10 research outputs found

    Reciprocal influence of the p53 and the hypoxic pathways

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    When cells sense a decrease in oxygen availability (hypoxia), they develop adaptive responses in order to sustain this condition and survive. If hypoxia lasts too long or is too severe, the cells eventually die. Hypoxia is also known to modulate the p53 pathway, in a manner dependent or not of HIF-1 (hypoxia-inducible factor-1), the main transcription factor activated by hypoxia. The p53 protein is a transcription factor, which is rapidly stabilised by cellular stresses and which has a major role in the cell responses to these stresses. The aim of this review is to compile what has been reported until now about the interconnection between these two important pathways. Indeed, according to the cell line, the severity and the duration of hypoxia, oxygen deficiency influences very differently p53 protein level and activity. Conversely, p53 is also described to affect HIF-1α stability, one of the two subunits of HIF-1, and HIF-1 activity. The direct and indirect interactions between HIF-1α and p53 are described as well as the involvement in this complex network of their respective ubiquitin ligases von Hippel Lindau protein and murine double minute 2. Finally, the synergistic or antagonistic effects of p53 and HIF-1 on some important cellular pathways are discussed

    Resistance to cancer chemotherapy: failure in drug response from ADME to P-gp

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    Threatened conservation scientists: the aftermath of an eye-opening publication on rewilding

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    ‘Rewilding’ is a nature conservation strategy gaining prominence worldwide. Established in the Northern Hemisphere, rewilding initiatives have increasingly been proposed in Argentina, but their relative merits, feasibility of implementation and accountability have lacked adequate analysis and discussion. Recently, 125 scientists and practitioners wrote an article to assess the justification and methods of current rewilding initiatives in Argentina. Rather than engaging in a constructive debate with the scientific community, one of the major organizations behind these initiatives threatened to sue the authors for libel. We strongly reject this baseless threat. Scientific discussions around this and other conservation topics of societal concern should be addressed in an academic context and conducted in a respectful and rational manner, embracing the right of scientists and practitioners to express themselves freely and without fear of coercion

    Restorative proctocolectomy and ileal pouch-anal anastomosis for familial adenomatous polyposis revisited

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