@article{ZebgerGongMuellerDierckeetal.2011, author = {Zebger-Gong, Hong and Mueller, Dominik and Diercke, Michaela and Haffner, Dieter and Hocher, Berthold and Verberckmoes, Steven and Schmidt, Sven and D'Haese, Patrick C. and Querfeld, Uwe}, title = {1,25-Dihydroxyvitamin D-3-induced aortic calcifications in experimental uremia: up-regulation of osteoblast markers, calcium-transporting proteins and osterix}, series = {Journal of hypertension}, volume = {29}, journal = {Journal of hypertension}, number = {2}, publisher = {Lippincott Williams \& Wilkins}, address = {Philadelphia}, issn = {0263-6352}, doi = {10.1097/HJH.0b013e328340aa30}, pages = {339 -- 348}, year = {2011}, abstract = {Background and objective Whether treatment with vitamin D receptor activators contributes to cardiovascular disease in patients with chronic kidney disease is a matter of debate. We studied mechanisms involved in vitamin D-related vascular calcifications in vivo and in vitro. Methods Aortic calcifications were induced in subtotally nephrectomized (SNX) rats by treatment with a high dose (0.25 mu g/kg per day) of 1,25-dihydroxyvitamin D-3 (calcitriol) given for 6 weeks. Likewise, primary rat vascular smooth muscle cells (VSMCs) were incubated with calcitriol at concentrations ranging from 10(-11) to 10(-7) mol/l. Immunohistochemistry revealed that the aortic expression of osteopontin, osteocalcin and bone sialoprotein was significantly increased in calcitriol-treated SNX rats compared to untreated SNX controls. In addition, aortic expression of the transient receptor potential vanilloid calcium channel 6 (TRPV6) and calbindin D9k was significantly up-regulated by treatment with calcitriol. Furthermore, calcitriol significantly increased expression of the osteogenic transcription factor osterix. In-vitro studies showed similar results, confirming that these effects could be attributed to treatment with calcitriol. Conclusions High-dose calcitriol treatment induces an osteoblastic phenotype in VSMC both in SNX rats and in vitro, associated with up-regulation of proteins regulating mineralization and calcium transport, and of the osteogenic transcription factor osterix.}, language = {en} } @misc{YangDarkoHuangetal.2017, author = {Yang, Xiaoping and Darko, Kwame Oteng and Huang, Yanjun and He, Caimei and Yang, Huansheng and He, Shanping and Li, Jianzhong and Li, Jian and Hocher, Berthold and Yin, Yulong}, title = {Resistant starch regulates gut microbiota}, series = {Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology}, volume = {42}, journal = {Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology}, number = {1}, publisher = {Karger}, address = {Basel}, issn = {1015-8987}, doi = {10.1159/000477386}, pages = {306 -- 318}, year = {2017}, abstract = {Starch is one of the most popular nutritional sources for both human and animals. Due to the variation of its nutritional traits and biochemical specificities, starch has been classified into rapidly digestible, slowly digestible and resistant starch. Resistant starch has its own unique chemical structure, and various forms of resistant starch are commercially available. It has been found being a multiple-functional regulator for treating metabolic dysfunction. Different functions of resistant starch such as modulation of the gut microbiota, gut peptides, circulating growth factors, circulating inflammatory mediators have been characterized by animal studies and clinical trials. In this mini-review, recent remarkable progress in resistant starch on gut microbiota, particularly the effect of structure, biochemistry and cell signaling on nutrition has been summarized, with highlights on its regulatory effect on gut microbiota.}, language = {en} } @article{YangLaiDengetal.2014, author = {Yang, Fang and Lai, Xinlong and Deng, Li and Liu, Xiaoxiao and Li, Jian and Zeng, Shuixiu and Zhang, Cheng and Hocher, Carl-Friedrich and Hocher, Berthold}, title = {Association of endothelin-1 gene polymorphisms with the clinical phenotype in primary nephrotic syndrome of children}, series = {Life sciences : molecular, cellular and functional basis of therapy}, volume = {118}, journal = {Life sciences : molecular, cellular and functional basis of therapy}, number = {2}, publisher = {Elsevier}, address = {Oxford}, issn = {0024-3205}, doi = {10.1016/j.lfs.2014.04.010}, pages = {446 -- 450}, year = {2014}, abstract = {Aims:This study aims to investigate the relationship between plasma endothelin-1 (ET-1) concentrations, ET-1 gene polymorphisms in loci rs5370, rs1630736, 3A/4A and clinical features of primary nephrotic syndrome (NS) in children. Materials and methods: Thirty-six children with primary NS were selected as case group, and 94 healthy children were selected as control group. All subjects were genotyped for three single nucleotide polymorphisms (SNPs) (rs5370, rs10478694 [3A4A) and rs 1630736) in the ET-1 gene by gene sequencing. The plasma ET-1 concentrations were measured using a radio-immunoassay. Key findings: Plasma ET-1 concentrations were higher in NS patients (P = 0.007) as compared to healthy children. The allele frequencies between control and NS patients were significantly different only with respect to the rs10478694 SNP of the ET-1 gene. The allele frequencies between control and NS patients for the rs5370 SNP showed a trend towards difference (P = 0.057). Plasma cholesterol in NS patients is associated with both: the Cl genotype in locus rs5370 and the 3A4A genotype in locus rs10478694 (P < 0.05 in both cases). Significance: The ET systems might play a disease modifying role in pediatric NS. Plasma cholesterol, a hallmark of NS. seems to be associated with genetic variations within the human ET-1 gene. (C) 2014 Elsevier Inc. All rights reserved.}, language = {en} } @article{YamamotoBaldermannYoshikawaetal.2014, author = {Yamamoto, Masayoshi and Baldermann, Susanne and Yoshikawa, Keisuke and Fujita, Akira and Mase, Nobuyuki and Watanabe, Naoharu}, title = {Determination of volatile compounds in four commercial samples of japanese green algae using solid phase microextraction gas chromatography mass spectrometry}, series = {The ScientificWorld journal}, journal = {The ScientificWorld journal}, publisher = {Hindawi Publishing Corp.