きな問題であり，腸管出血性大腸菌のO157:H7による集団食中毒は我国でも依然として多い。さらに21世紀になり，血清型がO157:H7以外の腸管出血性大腸菌による集団食中毒が世界的に急増しているためである。いずれも抗生物質を使用した後の残留トキシンによる病態悪化が指摘されており，トキシンを効率よく無毒化する事が急務である。[SUMMARY] Bacterial AB5 toxins are proteins, produced by pathogenic bacteria including of Vibrio cholerae, Shigella dysenteriae, and enterohaemorrhagic Escherichia coli, which are usually released into the extracellular medium and cause disease by killing or altering the metabolism of target eukaryotic cells. The toxins are usually composed of one A subunit（a toxic domain） and five B subunits（a receptor-binding domain）. This article overviews the characteristics and mode of actions of AB5 toxins including cholera toxin, Shiga-like toxin, and subtilase cytotoxin, and highlights a project on the novel inhibitors against these bacterial AB5 toxins

The complete mitochondrial genomes of two ghost moths, Thitarodes renzhiensis and Thitarodes yunnanensis: the ancestral gene arrangement in Lepidoptera

BACKGROUND: Lepidoptera encompasses more than 160,000 described species that have been classified into 45–48 superfamilies. The previously determined Lepidoptera mitochondrial genomes (mitogenomes) are limited to six superfamilies of the lineage Ditrysia. Compared with the ancestral insect gene order, these mitogenomes all contain a tRNA rearrangement. To gain new insights into Lepidoptera mitogenome evolution, we sequenced the mitogenomes of two ghost moths that belong to the non-ditrysian lineage Hepialoidea and conducted a comparative mitogenomic analysis across Lepidoptera. RESULTS: The mitogenomes of Thitarodes renzhiensis and T. yunnanensis are 16,173 bp and 15,816 bp long with an A + T content of 81.28 % and 82.34 %, respectively. Both mitogenomes include 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and the A + T-rich region. Different tandem repeats in the A + T-rich region mainly account for the size difference between the two mitogenomes. All the protein-coding genes start with typical mitochondrial initiation codons, except for cox1 (CGA) and nad1 (TTG) in both mitogenomes. The anticodon of trnS(AGN) in T. renzhiensis and T. yunnanensis is UCU instead of the mostly used GCU in other sequenced Lepidoptera mitogenomes. The 1,584-bp sequence from rrnS to nad2 was also determined for an unspecified ghost moth (Thitarodes sp.), which has no repetitive sequence in the A + T-rich region. All three Thitarodes species possess the ancestral gene order with trnI-trnQ-trnM located between the A + T-rich region and nad2, which is different from the gene order trnM-trnI-trnQ in all previously sequenced Lepidoptera species. The formerly identified conserved elements of Lepidoptera mitogenomes (i.e. the motif ‘ATAGA’ and poly-T stretch in the A + T-rich region and the long intergenic spacer upstream of nad2) are absent in the Thitarodes mitogenomes. CONCLUSION: The mitogenomes of T. renzhiensis and T. yunnanensis exhibit unusual features compared with the previously determined Lepidoptera mitogenomes. Their ancestral gene order indicates that the tRNA rearrangement event(s) likely occurred after Hepialoidea diverged from other lepidopteran lineages. Characterization of the two ghost moth mitogenomes has enriched our knowledge of Lepidoptera mitogenomes and contributed to our understanding of the mechanisms underlying mitogenome evolution, especially gene rearrangements

A generalized public goods game with coupling of individual ability and project benefit

Facing a heavy task, any single person can only make a limited contribution and team cooperation is needed. As one enjoys the benefit of the public goods, the potential benefits of the project are not always maximized and may be partly wasted. By incorporating individual ability and project benefit into the original public goods game, we study the coupling effect of the four parameters, the upper limit of individual contribution, the upper limit of individual benefit, the needed project cost and the upper limit of project benefit on the evolution of cooperation. Coevolving with the individual-level group size preferences, an increase in the upper limit of individual benefit promotes cooperation while an increase in the upper limit of individual contribution inhibits cooperation. The coupling of the upper limit of individual contribution and the needed project cost determines the critical point of the upper limit of project benefit, where the equilibrium frequency of cooperators reaches its highest level. Above the critical point, an increase in the upper limit of project benefit inhibits cooperation. The evolution of cooperation is closely related to the preferred group-size distribution. A functional relation between the frequency of cooperators and the dominant group size is found

Non-pollinator fig wasp impact on the reproductive success of an invasive fig tree: why so little?

