Temporal Variations of Skin Pigmentation in C57Bl/6 Mice Affect Optical Bioluminescence Quantitation

ABSTRACT PURPOSE: Depilation-induced skin pigmentation in C57Bl/6 mice is a known occurrence, and presents a unique problem for quantitative optical imaging of small animals, especially for bioluminescence. The work reported here quantitatively investigated the optical attenuation of bioluminescent light due to melanin pigmentation in the skin of transgenic C57B1/6 mice, modified such that luciferase expression is under the transcription control of a physiologically and pharmacologically inducible gene. PROCEDURE: Both in vivo and ex vivo experiments were performed to track bioluminescence signal attenuation through different stages of the mouse hair growth cycle. Simultaneous reflectance measurements were collected in vivo to estimate melanin levels. RESULTS: Biological variability of skin pigmentation was found to dramatically affect collected bioluminescent signal emerging through the skin of the mice. When compared to signal through skin with no pigmentation, the signal through highly-pigmented skin was attenuated an average of 90%. Correlation of reflectance signals to bioluminescence signal loss forms the basis of the proposed correction method. We observed, however, that variability in tissue composition, which results in inconsistent reflectance spectra, limits the accuracy of the correction method but can be improved by incorporating more complex analysis. CONCLUSION: Skin pigmentation is a significant variable in bioluminescent imaging, and should be considered in experimental design and implementation for longitudinal studies, and especially when sensitivity to small signal changes, or differences among animals, is required

The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention

The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention

A split horseradish peroxidase for detection of intercellular protein-protein interactions and sensitive visualization of synapses

Intercellular protein-protein interactions (PPIs) enable communication between cells in diverse biological processes, including cell proliferation, immune responses, infection and synaptic transmission, but they are challenging to visualize because existing techniques1,2,3 have insufficient sensitivity and/or specificity. Here we report split horseradish peroxidase (sHRP) as a sensitive and specific tool for detection of intercellular PPIs. The two sHRP fragments, engineered through screening of 17 cut sites in HRP followed by directed evolution, reconstitute into an active form when driven together by an intercellular PPI, producing bright fluorescence or contrast for electron microscopy. Fusing the sHRP fragments to the proteins neurexin (NRX) and neuroligin (NLG), which bind each other across the synaptic cleft4, enabled sensitive visualization of synapses between specific sets of neurons, including two classes of synapses in the mouse visual system. sHRP should be widely applicable for studying mechanisms of communication between a variety of cell types

The Chiricahua Gap and the Role of Easterly Water Vapor Transport in Southeastern Arizona Monsoon Precipitation

Between North America's Sierra Madre and Rocky Mountains exists a little-recognized terrain "gap.'' This study defines the gap, introduces the term "Chiricahua Gap,'' and documents the role of easterly transport of water vapor through the gap in modulating summer monsoon precipitation in southeastern Arizona. The gap is near the Arizona-New Mexico border north of Mexico and is approximately 250 km wide by 1 km deep. It is the lowest section along a 3000-km length of the Continental Divide from 168 to 45 degrees N and represents 80% of the total cross-sectional area below 2.5 km MSL open to horizontal water vapor transport in that region. This study uses reanalyses and unique upper-air observations in a case study and a 15-yr climatology to show that 72% (76%) of the top-quartile (decile) monsoon precipitation days in southeast Arizona during 2002-16 occurred in conditions with easterly water vapor transport through the Chiricahua Gap on the previous day.Scripps Institution of Oceanography; University of Arizona Office for Research and Discovery6 month embargo; published online: 20 September 2017This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

A Global Climatology of Baroclinically Influenced Tropical Cyclogenesis*

Tropical cyclogenesis is generally considered to occur in regions devoid of baroclinic structures; however, an appreciable number of tropical cyclones (TCs) form in baroclinic environments each year. A global climatology of these baroclinically influenced TC developments is presented in this study. An objective classification strategy is developed that focuses on the characteristics of the environmental state rather than on properties of the vortex, thus allowing for a pointwise “development pathway” classification of reanalysis data. The resulting climatology shows that variability within basins arises primarily as a result of local surface thermal contrasts and the positions of time-mean features on the subtropical tropopause. The pathway analyses are sampled to generate a global climatology of 1948–2010 TC developments classified by baroclinic influence: nonbaroclinic (70%), low-level baroclinic (9%), trough induced (5%), weak tropical transition (11%), and strong tropical transition (5%). All basins other than the North Atlantic are dominated by nonbaroclinic events; however, there is extensive interbasin variability in secondary development pathways. Within each basin, subregions and time periods are identified in which the relative importance of the development pathways also differs. The efficiency of tropical cyclogenesis is found to be highly dependent on development pathway. The peak efficiency defined in the classification subspace straddles the nonbaroclinic/trough-induced boundary, suggesting that the optimal environment for TC development includes a baroclinic contribution from an upper-level disturbance. By assessing the global distribution of baroclinically influenced TC formations, this study identifies regions and pathways whose further study could yield improvements in our understanding of this important subset of TC developments