Borrelia burgdorferi small lipoprotein Lp6.6 is a member of multiple protein complexes in the outer membrane and facilitates pathogen transmission from ticks to mice

Borrelia burgdorferi lipoprotein Lp6.6 is a differentially produced spirochete antigen. An assessment of lp6.6 expression covering representative stages of the infectious cycle of spirochetes demonstrates that the gene is solely expressed during pathogen persistence in ticks. Deletion of lp6.6 in infectious B. burgdorferi did not influence in vitro growth, or its ability to persist and induce inflammation in mice, migrate to larval or nymphal ticks or survive through the larval-nymphal molt. However, Lp6.6-deficient spirochetes displayed significant impairment in their ability to transmit from infected ticks to naïve mice, which was restored upon genetic complementation of the mutant with a wild-type copy of lp6.6, establishing that Lp6.6 plays a role in pathogen transmission from ticks to mammals. Lp6.6 is a subsurface, yet highly abundant, outer membrane antigen. Two-dimensional blue native/SDS-PAGE coupled with liquid chromatography-mass spectrometry (LC-MS/MS) analysis and protein cross-linking studies independently shows that Lp6.6 exists in multiple protein complexes in the outer membrane. We speculate that the function of Lp6.6 is connected to the physiological processes of these membrane complexes. Further characterization of differentially produced membrane antigens and associated protein complexes will likely aid in our understanding of the molecular details of B. burgdorferi persistence and transmission through a complex enzootic cycle

Pyridoacridines in the 21st Century

This minireview summarizes the work developed during this Century with compounds containing the pyridoacridine scaffold in its different isomeric forms. The isolation of natural products, syntheses, bioactivities, chelation capacity, and other properties of compounds containing this framework are discussed. For reasons of length, only compounds containing a maximum of seven condensed rings have been considered, with a few exceptions

The primary headaches: genetics, epigenetics and a behavioural genetic model

The primary headaches, migraine with (MA) and without aura (MO) and cluster headache, all carry a substantial genetic liability. Familial hemiplegic migraine (FHM), an autosomal dominant mendelian disorder classified as a subtype of MA, is due to mutations in genes encoding neural channel subunits. MA/MO are considered multifactorial genetic disorders, and FHM has been proposed as a model for migraine aetiology. However, a review of the genetic studies suggests that the FHM genes are not involved in the typical migraines and that FHM should be considered as a syndromic migraine rather than a subtype of MA. Adopting the concept of syndromic migraine could be useful in understanding migraine pathogenesis. We hypothesise that epigenetic mechanisms play an important role in headache pathogenesis. A behavioural model is proposed, whereby the primary headaches are construed as behaviours, not symptoms, evolutionarily conserved for their adaptive value and engendered out of a genetic repertoire by a network of pattern generators present in the brain and signalling homeostatic imbalance. This behavioural model could be incorporated into migraine genetic research

Preoperative Fasting Guidelines in Children: Should They Be Revised?

Children presenting with ingestion of foreign bodies need gastroscopy as a primary management modality. A controversy lies regarding guidelines for preoperative fasting among children with low risk of aspiration and intraoperative complications. This case report represents cases of children who ingested foreign bodies and underwent fasting at different times preoperatively. With mounting evidence questioning the benefits of long durations of fasting in decreasing the risk of aspiration and with studies showing that fasting for more than 2 hours after ingestion of clear fluid does not significantly alter gastric pH or volume, these incidental findings raise the question of whether it is safe to keep children NPO, for a shorter duration before the administration of anesthesia. In addition, this report shows that current guidelines are in need of revision

Synthèse et études physico-chimiques de complexes métalliques en série bismacrocyclique (application à la catalyse d oxydation de l eau en dioxygène)

