@phdthesis{Stoessel2018, author = {St{\"o}ßel, Daniel}, title = {Biomarker Discovery in Multiple Sclerosis and Parkinson's disease}, school = {Universit{\"a}t Potsdam}, pages = {135}, year = {2018}, abstract = {Neuroinflammatory and neurodegenerative diseases such as Parkinson's (PD) and multiple sclerosis (MS) often result in a severe impairment of the patient´s quality of life. Effective therapies for the treatment are currently not available, which results in a high socio-economic burden. Due to the heterogeneity of the disease subtypes, stratification is particularly difficult in the early phase of the disease and is mainly based on clinical parameters such as neurophysiological tests and central nervous imaging. Due to good accessibility and stability, blood and cerebrospinal fluid metabolite markers could serve as surrogates for neurodegenerative processes. This can lead to an improved mechanistic understanding of these diseases and further be used as "treatment response" biomarkers in preclinical and clinical development programs. Therefore, plasma and CSF metabolite profiles will be identified that allow differentiation of PD from healthy controls, association of PD with dementia (PDD) and differentiation of PD subtypes such as akinetic rigid and tremor dominant PD patients. In addition, plasma metabolites for the diagnosis of primary progressive MS (PPMS) should be investigated and tested for their specificity to relapsing-remitting MS (RRMS) and their development during PPMS progression. By applying untargeted high-resolution metabolomics of PD patient samples and in using random forest and partial least square machine learning algorithms, this study identified 20 plasma metabolites and 14 CSF metabolite biomarkers. These differentiate against healthy individuals with an AUC of 0.8 and 0.9 in PD, respectively. We also identify ten PDD specific serum metabolites, which differentiate against healthy individuals and PD patients without dementia with an AUC of 1.0, respectively. Furthermore, 23 akinetic-rigid specific plasma markers were identified, which differentiate against tremor-dominant PD patients with an AUC of 0.94 and against healthy individuals with an AUC of 0.98. These findings also suggest more severe disease pathology in the akinetic-rigid PD than in tremor dominant PD. In the analysis of MS patient samples a partial least square analysis yielded predictive models for the classification of PPMS and resulted in 20 PPMS specific metabolites. In another MS study unknown changes in human metabolism were identified after administration of the multiple sclerosis drug dimethylfumarate, which is used for the treatment of RRMS. These results allow to describe and understand the hitherto completely unknown mechanism of action of this new drug and to use these findings for the further development of new drugs and targets against RRMS. In conclusion, these results have the potential for improved diagnosis of these diseases and improvement of mechanistic understandings, as multiple deregulated pathways were identified. Moreover, novel Dimethylfumarate targets can be used to aid drug development and treatment efficiency. Overall, metabolite profiling in combination with machine learning identified as a promising approach for biomarker discovery and mode of action elucidation.}, language = {en} } @phdthesis{Schulze2018, author = {Schulze, Sven}, title = {Entwicklung und Charakterisierung optischer Biosensorplattformen basierend auf photonischen Kristallen und Faser-Bragg-Gitter}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-422139}, school = {Universit{\"a}t Potsdam}, pages = {xviii, 149, A-23, B-2, C-8}, year = {2018}, abstract = {In dieser Arbeit steht die Entwicklung einer Sensorplattform f{\"u}r biochemische Anwendungen, welche auf einem optischen Detektionsprinzips beruht, im Vordergrund. W{\"a}hrend der Entwicklung wurden zwei komplement{\"a}re Konzeptideen behandelt, zum einen ein Sensor, der auf photonischen Kristallen und Wellenleiterstrukturen basiert und zum anderen einen faserbasierten Sensor, der chemisch modifizierte Faser-Bragg-Gitter enth{\"a}lt. Das optische Detektionsprinzip in beiden Sensorideen ist die resultierende Brechungsindex{\"a}nderung als messbare physikochemische Kenngr{\"o}ße. Das aus der Natur bekannte Ph{\"a}nomen der photonischen Kristalle, das u. a. bei Opalen und bei Schmetterlingen zu finden ist, wurde bereits 1887 von Lord Rayleigh beschrieben. Er beschrieb die optischen Eigenschaften von periodischen mehrschichtigen Filmen, welche als vereinfachtes Modell eines eindimensionalen photonischen Kristalls verstanden werden k{\"o}nnen. Die Periodizit{\"a}t der Brechungsindex{\"a}nderung resultiert in einem optischen Filter f{\"u}r Frequenzen in einem bestimmten spektralen Bereich, weshalb dann dort keine Lichtausbreitung mehr m{\"o}glich ist. Wird dieses System aber durch eine Defektstelle in der Brechungsindexperiodizit{\"a}t gest{\"o}rt, sodass daraus zwei perfekt periodische Systeme entstehen, ist die Lichtausbreitung f{\"u}r eine bestimmte Frequenz