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Your search keyword '"Larsen, P."' showing total 126 results
Start Over Author "Larsen, P." Journal nature communications
126 results on '"Larsen, P."'

2. A systematic review of using population-level human mobility data to understand SARS-CoV-2 transmission

Author

Kostandova, Natalya, Schluth, Catherine, Arambepola, Rohan, Atuhaire, Fatumah, Bérubé, Sophie, Chin, Taylor, Cleary, Eimear, Cortes-Azuero, Oscar, García-Carreras, Bernardo, Grantz, Kyra H., Hitchings, Matt D. T., Huang, Angkana T., Kishore, Nishant, Lai, Shengjie, Larsen, Sophie L., Loisate, Stacie, Martinez, Pamela, Meredith, Hannah R., Purbey, Ritika, Ramiadantsoa, Tanjona, Read, Jonathan, Rice, Benjamin L., Rosman, Lori, Ruktanonchai, Nick, Salje, Henrik, Schaber, Kathryn L., Tatem, Andrew J., Wang, Jasmine, Cummings, Derek A. T., and Wesolowski, Amy

Published
2024
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3. The mitochondrial mRNA-stabilizing protein SLIRP regulates skeletal muscle mitochondrial structure and respiration by exercise-recoverable mechanisms

Author

Pham, Tang Cam Phung, Raun, Steffen Henning, Havula, Essi, Henriquez-Olguín, Carlos, Rubalcava-Gracia, Diana, Frank, Emma, Fritzen, Andreas Mæchel, Jannig, Paulo R., Andersen, Nicoline Resen, Kruse, Rikke, Ali, Mona Sadek, Irazoki, Andrea, Halling, Jens Frey, Ringholm, Stine, Needham, Elise J., Hansen, Solvejg, Lemminger, Anders Krogh, Schjerling, Peter, Petersen, Maria Houborg, de Almeida, Martin Eisemann, Jensen, Thomas Elbenhardt, Kiens, Bente, Hostrup, Morten, Larsen, Steen, Ørtenblad, Niels, Højlund, Kurt, Kjær, Michael, Ruas, Jorge L., Trifunovic, Aleksandra, Wojtaszewski, Jørgen Frank Pind, Nielsen, Joachim, Qvortrup, Klaus, Pilegaard, Henriette, Richter, Erik Arne, and Sylow, Lykke

Published
2024
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4. Enhanced production of 60Fe in massive stars

Author

Spyrou, A., Richman, D., Couture, A., Fields, C. E., Liddick, S. N., Childers, K., Crider, B. P., DeYoung, P. A., Dombos, A. C., Gastis, P., Guttormsen, M., Hermansen, K., Larsen, A. C., Lewis, R., Lyons, S., Midtbø, J. E., Mosby, S., Muecher, D., Naqvi, F., Palmisano-Kyle, A., Perdikakis, G., Prokop, C., Schatz, H., Smith, M. K., Sumithrarachchi, C., and Sweet, A.

Published
2024
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7. Hyper-recombination in ribosomal DNA is driven by long-range resection-independent RAD51 accumulation

Author

Gál, Zita, Boukoura, Stavroula, Oxe, Kezia Catharina, Badawi, Sara, Nieto, Blanca, Korsholm, Lea Milling, Geisler, Sille Blangstrup, Dulina, Ekaterina, Rasmussen, Anna Vestergaard, Dahl, Christina, Lv, Wei, Xu, Huixin, Pan, Xiaoguang, Arampatzis, Stefanos, Stratou, Danai-Eleni, Galanos, Panagiotis, Lin, Lin, Guldberg, Per, Bartek, Jiri, Luo, Yonglun, and Larsen, Dorthe H.

Published
2024
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10. PARP1-dependent DNA-protein crosslink repair

Author

Fábián, Zita, Kakulidis, Ellen S., Hendriks, Ivo A., Kühbacher, Ulrike, Larsen, Nicolai B., Oliva-Santiago, Marta, Wang, Junhui, Leng, Xueyuan, Dirac-Svejstrup, A. Barbara, Svejstrup, Jesper Q., Nielsen, Michael L., Caldecott, Keith, and Duxin, Julien P.

Published
2024
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13. Enhanced surface colonisation and competition during bacterial adaptation to a fungus

Author

Richter, Anne, Blei, Felix, Hu, Guohai, Schwitalla, Jan W., Lozano-Andrade, Carlos N., Xie, Jiyu, Jarmusch, Scott A., Wibowo, Mario, Kjeldgaard, Bodil, Surabhi, Surabhi, Xu, Xinming, Jautzus, Theresa, Phippen, Christopher B. W., Tyc, Olaf, Arentshorst, Mark, Wang, Yue, Garbeva, Paolina, Larsen, Thomas Ostenfeld, Ram, Arthur F. J., van den Hondel, Cees A. M., Maróti, Gergely, and Kovács, Ákos T.

