A Protective Allergy Vaccine Based on CpG- and Protamine-Containing PLGA Microparticles

Purpose: Allergen-specific immunotherapy (SIT) requires dozens of subcutaneous injections over 3 to 5years in order to control IgE-mediated hypersensitivity, which is a T-helper 2 (Th2)-associated pathology. This study investigates the use of poly(lactide-co-glycolide) (PLGA) microparticles combined with immunostimulatory oligodeoxynucleotide (CpG), as well as protamine in SIT. Materials and Methods: We prepared microparticle formulations with the major allergen of bee venom, phospholipase A2 (PLA2), and analyzed the effect of co-encapsulated or admixed CpG in both naïve and bee venom allergic mice. Results: Mice immunized with microparticles containing only PLA2 induced weak antibody responses. In contrast, the combination with CpG resulted in strong PLA2-specific antibody responses. The presence of CpG was required for the induction of the Th1-associated isotype IgG2a, and the titers of IgG2a in sensitized mice correlated with a better protection against an allergen challenge. The effect of CpG was further strengthened when protamine was co-encapsulated for complexation of CpG. Conclusions: This study shows that allergen-specific immunotherapy with a PLGA-based allergen-delivery system in combination with CpG enhanced the induction of protective IgG2a immune responses. This may improve SIT compliance and shorten its duratio

Whole-organism concentration ratios in wildlife inhabiting Australian uranium mining environments

Wildlife concentration ratios for 226Ra, 210Pb, 210Po and isotopes of Th and U from soil, water, and sediments were evaluated for a range of Australian uranium mining environments. Whole-organism concentration ratios (CRwo-media) were developed for 271 radionuclide-organism pairs within the terrestrial and freshwater wildlife groups. Australian wildlife often has distinct physiological attributes, such as the lower metabolic rates of macropod marsupials as compared with placental mammals. In addition, the Australian CRswo-media originate from tropical and semi-arid climates, rather than from the temperate-dominated climates of Europe and North America from which most (>90%) of internationally available CRwo-media values originate. When compared, the Australian and non-Australian CRs are significantly different for some wildlife categories (e.g. grasses, mammals) but not others (e.g. shrubs). Where differences exist, the Australian values were higher, suggesting that site-, or region-specific CRswo-media should be used in detailed Australian assessments. However, in screening studies, use of the international mean values in the Wildlife Transfer Database (WTD) appears to be appropriate, as long as the values used encompass the Australian 95th percentile values. Gaps in the Australian datasets include a lack of marine parameters, and no CR data are available for freshwater phytoplankton, zooplankton, insects, insect larvae or amphibians; for terrestrial environments, there are no data for amphibians, annelids, ferns, fungi or lichens & bryophytes. The new Australian specific parameters will aide in evaluating remediation plans and ongoing operations at mining and waste sites within Australia. They have also substantially bolstered the body of U- and Th-series CRwo-media data for use internationally

Architecture of Planetary Systems Based on Kepler Data: Number of Planets and Coplanarity

We investigated the underlying architecture of planetary systems by deriving the distribution of planet multiplicity (number of planets) and the distribution of orbital inclinations based on the sample of planet candidates discovered by the Kepler mission. The scope of our study included solar-like stars and planets with orbital periods less than 200 days and with radii between 1.5 and 30 Earth radii, and was based on Kepler planet candidates detected during Quarters 1 through 6. We created models of planetary systems with different distributions of planet multiplicity and inclinations, simulated observations of these systems by Kepler, and compared the properties of the transits of detectable objects to actual Kepler planet detections. Specifically, we compared with both the Kepler sample's transit numbers and normalized transit duration ratios in order to determine each model's goodness-of-fit. We did not include any constraints from radial velocity surveys. Based on our best-fit models, 75-80% of planetary systems have 1 or 2 planets with orbital periods less than 200 days. In addition, over 85% of planets have orbital inclinations less than 3 degrees (relative to a common reference plane). This high degree of coplanarity is comparable to that seen in our Solar System. These results have implications for planet formation and evolution theories. Low inclinations are consistent with planets forming in a protoplanetary disk, followed by evolution without significant and lasting perturbations from other bodies capable of increasing inclinations.Comment: 16 pages, 7 figures, accepted to Ap

Elevated serum YKL-40, IL-6, CRP, CEA, and CA19-9 combined as a prognostic biomarker panel after resection of colorectal liver metastases

Background The inflammatory biomarkers, YKL-40 and interleukin-6 (IL-6), are elevated in patients with metastatic colorectal cancer. We examined their associations with relapse-free survival and overall survival in combination with serum C-reactive protein (CRP), carcinoembryonic antigen (CEA), and carbohydrate antigen 19–9 (CA19-9) in patients with colorectal liver metastases. Methods Altogether 441 consecutive patients undergoing liver resection at Helsinki University Hospital between 1998 and 2013 were included in the study. Pre- and postoperative YKL-40 and IL-6 were determined from serum samples with commercially available enzyme-linked immunosorbent assay (ELISA) kits, and CRP, CEA, and CA19-9 by routine methods. Associations between these biomarkers and relapse-free and overall survival were examined using Cox regression analysis. Results Patients with 2–5 elevated biomarkers were at an increased risk of relapse compared to those with 0–1 elevated biomarkers, preoperatively (HR 1.37, 95% CI 1.1–1.72) or postoperatively (HR 1.54, 95% CI 1.23–1.92). Patients with 2–5 elevated biomarkers were also at an increased risk of death compared to those with 0–1 elevated biomarkers, preoperatively (HR 1.76, 95% CI 1.39–2.24) or postoperatively (HR 1.83, 95% CI 1.44–2.33). Conclusion The results suggest that a protein panel of the inflammatory biomarkers YKL-40, IL-6, and CRP, and the cancer biomarkers CEA and CA19-9 might identify patients that benefit from more aggressive treatment and surveillance, although the additional value of IL-6 and CRP in this aspect is limited.Peer reviewe