Ticagrelor alters the membrane of and enhances the activity of vancomycin and daptomycin without eliciting cross-resistance.

Infections with multidrug-resistant bacteria pose a major healthcare problem which urges the need for novel treatment options. Besides its potent antiplatelet properties, ticagrelor has antibacterial activity against Gram-positive bacteria, including methicillin- and vancomycin-resistant (MRSA and VRSA). Several retrospective studies in cardiovascular patients support an antibacterial effect of this drug which is not related to its antiplatelet activity.

The Spx stress regulator confers high-level β-lactam resistance and decreases susceptibility to last-line antibiotics in methicillin-resistant .

Infections caused by methicillin-resistant (MRSA) are a leading cause of mortality worldwide. MRSA has acquired resistance to next-generation β-lactam antibiotics through the horizontal acquisition of the resistance gene. Development of high resistance is, however, often associated with additional mutations in a set of chromosomal core genes, known as potentiators, which, through poorly described mechanisms, enhance resistance.

Fully iterative construction of a 24 kb-long artificial DNA sequence to store digital information.

In the absence of a DNA template, the production of long double-stranded DNA molecules of predefined sequences is particularly challenging. The DNA synthesis step remains a bottleneck for many applications such as functional assessment of ancestral genes, analysis of alternative splicing or DNA-based data storage. In this report we propose a fully protocol to generate very long double-stranded DNA molecules starting from commercially available short DNA blocks in less than 3 days using Golden Gate assembly.

Protective Effect of Ticagrelor Against Infective Endocarditis Induced by Virulent in Mice.

In addition to its potent antiplatelet activity, ticagrelor possesses antibacterial properties against gram-positive bacteria. We wondered whether the typical clinical dosage of ticagrelor could prevent the development of infective endocarditis caused by highly virulent . Ticagrelor prevented vegetation formation in a mouse model of inflammation-induced endocarditis.

Bioactive surface coating for preventing mechanical heart valve thrombosis.

Background: Prosthetic heart valves are the only treatment for most patients with severe valvular heart disease. Mechanical valves, made of metallic components, are the most long-lasting type of replacement valves. However, they are prone to thrombosis and require permanent anticoagulation and monitoring, which leads to higher risk of bleeding and impacts the patient's quality of life.

A Clinically Selected Staphylococcus aureus Mutant Survives Daptomycin Treatment by Reducing Binding of the Antibiotic and Adapting a Rod-Shaped Morphology.

Daptomycin is a last-resort antibiotic used for the treatment of infections caused by Gram-positive antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). Treatment failure is commonly linked to accumulation of point mutations; however, the contribution of single mutations to resistance and the mechanisms underlying resistance remain incompletely understood. Here, we show that a single nucleotide polymorphism (SNP) selected during daptomycin therapy inactivates the highly conserved ClpP protease and is causing reduced susceptibility of MRSA to daptomycin, vancomycin, and β-lactam antibiotics as well as decreased expression of virulence factors.

Quality of life after trigeminal nerve block in refractory trigeminal neuralgia: A retrospective cohort study and literature review.

Objective: To evaluate the effect of trigeminal nerve block (TNB) on patients' quality of life (QOL) 15 days after the procedure in patients with refractory TN.

Methods: This retrospective observational cohort study involved patients receiving TNB (levobupivacaine, clonidine, corticosteroid) between 2014 and 2018 at a postoperative pain clinic in France. Change in QOL from Day 0 (before block) to Day 15 was assessed according to SF-12.

The genomic basis of the Streptococcus thermophilus health-promoting properties.

Background: Streptococcus thermophilus is a Gram-positive bacterium widely used as starter in the dairy industry as well as in many traditional fermented products. In addition to its technological importance, it has also gained interest in recent years as beneficial bacterium due to human health-promoting functionalities. The objective of this study was to inventory the main health-promoting properties of S.

Finding and Characterizing Repeats in Plant Genomes.

Plant genomes contain a particularly high proportion of repeated structures of various types. This chapter proposes a guided tour of the available software that can help biologists to scan automatically for these repeats in sequence data or check hypothetical models intended to characterize their structures. Since transposable elements (TEs) are a major source of repeats in plants, many methods have been used or developed for this broad class of sequences.

Identification of isolated or mixed strains from long reads: a challenge met on using a MinION sequencer.

This study aimed to provide efficient recognition of bacterial strains on personal computers from MinION (Nanopore) long read data. Thanks to the fall in sequencing costs, the identification of bacteria can now proceed by whole genome sequencing. MinION is a fast, but highly error-prone sequencing device and it is a challenge to successfully identify the strain content of unknown simple or complex microbial samples.

Aspirin or Ticagrelor in Infective Endocarditis: Where Do We Stand?

Infective endocarditis is a challenging disease with a high mortality and morbidity rate. Antibiotic prophylaxis is currently recommended in high-risk infective endocarditis patients. However, the use of antibiotics faces the challenge of a low efficacy and contributes further to the emerging infection rate by antibiotic-resistant strains, emphasizing the need for new therapeutic strategies.

Sequencing DNA with nanopores: Troubles and biases.

Oxford Nanopore Technologies' (ONT) long read sequencers offer access to longer DNA fragments than previous sequencer generations, at the cost of a higher error rate. While many papers have studied read correction methods, few have addressed the detailed characterization of observed errors, a task complicated by frequent changes in chemistry and software in ONT technology. The MinION sequencer is now more stable and this paper proposes an up-to-date view of its error landscape, using the most mature flowcell and basecaller.

