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1. Vector-borne Trypanosoma brucei parasites develop in artificial human skin and persist as skin tissue forms

Author

Christian Reuter, Laura Hauf, Fabian Imdahl, Rituparno Sen, Ehsan Vafadarnejad, Philipp Fey, Tamara Finger, Nicola G. Jones, Heike Walles, Lars Barquist, Antoine-Emmanuel Saliba, Florian Groeber-Becker, and Markus Engstler

Subjects
Science
Abstract

Abstract Transmission of Trypanosoma brucei by tsetse flies involves the deposition of the cell cycle-arrested metacyclic life cycle stage into mammalian skin at the site of the fly’s bite. We introduce an advanced human skin equivalent and use tsetse flies to naturally infect the skin with trypanosomes. We detail the chronological order of the parasites’ development in the skin by single-cell RNA sequencing and find a rapid activation of metacyclic trypanosomes and differentiation to proliferative parasites. Here we show that after the establishment of a proliferative population, the parasites enter a reversible quiescent state characterized by slow replication and a strongly reduced metabolism. We term these quiescent trypanosomes skin tissue forms, a parasite population that may play an important role in maintaining the infection over long time periods and in asymptomatic infected individuals.

Published
2023
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2. Structural basis for assembly of vertical single β-barrel viruses

Author

Isaac Santos-Pérez, Diego Charro, David Gil-Carton, Mikel Azkargorta, Felix Elortza, Dennis H. Bamford, Hanna M. Oksanen, and Nicola G. A. Abrescia

Subjects
Science
Abstract

Here, the authors present the cryo-EM structures of two archaeal, halophilic, internal membrane-containing icosahedral viruses at 3.7 and 3.8 Å resolution, providing insights into the assembly process of these and related PRD1-adeno lineage viruses.

Published
2019
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3. Rules of engagement between αvβ6 integrin and foot-and-mouth disease virus

Author

Abhay Kotecha, Quan Wang, Xianchi Dong, Serban L. Ilca, Marina Ondiviela, Rao Zihe, Julian Seago, Bryan Charleston, Elizabeth E. Fry, Nicola G. A. Abrescia, Timothy A. Springer, Juha T. Huiskonen, and David I. Stuart

Subjects
Science
Abstract

Foot-and-mouth disease virus binds αvβ6 integrin, via a conserved RGD motif in the flexible, exposed GH loop of capsid protein VP1, for cell entry. Here Kotechaet al.visualize this interaction with the VP1 GH loop extending away from the viral surface, engaging αvβ6 in an open, active state.

Published
2017
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4. Identification and characterization of a heterotrimeric archaeal DNA polymerase holoenzyme

Author

Jiangyu Yan, Thomas R. Beattie, Adriana L. Rojas, Kelly Schermerhorn, Tamzin Gristwood, Jonathan C. Trinidad, Sonja V. Albers, Pietro Roversi, Andrew F. Gardner, Nicola G. A. Abrescia, and Stephen D. Bell

Subjects
Science
Abstract

The current model for B-family DNA polymerases in archaea is one of single-subunit enzymes in contrast to the multi-subunit complexes in eukaryotes. Here the authors show that PolB1 fromSulfolobus solfataricusexists as a heterotrimeric complex in cell extracts.

Published
2017
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5. N-glycosylation enables high lateral mobility of GPI-anchored proteins at a molecular crowding threshold

Author

Andreas J. W. Hartel, Marius Glogger, Nicola G. Jones, Wasim Abuillan, Christopher Batram, Anne Hermann, Susanne F. Fenz, Motomu Tanaka, and Markus Engstler

Subjects
Science
Abstract

How molecular crowding affects membrane protein diffusion and function is not known. Here the authors measure diffusion of variant surface glycoprotein on trypanosomes and discover a molecular crowding threshold that limits diffusion, and find that N-linked glycans help to prevent retarding intermolecular interactions.

Published
2016
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8. Octupole moment driven free charge generation in partially chlorinated subphthalocyanine for planar heterojunction organic photodetectors

Author

Aniket Rana, Song Yi Park, Chiara Labanti, Feifei Fang, Sungyoung Yun, Yifan Dong, Emily J. Yang, Davide Nodari, Nicola Gasparini, Jeong–Il Park, Jisoo Shin, Daiki Minami, Kyung-Bae Park, Ji-Seon Kim, and James R. Durrant

Subjects
Science
Abstract

Abstract In this study, high-performance organic photodetectors are presented which utilize a pristine chlorinated subphthalocyanine photoactive layer. Optical and optoelectronic analyses indicate that the device photocurrent is primarily generated through direct charge generation within the chlorinated subphthalocyanine layer, rather than exciton separation at layer interfaces. Molecular modelling suggests that this direct charge generation is facilitated by chlorinated subphthalocyanine high octupole moment (−80 DÅ2), which generates a 200 meV shift in molecular energetics. Increasing the thickness of chlorinated subphthalocyanine leads to faster response time, correlated with a decrease in trap density. Notably, photodetectors with a 50 nm thick chlorinated subphthalocyanine photoactive layer exhibit detectivities approaching 1013 Jones, with a dark current below 10−7 A cm−2 up to −5 V. Based on these findings, we conclude that high octupole moment molecular semiconductors are promising materials for high-performance organic photodetectors employing single-component photoactive layer.

Published
2024
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9. Stabilizing persistent currents in an atomtronic Josephson junction necklace

Author

Luca Pezzè, Klejdja Xhani, Cyprien Daix, Nicola Grani, Beatrice Donelli, Francesco Scazza, Diego Hernandez-Rajkov, Woo Jin Kwon, Giulia Del Pace, and Giacomo Roati

Subjects
Science
Abstract

Abstract Arrays of Josephson junctions are at the forefront of research on quantum circuitry for quantum computing, simulation, and metrology. They provide a testing bed for exploring a variety of fundamental physical effects where macroscopic phase coherence, nonlinearities, and dissipative mechanisms compete. Here we realize finite-circulation states in an atomtronic Josephson junction necklace, consisting of a tunable array of tunneling links in a ring-shaped superfluid. We study the stability diagram of the atomic flow by tuning both the circulation and the number of junctions. We predict theoretically and demonstrate experimentally that the atomic circuit withstands higher circulations (corresponding to higher critical currents) by increasing the number of Josephson links. The increased stability contrasts with the trend of the superfluid fraction – quantified by Leggett’s criterion – which instead decreases with the number of junctions and the corresponding density depletion. Our results demonstrate atomic superfluids in mesoscopic structured ring potentials as excellent candidates for atomtronics applications, with prospects towards the observation of non-trivial macroscopic superpositions of current states.

