TY - JOUR A1 - Warrington, Nicole A1 - Beaumont, Robin A1 - Horikoshi, Momoko A1 - Day, Felix R. A1 - Helgeland, Øyvind A1 - Laurin, Charles A1 - Bacelis, Jonas A1 - Peng, Shouneng A1 - Hao, Ke A1 - Feenstra, Bjarke A1 - Wood, Andrew R. A1 - Mahajan, Anubha A1 - Tyrrell, Jessica A1 - Robertson, Neil R. A1 - Rayner, N. William A1 - Qiao, Zhen A1 - Moen, Gunn-Helen A1 - Vaudel, Marc A1 - Marsit, Carmen A1 - Chen, Jia A1 - Nodzenski, Michael A1 - Schnurr, Theresia M. A1 - Zafarmand, Mohammad Hadi A1 - Bradfield, Jonathan P. A1 - Grarup, Niels A1 - Kooijman, Marjolein N. A1 - Li-Gao, Ruifang A1 - Geller, Frank A1 - Ahluwalia, Tarunveer Singh A1 - Paternoster, Lavinia A1 - Rueedi, Rico A1 - Huikari, Ville A1 - Hottenga, Jouke-Jan A1 - Lyytikäinen, Leo-Pekka A1 - Cavadino, Alana A1 - Metrustry, Sarah A1 - Cousminer, Diana L. A1 - Wu, Ying A1 - Thiering, Elisabeth Paula A1 - Wang, Carol A. A1 - Have, Christian Theil A1 - Vilor-Tejedor, Natalia A1 - Joshi, Peter K. A1 - Painter, Jodie N. A1 - Ntalla, Ioanna A1 - Myhre, Ronny A1 - Pitkänen, Niina A1 - van Leeuwen, Elisabeth M. A1 - Joro, Raimo A1 - Lagou, Vasiliki A1 - Richmond, Rebecca C. A1 - Espinosa, Ana A1 - Barton, Sheila J. A1 - Inskip, Hazel M. A1 - Holloway, John W. A1 - Santa-Marina, Loreto A1 - Estivill, Xavier A1 - Ang, Wei A1 - Marsh, Julie A. A1 - Reichetzeder, Christoph A1 - Marullo, Letizia A1 - Hocher, Berthold A1 - Lunetta, Kathryn L. A1 - Murabito, Joanne M. A1 - Relton, Caroline L. A1 - Kogevinas, Manolis A1 - Chatzi, Leda A1 - Allard, Catherine A1 - Bouchard, Luigi A1 - Hivert, Marie-France A1 - Zhang, Ge A1 - Muglia, Louis J. A1 - Heikkinen, Jani A1 - Morgen, Camilla S. A1 - van Kampen, Antoine H. C. A1 - van Schaik, Barbera D. C. A1 - Mentch, Frank D. A1 - Langenberg, Claudia A1 - Scott, Robert A. A1 - Zhao, Jing Hua A1 - Hemani, Gibran A1 - Ring, Susan M. A1 - Bennett, Amanda J. A1 - Gaulton, Kyle J. A1 - Fernandez-Tajes, Juan A1 - van Zuydam, Natalie R. A1 - Medina-Gomez, Carolina A1 - de Haan, Hugoline G. A1 - Rosendaal, Frits R. A1 - Kutalik, Zoltán A1 - Marques-Vidal, Pedro A1 - Das, Shikta A1 - Willemsen, Gonneke A1 - Mbarek, Hamdi A1 - Müller-Nurasyid, Martina A1 - Standl, Marie A1 - Appel, Emil V. R. A1 - Fonvig, Cilius Esmann A1 - Trier, Caecilie A1 - van Beijsterveldt, Catharina E. M. A1 - Murcia, Mario A1 - Bustamante, Mariona A1 - Bonàs-Guarch, Sílvia A1 - Hougaard, David M. A1 - Mercader, Josep M. A1 - Linneberg, Allan A1 - Schraut, Katharina E. A1 - Lind, Penelope A. A1 - Medland, Sarah Elizabeth A1 - Shields, Beverley M. A1 - Knight, Bridget A. A1 - Chai, Jin-Fang A1 - Panoutsopoulou, Kalliope A1 - Bartels, Meike A1 - Sánchez, Friman A1 - Stokholm, Jakob A1 - Torrents, David A1 - Vinding, Rebecca K. A1 - Willems, Sara M. A1 - Atalay, Mustafa A1 - Chawes, Bo L. A1 - Kovacs, Peter A1 - Prokopenko, Inga A1 - Tuke, Marcus A. A1 - Yaghootkar, Hanieh A1 - Ruth, Katherine S. A1 - Jones, Samuel E. A1 - Loh, Po-Ru A1 - Murray, Anna A1 - Weedon, Michael N. A1 - Tönjes, Anke A1 - Stumvoll, Michael A1 - Michaelsen, Kim Fleischer A1 - Eloranta, Aino-Maija A1 - Lakka, Timo A. A1 - van Duijn, Cornelia M. A1 - Kiess, Wieland A1 - Koerner, Antje A1 - Niinikoski, Harri A1 - Pahkala, Katja A1 - Raitakari, Olli T. A1 - Jacobsson, Bo A1 - Zeggini, Eleftheria A1 - Dedoussis, George V. A1 - Teo, Yik-Ying A1 - Saw, Seang-Mei A1 - Montgomery, Grant W. A1 - Campbell, Harry A1 - Wilson, James F. A1 - Vrijkotte, Tanja G. M. A1 - Vrijheid, Martine A1 - de Geus, Eco J. C. N. A1 - Hayes, M. Geoffrey A1 - Kadarmideen, Haja N. A1 - Holm, Jens-Christian A1 - Beilin, Lawrence J. A1 - Pennell, Craig E. A1 - Heinrich, Joachim A1 - Adair, Linda S. A1 - Borja, Judith B. A1 - Mohlke, Karen L. A1 - Eriksson, Johan G. A1 - Widen, Elisabeth E. A1 - Hattersley, Andrew T. A1 - Spector, Tim D. A1 - Kaehoenen, Mika A1 - Viikari, Jorma S. A1 - Lehtimaeki, Terho A1 - Boomsma, Dorret I. A1 - Sebert, Sylvain A1 - Vollenweider, Peter A1 - Sorensen, Thorkild I. A. A1 - Bisgaard, Hans A1 - Bonnelykke, Klaus A1 - Murray, Jeffrey C. A1 - Melbye, Mads A1 - Nohr, Ellen A. A1 - Mook-Kanamori, Dennis O. A1 - Rivadeneira, Fernando A1 - Hofman, Albert A1 - Felix, Janine F. A1 - Jaddoe, Vincent W. V. A1 - Hansen, Torben A1 - Pisinger, Charlotta A1 - Vaag, Allan A. A1 - Pedersen, Oluf A1 - Uitterlinden, Andre G. A1 - Jarvelin, Marjo-Riitta A1 - Power, Christine A1 - Hypponen, Elina A1 - Scholtens, Denise M. A1 - Lowe, William L. A1 - Smith, George Davey A1 - Timpson, Nicholas J. A1 - Morris, Andrew P. A1 - Wareham, Nicholas J. A1 - Hakonarson, Hakon A1 - Grant, Struan F. A. A1 - Frayling, Timothy M. A1 - Lawlor, Debbie A. A1 - Njolstad, Pal R. A1 - Johansson, Stefan A1 - Ong, Ken K. A1 - McCarthy, Mark I. A1 - Perry, John R. B. A1 - Evans, David M. A1 - Freathy, Rachel M. T1 - Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors JF - Nature genetics N2 - Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming. Y1 - 2019 SN - 1061-4036 SN - 1546-1718 VL - 51 IS - 5 SP - 804 EP - + PB - Nature Publ. Group CY - New York ER - TY - JOUR A1 - Li, Jian A1 - Lu, Yong-Ping A1 - Tsuprykov, Oleg A1 - Hasan, Ahmed Abdallah Abdalrahman Mohamed A1 - Reichetzeder, Christoph A1 - Tian, Mei A1 - Zhang, Xiao Li A1 - Zhang, Qin A1 - Sun, Guo-Ying A1 - Guo, Jingli A1 - Gaballa, Mohamed Mahmoud Salem Ahmed A1 - Peng, Xiao-Ning A1 - Lin, Ge A1 - Hocher, Berthold T1 - Folate treatment of pregnant rat dams abolishes metabolic effects in female offspring induced by a paternal pre-conception unhealthy diet JF - Diabetologia : journal of the European Association for the Study of Diabetes (EASD) N2 - Aims/hypothesis Paternal high-fat diet prior to mating programmes impaired glucose tolerance in female offspring. We examined whether the metabolic consequences in offspring could be abolished by folate treatment of either the male rats before mating or the corresponding female rats during pregnancy. Methods Male F0 rats were fed either control diet or high-fat, high-sucrose and high-salt diet (HFSSD), with or without folate, before mating. Male rats were mated with control-diet-fed dams. After mating, the F0 dams were fed control diet with or without folate during pregnancy. KW - Glucose tolerance KW - High-fat-sucrose-salt diet KW - Maternal folate treatment KW - Paternal programming Y1 - 2018 U6 - https://doi.org/10.1007/s00125-018-4635-x SN - 0012-186X SN - 1432-0428 VL - 61 IS - 8 SP - 1862 EP - 1876 PB - Springer CY - New York ER - TY - JOUR A1 - Zhang, Peng A1 - Najman, Yani A1 - Mei, Lianfu A1 - Millar, Ian A1 - Sobel, Edward A1 - Carter, Andrew A1 - Barfod, Dan A1 - Dhuime, Bruno A1 - Garzanti, Eduardo A1 - Govin, Gwladys A1 - Vezzoli, Giovanni A1 - Hu, Xiaolin T1 - Palaeodrainage evolution of the large rivers of East Asia, and Himalayan-Tibet tectonics JF - Earth science reviews N2 - A number of sedimentary provenance studies have been undertaken in order to determine whether the palaeo-Red River was once a river of continental proportions into