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1. 100 ancient genomes show repeated population turnovers in Neolithic Denmark

Author: Allentoft, Morten E, Sikora, Martin, Fischer, Anders, Sjögren, Karl-Göran, Ingason, Andrés, Macleod, Ruairidh, Rosengren, Anders, Schulz Paulsson, Bettina, Jørkov, Marie Louise Schjellerup, Novosolov, Maria, Stenderup, Jesper, Price, T Douglas, Fischer Mortensen, Morten, Nielsen, Anne Birgitte, Ulfeldt Hede, Mikkel, Sørensen, Lasse, Nielsen, Poul Otto, Rasmussen, Peter, Jensen, Theis Zetner Trolle, Refoyo-Martínez, Alba, Irving-Pease, Evan K, Barrie, William, Pearson, Alice, Sousa da Mota, Bárbara, Demeter, Fabrice, Henriksen, Rasmus A, Vimala, Tharsika, McColl, Hugh, Vaughn, Andrew, Vinner, Lasse, Renaud, Gabriel, Stern, Aaron, Johannsen, Niels Nørkjær, Ramsøe, Abigail Daisy, Schork, Andrew Joseph, Ruter, Anthony, Gotfredsen, Anne Birgitte, Henning Nielsen, Bjarne, Brinch Petersen, Erik, Kannegaard, Esben, Hansen, Jesper, Buck Pedersen, Kristoffer, Pedersen, Lisbeth, Klassen, Lutz, Meldgaard, Morten, Johansen, Morten, Uldum, Otto Christian, Lotz, Per, Lysdahl, Per, Bangsgaard, Pernille, Petersen, Peter Vang, Maring, Rikke, Iversen, Rune, Wåhlin, Sidsel, Anker Sørensen, Søren, Andersen, Søren H, Jørgensen, Thomas, Lynnerup, Niels, Lawson, Daniel J, Rasmussen, Simon, Korneliussen, Thorfinn Sand, Kjær, Kurt H, Durbin, Richard, Nielsen, Rasmus, Delaneau, Olivier, Werge, Thomas, Kristiansen, Kristian, and Willerslev, Eske
Subjects: Biological Sciences, Genetics, History, Heritage and Archaeology, Human Society, Archaeology, Historical Studies, Anthropology, Humans, Genomics, Genotype, Denmark, Emigrants and Immigrants, Scandinavians and Nordic People, General Science & Technology
Abstract: Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1-4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5-7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.
Published: 2024

2. Population genomics of post-glacial western Eurasia

Author: Allentoft, Morten E, Sikora, Martin, Refoyo-Martínez, Alba, Irving-Pease, Evan K, Fischer, Anders, Barrie, William, Ingason, Andrés, Stenderup, Jesper, Sjögren, Karl-Göran, Pearson, Alice, Sousa da Mota, Bárbara, Schulz Paulsson, Bettina, Halgren, Alma, Macleod, Ruairidh, Jørkov, Marie Louise Schjellerup, Demeter, Fabrice, Sørensen, Lasse, Nielsen, Poul Otto, Henriksen, Rasmus A, Vimala, Tharsika, McColl, Hugh, Margaryan, Ashot, Ilardo, Melissa, Vaughn, Andrew, Fischer Mortensen, Morten, Nielsen, Anne Birgitte, Ulfeldt Hede, Mikkel, Johannsen, Niels Nørkjær, Rasmussen, Peter, Vinner, Lasse, Renaud, Gabriel, Stern, Aaron, Jensen, Theis Zetner Trolle, Scorrano, Gabriele, Schroeder, Hannes, Lysdahl, Per, Ramsøe, Abigail Daisy, Skorobogatov, Andrei, Schork, Andrew Joseph, Rosengren, Anders, Ruter, Anthony, Outram, Alan, Timoshenko, Aleksey A, Buzhilova, Alexandra, Coppa, Alfredo, Zubova, Alisa, Silva, Ana Maria, Hansen, Anders J, Gromov, Andrey, Logvin, Andrey, Gotfredsen, Anne Birgitte, Henning Nielsen, Bjarne, González-Rabanal, Borja, Lalueza-Fox, Carles, McKenzie, Catriona J, Gaunitz, Charleen, Blasco, Concepción, Liesau, Corina, Martinez-Labarga, Cristina, Pozdnyakov, Dmitri V, Cuenca-Solana, David, Lordkipanidze, David O, En’shin, Dmitri, Salazar-García, Domingo C, Price, T Douglas, Borić, Dušan, Kostyleva, Elena, Veselovskaya, Elizaveta V, Usmanova, Emma R, Cappellini, Enrico, Brinch Petersen, Erik, Kannegaard, Esben, Radina, Francesca, Eylem Yediay, Fulya, Duday, Henri, Gutiérrez-Zugasti, Igor, Merts, Ilya, Potekhina, Inna, Shevnina, Irina, Altinkaya, Isin, Guilaine, Jean, Hansen, Jesper, Aura Tortosa, Joan Emili, Zilhão, João, Vega, Jorge, Buck Pedersen, Kristoffer, Tunia, Krzysztof, Zhao, Lei, Mylnikova, Liudmila N, Larsson, Lars, Metz, Laure, Yepiskoposyan, Levon, Pedersen, Lisbeth, Sarti, Lucia, Orlando, Ludovic, Slimak, Ludovic, Klassen, Lutz, Blank, Malou, González-Morales, Manuel, and Silvestrini, Mara
Subjects: Biological Sciences, Genetics, History, Heritage and Archaeology, Human Society, Historical Studies, Anthropology, Biotechnology, Humans, Genomics, Diploidy, Agriculture, Europe, Metagenomics, General Science & Technology
Abstract: Western Eurasia witnessed several large-scale human migrations during the Holocene1-5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes-mainly from the Mesolithic and Neolithic periods-from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a 'great divide' genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 BP, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 BP, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a 'Neolithic steppe' cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
Published: 2024

3. Projected land ice contributions to twenty-first-century sea level rise

Author: Edwards, Tamsin L, Nowicki, Sophie, Marzeion, Ben, Hock, Regine, Goelzer, Heiko, Seroussi, Hélène, Jourdain, Nicolas C, Slater, Donald A, Turner, Fiona E, Smith, Christopher J, McKenna, Christine M, Simon, Erika, Abe-Ouchi, Ayako, Gregory, Jonathan M, Larour, Eric, Lipscomb, William H, Payne, Antony J, Shepherd, Andrew, Agosta, Cécile, Alexander, Patrick, Albrecht, Torsten, Anderson, Brian, Asay-Davis, Xylar, Aschwanden, Andy, Barthel, Alice, Bliss, Andrew, Calov, Reinhard, Chambers, Christopher, Champollion, Nicolas, Choi, Youngmin, Cullather, Richard, Cuzzone, Joshua, Dumas, Christophe, Felikson, Denis, Fettweis, Xavier, Fujita, Koji, Galton-Fenzi, Benjamin K, Gladstone, Rupert, Golledge, Nicholas R, Greve, Ralf, Hattermann, Tore, Hoffman, Matthew J, Humbert, Angelika, Huss, Matthias, Huybrechts, Philippe, Immerzeel, Walter, Kleiner, Thomas, Kraaijenbrink, Philip, Le clec’h, Sébastien, Lee, Victoria, Leguy, Gunter R, Little, Christopher M, Lowry, Daniel P, Malles, Jan-Hendrik, Martin, Daniel F, Maussion, Fabien, Morlighem, Mathieu, O’Neill, James F, Nias, Isabel, Pattyn, Frank, Pelle, Tyler, Price, Stephen F, Quiquet, Aurélien, Radić, Valentina, Reese, Ronja, Rounce, David R, Rückamp, Martin, Sakai, Akiko, Shafer, Courtney, Schlegel, Nicole-Jeanne, Shannon, Sarah, Smith, Robin S, Straneo, Fiammetta, Sun, Sainan, Tarasov, Lev, Trusel, Luke D, Van Breedam, Jonas, van de Wal, Roderik, van den Broeke, Michiel, Winkelmann, Ricarda, Zekollari, Harry, Zhao, Chen, Zhang, Tong, and Zwinger, Thomas
Subjects: Earth Sciences, Physical Geography and Environmental Geoscience, Climate Action, General Science & Technology
Abstract: The land ice contribution to global mean sea level rise has not yet been predicted1 using ice sheet and glacier models for the latest set of socio-economic scenarios, nor using coordinated exploration of uncertainties arising from the various computer models involved. Two recent international projects generated a large suite of projections using multiple models2-8, but primarily used previous-generation scenarios9 and climate models10, and could not fully explore known uncertainties. Here we estimate probability distributions for these projections under the new scenarios11,12 using statistical emulation of the ice sheet and glacier models. We find that limiting global warming to 1.5 degrees Celsius would halve the land ice contribution to twenty-first-century sea level rise, relative to current emissions pledges. The median decreases from 25 to 13 centimetres sea level equivalent (SLE) by 2100, with glaciers responsible for half the sea level contribution. The projected Antarctic contribution does not show a clear response to the emissions scenario, owing to uncertainties in the competing processes of increasing ice loss and snowfall accumulation in a warming climate. However, under risk-averse (pessimistic) assumptions, Antarctic ice loss could be five times higher, increasing the median land ice contribution to 42 centimetres SLE under current policies and pledges, with the 95th percentile projection exceeding half a metre even under 1.5 degrees Celsius warming. This would severely limit the possibility of mitigating future coastal flooding. Given this large range (between 13 centimetres SLE using the main projections under 1.5 degrees Celsius warming and 42 centimetres SLE using risk-averse projections under current pledges), adaptation planning for twenty-first-century sea level rise must account for a factor-of-three uncertainty in the land ice contribution until climate policies and the Antarctic response are further constrained.
Published: 2021

4. SARS-CoV-2 evolution during treatment of chronic infection

Author: Baker, Stephen, Dougan, Gordon, Hess, Christoph, Kingston, Nathalie, Lehner, Paul J, Lyons, Paul A, Matheson, Nicholas J, Owehand, Willem H, Saunders, Caroline, Summers, Charlotte, Thaventhiran, James ED, Toshner, Mark, Weekes, Michael P, Bucke, Ashlea, Calder, Jo, Canna, Laura, Domingo, Jason, Elmer, Anne, Fuller, Stewart, Harris, Julie, Hewitt, Sarah, Kennet, Jane, Jose, Sherly, Kourampa, Jenny, Meadows, Anne, O’Brien, Criona, Price, Jane, Publico, Cherry, Rastall, Rebecca, Ribeiro, Carla, Rowlands, Jane, Ruffolo, Valentina, Tordesillas, Hugo, Bullman, Ben, Dunmore, Benjamin J, Fawke, Stuart, Gräf, Stefan, Hodgson, Josh, Huang, Christopher, Hunter, Kelvin, Jones, Emma, Legchenko, Ekaterina, Matara, Cecilia, Martin, Jennifer, Mescia, Federica, O’Donnell, Ciara, Pointon, Linda, Pond, Nicole, Shih, Joy, Sutcliffe, Rachel, Tilly, Tobias, Treacy, Carmen, Tong, Zhen, Wood, Jennifer, Wylot, Marta, Bergamaschi, Laura, Betancourt, Ariana, Bower, Georgie, Cossetti, Chiara, De Sa, Aloka, Epping, Madeline, Gleadall, Nick, Grenfell, Richard, Hinch, Andrew, Huhn, Oisin, Jackson, Sarah, Jarvis, Isobel, Lewis, Daniel, Marsden, Joe, Nice, Francesca, Okecha, Georgina, Omarjee, Ommar, Perera, Marianne, Richoz, Nathan, Romashova, Veronika, Yarkoni, Natalia Savinykh, Sharma, Rahul, Stefanucci, Luca, Stephens, Jonathan, Strezlecki, Mateusz, Turner, Lori, De Bie, Eckart MDD, Bunclark, Katherine, Josipovic, Masa, Mackay, Michael, Rossi, Sabrina, Selvan, Mayurun, Spencer, Sarah, Yong, Cissy, Ansaripour, Ali, Michael, Alice, Mwaura, Lucy, Patterson, Caroline, Polwarth, Gary, Polgarova, Petra, di Stefano, Giovanni, Fahey, Codie, Michel, Rachel, and Bong, Sze-How
Subjects: Immunization, Pneumonia & Influenza, Lung, Prevention, Genetics, Vaccine Related, Biotechnology, Pneumonia, Emerging Infectious Diseases, Biodefense, Infectious Diseases, 2.1 Biological and endogenous factors, Aetiology, Infection, Good Health and Well Being, Adenosine Monophosphate, Aged, Alanine, Antibodies, Neutralizing, Antibodies, Viral, COVID-19, Chronic Disease, Evolution, Molecular, Genome, Viral, High-Throughput Nucleotide Sequencing, Humans, Immune Evasion, Immune Tolerance, Immunization, Passive, Immunosuppression Therapy, Male, Mutagenesis, Mutant Proteins, Mutation, Phylogeny, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Time Factors, Viral Load, Virus Shedding, COVID-19 Drug Treatment, COVID-19 Serotherapy, CITIID-NIHR BioResource COVID-19 Collaboration, COVID-19 Genomics UK (COG-UK) Consortium, General Science & Technology
Abstract: The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for virus infection through the engagement of the human ACE2 protein1 and is a major antibody target. Here we show that chronic infection with SARS-CoV-2 leads to viral evolution and reduced sensitivity to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma, by generating whole-genome ultra-deep sequences for 23 time points that span 101 days and using in vitro techniques to characterize the mutations revealed by sequencing. There was little change in the overall structure of the viral population after two courses of remdesivir during the first 57 days. However, after convalescent plasma therapy, we observed large, dynamic shifts in the viral population, with the emergence of a dominant viral strain that contained a substitution (D796H) in the S2 subunit and a deletion (ΔH69/ΔV70) in the S1 N-terminal domain of the spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype were reduced in frequency, before returning during a final, unsuccessful course of convalescent plasma treatment. In vitro, the spike double mutant bearing both ΔH69/ΔV70 and D796H conferred modestly decreased sensitivity to convalescent plasma, while maintaining infectivity levels that were similar to the wild-type virus.The spike substitution mutant D796H appeared to be the main contributor to the decreased susceptibility to neutralizing antibodies, but this mutation resulted in an infectivity defect. The spike deletion mutant ΔH69/ΔV70 had a twofold higher level of infectivity than wild-type SARS-CoV-2, possibly compensating for the reduced infectivity of the D796H mutation. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy, which is associated with the emergence of viral variants that show evidence of reduced susceptibility to neutralizing antibodies in immunosuppressed individuals.
Published: 2021

5. Population genomics of the Viking world

Author: Margaryan, Ashot, Lawson, Daniel J, Sikora, Martin, Racimo, Fernando, Rasmussen, Simon, Moltke, Ida, Cassidy, Lara M, Jørsboe, Emil, Ingason, Andrés, Pedersen, Mikkel W, Korneliussen, Thorfinn, Wilhelmson, Helene, Buś, Magdalena M, de Barros Damgaard, Peter, Martiniano, Rui, Renaud, Gabriel, Bhérer, Claude, Moreno-Mayar, J Víctor, Fotakis, Anna K, Allen, Marie, Allmäe, Raili, Molak, Martyna, Cappellini, Enrico, Scorrano, Gabriele, McColl, Hugh, Buzhilova, Alexandra, Fox, Allison, Albrechtsen, Anders, Schütz, Berit, Skar, Birgitte, Arcini, Caroline, Falys, Ceri, Jonson, Charlotte Hedenstierna, Błaszczyk, Dariusz, Pezhemsky, Denis, Turner-Walker, Gordon, Gestsdóttir, Hildur, Lundstrøm, Inge, Gustin, Ingrid, Mainland, Ingrid, Potekhina, Inna, Muntoni, Italo M, Cheng, Jade, Stenderup, Jesper, Ma, Jilong, Gibson, Julie, Peets, Jüri, Gustafsson, Jörgen, Iversen, Katrine H, Simpson, Linzi, Strand, Lisa, Loe, Louise, Sikora, Maeve, Florek, Marek, Vretemark, Maria, Redknap, Mark, Bajka, Monika, Pushkina, Tamara, Søvsø, Morten, Grigoreva, Natalia, Christensen, Tom, Kastholm, Ole, Uldum, Otto, Favia, Pasquale, Holck, Per, Sten, Sabine, Arge, Símun V, Ellingvåg, Sturla, Moiseyev, Vayacheslav, Bogdanowicz, Wiesław, Magnusson, Yvonne, Orlando, Ludovic, Pentz, Peter, Jessen, Mads Dengsø, Pedersen, Anne, Collard, Mark, Bradley, Daniel G, Jørkov, Marie Louise, Arneborg, Jette, Lynnerup, Niels, Price, Neil, Gilbert, M Thomas P, Allentoft, Morten E, Bill, Jan, Sindbæk, Søren M, Hedeager, Lotte, Kristiansen, Kristian, Nielsen, Rasmus, Werge, Thomas, and Willerslev, Eske
Subjects: Biological Sciences, Genetics, History, Heritage and Archaeology, Archaeology, Historical Studies, Human Genome, Underpinning research, 1.1 Normal biological development and functioning, Alleles, Datasets as Topic, England, Evolution, Molecular, Gene Flow, Genetics, Population, Genome, Human, Genomics, Greenland, History, Medieval, Human Migration, Humans, Immunity, Ireland, Lactase, Male, Scandinavian and Nordic Countries, Selection, Genetic, Spatio-Temporal Analysis, Young Adult, General Science & Technology
Abstract: The maritime expansion of Scandinavian populations during the Viking Age (about AD 750-1050) was a far-flung transformation in world history1,2. Here we sequenced the genomes of 442 humans from archaeological sites across Europe and Greenland (to a median depth of about 1×) to understand the global influence of this expansion. We find the Viking period involved gene flow into Scandinavia from the south and east. We observe genetic structure within Scandinavia, with diversity hotspots in the south and restricted gene flow within Scandinavia. We find evidence for a major influx of Danish ancestry into England; a Swedish influx into the Baltic; and Norwegian influx into Ireland, Iceland and Greenland. Additionally, we see substantial ancestry from elsewhere in Europe entering Scandinavia during the Viking Age. Our ancient DNA analysis also revealed that a Viking expedition included close family members. By comparing with modern populations, we find that pigmentation-associated loci have undergone strong population differentiation during the past millennium, and trace positively selected loci-including the lactase-persistence allele of LCT and alleles of ANKA that are associated with the immune response-in detail. We conclude that the Viking diaspora was characterized by substantial transregional engagement: distinct populations influenced the genomic makeup of different regions of Europe, and Scandinavia experienced increased contact with the rest of the continent.
Published: 2020

6. Global chemical effects of the microbiome include new bile-acid conjugations

Author: Quinn, Robert A, Melnik, Alexey V, Vrbanac, Alison, Fu, Ting, Patras, Kathryn A, Christy, Mitchell P, Bodai, Zsolt, Belda-Ferre, Pedro, Tripathi, Anupriya, Chung, Lawton K, Downes, Michael, Welch, Ryan D, Quinn, Melissa, Humphrey, Greg, Panitchpakdi, Morgan, Weldon, Kelly C, Aksenov, Alexander, da Silva, Ricardo, Avila-Pacheco, Julian, Clish, Clary, Bae, Sena, Mallick, Himel, Franzosa, Eric A, Lloyd-Price, Jason, Bussell, Robert, Thron, Taren, Nelson, Andrew T, Wang, Mingxun, Leszczynski, Eric, Vargas, Fernando, Gauglitz, Julia M, Meehan, Michael J, Gentry, Emily, Arthur, Timothy D, Komor, Alexis C, Poulsen, Orit, Boland, Brigid S, Chang, John T, Sandborn, William J, Lim, Meerana, Garg, Neha, Lumeng, Julie C, Xavier, Ramnik J, Kazmierczak, Barbara I, Jain, Ruchi, Egan, Marie, Rhee, Kyung E, Ferguson, David, Raffatellu, Manuela, Vlamakis, Hera, Haddad, Gabriel G, Siegel, Dionicio, Huttenhower, Curtis, Mazmanian, Sarkis K, Evans, Ronald M, Nizet, Victor, Knight, Rob, and Dorrestein, Pieter C
Subjects: Biological Sciences, Biomedical and Clinical Sciences, Chemical Sciences, Microbiology, Medical Biochemistry and Metabolomics, Genetics, Digestive Diseases, Aetiology, 2.1 Biological and endogenous factors, Oral and gastrointestinal, Animals, Bile Acids and Salts, Cholic Acid, Cystic Fibrosis, Germ-Free Life, Humans, Inflammatory Bowel Diseases, Metabolomics, Mice, Microbiota, Receptors, Cytoplasmic and Nuclear, General Science & Technology
Abstract: A mosaic of cross-phylum chemical interactions occurs between all metazoans and their microbiomes. A number of molecular families that are known to be produced by the microbiome have a marked effect on the balance between health and disease1-9. Considering the diversity of the human microbiome (which numbers over 40,000 operational taxonomic units10), the effect of the microbiome on the chemistry of an entire animal remains underexplored. Here we use mass spectrometry informatics and data visualization approaches11-13 to provide an assessment of the effects of the microbiome on the chemistry of an entire mammal by comparing metabolomics data from germ-free and specific-pathogen-free mice. We found that the microbiota affects the chemistry of all organs. This included the amino acid conjugations of host bile acids that were used to produce phenylalanocholic acid, tyrosocholic acid and leucocholic acid, which have not previously been characterized despite extensive research on bile-acid chemistry14. These bile-acid conjugates were also found in humans, and were enriched in patients with inflammatory bowel disease or cystic fibrosis. These compounds agonized the farnesoid X receptor in vitro, and mice gavaged with the compounds showed reduced expression of bile-acid synthesis genes in vivo. Further studies are required to confirm whether these compounds have a physiological role in the host, and whether they contribute to gut diseases that are associated with microbiome dysbiosis.
Published: 2020

7. Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases.

