@article{AbebeHakiSchweigertetal.2019, author = {Abebe, Zeweter and Haki, Gulelat Desse and Schweigert, Florian J. and Henkel, Ina M. and Baye, Kaleab}, title = {Low breastmilk vitamin A concentration is prevalent in rural Ethiopia}, series = {European journal of clinical nutrition}, volume = {73}, journal = {European journal of clinical nutrition}, number = {8}, publisher = {Nature Publ. Group}, address = {London}, issn = {0954-3007}, doi = {10.1038/s41430-018-0334-4}, pages = {1110 -- 1116}, year = {2019}, abstract = {Background There is scant information on the breastmilk vitamin A (BMVA) concentration of lactating women in developing countries, partly due to lack of methods applicable in-field. Objective To assess BMVA concentrations of samples collected from lactating women of children aged 6-23 months, in Mecha district, Ethiopia. Subjects/methods Data on socio-demographic and anthropometric characteristics were collected from randomly selected lactating women (n = 104). Breast milk samples were collected and vitamin A concentrations were analyzed using HPLC and iCheck FLUORO then the two measurements were compared. Results The prevalence of underweight (BMI < 18.5 kg/m(2)) among lactating women was 17\%. Seventy six percent of the BMVA values were < 1.05 mu mol/l and 81\% were < 8 mu g/g fat. The mean BMVA concentration accounted to 41\% of the estimated average value for mothers in developing countries. The BMVA values from HPLC and iCheck were correlated (r = 0.59, p = < 0.001), but it was not strong. Conclusions The result indicates the low vitamin A status of the lactating women and their children. It further indicates that intake assessments should not use average BMVA composition. The possibility of using iCheck for monitoring interventions designed to improve vitamin A status of lactating women with low BMVA requires further investigation.}, language = {en} } @article{Abraham2003, author = {Abraham, Klaus}, title = {Minimal Inflammation, Acute Phase Response and Avoidance of Misclassification of Vitamin A and Iron Status in Infants-Importance of a High-Sensitivity C-Reactive Protein (CRP) Assay}, year = {2003}, language = {en} } @phdthesis{AgaBarfknecht2021, author = {Aga-Barfknecht, Heja}, title = {Investigation of the phenotype and genetic variant(s) of the diabetes locus Nidd/DBA}, school = {Universit{\"a}t Potsdam}, year = {2021}, abstract = {Diabetes is a major public health problem with increasing global prevalence. Type 2 diabetes (T2D), which accounts for 90\% of all diagnosed cases, is a complex polygenic disease also modulated by epigenetics and lifestyle factors. For the identification of T2D-associated genes, linkage analyses combined with mouse breeding strategies and bioinformatic tools were useful in the past. In a previous study in which a backcross population of the lean and diabetes-prone dilute brown non-agouti (DBA) mouse and the obese and diabetes-susceptible New Zealand obese (NZO) mouse was characterized, a major diabetes quantitative trait locus (QTL) was identified on chromosome 4. The locus was designated non-insulin dependent diabetes from DBA (Nidd/DBA). The aim of this thesis was (i) to perform a detailed phenotypic characterization of the Nidd/DBA mice, (ii) to further narrow the critical region and (iii) to identify the responsible genetic variant(s) of the Nidd/DBA locus. The phenotypic characterization of recombinant congenic mice carrying a 13.6 Mbp Nidd/DBA fragment with 284 genes presented a gradually worsening metabolic phenotype. Nidd/DBA allele carriers exhibited severe hyperglycemia (~19.9 mM) and impaired glucose clearance at 12 weeks of age. Ex vivo perifusion experiments with islets of 13-week-old congenic mice revealed a tendency towards reduced insulin secretion in homozygous DBA mice. In addition, 16-week-old mice showed a severe loss of β-cells and reduced pancreatic insulin content. Pathway analysis of transcriptome data from islets of congenic mice pointed towards a downregulation of cell survival genes. Morphological analysis of pancreatic sections displayed a reduced number of bi-hormonal cells co-expressing glucagon and insulin in homozygous DBA mice, which could indicate a reduced plasticity of endocrine cells in response to hyperglycemic stress. Further generation and phenotyping of recombinant congenic mice enabled the isolation of a 3.3 Mbp fragment that was still able to induce hyperglycemia and contained 61 genes. Bioinformatic analyses including haplotype mapping, sequence and transcriptome analysis were integrated in order to further reduce the number of candidate genes and to identify the presumable causative gene variant. Four putative candidate genes (Ttc39a, Kti12, Osbpl9, Calr4) were defined, which were either differentially expressed or carried a sequence variant. In addition, in silico ChIP-Seq analyses of the 3.3 Mbp region indicated a high number of SNPs located in active regions of binding sites of β-cell transcription factors. This points towards potentially altered cis-regulatory elements that could be responsible for the phenotype conferred by the Nidd/DBA locus. In summary, the Nidd/DBA locus mediates impaired glucose homeostasis and reduced insulin secretion capacity which finally leads to β-cell death. The downregulation of cell survival genes and reduced plasticity of endocrine cells could further contribute to the β-cell loss. The critical region was narrowed down to a 3.3 Mbp fragment containing 61 genes, of which four might be involved in the development of the diabetogenic Nidd/DBA phenotype.}, language = {en} } @article{AgaBarfknechtHallahanGottmannetal.2020, author = {Aga-Barfknecht, Heja and Hallahan, Nicole and Gottmann, Pascal and J{\"a}hnert, Markus and Osburg, Sophie and Schulze, Gunnar and Kamitz, Anne and Arends, Danny and Brockmann, Gudrun and Schallschmidt, Tanja and Lebek, Sandra and Chadt, Alexandra and Al-Hasani, Hadi and Joost, Hans-Georg and Sch{\"u}rmann, Annette and Vogel, Heike}, title = {Identification of novel potential type 2 diabetes genes mediating beta-cell loss and hyperglycemia using positional cloning}, series = {Frontiers in genetics}, volume = {11}, journal = {Frontiers in genetics}, publisher = {Frontiers Media}, address = {Lausanne}, issn = {1664-8021}, doi = {10.3389/fgene.2020.567191}, pages = {11}, year = {2020}, abstract = {Type 2 diabetes (T2D) is a complex metabolic disease regulated by an interaction of genetic predisposition and environmental factors. To understand the genetic contribution in the development of diabetes, mice varying in their disease susceptibility were crossed with the obese and diabetes-prone New Zealand obese (NZO) mouse. Subsequent whole-genome sequence scans revealed one major quantitative trait loci (QTL),Nidd/DBAon chromosome 4, linked to elevated blood glucose and reduced plasma insulin and low levels of pancreatic insulin. Phenotypical characterization of congenic mice carrying 13.6 Mbp of the critical fragment of DBA mice displayed severe hyperglycemia and impaired glucose clearance at week 10, decreased glucose response in week 13, and loss of beta-cells and pancreatic insulin in week 16. To identify the responsible gene variant(s), further congenic mice were generated and phenotyped, which resulted in a fragment of 3.3 Mbp that was sufficient to induce hyperglycemia. By combining transcriptome analysis and haplotype mapping, the number of putative responsible variant(s) was narrowed from initial 284 to 18 genes, including gene models and non-coding RNAs. Consideration of haplotype blocks reduced the number of candidate genes to four (Kti12,Osbpl9,Ttc39a, andCalr4) as potential T2D candidates as they display a differential expression in pancreatic islets and/or sequence variation. In conclusion, the integration of comparative analysis of multiple inbred populations such as haplotype mapping, transcriptomics, and sequence data substantially improved the mapping resolution of the diabetes QTLNidd/DBA. Future studies are necessary to understand the exact role of the different candidates in beta-cell function and their contribution in maintaining glycemic control.}, language = {en} } @article{AgaBarfknechtSoultoukisStadionetal.2022, author = {Aga-Barfknecht, Heja and Soultoukis, George A. and Stadion, Mandy and Garcia-Carrizo, Francisco and J{\"a}hnert, Markus and Gottmann, Pascal and Vogel, Heike and Schulz, Tim Julius and Sch{\"u}rmann, Annette}, title = {Distinct adipogenic and fibrogenic differentiation capacities of mesenchymal stromal cells from pancreas and white adipose tissue}, series = {International journal of molecular sciences}, volume = {23}, journal = {International journal of molecular sciences}, number = {4}, publisher = {Molecular Diversity Preservation International}, address = {Basel}, issn = {1422-0067}, doi = {10.3390/ijms23042108}, pages = {21}, year = {2022}, abstract = {Pancreatic steatosis associates with beta-cell failure and may participate in the development of type-2-diabetes. Our previous studies have shown that diabetes-susceptible mice accumulate more adipocytes in the pancreas than diabetes-resistant mice. In addition, we have demonstrated that the co-culture of pancreatic islets and adipocytes affect insulin secretion. The aim of this current study was to elucidate if and to what extent pancreas-resident mesenchymal stromal cells (MSCs) with adipogenic progenitor potential differ from the corresponding stromal-type cells of the inguinal white adipose tissue (iWAT). miRNA (miRNome) and mRNA expression (transcriptome) analyses of MSCs isolated by flow cytometry of both tissues revealed 121 differentially expressed miRNAs and 1227 differentially expressed genes (DEGs). Target prediction analysis estimated 510 DEGs to be regulated by 58 differentially expressed miRNAs. Pathway analyses of DEGs and miRNA target genes showed unique transcriptional and miRNA signatures in pancreas (pMSCs) and iWAT MSCs (iwatMSCs), for instance fibrogenic and adipogenic differentiation, respectively. Accordingly, iwatMSCs revealed a higher adipogenic lineage commitment, whereas pMSCs showed an elevated fibrogenesis. As a low degree of adipogenesis was also observed in pMSCs of diabetes-susceptible mice, we conclude that the development of pancreatic steatosis has to be induced by other factors not related to cell-autonomous transcriptomic changes and miRNA-based signals.}, language = {en} } @article{AhlbergRancanEppleetal.2016, author = {Ahlberg, Sebastian and Rancan, Fiorenza and Epple, Matthias and Loza, Kateryna and H{\"o}ppe, David and Lademann, J{\"u}rgen and Vogt, Annika and Kleuser, Burkhard and Gerecke, Christian and Meinke, Martina C.