A comparison of the peri-implant bone stress generated by the preload with screw tightening between ‘bonded’ and ‘contact’ model

A number of finite element analyses (FEAs) for the dental implant were performed without regard for preload and with all interfaces ‘fixed-bonded’. The purpose of this study was comparing the stress distributions between the conventional FEA model with all contacting interfaces ‘fixed-bonded’ (bonded model) and the model with the interfaces of the components in ‘contact’ with friction simulated as a preloaded implant (contact model). We further verified the accuracy of the result of the FEA using model experiment. In the contact model, the stress was more widely distributed than in the bonded model. From the model study, the preload induced by screw tightening generated strain at the peri-implant bone, even before the application of external force. As a result, the bonded model could not reproduce the mechanical phenomena, whereas the contact model is considered to be appropriate for analysing mechanical problems.     

Extent of invasion of Tasmanian native vegetation by the exotic bumblebee Bombus terrestris (Apoidea: Apidae)

Abstract Observations of the large earth bumblebee, Bombus terrestris (L.), in native vegetation were collated to determine the extent to which this exotic species has invaded Tasmanian native vegetation during the first 9 years after its introduction. The range of B. terrestris now encompasses all of Tasmania's major vegetation types, altitudes from sea level to 1260m a.s.L, and the entire breadth of annual precipitation in the state from more than 3200 mm to less than 600 mm. Observations of workers carrying pollen, together with the presence of large numbers of bumblebees at many localities across this range indicate that colonies are frequently established in native vegetation. Evidence that colonies are often successful was obtained from repeated observations of the species during more than 1 year at particular sites. Unequivocal evidence of colonies was obtained from six National Parks, including four of the five in the Tasmanian Wilderness World Heritage Area (WHA). Indeed, the species has been present in the WHA for at least as long as it has in the city of Hobart, where it was first recorded. In southwestern Tasmania, evidence of colonies was obtained up to 40km from gardens, 61 km from small towns and 93 km from large towns. Hence, contrary to previous suggestions, the species is established in the most remote parts of Tasmania and is not dependent on introduced garden plants. Given their strong record of invasion, it is likely that B. terrestris will form feral populations on the mainland of Australia and in many other parts of the world if introduced. Because of their likely negative impacts on native animals and plants, and potential to enhance seed production in weeds, the spread of bumblebees should be avoided.     

Metronomic chemotherapy with low-dose cyclophosphamide plus gemcitabine can induce anti-tumor T cell immunity in vivo

Several chemotherapeutic drugs have immune-modulating effects. For example, cyclophosphamide (CP) and gemcitabine (GEM) diminish immunosuppression by regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), respectively. Here, we show that intermittent (metronomic) chemotherapy with low-dose CP plus GEM can induce anti-tumor T cell immunity in CT26 colon carcinoma-bearing mice. Although no significant growth suppression was observed by injections of CP (100 mg/kg) at 8-day intervals or those of CP (50 mg/kg) at 4-day intervals, CP injection (100 mg/kg) increased the frequency of tumor peptide-specific T lymphocytes in draining lymph nodes, which was abolished by two injections of CP (50 mg/kg) at a 4-day interval. Alternatively, injection of GEM (50 mg/kg) was superior to that of GEM (100 mg/kg) in suppressing tumor growth in vivo, despite the smaller dose. When CT26-bearing mice were treated with low-dose (50 mg/kg) CP plus (50 mg/kg) GEM at 8-day intervals, tumor growth was suppressed without impairing T cell function; the effect was mainly T cell dependent. The metronomic combination chemotherapy cured one-third of CT26-bearing mice that acquired tumor-specific T cell immunity. The combination therapy decreased Foxp3 and arginase-1 mRNA levels but increased IFN-γ mRNA expression in tumor tissues. The percentages of tumor-infiltrating CD45⁺ cells, especially Gr-1^high CD11b⁺ MDSCs, were decreased. These results indicate that metronomic chemotherapy with low-dose CP plus GEM is a promising protocol to mitigate totally Treg- and MDSC-mediated immunosuppression and elicit anti-tumor T cell immunity in vivo.     

