Receptor tyrosine kinase inhibition leads to regression of acral melanoma by targeting the tumor microenvironment.

Background: Acral melanoma (AM) is an aggressive melanoma variant that arises from palmar, plantar, and nail unit melanocytes. Compared to non-acral cutaneous melanoma (CM), AM is biologically distinct, has an equal incidence across genetic ancestries, typically presents in advanced stage disease, is less responsive to therapy, and has an overall worse prognosis.

Methods: An independent analysis of published sequencing data was performed to evaluate the frequency of receptor tyrosine kinase (RTK) ligands and adapter protein gene variants and expression.

Real-time imaging reveals a role for macrophage protrusive motility in melanoma invasion.

Macrophages are primary cells of the innate immune system that mediate tumor progression. However, the motile behavior of macrophages and interactions with tumor cells are not well understood. Here, we exploit the optical transparency of larval zebrafish and perform real-time imaging of macrophage-melanoma interactions.

The Lipid Droplet Protein DHRS3 Is a Regulator of Melanoma Cell State.

Lipid droplets are fat storage organelles composed of a protein envelope and lipid-rich core. Regulation of this protein envelope underlies differential lipid droplet formation and function. In melanoma, lipid droplet formation has been linked to tumor progression and metastasis, but it is unknown whether lipid droplet proteins play a role.

Ancestry and somatic profile predict acral melanoma origin and prognosis.

Acral melanoma, which is not ultraviolet (UV)-associated, is the most common type of melanoma in several low- and middle-income countries including Mexico. Latin American samples are significantly underrepresented in global cancer genomics studies, which directly affects patients in these regions as it is known that cancer risk and incidence may be influenced by ancestry and environmental exposures. To address this, here we characterise the genome and transcriptome of 128 acral melanoma tumours from 96 Mexican patients, a population notable because of its genetic admixture.

Restraint of melanoma progression by cells in the local skin environment.

Keratinocytes, the dominant cell type in the melanoma microenvironment during tumor initiation, exhibit diverse effects on melanoma progression. Using a zebrafish model of melanoma and human cell co-cultures, we observed that keratinocytes undergo an Epithelial-Mesenchymal Transition (EMT)-like transformation in the presence of melanoma, reminiscent of their behavior during wound healing. Surprisingly, overexpression of the EMT transcription factor Twist in keratinocytes led to improved overall survival in zebrafish melanoma models, despite no change in tumor initiation rates.

Receptor tyrosine kinase inhibition leads to regression of acral melanoma by targeting the tumor microenvironment.

Acral melanoma (AM) is an aggressive melanoma variant that arises from palmar, plantar, and nail unit melanocytes. Compared to non-acral cutaneous melanoma (CM), AM is biologically distinct, has an equal incidence across genetic ancestries, typically presents in advanced stage disease, is less responsive to therapy, and has an overall worse prognosis. Independent analysis of published genomic and transcriptomic sequencing identified that receptor tyrosine kinase (RTK) ligands and adapter proteins are frequently amplified, translocated, and/or overexpressed in AM.

US Immigration Policy Stressors and Latinx Youth Mental Health.

Importance: The youth mental health crisis is exacerbated for Latinx adolescents, a group whose families are targets of anti-immigrant rhetoric and policy.

Objective: To investigate how immigration-related stressors are associated with disruptions in parent-child relationships and, in turn, the mental health symptoms of Latinx adolescents.

Design, Setting, And Participants: Data for this prospective cohort study of adolescent-mother dyads were derived from surveys completed at 3 time points spanning 4 years (time 1 [T1] in 2018, time 2 [T2] in 2020, and time 3 [T3] in 2022).

The lipid droplet protein DHRS3 is a regulator of melanoma cell state.

Lipid droplets are fat storage organelles composed of a protein envelope and lipid rich core. Regulation of this protein envelope underlies differential lipid droplet formation and function. In melanoma, lipid droplet formation has been linked to tumor progression and metastasis, but it is unknown whether lipid droplet proteins play a role.

Identifying genetic dependencies of melanocyte and melanoma development.

The advent of large-scale sequencing in both development and disease has identified large numbers of candidate genes that may be linked to important phenotypes. Validating the function of these candidates is challenging, due to low efficiency and low throughput of most model systems. We have developed a rapid, scalable system for assessing the role of candidate genes using zebrafish.

A mixed methods comparison of adolescents' and researchers' observations of neighborhood characteristics in Latinx neighborhoods.

We used a convergent mixed methods research design to compare and contrast researchers' neighborhood environmental assessments collected using systematic social observations with adolescents' neighborhood environmental assessments collected by semi-structured interviews with US Mexican adolescents. Using qualitative methods, we found that adolescents sometimes observed the same neighborhood environmental features as researchers. They also sometimes observed different environmental features altogether; in both cases they sometimes layered on additional meaning making.

Employer-Provided and Self-Initiated Job Accommodations for Workers with Serious Mental Illness.

