Saxon Academy of science

Leipzig, Germany

Saxon Academy of science

Leipzig, Germany
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Hellmann J.,Section of Clinical Neurobiology | Rommelspacher H.,Section of Clinical Neurobiology | Muhlbauer E.,Saxon Academy of science | Muhlbauer E.,Martin Luther University of Halle Wittenberg | Wernicke C.,Charité - Medical University of Berlin
Developmental Neuroscience | Year: 2010

Neuronal differentiation has evolved as an essential process even in the adult brain, once disturbed being associated with the pathogenesis of several psychiatric disorders. To study the effects of Raf kinase inhibitor protein (RKIP) on neuronal differentiation, we generated neuroblastoma cell lines overexpressing RKIP (RKIP+) and expressing RKIP-directed short hairpin RNA for downregulation of RKIP (RKIP-). During a 4-week time course of continuous differentiation by retinoic acid (RA), expression of neuronal and glial markers, intracellular cyclic adenosine monophosphate (cAMP) levels, protein kinase C (PKC) signal transduction to extracellular signal-regulated kinase 1/2 (ERK-1/2) and cellular morphology were investigated in relation to RKIP levels. RKIP+ cells showed accelerated neurite outgrowth, formation of elaborated neuronal networks and increased neuronal marker expression both in RA-induced differentiation and to some extent even in non-RA-treated cells. RKIP- cells showed glial-like cell bodies and increased glial fibrillary acidic protein, suggesting a shift from neuronal to glial phenotype. With respect to differentiation-inducing signal pathways, PKC-mediated ERK-1/2 activation significantly correlated with RKIP levels. Furthermore, basal and forskolin-stimulated intracellular cAMP was potently increased in RKIP+ cells versus controls. In conclusion, the conserved signal transduction modulator RKIP was shown to enhance several aspects of neuronal differentiation via enhanced crosstalk from PKC to ERK-1/2 and enhancement of G-protein-coupled receptor signaling. Copyright © 2009 S. Karger AG, Basel.

Novothny A.,Leibniz Institute for Applied Geophysics | Novothny A.,Eötvös Loránd University | Frechen M.,Leibniz Institute for Applied Geophysics | Horvath E.,Eötvös Loránd University | And 2 more authors.
Quaternary Geochronology | Year: 2010

Anomalous fading of the infrared stimulated luminescence (IRSL) signal from the polymineral fine-grain and K-feldspar fractions of aeolian sediments from Hungary has been studied. The samples in this study have previously been dated using the multiple aliquot additive dose (MAAD) protocol to measure the IRSL signal. The IRSL measurements using MAAD were conducted ∼4 weeks after the irradiation, making it difficult to assess to what extent these age estimates were affected by anomalous fading. In this study, equivalent doses were obtained using the single aliquot regenerative dose (SAR) protocol. The fading rate for each sample was calculated using the different IRSL components and different parts of the decay curve. For each sample, the middle part of the decay curve always showed a lower fading rate than the initial part of the decay curve. The difference between the fading rates for different parts of the decay curve was greater for the K-feldspars than for the polymineral fine grains. Fading corrected ages were calculated by integrating both the initial and the middle part of the decay curve. These ages were compared with optically stimulated luminescence (OSL) ages from quartz, infrared radiofluorescence (IR-RF) ages obtained from K-feldspars and also with independent ages, provided by radiocarbon dating of shells and charcoal, and uranium-series dating of travertine. © 2009 Elsevier Ltd. All rights reserved.

Phi van D.K.,Martin Luther University of Halle Wittenberg | Muhlbauer E.,Martin Luther University of Halle Wittenberg | Muhlbauer E.,Saxon Academy of science | Phi-van L.,Institute of Animal Welfare and Animal Husbandry
Biochimica et Biophysica Acta - Gene Regulatory Mechanisms | Year: 2015