Published
2024
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10. Disentangling oncogenic amplicons in esophageal adenocarcinoma

Author

Alvin Wei Tian Ng, Dylan Peter McClurg, Ben Wesley, Shahriar A. Zamani, Emily Black, Ahmad Miremadi, Olivier Giger, Rogier ten Hoopen, Ginny Devonshire, Aisling M. Redmond, Nicola Grehan, Sriganesh Jammula, Adrienn Blasko, Xiaodun Li, Samuel Aparicio, Simon Tavaré, Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium, Karol Nowicki-Osuch, and Rebecca C. Fitzgerald

Subjects
Science
Abstract

Abstract Esophageal adenocarcinoma is a prominent example of cancer characterized by frequent amplifications in oncogenes. However, the mechanisms leading to amplicons that involve breakage-fusion-bridge cycles and extrachromosomal DNA are poorly understood. Here, we use 710 esophageal adenocarcinoma cases with matched samples and patient-derived organoids to disentangle complex amplicons and their associated mechanisms. Short-read sequencing identifies ERBB2, MYC, MDM2, and HMGA2 as the most frequent oncogenes amplified in extrachromosomal DNAs. We resolve complex extrachromosomal DNA and breakage-fusion-bridge cycles amplicons by integrating of de-novo assemblies and DNA methylation in nine long-read sequenced cases. Complex amplicons shared between precancerous biopsy and late-stage tumor, an enrichment of putative enhancer elements and mobile element insertions are potential drivers of complex amplicons’ origin. We find that patient-derived organoids recapitulate extrachromosomal DNA observed in the primary tumors and single-cell DNA sequencing capture extrachromosomal DNA-driven clonal dynamics across passages. Prospectively, long-read and single-cell DNA sequencing technologies can lead to better prediction of clonal evolution in esophageal adenocarcinoma.

Published
2024
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11. Targeting DNA2 overcomes metabolic reprogramming in multiple myeloma

Author

Natthakan Thongon, Feiyang Ma, Natalia Baran, Pamela Lockyer, Jintan Liu, Christopher Jackson, Ashley Rose, Ken Furudate, Bethany Wildeman, Matteo Marchesini, Valentina Marchica, Paola Storti, Giannalisa Todaro, Irene Ganan-Gomez, Vera Adema, Juan Jose Rodriguez-Sevilla, Yun Qing, Min Jin Ha, Rodrigo Fonseca, Caleb Stein, Caleb Class, Lin Tan, Sergio Attanasio, Guillermo Garcia-Manero, Nicola Giuliani, David Berrios Nolasco, Andrea Santoni, Claudio Cerchione, Carlos Bueso-Ramos, Marina Konopleva, Philip Lorenzi, Koichi Takahashi, Elisabet Manasanch, Gabriella Sammarelli, Rashmi Kanagal-Shamanna, Andrea Viale, Marta Chesi, and Simona Colla

Subjects
Science
Abstract

Abstract DNA damage resistance is a major barrier to effective DNA-damaging therapy in multiple myeloma (MM). To discover mechanisms through which MM cells overcome DNA damage, we investigate how MM cells become resistant to antisense oligonucleotide (ASO) therapy targeting Interleukin enhancer binding factor 2 (ILF2), a DNA damage regulator that is overexpressed in 70% of MM patients whose disease has progressed after standard therapies have failed. Here, we show that MM cells undergo adaptive metabolic rewiring to restore energy balance and promote survival in response to DNA damage activation. Using a CRISPR/Cas9 screening strategy, we identify the mitochondrial DNA repair protein DNA2, whose loss of function suppresses MM cells’ ability to overcome ILF2 ASO−induced DNA damage, as being essential to counteracting oxidative DNA damage. Our study reveals a mechanism of vulnerability of MM cells that have an increased demand for mitochondrial metabolism upon DNA damage activation.

Published
2024
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12. Structural heterogeneity of the ion and lipid channel TMEM16F

Author

Zhongjie Ye, Nicola Galvanetto, Leonardo Puppulin, Simone Pifferi, Holger Flechsig, Melanie Arndt, Cesar Adolfo Sánchez Triviño, Michael Di Palma, Shifeng Guo, Horst Vogel, Anna Menini, Clemens M. Franz, Vincent Torre, and Arin Marchesi

Subjects
Science
Abstract

Abstract Transmembrane protein 16 F (TMEM16F) is a Ca2+-activated homodimer which functions as an ion channel and a phospholipid scramblase. Despite the availability of several TMEM16F cryogenic electron microscopy (cryo-EM) structures, the mechanism of activation and substrate translocation remains controversial, possibly due to restrictions in the accessible protein conformational space. In this study, we use atomic force microscopy under physiological conditions to reveal a range of structurally and mechanically diverse TMEM16F assemblies, characterized by variable inter-subunit dimerization interfaces and protomer orientations, which have escaped prior cryo-EM studies. Furthermore, we find that Ca2+-induced activation is associated to stepwise changes in the pore region that affect the mechanical properties of transmembrane helices TM3, TM4 and TM6. Our direct observation of membrane remodelling in response to Ca2+ binding along with additional electrophysiological analysis, relate this structural multiplicity of TMEM16F to lipid and ion permeation processes. These results thus demonstrate how conformational heterogeneity of TMEM16F directly contributes to its diverse physiological functions.

Published
2024
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13. Operando dynamics of trapped carriers in perovskite solar cells observed via infrared optical activation spectroscopy

Author

Jiaxin Pan, Ziming Chen, Tiankai Zhang, Beier Hu, Haoqing Ning, Zhu Meng, Ziyu Su, Davide Nodari, Weidong Xu, Ganghong Min, Mengyun Chen, Xianjie Liu, Nicola Gasparini, Saif A. Haque, Piers R. F. Barnes, Feng Gao, and Artem A. Bakulin

Subjects
Science
Abstract

Abstract Conventional spectroscopies are not sufficiently selective to comprehensively understand the behaviour of trapped carriers in perovskite solar cells, particularly under their working conditions. Here we use infrared optical activation spectroscopy (i.e., pump-push-photocurrent), to observe the properties and real-time dynamics of trapped carriers within operando perovskite solar cells. We compare behaviour differences of trapped holes in pristine and surface-passivated FA0.99Cs0.01PbI3 devices using a combination of quasi-steady-state and nanosecond time-resolved pump-push-photocurrent, as well as kinetic and drift-diffusion models. We find a two-step trap-filling process: the rapid filling (~10 ns) of low-density traps in the bulk of perovskite, followed by the slower filling (~100 ns) of high-density traps at the perovskite/hole transport material interface. Surface passivation by n-octylammonium iodide dramatically reduces the number of trap states (~50 times), improving the device performance substantially. Moreover, the activation energy (~280 meV) of the dominant hole traps remains similar with and without surface passivation.

