MCR: modern colistin resistance

Recently, plasmid-mediated and, therefore, transferable bacterial polymyxin resistance was discovered in strains from both humans and animals. Such a trait may widely spread geographically, while simultaneously crossing microbial species barriers. This may ultimately render the “last resort” polymyxin antibiotics therapeutically useless. Colistin is currently used to treat infections caused by Gram-negative carbapenemase producers and colistin resistance may lead to practical pan-antibiotic resistance. We here analyzed the medical and diagnostic consequences of (emerging) colistin resistance and propose pathways toward adequate diagnostics for timely detection of both asymptomatic carriage and infection. Culture-based testing using chromogenic and selective media for screening clinical (and veterinary) specimens may constitute key tools for that purpose. Relevant molecular tests are also discussed

Characteristics of Centrifugal Pumps Working in Direct or Reverse Mode: Focus on the Unsteady Radial Thrust

Experimental and numerical investigations have been carried out to study the behaviour of a centrifugal pump operating in direct mode or turbine mode. First of all, the complete characteristics (head, power, and efficiency) were measured experimentally using a specific test loop. The numerical data obtained from a CFD study performed with the ANSYS CFX software and based on steady state and unsteady approaches were compared to the experimental results. The representation in the 4 operating quadrants shows the various operating zones where the head is always positive. Then, the unsteady radial forces were analysed from transient computations. The results obtained for the pump operation are consistent with the literature and extended to the nonnormal operating conditions, namely, for very high flowrate values. The evolution of the radial load during turbine operation is presented for various partial flow operating points

Aberrant repair initiated by mismatch-specific thymine-DNA glycosylases provides a mechanism for the mutational bias observed in CpG islands

The human thymine-DNA glycosylase (TDG) initiates the base excision repair (BER) pathway to remove spontaneous and induced DNA base damage. It was first biochemically characterized for its ability to remove T mispaired with G in CpG context. TDG is involved in the epigenetic regulation of gene expressions by protecting CpG-rich promoters from de novo DNA methylation. Here we demonstrate that TDG initiates aberrant repair by excising T when it is paired with a damaged adenine residue in DNA duplex. TDG targets the non-damaged DNA strand and efficiently excises T opposite of hypoxanthine (Hx), 1,N6-ethenoadenine, 7,8-dihydro-8-oxoadenine and abasic site in TpG/CpX context, where X is a modified residue. In vitro reconstitution of BER with duplex DNA containing Hx•T pair and TDG results in incorporation of cytosine across Hx. Furthermore, analysis of the mutation spectra inferred from single nucleotide polymorphisms in human population revealed a highly biased mutation pattern within CpG islands (CGIs), with enhanced mutation rate at CpA and TpG sites. These findings demonstrate that under experimental conditions used TDG catalyzes sequence context-dependent aberrant removal of thymine, which results in TpG, CpA→CpGmutations, thus providing a plausible mechanism for the putative evolutionary origin of the CGIs in mammalian genomes

IS LEAF LITTER REMOVAL MORE EFFICIENT THAN LEAF LITTER SHREDDING TO CONTROL APPLE SCAB? A FIRST ANSWER IN A COMMERCIAL ORGANIC ORCHARD

In organic apple orchards, sanitation practices are a keystone of a sustainable scab management. Because the suppression of the inoculum by leaf litter removal could be a promising practice, we carried out an experiment to assess the interest of leaf removal versus leaf shredding on disease development and fruit damages. For one of the two cultivars studied, we showed that leaf litter removal can significantly decrease scab damages on fruit and leaf in comparison to leaf shredding

Controlling the Precision of Approximate Fast Nearest-Neighbor Searches

Disponible dans les fichiers attachés à ce documen

Hammerhead flatworms (Platyhelminthes, Geoplanidae, Bipaliinae): mitochondrial genomes and description of two new species from France, Italy, and Mayotte