Author: Lloyd-Price, Jason, Arze, Cesar, Ananthakrishnan, Ashwin N, Schirmer, Melanie, Avila-Pacheco, Julian, Poon, Tiffany W, Andrews, Elizabeth, Ajami, Nadim J, Bonham, Kevin S, Brislawn, Colin J, Casero, David, Courtney, Holly, Gonzalez, Antonio, Graeber, Thomas G, Hall, A Brantley, Lake, Kathleen, Landers, Carol J, Mallick, Himel, Plichta, Damian R, Prasad, Mahadev, Rahnavard, Gholamali, Sauk, Jenny, Shungin, Dmitry, Vázquez-Baeza, Yoshiki, White, Richard A, IBDMDB Investigators, Braun, Jonathan, Denson, Lee A, Jansson, Janet K, Knight, Rob, Kugathasan, Subra, McGovern, Dermot PB, Petrosino, Joseph F, Stappenbeck, Thaddeus S, Winter, Harland S, Clish, Clary B, Franzosa, Eric A, Vlamakis, Hera, Xavier, Ramnik J, and Huttenhower, Curtis
Subjects: IBDMDB Investigators, Animals, Humans, Viruses, Fungi, Inflammatory Bowel Diseases, Phylogeny, Species Specificity, Health, Transcriptome, Gastrointestinal Microbiome, General Science & Technology
Abstract: Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, affect several million individuals worldwide. Crohn's disease and ulcerative colitis are complex diseases that are heterogeneous at the clinical, immunological, molecular, genetic, and microbial levels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal molecular profiles of host and microbial activity during disease (up to 24 time points each; in total 2,965 stool, biopsy, and blood specimens). Here we present the results, which provide a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease activity. We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as molecular disruptions in microbial transcription (for example, among clostridia), metabolite pools (acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum. Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochemical shifts. Finally, integrative analysis identified microbial, biochemical, and host factors central to this dysregulation. The study's infrastructure resources, results, and data, which are available through the Inflammatory Bowel Disease Multi'omics Database ( http://ibdmdb.org ), provide the most comprehensive description to date of host and microbial activities in inflammatory bowel diseases.
Published: 2019

8. Repeated plague infections across six generations of Neolithic Farmers.

Author: Seersholm, Frederik Valeur, Sjögren, Karl-Göran, Koelman, Julia, Blank, Malou, Svensson, Emma M., Staring, Jacqueline, Fraser, Magdalena, Pinotti, Thomaz, McColl, Hugh, Gaunitz, Charleen, Ruiz-Bedoya, Tatiana, Granehäll, Lena, Villegas-Ramirez, Berenice, Fischer, Anders, Price, T. Douglas, Allentoft, Morten E., Iversen, Astrid K. N., Axelsson, Tony, Ahlström, Torbjörn, and Götherström, Anders
Abstract: In the period between 5,300 and 4,900 calibrated years before present (cal. bp), populations across large parts of Europe underwent a period of demographic decline1,2. However, the cause of this so-called Neolithic decline is still debated. Some argue for an agricultural crisis resulting in the decline3, others for the spread of an early form of plague4. Here we use population-scale ancient genomics to infer ancestry, social structure and pathogen infection in 108 Scandinavian Neolithic individuals from eight megalithic graves and a stone cist. We find that the Neolithic plague was widespread, detected in at least 17% of the sampled population and across large geographical distances. We demonstrate that the disease spread within the Neolithic community in three distinct infection events within a period of around 120 years. Variant graph-based pan-genomics shows that the Neolithic plague genomes retained ancestral genomic variation present in Yersinia pseudotuberculosis, including virulence factors associated with disease outcomes. In addition, we reconstruct four multigeneration pedigrees, the largest of which consists of 38 individuals spanning six generations, showing a patrilineal social organization. Lastly, we document direct genomic evidence for Neolithic female exogamy in a woman buried in a different megalithic tomb than her brothers. Taken together, our findings provide a detailed reconstruction of plague spread within a large patrilineal kinship group and identify multiple plague infections in a population dated to the beginning of the Neolithic decline.Population-scale ancient genomics are used to infer ancestry, social structure and pathogen infection in 108 Scandinavian Neolithic individuals from eight megalithic graves and a stone cist, showing that Neolithic plague was widespread. [ABSTRACT FROM AUTHOR]
Published: 2024
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9. Mutant phenotypes for thousands of bacterial genes of unknown function

Author: Price, Morgan N, Wetmore, Kelly M, Waters, R Jordan, Callaghan, Mark, Ray, Jayashree, Liu, Hualan, Kuehl, Jennifer V, Melnyk, Ryan A, Lamson, Jacob S, Suh, Yumi, Carlson, Hans K, Esquivel, Zuelma, Sadeeshkumar, Harini, Chakraborty, Romy, Zane, Grant M, Rubin, Benjamin E, Wall, Judy D, Visel, Axel, Bristow, James, Blow, Matthew J, Arkin, Adam P, and Deutschbauer, Adam M
Subjects: Microbiology, Biological Sciences, Bioinformatics and Computational Biology, Genetics, Biotechnology, Human Genome, 2.2 Factors relating to the physical environment, 1.1 Normal biological development and functioning, Generic health relevance, Bacteria, Bacterial Proteins, Conserved Sequence, DNA Repair, Genes, Bacterial, Genetic Fitness, Genome, Bacterial, Molecular Sequence Annotation, Mutant Proteins, Mutation, Phenotype, Uncertainty, General Science & Technology
Abstract: One-third of all protein-coding genes from bacterial genomes cannot be annotated with a function. Here, to investigate the functions of these genes, we present genome-wide mutant fitness data from 32 diverse bacteria across dozens of growth conditions. We identified mutant phenotypes for 11,779 protein-coding genes that had not been annotated with a specific function. Many genes could be associated with a specific condition because the gene affected fitness only in that condition, or with another gene in the same bacterium because they had similar mutant phenotypes. Of the poorly annotated genes, 2,316 had associations that have high confidence because they are conserved in other bacteria. By combining these conserved associations with comparative genomics, we identified putative DNA repair proteins; in addition, we propose specific functions for poorly annotated enzymes and transporters and for uncharacterized protein families. Our study demonstrates the scalability of microbial genetics and its utility for improving gene annotations.
Published: 2018

10. Erratum: Strains, functions and dynamics in the expanded Human Microbiome Project

Author: Lloyd-Price, Jason, Mahurkar, Anup, Rahnavard, Gholamali, Crabtree, Jonathan, Orvis, Joshua, Hall, A Brantley, Brady, Arthur, Creasy, Heather H, McCracken, Carrie, Giglio, Michelle G, McDonald, Daniel, Franzosa, Eric A, Knight, Rob, White, Owen, and Huttenhower, Curtis
Subjects: Biomedical and Clinical Sciences, Creative and Professional Writing, Creative Arts and Writing, General Science & Technology
Abstract: This corrects the article DOI: 10.1038/nature23889.
Published: 2017

11. Strains, functions and dynamics in the expanded Human Microbiome Project

Author: Lloyd-Price, Jason, Mahurkar, Anup, Rahnavard, Gholamali, Crabtree, Jonathan, Orvis, Joshua, Hall, A Brantley, Brady, Arthur, Creasy, Heather H, McCracken, Carrie, Giglio, Michelle G, McDonald, Daniel, Franzosa, Eric A, Knight, Rob, White, Owen, and Huttenhower, Curtis
Subjects: Microbiology, Biological Sciences, Genetics, Human Genome, Clinical Research, Good Health and Well Being, Datasets as Topic, Humans, Metagenome, Microbiota, Molecular Sequence Annotation, National Institutes of Health (U.S.), Organ Specificity, Phylogeny, Spatio-Temporal Analysis, Time Factors, United States, General Science & Technology
Abstract: The characterization of baseline microbial and functional diversity in the human microbiome has enabled studies of microbiome-related disease, diversity, biogeography, and molecular function. The National Institutes of Health Human Microbiome Project has provided one of the broadest such characterizations so far. Here we introduce a second wave of data from the study, comprising 1,631 new metagenomes (2,355 total) targeting diverse body sites with multiple time points in 265 individuals. We applied updated profiling and assembly methods to provide new characterizations of microbiome personalization. Strain identification revealed subspecies clades specific to body sites; it also quantified species with phylogenetic diversity under-represented in isolate genomes. Body-wide functional profiling classified pathways into universal, human-enriched, and body site-enriched subsets. Finally, temporal analysis decomposed microbial variation into rapidly variable, moderately variable, and stable subsets. This study furthers our knowledge of baseline human microbial diversity and enables an understanding of personalized microbiome function and dynamics.
Published: 2017

12. Most of the photons that reionized the Universe came from dwarf galaxies

Author: Atek, Hakim, primary, Labbé, Ivo, additional, Furtak, Lukas J., additional, Chemerynska, Iryna, additional, Fujimoto, Seiji, additional, Setton, David J., additional, Miller, Tim B., additional, Oesch, Pascal, additional, Bezanson, Rachel, additional, Price, Sedona H., additional, Dayal, Pratika, additional, Zitrin, Adi, additional, Kokorev, Vasily, additional, Weaver, John R., additional, Brammer, Gabriel, additional, Dokkum, Pieter van, additional, Williams, Christina C., additional, Cutler, Sam E., additional, Feldmann, Robert, additional, Fudamoto, Yoshinobu, additional, Greene, Jenny E., additional, Leja, Joel, additional, Maseda, Michael V., additional, Muzzin, Adam, additional, Pan, Richard, additional, Papovich, Casey, additional, Nelson, Erica J., additional, Nanayakkara, Themiya, additional, Stark, Daniel P., additional, Stefanon, Mauro, additional, Suess, Katherine A., additional, Wang, Bingjie, additional, and Whitaker, Katherine E., additional
Published: 2024
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13. A high black hole to host mass ratio in a lensed AGN in the early Universe

Author: Furtak, Lukas J., primary, Labbé, Ivo, additional, Zitrin, Adi, additional, Greene, Jenny E., additional, Dayal, Pratika, additional, Chemerynska, Iryna, additional, Kokorev, Vasily, additional, Miller, Tim B., additional, Goulding, Andy D., additional, Graaff, Anna de, additional, Bezanson, Rachel, additional, Brammer, Gabriel B., additional, Cutler, Sam E., additional, Leja, Joel, additional, Pan, Richard, additional, Price, Sedona H., additional, Wang, Bingjie, additional, Weaver, John R., additional, Whitaker, Katherine E., additional, Atek, Hakim, additional, Bogdán, Ákos, additional, Charlot, Stéphane, additional, Curtis-Lake, Emma, additional, Dokkum, Pieter van, additional, Endsley, Ryan, additional, Feldmann, Robert, additional, Fudamoto, Yoshinobu, additional, Fujimoto, Seiji, additional, Glazebrook, Karl, additional, Juneau, Stéphanie, additional, Marchesini, Danilo, additional, Maseda, Micheal V., additional, Nelson, Erica, additional, Oesch, Pascal A., additional, Plat, Adèle, additional, Setton, David J., additional, Stark, Daniel P., additional, and Williams, Christina C., additional
Published: 2024
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14. Publisher Correction: Population genomics of post-glacial western Eurasia

Author: Allentoft, Morten E., primary, Sikora, Martin, additional, Refoyo-Martínez, Alba, additional, Irving-Pease, Evan K., additional, Fischer, Anders, additional, Barrie, William, additional, Ingason, Andrés, additional, Stenderup, Jesper, additional, Sjögren, Karl-Göran, additional, Pearson, Alice, additional, Sousa da Mota, Bárbara, additional, Schulz Paulsson, Bettina, additional, Halgren, Alma, additional, Macleod, Ruairidh, additional, Jørkov, Marie Louise Schjellerup, additional, Demeter, Fabrice, additional, Sørensen, Lasse, additional, Nielsen, Poul Otto, additional, Henriksen, Rasmus A., additional, Vimala, Tharsika, additional, McColl, Hugh, additional, Margaryan, Ashot, additional, Ilardo, Melissa, additional, Vaughn, Andrew, additional, Fischer Mortensen, Morten, additional, Nielsen, Anne Birgitte, additional, Ulfeldt Hede, Mikkel, additional, Johannsen, Niels Nørkjær, additional, Rasmussen, Peter, additional, Vinner, Lasse, additional, Renaud, Gabriel, additional, Stern, Aaron, additional, Jensen, Theis Zetner Trolle, additional, Scorrano, Gabriele, additional, Schroeder, Hannes, additional, Lysdahl, Per, additional, Ramsøe, Abigail Daisy, additional, Skorobogatov, Andrei, additional, Schork, Andrew Joseph, additional, Rosengren, Anders, additional, Ruter, Anthony, additional, Outram, Alan, additional, Timoshenko, Aleksey A., additional, Buzhilova, Alexandra, additional, Coppa, Alfredo, additional, Zubova, Alisa, additional, Silva, Ana Maria, additional, Hansen, Anders J., additional, Gromov, Andrey, additional, Logvin, Andrey, additional, Gotfredsen, Anne Birgitte, additional, Henning Nielsen, Bjarne, additional, González-Rabanal, Borja, additional, Lalueza-Fox, Carles, additional, McKenzie, Catriona J., additional, Gaunitz, Charleen, additional, Blasco, Concepción, additional, Liesau, Corina, additional, Martinez-Labarga, Cristina, additional, Pozdnyakov, Dmitri V., additional, Cuenca-Solana, David, additional, Lordkipanidze, David O., additional, En’shin, Dmitri, additional, Salazar-García, Domingo C., additional, Price, T. Douglas, additional, Borić, Dušan, additional, Kostyleva, Elena, additional, Veselovskaya, Elizaveta V., additional, Usmanova, Emma R., additional, Cappellini, Enrico, additional, Brinch Petersen, Erik, additional, Kannegaard, Esben, additional, Radina, Francesca, additional, Eylem Yediay, Fulya, additional, Duday, Henri, additional, Gutiérrez-Zugasti, Igor, additional, Merts, Ilya, additional, Potekhina, Inna, additional, Shevnina, Irina, additional, Altinkaya, Isin, additional, Guilaine, Jean, additional, Hansen, Jesper, additional, Aura Tortosa, Joan Emili, additional, Zilhão, João, additional, Vega, Jorge, additional, Buck Pedersen, Kristoffer, additional, Tunia, Krzysztof, additional, Zhao, Lei, additional, Mylnikova, Liudmila N., additional, Larsson, Lars, additional, Metz, Laure, additional, Yepiskoposyan, Levon, additional, Pedersen, Lisbeth, additional, Sarti, Lucia, additional, Orlando, Ludovic, additional, Slimak, Ludovic, additional, Klassen, Lutz, additional, Blank, Malou, additional, González-Morales, Manuel, additional, Silvestrini, Mara, additional, Vretemark, Maria, additional, Nesterova, Marina S., additional, Rykun, Marina, additional, Rolfo, Mario Federico, additional, Szmyt, Marzena, additional, Przybyła, Marcin, additional, Calattini, Mauro, additional, Sablin, Mikhail, additional, Dobisíková, Miluše, additional, Meldgaard, Morten, additional, Johansen, Morten, additional, Berezina, Natalia, additional, Card, Nick, additional, Saveliev, Nikolai A., additional, Poshekhonova, Olga, additional, Rickards, Olga, additional, Lozovskaya, Olga V., additional, Gábor, Olivér, additional, Uldum, Otto Christian, additional, Aurino, Paola, additional, Kosintsev, Pavel, additional, Courtaud, Patrice, additional, Ríos, Patricia, additional, Mortensen, Peder, additional, Lotz, Per, additional, Persson, Per, additional, Bangsgaard, Pernille, additional, de Barros Damgaard, Peter, additional, Vang Petersen, Peter, additional, Martinez, Pilar Prieto, additional, Włodarczak, Piotr, additional, Smolyaninov, Roman V., additional, Maring, Rikke, additional, Menduiña, Roberto, additional, Badalyan, Ruben, additional, Iversen, Rune, additional, Turin, Ruslan, additional, Vasilyev, Sergey, additional, Wåhlin, Sidsel, additional, Borutskaya, Svetlana, additional, Skochina, Svetlana, additional, Sørensen, Søren Anker, additional, Andersen, Søren H., additional, Jørgensen, Thomas, additional, Serikov, Yuri B., additional, Molodin, Vyacheslav I., additional, Smrcka, Vaclav, additional, Merts, Victor, additional, Appadurai, Vivek, additional, Moiseyev, Vyacheslav, additional, Magnusson, Yvonne, additional, Kjær, Kurt H., additional, Lynnerup, Niels, additional, Lawson, Daniel J., additional, Sudmant, Peter H., additional, Rasmussen, Simon, additional, Korneliussen, Thorfinn Sand, additional, Durbin, Richard, additional, Nielsen, Rasmus, additional, Delaneau, Olivier, additional, Werge, Thomas, additional, Racimo, Fernando, additional, Kristiansen, Kristian, additional, and Willerslev, Eske, additional
Published: 2024
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15. A natively flexible 32-bit Arm microprocessor

Author: Biggs, John, Myers, James, Kufel, Jedrzej, Ozer, Emre, Craske, Simon, Sou, Antony, Ramsdale, Catherine, Williamson, Ken, Price, Richard, and White, Scott
Subjects: Central processing units -- Design and construction -- Forecasts and trends, Microprocessors -- Design and construction -- Forecasts and trends, Microprocessor, Microprocessor upgrade, Market trend/market analysis, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract: Nearly 50 years ago, Intel created the world's first commercially produced microprocessor--the 4004 (ref. .sup.1), a modest 4-bit CPU (central processing unit) with 2,300 transistors fabricated using 10 [mu]m process technology in silicon and capable only of simple arithmetic calculations. Since this ground-breaking achievement, there has been continuous technological development with increasing sophistication to the stage where state-of-the-art silicon 64-bit microprocessors now have 30 billion transistors (for example, the AWS Graviton2 (ref. .sup.2) microprocessor, fabricated using 7 nm process technology). The microprocessor is now so embedded within our culture that it has become a meta-invention--that is, it is a tool that allows other inventions to be realized, most recently enabling the big data analysis needed for a COVID-19 vaccine to be developed in record time. Here we report a 32-bit Arm (a reduced instruction set computing (RISC) architecture) microprocessor developed with metal-oxide thin-film transistor technology on a flexible substrate (which we call the PlasticARM). Separate from the mainstream semiconductor industry, flexible electronics operate within a domain that seamlessly integrates with everyday objects through a combination of ultrathin form factor, conformability, extreme low cost and potential for mass-scale production. PlasticARM pioneers the embedding of billions of low-cost, ultrathin microprocessors into everyday objects. Flexible electronic platforms would enable the integration of functional electronic circuitry with many everyday objects; here, a low-cost and fully flexible 32-bit microprocessor is produced., Author(s): John Biggs [sup.1] , James Myers [sup.1] , Jedrzej Kufel [sup.1] , Emre Ozer [sup.1] , Simon Craske [sup.1] , Antony Sou [sup.2] , Catherine Ramsdale [sup.2] , Ken [...]
Published: 2021
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16. Birth of protein folds and functions in the virome

Author: Nomburg, Jason, Doherty, Erin E., Price, Nathan, Bellieny-Rabelo, Daniel, Zhu, Yong K., and Doudna, Jennifer A.
Abstract: The rapid evolution of viruses generates proteins that are essential for infectivity and replication but with unknown functions, due to extreme sequence divergence1. Here, using a database of 67,715 newly predicted protein structures from 4,463 eukaryotic viral species, we found that 62% of viral proteins are structurally distinct and lack homologues in the AlphaFold database2,3. Among the remaining 38% of viral proteins, many have non-viral structural analogues that revealed surprising similarities between human pathogens and their eukaryotic hosts. Structural comparisons suggested putative functions for up to 25% of unannotated viral proteins, including those with roles in the evasion of innate immunity. In particular, RNA ligase T-like phosphodiesterases were found to resemble phage-encoded proteins that hydrolyse the host immune-activating cyclic dinucleotides 3′,3′- and 2′,3′-cyclic GMP-AMP (cGAMP). Experimental analysis showed that RNA ligase T homologues encoded by avian poxviruses similarly hydrolyse cGAMP, showing that RNA ligase T-mediated targeting of cGAMP is an evolutionarily conserved mechanism of immune evasion that is present in both bacteriophage and eukaryotic viruses. Together, the viral protein structural database and analyses presented here afford new opportunities to identify mechanisms of virus–host interactions that are common across the virome.
Published: 2024
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17. AI governance must deal with long-term risks as well

Author: Price, Huw, primary and Connelly, Matthew, additional
Published: 2023
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18. A novel multiple-stage antimalarial agent that inhibits protein synthesis