}, address = {New York}, issn = {1537-744X}, doi = {10.1155/2014/289780}, pages = {8}, year = {2014}, abstract = {Green algae are of great economic importance. Seaweed is consumed fresh or as seasoning in Japan. The commercial value is determined by quality, color, and flavor and is also strongly influenced by the production area. Our research, based on solid phase microextraction gas chromatography mass spectrometry (SPME-GC-MS), has revealed that volatile compounds differ intensely in the four varieties of commercial green algae. Accordingly, 41 major volatile compounds were identified. Heptadecene was the most abundant compound from Okayama (Ulva prolifera), Tokushima (Ulva prolifera), and Ehime prefecture (Ulva linza). Apocarotenoids, such as ionones, and their derivatives were prominent volatiles in algae from Okayama (Ulva prolifera) and Tokushima prefecture (Ulva prolifera). Volatile, short chained apocarotenoids are among the most potent flavor components and contribute to the flavor of fresh, processed algae, and algae-based products. Benzaldehyde was predominant in seaweed from Shizuoka prefecture (Monostroma nitidum). Multivariant statistical analysis (PCA) enabled simple discrimination of the samples based on their volatile profiles. This work shows the potential of SPME-GC-MS coupled with multivariant analysis to discriminate between samples of different geographical and botanical origins and form the basis for development of authentication methods of green algae products, including seasonings.}, language = {en} } @article{YadavDreherAthmeretal.2019, author = {Yadav, Heena and Dreher, Doroth{\´e}e and Athmer, Benedikt and Porzel, Andrea and Gavrin, Aleksandr and Baldermann, Susanne and Tissier, Alain and Hause, Bettina}, title = {Medicago TERPENE SYNTHASE 10 is involved in defense against an oomycete root pathogen}, series = {Plant physiology : an international journal devoted to physiology, biochemistry, cellular and molecular biology, biophysics and environmental biology of plants}, volume = {180}, journal = {Plant physiology : an international journal devoted to physiology, biochemistry, cellular and molecular biology, biophysics and environmental biology of plants}, number = {3}, publisher = {American Society of Plant Physiologists}, address = {Rockville}, issn = {0032-0889}, doi = {10.1104/pp.19.00278}, pages = {1598 -- 1613}, year = {2019}, abstract = {In nature, plants interact with numerous beneficial or pathogenic soil-borne microorganisms. Plants have developed various defense strategies to expel pathogenic microbes, some of which function soon after pathogen infection. We used Medicago truncatula and its oomycete pathogen Aphanomyces euteiches to elucidate early responses of the infected root. A. euteiches causes root rot disease in legumes and is a limiting factor in legume production. Transcript profiling of seedlings and adult plant roots inoculated with A. euteiches zoospores for 2 h revealed specific upregulation of a gene encoding a putative sesquiterpene synthase (M. truncatula TERPENE SYNTHASE 10 [MtTPS10]) in both developmental stages. MtTPS10 was specifically expressed in roots upon oomycete infection. Heterologous expression of MtTPS10 in yeast led to production of a blend of sesquiterpenes and sesquiterpene alcohols, with NMR identifying a major peak corresponding to himalachol. Moreover, plants carrying a tobacco (Nicotiana tabacum) retrotransposon Tnt1 insertion in MtTPS10 lacked the emission of sesquiterpenes upon A. euteiches infection, supporting the assumption that the identified gene encodes a multiproduct sesquiterpene synthase. Mttps10 plants and plants with reduced MtTPS10 transcript levels created by expression of an MtTPS10-artificial microRNA in roots were more susceptible to A. euteiches infection than were the corresponding wild-type plants and roots transformed with the empty vector, respectively. Sesquiterpenes produced by expression of MtTPS10 in yeast also inhibited mycelial growth and A. euteiches zoospore germination. These data suggest that sesquiterpene production in roots by MtTPS10 plays a previously unrecognized role in the defense response of M. truncatula against A. euteiches.}, language = {en} } @article{XuLuHasanetal.2017, author = {Xu, Mei and Lu, Yong-Ping and Hasan, Ahmed A. and Hocher, Berthold}, title = {Plasma ET-1 concentrations are elevated in patients with hypertension meta-analysis of clinical studies}, series = {Kidney \& blood pressure research : official organ of the Gesellschaft f{\"u}r Nephrologie ; official organ of the Deutsche Liga zur Bek{\"a}mpfung des Hohen Blutdruckes e.V., Deutsche Hypertonie-Gesellschaft}, volume = {42}, journal = {Kidney \& blood pressure research : official organ of the Gesellschaft f{\"u}r Nephrologie ; official organ of the Deutsche Liga zur Bek{\"a}mpfung des Hohen Blutdruckes e.V., Deutsche Hypertonie-Gesellschaft}, number = {2}, publisher = {Karger}, address = {Basel}, issn = {1420-4096}, doi = {10.1159/000477572}, pages = {304 -- 313}, year = {2017}, abstract = {Background/Aims: A recent study revealed that global overexpression of ET-1 causes a slight reduction in systemic blood pressure. Moreover, heterozygous ET-1 knockout mice are hypertensive. The role of ET-1 in human hypertension was so far not addressed by a strict meta-analysis of published human clinical studies. Methods: We included studies published between January 1, 1990 and February 28, 2017. We included case control studies analyzing untreated essential hypertension or hypertensive patients where antihypertensive medication was discontinued for at least two weeks. Based on the principle of Cochrane systematic reviews, case control studies (CCSs) in PubMed (Medline) and Google Scholar designed to identify the role of endothelin-1 (ET-1) in the pathophysiological of hypertension were screened. Review Manager Version 5.0 (Rev-Man 5.0) was applied for statistical analysis. Mean difference and 95\% confidence interval (CI) were shown in inverse variance (IV) fixed-effects model or IV random-effects models. Results: Eleven studies fulfilling our in-and exclusion criteria were eligible for this meta-analysis. These studies included 450 hypertensive patients and 328 controls. Our meta-analysis revealed that ET-1 plasma concentrations were higher in hypertensive patients as compared to the control patients [mean difference between groups 1.57 pg/mL, 95\%Ci [0.47 similar to 2.68, P = 0.005]. These finding were driven by patients having systolic blood pressure higher than 160 mmHg and diastolic blood pressure higher than 100 mmHg. Conclusions: This meta-analysis showed that hypertensive patients do have elevated plasma ET-1 concentrations. This finding is driven by those patients with high systolic/diastolic blood pressure. Given that the ET-1 gene did not appear in any of the whole genome association studies searching for hypertension associated gene loci, it is very likely that the elevated plasma ET-1 concentrations in hypertensive patients are secondary to hypertension and may reflect endothelial cell damage.