Published
2023
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14. Mutational signature dynamics shaping the evolution of oesophageal adenocarcinoma

Author

Sujath Abbas, Oriol Pich, Ginny Devonshire, Shahriar A. Zamani, Annalise Katz-Summercorn, Sarah Killcoyne, Calvin Cheah, Barbara Nutzinger, Nicola Grehan, Nuria Lopez-Bigas, OCCAMS Consortium, Rebecca C. Fitzgerald, and Maria Secrier

Subjects
Science
Abstract

Abstract A variety of mutational processes drive cancer development, but their dynamics across the entire disease spectrum from pre-cancerous to advanced neoplasia are poorly understood. We explore the mutagenic processes shaping oesophageal adenocarcinoma tumorigenesis in 997 instances comprising distinct stages of this malignancy, from Barrett Oesophagus to primary tumours and advanced metastatic disease. The mutational landscape is dominated by the C[T > C/G]T substitution enriched signatures SBS17a/b, which are linked with TP53 mutations, increased proliferation, genomic instability and disease progression. The APOBEC mutagenesis signature is a weak but persistent signal amplified in primary tumours. We also identify prevalent alterations in DNA damage repair pathways, with homologous recombination, base and nucleotide excision repair and translesion synthesis mutated in up to 50% of the cohort, and surprisingly uncoupled from transcriptional activity. Among these, the presence of base excision repair deficiencies show remarkably poor prognosis in the cohort. In this work, we provide insights on the mutational aetiology and changes enabling the transition from pre-neoplastic to advanced oesophageal adenocarcinoma.

Published
2023
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15. Author Correction: Disentangling oncogenic amplicons in esophageal adenocarcinoma

Author

Alvin Wei Tian Ng, Dylan Peter McClurg, Ben Wesley, Shahriar A. Zamani, Emily Black, Ahmad Miremadi, Olivier Giger, Rogier ten Hoopen, Ginny Devonshire, Aisling M. Redmond, Nicola Grehan, Sriganesh Jammula, Adrienn Blasko, Xiaodun Li, Samuel Aparicio, Simon Tavaré, Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium, Karol Nowicki-Osuch, and Rebecca C. Fitzgerald

Subjects
Science
Published
2024
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16. Rules of engagement between αvβ6 integrin and foot-and-mouth disease virus

Author

Kotecha, Abhay, Wang, Quan, Dong, Xianchi, Ilca, Serban L., Ondiviela, Marina, Zihe, Rao, Seago, Julian, Charleston, Bryan, Fry, Elizabeth E., Abrescia, Nicola G. A., Springer, Timothy A., Huiskonen, Juha T., and Stuart, David I.

Subjects
Integrins, Binding Sites, Science, viruses, Amino Acid Motifs, Cryoelectron Microscopy, CHO Cells, biochemical phenomena, metabolism, and nutrition, Virus Replication, Article, Capsid, Cricetulus, Antigens, Neoplasm, Foot-and-Mouth Disease Virus, Polysaccharides, Cricetinae, Animals, Receptors, Virus, Capsid Proteins, Hydrophobic and Hydrophilic Interactions, Oligopeptides, Protein Binding
Abstract

Foot-and-mouth disease virus (FMDV) mediates cell entry by attachment to an integrin receptor, generally αvβ6, via a conserved arginine–glycine–aspartic acid (RGD) motif in the exposed, antigenic, GH loop of capsid protein VP1. Infection can also occur in tissue culture adapted virus in the absence of integrin via acquired basic mutations interacting with heparin sulphate (HS); this virus is attenuated in natural infections. HS interaction has been visualized at a conserved site in two serotypes suggesting a propensity for sulfated-sugar binding. Here we determined the interaction between αvβ6 and two tissue culture adapted FMDV strains by cryo-electron microscopy. In the preferred mode of engagement, the fully open form of the integrin, hitherto unseen at high resolution, attaches to an extended GH loop via interactions with the RGD motif plus downstream hydrophobic residues. In addition, an N-linked sugar of the integrin attaches to the previously identified HS binding site, suggesting a functional role., Foot-and-mouth disease virus binds αvβ6 integrin, via a conserved RGD motif in the flexible, exposed GH loop of capsid protein VP1, for cell entry. Here Kotecha et al. visualize this interaction with the VP1 GH loop extending away from the viral surface, engaging αvβ6 in an open, active state.

Published
2017

17. Host-dependent resistance of Group A Streptococcus to sulfamethoxazole mediated by a horizontally-acquired reduced folate transporter

Author

M. Kalindu D. Rodrigo, Aarti Saiganesh, Andrew J. Hayes, Alisha M. Wilson, Jack Anstey, Janessa L. Pickering, Jua Iwasaki, Jessica Hillas, Scott Winslow, Tabitha Woodman, Philipp Nitschke, Jake A. Lacey, Karen J. Breese, Mark P. G. van der Linden, Philip M. Giffard, Steven Y. C. Tong, Nicola Gray, Keith A. Stubbs, Jonathan R. Carapetis, Asha C. Bowen, Mark R. Davies, and Timothy C. Barnett

Subjects
Science
Abstract

There is increasing evidence for metabolic processes mediating antimicrobial resistance. Here, the authors present a mechanism of sulfamethoxazole resistance in Group A Streptococcus that is dependent on acquiring end products of the host folate biosynthesis pathway.

Published
2022
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18. Identification and characterization of a heterotrimeric archaeal DNA polymerase holoenzyme

Author

Sonja-Verena Albers, Kelly M. Schermerhorn, Thomas R. Beattie, Pietro Roversi, Jiangyu Yan, Jonathan C. Trinidad, Adriana L. Rojas, Andrew F. Gardner, Stephen D. Bell, Nicola G. A. Abrescia, and Tamzin Gristwood

Subjects
0301 basic medicine, DNA Replication, Models, Molecular, Protein Conformation, alpha-Helical, DNA polymerase, DNA polymerase II, Protein subunit, Science, Archaeal Proteins, General Physics and Astronomy, Gene Expression, Succinimides, DNA-Directed DNA Polymerase, Crystallography, X-Ray, DNA polymerase delta, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Escherichia coli, Protein Interaction Domains and Motifs, Amino Acid Sequence, Polymerase, Genetics, Multidisciplinary, DNA clamp, Binding Sites, 030102 biochemistry & molecular biology, biology, DNA replication, General Chemistry, Recombinant Proteins, Thermococcus, Kinetics, Protein Subunits, 030104 developmental biology, Cross-Linking Reagents, DNA, Archaeal, Biochemistry, biology.protein, Sulfolobus solfataricus, Thermodynamics, Protein Conformation, beta-Strand, Primer (molecular biology), Protein Multimerization, Holoenzymes, Sequence Alignment, Protein Binding
Abstract

Since their initial characterization over 30 years ago, it has been believed that the archaeal B-family DNA polymerases are single-subunit enzymes. This contrasts with the multi-subunit B-family replicative polymerases of eukaryotes. Here we reveal that the highly studied PolB1 from Sulfolobus solfataricus exists as a heterotrimeric complex in cell extracts. Two small subunits, PBP1 and PBP2, associate with distinct surfaces of the larger catalytic subunit and influence the enzymatic properties of the DNA polymerase. Thus, multi-subunit replicative DNA polymerase holoenzymes are present in all three domains of life. We reveal the architecture of the assembly by a combination of cross-linking coupled with mass spectrometry, X-ray crystallography and single-particle electron microscopy. The small subunits stabilize the holoenzyme assembly and the acidic tail of one small subunit mitigates the ability of the enzyme to perform strand-displacement synthesis, with important implications for lagging strand DNA synthesis., The current model for B-family DNA polymerases in archaea is one of single-subunit enzymes in contrast to the multi-subunit complexes in eukaryotes. Here the authors show that PolB1 from Sulfolobus solfataricus exists as a heterotrimeric complex in cell extracts.

