TY - JOUR A1 - Shahid, Muhammad A1 - Manchi, G. A1 - Slunsky, Pavel A1 - Naseer, O. A1 - Fatima, A. A1 - Leo, B. A1 - Raila, Jens T1 - A systemic review of existing serological possibilities to diagnose canine osteoarthritis with a particular focus on extracellular matrix proteoglycans and protein JF - Polish journal of veterinary sciences : PJVS : the journal of Committee of Veterinary Sciences of Polish Academy of Sciences and University of Warmia and Mazury in Olsztyn N2 - Extra-cellular matrix (ECM) components are important and their stabilization is significant in maintaining normal healthy joint environment. In osteoarthritis (OA), ECM components are altered and indicate disease progression. The joint ECM is composed of proteoglycans (aggrecan, perlecan,inter α-trypsin inhibitor), glycoproteins (fibronectin, lubricin, COMP) and collagen types (most abundantly collagen type II) which represent structural and functional transformation during disease advancement. ECM investigation revealed significant biomarkers of OA that could be used as a diagnostic and therapeutic tool in different canine orthopedic diseases. This review deliberates our current findings of how the components of ECM change at the molecular level during disease progression in canine OA. KW - extra-cellular matrix KW - canine osteoarthritis KW - biomarker KW - synovial fluid KW - proteomix analysis Y1 - 2017 U6 - https://doi.org/10.1515/pjvs-2017-0024 SN - 1505-1773 SN - 2300-2557 VL - 20 IS - 1 SP - 189 EP - 201 PB - De Gruyter CY - Berlin ER - TY - JOUR A1 - Schulze, Sven A1 - Wehrhold, Michel A1 - Hille, Carsten T1 - Femtosecond-Pulsed laser written and etched fiber bragg gratings for fiber-optical biosensing JF - Sensors N2 - We present the development of a label-free, highly sensitive fiber-optical biosensor for online detection and quantification of biomolecules. Here, the advantages of etched fiber Bragg gratings (eFBG) were used, since they induce a narrowband Bragg wavelength peak in the reflection operation mode. The gratings were fabricated point-by-point via a nonlinear absorption process of a highly focused femtosecond-pulsed laser, without the need of prior coating removal or specific fiber doping. The sensitivity of the Bragg wavelength peak to the surrounding refractive index (SRI), as needed for biochemical sensing, was realized by fiber cladding removal using hydrofluoric acid etching. For evaluation of biosensing capabilities, eFBG fibers were biofunctionalized with a single-stranded DNA aptamer specific for binding the C-reactive protein (CRP). Thus, the CRP-sensitive eFBG fiber-optical biosensor showed a very low limit of detection of 0.82 pg/L, with a dynamic range of CRP detection from approximately 0.8 pg/L to 1.2 mu g/L. The biosensor showed a high specificity to CRP even in the presence of interfering substances. These results suggest that the proposed biosensor is capable for quantification of CRP from trace amounts of clinical samples. In addition, the adaption of this eFBG fiber-optical biosensor for detection of other relevant analytes can be easily realized. KW - fiber Bragg gratings KW - ultra-fast laser inscription KW - fiber etching KW - nanostructure fabrication KW - fiber-optical sensors KW - aptamers KW - C-reactive protein KW - biomarker Y1 - 2018 U6 - https://doi.org/10.3390/s18092844 SN - 1424-8220 VL - 18 IS - 9 PB - MDPI CY - Basel ER - TY - JOUR A1 - Stoessel, Daniel A1 - Schulte, Claudia A1 - dos Santos, Marcia C. Teixeira A1 - Scheller, Dieter A1 - Rebollo-Mesa, Irene A1 - Deuschle, Christian A1 - Walther, Dirk A1 - Schauer, Nicolas A1 - Berg, Daniela A1 - da Costa, Andre Nogueira A1 - Maetzler, Walter T1 - Promising Metabolite Profiles in the Plasma and CSF of Early Clinical JF - Frontiers in Aging Neuroscience N2 - Parkinson's disease (PD) shows high heterogeneity with regard to the underlying molecular pathogenesis involving multiple pathways and mechanisms. Diagnosis is still challenging and rests entirely on clinical features. Thus, there is an urgent need for robust diagnostic biofluid markers. Untargeted metabolomics allows establishing low-molecular compound biomarkers in a wide range of complex diseases by the measurement of various molecular classes in biofluids such as blood plasma, serum, and cerebrospinal fluid (CSF). Here, we applied untargeted high-resolution mass spectrometry to determine plasma and CSF metabolite profiles. We