Le but de ce travail était de synthétiser et étudier de nouveaux complexes de manganèse capables d oxyder l eau en dioxygène, en s inspirant du système naturel photosynthétique. Les systèmes que nous avons choisis incorporent soit deux porphyrines, soit une porphyrine et un corrole, soit deux corroles. Dans le premier chapitre, nous décrivons la synthèse de nouveaux bismacrocycles de manganèse. Les deux macrocycles sont liés à des espaceurs rigides de taille bien définie permettant d ajuster l angle d ouverture du système et la distance intermétallique et de maintenir les deux macrocycles considérés dans une géométrie donnée. Une méthode simple et efficace a été élaborée pour la synthèse d une série de biscorroles meso-substitués au départ de l espaceur diformylé et d un dipyrrométhane. Les porphyrinecorroles de manganèse ont été étudiées par électrochimie et il a été montré que ces complexes stabilisent comme attendu l espèce Mn(III) dans la porphyrine et dans le corrole. Dans la seconde partie de la thèse, nous nous sommes intéressés à la synthèse de récepteurs bisporphyriniques plus flexibles pour lesquels l espaceur liant les deux unités tétrapyrroliques est un ligand susceptible de complexer un métal de transition permettant ainsi aux deux macrocycles porphyriniques de se positionner face-à-face. Trois schémas de synthèse de la pince moléculaire ont été envisagés, mais un seul s est révélé être efficace. Il consiste en la condensation d une porphyrine porteuse d un motif pyridyle en position meso sur une diamine aliphatique. Deux complexes trismétalliques de nickel et de cuivre ont été synthétisés par métallation de la pince base libre.Our researches were inspired by the photosynthetic system and focused on the synthesis and characterization of a series of manganese bisporphyrin, biscorrole and porphyrincorrole dyads for an application as catalysts for water oxidation to dioxygen. In the first chapter, we described the synthesis of new manganese bismacrocycles where the two tetrapyrrolic ligands are covalently linked by a rigid spacer in a face-to-face orientation. A simple and efficient method was developed for the synthesis of a series of mesosubstituted biscorroles obtained from the dialdehyde linker and dipyrromethane. Electrochemical and spectroelectrochemical studies of di-manganese porphyrin-corroles have been carried out. It has been shown that these complexes stabilize, as expected, the Mn(III) ion in both porphyrin and corrole units. In the second chapter of this thesis, we were interested in the synthesis of a new flexible bisporphyrin receptor where the spacer is able to bind a third transition metal allowing the two macrocycles to be in a face-to-face arrangement. Three possible pathways for synthesis of our molecular tweezers were investigated, but only one has proven to be effective. It consists on the condensation of a meso-pyridyl porphyrin on an aliphatic diamine. Tris-nickel and tris-cupper complexes of the bispyridyl bisporphyrin system have been synthesized by metallation of the free base molecular tweezers. Compounds were characterized by MALDI-TOF and Electrospray Mass Spectroscopy.DIJON-BU Sciences Economie (212312102) / SudocSudocFranceF

Polydentate Analogues of 8-Hydroxyquinoline and Their Complexes with Ruthenium

Selective reduction of 2-nitro-3-methoxybenzaldehyde provides 2-amino-3-methoxybenzaldehyde that undergoes the Friedländer condensation with a variety of acetyl-substituted derivatives of pyridine and 1,10-phenanthroline. After cleavage of the methyl ether, the resulting polydentate analogues of 8-hydroxyquinoline are excellent ligands for ruthenium. The resulting oxidation state of the metal center depends on the anionic character of the ligands. The presence of two electron donating anionic ligands results in a Ru(III) complex as evidenced by paramagnetic NMR behavior. The electronic absorption and redox properties of the complexes were measured and found to be consistent with the anionic character of the 8-HQ moieties. A planar pentadentate ligand provides two Ru–O and two Ru–N bonds in the equatorial plane. An X-ray structure shows that the central pyridine of the ligand is oriented toward the metal but held at a distance of 2.44 Å

Mitochondrial Fission and Fusion: Molecular Mechanisms, Biological Functions, and Related Disorders

Mitochondria are dynamic organelles that undergo fusion and fission. These active processes occur continuously and simultaneously and are mediated by nuclear-DNA-encoded proteins that act on mitochondrial membranes. The balance between fusion and fission determines the mitochondrial morphology and adapts it to the metabolic needs of the cells. Therefore, these two processes are crucial to optimize mitochondrial function and its bioenergetics abilities. Defects in mitochondrial proteins involved in fission and fusion due to pathogenic variants in the genes encoding them result in disruption of the equilibrium between fission and fusion, leading to a group of mitochondrial diseases termed disorders of mitochondrial dynamics. In this review, the molecular mechanisms and biological functions of mitochondrial fusion and fission are first discussed. Then, mitochondrial disorders caused by defects in fission and fusion are summarized, including disorders related to MFN2, MSTO1, OPA1, YME1L1, FBXL4, DNM1L, and MFF genes

Efficient two-step synthesis of face-to-face meso-substituted bis(corrole) dyads

International audienc

Polydentate Analogues of 8-Hydroxyquinoline and Their Complexes with Ruthenium

Selective reduction of 2-nitro-3-methoxybenzaldehyde provides 2-amino-3-methoxybenzaldehyde that undergoes the Friedländer condensation with a variety of acetyl-substituted derivatives of pyridine and 1,10-phenanthroline. After cleavage of the methyl ether, the resulting polydentate analogues of 8-hydroxyquinoline are excellent ligands for ruthenium. The resulting oxidation state of the metal center depends on the anionic character of the ligands. The presence of two electron donating anionic ligands results in a Ru(III) complex as evidenced by paramagnetic NMR behavior. The electronic absorption and redox properties of the complexes were measured and found to be consistent with the anionic character of the 8-HQ moieties. A planar pentadentate ligand provides two Ru–O and two Ru–N bonds in the equatorial plane. An X-ray structure shows that the central pyridine of the ligand is oriented toward the metal but held at a distance of 2.44 Å