which the upper reaches of the Yangtze, Salween, Mekong, Irrawaddy, and Yarlung drained. We have assessed the evidence that the Yarlung originally flowed into the palaeo-Red river, and then sequentially into the Irrawaddy and Brahmaputra, connecting to the latter first via the Lohit and then the Siang. For this river system, we have integrated our new data from the Paleogene-Recent Irrawaddy drainage basin (detrital zircon U-Pb with Hf and fission track, rutile U-Pb, mica Ar-Ar, bulk rock Sr-Nd, and petrography) with previously published data, to produce a palaeodrainage model that is consistent with all datasets. In our model, the Yarlung never flowed into the Irrawaddy drainage: during the Paleogene, the Yarlung suture zone was an internally drained basin, and from Neogene times onwards the Yarlung drained into the Brahmaputra in the Bengal Basin. The Central Myanmar Basin, through which the Irrawaddy River flows today, received predominantly locally-derived detritus until the Middle Eocene, the Irrawaddy initiated as a through-going river draining the Mogok Metamorphic Belt and Bomi-Chayu granites to the north sometime in the Late Eocene to Early Oligocene, and the river was dominated by a stable MMB-dominated drainage throughout the Neogene to present day. Existing evidence does not support any connection between the Yarlung and the Red River in the past, but there is a paucity of suitable palaeo-Red River deposits with which to make a robust comparison. We argue that this limitation also precludes a robust assessment of a palaeo-connection between the Yangtze/ Salween/Mekong and the Red River; it is difficult to unequivocally interpret the recorded provenance changes as the result of specific drainage reorganisations. We highlight the palaeo-Red River deposits of the Hanoi Basin as a potential location for future research focus in view of the near-complete Cenozoic record of palaeo-Red River deposits at this location. A majority of previous studies consider that if a major continental-scale drainage ever existed at all, it fragmented early in the Cenozoic. Such a viewpoint would agree with the growing body of evidence from palaeoaltitude studies that large parts of SE Tibet were uplifted by this period. This then leads towards the intriguing question as to the mechanisms which caused the major period of river incision in the Miocene in this region. KW - Eastern Tibet KW - Palaeodrainage KW - Red River KW - Irrawaddy River KW - Yarlung Tsangpo KW - Central Myanmar Basin Y1 - 2019 U6 - https://doi.org/10.1016/j.earscirev.2019.02.003 SN - 0012-8252 SN - 1872-6828 VL - 192 SP - 601 EP - 630 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Tao, Ting A1 - Su, Qiongli A1 - Xu, Simeng A1 - Deng, Jun A1 - Zhou, Sichun A1 - Zhuang, Yu A1 - Huang, Yanjun A1 - He, Caimei A1 - He, Shanping A1 - Peng, Mei A1 - Hocher, Berthold A1 - Yang, Xiaoping T1 - Down-regulation of PKM2 decreases FASN expression in bladder cancer cells through AKT/mTOR/SREBP-1c axis JF - Journal of cellular physiology N2 - Fatty acid synthase (FASN) catalyzing the terminal steps in the de novo biogenesis of fatty acids is correlated with low survival and high disease recurrence in patients with bladder cancer. Pyruvate kinase M2 (PKM2) regulates the final step of glycolysis levels and provides a growth advantage to tumors. However, it is unclear whether the change of PKM2 has an effect on FASN and what is the mechanisms underlying. Here we describe a novel