Author: Baragaña, Beatriz, Hallyburton, Irene, Lee, Marcus CS, Norcross, Neil R, Grimaldi, Raffaella, Otto, Thomas D, Proto, William R, Blagborough, Andrew M, Meister, Stephan, Wirjanata, Grennady, Ruecker, Andrea, Upton, Leanna M, Abraham, Tara S, Almeida, Mariana J, Pradhan, Anupam, Porzelle, Achim, Martínez, María Santos, Bolscher, Judith M, Woodland, Andrew, Luksch, Torsten, Norval, Suzanne, Zuccotto, Fabio, Thomas, John, Simeons, Frederick, Stojanovski, Laste, Osuna-Cabello, Maria, Brock, Paddy M, Churcher, Tom S, Sala, Katarzyna A, Zakutansky, Sara E, Jiménez-Díaz, María Belén, Sanz, Laura Maria, Riley, Jennifer, Basak, Rajshekhar, Campbell, Michael, Avery, Vicky M, Sauerwein, Robert W, Dechering, Koen J, Noviyanti, Rintis, Campo, Brice, Frearson, Julie A, Angulo-Barturen, Iñigo, Ferrer-Bazaga, Santiago, Gamo, Francisco Javier, Wyatt, Paul G, Leroy, Didier, Siegl, Peter, Delves, Michael J, Kyle, Dennis E, Wittlin, Sergio, Marfurt, Jutta, Price, Ric N, Sinden, Robert E, Winzeler, Elizabeth A, Charman, Susan A, Bebrevska, Lidiya, Gray, David W, Campbell, Simon, Fairlamb, Alan H, Willis, Paul A, Rayner, Julian C, Fidock, David A, Read, Kevin D, and Gilbert, Ian H
Subjects: Medical Microbiology, Biomedical and Clinical Sciences, Clinical Sciences, Biotechnology, Infectious Diseases, Malaria, Orphan Drug, Vector-Borne Diseases, Rare Diseases, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Infection, Good Health and Well Being, Animals, Antimalarials, Drug Discovery, Female, Gene Expression Regulation, Life Cycle Stages, Liver, Male, Models, Molecular, Peptide Elongation Factor 2, Plasmodium, Plasmodium berghei, Plasmodium falciparum, Plasmodium vivax, Protein Biosynthesis, Quinolines, General Science & Technology
Abstract: There is an urgent need for new drugs to treat malaria, with broad therapeutic potential and novel modes of action, to widen the scope of treatment and to overcome emerging drug resistance. Here we describe the discovery of DDD107498, a compound with a potent and novel spectrum of antimalarial activity against multiple life-cycle stages of the Plasmodium parasite, with good pharmacokinetic properties and an acceptable safety profile. DDD107498 demonstrates potential to address a variety of clinical needs, including single-dose treatment, transmission blocking and chemoprotection. DDD107498 was developed from a screening programme against blood-stage malaria parasites; its molecular target has been identified as translation elongation factor 2 (eEF2), which is responsible for the GTP-dependent translocation of the ribosome along messenger RNA, and is essential for protein synthesis. This discovery of eEF2 as a viable antimalarial drug target opens up new possibilities for drug discovery.
Published: 2015

19. Population genomics of Bronze Age Eurasia

Author: Allentoft, Morten E, Sikora, Martin, Sjögren, Karl-Göran, Rasmussen, Simon, Rasmussen, Morten, Stenderup, Jesper, Damgaard, Peter B, Schroeder, Hannes, Ahlström, Torbjörn, Vinner, Lasse, Malaspinas, Anna-Sapfo, Margaryan, Ashot, Higham, Tom, Chivall, David, Lynnerup, Niels, Harvig, Lise, Baron, Justyna, Casa, Philippe Della, Dąbrowski, Paweł, Duffy, Paul R, Ebel, Alexander V, Epimakhov, Andrey, Frei, Karin, Furmanek, Mirosław, Gralak, Tomasz, Gromov, Andrey, Gronkiewicz, Stanisław, Grupe, Gisela, Hajdu, Tamás, Jarysz, Radosław, Khartanovich, Valeri, Khokhlov, Alexandr, Kiss, Viktória, Kolář, Jan, Kriiska, Aivar, Lasak, Irena, Longhi, Cristina, McGlynn, George, Merkevicius, Algimantas, Merkyte, Inga, Metspalu, Mait, Mkrtchyan, Ruzan, Moiseyev, Vyacheslav, Paja, László, Pálfi, György, Pokutta, Dalia, Pospieszny, Łukasz, Price, T Douglas, Saag, Lehti, Sablin, Mikhail, Shishlina, Natalia, Smrčka, Václav, Soenov, Vasilii I, Szeverényi, Vajk, Tóth, Gusztáv, Trifanova, Synaru V, Varul, Liivi, Vicze, Magdolna, Yepiskoposyan, Levon, Zhitenev, Vladislav, Orlando, Ludovic, Sicheritz-Pontén, Thomas, Brunak, Søren, Nielsen, Rasmus, Kristiansen, Kristian, and Willerslev, Eske
Subjects: History, Heritage and Archaeology, Human Society, Archaeology, Historical Studies, Anthropology, Asia, Asian People, Cultural Evolution, DNA, Europe, Fossils, Gene Frequency, Genetics, Population, Genome, Human, Genomics, History, Ancient, Human Migration, Humans, Lactose Intolerance, Language, Polymorphism, Single Nucleotide, Skin Pigmentation, White People, General Science & Technology
Abstract: The Bronze Age of Eurasia (around 3000-1000 BC) was a period of major cultural changes. However, there is debate about whether these changes resulted from the circulation of ideas or from human migrations, potentially also facilitating the spread of languages and certain phenotypic traits. We investigated this by using new, improved methods to sequence low-coverage genomes from 101 ancient humans from across Eurasia. We show that the Bronze Age was a highly dynamic period involving large-scale population migrations and replacements, responsible for shaping major parts of present-day demographic structure in both Europe and Asia. Our findings are consistent with the hypothesized spread of Indo-European languages during the Early Bronze Age. We also demonstrate that light skin pigmentation in Europeans was already present at high frequency in the Bronze Age, but not lactose tolerance, indicating a more recent onset of positive selection on lactose tolerance than previously thought.
Published: 2015

20. Precise interpolar phasing of abrupt climate change during the last ice age

Author: Buizert, Christo, Adrian, Betty, Ahn, Jinho, Albert, Mary, Alley, Richard B, Baggenstos, Daniel, Bauska, Thomas K, Bay, Ryan C, Bencivengo, Brian B, Bentley, Charles R, Brook, Edward J, Chellman, Nathan J, Clow, Gary D, Cole-Dai, Jihong, Conway, Howard, Cravens, Eric, Cuffey, Kurt M, Dunbar, Nelia W, Edwards, Jon S, Fegyveresi, John M, Ferris, Dave G, Fitzpatrick, Joan J, Fudge, TJ, Gibson, Chris J, Gkinis, Vasileios, Goetz, Joshua J, Gregory, Stephanie, Hargreaves, Geoffrey M, Iverson, Nels, Johnson, Jay A, Jones, Tyler R, Kalk, Michael L, Kippenhan, Matthew J, Koffman, Bess G, Kreutz, Karl, Kuhl, Tanner W, Lebar, Donald A, Lee, James E, Marcott, Shaun A, Markle, Bradley R, Maselli, Olivia J, McConnell, Joseph R, McGwire, Kenneth C, Mitchell, Logan E, Mortensen, Nicolai B, Neff, Peter D, Nishiizumi, Kunihiko, Nunn, Richard M, Orsi, Anais J, Pasteris, Daniel R, Pedro, Joel B, Pettit, Erin C, Price, P Buford, Priscu, John C, Rhodes, Rachael H, Rosen, Julia L, Schauer, Andrew J, Schoenemann, Spruce W, Sendelbach, Paul J, Severinghaus, Jeffrey P, Shturmakov, Alexander J, Sigl, Michael, Slawny, Kristina R, Souney, Joseph M, Sowers, Todd A, Spencer, Matthew K, Steig, Eric J, Taylor, Kendrick C, Twickler, Mark S, Vaughn, Bruce H, Voigt, Donald E, Waddington, Edwin D, Welten, Kees C, Wendricks, Anthony W, White, James WC, Winstrup, Mai, Wong, Gifford J, and Woodruff, Thomas E
Subjects: Earth Sciences, Physical Geography and Environmental Geoscience, Geology, Climate Action, WAIS Divide Project Members, General Science & Technology
Abstract: The last glacial period exhibited abrupt Dansgaard-Oeschger climatic oscillations, evidence of which is preserved in a variety of Northern Hemisphere palaeoclimate archives. Ice cores show that Antarctica cooled during the warm phases of the Greenland Dansgaard-Oeschger cycle and vice versa, suggesting an interhemispheric redistribution of heat through a mechanism called the bipolar seesaw. Variations in the Atlantic meridional overturning circulation (AMOC) strength are thought to have been important, but much uncertainty remains regarding the dynamics and trigger of these abrupt events. Key information is contained in the relative phasing of hemispheric climate variations, yet the large, poorly constrained difference between gas age and ice age and the relatively low resolution of methane records from Antarctic ice cores have so far precluded methane-based synchronization at the required sub-centennial precision. Here we use a recently drilled high-accumulation Antarctic ice core to show that, on average, abrupt Greenland warming leads the corresponding Antarctic cooling onset by 218 ± 92 years (2σ) for Dansgaard-Oeschger events, including the Bølling event; Greenland cooling leads the corresponding onset of Antarctic warming by 208 ± 96 years. Our results demonstrate a north-to-south directionality of the abrupt climatic signal, which is propagated to the Southern Hemisphere high latitudes by oceanic rather than atmospheric processes. The similar interpolar phasing of warming and cooling transitions suggests that the transfer time of the climatic signal is independent of the AMOC background state. Our findings confirm a central role for ocean circulation in the bipolar seesaw and provide clear criteria for assessing hypotheses and model simulations of Dansgaard-Oeschger dynamics.
Published: 2015

21. Biological insights from 108 schizophrenia-associated genetic loci

Author: Ripke, Stephan, Neale, Benjamin M, Corvin, Aiden, Walters, James TR, Farh, Kai-How, Holmans, Peter A, Lee, Phil, Bulik-Sullivan, Brendan, Collier, David A, Huang, Hailiang, Pers, Tune H, Agartz, Ingrid, Agerbo, Esben, Albus, Margot, Alexander, Madeline, Amin, Farooq, Bacanu, Silviu A, Begemann, Martin, Belliveau, Richard A Jr, Bene, Judit, Bergen, Sarah E, Bevilacqua, Elizabeth, Bigdeli, Tim B, Black, Donald W, Bruggeman, Richard, Buccola, Nancy G, Buckner, Randy L, Byerley, William, Cahn, Wiepke, Cai, Guiqing, Campion, Dominique, Cantor, Rita M, Carr, Vaughan J, Carrera, Noa, Catts, Stanley V, Chambert, Kimberly D, Chan, Raymond CK, Chen, Ronald YL, Chen, Eric YH, Cheng, Wei, Cheung, Eric FC, Chong, Siow Ann, Cloninger, C Robert, Cohen, David, Cohen, Nadine, Cormican, Paul, Craddock, Nick, Crowley, James J, Curtis, David, Davidson, Michael, Davis, Kenneth L, Degenhardt, Franziska, Del Favero, Jurgen, Demontis, Ditte, Dikeos, Dimitris, Dinan, Timothy, Djurovic, Srdjan, Donohoe, Gary, Drapeau, Elodie, Duan, Jubao, Dudbridge, Frank, Durmishi, Naser, Eichhammer, Peter, Eriksson, Johan, Escott-Price, Valentina, Essioux, Laurent, Fanous, Ayman H, Farrell, Martilias S, Frank, Josef, Franke, Lude, Freedman, Robert, Freimer, Nelson B, Friedl, Marion, Friedman, Joseph I, Fromer, Menachem, Genovese, Giulio, Georgieva, Lyudmila, Giegling, Ina, Giusti-Rodriguez, Paola, Godard, Stephanie, Goldstein, Jacqueline I, Golimbet, Vera, Gopal, Srihari, Gratten, Jacob, de Haan, Lieuwe, Hammer, Christian, Hamshere, Marian L, Hansen, Mark, Hansen, Thomas, Haroutunian, Vahram, Hartmann, Annette M, Henskens, Frans A, Herms, Stefan, Hirschhorn, Joel N, Hoffmann, Per, Hofman, Andrea, Hollegaard, Mads V, Hougaard, David M, Ikeda, Masashi, and Joa, Inge
Subjects: Human Genome, Brain Disorders, Serious Mental Illness, Prevention, Schizophrenia, Genetics, Neurosciences, Mental Health, 2.1 Biological and endogenous factors, Aetiology, Mental health, Alleles, Brain, Enhancer Elements, Genetic, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Glutamic Acid, Humans, Immunity, Multifactorial Inheritance, Mutation, Odds Ratio, Polymorphism, Single Nucleotide, Synaptic Transmission, Schizophrenia Working Group of the Psychiatric Genomics Consortium, General Science & Technology
Abstract: Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.
Published: 2014

22. Author Correction: Africa-specific human genetic variation near CHD1L associates with HIV-1 load

Author: McLaren, Paul J., primary, Porreca, Immacolata, additional, Iaconis, Gennaro, additional, Mok, Hoi Ping, additional, Mukhopadhyay, Subhankar, additional, Karakoc, Emre, additional, Cristinelli, Sara, additional, Pomilla, Cristina, additional, Bartha, István, additional, Thorball, Christian W., additional, Tough, Riley H., additional, Angelino, Paolo, additional, Kiar, Cher S., additional, Carstensen, Tommy, additional, Fatumo, Segun, additional, Porter, Tarryn, additional, Jarvis, Isobel, additional, Skarnes, William C., additional, Bassett, Andrew, additional, DeGorter, Marianne K., additional, Sathya Moorthy, Mohana Prasad, additional, Tuff, Jeffrey F., additional, Kim, Eun-Young, additional, Walter, Miriam, additional, Simons, Lacy M., additional, Bashirova, Arman, additional, Buchbinder, Susan, additional, Carrington, Mary, additional, Cossarizza, Andrea, additional, De Luca, Andrea, additional, Goedert, James J., additional, Goldstein, David B., additional, Haas, David W., additional, Herbeck, Joshua T., additional, Johnson, Eric O., additional, Kaleebu, Pontiano, additional, Kilembe, William, additional, Kirk, Gregory D., additional, Kootstra, Neeltje A., additional, Kral, Alex H., additional, Lambotte, Olivier, additional, Luo, Ma, additional, Mallal, Simon, additional, Martinez-Picado, Javier, additional, Meyer, Laurence, additional, Miro, José M., additional, Moodley, Pravi, additional, Motala, Ayesha A., additional, Mullins, James I., additional, Nam, Kireem, additional, Obel, Niels, additional, Pirie, Fraser, additional, Plummer, Francis A., additional, Poli, Guido, additional, Price, Matthew A., additional, Rauch, Andri, additional, Theodorou, Ioannis, additional, Trkola, Alexandra, additional, Walker, Bruce D., additional, Winkler, Cheryl A., additional, Zagury, Jean-François, additional, Montgomery, Stephen B., additional, Ciuffi, Angela, additional, Hultquist, Judd F., additional, Wolinsky, Steven M., additional, Dougan, Gordon, additional, Lever, Andrew M. L., additional, Gurdasani, Deepti, additional, Groom, Harriet, additional, Sandhu, Manjinder S., additional, and Fellay, Jacques, additional
Published: 2023
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23. Africa-specific human genetic variation near CHD1L associates with HIV-1 load

Author: McLaren, Paul J., primary, Porreca, Immacolata, additional, Iaconis, Gennaro, additional, Mok, Hoi Ping, additional, Mukhopadhyay, Subhankar, additional, Karakoc, Emre, additional, Cristinelli, Sara, additional, Pomilla, Cristina, additional, Bartha, István, additional, Thorball, Christian W., additional, Tough, Riley H., additional, Angelino, Paolo, additional, Kiar, Cher S., additional, Carstensen, Tommy, additional, Fatumo, Segun, additional, Porter, Tarryn, additional, Jarvis, Isobel, additional, Skarnes, William C., additional, Bassett, Andrew, additional, DeGorter, Marianne K., additional, Sathya Moorthy, Mohana Prasad, additional, Tuff, Jeffrey F., additional, Kim, Eun-Young, additional, Walter, Miriam, additional, Simons, Lacy M., additional, Bashirova, Arman, additional, Buchbinder, Susan, additional, Carrington, Mary, additional, Cossarizza, Andrea, additional, De Luca, Andrea, additional, Goedert, James J., additional, Goldstein, David B., additional, Haas, David W., additional, Herbeck, Joshua T., additional, Johnson, Eric O., additional, Kaleebu, Pontiano, additional, Kilembe, William, additional, Kirk, Gregory D., additional, Kootstra, Neeltje A., additional, Kral, Alex H., additional, Lambotte, Olivier, additional, Luo, Ma, additional, Mallal, Simon, additional, Martinez-Picado, Javier, additional, Meyer, Laurence, additional, Miro, José M., additional, Moodley, Pravi, additional, Motala, Ayesha A., additional, Mullins, James I., additional, Nam, Kireem, additional, Obel, Niels, additional, Pirie, Fraser, additional, Plummer, Francis A., additional, Poli, Guido, additional, Price, Matthew A., additional, Rauch, Andri, additional, Theodorou, Ioannis, additional, Trkola, Alexandra, additional, Walker, Bruce D., additional, Winkler, Cheryl A., additional, Zagury, Jean-François, additional, Montgomery, Stephen B., additional, Ciuffi, Angela, additional, Hultquist, Judd F., additional, Wolinsky, Steven M., additional, Dougan, Gordon, additional, Lever, Andrew M. L., additional, Gurdasani, Deepti, additional, Groom, Harriet, additional, Sandhu, Manjinder S., additional, and Fellay, Jacques, additional
Published: 2023
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24. A long-period radio transient active for three decades

Author: Hurley-Walker, N., primary, Rea, N., additional, McSweeney, S. J., additional, Meyers, B. W., additional, Lenc, E., additional, Heywood, I., additional, Hyman, S. D., additional, Men, Y. P., additional, Clarke, T. E., additional, Coti Zelati, F., additional, Price, D. C., additional, Horváth, C., additional, Galvin, T. J., additional, Anderson, G. E., additional, Bahramian, A., additional, Barr, E. D., additional, Bhat, N. D. R., additional, Caleb, M., additional, Dall’Ora, M., additional, de Martino, D., additional, Giacintucci, S., additional, Morgan, J. S., additional, Rajwade, K. M., additional, Stappers, B., additional, and Williams, A., additional
Published: 2023
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25. Projected land ice contributions to twenty-first-century sea level rise

Author: Tamsin L. Edwards, Sophie Nowicki, Ben Marzeion, Regine Hock, Heiko Goelzer, Hélène Seroussi, Nicolas C. Jourdain, Donald A. Slater, Fiona E. Turner, Christopher J. Smith, Christine M. McKenna, Erika Simon, Ayako Abe-Ouchi, Jonathan M Gregory, Eric Larour, William H. Lipscomb, Antony J. Payne, Andrew Shepherd, Cécile Agosta, Patrick Alexander, Torsten Albrecht, Brian Anderson, Xylar Asay-Davis, Andreas Aschwanden, Alice Barthel, Andrew Bliss, Reinhard Calov, Christopher Chambers, Nicolas Champollion, Youngmin Choi, Richard Cullather, Joshua Cuzzone, Christophe Dumas, Denis Felikson, Xavier Fettweis, Koji Fujita, Benjamin K. Galton-Fenzi, Rupert Gladstone, Nicolas R. Gollege, Ralf Greve, Tore Hattermann, Matthew J. Hoffman, Angelika Humbert, Matthias Huss, Philippe Huybrechts, Walter Immerzeel, Thomas Kleiner, Philip Kraaijenbrink, Sebastien Le clec'h, Victoria Lee, Gunter R. Leguy, Christopher M. Little, Daniel P. Lowry, Jan-Hendrik Malles, Daniel F. Martin, Fabien Maussion, Mathieu Morlighem, James F. O’Neill, Isabel Nias, Frank Pattyn, Tyler Pelle, Stephen F Price, Aurélien Quiquet, Valentina Radić, Ronja Reese, David R. Rounce, Martin Rückamp, Akiko Sakai, Courtney Shafer, Nicole-Jeanne Schlegel, Sarah Shannon, Robin S. Smith, Fiammetta Straneo, Sainan Sun, Lev Tarasov, Luke D. Trusel, Jonas Van Breedam, Roderik van de Wal, Michiel van den Broeke, Ricarda Winkelmann, Harry Zekollari, Chen Zhao, Tong Zhang, and Thomas Zwinger
Subjects: Earth Resources And Remote Sensing, Numerical Analysis
Abstract: The land ice contribution to global mean sea level rise has not yet been predicted1 using ice sheet and glacier models for the latest set of socio-economic scenarios, nor using coordinated exploration of uncertainties arising from the various computer models involved. Two recent international projects generated a large suite of projections using multiple models2,3,4,5,6,7,8, but primarily used previous-generation scenarios9 and climate models10, and could not fully explore known uncertainties. Here we estimate probability distributions for these projections under the new scenarios11,12 using statistical emulation of the ice sheet and glacier models. We find that limiting global warming to 1.5 degrees Celsius would halve the land ice contribution to twenty-first-century sea level rise, relative to current emissions pledges. The median decreases from 25 to 13 centimetres sea level equivalent (SLE) by 2100, with glaciers responsible for half the sea level contribution. The projected Antarctic contribution does not show a clear response to the emissions scenario, owing to uncertainties in the competing processes of increasing ice loss and snowfall accumulation in a warming climate. However, under risk-averse (pessimistic) assumptions, Antarctic ice loss could be five times higher, increasing the median land ice contribution to 42 centimetres SLE under current policies and pledges, with the 95th percentile projection exceeding half a metre even under 1.5 degrees Celsius warming. This would severely limit the possibility of mitigating future coastal flooding. Given this large range (between 13 centimetres SLE using the main projections under 1.5 degrees Celsius warming and 42 centimetres SLE using risk-averse projections under current pledges), adaptation planning for twenty-first-century sea level rise must account for a factor-of-three uncertainty in the land ice contribution until climate policies and the Antarctic response are further constrained.
Published: 2021
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26. Reconstructing Native American population history