Published
2024
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15. Functional connectivity development along the sensorimotor-association axis enhances the cortical hierarchy

Author

Luo, Audrey C., Sydnor, Valerie J., Pines, Adam, Larsen, Bart, Alexander-Bloch, Aaron F., Cieslak, Matthew, Covitz, Sydney, Chen, Andrew A., Esper, Nathalia Bianchini, Feczko, Eric, Franco, Alexandre R., Gur, Raquel E., Gur, Ruben C., Houghton, Audrey, Hu, Fengling, Keller, Arielle S., Kiar, Gregory, Mehta, Kahini, Salum, Giovanni A., Tapera, Tinashe, Xu, Ting, Zhao, Chenying, Salo, Taylor, Fair, Damien A., Shinohara, Russell T., Milham, Michael P., and Satterthwaite, Theodore D.

Published
2024
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17. A mutational atlas for Parkin proteostasis

Author

Clausen, Lene, Voutsinos, Vasileios, Cagiada, Matteo, Johansson, Kristoffer E., Grønbæk-Thygesen, Martin, Nariya, Snehal, Powell, Rachel L., Have, Magnus K. N., Oestergaard, Vibe H., Stein, Amelie, Fowler, Douglas M., Lindorff-Larsen, Kresten, and Hartmann-Petersen, Rasmus

Published
2024
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18. Amyloid-β aggregates activate peripheral monocytes in mild cognitive impairment

Author

Juul-Madsen, Kristian, Parbo, Peter, Ismail, Rola, Ovesen, Peter L., Schmidt, Vanessa, Madsen, Lasse S., Thyrsted, Jacob, Gierl, Sarah, Breum, Mihaela, Larsen, Agnete, Andersen, Morten N., Romero-Ramos, Marina, Holm, Christian K., Andersen, Gregers R., Zhao, Huaying, Schuck, Peter, Nygaard, Jens V., Sutherland, Duncan S., Eskildsen, Simon F., Willnow, Thomas E., Brooks, David J., and Vorup-Jensen, Thomas

Published
2024
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19. A zero-valent palladium cluster-organic framework

Author

Liu, Xiyue, McPherson, James N., Andersen, Carl Emil, Jørgensen, Mike S. B., Larsen, René Wugt, Yutronkie, Nathan J., Wilhelm, Fabrice, Rogalev, Andrei, Giménez-Marqués, Mónica, Mínguez Espallargas, Guillermo, Göb, Christian R., and Pedersen, Kasper S.

Published
2024
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20. Variants in the WDR44 WD40-repeat domain cause a spectrum of ciliopathy by impairing ciliogenesis initiation

Author

Accogli, Andrea, Shakya, Saurabh, Yang, Taewoo, Insinna, Christine, Kim, Soo Yeon, Bell, David, Butov, Kirill R., Severino, Mariasavina, Niceta, Marcello, Scala, Marcello, Lee, Hyun Sik, Yoo, Taekyeong, Stauffer, Jimmy, Zhao, Huijie, Fiorillo, Chiara, Pedemonte, Marina, Diana, Maria C., Baldassari, Simona, Zakharova, Viktoria, Shcherbina, Anna, Rodina, Yulia, Fagerberg, Christina, Roos, Laura Sønderberg, Wierzba, Jolanta, Dobosz, Artur, Gerard, Amanda, Potocki, Lorraine, Rosenfeld, Jill A., Lalani, Seema R., Scott, Tiana M., Scott, Daryl, Azamian, Mahshid S., Louie, Raymond, Moore, Hannah W., Champaigne, Neena L., Hollingsworth, Grace, Torella, Annalaura, Nigro, Vincenzo, Ploski, Rafal, Salpietro, Vincenzo, Zara, Federico, Pizzi, Simone, Chillemi, Giovanni, Ognibene, Marzia, Cooney, Erin, Do, Jenny, Linnemann, Anders, Larsen, Martin J., Specht, Suzanne, Walters, Kylie J., Choi, Hee-Jung, Choi, Murim, Tartaglia, Marco, Youkharibache, Phillippe, Chae, Jong-Hee, Capra, Valeria, Park, Sung-Gyoo, and Westlake, Christopher J.

Published
2024
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22. Step-by-step state-selective tracking of fragmentation dynamics of water dications by momentum imaging

Author

Severt, Travis, Streeter, Zachary L, Iskandar, Wael, Larsen, Kirk A, Gatton, Averell, Trabert, Daniel, Jochim, Bethany, Griffin, Brandon, Champenois, Elio G, Brister, Matthew M, Reedy, Dylan, Call, Demitri, Strom, Richard, Landers, Allen L, Dörner, Reinhard, Williams, Joshua B, Slaughter, Daniel S, Lucchese, Robert R, Weber, Thorsten, McCurdy, C William, and Ben-Itzhak, Itzik

Subjects
Physical Sciences, Chemical Sciences, Atomic, Molecular and Optical Physics, Physical Chemistry, CSD-01-AMOS-A, CSD-46-All CSGB, CSD-45-Featured
Abstract

The double photoionization of a molecule by one photon ejects two electrons and typically creates an unstable dication. Observing the subsequent fragmentation products in coincidence can reveal a surprisingly detailed picture of the dynamics. Determining the time evolution and quantum mechanical states involved leads to deeper understanding of molecular dynamics. Here in a combined experimental and theoretical study, we unambiguously separate the sequential breakup via D+ + OD+ intermediates, from other processes leading to the same D+ + D+ + O final products of double ionization of water by a single photon. Moreover, we experimentally identify, separate, and follow step by step, two pathways involving the b 1Σ+ and a 1Δ electronic states of the intermediate OD+ ion. Our classical trajectory calculations on the relevant potential energy surfaces reproduce well the measured data and, combined with the experiment, enable the determination of the internal energy and angular momentum distribution of the OD+ intermediate.