Serotonin (5-HT) has been reported to be involved in cancer progression by stimulating angiogenesis and cell growth. In this study, we examined the expression of the serotonin transporter (5-HTT) and the role of histone deacetylases (HDACs) in regulating the 5-HTT gene in tumor cells. The 5-HTT gene expression was almost silenced in chicken lymphoma DT40, myelomonocytic tumor HD11 and hepatoma DU249 cells, compared to their physiological counterpart. In contrast, HDAC1 mRNA expression was increased in these cell lines. Indeed, the pan-HDAC inhibitor trichostatin A (TSA) enhanced the 5-HTT mRNA expression in several tumor cell lines including the human cell lines HepG2 and THP-1 and increased the 5-HT uptake in HD11 cells. In addition, treatment with parthenolide, which is capable of depleting HDAC1, and knockdown of HDAC1 using siRNA resulted in increased 5-HTT mRNA expression, confirming the role of HDAC1 in the down-regulation of 5-HTT in the tumor cells. Deletion analysis of the 5-HTT promoter and site-directed mutagenesis revealed that the transcription factor CCAAT/enhancer binding protein beta (C/EBPß), in interacting with the 5-HTT promoter, mediated both the inhibition of the 5-HTT expression by HDAC1 and the activation by CREB-binding protein (CBP). Using a chromatin immunoprecipitation assay, we found increased acetylation of histone H4 associated with the 5-HTT promoter in cells treated with TSA. Our results suggest that the 5-HTT gene is epigenetically downregulated by HDAC1 in several types of cancer. © 2015 Elsevier B.V.

Luthgens C.,Free University of Berlin | Krbetschek M.,Saxon Academy of science | Bose M.,Free University of Berlin | Fuchs M.C.,TU Dresden
Quaternary Geochronology | Year: 2010

This study presents first results of a project which aims to develop an absolute chronology of the Weichselian ice marginal positions in north-eastern Germany using Optically Stimulated Luminescence (OSL) dating. Owing to the special geomorphological and stratigraphical setting, many of the sampling sites were situated close to the former ice margin. At some sections the sediments showed an incomplete resetting of the OSL signal. For this study the representative sandur sediment section from the Beelitz outwash cone was chosen to elaborate a strategy to reliably detect insufficient bleaching and to choose an appropriate age model for the calculation of the true burial dose of each sample. The age determined for the formation of the Beelitz outwash cone is 34.1 ± 3.0 ka. Although this age might still be a maximum age, this study shows that by applying the proposed methodological strategy, plausible ages can be derived from insufficiently bleached, ice proximal sandur sediments. © 2009 Elsevier Ltd. All rights reserved.

Bahr I.,Martin Luther University of Halle Wittenberg | Muhlbauer E.,Saxon Academy of science | Schucht H.,Martin Luther University of Halle Wittenberg | Peschke E.,Martin Luther University of Halle Wittenberg
Journal of Pineal Research | Year: 2011

Recent investigations have demonstrated that melatonin influences carbohydrate metabolism mediated by insulin-inhibiting effects on pancreatic β-cells. This study evaluated whether melatonin has also an effect on pancreatic α-cells and glucagon expression as well as the glucagon secretion in vitro and in vivo. Glucagon-producing pancreatic α-cell line αTC1 clone 9 (αTC1.9) was used, which was characterized as an appropriate model with glucose responsiveness and expression of the melatonin receptors MT1 and MT2. The results demonstrate that melatonin incubation significantly enhanced the expression as well as the secretion of glucagon. These effects appeared to be more pronounced under hyperglycemic conditions compared to basal glucose concentrations. Notably, in vivo studies demonstrated that long-term oral melatonin administration led to significantly elevated plasma glucagon concentrations in Wistar rats. In contrast, plasma glucagon levels were found to be slightly decreased in type 2 diabetic Goto-Kakizaki rats. Moreover, investigations measuring the relative glucagon receptor mRNA expression showed marked differences in the liver of melatonin-substituted rats as well as in melatonin receptor knockout mice. In conclusion, these findings revealed evidence that melatonin influences pancreatic glucagon expression and secretion as well as the peripheral glucagon action. © 2011 John Wiley & Sons A/S.

