MAU-8 is a Phosducin-like Protein required for G protein signaling in C. elegans

AbstractThe mau-8(qm57) mutation inhibits the function of GPB-2, a heterotrimeric G protein β subunit, and profoundly affects behavior through the Gαq/Gαo signaling network in C. elegans. mau-8 encodes a nematode Phosducin-like Protein (PhLP), and the qm57 mutation leads to the loss of a predicted phosphorylation site in the C-terminal domain of PhLP that binds the Gβγ surface implicated in membrane interactions. In developing embryos, MAU-8/PhLP localizes to the cortical region, concentrates at the centrosomes of mitotic cells and remains associated with the germline blastomere. In adult animals, MAU-8/PhLP is ubiquitously expressed in somatic tissues and germline cells. MAU-8/PhLP interacts with the PAR-5/14.3.3 protein and with the Gβ subunit GPB-1. In mau-8 mutants, the disruption of MAU-8/PhLP stabilizes the association of GPB-1 with the microtubules of centrosomes. Our results indicate that MAU-8/PhLP modulates G protein signaling, stability and subcellular location to regulate various physiological functions, and they suggest that MAU-8 might not be limited to the Gαq/Gαo network

Long-Lasting Fever and Lymphadenitis: Think about F. tularensis

We report the case of glandular tularemia that developed in a man supposedly infected by a tick bite in Western Switzerland. Francisella tularensis (F. tularensis) was identified. In Europe tularemia most commonly manifests itself as ulcero-glandular or glandular disease; the diagnosis of tularemia may be delayed in glandular form where skin or mucous lesion is absent, particularly in areas which are assumed to have a low incidence of the disease

Transcriptomic Signature Differences Between SARS-CoV-2 and Influenza Virus Infected Patients.

The reason why most individuals with COVID-19 have relatively limited symptoms while other develop respiratory distress with life-threatening complications remains unknown. Increasing evidence suggests that COVID-19 associated adverse outcomes mainly rely on dysregulated immunity. Here, we compared transcriptomic profiles of blood cells from 103 patients with different severity levels of COVID-19 with that of 27 healthy and 22 influenza-infected individuals. Data provided a complete overview of SARS-CoV-2-induced immune signature, including a dramatic defect in IFN responses, a reduction of toxicity-related molecules in NK cells, an increased degranulation of neutrophils, a dysregulation of T cells, a dramatic increase in B cell function and immunoglobulin production, as well as an important over-expression of genes involved in metabolism and cell cycle in patients infected with SARS-CoV-2 compared to those infected with influenza viruses. These features also differed according to COVID-19 severity. Overall and specific gene expression patterns across groups can be visualized on an interactive website (https://bix.unil.ch/covid/). Collectively, these transcriptomic host responses to SARS-CoV-2 infection are discussed in the context of current studies, thereby improving our understanding of COVID-19 pathogenesis and shaping the severity level of COVID-19

A first update on mapping the human genetic architecture of COVID-19

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Infrarenal Infected Aortic Aneurysm Caused by Streptococcus pyogenes

Infectious aneurysm is a rare entity associated with significant morbidity and mortality. Current knowledge on pathogenesis, outcome, diagnosis, management, and follow-up remains debatable. We report the case of a patient with Streptococcus pyogenes aneurysm who was successfully treated with a homograft implant and discuss microbiological characteristics, diagnostic methods, and treatment options currently available for this serious disease

Structural characterization of N-acyl-homoserine lactones involved in bacterial quorum sensing using LC-MS/MS or SFC-MS/MS after in-solution Paternò-Büchi derivatization

International audienceThe quorum sensing is a chemical language allowing bacteria to interact through the excretion of molecules called auto-inducers. Those molecules regulate bacterial gene expression, including resistance or virulence ones.Our study focuses on the auto-inducing N-acyl-homoserine lactones (AHLs) of Gram-negative bacteria from the Burkholderia and Paraburkholderia genus. The AHLs dier in their acylchain length and may be modied by a 3-oxo or 3-hydroxy substituent, or various degrees of unsaturation (1). As the bacterial signal specicity depends on all of these features, including the unsaturation position, it is mandatory to determine their complete structuralcharacterization to better understand the population regulation and virulence phenomenon. Therefore, this study aimed to develop a method enabling the localization of the C=C double bond while using signicantly low amount of biological material. Our method is based on LC-MS/MS or/and SFC-MS/MS analyses of bacterial extracts after in-solution derivatization by a Paterno-Buchi reaction which is a photochemical (2+2) addition of a ketone on a C=C double bond leading to the formation of an oxetane ring (2).To optimize the in-solution derivatization of AHLs, the influence of various parameters (UV wavelength, solvent, Paterno-Buchi reagent, AHL/reagent ratio, reaction time) was studied with a design of experiments on 12.5 pmol of an AHL standard per LC-MS/MS analysis. The best results were obtained after a 15-minute derivatization at 254 nm, in acetonitrile, and with 2-acetylpyridine at AHL/reagent ratio of 1/100. MS/MS of Paterno-Buchi products enabled the localization of the C=C double bond due to the specic fragmentation of the oxetane ring. As a proof of concept, LC-MS/MS and SFC-MS/MS analyses were performed on bacterial extracts after in-solution derivatization.Finally, the implementation of the Paterno-Buchi reaction post-column is currently under investigation.(1) Churchill et al., Chem. Rev., 2011, 111 (1), 68-85(2) Xu et al., Anal. Chim. Acta, 2018, 1028, 32-4

Structural characterization of N-acyl-homoserine lactones implied in bacterial quorum sensing using LC-MS/MS or/and SFC-MS/MS after in-solution derivatization by a Paternò-Büchi reaction

International audienc