From Tank to Treatment: Modeling Melanoma in Zebrafish

Melanoma is the deadliest form of skin cancer and one of few cancers with a growing incidence. A thorough understanding of its pathogenesis is fundamental to developing new strategies to combat mortality and morbidity. Zebrafish-due in large part to their tractable genetics, conserved pathways, and optical properties-have emerged as an excellent system to model melanoma. Zebrafish have been used to study melanoma from a single tumor initiating cell, through metastasis, remission, and finally into relapse. In this review, we examine seminal zebrafish studies that have advanced our understanding of melanoma

Images of Embedded Jovian Planet Formation At A Wide Separation Around AB Aurigae

Direct images of protoplanets embedded in disks around infant stars provide the key to understanding the formation of gas giant planets like Jupiter. Using the Subaru Telescope and Hubble Space Telescope, we find evidence for a jovian protoplanet around AB Aurigae orbiting at a wide projected separation (93 au), likely responsible for multiple planet-induced features in the disk. Its emission is reproducible as reprocessed radiation from an embedded protoplanet. We also identify two structures located at 430-580 au that are candidate sites of planet formation. These data reveal planet formation in the embedded phase and a protoplanet discovery at wide, > 50 au separations characteristic of most imaged exoplanets. With at least one clump-like protoplanet and multiple spiral arms, the AB Aur system may also provide the evidence for a long-considered alternative to the canonical model for Jupiter's formation: disk (gravitational) instability.Comment: Author's personal version: 19 pages, 5 Figures, 1 Table; 32 Supplementary pages, 18 Supplementary Figures, 1 Supplementary Table; Accepted for Publication in Nature Astronomy. Published version: https://www.nature.com/articles/s41550-022-01634-

Dissection of Zebrafish Adult Melanocyte Stem Cell Signaling During Regeneration

Tissue-resident stem cells are present in many adult organs, where they are important for organ homeostasis and repair in response to injury. However, the signals that activate these cells and the mechanisms governing how these cells self-renew or differentiate are highly context dependent and incompletely understood, particularly in non-hematopoietic tissues. In the skin, melanocyte stem cells (McSCs) are responsible for replenishing mature pigmented melanocytes. In mammals, these cells reside in the hair follicle bulge and bulb niches where they are activated during homeostatic hair follicle turnover and following melanocyte destruction, as occurs in vitiligo and other skin hypopigmentation disorders. Recently, we identified adult McSCs in the zebrafish. To elucidate mechanisms governing McSC self-renewal and differentiation fates we analyzed individual transcriptomes from thousands of melanocyte lineage cells during the regeneration process. We identified transcriptional signatures for McSCs, deciphered transcriptional changes and intermediate cell states during regeneration, and analyzed cell-cell signaling changes to discover mechanisms governing melanocyte regeneration. We identified KIT signaling via the RAS/MAPK pathway as a regulator of McSC direct differentiation. Analysis of the scRNAseq dataset also revealed a population of mitfa/aox5 co-expressing cells that divides following melanocyte destruction, likely corresponding to cells that undergo self-renewal. Our findings show how different subpopulations of mitfa-positive cells underlie regeneration and differentiation of at least one subpopulation requires reactivation of developmental KIT signaling to properly reconstitute the melanocyte stripe

BMP Signaling Promotes Neural Crest Identity and Accelerates Melanoma Onset

Currently, little is known about specific factors and pathways that act to initially promote neural crest identity during tumor initiation. Recently, GDF6-activated BMP signaling was shown to regulate differentiation and survival both in melanomas and during melanocyte development. Together, these results have implicated BMP signaling as a key regulator of neural crest and melanocyte programs in normal and pathologic states of the melanocyte lineage. However, it is unknown whether BMP signaling plays a role early in melanoma initiation and progression

Screen as Skin: The Somatechnics of Touchscreen Music Media

In this article I explore the way mobile music devices with touchscreen technology produce new somatechnical figurations that reshape emotional dynamics of music listening. Using research drawn from a cyberethnography of online users from Reddit.com, I argue that the changing relationships between the human-computer interface result in new affective schemas that expand and reconfigure how it feels to listen to music in a mobile setting. In particular, I focus on skin-on-screen contact in order to suggest that the screen acts as a reflexive surface producing intimate relations for the mobile listener. Touchscreens imply the relationship between skin on skin—the skin of our body (in particular the hands) against the skin of the screen. It follows that mobile touchscreen devices suggest a degree of sensuality—in the coming together of bodies, fluids and other organic materials which ‘stick’ to the touchscreen. Reading the mobile touchscreen player as a somatechnical figuration therefore suggests that the listening experience is developing along with the technologies that mediate music to the body in ways that continue to challenge our understanding of bodily borders and in ways that redefine what it means to feel the music. Therefore, the touchscreen-skin is a critical site of affective relations that dramatically reshape what it means to listening to music in a mobile setting; a private and intimate encounter between the user and their counterpart

A physical sciences network characterization of non-tumorigenic and metastatic cells.

To investigate the transition from non-cancerous to metastatic from a physical sciences perspective, the Physical Sciences-Oncology Centers (PS-OC) Network performed molecular and biophysical comparative studies of the non-tumorigenic MCF-10A and metastatic MDA-MB-231 breast epithelial cell lines, commonly used as models of cancer metastasis. Experiments were performed in 20 laboratories from 12 PS-OCs. Each laboratory was supplied with identical aliquots and common reagents and culture protocols. Analyses of these measurements revealed dramatic differences in their mechanics, migration, adhesion, oxygen response, and proteomic profiles. Model-based multi-omics approaches identified key differences between these cells' regulatory networks involved in morphology and survival. These results provide a multifaceted description of cellular parameters of two widely used cell lines and demonstrate the value of the PS-OC Network approach for integration of diverse experimental observations to elucidate the phenotypes associated with cancer metastasis

A physical sciences network characterization of non-tumorigenic and metastatic cells

To investigate the transition from non-cancerous to metastatic from a physical sciences perspective, the Physical Sciences–Oncology Centers (PS-OC) Network performed molecular and biophysical comparative studies of the non-tumorigenic MCF-10A and metastatic MDA-MB-231 breast epithelial cell lines, commonly used as models of cancer metastasis. Experiments were performed in 20 laboratories from 12 PS-OCs. Each laboratory was supplied with identical aliquots and common reagents and culture protocols. Analyses of these measurements revealed dramatic differences in their mechanics, migration, adhesion, oxygen response, and proteomic profiles. Model-based multi-omics approaches identified key differences between these cells' regulatory networks involved in morphology and survival. These results provide a multifaceted description of cellular parameters of two widely used cell lines and demonstrate the value of the PS-OC Network approach for integration of diverse experimental observations to elucidate the phenotypes associated with cancer metastasis.National Cancer Institute (U.S.) (Grant U54CA143874