Kaiser K.,German Academy of Science and Engineering | Lai Z.,CAS Qinghai Institute of Salt Lakes | Schneider B.,University of Leipzig | Junge F.W.,Saxon Academy of science
Quaternary Geochronology | Year: 2010

Knowledge on valley formation and palaeohydrology of the Yarlung Zhangbo (named Brahmaputra south of the Himalayas) is still in an early stage. Research was conducted in the middle valley reach around Gonggar in order to investigate the sediment properties, age and palaeoenvironmental implication of a widespread aggradational valley terrace. This heavily dissected terrace, lying c. 25 m above the present floodplain, consists of topping aeolian and colluvial deposits, intermediate lacustrine fines and basal fluvial sands. Sedimentological properties of the lacustrine layers suggest a cold-climate depositional environment. Geochemical data refer to a common provenance of all sediments investigated from a regional catchment area, implying a local provenance of topping loesses and sands by aeolian sorting of nearby fluvial deposits. OSL dates, representing the first luminescence dating effort partly applied to non-aeolian sediments in this valley, cluster closely in the interval 11.7 ± 0.8-17.4 ± 1.4 ka. During the Late Pleistocene (until c. 16 ka) the investigated middle valley reach around Gonggar was occupied by a lake attaining an extension of at least 100 km. © 2009 Elsevier Ltd. All rights reserved.

Peschke E.,Saxon Academy of science | Bahr I.,Martin Luther University of Halle Wittenberg | Muhlbauer E.,Saxon Academy of science
International Journal of Molecular Sciences | Year: 2013

The pineal hormone melatonin exerts its influence in the periphery through activation of two specific trans-membrane receptors: MT1 and MT2. Both isoforms are expressed in the islet of Langerhans and are involved in the modulation of insulin secretion from β-cells and in glucagon secretion from α-cells. De-synchrony of receptor signaling may lead to the development of type 2 diabetes. This notion has recently been supported by genome-wide association studies identifying particularly the MT2 as a risk factor for this rapidly spreading metabolic disturbance. Since melatonin is secreted in a clearly diurnal fashion, it is safe to assume that it also has a diurnal impact on the blood-glucose-regulating function of the islet. This factor has hitherto been underestimated; the disruption of diurnal signaling within the islet may be one of the most important mechanisms leading to metabolic disturbances. The study of melatonin-insulin interactions in diabetic rat models has revealed an inverse relationship: an increase in melatonin levels leads to a down-regulation of insulin secretion and vice versa. Elucidation of the possible inverse interrelationship in man may open new avenues in the therapy of diabetes. © 2013 by the authors; licensee MDPI, Basel, Switzerland.

Peschke E.,Martin Luther University of Halle Wittenberg | Schucht H.,Martin Luther University of Halle Wittenberg | Muhlbauer E.,Saxon Academy of science
Journal of Pineal Research | Year: 2010

This paper represents an essential aspect of recent investigations into the functional and clinical implications of insulin-melatonin interrelationships. The aim of the study was to analyze whether melatonin reduces insulin secretion in an animal in a manner comparable to the pattern observed in previous in vitro experiments; to this end, we used two models: Wistar and type 2-diabetic Goto-Kakizaki (GK) rats. Thirty-two Wistar and 32 GK rats were divided into two subgroups of 16 rats each; each subgroup was treated either with or without melatonin. The daily administration of melatonin, starting in 8- wk-old rats, was adjusted to 2.5 mg/kg body weight. Melatonin was given daily during the dark period for 12 hr. After 9 wk of treatment, the rats were sacrificed in the middle of the dark period. Melatonin administration strongly enhanced the plasma melatonin level and diminished the expression of pancreatic melatonin receptor-mRNA, whereas the expression of pineal AA-NAT and HIOMT was unchanged. Furthermore, the experiments showed in agreement with recent in vitro results of pancreatic islets that plasma insulin levels were diminished after melatonin treatment. However, the pineal insulin receptor expression was increased after melatonin administration. The pancreatic expression of glucagon, GLUT2, and glucokinase was decreased in GK rats, whereas the glucose levels, as well as the parameters of glucose sensing, GLUT2-mRNA, and glucokinase-mRNA, were unchanged after melatonin administration in both Wistar and GK rats. In summary, the results show that melatonin administration decreases plasma insulin levels in vivo and, furthermore, that an insulin-melatonin antagonism exists. © 2010 The Authors.

