During labor, monocytes infiltrate massively the myometrium and differentiate into macrophages secreting high levels of reactive oxygen species and of pro-inflammatory cytokines (i.e. IL-1β), leading ...to myometrial contraction. Although IL-1β is clearly implicated in labor, its function and that of the inflammasome complex that cleaves the cytokine in its active form, has never been studied on steps preceding contraction. In this work, we used our model of lipopolysaccharide-induced preterm labor to highlight their role. We demonstrated that IL-1β was secreted by the human myometrium during labor or in presence of infection and was essential for myometrial efficient contractions as its blockage with an IL-1 receptor antagonist (Anakinra) or a neutralizing antibody completely inhibited the induced contractions. We evaluated the implication of the inflammasome on myometrial contractions and differentiation stages of labor onset. We showed that the effects of macrophage-released IL-1β in myometrial cell transactivation were blocked by inhibition of the inflammasome, suggesting that the inflammasome by producing IL-1β was essential in macrophage/myocyte crosstalk during labor. These findings provide novel innovative approaches in the management of preterm labor, specifically the use of an inflammasome inhibitor to block the precursor stages of labor before the acquisition of the contractile phenotype.
Infectious agents develop intricate mechanisms to interact with host cell pathways and hijack their genetic and epigenetic machinery to change host cell phenotypic states. Among the Apicomplexa ...phylum of obligate intracellular parasites, which cause veterinary and human diseases, Theileria is the only genus that transforms its mammalian host cells. Theileria infection of bovine leukocytes induces proliferative and invasive phenotypes associated with activated signalling pathways, notably JNK and AP-1 (ref. 2). The transformed phenotypes are reversed by treatment with the theilericidal drug buparvaquone. We used comparative genomics to identify a homologue of the peptidyl-prolyl isomerase PIN1 in T. annulata (TaPIN1) that is secreted into the host cell and modulates oncogenic signalling pathways. Here we show that TaPIN1 is a bona fide prolyl isomerase and that it interacts with the host ubiquitin ligase FBW7, leading to its degradation and subsequent stabilization of c-JUN, which promotes transformation. We performed in vitro and in silico analysis and in vivo zebrafish xenograft experiments to demonstrate that TaPIN1 is directly inhibited by the anti-parasite drug buparvaquone (and other known PIN1 inhibitors) and is mutated in a drug-resistant strain. Prolyl isomerization is thus a conserved mechanism that is important in cancer and is used by Theileria parasites to manipulate host oncogenic signalling.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
•LA-ICP-MS via pressed pellets was validated for plant-based foods.•The presented protocol complies with “Green Chemistry” principles.•Milling treatment for particle size reduction and homogenisation ...was tested.•Sample pretreatment improved considerably signal stability and analysis results.•Optimal analytical parameters were determined for Mn, Ni, Cu, Zn, As, Se and Pb.
Here, we validated a protocol for the elemental analysis of plant and food materials using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) and pressed pellets in compliance with the Green Chemistry principles, i.e. avoiding the use of hazardous reagents. The protocol included sample pre-treatment, preparation of pellets, and LA-ICP-MS optimisation for the food sample matrix using leaf certified reference materials. Sample homogenisation and particle size reduction (∼10 µm) for samples with larger initial particle sizes proved crucial in improving signal stability and analytical results, whereas the raster mode was preferred over spot mode for greater accuracy. The validation of the technique was successful for determination of Mn, Ni, Cu, Zn, As, Se, Cd and Pb (z-score values ≤2). We propose LA-ICP-MS using pressed pellets as an alternative to ICP-MS in food analysis.
A 50‐year‐long (1958–2008) historical simulation of a climate‐to‐fish ecosystem model for anchovy (Eugralis encrasicolus) and sardine (Sardina pilchardus) populations in the upwelling ecosystem off ...NW Africa is revisited and analyzed. Anchovy and sardine annual adult abundances were correlated at interannual and decadal time scales in the historical run. A three‐step analysis method applied unraveled the environmental and life stage‐specific drivers underlying the bottom‐up mechanisms responsible for the simulated variability in anchovy and sardine populations. Changes in anchovy adult abundance were primarily controlled by larval survival, prey availability, and local upwelling strength, whereas sardine adult abundance was controlled by age‐1 growth affecting age‐2 fecundity and egg production via prey availability. Despite different diet preferences, the common sensitivity of anchovy and sardine to prey availability had a synchronizing effect on the two populations, with both anchovy and sardine doing better during years of higher plankton biomass and colder ocean temperatures. Analysis of potential links with modes of climate variability showed that anchovy dynamics were more tightly connected to the AMO while sardine dynamics were correlated to the NAO. This difference stemmed from the vulnerability of the anchovy population to enhanced coastal upwelling causing increased larval drift mortality. Finally, based on an earlier, similar modeling study for the Californian anchovy and Pacific sardine, we argue that the relatively warmer habitat off NW Africa compared to the coastal region off central California is a key feature explaining synchronous populations in the Canary Current versus out‐of‐phase anchovy and sardine cycles in the California Current.
Scientific advances have significantly improved the practice of medicine by providing objective and quantitative means for exploring the human body and disease states. These innovative technologies ...have already profoundly improved disease detection, imaging, treatment and patient follow-up. Today's analytical limits are at the nanoscale level (one-billionth of a meter) enabling a detailed exploration at the level of DNA, RNA, proteins and metabolites which are in fact nano-objects. This translational review aims at integrating some recent advances from micro- and nano-technologies with high potential for improving daily oncology practice.
