Nimesulide reduces interleukin-1β-induced cyclooxygenase-2 gene expression in human synovial fibroblasts

AbstractObjective To characterize the effects of nimesulide (NIM) on basal and induced cyclo-oxygenase-2 (COX-2) gene expression in human synovial fibroblasts (HSF) and to define the intracellular mechanisms that mediate the changes in COX-2 expression and synthesis in response to the drug.Design HSF were incubated with NIM and NS-398 (0, 0.03, 0.3, 3μg/ml) in the absence or presence of the COX-2 inducers interleukin-1β (IL-1β) or endotoxin (LPS). Treated cells were analysed for COX-2 mRNA and protein by Northern and Western blotting analysis, respectively. Putative transcriptional, post-transcriptional, and signaling effects of NIM on basal and induced-COX-2 expression were investigated by human COX-2 promoter studies, calcium studies, reactive oxygen species (ROS) evaluations, electrophoretic mobility shift analysis (EMSA) and half-life studies of COX-2 mRNA.Results NIM inhibited IL-1β-induced COX-2 expression and protein at sub and therapeutic concentrations (0.03–0.3μg/ml) while the non-specific NSAID, naproxen, did not. Both drugs suppressed PGE2 release by about 95%. NIM had no effect on (1) IL-1β-induced increases in NF-κB or c/EBP signaling, or (2) human COX-2 promoter activity. Stability of induced COX-2 mRNA was unaffected by NIM treatments. Pre-treatment of cells with O2radical scavengers (e.g. PDTC) or with Ca++channel blockers (e.g. verapamil) had a modest effect on IL-1β-induced COX-2 expression. NIM blocked ionomycin+thapsigargin and H2O2-induced increases in COX-2 protein synthesis.Conclusion NIM inhibits cytokine-induced COX-2 expression and protein at sub and therapeutic concentrations. At least part of this activity may be the result of NIM inhibition of calcium and/or free radical generation induced by cytokines

The effect of Bt-transgenic potatoes on the movement of the Colorado potato beetle [Coleoptera : Chrysomelidae]

Une étude de deux saisons au Centre de recherches sur la pomme de terre, Fredericton, Nouveau-Brunswick, a démontré que les adultes du doryphore de la pomme de terre ( Leptinotarsa decemlineata) susceptibles au Bacillus thuringiensis (Bt) avaient un temps de résidence quantifiable dans une parcelle de pomme de terre Bt-transgénique. Cinquante pour cent des doryphores susceptibles au Bt relâchés dans une parcelle de pommes de terre Russet Burbank transgéniques (NewLeaf TM) ont été recapturés de 4 à 7 jours plus tard tandis que la même proportion de recapture des doryphores relâchés dans la parcelle témoin non-transgénique a eu lieu de 7 à 11 jours après le lâcher. En dépit de la toxicité des plantes, les doryphores ont survécu pendant un laps de temps appréciable (jusqu'à 31 jours) dans la parcelle de pommes de terre transgéniques. De 25 à 30 % des doryphores relâchés dans la parcelle de pommes de terre Bt-transgéniques furent recapturés sur des plants-pièges ou dans des pièges-fosse en dehors de cette parcelle, ce qui démontre un niveau élevé de dispersion. La durée du temps de résidence et le haut niveau de dispersion pourraient permettre le développement d'une population de doryphores résistante à la pomme de terre Bt-transgénique. Nos résultats sont utiles pour le développement d'une stratégie de déploiement de la pomme de terre Bt-transgénique qui réduit les risques de résistance au Bt chez le doryphore de la pomme de terre.A two-year field study conducted at the Potato Research Centre in Fredericton, New Brunswick, demonstrated a quantifiable residency time for Bacillus thuringiensis (Bt) susceptible adult Colorado potato beetles (Leptinotarsa decemlineata) in a Bt-transgenic potato field. Fifty percent of Bt-susceptible beetles released in a transgenic Russet Burbank (NewLeafTM) potato plot were recaptured 4 to 7 days after release compared to 7 to 11 days for beetles released in a non-transgenic control plot. Beetles survived for long periods of time (up to 31 days) on transgenic potatoes in spite of the crop's toxicity. A significant number of beetles dispersed from transgenic plots. Twenty-five and 30% of the beetles released in the Bt-transgenic plot were recaptured in border rows or trench traps outside the plot indicating a high level of dispersal activity. The long residency time and the high level of dispersal activity could increase the chances of development of a Bt-resistant beetle population. These findings are important to the development of a deployment strategy that will reduce the risk of build-up of Bt resistance in the beetle population

Olfactory proteins mediating chemical communication in the Navel Orangeworm Moth, Amyelois transitella

