Investigation of grain orientations of melt-textured HTSC with addition of uranium oxide, Y2O3 and Y2BaCuO5

Local grain orientations were studied in melt-textured YBCO samples processed with various amounts of depleted uranuim oxide (DU) and Y 2O3 by means of electron backscatter diffraction (EBSD) analysis. The addition of DU leads to the formation of Ucontaining nanoparticles (Y2Ba4CuUOx) with sizes of around 200 nm, embedded in the superconducting Y-123 matrix. The orientation of the Y 2BaCuO5 (Y-211) particles, which are also present in the YBCO bulk microstructure, is generally random as is the case in other melttextured Y-123 samples. The presence of Y-211 particles, however, also affects the orientation of the Y-123 matrix in these samples

Antimicrobial residue assessment in 5, 357 commercialized meat samples from the Spain-France cross-border area: A new approach for effective monitoring

Although antimicrobials are valuable allies in animal production, their extended use has led to unexpected threats associated with the emergence and propagation of antimicrobial resistance. Moreover, when withdrawal periods in food-producing animals are not observed, antimicrobial residues can access the food chain, causing direct toxicity, allergies, and/or intestinal microbiota dysbiosis in consumers. Given that Spain and France are the largest meat producers in the EU and also count among the top consumers of meat, our study''s aim was to investigate the presence of antimicrobials in commercialized meat purchased in the Spain-France cross-border area (POCTEFA region). 5, 357 meat samples were collected from different animal species and a variety of different retailer types in Spain (Zaragoza, Bilbao, and Logroño) as well as in France (Toulouse and Perpignan). Meat samples were analysed by a screening method (Explorer®+QuinoScan®), yielding 194 positive samples, which were further evaluated by UPLC-QTOF (Ultra Performance Liquid Chromatography-Quadrupole Time of Flight) for confirmation. Chromatographic analyses found antimicrobial residues in 30 samples, although only 5 of them (0.093% of initial samples) were non-compliant according to the current legislation. Further studies suggested that this mismatch between screening and confirmatory analyses might be due to the presence of biologically active metabolites derived from degradation of antimicrobials that were not identified by the targeted UPLC-QTOF method, but which might play a decisive role in the inhibition of the biological Explorer® test. Although chromatographic techniques detect the marker compounds determined by European and national regulations, and although they are the methods selected for official control of antimicrobials in food, certain unknown metabolites might escape their monitoring. This thus suggests that biological tests are the most adequate ones in terms of ideal consumer health protection

Field-adapted sampling of whole blood to determine the levels of amodiaquine and its metabolite in children with uncomplicated malaria treated with amodiaquine plus artesunate combination

<p>Abstract</p> <p>Background</p> <p>Artemisinin combination therapy (ACT) has been widely adopted as first-line treatment for uncomplicated falciparum malaria. In Uganda, amodiaquine plus artesunate (AQ+AS), is the alternative first-line regimen to Coartem^®(artemether + lumefantrine) for the treatment of uncomplicated falciparum malaria. Currently, there are few field-adapted analytical techniques for monitoring amodiaquine utilization in patients. This study evaluates the field applicability of a new method to determine amodiaquine and its metabolite concentrations in whole blood dried on filter paper.</p> <p>Methods</p> <p>Twelve patients aged between 1.5 to 8 years with uncomplicated malaria received three standard oral doses of AQ+AS. Filter paper blood samples were collected before drug intake and at six different time points over 28 days period. A new field-adapted sampling procedure and liquid chromatographic method was used for quantitative determination of amodiaquine and its metabolite in whole blood.</p> <p>Results</p> <p>The sampling procedure was successively applied in the field. Amodiaquine could be quantified for at least three days and the metabolite up to 28 days. All parasites in all the 12 patients cleared within the first three days of treatment and no adverse drug effects were observed.</p> <p>Conclusion</p> <p>The methodology is suitable for field studies. The possibility to determine the concentration of the active metabolite of amodiaquine up to 28 days suggested that the method is sensitive enough to monitor amodiaquine utilization in patients. Amodiaquine plus artesunate seems effective for treatment of falciparum malaria.</p

Rarity of monodominance in hyperdiverse Amazonian forests.

