Search

PurposeThe aim is to expose the lack of recognition of archaeological sites as a symbolic identity and cultural integrator, showcasing how a deconstructed ideal of public policies and social practices resulted from mismanagement in the processes of safeguarding the historical culture of the sites. It is intended to highlight this discrepancy as to raise awareness on the equivocal direction these complications are heading to and to stress the advocacy for knowledge dissemination government sectors should aim on promoting.Design/methodology/approachThe article draws substantively on the analysis of case studies at state and national level. The archaeological cultural value interpretation is supported by the analysis of historical records such as exploration logs, government organizations’ workbooks, norms and regulations of archaeological conservation and literature review. The current deconstructed cultural value of archaeological sites is interpreted given trends of promotion of archaeological heritage, which ultimately resulted in a misconception of origins.FindingsThe subsequent analysis shows that present-day political and social activities on archaeological sites are predisposed by a mismanagement of cultural promotion. The preference for activities that differ from indigenous traditions, commercialization of culture and urban growth have diverged the ideal of culture integration and knowledge dissemination these sites were rescued for, leading to the ignorance of the population towards their cultural value. This phenomenon demonstrates that archaeology in Morelos is currently submerged in a misconception of origins.Originality/valueThe article aims to expose an array of references to issues of the usefulness of archaeological heritage for political and economic purposes as a referent for future studies.

Cell death can be executed by regulated apoptotic and non-apoptotic pathways, including the iron-dependent process of ferroptosis. Small molecules are essential tools for studying the regulation of cell death. Using time-lapse imaging, and a library of 1,833 bioactive compounds, we assembled a large compendium of kinetic cell death modulatory profiles for inducers of apoptosis and ferroptosis. From this dataset we identify dozens of ferroptosis suppressors, including numerous compounds that appear to act via cryptic off-target antioxidant or iron chelating activities. We show that the FDA-approved drug bazedoxifene acts as a potent radical trapping antioxidant inhibitor of ferroptosis both in vitro and in vivo. ATP-competitive mechanistic target of rapamycin (mTOR) inhibitors, by contrast, are on-target ferroptosis inhibitors. Further investigation revealed both mTOR-dependent and mTOR-independent mechanisms that link amino acid metabolism to ferroptosis sensitivity. These results highlight kinetic modulatory profiling as a useful tool to investigate cell death regulation.

This chapter presents the eDHR computerized system validation process (eDHR) in direct relation to the intended use of said software. This consists of electronically recording the history of medical devices that are manufactured in a company located in Tijuana. This work is referenced in the fifth version of the Good Automated Manufacturing Practice Guide 5 (GAMP5) of the International Society of Pharmaceutical Engineering (ISPE). This guide contains the implicit risk-based approach to the quality and labeling of medical devices. In addition, it is based on the regulations that companies regulated by the Food and Drug Administration (FDA) must abide by.

Cancer cells need a steady supply of nutrients to evade cell death and proliferate. Depriving cancer cells of the amino acid cystine can trigger the non-apoptotic cell death process of ferroptosis. Here, we report that cancer cells can evade cystine deprivation-induced ferroptosis by uptake and catabolism of the cysteine-rich extracellular protein albumin. This protective mechanism is enhanced by mTORC1 inhibition and involves albumin degradation in the lysosome, predominantly by cathepsin B (CTSB). CTSB-dependent albumin breakdown followed by export of cystine from the lysosome via the transporter cystinosin fuels the synthesis of glutathione, which suppresses lethal lipid peroxidation. When cancer cells are grown under non-adherent conditions as spheroids, mTORC1 pathway activity is reduced, and albumin supplementation alone affords considerable protection against ferroptosis. These results identify the catabolism of extracellular protein within the lysosome as a mechanism that can inhibit ferroptosis in cancer cells.

Ferroptosis is an important mediator of pathophysiological cell death and an emerging target for cancer therapy. Whether ferroptosis sensitivity is governed by a single regulatory mechanism is unclear. Here, based on the integration of 24 published chemical genetic screens combined with targeted follow-up experimentation, we find that the genetic regulation of ferroptosis sensitivity is highly variable and context-dependent. For example, the lipid metabolic gene acyl-coenzyme A (CoA) synthetase long chain family member 4 (ACSL4) appears far more essential for ferroptosis triggered by direct inhibition of the lipid hydroperoxidase glutathione peroxidase 4 (GPX4) than by cystine deprivation. Despite this, distinct pro-ferroptotic stimuli converge upon a common lethal effector mechanism: accumulation of lipid peroxides at the plasma membrane. These results indicate that distinct genetic mechanisms regulate ferroptosis sensitivity, with implications for the initiation and analysis of this process in vivo.

Nonapoptotic cell death is important for human health and disease. Here, we show how various tools and techniques drawn from the chemical biology field have played a central role in the discovery and characterization of nonapoptotic cell death pathways. Focusing on the example of ferroptosis, we describe how phenotypic screening, chemoproteomics, chemical genetic analysis, and other methods enabled the elucidation of this pathway. Synthetic small-molecule inducers and inhibitors of ferroptosis identified in early studies have now been leveraged to identify an even broader set of compounds that affect ferroptosis and to validate new chemical methods and probes for various ferroptosis-associated processes. A number of limitations associated with specific chemical biology tools or techniques have also emerged and must be carefully considered. Nevertheless, the study of ferroptosis provides a roadmap for how chemical biology methods may be used to discover and characterize nonapoptotic cell death mechanisms.