Published
2016

19. N-glycosylation enables high lateral mobility of GPI-anchored proteins at a molecular crowding threshold

Author

Marius Glogger, Motomu Tanaka, Anne Hermann, Andreas Hartel, Markus Engstler, Christopher Batram, Susanne F. Fenz, Nicola G. Jones, and Wasim Abuillan

Subjects
0301 basic medicine, Trypanosoma, Glycan, Glycosylation, genetic structures, Glycosylphosphatidylinositols, Science, General Physics and Astronomy, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, chemistry.chemical_compound, N-linked glycosylation, ddc:570, chemistry.chemical_classification, Multidisciplinary, biology, Biological membrane, General Chemistry, 030104 developmental biology, Membrane, chemistry, Biochemistry, Membrane protein, Biophysics, biology.protein, Glycoprotein, Variant Surface Glycoproteins, Trypanosoma, Function (biology)
Abstract

The protein density in biological membranes can be extraordinarily high, but the impact of molecular crowding on the diffusion of membrane proteins has not been studied systematically in a natural system. The diversity of the membrane proteome of most cells may preclude systematic studies. African trypanosomes, however, feature a uniform surface coat that is dominated by a single type of variant surface glycoprotein (VSG). Here we study the density-dependence of the diffusion of different glycosylphosphatidylinositol-anchored VSG-types on living cells and in artificial membranes. Our results suggest that a specific molecular crowding threshold (MCT) limits diffusion and hence affects protein function. Obstacles in the form of heterologous proteins compromise the diffusion coefficient and the MCT. The trypanosome VSG-coat operates very close to its MCT. Importantly, our experiments show that N-linked glycans act as molecular insulators that reduce retarding intermolecular interactions allowing membrane proteins to function correctly even when densely packed., How molecular crowding affects membrane protein diffusion and function is not known. Here the authors measure diffusion of variant surface glycoprotein on trypanosomes and discover a molecular crowding threshold that limits diffusion, and find that N-linked glycans help to prevent retarding intermolecular interactions.

Published
2016
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20. Pregnancy-induced maternal microchimerism shapes neurodevelopment and behavior in mice

Author

Steven Schepanski, Mattia Chini, Veronika Sternemann, Christopher Urbschat, Kristin Thiele, Ting Sun, Yu Zhao, Mareike Poburski, Anna Woestemeier, Marie-Theres Thieme, Dimitra E. Zazara, Malik Alawi, Nicole Fischer, Joerg Heeren, Nikita Vladimirov, Andrew Woehler, Victor G. Puelles, Stefan Bonn, Nicola Gagliani, Ileana L. Hanganu-Opatz, and Petra C. Arck

Subjects
Science
Abstract

During pregnancy, maternal cells are transferred to the fetus, where they can reach the developing brain. In this study, the authors demonstrate that these maternal cells play an important role in neurodevelopment.

Published
2022
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22. Clinical relevance of molecular characteristics in Burkitt lymphoma differs according to age

Author

Birgit Burkhardt, Ulf Michgehl, Jonas Rohde, Tabea Erdmann, Philipp Berning, Katrin Reutter, Marius Rohde, Arndt Borkhardt, Thomas Burmeister, Sandeep Dave, Alexandar Tzankov, Martin Dugas, Sarah Sandmann, Falko Fend, Jasmin Finger, Stephanie Mueller, Nicola Gökbuget, Torsten Haferlach, Wolfgang Kern, Wolfgang Hartmann, Wolfram Klapper, Ilske Oschlies, Julia Richter, Udo Kontny, Mathias Lutz, Britta Maecker-Kolhoff, German Ott, Andreas Rosenwald, Reiner Siebert, Arend von Stackelberg, Brigitte Strahm, Wilhelm Woessmann, Martin Zimmermann, Myroslav Zapukhlyak, Michael Grau, and Georg Lenz

Subjects
Science
Abstract

Survival outcomes in Burkitt lymphoma differ between adult and paediatric patients. Here, the authors show differences in mutational frequencies between age groups, and a transition between mutational profiles which occurs between 25 and 40 years.

Published
2022
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23. Periodic formation of epithelial somites from human pluripotent stem cells

Author

Marina Sanaki-Matsumiya, Mitsuhiro Matsuda, Nicola Gritti, Fumio Nakaki, James Sharpe, Vikas Trivedi, and Miki Ebisuya

Subjects
Science
Abstract

Somitogenesis has been well characterized in model organisms, resulting in detailed description of the somite segmentation clock. Here they generate somitogenic organoids from human pluripotent stem cells that recapitulate somitogenesis, periodic segmentation, and proper polarity.

Published
2022
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24. The spatial transcriptomic landscape of the healing mouse intestine following damage

Author

Sara M. Parigi, Ludvig Larsson, Srustidhar Das, Ricardo O. Ramirez Flores, Annika Frede, Kumar P. Tripathi, Oscar E. Diaz, Katja Selin, Rodrigo A. Morales, Xinxin Luo, Gustavo Monasterio, Camilla Engblom, Nicola Gagliani, Julio Saez-Rodriguez, Joakim Lundeberg, and Eduardo J. Villablanca

Subjects
Science
Abstract

Abstract The intestinal barrier is composed of a complex cell network defining highly compartmentalized and specialized structures. Here, we use spatial transcriptomics to define how the transcriptomic landscape is spatially organized in the steady state and healing murine colon. At steady state conditions, we demonstrate a previously unappreciated molecular regionalization of the colon, which dramatically changes during mucosal healing. Here, we identified spatially-organized transcriptional programs defining compartmentalized mucosal healing, and regions with dominant wired pathways. Furthermore, we showed that decreased p53 activation defined areas with increased presence of proliferating epithelial stem cells. Finally, we mapped transcriptomics modules associated with human diseases demonstrating the translational potential of our dataset. Overall, we provide a publicly available resource defining principles of transcriptomic regionalization of the colon during mucosal healing and a framework to develop and progress further hypotheses.