}, language = {en} } @article{XiongStibollerGlabonjatetal.2020, author = {Xiong, Chan and Stiboller, Michael and Glabonjat, Ronald A. and Rieger, Jaqueline and Paton, Lhiam and Francesconi, Kevin A.}, title = {Transport of arsenolipids to the milk of a nursing mother after consuming salmon fish}, series = {Journal of trace elements in medicine and biology}, volume = {61}, journal = {Journal of trace elements in medicine and biology}, publisher = {Elsevier}, address = {M{\"u}nchen}, issn = {0946-672X}, doi = {10.1016/j.jtemb.2020.126502}, pages = {6}, year = {2020}, abstract = {Objective: We address two questions relevant to infants' exposure to potentially toxic arsenolipids, namely, are the arsenolipids naturally present in fish transported intact to a mother's milk, and what is the efficiency of this transport. Methods: We investigated the transport of arsenolipids and other arsenic species present in fish to mother's milk by analyzing the milk of a single nursing mother at 15 sampling times over a 3-day period after she had consumed a meal of salmon. Total arsenic values were obtained by elemental mass spectrometry, and arsenic species were measured by HPLC coupled to both elemental and molecular mass spectrometry. Results: Total arsenic increased from background levels (0.1 mu g As kg(-1)) to a peak value of 1.72 lig As kg(-1) eight hours after the fish meal. The pattern for arsenolipids was similar to that of total arsenic, increasing from undetectable background levels (< 0.01 mu g As kg(-1)) to a peak after eight hours of 0.45 mu g As kg(-1). Most of the remaining total arsenic in the milk was accounted for by arsenobetaine. The major arsenolipids in the salmon were arsenic hydrocarbons (AsHCs; 55 \% of total arsenolipids), and these compounds were also the dominant arsenolipids in the milk where they contributed over 90 \% of the total arsenolipids. Conclusions: Our study has shown that ca 2-3 \% of arsenic hydrocarbons, natural constituents of fish, can be directly transferred unchanged to the milk of a nursing mother. In view of the potential neurotoxicity of AsHCs, the effects of these compounds on the brain developmental stage of infants need to be investigated.}, language = {en} } @article{WrightUlkeFontetal.2020, author = {Wright, Stephanie L. and Ulke, Jannis and Font, Anna and Chan, Ka Lung Andrew and Kelly, Frank J.}, title = {Atmospheric microplastic deposition in an urban environment and an evaluation of transport}, series = {Environment international}, volume = {136}, journal = {Environment international}, publisher = {Elsevier, Pergamon Press}, address = {New York, NY [u.a.]}, issn = {0160-4120}, doi = {10.1016/j.envint.2019.105411}, pages = {7}, year = {2020}, abstract = {Microplastics are a global environmental issue contaminating aquatic and terrestrial environments. They have been reported in atmospheric deposition, and indoor and outdoor air, raising concern for public health due to the potential for exposure. Moreover, the atmosphere presents a new vehicle for microplastics to enter the wider environment, yet our knowledge of the quantities, characteristics and pathways of airborne microplastics is sparse. Here we show microplastics in atmospheric deposition in a major population centre, central London. Microplastics were found in all samples, with deposition rates ranging from 575 to 1008 microplastics/m(2)/d. They were found in various shapes, of which fibrous microplastics accounted for the great majority (92\%). Across all samples, 15 different petrochemical-based polymers were identified. Bivariate polar plots indicated dependency on wind, with different source areas for fibrous and non-fibrous airborne microplastics. This is the first evidence of airborne microplastics in London and confirms the need to include airborne pathways when consolidating microplastic impacts on the wider environment and human health.}, language = {en} } @misc{WotingBlaut2016, author = {Woting, Anni and Blaut, Michael}, title = {The intestinal microbiota in metabolic disease}, series = {Nutrients}, journal = {Nutrients}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-407687}, pages = {19}, year = {2016}, abstract = {Gut bacteria exert beneficial and harmful effects in metabolic diseases as deduced from the comparison of germfree and conventional mice and from fecal transplantation studies. Compositional microbial changes in diseased subjects have been linked to adiposity, type 2 diabetes and dyslipidemia. Promotion of an increased expression of intestinal nutrient transporters or a modified lipid and bile acid metabolism by the intestinal microbiota could result in an increased nutrient absorption by the host. The degradation of dietary fiber and the subsequent fermentation of monosaccharides to short-chain fatty acids (SCFA) is one of the most controversially discussed mechanisms of how gut bacteria impact host physiology. Fibers reduce the energy density of the diet, and the resulting SCFA promote intestinal gluconeogenesis, incretin formation and subsequently satiety. However, SCFA also deliver energy to the host and support liponeogenesis. Thus far, there is little knowledge on bacterial species that promote or prevent metabolic disease. Clostridium ramosum and Enterococcus cloacae were demonstrated to promote obesity in gnotobiotic mouse models, whereas bifidobacteria and Akkermansia muciniphila were associated with favorable phenotypes in conventional mice, especially when oligofructose was fed. How diet modulates the gut microbiota towards a beneficial or harmful composition needs further research. Gnotobiotic animals are a valuable tool to elucidate mechanisms underlying diet-host-microbe interactions.