Published
2022

23. Personalized functional brain network topography is associated with individual differences in youth cognition

Author

Keller, Arielle S., Pines, Adam R., Shanmugan, Sheila, Sydnor, Valerie J., Cui, Zaixu, Bertolero, Maxwell A., Barzilay, Ran, Alexander-Bloch, Aaron F., Byington, Nora, Chen, Andrew, Conan, Gregory M., Davatzikos, Christos, Feczko, Eric, Hendrickson, Timothy J., Houghton, Audrey, Larsen, Bart, Li, Hongming, Miranda-Dominguez, Oscar, Roalf, David R., Perrone, Anders, Shetty, Alisha, Shinohara, Russell T., Fan, Yong, Fair, Damien A., and Satterthwaite, Theodore D.

Published
2023
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25. PAX3-FOXO1 dictates myogenic reprogramming and rhabdomyosarcoma identity in endothelial progenitors

Author

Searcy, Madeline B., Larsen, IV, Randolph K., Stevens, Bradley T., Zhang, Yang, Jin, Hongjian, Drummond, Catherine J., Langdon, Casey G., Gadek, Katherine E., Vuong, Kyna, Reed, Kristin B., Garcia, Matthew R., Xu, Beisi, Kimbrough, Darden W., Adkins, Grace E., Djekidel, Nadhir, Porter, Shaina N., Schreiner, Patrick A., Pruett-Miller, Shondra M., Abraham, Brian J., Rehg, Jerold E., and Hatley, Mark E.

Published
2023
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30. Viral infection switches the balance between bacterial and eukaryotic recyclers of organic matter during coccolithophore blooms

Author

Vincent, Flora, Gralka, Matti, Schleyer, Guy, Schatz, Daniella, Cabrera-Brufau, Miguel, Kuhlisch, Constanze, Sichert, Andreas, Vidal-Melgosa, Silvia, Mayers, Kyle, Barak-Gavish, Noa, Flores, J. Michel, Masdeu-Navarro, Marta, Egge, Jorun Karin, Larsen, Aud, Hehemann, Jan-Hendrik, Marrasé, Celia, Simó, Rafel, Cordero, Otto X., and Vardi, Assaf

Published
2023
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32. Structural basis of intron selection by U2 snRNP in the presence of covalent inhibitors.

Author

Cretu, Constantin, Gee, Patricia, Liu, Xiang, Agrawal, Anant, Nguyen, Tuong-Vi, Ghosh, Arun K, Cook, Andrew, Jurica, Melissa, Larsen, Nicholas A, and Pena, Vladimir

Subjects
Spliceosomes, Humans, Lactones, Pyrans, Pyrones, Spiro Compounds, Ribonucleoprotein, U2 Small Nuclear, DNA, Cryoelectron Microscopy, Crystallography, X-Ray, Nucleic Acid Conformation, Protein Conformation, Protein Binding, Introns, Models, Molecular
Abstract

Intron selection during the formation of prespliceosomes is a critical event in pre-mRNA splicing. Chemical modulation of intron selection has emerged as a route for cancer therapy. Splicing modulators alter the splicing patterns in cells by binding to the U2 snRNP (small nuclear ribonucleoprotein)-a complex chaperoning the selection of branch and 3' splice sites. Here we report crystal structures of the SF3B module of the U2 snRNP in complex with spliceostatin and sudemycin FR901464 analogs, and the cryo-electron microscopy structure of a cross-exon prespliceosome-like complex arrested with spliceostatin A. The structures reveal how modulators inactivate the branch site in a sequence-dependent manner and stall an E-to-A prespliceosome intermediate by covalent coupling to a nucleophilic zinc finger belonging to the SF3B subunit PHF5A. These findings support a mechanism of intron recognition by the U2 snRNP as a toehold-mediated strand invasion and advance an unanticipated drug targeting concept.

Published
2021

33. RCB initiates Arabidopsis thermomorphogenesis by stabilizing the thermoregulator PIF4 in the daytime.

Author

Qiu, Yongjian, Pasoreck, Elise K, Yoo, Chan Yul, He, Jiangman, Wang, He, Bajracharya, Abhishesh, Li, Meina, Larsen, Haley D, Cheung, Stacey, and Chen, Meng

Subjects
Chloroplasts, Arabidopsis, Chlorophyll, Arabidopsis Proteins, Transcription Factors, Temperature, Amino Acid Sequence, Morphogenesis, Genes, Suppressor, Light, Models, Biological, Photoperiod, Basic Helix-Loop-Helix Transcription Factors, Thioredoxins, Protein Stability, Seedlings
Abstract

