Search Results
Modulating Myeloid Immune Cell Migration Using Multivalently Presented Monosaccharide Ligands for Advanced Immunotherapy
2019, Taverno, I., Rodrigo, A.M., Kandziora, M., Kuntz, S., Dernedde, J., Trautwein, C., Tacke, F., Blas-Garcia, A., Bartneck, M.
Due to their importance for the outcome of the inflammatory response, the motile myeloid cells are a focus of novel treatment options. The interplay of selectins and their ligands with leukocytes and endothelial cells, which mediate endothelial attachment and transmigration of immune cells, can be modulated by selectin‐binding structures. Here, a library of selectin‐targeting ligands coupled to either gold, silver, iron oxide nanospheres, or quantum dots of 5–10 nm in size is used to systematically study their impact on immune cell motility. The multivalent presentation of the carbohydrate mimetics results in very low sub‐nanomolar binding to L ‐selectin. Using human primary monocytes, granulocytes, lymphocytes, and macrophages, it is shown that the ligands exhibit only minor effects on uptake, whereas the motility of leukocytes is critically affected as observed in migration assays evaluated by flow cytometry. The carbohydrate mimetic ring structure, sulfation, in particular, and the degree of ligand presentation, are constituents which cohere in this process. Specific carbohydrate ligands can thus selectively regulate leukocyte subsets. These data form the basis for advanced immunotherapy which inhibits the amplification of inflammation by restricting leukocyte influx to injured tissue sites. Furthermore, the targeting ligands may complement existing treatment options for inflammatory diseases.
How to minimize dye-induced perturbations while studying biomembrane structure and dynamics: PEG linkers as a rational alternative
2018, Mobarak, Edouard, Javanainen, Matti, Kulig, Waldemar, Honigmann, Alf, Sezgin, Erdinc, Aho, Noora, Eggeling, Christian, Rog, Tomasz, Vattulainen, Ilpo
Organic dye-tagged lipid analogs are essential for many fluorescence-based investigations of complex membrane structures, especially when using advanced microscopy approaches. However, lipid analogs may interfere with membrane structure and dynamics, and it is not obvious that the properties of lipid analogs would match those of non-labeled host lipids. In this work, we bridged atomistic simulations with super-resolution imaging experiments and biomimetic membranes to assess the performance of commonly used sphingomyelin-based lipid analogs. The objective was to compare, on equal footing, the relative strengths and weaknesses of acyl chain labeling, headgroup labeling, and labeling based on poly-ethyl-glycol (PEG) linkers in determining biomembrane properties. We observed that the most appropriate strategy to minimize dye-induced membrane perturbations and to allow consideration of Brownian-like diffusion in liquid-ordered membrane environments is to decouple the dye from a membrane by a PEG linker attached to a lipid headgroup. Yet, while the use of PEG linkers may sound a rational and even an obvious approach to explore membrane dynamics, the results also suggest that the dyes exploiting PEG linkers interfere with molecular interactions and their dynamics. Overall, the results highlight the great care needed when using fluorescent lipid analogs, in particular accurate controls.
Towards CMOS integrated microfluidics using dielectrophoretic immobilization
2019, Ettehad, Honeyeh Matbaechi, Yadav, Rahul Kumar, Guha, Subhajit, Wenger, Christian
Dielectrophoresis (DEP) is a nondestructive and noninvasive method which is favorable for point-of-care medical diagnostic tests. This technique exhibits prominent relevance in a wide range of medical applications wherein the miniaturized platform for manipulation (immobilization, separation or rotation), and detection of biological particles (cells or molecules) can be conducted. DEP can be performed using advanced planar technologies, such as complementary metal-oxide-semiconductor (CMOS) through interdigitated capacitive biosensors. The dielectrophoretically immobilization of micron and submicron size particles using interdigitated electrode (IDE) arrays is studied by finite element simulations. The CMOS compatible IDEs have been placed into the silicon microfluidic channel. A rigorous study of the DEP force actuation, the IDE’s geometrical structure, and the fluid dynamics are crucial for enabling the complete platform for CMOS integrated microfluidics and detection of micron and submicron-sized particle ranges. The design of the IDEs is performed by robust finite element analyses to avoid time-consuming and costly fabrication processes. To analyze the preliminary microfluidic test vehicle, simulations were first performed with non-biological particles. To produce DEP force, an AC field in the range of 1 to 5 V (peak-to-peak) is applied to the IDE. The impact of the effective external and internal properties, such as actuating DEP frequency and voltage, fluid flow velocity, and IDE’s geometrical parameters are investigated. The IDE based system will be used to immobilize and sense particles simultaneously while flowing through the microfluidic channel. The sensed particles will be detected using the capacitive sensing feature of the biosensor. The sensing and detecting of the particles are not in the scope of this paper and will be described in details elsewhere. However, to provide a complete overview of this system, the working principles of the sensor, the readout detection circuit, and the integration process of the silicon microfluidic channel are briefly discussed. © 2019 by the authors.
