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1. Understanding ice and water film formation on soil particles by combining DFT and Casimir-Lifshitz forces

Author

Boström, M., Kuthe, S., Carretero-Palacios, S., Esteso, V., Li, Y., Brevik, I., Gopidi, H. R., Malyi, O. I., Glaser, B., and Persson, C.

Subjects
Condensed Matter - Materials Science
Abstract

Thin films of ice and water on soil particles play crucial roles in environmental and technological processes. Understanding the fundamental physical mechanisms underlying their formation is essential for advancing scientific knowledge and engineering practices. Herein, we focus on the role of the Casimir-Lifshitz force, also referred to as dispersion force, in the formation and behavior of thin films of ice and water on soil particles at 273.16 K, arising from quantum fluctuations of the electromagnetic field and depending on the dielectric properties of interacting materials. We employ the first-principles density functional theory (DFT) to compute the dielectric functions for two model materials, CaCO$_3$ and Al$_2$O$_3$, essential constituents in various soils. These dielectric functions are used with the Kramers-Kronig relationship and different extrapolations to calculate the frequency-dependent quantities required for determining forces and free energies. Moreover, we assess the accuracy of the optical data based on the DFT to model dispersion forces effectively, such as those between soil particles. Our findings reveal that moisture can accumulate into almost micron-sized water layers on the surface of calcite (soil) particles, significantly impacting the average dielectric properties of soil particles. This research highlights the relevance of DFT-based data for understanding thin film formation in soil particles and offers valuable insights for environmental and engineering applications., Comment: 4

Published
2023

2. BLEMAB European project: muon imaging technique applied to blast furnaces

Author

BLEMAB Collaboration, Bonechi, L., Ambrosino, F., Andreetto, P., Bonomi, G., Borselli, D., Bottai, S., Buhles, T., Calliari, I., Checchia, P., Chiarotti, U., Cialdai, C., Ciaranfi, R., Cimmino, L., Ciulli, V., D'Alessandro, R., D'Errico, M., Ferretti, R., Finke, F., Franzen, A., Glaser, B., Gonzi, S., Liu, Y., Lorenzon, A., Masone, V., Nechyporuk, O., Pezzato, L., Rangavittal, B. V., Ressegotti, D., Saracino, G., Sauerwald, J., Starodubtsev, O., and Viliani, L.

Subjects
Physics - Instrumentation and Detectors, High Energy Physics - Experiment, Physics - Applied Physics
Abstract

The BLEMAB European project (BLast furnace stack density Estimation through online Muon ABsorption measurements), evolution of the previous MuBlast European project, is designed to investigate in detail the capability of muon radiography techniques applied to the imaging of a blast furnace's inner zone. In particular, the geometry and size of the so called cohesive zone, i.e. the spatial zone where the slowly downward moving material begins to soften and melt, that plays an important role in the performance of the blast furnace itself. Thanks to the high penetration power of the natural cosmic ray muon radiation, muon transmission radiography represents an appropriate non-invasive methodology for imaging large high-density structures such as blast furnaces, whose linear size can be up to a few tens of meters. A state-of-the-art muon tracking system, whose design profits from the long experience of our collaboration in this field, is currently under development and will be installed in 2022 at a blast furnace on the ArcelorMittal site in Bremen (Germany) for many months. Collected data will be exploited to monitor temporal variations of the average density distribution inside the furnace. Muon radiography results will also be compared with measurements obtained through an enhanced multipoint probe and standard blast furnace models., Comment: 12 pages, 15 figures, IWORID 2021 Workshop

Published
2021

3. Dynamics of Fungal and Bacterial Biomass Carbon in Natural Ecosystems: Site-Level Applications of the CLM-Microbe Model

Author

He, L, Lipson, DA, Mazza Rodrigues, JL, Mayes, M, Björk, RG, Glaser, B, Thornton, P, and Xu, X

Subjects
bacteria, biomass dynamics, fungi, model, sensitivity, Atmospheric Sciences
Abstract

Explicitly representing microbial processes has been recognized as a key improvement to Earth system models for the realistic projections of soil carbon (C) and climate dynamics. The CLM-Microbe model builds upon the CLM4.5 and explicitly represents two major soil microbial groups, fungi and bacteria. Based on the compiled time-series data of fungal (FBC) and bacterial (BBC) biomass C from nine biomes, we parameterized and validated the CLM-Microbe model, and further conducted sensitivity and uncertainty analysis for simulating C cycling. The model performance was evaluated with mean absolute error (MAE), root mean square error (RMSE), and coefficient of determination (R2) for relative change in FBC and BBC. The CLM-Microbe model is able to reasonably capture the seasonal dynamics of FBC and BBC across biomes, particularly for tropical/subtropical forest, temperate broadleaf forest, and grassland, with MAE

Published
2021

4. Study of Light Backgrounds from Relativistic Electrons in Air Light-Guides

Author

Riordan, S., Zhao, Y. X., Baunack, S., Becker, D., Clarke, C., Dehmelt, K., Deshpande, A., Gericke, M., Glaser, B., Imai, K., Kutz, T., Maas, F. E., McNulty, D., Pan, J., Park, S., Rahman, S., Souder, P. A., Wang, P., Wellman, B., and Kumar, K. S.

Subjects
Physics - Instrumentation and Detectors, High Energy Physics - Experiment, Nuclear Experiment
Abstract

The MOLLER experiment proposed at the Thomas Jefferson National Accelerator Facility plans a precision low energy determination of the weak mixing angle via the measurement of the parity-violating asymmetry in the scattering of high energy longitudinally polarized electrons from electrons bound in a liquid hydrogen target (M{\o}ller scattering). A relative measure of the scattering rate is planned to be obtained by intercepting the M{\o}ller scattered electrons with a circular array of thin fused silica tiles attached to air light guides, which facilitate the transport of Cherenkov photons generated within the tiles to photomultiplier tubes (PMTs). The scattered flux will also pass through the light guides of downstream tiles, generating additional Cherenkov as well as scintillation light and is a potential background. In order to estimate the rate of these backgrounds, a gas-filled tube detector was designed and deployed in an electron beam at the MAMI facility at Johannes Gutenberg University, Mainz, Germany. Described in this paper is the design of a detector to measure separately the scintillation and Cherenkov responses of gas mixtures from relativistic electrons, the results of studies of several gas mixtures with comparisons to simulations, and conclusions about the implications for the design of the MOLLER detector apparatus., Comment: Published in NIM.A

Published
2017
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7. Understanding ice and water film formation on soil particles by combining density functional theory and Casimir-Lifshitz forces

Author

European Commission, Foundation for Polish Science, Research Council of Norway, National Centre for Research and Development (Poland), Boström, M. [0000-0001-5111-4049], Kuthe, S. [0000-0003-2076-7228], Carretero-Palacios, S. [0000-0001-9915-5050], Esteso, V. [0000-0002-1976-8306], Li, Y. [0000-0001-5973-898], Brevik, I. [0000-0002-9793-8278], Gopidi, H. R. [0000-0003-0834-1507], Malyi, O. I. [0000-0002-2366-2838], Glaser, B.[0000-0002-6127-5812], Persson, C.[0000-0002-9050-5445], Boström, M., Kuthe, S., Carretero-Palacios, S., Esteso, V., Li, Y., Brevik, I., Gopidi, H. R., Malyi, O. I., Glaser, B., Persson, C., European Commission, Foundation for Polish Science, Research Council of Norway, National Centre for Research and Development (Poland), Boström, M. [0000-0001-5111-4049], Kuthe, S. [0000-0003-2076-7228], Carretero-Palacios, S. [0000-0001-9915-5050], Esteso, V. [0000-0002-1976-8306], Li, Y. [0000-0001-5973-898], Brevik, I. [0000-0002-9793-8278], Gopidi, H. R. [0000-0003-0834-1507], Malyi, O. I. [0000-0002-2366-2838], Glaser, B.[0000-0002-6127-5812], Persson, C.[0000-0002-9050-5445], Boström, M., Kuthe, S., Carretero-Palacios, S., Esteso, V., Li, Y., Brevik, I., Gopidi, H. R., Malyi, O. I., Glaser, B., and Persson, C.

Abstract

Thin films of ice and water on soil particles play crucial roles in environmental and technological processes. Understanding the fundamental physical mechanisms underlying their formation is essential for advancing scientific knowledge and engineering practices. Herein, we focus on the role of the Casimir-Lifshitz force, also referred to as dispersion force, in the formation and behavior of thin films of ice and water on soil particles at 273.16 K, arising from quantum fluctuations of the electromagnetic field and depending on the dielectric properties of interacting materials. We employ the first-principles density functional theory (DFT) to compute the dielectric functions for two model materials, CaCO3 and Al2O3, essential constituents in various soils. These dielectric functions are used with the Kramers-Kronig relationship and different extrapolations to calculate the frequency-dependent quantities required for determining forces and free energies. Moreover, we assess the accuracy of the optical data based on the DFT to model dispersion forces effectively, such as those between soil particles. Our findings reveal that moisture can accumulate into almost micron-sized water layers on the surface of calcite (soil) particles, significantly impacting the average dielectric properties of soil particles. This research highlights the relevance of DFT-based data for understanding thin film formation in soil particles and offers valuable insights for environmental and engineering applications.

Published
2023

8. Understanding Ice and Water Film Formation on Soil Particles by Combining Density Functional Theory and Casimir-Lifshitz Forces

Author

Universidad de Sevilla. Departamento de Física de la Materia Condensada, ENSEMBLE3 (Centre of Excellence for nanophotonics, advanced materials and novel crystal growth-based technologies). Polonia, European Union (UE). H2020, Norway Research Council, Boström, M., Kuthe, S., Carretero Palacios, S., Esteso Carrizo, Victoria, Li, Y., Brevik, I., Gopidi, H. R., Malyi, O. I., Glaser, B., Persson, C., Universidad de Sevilla. Departamento de Física de la Materia Condensada, ENSEMBLE3 (Centre of Excellence for nanophotonics, advanced materials and novel crystal growth-based technologies). Polonia, European Union (UE). H2020, Norway Research Council, Boström, M., Kuthe, S., Carretero Palacios, S., Esteso Carrizo, Victoria, Li, Y., Brevik, I., Gopidi, H. R., Malyi, O. I., Glaser, B., and Persson, C.

Abstract

Thin films of ice and water on soil particles play crucial roles in environmental and technological processes. Understanding the fundamental physical mechanisms underlying their formation is essential for advancing scientific knowledge and engineering practices. Herein, we focus on the role of the Casimir-Lifshitz force, also referred to as dispersion force, in the formation and behavior of thin films of ice and water on soil particles at 273.16 K, arising from quantum fluctuations of the electromagnetic field and depending on the dielectric properties of interacting materials. We employ the first-principles density functional theory (DFT) to compute the dielectric functions for two model materials, CaCO3 and Al2O3, essential constituents in various soils. These dielectric functions are used with the Kramers-Kronig relationship and different extrapolations to calculate the frequency-dependent quantities required for determining forces and free energies. Moreover, we assess the accuracy of the optical data based on the DFT to model dispersion forces effectively, such as those between soil particles. Our findings reveal that moisture can accumulate into almost micron-sized water layers on the surface of calcite (soil) particles, significantly impacting the average dielectric properties of soil particles. This research highlights the relevance of DFT-based data for understanding thin film formation in soil particles and offers valuable insights for environmental and engineering applications.

Published
2023

9. Vibrations Analysis of Bubble Evolution in Liquids of Varying Physical Properties

Author

Rigas, K., (0000-0003-0255-101X) Willers, B., (0000-0003-1639-5417) Eckert, S., Glaser, B., Rigas, K., (0000-0003-0255-101X) Willers, B., (0000-0003-1639-5417) Eckert, S., and Glaser, B.