}, language = {en} } @phdthesis{Wolf2020, author = {Wolf, Kristine}, title = {Produktentwicklung eines luteinhaltigen, kolloidalen Nahrungserg{\"a}nzungsmittels: physikochemische und ern{\"a}hrungsphysiologische Aspekte}, doi = {10.25932/publishup-48774}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-487743}, school = {Universit{\"a}t Potsdam}, pages = {xxi, 243}, year = {2020}, abstract = {Sekund{\"a}re Pflanzenstoffe und ihre gesundheitsf{\"o}rdernden Eigenschaften sind in den letzten zwei Jahrzehnten vielfach ern{\"a}hrungsphysiologisch untersucht und spezifische positive Effekte im humanen Organismus zum Teil sehr genau beschrieben worden. Zu den Carotinoiden z{\"a}hlend ist der sekund{\"a}re Pflanzenstoff Lutein insbesondere in der Pr{\"a}vention von ophthalmologischen Erkrankungen in den Mittelpunkt der Forschung ger{\"u}ckt. Das ausschließlich von Pflanzen und einigen Algen synthetisierte Xanthophyll wird {\"u}ber die pflanzliche Nahrung insbesondere gr{\"u}nes Blattgem{\"u}se in den humanen Organismus aufgenommen. Dort akkumuliert es bevorzugt im Makulapigment der Retina des menschlichen Auges und ist bedeutend im Prozess der Aufrechterhaltung der Funktionsf{\"a}higkeit der Photorezeptorzellen. Im Laufe des Alterns kann die Abnahme der Dichte des Makulapigments und der Abbau von Lutein beobachtet werden. Die dadurch eintretende Destabilisierung der Photorezeptorzellen im Zusammenhang mit einer ver{\"a}nderten Stoffwechsellage im alternden Organismus kann zur Auspr{\"a}gung der altersbedingten Makuladegeneration (AMD) f{\"u}hren. Die pathologische Symptomatik der Augenerkrankung reicht vom Verlust der Sehsch{\"a}rfe bis hin zum irreversiblen Erblinden. Da therapeutische Mittel ausschließlich ein Fortschreiten verhindern, bestehen hier Forschungsans{\"a}tze pr{\"a}ventive Maßnahmen zu finden. Die Supplementierung von luteinhaltigen Pr{\"a}paraten bietet dabei einen Ansatzpunkt. Auf dem Markt finden sich bereits Nahrungserg{\"a}nzungsmittel (NEM) mit Lutein in verschiedenen Applikationen. Limitierend ist dabei die Stabilit{\"a}t und Bioverf{\"u}gbarkeit von Lutein, welches teilweise kostenintensiv und mit unbekannter Reinheit zu erwerben ist. Aus diesem Grund w{\"a}re die Verwendung von Luteinestern als die pflanzliche Speicherform des Luteins im Rahmen eines NEMs vorteilhaft. Neben ihrer nat{\"u}rlichen, h{\"o}heren Stabilit{\"a}t sind Luteinester nachhaltig und kosteng{\"u}nstig einsetzbar. In dieser Arbeit wurden physikochemische und ern{\"a}hrungsphysiologisch relevante Aspekte in dem Produktentwicklungsprozess eines NEMs mit Luteinestern in einer kolloidalen Formulierung untersucht. Die bisher einzigartige Anwendung von Luteinestern in einem Mundspray sollte die Aufnahme des Wirkstoffes insbesondere f{\"u}r {\"a}ltere Menschen erleichtern und verbessern. Unter Beachtung der Ergebnisse und der ern{\"a}hrungsphysiologischen Bewertung sollten u.a. Empfehlungen f{\"u}r die Rezepturzusammensetzungen einer Miniemulsion (Emulsion mit Partikelgr{\"o}ßen <1,0 µm) gegeben werden. Eine Einsch{\"a}tzung der Bioverf{\"u}gbarkeit der Luteinester aus den entwickelten, kolloidalen Formulierungen konnte anhand von Studien zur Resorption- und Absorptionsverf{\"u}gbarkeit in vitro erm{\"o}glicht werden. In physikalischen Untersuchungen wurden zun{\"a}chst Basisbestandteile f{\"u}r die Formulierungen pr{\"a}zisiert. In ersten wirkstofffreien Musteremulsionen konnten ausgew{\"a}hlte {\"O}le als Tr{\"a}gerphase sowie Emulgatoren und L{\"o}slichkeitsvermittler (Peptisatoren) hinsichtlich ihrer Eignung zur Bereitstellung einer Miniemulsion physikalisch gepr{\"u}ft werden. Die beste Stabilit{\"a}t und optimale Eigenschaften einer Miniemulsion zeigten sich bei der Verwendung von MCT-{\"O}l (engl. medium chain triglyceride) bzw. Raps{\"o}l in der Tr{\"a}gerphase sowie des Emulgators Tween® 80 (Tween 80) allein oder in Kombination mit dem Molkenproteinhydrolysat Biozate® 1 (Biozate 1). Aus den physikalischen Untersuchungen der Musteremulsionen gingen die Pr{\"a}emulsionen als Prototypen hervor. Diese enthielten den Wirkstoff Lutein in verschiedenen Formen. So wurden Pr{\"a}emulsionen mit Lutein, mit Luteinestern sowie mit Lutein und Luteinestern konzipiert, welche den Emulgator Tween 80 oder die Kombination mit Biozate 1 enthielten. Bei der Herstellung der Pr{\"a}emulsionen f{\"u}hrte die Anwendung der Emulgiertechniken Ultraschall mit anschließender Hochdruckhomogenisation zu den gew{\"u}nschten Miniemulsionen. Beide eingesetzten Emulgatoren boten optimale Stabilisierungseffekte. Anschließend erfolgte die physikochemische Charakterisierung der Wirkstoffe. Insbesondere Luteinester aus Oleoresin erwiesen sich hier als stabil gegen{\"u}ber verschiedenen Lagerungsbedingungen. Ebenso konnte bei einer kurzzeitigen Behandlung der Wirkstoffe unter spezifischen mechanischen, thermischen, sauren und basischen Bedingungen eine Stabilit{\"a}t von Lutein und Luteinestern gezeigt werden. Die Zugabe von Biozate 1 bot dabei nur f{\"u}r Lutein einen zus{\"a}tzlichen Schutz. Bei l{\"a}ngerer physikochemischer Behandlung unterlagen die in den Miniemulsionen eingebrachten Wirkstoffe moderaten Abbauvorg{\"a}ngen. Markant war deren Sensitivit{\"a}t gegen{\"u}ber dem basischen Milieu. Im Rahmen der Rezepturentwicklung des NEMs war hier die Empfehlung, eine Miniemulsion mit einem leicht saurem pH-Milieu zum Schutz des Wirkstoffes durch kontrollierte Zugabe weiterer Inhaltstoffe zu gestalten. Im weiteren Entwicklungsprozess des NEMs wurden Fertigrezepturen mit dem Wirkstoff Luteinester aufgestellt. Die alleinige Anwendung des Emulgators Biozate 1 zeigte sich dabei als ungeeignet. Die weiterhin zur Verf{\"u}gung stehenden Fertigrezepturen enthielten in der {\"O}l-phase neben dem Wirkstoff das MCT-{\"O}L oder Raps{\"o}l sowie a-Tocopherol zur Stabilisierung. Die Wasserphase bestand aus dem Emulgator Tween 80 oder einer Kombination aus Tween 80 und Biozate 1. Zusatzstoffe waren zudem als mikrobiologischer Schutz Ascorbins{\"a}ure und Kaliumsorbat sowie f{\"u}r sensorische Effekte Xylitol und Orangenaroma. Die Anordnung der Basisrezeptur und das angewendete Emulgierverfahren lieferten stabile Miniemulsionen. Weiterhin zeigten langfristige Lagerungsversuche mit den Fertigrezepturen bei 4°C, dass eine Aufrechterhaltung der geforderten Luteinestermenge im Produkt gew{\"a}hrleistet war. Analoge Untersuchungen an einem luteinhaltigen, marktg{\"a}ngigen Pr{\"a}parat best{\"a}tigten dagegen eine bereits bei kurzfristiger Lagerung auftretende Instabilit{\"a}t von Lutein. Abschließend wurde durch Resorptions- und Absorptionsstudien in