Classical biological control agents fail to achieve an impact on their hosts for a variety of reasons and an understanding of why they fail can help shape decisions on subsequent releases. Ornamental Ficus microcarpa is a widely planted avenue fig tree that is invasive in countries where its pollinator (Eupristina verticillata) is also introduced. This tree also supports more than 20 species of non-pollinating fig wasps (NPFW) that feed in the figs and have the potential to reduce the plant’s reproduction. Odontofroggatia galili, one of the most widely introduced NPFW, has larvae that develop in galled ovules that might otherwise develop into seeds or support pollinator larvae. We examined the distribution and relative abundance of the pollinator and O. galili on F. microcarpa in China, towards the northern limit of the tree’s natural range, and in Italy where the two species have been introduced. Where they co-existed, we also recorded the impact of varying densities of O. galili on F. microcarpa seed and pollinator production. O. galili and E. verticillata displayed contrasting habitat preferences in China, with O. galili almost absent from warmer sites. O. galili abundance and sex ratios varied between the natural and introduced ranges. Figs with more O. galili contained fewer seeds and pollinator offspring, but reproduction was rarely inhibited totally. Additional species with a greater impact in the figs they occupy are needed if biocontrol of F. microcarpa is to be effective

Enhanced multiclass SVM with thresholding fusion for speech-based emotion classification

As an essential approach to understanding human interactions, emotion classification is a vital component of behavioral studies as well as being important in the design of context-aware systems. Recent studies have shown that speech contains rich information about emotion, and numerous speech-based emotion classification methods have been proposed. However, the classification performance is still short of what is desired for the algorithms to be used in real systems. We present an emotion classification system using several one-against-all support vector machines with a thresholding fusion mechanism to combine the individual outputs, which provides the functionality to effectively increase the emotion classification accuracy at the expense of rejecting some samples as unclassified. Results show that the proposed system outperforms three state-of-the-art methods and that the thresholding fusion mechanism can effectively improve the emotion classification, which is important for applications that require very high accuracy but do not require that all samples be classified. We evaluate the system performance for several challenging scenarios including speaker-independent tests, tests on noisy speech signals, and tests using non-professional acted recordings, in order to demonstrate the performance of the system and the effectiveness of the thresholding fusion mechanism in real scenarios.Peer ReviewedPreprin

A 160-kilobit molecular electronic memory patterned at 10^(11) bits per square centimetre

The primary metric for gauging progress in the various semiconductor integrated circuit technologies is the spacing, or pitch, between the most closely spaced wires within a dynamic random access memory (DRAM) circuit. Modern DRAM circuits have 140nm pitch wires and a memory cell size of 0.0408 μm^2. Improving integrated circuit technology will require that these dimensions decrease over time. However, at present a large fraction of the patterning and materials requirements that we expect to need for the construction of new integrated circuit technologies in 2013 have ‘no known solution’. Promising ingredients for advances in integrated circuit technology are nanowires, molecular electronics and defect-tolerant architectures, as demonstrated by reports of single devices and small circuits. Methods of extending these approaches to large-scale, high-density circuitry are largely undeveloped. Here we describe a 160,000-bit molecular electronic memory circuit, fabricated at a density of 10^(11) bits cm^(-2) (pitch 33 nm; memory cell size 0.0011 mm^2), that is, roughly analogous to the dimensions of a DRAM circuit projected to be available by 2020. A monolayer of bistable, [2]rotaxane molecules 10 served as the data storage elements. Although the circuit has large numbers of defects, those defects could be readily identified through electronic testing and isolated using software coding. The working bits were then configured to form a fully functional random access memory circuit for storing and retrieving information