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.     

Synthesis and structure-activity relationship of 7-azaindole piperidine derivatives as CCR2 antagonists

The synthesis and structure-activity relationship of a series of 7-azaindole piperidine derivatives are described. SAR studies led to the discovery of the potent CCR2 antagonists displaying IC(50) values in the nanomolar range. The representative compound 15 showed reasonable P450 and pharmacokinetics profile.     

The influence of multiple dispersal mechanisms and landscape structure on population clustering and connectivity in fragmented artesian spring snail populations

Many organisms occupy heterogeneous landscapes that contain both barriers to movement as well as corridors that facilitate dispersal. The extent to which such features determine population connectivity will depend on the mechanisms utilized by organisms to disperse. Here we examined the interaction between landscape structure and dispersal in the endemic aquatic snail, Fonscochlea accepta , in the fragmented artesian spring ecosystem of arid central Australia. We used frequentist and Bayesian analyses of microsatellite data to identify population structure and immigration for 1130 snails sampled from 50 springs across an entire spring complex. We introduce a modified isolation-by-distance analysis to test hypotheses about how populations are clustered and to distinguish the most likely dispersal pathways within and between those clusters. Highly significant differences in F _ST values and significant isolation-by-distance patterns were detected among springs across the entire complex, while Bayesian assignment tests revealed the presence of two hierarchical levels of spring clustering. Clusters were defined by the spatial aggregation of springs, dynamic aquatic habitat connections between springs and the ecology of the snails. Bayesian immigrant identification and our modified isolation-by-distance analysis revealed that dispersal occurs at two geographical scales via two very different mechanisms. Short range dispersal (usually ≤ 300 m) occurs via active movement facilitated by aquatic connections among springs while long-range dispersal (≥ 3 km) is likely facilitated by an animal vector (phoresy). These results underline the importance of both dispersal mode and landscape structure in influencing connectivity rates and patterns among populations.