vitro mit den Pr{\"a}emulsionen und Fertigrezepturen die Bioverf{\"u}gbarkeit von Luteinestern gepr{\"u}ft. Nach Behandlung in einem etablierten in vitro Verdaumodell konnte eine geringf{\"u}gige Resorptionsverf{\"u}gbarkeit der Luteinester definiert werden. Limitiert war eine Micellarisierung des Wirkstoffes aus den konzipierten Formulierungen zu beobachten. Eine enzymatische Spaltung der Luteinester zu freiem Lutein wurde nur begrenzt festgestellt. Spezifit{\"a}t und Aktivit{\"a}t von entsprechenden hydrolytischen Lipasen sind als {\"a}ußerst gering gegen{\"u}ber Luteinestern zu bewerten. In sich anschließenden Zellkulturversuchen mit der Zelllinie Caco-2 wurden keine zytotoxischen Effekte durch die relevanten Inhaltsstoffe in den Pr{\"a}emulsionen gezeigt. Dagegen konnten eine Sensibilit{\"a}t gegen{\"u}ber den Fertigrezepturen beobachtet werden. Diese sollte im Zusammenhang mit Irritationen der Schleimh{\"a}ute des Magen-Darm-Traktes bedacht werden. Eine weniger komplexe Rezeptur k{\"o}nnte die beobachteten Einschr{\"a}nkungen m{\"o}glicherweise minimieren. Abschließende Absorptionsstudien zeigten, dass grunds{\"a}tzlich eine geringf{\"u}gige Aufnahme von vorrangig Lutein, aber auch Luteinmonoestern in den Enterocyten aus Miniemulsionen erfolgen kann. Dabei hatte weder Tween 80 noch Biozate 1 einen f{\"o}rderlichen Einfluss auf die Absorptionsrate von Lutein oder Luteinestern. Die Metabolisierung der Wirkstoffe durch vorherigen in vitro-Verdau steigerte die zellul{\"a}re Aufnahme von Wirkstoffen aus Formulierungen mit Lutein und Luteinestern gleichermaßen. Die beobachtete Aufnahme von Lutein und Luteinmonoestern in den Enterocyten scheint {\"u}ber passive Diffusion zu erfolgen, wobei auch der aktive Transport nicht ausgeschlossen werden kann. Dagegen k{\"o}nnen Luteindiester aufgrund ihrer Molek{\"u}lgr{\"o}ße nicht {\"u}ber den Weg der Micellarisierung und einfachen Diffusion in die Enterocyten gelangen. Ihre Aufnahme in die D{\"u}nndarmepithelzellen bedarf einer vorherigen hydrolytischen Spaltung durch spezifische Lipasen. Dieser Schritt limitiert wiederum die effektive Aufnahme der Luteinester in die Zellen bzw. stellt eine Einschr{\"a}nkung in ihrer Bioverf{\"u}gbarkeit im Vergleich zu freiem Lutein dar. Zusammenfassend konnte f{\"u}r die physikochemisch stabilen Luteinester eine geringe Bioverf{\"u}gbarkeit aus kolloidalen Formulierungen gezeigt werden. Dennoch ist die Verwendung als Wirkstoffquelle f{\"u}r den sekund{\"a}ren Pflanzenstoff Lutein in einem NEM zu empfehlen. Im Zusammenhang mit der Aufnahme von luteinreichen, pflanzlichen Lebensmitteln kann trotz der zu erwartenden geringen Bioverf{\"u}gbarkeit der Luteinester aus dem NEM ein Beitrag zur Verbesserung des Luteinstatus erreicht werden. Entsprechende Publikationen zeigten eindeutige Korrelationen zwischen der Aufnahme von luteinesterhaltigen Pr{\"a}paraten und einem Anstieg der Luteinkonzentration im Serum bzw. der Makulapigmentdichte in vivo. Die geringf{\"u}gig bessere Bioverf{\"u}gbarkeit von freiem Lutein steht im kritischen Zusammenhang mit seiner Instabilit{\"a}t und Kostenintensit{\"a}t. Bilanzierend wurde im Rahmen dieser Arbeit das marktg{\"a}ngige Produkt Vita Culus® konzipiert. Im Ausblick sollten humane Interventionsstudien mit dem NEM die abschließende Bewertung der Bioverf{\"u}gbarkeit von Luteinestern aus dem Pr{\"a}parat m{\"o}glich machen.}, language = {de} } @phdthesis{Wohlgemuth2010, author = {Wohlgemuth, Steffen}, title = {Microbial and host factors associated with chronic intestinal inflammation of the Interleukin-10 deficient mouse}, address = {Potsdam}, pages = {IX, 125 Bl. : Ill., graph. Darst.}, year = {2010}, language = {en} } @article{WitzelStrehmelBaldermannetal.2017, author = {Witzel, Katja and Strehmel, Nadine and Baldermann, Susanne and Neugart, Susanne and Becker, Yvonne and Becker, Matthias and Berger, Beatrice and Scheel, Dierk and Grosch, Rita and Schreiner, Monika and Ruppel, Silke}, title = {Arabidopsis thaliana root and root exudate metabolism is altered by the growth-promoting bacterium Kosakonia radicincitans DSM 16656(T)}, series = {Plant and soil}, volume = {419}, journal = {Plant and soil}, publisher = {Springer}, address = {Dordrecht}, issn = {0032-079X}, doi = {10.1007/s11104-017-3371-1}, pages = {557 -- 573}, year = {2017}, abstract = {Plant growth-promoting bacteria (PGPB) affect host physiological processes in various ways. This study aims at elucidating the dependence of bacterial-induced growth promotion on the plant genotype and characterizing plant metabolic adaptations to PGPB. Eighteen Arabidopsis thaliana accessions were inoculated with the PGPB strain Kosakonia radicincitans DSM 16656(T). Colonisation pattern was assessed by enhanced green fluorescent protein (eGFP)-tagged K. radicincitans in three A. thaliana accessions differing in their growth response. Metabolic impact of bacterial colonisation was determined for the best responding accession by profiling distinct classes of plant secondary metabolites and root exudates. Inoculation of 18 A. thaliana accessions resulted in a wide range of growth responses, from repression to enhancement. Testing the bacterial colonisation of three accessions did not reveal a differential pattern. Profiling of plant secondary metabolites showed a differential accumulation of glucosinolates, phenylpropanoids and carotenoids in roots. Analysis of root exudates demonstrated that primary and secondary metabolites were predominantly differentially depleted by bacterial inoculation. The plant genotype controls the bacterial growth promoting traits. Levels of lutein and beta-carotene were elevated in inoculated roots. Supplementing a bacterial suspension with beta-carotene increased bacterial growth, while this was not the case when lutein was applied, indicating that beta-carotene could be a positive regulator of plant growth promotion.}, language = {en} } @misc{WitzelNeugartRuppeletal.2015, author = {Witzel, Katja and Neugart, Susanne and Ruppel, Silke and Schreiner, Monika and Wiesner, Melanie and Baldermann, Susanne}, title = {Recent progress in the use of 'omics technologies in brassicaceous vegetables}, series = {Frontiers in plant science}, volume = {6}, journal = {Frontiers in plant science}, publisher = {Frontiers Research Foundation}, address = {Lausanne}, issn = {1664-462X}, doi = {10.3389/fpls.2015.00244}, pages = {14}, year = {2015}, abstract = {Continuing advances in 'omics methodologies and instrumentation is enhancing the understanding of how plants cope with the dynamic nature of their growing environment. 