Daytime warm temperature elicits thermomorphogenesis in Arabidopsis by stabilizing the central thermoregulator PHYTOCHROME INTERACTING transcription FACTOR 4 (PIF4), whose degradation is otherwise promoted by the photoreceptor and thermosensor phytochrome B. PIF4 stabilization in the light requires a transcriptional activator, HEMERA (HMR), and is abrogated when HMR's transactivation activity is impaired in hmr-22. Here, we report the identification of a hmr-22 suppressor mutant, rcb-101, which surprisingly carries an A275V mutation in REGULATOR OF CHLOROPLAST BIOGENESIS (RCB). rcb-101/hmr-22 restores thermoresponsive PIF4 accumulation and reverts the defects of hmr-22 in chloroplast biogenesis and photomorphogenesis. Strikingly, similar to hmr, the null rcb-10 mutant impedes PIF4 accumulation and thereby loses the warm-temperature response. rcb-101 rescues hmr-22 in an allele-specific manner. Consistently, RCB interacts directly with HMR. Together, these results unveil RCB as a novel temperature signaling component that functions collaboratively with HMR to initiate thermomorphogenesis by selectively stabilizing PIF4 in the daytime.

Published
2021

34. TNK1 is a ubiquitin-binding and 14-3-3-regulated kinase that can be targeted to block tumor growth

Author

Chan, Tsz-Yin, Egbert, Christina M, Maxson, Julia E, Siddiqui, Adam, Larsen, Logan J, Kohler, Kristina, Balasooriya, Eranga Roshan, Pennington, Katie L, Tsang, Tsz-Ming, Frey, Madison, Soderblom, Erik J, Geng, Huimin, Müschen, Markus, Forostyan, Tetyana V, Free, Savannah, Mercenne, Gaelle, Banks, Courtney J, Valdoz, Jonard, Whatcott, Clifford J, Foulks, Jason M, Bearss, David J, O’Hare, Thomas, Huang, David CS, Christensen, Kenneth A, Moody, James, Warner, Steven L, Tyner, Jeffrey W, and Andersen, Joshua L

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Cancer, 2.1 Biological and endogenous factors, Aetiology, 14-3-3 Proteins, A549 Cells, Animals, Antineoplastic Agents, Cell Line, Tumor, Fetal Proteins, Fusion Proteins, bcr-abl, Gene Expression Regulation, Neoplastic, HEK293 Cells, Humans, Lymphocytes, Mice, Phospholipase C gamma, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Protein Binding, Protein Kinase Inhibitors, Protein-Tyrosine Kinases, Pyrimidines, STAT3 Transcription Factor, STAT5 Transcription Factor, Signal Transduction, Survival Analysis, Tumor Burden, Ubiquitin, Xenograft Model Antitumor Assays
Abstract

TNK1 is a non-receptor tyrosine kinase with poorly understood biological function and regulation. Here, we identify TNK1 dependencies in primary human cancers. We also discover a MARK-mediated phosphorylation on TNK1 at S502 that promotes an interaction between TNK1 and 14-3-3, which sequesters TNK1 and inhibits its kinase activity. Conversely, the release of TNK1 from 14-3-3 allows TNK1 to cluster in ubiquitin-rich puncta and become active. Active TNK1 induces growth factor-independent proliferation of lymphoid cells in cell culture and mouse models. One unusual feature of TNK1 is a ubiquitin-association domain (UBA) on its C-terminus. Here, we characterize the TNK1 UBA, which has high affinity for poly-ubiquitin. Point mutations that disrupt ubiquitin binding inhibit TNK1 activity. These data suggest a mechanism in which TNK1 toggles between 14-3-3-bound (inactive) and ubiquitin-bound (active) states. Finally, we identify a TNK1 inhibitor, TP-5801, which shows nanomolar potency against TNK1-transformed cells and suppresses tumor growth in vivo.

Published
2021

35. Ensuring scientific reproducibility in bio-macromolecular modeling via extensive, automated benchmarks

Author

Koehler Leman, Julia, Lyskov, Sergey, Lewis, Steven M, Adolf-Bryfogle, Jared, Alford, Rebecca F, Barlow, Kyle, Ben-Aharon, Ziv, Farrell, Daniel, Fell, Jason, Hansen, William A, Harmalkar, Ameya, Jeliazkov, Jeliazko, Kuenze, Georg, Krys, Justyna D, Ljubetič, Ajasja, Loshbaugh, Amanda L, Maguire, Jack, Moretti, Rocco, Mulligan, Vikram Khipple, Nance, Morgan L, Nguyen, Phuong T, Ó Conchúir, Shane, Roy Burman, Shourya S, Samanta, Rituparna, Smith, Shannon T, Teets, Frank, Tiemann, Johanna KS, Watkins, Andrew, Woods, Hope, Yachnin, Brahm J, Bahl, Christopher D, Bailey-Kellogg, Chris, Baker, David, Das, Rhiju, DiMaio, Frank, Khare, Sagar D, Kortemme, Tanja, Labonte, Jason W, Lindorff-Larsen, Kresten, Meiler, Jens, Schief, William, Schueler-Furman, Ora, Siegel, Justin B, Stein, Amelie, Yarov-Yarovoy, Vladimir, Kuhlman, Brian, Leaver-Fay, Andrew, Gront, Dominik, Gray, Jeffrey J, and Bonneau, Richard

Subjects
Information and Computing Sciences, Software Engineering, Networking and Information Technology R&D (NITRD), Bioengineering, Benchmarking, Binding Sites, Humans, Ligands, Macromolecular Substances, Molecular Docking Simulation, Protein Binding, Proteins, Reproducibility of Results, Software
Abstract

