Deoxynivalenol (DON) is one of the most abundant mycotoxins contaminating food and feed worldwide. Upon absorption, the major portion of the toxin is excreted by humans and animal species as ...glucuronide. However, consistent in vitro data on DON glucuronidation are lacking. In the present study, the metabolism of DON was investigated using liver microsomes from humans and six different animal species. It was shown that all animal and human liver microsomes led to the formation of up to three different mono-O-glucuronides with significant interspecies differences. While the activity of human liver microsomes was low (0.8 to 2.2 pmol·min–1·mg–1), bovine liver and rat liver microsomes conjugated DON with activities of 525 pmol·min–1·mg–1 and 80 pmol·min–1·mg–1, respectively.
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isolates have become resistant to antibiotics like carbapenem. As a consequence,
ranks in the top three of pathogens for which the development of novel antibiotics is the most crucial. ...The pathogen causes both acute and chronic infections, especially in patients who are the most vulnerable. Therefore, efforts are urgently needed to develop alternative therapies. One path explored in this article is the use of bacteriophages and, more specifically, phage-derived proteins. In this study, a phage-derived protein was studied that impacts key virulence factors of the pathogen via interaction with multiple histidine kinases of TCSs. The fundamental insights gained for this protein can therefore serve as inspiration for the development of an anti-virulence compound that targets the bacterial TCS.
Ergot alkaloids are mycotoxins formed by fungi of the Claviceps genus, which are some of the most common contaminants of food and feed worldwide. These toxins are a structurally heterogeneous group ...of compounds, sharing an ergoline backbone. Six structures and their corresponding stereoisomers are typically quantified by either HPLC-FLD or HPLC-MS/MS and the values subsequently summed up to determine the total ergot alkaloid content. For the development of a screening method targeting all ergot alkaloids simultaneously, the alkaloids need to be transferred to one homogeneous structure: a lysergic acid derivative. In this study, two promising cleaving methods—acidic esterification and hydrazinolysis—are compared, using dihydroergocristine as a model compound. While the acidic esterification proved to be unsuitable, due to long reaction times and oxidation sensitivity, hydrazinolysis reached a quantitative yield in 40‒60 min. Parallel workup of several samples is possible. An increasing effect on the reaction rate by the addition of ammonium iodide was demonstrated. Application of hydrazinolysis to a major ergot alkaloid mix solution showed that all ergopeptines were cleaved, but ergometrine/-inine was barely affected. Still, hydrazinolysis is a suitable tool for the development of a sum parameter screening method for ergot alkaloids in food and feed.
Avascular meniscus tears show poor intrinsic regenerative potential. Thus, lesions within this area predispose the patient to developing knee osteoarthritis. Current research focuses on regenerative ...approaches using growth factors or mesenchymal stem cells (MSCs) to enhance healing capacity within the avascular meniscus zone. The use of MSCs especially as progenitor cells and a source of growth factors has shown promising results. However, present studies use bone-marrow-derived BMSCs in a two-step procedure, which is limiting the transfer in clinical praxis. So, the aim of this study was to evaluate a one-step procedure using bone marrow aspirate concentrate (BMAC), containing BMSCs, for inducing the regeneration of avascular meniscus lesions. Longitudinal meniscus tears of 4 mm in size of the lateral New Zealand White rabbit meniscus were treated with clotted autologous PRP (platelet-rich plasma) or BMAC and a meniscus suture or a meniscus suture alone. Menisci were harvested at 6 and 12 weeks after initial surgery. Macroscopical and histological evaluation was performed according to an established Meniscus Scoring System. BMAC significantly enhanced regeneration of the meniscus lesions in a time-dependent manner and in comparison to the PRP and control groups, where no healing could be observed. Treatment of avascular meniscus lesions with BMAC and meniscus suturing seems to be a promising approach to promote meniscus regeneration in the avascular zone using a one-step procedure.
In vitro chondrogenically differentiated mesenchymal stem cells (MSCs) have a tendency to undergo hypertrophy, mirroring the fate of transient "chondrocytes" in the growth plate. As hypertrophy would ...result in ossification, this fact limits their use in cartilage tissue engineering applications. During limb development, retinoic acid receptor (RAR) signaling exerts an important influence on cell fate of mesenchymal progenitors. While retinoids foster hypertrophy, suppression of RAR signaling seems to be required for chondrogenic differentiation. Therefore, we hypothesized that treatment of chondrogenically differentiating hMSCs with the RAR inverse agonist, BMS204,493 (further named BMS), would attenuate hypertrophy. We induced hypertrophy in chondrogenic precultured MSC pellets by the addition of bone morphogenetic protein 4. Direct activation of the RAR pathway by application of the physiological RAR agonist retinoic acid (RA) further enhanced the hypertrophic phenotype. However, BMS treatment reduced hypertrophic conversion in hMSCs, shown by decreased cell size, number of hypertrophic cells, and collagen type X deposition in histological analyses. BMS effects were dependent on the time point of application and strongest after early treatment during chondrogenic precultivation. The possibility of modifing hypertrophic cartilage via attenuation of RAR signaling by BMS could be helpful in producing stable engineered tissue for cartilage regeneration.