}, title = {Comparison of different methods to study effects of silver nanoparticles on the pro- and antioxidant status of human keratinocytes and fibroblasts}, series = {Methods : focusing on rapidly developing techniques}, volume = {109}, journal = {Methods : focusing on rapidly developing techniques}, publisher = {Elsevier}, address = {San Diego}, issn = {1046-2023}, doi = {10.1016/j.ymeth.2016.05.015}, pages = {55 -- 63}, year = {2016}, language = {en} } @article{AlFadelFayyazJaptoketal.2016, author = {Al Fadel, Frdoos and Fayyaz, Susann and Japtok, Lukasz and Kleuser, Burkhard}, title = {Involvement of Sphingosine 1-Phosphate in Palmitate-Induced Non-Alcoholic Fatty Liver Disease}, series = {Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology}, volume = {40}, journal = {Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology}, publisher = {Karger}, address = {Basel}, issn = {1015-8987}, doi = {10.1159/000453213}, pages = {1637 -- 1645}, year = {2016}, abstract = {Background/Aims: Ectopic lipid accumulation in hepatocytes has been identified as a risk factor for the progression of liver fibrosis and is strongly associated with obesity. In particular, the saturated fatty acid palmitate is involved in initiation of liver fibrosis via formation of secondary metabolites by hepatocytes that in turn activate hepatic stellate cells (HSCs) in a paracrine manner Methods: a-smooth muscle actin-expression (alpha-SMA) as a marker of liver fibrosis was investigated via western blot analysis and immunofluorescence microscopy in HSCs (LX-2). Sphingolipid metabolism and the generation of the bioactive secondary metabolite sphingosine I-phosphate (SIP) in response to palmitate were analyzed by LC-MS/MS in hepatocytes (HepG2). To identify the molecular mechanism involved in the progression of liver fibrosis real-time PCR analysis and pharmacological modulation of SIP receptors were performed. Results: Palmitate oversupply increased intra- and extracellular SIP-concentrations in hepatocytes. Conditioned medium from HepG2 cells initiated fibrosis by enhancing alpha-SMA-expression in LX-2 in a S1P-dependent manner In accordance, fibrotic response in the presence of SIP was also observed in HSCs. Pharmacological inhibition of SIP receptors demonstrated that S1P(3) is the crucial receptor subtype involved in this process. Conclusion: SIP is synthesized in hepatocytes in response to palmitate and released into the extracellular environment leading to an activation of HSCs via the S1P(3) receptor (C) 2016 The Author(s) Published by S. Karger AG, Basel}, language = {en} } @phdthesis{Alfine2021, author = {Alfine, Eugenia}, title = {Investigation of Sirtuin 3 overexpression as a genetic model of fasting in hypothalamic neurons}, school = {Universit{\"a}t Potsdam}, pages = {134}, year = {2021}, language = {en} } @misc{AlkerSchwerdtleSchomburgetal.2019, author = {Alker, Wiebke and Schwerdtle, Tanja and Schomburg, Lutz and Haase, Hajo}, title = {A Zinpyr-1-based fluorimetric microassay for free zinc in human serum}, series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {1086}, issn = {1866-8372}, doi = {10.25932/publishup-47283}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-472833}, pages = {15}, year = {2019}, abstract = {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.}, language = {en} } @article{AlterKretschmerVonWebskyetal.2012, author = {Alter, Markus L. and Kretschmer, Axel and Von Websky, Karoline and Tsuprykov, Oleg and Reichetzeder, Christoph and Simon, Alexandra and Stasch, Johannes-Peter and Hocher, Berthold}, title = {Early urinary and plasma biomarkers for experimental diabetic Nephropathy}, series = {Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion}, volume = {58}, journal = {Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion}, number = {7-8}, publisher = {Clin Lab Publ., Verl. Klinisches Labor}, address = {Heidelberg}, issn = {1433-6510}, doi = {10.7754/Clin.Lab.2011.111010}, pages = {659 -- 671}, year = {2012}, abstract = {Background: As the prevalence of diabetes rises, its complications such as diabetic nephropathy affect an increaseing number of patients. Consequently, the need for biomarkers in rodent models which reflect the stage and course of diabetic nephropathy is high. This article focuses on Heart-type fatty acid binding protein (H-FABP), osteopontin (OPN), nephrin, and Neutrophil gelatinase-associated lipocalin (NGAL) in urine, and kidney injury molecule (KIM)-1, clusterin, and tissue inhibitior of metalloproteinases (TIMP) 1 in plasma in uni-nephrectomized rats with streptocotozin-induced type 1 diabetes mellitus, a common animal model to explore renal impairment in the setting of diabetes mellitus. Methods: 23 male Wistar rats were uni-nephrectomized and subsequently divided into two study groups. The diabetic group received streptozotocin (STZ) via tail-vein injection, the non-diabetic group received citrate buffer without STZ. Subsequently, blood glucose, body weight, and blood pressure were checked regularly. After 18 weeks, animals were placed in metabolic cages, blood and urine obtained and subsequently organs were harvested after sacrifice. Results: Blood glucose levels were highly increased in diabetic animals throughout the experiment, whereas systolic blood pressure did not differ between the study groups. At study end, classical biomarkers such as urinary albumin and protein and plasma cystatin c were only slightly but not significantly different between groups indicating a very early disease state. In contrast, urinary excretion of H-FABP, OPN, nephrin, and NGAL were highly increased in diabetic animals with a highly significant p-value (p<0.01 each) compared to non-diabetic animals. In plasma, differences were found for calbindin, KIM-1, clusterin, TIMP-1, and OPN. These findings were confirmed by means of the area under the receiver operating characteristic curve (ROC-AUC) analysis. Conclusions: In summary, our study revealed elevated levels of new plasma and urinary biomarkers (urinary osteopontin, urinary nephrin, urinary NGAL, urinary H-FABP, plasma KIM-1, plasma TIMP-1) in uni-nephrectomized diabetic rats, an established rat model of diabetic nephropathy. These biomarkers appeared even before the classical biomarkers of diabetic nephropathy such as albuminuria and urinary protein excretion. The new biomarkers might offer advantage to urinary albumin and plasma cystatin c with respect to early detection.}, language = {en} } @article{AlterOttvonWebskyetal.2012, author = {Alter, Markus L. and Ott, Ina M. and von Websky, Karoline and Tsuprykov, Oleg and Sharkovska, Yuliya and Krause-Relle, Katharina and Raila, Jens and Henze, Andrea and Klein, Thomas and Hocher, Berthold}, title = {DPP-4 Inhibition on top of angiotensin receptor blockade offers a new therapeutic approach for diabetic nephropathy}, series = {Kidney \& blood pressure research : official organ of the Gesellschaft f{\"u}r Nephrologie}, volume = {36}, journal = {Kidney \& blood pressure research : official organ of the Gesellschaft f{\"u}r Nephrologie}, number = {1}, publisher = {Karger}, address = {Basel}, issn = {1420-4096}, doi = {10.1159/000341487}, pages = {119 -- 130}, year = {2012}, abstract = {Background: The need for an improved treatment for diabetic nephropathy is greatest in patients who do not adequately respond to angiotensin II receptor blockers (ARBs). This study investigated the effect of the novel dipeptidyl peptidase-4 inhibitor linagliptin alone and in combination with the ARB telmisartan on the progression of diabetic nephropathy in diabetic endothelial nitric oxide synthase (eNOS) knockout mice. Methods: Sixty male eNOS knockout C57BL/6J mice were divided into four groups after receiving intraperitoneal high-dose streptozotocin: telmisartan (1 mg/kg), linagliptin (3 mg/kg), linagliptin + telmisartan (3 mg/kg + 1 mg/kg) and vehicle. Fourteen mice were used as non-diabetic controls. Results: After 12 weeks, urine and blood were obtained and blood pressure measured. Glucose concentrations were increased and similar in all diabetic groups. Telmisartan alone reduced systolic blood pressure by 5.9 mmHg versus diabetic controls (111.2 +/- 2.3 mmHg vs 117.1 +/- 2.2 mmHg; mean +/- SEM; P = 0.071). Combined treatment significantly reduced albuminuria compared with diabetic controls (71.7 +/- 15.3 mu g/24 h vs 170.8 +/- 34.2 mu g/24 h; P = 0.017), whereas the effects of single treatment with either telmisartan (97.8 +/- 26.4 mu g/24 h) or linagliptin (120.8 +/- 37.7 mu g/24 h) were not statistically significant. DPP-4 inhibition, alone and in combination, led to significantly lower plasma osteopontin levels compared with telmisartan alone. Histological analysis revealed reduced glomerulosclerosis after Linagliptin alone and in combination with telmisartan in comparison to non treated diabetic animals (p < 0.01 and p < 0.05). Kidney malonaldehyde immune-reactivity, a marker of oxidative stress, was significantly lower in animals treated with linagliptin. Conclusions: DPP-4 inhibition on top of ARB treatment significantly reduced urinary albumin excretion and oxidative stress in diabetic eNOS knockout mice. Linagliptin on top of an angiotensin II receptor blocker may offer a new therapeutic approach for patients with diabetic nephropathy.}, language = {en} } @phdthesis{Ambrosi2016, author = {Ambrosi, Thomas H.}, title = {The Role of Bone-residing Adipocyte Progenitors in Age-related Stem Cell Dysfunction and Regenerative Processes}, school = {Universit{\"a}t Potsdam}, pages = {132}, year = {2016}, language = {en} } @article{AndertSanchaisuriyaSanchaisuriyaetal.2006, author = {Andert, Christoph U. and Sanchaisuriya, Pattara and Sanchaisuriya, Kanokwan and Schelp, Frank P. and Schweigert, Florian J.}, title = {Nutritional status of pregnant women in Northeast Thailand}, issn = {0964-7058}, year = {2006}, abstract = {A comparative study on the nutritional status of primiparous and multiparous women in the first trimester of pregnancy was conducted in the northeastern province of Thailand, Khon Kaen, to investigate differences in protein- energy-mal nutrition, iron deficiency anaemia, vitamin A deficiency and carotenoid status between both parity groups. 