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Now showing 1 - 10 of 47
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    Artificial micro-cinderella based on self-propelled micromagnets for the active separation of paramagnetic particles
    (Cambridge : RSC, 2013) Zhao, G.; Wang, H.; Sanchez, S.; Schmidt, O.G.; Pumera, M.
    In this work, we will show that ferromagnetic microjets can pick-up paramagnetic beads while not showing any interaction with diamagnetic silica microparticles for the active separation of microparticles in solution.
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    Real-time image processing for label-free enrichment of Actinobacteria cultivated in picolitre droplets
    (London [u.a.] : Royal Society of Chemistry, 2013) Zang, E.; Brandes, S.; Tovar, M.; Martin, K.; Mech, F.; Horbert, P.; Henkel, T.; Figge, M.T.; Roth, M.
    The majority of today's antimicrobial therapeutics is derived from secondary metabolites produced by Actinobacteria. While it is generally assumed that less than 1% of Actinobacteria species from soil habitats have been cultivated so far, classic screening approaches fail to supply new substances, often due to limited throughput and frequent rediscovery of already known strains. To overcome these restrictions, we implement high-throughput cultivation of soil-derived Actinobacteria in microfluidic pL-droplets by generating more than 600000 pure cultures per hour from a spore suspension that can subsequently be incubated for days to weeks. Moreover, we introduce triggered imaging with real-time image-based droplet classification as a novel universal method for pL-droplet sorting. Growth-dependent droplet sorting at frequencies above 100 Hz is performed for label-free enrichment and extraction of microcultures. The combination of both cultivation of Actinobacteria in pL-droplets and real-time detection of growing Actinobacteria has great potential in screening for yet unknown species as well as their undiscovered natural products.
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    Time-resolved photoelectron spectroscopy of adenine and adenosine in aqueous solution
    (London [u.a.] : Royal Society of Chemistry, 2013) Buchner, F.; Ritze, H.-H.; Lahl, J.; Lübcke, A.
    Time-resolved photoelectron spectroscopy is applied to study the excited state dynamics of the DNA base adenine and its ribonucleoside adenosine in aqueous solution for pump and probe photon energies in the range between 4.66 eV and 5.21 eV. We follow the evolution of the prepared excited state on the potential energy surface and retrieve lifetimes of the S1 state under different excitation conditions.
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    Charge isomers of myelin basic protein: Structure and interactions with membranes, nucleotide analogues, and calmodulin
    (San Francisco, CA : Public Library of Science, 2011) Wang, C.; Neugebauer, U.; Bürck, J.; Myllykoski, M.; Baumgärtel, P.; Popp, J.; Kursula, P.
    As an essential structural protein required for tight compaction of the central nervous system myelin sheath, myelin basic protein (MBP) is one of the candidate autoantigens of the human inflammatory demyelinating disease multiple sclerosis, which is characterized by the active degradation of the myelin sheath. In this work, recombinant murine analogues of the natural C1 and C8 charge components (rmC1 and rmC8), two isoforms of the classic 18.5-kDa MBP, were used as model proteins to get insights into the structure and function of the charge isomers. Various biochemical and biophysical methods such as size exclusion chromatography, calorimetry, surface plasmon resonance, small angle X-ray and neutron scattering, Raman and fluorescence spectroscopy, and conventional as well as synchrotron radiation circular dichroism were used to investigate differences between these two isoforms, both from the structural point of view, and regarding interactions with ligands, including calmodulin (CaM), various detergents, nucleotide analogues, and lipids. Overall, our results provide further proof that rmC8 is deficient both in structure and especially in function, when compared to rmC1. While the CaM binding properties of the two forms are very similar, their interactions with membrane mimics are different. CaM can be used to remove MBP from immobilized lipid monolayers made of synthetic lipids - a phenomenon, which may be of relevance for MBP function and its regulation. Furthermore, using fluorescently labelled nucleotides, we observed binding of ATP and GTP, but not AMP, by MBP; the binding of nucleoside triphosphates was inhibited by the presence of CaM. Together, our results provide important further data on the interactions between MBP and its ligands, and on the differences in the structure and function between MBP charge isomers.