Author: Reich, David, Patterson, Nick, Campbell, Desmond, Tandon, Arti, Mazieres, Stéphane, Ray, Nicolas, Parra, Maria V, Rojas, Winston, Duque, Constanza, Mesa, Natalia, García, Luis F, Triana, Omar, Blair, Silvia, Maestre, Amanda, Dib, Juan C, Bravi, Claudio M, Bailliet, Graciela, Corach, Daniel, Hünemeier, Tábita, Bortolini, Maria Cátira, Salzano, Francisco M, Petzl-Erler, María Luiza, Acuña-Alonzo, Victor, Aguilar-Salinas, Carlos, Canizales-Quinteros, Samuel, Tusié-Luna, Teresa, Riba, Laura, Rodríguez-Cruz, Maricela, Lopez-Alarcón, Mardia, Coral-Vazquez, Ramón, Canto-Cetina, Thelma, Silva-Zolezzi, Irma, Fernandez-Lopez, Juan Carlos, Contreras, Alejandra V, Jimenez-Sanchez, Gerardo, Gómez-Vázquez, Maria José, Molina, Julio, Carracedo, Ángel, Salas, Antonio, Gallo, Carla, Poletti, Giovanni, Witonsky, David B, Alkorta-Aranburu, Gorka, Sukernik, Rem I, Osipova, Ludmila, Fedorova, Sardana A, Vasquez, René, Villena, Mercedes, Moreau, Claudia, Barrantes, Ramiro, Pauls, David, Excoffier, Laurent, Bedoya, Gabriel, Rothhammer, Francisco, Dugoujon, Jean-Michel, Larrouy, Georges, Klitz, William, Labuda, Damian, Kidd, Judith, Kidd, Kenneth, Di Rienzo, Anna, Freimer, Nelson B, Price, Alkes L, and Ruiz-Linares, Andrés
Subjects: Biological Sciences, Genetics, History, Heritage and Archaeology, Human Society, Historical Studies, Anthropology, American Indian or Alaska Native, Americas, Asia, Cluster Analysis, Emigration and Immigration, Gene Flow, Genetics, Population, History, Ancient, Humans, Indians, North American, Models, Genetic, Phylogeny, Polymorphism, Single Nucleotide, Siberia, General Science & Technology
Abstract: The peopling of the Americas has been the subject of extensive genetic, archaeological and linguistic research; however, central questions remain unresolved. One contentious issue is whether the settlement occurred by means of a single migration or multiple streams of migration from Siberia. The pattern of dispersals within the Americas is also poorly understood. To address these questions at a higher resolution than was previously possible, we assembled data from 52 Native American and 17 Siberian groups genotyped at 364,470 single nucleotide polymorphisms. Here we show that Native Americans descend from at least three streams of Asian gene flow. Most descend entirely from a single ancestral population that we call 'First American'. However, speakers of Eskimo-Aleut languages from the Arctic inherit almost half their ancestry from a second stream of Asian gene flow, and the Na-Dene-speaking Chipewyan from Canada inherit roughly one-tenth of their ancestry from a third stream. We show that the initial peopling followed a southward expansion facilitated by the coast, with sequential population splits and little gene flow after divergence, especially in South America. A major exception is in Chibchan speakers on both sides of the Panama isthmus, who have ancestry from both North and South America.
Published: 2012

27. The landscape of recombination in African Americans

Author: Hinch, Anjali G, Tandon, Arti, Patterson, Nick, Song, Yunli, Rohland, Nadin, Palmer, Cameron D, Chen, Gary K, Wang, Kai, Buxbaum, Sarah G, Akylbekova, Ermeg L, Aldrich, Melinda C, Ambrosone, Christine B, Amos, Christopher, Bandera, Elisa V, Berndt, Sonja I, Bernstein, Leslie, Blot, William J, Bock, Cathryn H, Boerwinkle, Eric, Cai, Qiuyin, Caporaso, Neil, Casey, Graham, Adrienne Cupples, L, Deming, Sandra L, Ryan Diver, W, Divers, Jasmin, Fornage, Myriam, Gillanders, Elizabeth M, Glessner, Joseph, Harris, Curtis C, Hu, Jennifer J, Ingles, Sue A, Isaacs, William, John, Esther M, Linda Kao, WH, Keating, Brendan, Kittles, Rick A, Kolonel, Laurence N, Larkin, Emma, Le Marchand, Loic, McNeill, Lorna H, Millikan, Robert C, Murphy, Musani, Solomon, Neslund-Dudas, Christine, Nyante, Sarah, Papanicolaou, George J, Press, Michael F, Psaty, Bruce M, Reiner, Alex P, Rich, Stephen S, Rodriguez-Gil, Jorge L, Rotter, Jerome I, Rybicki, Benjamin A, Schwartz, Ann G, Signorello, Lisa B, Spitz, Margaret, Strom, Sara S, Thun, Michael J, Tucker, Margaret A, Wang, Zhaoming, Wiencke, John K, Witte, John S, Wrensch, Margaret, Wu, Xifeng, Yamamura, Yuko, Zanetti, Krista A, Zheng, Wei, Ziegler, Regina G, Zhu, Xiaofeng, Redline, Susan, Hirschhorn, Joel N, Henderson, Brian E, Taylor Jr, Herman A, Price, Alkes L, Hakonarson, Hakon, Chanock, Stephen J, Haiman, Christopher A, Wilson, James G, Reich, David, and Myers, Simon R
Subjects: Biological Sciences, Genetics, Human Genome, Biotechnology, Africa, Western, Black or African American, Alleles, Amino Acid Motifs, Base Sequence, Chromosome Mapping, Crossing Over, Genetic, Europe, Evolution, Molecular, Female, Gene Frequency, Genetics, Population, Genome, Human, Genomics, Haplotypes, Histone-Lysine N-Methyltransferase, Humans, Male, Molecular Sequence Data, Pedigree, Polymorphism, Single Nucleotide, Probability, White People, General Science & Technology
Abstract: Recombination, together with mutation, gives rise to genetic variation in populations. Here we leverage the recent mixture of people of African and European ancestry in the Americas to build a genetic map measuring the probability of crossing over at each position in the genome, based on about 2.1 million crossovers in 30,000 unrelated African Americans. At intervals of more than three megabases it is nearly identical to a map built in Europeans. At finer scales it differs significantly, and we identify about 2,500 recombination hotspots that are active in people of West African ancestry but nearly inactive in Europeans. The probability of a crossover at these hotspots is almost fully controlled by the alleles an individual carries at PRDM9 (P value
Published: 2011

28. In situ tumour arrays reveal early environmental control of cancer immunity

Author: Ortiz-Muñoz, Guadalupe, primary, Brown, Markus, additional, Carbone, Catherine B., additional, Pechuan-Jorge, Ximo, additional, Rouilly, Vincent, additional, Lindberg, Henrik, additional, Ritter, Alex T., additional, Raghupathi, Gautham, additional, Sun, Qianbo, additional, Nicotra, Tess, additional, Mantri, Shreya R., additional, Yang, Angela, additional, Doerr, Jonas, additional, Nagarkar, Deepti, additional, Darmanis, Spyros, additional, Haley, Benjamin, additional, Mariathasan, Sanjeev, additional, Wang, Yulei, additional, Gomez-Roca, Carlos, additional, de Andrea, Carlos Eduardo, additional, Spigel, David, additional, Wu, Thomas, additional, Delamarre, Lelia, additional, Schöneberg, Johannes, additional, Modrusan, Zora, additional, Price, Richard, additional, Turley, Shannon J., additional, Mellman, Ira, additional, and Moussion, Christine, additional
Published: 2023
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29. In situ tumour arrays reveal early environmental control of cancer immunity

Author: Guadalupe Ortiz-Muñoz, Markus Brown, Catherine B. Carbone, Ximo Pechuan-Jorge, Vincent Rouilly, Henrik Lindberg, Alex T. Ritter, Gautham Raghupathi, Qianbo Sun, Tess Nicotra, Shreya R. Mantri, Angela Yang, Jonas Doerr, Deepti Nagarkar, Spyros Darmanis, Benjamin Haley, Sanjeev Mariathasan, Yulei Wang, Carlos Gomez-Roca, Carlos Eduardo de Andrea, David Spigel, Thomas Wu, Lelia Delamarre, Johannes Schöneberg, Zora Modrusan, Richard Price, Shannon J. Turley, Ira Mellman, and Christine Moussion
Subjects: Multidisciplinary
Abstract: The immune phenotype of a tumour is a key predictor of its response to immunotherapy1–4. Patients who respond to checkpoint blockade generally present with immune-inflamed5–7 tumours that are highly infiltrated by T cells. However, not all inflamed tumours respond to therapy, and even lower response rates occur among tumours that lack T cells (immune desert) or that spatially exclude T cells to the periphery of the tumour lesion (immune excluded)8. Despite the importance of these tumour immune phenotypes in patients, little is known about their development, heterogeneity or dynamics owing to the technical difficulty of tracking these features in situ. Here we introduce skin tumour array by microporation (STAMP)—a preclinical approach that combines high-throughput time-lapse imaging with next-generation sequencing of tumour arrays. Using STAMP, we followed the development of thousands of arrayed tumours in vivo to show that tumour immune phenotypes and outcomes vary between adjacent tumours and are controlled by local factors within the tumour microenvironment. Particularly, the recruitment of T cells by fibroblasts and monocytes into the tumour core was supportive of T cell cytotoxic activity and tumour rejection. Tumour immune phenotypes were dynamic over time and an early conversion to an immune-inflamed phenotype was predictive of spontaneous or therapy-induced tumour rejection. Thus, STAMP captures the dynamic relationships of the spatial, cellular and molecular components of tumour rejection and has the potential to translate therapeutic concepts into successful clinical strategies.
Published: 2023

30. Exploring 4D quantum Hall physics with a 2D topological charge pump

Author: Lohse, Michael, Schweizer, Christian, Price, Hannah M., Zilberberg, Oded, and Bloch, Immanuel
Subjects: Quantum Hall effect -- Research, Physics research, Topology -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract: Author(s): Michael Lohse [1, 2]; Christian Schweizer [1, 2]; Hannah M. Price [3, 4]; Oded Zilberberg [5]; Immanuel Bloch (corresponding author) [1, 2] The discovery of topological states of matter [...]
Published: 2018
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31. Measurement of the multi-TeV neutrino interaction cross-section with IceCube using Earth absorption