Abstract

In recent years there is an attempt to control the gas stirring intensity in metal-making ladles with the aid of vibration measurements. Understanding better the induced vibrations in two-phase flows can substantially improve the existing models for gas stirring control. In this work, highly sensitive accelerometers were used for the vibration measurements in a liquid metal alloy; Sn–40 wt pctBi alloy at 200 °C and water at 20 °C. The examination of the liquids was conducted in the ladle mockup integrated into the Liquid Metal Model for Steel Casting facility at Helmholtz-Zentrum Dresden Rossendorf. Single bubbles were generated in the respective liquids by controlled argon injection at low flow rates in the range of 0.01 to 0.15 NL/min through a single nozzle installed at the bottom of the ladle. Obtained results demonstrate differences between the induced vibrations in the examined liquids in terms of the magnitude of the root mean square values of vibration amplitude and the shape of the resulting curves with increasing flow rate. Furthermore, continuous wavelet transform reveals variations in the duration and vibrational frequency of the evolved bubble phenomena. The findings suggest that differences in the physical properties of the examined liquids result in variations in the vibrations induced during bubble evolution.

Published
2023

10. Investigations on Vibrational Interpretations of Bubbles in Metal-Making Processes

Author

Rigas, K., (0000-0003-0255-101X) Willers, B., (0000-0003-1639-5417) Eckert, S., Glaser, B., Rigas, K., (0000-0003-0255-101X) Willers, B., (0000-0003-1639-5417) Eckert, S., and Glaser, B.

Abstract

Vibration measurements were carried out using highly sensitive accelerometers in an experimental ladle integrated into the LIMMCAST (Liquid Metal Model for Steel Casting) facility at HZDR. The model is operated with liquid Sn–40 wt pctBi alloy at 200°C, whose physical properties are close to those of molten steel. Three accelerometers were attached to the outer wall of the LIMMCAST vessel to record the vibrations caused by the argon bubble flow in the liquid metal at different process parameters. The results obtained at the liquid metal experiments differ from those reported for water models where the relationship between root mean square (RMS) value of the vibration amplitude and the gas flow rate follows different curve shapes. Furthermore, the results of vibration measurements in the LIMMCAST model are compared with vibration measurements in a steel plant during vacuum degassing. The comparison of the RMS data shows a fairly good agreement. This indicates that the vibrations in both the industrial process and the laboratory model are caused by the same physical mechanisms, and thus, the vibration behavior in an industrial steelmaking ladle can be reproduced quite well by suitable liquid metal models. These studies on bubble flows can help to improve the understanding of industrial stirring processes and thus contribute to a better process control.

Published
2023

11. Degradation of bio-based and biodegradable plastic and its contribution to soil organic carbon stock

Author

Guliyev, Vusal, Tanunchai, Benjawan, Udovenko, Maria, Menyailo, O., Glaser, B., Purahong, Witoon, Buscot, Francois, Blagodatskaya, Evgenia, Guliyev, Vusal, Tanunchai, Benjawan, Udovenko, Maria, Menyailo, O., Glaser, B., Purahong, Witoon, Buscot, Francois, and Blagodatskaya, Evgenia

Abstract

Expanding the use of environmentally friendly materials to protect the environment is one of the key factors in maintaining a sustainable ecological balance. Poly(butylene succinate-co-adipate) (PBSA) is considered among the most promising bio-based and biodegradable plastics for the future with a high number of applications in soil and agriculture. Therefore, the decomposition process of PBSA and its consequences for the carbon stored in soil require careful monitoring. For the first time, the stable isotope technique was applied in the current study to partitioning plastic- and soil-originated C in the CO2 released during 80 days of PBSA decomposition in a Haplic Chernozem soil as dependent on nitrogen availability. The decomposition of the plastic was accompanied by the C loss from soil organic matter (SOM) through priming, which in turn was dependent on added N. Nitrogen facilitated PBSA decomposition and reduced the priming effect during the first 6 weeks of the experiment. During the 80 days of plastic decomposition, 30% and 49% of the released CO2 were PBSA-derived, while the amount of SOM-derived CO2 exceeded the corresponding controls by 100.2 and 132.3% in PBSA-amended soil without and with N fertilization, respectively. Finally, only 4.1% and 5.4% of the PBSA added into the soil was mineralized to CO2, in the treatments without and with N amendment, respectively.

Published
2023

12. Imaging of the Inner Zone of Blast Furnaces Using MuonRadiography: The BLEMAB Project

Author

Gonzi, S., Ambrosino, F., Andreetto, P., Bonechi, L., Bonomi, G., Borselli, D., Bottai, S., Buhles, T., Calliari, I., Checchia, P., Chiarotti, U., C. Cialdai, 2 C., Ciaranfi, R., Cimmino, L., Ciulli, V., D’Alessandro, R., D’Errico, M., Finke, F., Franzen, A, Glaser, B., Lorenzon, A., Masone, V., Moroli, V., Nechyporuk, O., Pezzato, L., V. Rangavittal, B., Ressegotti, D., Saracino, G., Sauerwald, J., Starodubtsev, O., Viliani, L., Volzone, F., Gonzi, S., Ambrosino, F., Andreetto, P., Bonechi, L., Bonomi, G., Borselli, D., Bottai, S., Buhles, T., Calliari, I., Checchia, P., Chiarotti, U., C., Cialdai, 2, C., Ciaranfi, R., Cimmino, L., Ciulli, V., D’Alessandro, R., D’Errico, M., Finke, F., Franzen, A, Glaser, B., Lorenzon, A., Masone, V., Moroli, V., Nechyporuk, O., Pezzato, L., V. Rangavittal, B., Ressegotti, D., Saracino, G., Sauerwald, J., Starodubtsev, O., Viliani, L., and Volzone, F.

Abstract

The aim of the BLEMAB project (BLast furnace stack density Estimation through online Muons ABsorption measurements) is the application of muon radiography techniques, to image a blast furnace’s inner zone. In particular, the goal of the study is to characterize the geometry and size of the so-called “cohesive zone”, i.e., the spatial region where the slowly downward-moving material begins to soften and melt, which plays such an important role in the performance of the blast furnace itself. Thanks to the high penetration power of natural cosmic-ray muon radiation, muon transmission radiography could be an appropriate non invasive methodology for the imaging of large high-density structures such as a blast furnace, whose linear dimensions can be up to a few tens of meters. A state-of-the-art muon tracking system is currently in development and will be installed at a blast furnace on the ArcelorMittal site in Bremen (Germany), where it will collect data for a period of various months. In this paper, the status of the project and the expectations based on preliminary simulations are presented and briefly discussed.

Published
2022

13. The BLEMAB European project: Muon radiography as an imaging tool in the industrial field

Author

Borselli D., Ambrosino F., Andreetto P., Bonechi L., Bonomi G., Bottai S., Buhles T., Calliari I., Checchia P., Chiarotti U., Cialdai C., Ciaranfi R., Cimmino L., Ciulli V., D'Alessandro R., D'Errico M., Ferretti R., Finke F., Franzen A., Glaser B., Gonzi S., Liu Y., Lorenzon A., Masone V., Moroli V., Nechyporuk O., Pezzato L., Rangavittal B. V., Ressegotti D., Saracino G., Sauerwald J., Starodubtsev O., Vasudev B., Viliani L., Volzone F., Borselli, D., Ambrosino, F., Andreetto, P., Bonechi, L., Bonomi, G., Bottai, S., Buhles, T., Calliari, I., Checchia, P., Chiarotti, U., Cialdai, C., Ciaranfi, R., Cimmino, L., Ciulli, V., D'Alessandro, R., D'Errico, M., Ferretti, R., Finke, F., Franzen, A., Glaser, B., Gonzi, S., Liu, Y., Lorenzon, A., Masone, V., Moroli, V., Nechyporuk, O., Pezzato, L., Rangavittal, B. V., Ressegotti, D., Saracino, G., Sauerwald, J., Starodubtsev, O., Vasudev, B., Viliani, L., and Volzone, F.

Abstract

The European project called BLEMAB (BLast furnace stack density Estimation through on-line Muons ABsorption measurements), provides for the application of the muon radiography technique in the industrial environment. The project represents a non-invasive way of monitoring a blast furnace and in particular aims to study the geometric and density development of the so-called “cohesive zone”, which is important for the performance of the blast furnace itself. The installation of the detectors is expected in 2022 at the ArcelorMittal site in Bremen (Germany). This paper describes the status of the project, the experimental setup and the first results obtained with preliminary simulations. © 2022 Societa Italiana di Fisica. All rights reserved.

Published
2022

14. Large-scale sequencing identifies multiple genes and rare variants associated with Crohn’s disease susceptibility

Author

Sazonovs, A., Stevens, C.R., Venkataraman, G.R., Yuan, K., Avila, B., Abreu, M.T., Ahmad, T., Allez, M., Ananthakrishnan, A.N., Atzmon, G., Baras, A., Barrett, J.C., Barzilai, N., Beaugerie, L., Beecham, A., Bernstein, C.N., Bitton, A., Bokemeyer, B., Chan, A., Chung, D., Cleynen, I., Cosnes, J., Cutler, D.J., Daly, A., Damas, O.M., Datta, L.W., Dawany, N., Devoto, M., Dodge, S., Ellinghaus, E., Fachal, L., Farkkila, M., Faubion, W., Ferreira, M., Franchimont, D., Gabriel, S.B., Ge, T., Georges, M., Gettler, K., Giri, M., Glaser, B., Goerg, S., Goyette, P., Graham, D., Hamalainen, E., Haritunians, T., Heap, G.A., Hiltunen, M., Hoeppner, M., Horowitz, J.E., Irving, P., Iyer, V., Jalas, C., Kelsen, J., Khalili, H., Kirschner, B.S., Kontula, K., Koskela, J.T., Kugathasan, S., Kupcinskas, J., Lamb, C.A., Laudes, M., Levesque, C., Levine, A.P., Lewis, J.D., Liefferinckx, C., Loescher, B.S., Louis, E., Mansfield, J., May, S., McCauley, J.L., Mengesha, E., Mni, M., Moayyedi, P., Moran, C.J., Newberry, R.D., O'Charoen, S., Okou, D.T., Oldenburg, B., Ostrer, H., Palotie, A., Paquette, J., Pekow, J., Peter, I., Pierik, M.J., Ponsioen, C.Y., Pontikos, N., Prescott, N., Pulver, A.E., Rahmouni, S., Rice, D.L., Saavalainen, P., Sands, B., Sartor, R.B., Schiff, E.R., Schreiber, S., Schumm, L.P., Segal, A.W., Seksik, P., Shawky, R., Sheikh, S.Z., Silverberg, M.S., Simmons, A., Skeiceviciene, J., Sokol, H., Solomonson, M., Somineni, H., Sun, D., Targan, S., Turner, D., Uhlig, H.H., Meulen, A.E. van der, Vermeire, S., Verstockt, S., Voskuil, M.D., Winter, H.S., Young, J., Duerr, R.H., Franke, A., Brant, S.R., Cho, J., Weersma, R.K., Parkes, M., Xavier, R.J., Rivas, M.A., Rioux, J.D., McGovern, D.P.B., Huang, H.L., Anderson, C.A., Daly, M.J., Belgium IBD Consortium, Cedars-Sinai IBD, International IBD Genetics Consortium, NIDDK IBD Genetics Consortium, NIHR IBD BioResource, Regeneron Genetics Center, SHARE Consortium, SPARC IBD Network, UK IBD Genetics Consortium, Interne Geneeskunde, MUMC+: MA Maag Darm Lever (9), RS: NUTRIM - R2 - Liver and digestive health, Gastroenterology and Hepatology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)

Subjects
Crohn Disease, Genetics, Humans, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Article, Genome-Wide Association Study
Abstract

Genome-wide association studies (GWASs) have identified hundreds of loci associated with Crohn's disease (CD). However, as with all complex diseases, robust identification of the genes dysregulated by noncoding variants typically driving GWAS discoveries has been challenging. Here, to complement GWASs and better define actionable biological targets, we analyzed sequence data from more than 30,000 patients with CD and 80,000 population controls. We directly implicate ten genes in general onset CD for the first time to our knowledge via association to coding variation, four of which lie within established CD GWAS loci. In nine instances, a single coding variant is significantly associated, and in the tenth, ATG4C, we see additionally a significantly increased burden of very rare coding variants in CD cases. In addition to reiterating the central role of innate and adaptive immune cells as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation.Large-scale sequence-based analyses identify novel risk variants and susceptibility genes for Crohn's disease, and implicate mesenchymal cell-mediated intestinal homeostasis in disease etiology.

