Showing papers by "Armando Aranda-Anzaldo published in 2021"

SARS-COV-2 and the sorcerer’s apprentices

Abstract: At the time of writing these lines, the World Health Organization (WHO) has just released the conclusions of an international team of experts, sent to the Chinese city of Wuhan, on a mission to gather and evaluate any evidence that may answer the fundamental scientific question of where do the SARS-CoV-2 virus came from. After a quarantine of fourteen days and then another ten, what in principle should have been a systematic forensic enquiry became a sort of enforced touristic experience 1. The team produced a lackluster document whose conclusions seem too close to the standing narrative of the Chinese authorities on this issue, and too far from providing a definitive answer to the original question 2. In late 2019, the sudden appearance in Wuhan of a virus with all the hallmarks of a coronavirus from bat origin (the mammalian order known to be the largest reservoir of such type of viruses), but that displayed an enhanced ability to infect human cells thanks to a receptor-binding motif (RBM) found in the virus’s spike protein (that mediates the virus entry into host cells) which happened to be quite similar to that of SARS-CoV (the virus responsible for the 2003 SARS outbreak), was an upsetting biological oddity 3. Furthermore, the spike protein of the new SARS-CoV-2 virus contains a unique cleavage site for the furin protease, an enzyme highly expressed in several human tissues such as brain, lung, pancreas, gut and kidney. The cleavage by furin renders the spike protein fully active and it is essential for the efficient infection of human lung cells. Such a cleavage site is completely absent in other coronaviruses of the same class, as well as in all coronaviruses from bats known to date 4. Yet, the three codons specifying the furin cleavage site are also present in two human coronaviruses (OC43; HKU1) responsible for upper respiratory tract infections (common colds). Remarkably, such codons are fitted in the right frame, within the SARS-CoV-2 genomic sequence, so as not to modify all the other functional features of the resulting spike protein 5. This fact begs the question of how

Is cancer a disease set up by cellular stress responses

Abstract: For several decades, the somatic mutation theory (SMT) has been the dominant paradigm on cancer research, leading to the textbook notion that cancer is fundamentally a genetic disease. However, recent discoveries indicate that mutations, including "oncogenic" ones, are widespread in normal somatic cells, suggesting that mutations may be necessary but not sufficient for cancer to develop. Indeed, a fundamental but as yet unanswered question is whether or not the first step in oncogenesis corresponds to a mutational event. On the other hand, for some time, it has been acknowledged the important role in cancer progression of molecular processes that participate in buffering cellular stress. However, their role is considered secondary or complementary to that of putative oncogenic mutations. Here we present and discuss evidence that cancer may have its origin in epigenetic processes associated with cellular adaptation to stressful conditions, and so it could be a direct consequence of stress-buffering mechanisms that allow cells with aberrant phenotypes (not necessarily associated with genetic mutations) to survive and propagate within the organism. We put forward the hypothesis that there would be an inverse correlation between the activation threshold of the cellular stress responses (CSRs) and the risk of cancer, so that species or individuals with low-threshold CSRs will display a higher incidence or risk of cancer.