Is hypoimmunogenic stem cell therapy safe in times of pandemics?

The manipulation of human leukocyte antigens (HLAs) and immune modulatory factors in "universal" human pluripotent stem cells (PSCs) holds promise for immunological tolerance without HLA matching. This paradigm raises concerns should "universal" grafts become virally infected. Furthermore, immunological manipulation might functionally impair certain progeny, such as hematopoietic stem cells. We discuss the risks and benefits of hypoimmunogenic PSCs, and the need to further advance HLA matching and autologous strategies.Toxicolog

c-FOS drives reversible basal to squamous cell carcinoma transition.

While squamous transdifferentiation within subpopulations of adenocarcinomas represents an important drug resistance problem, its underlying mechanism remains poorly understood. Here, using surface markers of resistant basal cell carcinomas (BCCs) and patient single-cell and bulk transcriptomic data, we uncover the dynamic roadmap of basal to squamous cell carcinoma transition (BST). Experimentally induced BST identifies activator protein 1 (AP-1) family members in regulating tumor plasticity, and we show that c-FOS plays a central role in BST by regulating the accessibility of distinct AP-1 regulatory elements. Remarkably, despite prominent changes in cell morphology and BST marker expression, we show using inducible model systems that c-FOS-mediated BST demonstrates reversibility. Blocking EGFR pathway activation after c-FOS induction partially reverts BST in vitro and prevents BST features in both mouse models and human tumors. Thus, by identifying the molecular basis of BST, our work reveals a therapeutic opportunity targeting plasticity as a mechanism of tumor resistance

Influence of management practices and of scavenging seabirds on availability of fisheries discards to benthic scavengers

There is great variation in discarding practice among fisheries in different parts of the world. Management systems result in some fisheries discarding mostly fish offal, much of which is macerated into small chunks, while other fisheries discard large (ca. 25 cm) whole fish. Scavenging seabirds consume high proportions of most categories of discarded fish and offal (typically 60 to 80% of discarded roundfish, 70 to 95% of discarded offal), but tend to avoid discarded benthic invertebrates and fish that are difficult to swallow, such as species with long spines or large flatfish. Amounts and composition of fishery discards and offal reaching benthic scavenging communities are clearly very strongly influenced by the intense but selective consumption by seabirds, and this alteration will depend strongly on details of the fishery management regulations and customs, such as whether or not waste is macerated. There is scope to adjust fisheries management practices to reduce the impact of offal and discards on scavenger communitie

TGFβ, Fibronectin and Integrin α5β1 Promote Invasion in Basal Cell Carcinoma.

Basal cell carcinoma (BCC) is the most frequent human cancer and is becoming an important health problem in an aging population. Based on their clinical and histological characteristics, thick BCC are typically divided into low-risk nodular and high-risk infiltrative subtypes, although the underlying mechanisms are poorly understood. We have identified molecular mechanisms that explain the aggressiveness of high-risk infiltrative BCC, with a potential direct clinical impact. In this study, we first show that fibroblasts, transforming growth factor-β, and fibronectin are found preferentially in infiltrative human BCC. This allowed us to develop in vivo models for the study of infiltrative BCC, which in turn let us confirm the role of transforming growth factor-β in inducing peritumoral fibronectin deposition and tumor infiltration. We then show that fibronectin promotes adhesion and migration of BCC cell lines through integrin α5β1-mediated phosphorylation of focal adhesion kinase. Fittingly, both inhibition of integrin α5β1 and phospho-focal adhesion kinase prevent fibronectin-induced migration of BCC cells in vitro as well as BCC infiltration in vivo. Altogether, our results open important insights into the pathogenesis of aggressive infiltrative BCC and identify integrin α5β1 or focal adhesion kinase inhibition as promising strategies for the treatment of advanced BCC