High-Performance Liquid Chromatography Assay for Moxifloxacin in Brain Tissue and Plasma: Validation in a Pharmacokinetic Study in a Murine Model of Cerebral Listeriosis

Moxifloxacin is a broad-spectrum antibacterial 8-methoxy-fluoroquinolone. In order to evaluate the pharmacokinetic properties of moxifloxacin in mouse plasma and brain tissue, we developed a high-performance liquid chromatography (HPLC) method. This study was based on single-drug delivery, intravenously dosed in a central listeriosis murine model. The method employed a reversed-phase Lichrospher RP-18 with a precolumn (250 × 4.6 mm) and a mobile phase composed of a mixture of acetonitrile, methanol, and citric buffer (pH = 3.5) with sodium dodecyl sulfate and tetrabutylammonium bromide. Fluorescence detection was performed at an excitation wavelength of 290 nm and an emission wavelength of 550 nm. The relative standard deviation of intra- and inter-day assays was <10%. This validated method led to a short retention time (8.0 min) for moxifloxacin. The standard curves were linear from 5–250 μg/L in plasma and from 0.1–2.5 μg/g of brain tissue. The limits of quantification were 5 μg/L in plasma and 0.1 μg/g in brain tissue. The method enabled the detection of systemic antimicrobial in plasma and in CNS in Listeria-infected mice. Injected moxifloxacin passed through the encephalic barrier within a 30 to 60 min after injection time frame. Moxifloxacin pharmacokinetics are modeled in an infected model compared to control mice

Resolving the gap and AU-scale asymmetries in the pre-transitional disk of V1247 Orionis

Pre-transitional disks are protoplanetary disks with a gapped disk structure, potentially indicating the presence of young planets in these systems. In order to explore the structure of these objects and their gap-opening mechanism, we observed the pre-transitional disk V1247 Orionis using the Very Large Telescope Interferometer, the Keck Interferometer, Keck-II, Gemini South, and IRTF. This allows us spatially resolve the AU-scale disk structure from near- to mid-infrared wavelengths (1.5 to 13 {\mu}m), tracing material at different temperatures and over a wide range of stellocentric radii. Our observations reveal a narrow, optically-thick inner-disk component (located at 0.18 AU from the star) that is separated from the optically thick outer disk (radii >46 AU), providing unambiguous evidence for the existence of a gap in this pre-transitional disk. Surprisingly, we find that the gap region is filled with significant amounts of optically thin material with a carbon-dominated dust mineralogy. The presence of this optically thin gap material cannot be deduced solely from the spectral energy distribution, yet it is the dominant contributor at mid-infrared wavelengths. Furthermore, using Keck/NIRC2 aperture masking observations in the H, K', and L' band, we detect asymmetries in the brightness distribution on scales of about 15-40 AU, i.e. within the gap region. The detected asymmetries are highly significant, yet their amplitude and direction changes with wavelength, which is not consistent with a companion interpretation but indicates an inhomogeneous distribution of the gap material. We interpret this as strong evidence for the presence of complex density structures, possibly reflecting the dynamical interaction of the disk material with sub-stellar mass bodies that are responsible for the gap clearing.Comment: 16 pages, 17 Figures, accepted by Astrophysical Journa

Modification des traits racinaires le long d’une succession secondaire sur des talus routiers: implications dans la dynamique des communautés et la protection des sols contre l’érosion

Les traits fonctionnels des plantes varient au cours des successions secondaires végétales. Alors que certains traits ont été largement étudiés, les variations des traits racinaires au cours des successions restent relativement peu documentées. L’objectif de cette étude vise à mieux comprendre en quoi des variations de traits racinaires le long d’une succession secondaire contribuent à la dynamique de communautés végétales méditerranéennes. Pour cela, quinze communautés végétales, âgées de 0 à 69 ans, ont été repérées sur des talus en bordures de routes, dans le nord Montpelliérain. Sur cette chronoséquence, nous nous intéressons à des traits racinaires morphologiques et architecturaux des espèces dominantes, représentant 70% de l’abondance végétale. Nous faisons l’hypothèse que des traits morphologiques des racines fines (< 2 mm) permettent de mieux comprendre les modifications des stratégies d’acquisition et de conservation des ressources en nutriments et en eau. Des traits architecturaux, tels que la présence d’un pivot, de racines traçantes et/ou adventives, permettent d’étudier le rôle des racines dans l’ancrage et la capacité des espèces à coloniser le milieu en réponse aux contraintes topographiques liées à la pente des talus. Dans cette communication, nous présentons (i) la méthode retenue pour l’étude des traits racinaires morphologiques et architecturaux sur des espèces de formes de croissance diverses (herbacées, buissons, arbres) et (ii) discutons des limites et atouts de ces méthodes. Enfin, nous discutons de l’implication de ces traits racinaires dans la capacité des communautés à limiter l’érosion superficielle des talu