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    Out of the lab and into the bathroom: Evening short-term exposure to conventional light suppresses melatonin and increases alertness perception
    (Basel : MDPI AG, 2013) Wahnschaffe, A.; Haedel, S.; Rodenbeck, A.; Stoll, C.; Rudolph, H.; Kozakov, R.; Schoepp, H.; Kunz, D.
    Life in 24-h society relies on the use of artificial light at night that might disrupt synchronization of the endogenous circadian timing system to the solar day. This could have a negative impact on sleep-wake patterns and psychiatric symptoms. The aim of the study was to investigate the influence of evening light emitted by domestic and work place lamps in a naturalistic setting on melatonin levels and alertness in humans. Healthy subjects (6 male, 3 female, 22-33 years) were exposed to constant dim light (<10 lx) for six evenings from 7:00 p.m. to midnight. On evenings 2 through 6, 1 h before habitual bedtime, they were also exposed to light emitted by 5 different conventional lamps for 30 min. Exposure to yellow light did not alter the increase of melatonin in saliva compared to dim light baseline during (38 ± 27 pg/mL vs. 39 ± 23 pg/mL) and after light exposure (39 ± 22 pg/mL vs. 44 ± 26 pg/mL). In contrast, lighting conditions including blue components reduced melatonin increase significantly both during (office daylight white: 25 ± 16 pg/mL, bathroom daylight white: 24 ± 10 pg/mL, Planon warm white: 26 ± 14 pg/mL, hall daylight white: 22 ± 14 pg/mL) and after light exposure (office daylight white: 25 ± 15 pg/mL, bathroom daylight white: 23 ± 9 pg/mL, Planon warm white: 24 ± 13 pg/mL, hall daylight white: 22 ± 26 pg/mL). Subjective alertness was significantly increased after exposure to three of the lighting conditions which included blue spectral components in their spectra. Evening exposure to conventional lamps in an everyday setting influences melatonin excretion and alertness perception within 30 min.
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    Bio-responsive polymer hydrogels homeostatically regulate blood coagulation
    (London : Nature Publishing Group, 2013) Maitz, Manfred F.; Freudenberg, U.; Tsurkan, M.V.; Fischer, M.; Beyrich, T.; Werner, C.
    Bio-responsive polymer architectures can empower medical therapies by engaging molecular feedback-response mechanisms resembling the homeostatic adaptation of living tissues to varying environmental constraints. Here we show that a blood coagulation-responsive hydrogel system can deliver heparin in amounts triggered by the environmental levels of thrombin, the key enzyme of the coagulation cascade, which - in turn - becomes inactivated due to released heparin. The bio-responsive hydrogel quantitatively quenches blood coagulation over several hours in the presence of pro-coagulant stimuli and during repeated incubation with fresh, non-anticoagulated blood. These features enable the introduced material to provide sustainable, autoregulated anticoagulation, addressing a key challenge of many medical therapies. Beyond that, the explored concept may facilitate the development of materials that allow the effective and controlled application of drugs and biomolecules.
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    The plant phenological online database (PPODB): An online database for long-term phenological data
    (Heidelberg : Springer Verlag, 2013) Dierenbach, J.; Badeck, F.-W.; Schaber, J.
    We present an online database that provides unrestricted and free access to over 16 million plant phenological observations from over 8,000 stations in Central Europe between the years 1880 and 2009. Unique features are (1) a flexible and unrestricted access to a full-fledged database, allowing for a wide range of individual queries and data retrieval, (2) historical data for Germany before 1951 ranging back to 1880, and (3) more than 480 curated long-term time series covering more than 100 years for individual phenological phases and plants combined over Natural Regions in Germany. Time series for single stations or Natural Regions can be accessed through a user-friendly graphical geo-referenced interface. The joint databases made available with the plant phenological database PPODB render accessible an important data source for further analyses of long-term changes in phenology. The database can be accessed via www.ppodb.de.
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    Structure formation of ultrathin PEO films at solid interfaces-complex pattern formation by dewetting and crystallization
    (Basel : MDPI AG, 2013) Braun, H.-G.; Meyer, E.
