Behaviour of adipose-derived canine mesenchymal stem cells after superparamagnetic iron oxide nanoparticles labelling for magnetic resonance imaging

Background: Therapy with mesenchymal stem cells (MSCs) has been reported to provide beneficial effects in the treatment of neurological and orthopaedic disorders in dogs. The exact mechanism of action is poorly understood. Magnetic resonance imaging (MRI) gives the opportunity to observe MSCs after clinical administration. To visualise MSCs with the help of MRI, labelling with an MRI contrast agent is necessary. However, it must be clarified whether there is any negative influence on cell function and viability after labelling prior to clinical administration. Results: For the purpose of the study, seven samples with canine adipose-derived stem cells were incubated with superparamagnetic iron oxide nanoparticles (SPIO: 319.2 µg/mL Fe) for 24 h. The internalisation of the iron particles occurred via endocytosis. SPIO particles were localized as free clusters in the cytoplasm or within lysosomes depending on the time of investigation. The efficiency of the labelling was investigated using Prussian blue staining and MACS assay. After 3 weeks the percentage of SPIO labelled canine stem cells decreased. Phalloidin staining showed no negative effect on the cytoskeleton. Labelled cells underwent osteogenic and adipogenic differentiation. Chondrogenic differentiation occurred to a lesser extent compared with a control sample. MTT-Test and wound healing assay showed no influence of labelling on the proliferation. The duration of SPIO labelling was assessed using a 1 Tesla clinical MRI scanner and T2 weighted turbo spin echo and T2 weighted gradient echo MRI sequences 1, 2 and 3 weeks after labelling. The hypointensity caused by SPIO lasted for 3 weeks in both sequences. Conclusions: An Endorem labelling concentration of 319.2 µg/mL Fe (448 µg/mL SPIO) had no adverse effects on the viability of canine ASCs. Therefore, this contrast agent could be used as a model for iron oxide labelling agents. However, the tracking ability in vivo has to be evaluated in further studies

Eine Analyse der verschiedenen Charaktere in ausgewählten Romanen von Nagib Machfus

Die Arbeit befasst sich mit Charakteranalysen aus drei verschiedenen Romanen. Des Weiteren beinhaltet sie einen Charaktervergleich und die Veränderungen, die die Charaktere im Laufe ihres Lebens durchlaufen. Auch kommt es zu Interpretationen bezüglich der fiktiven Romanfiguren und mit dem Lebenslauf des Autors, sowie der politischen Situation und dem gesellschaftlichen Leben zur Zeit, in der die Romane "spielen" und der tatsächlichen Situation in Ägypten

Comparison of the endocranial- and brain volumes in brachycephalic dogs, mesaticephalic dogs and Cavalier King Charles spaniels in relation to their body weight

BACKGROUND: A number of studies have attempted to quantify the relative volumes of the endocranial volume and brain parenchyma in association with the pathogenesis of the Chiari-like malformation (CLM) in the Cavalier King Charles spaniel (CKCS). In our study we examine the influence of allometric scaling of the brain and cranial cavity volume on morphological parameters in different dog breeds. MRI scans of 110 dogs (35 mesaticephalic dogs, 35 brachycephalic dogs, 20 CKCSs with SM, and 20 CKCSs without SM) have been used to create 3-dimensional volumetric models of skull and brain parts. Volumes were related to body weight calculating the adjusted means for different breeds. RESULTS: There was a strong global dependency of all volumes to body weight (P<0.0001). The adjusted means of the absolute and relative volumes of brain parenchyma and cranial compartments are not significantly larger in CKCSs in comparison to brachycephalic and mesaticephalic dogs. A difference in absolute or relative volumes between CKCSs with and without SM after relating these values to body weight could not be identified. The relative volume of the hindbrain parenchyma (caudal fossa parenchyma percentage) was larger in brachycephalic dogs than in CKCSs, without causing herniation or SM. CONCLUSION: An influence of body weight exist in dogs, which can be sufficiently large to render conclusions on the difference in volumes of the brain and skull unsafe unless some account of the body weight is taken in the analysis. The results of this study challenge the role of overcrowding for the development of SM in dogs

Jobnomaden

Viele Jobs erfordern heute ein hohes Maß an Mobilität und Flexibilität. Insbesondere Saisonarbeiter, Erntehelfer, Pflegepersonal sowie Arbeiter auf Großbaustellen benötigen temporäre Wohnräume um ihrer Tätigkeit nachzukommen. Wie sehen die Lebenswelten dieser Jobnomaden aus? Welche Anforderung stellen sie an ihren Wohnraum und ihre Umgebung? Welche Rolle spielen die Arbeitgeber? Gibt es Unterschiede zwischen Stadt und Land? Das arch.lab ist eine Plattform für Forschung in der Lehre an der Fakultät Architektur. Es hat die Aufgabe, forschungsorientiertes Studieren und Lehren im Kontext der Studiengänge Architektur und der Kunstgeschichte zu entwickeln und zu fördern. Je Studienjahr vergibt das arch.lab bis zu sechs Förderungen an Seminarkonzepte der Fakultät, die für das neu eingeführte Modul „Forschungsfelder“ im Masterstudiengang Architektur entwickelt werden

