Salmonella genomic island 1 (SGI1) reshapes the mating apparatus of IncC conjugative plasmids to promote self-propagation.

IncC conjugative plasmids and Salmonella genomic island 1 (SGI1) and relatives are frequently associated with multidrug resistance of clinical isolates of pathogenic Enterobacteriaceae. SGI1 is specifically mobilized in trans by IncA and IncC plasmids (commonly referred to as A/C plasmids) following its excision from the chromosome, an event triggered by the transcriptional activator complex AcaCD encoded by these helper plasmids. Although SGI1 is not self-transmissible, it carries three genes, traNS, traHS and traGS, coding for distant homologs of the predicted mating pore subunits TraNC, TraHC and TraGC, respectively, encoded by A/C plasmids. Here we investigated the regulation of traNS and traHGS and the role of these three genes in the transmissibility of SGI1. Transcriptional fusion of the promoter sequences of traNS and traHGS to the reporter gene lacZ confirmed that expression of these genes is inducible by AcaCD. Mating experiments using combinations of deletion mutants of SGI1 and the helper IncC plasmid pVCR94 revealed complex interactions between these two mobile genetic elements. Whereas traNC and traHGC are essential for IncC plasmid transfer, SGI1 could rescue null mutants of each individual gene revealing that TraNS, TraHS and TraGS are functional proteins. Complementation assays of individual traC and traS mutants showed that not only do TraNS/HS/GS replace TraNC/HC/GC in the mating pore encoded by IncC plasmids but also that traGS and traHS are both required for SGI1 optimal transfer. In fact, remodeling of the IncC-encoded mating pore by SGI1 was found to be essential to enhance transfer rate of SGI1 over the helper plasmid. Furthermore, traGS was found to be crucial to allow DNA transfer between cells bearing IncC helper plasmids, thereby suggesting that by remodeling the mating pore SGI1 disables an IncC-encoded entry exclusion mechanism. Hence traS genes facilitate the invasion by SGI1 of cell populations bearing IncC plasmids

Independent control of polar and azimuthal anchoring

Monte Carlo simulation, experiment and continuum theory are used to examine the anchoring exhibited by a nematic liquid crystal at a patterned substrate comprising a periodic array of rectangles that, respectively, promote vertical and planar alignment. It is shown that the easy axis and effective anchoring energy promoted by such surfaces can be readily controlled by adjusting the design of the pattern. The calculations reveal rich behavior: for strong anchoring, as exhibited by the simulated system, for rectangle ratios $\geq 2$ the nematic aligns in the direction of the long edge of the rectangles, the azimuthal anchoring coefficient changing with pattern shape. In weak anchoring scenarios, however, including our experimental systems, preferential anchoring is degenerate between the two rectangle diagonals. Bistability between diagonally-aligned and edge-aligned arrangement is predicted for intermediate combinations of anchoring coefficient and system length-scale.Comment: 12 pages, 12 figure

Ordering of oblate hard particles between symmetric penetrable walls

We find the structure of a model discotic liquid crystal (DLC) confined between symmetric walls of controllable penetrability. The model consists of oblate hard Gaussian overlap (HGO) particles. Particle-substrate interactions are modelled as follows: each substrate sees a particle as a disc of zero thickness and diameter (Formula presented.) less than or equal to that of the actual particle, (Formula presented.), embedded inside the particle and located halfway along, and perpendicular to, its minor axis. This allows us to control the anchoring properties of the substrates, from planar (edge-on) for (Formula presented.) to homeotropic (face-on) for (Formula presented.). This system is investigated using both Monte Carlo simulation and density-functional theory, the latter implemented at the level of Onsager’s second-virial approximation with Parsons-Lee rescaling. We find that the agreement between theory and simulation is substantially less good than for prolate HGOs; in particular, the crossover from edge-on to face-on alignment is predicted by theory to occur at (Formula presented.), but simulation finds it for (Formula presented.). These discrepancies are likely a consequence of the fact that Onsager’s theory is less accurate for discs than for rods. We quantify this by computing the bulk isotropic-nematic phase diagram of oblate HGOs

Heteroglossia n°16. Langues et cultures dans l'internationalisation de l'enseignement supérieur au XXIe siècle. Volume 2. Analyser les politiques linguistiques: études de cas sur le plurilinguisme et l'anglais.

Secondo volume degli atti selezionati del convegno internazionale "Le plurilinguisme, le pluriculturalisme et l'angalis dans la mondialisation: dispositifs, pratiques et problématiques de l'internationalisation dans l'enseignement supérieur européen" organizzato all'Università di Angers (Francia). M. ANquetil è stata membro del comitato internazionale scientifico e organizzativo, e co-editrice della selezione di atti del convegno per il primo volume edito presso Peter Lang (Berne, Svizzera) e del secondo volume presso Heteroglossia

Neural-network approach to modeling liquid crystals in complex confinement

Finding the structure of a confined liquid crystal is a difficult task since both the density and order parameter profiles are non-uniform. Starting from a microscopic model and density-functional theory, one has to either (i) solve a non-linear, integral Euler-Lagrange equation, or (ii) perform a direct multi-dimensional free energy minimisation. The traditional implementations of both approaches are computationally expensive and plagued with convergence problems. Here, as an alternative, we introduce an unsupervised variant of the Multi-Layer Perceptron (MLP) artificial neural network for minimising the free energy of a fluid of hard non-spherical particles confined between planar substrates of variable penetrability. We then test our algorithm by comparing its results for the structure (density-orientation profiles) and equilibrium free energy with those obtained by standard iterative solution of the Euler-Lagrange equations and with Monte Carlo simulation results. Very good agreement is found and the MLP method proves competitively fast, flexible and refinable. Furthermore, it can be readily generalised to the richer experimental patterned-substrate geometries that are now experimentally realisable but very problematic to conventional theoretical treatments