Confirmation of a gapped primordial disk around LkCa 15

Recently, analysis of near-infrared broad-band photometry and Spitzer IRS spectra has led to the identification of a new "pre-transitional disk" class whose members have an inner optically thick disk separated from an outer optically thick disk by an optically thin gap. This is in contrast to the "transitional disks" which have inner disk holes (i.e. large reductions of small dust from the star out to an outer optically thick wall). In LkCa 15, one of these proposed pre-transitional disks, detailed modeling showed that although the near-infrared fluxes could be understood in terms of optically thick material at the dust sublimation radius, an alternative model of emission from optically thin dust over a wide range of radii could explain the observations as well. To unveil the true nature of LkCa 15's inner disk we obtained a medium-resolution near-infrared spectrum spanning the wavelength range 2-5 microns using SpeX at the NASA Infrared Telescope Facility. We report that the excess near-infrared emission above the photosphere of LkCa 15 is a black-body continuum which can only be due to optically thick material in an inner disk around the star. When this confirmation of a primordial inner disk is combined with earlier observations of an inner edge to LkCa 15's outer disk it reveals a gapped structure. Forming planets emerge as the most likely mechanism for clearing the gap we detect in this evolving disk.Comment: accepted ApJ

Genetic Evidence for a Link Between Glycolysis and DNA Replication

BACKGROUND: A challenging goal in biology is to understand how the principal cellular functions are integrated so that cells achieve viability and optimal fitness in a wide range of nutritional conditions. METHODOLOGY/PRINCIPAL FINDINGS: We report here a tight link between glycolysis and DNA synthesis. The link, discovered during an analysis of suppressors of thermosensitive replication mutants in bacterium Bacillus subtilis, is very strong as some metabolic alterations fully restore viability to replication mutants in which a lethal arrest of DNA synthesis otherwise occurs at a high, restrictive, temperature. Full restoration of viability by such alterations was limited to cells with mutations in three elongation factors (the lagging strand DnaE polymerase, the primase and the helicase) out of a large set of thermosensitive mutants affected in most of the replication proteins. Restoration of viability resulted, at least in part, from maintenance of replication protein activity at high temperature. Physiological studies suggested that this restoration depended on the activity of the three-carbon part of the glycolysis/gluconeogenesis pathway and occurred in both glycolytic and gluconeogenic regimens. Restoration took place abruptly over a narrow range of expression of genes in the three-carbon part of glycolysis. However, the absolute value of this range varied greatly with the allele in question. Finally, restoration of cell viability did not appear to be the result of a decrease in growth rate or an induction of major stress responses. CONCLUSIONS/SIGNIFICANCE: Our findings provide the first evidence for a genetic system that connects DNA chain elongation to glycolysis. Its role may be to modulate some aspect of DNA synthesis in response to the energy provided by the environment and the underlying mechanism is discussed. It is proposed that related systems are ubiquitous

Five distinct biological processes and 14 differentially expressed genes characterize TEL/AML1-positive leukemia

<p>Abstract</p> <p>Background</p> <p>The t(12;21)(p13;q22) translocation is found in 20 to 25% of cases of childhood B-lineage acute lymphoblastic leukemia (B-ALL). This rearrangement results in the fusion of <it>ETV6 </it>(<it>TEL</it>) and <it>RUNX1 </it>(<it>AML1</it>) genes and defines a relatively uniform category, although only some patients suffer very late relapse. <it>TEL/AML1</it>-positive patients are thus an interesting subgroup to study, and such studies should elucidate the biological processes underlying TEL/AML1 pathogenesis. We report an analysis of gene expression in 60 children with B-lineage ALL using Agilent whole genome oligo-chips (44K-G4112A) and/or real time RT-PCR.</p> <p>Results</p> <p>We compared the leukemia cell gene expression profiles of 16 <it>TEL/AML1</it>-positive ALL patients to those of 44 <it>TEL/AML1</it>-negative patients, whose blast cells did not contain any additional recurrent translocation. Microarray analyses of 26 samples allowed the identification of genes differentially expressed between the TEL/AML1-positive and negative ALL groups. Gene enrichment analysis defined five enriched GO categories: cell differentiation, cell proliferation, apoptosis, cell motility and response to wounding, associated with 14 genes -<it>RUNX1, TCFL5, TNFRSF7, CBFA2T3</it>, <it>CD9</it>, <it>SCARB1, TP53INP1, ACVR1C, PIK3C3, EGFL7</it>, <it>SEMA6A, CTGF, LSP1, TFPI </it>– highlighting the biology of the <it>TEL/AML1 </it>sub-group. These results were first confirmed by the analysis of an additional microarray data-set (7 patient samples) and second by real-time RT-PCR quantification and clustering using an independent set (27 patient samples). Over-expression of <it>RUNX1 (AML1) </it>was further investigated and in one third of the patients correlated with cytogenetic findings.</p> <p>Conclusion</p> <p>Gene expression analyses of leukemia cells from 60 children with <it>TEL/AML1</it>-positive and -negative B-lineage ALL led to the identification of five biological processes, associated with 14 validated genes characterizing and highlighting the biology of the <it>TEL/AML1</it>-positive ALL sub-group.</p

A prospective, observational study of fidaxomicin use for Clostridioides difficile infection in France.