Published
2022

16. Nitrogen fixing bacteria facilitate microbial biodegradation of a bio-based and biodegradable plastic in soils under ambient and future climatic conditions

Author

Tanunchai, Benjawan, Kalkhof, S., Guliyev, Vusal, Wahdan, Sara Fareed Mohamed, Krstic, D., Schädler, Martin, Geissler, A., Glaser, B., Buscot, Francois, Blagodatskaya, Evgenia, Noll, M., Purahong, Witoon, Tanunchai, Benjawan, Kalkhof, S., Guliyev, Vusal, Wahdan, Sara Fareed Mohamed, Krstic, D., Schädler, Martin, Geissler, A., Glaser, B., Buscot, Francois, Blagodatskaya, Evgenia, Noll, M., and Purahong, Witoon

Abstract

We discovered a biological mechanism supporting microbial degradation of bio-based poly(butylene succinate-co-adipate) (PBSA) plastic in soils under ambient and future climates. Here, we show that nitrogen-fixing bacteria facilitate the microbial degradation of PBSA by enhancing fungal abundance, accelerating plastic-degrading enzyme activities, and shaping/interacting with plastic-degrading fungal communities.

Published
2022

17. What is a β cell? - Chapter I in the Human Islet Research Network (HIRN) review series

Author

Kaestner, K.H., Campbell-Thompson, M., Dor, Y., Gill, R.G., Glaser, B., Kim, S.K., Sander, M., Stabler, C., Stewart, A.F., and Powers, A.C.

Subjects
Cardiovascular and Metabolic Diseases
Abstract

BACKGROUND: The pancreatic β cell, as the sole source of the vital hormone insulin, has been under intensive study for more than a century. Given the potential of newly created insulin-producing cells as a treatment or even cure of type 1 diabetes (T1D) and possibly in severe cases of type 2 diabetes (T2D), multiple academic and commercial laboratories are working to derive surrogate glucose-responsive, insulin-producing cells. SCOPE OF REVIEW: The recent development of advanced phenotyping technologies, including molecular, epigenomic, histological, or functional, have greatly improved our understanding of the critical properties of human β cells. Using this information, here we summarize the salient features of normal, fully functional adult human β cells, and propose minimal criteria for what should rightfully be termed 'β cells' as opposed to insulin-producing but not fully-functional surrogates that we propose should be referred to as 'β-like' cells or insulin-producing cells. MAJOR CONCLUSIONS: Clear criteria can be established to differentiate fully functional, mature β cells from 'β-like' surrogates. In addition, we outline important knowledge gaps that must be addressed to enable a greater understanding of the β cell.

Published
2021

18. Validation of a coupled δ2Hn-alkane–δ18Osugar paleohygrometer approach based on a climate chamber experiment

Author

Hepp, J., Mayr. C., Rozanski, K., Schaefer, I.K., Tuthorn, M., Glaser, B., Juchelka, D., Stichler, W., Zech, R., and Zech, M.

Subjects
TheoryofComputation_MATHEMATICALLOGICANDFORMALLANGUAGES, TheoryofComputation_ANALYSISOFALGORITHMSANDPROBLEMCOMPLEXITY
Abstract

The hydrogen isotope composition of leaf-wax-derived biomarkers, e.g., long-chain n-alkanes (δ2Hn-alkane), is widely applied in paleoclimate. However, a direct reconstruction of the isotope composition of source water based on δ2Hn-alkane alone is challenging due to the enrichment of heavy isotopes during evaporation. The coupling of δ2Hn-alkane with δ18O of hemicellulose-derived sugars (δ18Osugar) has the potential to disentangle this limitation and additionally to allow relative humidity reconstructions. Here, we present δ2Hn-alkane as well as δ18Osugar results obtained from leaves of Eucalyptus globulus, Vicia faba, and Brassica oleracea, which grew under controlled conditions. We addressed the questions of (i) whether δ2Hn-alkane and δ18Osugar values allow reconstructions of leaf water isotope composition, (ii) how accurately the reconstructed leaf water isotope composition enables relative humidity (RH) reconstruction, and (iii) whether the coupling of δ2Hn-alkane and δ18Osugar enables a robust source water calculation. For all investigated species, the n-alkane n-C29 was most abundant and therefore used for compound-specific δ2H measurements. For Vicia faba, additionally the δ2H values of n-C31 could be evaluated robustly. Regarding hemicellulose-derived monosaccharides, arabinose and xylose were most abundant, and their δ18O values were therefore used to calculate weighted mean leaf δ18Osugar values. Both δ2Hn-alkane and δ18Osugar yielded significant correlations with δ2Hleaf water and δ18Oleaf water, respectively (r2=0.45 and 0.85, respectively; p, n=24). Mean fractionation factors between biomarkers and leaf water were found to be −156 ‰ (ranging from −133 ‰ to −192 ‰) for εn-alkane/leaf water and +27.3 ‰ (ranging from +23.0 ‰ to 32.3 ‰) for εsugar/leaf water, respectively. Modeled RHair values from a Craig–Gordon model using measured Tair, δ2Hleaf water and δ18Oleaf water as input correlate highly significantly with modeled RHair values (R2=0.84, p, RMSE = 6 %). When coupling δ2Hn-alkane and δ18Osugar values, the correlation of modeled RHair values with measured RHair values is weaker but still highly significant, with R2=0.54 (p, RMSE = 10 %). Finally, the reconstructed source water isotope composition (δ2Hs and δ18Os) as calculated from our coupled approach matches the source water in the climate chamber experiment (δ2Htank water and δ18Otank water). This highlights the great potential of the coupled δ2Hn-alkane–δ18Osugar paleohygrometer approach for paleoclimate and relative humidity reconstructions.

Published
2021

20. The Holocene lake-evaporation history of the afro-alpine Lake Garba Guracha in the Bale Mountains, Ethiopia, based on δ18O records of sugar biomarkers and diatoms

Author

Bittner, L., Gil-Romera, G., Grady, D., Lamb, H. F., Lorenz, E., Weiner, Mikaela, Meyer, Hanno, Bromm, T., Glaser, B., Zech, Michael, Bittner, L., Gil-Romera, G., Grady, D., Lamb, H. F., Lorenz, E., Weiner, Mikaela, Meyer, Hanno, Bromm, T., Glaser, B., and Zech, Michael

Abstract

In eastern Africa, there are few long, high-quality records of environmental change at high altitudes, inhibiting a broader understanding of regional climate change. We investigated a Holocene lacustrine sediment archive from Lake Garba Guracha, Bale Mountains, Ethiopia, (3,950 m a.s.l.), and reconstructed high-altitude lake evaporation history using δ18O records derived from the analysis of compound-specific sugar biomarkers and diatoms. The δ18Odiatom and δ18Ofuc records are clearly correlated and reveal similar ranges (7.9‰ and 7.1‰, respectively). The lowest δ18O values occurred between 10 and 7 cal ka BP and were followed by a continuous shift towards more positive δ18O values. Due to the aquatic origin of the sugar biomarker and the similar trends of δ18Odiatom, we suggest that our lacustrine δ18Ofuc record reflects δ18Olake water. Therefore, without completely excluding the influence of the ‘amount-effect’ and the ‘source-effect‘, we interpret our record to reflect primarily the precipitation-to-evaporation ratio (P/E). We conclude that precipitation increased at the beginning of the Holocene, leading to an overflowing lake between ~10 and ~8 cal ka BP, indicated by low δ18Olake water values interpreted as reduced evaporative enrichment. This is followed by a continuous trend towards drier conditions, indicating at least a seasonally closed lake system.

Published
2021

21. Analysis of microbial populations in plastic–soil systems after exposure to high poly(butylene succinate-co-adipate) load using high-resolution molecular technique

Author

Tanunchai, Benjawan, Juncheed, K., Wahdan, Sara Fareed Mohamed, Guliyev, Vusal, Udovenko, Maria, Lehnert, A.-S., Gomes Alves, E., Glaser, B., Noll, M., Buscot, Francois, Blagodatskaya, Evgenia, Purahong, Witoon, Tanunchai, Benjawan, Juncheed, K., Wahdan, Sara Fareed Mohamed, Guliyev, Vusal, Udovenko, Maria, Lehnert, A.-S., Gomes Alves, E., Glaser, B., Noll, M., Buscot, Francois, Blagodatskaya, Evgenia, and Purahong, Witoon

Abstract

Background Bio-based and biodegradable plastics are considered as plastics of the future owing to their ability to decompose under various environmental conditions. However, their effects on the soil microbiome are poorly characterised. In this study, we aimed to investigate the effects of an important bio-based and biodegradable plastic, polybutylene succinate-co-adipate (PBSA), on soil microbial diversity and community composition using high-resolution molecular technique (Illumina sequencing) targeting all three microbial domains: archaea, bacteria, and fungi. Results Adding high load of PBSA to soil (6% (w/w)) caused a significant decline in archaeal (13%) and fungal (45%) richness and substantial changes in both bacterial (Proteobacteria, Actinobacteria, and Acidobacteria) and fungal (Eurotiomycetes, Sordariomycetes, Leotiomycetes, and Dothideomycetes) community composition compared with no PBSA addition to soil. The combined effects of PBSA and (NH4)2SO4 fertilisation on the soil microbiome were much greater than the effects of PBSA alone. We only detected opportunistic human pathogens in low abundance on PBSA and in the surrounding soil. However, some plant pathogenic fungi were detected and/or enriched on the PBSA films and in surrounding soil. Apart from plant pathogens, many potential microbial control agents and plant growth-promoting microorganisms were also detected/enriched owing to PBSA addition. Adding high load of PBSA together with (NH4)2SO4 fertilisation can either eliminate some plant pathogens or enrich specific pathogens, especially Fusarium solani, which is economically important. Conclusions We conclude that high load of bio-based and biodegradable PBSA plastic may negatively affect soil microbiome.   &nbsp

Published
2021

22. Reconstructing Late Quaternary precipitation and its source on the southern Cape coast of South Africa: A multi-proxy paleoenvironmental record from Vankervelsvlei

Author

Strobel, P., Bliedtner, M., Carr, A. S., Struck, J., Du Plessis, N., Glaser, B., Meadows, M. E., Quick, L. J., Zech, M., Zech, R., and Haberzettl, T.