Published
2022
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26. Subclone-specific microenvironmental impact and drug response in refractory multiple myeloma revealed by single‐cell transcriptomics

Author

Stephan M. Tirier, Jan-Philipp Mallm, Simon Steiger, Alexandra M. Poos, Mohamed H. S. Awwad, Nicola Giesen, Nicola Casiraghi, Hana Susak, Katharina Bauer, Anja Baumann, Lukas John, Anja Seckinger, Dirk Hose, Carsten Müller-Tidow, Hartmut Goldschmidt, Oliver Stegle, Michael Hundemer, Niels Weinhold, Marc S. Raab, and Karsten Rippe

Subjects
Science
Abstract

Abstract Virtually all patients with multiple myeloma become unresponsive to treatment over time. Relapsed/refractory multiple myeloma (RRMM) is accompanied by the clonal evolution of myeloma cells with heterogeneous genomic aberrations and profound changes of the bone marrow microenvironment (BME). However, the molecular mechanisms that drive drug resistance remain elusive. Here, we analyze the heterogeneous tumor cell population and its complex interaction network with the BME of 20 RRMM patients by single cell RNA-sequencing before/after treatment. Subclones with chromosome 1q-gain express a specific transcriptomic signature and frequently expand during treatment. Furthermore, RRMM cells shape an immune suppressive BME by upregulation of inflammatory cytokines and close interaction with the myeloid compartment. It is characterized by the accumulation of PD1+ γδ T-cells and tumor-associated macrophages as well as the depletion of hematopoietic progenitors. Thus, our study resolves transcriptional features of subclones in RRMM and mechanisms of microenvironmental reprogramming with implications for clinical decision-making.

Published
2021
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27. CD73-mediated adenosine production by CD8 T cell-derived extracellular vesicles constitutes an intrinsic mechanism of immune suppression

Author

Enja Schneider, Riekje Winzer, Anne Rissiek, Isabell Ricklefs, Catherine Meyer-Schwesinger, Franz L. Ricklefs, Andreas Bauche, Jochen Behrends, Rudolph Reimer, Santra Brenna, Hauke Wasielewski, Melchior Lauten, Björn Rissiek, Berta Puig, Filippo Cortesi, Tim Magnus, Ralf Fliegert, Christa E. Müller, Nicola Gagliani, and Eva Tolosa

Subjects
Science
Abstract

Ectonucleotidases associated to regulatory T cells are known modulators in the inflammatory environment. Here the authors describe CD8 T cell-derived extracellular vesicles bearing CD73 and suggest they function as an additional intrinsic modulator of immune responses.

Published
2021
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28. High efficiency blue organic light-emitting diodes with below-bandgap electroluminescence

Author

Maria Vasilopoulou, Abd. Rashid bin Mohd Yusoff, Matyas Daboczi, Julio Conforto, Anderson Emanuel Ximim Gavim, Wilson Jose da Silva, Andreia Gerniski Macedo, Anastasia Soultati, George Pistolis, Fabio Kurt Schneider, Yifan Dong, Polina Jacoutot, Georgios Rotas, Jin Jang, Georgios C. Vougioukalakis, Christos L. Chochos, Ji-Seon Kim, and Nicola Gasparini

Subjects
Science
Abstract

Thermally activated delayed fluorescence organic light-emitting diodes (TADF-OLEDs) rely on high triplet energy interlayers to confine excitons, which results in reduced performance. Here, the authors report high-performance blue TADF-OLEDs with below bandgap electroluminescence.

Published
2021
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29. Adjusting the energy of interfacial states in organic photovoltaics for maximum efficiency

Author

Nicola Gasparini, Franco V. A. Camargo, Stefan Frühwald, Tetsuhiko Nagahara, Andrej Classen, Steffen Roland, Andrew Wadsworth, Vasilis G. Gregoriou, Christos L. Chochos, Dieter Neher, Michael Salvador, Derya Baran, Iain McCulloch, Andreas Görling, Larry Lüer, Giulio Cerullo, and Christoph J. Brabec

Subjects
Science
Abstract

Understanding the mechanism of non-radiative losses in organic photovoltaics is crucial to improve the performance further. Here, the authors use combined device and spectroscopic data to reveal universal model to maximise exciton splitting and charge separation by adjusting the energy of charge transfer state.

Published
2021
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30. The induction and function of the anti-inflammatory fate of TH17 cells

Author

Hao Xu, Theodora Agalioti, Jun Zhao, Babett Steglich, Ramez Wahib, Maria Carolina Amezcua Vesely, Piotr Bielecki, Will Bailis, Ruaidhri Jackson, Daniel Perez, Jakob Izbicki, Paula Licona-Limón, Vesa Kaartinen, Jens Geginat, Enric Esplugues, Eva Tolosa, Samuel Huber, Richard A. Flavell, and Nicola Gagliani

Subjects
Science
Abstract

CD4+ T helper cells producing IL-17A (TH17 cells) can take on pathogenic or anti-inflammatory functions in context-specific manners. Here the authors show that the anti-inflammatory fate of TH17 cells contributes, via TGF-β signaling and induction of IL-10, to host immune tolerance, but also simultaneously dampens protective immunity against S. aureus.

Published
2020
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31. TGF-β signaling in Th17 cells promotes IL-22 production and colitis-associated colon cancer

Author

Laura Garcia Perez, Jan Kempski, Heather M. McGee, Penelope Pelzcar, Theodora Agalioti, Anastasios Giannou, Leonie Konczalla, Leonie Brockmann, Ramez Wahib, Hao Xu, Maria Carolina Amezcua Vesely, Shiwa Soukou, Babett Steglich, Tanja Bedke, Carolin Manthey, Oliver Seiz, Björn-Philipp Diercks, Stylianos Gnafakis, Andreas H. Guse, Daniel Perez, Jakob R. Izbicki, Nicola Gagliani, Richard A. Flavell, and Samuel Huber

Subjects
Science
Abstract

Poly-functional helper T cells can have a stronger effect than mono-functional T cells, but whether the response is qualitatively different is not clear. Here the authors show that a population of IL-17+IL-22+, but not single IL-22+, CD4+ T cells are induced by TGF-β, enriched in patients with colorectal cancer (CRC) and drive CRC progression in mice.

Published
2020
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32. Transcriptomic profiling of the myeloma bone-lining niche reveals BMP signalling inhibition to improve bone disease

Author

Sarah Gooding, Sam W. Z. Olechnowicz, Emma V. Morris, Andrew E. Armitage, Joao Arezes, Joe Frost, Emmanouela Repapi, James R. Edwards, Neil Ashley, Craig Waugh, Nicola Gray, Erik Martinez-Hackert, Pei Jin Lim, Sant-Rayn Pasricha, Helen Knowles, Adam J. Mead, Karthik Ramasamy, Hal Drakesmith, and Claire M. Edwards

Subjects
Science
Abstract

Multiple myeloma is a cancer of the bone marrow that can induce bone disease. Here, the authors profile the transcriptome of bone-lining cells and find a targetable role of bone morphogenetic protein (BMP) signalling in myeloma-induced bone-disease

Published
2019
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33. Conserved transcriptomic profile between mouse and human colitis allows unsupervised patient stratification

Author

Paulo Czarnewski, Sara M. Parigi, Chiara Sorini, Oscar E. Diaz, Srustidhar Das, Nicola Gagliani, and Eduardo J. Villablanca

Subjects
Science
Abstract

Clinical and molecular heterogeneity of ulcerative colitis presents unresolved challenges to identify predictive biomarkers of response to therapies. Here, the authors combine mouse colitis time course with patient biopsy transcriptomes, achieving unsupervised clustering of UC patients correlating with therapeutic outcomes in independent data sets.