To describe the characteristics, management and outcomes of hospitalised patients with Clostridioides difficile infection (CDI) treated with and without fidaxomicin. This prospective, multicentre, observational study (DAFNE) enrolled hospitalised patients with CDI, including 294 patients treated with fidaxomicin (outcomes recorded over a 3-month period) and 150 patients treated with other CDI therapies during three 1-month periods. The primary endpoint was baseline and CDI characteristics of fidaxomicin-treated patients. At baseline, the fidaxomicin-treated population included immunocompromised patients (39.1%) and patients with severe (59.2%) and recurrent (36.4%) CDI. Fidaxomicin was associated with a high rate of clinical cure (92.2%) and low CDI recurrence (16.3% within 3 months). Clinical cure rates were ≥90% in patients aged ≥65 years, those receiving concomitant antibiotics and those with prior or severe CDI. There were 121/296 (40.9%) patients with adverse events (AEs), 5.4% with fidaxomicin-related AEs and 1.0% with serious fidaxomicin-related AEs. No fidaxomicin-related deaths were reported. Fidaxomicin is an effective and well-tolerated CDI treatment in a real-world setting in France, which included patients at high risk of adverse outcomes.Trial registration: Description of the use of fidaxomicin in hospitalised patients with documented Clostridium difficile infection and the management of these patients (DAFNE), NCT02214771, www.ClinicalTrials.gov

Planet Formation Imager (PFI): Science vision and key requirements

The Planet Formation Imager (PFI) project aims to provide a strong scientific vision for ground-based optical astronomy beyond the upcoming generation of Extremely Large Telescopes. We make the case that a breakthrough in angular resolution imaging capabilities is required in order to unravel the processes involved in planet formation. PFI will be optimised to provide a complete census of the protoplanet population at all stellocentric radii and over the age range from 0.1 to ∼100 Myr. Within this age period, planetary systems undergo dramatic changes and the final architecture of planetary systems is determined. Our goal is to study the planetary birth on the natural spatial scale where the material is assembled, which is the Hill Sphere of the forming planet, and to characterise the protoplanetary cores by measuring their masses and physical properties. Our science working group has investigated the observational characteristics of these young protoplanets as well as the migration mechanisms that might alter the system architecture. We simulated the imprints that the planets leave in the disk and study how PFI could revolutionise areas ranging from exoplanet to extragalactic science. In this contribution we outline the key science drivers of PFI and discuss the requirements that will guide the technology choices, the site selection, and potential science/technology tradeoffs

Experimental Assessment of the Water Quality Influence on the Phosphorus Uptake of an Invasive Aquatic Plant: Biological Responses throughout Its Phenological Stage

International audienceUnderstanding how an invasive plant can colonize a large range of environments is still a great challenge in freshwater ecology. For the first time, we assessed the relative importance of four factors on the phosphorus uptake and growth of an invasive macrophyte Elodea nuttallii (Planch.) St. John. This study provided data on its phenotypic plasticity, which is frequently suggested as an important mechanism but remains poorly investigated. The phosphorus uptake of two Elodea nuttallii subpopulations was experimentally studied under contrasting environmental conditions. Plants were sampled in the Rhine floodplain and in the Northern Vosges mountains, and then maintained in aquaria in hard (Rhine) or soft (Vosges) water. Under these conditions, we tested the influence of two trophic states (eutrophic state, 100 mu g.l(-1) P-PO43- and hypertrophic state, 300 mu g.l(-1) P-PO43-) on the P metabolism of plant subpopulations collected at three seasons (winter, spring and summer). Elodea nuttallii was able to absorb high levels of phosphorus through its shoots and enhance its phosphorus uptake, continually, after an increase of the resource availability (hypertrophic > eutrophic). The lowest efficiency in nutrient use was observed in winter, whereas the highest was recorded in spring, what revealed thus a storage strategy which can be beneficial to new shoots. This experiment provided evidence that generally, the water trophic state is the main factor governing P uptake, and the mineral status (softwater > hardwater) of the stream water is the second main factor. The phenological stage appeared to be a confounding factor to P level in water. Nonetheless, phenology played a role in P turnover in the plant. Finally, phenotypic plasticity allows both subpopulations to adapt to a changing environment