Subjects
Archeology, Global and Planetary Change, Geology, Ecology, Evolution, Behavior and Systematics
Abstract

The Late Quaternary climate history of South Africa and, in particular, potential changes in atmospheric circulation have been subject to considerable debate. To some extent, this is due to a scarcity of natural archives, and on the other hand the available indirect hydrological proxies are not suited to distinguishing between precipitation originating from temperate Westerlies and tropical Easterlies. This study presents a paleoenvironmental record from Vankervelsvlei, a wetland located on the southern Cape coast in the year-round rainfall zone of South Africa. A 15 m long sediment record was retrieved from this site and analysed using a multi-proxy approach. This includes, for the first time in this region, analysis of both compound-specific δ2H and δ18O from leaf wax-derived n-alkanes and hemicellulose-derived sugars, respectively, to investigate hydrological changes during the Late Quaternary. Our data suggest the driest conditions of the past ∼250 ka likely occurred from MIS 6 to MIS 5e, which still caused sediment deposition at Vankervelsvlei, and MIS 2, during which time there was an absence of sedimentation. Moist conditions occurred from MIS 5e to 5a and during parts of MIS 3, while drier conditions prevailed between MIS 5a and early MIS 3 and at the transition from MIS 3 to MIS 2. Besides changes in the amount and proportional contribution of precipitation contributions from Westerlies during glacial and Easterlies during interglacial periods, relative sea-level change affected the continentality of Vankervelsvlei, with a distinct impact on the sites hydrological balance. High-resolution analyses of the Middle- and Late-Holocene parts of the record show moist conditions and increased Easterly/locally-derived summer precipitation contributions from 7230 +160/−210 to 4890 +280/−180 cal BP and after 2840 +350/−330 cal BP. Dry conditions, accompanied by the reduction of Easterly/locally-derived summer rainfall and increased seasonality occurred from 4890 +280/−180 to 2840 +350/−330 cal BP. Our findings highlight that source and seasonality of precipitation play a major role in the hydrological balance of the southern Cape coastal region. By comparing the Vankervelsvlei record to other regional studies, we infer a coherent trend in the overall moisture evolution along South Africa's southern Cape coast during the Late Quaternary.

Published
2022

23. Revisiting afro-alpine Lake Garba Guracha in the Bale Mountains of Ethiopia: rationale, chronology, geochemistry, and paleoenvironmental implications

Author

Bittner, L., Bliedtner, M., Grady, D., Gil-Romera, G., Martin-Jones, C., Lemma, B., Mekonnen, B., Lamb, H. F., Yang, H., Glaser, B., Szidat, S., Salazar, G., Rose, N. L., Opgenoorth, L., Miehe, G., Zech, W., Zech, M., Heisenberg Chair of Physical Geography with Focus on Paleoenvironmental Research, Institute of Geography, Technical University of Dresden, Dresden, Germany, Department of Physical Geography, Institute of Geography, Friedrich-Schiller-University Jena, Jena, Germany, Department of Geography and Earth Sciences, Aberystwyth University, Aberystwyth, UK, Department of Geo-Environmental Processes and Global Change, CSIC, Pyrenean Institute of Ecology, Zaragoza, Spain, Limnology Unit, Department of Biology, Ghent University, Gent, Belgium, Institute of Agronomy and Nutritional Sciences, Soil Biogeochemistry, Martin-Luther-Universität Halle-Wittenberg, Halle, Germany, Environmental Change Research Centre, University College London, London, UK, Department of Chemistry and Biochemistry and Oeschger Centre for Climate Change Research, University of Bern, Bern, Switzerland, Department of Geography, University of Marburg, Marburg, Germany, Institute of Soil Science and Soil Geography, University of Bayreuth, Bayreuth, Germany, Bittner, L [0000-0003-2521-5596], Apollo - University of Cambridge Repository, and Bittner, L. [0000-0003-2521-5596]

Subjects
Radiocarbon dating, 010506 paleontology, 010504 meteorology & atmospheric sciences, Sedimentation rate, Aquatic Science, 01 natural sciences, law.invention, law, 540 Chemistry, Paleoclimatology, Afro-alpine, Sedimentary organic matter, Glacial period, Younger Dryas, Paleolimnology, Sedimentology, Holocene, 0105 earth and related environmental sciences, Earth-Surface Processes, Original Paper, ddc:551, XRF scanning, 570 Life sciences, biology, Physical geography, Geology, Biomarkers, Chronology
Abstract

Previous paleolimnological studies demonstrated that the sediments of Garba Guracha, situated at 3950 m asl in the afro-alpine zone of the Bale Mountains of Ethiopia, provide a complete Late Glacial and Holocene paleoclimate and environmental archive. We revisited Garba Guracha in order to retrieve new sediment cores and to apply new environmental proxies, e.g. charcoal, diatoms, biomarkers, and stable isotopes. Our chronology is established using 210Pb dating and radiocarbon dating of bulk sedimentary organic matter, bulk n-alkanes, and charcoal. Although bedrock was not reached during coring, basal ages confirm that sedimentation started at the earliest ~ 16 cal kyr BP. The absence of a systematic age offset for the n-alkanes suggests that “pre-aging” is not a prominent issue in this lake, which is characterised by a very small afro-alpine catchment. X-ray fluorescence scans and total organic carbon contents show a prominent transition from minerogenic to organic-rich sediments around 11 cal kyr BP coinciding with the Holocene onset. While an unambiguous terrestrial versus aquatic source identification seems challenging, the n-alkane-based Paq proxy, TOC/N ratios, δ13C values, and the sugar biomarker patterns suggest a predominantly autochthonous organic matter source. Supraregional climate events, such as the African Humid Period, the Younger Dryas (YD), a 6.5 cal kyr BP short drying event, and the 4.2 cal kyr BP transition to overall drier climate are recorded in our archive. The Garba Guracha record suggests that northern hemisphere forcings played a role in the Eastern African highland paleoclimate., Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659

Published
2020

24. Goethite-bound phosphorus in an acidic subsoil is not available to beech (Fagus sylvatica L.)

Author

Klotzbücher, A., Schunck, Florian, Klotzbücher, T., Kaiser, K., Glaser, B., Spohn, M., Widdig, M., Mikutta, R., Klotzbücher, A., Schunck, Florian, Klotzbücher, T., Kaiser, K., Glaser, B., Spohn, M., Widdig, M., and Mikutta, R.

Abstract

In forests, where the supply of bioavailable phosphorus (P) from easily weatherable primary minerals is small, plants are thought to recycle P efficiently by uptake of P released from decomposing forest floor material. Yet a share of the P is leached into the subsoil, where it is strongly adsorbed onto the reactive surfaces of pedogenic Fe and Al oxides. This raises the question of whether P leached into subsoil is also recycled. To investigate the mobilization of P bound to hydrous Fe oxides, we conducted a mesocosm experiment in a greenhouse. Beech saplings were grown for 14 months in subsoil material (Bw horizon from the P-poor Lüss beech forest) with added goethite-P adsorption complexes, in either inorganic (orthophosphate) or organic (phytate) form. Four types of control mesocosms were run: soil only and soil mixed with either dissolved orthophosphate or dissolved phytate or goethite. At the end of the experiment, neither total P mass in trees nor P contents in leaves differed between the treatments. According to leaf nutrient contents, plant growth was strongly limited by P in all treatments. Yet total P mass in trees did not increase over the course of the experiment. Thus, despite its P demand, beech was not able to acquire P from goethite surfaces within two vegetation periods. Also P added in dissolved form to the soil before transplanting as well as native soil P were not available. This suggests that, once inorganic and organic P is bound to pedogenic metal oxides in mineral soil, it is not or hardly recycled, which can be an explanation for field data demonstrating quantitatively significant stocks of P in the subsoil of P-deficient forests.

Published
2020

29. Turnover of microbial groups and cell components in soil: 13C analysis of cellular biomarkers

Author

Gunina A., Dippold M., Glaser B., and Kuzyakov Y.

Subjects
lcsh:Geology, microbial groups, soil, cell components, 13C, biomarkers, lcsh:QH501-531, lcsh:QH540-549.5, lcsh:QE1-996.5, lcsh:Life, lcsh:Ecology
Abstract

Microorganisms regulate the carbon (C) cycle in soil, controlling the utilization and recycling of organic substances. To reveal the contribution of particular microbial groups to C utilization and turnover within the microbial cells, the fate of 13C-labelled glucose was studied under field conditions. Glucose-derived 13C was traced in cytosol, amino sugars and phospholipid fatty acid (PLFA) pools at intervals of 3, 10 and 50 days after glucose addition into the soil. 13C enrichment in PLFAs ( ∼ 1.5 % of PLFA C at day 3) was an order of magnitude greater than in cytosol, showing the importance of cell membranes for initial C utilization. The 13C enrichment in amino sugars of living microorganisms at day 3 accounted for 0.57 % of total C pool; as a result, we infer that the replacement of C in cell wall components is 3 times slower than that of cell membranes. The C turnover time in the cytosol (150 days) was 3 times longer than in PLFAs (47 days). Consequently, even though the cytosol pool has the fastest processing rates compared to other cellular compartments, intensive recycling of components here leads to a long C turnover time. Both PLFA and amino-sugar profiles indicated that bacteria dominated in glucose utilization. 13C enrichment decreased with time for bacterial cell membrane components, but it remained constant or even increased for filamentous microorganisms. 13C enrichment of muramic acid was the 3.5 times greater than for galactosamine, showing a more rapid turnover of bacterial cell wall components compared to fungal. Thus, bacteria utilize a greater proportion of low-molecular-weight organic substances, whereas filamentous microorganisms are responsible for further C transformations. Thus, tracing 13C in cellular compounds with contrasting turnover rates elucidated the role of microbial groups and their cellular compartments in C utilization and recycling in soil. The results also reflect that microbial C turnover is not restricted to the death or growth of new cells. Indeed, even within living cells, highly polymeric cell compounds are constantly replaced and renewed. This is especially important for assessing C fluxes in soil and the contribution of C from microbial residues to soil organic matter.

Published
2017

32. Investment Timing and Incentive Costs

Author

Gryglewicz, S. (Sebastian), Hartman-Glaser, B., Gryglewicz, S. (Sebastian), and Hartman-Glaser, B.

Abstract

We analyze how the costs of smoothly adjusting capital, such as incentive costs, affect investment timing. In our model, the owner of a firm holds a real option to increase a lumpy form of capital and can also smoothly adjust an incremental form of capital. Increasing the cost of incremental capital can delay or accelerate investment in lumpy capital. Incentive costs due to moral hazard are a natural source of costs for the accumulation of incremental capital. When moral hazard is severe, delaying investment in lumpy capital is costly, and it is optimal to overinvest relative to the first-best case.

Published
2019

33. Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls.