Author: Aartsen, M. G., Hill, G. C., Kyriacou, A., Robertson, S., Wallace, A., Whelan, B. J., Ackermann, M., Bernardini, E., Blot, S., Bradascio, F., Bretz, H.-P., Brostean-Kaiser, J., Franckowiak, A., Jacobi, E., Karg, T., Kintscher, T., Kunwar, S., Nahnhauer, R., Satalecka, K., Spiering, C., Stachurska, J., Stasik, A., Strotjohann, N. L., Terliuk, A., Usner, M., van Santen, J., Adams, J., Bagherpour, H., Aguilar, J. A., Ansseau, I., Heereman, D., Meagher, K., Meures, T., OMurchadha, A., Pinat, E., Raab, C., Ahlers, M., Koskinen, D. J., Larson, M. J., Medici, M., Rameez, M., Ahrens, M., Bohm, C., Dumm, J. P., Finley, C., Flis, S., Hultqvist, K., Walck, C., Zoll, M., Al Samarai, I., Bron, S., Carver, T., Christov, A., Montaruli, T., Altmann, D., Anton, G., Glsenkamp, T., Katz, U., Kittler, T., Tselengidou, M., Andeen, K., Plum, M., Anderson, T., DeLaunay, J. J., Dunkman, M., Eller, P., Huang, F., Keivani, A., Lanfranchi, J. L., Pankova, D. V., Teic, G., Turley, C. F., Weiss, M. J., Argelles, C., Axani, S., Collin, G. H., Conrad, J. M., Moulai, M., Auffenberg, J., Brenzke, M., Glauch, T., Haack, C., Kalaczynski, P., Koschinsky, J. P., Leuermann, M., Rdel, L., Reimann, R., Rongen, M., Slzer, T., Schoenen, S., Schumacher, L., Stettner, J., Vehring, M., Vogel, E., Wallraff, M., Waza, A., Wiebusch, C. H., Bai, X., Barron, J. P., Giang, W., Grant, D., Kopper, C., Moore, R. W., Nowicki, S. C., Herrera, S. E. Sanchez, Sarkar, S., Wandler, F. D., Weaver, C., Wood, T. R., Woolsey, E., Yanez, J. P., Barwick, S. W., Yodh, G., Baum, V., Bser, S., di Lorenzo, V., Eberhardt, B., Ehrhardt, T., Kpke, L., Krckl, G., Moment, G., Peiffer, P., Sandroos, J., Steuer, A., Wiebe, K., Bay, R., Filimonov, K., Price, P. B., Woschnagg, K., Beatty, J. J., Tjus, J. Becker, Bos, F., Eichmann, B., Kroll, M., Schneberg, S., Tenholt, F., Becker, K.-H., Bindig, D., Helbing, K., Hickford, S., Hoffmann, R., Lauber, F., Naumann, U., Pollmann, A. Obertacke, Soldin, D., BenZvi, S., Cross, R., Berley, D., Blaufuss, E., Cheung, E., Felde, J., Friedman, E., Hellauer, R., Hoffman, K. D., Maunu, R., Olivas, A., Schmidt, T., Song, M., Sullivan, G. W., Besson, D. Z., Binder, G., Klein, S. R., Miarecki, S., Palczewski, T., Tatar, J., Brner, M., Fuchs, T., Hnnefeld, M., Meier, M., Menne, T., Pieloth, D., Rhode, W., Ruhe, T., Sandrock, A., Schlunder, P., Soedingrekso, J., Werthebach, J., Bose, D., Dujmovic, H., In, S., Jeong, M., Kang, W., Kim, J., Rott, C., Botner, O., Burgman, A., Hallgren, A., Prez de los Heros, C., Unger, E., Bourbeau, J., Braun, J., Casey, J., Chirkin, D., Day, M., Desiati, P., Daz-Vlez, J. C., Fahey, S., Ghorbani, K., Griffith, Z., Halzen, F., Hanson, K., Hokanson-Fasig, B., Hoshina, K., Jero, K., Karle, A., Kauer, M., Kelley, J. L., Kheirandish, A., Liu, Q. R., Luszczak, W., Mancina, S., McNally, F., Merino, G., Schneider, A., Tobin, M. N., Tosi, D., Ty, B., Vandenbroucke, J., Wandkowsky, N., Wendt, C., Westerhoff, S., Wille, L., Wolf, M., Wood, J., Xu, D. L., Yuan, T., Brayeur, L., Casier, M., De Clercq, C., de Vries, K. D., de Wasseige, G., Kunnen, J., Lnemann, J., Maggi, G., Toscano, S., van Eijndhoven, N., Clark, K., Classen, L., Kappes, A., Coenders, S., Huber, M., Krings, K., Rea, I. C., Resconi, E., Turcati, A., Cowen, D. F., de Andr, J. P. A. M., DeYoung, T., Hignight, J., Lennarz, D., Mahn, K. B. M., Micallef, J., Neer, G., Rysewyk, D., Dembinski, H., Evenson, P. A., Gaisser, T. K., Gonzalez, J. G., Koirala, R., Pandya, H., Seckel, D., Stanev, T., Tilav, S., De Ridder, S., Labare, M., Ryckbosch, D., Van Driessche, W., Vanheule, S., Vraeghe, M., de With, M., Hebecker, D., Kolanoski, H., Fazely, A. R., Ter-Antonyan, S., Xu, X. W., Gallagher, J., Gerhardt, L., Goldschmidt, A., Nygren, D. R., Przybylski, G. T., Stezelberger, T., Stokstad, R. G., Ishihara, A., Kim, M., Kuwabara, T., Lu, L., Mase, K., Relich, M., Stl, A., Yoshida, S., Japaridze, G. S., Jones, B. J. P., Kiryluk, J., Lesiak-Bzdak, M., Niederhausen, H., Xu, Y., Kohnen, G., Kopper, S., Nakarmi, P., Pepper, J. A., Toale, P. A., Williams, D. R., Kowalski, M., Kurahashi, N., Relethford, B., Richman, M., Wills, L., Madsen, J., Seunarine, S., Spiczak, G. M., Maruyama, R., Rawlins, K., Sutherland, M., Taboada, I., and Tung, C. F.
Subjects: Neutrinos -- Properties, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract: Author(s): The IceCube Collaboration; M. G. Aartsen [1]; G. C. Hill [1]; A. Kyriacou [1]; S. Robertson [1]; A. Wallace [1]; B. J. Whelan [1]; M. Ackermann [2]; E. Bernardini [...]
Published: 2017
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32. Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Author: Trubetskoy, Vassily, Panagiotaropoulou, Georgia, Awasthi, Swapnil, Braun, Alice, Kraft, Julia, Skarabis, Nora, Walter, Henrik, Ripke, Stephan, Pardiñas, Antonio F., Dennison, Charlotte A., Hall, Lynsey S., Harwood, Janet C., Richards, Alexander L., Legge, Sophie E., Lynham, Amy, Williams, Nigel M., Bray, Nicholas J., Escott-Price, Valentina, Kirov, George, Holmans, Peter A., Pocklington, Andrew J., Owen, Michael J., Walters, James T. R., O’Donovan, Michael C., Qi, Ting, Sidorenko, Julia, Wu, Yang, Zeng, Jian, Gratten, Jacob, Visscher, Peter M., Yang, Jian, Wray, Naomi R., Bigdeli, Tim B., Fanous, Ayman H., Bryois, Julien, Bergen, Sarah E., Kähler, Anna K., Magnusson, Patrik K. E., Hultman, Christina M., Sullivan, Patrick F., Chen, Chia-Yen, Atkinson, Elizabeth G., Goldstein, Jacqueline I., Howrigan, Daniel P., Martin, Alicia R., Daly, Mark J., Huang, Hailiang, Neale, Benjamin M., Ge, Tian, Lam, Max, Belliveau, Richard A., Chambert, Kimberley D., Genovese, Giulio, Lee, Phil H., Pietiläinen, Olli, McCarroll, Steven A., Moran, Jennifer L., Smoller, Jordan W., Brown, Tyler C., Feng, Guoping, Hyman, Steven E., Sheng, Morgan, Chong, Siow Ann, Subramaniam, Mythily, Lencz, Todd, Malhotra, Anil K., Watanabe, Kyoko, Frei, Oleksandr, Agartz, Ingrid, Athanasiu, Lavinia, Melle, Ingrid, Andreassen, Ole A., Steen, Nils Eiel, DeLisi, Lynn E., Mesholam-Gately, Raquelle I., Seidman, Larry J., Koopmans, Frank, Magnusson, Sigurdur, Stefánsson, Hreinn, Stefansson, Kari, Grove, Jakob, Agerbo, Esben, Als, Thomas D., Bybjerg-Grauholm, Jonas, Demontis, Ditte, Hougaard, David M., Mors, Ole, Mortensen, Preben B., Nordentoft, Merete, Børglum, Anders D., Mattheisen, Manuel, Kim, Minsoo, Gandal, Michael J., Li, Zhiqiang, Shi, Yongyong, Zhou, Wei, Qin, Shengying, Voloudakis, Georgios, Zhang, Wen, Roussos, Panos, Adams, Mark, McIntosh, Andrew, Söderman, Erik, Jönsson, Erik G., McGrath, John J., Al Eissa, Mariam, Bass, Nicholas J., Fiorentino, Alessia, O’Brien, Niamh Louise, Pimm, Jonathan, Sharp, Sally Isabel, McQuillin, Andrew, Albus, Margot, Alexander, Madeline, Alizadeh, Behrooz Z., Bruggeman, Richard, Alptekin, Köksal, Amin, Farooq, Arolt, Volker, Lencer, Rebecca, Rothermundt, Matthias, Baune, Bernhard T., Arrojo, Manuel, Azevedo, Maria Helena, Bacanu, Silviu A., Webb, Bradley T., Wormley, Brandon K., Riley, Brien P., Kendler, Kenneth S., Begemann, Martin, Mitjans, Marina, Steixner-Kumar, Agnes A., Ehrenreich, Hannelore, Bene, Judit, Benyamin, Beben, Blasi, Giuseppe, Rampino, Antonio, Torretta, Silvia, Bertolino, Alessandro, Bobes, Julio, Bonassi, Stefano, Bressan, Rodrigo Affonseca, Gadelha, Ary, Noto, Cristiano, Ota, Vanessa Kiyomi, Santoro, Marcos Leite, Belangero, Sintia Iole, Bromet, Evelyn J., Buckley, Peter F., Buckner, Randy L., Cahn, Wiepke, Kahn, René S., Cairns, Murray J., Scott, Rodney J., Tooney, Paul A., Schall, Ulrich, Calkins, Monica E., Gur, Raquel E., Gur, Ruben C., Turetsky, Bruce I., Carr, Vaughan J., Castle, David, Harvey, Carol, Catts, Stanley V., Chan, Raymond C. K., Chaumette, Boris, Kebir, Oussama, Krebs, Marie-Odile, Cheng, Wei, Cheung, Eric F. C., Cohen, David, Consoli, Angèle, Giannitelli, Marianna, Laurent-Levinson, Claudine, Cordeiro, Quirino, Costas, Javier, Curtis, Charles, Quattrone, Diego, Breen, Gerome, Collier, David A., Di Forti, Marta, Vassos, Evangelos, Mondelli, Valeria, van Amelsvoort, Therese, Murray, Robin M., Davidson, Michael, Davis, Kenneth L., Haroutunian, Vahram, Malaspina, Dolores, Reichenberg, Abraham, Siever, Larry J., Silverman, Jeremy M., Buxbaum, Joseph D., de Haan, Lieuwe, Degenhardt, Franziska, Forstner, Andreas, Nöthen, Markus M., Dickerson, Faith, Dikeos, Dimitris, Papadimitriou, George N., Dinan, Timothy, Djurovic, Srdjan, Duan, Jubao, Gejman, Pablo V., Sanders, Alan R., Ducci, Giuseppe, Dudbridge, Frank, Eriksson, Johan G., Fañanás, Lourdes, Peñas, Javier González, González-Pinto, Ana, Molto, María Dolores, Moreno, Carmen, Parellada, Mara, Sanjuan, Julio, Crepo-Facorro, Benedicto, Mata, Ignacio, Arango, Celso, Faraone, Stephen V., Frank, Josef, Streit, Fabian, Witt, Stephanie H., Rietschel, Marcella, Freimer, Nelson B., Ophoff, Roel A., Fromer, Menachem, Stahl, Eli A., Frustaci, Alessandra, Gershon, Elliot S., Giegling, Ina, Hartmann, Annette M., Konte, Bettina, Rujescu, Dan, Giusti-Rodríguez, Paola, Szatkiewicz, Jin P., Godard, Stephanie, González Peñas, Javier, Gopal, Srihari, Savitz, Adam, Li, Qingqin S., Green, Michael F., Nuechterlein, Keith H., Sugar, Catherine A., Greenwood, Tiffany A., Light, Gregory A., Swerdlow, Neal R., Braff, David, Guillin, Olivier, Campion, Dominique, Gülöksüz, Sinan, Luykx, Jurjen J., Rutten, Bart P. F., van Winkel, Ruud, Gutiérrez, Blanca, Hahn, Eric, Hakonarson, Hakon, Pellegrino, Renata, Pantelis, Christos, Hayward, Caroline, Henskens, Frans A., Kelly, Brian J., Herms, Stefan, Hoffmann, Per, Ikeda, Masashi, Iwata, Nakao, Iyegbe, Conrad, van Os, Jim, Joa, Inge, Julià, Antonio, Marsal, Sara, Kam-Thong, Tony, Rautanen, Anna, Kamatani, Yoichiro, Karachanak-Yankova, Sena, Toncheva, Draga, Keller, Matthew C., Khrunin, Andrey, Limborska, Svetlana, Slominsky, Petr, Kim, Sung-Wan, Klovins, Janis, Nikitina-Zake, Liene, Kondratiev, Nikolay, Golimbet, Vera, Kubo, Michiaki, Kučinskas, Vaidutis, Kučinskiene, Zita Ausrele, Kusumawardhani, Agung, Kuzelova-Ptackova, Hana, Landi, Stefano, Lazzeroni, Laura C., Levinson, Douglas F., Petryshen, Tracey L., Lehrer, Douglas S., Lerer, Bernard, Li, Miaoxin, Lieberman, Jeffrey, Stroup, T. Scott, Liu, Chih-Min, Hwu, Hai-Gwo, Lönnqvist, Jouko, Loughland, Carmel M., Lubinski, Jan, Bakker, Steven, Kahn, René, Macek, Milan, Mackinnon, Andrew, Maher, Brion S., Maier, Wolfgang, Atbaşoğlu, Eşref Cem, Mallet, Jacques, Marder, Stephen R., Martorell, Lourdes, Muntané, Gerard, Vilella, Elisabet, Meier, Sandra, Schulze, Thomas G., McCarley, Robert W., McDonald, Colm, Donohoe, Gary, Morris, Derek W., Periyasamy, Sathish, Mowry, Bryan J., Medeiros, Helena, Sobell, Janet L., Melegh, Bela, Metspalu, Andres, Milani, Lili, Esko, Tõnu, Michie, Patricia T., Milanova, Vihra, Molden, Espen, Molina, Esther, Morley, Christopher P., Murphy, Kieran C., Myin-Germeys, Inez, Nenadić, Igor, Nestadt, Gerald, Pulver, Ann E., O’Neill, F. Anthony, Oh, Sang-Yun, Olincy, Ann, Freedman, Robert, Paunio, Tiina, Perkins, Diana O., Pfuhlmann, Bruno, Benner, Christian, Pirinen, Matti, Palotie, Aarno, Porteous, David, Powell, John, Quested, Digby, Radant, Allen D., Tsuang, Debby W., Rapaport, Mark H., Roe, Cheryl, Liu, Chunyu, Roffman, Joshua L., Roth, Julian, Gawlik, Micha, Saker-Delye, Safaa, Salomaa, Veikko, Suvisaari, Jaana, Shi, Jianxin, Sigurdsson, Engilbert, Sim, Kang, So, Hon-Cheong, Stain, Helen J., Stögmann, Elisabeth, Zimprich, Fritz, Stone, William S., Straub, Richard E., Hyde, Thomas, Jaffe, Andrew, Weinberger, Daniel R., Strengman, Eric, Svrakic, Dragan M., Cloninger, C. Robert, Ta, Thi Minh Tam, Takahashi, Atsushi, Terao, Chikashi, Thibaut, Florence, Tosato, Sarah, Tura, Gian Battista, Üçok, Alp, Vaaler, Arne, Veijola, Juha, Waddington, John, Waterreus, Anna, Morgan, Vera A., Jablensky, Assen V., Weiser, Mark, Wu, Jing Qin, Xu, Zhida, Yolken, Robert, Zai, Clement C., Kennedy, James L., Zhu, Feng, Saka, Meram C., Ayub, Muhammad, Black, Donald W., Buccola, Nancy G., Byerley, William F., Chen, Wei J., Crespo-Facorro, Benedicto, Galletly, Cherrie, Gennarelli, Massimo, Müller-Myhsok, Bertram, Neil, Amanda L., Pato, Michele T., Pato, Carlos N., Wang, Shi-Heng, Xu, Shuhua, Adolfsson, Rolf, Bramon, Elvira, Cervilla, Jorge A., Cichon, Sven, Corvin, Aiden, Gill, Michael, Curtis, David, Domenici, Enrico, Gareeva, Anna, Khusnutdinova, Elza, Glatt, Stephen J., Hong, Kyung Sue, Knowles, James A., Lee, Jimmy, Liu, Jianjun, Malhotra, Dheeraj, Menezes, Paulo R., Nimgaonkar, Vishwajit, Paciga, Sara A., Rivera, Margarita, Schwab, Sibylle G., Serretti, Alessandro, Sham, Pak C., Clair, David St, Tsuang, Ming T., Vawter, Marquis P., Werge, Thomas, Wildenauer, Dieter B., Yu, Xin, Yue, Weihua, Verhage, Matthijs, Sahasrabudhe, Dnyanada, Toonen, Ruud F., Posthuma, Danielle, Dai, Nan, Wenwen, Qin, Wildenauer, D. B., Agiananda, Feranindhya, Amir, Nurmiati, Antoni, Ronald, Arsianti, Tiana, Asmarahadi, Asmarahadi, Diatri, H., Djatmiko, Prianto, Irmansyah, Irmansyah, Khalimah, Siti, Kusumadewi, Irmia, Kusumaningrum, Profitasari, Lukman, Petrin R., Nasrun, Martina W., Safyuni, N. S., Prasetyawan, Prasetyawan, Semen, G., Siste, Kristiana, Tobing, Heriani, Widiasih, Natalia, Wiguna, Tjhin, Wulandari, D., Evalina, None, Hananto, A. J., Ismoyo, Joni H., Marini, T. M., Henuhili, Supiyani, Reza, Muhammad, Yusnadewi, Suzy, Abyzov, Alexej, Akbarian, Schahram, van Bakel, Harm, Breen, Michael, Charney, Alex, Dracheva, Stella, Girdhar, Kiran, Hoffman, Gabriel, Jiang, Yan, Pinto, Dalila, Purcell, Shaun, Roussos, Panagiotis, Wiseman, Jennifer, Ashley-Koch, Allison, Crawford, Gregory, Reddy, Tim, Brown, Miguel, Grennan, Kay, Carlyle, Becky, Emani, Prashant, Galeev, Timur, Gerstein, Mark, Gu, Mengting, Guerra, Brittney, Gursoy, Gamze, Kitchen, Robert, Lee, Donghoon, Li, Mingfeng, Liu, Shuang, Navarro, Fabio, Pan, Xinghua, Pochareddy, Sirisha, Rozowsky, Joel, Sestan, Nenad, Sethi, Anurag, Shi, Xu, Szekely, Anna, Wang, Daifeng, Warrell, Jonathan, Weissman, Sherman, Wu, Feinan, Xu, Xuming, Coetzee, Gerard, Farnham, Peggy, Lay, Fides, Rhie, Suhn, Witt, Heather, Wood, Shannon, Yao, Lijing, Gandal, Mike, Polioudakis, Damon, Swarup, Vivek, Won, Hyejung, Giase, Gina, Jiang, Shan, Kefi, Amira, Shieh, Annie, Goes, Fernando, Zandi, Peter, Kim, Yunjung, Mattei, Eugenio, Purcaro, Michael, Pratt, Henry, Peters, Mette A., Sanders, Stephan, Weng, Zhiping, White, Kevin, Arranz, Maria J., Lewis, Cathryn, Lin, Kuang, Walshe, Muriel, Bender, Stephan, Weisbrod, Matthias, Hall, Jeremy, Lawrie, Stephen, Linszen, Don H., Achsel, Tilmann, Bagni, Claudia, Andres-Alonso, Maria, Kreutz, Michael R., Bayés, Àlex, Biederer, Thomas, Brose, Nils, Chua, John Jia En, Coba, Marcelo P., Cornelisse, L. Niels, van Weering, Jan R. T., de Jong, Arthur P. H., MacGillavry, Harold D., de Juan-Sanz, Jaime, Dieterich, Daniela C., Pielot, Rainer, Smalla, Karl-Heinz, Gundelfinger, Eckart D., Goldschmidt, Hana L., Huganir, Richard L., Hoogenraad, Casper, Imig, Cordelia, Jahn, Reinhard, Jung, Hwajin, Kim, Eunjoon, Kaeser, Pascal S., Lipstein, Noa, Malenka, Robert, McPherson, Peter S., O’Connor, Vincent, Ryan, Timothy A., Sala, Carlo, Verpelli, Chiara, Smit, August B., Südhof, Thomas C., Thomas, Paul D., Medical Research Council (UK), National Natural Science Foundation of China, Royal Society (UK), Chinese Academy of Sciences, Shanghai Science and Technology Committee, Research Council of Norway, European Commission, Fundação de Amparo à Pesquisa do Estado de São Paulo, Ministerio de Ciencia e Innovación (España), Instituto de Salud Carlos III, Comunidad de Madrid, Fundación Alicia Koplowitz, Fundación Alonso Lozano, Mental Health Research UK, Wellcome Trust, Brain and Behavior Research Foundation, NIHR Biomedical Research Centre (UK), University College London, Generalitat Valenciana, Internal medicine, Human genetics, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Reproduction & Development (AR&D), Life Course Epidemiology (LCE), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Psychiatry, Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, RS: MHeNs - R3 - Neuroscience, MUMC+: MA Psychiatrie (3), MUMC+: MA Med Staf Spec Psychiatrie (9), MUMC+: Hersen en Zenuw Centrum (3), Trubetskoy, Vassily, Pardiñas, Antonio F., Qi, Ting, Panagiotaropoulou, Georgia, Benyamin, Beben, O'Donovan, Michael C, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Adult Psychiatry, APH - Mental Health, ANS - Complex Trait Genetics, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Molecular and Cellular Neurobiology, Functional Genomics, and Complex Trait Genetics
Subjects: Genetics of the nervous system, Schizophrenia/genetics, VARIANTS, PROFILE, Polymorphism, Single Nucleotide, Genome-wide association studies, Article, DISEASE, SDG 3 - Good Health and Well-being, Humans, Genetic Predisposition to Disease, Alleles, Genomics, Genome-Wide Association Study, Schizophrenia, Polymorphism, RISK, ARCHITECTURE, Science & Technology, Multidisciplinary, MUTATIONS, Genetic Predisposition to Disease/genetics, Settore BIO/13, Single Nucleotide, ASSOCIATION, Polymorphism, Single Nucleotide/genetics, STATISTICS, Multidisciplinary Sciences, INDIVIDUALS, Science & Technology - Other Topics, Diseases of the nervous system, ddc:500, Single Nucleotide/genetics, INTEGRATION
Abstract: Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies., The work at Cardiff University was additionally supported by Medical Research Council Centre grant no. MR/L010305/1 and program grant no. G0800509. S. Xu also gratefully acknowledges the support of the National Natural Science Foundation of China (NSFC) grants (31525014, 91731303, 31771388, 31961130380 and 32041008), the UK Royal Society-Newton Advanced Fellowship (NAF\R1\191094), the Key Research Program of Frontier Sciences (QYZDJ-SSW-SYS009) and the Strategic Priority Research Program (XDB38000000) of the Chinese Academy of Sciences, and the Shanghai Municipal Science and Technology Major Project (2017SHZDZX01). O. A. Andreassen was supported by the Research Council of Norway (283798, 262656, 248980, 273291, 248828, 248778, 223273); KG Jebsen Stiftelsen, South-East Norway Health Authority, EU H2020 no. 847776. B. Melegh was supported in part by the National Scientific Research Program (NKFIH) K 138669. S. V. Faraone is supported by the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 602805, the European Union’s Horizon 2020 research and innovation programme under grant agreements 667302 and 728018 and NIMH grants 5R01MH101519 and U01 MH109536-01. S. I. Belangero was supported by FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo), grant numbers: 2010/08968-6; 2014/07280-1 2011/50740-5 (including R. A. Bressan). The Singapore team (J. Lee, J. Liu, K. Sim, S. A. Chong and M. Subramanian) acknowledges the National Medical Research Council Translational and Clinical Research Flagship Programme (grant no.: NMRC/TCR/003/2008). M. Macek was supported by LM2018132, CZ.02.1.01/0.0/0.0/18_046/0015515 and IP6003 –VZFNM00064203. C. Arango has been funded by the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, PI19/024), co-financed by ERDF Funds from the European Commission, ‘A way of making Europe’, CIBERSAM, Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), European Union Structural Funds, European Union Seventh Framework Program and European Union H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement no 115916, project PRISM; and grant agreement no. 777394, project AIMS-2-TRIALS), Fundación Familia Alonso and Fundación Alicia Koplowitz. E. Bramon acknowledges support from the National Institute of Health Research UK (grant NIHR200756); Mental Health Research UK John Grace QC Scholarship 2018; an ESRC collaborative award 2020; BMA Margaret Temple Fellowship 2016; Medical Research Council New Investigator Award (G0901310); MRC Centenary Award (G1100583); MRC project grant G1100583; National Institute of Health Research UK post-doctoral fellowship (PDA/02/06/016); NARSAD Young Investigator awards 2005 and 2008; Wellcome Trust Research Training Fellowship; Wellcome Trust Case Control Consortium awards (085475/B/08/Z, 085475/Z/08/Z); European Commission Horizon 2020 (747429); NIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and King’s College London; and NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London (UCLH BRC - Mental Health Theme). D. Molto is funded by the European Regional Development Fund (ERDF)–Valencian Community 2014–2020, Spain. E. G. Atkinson was supported by the NIMH K01MH121659.
Published: 2022

33. Silent mutations reveal therapeutic vulnerability in RAS Q61 cancers

Author: Yoshihisa Kobayashi, Chhayheng Chhoeu, Jiaqi Li, Kristin S. Price, Lesli A. Kiedrowski, Jamie L. Hutchins, Aaron I. Hardin, Zihan Wei, Fangxin Hong, Magda Bahcall, Prafulla C. Gokhale, and Pasi A. Jänne
Subjects: Multidisciplinary
Published: 2022

34. Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity

Author: Meng, B., Abdullahi, A., Ferreira, I. A. T. M., Goonawardane, N., Saito, A., Kimura, I., Yamasoba, D., Gerber, P. P., Fatihi, S., Rathore, S., Zepeda, S. K., Papa, G., Kemp, S. A., Ikeda, T., Toyoda, M., Tan, T. S., Kuramochi, J., Mitsunaga, S., Ueno, T., Shirakawa, K., Takaori-Kondo, A., Brevini, T., Mallery, D. L., Charles, O. J., Baker, S., Dougan, G., Hess, C., Kingston, N., Lehner, P. J., Lyons, P. A., Matheson, N. J., Ouwehand, W. H., Saunders, C., Summers, C., Thaventhiran, J. E. D., Toshner, M., Weekes, M. P., Maxwell, P., Shaw, A., Bucke, A., Calder, J., Canna, L., Domingo, J., Elmer, A., Fuller, S., Harris, J., Hewitt, S., Kennet, J., Jose, S., Kourampa, J., Meadows, A., O'Brien, C., Price, J., Publico, C., Rastall, R., Ribeiro, C., Rowlands, J., Ruffolo, V., Tordesillas, H., Bullman, B., Dunmore, B. J., Graf, S., Hodgson, J., Huang, C., Hunter, K., Jones, E., Legchenko, E., Matara, C., Martin, J., Mescia, F., O'Donnell, C., Pointon, L., Shih, J., Sutcliffe, R., Tilly, T., Treacy, C., Tong, Z., Wood, J., Wylot, M., Betancourt, A., Bower, G., Cossetti, C., De Sa, A., Epping, M., Fawke, S., Gleadall, N., Grenfell, R., Hinch, A., Jackson, S., Jarvis, I., Krishna, B., Nice, F., Omarjee, O., Perera, M., Potts, M., Richoz, N., Romashova, V., Stefanucci, L., Strezlecki, M., Turner, L., De Bie, E. M. D. D., Bunclark, K., Josipovic, M., Mackay, M., Butcher, H., Caputo, D., Chandler, M., Chinnery, P., Clapham-Riley, D., Dewhurst, E., Fernandez, C., Furlong, A., Graves, B., Gray, J., Hein, S., Ivers, T., Le Gresley, E., Linger, R., Kasanicki, M., King, R., Meloy, S., Moulton, A., Muldoon, F., Ovington, N., Papadia, S., Penkett, C. J., Phelan, I., Ranganath, V., Paraschiv, R., Sage, A., Sambrook, J., Scholtes, I., Schon, K., Stark, H., Stirrups, K. E., Townsend, P., Walker, N., Webster, J., Butlertanaka, E. P., Tanaka, Y. L., Ito, J., Uriu, K., Kosugi, Y., Suganami, M., Oide, A., Yokoyama, M., Chiba, M., Motozono, C., Nasser, H., Shimizu, R., Kitazato, K., Hasebe, H., Irie, T., Nakagawa, S., Wu, J., Takahashi, M., Fukuhara, T., Shimizu, K., Tsushima, K., Kubo, H., Kazuma, Y., Nomura, R., Horisawa, Y., Nagata, K., Kawai, Y., Yanagida, Y., Tashiro, Y., Tokunaga, K., Ozono, S., Kawabata, R., Morizako, N., Sadamasu, K., Asakura, H., Nagashima, M., Yoshimura, K., Cardenas, P., Munoz, E., Barragan, V., Marquez, S., Prado-Vivar, B., Becerra-Wong, M., Caravajal, M., Trueba, G., Rojas-Silva, P., Grunauer, M., Gutierrez, B., Guadalupe, J. J., Fernandez-Cadena, J. C., Andrade-Molina, D., Baldeon, M., Pinos, A., Bowen, J. E., Joshi, A., Walls, A. C., Jackson, L., Martin, D., Smith, K. G. C., Bradley, J., Briggs, J. A. G., Choi, J., Madissoon, E., Meyer, K. B., Mlcochova, P., Ceron-Gutierrez, L., Doffinger, R., Teichmann, S. A., Fisher, A. J., Pizzuto, M. S., de Marco, A., Corti, D., Hosmillo, M., Lee, J. H., James, L. C., Thukral, L., Veesler, D., Sigal, A., Sampaziotis, F., Goodfellow, I. G., Sato, K., and Gupta, R. K.
Subjects: Adult, Male, COVID-19 Vaccines, Virus Replication, Membrane Fusion, Antibodies, Cell Line, Tissue Culture Techniques, Chlorocebus aethiops, 80 and over, Animals, Humans, Viral, Neutralizing, Lung, Aged, Multidisciplinary, Virulence, SARS-CoV-2, Immune Sera, Cell Membrane, Serine Endopeptidases, COVID-19, Convalescence, Middle Aged, Virus Internalization, Spike Glycoprotein, Intestines, Coronavirus, Nasal Mucosa, Mutation, Female, Angiotensin-Converting Enzyme 2, Aged, 80 and over, Antibodies, Neutralizing, Antibodies, Viral, Spike Glycoprotein, Coronavirus
Abstract: The SARS-CoV-2 Omicron BA.1 variant emerged in 20211 and has multiple mutations in its spike protein2. Here we show that the spike protein of Omicron has a higher affinity for ACE2 compared with Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralizing antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralization. Importantly, the antiviral drugs remdesivir and molnupiravir retain efficacy against Omicron BA.1. Replication was similar for Omicron and Delta virus isolates in human nasal epithelial cultures. However, in lung cells and gut cells, Omicron demonstrated lower replication. Omicron spike protein was less efficiently cleaved compared with Delta. The differences in replication were mapped to the entry efficiency of the virus on the basis of spike-pseudotyped virus assays. The defect in entry of Omicron pseudotyped virus to specific cell types effectively correlated with higher cellular RNA expression of TMPRSS2, and deletion of TMPRSS2 affected Delta entry to a greater extent than Omicron. Furthermore, drug inhibitors targeting specific entry pathways3 demonstrated that the Omicron spike inefficiently uses the cellular protease TMPRSS2, which promotes cell entry through plasma membrane fusion, with greater dependency on cell entry through the endocytic pathway. Consistent with suboptimal S1/S2 cleavage and inability to use TMPRSS2, syncytium formation by the Omicron spike was substantially impaired compared with the Delta spike. The less efficient spike cleavage of Omicron at S1/S2 is associated with a shift in cellular tropism away from TMPRSS2-expressing cells, with implications for altered pathogenesis.
Published: 2022