Background: New records of alien land planarians are regularly reported worldwide, and some correspond to undescribed species of unknown geographic origin. The description of new species of land planarians (Geoplanidae) should classically be based on both external morphology and histology of anatomical structures, especially the copulatory organs, ideally with the addition of molecular data. Methods: Here, we describe the morphology and reproductive anatomy of a species previously reported as Diversibipalium “black”, and the morphology of a species previously reported as Diversibipalium “blue”. Based on next generation sequencing, we obtained the complete mitogenome of five species of Bipaliinae, including these two species. Results: The new species Humbertium covidum n. sp. (syn: Diversibipalium “black” of Justine et al., 2018) is formally described on the basis of morphology, histology and mitogenome, and is assigned to Humbertium on the basis of its reproductive anatomy. The type-locality is Casier, Italy, and other localities are in the Department of Pyrénées-Atlantiques, France; some published or unpublished records suggest that this species might also be present in Russia, China, and Japan. The mitogenomic polymorphism of two geographically distinct specimens (Italy vs France) is described; the cox1 gene displayed 2.25% difference. The new species Diversibipalium mayottensis n. sp. (syn: Diversibipalium “blue” of Justine et al., 2018) is formally described on the basis of external morphology and complete mitogenome and is assigned to Diversibipalium on the basis of an absence of information on its reproductive anatomy. The type- and only known locality is the island of Mayotte in the Mozambique Channel off Africa. Phylogenies of bipaliine geoplanids were constructed on the basis of SSU, LSU, mitochondrial proteins and concatenated sequences of cox1, SSU and LSU. In all four phylogenies, D. mayottensis was the sister-group to all the other bipaliines. With the exception of D. multilineatum which could not be circularised, the complete mitogenomes of B. kewense, B. vagum, B. adventitium, H. covidum and D. mayottensis were colinear. The 16S gene in all bipaliine species was problematic because usual tools were unable to locate its exact position. Conclusion: Next generation sequencing, which can provide complete mitochondrial genomes as well as traditionally used genes such as SSU, LSU and cox1, is a powerful tool for delineating and describing species of Bipaliinae when the reproductive structure cannot be studied, which is sometimes the case of asexually reproducing invasive species. The unexpected position of the new species D. mayottensis as sister-group to all other Bipaliinae in all phylogenetic analyses suggests that the species could belong to a new genus, yet to be described

Multiple colonization with highly resistant bacteria: carbapenemase-producing Enterobacteriaceae, carbapenemase-producing Pseudomonas aeruginosa, carbapenemase-producing Acinetobacter baumannii, and glycopeptide-resistant Enterococcus faecium

The dissemination of carbapenemase-producing bacteria worldwide is an important source of concern because carbapenemase producers are multidrug resistant (Nordmann and Poirel, 2014). National guidelines increasingly recommend a systematic screening of at least carbapenemase-producing Enterobacteriaceae (CPE) and glycopeptide-resistant enterococci (GRE) in patients admitted to hospitals who have been hospitalized aboard during the preceding 12 months (Lepelletier et al., 2011). We have investigated the occurrence of colonization and infection with multiple highly resistant bacteria of more than 4 different genus in 2 patients directly transferred from a foreign country.In June 2014, a 33-year-old French man (patient A) was admitted for a suicide attempt in a Vietnamese hospital where he was treated during 10 days for pneumonia with piperacillin + tazobactam before his transfer to Necker-Enfants Malades University Hospital in Paris, France. At the day of his hospitalization in France, distal protected pulmonary samples were collected, and imipenem was administered subsequently to a persistent fever. In addition, systematic screening to detect carbapenemase producers and GRE was also performed. Screening of extended spectrum β-lactamase (ESBL) producing Enterobacteriaceae, carbapenemase producers, and GRE was done on selective media (bioMérieux, La Balme-les-Grottes, France) ChromID ESBL, ChromID Carba Smart, and VRE medium, respectively. Carbapenemase production was identified using the Carba NP test for Enterobacteriaceae (Dortet et al., 2014a) and Pseudomonas aeruginosa ( Dortet et al., 2012) and CarbAcineto NP test for Acinetobacter baumannii ( Dortet et al., 2014b). Definitive identifications of resistance determinant were done by PCR amplifications followed by sequencing. Pulmonary samples grew an OXA-23–producing A. baumannii isolate and an IMP-1–producing P. aeruginosa ( Table 1). Screening identified also that the patient was colonized with a KPC-2–producing Klebsiella pneumoniae, a CTX-M-15–producing K. pneumoniae, and a VanA-positive glycopeptide-resistant Enterococcus faecium ( Table 1)