94 subjects were recruited at first attendance of antenatal clinic. Data about weight, height, haemoglobin and haematocrit were obtained from hospital records. Anthropometric measurements of mid-upper arm circumference and triceps skinfold were done on a sub sample. Retinol, carotenoids and alpha-tocopherol were analysed using a reversed-phase high- performance liquid chromatography method. Ferritin, transthyretin and retinol-binding protein were determined by enzyme- linked immunosorbent assay. Primiparous women showed lower body mass index, mid-upper arm circumference, corrected arm muscle area (P <0.001) as well as lower retinol, cholesterol and triceps skinfold (P <0.05). After adjusting for age and socio-economical status the significant difference persisted for all parameters but triceps skinfold. No significant differences of alpha-tocopherol, serum proteins, carotenoids and iron indices could be observed, even though a tendency to higher values for ferritin, haemoglobin and haematocrit was shown in multiparous women. Prevalence of protein-energy- malnutrition (body mass index <18.5 kg/m(2)) in the primiparous group was significantly higher compared to the multiparous group (P<0.05). Prevalence of protein-energy-malnutrition, iron deficiency anaemia and vitamin A deficiency were 15.1\%, 6.3\% and 3.3\%, respectively, in the total study population. No differences between parity groups could be observed for prevalence of iron deficiency anaemia and vitamin A deficiency}, language = {en} } @article{AngerWalzelKahrmann1994, author = {Anger, Horst and Walzel, Erwin and Kahrmann, Bettina}, title = {About the absorption of oligogalacturonates from the caecum of rats}, year = {1994}, language = {en} } @phdthesis{Appl2007, author = {Appl, Thomas}, title = {Neurochemical and functional characterisation of the Melanin-concentrating hormone system in the rat brain}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-14604}, school = {Universit{\"a}t Potsdam}, year = {2007}, abstract = {The central melanin-concentrating hormone (MCH) system has been intensively studied for its involvement in the regulation of feeding behaviour and body weight regulation. The importance of the neuropeptide MCH in the control of energy balance has been underlined by MCH knock out and Melanin-concentrating hormone receptor subtype 1 (MCHR-1) knock-out animals. The anorectic and anti-obesity effects of selective MCHR-1 antagonists have confirmed the notion that pharmacological blockade of MCHR-1 is a potential therapeutic approach for obesity. First aim of this work is to study the neurochemical "equipment" of MCHR-1 immunoreactive neurons by double-labelling immunohistochemistry within the rat hypothalamus. Of special interest is the neuroanatomical identification of other hypothalamic neuropeptides that are co-distributed with MCHR-1. A second part of this study deals with the examination of neuronal activation patterns after pharmacological or physiological, feeding-related stimuli and was introduced to further understand central regulatory mechanisms of the MCH system. In the first part of work, I wanted to neurochemically characterize MCHR-1 immunoreactive neurons in the rat hypothalamus for colocalisation with neuropeptides of interest. Therefore I performed an immunohistochemical colocalisation study using a specific antibody against MCHR-1 in combination with antibodies against hypothalamic neuropeptides. I showed that MCHR-1 immunoreactivity (IR) was co-localised with orexin A in the lateral hypothalamus, and with adrenocorticotropic hormone and neuropeptide Y in the arcuate nucleus. Additionally, MCHR-1 IR was co-localised with the neuropeptides vasopressin and oxytocin in magnocellular neurons of the supraoptic and paraventricular hypothalamic nucleus and corticotrophin releasing hormone in the parvocellular division of the paraventricular hypothalamic nucleus. Moreover, for the first time MCHR-1 immunoreactivity was found in both the adenohypophyseal and neurohypophyseal part of the rat pituitary. These results provide the neurochemical basis for previously described potential physiological actions of MCH at its target receptor. In particular, the MCHR-1 may be involved not only in food intake regulation, but also in other physiological actions such as fluid regulation, reproduction and stress response, possibly through here examined neuropeptides. Central activation patterns induced by pharmacological or physiological stimulation can be mapped using c-Fos immunohistochemistry. In the first experimental design, central administration (icv) of MCH in the rat brain resulted in acute and significant increase of food and water intake, but this animal treatment did not induce a specific c-Fos induction pattern in hypothalamic nuclei. In contrast, sub-chronic application of MCHR-1 antagonist promoted a significant decrease in food- and water intake during an eight day treatment period. A qualitative analysis of c-Fos immunohistochemistry of sections derived from MCHR-1 antagonist treated animals showed a specific neuronal activation in the paraventricular nucleus, the supraoptic nucleus and the dorsomedial hypothalamus. These results could be substantiated by quantitative evaluation of an automated, software-supported analysis of the c-Fos signal. Additionally, I examined the activation pattern of rats in a restricted feeding schedule (RFS) to identify pathways involved in hunger and satiety. Animals were trained for 9 days to feed during a three hour period. On the last day, food restricted animals was also allowed to feed for the three hours, while food deprived (FD) animals did not receive food. Mapping of neuronal activation showed a clear difference between stareved (FD) and satiated (FR) rats. FD animals showed significant induction of c-Fos in forebrain regions, several hypothalamic nuclei, amygdaloid thalamus and FR animals in the supraoptic nucleus and the paraventricular nucleus of the hypothalamus, and the nucleus of the solitary tract. In the lateral hypothalamus of FD rats, c-Fos IR showed strong colocalisation for Orexin A, but no co-staining for MCH immunoreactivity. However, a large number of c-Fos IR neurons within activated regions of FD and FR animals was co-localised with MCHR-1 within selected regions. To conclude, the experimental set-up of scheduled feeding can be used to induce a specific hunger or satiety activation pattern within the rat brain. My results show a differential activation by hunger signals of MCH neurons and furthermore, demonstrates that MCHR-1 expressing neurons may be essential parts of downstream processing of physiological feeding/hunger stimuli. In the final part of my work, the relevance of here presented studies is discussed with respect to possible introduction of MCHR-1 antagonists as drug candidates for the treatment of obesity.}, language = {en} } @misc{AschnerPalinskiSperlingetal.2017, author = {Aschner, Michael A. and Palinski, Catherine and Sperling, Michael and Karst, U. and Schwerdtle, Tanja and Bornhorst, Julia}, title = {Imaging metals in Caenorhabditis elegans}, series = {Metallomics : integrated biometal science}, volume = {9}, journal = {Metallomics : integrated biometal science}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {1756-5901}, doi = {10.1039/c6mt00265j}, pages = {357 -- 364}, year = {2017}, abstract = {Systemic trafficking and storage of essential metal ions play fundamental roles in living organisms by serving as essential cofactors in various cellular processes. Thereby metal quantification and localization are critical steps in understanding metal homeostasis, and how their dyshomeostasis might contribute to disease etiology and the ensuing pathologies. Furthermore, the amount and distribution of metals in organisms can provide insight into their underlying mechanisms of toxicity and toxicokinetics. While in vivo studies on metal imaging in mammalian experimental animals are complex, time- and resource-consuming, the nematode Caenorhabditis elegans (C. elegans) provides a suitable comparative and complementary model system. Expressing homologous genes to those inherent to mammals, including those that regulate metal homeostasis and transport, C. elegans has become a powerful tool to study metal homeostasis and toxicity. A number of recent technical advances have been made in the development and application of analytical methods to visualize metal ions in C. elegans. Here, we briefly summarize key findings and challenges of the three main techniques and their application to the nematode, namely sensing fluorophores, microbeam synchrotron radiation X-ray fluorescence as well as laser ablation ( LA) coupled to inductively coupled plasma-mass spectrometry (ICP-MS).}, language = {en} } @article{AuyyuenyongHenzeUngruetal.2017, author = {Auyyuenyong, Ratchada and Henze, Andrea and Ungru, Julia and Schweigert, Florian Johannes and Raila, Jens and Vervuert, Ingrid}, title = {Determination of lipid profiles in serum of obese ponies before and after weight reduction by using multi-one-dimensional thin-layer chromatography}, series = {Research in veterinary science}, volume = {117}, journal = {Research in veterinary science}, publisher = {Elsevier}, address = {Oxford}, issn = {0034-5288}, doi = {10.1016/j.rvsc.2017.11.013}, pages = {111 -- 117}, year = {2017}, abstract = {Obesity is a key component of equine metabolic syndrome, which is highly associated with laminitis. Feed restriction and/or exercise are known to alleviate the detrimental effects of insulin resistance in obese ponies. However, little is known about changes in the serum lipid patterns due to weight reduction and its association with disease outcomes. Therefore, the lipid patterns in the serum of 14 mature ponies before and after a 14-week body weight reduction program (BWRP) were investigated by multi-one-dimensional thin-layer chromatography (MOD-TLC). Additionally, sensitivity to insulin (SI), body condition scores (BCS) and cresty neck scores (CNS) were measured. A BWRP resulted in a significant loss of body weight (P < 0.001), which was associated with beneficial decreases in BCS and CNS (both, P < 0.001). Serum lipid compositions revealed significantly increased free fatty acid (FFA), sphingomyelin (SM; both P < 0.001), total cholesterol (C) and cholesterol ester (CE) (both P < 0.01) and triacylglycerol (TG; P < 0.05) densities. Improvement of SI after the BWRP was associated with increases in neutral lipids (C, CE and TG, all P < 0.01), FFA and the phospholipid SM (both, P < 0.001). The results show that a BWRP in obese ponies was effective and associated with changes in the concentrations of neutral lipids and the phospholipid SM, indicating that SM may play a role in insulin signaling pathways and thus in the pathogenesis of insulin resistance and the progression of metabolic syndrome in obese ponies.}, language = {en} } @misc{AvilaBenedettoAuetal.2016, author = {Avila, Daiana Silva and Benedetto, Alexandre and Au, Catherine and Bornhorst, Julia and Aschner, Michael A.