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

Additional file 4: of Genetic composition of captive panda population

Habitat contributions and inbreeding coefficients of hypothetical offspring of all 17,640 possible mating pairs between 140 male and 126 female breeding candidates. (XLSX 5238 kb

Additional file 6: of Genetic composition of captive panda population

Genetic composition of the new generation from three plans of habitat-controlled breeding. (XLSX 58 kb

Additional file 5: of Genetic composition of captive panda population

Genetic composition and inbreeding coefficients of hypothetical offspring of the 1630 mating pairs free of pedigree and hidden inbreeding. (XLSX 463 kb

Additional file 3: of Genetic composition of captive panda population

Genetic composition of the new generation from the recommended mating pairs based on the MSI scores. (XLSX 3317 kb

Additional file 7: of Genetic composition of captive panda population

Living wild founders without descendants in the captive population. (PDF 17 kb

Effects of Pump-turbine S-shaped Characteristics on Transient Behaviours: Experimental Investigation

Effects of Pump-turbine S-shaped Characteristics on Transient Behaviours: Experimental Investigatio

Investigation of the Antioxidant Property of Ascorbic Acid

The antioxidant property of ascorbic acid (AA) was demonstrated during the process of electron transfer (ET) and the corresponding effects of AA were visibly affected by using porphyrin zinc with various substitutes as oxidants. As electron receptors, porphyrin zinc molecules obtained the electron that came from the electron donor AA, which was perfectly convenient for the simulated antioxidant reaction. The results of the obtained kinetics data showed that the antioxidant property of AA may be affected owing to the difference of the oxidants. Experimental results showed that thin-layer cyclic voltammetry (TLCV) and scanning electrochemical microscopy (SECM) were applied as investigating means to evaluate the rate constant of electron transfer achieved and expressed concerns about the simplicity and reliability, and they were also more vigorous methods to study the simulated biomembrane

Fluorinated α‑Helical Polypeptides Synchronize Mucus Permeation and Cell Penetration toward Highly Efficient Pulmonary siRNA Delivery against Acute Lung Injury

The mucus layer and cell membrane are two major barriers against pulmonary siRNA delivery. Commonly used polycationic gene vectors can hardly penetrate the mucus layer due to the adsorption of mucin glycoproteins that trap and destabilize the polyplexes. Herein, guanidinated and fluorinated bifunctional helical polypeptides were developed to synchronizingly overcome these two barriers. The guanidine domain and α-helix facilitated trans-membrane siRNA delivery into macrophages, whereas fluorination of the polypeptides dramatically enhanced the mucus permeation capability by ∼240 folds, because incorporated fluorocarbon segments prevented adsorption of mucin glycoproteins onto polyplexes surfaces. Thus, when delivering TNF-α siRNA intratracheally, the top-performing polypeptide P7F7 provoked highly efficient gene knockdown by ∼96% at 200 μg/kg siRNA and exerted pronounced anti-inflammatory effect against acute lung injury. This study thus provides an effective strategy for transmucosal gene delivery, and it also renders promising utilities for the noninvasive, localized treatment of inflammatory pulmonary diseases

Self-Assembled Cobalt–Nickel Bimetallic-Organic Framework Materials with High Supercapacitor Performance

Two new metal–organic frameworks (MOFs), [Co(bcpp)(bbip)]·H2O (Co-MOF) and [Ni(bcpp)(bbip)]·H2O (Ni-MOF), have been generated based on a V-type flexible carboxylic ligand 3,5-bis(4-carboxyl phenoxy) pyridine (H2bcpp) and a rigid N-donor ligand 1,1′-(1,4-phenylene)bis(1H-benzimidazole) (bbip) by a solvothermal method. Co-MOF and Ni-MOF are isostructural with a 2-fold interpenetrated layered structure. Moreover, a series of bimetallic CoxNiy-MOFs (x/y = 1:1, 2.5:1, 2.75:1, 3:1, 3.25:1, and 3.5:1) were obtained by using one-pot synthesis. Owing to their mixed metallic components and internal layered structure, the bimetallic CoxNiy-MOFs possess a remarkable electrochemical storage property. Significantly, the Co2.75Ni1-MOF has high specific capacitance (699 F g–1) at 0.5 A g–1 and good cycling durability (retained 72.7% over 3100 turns). Additionally, an asymmetrical ultra-capacitor based on Co2.75Ni1-MOF and activated carbon (AC) delivers a maximum energy density of 20.44 Wh kg–1 at 387.49 W kg–1 and a high cycle-to-cycle stability with 85.4% of the primary capacitance over 15,000 turns