semiquantitatively determined small-molecule levels (<= 1.5 kDa) in the plasma and CSF from early PD patients (disease duration 0-4 years; n = 80 and 40, respectively), and sex-and age-matched controls (n = 76 and 38, respectively). We performed statistical analyses utilizing partial least square and random forest analysis with a 70/30 training and testing split approach, leading to the identification of 20 promising plasma and 14 CSF metabolites. The semetabolites differentiated the test set with an AUC of 0.8 (plasma) and 0.9 (CSF). Characteristics of the metabolites indicate perturbations in the glycerophospholipid, sphingolipid, and amino acid metabolism in PD, which underscores the high power of metabolomic approaches. Further studies will enable to develop a potential metabolite-based biomarker panel specific for PD KW - biomarker KW - untargeted metabolomics KW - neurodegeneration KW - plasma KW - CSF KW - machinelearning Y1 - 2018 U6 - https://doi.org/10.3389/fnagi.2018.00051 SN - 1663-4365 VL - 10 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Stoessel, Daniel A1 - Stellmann, Jan-Patrick A1 - Willing, Anne A1 - Behrens, Birte A1 - Rosenkranz, Sina C. A1 - Hodecker, Sibylle C. A1 - Stuerner, Klarissa H. A1 - Reinhardt, Stefanie A1 - Fleischer, Sabine A1 - Deuschle, Christian A1 - Maetzler, Walter A1 - Berg, Daniela A1 - Heesen, Christoph A1 - Walther, Dirk A1 - Schauer, Nicolas A1 - Friese, Manuel A. A1 - Pless, Ole T1 - Metabolomic Profiles for Primary Progressive Multiple Sclerosis Stratification and Disease Course Monitoring JF - Frontiers in human neuroscienc N2 - Primary progressive multiple sclerosis (PPMS) shows a highly variable disease progression with poor prognosis and a characteristic accumulation of disabilities in patients. These hallmarks of PPMS make it difficult to diagnose and currently impossible to efficiently treat. This study aimed to identify plasma metabolite profiles that allow diagnosis of PPMS and its differentiation from the relapsing remitting subtype (RRMS), primary neurodegenerative disease (Parkinson’s disease, PD), and healthy controls (HCs) and that significantly change during the disease course and could serve as surrogate markers of multiple sclerosis (MS)-associated neurodegeneration over time. We applied untargeted high-resolution metabolomics to plasma samples to identify PPMS-specific signatures, validated our findings in independent sex- and age-matched PPMS and HC cohorts and built discriminatory models by partial least square discriminant analysis (PLS-DA). This signature was compared to sex- and age-matched RRMS patients, to patients with PD and HC. Finally, we investigated these metabolites in a longitudinal cohort of PPMS patients over a 24-month period. PLS-DA yielded predictive models for classification along with a set of 20 PPMS-specific informative metabolite markers. These metabolites suggest disease-specific alterations in glycerophospholipid and linoleic acid pathways. Notably, the glycerophospholipid LysoPC(20:0) significantly decreased during the observation period. These findings show potential for diagnosis and disease course monitoring, and might serve as biomarkers to assess treatment efficacy in future clinical trials for neuroprotective MS therapies. KW - untargeted metabolomics KW - biomarker KW - PPMS KW - MS neurodegeneration KW - LysoPC(20:0) Y1 - 2018 U6 - https://doi.org/10.3389/fnhum.2018.00226 SN - 1662-5161 VL - 12 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Schulze-Makuch, Dirk A1 - Wagner, Dirk A1 - Kounaves, Samuel P. A1 - Mangelsdorf, Kai A1 - Devine, Kevin G. A1 - de Vera, Jean-Pierre A1 - Schmitt-Kopplin, Philippe A1 - Grossart, Hans-Peter A1 - Parro, Victor A1 - Kaupenjohann, Martin A1 - Galy, Albert A1 - Schneider, Beate A1 - Airo, Alessandro A1 - Froesler, Jan A1 - Davila, Alfonso F. A1 - Arens, Felix L. A1 - Caceres, Luis A1 - Cornejo, Francisco Solis A1 - Carrizo, Daniel A1 - Dartnell, Lewis A1 - DiRuggiero, Jocelyne A1 - Flury, Markus A1 - Ganzert, Lars A1 - Gessner, Mark O. A1 - Grathwohl, Peter A1 - Guan, Lisa A1 - Heinz, Jacob A1 - Hess, Matthias A1 - Keppler, Frank A1 - Maus, Deborah A1 - McKay, Christopher P. A1 - Meckenstock, Rainer U. A1 - Montgomery, Wren A1 - Oberlin, Elizabeth A. A1 - Probst, Alexander J. A1 - Saenz, Johan S. A1 - Sattler, Tobias A1 - Schirmack, Janosch A1 - Sephton, Mark A. A1 - Schloter, Michael A1 - Uhl, Jenny A1 - Valenzuela, Bernardita A1 - Vestergaard, Gisle A1 - Woermer, Lars A1 - Zamorano, Pedro T1 - Transitory microbial habitat in the hyperarid Atacama Desert JF - Proceedings of the National Academy of Sciences of the United States of America KW - habitat KW - aridity KW - microbial activity KW - biomarker KW - Mars Y1 - 2018 U6 - https://doi.org/10.1073/pnas.1714341115 SN - 0027-8424 VL - 115 IS - 11 SP - 2670 EP - 2675 PB - National Acad. of Sciences CY - Washington ER - TY - JOUR A1 - Alker, Wiebke A1 - Schwerdtle, Tanja A1 - Schomburg, Lutz A1 - Haase, Hajo T1 - A Zinpyr-1-based Fluorimetric Microassay for Free Zinc in Human Serum JF - International journal of molecular sciences N2 - Zinc is an essential trace element, making it crucial to have a reliable biomarker for evaluating an individual’s zinc status. The total serum zinc concentration, which is presently the most commonly used biomarker, is not ideal for this purpose, but a superior alternative is still missing. The free zinc concentration, which describes the fraction of zinc that is only loosely bound and easily exchangeable, has been proposed for this purpose, as it reflects the highly bioavailable part of serum zinc. This report presents a fluorescence-based method for determining the free zinc concentration in human serum samples, using the fluorescent probe Zinpyr-1. The assay has been applied on 154 commercially obtained human serum samples. Measured free zinc concentrations ranged from 0.09 to 0.42 nM with a mean of 0.22 ± 0.05 nM. It did not correlate with age or the total serum concentrations of zinc, manganese, iron or selenium. A negative correlation between the concentration of free zinc and total copper has been seen for sera from females. In addition, the free zinc concentration in sera from females (0.21 ± 0.05 nM) was significantly lower than in males (0.23 ± 0.06 nM). The assay uses a sample volume of less than 10 µL, is rapid and cost-effective and allows us to address questions regarding factors influencing the free serum zinc concentration, its connection with the body’s zinc status, and its suitability as a future biomarker for an individual’s zinc status. KW - zinc KW - free zinc KW - serum KW - biomarker KW - fluorescent probe KW - Zinypr-1 Y1 - 2019 U6 - https://doi.org/10.3390/ijms20164006 SN - 1661-6596 SN - 1422-0067 VL - 20 IS - 16 PB - MDPI CY - Basel ER - TY - JOUR A1 - Aichner, Bernhard A1 - Makhmudov, Zafar A1 - Rajabov, Iljomjon A1 - Zhang, Qiong A1 - Pausata, Francesco Salvatore R. A1 - Werner, Martin A1 - Heinecke, Liv A1 - Kuessner, Marie L. A1 - Feakins, Sarah J. A1 - Sachse, Dirk A1 - Mischke, Steffen T1 - Hydroclimate in the Pamirs Was Driven by Changes in Precipitation-Evaporation Seasonality Since theLast Glacial Period JF - Geophysical research letters N2 - The Central Asian Pamir Mountains (Pamirs) are a high-altitude region sensitive to climatic change, with only few paleoclimatic records available. To examine the glacial-interglacial hydrological changes in the region, we analyzed the geochemical parameters of a 31-kyr record from Lake Karakul and performed a set of experiments with climate models to interpret the results. delta D values of terrestrial biomarkers showed insolation-driven trends reflecting major shifts of water vapor sources. For aquatic biomarkers, positive delta D shifts driven by changes in precipitation seasonality were observed at ca. 31-30, 28-26, and 17-14 kyr BP. Multiproxy paleoecological data and modelling results suggest that increased water availability, induced by decreased summer evaporation, triggered higher lake levels during those episodes, possibly synchronous to northern hemispheric rapid climate events. We conclude that seasonal changes in precipitation-evaporation balance significantly influenced the hydrological state of a large waterbody such as Lake Karakul, while annual precipitation amount and inflows remained fairly constant. KW - climate KW - biomarker KW - geochemistry KW - modelling KW - paleoclimate KW - hydrology Y1 - 2019 U6 - https://doi.org/10.1029/2019GL085202 SN - 0094-8276 SN - 1944-8007 VL - 46 IS - 23 SP - 13972 EP - 13983 PB - American Geophysical Union CY - Washington ER - TY - JOUR A1 - Liu, Qi A1 - Adler, Karsten A1 - Lipus, Daniel A1 - Kämpf, Horst A1 - Bussert, Robert A1 - Plessen, Birgit A1 - Schulz, Hans-Martin A1 - Krauze, Patryk A1 - Horn, Fabian A1 - Wagner, Dirk A1 - Mangelsdorf, Kai