Duarte-Vogel, S. | bioRxiv Science

bioRxiv2020

Genetics of white color and iridophoroma in "Lemon Frost" leopard geckos

The squamates (lizards and snakes) are close relatives of birds and mammals, with more than 10,000 described species that display extensive variation in a number of important biological traits, including coloration, venom production, and regeneration. Due to a lack of genomic tools, few genetic studies in squamates have been carried out. The leopard gecko1, Eublepharis macularius, is a popular companion animal, and displays a variety of coloration patterns. We took advantage of a large breeding colony and used linkage analysis, synteny, and homozygosity mapping to investigate a spontaneous semi-dominant mutation, "Lemon Frost", that produces white coloration and causes skin tumors (iridophoroma). We localized the mutation to a single locus which contains a strong candidate gene, SPINT12,3, a tumor suppressor implicated in human skin cutaneous melanoma (SKCM) and over-proliferation of epithelial cells in mice and zebrafish4-16. Our work establishes the leopard gecko as a tractable genetic system and suggests that a tumor suppressor in melanocytes in humans can also suppress tumor development in iridophores in lizards.

genetics↗

bioRxiv2020

Three-Dimensional Impedance Tomographic Mapping of Metabolically Active Endolumen

Real-time detection of vulnerable atherosclerotic lesions, characterized by a high content of oxidized low-density lipoprotein (oxLDL)-laden macrophages or foam cells, remains an unmet clinical need. While fractional flow reserve (FFR)-guided revascularization in angiographically intermediate stenoses is utilized to assess hemodynamic significance, in vivo detection of oxLDL-rich plaques may provide a new paradigm for treating metabolically unstable lesions. Herein, we have demonstrated endoluminal mapping of lipid-laden lesions using 3-D electrical impedance spectroscopy-derived impedance tomography (EIT) in a pre-clinical swine model. We performed surgical banding of the right carotid arteries of Yucatan mini-pigs, followed by 16 weeks of high-fat diet, to promote the development of lipid-rich lesions. We implemented an intravascular sensor combining an FFR pressure transducer with a 6-point micro-electrode array for electrical impedance spectroscopy (EIS) measurements. 3-D EIT mapping was achieved using an EIS-based reconstruction algorithm. We demonstrated that EIT mapping corresponds to endoluminal histology for oxLDL-laden lesions. We further used computational models to theoretically predict and validate EIS measurements. Thus, our 3-D EIS-derived EIT provides in vivo detection of metabolically active plaques with the goal of guiding optimal intravascular intervention. One Sentence SummaryThis work demonstrates in vivo mapping of oxidized LDL-laden endolumen by deploying an intravascular dual-sensor to a swine model of atherosclerosis.

bioengineering↗