TY - GEN A1 - Biterova, Ekaterina A1 - Esmaeeli Moghaddam Tabalvandani, Mariam A1 - Alanen, Heli I. A1 - Saaranen, Mirva A1 - Ruddock, Lloyd W. T1 - Structures of Angptl3 and Angptl4 BT - modulators of triglyceride levels and coronary artery disease T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Coronary artery disease is the most common cause of death globally and is linked to a number of risk factors including serum low density lipoprotein, high density lipoprotein, triglycerides and lipoprotein(a). Recently two proteins, angiopoietin-like protein 3 and 4, have emerged from genetic studies as being factors that significantly modulate plasma triglyceride levels and coronary artery disease. The exact function and mechanism of action of both proteins remains to be elucidated, however, mutations in these proteins results in up to 34% reduction in coronary artery disease and inhibition of function results in reduced plasma triglyceride levels. Here we report the crystal structures of the fibrinogen-like domains of both proteins. These structures offer new insights into the reported loss of function mutations, the mechanisms of action of the proteins and open up the possibility for the rational design of low molecular weight inhibitors for intervention in coronary artery disease. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1048 KW - angiopoitin-like 4 KW - of-function mutations KW - cardiovascular-disease KW - lipoprotein-lipase KW - heart-disease KW - risk KW - recognition KW - protein KW - metaanalysis KW - association KW - cardiovascular biology KW - x-ray crystallography Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-467943 SN - 1866-8372 IS - 1048 ER - TY - GEN A1 - Kreibich, Heidi A1 - Müller, Meike A1 - Schröter, Kai A1 - Thieken, Annegret T1 - New insights into flood warning reception and emergency response by affected parties T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Flood damage can be mitigated if the parties at risk are reached by flood warnings and if they know how to react appropriately. To gain more knowledge about warning reception and emergency response of private households and companies, surveys were undertaken after the August 2002 and the June 2013 floods in Germany. Despite pronounced regional differences, the results show a clear overall picture: in 2002, early warnings did not work well; e.g. many households (27 %) and companies (45 %) stated that they had not received any flood warnings. Additionally, the preparedness of private households and companies was low in 2002, mainly due to a lack of flood experience. After the 2002 flood, many initiatives were launched and investments undertaken to improve flood risk management, including early warnings and an emergency response in Germany. In 2013, only a small share of the affected households (5 %) and companies (3 %) were not reached by any warnings. Additionally, private households and companies were better prepared. For instance, the share of companies which have an emergency plan in place has increased from 10% in 2002 to 34% in 2013. However, there is still room for improvement, which needs to be triggered mainly by effective risk and emergency communication. The challenge is to continuously maintain and advance an integrated early warning and emergency response system even without the occurrence of extreme floods. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 659 KW - june 2013 Flood KW - circulation patterns KW - affected residents KW - extreme flood KW - august 2002 KW - Germany KW - risk KW - damage KW - preparedness KW - recovery Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-418381 SN - 1866-8372 IS - 659 ER - TY - GEN A1 - Li, Chen A1 - Stoma, Svetlana A1 - Lotta, Luca A. A1 - Warner, Sophie A1 - Albrecht, Eva A1 - Allione, Alessandra A1 - Arp, Pascal P. A1 - Broer, Linda A1 - Buxton, Jessica L. A1 - Boeing, Heiner A1 - Langenberg, Claudia A1 - Codd, Veryan T1 - Genome-wide association analysis in humans links nucleotide metabolism to leukocyte telomere length T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1 , PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1205 KW - Mendelian randomization KW - risk KW - variants KW - disease KW - cancer KW - loci KW - database KW - genes KW - heart KW - gwas Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-526843 SN - 1866-8372 IS - 3 ER - TY - GEN A1 - Moser, Othmar A1 - Tschakert, Gerhard A1 - Mueller, Alexander A1 - Groeschl, Werner A1 - Pieber, Thomas R. A1 - Obermayer-Pietsch, Barbara A1 - Koehler, Gerd A1 - Hofmann, Peter T1 - Effects of high-intensity interval exercise versus moderate continuous exercise on glucose homeostasis and hormone response in patients with type 1 diabetes mellitus using novel ultra-long-acting insulin T2 - Postprints der Universität Potsdam : Humanwissenschaftliche Reihe N2 - Introduction We investigated blood glucose (BG) and hormone response to aerobic high-intensity interval exercise (HIIE) and moderate continuous exercise (CON) matched for mean load and duration in type 1 diabetes mellitus (T1DM). Material and Methods Seven trained male subjects with T1DM performed a maximal incremental exercise test and HIIE and CON at 3 different mean intensities below (A) and above (B) the first lactate turn point and below the second lactate turn point (C) on a cycle ergometer. Subjects were adjusted to ultra-long-acting insulin Degludec (Tresiba/Novo Nordisk, Denmark). Before exercise, standardized meals were administered, and short-acting insulin dose was reduced by 25% (A), 50% (B), and 75% (C) dependent on mean exercise intensity. During exercise, BG, adrenaline, noradrenaline, dopamine, cortisol, glucagon, and insulin-like growth factor-1, blood lactate, heart rate, and gas exchange variables were measured. For 24 h after exercise, interstitial glucose was measured by continuous glucose monitoring system. Results BG decrease during HIIE was significantly smaller for B (p = 0.024) and tended to be smaller for A and C compared to CON. No differences were found for post-exercise interstitial glucose, acute hormone response, and carbohydrate utilization between HIIE and CON for A, B, and C. In HIIE, blood lactate for A (p = 0.006) and B (p = 0.004) and respiratory exchange ratio for A (p = 0.003) and B (p = 0.003) were significantly higher compared to CON but not for C. Conclusion Hypoglycemia did not occur during or after HIIE and CON when using ultra-long-acting insulin and applying our methodological approach for exercise prescription. HIIE led to a smaller BG decrease compared to CON, although both exercises modes were matched for mean load and duration, even despite markedly higher peak workloads applied in HIIE. Therefore, HIIE and CON could be safely performed in T1DM. T3 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe - 497 KW - target heart-rate KW - failure KW - recommendations KW - hypoglycemia KW - individuals KW - performance KW - risk Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-408342 SN - 1866-8364 IS - 497 ER -