Background: Many individuals with serious mental illness (SMI) are capable of employment in regular jobs (i.e. jobs paying at least minimum wage, not set aside for persons with disabilities, and not obtained with assistance from mental health services), but they may need job accommodations to be successful.

Desmosome mutations impact the tumor microenvironment to promote melanoma proliferation.

Desmosomes are transmembrane protein complexes that contribute to cell-cell adhesion in epithelia and other tissues. Here, we report the discovery of frequent genetic alterations in the desmosome in human cancers, with the strongest signal seen in cutaneous melanoma where desmosomes are mutated in >70% of cases. In primary but not metastatic melanoma biopsies, the burden of coding mutations in desmosome genes associates with a strong reduction in desmosome gene expression.

Cancer Modeling by Transgene Electroporation in Adult Zebrafish (TEAZ).

Transgenic expression of genes is a mainstay of cancer modeling in zebrafish. Traditional transgenic techniques rely upon injection into one-cell embryos, but ideally these transgenes would be expressed only in adult somatic tissues. We provide a method to model cancer in adult zebrafish in which transgenes can be expressed via electroporation.

GABA Regulates Electrical Activity and Tumor Initiation in Melanoma.

Unlabelled: Oncogenes can initiate tumors only in certain cellular contexts, which is referred to as oncogenic competence. In melanoma, whether cells in the microenvironment can endow such competence remains unclear. Using a combination of zebrafish transgenesis coupled with human tissues, we demonstrate that GABAergic signaling between keratinocytes and melanocytes promotes melanoma initiation by BRAFV600E.

Adult zebrafish as advanced models of human disease.

Modelling adult diseases to understand their aetiology and progression, and to develop new therapies, is a major challenge for medical biology. We are excited by new efforts in the zebrafish community to develop models of adult diseases that range from cancer to heart, infectious and age-related diseases, and those that relate to toxicology and complex social behaviours. Here, we discuss some of the advances in the field of zebrafish models of adult disease, and where we see opportunities and challenges ahead.

BayesTME: An end-to-end method for multiscale spatial transcriptional profiling of the tissue microenvironment.

Spatial variation in cellular phenotypes underlies heterogeneity in immune recognition and response to therapy in cancer and many other diseases. Spatial transcriptomics holds the potential to quantify such variation, but existing analysis methods are limited by their focus on individual tasks such as spot deconvolution. We present BayesTME, an end-to-end Bayesian method for analyzing spatial transcriptomics data.

Familism Values, Family Assistance, and Prosocial Behaviors Among U.S. Latinx Adolescents.

Among U.S. Mexican adolescents living in established immigrant communities, high familism values are positively associated with compliant, emotional, and dire prosocial behaviors via sociocognitive and cultural psychological mechanisms.

Lipid droplets are a metabolic vulnerability in melanoma.

Melanoma exhibits numerous transcriptional cell states including neural crest-like cells as well as pigmented melanocytic cells. How these different cell states relate to distinct tumorigenic phenotypes remains unclear. Here, we use a zebrafish melanoma model to identify a transcriptional program linking the melanocytic cell state to a dependence on lipid droplets, the specialized organelle responsible for lipid storage.

Familism values and psychological adjustment of Latinx adolescents in an emerging immigrant community: A five wave longitudinal study.

This study examined the relations between normative developmental changes of familism values and later internalizing and externalizing behaviors in Latinx adolescents from an emerging immigrant community. The sample included 547 Latinx adolescents (55.4% female; baseline = 12.

Workers' Perspectives on Workplace Disclosure of Serious Mental Illness and Their Employers' Responses.

Persons with serious mental illness are often reluctant to disclose their disability to an employer because of the intense stigma associated with their illness. Yet, disclosure may be desirable to gain access to employer-provided job accommodations, or to achieve other goals. In this article, we aimed to (1) describe the contexts in which workers in regular employment disclose a mental illness to their employer and (2) describe employer responses to disclosure, as perceived by the workers themselves.

hPSC-derived sacral neural crest enables rescue in a severe model of Hirschsprung's disease.

The enteric nervous system (ENS) is derived from both the vagal and sacral component of the neural crest (NC). Here, we present the derivation of sacral ENS precursors from human PSCs via timed exposure to FGF, WNT, and GDF11, which enables posterior patterning and transition from posterior trunk to sacral NC identity, respectively. Using a SOX2::H2B-tdTomato/T::H2B-GFP dual reporter hPSC line, we demonstrate that both trunk and sacral NC emerge from a double-positive neuro-mesodermal progenitor (NMP).

Surface chemistry in Ti-6Al-4V feedstock as influenced by powder reuse in electron beam additive manufacturing.

X-ray photoelectron spectroscopy (XPS) as well as scanning and transmission electron microscopy (SEM/TEM) analysis was carried out on four Ti-6Al-4V powders used in electron beam powder-bed fusion (PBF-EB) production environments: virgin low oxygen (0.080 wt% O), reused medium oxygen (0.140 wt% O), reused high oxygen (0.