Synthesis of ticagrelor analogues belonging to 1,2,3-triazolo[4,5-d]pyrimidines and study of their antiplatelet and antibacterial activity.

Based on the recent observation that the antiplatelet agent ticagrelor and one of its metabolite exert bactericidal activity against gram-positive bacteria, a series of 1,2,3-triazolo[4,5-d]pyrimidines structurally related to ticagrelor were synthesized and examined as putative antiplatelet and antibacterial agents. The aim was to assess the possibility of dissociating the two biological properties and to find novel 1,2,3-triazolo[4,5-d]pyrimidines expressing antiplatelet activity and devoid of in vitro antibacterial activity. The new compounds synthesized were known metabolites of ticagrelor as well as structurally simplified analogues.

Inferring Biochemical Reactions and Metabolite Structures to Understand Metabolic Pathway Drift.

Inferring genome-scale metabolic networks in emerging model organisms is challenged by incomplete biochemical knowledge and partial conservation of biochemical pathways during evolution. Therefore, specific bioinformatic tools are necessary to infer biochemical reactions and metabolic structures that can be checked experimentally. Using an integrative approach combining genomic and metabolomic data in the red algal model Chondrus crispus, we show that, even metabolic pathways considered as conserved, like sterols or mycosporine-like amino acid synthesis pathways, undergo substantial turnover.

Peripheral Nerve Block Efficacy on Refractory Neuralgia Complicating Ramsay Hunt Syndrome: A Case Report.

Several case studies have suggested the usefulness of peripheral nerve blocks in the management of various types of chronic pain that are unresponsive to standard medical treatment. We report here the case of a patient with severe neuralgia, secondary to Ramsay Hunt syndrome that was refractory to standard drug therapy. As a last resort, a block of the terminal branches of nervus intermedius was performed.

Antibacterial Activity of Ticagrelor in Conventional Antiplatelet Dosages Against Antibiotic-Resistant Gram-Positive Bacteria.

This study uses in vitro assays and a mouse model to investigate antibacterial properties of ticagrelor to follow up findings from 2 clinical trials that showed patients taking ticagrelor for cardiovascular disease had a lower risk of infection-related death and improved lung function compared with patients treated with clopidogrel.

Formalizing and enriching phenotype signatures using Boolean networks.

In order to predict the behavior of a biological system, one common approach is to perform a simulation on a dynamic model. Boolean networks allow to analyze the qualitative aspects of the model by identifying its steady states and attractors. Each of them, when possible, is associated with a phenotype which conveys a biological interpretation.

De novo clustering of long reads by gene from transcriptomics data.

Long-read sequencing currently provides sequences of several thousand base pairs. It is therefore possible to obtain complete transcripts, offering an unprecedented vision of the cellular transcriptome. However the literature lacks tools for de novo clustering of such data, in particular for Oxford Nanopore Technologies reads, because of the inherent high error rate compared to short reads.

Prosthetic Aortic Valves: Challenges and Solutions.

Aortic Valve Disease (AVD) is the most common Valvular Heart Disease (VHD), affecting millions of people worldwide. Severe AVD is treated in most cases with prosthetic aortic valve replacement, which involves the substitution of the native aortic valve with a prosthetic one. In this review we will discuss the different types of prosthetic aortic valves available for implantation and the challenges faced by patients, medical doctors, researchers and manufacturers, as well as the approaches that are taken to overcome them.

Combining graph and flux-based structures to decipher phenotypic essential metabolites within metabolic networks.

Background: The emergence of functions in biological systems is a long-standing issue that can now be addressed at the cell level with the emergence of high throughput technologies for genome sequencing and phenotyping. The reconstruction of complete metabolic networks for various organisms is a key outcome of the analysis of these data, giving access to a global view of cell functioning. The analysis of metabolic networks may be carried out by simply considering the architecture of the reaction network or by taking into account the stoichiometry of reactions.

3D-front-face fluorescence spectroscopy and independent components analysis: A new way to monitor bread dough development.

Following bread dough development can be a hard task as no reliable method exists to give the optimal mixing time. Dough development is linked to the evolution of gluten proteins, carbohydrates and lipids which can result in modifications in the spectral properties of the various fluorophores naturally present in the system. In this paper, we propose to use 3-D-front-face-fluorescence (3D-FFF) spectroscopy in the 250-550nm domain to follow the dough development as influenced by formulation (addition or not of glucose, glucose oxidase and ferulic acid in the dough recipe) and mixing time (2, 4, 6 and 8min).

Elp3 drives Wnt-dependent tumor initiation and regeneration in the intestine.

Tumor initiation in the intestine can rapidly occur from Lgr5(+) crypt columnar stem cells. Dclk1 is a marker of differentiated Tuft cells and, when coexpressed with Lgr5, also marks intestinal cancer stem cells. Here, we show that Elp3, the catalytic subunit of the Elongator complex, is required for Wnt-driven intestinal tumor initiation and radiation-induced regeneration by maintaining a subpool of Lgr5(+)/Dclk1(+)/Sox9(+) cells.

Finding and Characterizing Repeats in Plant Genomes.

Plant genomes contain a particularly high proportion of repeated structures of various types. This chapter proposes a guided tour of available software that can help biologists to look for these repeats and check some hypothetical models intended to characterize their structures. Since transposable elements are a major source of repeats in plants, many methods have been used or developed for this large class of sequences.