dennoch m{\"o}glich. In der Folge resultiert daraus ein schmalbandiges Signal im Transmissionsspektrum. Die erlaubte Frequenz ist dabei u. a. abh{\"a}ngig vom Brechungsindexunterschied des periodischen Systems, d.h. Ver{\"a}nderung des Brechungsindexes einer Schicht f{\"u}hrt zu einer spektralen Verschiebung der erlaubten Frequenz, dadurch kann dieses Sensorkonzept f{\"u}r biochemische Sensorik ausgenutzt werden [1]. Diese Entwicklung des auf photonischen Kristallen basierenden Sensors war eine Kooperation mit dem Industriepartner „Nanoplus GmbH". In der Doktorarbeit wurden Simulationen und praktischen Arbeiten zur Designentwicklung des Sensors und die Arbeiten an einem ersten Modellaufbau f{\"u}r die biochemischen Anwendungen durchgef{\"u}hrt. F{\"u}r den faserbasierten Sensor wurden Faser-Bragg-Gitter in den Faserkern hineingeschrieben. Hill et al. entdeckten 1978, dass solche Gitterstrukturen genau wie photonische Kristalle als optische Filter fungieren [2]. Die Gitter bestehen dabei aus {\"A}nderungen des Brechungsindexes im Faserkern. Im Laufe der n{\"a}chsten vierzig Jahren wurden verschiedene Einschreibetechniken und Gitterstrukturen entwickelt, weshalb die Eigenschaften der jeweiligen Gitterstrukturen variieren. Eine solche Gitterstruktur sind u. a. die Faser-Bragg-Gitter, deren Gitterperiode, d. h. die Abst{\"a}nde der Brechungsindexmodifikationen, sich im Nanometer- bis Mikrometerbereich befinden. Aufgrund der kleinen Gitterperiode wird eine r{\"u}ckw{\"a}rtsf{\"u}hrende Welle im Kern f{\"u}r eine bestimmte Frequenz bzw. Wellenl{\"a}nge, der Bragg-Wellenl{\"a}nge, erzeugt. Im Endeffekt resultiert daraus ein schmalbandiges Signal sowohl im Transmissionsspektrum, als auch im Reflexionsspektrum. Die Resonanzwellenl{\"a}nge ist dabei proportional zu der Gitterperiode und dem effektiven Brechungsindex, welcher vom Brechungsindex des Kerns und des kernumgebenen Materials abh{\"a}ngig ist. Letztlich eignet sich diese Technik f{\"u}r physikochemische Sensorik. Im Rahmen dieser Arbeit wurden die Gitter mit Hilfe einer relativen neuen Herstellungsmethode in die Fasern geschrieben [3]. Anschließend stand die Entwicklung eines Biosensors im Vordergrund, wobei zun{\"a}chst ein Protokoll zum {\"A}tzen der Faser mit Flusss{\"a}ure entwickelt worden ist, dass das System sensitiv zum umgebenen Brechungsindex macht. Am Ende wurde ein Modellaufbau realisiert, indem ein Modellsystem, hier die Detektion vom C-reaktiven Protein mittels spezifischen einzelstr{\"a}ngigen DNS-Aptameren, erfolgreich getestet und quantifiziert worden ist. 1 Mandal, S.; Erickson, D. Nanoscale Optofluidic Sensor Arrays. Opt. Express 2008, 16 (3), 1623-1631. 2 Hill, K. O.; Fujii, Y.; Johnson, D. C.; Kawasaki, B. S. Photosensitivity in Optical Fiber Waveguides: Application to Reflection Filter Fabrication. Appl. Phys. Lett. 1978, 32 (10), 647-649. 3 Mart{\´i}nez, A.; Dubov, M.; Khrushchev, I.; Bennion, I. Direct Writing of Fibre Bragg Gratings by Femtosecond Laser. Electron. Lett. 2004, 40 (19), 1170.}, language = {de} } @phdthesis{Genderjahn2018, author = {Genderjahn, Steffi}, title = {Biosignatures of Present and Past Microbial Life in Southern African Geoarchives}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-410110}, school = {Universit{\"a}t Potsdam}, pages = {XI, 166, xxii}, year = {2018}, abstract = {Global climate change is one of the greatest challenges of the 21st century, with influence on the environment, societies, politics and economies. The (semi-)arid areas of Southern Africa already suffer from water scarcity. There is a great variety of ongoing research related to global climate history but important questions on regional differences still exist. In southern African regions terrestrial climate archives are rare, which makes paleoclimate studies challenging. Based on the assumption that continental pans (sabkhas) represent a suitable geo-archive for the climate history, two different pans were studied in the southern and western Kalahari Desert. A combined approach of molecular biological and biogeochemical analyses is utilized to investigate the diversity and abundance of microorganisms and to trace temporal and spatial changes in paleoprecipitation in arid environments. The present PhD thesis demonstrates the applicability of pan sediments as a late Quaternary geo-archive based on microbial signature lipid biomarkers, such as archaeol, branched and isoprenoid glycerol dialkyl glycerol tetraethers (GDGTs) as well as phospholipid fatty acids (PLFA). The microbial signatures contained in the sediment provide information on the current or past microbial community from the Last Glacial Maximum to the recent epoch, the Holocene. The results are discussed in the context of regional climate evolution in southwestern Africa. The seasonal shift of the Innertropical Convergence Zone (ITCZ) along the equator influences the distribution of precipitation- and climate zones. The different expansion of the winter- and summer rainfall zones in southern Africa was confirmed by the frequency of certain microbial biomarkers. A