    The direct contact of ultrathin polymer films with a solid substrate may result in thin film rupture caused by dewetting. With crystallisable polymers such as polyethyleneoxide (PEO), molecular self-assembly into partial ordered lamella structures is studied as an additional source of pattern formation. Morphological features in ultrathin PEO films (thickness < 10 nm) result from an interplay between dewetting patterns and diffusion limited growth pattern of ordered lamella growing within the dewetting areas. Besides structure formation of hydrophilic PEO molecules, n-alkylterminated (hydrophobic) PEO oligomers are investigated with respect to self-organization in ultrathin films. Morphological features characteristic for pure PEO are not changed by the presence of the n-alkylgroups.
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    Anti-Prion Drug mPPIg5 Inhibits PrPC Conversion to PrPSc
    (San Francisco, CA : Public Library of Science, 2013) McCarthy, J.M.; Franke, M.; Resenberger, U.K.; Waldron, S.; Simpson, J.C.; Tatzelt, J.; Appelhans, D.; Rogers, M.S.
    Prion diseases, also known as transmissible spongiform encephalopathies, are a group of fatal neurodegenerative diseases that include scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle and Creutzfeldt-Jakob disease (CJD) in humans. The 'protein only hypothesis' advocates that PrPSc, an abnormal isoform of the cellular protein PrPC, is the main and possibly sole component of prion infectious agents. Currently, no effective therapy exists for these diseases at the symptomatic phase for either humans or animals, though a number of compounds have demonstrated the ability to eliminate PrPSc in cell culture models. Of particular interest are synthetic polymers known as dendrimers which possess the unique ability to eliminate PrPSc in both an intracellular and in vitro setting. The efficacy and mode of action of the novel anti-prion dendrimer mPPIg5 was investigated through the creation of a number of innovative bio-assays based upon the scrapie cell assay. These assays were used to demonstrate that mPPIg5 is a highly effective anti-prion drug which acts, at least in part, through the inhibition of PrPC to PrPSc conversion. Understanding how a drug works is a vital component in maximising its performance. By establishing the efficacy and method of action of mPPIg5, this study will help determine which drugs are most likely to enhance this effect and also aid the design of dendrimers with anti-prion capabilities for the future.
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    In vitro model of metastasis to bone marrow mediates prostate cancer castration resistant growth through paracrine and extracellular matrix factors
    (San Francisco, CA : Public Library of Science, 2012) Lescarbeau, R.M.; Seib, F.P.; Prewitz, M.; Werner, C.; Kaplan, D.L.
    The spread of prostate cancer cells to the bone marrow microenvironment and castration resistant growth are key steps in disease progression and significant sources of morbidity. However, the biological significance of mesenchymal stem cells (MSCs) and bone marrow derived extracellular matrix (BM-ECM) in this process is not fully understood. We therefore established an in vitro engineered bone marrow tissue model that incorporates hMSCs and BM-ECM to facilitate mechanistic studies of prostate cancer cell survival in androgen-depleted media in response to paracrine factors and BM-ECM. hMSC-derived paracrine factors increased LNCaP cell survival, which was in part attributed to IGFR and IL6 signaling. In addition, BM-ECM increased LNCaP and MDA-PCa-2b cell survival in androgen-depleted conditions, and induced chemoresistance and morphological changes in LNCaPs. To determine the effect of BM-ECM on cell signaling, the phosphorylation status of 46 kinases was examined. Increases in the phosphorylation of MAPK pathway-related proteins as well as sustained Akt phosphorylation were observed in BM-ECM cultures when compared to cultures grown on plasma-treated polystyrene. Blocking MEK1/2 or the PI3K pathway led to a significant reduction in LNCaP survival when cultured on BM-ECM in androgen-depleted conditions. The clinical relevance of these observations was determined by analyzing Erk phosphorylation in human bone metastatic prostate cancer versus non-metastatic prostate cancer, and increased phosphorylation was seen in the metastatic samples. Here we describe an engineered bone marrow model that mimics many features observed in patients and provides a platform for mechanistic in vitro studies.