Each year vast international resources are wasted on irreproducible research. The scientific community has been slow to adopt standard software engineering practices, despite the increases in high-dimensional data, complexities of workflows, and computational environments. Here we show how scientific software applications can be created in a reproducible manner when simple design goals for reproducibility are met. We describe the implementation of a test server framework and 40 scientific benchmarks, covering numerous applications in Rosetta bio-macromolecular modeling. High performance computing cluster integration allows these benchmarks to run continuously and automatically. Detailed protocol captures are useful for developers and users of Rosetta and other macromolecular modeling tools. The framework and design concepts presented here are valuable for developers and users of any type of scientific software and for the scientific community to create reproducible methods. Specific examples highlight the utility of this framework, and the comprehensive documentation illustrates the ease of adding new tests in a matter of hours.

Published
2021

36. Centennial response of Greenland's three largest outlet glaciers.

Author

Khan, Shfaqat A, Bjørk, Anders A, Bamber, Jonathan L, Morlighem, Mathieu, Bevis, Michael, Kjær, Kurt H, Mouginot, Jérémie, Løkkegaard, Anja, Holland, David M, Aschwanden, Andy, Zhang, Bao, Helm, Veit, Korsgaard, Niels J, Colgan, William, Larsen, Nicolaj K, Liu, Lin, Hansen, Karina, Barletta, Valentina, Dahl-Jensen, Trine S, Søndergaard, Anne Sofie, Csatho, Beata M, Sasgen, Ingo, Box, Jason, and Schenk, Toni

Abstract

The Greenland Ice Sheet is the largest land ice contributor to sea level rise. This will continue in the future but at an uncertain rate and observational estimates are limited to the last few decades. Understanding the long-term glacier response to external forcing is key to improving projections. Here we use historical photographs to calculate ice loss from 1880-2012 for Jakobshavn, Helheim, and Kangerlussuaq glacier. We estimate ice loss corresponding to a sea level rise of 8.1 ± 1.1 millimetres from these three glaciers. Projections of mass loss for these glaciers, using the worst-case scenario, Representative Concentration Pathways 8.5, suggest a sea level contribution of 9.1-14.9 mm by 2100. RCP8.5 implies an additional global temperature increase of 3.7 °C by 2100, approximately four times larger than that which has taken place since 1880. We infer that projections forced by RCP8.5 underestimate glacier mass loss which could exceed this worst-case scenario.

Published
2020

37. A comparative genomics study of 23 Aspergillus species from section Flavi.

Author

Kjærbølling, Inge, Vesth, Tammi, Frisvad, Jens C, Nybo, Jane L, Theobald, Sebastian, Kildgaard, Sara, Petersen, Thomas Isbrandt, Kuo, Alan, Sato, Atsushi, Lyhne, Ellen K, Kogle, Martin E, Wiebenga, Ad, Kun, Roland S, Lubbers, Ronnie JM, Mäkelä, Miia R, Barry, Kerrie, Chovatia, Mansi, Clum, Alicia, Daum, Chris, Haridas, Sajeet, He, Guifen, LaButti, Kurt, Lipzen, Anna, Mondo, Stephen, Pangilinan, Jasmyn, Riley, Robert, Salamov, Asaf, Simmons, Blake A, Magnuson, Jon K, Henrissat, Bernard, Mortensen, Uffe H, Larsen, Thomas O, de Vries, Ronald P, Grigoriev, Igor V, Machida, Masayuki, Baker, Scott E, and Andersen, Mikael R

Subjects
Aspergillus flavus, Aspergillus oryzae, Crops, Agricultural, Fungal Proteins, DNA, Fungal, Bioreactors, Genomics, Phylogeny, Plant Diseases, Fermentation, Phenotype, Genome, Fungal, Multigene Family, Carbohydrate Metabolism, Metabolic Networks and Pathways, Secondary Metabolism, Fermented Foods and Beverages
Abstract

Section Flavi encompasses both harmful and beneficial Aspergillus species, such as Aspergillus oryzae, used in food fermentation and enzyme production, and Aspergillus flavus, food spoiler and mycotoxin producer. Here, we sequence 19 genomes spanning section Flavi and compare 31 fungal genomes including 23 Flavi species. We reassess their phylogenetic relationships and show that the closest relative of A. oryzae is not A. flavus, but A. minisclerotigenes or A. aflatoxiformans and identify high genome diversity, especially in sub-telomeric regions. We predict abundant CAZymes (598 per species) and prolific secondary metabolite gene clusters (73 per species) in section Flavi. However, the observed phenotypes (growth characteristics, polysaccharide degradation) do not necessarily correlate with inferences made from the predicted CAZyme content. Our work, including genomic analyses, phenotypic assays, and identification of secondary metabolites, highlights the genetic and metabolic diversity within section Flavi.