The INTEGRAL/IBIS Scientific Data Analysis

The gamma-ray astronomical observatory INTEGRAL, succesfully launched on 17th October 2002, carries two large gamma-ray telescopes. One of them is the coded-mask imaging gamma-ray telescope onboard the INTEGRAL satellite (IBIS) which provides high-resolution (~ 12') sky images of 29deg x 29deg in the energy range from 15 keV to 10 MeV with typical on-axis sensitivity of ~ 1 mCrab at 100 keV (3 sigma, 10E6 s exposure). We report here the general description of the IBIS coded-mask imaging system and of the standard IBIS science data analysis procedures. These procedures reconstruct, clean and combine IBIS sky images providing at the same time detection, identification and preliminary analysis of point-like sources present in the field. Spectral extraction has also been implemented and is based on simultaneous fitting of source and background shadowgram models to detector images. The procedures are illustrated using some of the IBIS data collected during the inflight calibrations and present performance is discussed. The analysis programs described here have been integrated as instrument specific software in the Integral Science Data Center (ISDC) analysis software packages currently used for the Quick Look, Standard and Off-line Scientific Analysis.Comment: 7 pages, 13 figures (6 color), accepted for publication in A&A Lett (INTEGRAL special issue). Full resulution color figures can be found in the printed version of the paper (see http://www.edpsciences.org/articles/aa/abs/2003/43/contents/contents.html

New insights on the mechanism of quinoline-based DNA methyltransferase inhibitors

Among the epigenetic marks, DNA methylation is one of the most studied. It is highly deregulated in numerous diseases, including cancer. Indeed, it has been shown that hypermethylation of tumor suppressor genes promoters is a common feature of cancer cells. Because DNA methylation is reversible, the DNA methyltransferases (DNMTs), responsible for this epigenetic mark, are considered promising therapeutic targets. Several molecules have been identified as DNMT inhibitors and, among the non-nucleoside inhibitors, 4-aminoquinoline-based inhibitors, such as SGI-1027 and its analogs, showed potent inhibitory activity. Here we characterized the in vitro mechanism of action of SGI-1027 and two analogs. Enzymatic competition studies with the DNA substrate and the methyl donor cofactor, S-adenosyl-L-methionine (AdoMet), displayed AdoMet non-competitive and DNA competitive behavior. In addition, deviations from the Michaelis-Menten model in DNA competition experiments suggested an interaction with DNA. Thus their ability to interact with DNA was established; although SGI-1027 was a weak DNA ligand, analog 5, the most potent inhibitor, strongly interacted with DNA. Finally, as 5 interacted with DNMT only when the DNA duplex was present, we hypothesize that this class of chemical compounds inhibit DNMTs by interacting with the DNA substrate

Numerical Flow Analysis of the GAMM Turbine at nominal and off-design Operating Conditions

The flow in a Francis turbine runner (GAMM Turbine) is analysed numerically. Different operating points are calculated using two industrial software packages based respectively on a finite element method (N3S) and a finite volume method (TASCflow®) and compared to experimental results. The numerical results allow to observe physical phenomena in the runner that are important in the process of hydraulic turbomachinery design. Values of Cu and Cm velocity components, blade pressure distribution and recirculation in the flow are compared to experimental results at nominal and off-design flow conditions. The experimental and numerical results show a similar efficiency evolution in function of flow rate and head, however the absolute level of energetic losses are overestimated by the two numerical codes