Transcriptomics analysis of hepatotoxicity induced by the pesticides imazalil, thiacloprid and clothianidin alone or in binary mixtures in a 28-day study in female Wistar rats

Co-occurrence of pesticide residues in food commodities raises a potential safety issue as their mixture effects on human health are largely unknown. In a previous study, we reported the toxicological effects (pathology and histopathology) of imazalil (IMZ), thiacloprid (THI), and clothianidin (CTD) alone and in binary mixtures in a 28-day oral gavage study in female Wistar rats. Five dose levels (up to 350 mg/kg body weight/day) ranging from a typical toxicological reference value to a clear effect dose were applied. In the present study, we undertook a transcriptomics analysis of rat livers by means of total RNA sequencing (RNA-Seq). Bioinformatic data analysis involving Ingenuity Pathway Analysis (IPA) was used to gain mechanistic information on hepatotoxicity-related pathways affected after treatment with the pesticides, alone and in mixtures. Our data show that 2986 genes were differentially regulated by CTD while IMZ and THI had effects on 194 and 225 genes, respectively. All three individual compounds shared a common subset of genes whose network is associated with xenobiotic metabolism and nuclear receptor activation. Similar networks were retrieved for the mixtures. Alterations in the expression of individual genes were in line with the assumption of dose addition. Our results bring new insight into the hepatotoxicity mechanisms of IMZ, THI, and CTD and their mixtures

Hepatotoxicity of the pesticides imazalil, thiacloprid and clothianidin – Individual and mixture effects in a 28-day study in female Wistar rats

Humans are exposed to pesticide residues through various food products. As these residues can occur in mixtures, there is a need to investigate possible mixture effects on human health. Recent exposure studies revealed the preponderance of imazalil, thiacloprid, and clothianidin in food diets. In this study, we assessed their toxicity alone and in binary mixtures in a 28-day gavage study in female Wistar rats. Five dose levels (up to 350 mg/kg bw/day) ranging from a typical toxicological reference value to a clear effect dose were applied. Data show that the liver was a target organ of all pesticides and their mixtures. Increases in liver weight were observed and histopathological examination revealed centrilobular hepatocellular hypertrophy and cytoplasm degeneration for all treatment conditions. No accumulation of hepatic triglycerides was reported. Tissue residue analysis showed altered pesticide residues in the liver and the kidney when being in mixture as compared to the levels of pesticide residues for the single compound treatment, indicating possible toxicokinetic interactions. Overall, all mixtures appeared to follow the additivity concept, even though quantitative analysis was limited for some endpoints due to the semi-quantitative nature of the data, raising no specific concern for the risk assessment of the examined pesticides.</p

Feeding the city: food cycles and the production of urban space

Städte bilden Schnittpunkte in translokalen Güterflüssen und Versorgungssystemen. Insbesondere die Versorgung der Stadtbevölkerung mit Lebensmitteln ist – wie die Wasser- oder Energieversorgung – eine Grundvoraussetzung für das Funktionieren städtischer Lebensweisen. Sie prägt die Beziehungen von Städten zu ihrem Hinterland. In der Geschichte bildete die ständige Expansion der Landwirtschaft und der Mittel des Warentransports eine wesentliche Bedingung für städtisches Wachstum, und heute hat die Lebensmittelversorgung längst eine planetarische Dimension angenommen. Ihre Formen und Abläufe, wie auch die Rituale des Essens, haben sich seit Jahrhunderten in die Architektur der Städte eingeschrieben. Dennoch bleiben die Strukturen der Lebensmittelversorgung meist unter dem Radar der Stadtforschung und -planung. Im Seminar „Feeding the City“ haben wir uns mit den Lieferketten konventioneller Lebensmittel befasst, wie wir sie im Supermarkt oder Discounter in großer Zahl und zu niedrigen Preisen kaufen können: abgepacktes Fabrikbrot, H-Milch, Hähnchenbrust, Bananen oder Fruchtgummis. Wo kommen sie her, welchen Weg nehmen sie und wie formen sie die Räume, durch die sie zirkulieren? Welche Akteur*innen und Regularien bestimmen diese Vorgänge und Zusammenhänge? Studierende der Stadtplanung und Architektur der BTU Cottbus-Senftenberg haben zehn alltägliche Lebensmittel verfolgt: Vom Ort ihres Anbaus oder der Tierhaltung über die Stationen der Lebensmittelindustrie und Distribution bis hin zum Einzelhandel, dem privaten Kühlschrank oder Esstisch und zur Entsorgung der Überbleibsel. Anhand von Kartierungen und Netzwerkdiagrammen haben sie die räumliche Reichweite und die Komplexität der Lieferketten betrachtet, sie haben die gebauten Räume einzelner Stationen und ihre städtischen Kontexte analysiert und schließlich nach der aktuellen oder historischen Präsenz des jeweiligen Produkts in der Stadt Cottbus gefragt.Cities form intersections in translocal flows of goods and supply systems. Food supply shapes the relationships between cities and their hinterlands and is a basic prerequisite for the functioning of urban lifestyles. Throughout history, urban growth has been accompanied by the constant expansion of agriculture and transportation networks. By now, these expansive dynamics of food supply systems have reached planetary dimensions. Food supply and processing, as well as eating rituals have been inscribed in the architecture of cities for centuries. Yet, these complex supply systems have largely remained under the radar of urban planning and urban research. In the seminar "Feeding the City", we explored the supply chains of conventional food items, which are commonly found in large numbers and at low prices in supermarkets, such as packaged and sliced bread, UHT milk, chicken breast, bananas or fruit gums. We followed ten products and looked at the places where they are produced and processed, the routes they take, and how they shape the spaces through which they circulate. We also zoomed in on the actors, regulations and power relations that determine these processes and contexts. Students of urban planning and architecture at the BTU Cottbus-Senftenberg have set out on a (mostly virtual) journey to trace everyday foodstuffs from the places where they are grown or raised, to the supermarkets in Cottbus, Germany. Using various mapping methods and network diagrams, they have developed a set of maps that illustrate the wide reach of supply chains around the world, complex actor-networks within food systems, the architectures of particular stations as well as their urban context, and the current or historical presence of the respective products in the city of Cottbus