}, title = {Involvement of heat shock proteins on Mn-induced toxicity in Caenorhabditis elegans}, series = {BMC pharmacology and toxicology}, journal = {BMC pharmacology and toxicology}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-407286}, pages = {9}, year = {2016}, abstract = {Background: All living cells display a rapid molecular response to adverse environmental conditions, and the heat shock protein family reflects one such example. Hence, failing to activate heat shock proteins can impair the cellular response. In the present study, we evaluated whether the loss of different isoforms of heat shock protein ( hsp ) genes in Caenorhabditis elegans would affect their vulnerability to Manganese (Mn) toxicity. Methods: We exposed wild type and selected hsp mutant worms to Mn (30 min) and next evaluated further the most susceptible strains. We analyzed survi val, protein carbonylation (as a marker of oxidative stress) and Parkinson ' s disease related gene expression immediately after Mn exposure. Lastly, we observed dopaminergic neurons in wild type worms and in hsp-70 mutants following Mn treatment. Analysis of the data was performed by one-way or two way ANOVA, depending on the case, followed by post-hoc Bonferroni test if the overall p value was less than 0.05. Results: We verified that the loss of hsp-70, hsp-3 and chn-1 increased the vulnerability to Mn, as exposed mutant worms showed lower survival rate and increased protein oxidation. The importance of hsp-70 against Mn toxicity was then corroborated in dopaminergic neurons, where Mn neurotoxicity was aggravated. The lack of hsp-70 also blocked the transcriptional upregulation of pink1 , a gene that has been linked to Parkinson ' sdisease. Conclusions: Taken together, our data suggest that Mn exposu re modulates heat shock protein expression, particularly HSP-70, in C. elegans .Furthermore,lossof hsp-70 increases protein oxidation and dopaminergic neuronal degeneration following manganese exposure, which is associated with the inhibition of pink1 increased expression, thus pot entially exacerbating the v ulnerability to this metal.}, language = {en} } @article{AvilaBenedettoAuetal.2016, author = {Avila, Daiana Silva and Benedetto, Alexandre and Au, Catherine and Bornhorst, Julia and Aschner, Michael A.}, title = {Involvement of heat shock proteins on Mn-induced toxicity in Caenorhabditis elegans}, series = {Plant Methods}, volume = {17}, journal = {Plant Methods}, publisher = {BioMed Central}, address = {London}, issn = {2050-6511}, doi = {10.1186/s40360-016-0097-2}, pages = {9}, year = {2016}, abstract = {Background: All living cells display a rapid molecular response to adverse environmental conditions, and the heat shock protein family reflects one such example. Hence, failing to activate heat shock proteins can impair the cellular response. In the present study, we evaluated whether the loss of different isoforms of heat shock protein (hsp) genes in Caenorhabditis elegans would affect their vulnerability to Manganese (Mn) toxicity. Conclusions: Taken together, our data suggest that Mn exposure modulates heat shock protein expression, particularly HSP-70, in C. elegans. Furthermore, loss of hsp-70 increases protein oxidation and dopaminergic neuronal degeneration following manganese exposure, which is associated with the inhibition of pink1 increased expression, thus potentially exacerbating the vulnerability to this metal.}, language = {en} } @article{BachmannHomeierArltetal.2009, author = {Bachmann, Lutz and Homeier, Timo and Arlt, Sebastian and Brueckner, Monika and Rawel, Harshadrai Manilal and Deiner, Carolin and Hartmann, Helmut}, title = {Influence of different oral rehydration solutions on abomasal conditions and the acid-base status of suckling calves}, issn = {0022-0302}, doi = {10.3168/jds.2008-1487}, year = {2009}, abstract = {The aim of the study was to investigate the influence of oral rehydration solutions (ORS) on milk clotting, abomasal pH, electrolyte concentrations, and osmolality, as well as on the acid-base status in blood of suckling calves, as treatment with ORS is the most common therapy of diarrhea in calves to correct dehydration and metabolic acidosis. Oral rehydration solutions are suspected to inhibit abomasal clotting of milk; however, it is recommended to continue feeding cow's milk or milk replacer (MR) to diarrheic calves to prevent body weight losses. Three calves with abomasal cannulas were fed MR, MR-ORS mixtures, or water-ORS mixtures, respectively. Samples of abomasal fluid were taken before and after feeding at various time points, and pH, electrolyte concentrations, and osmolality were measured. The interference of ORS with milk clotting was examined in vivo and in vitro. To evaluate the effects of ORS on systemic acid-base status, the Stewart variables strong ion difference ([SID]), acid total ([A(tot)]), and partial pressure of CO2 (pCO(2)) were quantified in venous blood samples drawn before and after feeding. Calves reached higher abomasal pH values when fed with MR-ORS mixtures than when fed MR. Preprandial pH values were re-established after 4 to 6 h. Oral rehydration solutions prepared in water increased the abomasal fluid pH only for 1 to 2 h. Oral rehydration solutions with high [SID3] ([Na+] + [K+] - [Cl-]) values produced significantly higher abomasal pH values and area under the curve data of the pH time course. Caseinomacropeptide, an indicator of successful enzymatic milk clotting, could be identified in every sample of abomasal fluid after feeding MR-ORS mixtures. The MR-ORS mixtures with [SID3] values >= 92 mmol/L increased serum [SID3] but did not change venous blood pH. Oral rehydration solutions do not interfere with milk clotting in the abomasum and can, therefore, be administered with milk. In this study, MR-ORS mixtures with high [SID3] values caused an increase of serum [SID3] in healthy suckling calves and may be an effective treatment for metabolic acidosis in calves suffering from diarrhea.}, language = {en} } @phdthesis{Backes2002, author = {Backes, Gunda}, title = {Microbial lysine synthesis and its conribution to lysine homeostatisis in minipigs : the effect of dietary lysine level and dietary adaptation period}, publisher = {Logos-Verl.}, address = {Berlin}, isbn = {3-89722-977-3}, pages = {101 S.}, year = {2002}, language = {en} } @phdthesis{Baeseler2021, author = {Baeseler, Jessica}, title = {Trace element effects on longevity and neurodegeneration with focus on C. elegans}, school = {Universit{\"a}t Potsdam}, pages = {X,114,VIII}, year = {2021}, abstract = {The trace elements zinc and manganese are essential for human health, especially due to their enzymatic and protein stabilizing functions. If these elements are ingested in amounts exceeding the requirements, regulatory processes for maintaining their physiological concentrations (homeostasis) can be disturbed. Those homeostatic dysregulations can cause severe health effects including the emergence of neurodegenerative disorders such as Parkinson's disease (PD). The concentrations of essential trace elements also change during the aging process. However, the relations of cause and consequence between increased manganese and zinc uptake and its influence on the aging process and the emergence of the aging-associated PD are still rarely understood. This doctoral thesis therefore aimed to investigate the influence of a nutritive zinc and/or manganese oversupply on the metal homeostasis during the aging process. For that, the model organism Caenorhabditis elegans (C. elegans) was applied. This nematode suits well as an aging and PD model due to properties such as its short life cycle and its completely sequenced, genetically amenable genome. Different protocols for the propagation of zinc- and/or manganese-supplemented young, middle-aged and aged C. elegans were established. Therefore, wildtypes, as well as genetically modified worm strains modeling inheritable forms of parkinsonism were applied. To identify homeostatic and neurological alterations, the nematodes were investigated with different methods including the analysis of total metal contents via inductively-coupled plasma tandem mass spectrometry, a specific probe-based method for quantifying labile zinc, survival assays, gene expression analysis as well as fluorescence microscopy for the identification and quantification of dopaminergic neurodegeneration.. During aging, the levels of iron, as well as zinc and manganese increased.. Furthermore, the simultaneous oversupply with zinc and manganese increased the total zinc and manganese contents to a higher extend than the single metal supplementation. In this relation the C. elegans metallothionein 1 (MTL-1) was identified as an important regulator of metal homeostasis. The total zinc content and the concentration of labile zinc were age-dependently, but differently regulated. This elucidates the importance of distinguishing these parameters as two independent biomarkers for the zinc status. Not the metal oversupply, but aging increased the levels of dopaminergic neurodegeneration. Additionally, nearly all these results yielded differences in the aging-dependent regulation of trace element homeostasis between wildtypes and PD models. This confirms that an increased zinc and manganese intake can influence the aging process as well as parkinsonism by altering homeostasis although the underlying mechanisms need to be clarified in further studies.}, language = {en} } @article{BaeslerKoppPohletal.2019, author = {Baesler, Jessica and Kopp, Johannes F. and Pohl, Gabriele and Aschner, Michael and Haase, Hajo and Schwerdtle, Tanja and Bornhorst, Julia}, title = {Zn homeostasis in genetic models of Parkinson's disease in Caenorhabditis elegans}, series = {Journal of trace elements in medicine and biology}, volume = {55}, journal = {Journal of trace elements in medicine and biology}, publisher = {Elsevier GMBH}, address = {M{\"u}nchen}, issn = {0946-672X}, doi = {10.1016/j.jtemb.2019.05.005}, pages = {44 -- 49}, year = {2019}, language = {en} } @article{BaeslerKoppPohletal.2019, author = {Baesler, Jessica and Kopp, Johannes Florian and Pohl, Gabriele and Aschner, Michael and Haase, Hajo and Schwerdtle, Tanja and Bornhorst, Julia}, title = {Zn homeostasis in genetic models of Parkinson's disease in Caenorhabditis elegans}, series = {Journal of Trace Elements in Medicine and Biology}, volume = {55}, journal = {Journal of Trace Elements in Medicine and Biology}, publisher = {Elsevier}, address = {M{\"u}nchen}, doi = {10.1016/j.jtemb.2019.05.005}, pages = {44 -- 49}, year = {2019}, abstract = {While the underlying mechanisms of Parkinson's disease (PD) are still insufficiently studied, a complex interaction between genetic and environmental factors is emphasized. Nevertheless, the role of the essential trace element zinc (Zn) in this regard remains controversial. In this study we altered Zn balance within PD models of the versatile model organism Caenorhabditis elegans (C. elegans) in order to examine whether a genetic predisposition in selected genes with relevance for PD affects Zn homeostasis. Protein-bound and labile Zn species act in various areas, such as enzymatic catalysis, protein stabilization pathways and cell signaling. Therefore, total Zn and labile Zn were quantitatively determined in living nematodes as individual biomarkers of Zn uptake and bioavailability with inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) or a multi-well method using the fluorescent probe ZinPyr-1. Young and middle-aged deletion mutants of catp-6 and pdr-1, which are orthologues of mammalian ATP13A2 (PARK9) and parkin (PARK2), showed altered Zn homeostasis following Zn exposure compared to wildtype worms. Furthermore, age-specific differences in Zn uptake were observed in wildtype worms for total as well as labile Zn species. These data emphasize the importance of differentiation between Zn species as meaningful biomarkers of Zn uptake as well as the need for further studies investigating the role of dysregulated Zn homeostasis in the etiology of PD.