Abstract
One of the largest and most persistent features in the Alboran Sea is the Western Alboran Gyre (WAG), an anticyclonic recirculation bounded by the Atlantic Jet (AJ) to the north and the ...Moroccan coast to the south. Eulerian budgets from several months of a high-resolution model run are used to examine the exchange of water across the Eulerian WAG’s boundary and the processes affecting the salinity, temperature, and vorticity of the WAG. The volume transport across the sides of the WAG is found to be related to vertical isopycnal movement at the base of the gyre. Advection is found to drive a decay in the salinity minimum and anticyclonic vorticity of the Eulerian WAG. Given the large contributions of advection, a Lagrangian analysis is performed, revealing geometric aspects of the exchange that are hidden in an Eulerian view. In particular, stable and unstable manifolds identify a stirring region around the outer reaches of the gyre where water is exchanged with the WAG on a time scale of weeks. Its complement is an inner core that expands with depth and exchanges water with its surroundings on much longer time scales. The 3D evolution of one parcel, or lobe, of water as it enters the WAG is also described, identifying a general Lagrangian subduction pathway.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Adverse effects of pharmaceuticals evaluated in bacteria, microalgae and sea urchin.•Environmental concentrations of pharmaceuticals produce teratogenic effect in sea urchin.•Standard acute toxicity ...tests are not sensitive enough to evaluate effects of pharmaceuticals in aquatic biota.•Endpoints applied in current guidelines are not suitable to evaluate effect of pharmaceuticals.
Nowadays, the presence of pharmaceutical products in aquatic environments is not only common, but is also of significant concern regarding the adverse effect they may produce to aquatic biota. In order to determine the adverse effects of caffeine (CAF), ibuprofen (IBU), carbamazepine (CBZ) and novobiocin (NOV), at environmental occurring concentrations, standardized endpoints applied in current guidelines were evaluated in four organisms including bioluminescence response in Vibrio fischeri, growth inhibition in Isochrysis galbana (marine water) and Pseudokirchneriella subcapitata (fresh water) and fertilization and embryo-larval development in Paracentrotus lividus. To reach this aim bioassays were implemented by exposing organisms to water spiked with drugs dissolved in DMSO (0.001% v/v). Risk characterization was performed, calculating the environmental impact of drugs by calculating environmental concentration and predicted no effect concentration ratio (MEC/PNEC). Results indicate that acute toxicity was found above environmental concentrations in the order of mgL−1 for bacteria bioluminescence, microalgae growth inhibition and sea urchin fertilization. However, teratogenicity was observed on sea urchin after exposure to environmental concentrations of drugs at 0.00001mgL−1; at this concentration CBZ and IBU were found to reduce significantly the embryo-larval development compared to controls (p<0.01). The risk calculated for selected drugs suggested they are harmless for aquatic environment except when applying the embryo-larval development endpoint. Endpoints applied in this study showed the necessity of using more sensitive responses, when assessing risk of pharmaceuticals in aquatic environments, since endpoints applied in current guidelines may not be suitable.
•We cultured S. obliquus in different conditions in treated urban wastewater in batch.•We studied the effect of light, dark and biomass concentration in nutrient removal.•Nutrient uptake can take ...place in the absence of light.•Internal nutrient content was more relevant than light presence or biomass density.•These findings could lead to new configurations of reactors aimed to wastewater treatment.
This work was aimed at studying the effect of light–darkness and high–low biomass concentrations in the feasibility of removing nitrogen and phosphorus from urban treated wastewater by the microalga Scenedesmus obliquus. Laboratory experiments were conducted in batch, where microalgae were cultured under different initial biomass concentrations (150 and 1500mgSSl−1) and light conditions (dark or illuminated). Nutrient uptake was more dependent on internal nutrient content of the biomass than on light presence or biomass concentration. When a maximum nitrogen or phosphorus content in the biomass was reached (around 8% and 2%, respectively), the removal of that nutrient was almost stopped. Biomass concentration affected more than light presence on the nutrient removal rate, increasing significantly with its increase. Light was only required to remove nutrients when the maximum nutrient storage capacity of the cells was reached and further growth was therefore needed. Residence times to maintain a stable biomass concentration, avoiding the washout of the reactor, were much higher than those needed to remove the nutrients from the wastewater. This ability to remove nutrients in the absence of light could lead to new configurations of reactors aimed to wastewater treatment.
Electron tomography (ET) has rapidly developed into a powerful technique to characterize the three-dimensional (3D) structure of complex materials, with nanometer resolution, for a wide range of ...applications including heterogeneous catalysis. In these 3D studies, scanning transmission electron microscopy (STEM) has been the most widely used imaging mode, due to both its incoherent nature, which avoids the appearance of diffraction-related artefacts, and its sensitivity to composition, an important question for most catalytic systems. Though initially used as a qualitative tool to visualize 3D nanostructures, more recently STEM tomography is being also exploited to retrieve quantitative information in 3D. In this article, we review recent developments of STEM-based tomography for the understanding of heterogeneous catalysts at the nanometer level. The new possibilities opened by quantitative analysis will be illustrated by selected cases in which different parameters are calculated from 3D reconstructions and compared to their macroscopic measurements. The key influence of the latest developments in reconstruction and segmentation methods to assess reliability and accuracy in the quantification process is highlighted.
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