Author

Flannick, J, Mercader, JM, Fuchsberger, C, Udler, MS, Mahajan, A, Wessel, J, Teslovich, TM, Caulkins, L, Koesterer, R, Barajas-Olmos, F, Blackwell, TW, Boerwinkle, E, Brody, JA, Centeno-Cruz, F, Chen, L, Chen, S, Contreras-Cubas, C, Córdova, E, Correa, A, Cortes, M, DeFronzo, RA, Dolan, L, Drews, KL, Elliott, A, Floyd, JS, Gabriel, S, Garay-Sevilla, ME, García-Ortiz, H, Gross, M, Han, S, Heard-Costa, NL, Jackson, AU, Jørgensen, ME, Kang, HM, Kelsey, M, Kim, B-J, Koistinen, HA, Kuusisto, J, Leader, JB, Linneberg, A, Liu, C-T, Liu, J, Lyssenko, V, Manning, AK, Marcketta, A, Malacara-Hernandez, JM, Martínez-Hernández, A, Matsuo, K, Mayer-Davis, E, Mendoza-Caamal, E, Mohlke, KL, Morrison, AC, Ndungu, A, Ng, MCY, O'Dushlaine, C, Payne, AJ, Pihoker, C, Broad Genomics Platform, Post, WS, Preuss, M, Psaty, BM, Vasan, RS, Rayner, NW, Reiner, AP, Revilla-Monsalve, C, Robertson, NR, Santoro, N, Schurmann, C, So, WY, Soberón, X, Stringham, HM, Strom, TM, Tam, CHT, Thameem, F, Tomlinson, B, Torres, JM, Tracy, RP, van Dam, RM, Vujkovic, M, Wang, S, Welch, RP, Witte, DR, Wong, T-Y, Atzmon, G, Barzilai, N, Blangero, J, Bonnycastle, LL, Bowden, DW, Chambers, JC, Chan, E, Cheng, C-Y, Cho, YS, Collins, FS, de Vries, PS, Duggirala, R, Glaser, B, Gonzalez, C, Gonzalez, ME, Groop, L, Kooner, JS, Kwak, SH, Laakso, M, Lehman, DM, Nilsson, P, Spector, TD, Tai, ES, Tuomi, T, Tuomilehto, J, Wilson, JG, Aguilar-Salinas, CA, Bottinger, E, Burke, B, Carey, DJ, Chan, JCN, Dupuis, J, Frossard, P, Heckbert, SR, Hwang, MY, Kim, YJ, Kirchner, HL, Lee, J-Y, Lee, J, Loos, RJF, Ma, RCW, Morris, AD, O'Donnell, CJ, Palmer, CNA, Pankow, J, Park, KS, Rasheed, A, Saleheen, D, Sim, X, Small, KS, Teo, YY, Haiman, C, Hanis, CL, Henderson, BE, Orozco, L, Tusié-Luna, T, Dewey, FE, Baras, A, Gieger, C, Meitinger, T, Strauch, K, Lange, L, Grarup, N, Hansen, T, Pedersen, O, Zeitler, P, Dabelea, D, Abecasis, G, Bell, GI, Cox, NJ, Seielstad, M, Sladek, R, Meigs, JB, Rich, SS, Rotter, JI, DiscovEHR Collaboration, CHARGE, LuCamp, ProDiGY, GoT2D, ESP, SIGMA-T2D, T2D-GENES, AMP-T2D-GENES, Altshuler, D, Burtt, NP, Scott, LJ, Morris, AP, Florez, JC, McCarthy, MI, Boehnke, M, Flannick, J, Mercader, JM, Fuchsberger, C, Udler, MS, Mahajan, A, Wessel, J, Teslovich, TM, Caulkins, L, Koesterer, R, Barajas-Olmos, F, Blackwell, TW, Boerwinkle, E, Brody, JA, Centeno-Cruz, F, Chen, L, Chen, S, Contreras-Cubas, C, Córdova, E, Correa, A, Cortes, M, DeFronzo, RA, Dolan, L, Drews, KL, Elliott, A, Floyd, JS, Gabriel, S, Garay-Sevilla, ME, García-Ortiz, H, Gross, M, Han, S, Heard-Costa, NL, Jackson, AU, Jørgensen, ME, Kang, HM, Kelsey, M, Kim, B-J, Koistinen, HA, Kuusisto, J, Leader, JB, Linneberg, A, Liu, C-T, Liu, J, Lyssenko, V, Manning, AK, Marcketta, A, Malacara-Hernandez, JM, Martínez-Hernández, A, Matsuo, K, Mayer-Davis, E, Mendoza-Caamal, E, Mohlke, KL, Morrison, AC, Ndungu, A, Ng, MCY, O'Dushlaine, C, Payne, AJ, Pihoker, C, Broad Genomics Platform, Post, WS, Preuss, M, Psaty, BM, Vasan, RS, Rayner, NW, Reiner, AP, Revilla-Monsalve, C, Robertson, NR, Santoro, N, Schurmann, C, So, WY, Soberón, X, Stringham, HM, Strom, TM, Tam, CHT, Thameem, F, Tomlinson, B, Torres, JM, Tracy, RP, van Dam, RM, Vujkovic, M, Wang, S, Welch, RP, Witte, DR, Wong, T-Y, Atzmon, G, Barzilai, N, Blangero, J, Bonnycastle, LL, Bowden, DW, Chambers, JC, Chan, E, Cheng, C-Y, Cho, YS, Collins, FS, de Vries, PS, Duggirala, R, Glaser, B, Gonzalez, C, Gonzalez, ME, Groop, L, Kooner, JS, Kwak, SH, Laakso, M, Lehman, DM, Nilsson, P, Spector, TD, Tai, ES, Tuomi, T, Tuomilehto, J, Wilson, JG, Aguilar-Salinas, CA, Bottinger, E, Burke, B, Carey, DJ, Chan, JCN, Dupuis, J, Frossard, P, Heckbert, SR, Hwang, MY, Kim, YJ, Kirchner, HL, Lee, J-Y, Lee, J, Loos, RJF, Ma, RCW, Morris, AD, O'Donnell, CJ, Palmer, CNA, Pankow, J, Park, KS, Rasheed, A, Saleheen, D, Sim, X, Small, KS, Teo, YY, Haiman, C, Hanis, CL, Henderson, BE, Orozco, L, Tusié-Luna, T, Dewey, FE, Baras, A, Gieger, C, Meitinger, T, Strauch, K, Lange, L, Grarup, N, Hansen, T, Pedersen, O, Zeitler, P, Dabelea, D, Abecasis, G, Bell, GI, Cox, NJ, Seielstad, M, Sladek, R, Meigs, JB, Rich, SS, Rotter, JI, DiscovEHR Collaboration, CHARGE, LuCamp, ProDiGY, GoT2D, ESP, SIGMA-T2D, T2D-GENES, AMP-T2D-GENES, Altshuler, D, Burtt, NP, Scott, LJ, Morris, AP, Florez, JC, McCarthy, MI, and Boehnke, M

Abstract

Protein-coding genetic variants that strongly affect disease risk can yield relevant clues to disease pathogenesis. Here we report exome-sequencing analyses of 20,791 individuals with type 2 diabetes (T2D) and 24,440 non-diabetic control participants from 5 ancestries. We identify gene-level associations of rare variants (with minor allele frequencies of less than 0.5%) in 4 genes at exome-wide significance, including a series of more than 30 SLC30A8 alleles that conveys protection against T2D, and in 12 gene sets, including those corresponding to T2D drug targets (P = 6.1 × 10-3) and candidate genes from knockout mice (P = 5.2 × 10-3). Within our study, the strongest T2D gene-level signals for rare variants explain at most 25% of the heritability of the strongest common single-variant signals, and the gene-level effect sizes of the rare variants that we observed in established T2D drug targets will require 75,000-185,000 sequenced cases to achieve exome-wide significance. We propose a method to interpret these modest rare-variant associations and to incorporate these associations into future target or gene prioritization efforts.

Published
2019

38. expression in normal islet cells and in hyperinsulinism of infancy

Author

Kassem, S.A., Ariel, I., Thornton, P.S., Hussain, K., Smith, V., Lindley, K.J., Aynsley-Green, A., and Glaser, B.

Subjects
Genetic research -- Health aspects, Infants -- Health aspects, Metabolic diseases -- Risk factors -- Care and treatment, Health, Care and treatment, Risk factors, Health aspects
Abstract

Most cases of hyperinsulinism of infancy (HI) are caused by mutations in either the sulfonylurea receptor-1 (SUR1) or the inward rectifying [K.sup.+] channel Kir6.2, two subunits of the β-cell ATP-sensitive [K.sup.+] channel ([K.sub.ATP] channel). Histologically, HI can be divided into two major subtypes. The diffuse form is recessively inherited and involves all β-cells within the pancreas. Focal HI consists of adenomatous hyperplasia within a limited region of the pancreas, and it is caused by somatic loss of heterozygosity (LOH), including maternal Ch11p15-ter in a β-cell precursor carrying a germ-line mutation in the paternal allele of SUR1 or Kir6.2. Several imprinted genes are located within this chromosomal region, some of which, including [p57.sup.KIP2] and IGF-II, have been associated with the regulation of cell proliferation. Using double immunostaining, we examined [p57.sup.KIP2] expression in different islet cell types, in control pancreases from different developmental stages (n = 15), and in pancreases from patients with both diffuse (n = 4) and focal HI (n = 9). Using immunofluorescence and computerized image analysis, we quantified IGF-II expression in β-cells from patients with focal HI (n = 8). Within the pancreas, [p57.sup.KIP2] was specifically localized to the endocrine portion. β-Cells demonstrated the highest frequency of expression (34.9 ± 2.7%) compared with ~1-3% in other cell types. The fraction of β-cells expressing [p57.sup.KIP2] did not vary significantly during development. β-cells within the focal lesions did not express [p57.sup.KIP2], whereas IGF-II staining inside focal lesions was mildly increased compared with unaffected surrounding tissue. In conclusion, we demonstrate that [p57.sup.KIP2] is expressed and is paternally imprinted in human pancreatic β-cells. Loss of expression in focal HI is caused by LOH and is associated with increased proliferation and increased IGF-II expression. Manipulation of [p57.sup.KIP2] expression in β-cells may provide a mechanism by which proliferation can be modulated, and thus this gene is a potential therapeutic target for reversing the β-cell failure observed in diabetes., Hyperinsulinism of infancy (HI) is a rare genetic disorder with a prevalence in outbred populations of ~1/50,000 live births (1,2). An incidence as high as 1/2,500 has been reported in [...]

Published
2001

40. Fluxes and 13C isotopic composition of dissolved carbon and pathways of methanogenesis in a fen soil exposed to experimental drought

Author

Knorr, K.-H., Glaser, B., and Blodau, C.

Abstract

Peatlands contain a carbon stock of global concern and significantly contribute to the global methane burden. The impact of drought and rewetting on carbon cycling in peatland ecosystems is thus currently debated. We studied the impact of experimental drought and rewetting on intact monoliths from a temperate fen over a period of ~300 days, using a permanently wet treatment and two treatments undergoing drought for 50 days. In one of the mesocosms, vegetation had been removed. Net production of CH4 was calculated from mass balances in the peat and emission using static chamber measurements. Results were compared to 13C isotope budgets of CO2 and CH4 and energy yields of acetoclastic and hydrogenotrophic methanogenesis. Drought retarded methane production after rewetting for days to weeks and promoted methanotrophic activity. Based on isotope and flux budgets, aerobic soil respiration contributed 32–96% in the wet treatment and 86–99% in the other treatments. Drying and rewetting did not shift methanogenic pathways according to δ13C ratios of CH4 and CO2. Although δ13C ratios indicated a prevalence of hydrogenotrophic methanogenesis, free energies of this process were small and often positive on the horizon scale. This suggests that methane was produced very locally. Fresh plant-derived carbon input apparently supported respiration in the rhizosphere and sustained methanogenesis in the unsaturated zone, according to a 13C-CO2 labelling experiment. The study documents that drying and rewetting in a rich fen soil may have little effect on methanogenic pathways, but result in rapid shifts between methanogenesis and methanotrophy. Such shifts may be promoted by roots and soil heterogeneity, as hydrogenotrophic methanogenesis occurred locally even when conditions were not conducive for this process in the bulk peat.

