Acute effects of ferumoxytol on regulation of renal hemodynamics and oxygenation

The superparamagnetic iron oxide nanoparticle ferumoxytol is increasingly used as intravascular contrast agent in magnetic resonance imaging (MRI). This study details the impact of ferumoxytol on regulation of renal hemodynamics and oxygenation. In 10 anesthetized rats, a single intravenous injection of isotonic saline (used as volume control) was followed by three consecutive injections of ferumoxytol to achieve cumulative doses of 6, 10, and 41 mg Fe/kg body mass. Arterial blood pressure, renal blood flow, renal cortical and medullary perfusion and oxygen tension were continuously measured. Regulation of renal hemodynamics and oxygenation was characterized by dedicated interventions: brief periods of suprarenal aortic occlusion, hypoxia, and hyperoxia. None of the three doses of ferumoxytol resulted in significant changes in any of the measured parameters as compared to saline. Ferumoxytol did not significantly alter regulation of renal hemodynamics and oxygenation as studied by aortic occlusion and hypoxia. The only significant effect of ferumoxytol at the highest dose was a blunting of the hyperoxia-induced increase in arterial pressure. Taken together, ferumoxytol has only marginal effects on the regulation of renal hemodynamics and oxygenation. This makes ferumoxytol a prime candidate as contrast agent for renal MRI including the assessment of renal blood volume fraction

Necessary conditions for variational regularization schemes

We study variational regularization methods in a general framework, more precisely those methods that use a discrepancy and a regularization functional. While several sets of sufficient conditions are known to obtain a regularization method, we start with an investigation of the converse question: How could necessary conditions for a variational method to provide a regularization method look like? To this end, we formalize the notion of a variational scheme and start with comparison of three different instances of variational methods. Then we focus on the data space model and investigate the role and interplay of the topological structure, the convergence notion and the discrepancy functional. Especially, we deduce necessary conditions for the discrepancy functional to fulfill usual continuity assumptions. The results are applied to discrepancy functionals given by Bregman distances and especially to the Kullback-Leibler divergence.Comment: To appear in Inverse Problem

Structural basis for assembly and function of the Nup82 complex in the nuclear pore scaffold

Nuclear pore complexes (NPCs) are huge assemblies formed from ∼30 different nucleoporins, typically organized in subcomplexes. One module, the conserved Nup82 complex at the cytoplasmic face of NPCs, is crucial to terminate mRNA export. To gain insight into the structure, assembly, and function of the cytoplasmic pore filaments, we reconstituted in yeast the Nup82–Nup159–Nsp1–Dyn2 complex, which was suitable for biochemical, biophysical, and electron microscopy analyses. Our integrative approach revealed that the yeast Nup82 complex forms an unusual asymmetric structure with a dimeric array of subunits. Based on all these data, we developed a three-dimensional structural model of the Nup82 complex that depicts how this module might be anchored to the NPC scaffold and concomitantly can interact with the soluble nucleocytoplasmic transport machinery

Ceramics and its dimensions : shaping the future

European ceramics traditions and cultures are facing challenges, many of them linked to the recent development of digital technology that is changing the rules of our everyday life as well as all aspects of trade. The publication shares, shows and discusses the ideas and processes that have evolved during the project Ceramics and its Dimensions and the related sub-project Shaping the Future. The sub-project began with a workshop on the premises of the KAHLA Porcelain factory in Germany gathering together international team of students, teachers and other stakeholders with the aim of exploring the material of ceramics and the associated new technologies. These experiments resulted in diverse new ceramic pieces yet even more important were the shared experiences and ideas that gave birth to new creative processes. The articles of the publication discuss the topics of design, education, 3D printing and food. The publication includes also a catalogue of the works that are on display in a touring exhibition Ceramics and its Dimensions: Shaping the Future. The aim of the publication is to challenge and reposition the role of ceramics and its future

In vitro neurotoxicity of particles from diesel and biodiesel fueled engines following direct and simulated inhalation exposure

