Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Investigation of the Genotoxic Potential of the Marine Toxin C17-SAMT Using the In Vivo Comet and Micronucleus Assays

The contaminant responsible for the atypical toxicity reported in mussels from Bizerte Lagoon (Northern Tunisia) during the last decade has been characterized as C17-sphinganine analog mycotoxin (C17-SAMT). This neurotoxin showed common mouse toxic symptoms, including flaccid paralysis and severe dyspnea, followed by rapid death. For hazard assessment on human health, in this work we aimed to evaluate the in vivo genotoxic effects of this marine biotoxin using the classical alkaline and modified Fpg comet assays performed to detect DNA breaks and alkali-labile sites as well as oxidized bases. The micronucleus assay was used on bone marrow to detect chromosome and genome damage. C17-SAMT induces a statistically insignificant increase in DNA tail intensity at all doses in the duodenum, and in the spleen contrary to the liver, the percentage of tail DNA increased significantly at the mid dose of 300 µg/kg b.w/d. C17-SAMT did not affect the number of micronuclei in the bone marrow. Microscopic observations of the liver showed an increase in the number of mitosis and hepatocytes’ cytoplasm clarification. At this level of study, we confirm that C17-SAMT induced DNA damage in the liver but there was no evidence of effects causing DNA oxidation or chromosome and genome damage

Toxic responses of metabolites produced by Ostreopsis cf. ovata on a panel of cell types

Blooms of the dinoflagellate Ostreopsis cf. ovata are regularly associated with human intoxications that are attributed to ovatoxins (OVTXs), the main toxic compounds produced this organism and close analogs to palytoxin (PlTX). Unlike for PlTX, information on OVTXs'toxicity are scarce due to the absence of commercial standards. Extracts from two cultures of Mediterranean strains of O. cf. ovata (MCCV54 and MCCV55), two fractions containing or not OVTXs (prepared from the MCCV54 extract) and OVTX-a and -d (isolated from the MCCV55 extract) were generated. These chemical samples and PlTX were tested on a panel of cell types from several organs and tissues (skin, intestine, lung, liver and nervous system). The MCCV55 extract, containing a 2-fold higher amount of OVTXs than MCCV54 extract, was shown to be more cytotoxic on all the cell lines and more prone to increase interleukin-8 (IL-8) release in keratinocytes. The fraction containing OVTXs was also cytotoxic on the cell lines tested but induced IL-8 release only in liver cells. Unexpectedly, the cell lines tested showed the same sensitivity to the fraction that does not contain OVTXs. With this fraction, a pro-inflammatory effect was shown both in lung and liver cells. The level of cytotoxicity was similar for OVTX-a and –d, except on intestinal and skin cells where a weak difference of toxicity was observed. Among the 3 toxins, only PlTX induced a pro-inflammatory effect mostly on keratinocytes. These results suggest that the ubiquitous Na+/K+ ATPase target of PlTX is likely shared with OVTX-a and -d, although the differences in pro-inflammatory effect must be explained by other mechanisms

EFSA Project on the use of New Approach Methodologies (NAMs) for the hazard assessment of nanofibres. Lot 1, nanocellulose oral exposure: gastrointestinal digestion, nanofibres uptake and local effects

Question number: EFSA-Q-2023-00528International audienceNanocellulose (NC) is an emerging material in the food sector with several prospective application areas. Three main types of NC exist, i.e. bacterial NC (BNC), nanofibrillated cellulose (NFC), and cellulose nanocrystals (CNC). The biological sources and processing conditions affect several physicochemical parameters of NC. In the present project, a NAM-based IATA for addressing data gaps in the assessment of potential hazards associated to NC oral exposure was considered. This IATA focused on three main pillars, i.e. (i) assessment of the uptake and potential crossing of the intestinal barrier by NC, (ii) assessment of local effects, including inflammation and genotoxicity, on the gastrointestinal epithelia, and (iii) assessment of any digestion or degradation of NC by the human microbiome. Eight NC samples belonging to the three NC types, plus a comparator in the micro-range, were selected as study materials and EFSA NAMs Project on Nanofibres, Lot 1 www.efsa.europa.eu/publications EFSA Supporting publication 2023:EN-8258 2 submitted to a thorough physicochemical characterisation. A battery of in vitro tests was used to provide insight into NC hazard and mode of action according to a tiered approach, which lead to selection of three materials belonging to the three main NC types for in depth-testing. Cell uptake of these materials was demonstrated, and such uptake was greater in a triculture model, which better simulates the barrier properties of the human intestinal epithelium, as compared to Caco-2 monolayers. Uptake was the greatest in repeated exposure conditions, in which intestinal barrier crossing was demonstrated for CNC. Pro-inflammatory responses accompanied by massive NC uptake in macrophages, indicative for potential immunotoxicological effects, and barrier function impairment were observed, whereas no indications for genotoxicity were obtained. Finally, no formation of smaller particles following colonic fermentation of NC was observed. For the integration of these results in regulatory hazard assessment of NC after oral exposure, prospective use of NC as novel food or as food additive was considered

