Ambiguity crisis

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Ambiguity crisis

Description

Graphical ambiguity: Fliegende Blรคtter (1892-10-23): Perception versus interpretation (Ludwig Wittgenstein) or paradigm shift (Thomas Kuhn)

The ambiguity crisis is a contemporary crisis comparable to the credibility or reproducibility crisis in the biomedical sciences. The term 'crisis' is rooted etymologically in the Greek word krinein: meaning to 'separate, decide, judge'. In this sense, science and communication in general are a continuous crisis at the edge of separating clarity or certainty from confusing double meaning, or obscure 'alchemical' gibberish, or even fake-news. Reproducibility relates to the condition of repeating and confirming calculations or experiments presented in a published resource. While ambiguity is linked to relevant issues of reproducibility, it extends to the communications space of terminological and graphical representations of concepts. Type 1 ambiguities are the inevitable consequence of conceptual evolution, in the process of which ambiguities are replaced by experimentally and theoretically supported paradigm shifts to clear-cut theorems. In contrast, type 2 ambiguities are traced in publications that reflect merely a disregard and ignorance of established concepts without an attempt to justify the inherent deviations from high-quality science. There are many shades of grey between these types of ambiguity.


Reference: Gnaiger E (2024) Complex II ambiguities โ€• FADH2 in the electron transfer system. J Biol Chem 300:105470. https://doi.org/10.1016/j.jbc.2023.105470

Navigating the ambiguity crisis

Here are 10 topics that illustrate ambiguities of type 1 and type 2.
  1. Complex II ambiguities (Gnaiger 2024): The prosthetic group FADH2 appears erroneously as the substrate of CII in the ETS linked to succinate oxidation in many publications (2001 to 2023) and numerous educational websites (Gnaiger 2023). In fact, the succinate dehydrogenase - synonymous with CII - oxidizes succinate and reduces the covalently bound prosthetic group FAD to FADH2 in the canonical forward tricarboxylic acid cycle at the entry to the membrane-bound ETS with further electron transfer into the Q-junction.
  2. The elusive chemical proton (Complex I and hydrogen ion ambiguities in the electron transfer system): The current literature contains inconsistencies regarding H+ formation on the matrix side of the mitochondrial inner membrane, when NADH is oxidized during oxidative phosphorylation (OXPHOS). Ambiguities arise when examining the oxidation of NADH by respiratory Complex I or succinate by Complex II.
  3. Oxidative stress (Azzi 2022): A prominent case of ambiguity in the grey zone between types 1 and 2 has been uniquely demonstrated by analysis of the popular notion of 'oxidative stress' - a term more frequently found in PubMed than 'mitochondria', widely used with vague definition and without expression by numerical values and corresponding units.
  4. Normoxia and hypoxia (Donnelly et al 2022): Anthropocentric and clinical perspectives on hypoxia clash with an evolutionary view of life in environments of different oxygen regimes. Microenvironmental oxygenation is in stark contrast to the ambient oxygen level in our macroscopic environment, which we often apply uncritically in studies with isolated mitochondria or cultured cells, when ambient normoxia implies effectively hyperoxic experimental conditions.
  5. The force-pressure ambiguity (Gnaiger 2020 Chapter 8): The ambiguous use (type 1) of the terms force and pressure has deep consequences on the enigmatic concept of non-ohmic flux-force relationships in the context of mitochondrial membrane potential and the protonmotive force.
  6. The force-energy ambiguity: Gibbs energy or Gibbs force? (Gnaiger 2020 Chapter 8): The ambiguous use (type 2) of the term Gibbs energy [J] instead of Gibbs force [Jยทmol-1] is widespread in textbooks of physical chemistry, biochemistry, and bioenergetics.
  7. Uncoupling, decoupling, dyscoupling (Gnaiger et al 2020 Section 2.4): Rigorous definition is warranted.
  8. Respiratory State 2 - ROX or LEAK? (Gnaiger et al 2020 Section 2.6.2): Rigorous definition is warranted with reference to the original definition by Chance, Williams 1955).
  9. Respiratory State 3 - high or saturating [ADP]? (Gnaiger et al 2020 Section 2.6.3): Rigorous definition is warranted where the OXPHOS state is distinguished from State 3 as originally defined by Chance, Williams 1955).
  10. Negative entropy (Negative entropy for living systems: controversy between nobel laureates Schrรถdinger, Pauling and Perutz): 'Entropy is a simple and clear concept, whereas discussing about entropy is not simple and not always clear. I leave this to Wittgenstein for comment.'


Science communication: Addressing the ambiguity crisis

The dissemination of scientific disinformation from peer-reviewed literature infiltrates textbooks, educational platforms, and social media. Countering disinformation demands a strategy that raises "awareness of the inherent ambiguity crisis, complementing efforts to address the well-acknowledged issues of credibility and reproducibility" (1, 2).
The erosion of public trust in science intensifies when even scientists find it challenging to rely on the scientific literature. To combat this escalating issue, scientists must unite to spotlight ambiguities within their own field (3, 4). Beyond physical disease outbreaks, a scientific infodemic spreads with the exponential increase of insufficiently quality-controlled publications (5).
Institutions, such as the National Academies and International Scientific Societies, should spearhead initiatives to combat the ambiguity crisis (6). Committees ought to be established to identify ambiguity hotspots, publish guidelines to address specific ambiguities, and prompt journal editors to rectify ambiguities post-publication when peer review falls short. Adhering to the principles of "Addressing the ambiguity crisis" can bestow a quality management label on scientific journals. This serves as an effective measure to safeguard the integrity of the invaluable work of the scientific community, wielding awareness, and implementing a proactive deterrent against the uncontrolled spread of ambiguities or disinformation into educational materials and social media.
  1. Gnaiger E (2024) Complex II ambiguities โ€• FADH2 in the electron transfer system. J Biol Chem 300:105470. https://doi.org/10.1016/j.jbc.2023.105470 - ยปBioblast link
  2. Gall T, Ioannidis JPA, Maniadis Z (2017) The credibility crisis in research: Can economics tools help? PloS Biol 15:e2001846. https://doi.org/10.1371/journal.pbio.2001846
  3. https://www.bioblast.at/index.php/Ambiguity_crisis
  4. Azzi A (2022) Oxidative stress: What is it? Can it be measured? Where is it located? Can it be good or bad? Can it be prevented? Can it be cured? Antioxidants (Basel) 11: 1431.
  5. Gnaiger E (2021) Beyond counting papers โ€“ a mission and vision for scientific publication. Bioenerg Commun 2021.5. https://doi.org/10.26124/bec:2021-0005
  6. National Academies of Sciences, Engineering, and Medicine (2023) Navigating infodemics and building trust during public health emergencies: proceedings of a workshop in brief. National Academies Press, Washington, DC. https://doi.org/10.17226/27188


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