Peschke E.,Martin Luther University of Halle Wittenberg | Hofmann K.,Martin Luther University of Halle Wittenberg | Ponicke K.,Martin Luther University of Halle Wittenberg | Wedekind D.,Hannover Medical School | Muhlbauer E.,Saxon Academy of science
Journal of Pineal Research | Year: 2012

In this paper, we analyze the biological relevance of melatonin in diabetogenesis. As has recently been demonstrated, melatonin decreases insulin secretion via specific melatonin receptor isoforms (MT1 and MT2) in the pancreatic β-cells. In addition, type 2 diabetic rats, as well as patients, exhibit decreased melatonin levels, whereas the levels in type 1 diabetic rats are increased. The latter effects were normalized by insulin substitution, which signifies that a specific receptor-mediated insulin-melatonin antagonism exists. These results are in agreement with several recent genome-wide association studies, which have identified a number of single nucleotide polymorphisms in the MTNR1B gene, encoding the MT2 receptor, that were closely associated with a higher prognostic risk of developing type 2 diabetes. We hypothesize that catecholamines, which decrease insulin levels and stimulate melatonin synthesis, control insulin-melatonin interactions. The present results support this assertion as we show that catecholamines are increased in type 1 but are diminished in type 2 diabetes. Another important line of inquiry involves the fact that melatonin protects the β-cells against functional overcharge and, consequently, hinders the development of type 2 diabetes. In this context, it is striking that at advanced ages, melatonin levels are reduced and the incidence of type 2 diabetes is increased. Thus, melatonin appears to have a protective biological role. Here, we strongly repudiate misconceptions, resulting from observations that melatonin reduces the plasma insulin level, that the blockage of melatonin receptors would be of benefit in the treatment of type 2 diabetes. © 2011 John Wiley & Sons A/S.

Schirrmeister L.,Alfred Wegener Institute for Polar and Marine Research | Grosse G.,University of Alaska Fairbanks | Schnelle M.,Alfred Wegener Institute for Polar and Marine Research | Fuchs M.,TU Bergakademie Freiberg | And 12 more authors.
Palaeogeography, Palaeoclimatology, Palaeoecology | Year: 2011

The three main Lena Delta terraces were formed during different stages of the late Quaternary. While only the first floodplain terrace is connected with active deltaic processes, the second and third terraces, which dominate the western part of the delta, are erosional remnants of arctic paleolandscapes affected by periglacial processes. The landscape dynamics of the second and the third terraces, and their relationship to each other, are of particular importance in any effort to elucidate the late Quaternary paleoenvironment of western Beringia.Multidisciplinary studies of permafrost deposits on the second terrace were carried out at several sites of the Arga Complex, named after the largest delta island, Arga-Muora-Sise. The frozen sediments predominantly consist of fluvial sands several tens of meters thick, radiocarbon-dated from > 52 to 16. kyr BP. These sands were deposited under changing fluvial conditions in a dynamic system of shifting river channels, and have been additionally modified by synsedimentary and postsedimentary cryogenesis. Later thermokarst processes affected this late Pleistocene fluvial landscape during the Lateglacial and the Holocene. In addition, eolian activity reworked the fluvial sands on exposed surfaces at least since the Lateglacial, resulting in dune formation in some areas. Contrary to the Arga Complex, the third terrace is mainly composed of polygenetic alluvial and proluvial ice-rich permafrost sequences (Ice Complex deposits) radiocarbon-dated from 50 to 17. kyr BP which cover older fluvial sand units luminescence-dated to about 100-50. kyr BP. Paleoecological records reflect tundra-steppe conditions that varied locally, depending on landscape dynamics, during the Marine Isotope Stage (MIS) 4 and 3 periods, and a persistent change to shrub and arctic tundra during Lateglacial and Holocene periods.The study results indicate a continuous fluvial sedimentation environment for the Laptev Sea shelf in the region of the second Lena Delta terrace during the late Pleistocene, and confirm the presence of a dynamic channel system of the paleo-Lena River that flowed at the same time as the nearby subaerial Ice Complex deposits were being formed. © 2010 Elsevier B.V.

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