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- Casewell, Nicholas R, et al.
(författare)
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Solenodon genome reveals convergent evolution of venom in eulipotyphlan mammals.
- 2019
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:51, s. 25745-25755
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Tidskriftsartikel (refereegranskat)abstract
- Venom systems are key adaptations that have evolved throughout the tree of life and typically facilitate predation or defense. Despite venoms being model systems for studying a variety of evolutionary and physiological processes, many taxonomic groups remain understudied, including venomous mammals. Within the order Eulipotyphla, multiple shrew species and solenodons have oral venom systems. Despite morphological variation of their delivery systems, it remains unclear whether venom represents the ancestral state in this group or is the result of multiple independent origins. We investigated the origin and evolution of venom in eulipotyphlans by characterizing the venom system of the endangered Hispaniolan solenodon (Solenodon paradoxus). We constructed a genome to underpin proteomic identifications of solenodon venom toxins, before undertaking evolutionary analyses of those constituents, and functional assessments of the secreted venom. Our findings show that solenodon venom consists of multiple paralogous kallikrein 1 (KLK1) serine proteases, which cause hypotensive effects in vivo, and seem likely to have evolved to facilitate vertebrate prey capture. Comparative analyses provide convincing evidence that the oral venom systems of solenodons and shrews have evolved convergently, with the 4 independent origins of venom in eulipotyphlans outnumbering all other venom origins in mammals. We find that KLK1s have been independently coopted into the venom of shrews and solenodons following their divergence during the late Cretaceous, suggesting that evolutionary constraints may be acting on these genes. Consequently, our findings represent a striking example of convergent molecular evolution and demonstrate that distinct structural backgrounds can yield equivalent functions.
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| 2. |
- Swales, John G., et al.
(författare)
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Quantitation of Endogenous Metabolites in Mouse Tumors Using Mass-Spectrometry Imaging
- 2018
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Ingår i: Analytical Chemistry. - : AMER CHEMICAL SOC. - 0003-2700 .- 1520-6882. ; 90:10, s. 6051-6058
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Tidskriftsartikel (refereegranskat)abstract
- Described is a quantitative-mass-spectrometry-imaging (qMSI) methodology for the analysis of lactate and glutamate distributions in order to delineate heterogeneity among mouse tumor models used to support drug-discovery efficacy testing. We evaluate and report on preanalysis-stabilization methods aimed at improving the reproducibility and efficiency of quantitative assessments of endogenous molecules in tissues. Stability experiments demonstrate that optimum stabilization protocols consist of frozen-tissue embedding, post-tissue-sectioning desiccation, and storage at -80 degrees C of tissue sections sealed in vacuum-tight containers. Optimized stabilization protocols are used in combination with qMSI methodology for the absolute quantitation of lactate and glutamate in tumors, incorporating the use of two different stable-isotope-labeled versions of each analyte and spectral-clustering performed on each tissue section using k-means clustering to allow region-specific, pixel-by-pixel quantitation. Region-specific qMSI was used to screen different tumor models and identify a phenotype that has low lactate heterogeneity, which will enable accurate measurements of lactate modulation in future drug-discovery studies. We conclude that using optimized qMSI protocols, it is possible to quantify endogenous metabolites within tumors, and region-specific quantitation can provide valuable insight into tissue heterogeneity and the tumor microenvironment.
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| 3. |
- Warner, John J., et al.
(författare)
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3D printable non-isocyanate polyurethanes with tunable material properties
- 2019
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Ingår i: Polymer Chemistry. - : Royal Society of Chemistry (RSC). - 1759-9954 .- 1759-9962. ; 10:34, s. 4665-4674
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Tidskriftsartikel (refereegranskat)abstract
- Green chemistry-based non-isocyanate polyurethanes (NIPU) are synthesized and 3D-printed via rapid, projection photopolymerization into compliant mechanisms of 3D structure with spatially-localized material properties. Trimethylolpropane allyl ether-cyclic carbonate is used to couple the unique properties of two types of reaction chemistry: (1) primary diamine-cyclic carbonate ring-opening conjugation for supplanting conventional isocyanate-polyol reactions in creating urethane groups, with the additional advantage of enabling modular segment interchangeability within the diurethane prepolymers; and (2) thiol-ene (click) conjugation for non-telechelic, low monodispersity, quasi-crystalline-capable, and alternating step-growth co-photopolymerization. Fourier transform infrared spectroscopy is used to monitor the functional group transformation in reactions, and to confirm these process-associated molecular products. The extent of how these processes utilize molecular tunability to affect material properties were investigated through measurement-based comparison of the various polymer compositions: frequency-related dynamic mechanical analysis, tension-related elastic-deformation mechanical analysis, and material swelling analysis. Stained murine myoblasts cultured on NIPU slabs were evaluated via fluorescent microscopy for "green-chemistry" affects on cytocompatibility and cell adhesion to assess potential biofouling resistance. 3D multi-material structures with micro-features were printed, thus demonstrating the capability to spatially pattern different NIPU materials in a controlled manner and build compliant mechanisms.
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