Combustion-derived particulate matter (PM) is a major source of air pollution. Efforts to reduce diesel engine emission include the application of biodiesel. However, while urban PM exposure has been linked to adverse brain effects, little is known about the direct effects of PM from regular fossil diesel (PMDEP) and biodiesel (PMBIO) on neuronal function. Furthermore, it is unknown to what extent the PM-induced effects in the lung (e.g., inflammation) affect the brain. This in vitro study investigates direct and indirect toxicity of PMDEP and PMBIO on the lung and brain and compared it with effects of clean carbon particles (CP). PM were generated using a common rail diesel engine. CP was sampled from a spark generator. First, effects of 48 h exposure to PM and CP (1.2–3.9 µg/cm2) were assessed in an in vitro lung model (air–liquid interface co-culture of Calu-3 and THP1 cells) by measuring cell viability, cytotoxicity, barrier function, inflammation, and oxidative and cell stress. None of the exposures caused clear adverse effects and only minor changes in gene expression were observed. Next, the basal medium was collected for subsequent simulated inhalation exposure of rat primary cortical cells. Neuronal activity, recorded using microelectrode arrays (MEA), was increased after acute (0.5 h) simulated inhalation exposure. In contrast, direct exposure to PMDEP and PMBIO (1–100 µg/mL; 1.2–119 µg/cm2) reduced neuronal activity after 24 h with lowest observed effect levels of respectively 10 µg/mL and 30 µg/mL, indicating higher neurotoxic potency of PMDEP, whereas neuronal activity remained unaffected following CP exposure. These findings indicate that combustion-derived PM potently inhibit neuronal function following direct exposure, while the lung serves as a protective barrier. Furthermore, PMDEP exhibit a higher direct neurotoxic potency than PMBIO, and the data suggest that the neurotoxic effects is caused by adsorbed chemicals rather than the pure carbon core

Two structurally distinct domains of the nucleoporin Nup170 cooperate to tether a subset of nucleoporins to nuclear pores

How individual nucleoporins (Nups) perform their role in nuclear pore structure and function is largely unknown. In this study, we examined the structure of purified Nup170 to obtain clues about its function. We show that Nup170 adopts a crescent moon shape with two structurally distinct and separable domains, a β-propeller N terminus and an α-solenoid C terminus. To address the individual roles of each domain, we expressed these domains separately in yeast. Notably, overexpression of the Nup170 C domain was toxic in nup170Δ cells and caused accumulation of several Nups in cytoplasmic foci. Further experiments indicated that the C-terminal domain anchors Nup170 to nuclear pores, whereas the N-terminal domain functions to recruit or retain a subset of Nups, including Nup159, Nup188, and Pom34, at nuclear pores. We conclude that Nup170 performs its role as a structural adapter between cytoplasmically oriented Nups and the nuclear pore membrane

Structural basis for assembly and function of the Nup82 complex in the nuclear pore scaffold

Nuclear pore complexes (NPCs) are huge assemblies formed from ~30 different nucleoporins, typically organized in subcomplexes. One module, the conserved Nup82 complex at the cytoplasmic face of NPCs, is crucial to terminate mRNA export. To gain insight into the structure, assembly, and function of the cytoplasmic pore filaments, we reconstituted in yeast the Nup82–Nup159–Nsp1–Dyn2 complex, which was suitable for biochemical, biophysical, and electron microscopy analyses. Our integrative approach revealed that the yeast Nup82 complex forms an unusual asymmetric structure with a dimeric array of subunits. Based on all these data, we developed a three-dimensional structural model of the Nup82 complex that depicts how this module might be anchored to the NPC scaffold and concomitantly can interact with the soluble nucleocytoplasmic transport machinery

Honey bee colony winter loss rates for 35 countries participating in the COLOSS survey for winter 2018–2019, and the effects of a new queen on the risk of colony winter loss

peer-reviewedThis article presents managed honey bee colony loss rates over winter 2018/19 resulting from using the standardised COLOSS questionnaire in 35 countries (31 in Europe). In total, 28,629 beekeepers supplying valid loss data wintered 738,233 colonies, and reported 29,912 (4.1%, 95% confidence interval (CI) 4.0–4.1%) colonies with unsolvable queen problems 79,146 (10.7%, 95% CI 10.5–10.9%) dead colonies after winter and 13,895 colonies (1.9%, 95% CI 1.8–2.0%) lost through natural disaster. This gave an overall colony winter loss rate of 16.7% (95% CI 16.4–16.9%), varying greatly between countries, from 5.8% to 32. 0%. We modelled the risk of loss as a dead/empty colony or from unresolvable queen problems and found that, overall, larger beekeeping operations with more than 150 colonies experienced significantly lower losses (p<0.001), consistent with earlier studies. Additionally, beekeepers included in this survey who did not migrate their colonies at least once in 2018 had significantly lower losses than those migrating (p<0.001). The percentage of new queens from 2018 in wintered colonies was also examined as a potential risk factor. The percentage of colonies going into winter with a new queen was estimated as 55.0% over all countries. Higher percentages of young queens corresponded to lower overall losses (excluding losses from natural disaster), but also lower losses from unresolvable queen problems, and lower losses from winter mortality (p<0.001). Detailed results for each country and overall are given in a table, and a map shows relative risks of winter loss at regional level