Synthesis, structure and pyrolysis of stabilised phosphonium ylides containing saturated oxygen heterocycles

yesA range of twelve stabilised phosphonium ylides containing tetrahydrofuran, tetrahydropyran or 2,2- dimethyl-1,3-dioxolane rings have been prepared and fully characterised, including one X-ray structure determination of each type. The X-ray structures confirm the PvC and CvO functions to be syn and all the compounds undergo thermal extrusion of Ph3PO to give the corresponding alkynes. In some cases there is also competing loss of Ph3P to give different carbene-derived products and evidence has been obtained for the generation of 2-phenyloxete in this way. Raising the pyrolysis temperature leads in several cases to new secondary reactions of the alkyne products involving a sequence of alkyne to vinylidene isomerisation, intramolecular CH insertion, and retro Diels Alder reaction

Antisense pre-treatment increases gene therapy efficacy in dystrophic muscles

International audienceIn preclinical models for Duchenne muscular dystrophy, dystrophin restoration during adeno-associated virus (AAV)-U7-mediated exon-skipping therapy was shown to decrease drastically after six months in treated muscles. This decline in efficacy is strongly correlated with the loss of the therapeutic AAV genomes, probably due to alterations of the dystrophic myofiber membranes. To improve the membrane integrity of the dystrophic myofibers at the time of AAV-U7 injection, mdx muscles were pre-treated with a single dose of the peptide-phosphorodiamidate morpholino (PPMO) antisense oligonucleotides that induced temporary dystrophin expression at the sarcolemma. The PPMO pre-treatment allowed efficient maintenance of AAV genomes in mdx muscles and enhanced the AAV-U7 therapy effect with a ten-fold increase of the protein level after 6 months. PPMO pre-treatment was also beneficial to AAV-mediated gene therapy with transfer of micro-dystrophin cDNA into muscles. Therefore, avoiding vector genome loss after AAV injection by PPMO pre-treatment would allow efficient long-term restoration of dystrophin and the use of lower and thus safer vector doses for Duchenne patients

Semi-groupe de Lie associé à un cône symétrique

Volcanic arcs are the surface expression of magmatic systems that result from the subduction of mostly oceanic lithosphere at convergent plate boundaries. Arcs with a submarine component include intraoceanic arcs and island arcs that span almost 22,000 km on Earth\u27s surface, the vast majority of which are located in the Pacific region. Hydrothermal systems hosted by submarine arc volcanoes commonly contain a large component of magmatic fluid. This magmatic-hydrothermal signature, coupled with the shallow water depths of arc volcanoes and their high volatile contents, strongly influences the chemistry of the fluids and resulting mineralization and likely has important consequences for the biota associated with these systems. The high metal contents and very acidic fluids in these hydrothermal systems are thought to be important analogs to numerous porphyry copper and epithermal gold deposits mined today on land

A new device for real-time peroperative monitoring of ossicular chain reconstruction during middle ear surgery

International audienceTo limit functional surgical failure and reduce the rate of revision surgery in case of surgical ossicular chain reconstruction, a piezoelectric device was developed for assessment of ossicular chain vibrations during the middle ear surgery. The device resembled a pen and consisted of a reusable main body and a disposable sensitive head including piezoelectric polymer sensor. Almost all of components of the device were made of polymer for light weight and for acoustic impedance matching to the middle ear system. Several frequencies can be analyzed simultaneously and several measures can be taken by time. The results showed that the device can record normal and reconstructed ossicular chain vibration in response to an acoustic stimulation, with similar results to those achieved by laser Doppler vibrometer. This light, handheld and low-cost device allows fast, easy and safe assessments of normal ossicular chain mobility and ossicular chain reconstruction efficiency. Primary pre-clinical trial showed very promising performance of the device that could be used to qualitatively control ossiculoplasty during real-time surgical procedure. Clinical assessments will be done to further evaluate the real-life performance of the device

RFX1 and RFX3 Transcription Factors Interact with the D Sequence of Adeno-Associated Virus Inverted Terminal Repeat and Regulate AAV Transduction

Abstract Adeno-associated virus (AAV) transduction efficiency depends on the way in which cellular proteins process viral genomes in the nucleus. In this study, we have investigated the binding of nuclear proteins to the double stranded D (dsD) sequence of the AAV inverted terminal repeat (ITRs) by electromobility shift assay. We present here several lines of evidence that transcription factors belonging to the RFX protein family bind specifically and selectively to AAV2 and AAV1 dsD sequences. Using supershift experiments, we characterize complexes containing RFX1 homodimers and RFX1/RFX3 heterodimers. Following transduction of HEK-293 cells, the AAV genome can be pulled-down by RFX1 and RFX3 antibodies. Moreover, our data suggest that RFX proteins which interact with transcriptional enhancers of several mammalian DNA viruses, can act as regulators of AAV mediated transgene expression