function of PKM2 in control of lipid metabolism by mediating transcriptional activation of FASN, showing the reduced expression of sterol regulatory element binding protein 1c (SREBP-1c). We first discovered that PKM2 physically interacts with the SREBP-1c using biochemical approaches, and downregulation of PKM2 reduced the expression of SREBP-1c by inactivating the AKT/mTOR signaling pathway, which in turn directly suppressed the transcription of major lipogenic genes FASN to reduce tumor growths. Furthermore, either PKM2 inhibitor-Shikonin or FASN inhibitor-TVB-3166 alone induced a strong antiproliferative and anticolony forming effect in bladder cancer cell line. The combination of both inhibitors exhibits a super synergistic effect on blocking the bladder cancer cells growth. It provides a new target and scientific basis for the treatment of bladder cancer. KW - bladder cancer cells KW - FASN KW - p-AKT KW - PKM2 KW - p-mTOR KW - SREBP-1c Y1 - 2018 U6 - https://doi.org/10.1002/jcp.27129 SN - 0021-9541 SN - 1097-4652 VL - 234 IS - 3 SP - 3088 EP - 3104 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Li, Jian A1 - Shen, Jinhua A1 - Zhang, Xiaoli A1 - Peng, Yangqin A1 - Zhang, Qin A1 - Hu, Liang A1 - Reichetzeder, Christoph A1 - Zeng, Suimin A1 - Li, Jing A1 - Tian, Mei A1 - Gong, Fei A1 - Lin, Ge A1 - Hocher, Berthold T1 - Risk factors associated with preterm birth after IVF/ICSI JF - Scientific reports N2 - In vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) is associated with an increased risk of preterm (33rd-37th gestational week) and early preterm birth (20th-32nd gestational week). The underlying general and procedure related risk factors are not well understood so far. 4328 infertile women undergoing IVF/ICSI were entered into this study. The study population was divided into three groups: (a) early preterm birth group (n = 66), (b) preterm birth group (n = 675) and (c) full-term birth group (n = 3653). Odds for preterm birth were calculated by stepwise multivariate logistic regression analysis. We identified seven independent risk factors for preterm birth and four independent risk factors for early preterm birth. Older (> 39) or younger (< 25) maternal age (OR: 1.504, 95% CI 1.108-2.042, P = 0.009; OR: 2.125, 95% CI 1.049-4.304, P = 0.036, respectively), multiple pregnancy (OR: 9.780, 95% CI 8.014-11.935, P < 0.001; OR: 8.588, 95% CI 4.866-15.157, P < 0.001, respectively), placenta previa (OR: 14.954, 95% CI 8.053-27.767, P < 0.001; OR: 16.479, 95% CI 4.381-61.976, P < 0.001, respectively), and embryo reduction (OR: 3.547, 95% CI 1.736-7.249, P = 0.001; OR: 7.145, 95% CI 1.990-25.663, P = 0.003, respectively) were associated with preterm birth and early preterm birth, whereas gestational hypertension (OR: 2.494, 95% CI 1.770-3.514, P < 0.001), elevated triglycerides (OR: 1.120, 95% CI 1.011-1.240, P = 0.030) and shorter activated partial thromboplastin time (OR: 0.967, 95% CI 0.949-0.985, P < 0.001) were associated only with preterm birth. In conclusion, preterm and early preterm birth risk factors in patients undergoing assisted IVF/ICSI are in general similar to those in natural pregnancy. The lack of some associations in the early preterm group was most likely due to the lower number of early preterm birth cases. Only embryo reduction represents an IVF/ICSI specific risk factor. Y1 - 2022 U6 - https://doi.org/10.1038/s41598-022-12149-w SN - 2045-2322 VL - 12 IS - 1 PB - Nature Research CY - Berlin ER -