Coupled effects of local movement and global interaction on contagion

By incorporating segregated spatial domain and individual-based linkage into the SIS (susceptible-infected-susceptible) model, we investigate the coupled effects of random walk and intragroup interaction on contagion. Compared with the situation where only local movement or individual-based linkage exists, the coexistence of them leads to a wider spread of infectious disease. The roles of narrowing segregated spatial domain and reducing mobility in epidemic control are checked, these two measures are found to be conducive to curbing the spread of infectious disease. Considering heterogeneous time scales between local movement and global interaction, a log-log relation between the change in the number of infected individuals and the timescale $\tau$ is found. A theoretical analysis indicates that the evolutionary dynamics in the present model is related to the encounter probability and the encounter time. A functional relation between the epidemic threshold and the ratio of shortcuts, and a functional relation between the encounter time and the timescale $\tau$ are found

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

EFFECT OF SECOND TOE-TO-HAND TRANSFER ON THE PLANTAR PRESSURE DISTRIBUTION OF THE DONOR FOOT

ABSTRACT Objective: To investigate the effect of second toe-to-hand transfer on the plantar pressure distribution of the donor foot. Methods: Twelve normal fresh-frozen cadaveric foot specimens were subjected to an axial load of 600 N. An F-Scan plantar pressure analysis system was used to measure the forefoot plantar pressure. The testing was performed under the conditions of intact second toe, second toe removal with the second metatarsal head reserved, and second toe removal in combination with the distal one-third of the second metatarsal, respectively. Results: The peak pressure of the second metatarsal head was greater than other four forefoot plantar regions. There was no statistically significant change in the forefoot plantar pressure distribution after the second toe was removed (p > 0.05). When the second toe and the distal one-third of the second metatarsal were removed, the forefoot plantar pressure distribution changed significantly (p < 0.05). Conclusions: An intact second metatarsal is essential for the normal distribution of plantar pressure. Removal of the second toe with the second metatarsal head reserved had little influence on the plantar pressure distribution of the donor foot. Removal of the second toe and distal one-third of the second metatarsal resulted in abnormal plantar pressure distribution. Level of Evidence II, Experimental Study

Pharmacokinetics of diltiazem hydrochloride delay-onset sustained-release pellet capsules in healthy volunteers

Embora a farmacocinética (PK) do cloridrato de diltiazem nas formas de comprimidos de liberação imediata e cápsulas de liberação modificada em ensaios clínicos já tenha sido relatada, a pesquisa da PK do cloridrato de diltiazem na forma de cápsulas com peletes de liberação retardada e sustentada ainda é muito importante. Neste trabalho, propusemos avaliar a farmacocinética do cloridrato de diltiazem administrado através desta nova forma farmacêutica em voluntários chineses sadios, assim como a influência da ingestão de alimentos neste perfil farmacocinético. Foi realizado um ensaio clínico aberto, randomizado e paralelo em 36 voluntários, que receberam dose oral única de 90 mg, 180 mg ou 270 mg e dose múltiplas (90 mg/d × 6 d) pela mesma via de administração. Para avaliar o efeito da ingestão de alimentos sobre a PK do diltiazem foi realizada a administração de dose única (360 mg) em 24 voluntários chineses sadios. A concentração plasmática do diltiazem foi determinada por Cromatografia Liquida de Alta Eficiência em fase reversa (CLAE-FR) e os principais parâmetros farmacocinéticos foram analisados através do emprego do software PKSolver (Ver 2.0). O ensaio de farmacocinética clínica foi conduzido na clínica Pharmacological Center (No.JDX1999064) do Hospital de Xiangya, Central South University, China. Os parâmetros PK obtidos indicaram que a nova formulação de cápsulas de liberação retardada e sustentada de cloridrato de diltiazem possue marcantes características de liberação retardada e controlada do fármaco.The pharmacokinetics (PK) of ordinary tablets and sustained release capsules of diltiazem hydrochloride in human clinical trials had been studied. The PK of diltiazem hydrochloride delay-onset sustained-release pellet capsules, a new dosage form, has not been reported, although it is very important to clinical use. In this paper, we investigated the PK of diltiazem hydrochloride delay-onset sustained-release pellet capsules and the food influence in Chinese healthy volunteers. The PK parameters indicated that the diltiazem hydrochloride delay-onset sustained-release pellet capsules appeared marked characteristics of delayed and controlled release. An opened-label, randomized and parallel clinical trial was conducted in 36 Chinese healthy volunteers with single oral dose (90 mg, 180 mg or 270 mg) and a multiple oral dose (90 mg d-1×6 d) administration. The effect of food on the PK of one single oral dose (360 mg) was investigated in 24 healthy Chinese volunteers. Plasma diltiazem concentration was determined by reversed-phase high-performance liquid chromatography (RP-HPLC) and the main pharmacokinetic parameters were analyzed by PKSolver (Ver 2.0). All clinical studies were conducted in the Clinical Pharmacological Center (No. JDX1999064) of Xiangya Hospital Affiliated Central South University, China. The PK parameters suggested that the new formulation had marked characteristics of delayed and controlled release of diltiazem, and food intake did not alter significantly diltiazem pharmacokinetic parameters