New insights into the structure and chemistry of Titan's tholins via C-13 and N-15 solid state nuclear magnetic resonance spectroscopy

Tholins are complex C,N-containing organic compounds produced in the laboratory. They are considered to provide materials that are analogous to those responsible for the haze observed in Titan’s atmosphere. These compounds present an astrobiological interest due to their ability to release amino acids upon hydrolysis. Their chemical structure has been investigated using a large number of techniques. However, to date no detailed nuclear magnetic resonance (NMR) study has been performed on these materials despite the high potential of this technique for investigating the environment of given nuclei. Here 13C and 15N solid state NMR spectroscopy was applied to obtain new insights into the chemical structure of tholins produced through plasma discharge in gaseous N2single bondCH4 mixtures designed to simulate the atmosphere of Titan. Due to the low natural abundance of these isotopes, a 13C and 15N-enriched tholin sample was synthesized using isotopically enriched gas precursors. Various pulse sequences including 13C and 15N single pulse, 1Hsingle bond13C and 1Hsingle bond15N cross-polarisation and 1Hsingle bond15Nsingle bond13C double cross-polarisation were used. These techniques allowed complete characterisation of the chemical and structural environments of the carbon and nitrogen atoms. The NMR assignments were supplemented and confirmed by ab initio electronic structure calculations for model structures and molecular fragments

Nematic liquid crystal alignment on chemical patterns

Patterned Self-Assembled Monolayers (SAMs) promoting both homeotropic and planar degenerate alignment of 6CB and 9CB in their nematic phase, were created using microcontact printing of functionalised organothiols on gold films. The effects of a range of different pattern geometries and sizes were investigated, including stripes, circles and checkerboards. EvanescentWave Ellipsometry was used to study the orientation of the liquid crystal (LC) on these patterned surfaces during the isotropic-nematic phase transition. Pretransitional growth of a homeotropic layer was observed on 1 ¹m homeotropic aligning stripes, followed by a homeotropic mono-domain state prior to the bulk phase transition. Accompanying Monte-Carlo simulations of LCs aligned on nano-patterned surfaces were also performed. These simulations also showed the presence of the homeotropic mono-domain state prior to the transition.</p

Impact of PI3K (Phosphoinositide 3-Kinase Alpha) Inhibition on Hemostasis and Thrombosis

Objective— PI3Kα (phosphoinositide 3-kinase alpha) is a therapeutic target in oncology, but its role in platelets and thrombosis remains ill characterized. In this study, we have analyzed the role of PI3Kα in vitro, ex vivo, and in vivo in 2 models of arterial thrombosis. Approach and Results— Using mice selectively deficient in p110α in the megakaryocyte lineage and isoform-selective inhibitors, we confirm that PI3Kα is not mandatory but participates to thrombus growth over a collagen matrix at arterial shear rate. Our data uncover a role for PI3Kα in low-level activation of the GP (glycoprotein) VI-collagen receptor by contributing to ADP secretion and in turn full activation of PI3Kβ and Akt/PKB (protein kinase B). This effect was no longer observed at high level of GP VI agonist concentration. Our study also reveals that over a vWF (von Willebrand factor) matrix, PI3Kα regulates platelet stationary adhesion contacts under arterial flow through its involvement in the outside-in signaling of vWF-engaged αIIbβ3 integrin. In vivo, absence or inhibition of PI3Kα resulted in a modest but significant decrease in thrombus size after superficial injuries of mouse mesenteric arteries and an increased time to arterial occlusion after carotid lesion, without modification in the tail bleeding time. Considering the more discrete and nonredundant role of PI3Kα compared with PI3Kβ, selective PI3Kα inhibitors are unlikely to increase the bleeding risk at least in the absence of combination with antiplatelet drugs or thrombopenia. Conclusions— This study provides mechanistic insight into the role of PI3Kα in platelet activation and arterial thrombosis

Development of global temperature and pH calibrations based on bacterial 3-hydroxy fatty acids in soils

Gram-negative bacteria produce specific membrane lipids, i.e. 3-hydroxy fatty acids with 10 to 18 C atoms. They have been recently proposed as temperature and pH proxies in terrestrial settings. Nevertheless, the existing correlations between pH or temperature and indices derived from 3-OH FA distribution are based on a small soil dataset (ca. 70 samples) and only applicable regionally. The aim of this study was to investigate the applicability of 3-OH FAs as mean annual air temperature (MAAT) and pH proxies at the global level. This was achieved using an extended soil dataset of 168 topsoils distributed worldwide, covering a wide range of temperatures (5 to 30 ∘C) and pH (3 to 8). The response of 3-OH FAs to temperature and pH was compared to that of established branched glycerol dialkyl glycerol tetraether (GDGT)-based proxies (MBT'5Me/CBT). Strong linear relationships between 3-OH-FA-derived indices (RAN15, RAN17 and RIAN) and MAAT or pH could only be obtained locally for some of the individual transects. This suggests that these indices cannot be used as palaeoproxies at the global scale using simple linear regression models, in contrast with the MBT'5Me and CBT. However, strong global correlations between 3-OH FA relative abundances and MAAT or pH were shown by using other algorithms (multiple linear regression, k-NN and random forest models). The applicability of the three aforementioned models for palaeotemperature reconstruction was tested and compared with the MAAT record from a Chinese speleothem. The calibration based on the random forest model appeared to be the most robust. It generally showed similar trends with previously available records and highlighted known climatic events poorly visible when using local 3-OH FA calibrations. Altogether, these results demonstrate the potential of 3-OH FAs as palaeoproxies in terrestrial settings