Published
2019
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34. Molecular and functional heterogeneity of IL-10-producing CD4 + T cells

Author

Leonie Brockmann, Shiwa Soukou, Babett Steglich, Paulo Czarnewski, Lilan Zhao, Sandra Wende, Tanja Bedke, Can Ergen, Carolin Manthey, Theodora Agalioti, Maria Geffken, Oliver Seiz, Sara M. Parigi, Chiara Sorini, Jens Geginat, Keishi Fujio, Thomas Jacobs, Thomas Roesch, Jacob R. Izbicki, Ansgar W. Lohse, Richard A. Flavell, Christian Krebs, Jan-Ake Gustafsson, Per Antonson, Maria Grazia Roncarolo, Eduardo J. Villablanca, Nicola Gagliani, and Samuel Huber

Subjects
Science
Abstract

Tr1 cells are considered an immunosuppressive CD4 T cell population producing IL-10. Here the authors show that IL-10 is insufficient for Tr1 immunosuppression, define surface markers and transcriptional program of the immunosuppressive subset within Tr1, and reveal its deficiency in patients with IBD.

Published
2018
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35. Organoid cultures recapitulate esophageal adenocarcinoma heterogeneity providing a model for clonality studies and precision therapeutics

Author

Xiaodun Li, Hayley E. Francies, Maria Secrier, Juliane Perner, Ahmad Miremadi, Núria Galeano-Dalmau, William J. Barendt, Laura Letchford, Genevieve M. Leyden, Emma K. Goffin, Andrew Barthorpe, Howard Lightfoot, Elisabeth Chen, James Gilbert, Ayesha Noorani, Ginny Devonshire, Lawrence Bower, Amber Grantham, Shona MacRae, Nicola Grehan, David C. Wedge, Rebecca C. Fitzgerald, and Mathew J. Garnett

Subjects
Science
Abstract

Esophageal adenocarcinoma (EAC) has a poor 5-year survival rate and lacks robust preclinical models for use in research. Here, the authors show that newly derived organoids recapitulate the transcriptomic, genetic, and morphological landscape of the primary EAC tumors and provide a platform to test drug sensitivity and study tumor clonality.

Published
2018
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36. Robust nonfullerene solar cells approaching unity external quantum efficiency enabled by suppression of geminate recombination

Author

Derya Baran, Nicola Gasparini, Andrew Wadsworth, Ching Hong Tan, Nimer Wehbe, Xin Song, Zeinab Hamid, Weimin Zhang, Marios Neophytou, Thomas Kirchartz, Christoph J. Brabec, James R. Durrant, and Iain McCulloch

Subjects
Science
Abstract

The nonfullerene-based small molecules start to attract more attention for solar cell research than the fullerene acceptors due to their wider tunability. Here Baran et al. demonstrate nonfullerene-based solar cells with high power conversion efficiency of 12% and quantum efficiencies approaching 100%.

Published
2018
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37. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Author

