Molecular structure refinement by direct fitting of atomic coordinates to experimental ESR spectra

An attempt is made to bypass spectral analysis and fit internal coordinates of radicals directly to experimental liquid- and solid-state electron spin resonance (ESR) spectra. We take advantage of the recently introduced large-scale spin dynamics simulation algorithms and of the fact that the accuracy of quantum mechanical calculations of ESR parameters has improved to the point of quantitative correctness. Partial solutions are offered to the local minimum problem in spectral fitting and to the problem of spin interaction parameters (hyperfine couplings, chemical shifts, etc.) being very sensitive to distortions in molecular geometry.Comment: Submitted for publicatio

Computational Modeling of Silicate Glasses: A Quantitative Structure-Property Relationship Perspective

This article reviews the present state of Quantitative Structure-Property Relationships (QSPR) in glass design and gives an outlook into future developments. First an overview is given of the statistical methodology, with particular emphasis to the integration of QSPR with molecular dynamics simulations to derive informative structural descriptors. Then, the potentiality of this approach as a tool for interpretative and predictive purposes is highlighted by a number of recent inspiring applications

Factors influencing the adoption of artificial nests in Polistes dominulus (Christ)

Nest recognition is critical to the sociality of wasps. Studies on Polistes have shown that is essentially based on chemoreception. Moreover, wasps are also able to recognise the nest's contents and this could also participate in nest recognition, By the method of the artificial nest adoption, we examined which natural nest stimuli (hydrocarbons from paper nests, hydrocarbons from immature broods or eggs, and the physical presence of both) act consistently in nest recognition. Since these stimuli change with the age of colony, we also considered its maturity. Our results show that the presence of eggs have a stronger effect to induce artificial nest adoption. Surprisingly, the paper nest hydrocarbons alone were weakly attractive. On the contrary, paper nest hydrocarbons combined with immature brood hydrocarbons, increased significantly the adoption of artificial nests. Finally, previous experiences of the wasps and the maturity of the nest they come from appear as influential factors in adoption and probably in nest recognition. In conclusion, some biological and practical implications of these results are discussed that underlined the necessary combination of various nests features to insure nest recognition. (C) 2001 Published by Elsevier Science B.V

Cyclic C-amino phosphorus ylides as a source of bidentate heteroditopic ligands (phosphine/aminocarbene) for transition metals

International audienc

Motility of liquid stored ram spermatozoa is altered by dilution rate independent of seminal plasma concentration

The fertility after use of liquid stored ram semen following cervical AI rapidly decreases if semen is stored beyond 12 h. The dilution of seminal plasma is often cited as a key contributor to the diminished motility and fertility of ram spermatozoa subjected to liquid preservation. Two experiments were conducted to assess the effect of spermatozoa concentration (i.e. dilution rate) and percentage of seminal plasma on the motility and viability of liquid stored ram spermatozoa. In Experiment 1, semen was diluted to one of seven concentrations ranging from 0.2 to 1.4 × 109 spermatozoa/ml with milk and assessed for motility after 3 or 24 h of storage at 15 °C. In Experiment 2, semen was collected and washed to remove seminal plasma before re-dilution to 0.2–1.4 × 109 spermatozoa/ml with milk containing 0%, 20% or 40% (final v/v ratio) seminal plasma and assessed for viability and motility after 3 or 24 h of storage at 15 °C. Whereas motility was not affected by spermatozoa concentration after 3 h of storage, the proportion of progressive spermatozoa decreased after 24 h of storage when spermatozoa concentration was greater than 1.0 × 109 spermatozoa/ml. The duration of preservation and the spermatozoa concentration affected spermatozoa motility but had no impact on spermatozoa viability. This negative effect of greater spermatozoa concentrations on motility was independent of the presence and the concentration of seminal plasma. The seminal plasma at both concentrations (20% and 40%) had a protective effect on spermatozoa motility after 24 h of storage. These findings have the potential to improve the efficiency of cervical AI with liquid stored ram semen

The antipsychotic medications aripiprazole, brexpiprazole and cariprazine are off-target respiratory chain complex I inhibitors.

Acknowledgements: We would like to thank Dr Lucia Pinon (MRC Toxicology Unit) for assistance with flow cytometry and confocal microscopy, Tim Smith and Maria Guerra Martin for help with processing of Electron Microscopy samples and Tim Ashby and Munisha Patel for preparing the fly food.Antipsychotic drugs are the mainstay of treatment for schizophrenia and provide adjunct therapies for other prevalent psychiatric conditions, including bipolar disorder and major depressive disorder. However, they also induce debilitating extrapyramidal syndromes (EPS), such as Parkinsonism, in a significant minority of patients. The majority of antipsychotic drugs function as dopamine receptor antagonists in the brain while the most recent 'third'-generation, such as aripiprazole, act as partial agonists. Despite showing good clinical efficacy, these newer agents are still associated with EPS in ~ 5 to 15% of patients. However, it is not fully understood how these movement disorders develop. Here, we combine clinically-relevant drug concentrations with mutliscale model systems to show that aripiprazole and its primary active metabolite induce mitochondrial toxicity inducing robust declines in cellular ATP and viability. Aripiprazole, brexpiprazole and cariprazine were shown to directly inhibit respiratory complex I through its ubiquinone-binding channel. Importantly, all three drugs induced mitochondrial toxicity in primary embryonic mouse neurons, with greater bioenergetic inhibition in ventral midbrain neurons than forebrain neurons. Finally, chronic feeding with aripiprazole resulted in structural damage to mitochondria in the brain and thoracic muscle of adult Drosophila melanogaster consistent with locomotor dysfunction. Taken together, we show that antipsychotic drugs acting as partial dopamine receptor agonists exhibit off-target mitochondrial liabilities targeting complex I