Transformation of Polyoxins D,E, and F with Sodium Bisulfite

Polyoxins D, E, and F which possess 5-carboxyuracil as the nucleobase were reacted selectively with sodium bisulfite at pH 4.0 resulting in facile decarboxylation to afford corresponding 5,6-dihydrouracil-6-sulfonates and uracil type polyoxins (polyoxins L, M, and K) in good yield. The former compounds were also converted to the latter almost quantitatively with mild alkali treatment. Biological activities of the transformed compounds were described.     

Instrumental outcome devaluation with representation-mediated conditioning

In three experiments, rats were trained to perform two instrumental behaviours (R1 and R2) in the presence of discriminative stimuli (Sd1 and Sd2, respectively) to obtain a common food outcome (O1). Acquisition of the two discriminations was followed by switching the outcome accompanying R2 performance from O1 to a new one (O2). Experiment 1 showed paired presentations of O2 with a lithium chloride (LiCl) injection resulted in a reduction in the R2 performance. In the subsequent two experiments, each Sd was paired with LiCl injection and its effects on outcome consumption and instrumental performance were investigated. A reduction in the O2 consumption subsequent to the Sd devaluation was found in Experiments 2 and 3. Experiment 3 revealed a reduced R2 performance in an extinction test, following the animals’ consummatory access to the outcomes in training context. These results demonstrate representation-mediated outcome devaluation in the course of the Sd devaluation.     

Antibiotics LL-Z1272 identified as novel inhibitors discriminating bacterial and mitochondrial quinol oxidases

To counter antibiotic-resistant bacteria, we screened the Kitasato Institute for Life Sciences Chemical Library with bacterial quinol oxidase, which does not exist in the mitochondrial respiratory chain. We identified five prenylphenols, LL-Z1272β, γ, δ, ? and ζ, as new inhibitors for the Escherichia coli cytochrome bd. We found that these compounds also inhibited the E. coli bo-type ubiquinol oxidase and trypanosome alternative oxidase, although these three oxidases are structurally unrelated. LL-Z1272β and ? (dechlorinated derivatives) were more active against cytochrome bd while LL-Z1272γ, δ, and ζ (chlorinated derivatives) were potent inhibitors of cytochrome bo and trypanosome alternative oxidase. Thus prenylphenols are useful for the selective inhibition of quinol oxidases and for understanding the molecular mechanisms of respiratory quinol oxidases as a probe for the quinol oxidation site. Since quinol oxidases are absent from mammalian mitochondria, LL-Z1272β and δ, which are less toxic to human cells, could be used as lead compounds for development of novel chemotherapeutic agents against pathogenic bacteria and African trypanosomiasis.     

Mutation underlying resistance of Plasmodium berghei to atovaquone in the quinone binding domain 2 (Qo(2)) of the cytochrome b gene

The anti-malarial agent atovaquone specifically targets the cytochrome bc₁ complex and inhibits the parasite respiration. Resistance to this drug, a coenzyme Q analogue, is associated with mutations in the mitochondrial cytochrome b gene. We previously reported atovaquone resistant mutations in Plasmodium berghei, in the first quinone binding domain (Qo₁) of the cytochrome b gene (M133I and L144S) with V284F in the sixth transmembrane domain. However, in P. falciparum the most common mutations are found in the Qo₂ region. To obtain a better model for biochemical and genetic studies, we have now extended our study to isolate a wider range of P. berghei resistant strains, in particular those in the Qo₂. Here we report four new mutations (Y268N, Y268C, L271V and K272R), all in the Qo₂ domain. Two of these mutations are convergent to codon 268 (nt802–804) drug-induced mutation in P. falciparum.     

Catenation and supercoiling in the products of bacteriophage λ integrative recombination in vitro

Catenanes (interlocked circular DNA molecules) are the exclusive products of the bacteriophage λ integrative recombination reaction in vitro when the substrate is a supercoiled DNA molecule containing both the attP and attB sites. It is proposed that the catenation results from the superhelical form of the substrate DNA. We also show that both circular DNA products of a single recombination event can be recovered as superhelical molecules with a superhelical density approximately that of the substrate DNA. The recombination reaction must therefore occur as a coupled process which does not permit free rotation around single-strand breaks at any stage.