}, language = {en} } @misc{BaeslerMichaelisStibolleretal.2021, author = {Baesler, Jessica and Michaelis, Vivien and Stiboller, Michael and Haase, Hajo and Aschner, Michael and Schwerdtle, Tanja and Sturzenbaum, Stephen R. and Bornhorst, Julia}, title = {Nutritive manganese and zinc overdosing in aging c. elegans result in a metallothionein-mediated alteration in metal homeostasis}, series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {8}, issn = {1866-8372}, doi = {10.25932/publishup-51499}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-514995}, pages = {13}, year = {2021}, abstract = {Manganese (Mn) and zinc (Zn) are not only essential trace elements, but also potential exogenous risk factors for various diseases. Since the disturbed homeostasis of single metals can result in detrimental health effects, concerns have emerged regarding the consequences of excessive exposures to multiple metals, either via nutritional supplementation or parenteral nutrition. This study focuses on Mn-Zn-interactions in the nematode Caenorhabditis elegans (C. elegans) model, taking into account aspects related to aging and age-dependent neurodegeneration.}, language = {en} } @article{BaeslerMichaelisStibolleretal.2021, author = {Baesler, Jessica and Michaelis, Vivien and Stiboller, Michael and Haase, Hajo and Aschner, Michael and Schwerdtle, Tanja and Sturzenbaum, Stephen R. and Bornhorst, Julia}, title = {Nutritive manganese and zinc overdosing in aging c. elegans result in a metallothionein-mediated alteration in metal homeostasis}, series = {Molecular Nutrition and Food Research}, volume = {65}, journal = {Molecular Nutrition and Food Research}, number = {8}, publisher = {Wiley-VCH GmbH}, address = {Weinheim}, issn = {1613-4133}, doi = {10.1002/mnfr.202001176}, pages = {1 -- 11}, year = {2021}, abstract = {Manganese (Mn) and zinc (Zn) are not only essential trace elements, but also potential exogenous risk factors for various diseases. Since the disturbed homeostasis of single metals can result in detrimental health effects, concerns have emerged regarding the consequences of excessive exposures to multiple metals, either via nutritional supplementation or parenteral nutrition. This study focuses on Mn-Zn-interactions in the nematode Caenorhabditis elegans (C. elegans) model, taking into account aspects related to aging and age-dependent neurodegeneration.}, language = {en} } @article{BaierPurschkeSchmittetal.2015, author = {Baier, Daniel and Purschke, Benedict and Schmitt, Christophe and Rawel, Harshadrai Manilal and Knorr, Dietrich}, title = {Effect of high pressure - low temperature treatments on structural characteristics of whey proteins and micellar caseins}, series = {Food chemistry}, volume = {187}, journal = {Food chemistry}, publisher = {Elsevier}, address = {Oxford}, issn = {0308-8146}, doi = {10.1016/j.foodchem.2015.04.049}, pages = {354 -- 363}, year = {2015}, abstract = {In this study, structural changes in micellar caseins and whey proteins due to high pressure - low temperature treatments (HPLT) were investigated and compared to changes caused by high pressure treatments at room temperature. Whey protein isolate (WPI) solutions as well as micellar casein (MC) dispersions and mixtures were treated at 500 MPa (pH 7.0 and 5.8) at room temperature, -15 degrees C and -35 degrees C. Surface hydrophobicity and accessible thiol groups remained nearly unchanged after HPLT treatments whereas HP treatments at room temperature caused an unfolding of the WPI, resulting in an increase in surface hydrophobicity and exposure of the thiol groups. For HPLT treatments, distinct changes in the secondary structure (increase in the amount of beta-sheets) were observed while the tertiary structure remained unchanged. Large flocs, stabilized by hydrophobic interactions and hydrogen bonds, were formed in casein containing samples due to HPLT treatments. Depending on the pH and the applied HPLT treatment parameters, these interactions differed significantly from the interactions determined in native micelles. (C) 2015 Elsevier Ltd. All rights reserved.}, language = {en} } @misc{BaldermannBlagojevicFredeetal.2016, author = {Baldermann, Susanne and Blagojevic, Lara and Frede, Katja and Klopsch, R. and Neugart, Susanne and Neumann, A. and Ngwene, Benard and Norkeweit, Jessica and Schroeter, D. and Schroeter, A. and Schweigert, Florian J. and Wiesner, M. and Schreiner, Monika}, title = {Are Neglected Plants the Food for the Future?}, series = {Critical reviews in plant sciences}, volume = {35}, journal = {Critical reviews in plant sciences}, publisher = {Institut d'Estudis Catalans}, address = {Philadelphia}, issn = {0735-2689}, doi = {10.1080/07352689.2016.1201399}, pages = {106 -- 119}, year = {2016}, abstract = {Malnutrition, poor health, hunger, and even starvation are still the world's greatest challenges. Malnutrition is defined as deficiency of nutrition due to not ingesting the proper amounts of nutrients by simply not eating enough food and/or by consuming nutrient-poor food in respect to the daily nutritional requirements. Moreover, malnutrition and disease are closely associated and incidences of such diet-related diseases increase particularly in low- and middle-income states. While foods of animal origin are often unaffordable to low-income families, various neglected crops can offer an alternative source of micronutrients, vitamins, as well as health-promoting secondary plant metabolites. Therefore, agricultural and horticultural research should develop strategies not only to produce more food, but also to improve access to more nutritious food. In this context, one promising approach is to promote biodiversity in the dietary pattern of low-income people by getting access to nutritional as well as affordable food and providing recommendations for food selection and preparation. Worldwide, a multitude of various plant species are assigned to be consumed as grains, vegetables, and fruits, but only a limited number of these species are used as commercial cash crops. Consequently, numerous neglected and underutilized species offer the potential to diversify not only the human diet, but also increase food production levels, and, thus, enable more sustainable and resilient agro- and horti-food systems. To exploit the potential of neglected plant (NP) species, coordinated approaches on the local, regional, and international level have to be integrated that consequently demand the involvement of numerous multi-stakeholders. Thus, the objective of the present review is to evaluate whether NP species are important as "Future Food" for improving the nutritional status of humans as well as increasing resilience of agro- and horti-food systems.}, language = {en} } @misc{BaldermannHomannNeugartetal.2018, author = {Baldermann, Susanne and Homann, Thomas and Neugart, Susanne and Chmielewski, Frank M. and G{\"o}tz, Klaus-Peter and G{\"o}deke, Kristin and Huschek, Gerd and Morlock, Gertrud E. and Rawel, Harshadrai Manilal}, title = {Selected Plant Metabolites Involved in Oxidation-Reduction Processes during Bud Dormancy and Ontogenetic Development in Sweet Cherry Buds (Prunus avium L.)}, series = {Molecules}, journal = {Molecules}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-417442}, pages = {19}, year = {2018}, abstract = {Many biochemical processes are involved in regulating the consecutive transition of different phases of dormancy in sweet cherry buds. An evaluation based on a metabolic approach has, as yet, only been partly addressed. The aim of this work, therefore, was to determine which plant metabolites could serve as biomarkers for the different transitions in sweet cherry buds. The focus here was on those metabolites involved in oxidation-reduction processes during bud dormancy, as determined by targeted and untargeted mass spectrometry-based methods. The metabolites addressed included phenolic compounds, ascorbate/dehydroascorbate, reducing sugars, carotenoids and chlorophylls. The results demonstrate that the content of phenolic compounds decrease until the end of endodormancy. After a long period of constancy until the end of ecodormancy, a final phase of further decrease followed up to the phenophase open cluster. The main phenolic compounds were caffeoylquinic acids, coumaroylquinic acids and catechins, as well as quercetin and kaempferol derivatives. The data also support the protective role of ascorbate and glutathione in the para- and endodormancy phases. Consistent trends in the content of reducing sugars can be elucidated for the different phenophases of dormancy, too. The untargeted approach with principle component analysis (PCA) clearly differentiates the different timings of dormancy giving further valuable information.}, language = {en} } @article{BaldermannHomannNeugartetal.2018, author = {Baldermann, Susanne and Homann, Thomas and Neugart, Susanne and Chmielewski, Frank M. and G{\"o}tz, Klaus-Peter and G{\"o}deke, Kristin and Huschek, Gerd and Morlock, Gertrud E. and Rawel, Harshadrai Manilal}, title = {Selected Plant Metabolites Involved in Oxidation-Reduction Processes during Bud Dormancy and Ontogenetic Development in Sweet Cherry Buds (Prunus avium L.)