Second-generation nitazoxanide derivatives: thiazolides are effective inhibitors of the influenza A virus

Aim: The only small molecule drugs currently available for treatment of influenza A virus (IAV) are M2 ion channel blockers and sialidase inhibitors. The prototype thiazolide, nitazoxanide, has successfully completed Phase III clinical trials against acute uncomplicated influenza. Results: We report the activity of seventeen thiazolide analogs against A/PuertoRico/8/1934(H1N1), a laboratory-adapted strain of the H1N1 subtype of IAV, in a cell culture-based assay. A total of eight analogs showed IC50s in the range of 0.14–5.0 μM. Additionally a quantitative structure–property relationship study showed high correlation between experimental and predicted activity based on a molecular descriptor set. Conclusion: A range of thiazolides show useful activity against an H1N1 strain of IAV. Further evaluation of these molecules as potential new small molecule therapies is justified

Chloroquine-Resistant Haplotype Plasmodium falciparum Parasites, Haiti

Chloroquine resistance is now present in this country

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

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

Le tsunami moléculaire: L'impact de la biologie moléculaire sur les sciences du cancer, du développement et de l'évolution ces cinquante dernières années.

Il y a cinquante ans, la biologie moléculaire a commencé à explorer des questions qui étaient considérées comme relevant d'autres disciplines, parfois en s'aventurant au-delà du domaine de la biologie. Ce fut un tsunami. Ce texte examine l'impact de ce tsunami sur les domaines de la biologie du développement, de la biologie évolutive et du problème du cancer. La biologie moléculaire a-t-elle changé ces disciplines au cours des cinquante dernières années ? Quels résultats peuvent lui être attribués, et ces résultats ont-ils affecté leurs concepts ? (voir aussi Jean Francois Daniel Nicolas. L'embryologie : d'un vertige l'autre. 2021). ⟨hal-03501390

Aleuroclava aucubae (Aleyrodidae) nouveau pour la France, et Parlatoria oleae (Diaspididae) nouveau pour la Corse (Hemiptera)

National audienceTwo Hemiptera are newly recorded from Corsica: Aleuroclava aucubae (Kuwana) (Aleyrodidae) on Citrus sp. and Parlatoria oleae (Colvée) (Diaspididae) on Prunus domestica L.Deux Hémiptères nouveaux pour la Corse sont signalés, Aleuroclava aucubae (Kuwana) (Aleyrodidae) sur Citrus sp. et Parlaroria oleae (Colvée) (Diaspididae) sur Prunus domestica L

Influence of cropping system on Fusarium head blight and mycotoxin levels in winter wheat

In this study, we investigated the effects of various wheat cropping systems on Fusarium head blight severity and mycotoxin (deoxynivalenol, nivalenol, zearalenone) levels. We investigated four wheat-cropping systems: a conventional system, an integrated system, a direct drilling system and an organic system, in fields with natural contamination. The study was carried out over three 1-year periods: 1999–2000, 2000–2001 and 2001–2002. The severity of Fusarium head blight and toxin levels differed considerably between years, reflecting climatic effects. In a given year, the severity of Fusarium head blight also differed between cropping systems, with the most severe disease observed in the direct drilling and conventional system plots in 2000. The level of grain contamination by mycotoxins therefore depends on both climate and cropping system. Mycotoxin levels were highest in the year with the highest disease severity: 2000. Contamination levels were highest with the direct drilling system. We were unable to rank the organic and conventional systems, because neither was consistently more contaminated than the other. Moreover, no clear relationship was found between disease severity and levels of contamination with deoxynivalenol, nivalenol or zearalenone underconditions of natural contamination