period of increased precipitation in the south-western Kalahari could be described as a result of the extension of the winter rainfall zone during the last glacial maximum (21 ± 2 ka). Instead a period of increased paleoprecipitation in the western Kalahari was indicated during the Late Glacial to Holocene transition. This was possibly caused by a southwestern shift in the position of the summer rainfall zone associated to the southward movement of the ITCZ. Furthermore, for the first time this study characterizes the bacterial and archaeal life based on 16S rRNA gene high-throughput sequencing in continental pan sediments and provides an insight into the recent microbial community structure. Near-surface processes play an important role for the modern microbial ecosystem in the pans. Water availability as well as salinity might determine the abundance and composition of the microbial communities. The microbial community of pan sediments is dominated by halophilic and dry-adapted archaea and bacteria. Frequently occurring microorganisms such as, Halobacteriaceae, Bacillus and Gemmatimonadetes are described in more detail in this study.}, language = {en} } @article{FranzOstOttenetal.2018, author = {Franz, Kristina and Ost, Mario and Otten, Lindsey and Herpich, Catrin and Coleman, Verena and Endres, Anne-Sophie and Klaus, Susanne and M{\"u}ller-Werdan, Ursula and Norman, Kristina}, title = {Higher serum levels of fibroblast growth factor 21 in old patients with cachexia}, series = {Nutrition : the international journal of applied and basic nutritional sciences}, volume = {63-64}, journal = {Nutrition : the international journal of applied and basic nutritional sciences}, publisher = {Elsevier}, address = {New York}, issn = {0899-9007}, doi = {10.1016/j.nut.2018.11.004}, pages = {81 -- 86}, year = {2018}, abstract = {Objective: Fibroblast growth factor (FGF)21 is promptly induced by short fasting in animal models to regulate glucose and fat metabolism. Data on FGF21 in humans are inconsistent and FGF21 has not yet been investigated in old patients with cachexia, a complex syndrome characterized by inflammation and weight loss. The aim of this study was to explore the association of FGF21 with cachexia in old patients compared with their healthy counterparts. Methods: Serum FGF21 and its inactivating enzyme fibroblast activation protein (FAP)-cc were measured with enzyme-linked immunoassays. Cachexia was defined as >= 5\% weight loss in the previous 3 mo and concurrent anorexia (Council on Nutrition appetite questionnaire). Results: We included 103 patients with and without cachexia (76.9 +/- 5.2 y of age) and 56 healthy controls (72.9 +/- 5.9 y of age). Cachexia was present in 16.5\% of patients. These patients had significantly higher total FGF21 levels than controls (952.1 +/- 821.3 versus 525.2 +/- 560.3 pg/mL; P= 0.012) and the lowest FGF21 levels (293.3 +/- 150.9 pg/mL) were found in the control group (global P < 0.001). Although FAP-alpha did not differ between the three groups (global P = 0.082), bioactive FGF21 was significantly higher in patients with cachexia (global P = 0.002). Risk factor-adjusted regression analyses revealed a significant association between cachexia and total ((beta = 649.745 pg/mL; P < 0.001) and bioactive FGF21 (beta = 393.200 pg/mL; P <0.001), independent of sex, age, and body mass index. Conclusions: Patients with cachexia exhibited the highest FGF21 levels. Clarification is needed to determine whether this is an adaptive response to nutrient deprivation in disease-related cachexia or whether the increased FGF21 values contribute to the catabolic state. (C) 2018 Elsevier Inc. All rights reserved.}, language = {en} } @misc{BornhorstKippHaaseetal.2018, author = {Bornhorst, Julia and Kipp, Anna P. and Haase, Hajo and Meyer, Soeren and Schwerdtle, Tanja}, title = {The crux of inept biomarkers for risks and benefits of trace elements}, series = {Trends in Analytical Chemistry}, volume = {104}, journal = {Trends in Analytical Chemistry}, publisher = {Elsevier}, address = {Oxford}, issn = {0165-9936}, doi = {10.1016/j.trac.2017.11.007}, pages = {183 -- 190}, year = {2018}, abstract = {Nowadays, the role of trace elements (TE) is of growing interest because dyshomeostasis of selenium (Se), manganese (Mn), zinc (Zn), and copper (Cu) is supposed to be a risk factor for several diseases. Thereby, research focuses on identifying new biomarkers for the TE status to allow for a more reliable description of the individual TE and health status. This review mirrors a lack of well-defined, sensitive, and selective biomarkers and summarizes technical limitations to measure them. Thus, the capacity to assess the relationship between dietary TE intake, homeostasis, and health is restricted, which would otherwise provide the basis to define adequate intake levels of single TE in both healthy and diseased humans. Besides that, our knowledge is even more limited with respect to the real life situation of combined TE intake and putative interactions between single TE.}, language = {en} }