Published
2018

43. Erratum: Sequence data and association statistics from 12,940 type 2 diabetes cases and controls.

Author

Flannick, J, Fuchsberger, C, Mahajan, A, Teslovich, TM, Agarwala, V, Gaulton, KJ, Caulkins, L, Koesterer, R, Ma, C, Moutsianas, L, McCarthy, DJ, Rivas, MA, Perry, JRB, Sim, X, Blackwell, TW, Robertson, NR, Rayner, NW, Cingolani, P, Locke, AE, Tajes, JF, Highland, HM, Dupuis, J, Chines, PS, Lindgren, CM, Hartl, C, Jackson, AU, Chen, H, Huyghe, JR, van de Bunt, M, Pearson, RD, Kumar, A, Mueller-Nurasyid, M, Grarup, N, Stringham, HM, Gamazon, ER, Lee, J, Chen, Y, Scott, RA, Below, JE, Chen, P, Huang, J, Go, MJ, Stitzel, ML, Pasko, D, Parker, SCJ, Varga, TV, Green, T, Beer, NL, Day-Williams, AG, Ferreira, T, Fingerlin, T, Horikoshi, M, Hu, C, Huh, I, Ikram, MK, Kim, B-J, Kim, Y, Kim, YJ, Kwon, M-S, Lee, S, Lin, K-H, Maxwell, TJ, Nagai, Y, Wang, X, Welch, RP, Yoon, J, Zhang, W, Barzilai, N, Voight, BF, Han, B-G, Jenkinson, CP, Kuulasmaa, T, Kuusisto, J, Manning, A, Ng, MCY, Palmer, ND, Balkau, B, Stancakova, A, Abboud, HE, Boeing, H, Giedraitis, V, Prabhakaran, D, Gottesman, O, Scott, J, Carey, J, Kwan, P, Grant, G, Smith, JD, Neale, BM, Purcell, S, Butterworth, AS, Howson, JMM, Lee, HM, Lu, Y, Kwak, S-H, Zhao, W, Danesh, J, Lam, VKL, Park, KS, Saleheen, D, So, WY, Tam, CHT, Afzal, U, Aguilar, D, Arya, R, Aung, T, Chan, E, Navarro, C, Cheng, C-Y, Palli, D, Correa, A, Curran, JE, Rybin, D, Farook, VS, Fowler, SP, Freedman, BI, Griswold, M, Hale, DE, Hicks, PJ, Khor, C-C, Kumar, S, Lehne, B, Thuillier, D, Lim, WY, Liu, J, Loh, M, Musani, SK, Puppala, S, Scott, WR, Yengo, L, Tan, S-T, Taylor, HA, Thameem, F, Wilson, G, Wong, TY, Njolstad, PR, Levy, JC, Mangino, M, Bonnycastle, LL, Schwarzmayr, T, Fadista, J, Surdulescu, GL, Herder, C, Groves, CJ, Wieland, T, Bork-Jensen, J, Brandslund, I, Christensen, C, Koistinen, HA, Doney, ASF, Kinnunen, L, Esko, T, Farmer, AJ, Hakaste, L, Hodgkiss, D, Kravic, J, Lyssenko, V, Hollensted, M, Jorgensen, ME, Jorgensen, T, Ladenvall, C, Justesen, JM, Karajamaki, A, Kriebel, J, Rathmann, W, Lannfelt, L, Lauritzen, T, Narisu, N, Linneberg, A, Melander, O, Milani, L, Neville, M, Orho-Melander, M, Qi, L, Qi, Q, Roden, M, Rolandsson, O, Swift, A, Rosengren, AH, Stirrups, K, Wood, AR, Mihailov, E, Blancher, C, Carneiro, MO, Maguire, J, Poplin, R, Shakir, K, Fennell, T, DePristo, M, de Angelis, MH, Deloukas, P, Gjesing, AP, Jun, G, Nilsson, PM, Murphy, J, Onofrio, R, Thorand, B, Hansen, T, Meisinger, C, Hu, FB, Isomaa, B, Karpe, F, Liang, L, Peters, A, Huth, C, O'Rahilly, SP, Palmer, CNA, Pedersen, O, Rauramaa, R, Tuomilehto, J, Salomaa, V, Watanabe, RM, Syvanen, A-C, Bergman, RN, Bharadwaj, D, Bottinger, EP, Cho, YS, Chandak, GR, Chan, JC, Chia, KS, Daly, MJ, Ebrahim, SB, Langenberg, C, Elliott, P, Jablonski, KA, Lehman, DM, Jia, W, Ma, RCW, Pollin, TI, Sandhu, M, Tandon, N, Froguel, P, Barroso, I, Teo, YY, Zeggini, E, Loos, RJF, Small, KS, Ried, JS, DeFronzo, RA, Grallert, H, Glaser, B, Metspalu, A, Wareham, NJ, Walker, M, Banks, E, Gieger, C, Ingelsson, E, Im, HK, Illig, T, Franks, PW, Buck, G, Trakalo, J, Buck, D, Prokopenko, I, Magi, R, Lind, L, Farjoun, Y, Owen, KR, Gloyn, AL, Strauch, K, Tuomi, T, Kooner, JS, Lee, J-Y, Park, T, Donnelly, P, Morris, AD, Hattersley, AT, Bowden, DW, Collins, FS, Atzmon, G, Chambers, JC, Spector, TD, Laakso, M, Strom, TM, Bell, GI, Blangero, J, Duggirala, R, Tai, E, McVean, G, Hanis, CL, Wilson, JG, Seielstad, M, Frayling, TM, Meigs, JB, Cox, NJ, Sladek, R, Lander, ES, Gabriel, S, Mohlke, KL, Meitinger, T, Groop, L, Abecasis, G, Scott, LJ, Morris, AP, Kang, HM, Altshuler, D, Burtt, NP, Florez, JC, Boehnke, M, McCarthy, MI, Flannick, J, Fuchsberger, C, Mahajan, A, Teslovich, TM, Agarwala, V, Gaulton, KJ, Caulkins, L, Koesterer, R, Ma, C, Moutsianas, L, McCarthy, DJ, Rivas, MA, Perry, JRB, Sim, X, Blackwell, TW, Robertson, NR, Rayner, NW, Cingolani, P, Locke, AE, Tajes, JF, Highland, HM, Dupuis, J, Chines, PS, Lindgren, CM, Hartl, C, Jackson, AU, Chen, H, Huyghe, JR, van de Bunt, M, Pearson, RD, Kumar, A, Mueller-Nurasyid, M, Grarup, N, Stringham, HM, Gamazon, ER, Lee, J, Chen, Y, Scott, RA, Below, JE, Chen, P, Huang, J, Go, MJ, Stitzel, ML, Pasko, D, Parker, SCJ, Varga, TV, Green, T, Beer, NL, Day-Williams, AG, Ferreira, T, Fingerlin, T, Horikoshi, M, Hu, C, Huh, I, Ikram, MK, Kim, B-J, Kim, Y, Kim, YJ, Kwon, M-S, Lee, S, Lin, K-H, Maxwell, TJ, Nagai, Y, Wang, X, Welch, RP, Yoon, J, Zhang, W, Barzilai, N, Voight, BF, Han, B-G, Jenkinson, CP, Kuulasmaa, T, Kuusisto, J, Manning, A, Ng, MCY, Palmer, ND, Balkau, B, Stancakova, A, Abboud, HE, Boeing, H, Giedraitis, V, Prabhakaran, D, Gottesman, O, Scott, J, Carey, J, Kwan, P, Grant, G, Smith, JD, Neale, BM, Purcell, S, Butterworth, AS, Howson, JMM, Lee, HM, Lu, Y, Kwak, S-H, Zhao, W, Danesh, J, Lam, VKL, Park, KS, Saleheen, D, So, WY, Tam, CHT, Afzal, U, Aguilar, D, Arya, R, Aung, T, Chan, E, Navarro, C, Cheng, C-Y, Palli, D, Correa, A, Curran, JE, Rybin, D, Farook, VS, Fowler, SP, Freedman, BI, Griswold, M, Hale, DE, Hicks, PJ, Khor, C-C, Kumar, S, Lehne, B, Thuillier, D, Lim, WY, Liu, J, Loh, M, Musani, SK, Puppala, S, Scott, WR, Yengo, L, Tan, S-T, Taylor, HA, Thameem, F, Wilson, G, Wong, TY, Njolstad, PR, Levy, JC, Mangino, M, Bonnycastle, LL, Schwarzmayr, T, Fadista, J, Surdulescu, GL, Herder, C, Groves, CJ, Wieland, T, Bork-Jensen, J, Brandslund, I, Christensen, C, Koistinen, HA, Doney, ASF, Kinnunen, L, Esko, T, Farmer, AJ, Hakaste, L, Hodgkiss, D, Kravic, J, Lyssenko, V, Hollensted, M, Jorgensen, ME, Jorgensen, T, Ladenvall, C, Justesen, JM, Karajamaki, A, Kriebel, J, Rathmann, W, Lannfelt, L, Lauritzen, T, Narisu, N, Linneberg, A, Melander, O, Milani, L, Neville, M, Orho-Melander, M, Qi, L, Qi, Q, Roden, M, Rolandsson, O, Swift, A, Rosengren, AH, Stirrups, K, Wood, AR, Mihailov, E, Blancher, C, Carneiro, MO, Maguire, J, Poplin, R, Shakir, K, Fennell, T, DePristo, M, de Angelis, MH, Deloukas, P, Gjesing, AP, Jun, G, Nilsson, PM, Murphy, J, Onofrio, R, Thorand, B, Hansen, T, Meisinger, C, Hu, FB, Isomaa, B, Karpe, F, Liang, L, Peters, A, Huth, C, O'Rahilly, SP, Palmer, CNA, Pedersen, O, Rauramaa, R, Tuomilehto, J, Salomaa, V, Watanabe, RM, Syvanen, A-C, Bergman, RN, Bharadwaj, D, Bottinger, EP, Cho, YS, Chandak, GR, Chan, JC, Chia, KS, Daly, MJ, Ebrahim, SB, Langenberg, C, Elliott, P, Jablonski, KA, Lehman, DM, Jia, W, Ma, RCW, Pollin, TI, Sandhu, M, Tandon, N, Froguel, P, Barroso, I, Teo, YY, Zeggini, E, Loos, RJF, Small, KS, Ried, JS, DeFronzo, RA, Grallert, H, Glaser, B, Metspalu, A, Wareham, NJ, Walker, M, Banks, E, Gieger, C, Ingelsson, E, Im, HK, Illig, T, Franks, PW, Buck, G, Trakalo, J, Buck, D, Prokopenko, I, Magi, R, Lind, L, Farjoun, Y, Owen, KR, Gloyn, AL, Strauch, K, Tuomi, T, Kooner, JS, Lee, J-Y, Park, T, Donnelly, P, Morris, AD, Hattersley, AT, Bowden, DW, Collins, FS, Atzmon, G, Chambers, JC, Spector, TD, Laakso, M, Strom, TM, Bell, GI, Blangero, J, Duggirala, R, Tai, E, McVean, G, Hanis, CL, Wilson, JG, Seielstad, M, Frayling, TM, Meigs, JB, Cox, NJ, Sladek, R, Lander, ES, Gabriel, S, Mohlke, KL, Meitinger, T, Groop, L, Abecasis, G, Scott, LJ, Morris, AP, Kang, HM, Altshuler, D, Burtt, NP, Florez, JC, Boehnke, M, and McCarthy, MI

Abstract

This corrects the article DOI: 10.1038/sdata.2017.179.