Anne E. Justice, Thomas W. Winkler, Mary F. Feitosa, Misa Graff, Virginia A. Fisher, Kristin Young, Llilda Barata, Xuan Deng, Jacek Czajkowski, David Hadley, Julius S. Ngwa, Tarunveer S. Ahluwalia, Audrey Y. Chu, Nancy L. Heard-Costa, Elise Lim, Jeremiah Perez, John D. Eicher, Zoltán Kutalik, Luting Xue, Anubha Mahajan, Frida Renström, Joseph Wu, Qibin Qi, Shafqat Ahmad, Tamuno Alfred, Najaf Amin, Lawrence F. Bielak, Amelie Bonnefond, Jennifer Bragg, Gemma Cadby, Martina Chittani, Scott Coggeshall, Tanguy Corre, Nese Direk, Joel Eriksson, Krista Fischer, Mathias Gorski, Marie Neergaard Harder, Momoko Horikoshi, Tao Huang, Jennifer E. Huffman, Anne U. Jackson, Johanne Marie Justesen, Stavroula Kanoni, Leena Kinnunen, Marcus E. Kleber, Pirjo Komulainen, Meena Kumari, Unhee Lim, Jian'an Luan, Leo-Pekka Lyytikäinen, Massimo Mangino, Ani Manichaikul, Jonathan Marten, Rita P. S. Middelberg, Martina Müller-Nurasyid, Pau Navarro, Louis Pérusse, Natalia Pervjakova, Cinzia Sarti, Albert Vernon Smith, Jennifer A. Smith, Alena Stančáková, Rona J. Strawbridge, Heather M. Stringham, Yun Ju Sung, Toshiko Tanaka, Alexander Teumer, Stella Trompet, Sander W. van der Laan, Peter J. van der Most, Jana V. Van Vliet-Ostaptchouk, Sailaja L. Vedantam, Niek Verweij, Jacqueline M. Vink, Veronique Vitart, Ying Wu, Loic Yengo, Weihua Zhang, Jing Hua Zhao, Martina E. Zimmermann, Niha Zubair, Gonçalo R. Abecasis, Linda S. Adair, Saima Afaq, Uzma Afzal, Stephan J. L. Bakker, Traci M. Bartz, John Beilby, Richard N. Bergman, Sven Bergmann, Reiner Biffar, John Blangero, Eric Boerwinkle, Lori L. Bonnycastle, Erwin Bottinger, Daniele Braga, Brendan M. Buckley, Steve Buyske, Harry Campbell, John C. Chambers, Francis S. Collins, Joanne E. Curran, Gert J. de Borst, Anton J. M. de Craen, Eco J. C. de Geus, George Dedoussis, Graciela E. Delgado, Hester M. den Ruijter, Gudny Eiriksdottir, Anna L. Eriksson, Tõnu Esko, Jessica D. Faul, Ian Ford, Terrence Forrester, Karl Gertow, Bruna Gigante, Nicola Glorioso, Jian Gong, Harald Grallert, Tanja B. Grammer, Niels Grarup, Saskia Haitjema, Göran Hallmans, Anders Hamsten, Torben Hansen, Tamara B. Harris, Catharina A. Hartman, Maija Hassinen, Nicholas D. Hastie, Andrew C. Heath, Dena Hernandez, Lucia Hindorff, Lynne J. Hocking, Mette Hollensted, Oddgeir L. Holmen, Georg Homuth, Jouke Jan Hottenga, Jie Huang, Joseph Hung, Nina Hutri-Kähönen, Erik Ingelsson, Alan L. James, John-Olov Jansson, Marjo-Riitta Jarvelin, Min A. Jhun, Marit E. Jørgensen, Markus Juonala, Mika Kähönen, Magnus Karlsson, Heikki A. Koistinen, Ivana Kolcic, Genovefa Kolovou, Charles Kooperberg, Bernhard K. Krämer, Johanna Kuusisto, Kirsti Kvaløy, Timo A. Lakka, Claudia Langenberg, Lenore J. Launer, Karin Leander, Nanette R. Lee, Lars Lind, Cecilia M. Lindgren, Allan Linneberg, Stephane Lobbens, Marie Loh, Mattias Lorentzon, Robert Luben, Gitta Lubke, Anja Ludolph-Donislawski, Sara Lupoli, Pamela A. F. Madden, Reija Männikkö, Pedro Marques-Vidal, Nicholas G. Martin, Colin A. McKenzie, Barbara McKnight, Dan Mellström, Cristina Menni, Grant W. Montgomery, AW (Bill) Musk, Narisu Narisu, Matthias Nauck, Ilja M. Nolte, Albertine J. Oldehinkel, Matthias Olden, Ken K. Ong, Sandosh Padmanabhan, Patricia A. Peyser, Charlotta Pisinger, David J. Porteous, Olli T. Raitakari, Tuomo Rankinen, D. C. Rao, Laura J. Rasmussen-Torvik, Rajesh Rawal, Treva Rice, Paul M. Ridker, Lynda M. Rose, Stephanie A. Bien, Igor Rudan, Serena Sanna, Mark A. Sarzynski, Naveed Sattar, Kai Savonen, David Schlessinger, Salome Scholtens, Claudia Schurmann, Robert A. Scott, Bengt Sennblad, Marten A. Siemelink, Günther Silbernagel, P Eline Slagboom, Harold Snieder, Jan A. Staessen, David J. Stott, Morris A. Swertz, Amy J. Swift, Kent D. Taylor, Bamidele O. Tayo, Barbara Thorand, Dorothee Thuillier, Jaakko Tuomilehto, Andre G. Uitterlinden, Liesbeth Vandenput, Marie-Claude Vohl, Henry Völzke, Judith M. Vonk, Gérard Waeber, Melanie Waldenberger, R. G. J. Westendorp, Sarah Wild, Gonneke Willemsen, Bruce H. R. Wolffenbuttel, Andrew Wong, Alan F. Wright, Wei Zhao, M Carola Zillikens, Damiano Baldassarre, Beverley Balkau, Stefania Bandinelli, Carsten A. Böger, Dorret I. Boomsma, Claude Bouchard, Marcel Bruinenberg, Daniel I. Chasman, Yii-DerIda Chen, Peter S. Chines, Richard S. Cooper, Francesco Cucca, Daniele Cusi, Ulf de Faire, Luigi Ferrucci, Paul W. Franks, Philippe Froguel, Penny Gordon-Larsen, Hans- Jörgen Grabe, Vilmundur Gudnason, Christopher A. Haiman, Caroline Hayward, Kristian Hveem, Andrew D. Johnson, J Wouter Jukema, Sharon L. R. Kardia, Mika Kivimaki, Jaspal S. Kooner, Diana Kuh, Markku Laakso, Terho Lehtimäki, Loic Le Marchand, Winfried März, Mark I. McCarthy, Andres Metspalu, Andrew P. Morris, Claes Ohlsson, Lyle J. Palmer, Gerard Pasterkamp, Oluf Pedersen, Annette Peters, Ulrike Peters, Ozren Polasek, Bruce M. Psaty, Lu Qi, Rainer Rauramaa, Blair H. Smith, Thorkild I. A. Sørensen, Konstantin Strauch, Henning Tiemeier, Elena Tremoli, Pim van der Harst, Henrik Vestergaard, Peter Vollenweider, Nicholas J. Wareham, David R. Weir, John B. Whitfield, James F. Wilson, Jessica Tyrrell, Timothy M. Frayling, Inês Barroso, Michael Boehnke, Panagiotis Deloukas, Caroline S. Fox, Joel N. Hirschhorn, David J. Hunter, Tim D. Spector, David P. Strachan, Cornelia M. van Duijn, Iris M. Heid, Karen L. Mohlke, Jonathan Marchini, Ruth J. F. Loos, Tuomas O. Kilpeläinen, Ching-Ti Liu, Ingrid B. Borecki, Kari E. North, and L Adrienne Cupples

Subjects
Science
Abstract

Genome-wide association studies (GWAS) have become a key tool to discover genetic markers for complex traits; however, environmental factors that interact with genes are rarely considered. Here, the authors conduct a GWAS of obesity traits, and find that smoking may alter genetic susceptibilities.

Published
2017
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38. Publisher Correction: TGF-β signaling in Th17 cells promotes IL-22 production and colitis-associated colon cancer

Author

Laura Garcia Perez, Jan Kempski, Heather M. McGee, Penelope Pelzcar, Theodora Agalioti, Anastasios Giannou, Leonie Konczalla, Leonie Brockmann, Ramez Wahib, Hao Xu, Maria Carolina Amezcua Vesely, Shiwa Soukou, Babett Steglich, Tanja Bedke, Carolin Manthey, Oliver Seiz, Björn-Philipp Diercks, Stylianos Gnafakis, Andreas H. Guse, Daniel Perez, Jakob R. Izbicki, Nicola Gagliani, Richard A. Flavell, and Samuel Huber

Subjects
Science
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020
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39. A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