'Omics platforms have been only recently extended to cover horticultural crop species. Many of the most widely cultivated vegetable crops belong to the genus Brassica: these include plants grown for their root (turnip, rutabaga/swede), their swollen stem base (kohlrabi), their leaves (cabbage, kale, pak choi) and their inflorescence (cauliflower, broccoli). Characterization at the genome, transcript, protein and metabolite levels has illustrated the complexity of the cellular response to a whole series of environmental stresses, including nutrient deficiency, pathogen attack, heavy metal toxicity, cold acclimation, and excessive and sub optimal irradiation. This review covers recent applications of omics technologies to the brassicaceous vegetables, and discusses future scenarios in achieving improvements in crop end-use quality.}, language = {en} } @article{WittenbecherOuniKuxhausetal.2019, author = {Wittenbecher, Clemens and Ouni, Meriem and Kuxhaus, Olga and J{\"a}hnert, Markus and Gottmann, Pascal and Teichmann, Andrea and Meidtner, Karina and Kriebel, Jennifer and Grallert, Harald and Pischon, Tobias and Boeing, Heiner and Schulze, Matthias Bernd and Sch{\"u}rmann, Annette}, title = {Insulin-Like Growth Factor Binding Protein 2 (IGFBP-2) and the Risk of Developing Type 2 Diabetes}, series = {Diabetes : a journal of the American Diabetes Association}, volume = {68}, journal = {Diabetes : a journal of the American Diabetes Association}, number = {1}, publisher = {American Diabetes Association}, address = {Alexandria}, issn = {0012-1797}, doi = {10.2337/db18-0620}, pages = {188 -- 197}, year = {2019}, abstract = {Recent studies suggest that insulin-like growth factor binding protein 2 (IGFBP-2) may protect against type 2 diabetes, but population-based human studies are scarce. We aimed to investigate the prospective association of circulating IGFBP-2 concentrations and of differential methylation in the IGFBP-2 gene with type 2 diabetes risk.}, language = {en} } @article{WittenbecherKuxhausBoeingetal.2019, author = {Wittenbecher, Clemens and Kuxhaus, Olga and Boeing, Heiner and Stefan, Norbert and Schulze, Matthias Bernd}, title = {Associations of short stature and components of height with incidence of type 2 diabetes}, series = {Diabetologia : journal of the European Association for the Study of Diabetes (EASD)}, volume = {62}, journal = {Diabetologia : journal of the European Association for the Study of Diabetes (EASD)}, number = {12}, publisher = {Springer}, address = {New York}, issn = {0012-186X}, doi = {10.1007/s00125-019-04978-8}, pages = {2211 -- 2221}, year = {2019}, abstract = {Aims/hypothesis This study aimed to evaluate associations of height as well as components of height (sitting height and leg length) with risk of type 2 diabetes and to explore to what extent associations are explainable by liver fat and cardiometabolic risk markers. Methods A case-cohort study within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study comprising 26,437 participants who provided blood samples was designed. We randomly selected a subcohort of 2500 individuals (2029 diabetes-free at baseline and with anamnestic, anthropometrical and metabolic data for analysis). Of the 820 incident diabetes cases identified in the full cohort during 7 years of follow-up, 698 remained for analyses after similar exclusions. Results After adjustment for age, potential lifestyle confounders, education and waist circumference, greater height was related to lower diabetes risk (HR per 10 cm, men 0.59 [95\% CI 0.47, 0.75] and women 0.67 [0.51, 0.88], respectively). Leg length was related to lower risk among men and women, but only among men if adjusted for total height. Adjustment for liver fat and triacylglycerols, adiponectin and C-reactive protein substantially attenuated associations between height and diabetes risk, particularly among women. Conclusions/interpretation We observed inverse associations between height and risk of type 2 diabetes, which was largely related to leg length among men. The inverse associations may be partly driven by lower liver fat content and a more favourable cardiometabolic profile.}, language = {en} } @phdthesis{Wittenbecher2017, author = {Wittenbecher, Clemens}, title = {Linking whole-grain bread, coffee, and red meat to the risk of type 2 diabetes}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-404592}, school = {Universit{\"a}t Potsdam}, pages = {XII, 194, ii}, year = {2017}, abstract = {Background: Consumption of whole-grain, coffee, and red meat were consistently related to the risk of developing type 2 diabetes in prospective cohort studies, but potentially underlying biological mechanisms are not well understood. Metabolomics profiles were shown to be sensitive to these dietary exposures, and at the same time to be informative with respect to the risk of type 2 diabetes. Moreover, graphical network-models were demonstrated to reflect the biological processes underlying high-dimensional metabolomics profiles. Aim: The aim of this study was to infer hypotheses on the biological mechanisms that link consumption of whole-grain bread, coffee, and red meat, respectively, to the risk of developing type 2 diabetes. More specifically, it was aimed to consider network models of amino acid and lipid profiles as potential mediators of these risk-relations. Study population: Analyses were conducted in the prospective EPIC-Potsdam cohort (n = 27,548), applying a nested case-cohort design (n = 2731, including 692 incident diabetes cases). Habitual diet was assessed with validated semiquantitative food-frequency questionnaires. Concentrations of 126 metabolites (acylcarnitines, phosphatidylcholines, sphingomyelins, amino acids) were determined in baseline-serum samples. Incident type 2 diabetes cases were assed and validated in an active follow-up procedure. The median follow-up time was 6.6 years. Analytical design: The methodological approach was conceptually based on counterfactual causal inference theory. Observations on the network-encoded conditional independence structure restricted the space of possible causal explanations of observed metabolomics-data patterns. Given basic directionality assumptions (diet affects metabolism; metabolism