A customizable microfluidic platform for medium-throughput modeling of neuromuscular circuits
2019, Bellmann, Jessica, Goswami, Ruchi Y., Girardo, Salvatore, Rein, Nelly, Hosseinzadeh, Zohreh, Hicks, Michael R., Busskamp, Volker, Pyle, April D., Werner, Carsten, Sterneckert, Jared
Neuromuscular circuits (NMCs) are vital for voluntary movement, and effective models of NMCs are needed to understand the pathogenesis of, as well as to identify effective treatments for, multiple diseases, including Duchenne's muscular dystrophy and amyotrophic lateral sclerosis. Microfluidics are ideal for recapitulating the central and peripheral compartments of NMCs, but myotubes often detach before functional NMCs are formed. In addition, microfluidic systems are often limited to a single experimental unit, which significantly limits their application in disease modeling and drug discovery. Here, we developed a microfluidic platform (MFP) containing over 100 experimental units, making it suitable for medium-throughput applications. To overcome detachment, we incorporated a reactive polymer surface allowing customization of the environment to culture different cell types. Using this approach, we identified conditions that enable long-term co-culture of human motor neurons and myotubes differentiated from human induced pluripotent stem cells inside our MFP. Optogenetics demonstrated the formation of functional NMCs. Furthermore, we developed a novel application of the rabies tracing assay to efficiently identify NMCs in our MFP. Therefore, our MFP enables large-scale generation and quantification of functional NMCs for disease modeling and pharmacological drug targeting. © 2019 The Authors
Leben und Werk des Karl Hahn
2017, Mensing, Petra
Von 1905 bis zu seinem Lebensende 1946 stellte der Musiklehrer und Botaniker Karl Hahn eine umfangreiche Sammlung der Mecklenburger Flora insbesondere der Moose in der Umgebung von Neukloster und Grabow zusammen. Neben den noch vorhandenen Belegen hat er diverse Veröffentlichungen im Archiv der Freunde der Naturgeschichte in Mecklenburg hinterlassen, die neben der Beschreibung der einzelnen Funde auch Wanderbeschreibungen und Naturbeobachtungen thematisierten. In diesem Beitrag werden alle von ihm als „Neu für Mecklenburg“ bezeichneten Moosarten erstmals in einer Veröffentlichung zusammengetragen sowie Anregungen für zukünftige Arbeiten gegeben.
PH-Responsive Biohybrid Carrier Material for Phenol Decontamination in Wastewater
2018, Pretscher, Martin, Pineda-Contreras, Beatriz A., Kaiser, Patrick, Reich, Steffen, Schöbel, Judith, Kuttner, Christian, Freitag, Ruth, Fery, Andreas, Schmalz, Holger, Agarwal, Seema
Smart polymers are a valuable platform to protect and control the activity of biological agents over a wide range of conditions, such as low pH, by proper encapsulation. Such conditions are present in olive oil mill wastewater with phenol as one of the most problematic constituents. We show that elastic and pH-responsive diblock copolymer fibers are a suitable carrier for Corynebacterium glutamicum, i.e., bacteria which are known for their ability to degrade phenol. Free C. glutamicum does not survive low pH conditions and fails to degrade phenol at low pH conditions. Our tea-bag like biohybrid system, where the pH-responsive diblock copolymer acts as a protecting outer shell for the embedded bacteria, allows phenol degradation even at low pH. Utilizing a two-step encapsulation process, planktonic cells were first encapsulated in poly(vinyl alcohol) to protect the bacteria against the organic solvents used in the second step employing coaxial electrospinning.