Published
2020

39. Modeling of waning immunity after SARS-CoV-2 vaccination and influencing factors

Author

Pérez-Alós, Laura, Armenteros, Jose Juan Almagro, Madsen, Johannes Roth, Hansen, Cecilie Bo, Jarlhelt, Ida, Hamm, Sebastian Rask, Heftdal, Line Dam, Pries-Heje, Mia Marie, Møller, Dina Leth, Fogh, Kamille, Hasselbalch, Rasmus Bo, Rosbjerg, Anne, Brunak, Søren, Sørensen, Erik, Larsen, Margit Anita Hørup, Ostrowski, Sisse Rye, Frikke-Schmidt, Ruth, Bayarri-Olmos, Rafael, Hilsted, Linda Maria, Iversen, Kasper Karmark, Bundgaard, Henning, Nielsen, Susanne Dam, and Garred, Peter

Published
2022
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40. Identification of risk loci for primary aldosteronism in genome-wide association studies

Author

Le Floch, Edith, Cosentino, Teresa, Larsen, Casper K., Beuschlein, Felix, Reincke, Martin, Amar, Laurence, Rossi, Gian-Paolo, De Sousa, Kelly, Baron, Stéphanie, Chantalat, Sophie, Saintpierre, Benjamin, Lenzini, Livia, Frouin, Arthur, Giscos-Douriez, Isabelle, Ferey, Matthis, Abdellatif, Alaa B., Meatchi, Tchao, Empana, Jean-Philippe, Jouven, Xavier, Gieger, Christian, Waldenberger, Melanie, Peters, Annette, Cusi, Daniele, Salvi, Erika, Meneton, Pierre, Touvier, Mathilde, Deschasaux, Mélanie, Druesne-Pecollo, Nathalie, Boulkroun, Sheerazed, Fernandes-Rosa, Fabio L., Deleuze, Jean-François, Jeunemaitre, Xavier, and Zennaro, Maria-Christina

Published
2022
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41. Biomarkers of nanomaterials hazard from multi-layer data

Author

Fortino, Vittorio, Kinaret, Pia Anneli Sofia, Fratello, Michele, Serra, Angela, Saarimäki, Laura Aliisa, Gallud, Audrey, Gupta, Govind, Vales, Gerard, Correia, Manuel, Rasool, Omid, Ytterberg, Jimmy, Monopoli, Marco, Skoog, Tiina, Ritchie, Peter, Moya, Sergio, Vázquez-Campos, Socorro, Handy, Richard, Grafström, Roland, Tran, Lang, Zubarev, Roman, Lahesmaa, Riitta, Dawson, Kenneth, Loeschner, Katrin, Larsen, Erik Husfeldt, Krombach, Fritz, Norppa, Hannu, Kere, Juha, Savolainen, Kai, Alenius, Harri, Fadeel, Bengt, and Greco, Dario

Published
2022
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42. Assembly and coherent control of a register of nuclear spin qubits

Author

Barnes, Katrina, Battaglino, Peter, Bloom, Benjamin J., Cassella, Kayleigh, Coxe, Robin, Crisosto, Nicole, King, Jonathan P., Kondov, Stanimir S., Kotru, Krish, Larsen, Stuart C., Lauigan, Joseph, Lester, Brian J., McDonald, Mickey, Megidish, Eli, Narayanaswami, Sandeep, Nishiguchi, Ciro, Notermans, Remy, Peng, Lucas S., Ryou, Albert, Wu, Tsung-Yao, and Yarwood, Michael

Published
2022
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44. Dissociable multi-scale patterns of development in personalized brain networks

Author

Pines, Adam R., Larsen, Bart, Cui, Zaixu, Sydnor, Valerie J., Bertolero, Maxwell A., Adebimpe, Azeez, Alexander-Bloch, Aaron F., Davatzikos, Christos, Fair, Damien A., Gur, Ruben C., Gur, Raquel E., Li, Hongming, Milham, Michael P., Moore, Tyler M., Murtha, Kristin, Parkes, Linden, Thompson-Schill, Sharon L., Shanmugan, Sheila, Shinohara, Russell T., Weinstein, Sarah M., Bassett, Danielle S., Fan, Yong, and Satterthwaite, Theodore D.

Published
2022
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46. Convergent Akt activation drives acquired EGFR inhibitor resistance in lung cancer.

Author

Jacobsen, Kirstine, Bertran-Alamillo, Jordi, Molina, Miguel Angel, Teixidó, Cristina, Karachaliou, Niki, Pedersen, Martin Haar, Castellví, Josep, Garzón, Mónica, Codony-Servat, Carles, Codony-Servat, Jordi, Giménez-Capitán, Ana, Drozdowskyj, Ana, Viteri, Santiago, Larsen, Martin R, Lassen, Ulrik, Felip, Enriqueta, Bivona, Trever G, Ditzel, Henrik J, and Rosell, Rafael

Subjects
Cell Line, Tumor, Animals, Humans, Mice, Mice, SCID, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Receptor, Epidermal Growth Factor, DNA Mutational Analysis, Neoplasm Transplantation, Proteomics, Signal Transduction, Apoptosis, Enzyme Activation, Drug Resistance, Neoplasm, Mutation, Female, Proto-Oncogene Proteins c-akt, ErbB Receptors, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, Drug Resistance, Neoplasm, SCID
Abstract