affects future diabetes incidence), adjustment for a subset of direct neighbours was sufficient to consistently estimate network-independent direct effects. Further model-specification, however, was limited due to missing directionality information on the links between metabolites. Therefore, a multi-model approach was applied to infer the bounds of possible direct effects. All metabolite-exposure links and metabolite-outcome links, respectively, were classified into one of three categories: direct effect, ambiguous (some models indicated an effect others not), and no-effect. Cross-sectional and longitudinal relations were evaluated in multivariable-adjusted linear regression and Cox proportional hazard regression models, respectively. Models were comprehensively adjusted for age, sex, body mass index, prevalence of hypertension, dietary and lifestyle factors, and medication. Results: Consumption of whole-grain bread was related to lower levels of several lipid metabolites with saturated and monounsaturated fatty acids. Coffee was related to lower aromatic and branched-chain amino acids, and had potential effects on the fatty acid profile within lipid classes. Red meat was linked to lower glycine levels and was related to higher circulating concentrations of branched-chain amino acids. In addition, potential marked effects of red meat consumption on the fatty acid composition within the investigated lipid classes were identified. Moreover, potential beneficial and adverse direct effects of metabolites on type 2 diabetes risk were detected. Aromatic amino acids and lipid metabolites with even-chain saturated (C14-C18) and with specific polyunsaturated fatty acids had adverse effects on type 2 diabetes risk. Glycine, glutamine, and lipid metabolites with monounsaturated fatty acids and with other species of polyunsaturated fatty acids were classified as having direct beneficial effects on type 2 diabetes risk. Potential mediators of the diet-diabetes links were identified by graphically overlaying this information in network models. Mediation analyses revealed that effects on lipid metabolites could potentially explain about one fourth of the whole-grain bread effect on type 2 diabetes risk; and that effects of coffee and red meat consumption on amino acid and lipid profiles could potentially explain about two thirds of the altered type 2 diabetes risk linked to these dietary exposures. Conclusion: An algorithm was developed that is capable to integrate single external variables (continuous exposures, survival time) and high-dimensional metabolomics-data in a joint graphical model. Application to the EPIC-Potsdam cohort study revealed that the observed conditional independence patterns were consistent with the a priori mediation hypothesis: Early effects on lipid and amino acid metabolism had the potential to explain large parts of the link between three of the most widely discussed diabetes-related dietary exposures and the risk of developing type 2 diabetes.}, language = {en} } @phdthesis{Wittek2023, author = {Wittek, Laura}, title = {Comparison of metabolic cages - analysis of refinement measures on the welfare and metabolic parameters of laboratory mice}, doi = {10.25932/publishup-61120}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-611208}, school = {Universit{\"a}t Potsdam}, pages = {IV, 160}, year = {2023}, abstract = {Housing in metabolic cages can induce a pronounced stress response. Metabolic cage systems imply housing mice on metal wire mesh for the collection of urine and feces in addition to monitoring food and water intake. Moreover, mice are single-housed, and no nesting, bedding, or enrichment material is provided, which is often argued to have a not negligible impact on animal welfare due to cold stress. We therefore attempted to reduce stress during metabolic cage housing for mice by comparing an innovative metabolic cage (IMC) with a commercially available metabolic cage from Tecniplast GmbH (TMC) and a control cage. Substantial refinement measures were incorporated into the IMC cage design. In the frame of a multifactorial approach for severity assessment, parameters such as body weight, body composition, food intake, cage and body surface temperature (thermal imaging), mRNA expression of uncoupling protein 1 (Ucp1) in brown adipose tissue (BAT), fur score, and fecal corticosterone metabolites (CMs) were included. Female and male C57BL/6J mice were single-housed for 24 h in either conventional Macrolon cages (control), IMC, or TMC for two sessions. Body weight decreased less in the IMC (females—1st restraint: 6.94\%; 2nd restraint: 6.89\%; males—1st restraint: 8.08\%; 2nd restraint: 5.82\%) compared to the TMC (females—1st restraint: 13.2\%; 2nd restraint: 15.0\%; males—1st restraint: 13.1\%; 2nd restraint: 14.9\%) and the IMC possessed a higher cage temperature (females—1st restraint: 23.7°C; 2nd restraint: 23.5 °C; males—1st restraint: 23.3 °C; 2nd restraint: 23.5 °C) compared with the TMC (females—1st restraint: 22.4 °C; 2nd restraint: 22.5 °C; males—1st restraint: 22.6 °C; 2nd restraint: 22.4 °C). The concentration of fecal corticosterone metabolites in the TMC (females—1st restraint: 1376 ng/g dry weight (DW); 2nd restraint: 2098 ng/g DW; males—1st restraint: 1030 ng/g DW; 2nd restraint: 1163 ng/g DW) was higher compared to control cage housing (females—1st restraint: 640 ng/g DW; 2nd restraint: 941 ng/g DW; males—1st restraint: 504 ng/g DW; 2nd restraint: 537 ng/g DW). Our results show the stress potential induced by metabolic cage restraint that is markedly influenced by the lower housing temperature. The IMC represents a first attempt to target cold stress reduction during metabolic cage application thereby producing more animal welfare friendly data.