}, series = {Molecules}, volume = {23}, journal = {Molecules}, number = {5}, publisher = {Molecular Diversity Preservation International}, address = {Basel}, issn = {1420-3049}, doi = {10.3390/molecules23051197}, pages = {1 -- 19}, year = {2018}, abstract = {Many biochemical processes are involved in regulating the consecutive transition of different phases of dormancy in sweet cherry buds. An evaluation based on a metabolic approach has, as yet, only been partly addressed. The aim of this work, therefore, was to determine which plant metabolites could serve as biomarkers for the different transitions in sweet cherry buds. The focus here was on those metabolites involved in oxidation-reduction processes during bud dormancy, as determined by targeted and untargeted mass spectrometry-based methods. The metabolites addressed included phenolic compounds, ascorbate/dehydroascorbate, reducing sugars, carotenoids and chlorophylls. The results demonstrate that the content of phenolic compounds decrease until the end of endodormancy. After a long period of constancy until the end of ecodormancy, a final phase of further decrease followed up to the phenophase open cluster. The main phenolic compounds were caffeoylquinic acids, coumaroylquinic acids and catechins, as well as quercetin and kaempferol derivatives. The data also support the protective role of ascorbate and glutathione in the para- and endodormancy phases. Consistent trends in the content of reducing sugars can be elucidated for the different phenophases of dormancy, too. The untargeted approach with principle component analysis (PCA) clearly differentiates the different timings of dormancy giving further valuable information.}, language = {en} } @article{BalzusSahleHoenzkeetal.2017, author = {Balzus, Benjamin and Sahle, Fitsum Feleke and H{\"o}nzke, Stefan and Gerecke, Christian and Schumacher, Fabian and Hedtrich, Sarah and Kleuser, Burkhard and Bodmeier, Roland}, title = {Formulation and ex vivo evaluation of polymeric nanoparticles for controlled delivery of corticosteroids to the skin and the corneal epithelium}, series = {European journal of pharmaceutics and biopharmaceutics : EJPB ; official journal of the International Association for Pharmaceutical Technology}, volume = {115}, journal = {European journal of pharmaceutics and biopharmaceutics : EJPB ; official journal of the International Association for Pharmaceutical Technology}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0939-6411}, doi = {10.1016/j.ejpb.2017.02.001}, pages = {122 -- 130}, year = {2017}, abstract = {Controlled delivery of corticosteroids using nanoparticles to the skin and corneal epithelium may reduce their side effects and maximize treatment effectiveness. Dexamethasone-loaded ethyl cellulose, Eudragit® RS and ethyl cellulose/Eudragit® RS nanoparticles were prepared by the solvent evaporation method. Dexamethasone release from the polymeric nanoparticles was investigated in vitro using Franz diffusion cells. Drug penetration was also assessed ex vivo using excised human skin. Nanoparticle toxicity was determined by MTT and H2DCFDA assays. Eudragit® RS nanoparticles were smaller and positively charged but had a lower dexamethasone loading capacity (0.3-0.7\%) than ethyl cellulose nanoparticles (1.4-2.2\%). By blending the two polymers (1:1), small (105 nm), positively charged (+37 mV) nanoparticles with sufficient dexamethasone loading (1.3\%) were obtained. Dexamethasone release and penetration significantly decreased with decreasing drug to polymer ratio and increased when Eudragit® RS was blended with ethyl cellulose. Ex vivo, drug release and penetration from the nanoparticles was slower than a conventional cream. The nanoparticles bear no toxicity potentials except ethyl cellulose nanoparticles had ROS generation potential at high concentration. In conclusion, the nanoparticles showed great potential to control the release and penetration of corticosteroids on the skin and mucus membrane and maximize treatment effectiveness.}, language = {en} } @article{BanningDeubelKluthetal.2005, author = {Banning, Anja and Deubel, S. and Kluth, Dirk and Zhou, Z. W. and Brigelius-Floh{\´e}, Regina}, title = {The GI-GPx gene is a target for Nrf2}, issn = {0270-7306}, year = {2005}, abstract = {The gastrointestinal glutathione peroxidase (GI-GPx, GPx2) is a selenoprotein that was suggested to act as barrier against hydroperoxide absorption but has also been implicated in the control of inflammation and malignant growth. In CaCo-2 cells, GI-GPx was induced by t-butyl hydroquinone (tBHQ) and sulforaphane (SFN), i.e., "antioxidants" known to activate the "antioxidant response element" (ARE) via electrophilic thiol modification of Keap1 in the Nrf2/ Keap1 system. The functional significance of a putative ARE in the GI-GPx promoter was validated by transcriptional activation of reporter gene constructs upon exposure to electrophiles (tBHQ, SFN, and curcumin) or overexpression of Nrf2 and by reversal of these effects by mutation of the ARE in the promoter and by overexpressed Keap1. Binding of Nrf2 to the ARE sequence in authentic gpx2 was corroborated by chromatin immunoprecipitation. Thus, the presumed natural antioxidants sulforaphane and curcumin may exert their anti-inflammatory and anticarcinogenic effects not only by induction of phase 2 enzymes but also by the up-regulation of the selenoprotein GI-GPx}, language = {en} } @inproceedings{BaranyaiGoedtelArmbrustNestleretal.2014, author = {Baranyai, Dorothea and Goedtel-Armbrust, Ute and Nestler, Sebastian and Kleuser, Burkhard and Wojnowski, Leszek}, title = {A role for cutaneous CYP3A in vitamin D homeostasis?}, series = {NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY}, volume = {387}, booktitle = {NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY}, publisher = {Springer}, address = {New York}, issn = {0028-1298}, pages = {S27 -- S27}, year = {2014}, language = {en} } @article{BarceloCoblijnLauraMartindeAlmeidaetal.2011, author = {Barcelo-Coblijn, Gwendolyn and Laura Martin, Maria and de Almeida, Rodrigo F. M. and Antonia Noguera-Salva, Maria and Marcilla-Etxenike, Amaia and Guardiola-Serrano, Francisca and Lueth, Anja and Kleuser, Burkhard and Halver, John E. and Escriba, Pablo V.}, title = {Sphingomyelin and sphingomyelin synthase (SMS) in the malignant transformation of glioma cells and in 2-hydroxyoleic acid therapy}, series = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {108}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {49}, publisher = {National Acad. of Sciences}, address = {Washington}, issn = {0027-8424}, doi = {10.1073/pnas.1115484108}, pages = {19569 -- 19574}, year = {2011}, abstract = {The mechanism of action of 2-hydroxyoleic acid (2OHOA), a potent antitumor compound, has not yet been fully elucidated. Here, we show that human cancer cells have markedly lower levels of sphingomyelin (SM) than nontumor (MRC-5) cells. In this context, 2OHOA treatment strongly augments SM mass (4.6-fold), restoring the levels found in MRC-5 cells, while a loss of phosphatidylethanolamine and phosphatidylcholine is observed (57 and 30\%, respectively). The increased SM mass was due to a rapid and highly specific activation of SM synthases (SMS). This effect appeared to be specific against cancer cells as it did not affect nontumor MRC-5 cells. Therefore, low SM levels are associated with the tumorigenic transformation that produces cancer cells. SM accumulation occurred at the plasma membrane and caused an increase in membrane global order and lipid raft packing in model membranes. These modifications would account for the observed alteration by 2OHOA in the localization of proteins involved in cell apoptosis (Fas receptor) or differentiation (Ras). Importantly, SMS inhibition by D609 diminished 2OHOA effect on cell cycle. Therefore, we propose that the regulation of SMS activity in tumor cells is a critical upstream event in 2OHOA antitumor mechanism, which also explains its specificity for cancer cells, its potency, and the lack of undesired side effects. Finally, the specific activation of SMS explains the ability of this compound to trigger cell cycle arrest, cell differentiation, and autophagy or apoptosis in cancer cells.}, language = {en} } @article{BarlowGreigBridgesetal.2002, author = {Barlow, S. M. and Greig, J. B. and Bridges, J. W. and Carere, A. and Carpy, A. J. and Galli, Corrado L. and Kleiner, J. and Knudsen, I. and Koeter, H. B. and Levy, L. S. and Madsen, C. and Mayer, S. and Narbonne, J. F. and Pfannkuch, F. and Prodanchuk, M. G. and Smith, Mason R. and Steinberg, Pablo}, title = {Hazard identification by methods of animal-based toxicology}, year = {2002}, language = {en} } @article{Barth2009, author = {Barth, Christian A.}, title = {Nutritional value of rapeseed oil and its high oleic/low linolenic variety : a call for differentiation}, issn = {1438-7697}, doi = {10.1002/ejlt.200900019}, year = {2009}, abstract = {To offer the best choice of healthy and acceptable food to the consumer a coordination of plant breeding, food processing and nutrition science is required. Here the nutritional aspects of the high oleic/low linolenic (HOLLi) varieties of rapeseed with a low alpha-linolenic acid content of about 3\% are reviewed. The content of alpha-linolenic acid amounting to around 9\% is the hallmark of the positive nutritional value of the original (erucic acid free) 00 varieties of rapeseed oil ("canola" quality in North America). n-3 fatty acids are endowed with the property to protect the cardiovascular system from chronic disease and the consumption of food containing n-3 fatty acids is explicitly recommended by national and international nutritional and medical authorities. Although the use of HOLLi with a low n-3 fatty acid content can be unavoidable for specific purposes, because of technological and health considerations the continuous future consumption of the original rapeseed oil with around 9\% of alpha-linolenic acid by the consumer should have high priority from the standpoint of public health. To pursue this aim confusion of the consumer must be avoided by creating a new name and a new brand for HOLLi varieties.