Non-small-cell lung cancer patients with activating epidermal growth factor receptor (EGFR) mutations typically benefit from EGFR tyrosine kinase inhibitor treatment. However, virtually all patients succumb to acquired EGFR tyrosine kinase inhibitor resistance that occurs via diverse mechanisms. The diversity and unpredictability of EGFR tyrosine kinase inhibitor resistance mechanisms presents a challenge for developing new treatments to overcome EGFR tyrosine kinase inhibitor resistance. Here, we show that Akt activation is a convergent feature of acquired EGFR tyrosine kinase inhibitor resistance, across a spectrum of diverse, established upstream resistance mechanisms. Combined treatment with an EGFR tyrosine kinase inhibitor and Akt inhibitor causes apoptosis and synergistic growth inhibition in multiple EGFR tyrosine kinase inhibitor-resistant non-small-cell lung cancer models. Moreover, phospho-Akt levels are increased in most clinical specimens obtained from EGFR-mutant non-small-cell lung cancer patients with acquired EGFR tyrosine kinase inhibitor resistance. Our findings provide a rationale for clinical trials testing Akt and EGFR inhibitor co-treatment in patients with elevated phospho-Akt levels to therapeutically combat the heterogeneity of EGFR tyrosine kinase inhibitor resistance mechanisms.EGFR-mutant non-small cell lung cancer are often resistant to EGFR tyrosine kinase inhibitor treatment. In this study, the authors show that resistant tumors display high Akt activation and that a combined treatment with AKT inhibitors causes synergistic tumour growth inhibition in vitro and in vivo.

Published
2017

47. Agricultural pesticide use and adverse birth outcomes in the San Joaquin Valley of California.

Author

Larsen, Ashley E, Gaines, Steven D, and Deschênes, Olivier

Subjects
Humans, Prenatal Exposure Delayed Effects, Birth Weight, Fetal Weight, Pesticides, Environmental Exposure, Maternal Exposure, Fetal Development, Pregnancy, Dose-Response Relationship, Drug, Agriculture, Infant, Newborn, California, Female, Dose-Response Relationship, Drug, Infant, Newborn, Rural Health, Perinatal Period - Conditions Originating in Perinatal Period, Infant Mortality, Climate-Related Exposures and Conditions, Pediatric Research Initiative, Pediatric, Reproductive Health and Childbirth, MD Multidisciplinary
Abstract

Virtually all agricultural communities worldwide are exposed to agricultural pesticides. Yet, the health consequences of such exposure are poorly understood, and the scientific literature remains ambiguous. Using individual birth and demographic characteristics for over 500 000 birth observations between 1997-2011 in the agriculturally dominated San Joaquin Valley, California, we statistically investigate if residential agricultural pesticide exposure during gestation, by trimester, and by toxicity influences birth weight, gestational length, or birth abnormalities. Overall, our analysis indicates that agricultural pesticide exposure increases adverse birth outcomes by 5-9%, but only among the population exposed to very high quantities of pesticides (e.g., top 5th percentile, i.e., ~4200 kg applied over gestation). Thus, policies and interventions targeting the extreme right tail of the pesticide distribution near human habitation could largely eliminate the adverse birth outcomes associated with agricultural pesticide exposure documented in this study.The health consequences of exposure to pesticides are uncertain and subject to much debate. Here, the effect of exposure during pregnancy is investigated in an agriculturally dominated residential area, showing that an increase in adverse birth outcomes is observed with very high levels of pesticide exposure.

Published
2017

48. Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia.

Author

Gu, Zhaohui, Churchman, Michelle, Roberts, Kathryn, Li, Yongjin, Liu, Yu, Harvey, Richard C, McCastlain, Kelly, Reshmi, Shalini C, Payne-Turner, Debbie, Iacobucci, Ilaria, Shao, Ying, Chen, I-Ming, Valentine, Marcus, Pei, Deqing, Mungall, Karen L, Mungall, Andrew J, Ma, Yussanne, Moore, Richard, Marra, Marco, Stonerock, Eileen, Gastier-Foster, Julie M, Devidas, Meenakshi, Dai, Yunfeng, Wood, Brent, Borowitz, Michael, Larsen, Eric E, Maloney, Kelly, Mattano, Leonard A, Angiolillo, Anne, Salzer, Wanda L, Burke, Michael J, Gianni, Francesca, Spinelli, Orietta, Radich, Jerald P, Minden, Mark D, Moorman, Anthony V, Patel, Bella, Fielding, Adele K, Rowe, Jacob M, Luger, Selina M, Bhatia, Ravi, Aldoss, Ibrahim, Forman, Stephen J, Kohlschmidt, Jessica, Mrózek, Krzysztof, Marcucci, Guido, Bloomfield, Clara D, Stock, Wendy, Kornblau, Steven, Kantarjian, Hagop M, Konopleva, Marina, Paietta, Elisabeth, Willman, Cheryl L, Loh, Mignon L, Hunger, Stephen P, and Mullighan, Charles G

Subjects
NIH 3T3 Cells, Animals, Humans, Mice, Luciferases, Oncogene Proteins, Fusion, Treatment Outcome, Sequence Analysis, RNA, Genomics, Gene Expression Regulation, Leukemic, Gene Rearrangement, Base Sequence, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Histone Deacetylase Inhibitors, Transcriptome, MEF2 Transcription Factors, Genetics, Pediatric Cancer, Cancer, Pediatric, 2.1 Biological and endogenous factors
Abstract