Flexible Over-Moded Resonators Based on P(VDF-TrFE) Thin Films With Very High Temperature Coefficient

International audienceThis work presents for the first time a flexible over-moded resonator (OMR) based on P(VDF-TrFE) thin films. The devices were manufactured on commercially available elastic substrate with inkjet-printed electrodes. The sensing copolymer films used in the devices were polarized by the corona method after electrode deposition. The main performance parameters of the component were then determined. The manufactured OMRs on P(VDF-TrFE) exhibited a linear variation of frequency versus temperature and a very large value of temperature coefficient of frequency (TCF > 1600 ppm/degrees C). These properties suggest a great potential for using such components as low-cost and high-precision temperature sensors. The electromechanical coupling coefficient and the quality factor of the resonator were also characterized versus temperature

Prenatal exposure to persistent organic pollutants and body mass index trajectories from birth to age 12

International audienceBACKGROUND AND AIM[|]Several studies have explored the association between prenatal exposure to persistent organic pollutants (POPs) and body mass index (BMI) at a given age but very few have evaluated the dynamic of growth across ages. Our objective was to study the associations between prenatal exposure to multiple POPs and growth BMI trajectories from birth to adolescence.[¤]METHOD[|]This study included 430 mother-child pairs enrolled in the PELAGIE cohort (France). Polychlorinated biphenyls (PCBs), organochlorine pesticides (OCs), and per- and polyfluorinated substances (PFASs) were measured in cord blood. Latent class growth model was used to identify BMI z-score (zBMI) trajectories. Multinomial regressions evaluated the associations between each POP and the resulting zBMI trajectories, as well as Quantile G-computation to evaluate POP mixture effects. All analyses were stratified by sex and adjusted for confounders.[¤]RESULTS[|]Four classes of zBMI trajectories were identified and the “average zBMI at birth and lower zBMI up to age 12” trajectory was considered as the reference. In single-exposure models, higher exposure to beta-hexachlorocyclohexane (b-HCH) was associated with a higher odds of following the “higher zBMI from birth to age 12” trajectory (OR=1.5 [1.1;2.1]). In girls, higher exposure to all PCBs was associated with higher odds of following the trajectory “lower zBMI at birth with accelerated zBMI gain in early childhood before stabilization up to age 12”; this association was also observed in the mixture analysis (OR=1.2 [1.0;1.5]). In boys, higher exposure to some PFASs was associated with higher odds of following the “higher zBMI from birth to adolescence” trajectory and lower odds of following the “lower zBMI from birth to adolescence” trajectory.[¤]CONCLUSIONS[|]Prenatal exposure to POPs may be associated with some specific growth dynamics, known as risk factors for adult cardiovascular health

Anaplasma phagocytophilum in urban and peri-urban passerine birds in Ile-de-France

International audienceWild animals in general, birds in particular, play a key role in transporting ticks and propagating tick-borne pathogens. Several studies have confirmed the infection of birds with Anaplasma phagocytophilum, with overall prevalence varying widely from country to country and/or study to study. This zoonotic bacterium, transmitted mainly by ticks of the genus Ixodes, is responsible for granulocytic anaplasmosis in humans (HGA) and domestic animals (cats, dogs, horses). The disease is also called tick-borne fever (TBF) in ruminants. Extremely rare in the USA, TBF is very common in Europe, where it causes economic losses in livestock. Conversely, HGA is well established in the USA whereas only a few less severe cases have been observed in Europe. Current typing techniques support the existence of multiple variants with differences in virulence/pathogenicity and tropism for certain tick and host species. However, epidemiological cycles remain difficult to characterize in Europe. Several studies describe a cycle apparently involving only birds in Europe, but no such study has been conducted in mainland France. Our objectives were to search for A. phagocytophilum in passerine birds in the Ile-de-France region and to explore their diversity using groEL and ankA gene typing and multilocus sequence typing (MLST). Various tissues (spleen, liver, and skin) were collected from cadavers of 680 passerines between March and December 2021. The presence of A. phagocytophilum was detected by qPCR Taqman targeting the msp2 gene. Three blackbirds (Turdus merula) were found positive, representing detection rates of 0.4 % in all birds tested and 3.3 % in blackbirds. The higher frequency of detection in blackbirds could be at least partially explained by their lifestyle, as they feed on the ground. Analysis of the results of groEL and ankA typing and MLST from positive blackbirds support the hypothesis that the avian A. phagocytophilum strains in Ile-de-France are distinct from those found in mammals, and that they form their own cluster in Europe