}, language = {en} } @article{BartschZschalerHaseloffetal.2003, author = {Bartsch, Ingrid and Zschaler, Ingrid and Haseloff, Monika and Steinberg, Pablo}, title = {Establishment of a long-term culture system for rat colon epithelial cells}, issn = {1071-2690}, doi = {10.1290/0404035.1}, year = {2003}, abstract = {The aim of this study was to establish a long-term culture. system for rat colon epithelia isolaled by incubating a 4-cm-long rat colon segment cut longitudinally with all ethylenediaminetetraacetic acid [disodium salt]- containing buffer, taken up in conditioned medium from the normal rat kidney fibroblast cell line NRK (i.e., the supernatant Of pure NRK cultures), directly plated on mitomycin C-treated NRK cells and subcultured with conditioned medium from NRK cells. Cells started to migrate out of the crypts shortly after plating them on NRK feeder layers. Some of the crypts fell apart during the isolation procedure. whereas the vast majority of them did it within I to 2 Ill after plating. The cells proliferated extremely slowly but continuously over a period of 4 mo and were epithelial because they expressed cytokeratin 19 and were stained by crystal violet at pH 2.8. In conclusion, the experimental system described ill this study allows to maintain rat colon epithelial cells for up to 4 mo in culture and can be used to Study the effects of a variety of tumor-modulating factors on growth and gene expression of normal colon epithelial cells in vitro}, language = {en} } @article{BasaranDuyduUstundagetal.2019, author = {Basaran, Nursen and Duydu, Yalcin and Ustundag, Aylin and Taner, Gokce and Aydin, Sevtap and Anlar, Hatice Gul and Yalcin, Can {\"O}zg{\"u}r and Bacanli, Merve and Aydos, Kaan and Atabekoglu, Cem Somer and Golka, Klaus and Ickstadt, Katja and Schwerdtle, Tanja and Werner, Matthias and Meyer, S{\"o}ren and Bolt, Hermann M.}, title = {Evaluation of the DNA damage in lymphocytes, sperm and buccal cells of workers under environmental and occupational boron exposure conditions}, series = {Mutation Research/Genetic Toxicology and Environmental Mutagenesis}, volume = {843}, journal = {Mutation Research/Genetic Toxicology and Environmental Mutagenesis}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1383-5718}, doi = {10.1016/j.mrgentox.2018.12.013}, pages = {33 -- 39}, year = {2019}, abstract = {Industrial production and use of boron compounds have increased during the last decades, especially for the manufacture of borosilicate glass, fiberglass, metal alloys and flame retardants. This study was conducted in two districts of Balikesir; Bandirma and Bigadic, which geographically belong to the Marmara Region of Turkey. Bandirma is the production and exportation zone for the produced boric acid and some borates and Bigadic has the largest B deposits in Turkey. 102 male workers who were occupationally exposed to boron from Bandirma and 110 workers who were occupationally and environmentally exposed to boron from Bigadic participated to our study. In this study the DNA damage in the sperm, blood and buccal cells of 212 males was evaluated by comet and micronucleus assays. No significant increase in the DNA damage in blood, sperm and buccal cells was observed in the residents exposed to boron both occupationally and environmentally (p = 0.861) for Comet test in the sperm samples, p = 0.116 for Comet test in the lymphocyte samples, p = 0.042 for micronucleus (MN) test, p = 0.955 for binucleated cells (BN), p = 1.486 for condensed chromatin (CC), p = 0.455 for karyorrhectic cells (KHC), p = 0.541 for karyolitic cells (KLY), p = 1.057 for pyknotic cells (PHC), p = 0.331 for nuclear bud (NBUD)). No correlations were seen between blood boron levels and tail intensity values of the sperm samples, lymphocyte samples, frequencies of MN, BN, KHC, KYL, PHC and NBUD. The results of this study came to the same conclusions of the previous studies that boron does not induce DNA damage even under extreme exposure conditions.}, language = {en} } @phdthesis{Baumeier2015, author = {Baumeier, Christian}, title = {Dietary and Pharmacological Strategies for the Prevention and Treatment of Type 2 Diabetes in a Diabetes-Susceptible Mouse Model}, school = {Universit{\"a}t Potsdam}, pages = {148}, year = {2015}, language = {en} } @article{BaşaranDuyduUestuendağetal.2019, author = {Ba{\c{s}}aran, Nur{\c{s}}en and Duydu, Yal{\c{c}}{\i}n and {\"U}st{\"u}ndağ, Aylin and Taner, G{\"o}k{\c{c}}e and Aydin Dilsiz, Sevtap and Anlar, Hatice G{\"u}l and Yal{\c{c}}in, Can {\"O}zg{\"u}r and Bacanli, Merve and Golka, Klaus and Schwerdtle, Tanja and Bolt, Hermann M.}, title = {Environmental boron exposure does not induce DNA damage in lymphocytes and buccal cells of females DNA damage in lymphocytes and buccal cells of boron exposed females}, series = {Journal of trace elements in medicine and biology}, volume = {53}, journal = {Journal of trace elements in medicine and biology}, publisher = {Elsevier B.V.}, address = {M{\"u}nchen}, issn = {0946-672X}, doi = {10.1016/j.jtemb.2019.03.004}, pages = {150 -- 153}, year = {2019}, abstract = {Boron (B) compounds are essential for plants and animals and beneficial for humans in nutritional amounts. I animals and humans increasing evidence have shown beneficial effects on B compounds on nutrition and on antioxidant status. The genotoxic effects of environmental B exposure in women living in boron-rich and boronpoor areas was examined in this study. For this purpose, the DNA damage in the lymphocytes and buccal cells of females were assessed by Comet and micronucleus (MN) assays respectively. No significant difference was observed in the DNA damage of the lymphocytes of B exposed groups of female volunteers in Comet assay. Even buccal micronucleus (MN) frequency observed in the high exposure group was significantly lower than the low exposure group (p < 0.05). The results of this study came to the same conclusions of the previous studies that boron does not induce DNA damage even under extreme exposure conditions.}, language = {en} } @article{BechirSchellingKraemeretal.2012, author = {Bechir, Mahamat and Schelling, E. and Kr{\"a}mer, K. and Schweigert, Florian J. and Bonfoh, Bassirou and Crump, L. and Tanner, M. and Zinsstag, J.}, title = {Retinol assessment among women and children in sahelian mobile pastoralists}, series = {EcoHealth : conservation medicine, human health, ecosystem sustainability}, volume = {9}, journal = {EcoHealth : conservation medicine, human health, ecosystem sustainability}, number = {2}, publisher = {Springer}, address = {New York}, issn = {1612-9202}, doi = {10.1007/s10393-012-0781-7}, pages = {113 -- 121}, year = {2012}, abstract = {Micronutrient deficiencies are widespread in developing countries, particularly in remote communities such as mobile pastoralists. The nutritional and vitamin A status of this population is not well-documented in Chad. This study assessed serum retinol levels among women and children under five-year-old in nomadic and semi-nomadic pastoralist and rural-settled communities, who are similarly exposed to risk factors such as gastrointestinal parasitic infection, anaemia and emaciation. The novel method of portable fluorometry was used for the first time to measure beta-carotene and retinol levels in a pastoral nomadic area. Moderate level blood retinol deficiency (< 0.7 mu mol/L) was observed in 5\% (CI 1-11) of nomadic, 29\% (CI 13-45) of semi-nomadic and 22\% (CI 8-35) of sedentary women. In children, 1\% (CI 0.1-4), 17\% (CI 9-25) and 28\% (CI 18-39), respectively, had moderate level blood retinol deficiency. In nomadic communities, women and children had blood retinol levels close to normal. Deficiency of retinol was strongly linked with lifestyle (nomadic, semi-nomadic and settled) among women and lifestyle and age among children. The results support an ecological linkage between human retinol levels and livestock milk retinol. This study shows the feasibility of portable retinol and beta-carotene measurement in human blood as well as human and animal milk under remote field conditions, but the approach requires further validation.}, language = {en} } @misc{BeckerRiethmuellerSeitzetal.2018, author = {Becker, Katrin Anne and Riethmueller, Joachim and Seitz, Aaron P. and Gardner, Aaron and Boudreau, Ryan and Kamler, Markus and Kleuser, Burkhard and Schuchman, Edward and Caldwell, Charles C. and Edwards, Michael J. and Grassme, Heike and Brodlie, Malcolm and Gulbins, Erich}, title = {Sphingolipids as targets for inhalation treatment of cystic fibrosis}, series = {Advanced drug delivery reviews}, volume = {133}, journal = {Advanced drug delivery reviews}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0169-409X}, doi = {10.1016/j.addr.2018.04.015}, pages = {66 -- 75}, year = {2018}, abstract = {Studies over the past several years have demonstrated the important role of sphingolipids in cystic fibrosis (CF), chronic obstructive pulmonary disease and acute lung injury. Ceramide is increased in airway epithelial cells and alveolar macrophages of CF mice and humans, while sphingosine is dramatically decreased. This increase in ceramide results in chronic inflammation, increased death of epithelial cells, release of DNA into the bronchial lumen and thereby an impairment of mucociliary clearance; while the lack of sphingosine in airway epithelial cells causes high infection susceptibility in CF mice and possibly patients. The increase in ceramide mediates an ectopic expression of beta 1-integrins in the luminal membrane of CF epithelial cells, which results, via an unknown mechanism, in a down-regulation of acid ceramidase. It is predominantly this down-regulation of acid ceramidase that results in the imbalance of ceramide and sphingosine in CF cells. Correction of ceramide and sphingosine levels can be achieved by inhalation of functional acid sphingomyelinase inhibitors, recombinant acid ceramidase or by normalization of beta 1-integrin expression and subsequent re-expression of endogenous acid ceramidase. These treatments correct pulmonary inflammation and prevent or treat, respectively, acute and chronic pulmonary infections in CF mice with Staphylococcus aureus and mucoid or non-mucoid Pseudomonas aeruginosa. Inhalation of sphingosine corrects sphingosine levels only and seems to mainly act against the infection. Many antidepressants are functional inhibitors of the acid sphingomyelinase and were designed for systemic treatment of major depression. These drugs could be repurposed to treat CF by inhalation.