In order to achieve a high renewable share in the electricity system, a significant expansion of cross-border exchange capacities is planned. Historically, the actual expansion of interconnector ...capacities has significantly lagged behind the planned expansion. This study examines the impact that such continued delays would have when compared to a strong interconnector expansion in an ambitious energy transition scenario. For this purpose, scenarios for the years 2030, 2040, and 2050 are examined using the electricity market model PowerFlex EU. The analysis reveals that both CO2 emissions and variable costs of electricity generation increase if interconnector expansion is delayed. This effect is most significant in the scenario year 2050, where lower connectivity leads roughly to a doubling of both CO2 emissions and variable costs of electricity generation. This increase results from a lower level of European electricity trading, a curtailment of electricity from a renewable energy source (RES-E), and a corresponding higher level of conventional electricity generation. Most notably, in Southern and Central Europe, less interconnection leads to higher use of natural gas power plants since less renewable electricity from Northern Europe can be integrated into the European grid.
Individual in situ polymerized fluorene chains 10—100 nm long linked by C—C bonds are pulled verticaly from an Au(111) substrate by the tip of a low-temperature atomic force microscope. The ...conformation of the selected chains is imaged before and after manipulation using scanning tunneling microscopy. The measured force gradient shows strong and periodic variations that correspond to the step-by-step detachment of individual fluorene repeat units. These variations persist at constant intensity until the entire polymer is completely removed from the surface. Calculations based on an extended Frenkel—Kontorova model reproduce the periodicity and magnitude of these features and allow us to relate them to the detachment force and desorption energy of the repeat units. The adsorbed part of the polymer slides easily along the surface during the pulling process, leading to only small oscillations as a result of the high stiffness of the fluorenes and of their length mismatch with respect to the substrate surface structure. A significant lateral force also is caused by the sequential detachment of individual units. The gained insight into the molecule—surface interactions during sliding and pulling should aid the design of mechanoresponsive nanosystems and devices.
Phomopsin A (PHO-A), produced by the fungus Diaporthe toxica, is a mycotoxin known to be responsible for fatal liver disease of lupin-fed sheep. The full spectrum of the toxic secondary metabolites ...produced by D. toxica is still unknown. PHO-A and the naturally occurring derivatives B–E have been subject to several studies to reveal their structures as well as chemical and toxicological properties. In this work, a methylated derivative (1) of PHO-A isolated from lupin seeds inoculated with D. toxica is described. It was characterized by high-resolution mass and NMR data and shown to be the N-methylated derivative of PHO-A. 1 is cytotoxic against HepG2 cells.
Agriculture is one of the major sectors of the global economy and also a software-intensive domain. The digital landscape of agriculture is composed of multiple digital ecosystems, which together ...constitute an agricultural domain ecosystem, also referred to as the “Agricultural Data Space’’ (ADS). As the domain is so huge, there are several sub-domains and specialized solutions, and each of them poses challenges to interoperability. Additionally, farmers have increasing concerns about data sovereignty. In the context of the research project COGNAC, we elicited architecture drivers for interoperability and data sovereignty in agriculture and designed a reference architecture of a platform that aims to address these qualities in the ADS. In this paper, we present the solution concepts and design decisions that characterize the reference architecture. Early prototypes have been developed and made available to support the validation of the concept.
Bacterial populations are highly adaptive. They can respond to stress and survive in shifting environments. How the behaviours of individual bacteria vary during stress, however, is poorly ...understood. To identify and characterize rare bacterial subpopulations, technologies for single-cell transcriptional profiling have been developed. Existing approaches show some degree of limitation, for example, in terms of number of cells or transcripts that can be profiled. Due in part to these limitations, few conditions have been studied with these tools. Here we develop massively-parallel, multiplexed, microbial sequencing (M3-seq)-a single-cell RNA-sequencing platform for bacteria that pairs combinatorial cell indexing with post hoc rRNA depletion. We show that M3-seq can profile bacterial cells from different species under a range of conditions in single experiments. We then apply M3-seq to hundreds of thousands of cells, revealing rare populations and insights into bet-hedging associated with stress responses and characterizing phage infection.
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