Published
2018

44. Insights into the genetic epidemiology of Crohn's and rare diseases in the Ashkenazi Jewish population.

Author

Williams, SM, Rivas, MA, Avila, BE, Koskela, J, Huang, H, Stevens, C, Pirinen, M, Haritunians, T, Neale, BM, Kurki, M, Ganna, A, Graham, D, Glaser, B, Peter, I, Atzmon, G, Barzilai, N, Levine, AP, Schiff, E, Pontikos, N, Weisburd, B, Lek, M, Karczewski, KJ, Bloom, J, Minikel, EV, Petersen, B-S, Beaugerie, L, Seksik, P, Cosnes, J, Schreiber, S, Bokemeyer, B, Bethge, J, International IBD Genetics Consortium, NIDDK IBD Genetics Consortium, T2D-GENES Consortium, Heap, G, Ahmad, T, Plagnol, V, Segal, AW, Targan, S, Turner, D, Saavalainen, P, Farkkila, M, Kontula, K, Palotie, A, Brant, SR, Duerr, RH, Silverberg, MS, Rioux, JD, Weersma, RK, Franke, A, Jostins, L, Anderson, CA, Barrett, JC, MacArthur, DG, Jalas, C, Sokol, H, Xavier, RJ, Pulver, A, Cho, JH, McGovern, DPB, Daly, MJ, Williams, SM, Rivas, MA, Avila, BE, Koskela, J, Huang, H, Stevens, C, Pirinen, M, Haritunians, T, Neale, BM, Kurki, M, Ganna, A, Graham, D, Glaser, B, Peter, I, Atzmon, G, Barzilai, N, Levine, AP, Schiff, E, Pontikos, N, Weisburd, B, Lek, M, Karczewski, KJ, Bloom, J, Minikel, EV, Petersen, B-S, Beaugerie, L, Seksik, P, Cosnes, J, Schreiber, S, Bokemeyer, B, Bethge, J, International IBD Genetics Consortium, NIDDK IBD Genetics Consortium, T2D-GENES Consortium, Heap, G, Ahmad, T, Plagnol, V, Segal, AW, Targan, S, Turner, D, Saavalainen, P, Farkkila, M, Kontula, K, Palotie, A, Brant, SR, Duerr, RH, Silverberg, MS, Rioux, JD, Weersma, RK, Franke, A, Jostins, L, Anderson, CA, Barrett, JC, MacArthur, DG, Jalas, C, Sokol, H, Xavier, RJ, Pulver, A, Cho, JH, McGovern, DPB, and Daly, MJ

Abstract

As part of a broader collaborative network of exome sequencing studies, we developed a jointly called data set of 5,685 Ashkenazi Jewish exomes. We make publicly available a resource of site and allele frequencies, which should serve as a reference for medical genetics in the Ashkenazim (hosted in part at https://ibd.broadinstitute.org, also available in gnomAD at http://gnomad.broadinstitute.org). We estimate that 34% of protein-coding alleles present in the Ashkenazi Jewish population at frequencies greater than 0.2% are significantly more frequent (mean 15-fold) than their maximum frequency observed in other reference populations. Arising via a well-described founder effect approximately 30 generations ago, this catalog of enriched alleles can contribute to differences in genetic risk and overall prevalence of diseases between populations. As validation we document 148 AJ enriched protein-altering alleles that overlap with "pathogenic" ClinVar alleles (table available at https://github.com/macarthur-lab/clinvar/blob/master/output/clinvar.tsv), including those that account for 10-100 fold differences in prevalence between AJ and non-AJ populations of some rare diseases, especially recessive conditions, including Gaucher disease (GBA, p.Asn409Ser, 8-fold enrichment); Canavan disease (ASPA, p.Glu285Ala, 12-fold enrichment); and Tay-Sachs disease (HEXA, c.1421+1G>C, 27-fold enrichment; p.Tyr427IlefsTer5, 12-fold enrichment). We next sought to use this catalog, of well-established relevance to Mendelian disease, to explore Crohn's disease, a common disease with an estimated two to four-fold excess prevalence in AJ. We specifically attempt to evaluate whether strong acting rare alleles, particularly protein-truncating or otherwise large effect-size alleles, enriched by the same founder-effect, contribute excess genetic risk to Crohn's disease in AJ, and find that ten rare genetic risk factors in NOD2 and LRRK2 are enriched in AJ (p < 0.005), including several novel con

Published
2018

46. Data Descriptor: Sequence data and association statistics from 12,940 type 2 diabetes cases and controls

Author

Flannick, J, Fuchsberger, C, Mahajan, A, Teslovich, TM, Agarwala, V, Gaulton, KJ, Caulkins, L, Koesterer, R, Ma, C, Moutsianas, L, McCarthy, DJ, Rivas, MA, Perry, JRB, Sim, X, Blackwell, TW, Robertson, NR, Rayner, NW, Cingolani, P, Locke, AE, Tajes, JF, Highland, HM, Dupuis, J, Chines, PS, Lindgren, CM, Hartl, C, Jackson, AU, Chen, H, Huyghe, JR, De Bunt, MV, Pearson, RD, Kumar, A, Muller-Nurasyid, M, Grarup, N, Stringham, HM, Gamazon, ER, Lee, J, Chen, Y, Scott, RA, Below, JE, Chen, P, Huang, J, Go, MJ, Stitzel, ML, Pasko, D, Parker, SCJ, Varga, TV, Green, T, Beer, NL, Day-Williams, AG, Ferreira, T, Fingerlin, T, Horikoshi, M, Hu, C, Huh, I, Ikram, MK, Kim, B-J, Kim, Y, Kim, YJ, Kwon, M-S, Lee, S, Lin, K-H, Maxwell, TJ, Nagai, Y, Wang, X, Welch, RP, Yoon, J, Zhang, W, Barzilai, N, Voight, BF, Han, B-G, Jenkinson, CP, Kuulasmaa, T, Kuusisto, J, Manning, A, Ng, MCY, Palmer, ND, Balkau, B, Stancakova, A, Abboud, HE, Boeing, H, Giedraitis, V, Prabhakaran, D, Gottesman, O, Scott, J, Carey, J, Kwan, P, Grant, G, Smith, JD, Neale, BM, Purcell, S, Butterworth, AS, Howson, JMM, Lee, HM, Lu, Y, Kwak, S-H, Zhao, W, Danesh, J, Lam, VKL, Park, KS, Saleheen, D, So, WY, Tam, CHT, Afzal, U, Aguilar, D, Arya, R, Aung, T, Chan, E, Navarro, C, Cheng, C-Y, Palli, D, Correa, A, Curran, JE, Rybin, D, Farook, VS, Fowler, SP, Freedman, BI, Griswold, M, Hale, DE, Hicks, PJ, Khor, C-C, Kumar, S, Lehne, B, Thuillier, D, Lim, WY, Liu, J, Loh, M, Musani, SK, Puppala, S, Scott, WR, Yengo, L, Tan, S-T, Taylor, HA, Thameem, F, Wilson, G, Wong, TY, Njolstad, PR, Levy, JC, Mangino, M, Bonnycastle, LL, Schwarzmayr, T, Fadista, J, Surdulescu, GL, Herder, C, Groves, CJ, Wieland, T, Bork-Jensen, J, Brandslund, I, Christensen, C, Koistinen, HA, Doney, ASF, Kinnunen, L, Esko, T, Farmer, AJ, Hakaste, L, Hodgkiss, D, Kravic, J, Lyssenko, V, Hollensted, M, Jorgensen, ME, Jorgensen, T, Ladenvall, C, Justesen, JM, Karajamaki, A, Kriebel, J, Rathmann, W, Lannfelt, L, Lauritzen, T, Narisu, N, Linneberg, A, Melander, O, Milani, L, Neville, M, Orho-Melander, M, Qi, L, Qi, Q, Roden, M, Rolandsson, O, Swift, A, Rosengren, AH, Stirrups, K, Wood, AR, Mihailov, E, Blancher, C, Carneiro, MO, Maguire, J, Poplin, R, Shakir, K, Fennell, T, DePristo, M, De Angelis, MH, Deloukas, P, Gjesing, AP, Jun, G, Nilsson, PM, Murphy, J, Onofrio, R, Thorand, B, Hansen, T, Meisinger, C, Hu, FB, Isomaa, B, Karpe, F, Liang, L, Peters, A, Huth, C, O'Rahilly, SP, Palmer, CNA, Pedersen, O, Rauramaa, R, Tuomilehto, J, Salomaa, V, Watanabe, RM, Syvanen, A-C, Bergman, RN, Bharadwaj, D, Bottinger, EP, Cho, YS, Chandak, GR, Chan, JC, Chia, KS, Daly, MJ, Ebrahim, SB, Langenberg, C, Elliott, P, Jablonski, KA, Lehman, DM, Jia, W, Ma, RC, Pollin, TI, Sandhu, M, Tandon, N, Froguel, P, Barroso, I, Teo, YY, Zeggini, E, Loos, RJF, Small, KS, Ried, JS, DeFronzo, RA, Grallert, H, Glaser, B, Metspalu, A, Wareham, NJ, Walker, M, Banks, E, Gieger, C, Ingelsson, E, Im, HK, Illig, T, Franks, PW, Buck, G, Trakalo, J, Buck, D, Prokopenko, I, Magi, R, Lind, L, Farjoun, Y, Owen, KR, Gloyn, AL, Strauch, K, Tuomi, T, Kooner, JS, Lee, J-Y, Park, T, Donnelly, P, Morris, AD, Hattersley, AT, Bowden, DW, Collins, FS, Atzmon, G, Chambers, JC, Spector, TD, Laakso, M, Strom, TM, Bell, GI, Blangero, J, Duggirala, R, Tai, E, McVean, G, Hanis, CL, Wilson, JG, Seielstad, M, Frayling, TM, Meigs, JB, Cox, NJ, Sladek, R, Lander, ES, Gabriel, S, Mohlke, KL, Meitinger, T, Groop, L, Abecasis, G, Scott, LJ, Morris, AP, Kang, HM, Altshuler, D, Burtt, NP, Florez, JC, Boehnke, M, McCarthy, MI, Flannick, J, Fuchsberger, C, Mahajan, A, Teslovich, TM, Agarwala, V, Gaulton, KJ, Caulkins, L, Koesterer, R, Ma, C, Moutsianas, L, McCarthy, DJ, Rivas, MA, Perry, JRB, Sim, X, Blackwell, TW, Robertson, NR, Rayner, NW, Cingolani, P, Locke, AE, Tajes, JF, Highland, HM, Dupuis, J, Chines, PS, Lindgren, CM, Hartl, C, Jackson, AU, Chen, H, Huyghe, JR, De Bunt, MV, Pearson, RD, Kumar, A, Muller-Nurasyid, M, Grarup, N, Stringham, HM, Gamazon, ER, Lee, J, Chen, Y, Scott, RA, Below, JE, Chen, P, Huang, J, Go, MJ, Stitzel, ML, Pasko, D, Parker, SCJ, Varga, TV, Green, T, Beer, NL, Day-Williams, AG, Ferreira, T, Fingerlin, T, Horikoshi, M, Hu, C, Huh, I, Ikram, MK, Kim, B-J, Kim, Y, Kim, YJ, Kwon, M-S, Lee, S, Lin, K-H, Maxwell, TJ, Nagai, Y, Wang, X, Welch, RP, Yoon, J, Zhang, W, Barzilai, N, Voight, BF, Han, B-G, Jenkinson, CP, Kuulasmaa, T, Kuusisto, J, Manning, A, Ng, MCY, Palmer, ND, Balkau, B, Stancakova, A, Abboud, HE, Boeing, H, Giedraitis, V, Prabhakaran, D, Gottesman, O, Scott, J, Carey, J, Kwan, P, Grant, G, Smith, JD, Neale, BM, Purcell, S, Butterworth, AS, Howson, JMM, Lee, HM, Lu, Y, Kwak, S-H, Zhao, W, Danesh, J, Lam, VKL, Park, KS, Saleheen, D, So, WY, Tam, CHT, Afzal, U, Aguilar, D, Arya, R, Aung, T, Chan, E, Navarro, C, Cheng, C-Y, Palli, D, Correa, A, Curran, JE, Rybin, D, Farook, VS, Fowler, SP, Freedman, BI, Griswold, M, Hale, DE, Hicks, PJ, Khor, C-C, Kumar, S, Lehne, B, Thuillier, D, Lim, WY, Liu, J, Loh, M, Musani, SK, Puppala, S, Scott, WR, Yengo, L, Tan, S-T, Taylor, HA, Thameem, F, Wilson, G, Wong, TY, Njolstad, PR, Levy, JC, Mangino, M, Bonnycastle, LL, Schwarzmayr, T, Fadista, J, Surdulescu, GL, Herder, C, Groves, CJ, Wieland, T, Bork-Jensen, J, Brandslund, I, Christensen, C, Koistinen, HA, Doney, ASF, Kinnunen, L, Esko, T, Farmer, AJ, Hakaste, L, Hodgkiss, D, Kravic, J, Lyssenko, V, Hollensted, M, Jorgensen, ME, Jorgensen, T, Ladenvall, C, Justesen, JM, Karajamaki, A, Kriebel, J, Rathmann, W, Lannfelt, L, Lauritzen, T, Narisu, N, Linneberg, A, Melander, O, Milani, L, Neville, M, Orho-Melander, M, Qi, L, Qi, Q, Roden, M, Rolandsson, O, Swift, A, Rosengren, AH, Stirrups, K, Wood, AR, Mihailov, E, Blancher, C, Carneiro, MO, Maguire, J, Poplin, R, Shakir, K, Fennell, T, DePristo, M, De Angelis, MH, Deloukas, P, Gjesing, AP, Jun, G, Nilsson, PM, Murphy, J, Onofrio, R, Thorand, B, Hansen, T, Meisinger, C, Hu, FB, Isomaa, B, Karpe, F, Liang, L, Peters, A, Huth, C, O'Rahilly, SP, Palmer, CNA, Pedersen, O, Rauramaa, R, Tuomilehto, J, Salomaa, V, Watanabe, RM, Syvanen, A-C, Bergman, RN, Bharadwaj, D, Bottinger, EP, Cho, YS, Chandak, GR, Chan, JC, Chia, KS, Daly, MJ, Ebrahim, SB, Langenberg, C, Elliott, P, Jablonski, KA, Lehman, DM, Jia, W, Ma, RC, Pollin, TI, Sandhu, M, Tandon, N, Froguel, P, Barroso, I, Teo, YY, Zeggini, E, Loos, RJF, Small, KS, Ried, JS, DeFronzo, RA, Grallert, H, Glaser, B, Metspalu, A, Wareham, NJ, Walker, M, Banks, E, Gieger, C, Ingelsson, E, Im, HK, Illig, T, Franks, PW, Buck, G, Trakalo, J, Buck, D, Prokopenko, I, Magi, R, Lind, L, Farjoun, Y, Owen, KR, Gloyn, AL, Strauch, K, Tuomi, T, Kooner, JS, Lee, J-Y, Park, T, Donnelly, P, Morris, AD, Hattersley, AT, Bowden, DW, Collins, FS, Atzmon, G, Chambers, JC, Spector, TD, Laakso, M, Strom, TM, Bell, GI, Blangero, J, Duggirala, R, Tai, E, McVean, G, Hanis, CL, Wilson, JG, Seielstad, M, Frayling, TM, Meigs, JB, Cox, NJ, Sladek, R, Lander, ES, Gabriel, S, Mohlke, KL, Meitinger, T, Groop, L, Abecasis, G, Scott, LJ, Morris, AP, Kang, HM, Altshuler, D, Burtt, NP, Florez, JC, Boehnke, M, and McCarthy, MI

