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.

Shifting the focus of zebrafish toward a model of the tumor microenvironment.

Cancer cells exist in a complex ecosystem with numerous other cell types in the tumor microenvironment (TME). The composition of this tumor/TME ecosystem will vary at each anatomic site and affects phenotypes such as initiation, metastasis, and drug resistance. A mechanistic understanding of the large number of cell-cell interactions between tumor and TME requires models that allow us to both characterize as well as genetically perturb this complexity.

Anatomic position determines oncogenic specificity in melanoma.

Oncogenic alterations to DNA are not transforming in all cellular contexts. This may be due to pre-existing transcriptional programmes in the cell of origin. Here we define anatomic position as a major determinant of why cells respond to specific oncogenes.

Spatially resolved transcriptomics reveals the architecture of the tumor-microenvironment interface.

During tumor progression, cancer cells come into contact with various non-tumor cell types, but it is unclear how tumors adapt to these new environments. Here, we integrate spatially resolved transcriptomics, single-cell RNA-seq, and single-nucleus RNA-seq to characterize tumor-microenvironment interactions at the tumor boundary. Using a zebrafish model of melanoma, we identify a distinct "interface" cell state where the tumor contacts neighboring tissues.

Developmental chromatin programs determine oncogenic competence in melanoma.

Oncogenes only transform cells under certain cellular contexts, a phenomenon called oncogenic competence. Using a combination of a human pluripotent stem cell–derived cancer model along with zebrafish transgenesis, we demonstrate that the transforming ability of BRAF along with additional mutations depends on the intrinsic transcriptional program present in the cell of origin. In both systems, melanocytes are less responsive to mutations, whereas both neural crest and melanoblast populations are readily transformed.

An in vivo reporter for tracking lipid droplet dynamics in transparent zebrafish.

Lipid droplets are lipid storage organelles found in nearly all cell types from adipocytes to cancer cells. Although increasingly implicated in disease, current methods to study lipid droplets in vertebrate models rely on static imaging or the use of fluorescent dyes, limiting investigation of their rapid in vivo dynamics. To address this, we created a lipid droplet transgenic reporter in whole animals and cell culture by fusing tdTOMATO to Perilipin-2 (PLIN2), a lipid droplet structural protein.

Extracellular Vesicles in Cancer: Cell-to-Cell Mediators of Metastasis.

Tumor-secreted extracellular vesicles (EVs) are critical mediators of intercellular communication between tumor cells and stromal cells in local and distant microenvironments. Accordingly, EVs play an essential role in both primary tumor growth and metastatic evolution. EVs orchestrate multiple systemic pathophysiological processes, such as coagulation, vascular leakiness, and reprogramming of stromal recipient cells to support pre-metastatic niche formation and subsequent metastasis.

Tumour exosome integrins determine organotropic metastasis.

Ever since Stephen Paget's 1889 hypothesis, metastatic organotropism has remained one of cancer's greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche.

Validation of the HCR-20 Scale for Assessing Risk of Violent Behavior in Israeli Psychiatric Inpatients.

Background: Assessment of risk of violent behavior in forensic psychiatric practice is a complex and responsible clinical task and the use of a valid instrument can make the expert's work more effective. The Historical Clinical and Risk Management scale 20 (HCR-20) is a widely accepted measure of the risk of violence, sexual and criminal behavior. The aim of this study was to validate the HCR-20 in Israeli psychiatric inpatient settings.

Effects of iron depletion on CALM-AF10 leukemias.

Iron, an essential nutrient for cellular growth and proliferation, enters cells via clathrin-mediated endocytosis. The clathrin assembly lymphoid myeloid (CALM) protein plays an essential role in the cellular import of iron by clathrin-mediated endocytosis. CALM-AF10 leukemias harbor a single copy of the normal CALM gene and therefore may be more sensitive to the growth-inhibitory effect of iron restriction compared with normal hematopoietic cells.

Iron deprivation in cancer--potential therapeutic implications.

Iron is essential for normal cellular function. It participates in a wide variety of cellular processes, including cellular respiration, DNA synthesis, and macromolecule biosynthesis. Iron is required for cell growth and proliferation, and changes in intracellular iron availability can have significant effects on cell cycle regulation, cellular metabolism, and cell division.

Differentiating offenders by index offense and personality inventories: the characteristics of adult probationers in Israel.

The current study examines the differences between four groups of offenders (N = 230) according to the type of crime they committed: domestic violence, sex offenses, traffic violations, and nonspecific violence offenses. The study was conducted on the offenders undergoing treatment in the Israeli Adult Probation Service. A comparison between the groups included an examination of the differences in aggression levels, anxiety levels, and two Minnesota Multiphasic Personality Inventory-2 (MMPI-2) scales-the Psychopathic Deviate (PD-4) and the Antisocial Practices (ASP) scales.

Sociolinguistic and psycholinguistic indications of behavior disorders: analysis of a prisoner's discourse.

Human verbal language communicates both manifest and latent messages concerning the speaker's world and behavior. To understand his world and analyze his problems,(1) it is important to decode the latent messages as they may hint at the root causes. The authors present a discourse analysis of a prisoner's text and a semantic and morphological analysis of it.