Author

Janina S. Ried, Janina Jeff M., Audrey Y. Chu, Jennifer L. Bragg-Gresham, Jenny van Dongen, Jennifer E. Huffman, Tarunveer S. Ahluwalia, Gemma Cadby, Niina Eklund, Joel Eriksson, Tõnu Esko, Mary F. Feitosa, Anuj Goel, Mathias Gorski, Caroline Hayward, Nancy L. Heard-Costa, Anne U. Jackson, Eero Jokinen, Stavroula Kanoni, Kati Kristiansson, Zoltán Kutalik, Jari Lahti, Jian'an Luan, Reedik Mägi, Anubha Mahajan, Massimo Mangino, Carolina Medina-Gomez, Keri L. Monda, Ilja M. Nolte, Louis Pérusse, Inga Prokopenko, Lu Qi, Lynda M. Rose, Erika Salvi, Megan T. Smith, Harold Snieder, Alena Stančáková, Yun Ju Sung, Ioanna Tachmazidou, Alexander Teumer, Gudmar Thorleifsson, Pim van der Harst, Ryan W. Walker, Sophie R. Wang, Sarah H. Wild, Sara M. Willems, Andrew Wong, Weihua Zhang, Eva Albrecht, Alexessander Couto Alves, Stephan J. L. Bakker, Cristina Barlassina, Traci M. Bartz, John Beilby, Claire Bellis, Richard N. Bergman, Sven Bergmann, John Blangero, Matthias Blüher, Eric Boerwinkle, Lori L. Bonnycastle, Stefan R. Bornstein, Marcel Bruinenberg, Harry Campbell, Yii-Der Ida Chen, Charleston W. K. Chiang, Peter S. Chines, Francis S Collins, Fracensco Cucca, L Adrienne Cupples, Francesca D’Avila, Eco J .C. de Geus, George Dedoussis, Maria Dimitriou, Angela Döring, Johan G. Eriksson, Aliki-Eleni Farmaki, Martin Farrall, Teresa Ferreira, Krista Fischer, Nita G. Forouhi, Nele Friedrich, Anette Prior Gjesing, Nicola Glorioso, Mariaelisa Graff, Harald Grallert, Niels Grarup, Jürgen Gräßler, Jagvir Grewal, Anders Hamsten, Marie Neergaard Harder, Catharina A. Hartman, Maija Hassinen, Nicholas Hastie, Andrew Tym Hattersley, Aki S. Havulinna, Markku Heliövaara, Hans Hillege, Albert Hofman, Oddgeir Holmen, Georg Homuth, Jouke-Jan Hottenga, Jennie Hui, Lise Lotte Husemoen, Pirro G. Hysi, Aaron Isaacs, Till Ittermann, Shapour Jalilzadeh, Alan L. James, Torben Jørgensen, Pekka Jousilahti, Antti Jula, Johanne Marie Justesen, Anne E. Justice, Mika Kähönen, Maria Karaleftheri, Kay Tee Khaw, Sirkka M. Keinanen-Kiukaanniemi, Leena Kinnunen, Paul B. Knekt, Heikki A. Koistinen, Ivana Kolcic, Ishminder K. Kooner, Seppo Koskinen, Peter Kovacs, Theodosios Kyriakou, Tomi Laitinen, Claudia Langenberg, Alexandra M. Lewin, Peter Lichtner, Cecilia M. Lindgren, Jaana Lindström, Allan Linneberg, Roberto Lorbeer, Mattias Lorentzon, Robert Luben, Valeriya Lyssenko, Satu Männistö, Paolo Manunta, Irene Mateo Leach, Wendy L. McArdle, Barbara Mcknight, Karen L. Mohlke, Evelin Mihailov, Lili Milani, Rebecca Mills, May E. Montasser, Andrew P. Morris, Gabriele Müller, Arthur W. Musk, Narisu Narisu, Ken K. Ong, Ben A. Oostra, Clive Osmond, Aarno Palotie, James S. Pankow, Lavinia Paternoster, Brenda W. Penninx, Irene Pichler, Maria G. Pilia, Ozren Polašek, Peter P. Pramstaller, Olli T Raitakari, Tuomo Rankinen, D. C. Rao, Nigel W. Rayner, Rasmus Ribel-Madsen, Treva K. Rice, Marcus Richards, Paul M. Ridker, Fernando Rivadeneira, Kathy A. Ryan, Serena Sanna, Mark A. Sarzynski, Salome Scholtens, Robert A. Scott, Sylvain Sebert, Lorraine Southam, Thomas Hempel Sparsø, Valgerdur Steinthorsdottir, Kathleen Stirrups, Ronald P. Stolk, Konstantin Strauch, Heather M. Stringham, Morris A. Swertz, Amy J. Swift, Anke Tönjes, Emmanouil Tsafantakis, Peter J. van der Most, Jana V. Van Vliet-Ostaptchouk, Liesbeth Vandenput, Erkki Vartiainen, Cristina Venturini, Niek Verweij, Jorma S. Viikari, Veronique Vitart, Marie-Claude Vohl, Judith M. Vonk, Gérard Waeber, Elisabeth Widén, Gonneke Willemsen, Tom Wilsgaard, Thomas W. Winkler, Alan F. Wright, Laura M. Yerges-Armstrong, Jing Hua Zhao, M. Carola Zillikens, Dorret I. Boomsma, Claude Bouchard, John C. Chambers, Daniel I. Chasman, Daniele Cusi, Ron T. Gansevoort, Christian Gieger, Torben Hansen, Andrew A. Hicks, Frank Hu, Kristian Hveem, Marjo-Riitta Jarvelin, Eero Kajantie, Jaspal S. Kooner, Diana Kuh, Johanna Kuusisto, Markku Laakso, Timo A. Lakka, Terho Lehtimäki, Andres Metspalu, Inger Njølstad, Claes Ohlsson, Albertine J. Oldehinkel, Lyle J. Palmer, Oluf Pedersen, Markus Perola, Annette Peters, Bruce M. Psaty, Hannu Puolijoki, Rainer Rauramaa, Igor Rudan, Veikko Salomaa, Peter E. H. Schwarz, Alan R. Shudiner, Jan H. Smit, Thorkild I. A. Sørensen, Timothy D. Spector, Kari Stefansson, Michael Stumvoll, Angelo Tremblay, Jaakko Tuomilehto, André G. Uitterlinden, Matti Uusitupa, Uwe Völker, Peter Vollenweider, Nicholas J. Wareham, Hugh Watkins, James F. Wilson, Eleftheria Zeggini, Goncalo R. Abecasis, Michael Boehnke, Ingrid B. Borecki, Panos Deloukas, Cornelia M. van Duijn, Caroline Fox, Leif C. Groop, Iris M. Heid, David J. Hunter, Robert C. Kaplan, Mark I. McCarthy, Kari E. North, Jeffrey R. O'Connell, David Schlessinger, Unnur Thorsteinsdottir, David P. Strachan, Timothy Frayling, Joel N. Hirschhorn, Martina Müller-Nurasyid, and Ruth J. F. Loos

Subjects
Science
Abstract

Past genome-wide associate studies have identified hundreds of genetic loci that influence body size and shape when examined one trait at a time. Here, Jeff and colleagues develop an aggregate score of various body traits, and use meta-analysis to find new loci linked to body shape.

Published
2016
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40. Long-term time-lapse microscopy of C. elegans post-embryonic development

Author

Nicola Gritti, Simone Kienle, Olga Filina, and Jeroen Sebastiaan van Zon

Subjects
Science
Abstract

Long-term time-lapse imaging of motile developing organisms at the single cell level is challenging. Here the authors culture free-moving C. eleganslarvae in hydrogel chambers containing a food source, and use fast image acquisition to follow developmental processes.

Published
2016
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41. High-efficiency and air-stable P3HT-based polymer solar cells with a new non-fullerene acceptor

Author

Sarah Holliday, Raja Shahid Ashraf, Andrew Wadsworth, Derya Baran, Syeda Amber Yousaf, Christian B. Nielsen, Ching-Hong Tan, Stoichko D. Dimitrov, Zhengrong Shang, Nicola Gasparini, Maha Alamoudi, Frédéric Laquai, Christoph J. Brabec, Alberto Salleo, James R. Durrant, and Iain McCulloch

Subjects
Science
Abstract

In organic photovoltaics, the best performing devices usually involve low-bandgap polymers whose limited solubility and stability constrain the scalability of organic solar cells. Here, Holliday et al. develop a new acceptor and pair it with canonical P3HT to obtain 6.4% efficient and stable devices.

Published
2016
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