A1 - Alawi, Mashal T1 - Microbial signatures in deep CO2-saturated miocene sediments of the active Hartousov mofette system (NW Czech Republic) JF - Frontiers in microbiology N2 - The Hartousov mofette system is a natural CO2 degassing site in the central Cheb Basin (Eger Rift, Central Europe). In early 2016 a 108 m deep core was obtained from this system to investigate the impact of ascending mantle-derived CO2 on indigenous deep microbial communities and their surrounding life habitat. During drilling, a CO2 blow out occurred at a depth of 78.5 meter below surface (mbs) suggesting a CO2 reservoir associated with a deep low-permeable CO2-saturated saline aquifer at the transition from Early Miocene terrestrial to lacustrine sediments. Past microbial communities were investigated by hopanoids and glycerol dialkyl glycerol tetraethers (GDGTs) reflecting the environmental conditions during the time of deposition rather than showing a signal of the current deep biosphere. The composition and distribution of the deep microbial community potentially stimulated by the upward migration of CO2 starting during Mid Pleistocene time was investigated by intact polar lipids (IPLs), quantitative polymerase chain reaction (qPCR), and deoxyribonucleic acid (DNA) analysis. The deep biosphere is characterized by microorganisms that are linked to the distribution and migration of the ascending CO2-saturated groundwater and the availability of organic matter instead of being linked to single lithological units of the investigated rock profile. Our findings revealed high relative abundances of common soil and water bacteria, in particular the facultative, anaerobic and potential iron-oxidizing Acidovorax and other members of the family Comamonadaceae across the whole recovered core. The results also highlighted the frequent detection of the putative sulfate-oxidizing and CO2-fixating genus Sulfuricurvum at certain depths. A set of new IPLs are suggested to be indicative for microorganisms associated to CO2 accumulation in the mofette system. KW - geo-bio interaction KW - CO2 KW - mofette systems KW - Eger Rift KW - microbial lipid KW - biomarker KW - microbial diversity KW - deep biosphere KW - saline groundwater Y1 - 2020 U6 - https://doi.org/10.3389/fmicb.2020.543260 SN - 1664-302X VL - 11 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Dreymann, Nico A1 - Wuensche, Julia A1 - Sabrowski, Wiebke A1 - Moeller, Anja A1 - Czepluch, Denise A1 - Vu Van, Dana A1 - Füssel, Susanne A1 - Menger, Marcus M. T1 - Inhibition of Human Urokinase-Type Plasminogen Activator (uPA) Enzyme Activity and Receptor Binding by DNA Aptamers as Potential Therapeutics through Binding to the Different Forms of uPA JF - International journal of molecular sciences N2 - Urokinase-type plasminogen activator is widely discussed as a marker for cancer prognosis and diagnosis and as a target for cancer therapies. Together with its receptor, uPA plays an important role in tumorigenesis, tumor progression and metastasis. In the present study, systematic evolution of ligands by exponential enrichment (SELEX) was used to select single-stranded DNA aptamers targeting different forms of human uPA. Selected aptamers allowed the distinction between HMW-uPA and LMW-uPA, and therefore, presumably, have different binding regions. Here, uPAapt-02-FR showed highly affine binding with a K-D of 0.7 nM for HMW-uPA and 21 nM for LMW-uPA and was also able to bind to pro-uPA with a K-D of 14 nM. Furthermore, no cross-reactivity to mouse uPA or tissue-type plasminogen activator (tPA) was measured, demonstrating high specificity. Suppression of the catalytic activity of uPA and inhibition of uPAR-binding could be demonstrated through binding with different aptamers and several of their truncated variants. Since RNA aptamers are already known to inhibit uPA-uPAR binding and other pathological functions of the uPA system, these aptamers represent a novel, promising tool not only for detection of uPA but also for interfering with the pathological functions of the uPA system by additionally inhibiting uPA activity. KW - biomarker KW - cancer KW - cancer therapy KW - DNA aptamer KW - microscale thermophoresis (MST) KW - SELEX KW - surface plasmon resonance spectroscopy (SPR) KW - uPA KW - uPAR KW - urokinase Y1 - 2022 U6 - https://doi.org/10.3390/ijms23094890 SN - 1661-6596 SN - 1422-0067 VL - 23 IS - 9 PB - MDPI CY - Basel ER -