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Cameron, B.

Publications and source records attributed to Cameron, B..

4 recordsLinked to original sources

Suppression of T cell function by phosphoethanolamine, a metabolite enriched in tumor interstitial fluid

Nutrient stress represents a significant barrier for antitumor immunity, and tumor interstitial fluid (TIF) often contains metabolites that hinder immune function. However, it is difficult to isolate the effects of tumor nutrient stress from other suppressive factors. Thus, we employed a chemically-defined cell culture medium based on the metabolomic profile of TIF: Tumor Interstitial Fluid Medium (TIFM). Culture of CD8+ T cells in TIFM limited cell expansion and impaired CD8+ T cell effector functions upon restimulation, suggesting tumor nutrient stress alone is sufficient to drive T cell dysfunction. We identified phosphoethanolamine (pEtn), a phospholipid intermediate, as a driver of T cell dysfunction. pEtn dampened TCR signaling by depleting T cells of diacylglycerol required for TCR signal transduction. Reduction of pEtn accumulation in tumors improved intratumoral T cell function and tumor control, suggesting pEtn accumulation plays a dominant role in TME immunosuppression.

immunology↗

Epithelial-Mesenchymal Transition: An Organizing Principle of Mammalian Regeneration

The MRL mouse strain is one of the few examples of a mammal capable of healing appendage wounds by regeneration, a process that begins with the formation of a blastema, a structure containing de-differentiating mesenchymal cells. HIF-1 expression in the nascent MRL wound site blastema is one of the earliest identified events and is sufficient to initiate the complete regenerative program. However, HIF-1 regulates many cellular processes modulating the expression of hundreds of genes. A later signal event is the absence of a functional G1 checkpoint leading to G2 cell cycle arrest with increased cellular DNA but little cell division seen in the blastema. This lack of mitosis in MRL blastema cells is also a hallmark of regeneration in classical invertebrate and vertebrate regenerators such as the planaria, hydra, and newt. Here, we explore the cellular events occurring between HIF-1 upregulation and its regulation of the genes involved in G2 arrest (EVI-5, {gamma}H3, Wnt5a, and ROR2), and identify EMT (Twist, Slug) and chromatin remodeling (EZH-2 and H3K27me3) as key intermediary processes. The locus of these cellular events is highly regionalized within the blastema, occurring in the same cells as determined by double staining using immunohistochemistry and FACS analysis, and appear as EMT and chromatin remodeling followed by G2 arrest determined by kinetic expression studies.

developmental biology↗

Temperature and depth dependence of the spatial distribution of snow crab

The cascading effects of rapid climate change is a reality with which all biota are challenged. In this context, we examine the spatiotemporal probability of occurrence of snow crab as a means to express viable habitat. This is attempted for three demographic components, morphometrically mature males and females and immature adolescent crab in the Scotian Shelf region of the northwest Atlantic, Canada. We use a robust approach, known as Conditional AutoRegressive models, to define viable habitat. Further, we focus upon viable habitat, conditioned on the marginal influence of temperature and depth as they are known to be important constraints on snow crab. We observe some niche partitioning in terms of depth and temperature. We also note declines in viable habitat marginal to depth and temperature since 2010 for all demographic groups. This population representing the southern-most distribution of snow crab in the northwest Atlantic are vulnerable to degradation of viable habitat attributable to rapid climate change. One-Sentence SummaryRapid climate change and a decadal scale change in the viable habitat of snow crab of the Scotian Shelf ecosystem.

ecology↗

Ocean currents drive the worldwide colonization of the most widespread marine plant, eelgrass (Zostera marina)

Currents are unique drivers of oceanic phylogeography and so determine the distribution of marine coastal species, along with past glaciations and sea level changes. Here, we reconstruct the worldwide colonization history of eelgrass (Zostera marina L.), the most widely distributed marine flowering plant or seagrass from its origin in the Northwest Pacific, based on nuclear and chloroplast genomes. We identified two divergent Pacific clades with evidence for admixture along the East Pacific coast. Multiple west to east (trans-Pacific) colonization events support the key role of the North Pacific Current. Time-calibrated nuclear and chloroplast phylogenies yielded concordant estimates of the arrival of Z. marina in the Atlantic through the Canadian Arctic, suggesting that eelgrass-based ecosystems, hotspots of biodiversity and carbon sequestration, have only been present since [~]208 Kya (thousand years ago). Mediterranean populations were founded [~]53 Kya while extant distributions along western and eastern Atlantic shores coincide with the end of the Last Glacial Maximum ([~]20 Kya). The recent colonization and 5-to 7-fold lower genomic diversity of Atlantic compared to the Pacific populations raises concern and opportunity about how Atlantic eelgrass might respond to rapidly warming coastal oceans.

evolutionary biology↗