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Starvation resistance is a life-saving mechanism for many organisms facing food availability fluctuation in the natural environment. Different strategies have been episodically identified for some model organisms, the first of which was the ability to suppress metabolic rate. Among the identified strategies, the ability of planarians to shrink their body under fasting conditions and revert the process after feeding (the growth-degrowth process) represents a fascinating mechanism to face long periods of fasting. The growth-degrowth process is strictly related to the capability of planarians to continuously maintain tissue homeostasis and body proportions even in challenging conditions, thanks to the presence of a population of pluripotent stem cells. Here, we take advantage of several previous studies describing the growth-degrowth process and of recent progress in the understanding of planarian homeostasis mechanisms, to identify tissueselective transcriptional downregulation as a driving strategy for the development of a thrifty phenotype, and the p53 transcription factor as a player in adjusting tissue homeostasis in accordance with food availability. [ABSTRACT FROM AUTHOR]

Gravity alterations elicit complex and mostly detrimental effects on biological systems. Among these, a prominent role is occupied by oxidative stress, with consequences for tissue homeostasis and development. Studies in altered gravity are relevant for both Earth and space biomedicine, but their implementation using whole organisms is often troublesome. Here we utilize planarians, simple worm model for stem cell and regeneration biology, to characterize the pathogenic mechanisms brought by artificial gravity alterations. In particular, we provide a comprehensive evaluation of molecular responses in intact and regenerating specimens, and demonstrate a protective action from the space‐apt for nanotechnological antioxidant cerium oxide nanoparticles. [ABSTRACT FROM AUTHOR]

Planarians are able to stand long periods of starvation by maintaining adult stem cell pools and regenerative capacity. The molecular pathways that are needed for the maintenance of regeneration during starvation are not known. Here, we show that down‐regulation of chaperonin TRiC/CCT subunits abrogates the regeneration capacity of planarians during starvation, but TRiC/CCT subunits are dispensable for regeneration in fed planarians. Under starvation, they are required to maintain mitotic fidelity and for blastema formation. We show that TRiC subunits modulate the unfolded protein response (UPR) and are required to maintain ATP levels in starved planarians. Regenerative defects in starved CCT‐depleted planarians can be rescued by either chemical induction of mild endoplasmic reticulum stress, which leads to induction of the UPR, or by the supplementation of fatty acids. Together, these results indicate that CCT‐dependent UPR induction promotes regeneration of planarians under food restriction. SYNOPSIS: It is unknown how starved planarians maintain their ability to regenerate. This study shows that CCT‐dependent UPR induction promotes planarian regeneration specifically under food restriction. Down‐regulation of TRiC/CCT subunits impedes planarian regeneration only during starvation and down‐regulates the unfolded protein response (UPR).Under starvation, TRiC/CCT subunits are required to maintain mitotic fidelity and blastema formation.CCT depletion also abrogates UPR activation in mouse hematopoietic stem and progenitor cells (HSPCs) under glucose deprivation, a mammalian regenerative system.Feeding, supplementation of fatty acids or chemical induction of mild ER stress partially rescue impairments in survival and regeneration of CCT‐depleted planarians exposed to food starvation. [ABSTRACT FROM AUTHOR]

Background Information: Planarians are a sound, well‐established model system for molecular studies in the field of stem cells, cell differentiation, developmental biology and translational research. Treated stem cell‐less planarians produced by X‐ray treatment are commonly used to study stem cell transcriptional profile and their role in planarian biological processes. X‐ray induces oxidative and DNA damage to differentiated cells, requires expensive radiation machines that are not available in most of the research centres and demand rigorous risk management and dedicated staff. Results: We tested the use of the well‐known antimetabolite genotoxic drug 5‐fluorouracil which mainly affects proliferating cells in way to demonstrate its use in replacing X‐ray treatment. We succeeded in demonstrating ability of high doses of 5‐fluorouracil to deplete Dugesia japonica stem cells and in identifying a 5‐fluorouracil transiently resistant population of lineage committed stem cells. Conclusions and Significance: Our results encourage the use of 5‐fluorouracil‐treated planarians as a model system for studying mechanisms of resistance to genotoxicants, planarian stem cell heterogeneity and molecular cascades of tissue aging. [ABSTRACT FROM AUTHOR]

Targeting the interaction of p53 with its natural inhibitor MDM2 by the use of small synthetic molecules has emerged as a promising pharmacological approach to restore p53 oncosuppressor function in cancers retaining wild-type p53. The first critical step in the experimental validation of newly synthesized small molecules developed to inhibit MDM2-p53 interaction is represented by the evaluation of their efficacy in preventing the formation of the MDM2-p53 complex. This can be achieved using the in vitro reconstructed recombinant MDM2-p53 complex in cell-free assays. A number of possible approaches have been proposed, which are however not suitable for screening large chemical libraries, due to the high costs of reagents and instrumentations, or the need of large amounts of highly pure recombinant proteins. Here we describe a rapid and cheap method for high-throughput screening of putative inhibitors of MDM2-p53 complex formation - based on the use of GST-recombinant proteins - that does not require antibodies and recombinant protein purification steps from bacterial cell lysates. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Adenine nucleotide translocases (ANTs) are multitask proteins involved in several aspects of cell metabolism, as well as in the regulation of cell death/survival processes. We investigated the role played by ANT isoforms 1 and 2 in the growth of a human glioblastoma cell line (ADF cells). The silencing of ANT2 isoform, by small interfering RNA, did not produce significant changes in ADF cell viability. By contrast, the silencing of ANT1 isoform strongly reduced ADF cell viability by inducing a non-apoptotic cell death process resembling paraptosis. We demonstrated that cell death induced by ANT1 depletion cannot be ascribed to the loss of the ATP/ADP exchange function of this protein. By contrast, our findings indicate that ANT1-silenced cells experience oxidative stress, thus allowing us to hypothesize that the effect of ANT1-silencing on ADF is mediated by the loss of the ANT1 uncoupling function. Several studies ascribe a pro-apoptotic role to ANT1 as a result of the observation that ANT1 overexpression sensitizes cells to mitochondrial depolarization or to apoptotic stimuli. In the present study, we demonstrate that, despite its pro-apoptotic function at a high expression level, the reduction of ANT1 density below a physiological baseline impairs fundamental functions of this protein in ADF cells, leading them to undertake a cell death process. [ABSTRACT FROM AUTHOR]

The cover image is based on the Research Article Artificially altered gravity elicits cell homeostasis unbalance in planarian worms, and cerium oxide nanoparticles counteract this effect by Gianni Ciofani et al., https://doi.org/10.1002/jbm.a.37215. [ABSTRACT FROM AUTHOR]