Raw data of the EFSA NAMs Project on Nanofibres Lot 1 (Annex T) (GP/EFSA/SCER/2020/04) (Vincentini et al., 2023)

Raw data of the in vitro experiments produced in the context of the 'EFSA Project on the use of New Approach Methodologies (NAMs) for the hazard assessment of nanofibres. Lot 1, nanocellulose oral exposure: gastrointestinal digestion, nanofibres uptake and local effects' outsourced by EFSA to a consortia of EU organisations coordinated by the National Institute of Health (ISS) of Italy (Annex T) (GP/EFSA/SCER/2020/04) (Vincentini et al., 2023).IT; en; XLSX; [email protected]

This is our story: iconography of carved doors and panels in Òyó Palace

This saying or prayer is one of the numerous expressions among the Yorùbá about the door and its significance, not only as a physical and important aspect of their architecture, but also in their language and culture. It also alludes to its pride of place as perhaps the most decorated element of Yorùbá architecture. From private homes, to the homes of the rich, shrines, and palaces, Yorùbá doors are usually imbued with a considerable array of images and icons that proclaims the owner's identity, religion, occupation. The Yorùbá are not unique in this respect. For example, among the Dogon, the door is as important as the house on which it is affixed. The granary, according to Willett (2002: 176), protects the the food stored inside it, while the door is seen or referred to as an element not only for physical protection, but also as a spiritual means of warding off unwanted spirits. It is reasonable, therefore, to expect the door to receive aesthetic attention by embellishment with an array of images

A multi-country analysis of COVID-19 hospitalizations by vaccination status

Background: Individuals vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), when infected, can still develop disease that requires hospitalization. It remains unclear whether these patients differ from hospitalized unvaccinated patients with regard to presentation, coexisting comorbidities, and outcomes. Methods: Here, we use data from an international consortium to study this question and assess whether differences between these groups are context specific. Data from 83,163 hospitalized COVID-19 patients (34,843 vaccinated, 48,320 unvaccinated) from 38 countries were analyzed. Findings: While typical symptoms were more often reported in unvaccinated patients, comorbidities, including some associated with worse prognosis in previous studies, were more common in vaccinated patients. Considerable between-country variation in both in-hospital fatality risk and vaccinated-versus-unvaccinated difference in this outcome was observed. Conclusions: These findings will inform allocation of healthcare resources in future surges as well as design of longer-term international studies to characterize changes in clinical profile of hospitalized COVID-19 patients related to vaccination history. Funding: This work was made possible by the UK Foreign, Commonwealth and Development Office and Wellcome (215091/Z/18/Z, 222410/Z/21/Z, 225288/Z/22/Z, and 220757/Z/20/Z); the Bill & Melinda Gates Foundation (OPP1209135); and the philanthropic support of the donors to the University of Oxford's COVID-19 Research Response Fund (0009109). Additional funders are listed in the "acknowledgments" section

An international observational study to assess the impact of the Omicron variant emergence on the clinical epidemiology of COVID-19 in hospitalised patients

Background: Whilst timely clinical characterisation of infections caused by novel SARS-CoV-2 variants is necessary for evidence-based policy response, individual-level data on infecting variants are typically only available for a minority of patients and settings. Methods: Here, we propose an innovative approach to study changes in COVID-19 hospital presentation and outcomes after the Omicron variant emergence using publicly available population-level data on variant relative frequency to infer SARS-CoV-2 variants likely responsible for clinical cases. We apply this method to data collected by a large international clinical consortium before and after the emergence of the Omicron variant in different countries. Results: Our analysis, that includes more than 100,000 patients from 28 countries, suggests that in many settings patients hospitalised with Omicron variant infection less often presented with commonly reported symptoms compared to patients infected with pre-Omicron variants. Patients with COVID-19 admitted to hospital after Omicron variant emergence had lower mortality compared to patients admitted during the period when Omicron variant was responsible for only a minority of infections (odds ratio in a mixed-effects logistic regression adjusted for likely confounders, 0.67 [95% confidence interval 0.61-0.75]). Qualitatively similar findings were observed in sensitivity analyses with different assumptions on population-level Omicron variant relative frequencies, and in analyses using available individual-level data on infecting variant for a subset of the study population. Conclusions: Although clinical studies with matching viral genomic information should remain a priority, our approach combining publicly available data on variant frequency and a multi-country clinical characterisation dataset with more than 100,000 records allowed analysis of data from a wide range of settings and novel insights on real-world heterogeneity of COVID-19 presentation and clinical outcome