Background The navel orangeworm, Amyelois transitella Walker (Lepidoptera: Pyralidae), is the most serious insect pest of almonds and pistachios in California for which environmentally friendly alternative methods of control — like pheromone-based approaches — are highly desirable. Some constituents of the sex pheromone are unstable and could be replaced with parapheromones, which may be designed on the basis of molecular interaction of pheromones and pheromone-detecting olfactory proteins. Methodology By analyzing extracts from olfactory and non-olfactory tissues, we identified putative olfactory proteins, obtained their N-terminal amino acid sequences by Edman degradation, and used degenerate primers to clone the corresponding cDNAs by SMART RACE. Additionally, we used degenerate primers based on conserved sequences of known proteins to fish out other candidate olfactory genes. We expressed the gene encoding a newly identified pheromone-binding protein, which was analyzed by circular dichroism, fluorescence, and nuclear magnetic resonance, and used in a binding assay to assess affinity to pheromone components. Conclusion We have cloned nine cDNAs encoding olfactory proteins from the navel orangeworm, including two pheromone-binding proteins, two general odorant-binding proteins, one chemosensory protein, one glutathione S-transferase, one antennal binding protein X, one sensory neuron membrane protein, and one odorant receptor. Of these, AtraPBP1 is highly enriched in male antennae. Fluorescence, CD and NMR studies suggest a dramatic pH-dependent conformational change, with high affinity to pheromone constituents at neutral pH and no binding at low pH

Chronic sciatic nerve injury impairs the local cutaneous neurovascular interaction in rats

Most studies of chronic nerve compression focus on large nerve function in painful conditions, and only few studies have assessed potential changes in the function of small nerve fibers during chronic nerve compression and recovery from compression. Cutaneous pressure-induced vasodilation is a neurovascular phenomenon that relies on small neuropeptidergic fibers controlling the cutaneous microvasculature. We aimed to characterize potential changes in function of these small fibers and/or in cutaneous microvascular function following short-term (1-month) and long-term (6-month) nerve compression and after release of compression (ie, potential recovery of function). A compressive tube was left on one sciatic nerve for 1 or 6 months and then removed for 1-month recovery in Wistar rats. Cutaneous vasodilator responses were measured by laser Doppler flowmetry in hind limb skin innervated by the injured nerve to assess neurovascular function. Nociceptive thermal and low mechanical thresholds were evaluated to assess small and large nerve fiber functions, respectively. Pressure-induced vasodilation was impaired following nerve compression and restored following nerve release; both impairment and restoration were strongly related to duration of compression. Small and large nerve fiber functions were less closely related to duration of compression. Our data therefore suggest that cutaneous pressure-induced vasodilation provides a non-invasive and mechanistic test of neurovascular function that gives direct information regarding extent and severity of damage during chronic nerve compression and recovery, and may ultimately provide a clinically useful tool in the evaluation of nerve injury such as carpal tunnel syndrome

Landau levels in the case of two degenerate coupled bands: kagome lattice tight-binding spectrum

The spectrum of charged particles hopping on a kagome lattice in a uniform transverse magnetic field shows an unusual set of Landau levels at low field. They are unusual in two respects: the lowest Landau levels are paramagnetic so their energies decrease linearly with increasing field magnitude, and the spacings between the levels are not equal. These features are shown to follow from the degeneracy of the energy bands in zero magnetic field. We give a general discussion of Landau levels in the case of two degenerate bands, and show how the kagome lattice tight-binding model includes one special case of this more general problem. We also discuss the consequences of this for the behavior of the critical temperature of a kagome grid superconducting wire network, which is the experimental system that originally motivated this work.Comment: 18 pages, 8 figure

A model-based evaluation of Marine Protected Areas: the example of eastern Baltic cod (Gadus morhua callarias L.).

The eastern Baltic cod stock collapsed as a consequence of climate-driven adverse hydrographic conditions and overfishing and has remained at historically low levels. Spatio-temporal fishing closures [Marine Protected Areas (MPAs)] have been implemented since 1995, to protect and restore the spawning stock. However, no signs of recovery have been observed yet, either suggesting that MPAs are an inappropriate management measure or pointing towards suboptimal closure design. We used the spatially explicit fishery simulation model ISIS-Fish to evaluate proposed and implemented fishery closures, combining an age-structured population module with a multifleet exploitation module and a management module in a single model environment. The model is parameterized based on (i) the large amount of biological knowledge available for cod and (ii) an analysis of existing spatially disaggregated fishery data. As the population dynamics of eastern Baltic cod depend strongly on the climate-driven hydrographic regime, we considered two production regimes of the stock. MPAs were only effective for stock recovery when they reduced overall fishing effort. The performance of MPAs needs to be evaluated relative to environmental regimes, especially for stocks facing strong environmental variability