Abstract

To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (>80% of low-frequency coding variants in ~82 K Europeans via the exome chip, and ~90% of low-frequency non-coding variants in ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.

Published
2017

47. Source monitoring for actions in adolescents with 22q11.2 deletion syndrome (22q11DS)

Author

Debbané, M., Van der Linden, M., Glaser, B., Eliez, S., Debbané, M., Van der Linden, M., Glaser, B., and Eliez, S.

Abstract

Background Source monitoring consists in identifying the origin of mental events. Recent research suggests that confusions over internally generated mental events may represent a cognitive marker for increased proneness to psychotic symptoms and disorders. We have examined source monitoring for actions in adolescents with the 22q11.2 deletion syndrome (22q11DS), a neurogenetic disease associated with high rates of schizophrenia during adulthood, and expected to observe source monitoring deficits in comparison to IQ-matched and typically developing controls. Method Eighteen adolescents with 22q11DS, 17 adolescents matched for age and IQ, and also 17 adolescents matched for age participated in this study. Our adapted action monitoring paradigm asked subjects to visualize a series of actions in three different conditions: (1) visualize themselves performing the action; (2) visualize the experimenter performing the action; or (3) simply repeat the action statements without visualization of the action performer. Results The adolescents with 22q11DS performed adequately in terms of recognition (hits), but in comparison to both control groups, they committed more source confusions on correctly recognized items. Further examination revealed that the adolescents were more likely to demonstrate confusions between exterior sources in which the self was not involved. Conclusions Source monitoring deficits can be observed in adolescents with 22q11DS, a syndrome putting them at high risk for developing schizophrenia. These deficits are discussed in terms of early cognitive processes associated with genetic risk for schizophrenia

Published
2017

48. Population-specific risk of type 2 diabetes conferred by HNF4A P2 promoter variants: a lesson for replication studies

Author

Barroso, I, Luan, J, Wheeler, E, Whittaker, P, Wasson, J, Zeggini, E, Weedon, MN, Hunt, S, Venkatesh, R, Frayling, TM, Delgado, M, Neuman, RJ, Zhao, J, Sherva, R, Glaser, B, Walker, M, Hitman, G, McCarthy, MI, Hattersley, AT, Permutt, MA, Wareham, NJ, and Deloukas, P

Abstract

OBJECTIVE: Single nucleotide polymorphisms (SNPs) in the P2 promoter region of HNF4A were originally shown to be associated with predisposition for type 2 diabetes in Finnish, Ashkenazi, and, more recently, Scandinavian populations, but they generated conflicting results in additional populations. We aimed to investigate whether data from a large-scale mapping approach would replicate this association in novel Ashkenazi samples and in U.K. populations and whether these data would allow us to refine the association signal. RESEARCH DESIGN AND METHODS: Using a dense linkage disequilibrium map of 20q, we selected SNPs from a 10-Mb interval centered on HNF4A. In a staged approach, we first typed 4,608 SNPs in case-control populations from four U.K. populations and an Ashkenazi population (n = 2,516). In phase 2, a subset of 763 SNPs was genotyped in 2,513 additional samples from the same populations. RESULTS: Combined analysis of both phases demonstrated association between HNF4A P2 SNPs (rs1884613 and rs2144908) and type 2 diabetes in the Ashkenazim (n = 991; P < 1.6 x 10(-6)). Importantly, these associations are significant in a subset of Ashkenazi samples (n = 531) not previously tested for association with P2 SNPs (odds ratio [OR] approximately 1.7; P < 0.002), thus providing replication within the Ashkenazim. In the U.K. populations, this association was not significant (n = 4,022; P > 0.5), and the estimate for the OR was much smaller (OR 1.04; [95%CI 0.91-1.19]). CONCLUSIONS: These data indicate that the risk conferred by HNF4A P2 is significantly different between U.K. and Ashkenazi populations (P < 0.00007), suggesting that the underlying causal variant remains unidentified. Interactions with other genetic or environmental factors may also contribute to this difference in risk between populations.

Published
2016

49. Identification of a G-Protein Subunit-α11 Gain-of-Function Mutation, Val340Met, in a Family with Autosomal Dominant Hypocalcemia Type 2 (ADH2)

Author

Piret, SE, Gorvin, CM, Pagnamenta, AT, Howles, SA, Cranston, T, Rust, N, Nesbit, MA, Glaser, B, Taylor, JC, Buchs, AE, Hannan, F, and Thakker, RV

Abstract

Autosomal dominant hypocalcemia (ADH) is characterized by hypocalcemia, inappropriately low serum parathyroid hormone concentrations and hypercalciuria. ADH is genetically heterogeneous with ADH type 1 (ADH1), the predominant form, being caused by germline gain-of-function mutations of the G-protein coupled calcium-sensing receptor (CaSR), and ADH2 caused by germline gain-of-function mutations of G-protein subunit α-11 (Gα11 ). To date Gα11 mutations causing ADH2 have been reported in only five probands. We investigated a multi-generational non-consanguineous family, from Iran, with ADH and keratoconus which are not known to be associated, for causative mutations by whole-exome sequencing in two individuals with hypoparathyroidism, of whom one also had keratoconus, followed by cosegregation analysis of variants. This identified a novel heterozygous germline Val340Met Gα11 mutation in both individuals, and this was also present in the other 2 relatives with hypocalcemia that were tested. Three-dimensional modeling revealed the Val340Met mutation to likely alter the conformation of the C-terminal α5 helix, which may affect G-protein coupled receptor binding and G-protein activation. In vitro functional expression of wild-type (Val340) and mutant (Met340) Gα11 proteins in HEK293 cells stably expressing the CaSR, demonstrated that the intracellular calcium responses following stimulation with extracellular calcium, of the mutant Met340 Gα11 led to a leftward shift of the concentration-response curve with a significantly (p

Published
2016

50. Fluxes and 13C isotopic composition of dissolved carbon and pathways of methanogenesis in a fen soil exposed to experimental drought

Author

Knorr, K.-H., Glaser, B., Blodau, C., and EGU, Publication

Subjects
lcsh:Geology, lcsh:QH501-531, [PHYS.ASTR.CO] Physics [physics]/Astrophysics [astro-ph]/Cosmology and Extra-Galactic Astrophysics [astro-ph.CO], [SDU.OCEAN] Sciences of the Universe [physics]/Ocean, Atmosphere, lcsh:QH540-549.5, lcsh:QE1-996.5, [SDU.STU] Sciences of the Universe [physics]/Earth Sciences, lcsh:Life, lcsh:Ecology, [SDU.ASTR] Sciences of the Universe [physics]/Astrophysics [astro-ph], [SDU.ENVI] Sciences of the Universe [physics]/Continental interfaces, environment
Abstract

Peatlands contain a carbon stock of global concern and significantly contribute to the global methane burden. The impact of drought and rewetting on carbon cycling in peatland ecosystems is thus currently debated. We studied the impact of experimental drought and rewetting on intact monoliths from a temperate fen over a period of ~300 days, using a permanently wet treatment and two treatments undergoing drought for 50 days. In one of the mesocosms, vegetation had been removed. Net production of CH4 was calculated from mass balances in the peat and emission using static chamber measurements. Results were compared to 13C isotope budgets of CO2 and CH4 and energy yields of acetoclastic and hydrogenotrophic methanogenesis. Drought retarded methane production after rewetting for days to weeks and promoted methanotrophic activity. Based on isotope and flux budgets, aerobic soil respiration contributed 32–96% in the wet treatment and 86–99% in the other treatments. Drying and rewetting did not shift methanogenic pathways according to δ13C ratios of CH4 and CO2. Although δ13C ratios indicated a prevalence of hydrogenotrophic methanogenesis, free energies of this process were small and often positive on the horizon scale. This suggests that methane was produced very locally. Fresh plant-derived carbon input apparently supported respiration in the rhizosphere and sustained methanogenesis in the unsaturated zone, according to a 13C-CO2 labelling experiment. The study documents that drying and rewetting in a rich fen soil may have little effect on methanogenic pathways, but result in rapid shifts between methanogenesis and methanotrophy. Such shifts may be promoted by roots and soil heterogeneity, as hydrogenotrophic methanogenesis occurred locally even when conditions were not conducive for this process in the bulk peat.

Published
2008

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