Allergy Modulation by N-3 Long Chain Polyunsaturated Fatty Acids and Fat Soluble Nutrients of the Mediterranean Diet

The Mediterranean diet, containing valuable nutrients such as n-3 long chain poly-unsaturated fatty acids (LCPUFAs) and other fat-soluble micronutrients, is known for its health promoting and anti-inflammatory effects. Its valuable elements might help in the battle against the rising prevalence of non-communicable diseases (NCD), including the development of allergic diseases and other (chronic) inflammatory diseases. The fat fraction of the Mediterranean diet contains bioactive fatty acids but can also serve as a matrix to dissolve and increase the uptake of fat-soluble vitamins and phytochemicals, such as luteolin, quercetin, resveratrol and lycopene with known immunomodulatory and anti-inflammatory capacities. Especially n-3 LCPUFAs such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) derived from marine oils can target specific receptors or signaling cascades, act as eicosanoid precursors and/or alter membrane fluidity and lipid raft formation, hereby exhibiting anti-inflammatory properties. Beyond n-3 LCPUFAs, fat-soluble vitamins A, D, E, and K1/2 have the potential to affect pro-inflammatory signaling cascades by interacting with receptors or activating/inhibiting signaling proteins or phosphorylation in immune cells (DCs, T-cells, mast cells) involved in allergic sensitization or the elicitation/effector phase of allergic reactions. Moreover, fat-soluble plant-derived phytochemicals can manipulate signaling cascades, mostly by interacting with other receptors or signaling proteins compared to those modified by fat-soluble vitamins, suggesting potential additive or synergistic actions by applying a combination of these nutrients which are all part of the regular Mediterranean diet. Research concerning the effects of phytochemicals such as polyphenols has been hampered due to their poor bio-availability. However, their solubility and uptake are improved by applying them within the dietary fat matrix. Alternatively, they can be prepared for targeted delivery by means of pharmaceutical approaches such as encapsulation within liposomes or even unique nanoparticles. This review illuminates the molecular mechanisms of action and possible immunomodulatory effects of n-3 LCPUFAs and fat-soluble micronutrients from the Mediterranean diet in allergic disease development and allergic inflammation. This will enable us to further appreciate how to make use of the beneficial effects of n-3 LCPUFAs, fat-soluble vitamins and a selection of phytochemicals as active biological components in allergy prevention and/or symptom reduction

Measurements of the Total and Differential Higgs Boson Production Cross Sections Combining the H??????? and H???ZZ*???4??? Decay Channels at s\sqrt{s}=8??????TeV with the ATLAS Detector

Measurements of the total and differential cross sections of Higgs boson production are performed using 20.3~fb$^{-1}$ of $pp$ collisions produced by the Large Hadron Collider at a center-of-mass energy of $\sqrt{s} = 8$ TeV and recorded by the ATLAS detector. Cross sections are obtained from measured $H \rightarrow \gamma \gamma$ and $H \rightarrow ZZ ^{*}\rightarrow 4\ell$ event yields, which are combined accounting for detector efficiencies, fiducial acceptances and branching fractions. Differential cross sections are reported as a function of Higgs boson transverse momentum, Higgs boson rapidity, number of jets in the event, and transverse momentum of the leading jet. The total production cross section is determined to be $\sigma_{pp \to H} = 33.0 \pm 5.3 \, ({\rm stat}) \pm 1.6 \, ({\rm sys}) \mathrm{pb}$. The measurements are compared to state-of-the-art predictions.Measurements of the total and differential cross sections of Higgs boson production are performed using 20.3  fb-1 of pp collisions produced by the Large Hadron Collider at a center-of-mass energy of s=8  TeV and recorded by the ATLAS detector. Cross sections are obtained from measured H→γγ and H→ZZ*→4ℓ event yields, which are combined accounting for detector efficiencies, fiducial acceptances, and branching fractions. Differential cross sections are reported as a function of Higgs boson transverse momentum, Higgs boson rapidity, number of jets in the event, and transverse momentum of the leading jet. The total production cross section is determined to be σpp→H=33.0±5.3 (stat)±1.6 (syst)  pb. The measurements are compared to state-of-the-art predictions.Measurements of the total and differential cross sections of Higgs boson production are performed using 20.3 fb$^{-1}$ of $pp$ collisions produced by the Large Hadron Collider at a center-of-mass energy of $\sqrt{s} = 8$ TeV and recorded by the ATLAS detector. Cross sections are obtained from measured $H \rightarrow \gamma \gamma$ and $H \rightarrow ZZ ^{*}\rightarrow 4\ell$ event yields, which are combined accounting for detector efficiencies, fiducial acceptances and branching fractions. Differential cross sections are reported as a function of Higgs boson transverse momentum, Higgs boson rapidity, number of jets in the event, and transverse momentum of the leading jet. The total production cross section is determined to be $\sigma_{pp \to H} = 33.0 \pm 5.3 \, ({\rm stat}) \pm 1.6 \, ({\rm sys}) \mathrm{pb}$. The measurements are compared to state-of-the-art predictions