35. Assembly of functional diversity in an oceanic island flora.

Author: Barajas Barbosa, Martha Paola, Craven, Dylan, Weigelt, Patrick, Denelle, Pierre, Otto, Rüdiger, Díaz, Sandra, Price, Jonathan, Fernández-Palacios, José María, and Kreft, Holger
Abstract: Oceanic island floras are well known for their morphological peculiarities and exhibit striking examples of trait evolution1–3. These morphological shifts are commonly attributed to insularity and are thought to be shaped by the biogeographical processes and evolutionary histories of oceanic islands2,4. However, the mechanisms through which biogeography and evolution have shaped the distribution and diversity of plant functional traits remain unclear5. Here we describe the functional trait space of the native flora of an oceanic island (Tenerife, Canary Islands, Spain) using extensive field and laboratory measurements, and relate it to global trade-offs in ecological strategies. We find that the island trait space exhibits a remarkable functional richness but that most plants are concentrated around a functional hotspot dominated by shrubs with a conservative life-history strategy. By dividing the island flora into species groups associated with distinct biogeographical distributions and diversification histories, our results also suggest that colonization via long-distance dispersal and the interplay between inter-island dispersal and archipelago-level speciation processes drive functional divergence and trait space expansion. Contrary to our expectations, speciation via cladogenesis has led to functional convergence, and therefore only contributes marginally to functional diversity by densely packing trait space around shrubs. By combining biogeography, ecology and evolution, our approach opens new avenues for trait-based insights into how dispersal, speciation and persistence shape the assembly of entire native island floras.On the oceanic island of Tenerife, dispersal, speciation and persistence drive the diversity and distribution of plant functional traits. [ABSTRACT FROM AUTHOR]
Published: 2023
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36. SARS-CoV-2 evolution during treatment of chronic infection

Author: Kemp, S. A., Collier, D. A., Datir, R. P., Ferreira, I. A. T. M., Gayed, S., Jahun, A., Hosmillo, M., Rees-Spear, C., Mlcochova, P., Lumb, I. U., Roberts, D. J., Chandra, A., Temperton, N., Baker, S., Dougan, G., Hess, C., Kingston, N., Lehner, P. J., Lyons, P. A., Matheson, N. J., Owehand, W. H., Saunders, C., Summers, C., Thaventhiran, J. E. D., Toshner, M., Weekes, M. P., Bucke, A., Calder, J., Canna, L., Domingo, J., Elmer, A., Fuller, S., Harris, J., Hewitt, S., Kennet, J., Jose, S., Kourampa, J., Meadows, A., O'Brien, C., Price, J., Publico, C., Rastall, R., Ribeiro, C., Rowlands, J., Ruffolo, V., Tordesillas, H., Bullman, B., Dunmore, B. J., Fawke, S., Graf, S., Hodgson, J., Huang, C., Hunter, K., Jones, E., Legchenko, E., Matara, C., Martin, J., Mescia, F., O'Donnell, C., Pointon, L., Pond, N., Shih, J., Sutcliffe, R., Tilly, T., Treacy, C., Tong, Z., Wood, J., Wylot, M., Bergamaschi, L., Betancourt, A., Bower, G., Cossetti, C., De Sa, A., Epping, M., Gleadall, N., Grenfell, R., Hinch, A., Huhn, O., Jackson, S., Jarvis, I., Lewis, D., Marsden, J., Nice, F., Okecha, G., Omarjee, O., Perera, M., Richoz, N., Romashova, V., Yarkoni, N. S., Sharma, R., Stefanucci, L., Stephens, J., Strezlecki, M., Turner, L., De Bie, E. M. D. D., Bunclark, K., Josipovic, M., Mackay, M., Rossi, S., Selvan, M., Spencer, S., Yong, C., Ansaripour, A., Michael, A., Mwaura, L., Patterson, C., Polwarth, G., Polgarova, P., di Stefano, G., Fahey, C., Michel, R., Bong, S. -H., Coudert, J. D., Holmes, E., Allison, J., Butcher, H., Caputo, D., Clapham-Riley, D., Dewhurst, E., Furlong, A., Graves, B., Gray, J., Ivers, T., Kasanicki, M., Le Gresley, E., Linger, R., Meloy, S., Muldoon, F., Ovington, N., Papadia, S., Phelan, I., Stark, H., Stirrups, K. E., Townsend, P., Walker, N., Webster, J., Robson, S. C., Loman, N. J., Connor, T. R., Golubchik, T., Martinez Nunez, R. T., Ludden, C., Corden, S., Johnston, I., Bonsall, D., Smith, C. P., Awan, A. R., Bucca, G., Estee Torok, M., Saeed, K., Prieto, J. A., Jackson, D. K., Hamilton, W. L., Snell, L. B., Moore, C., Harrison, E. M., Goncalves, S., Fairley, D. J., Loose, M. W., Watkins, J., Livett, R., Moses, S., Amato, R., Nicholls, S., Bull, M., Smith, D. L., Barrett, J., Aanensen, D. M., Curran, M. D., Parmar, S., Aggarwal, D., Shepherd, J. G., Parker, M. D., Glaysher, S., Bashton, M., Underwood, A. P., Pacchiarini, N., Loveson, K. F., Carabelli, A. M., Templeton, K. E., Langford, C. F., Sillitoe, J., de Silva, T. 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K., Medical Microbiology and Infection Prevention, AII - Infectious diseases, Collier, Dami A [0000-0001-5446-4423], Jahun, Aminu [0000-0002-4585-1701], Temperton, Nigel [0000-0002-7978-3815], Modis, Yorgo [0000-0002-6084-0429], Briggs, John AG [0000-0003-3990-6910], Goldstein, Richard A [0000-0001-5148-4672], Skittrall, Jordan P [0000-0002-8228-3758], Gkrania-Klotsas, Effrossyni [0000-0002-0930-8330], McCoy, Laura E [0000-0001-9503-7946], Gupta, Ravindra K [0000-0001-9751-1808], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, Male, Time Factors, viruses, Passive, Antibodies, Viral, CITIID-NIHR BioResource COVID-19 Collaboration, 2.1 Biological and endogenous factors, Viral, Aetiology, Neutralizing, Lung, Phylogeny, neutralising antibodies, Infectivity, education.field_of_study, Genome, Multidisciplinary, Alanine, biology, High-Throughput Nucleotide Sequencing, Viral Load, Spike Glycoprotein, Virus Shedding, Adenosine Monophosphate, Aged, Antibodies, Neutralizing, COVID-19, Chronic Disease, Genome, Viral, Humans, Immune Evasion, Immune Tolerance, Immunization, Passive, Immunosuppression Therapy, Mutagenesis, Mutant Proteins, Mutation, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Evolution, Molecular, Infectious Diseases, Pneumonia & Influenza, Antibody, Infection, Viral load, Biotechnology, Evolution, General Science & Technology, antibody escape, Convalescent plasma, 030106 microbiology, Population, evasion, Antibodies, Virus, Article, Vaccine Related, resistance, 03 medical and health sciences, Immune system, COVID-19 Genomics UK (COG-UK) Consortium, Biodefense, Genetics, Viral shedding, education, COVID-19 Serotherapy, QR355, Prevention, Wild type, Molecular, Pneumonia, Virology, COVID-19 Drug Treatment, Coronavirus, Emerging Infectious Diseases, Good Health and Well Being, 030104 developmental biology, biology.protein, Immunization, immune suppression, mutation
Abstract: The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for virus infection through the engagement of the human ACE2 protein1 and is a major antibody target. Here we show that chronic infection with SARS-CoV-2 leads to viral evolution and reduced sensitivity to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma, by generating whole-genome ultra-deep sequences for 23 time points that span 101 days and using in vitro techniques to characterize the mutations revealed by sequencing. There was little change in the overall structure of the viral population after two courses of remdesivir during the first 57 days. However, after convalescent plasma therapy, we observed large, dynamic shifts in the viral population, with the emergence of a dominant viral strain that contained a substitution (D796H) in the S2 subunit and a deletion (ΔH69/ΔV70) in the S1 N-terminal domain of the spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype were reduced in frequency, before returning during a final, unsuccessful course of convalescent plasma treatment. In vitro, the spike double mutant bearing both ΔH69/ΔV70 and D796H conferred modestly decreased sensitivity to convalescent plasma, while maintaining infectivity levels that were similar to the wild-type virus.The spike substitution mutant D796H appeared to be the main contributor to the decreased susceptibility to neutralizing antibodies, but this mutation resulted in an infectivity defect. The spike deletion mutant ΔH69/ΔV70 had a twofold higher level of infectivity than wild-type SARS-CoV-2, possibly compensating for the reduced infectivity of the D796H mutation. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy, which is associated with the emergence of viral variants that show evidence of reduced susceptibility to neutralizing antibodies in immunosuppressed individuals.
Published: 2021

37. Genetic mechanisms of critical illness in COVID-19

Author: Pairo-Castineira, Erola, Clohisey, Sara, Klaric, Lucija, Bretherick, Andrew D, Rawlik, Konrad, Pasko, Dorota, Walker, Susan, Parkinson, Nick, Fourman, Max Head, Russell, Clark D, Furniss, James, Richmond, Anne, Gountouna, Elvina, Wrobel, Nicola, Harrison, David, Wang, Bo, Yang, Wu, Meynert, Alison, Griffiths, Fiona, Oosthuyzen, Wilna, Kousathanas, Athanasios, Moutsianas, Loukas, Yang, Zhijian, Zhai, Ranran, Zheng, Chenqing, Grimes, Graeme, Beale, Rupert, Millar, Jonathan, Shih, Barbara, Keating, Sean, Zechner, Marie, Haley, Chris, Porteous, David J, Hayward, Caroline, Yang, Jian, Knight, Julian, Summers, Charlotte, Shankar-Hari, Manu, Klenerman, Paul, Turtle, Lance, Antonia, Ho, Moore, Shona C, Hinds, Charles, Horby, Peter, Nichol, Alistair, Maslove, David, Ling, Lowell, Mcauley, Danny, Montgomery, Hugh, Walsh, Timothy, Pereira, Alexandre C, Renieri, Johnny, Millar, Alistair, Nichol, Tim, Walsh, Manu, Shankar-Hari, Chris, Ponting, Jen, Meikle, Paul, Finernan, Ellie, Mcmaster, Andy, Law, J Kenneth Baillie, Trevor, Paterson, Tony, Wackett, Ruth, Armstrong, Richard, Clark, Audrey, Coutts, Lorna, Donnelly, Tammy, Gilchrist, Katarzyna, Hafezi, Louise, Macgillivray, Alan, Maclean, Sarah, Mccafferty, Kirstie, Morrice, Jane, Weaver, Ceilia, Boz, Ailsa, Golightly, Mari, Ward, Hanning, Mal, Helen, Szoor-McElhinney, Adam, Brown, Ross, Hendry, Andrew, Stenhouse, Louise, Cullum, Dawn, Law, Sarah, Law, Rachel, Law, Maaike, Swets, Nicky, Day, Filip, Taneski, Esther, Duncan, Nicholas, Parkinson, Collier, D, Wood, S, Zak, A, Borra, C, Matharu, M, May, P, Alldis, Z, Mitchelmore, O, Bowles, R, Easthope, A, Bibi, F, Lancoma-Malcolm, I, Gurasashvili, J, Pheby, J, Shiel, J, Bolton, M, Patel, M, Taylor, M, Zongo, O, Ebano, P, Harding, P, Astin-Chamberlain, R, Choudhury, Y, Cox, A, Kallon, D, Burton, M, Hall, R, Blowes, S, Prime, Z, Biddle, J, Prysyazhna, O, Newman, T, Tierney, C, Kassam, J, Shankar-Hari, M, Ostermann, M, Campos, S, Bociek, A, Lim, R, Grau, N, O Jones, T, Whitton, 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Konrad [0000-0002-0010-370X], Walker, Susan [0000-0002-5016-6426], Fourman, Max Head [0000-0001-7381-2278], Russell, Clark D [0000-0002-9873-8243], Gountouna, Elvina [0000-0001-7870-2780], Wang, Bo [0000-0002-1580-797X], Wu, Yang [0000-0002-0128-7280], Kousathanas, Athanasios [0000-0001-6265-6521], Moutsianas, Loukas [0000-0001-5453-345X], Zhai, Ranran [0000-0002-5834-9120], Beale, Rupert [0000-0002-6705-8560], Keating, Sean [0000-0001-8552-5604], Haley, Chris [0000-0002-9811-0210], Porteous, David J [0000-0003-1249-6106], Hayward, Caroline [0000-0002-9405-9550], Yang, Jian [0000-0003-2001-2474], Knight, Julian [0000-0002-0377-5536], Summers, Charlotte [0000-0002-7269-2873], Shankar-Hari, Manu [0000-0002-5338-2538], Turtle, Lance [0000-0002-0778-1693], Moore, Shona C [0000-0001-8610-2806], Hinds, Charles [0000-0001-5094-8324], McAuley, Danny [0000-0002-3283-1947], Montgomery, Hugh [0000-0001-8797-5019], Renieri, Alessandra [0000-0002-0846-9220], Shen, Xia [0000-0003-4390-1979], 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J., Ye, C., Weldon, C. H., Filshtein-Sonmez, T., Coker, D., Symons, A., Esparza-Gordillo, J., Aslibekyan, S., Auton, A., Krieger, J. E., Marques, E., Jannes, C. E., Mari, F., Daga, S., Baldassarri, M., Benetti, E., Furini, S., Fallerini, C., Fava, F., Valentino, F., Doddato, G., Giliberti, A., Tita, R., Amitrano, S., Bruttini, M., Croci, S., Meloni, I., Pinto, A. M., Frullanti, E., Mencarelli, M. A., Rizzo, C. L., Montagnani, F., Di Sarno, L., Tommasi, A., Palmieri, M., Emiliozzi, A., Fabbiani, M., Rossetti, B., Zanelli, G., Bargagli, E., Bergantini, L., D'Alessandro, M., Cameli, P., Bennet, D., Anedda, F., Marcantonio, S., Scolletta, S., Franchi, F., Mazzei, M. A., Guerrini, S., Conticini, E., Cantarini, L., Frediani, B., Tacconi, D., Spertilli, C., Feri, M., Donati, A., Scala, R., Guidelli, L., Spargi, G., Corridi, M., Nencioni, C., Croci, L., Caldarelli, G. P., Spagnesi, M., Piacentini, P., Bandini, M., Desanctis, E., Cappelli, S., Canaccini, A., Verzuri, A., Anemoli, V., Ognibene, A., Vaghi, M., D'Arminio Monforte, A., Merlini, E., Mondelli, M. U., Mantovani, S., Ludovisi, S., Girardis, M., Venturelli, S., Sita, M., Cossarizza, A., Antinori, A., Vergori, A., Rusconi, S., Siano, M., Gabrieli, A., Riva, A., Francisci, D., Schiaroli, E., Scotton, P. G., Andretta, F., Panese, S., Scaggiante, R., Gatti, F., Parisi, S. G., Castelli, F., Quiros-Roldan, M. E., Magro, P., Zanella, I., Della Monica, M., Piscopo, C., Capasso, M., Russo, R., Andolfo, I., Iolascon, A., Fiorentino, G., Carella, M., Castori, M., Merla, G., Aucella, F., Raggi, P., Marciano, C., Perna, R., Bassetti, M., Di Biagio, A., Sanguinetti, M., Masucci, L., Valente, S., Mandala, M., Giorli, A., Salerni, L., Zucchi, P., Parravicini, P., Menatti, E., Baratti, S., Trotta, T., Giannattasio, F., Coiro, G., Lena, F., Coviello, D. A., Mussini, C., Bosio, G., Martinelli, E., Mancarella, S., Tavecchia, L., Crotti, L., Picchiotti, N., Gori, M., Gabbi, C., Sanarico, M., Ceri, S., Pinoli, P., Raimondi, F., Biscarini, F., Stella, A., Shen, X., Ponting, C. P., Fawkes, A., Tenesa, A., Caulfield, M., Scott, R., Rowan, K., Murphy, L., Openshaw, P. J. M., Semple, M. G., Vitart, V., and Wilson, J. F.
Subjects: 0301 basic medicine, Male, CCR2, Chromosomes, Human, Pair 21, Genome-wide association study, Receptor, Interferon alpha-beta, Disease, Bioinformatics, Genome-wide association studies, 23andMe Investigators, Interferon alpha-beta, 0302 clinical medicine, Receptors, 2',5'-Oligoadenylate Synthetase, Pair 12, genetics, Lung, BRACOVID Investigators, Multidisciplinary, GenOMICC Investigators, Tyrosine kinase 2, 030220 oncology & carcinogenesis, Multigene Family, Medical genetics, Female, Dipeptidyl-Peptidases and Tripeptidyl-Peptidase, 5'-Oligoadenylate Synthetase, Human, Receptor, medicine.medical_specialty, Critical Care, Receptors, CCR2, General Science & Technology, Critical Illness, Chromosomes, 03 medical and health sciences, Intensive care, Mendelian randomization, Immunogenetics, medicine, Humans, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases, Gen-COVID Investigators, Inflammation, TYK2 Kinase, Chromosomes, Human, Pair 12, Pair 19, SARS-CoV-2, business.industry, Drug Repositioning, COVID-19, United Kingdom, COVID-19 Human Genetics Initiative, 030104 developmental biology, Viral infection, Chromosomes, Human, Pair 19, Genome-Wide Association Study, Pharmacogenomics, ISARICC Investigators, Pair 21, 2', business
Abstract: Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079,P=1.65×10−8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1,OAS2andOAS3); on chromosome 19p13.2 (rs74956615,P=2.3×10−8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069,P=3.98× 10−12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757,P=4.99×10−8) in the interferon receptor geneIFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression ofIFNAR2, or high expression ofTYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte–macrophage chemotactic receptorCCR2is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice.
Published: 2020
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38. Unextractable fossil fuels in a 1.5 °C world

Author: Steve Pye, Dan Welsby, James Price, and Paul Ekins
Subjects: Fossil Fuels, Paris, Global energy, Time Factors, Natural resource economics, International Cooperation, Conservation of Energy Resources, Geographic Mapping, Global Warming, Production (economics), Coal, Oil and gas production, Methane gas, Probability, Multidisciplinary, business.industry, Fossil fuel, Global warming, Temperature, Uncertainty, Limiting, Models, Theoretical, Environmental science, business, Methane, Fuel Oils
Abstract: Parties to the 2015 Paris Agreement pledged to limit global warming to well below 2 °C and to pursue efforts to limit the temperature increase to 1.5 °C relative to pre-industrial times1. However, fossil fuels continue to dominate the global energy system and a sharp decline in their use must be realized to keep the temperature increase below 1.5 °C (refs. 2–7). Here we use a global energy systems model8 to assess the amount of fossil fuels that would need to be left in the ground, regionally and globally, to allow for a 50 per cent probability of limiting warming to 1.5 °C. By 2050, we find that nearly 60 per cent of oil and fossil methane gas, and 90 per cent of coal must remain unextracted to keep within a 1.5 °C carbon budget. This is a large increase in the unextractable estimates for a 2 °C carbon budget9, particularly for oil, for which an additional 25 per cent of reserves must remain unextracted. Furthermore, we estimate that oil and gas production must decline globally by 3 per cent each year until 2050. This implies that most regions must reach peak production now or during the next decade, rendering many operational and planned fossil fuel projects unviable. We probably present an underestimate of the production changes required, because a greater than 50 per cent probability of limiting warming to 1.5 °C requires more carbon to stay in the ground and because of uncertainties around the timely deployment of negative emission technologies at scale. A global energy system model finds that planned fossil fuel extraction is inconsistent with limiting global warming to 1.5 °C, because the majority of fossil fuel reserves must stay in the ground.
Published: 2021

39. A natively flexible 32-bit Arm microprocessor

Author: James Myers, Scott R. White, Jedrzej Kufel, Emre Ozer, John Philip Biggs, Antony Sou, Catherine Ramsdale, Richard H. Price, Ken Williamson, and Simon Craske
Subjects: Multidisciplinary, Reduced instruction set computing, Computer science, business.industry, Transistor, 32-bit, Flexible electronics, law.invention, ARM architecture, Form factor (design), Microprocessor, law, Central processing unit, business, Computer hardware
Abstract: Nearly 50 years ago, Intel created the world’s first commercially produced microprocessor—the 4004 (ref. 1), a modest 4-bit CPU (central processing unit) with 2,300 transistors fabricated using 10 μm process technology in silicon and capable only of simple arithmetic calculations. Since this ground-breaking achievement, there has been continuous technological development with increasing sophistication to the stage where state-of-the-art silicon 64-bit microprocessors now have 30 billion transistors (for example, the AWS Graviton2 (ref. 2) microprocessor, fabricated using 7 nm process technology). The microprocessor is now so embedded within our culture that it has become a meta-invention—that is, it is a tool that allows other inventions to be realized, most recently enabling the big data analysis needed for a COVID-19 vaccine to be developed in record time. Here we report a 32-bit Arm (a reduced instruction set computing (RISC) architecture) microprocessor developed with metal-oxide thin-film transistor technology on a flexible substrate (which we call the PlasticARM). Separate from the mainstream semiconductor industry, flexible electronics operate within a domain that seamlessly integrates with everyday objects through a combination of ultrathin form factor, conformability, extreme low cost and potential for mass-scale production. PlasticARM pioneers the embedding of billions of low-cost, ultrathin microprocessors into everyday objects. Flexible electronic platforms would enable the integration of functional electronic circuitry with many everyday objects; here, a low-cost and fully flexible 32-bit microprocessor is produced.
Published: 2021

40. Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2

Author: Collier, D. A., Ferreira, I. A. T. M., Kotagiri, P., Datir, R. P., Lim, E. Y., Touizer, E., Meng, B., Abdullahi, A., Baker, S., Dougan, G., Hess, C., Kingston, N., Lehner, P. J., Lyons, P. A., Matheson, N. J., Owehand, W. H., Saunders, C., Summers, C., Thaventhiran, J. E. D., Toshner, M., Weekes, M. P., Maxwell, P., Shaw, A., Bucke, A., Calder, J., Canna, L., Domingo, J., Elmer, A., Fuller, S., Harris, J., Hewitt, S., Kennet, J., Jose, S., Kourampa, J., Meadows, A., O'Brien, C., Price, J., Publico, C., Rastall, R., Ribeiro, C., Rowlands, J., Ruffolo, V., Tordesillas, H., Bullman, B., Dunmore, B. J., Fawke, S., Graf, S., Hodgson, J., Huang, C., Hunter, K., Jones, E., Legchenko, E., Matara, C., Martin, J., Mescia, F., O'Donnell, C., Pointon, L., Pond, N., Shih, J., Sutcliffe, R., Tilly, T., Treacy, C., Tong, Z., Wood, J., Wylot, M., Bergamaschi, L., Betancourt, A., Bower, G., Cossetti, C., De Sa, A., Epping, M., Gleadall, N., Grenfell, R., Hinch, A., Huhn, O., Jackson, S., Jarvis, I., Krishna, B., Lewis, D., Marsden, J., Nice, F., Okecha, G., Omarjee, O., Perera, M., Potts, M., Richoz, N., Romashova, V., Yarkoni, N. S., Sharma, R., Stefanucci, L., Stephens, J., Strezlecki, M., Turner, L., D. D. De Bie E. M., Bunclark, K., Josipovic, M., Mackay, M., Michael, A., Rossi, S., Selvan, M., Spencer, S., Yong, C., Ansaripour, A., Mwaura, L., Patterson, C., Polwarth, G., Polgarova, P., di Stefano, G., Fahey, C., Michel, R., Bong, S. -H., Coudert, J. D., Holmes, E., Allison, J., Butcher, H., Caputo, D., Clapham-Riley, D., Dewhurst, E., Furlong, A., Graves, B., Gray, J., Ivers, T., Kasanicki, M., Le Gresley, E., Linger, R., Meloy, S., Muldoon, F., Ovington, N., Papadia, S., Phelan, I., Stark, H., Stirrups, K. E., Townsend, P., Walker, N., Webster, J., Smith, K. G. C., Bradley, J. R., Ceron-Gutierrez, L., Cortes-Acevedo, P., Barcenas-Morales, G., Linterman, M. A., Mccoy, L. E., Davis, C., Thomson, E., Mckinney, E., Doffinger, R., Wills, M., Gupta, R. K., Collier, Dami A [0000-0001-5446-4423], Datir, Rawlings P [0000-0003-0521-2144], Smith, Kenneth GC [0000-0003-3829-4326], Linterman, Michelle A [0000-0001-6047-1996], McCoy, Laura E [0000-0001-9503-7946], Thomson, Emma [0000-0003-1482-0889], Lyons, Paul A [0000-0001-7035-8997], Gupta, Ravindra K [0000-0001-9751-1808], and Apollo - University of Cambridge Repository
Subjects: Male, 0301 basic medicine, Aging, Secondary, T-Lymphocytes, Antibodies, Viral, Neutralization, 0302 clinical medicine, 80 and over, Medicine, Viral, Neutralizing, Adult, Aged, Aged, 80 and over, Antibodies, Neutralizing, Autoantibodies, B-Lymphocytes, BNT162 Vaccine, COVID-19 Vaccines, Female, Health Personnel, Humans, Immunization, Secondary, Immunoglobulin A, Immunoglobulin Class Switching, Immunoglobulin G, Immunologic Memory, Inflammation, Interferon-gamma, Interleukin-2, Middle Aged, SARS-CoV-2, Somatic Hypermutation, Immunoglobulin, Spike Glycoprotein, Coronavirus, Vaccination, Vaccines, Synthetic, Immunity, Sars-Cov-2, Vaccines, education.field_of_study, Multidisciplinary, biology, Spike Glycoprotein, 030220 oncology & carcinogenesis, Antibody, Population, Article, Antibodies, 03 medical and health sciences, Immune system, Immunoglobulin, education, business.industry, Synthetic, Somatic Hypermutation, Vaccine efficacy, Coronavirus, 030104 developmental biology, Immunization, Immunology, biology.protein, business
Abstract: Although two-dose mRNA vaccination provides excellent protection against SARS-CoV-2, there is little information about vaccine efficacy against variants of concern (VOC) in individuals above eighty years of age1. Here we analysed immune responses following vaccination with the BNT162b2 mRNA vaccine2 in elderly participants and younger healthcare workers. Serum neutralization and levels of binding IgG or IgA after the first vaccine dose were lower in older individuals, with a marked drop in participants over eighty years old. Sera from participants above eighty showed lower neutralization potency against the B.1.1.7 (Alpha), B.1.351 (Beta) and P.1. (Gamma) VOC than against the wild-type virus and were more likely to lack any neutralization against VOC following the first dose. However, following the second dose, neutralization against VOC was detectable regardless of age. The frequency of SARS-CoV-2 spike-specific memory B cells was higher in elderly responders (whose serum showed neutralization activity) than in non-responders after the first dose. Elderly participants showed a clear reduction in somatic hypermutation of class-switched cells. The production of interferon-γ and interleukin-2 by SARS-CoV-2 spike-specific T cells was lower in older participants, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high-risk population and that specific measures to boost vaccine responses in this population are warranted, particularly where variants of concern are circulating., Nature, 596 (7872), ISSN:0028-0836, ISSN:1476-4687
Published: 2021

41. Big data little help in megafauna mysteries

Author: Price, Gilbert J., Louys, Julien, Faith, J. Tyler, Lorenzen, Eline, and Westaway, Michael C.
Subjects: Big data -- Usage, Megafauna -- Identification and classification, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract: Too many meta-analyses of extinctions of giant kangaroos or huge sloths use data that are poor or poorly understood, warn Gilbert J. Price and colleagues. Too many meta-analyses of extinctions of giant kangaroos or huge sloths usedata that are poor or poorly understood, warn Gilbert J. Price and colleagues., Author(s): Gilbert J. Price, Julien Louys, J. Tyler Faith, Eline Lorenzen, Michael C. WestawayAuthor Affiliations:Big data little help in megafauna mysteries An artist's impression of the extinct woolly rhinoceros (Coelodonta [...]
Published: 2018
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42. Codon influence on protein expression in E. coli correlates with mRNA levels

Author: Boel, Gregory, Letso, Reka, Neely, Helen, Price, W. Nicholson, Wong, Kam-Ho, Su, Min, Luff, Jon D., Valecha, Mayank, Everett, John K., Acton, Thomas B., Xiao, Rong, Montelione, Gaetano T., Aalberts, Daniel P., and Hunt, John F.
Subjects: Messenger RNA -- Research, Codon -- Research, Proteins -- Genetic aspects, Microbiological research, Escherichia coli -- Genetic aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract: Degeneracy in the genetic code, which enables a single protein to be encoded by a multitude of synonymous gene sequences, has an important role in regulating protein expression, but substantial uncertainty exists concerning the details of this phenomenon. Here we analyse the sequence features influencing protein expression levels in 6,348 experiments using bacteriophage T7 polymerase to synthesize messenger RNA in Escherichia coli. Logistic regression yields a new codon-influence metric that correlates only weakly with genomic codon-usage frequency, but strongly with global physiological protein concentrations and also mRNA concentrations and lifetimes in vivo. Overall, the codon content influences protein expression more strongly than mRNA-folding parameters, although the latter dominate in the initial ~16 codons. Genes redesigned based on our analyses are transcribed with unaltered efficiency but translated with higher efficiency in vitro. The less efficiently translated native sequences show greatly reduced mRNA levels in vivo. Our results suggest that codon content modulates a kinetic competition between protein elongation and mRNA degradation that is a central feature of the physiology and also possibly the regulation of translation in E. coli., Degenerate encoding of 20 amino acids by 61 triplet nucleotide codons enables the same protein sequence to be synthesized by a vast number of synonymous mRNAs. While variations between synonymous [...]
Published: 2016
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43. Africa-specific human genetic variation near CHD1Lassociates with HIV-1 load

Author: McLaren, Paul J., Porreca, Immacolata, Iaconis, Gennaro, Mok, Hoi Ping, Mukhopadhyay, Subhankar, Karakoc, Emre, Cristinelli, Sara, Pomilla, Cristina, Bartha, István, Thorball, Christian W., Tough, Riley H., Angelino, Paolo, Kiar, Cher S., Carstensen, Tommy, Fatumo, Segun, Porter, Tarryn, Jarvis, Isobel, Skarnes, William C., Bassett, Andrew, DeGorter, Marianne K., Sathya Moorthy, Mohana Prasad, Tuff, Jeffrey F., Kim, Eun-Young, Walter, Miriam, Simons, Lacy M., Bashirova, Arman, Buchbinder, Susan, Carrington, Mary, Cossarizza, Andrea, De Luca, Andrea, Goedert, James J., Goldstein, David B., Haas, David W., Herbeck, Joshua T., Johnson, Eric O., Kaleebu, Pontiano, Kilembe, William, Kirk, Gregory D., Kootstra, Neeltje A., Kral, Alex H., Lambotte, Olivier, Luo, Ma, Mallal, Simon, Martinez-Picado, Javier, Meyer, Laurence, Miro, José M., Moodley, Pravi, Motala, Ayesha A., Mullins, James I., Nam, Kireem, Obel, Niels, Pirie, Fraser, Plummer, Francis A., Poli, Guido, Price, Matthew A., Rauch, Andri, Theodorou, Ioannis, Trkola, Alexandra, Walker, Bruce D., Winkler, Cheryl A., Zagury, Jean-François, Montgomery, Stephen B., Ciuffi, Angela, Hultquist, Judd F., Wolinsky, Steven M., Dougan, Gordon, Lever, Andrew M. L., Gurdasani, Deepti, Groom, Harriet, Sandhu, Manjinder S., and Fellay, Jacques
Abstract: HIV-1 remains a global health crisis1, highlighting the need to identify new targets for therapies. Here, given the disproportionate HIV-1 burden and marked human genome diversity in Africa2, we assessed the genetic determinants of control of set-point viral load in 3,879 people of African ancestries living with HIV-1 participating in the international collaboration for the genomics of HIV3. We identify a previously undescribed association signal on chromosome 1 where the peak variant associates with an approximately 0.3 log10-transformed copies per ml lower set-point viral load per minor allele copy and is specific to populations of African descent. The top associated variant is intergenic and lies between a long intergenic non-coding RNA (LINC00624) and the coding gene CHD1L, which encodes a helicase that is involved in DNA repair4. Infection assays in iPS cell-derived macrophages and other immortalized cell lines showed increased HIV-1 replication in CHD1L-knockdown and CHD1L-knockout cells. We provide evidence from population genetic studies that Africa-specific genetic variation near CHD1Lassociates with HIV replication in vivo. Although experimental studies suggest that CHD1L is able to limit HIV infection in some cell types in vitro, further investigation is required to understand the mechanisms underlying our observations, including any potential indirect effects of CHD1L on HIV spread in vivo that our cell-based assays cannot recapitulate.
Published: 2023
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44. Single-cell eQTL models reveal dynamic T cell state dependence of disease loci

Author: Nathan, Aparna, primary, Asgari, Samira, additional, Ishigaki, Kazuyoshi, additional, Valencia, Cristian, additional, Amariuta, Tiffany, additional, Luo, Yang, additional, Beynor, Jessica I., additional, Baglaenko, Yuriy, additional, Suliman, Sara, additional, Price, Alkes L., additional, Lecca, Leonid, additional, Murray, Megan B., additional, Moody, D. Branch, additional, and Raychaudhuri, Soumya, additional
Published: 2022
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45. Prevalence and architecture of de novo mutations in developmental disorders

Author: McRae, Jeremy F., Clayton, Stephen, Fitzgerald, Tomas W., Kaplanis, Joanna, Prigmore, Elena, Rajan, Diana, Sifrim, Alejandro, Aitken, Stuart, Akawi, Nadia, Alvi, Mohsan, Ambridge, Kirsty, Barrett, Daniel M., Bayzetinova, Tanya, Jones, Philip, Jones, Wendy D., King, Daniel, Krishnappa, Netravathi, Mason, Laura E., Singh, Tarjinder, Tivey, Adrian R., Ahmed, Munaza, Anjum, Uruj, Archer, Hayley, Armstrong, Ruth, Awada, Jana, Balasubramanian, Meena, Banka, Siddharth, Baralle, Diana, Barnicoat, Angela, Batstone, Paul, Baty, David, Bennett, Chris, Berg, Jonathan, Bernhard, Birgitta, Bevan, Paul A., Bitner-Glindzicz, Maria, Blair, Edward, Blyth, Moira, Bohanna, David, Bourdon, Louise, Bourn, David, Bradley, Lisa, Brady, Angela, Brent, Simon, Brewer, Carole, Brunstrom, Kate, Bunyan, David J., Burn, John, Canham, Natalie, Castle, Bruce, Chandler, Kate, Chatzimichali, Elena, Cilliers, Deirdre, Clarke, Angus, Clasper, Susan, Clayton-Smith, Jill, Clowes, Virginia, Coates, Andrea, Cole, Trevor, Colgiu, Irina, Collins, Amanda, Collinson, Morag N., Connell, Fiona, Cooper, Nicola, Cox, Helen, Cresswell, Lara, Cross, Gareth, Crow, Yanick, D’Alessandro, Mariella, Dabir, Tabib, Davidson, Rosemarie, Davies, Sally, de Vries, Dylan, Dean, John, Deshpande, Charu, Devlin, Gemma, Dixit, Abhijit, Dobbie, Angus, Donaldson, Alan, Donnai, Dian, Donnelly, Deirdre, Donnelly, Carina, Douglas, Angela, Douzgou, Sofia, Duncan, Alexis, Eason, Jacqueline, Ellard, Sian, Ellis, Ian, Elmslie, Frances, Evans, Karenza, Everest, Sarah, Fendick, Tina, Fisher, Richard, Flinter, Frances, Foulds, Nicola, Fry, Andrew, Fryer, Alan, Gardiner, Carol, Gaunt, Lorraine, Ghali, Neeti, Gibbons, Richard, Gill, Harinder, Goodship, Judith, Goudie, David, Gray, Emma, Green, Andrew, Greene, Philip, Greenhalgh, Lynn, Gribble, Susan, Harrison, Rachel, Harrison, Lucy, Harrison, Victoria, Hawkins, Rose, He, Liu, Hellens, Stephen, Henderson, Alex, Hewitt, Sarah, Hildyard, Lucy, Hobson, Emma, Holden, Simon, Holder, Muriel, Holder, Susan, Hollingsworth, Georgina, Homfray, Tessa, Humphreys, Mervyn, Hurst, Jane, Hutton, Ben, Ingram, Stuart, Irving, Melita, Islam, Lily, Jackson, Andrew, Jarvis, Joanna, Jenkins, Lucy, Johnson, Diana, Jones, Elizabeth, Josifova, Dragana, Joss, Shelagh, Kaemba, Beckie, Kazembe, Sandra, Kelsell, Rosemary, Kerr, Bronwyn, Kingston, Helen, Kini, Usha, Kinning, Esther, Kirby, Gail, Kirk, Claire, Kivuva, Emma, Kraus, Alison, Kumar, Dhavendra, Ajith Kumar, V. K., Lachlan, Katherine, Lam, Wayne, Lampe, Anne, Langman, Caroline, Lees, Melissa, Lim, Derek, Longman, Cheryl, Lowther, Gordon, Lynch, Sally A., Magee, Alex, Maher, Eddy, Male, Alison, Mansour, Sahar, Marks, Karen, Martin, Katherine, Maye, Una, McCann, Emma, McConnell, Vivienne, McEntagart, Meriel, McGowan, Ruth, McKay, Kirsten, McKee, Shane, McMullan, Dominic J., McNerlan, Susan, McWilliam, Catherine, Mehta, Sarju, Metcalfe, Kay, Middleton, Anna, Miedzybrodzka, Zosia, Miles, Emma, Mohammed, Shehla, Montgomery, Tara, Moore, David, Morgan, Sian, Morton, Jenny, Mugalaasi, Hood, Murday, Victoria, Murphy, Helen, Naik, Swati, Nemeth, Andrea, Nevitt, Louise, Newbury-Ecob, Ruth, Norman, Andrew, O’Shea, Rosie, Ogilvie, Caroline, Ong, Kai-Ren, Park, Soo-Mi, Parker, Michael J., Patel, Chirag, Paterson, Joan, Payne, Stewart, Perrett, Daniel, Phipps, Julie, Pilz, Daniela T., Pollard, Martin, Pottinger, Caroline, Poulton, Joanna, Pratt, Norman, Prescott, Katrina, Price, Sue, Pridham, Abigail, Procter, Annie, Purnell, Hellen, Quarrell, Oliver, Ragge, Nicola, Rahbari, Raheleh, Randall, Josh, Rankin, Julia, Raymond, Lucy, Rice, Debbie, Robert, Leema, Roberts, Eileen, Roberts, Jonathan, Roberts, Paul, Roberts, Gillian, Ross, Alison, Rosser, Elisabeth, Saggar, Anand, Samant, Shalaka, Sampson, Julian, Sandford, Richard, Sarkar, Ajoy, Schweiger, Susann, Scott, Richard, Scurr, Ingrid, Selby, Ann, Seller, Anneke, Sequeira, Cheryl, Shannon, Nora, Sharif, Saba, Shaw-Smith, Charles, Shearing, Emma, Shears, Debbie, Sheridan, Eamonn, Simonic, Ingrid, Singzon, Roldan, Skitt, Zara, Smith, Audrey, Smith, Kath, Smithson, Sarah, Sneddon, Linda, Splitt, Miranda, Squires, Miranda, Stewart, Fiona, Stewart, Helen, Straub, Volker, Suri, Mohnish, Sutton, Vivienne, Swaminathan, Ganesh Jawahar, Sweeney, Elizabeth, Tatton-Brown, Kate, Taylor, Cat, Taylor, Rohan, Tein, Mark, Temple, Karen I., Thomson, Jenny, Tischkowitz, Marc, Tomkins, Susan, Torokwa, Audrey, Treacy, Becky, Turner, Claire, Turnpenny, Peter, Tysoe, Carolyn, Vandersteen, Anthony, Varghese, Vinod, Vasudevan, Pradeep, Vijayarangakannan, Parthiban, Vogt, Julie, Wakeling, Emma, Wallwark, Sarah, Waters, Jonathon, Weber, Astrid, Wellesley, Diana, Whiteford, Margo, Widaa, Sara, Wilcox, Sarah, Wilkinson, Emily, Williams, Denise, Williams, Nicola, Wilson, Louise, Woods, Geoff, Wragg, Christopher, Wright, Michael, Yates, Laura, Yau, Michael, Nellåker, Chris, Parker, Michael, Firth, Helen V., Wright, Caroline F., FitzPatrick, David R., Barrett, Jeffrey C., and Hurles, Matthew E.
Published: 2017
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46. Plasmodium malariae and P. ovale genomes provide insights into malaria parasite evolution

Author: Rutledge, Gavin G., Böhme, Ulrike, Sanders, Mandy, Reid, Adam J., Cotton, James A., Maiga-Ascofare, Oumou, Djimdé, Abdoulaye A., Apinjoh, Tobias O., Amenga-Etego, Lucas, Manske, Magnus, Barnwell, John W., Renaud, François, Ollomo, Benjamin, Prugnolle, Franck, Anstey, Nicholas M., Auburn, Sarah, Price, Ric N., McCarthy, James S., Kwiatkowski, Dominic P., Newbold, Chris I., Berriman, Matthew, and Otto, Thomas D.
Published: 2017
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47. Silent mutations reveal therapeutic vulnerability in RAS Q61 cancers

Author: Kobayashi, Yoshihisa, primary, Chhoeu, Chhayheng, additional, Li, Jiaqi, additional, Price, Kristin S., additional, Kiedrowski, Lesli A., additional, Hutchins, Jamie L., additional, Hardin, Aaron I., additional, Wei, Zihan, additional, Hong, Fangxin, additional, Bahcall, Magda, additional, Gokhale, Prafulla C., additional, and Jänne, Pasi A., additional
Published: 2022
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48. Author Correction: Unextractable fossil fuels in a 1.5 °C world

Author: Welsby, Dan, primary, Price, James, additional, Pye, Steve, additional, and Ekins, Paul, additional
Published: 2022
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49. Author Correction: Multiple hominin dispersals into Southwest Asia over the past 400,000 years