Modeling of biocatalytic reactions: A workflow for model calibration, selection and validation using Bayesian statistics

We present a workflow for kinetic modeling of biocatalytic reactions which combines methods from Bayesian learning and uncertainty quantification for model calibration, model selection, evaluation, and model reduction in a consistent statistical framework. Our workflow is particularly tailored to sparse data settings in which a considerable variability of the parameters remains after the models have been adapted to available data, a ubiquitous problem in many real‐world applications. Our workflow is exemplified on an enzyme‐catalyzed two‐substrate reaction mechanism describing the symmetric carboligation of 3,5‐dimethoxy‐benzaldehyde to (R )‐3,3′,5,5′‐tetramethoxybenzoin catalyzed by benzaldehyde lyase from Pseudomonas fluorescens . Results indicate a substrate‐dependent inactivation of enzyme, which is in accordance with other recent studies

Simulation of Organ Patterning on the Floral Meristem Using a Polar Auxin Transport Model

An intriguing phenomenon in plant development is the timing and positioning of lateral organ initiation, which is a fundamental aspect of plant architecture. Although important progress has been made in elucidating the role of auxin transport in the vegetative shoot to explain the phyllotaxis of leaf formation in a spiral fashion, a model study of the role of auxin transport in whorled organ patterning in the expanding floral meristem is not available yet. We present an initial simulation approach to study the mechanisms that are expected to play an important role. Starting point is a confocal imaging study of Arabidopsis floral meristems at consecutive time points during flower development. These images reveal auxin accumulation patterns at the positions of the organs, which strongly suggests that the role of auxin in the floral meristem is similar to the role it plays in the shoot apical meristem. This is the basis for a simulation study of auxin transport through a growing floral meristem, which may answer the question whether auxin transport can in itself be responsible for the typical whorled floral pattern. We combined a cellular growth model for the meristem with a polar auxin transport model. The model predicts that sepals are initiated by auxin maxima arising early during meristem outgrowth. These form a pre-pattern relative to which a series of smaller auxin maxima are positioned, which partially overlap with the anlagen of petals, stamens, and carpels. We adjusted the model parameters corresponding to properties of floral mutants and found that the model predictions agree with the observed mutant patterns. The predicted timing of the primordia outgrowth and the timing and positioning of the sepal primordia show remarkable similarities with a developing flower in nature

Breaking Up the C Complex Spliceosome Shows Stable Association of Proteins with the Lariat Intron Intermediate

Spliceosome assembly requires several structural rearrangements to position the components of the catalytic core. Many of these rearrangements involve successive strengthening and weakening of different RNA∶RNA and RNA∶proteins interactions within the complex. To gain insight into the organization of the catalytic core of the spliceosome arrested between the two steps of splicing chemistry (C complex), we investigated the effects of exposing C complex to low concentrations of urea. We find that in the presence of 3M urea C complex separates into at least three sub-complexes. One sub-complex contains the 5′exon, another contains the intron-lariat intermediate, and U2/U5/U6 snRNAs likely comprise a third sub-complex. We purified the intron-lariat intermediate sub-complex and identified several proteins, including U2 snRNP and PRP19 complex (NTC) components. The data from our study indicate that U2 snRNP proteins in C complex are more stably associated with the lariat-intron intermediate than the U2 snRNA. The results also suggest a set of candidate proteins that hold the lariat-intron intermediate together in C complex. This information is critical for further interpreting the complex architecture of the mammalian spliceosome

Drug Metabolism of Hepatocyte-like Organoids and Their Applicability in In Vitro Toxicity Testing

Emerging advances in the field of in vitro toxicity testing attempt to meet the need for reliable human-based safety assessment in drug development. Intrahepatic cholangiocyte organoids (ICOs) are described as a donor-derived in vitro model for disease modelling and regenerative medicine. Here, we explored the potential of hepatocyte-like ICOs (HL-ICOs) in in vitro toxicity testing by exploring the expression and activity of genes involved in drug metabolism, a key determinant in drug-induced toxicity, and the exposure of HL-ICOs to well-known hepatotoxicants. The current state of drug metabolism in HL-ICOs showed levels comparable to those of PHHs and HepaRGs for CYP3A4; however, other enzymes, such as CYP2B6 and CYP2D6, were expressed at lower levels. Additionally, EC50 values were determined in HL-ICOs for acetaminophen (24.0–26.8 mM), diclofenac (475.5–>500 µM), perhexiline (9.7–>31.5 µM), troglitazone (23.1–90.8 µM), and valproic acid (>10 mM). Exposure to the hepatotoxicants showed EC50s in HL-ICOs comparable to those in PHHs and HepaRGs; however, for acetaminophen exposure, HL-ICOs were less sensitive. Further elucidation of enzyme and transporter activity in drug metabolism in HL-ICOs and exposure to a more extensive compound set are needed to accurately define the potential of HL-ICOs in in vitro toxicity testing