Mass-losing accretion discs around supermassive black holes

We study the effects of outflow/wind on the gravitational stability of accretion discs around supermassive black holes using a set of analytical steady-state solutions. Mass-loss rate by the outflow from the disc is assumed to be a power-law of the radial distance and the amount of the energy and the angular momentum which are carried away by the wind are parameterized phenomenologically. We show that the mass of the first clumps at the self-gravitating radius linearly decreases with the total mass-loss rate of the outflow. Except for the case of small viscosity and high accretion rate, generally, the self-gravitating radius increases as the amount of mass-loss by the outflow increases. Our solutions show that as more angular momentum is lost by the outflow, then reduction to the mass of the first clumps is more significant.Comment: Accepted for publication in Astrophysics & Space Scienc

Intrinsic correlation between the fraction of liquidlike zones and the beta relaxation in high-entropy metallic glasses

Lacking the structural information of crystalline solids, the origin of the relaxation dynamics of metallic glasses is unclear. Here, we report the evolution of stress relaxation of high-entropy metallic glasses with distinct ß relaxation behavior. The fraction of liquidlike zones, determined at each temperature by the intensity of stress decay, is shown to be directly related to both the aging process and the spectrum of relaxation modes obtained by mechanical spectroscopy. The results shed light on the intrinsic correlation between the static and dynamic mechanical response in high-entropy and conventional metallic glasses, pointing toward a sluggish diffusion high-entropy effect in the liquid dynamics.Postprint (author's final draft

Active oceanic spreading in the northern north Fiji basin : results of the NOFI cruise of R/V l'Atalante (Newstarmer project)

The South Pandora and the Tripartite Ridges are active spreading centers located in the northern part of the North Fiji Basin. These spreading centers were surveyed over a distance of 750 km during the NOFI cruise of R/V L'Atalante (August-September 1994) which was conducted in the frame of the french-japanese Newstarmer cooperation project. SIMRAD EM12-dual full coverage swath bathymetric and imagery data as well as airgun 6-channel seismic, magnetics and gravity profiles were recorded along an off-axis from 170°40'E to 178°E. Dredging and piston coring were also performed along and off-axis. The axial domain of the South Pandora Ridge is divided into 5 first-order segments characterized by contrasted morphologies. The average width of the active domain is 20 km and corresponds either to bathymetric highs or to deep elongated grabens. The bathymetric highs are volcanic constructions, locally faulted and rifted, which can obstruct totally the axial valley. The grabens show the typical morphology of slow spreading axes, with two steep walls flanking a deep axial valley. Elongated lateral ridges may be present on both sides of the grabens. Numerous volcanoes, up to several kilometers in diameter, occur on both flanks of the South Pandora Ridge. The Tripartite Ridge consists of three main segments showing a sigmoid shape. Major changes in the direction of the active zones are observed at the segment discontinuities. These discontinuities show various geometrical patterns which suggest complex transform relay zones. Preliminary analysis of seismic reflection profiles suggest that the Tripartite Ridge is a very young feature which propagates into an older oceanic domain characterized by a significant sedimentary cover. By contrast, a very thin to absent sedimentary cover is observed about 100 km on both flanks of the South Pandora Ridge active axis. The magnetic anomaly profiles give evidence of long and continuous lineations, parallel to the South Pandora Ridge spreading axis. (Résumé d'auteur

Refining the phenotype associated with biallelic DNAJC21 mutations

Accepted manuscriptInherited bone marrow failure syndromes (IBMFS) are caused by mutations in genes involved in genomic stability. Although they may be recognized by the association of typical clinical features, variable penetrance and expressivity are common, and clinical diagnosis is often challenging. DNAJC21, which is involved in ribosome biogenesis, was recently linked to bone marrow failure. However, the specific phenotype and natural history remain to be defined. We correlate molecular data, phenotype, and clinical history of 5 unreported affected children and all individuals reported in the literature. All patients present features consistent with IBMFS: bone marrow failure, growth retardation, failure to thrive, developmental delay, recurrent infections, and skin, teeth or hair abnormalities. Additional features present in some individuals include retinal abnormalities, pancreatic insufficiency, liver cirrhosis, skeletal abnormalities, congenital hip dysplasia, joint hypermobility, and cryptorchidism. We suggest that DNAJC21-related diseases constitute a distinct IBMFS, with features overlapping Shwachman-Diamond syndrome and Dyskeratosis congenita, and additional characteristics that are specific to DNAJC21 mutations. The full phenotypic spectrum, natural history, and optimal management will require more reports. Considering the aplastic anemia, the possible increased risk for leukemia, and the multisystemic features, we provide a checklist for clinical evaluation at diagnosis and regular follow-up.FCT—Fundação para a Ciência e a Tecnologia (SFRH/BD/84650/2010)info:eu-repo/semantics/publishedVersio