Chromosomal rearrangements are initiating events in acute lymphoblastic leukaemia (ALL). Here using RNA sequencing of 560 ALL cases, we identify rearrangements between MEF2D (myocyte enhancer factor 2D) and five genes (BCL9, CSF1R, DAZAP1, HNRNPUL1 and SS18) in 22 B progenitor ALL (B-ALL) cases with a distinct gene expression profile, the most common of which is MEF2D-BCL9. Examination of an extended cohort of 1,164 B-ALL cases identified 30 cases with MEF2D rearrangements, which include an additional fusion partner, FOXJ2; thus, MEF2D-rearranged cases comprise 5.3% of cases lacking recurring alterations. MEF2D-rearranged ALL is characterized by a distinct immunophenotype, DNA copy number alterations at the rearrangement sites, older diagnosis age and poor outcome. The rearrangements result in enhanced MEF2D transcriptional activity, lymphoid transformation, activation of HDAC9 expression and sensitive to histone deacetylase inhibitor treatment. Thus, MEF2D-rearranged ALL represents a distinct form of high-risk leukaemia, for which new therapeutic approaches should be considered.

Published
2016

49. A general strategy for expanding polymerase function by droplet microfluidics.

Author

Larsen, Andrew C, Dunn, Matthew R, Hatch, Andrew, Sau, Sujay P, Youngbull, Cody, and Chaput, John C

Subjects
Cells, Immobilized, Escherichia coli, DNA-Directed DNA Polymerase, Monosaccharides, Nucleic Acids, Biological Assay, Protein Engineering, Microfluidics, Base Pairing, Biomimetic Materials, Optical Devices, Cells, Immobilized, Genetics, Bioengineering, Biotechnology, Generic Health Relevance
Abstract

Polymerases that synthesize artificial genetic polymers hold great promise for advancing future applications in synthetic biology. However, engineering natural polymerases to replicate unnatural genetic polymers is a challenging problem. Here we present droplet-based optical polymerase sorting (DrOPS) as a general strategy for expanding polymerase function that employs an optical sensor to monitor polymerase activity inside the microenvironment of a uniform synthetic compartment generated by microfluidics. We validated this approach by performing a complete cycle of encapsulation, sorting and recovery on a doped library and observed an enrichment of ∼1,200-fold for a model engineered polymerase. We then applied our method to evolve a manganese-independent α-L-threofuranosyl nucleic acid (TNA) polymerase that functions with >99% template-copying fidelity. Based on our findings, we suggest that DrOPS is a versatile tool that could be used to evolve any polymerase function, where optical detection can be achieved by Watson-Crick base pairing.

Published
2016

50. Inherited coding variants at the CDKN2A locus influence susceptibility to acute lymphoblastic leukaemia in children.

Author

Xu, Heng, Zhang, Hui, Yang, Wenjian, Yadav, Rachita, Morrison, Alanna C, Qian, Maoxiang, Devidas, Meenakshi, Liu, Yu, Perez-Andreu, Virginia, Zhao, Xujie, Gastier-Foster, Julie M, Lupo, Philip J, Neale, Geoff, Raetz, Elizabeth, Larsen, Eric, Bowman, W Paul, Carroll, William L, Winick, Naomi, Williams, Richard, Hansen, Torben, Holm, Jens-Christian, Mardis, Elaine, Fulton, Robert, Pui, Ching-Hon, Zhang, Jinghui, Mullighan, Charles G, Evans, William E, Hunger, Stephen P, Gupta, Ramneek, Schmiegelow, Kjeld, Loh, Mignon L, Relling, Mary V, and Yang, Jun J

Subjects
Hematopoietic Stem Cells, Animals, Humans, Mice, Genetic Predisposition to Disease, DNA-Binding Proteins, Transcription Factors, Case-Control Studies, Mutagenesis, Site-Directed, Genotype, Germ-Line Mutation, Mutation, Missense, Child, Cyclin-Dependent Kinase Inhibitor p16, Cyclin-Dependent Kinase Inhibitor p15, Ikaros Transcription Factor, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Genetic Variation, Genome-Wide Association Study, HEK293 Cells, Mutagenesis, Site-Directed, Mutation, Missense
Abstract

There is increasing evidence from genome-wide association studies for a strong inherited genetic basis of susceptibility to acute lymphoblastic leukaemia (ALL) in children, yet the effects of protein-coding variants on ALL risk have not been systematically evaluated. Here we show a missense variant in CDKN2A associated with the development of ALL at genome-wide significance (rs3731249, P=9.4 × 10(-23), odds ratio=2.23). Functional studies indicate that this hypomorphic variant results in reduced tumour suppressor function of p16(INK4A), increases the susceptibility to leukaemic transformation of haematopoietic progenitor cells, and is preferentially retained in ALL tumour cells. Resequencing the CDKN2A-CDKN2B locus in 2,407 childhood ALL cases reveals 19 additional putative functional germline variants. These results provide direct functional evidence for the influence of inherited genetic variation on ALL risk, highlighting the important and complex roles of CDKN2A-CDKN2B tumour suppressors in leukaemogenesis.

Published
2015

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