Tropical forests are known for their high diversity. Yet, forest patches do occur in the tropics where a single tree species is dominant. Such "monodominant" forests are known from all of the main tropical regions. For Amazonia, we sampled the occurrence of monodominance in a massive, basin-wide database of forest-inventory plots from the Amazon Tree Diversity Network (ATDN). Utilizing a simple defining metric of at least half of the trees ≥ 10 cm diameter belonging to one species, we found only a few occurrences of monodominance in Amazonia, and the phenomenon was not significantly linked to previously hypothesized life history traits such wood density, seed mass, ectomycorrhizal associations, or Rhizobium nodulation. In our analysis, coppicing (the formation of sprouts at the base of the tree or on roots) was the only trait significantly linked to monodominance. While at specific locales coppicing or ectomycorrhizal associations may confer a considerable advantage to a tree species and lead to its monodominance, very few species have these traits. Mining of the ATDN dataset suggests that monodominance is quite rare in Amazonia, and may be linked primarily to edaphic factors

Drosha drives the formation of DNA:RNA hybrids around DNA break sites to facilitate DNA repair

The error-free and efficient repair of DNA double-stranded breaks (DSBs) is extremely important for cell survival. RNA has been implicated in the resolution of DNA damage but the mechanism remains poorly understood. Here, we show that miRNA biogenesis enzymes, Drosha and Dicer, control the recruitment of repair factors from multiple pathways to sites of damage. Depletion of Drosha significantly reduces DNA repair by both homologous recombination (HR) and non-homologous end joining (NHEJ). Drosha is required within minutes of break induction, suggesting a central and early role for RNA processing in DNA repair. Sequencing of DNA:RNA hybrids reveals RNA invasion around DNA break sites in a Drosha-dependent manner. Removal of the RNA component of these structures results in impaired repair. These results show how RNA can be a direct and critical mediator of DNA damage repair in human cells

Cohesin Protects Genes against γH2AX Induced by DNA Double-Strand Breaks

Chromatin undergoes major remodeling around DNA double-strand breaks (DSB) to promote repair and DNA damage response (DDR) activation. We recently reported a high-resolution map of γH2AX around multiple breaks on the human genome, using a new cell-based DSB inducible system. In an attempt to further characterize the chromatin landscape induced around DSBs, we now report the profile of SMC3, a subunit of the cohesin complex, previously characterized as required for repair by homologous recombination. We found that recruitment of cohesin is moderate and restricted to the immediate vicinity of DSBs in human cells. In addition, we show that cohesin controls γH2AX distribution within domains. Indeed, as we reported previously for transcription, cohesin binding antagonizes γH2AX spreading. Remarkably, depletion of cohesin leads to an increase of γH2AX at cohesin-bound genes, associated with a decrease in their expression level after DSB induction. We propose that, in agreement with their function in chromosome architecture, cohesin could also help to isolate active genes from some chromatin remodelling and modifications such as the ones that occur when a DSB is detected on the genome

A High Throughput Screen Identifies Nefopam as Targeting Cell Proliferation in β-Catenin Driven Neoplastic and Reactive Fibroproliferative Disorders

Fibroproliferative disorders include neoplastic and reactive processes (e.g. desmoid tumor and hypertrophic scars). They are characterized by activation of β-catenin signaling, and effective pharmacologic approaches are lacking. Here we undertook a high throughput screen using human desmoid tumor cell cultures to identify agents that would inhibit cell viability in tumor cells but not normal fibroblasts. Agents were then tested in additional cell cultures for an effect on cell proliferation, apoptosis, and β-catenin protein level. Ultimately they were tested in Apc1638N mice, which develop desmoid tumors, as well as in wild type mice subjected to full thickness skin wounds. The screen identified Neofopam, as an agent that inhibited cell numbers to 42% of baseline in cell cultures from β-catenin driven fibroproliferative disorders. Nefopam decreased cell proliferation and β-catenin protein level to 50% of baseline in these same cell cultures. The half maximal effective concentration in-vitro was 0.5 uM and there was a plateau in the effect after 48 hours of treatment. Nefopam caused a 45% decline in tumor number, 33% decline in tumor volume, and a 40% decline in scar size when tested in mice. There was also a 50% decline in β-catenin level in-vivo. Nefopam targets β-catenin protein level in mesenchymal cells in-vitro and in-vivo, and may be an effective therapy for neoplastic and reactive processes driven by β-catenin mediated signaling

Fast demographic traits promote high diversification rates of Amazonian trees.

The Amazon rain forest sustains the world's highest tree diversity, but it remains unclear why some clades of trees are hyperdiverse, whereas others are not. Using dated phylogenies, estimates of current species richness and trait and demographic data from a large network of forest plots, we show that fast demographic traits ? short turnover times ? are associated with high diversification rates across 51 clades of canopy trees. This relationship is robust to assuming that diversification rates are either constant or decline over time, and occurs in a wide range of Neotropical tree lineages. This finding reveals the crucial role of intrinsic, ecological variation among clades for understanding the origin of the remarkable diversity of Amazonian trees and forests