Induction of PrPSc-specific systemic and mucosal immune responses in white-tailed deer with an oral vaccine for chronic wasting disease

The ongoing epidemic of chronic wasting disease (CWD) within cervid populations indicates the need for novel approaches for disease management. A vaccine that either reduces susceptibility to infection or reduces shedding of prions by infected animals, or a combination of both, could be of benefit for disease control. The development of such a vaccine is challenged by the unique nature of prion diseases and the requirement for formulation and delivery in an oral format for application in wildlife settings. To address the unique nature of prions, our group targets epitopes, termed disease specific epitopes (DSEs), whose exposure for antibody binding depends on disease-associated misfolding of PrP^C into PrP^Sc. Here, a DSE corresponding to the rigid loop (RL) region, which was immunogenic following parenteral vaccination, was translated into an oral vaccine. This vaccine consists of a replication-incompetent human adenovirus expressing a truncated rabies glycoprotein G recombinant fusion with the RL epitope (hAd5:tgG-RL). Oral immunization of white-tailed deer with hAd5:tgG-RL induced PrP^Sc-specific systemic and mucosal antibody responses with an encouraging safety profile in terms of no adverse health effects nor prolonged vector shedding. By building upon proven strategies of formulation for wildlife vaccines, these efforts generate a particular PrP^Sc-specific oral vaccine for CWD as well as providing a versatile platform, in terms of carrier protein and biological vector, for generation of other oral, peptide-based CWD vaccines.     

A fence barrier method of leading edge cell capture for explorative biochemical research

The scratch or wound-healing assay is used ubiquitously for investigating re-epithelialisation and has already revealed the importance of cells comprising the leading edge of healing epithelial wounds. However it is currently limited to studying the effect of known biochemical agents on the tissue of choice. Here we present an adaptation that extends the utility of this model to encompass the collection of cells from the leading edge of migrating epithelial sheets making available explorative biochemical analyses. The method is scalable and does not require expensive apparatus, making it suitable for large and small laboratories alike. We detail the application of our method and exemplify proof of principle data derived from primary human keratinocyte cultures.     

Serological evidence of typhus group rickettsia in a homeless population in Houston, Texas

We tested sera from 176 homeless people in Houston for antibodies against typhus group rickettsiae (TGR). Sera from 19 homeless people were reactive to TGR antigens by ELISA and IFA. Two people had antibodies against Rickettsia prowazekii (epidemic typhus) and the remaining 17 had antibodies against Rickettsia typhi (murine typhus).     

Skin-impedance in Fabry Disease: A prospective,controlled, non-randomized clinical study

Background

We previously demonstrated improved sweating after enzyme replacement therapy (ERT) in Fabry disease using the thermo-regularity sweat and quantitative sudomotor axon reflex tests. Skin-impedance, a measure skin-moisture (sweating), has been used in the clinical evaluation of burns and pressure ulcers using the portable dynamic dermal impedance monitor (DDIM) system.

Methods

We compared skin impedance measurements in hemizygous patients with Fabry disease (22 post 3-years of bi-weekly ERT and 5 ERT naive) and 22 healthy controls. Force compensated skin-moisture values were used for statistical analysis. Outcome measures included 1) moisture reading of the 100^th repetitive reading, 2) rate of change, 3) average of 60–110^th reading and 4) overall average of all readings.

Results

All outcome measures showed a significant difference in skin-moisture between Fabry patients and control subjects (p < 0.0001). There was no difference between Fabry patients on ERT and patients naïve to ERT. Increased skin-impedance values for the four skin-impedance outcome measures were found in a small number of dermatome test-sites two days post-enzyme infusions.

Conclusion

The instrument portability, ease of its use, a relatively short time required for the assessment, and the fact that DDIM system was able to detect the difference in skin-moisture renders the instrument a useful clinical tool.

     

Co-expression and promoter content analyses assign a role in biotic and abiotic stress responses to plant natriuretic peptides

Background  

Plant natriuretic peptides (PNPs) are a class of systemically mobile molecules distantly related to expansins. While several physiological responses to PNPs have been reported, their biological role has remained elusive. Here we use a combination of expression correlation analysis, meta-analysis of gene expression profiles in response to specific stimuli and in selected mutants, and promoter content analysis to infer the biological role of the Arabidopsis thaliana PNP, AtPNP-A.     

Hydrodynamic flow control in marine mammals

The ability to control the flow of water around the body dictates the performance of marine mammals in the aquatic environment. Morphological specializations of marine mammals afford mechanisms for passive flow control. Aside from the design of the body, which minimizes drag, the morphology of the appendages provides hydrodynamic advantages with respect to drag, lift, thrust, and stall. The flukes of cetaceans and sirenians and flippers of pinnipeds possess geometries with flexibility, which enhance thrust production for high efficiency swimming. The pectoral flippers provide hydrodynamic lift for maneuvering. The design of the flippers is constrained by performance associated with stall. Delay of stall can be accomplished passively by modification of the flipper leading edge. Such a design is exhibited by the leading edge tubercles on the flippers of humpback whales (Megaptera novaeangliae). These novel morphological structures induce a spanwise flow field of separated vortices alternating with regions of accelerated flow. The coupled flow regions maintain areas of attached flow and delay stall to high angles of attack. The delay of stall permits enhanced turning performance with respect to both agility and maneuverability. The morphological features of marine mammals for flow control can be utilized in the biomimetic design of engineered structures for increased power production and increased efficiency.