Assaying three new fungi against citrus mites in the laboratory,and a field trial

The Basidiomycotine fungi Meira geulakonigii, Meira argovae and Acaromyces ingoldii were assayed in the laboratory against five species of herbivorous mites: Phyllocoptruta oleivora (Eriophyidae), Panonychus citri, Eutetranychus orientalis, Tetranychus urticae and Tetranychus cinnabarinus (all four Tetranychidae). All fungi caused significantly high mortality rates (as compared to controls) after 14 days, some after 1 week. Phyllocoptruta oleivora was the most susceptible, showing >80% mortality even after 1 week. In a field trial, grapefruits sprayed either once a month or once a season with M. geulakonigii had significantly fewer P. oleivora and less damage than unsprayed fruit. These results suggest that M. geulakonigii may protect grapefruits against the injurious P. oleivora.     

Pulmonary hemodynamic reaction to foreign blood in goats and rabbits.

We have found that the goat is extraordinarily sensitive to very small quantities of rabbit or rat blood. As little as 0.004 ml/kg induces transient pulmonary hypertension [maximal rise in pulmonary arterial pressure 32 +/- 10 (SD) cmH2O] in goats. We hypothesized that this reaction may be related to the presence of the resident population of intravascular macrophages that reside in the pulmonary capillaries of goats. If that is so, then rabbits or rats, which have few or no intravascular macrophages, should not be reactive to foreign blood. We compared pulmonary hemodynamics and changes in blood thromboxane B2 concentrations among goats, rabbits, and rats in response to graded doses of foreign blood. The pulmonary reaction to foreign blood was much greater in goats than in rabbits or rats, even though we injected up to 10- or 60-fold larger amounts into the latter species. In goats the pulmonary vascular pressure response to rabbit blood was dose dependent in goats and correlated well with changes in systemic arterial thromboxane B2 concentrations [change in pulmonary arterial pressure = 0.07 (thromboxane B2) + 8.3, r = 0.79]. We also tested the prostaglandin H2 endoperoxide analogue (U-46619) and found that the goats are somewhat more reactive than rabbits. We conclude that the pulmonary hemodynamic reaction to foreign blood is consistent with the concept that the foreign erythrocytes are reacting with the pulmonary intravascular macrophages in goats. The lower reactivity of the rabbit pulmonary circulation to thromboxane may also have a role.     

Auto-adaptive Alpha Allocation: A Strategy to Mitigate Risk on Study Assumptions

In some clinical development programs, there are potential biomarkers with promising but uncertain predictive effect, while the probability of success in the overall population cannot be readily dismissed. It is risky to focus only on the overall population, or just the biomarker subpopulation. In 2009, Chen and Beckman proposed a Bayesian decision framework to optimize the type I error rate (alpha) allocation in a Phase III clinical study with possible predictive subset effect. The utilization of internal data in this framework is of particular interest because it provides an opportunity to mitigate the potential risk of misspecified study assumptions using an auto-adaptive strategy. In this paper, we examine this auto-adaptive strategy in detail through extensive numerical case studies and provide guidance on the appropriate use of partial current trial (internal) data in this data-driven optimization framework. We show that internal data can be used to inform the alpha allocation to hypothesis testing in the overall population and the subgroup. The resulting adaptive testing strategy is robust with respect to the uncertainty in the predictive subgroup effect and biomarker prevalence.     

High level soluble expression and one-step purification of IBDV VP2 protein in <Emphasis Type="Italic">Escherichia coli</Emphasis>

Objectives

To improve the expression of soluble IBDV VP2 protein by using different tagged vectors in Escherichia coli.

Results

Fusion tags, Grifin, MBP, SUMO, thioredoxin, γ-crystallin, ArsC and PpiB, enhanced the expression and solubility of VP2 protein. The fusion proteins were purified by Ni–NTA chromatography, MBP-VP2 showed the highest purity about 90 %. After removing the MBP tag, VP2 self-assembled into virus-like particles, ~25 nm diam. Results from AGP suggested the recombinant IBDV VP2 protein identified by reference serum like IBDV.

Conclusion

All the seven tags enhanced the expression and solubility of IBDV VP2 protein. The recombinant protein self-assembly into virus like particles and possess antigenicity as reference IBDV.

     

The Dynamics of a SEIR–SIRC Antigenic Drift Influenza Model

We consider the dynamics of an influenza model with antigenic drift mechanism. Antigenic drift is an antigen mutation on the skin surface of the influenza virus that do not produce a new virus strain. The mutation produces the same virus but with slightly different antigens that cannot be recognized by the immune receptors formed by the previous infection. There are some type of influenza that involve the interaction between two populations such as human and animal. In this paper, we construct an influenza model with antigenic drift mechanism on the human population that has interaction with the animal population. The animal population is assumed to follow the SEIR epidemic model. Our model is motivated by the fact that some of the influenza cases in human come from the animal such as the swine and the avian. The transmission parameter that shows number of contact between the susceptible human and the infectious animals are important to study. The parameter plays an important role to detect the cycle of infection of the disease. The other important parameters are the seasonality degree, which shows the pathogen appearance and disappearance via annual migration, and the infection rate on the human population. We employ the bifurcation theory to analyze the behavior of the system and to detect the cycle of infection types when the parameters values are varied.     

Nitidine chloride inhibited the expression of S phase kinase-associated protein 2 in ovarian cancer cells

Nitidine chloride (NC) has been reported to exert its anti-tumor activity in various types of human cancers. However, the molecular mechanism of NC-mediated tumor suppressive function is largely unclear. In the current study, we used several approaches such as MTT, FACS, RT-PCR, Western blotting analysis, invasion assay, transfection, to explore the molecular basis of NC-triggered anti-cancer activity. We found that NC inhibited cell growth, induced cell apoptosis, caused cell cycle arrest in ovarian cancer cells. Emerging evidence has demonstrated that Skp2 plays an important oncogenic role in ovarian cancer. Therefore, we also explored whether NC exerts its biologic function via downregulation of Skp2 in ovarian cancer cells. We observed that NC significantly inhibited the expression of Skp2 in ovarian cancer cells. Notably, overexpression of Skp2 abrogated the anti-cancer activity induced by NC in ovarian cancer cells. Consistently, downregulation of Skp2 expression enhanced the sensitivity of ovarian cancer cells to NC treatment. Thus, inactivation of Skp2 by NC could be a novel strategy for the treatment of human ovarian cancer.     

Metabolic flux modeling of detoxification of acetic acid by Ralstonia eutropha at slightly alkaline pH levels

Ralstonia eutropha grows on and produces polyhydroxyalkanoates (PHAs) from fermentation acids. Acetic acid, one major organic acid from acidogenesis of organic wastes, has an inhibitory effect on the bacterium at slightly alkaline pH (6 g HAc/L at pH 8). The tolerance of R. eutropha to acetate, however, was increased significantly up to 15 g/L at the slightly alkaline pH level with high cell mass concentration. A metabolic cell model with five fluxes is proposed to depict the detoxification mechanism including mass transfer and acetyl-CoA formation of acetic acid and the formation of three final metabolic products, polyhydroxybutyrate (PHB), active biomass, and CO(2). The fluxes were measured under different conditions such as cell mass concentration, acetic acid concentration, and medium composition. The experimental results indicate that the acetate detoxification by high cell mass concentration is attributed to the increased fluxes at high extracellular acetate concentrations. The fluxes could be doubled to reduce and hence detoxify the accumulated intracellular acetate anions.