}, language = {en} } @article{WittStibollerRaschkeetal.2021, author = {Witt, Barbara and Stiboller, Michael and Raschke, Stefanie and Friese, Sharleen and Ebert, Franziska and Schwerdtle, Tanja}, title = {Characterizing effects of excess copper levels in a human astrocytic cell line with focus on oxidative stress markers}, series = {Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements, GMS}, volume = {65}, journal = {Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements, GMS}, publisher = {Elsevier}, address = {M{\"u}nchen}, issn = {1878-3252}, doi = {10.1016/j.jtemb.2021.126711}, pages = {9}, year = {2021}, abstract = {Background: Being an essential trace element, copper is involved in diverse physiological processes. However, excess levels might lead to adverse effects. Disrupted copper homeostasis, particularly in the brain, has been associated with human diseases including the neurodegenerative disorders Wilson and Alzheimer?s disease. In this context, astrocytes play an important role in the regulation of the copper homeostasis in the brain and likely in the prevention against neuronal toxicity, consequently pointing them out as a potential target for the neurotoxicity of copper. Major toxic mechanisms are discussed to be directed against mitochondria probably via oxidative stress. However, the toxic potential and mode of action of copper in astrocytes is poorly understood, so far. Methods: In this study, excess copper levels affecting human astrocytic cell model and their involvement in the neurotoxic mode of action of copper, as well as, effects on the homeostasis of other trace elements (Mn, Fe, Ca and Mg) were investigated. Results: Copper induced substantial cytotoxic effects in the human astrocytic cell line following 48 h incubation (EC30: 250 ?M) and affected mitochondrial function, as observed via reduction of mitochondrial membrane potential and increased ROS production, likely originating from mitochondria. Moreover, cellular GSH metabolism was altered as well. Interestingly, not only cellular copper levels were affected, but also the homeostasis of other elements (Ca, Fe and Mn) were disrupted. Conclusion: One potential toxic mode of action of copper seems to be effects on the mitochondria along with induction of oxidative stress in the human astrocytic cell model. Moreover, excess copper levels seem to interact with the homeostasis of other essential elements such as Ca, Fe and Mn. Disrupted element homeostasis might also contribute to the induction of oxidative stress, likely involved in the onset and progression of neurodegenerative disorders. These insights in the toxic mechanisms will help to develop ideas and approaches for therapeutic strategies against copper-mediated diseases.}, language = {en} } @article{WittSchaumloeffelSchwerdtle2020, author = {Witt, Barbara and Schauml{\"o}ffel, Dirk and Schwerdtle, Tanja}, title = {Subcellular Localization of Copper}, series = {International Journal of Molecular Sciences}, volume = {21}, journal = {International Journal of Molecular Sciences}, number = {7}, publisher = {Molecular Diversity Preservation International}, address = {Basel}, issn = {1422-0067}, doi = {10.3390/ijms21072341}, pages = {25}, year = {2020}, abstract = {As an essential trace element, copper plays a pivotal role in physiological body functions. In fact, dysregulated copper homeostasis has been clearly linked to neurological disorders including Wilson and Alzheimer's disease. Such neurodegenerative diseases are associated with progressive loss of neurons and thus impaired brain functions. However, the underlying mechanisms are not fully understood. Characterization of the element species and their subcellular localization is of great importance to uncover cellular mechanisms. Recent research activities focus on the question of how copper contributes to the pathological findings. Cellular bioimaging of copper is an essential key to accomplish this objective. Besides information on the spatial distribution and chemical properties of copper, other essential trace elements can be localized in parallel. Highly sensitive and high spatial resolution techniques such as LA-ICP-MS, TEM-EDS, S-XRF and NanoSIMS are required for elemental mapping on subcellular level. This review summarizes state-of-the-art techniques in the field of bioimaging. Their strengths and limitations will be discussed with particular focus on potential applications for the elucidation of copper-related diseases. Based on such investigations, further information on cellular processes and mechanisms can be derived under physiological and pathological conditions. Bioimaging studies might enable the clarification of the role of copper in the context of neurodegenerative diseases and provide an important basis to develop therapeutic strategies for reduction or even prevention of copper-related disorders and their pathological consequences.}, language = {en} } @misc{WittSchaumloeffelSchaumloeffeletal.2020, author = {Witt, Barbara and Schauml{\"o}ffel, Dirk and Schauml{\"o}ffel, Dirk and Schwerdtle, Tanja}, title = {Subcellular Localization of Copper}, series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {862}, issn = {1866-8372}, doi = {10.25932/publishup-45954}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-459544}, pages = {27}, year = {2020}, abstract = {As an essential trace element, copper plays a pivotal role in physiological body functions. In fact, dysregulated copper homeostasis has been clearly linked to neurological disorders including Wilson and Alzheimer's disease. Such neurodegenerative diseases are associated with progressive loss of neurons and thus impaired brain functions. However, the underlying mechanisms are not fully understood. Characterization of the element species and their subcellular localization is of great importance to uncover cellular mechanisms. Recent research activities focus on the question of how copper contributes to the pathological findings. Cellular bioimaging of copper is an essential key to accomplish this objective. Besides information on the spatial distribution and chemical properties of copper, other essential trace elements can be localized in parallel. Highly sensitive and high spatial resolution techniques such as LA-ICP-MS, TEM-EDS, S-XRF and NanoSIMS are required for elemental mapping on subcellular level. This review summarizes state-of-the-art techniques in the field of bioimaging. Their strengths and limitations will be discussed with particular focus on potential applications for the elucidation of copper-related diseases. Based on such investigations, further information on cellular processes and mechanisms can be derived under physiological and pathological conditions. Bioimaging studies might enable the clarification of the role of copper in the context of neurodegenerative diseases and provide an important basis to develop therapeutic strategies for reduction or even prevention of copper-related disorders and their pathological consequences.}, language = {en} }