}, language = {en} } @misc{BeckmannBeckerKadowetal.2019, author = {Beckmann, Nadine and Becker, Katrin Anne and Kadow, Stephanie and Schumacher, Fabian and Kramer, Melanie and K{\"u}hn, Claudine and Schulz-Schaeffer, Walter J. and Edwards, Michael J. and Kleuser, Burkhard and Gulbins, Erich and Carpinteiro, Alexander}, title = {Acid sphingomyelinase deficiency ameliorates Farber disease}, series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {1087}, issn = {1866-8372}, doi = {10.25932/publishup-44128}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-441282}, pages = {20}, year = {2019}, abstract = {Farber disease is a rare lysosomal storage disorder resulting from acid ceramidase deficiency and subsequent ceramide accumulation. No treatments for Farber disease are clinically available, and affected patients have a severely shortened lifespan. We have recently reported a novel acid ceramidase deficiency model that mirrors the human disease closely. Acid sphingomyelinase is the enzyme that generates ceramide upstream of acid ceramidase in the lysosomes. Using our acid ceramidase deficiency model, we tested if acid sphingomyelinase could be a potential novel therapeutic target for the treatment of Farber disease. A number of functional acid sphingomyelinase inhibitors are clinically available and have been used for decades to treat major depression. Using these as a therapeutic for Farber disease, thus, has the potential to improve central nervous symptoms of the disease as well, something all other treatment options for Farber disease can't achieve so far. As a proof-of-concept study, we first cross-bred acid ceramidase deficient mice with acid sphingomyelinase deficient mice in order to prevent ceramide accumulation. Double-deficient mice had reduced ceramide accumulation, fewer disease manifestations, and prolonged survival. We next targeted acid sphingomyelinase pharmacologically, to test if these findings would translate to a setting with clinical applicability. Surprisingly, the treatment of acid ceramidase deficient mice with the acid sphingomyelinase inhibitor amitriptyline was toxic to acid ceramidase deficient mice and killed them within a few days of treatment. In conclusion, our study provides the first proof-of-concept that acid sphingomyelinase could be a potential new therapeutic target for Farber disease to reduce disease manifestations and prolong survival. However, we also identified previously unknown toxicity of the functional acid sphingomyelinase inhibitor amitriptyline in the context of Farber disease, strongly cautioning against the use of this substance class for Farber disease patients}, language = {en} } @phdthesis{Bendadani2015, author = {Bendadani, Carolin}, title = {1-Methylpyren: Biotransformation und Gentoxizit{\"a}t}, school = {Universit{\"a}t Potsdam}, pages = {188}, year = {2015}, language = {en} } @phdthesis{Benz2014, author = {Benz, Verena}, title = {Sex-specific differences in the regulation of body weight dynamics and adipose tissue metabolism}, address = {Potsdam}, pages = {119 S.}, year = {2014}, language = {en} } @article{BergerBaldermannRuppel2017, author = {Berger, Beatrice and Baldermann, Susanne and Ruppel, Silke}, title = {The plant growth-promoting bacterium Kosakonia radicincitans improves fruit yield and quality of Solanum lycopersicum}, series = {Journal of the Science of Food and Agriculture}, volume = {97}, journal = {Journal of the Science of Food and Agriculture}, publisher = {Wiley}, address = {Hoboken}, issn = {0022-5142}, doi = {10.1002/jsfa.8357}, pages = {4865 -- 4871}, year = {2017}, abstract = {BACKGROUNDProduction and the quality of tomato fruits have a strong economic relevance. Microorganisms such as the plant growth-promoting bacterium (PGPB) Kosakonia radicincitans (DSM 16656) have been demonstrated to improve shoot and root growth of young tomato plants, but data on yield increase and fruit quality by K. radicincitans are lacking. RESULTSThis study investigated how K. radicincitans affects tomato fruits. After inoculation of tomato seeds with K. radicincitans or a sodium chloride buffer control solution, stalk length, first flowering and the amount of ripened fruits produced by inoculated and non-inoculated plants were monitored over a period of 21 weeks. Inoculation of tomato seeds with K. radicincitans accelerated flowering and ripening of tomato fruits. Sugars, acidity, amino acids, volatile organic compounds and carotenoids in the fruits were also analyzed. CONCLUSIONIt was found that the PGPBK. radicincitans affected the amino acid, sugar and volatile composition of ripened fruits, contributing to a more pleasant-tasting fruit without forfeiting selected quality indicators. (c) 2017 Society of Chemical Industry}, language = {en} } @article{BernacchioniGhiniCencettietal.2017, author = {Bernacchioni, Caterina and Ghini, Veronica and Cencetti, Francesca and Japtok, Lukasz and Donati, Chiara and Bruni, Paola and Turano, Paola}, title = {NMR metabolomics highlights sphingosine kinase-1 as a new molecular switch in the orchestration of aberrant metabolic phenotype in cancer cells}, series = {Molecular oncology / Federation of European Biochemical Societies}, volume = {11}, journal = {Molecular oncology / Federation of European Biochemical Societies}, publisher = {Wiley}, address = {Hoboken}, issn = {1878-0261}, doi = {10.1002/1878-0261.12048}, pages = {517 -- 533}, year = {2017}, abstract = {Strong experimental evidence in animal and cellular models supports a pivotal role of sphingosine kinase-1 (SK1) in oncogenesis. In many human cancers, SK1 levels are upregulated and these increases are linked to poor prognosis in patients. Here, by employing untargeted NMR- based metabolomic profiling combined with functional validations, we report the crucial role of SK1 in the metabolic shift known as the Warburg effect in A2780 ovarian cancer cells. Indeed, expression of SK1 induced a high glycolytic rate, characterized by increased levels of lactate along with increased expression of the proton/monocarboxylate symporter MCT1, and decreased oxidative metabolism, associated with the accumulation of intermediates of the tricarboxylic acid cycle and reduction in CO2 production. Additionally, SK1-expressing cells displayed a significant increase in glucose uptake paralleled by GLUT3 transporter upregulation. The role of SK1 is not limited to the induction of aerobic glycolysis, affecting metabolic pathways that appear to support the biosynthesis of macromolecules. These findings highlight the role of SK1 signaling axis in cancer metabolic reprogramming, pointing out innovative strategies for cancer therapies.}, language = {en} } @article{BijleveldHuschekLiefbroer2016, author = {Bijleveld, Catrien and Huschek, Doreen and Liefbroer, Aart C.}, title = {Parental criminality and entry into parenthood among sons and daughters}, series = {Advances in life course research}, volume = {28}, journal = {Advances in life course research}, publisher = {Elsevier}, address = {Oxford}, issn = {1569-4909}, doi = {10.1016/j.alcr.2016.03.006}, pages = {81 -- 90}, year = {2016}, abstract = {In this article, we examined to what extent parental offending influences the timing of entry into parenthood of children. Based on a literature review, we hypothesized that children of delinquent parents would be more likely to enter into parenthood at a relatively young age, and that part of that association could be explained by differences between children of delinquent and non-delinquent parents in the timing of entry into marriage and in their own delinquent behaviour. Using data from a five-generation study of high risk families in the Netherlands, we found that parental delinquency increases the chance of early childbearing among daughters, but not among sons. Among sons, parental delinquency increased son's delinquency, suggesting that parental delinquency has different consequences for the life courses of their sons and daughters.}, language = {en} } @misc{BijleveldZoutewelleTerovanHuscheketal.2016, author = {Bijleveld, Catrien and Zoutewelle-Terovan, Mioara and Huschek, Doreen and Liefbroer, Aart C.}, title = {Criminal careers and demographic outcomes: An introduction to the special issue}, series = {Advances in life course research}, volume = {28}, journal = {Advances in life course research}, publisher = {Elsevier}, address = {Oxford}, issn = {1569-4909}, doi = {10.1016/j.alcr.2016.05.001}, pages = {1 -- 5}, year = {2016}, language = {en} } @article{BirukovCuadratPolemitietal.2021, author = {Birukov, Anna and Cuadrat, Rafael R. C. and Polemiti, Elli and Eichelmann, Fabian and Schulze, Matthias Bernd}, title = {Advanced glycation end-products, measured as skin autofluorescence, associate with vascular stiffness in diabetic, pre-diabetic and normoglycemic individuals}, series = {Cardiovascular diabetology}, volume = {20}, journal = {Cardiovascular diabetology}, number = {1}, publisher = {BioMed Central}, address = {London}, issn = {1475-2840}, doi = {10.1186/s12933-021-01296-5}, pages = {11}, year = {2021}, abstract = {Background Advanced glycation end-products are proteins that become glycated after contact with sugars and are implicated in endothelial dysfunction and arterial stiffening. We aimed to investigate the relationships between advanced glycation end-products, measured as skin autofluorescence, and vascular stiffness in various glycemic strata. Methods We performed a cross-sectional analysis within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort, comprising n = 3535 participants (median age 67 years, 60\% women). Advanced glycation end-products were measured as skin autofluorescence with AGE-Reader (TM), vascular stiffness was measured as pulse wave velocity, augmentation index and ankle-brachial index with Vascular Explorer (TM). A subset of 1348 participants underwent an oral glucose tolerance test. Participants were sub-phenotyped into normoglycemic, prediabetes and diabetes groups. Associations between skin autofluorescence and various indices of vascular stiffness were assessed by multivariable regression analyses and were adjusted for age, sex, measures of adiposity and lifestyle, blood pressure, prevalent conditions, medication use and blood biomarkers. Results Skin autofluorescence associated with pulse wave velocity, augmentation index and ankle-brachial index, adjusted beta coefficients (95\% CI) per unit skin autofluorescence increase: 0.38 (0.21; 0.55) for carotid-femoral pulse wave velocity, 0.25 (0.14; 0.37) for aortic pulse wave velocity, 1.00 (0.29; 1.70) for aortic augmentation index, 4.12 (2.24; 6.00) for brachial augmentation index and - 0.04 (- 0.05; - 0.02) for ankle-brachial index. The associations were strongest in men, younger individuals and were consistent across all glycemic strata: for carotid-femoral pulse wave velocity 0.36 (0.12; 0.60) in normoglycemic, 0.33 (- 0.01; 0.67) in prediabetes and 0.45 (0.09; 0.80) in diabetes groups; with similar estimates for aortic pulse wave velocity. Augmentation index was associated with skin autofluorescence only in normoglycemic and diabetes groups. Ankle-brachial index inversely associated with skin autofluorescence across all sex, age and glycemic strata. Conclusions Our findings indicate that advanced glycation end-products measured as skin autofluorescence might be involved in vascular stiffening independent of age and other cardiometabolic risk factors not only in individuals with diabetes but also in normoglycemic and prediabetic conditions. Skin autofluorescence might prove as a rapid and non-invasive method for assessment of macrovascular disease progression across all glycemic strata.}, language = {en} }