Uncertainty in the measurement of indoor temperature and humidity in naturally ventilated dairy buildings as influenced by measurement technique and data variability
2017, Hempel, Sabrina, König, Marcel, Menz, Christoph, Janke, David, Amon, Barbara, Banhazi, Thomas M., Estellés, Fernando, Amon, Thomas
The microclimatic conditions in dairy buildings affect animal welfare and gaseous emissions. Measurements are highly variable due to the inhomogeneous distribution of heat and humidity sources (related to farm management) and the turbulent inflow (associated with meteorologic boundary conditions). The selection of the measurement strategy (number and position of the sensors) and the analysis methodology adds to the uncertainty of the applied measurement technique. To assess the suitability of different sensor positions, in situations where monitoring in the direct vicinity of the animals is not possible, we collected long-term data in two naturally ventilated dairy barns in Germany between March 2015 and April 2016 (horizontal and vertical profiles with 10 to 5 min temporal resolution). Uncertainties related to the measurement setup were assessed by comparing the device outputs under lab conditions after the on-farm experiments. We found out that the uncertainty in measurements of relative humidity is of particular importance when assessing heat stress risk and resulting economic losses in terms of temperature-humidity index. Measurements at a height of approximately 3 m–3.5 m turned out to be a good approximation for the microclimatic conditions in the animal occupied zone (including the air volume close to the emission active zone). However, further investigation along this cross-section is required to reduce uncertainties related to the inhomogeneous distribution of humidity. In addition, a regular sound cleaning (and if possible recalibration after few months) of the measurement devices is crucial to reduce the instrumentation uncertainty in long-term monitoring of relative humidity in dairy barns. © 2017 The Authors
Footprint-weighted tile approach for a spruce forest and a nearby patchy clearing using the ACASA model
2018, Gatzsche, Kathrin, Babel, Wolfgang, Falge, Eva, Pyles, Rex David, Paw U., Kyaw Tha, Raabe, Armin, Foken, Thomas
The ACASA (Advanced Canopy-Atmosphere-Soil Algorithm) model, with a higher-order closure for tall vegetation, has already been successfully tested and validated for homogeneous spruce forests. The aim of this paper is to test the model using a footprint-weighted tile approach for a clearing with a heterogeneous structure of the underlying surface. The comparison with flux data shows a good agreement with a footprint-aggregated tile approach of the model. However, the results of a comparison with a tile approach on the basis of the mean land use classification of the clearing is not significantly different. It is assumed that the footprint model is not accurate enough to separate small-scale heterogeneities. All measured fluxes are corrected by forcing the energy balance closure of the test data either by maintaining the measured Bowen ratio or by the attribution of the residual depending on the fractions of sensible and latent heat flux to the buoyancy flux. The comparison with the model, in which the energy balance is closed, shows that the buoyancy correction for Bowen ratios > 1.5 better fits the measured data. For lower Bowen ratios, the correction probably lies between the two methods, but the amount of available data was too small to make a conclusion. With an assumption of similarity between water and carbon dioxide fluxes, no correction of the net ecosystem exchange is necessary for Bowen ratios > 1.5.
Printability study of metal ion crosslinked PEG-catechol based inks
2019, Włodarczyk-Biegun, Malgorzata K., Paez, Julieta I., Villiou, Maria, Feng, Jun, del Campo, Aranzazu
Inspired by reversible networks present in nature, we have explored the printability of catechol functionalized polyethylene glycol (PEG) based inks with metal-coordination crosslinking. Material formulations containing Al3+, Fe3+ or V3+ as crosslinking ions were tested. The printability and shape fidelity were dependent on the ink composition (metal ion type, pH, PEG molecular weight) and printing parameters (extrusion pressure and printing speed). The relaxation time, recovery rate and viscosity of the inks were analyzed in rheology studies and correlated with thermodynamic and ligand exchange kinetic constants of the dynamic bonds and the printing performance (i.e. shape fidelity of the printed structures). The relevance of the relaxation time and ligand exchange kinetics for printability was demonstrated. Cells seeded on the crosslinked materials were viable, indicating the potential of the formulations to be used as inks for cell encapsulation. The proposed dynamic ink design offers significant flexibility for 3D (bio)printing, and enables straightforward adjustment of the printable formulation to meet application-specific needs.
A Review on Passive and Integrated Near-Field Microwave Biosensors
2017, Guha, Subhajit, Jamal, Farabi Ibne, Wenger, Christian
In this paper we review the advancement of passive and integrated microwave biosensors. The interaction of microwave with biological material is discussed in this paper. Passive microwave biosensors are microwave structures, which are fabricated on a substrate and are used for sensing biological materials. On the other hand, integrated biosensors are microwave structures fabricated in standard semiconductor technology platform (CMOS or BiCMOS). The CMOS or BiCMOS sensor technology offers a more compact sensing approach which has the potential in the future for point of care testing systems. Various applications of the passive and the integrated sensors have been discussed in this review paper.