Author: Groucutt, Huw S., primary, White, Tom S., additional, Scerri, Eleanor M. L., additional, Andrieux, Eric, additional, Clark-Wilson, Richard, additional, Breeze, Paul S., additional, Armitage, Simon J., additional, Stewart, Mathew, additional, Drake, Nick, additional, Louys, Julien, additional, Price, Gilbert J., additional, Duval, Mathieu, additional, Parton, Ash, additional, Candy, Ian, additional, Carleton, W. Christopher, additional, Shipton, Ceri, additional, Jennings, Richard P., additional, Zahir, Muhammad, additional, Blinkhorn, James, additional, Blockley, Simon, additional, Al-Omari, Abdulaziz, additional, Alsharekh, Abdullah M., additional, and Petraglia, Michael D., additional
Published: 2022
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50. Observation of the rare B0s→μ+μ− decay from the combined analysis of CMS and LHCb data

Author: Khachatryan, V., Sirunyan, A. M., Tumasyan, A., Adam, W., Bergauer, T., Dragicevic, M., Erö, J., Friedl, M., Frühwirth, R., Ghete, V. M., Hartl, C., Hörmann, N., Hrubec, J., Jeitler, M., Kiesenhofer, W., Knünz, V., Krammer, M., Krätschmer, I., Liko, D., Mikulec, I., Rabady, D., Rahbaran, B., Rohringer, H., Schöfbeck, R., Strauss, J., Treberer-Treberspurg, W., Waltenberger, W., Wulz, C.-E., Mossolov, V., Shumeiko, N., Suarez Gonzalez, J., Alderweireldt, S., Bansal, S., Cornelis, T., De Wolf, E. A., Janssen, X., Knutsson, A., Lauwers, J., Luyckx, S., Ochesanu, S., Rougny, R., Van De Klundert, M., Van Haevermaet, H., Van Mechelen, P., Van Remortel, N., Van Spilbeeck, A., Blekman, F., Blyweert, S., DʼHondt, J., Daci, N., Heracleous, N., Keaveney, J., Lowette, S., Maes, M., Olbrechts, A., Python, Q., Strom, D., Tavernier, S., Van Doninck, W., Van Mulders, P., Van Onsem, G. P., Villella, I., Caillol, C., Clerbaux, B., De Lentdecker, G., Dobur, D., Favart, L., Gay, A. P.R., Grebenyuk, A., Léonard, A., Mohammadi, A., Perniè, L., Randle-conde, A., Reis, T., Seva, T., Thomas, L., Vander Velde, C., Vanlaer, P., Wang, J., Zenoni, F., Adler, V., Beernaert, K., Benucci, L., Cimmino, A., Costantini, S., Crucy, S., Dildick, S., Fagot, A., Garcia, G., Mccartin, J., Ocampo Rios, A. A., Ryckbosch, D., Salva Diblen, S., Sigamani, M., Strobbe, N., Thyssen, F., Tytgat, M., Yazgan, E., Zaganidis, N., Basegmez, S., Beluffi, C., Bruno, G., Castello, R., Caudron, A., Ceard, L., Da Silveira, G. G., Delaere, C., du Pree, T., Favart, D., Forthomme, L., Giammanco, A., Hollar, J., Jafari, A., Jez, P., Komm, M., Lemaitre, V., Nuttens, C., Pagano, D., Perrini, L., Pin, A., Piotrzkowski, K., Popov, A., Quertenmont, L., Selvaggi, M., Vidal Marono, M., Vizan Garcia, J. M., Beliy, N., Caebergs, T., Daubie, E., Hammad, G. H., Aldá Júnior, W. L., Alves, G. A., Brito, L., Correa Martins Junior, M., Dos Reis Martins, T., Mora Herrera, C., Pol, M. E., Rebello Teles, P., Carvalho, W., Chinellato, J., Custódio, A., Da Costa, E. M., De Jesus Damiao, D., De Oliveira Martins, C., Fonseca De Souza, S., Malbouisson, H., Matos Figueiredo, D., Mundim, L., Nogima, H., Prado Da Silva, W. L., Santaolalla, J., Santoro, A., Sznajder, A., Tonelli Manganote, E. J., Vilela Pereira, A., Bernardes, C. A., Dogra, S., Fernandez Perez Tomei, T. R., Gregores, E. M., Mercadante, P. G., Novaes, S. F., Padula, Sandra S., Aleksandrov, A., Genchev, V., Hadjiiska, R., Iaydjiev, P., Marinov, A., Piperov, S., Rodozov, M., Sultanov, G., Vutova, M., Dimitrov, A., Glushkov, I., Litov, L., Pavlov, B., Petkov, P., Bian, J. G., Chen, G. M., Chen, H. S., Chen, M., Cheng, T., Du, R., Jiang, C. H., Plestina, R., Romeo, F., Tao, J., Wang, Z., Asawatangtrakuldee, C., Ban, Y., Li, Q., Liu, S., Mao, Y., Qian, S. J., Wang, D., Xu, Z., Zou, W., Avila, C., Cabrera, A., Chaparro Sierra, L. F., Florez, C., Gomez, J. P., Gomez Moreno, B., Sanabria, J. C., Godinovic, N., Lelas, D., Polic, D., Puljak, I., Antunovic, Z., Kovac, M., Brigljevic, V., Kadija, K., Luetic, J., Mekterovic, D., Sudic, L., Attikis, A., Mavromanolakis, G., Mousa, J., Nicolaou, C., Ptochos, F., Razis, P. A., Bodlak, M., Finger, M., Finger, M., Jr., Assran, Y., Ellithi Kamel, A., Mahmoud, M. A., Radi, A., Kadastik, M., Murumaa, M., Raidal, M., Tiko, A., Eerola, P., Fedi, G., Voutilainen, M., Härkönen, J., Karimäki, V., Kinnunen, R., Kortelainen, M. J., Lampén, T., Lassila-Perini, K., Lehti, S., Lindén, T., Luukka, P., Mäenpää, T., Peltola, T., Tuominen, E., Tuominiemi, J., Tuovinen, E., Wendland, L., Talvitie, J., Tuuva, T., Besancon, M., Couderc, F., Dejardin, M., Denegri, D., Fabbro, B., Faure, J. L., Favaro, C., Ferri, F., Ganjour, S., Givernaud, A., Gras, P., Hamel de Monchenault, G., Jarry, P., Locci, E., Malcles, J., Rander, J., Rosowsky, A., Titov, M., Baffioni, S., Beaudette, F., Busson, P., Charlot, C., Dahms, T., Dalchenko, M., Dobrzynski, L., Filipovic, N., Florent, A., Granier de Cassagnac, R., Mastrolorenzo, L., Miné, P., Mironov, C., Naranjo, I. N., Nguyen, M., Ochando, C., Ortona, G., Paganini, P., Regnard, S., Salerno, R., Sauvan, J. B., Sirois, Y., Veelken, C., Yilmaz, Y., Zabi, A., Agram, J.-L., Andrea, J., Aubin, A., Bloch, D., Brom, J.-M., Chabert, E. C., Collard, C., Conte, E., Fontaine, J.-C., Gelé, D., Goerlach, U., Goetzmann, C., Le Bihan, A.-C., Skovpen, K., Van Hove, P., Gadrat, S., Beauceron, S., Beaupere, N., Boudoul, G., Bouvier, E., Brochet, S., Carrillo Montoya, C. A., Chasserat, J., Chierici, R., Contardo, D., Depasse, P., El Mamouni, H., Fan, J., Fay, J., Gascon, S., Gouzevitch, M., Ille, B., Kurca, T., Lethuillier, M., Mirabito, L., Perries, S., Ruiz Alvarez, J. D., Sabes, D., Sgandurra, L., Sordini, V., Vander Donckt, M., Verdier, P., Viret, S., Xiao, H., Tsamalaidze, Z., Autermann, C., Beranek, S., Bontenackels, M., Edelhoff, M., Feld, L., Heister, A., Hindrichs, O., Klein, K., Ostapchuk, A., Raupach, F., Sammet, J., Schael, S., Schulte, J. F., Weber, H., Wittmer, B., Zhukov, V., Ata, M., Brodski, M., Dietz-Laursonn, E., Duchardt, D., Erdmann, M., Fischer, R., Güth, A., Hebbeker, T., Heidemann, C., Hoepfner, K., Klingebiel, D., Knutzen, S., Kreuzer, P., Merschmeyer, M., Meyer, A., Millet, P., Olschewski, M., Padeken, K., Papacz, P., Reithler, H., Schmitz, S. A., Sonnenschein, L., Teyssier, D., Thüer, S., Weber, M., Cherepanov, V., Erdogan, Y., Flügge, G., Geenen, H., Geisler, M., Haj Ahmad, W., Hoehle, F., Kargoll, B., Kress, T., Kuessel, Y., Künsken, A., Lingemann, J., Nowack, A., Nugent, I. M., Pooth, O., Stahl, A., Aldaya Martin, M., Asin, I., Bartosik, N., Behr, J., Behrens, U., Bell, A. J., Bethani, A., Borras, K., Burgmeier, A., Cakir, A., Calligaris, L., Campbell, A., Choudhury, S., Costanza, F., Diez Pardos, C., Dolinska, G., Dooling, S., Dorland, T., Eckerlin, G., Eckstein, D., Eichhorn, T., Flucke, G., Garay Garcia, J., Geiser, A., Gunnellini, P., Hauk, J., Hempel, M., Jung, H., Kalogeropoulos, A., Kasemann, M., Katsas, P., Kieseler, J., Kleinwort, C., Korol, I., Krücker, D., Lange, W., Leonard, J., Lipka, K., Lobanov, A., Lohmann, W., Lutz, B., Mankel, R., Marfin, I., Melzer-Pellmann, I.-A., Meyer, A. B., Mittag, G., Mnich, J., Mussgiller, A., Naumann-Emme, S., Nayak, A., Ntomari, E., Perrey, H., Pitzl, D., Placakyte, R., Raspereza, A., Ribeiro Cipriano, P. M., Roland, B., Ron, E., Sahin, M. Ö., Salfeld-Nebgen, J., Saxena, P., Schoerner-Sadenius, T., Schröder, M., Seitz, C., Spannagel, S., Vargas Trevino, A. D.R., Walsh, R., Wissing, C., Blobel, V., Centis Vignali, M., Draeger, A. R., Erfle, J., Garutti, E., Goebel, K., Görner, M., Haller, J., Hoffmann, M., Höing, R. S., Junkes, A., Kirschenmann, H., Klanner, R., Kogler, R., Lange, J., Lapsien, T., Lenz, T., Marchesini, I., Ott, J., Peiffer, T., Perieanu, A., Pietsch, N., Poehlsen, J., Poehlsen, T., Rathjens, D., Sander, C., Schettler, H., Schleper, P., Schlieckau, E., Schmidt, A., Seidel, M., Sola, V., Stadie, H., Steinbrück, G., Troendle, D., Usai, E., Vanelderen, L., Vanhoefer, A., Barth, C., Baus, C., Berger, J., Böser, C., Butz, E., Chwalek, T., De Boer, W., Descroix, A., Dierlamm, A., Feindt, M., Frensch, F., Giffels, M., Gilbert, A., Hartmann, F., Hauth, T., Husemann, U., Katkov, I., Kornmayer, A., Kuznetsova, E., Lobelle Pardo, P., Mozer, M. U., Müller, T., Müller, Th., Nürnberg, A., Quast, G., Rabbertz, K., Röcker, S., Simonis, H. J., Stober, F. M., Ulrich, R., Wagner-Kuhr, J., Wayand, S., Weiler, T., Wolf, R., Anagnostou, G., Daskalakis, G., Geralis, T., Giakoumopoulou, V. A., Kyriakis, A., Loukas, D., Markou, A., Markou, C., Psallidas, A., Topsis-Giotis, I., Agapitos, A., Kesisoglou, S., Panagiotou, A., Saoulidou, N., Stiliaris, E., Aslanoglou, X., Evangelou, I., Flouris, G., Foudas, C., Kokkas, P., Manthos, N., Papadopoulos, I., Paradas, E., Strologas, J., Bencze, G., Hajdu, C., Hidas, P., Horvath, D., Sikler, F., Veszpremi, V., Vesztergombi, G., Zsigmond, A. J., Beni, N., Czellar, S., Karancsi, J., Molnar, J., Palinkas, J., Szillasi, Z., Makovec, A., Raics, P., Trocsanyi, Z. L., Ujvari, B., Sahoo, N., Swain, S. K., Beri, S. B., Bhatnagar, V., Gupta, R., Bhawandeep, U., Kalsi, A. K., Kaur, M., Kumar, R., Mittal, M., Nishu, N., Singh, J. B., Kumar, Ashok, Kumar, Arun, Ahuja, S., Bhardwaj, A., Choudhary, B. C., Kumar, A., Malhotra, S., Naimuddin, M., Ranjan, K., Sharma, V., Banerjee, S., Bhattacharya, S., Chatterjee, K., Dutta, S., Gomber, B., Jain, Sa., Jain, Sh., Khurana, R., Modak, A., Mukherjee, S., Roy, D., Sarkar, S., Sharan, M., Abdulsalam, A., Dutta, D., Kailas, S., Kumar, V., Mohanty, A. K., Pant, L. M., Shukla, P., Topkar, A., Aziz, T., Bhowmik, S., Chatterjee, R. M., Dewanjee, R. K., Dugad, S., Ganguly, S., Ghosh, S., Guchait, M., Gurtu, A., Kole, G., Kumar, S., Maity, M., Majumder, G., Mazumdar, K., Mohanty, G. B., Parida, B., Sudhakar, K., Wickramage, N., Bakhshiansohi, H., Behnamian, H., Etesami, S. M., Fahim, A., Goldouzian, R., Khakzad, M., Mohammadi Najafabadi, M., Naseri, M., Paktinat Mehdiabadi, S., Rezaei Hosseinabadi, F., Safarzadeh, B., Zeinali, M., Felcini, M., Grunewald, M., Abbrescia, M., Calabria, C., Chhibra, S. S., Colaleo, A., Creanza, D., De Filippis, N., De Palma, M., Fiore, L., Iaselli, G., Maggi, G., Maggi, M., My, S., Nuzzo, S., Pompili, A., Pugliese, G., Radogna, R., Selvaggi, G., Sharma, A., Silvestris, L., Venditti, R., Verwilligen, P., Abbiendi, G., Benvenuti, A. C., Bonacorsi, D., Braibant-Giacomelli, S., Brigliadori, L., Campanini, R., Capiluppi, P., Castro, A., Cavallo, F. R., Codispoti, G., Cuffiani, M., Dallavalle, G. M., Fabbri, F., Fanfani, A., Fasanella, D., Giacomelli, P., Grandi, C., Guiducci, L., Marcellini, S., Masetti, G., Montanari, A., Navarria, F. L., Perrotta, A., Primavera, F., Rossi, A. M., Rovelli, T., Siroli, G. P., Tosi, N., Travaglini, R., Albergo, S., Cappello, G., Chiorboli, M., Costa, S., Giordano, F., Potenza, R., Tricomi, A., Tuve, C., Barbagli, G., Ciulli, V., Civinini, C., DʼAlessandro, R., Focardi, E., Gallo, E., Gonzi, S., Gori, V., Lenzi, P., Meschini, M., Paoletti, S., Sguazzoni, G., Tropiano, A., Benussi, L., Bianco, S., Piccolo, D., Ferretti, R., Ferro, F., Lo Vetere, M., Robutti, E., Tosi, S., Dinardo, M. E., Fiorendi, S., Gennai, S., Gerosa, R., Ghezzi, A., Govoni, P., Lucchini, M. T., Malvezzi, S., Manzoni, R. A., Martelli, A., Marzocchi, B., Menasce, D., Moroni, L., Paganoni, M., Pedrini, D., Ragazzi, S., Redaelli, N., Tabarelli de Fatis, T., Buontempo, S., Cavallo, N., Di Guida, S., Fabozzi, F., Iorio, A. O.M., Lista, L., Meola, S., Merola, M., Paolucci, P., Azzi, P., Bacchetta, N., Bisello, D., Branca, A., Carlin, R., Checchia, P., DallʼOsso, M., Dorigo, T., Dosselli, U., Galanti, M., Gasparini, F., Gasparini, U., Giubilato, P., Gozzelino, A., Kanishchev, K., Lacaprara, S., Margoni, M., Meneguzzo, A. T., Pazzini, J., Pozzobon, N., Ronchese, P., Simonetto, F., Torassa, E., Tosi, M., Zotto, P., Zucchetta, A., Zumerle, G., Gabusi, M., Ratti, S. P., Re, V., Riccardi, C., Salvini, P., Vitulo, P., Biasini, M., Bilei, G. M., Ciangottini, D., Fanò, L., Lariccia, P., Mantovani, G., Menichelli, M., Saha, A., Santocchia, A., Spiezia, A., Androsov, K., Azzurri, P., Bagliesi, G., Bernardini, J., Boccali, T., Broccolo, G., Castaldi, R., Ciocci, M. A., DellʼOrso, R., Donato, S., Fiori, F., Foà, L., Giassi, A., Grippo, M. T., Ligabue, F., Lomtadze, T., Martini, L., Messineo, A., Moon, C. S., Palla, F., Rizzi, A., Savoy-Navarro, A., Serban, A. T., Spagnolo, P., Squillacioti, P., Tenchini, R., Tonelli, G., Venturi, A., Verdini, P. G., Vernieri, C., Barone, L., Cavallari, F., Dʼimperio, G., Del Re, D., Diemoz, M., Jorda, C., Longo, E., Margaroli, F., Meridiani, P., Micheli, F., Nourbakhsh, S., Organtini, G., Paramatti, R., Rahatlou, S., Rovelli, C., Santanastasio, F., Soffi, L., Traczyk, P., Amapane, N., Arcidiacono, R., Argiro, S., Arneodo, M., Bellan, R., Biino, C., Cartiglia, N., Casasso, S., Costa, M., Degano, A., Demaria, N., Finco, L., Mariotti, C., Maselli, S., Migliore, E., Monaco, V., Musich, M., Obertino, M. M., Pacher, L., Pastrone, N., Pelliccioni, M., Pinna Angioni, G. L., Potenza, A., Romero, A., Ruspa, M., Sacchi, R., Solano, A., Staiano, A., Tamponi, U., Belforte, S., Candelise, V., Casarsa, M., Cossutti, F., Della Ricca, G., Gobbo, B., La Licata, C., Marone, M., Schizzi, A., Umer, T., Zanetti, A., Chang, S., Kropivnitskaya, A., Nam, S. K., Kim, D. H., Kim, G. N., Kim, M. S., Kong, D. J., Lee, S., Oh, Y. D., Park, H., Sakharov, A., Son, D. C., Kim, T. J., Kim, J. Y., Song, S., Choi, S., Gyun, D., Hong, B., Jo, M., Kim, H., Kim, Y., Lee, B., Lee, K. S., Park, S. K., Roh, Y., Yoo, H. D., Choi, M., Kim, J. H., Park, I. C., Ryu, G., Ryu, M. S., Choi, Y., Choi, Y. K., Goh, J., Kim, D., Kwon, E., Lee, J., Yu, I., Juodagalvis, A., Komaragiri, J. R., Md Ali, M. A.B., Casimiro Linares, E., Castilla-Valdez, H., De La Cruz-Burelo, E., Heredia-de La Cruz, I., Hernandez-Almada, A., Lopez-Fernandez, R., Sanchez-Hernandez, A., Carrillo Moreno, S., Vazquez Valencia, F., Pedraza, I., Salazar Ibarguen, H. A., Morelos Pineda, A., Krofcheck, D., Butler, P. H., Reucroft, S., Ahmad, A., Ahmad, M., Hassan, Q., Hoorani, H. R., Khan, W. A., Khurshid, T., Shoaib, M., Bialkowska, H., Bluj, M., Boimska, B., Frueboes, T., Górski, M., Kazana, M., Nawrocki, K., Romanowska-Rybinska, K., Szleper, M., Zalewski, P., Brona, G., Bunkowski, K., Cwiok, M., Dominik, W., Doroba, K., Kalinowski, A., Konecki, M., Krolikowski, J., Misiura, M., Olszewski, M., Wolszczak, W., Bargassa, P., Beirão Da Cruz E Silva, C., Faccioli, P., Ferreira Parracho, P. G., Gallinaro, M., Lloret Iglesias, L., Nguyen, F., Rodrigues Antunes, J., Seixas, J., Varela, J., Vischia, P., Afanasiev, S., Bunin, P., Gavrilenko, M., Golutvin, I., Gorbunov, I., Kamenev, A., Karjavin, V., Konoplyanikov, V., Lanev, A., Malakhov, A., Matveev, V., Moisenz, P., Palichik, V., Perelygin, V., Shmatov, S., Skatchkov, N., Smirnov, V., Zarubin, A., Golovtsov, V., Ivanov, Y., Kim, V., Levchenko, P., Murzin, V., Oreshkin, V., Smirnov, I., Sulimov, V., Uvarov, L., Vavilov, S., Vorobyev, A., Vorobyev, An., Andreev, Yu., Dermenev, A., Gninenko, S., Golubev, N., Kirsanov, M., Krasnikov, N., Pashenkov, A., Tlisov, D., Toropin, A., Epshteyn, V., Gavrilov, V., Lychkovskaya, N., Popov, V., Pozdnyakov, I., Safronov, G., Semenov, S., Spiridonov, A., Stolin, V., Vlasov, E., Zhokin, A., Andreev, V., Azarkin, M., Dremin, I., Kirakosyan, M., Leonidov, A., Mesyats, G., Rusakov, S. V., Vinogradov, A., Belyaev, A., Boos, E., Dubinin, M., Dudko, L., Ershov, A., Gribushin, A., Klyukhin, V., Kodolova, O., Lokhtin, I., Obraztsov, S., Petrushanko, S., Savrin, V., Snigirev, A., Azhgirey, I., Bayshev, I., Bitioukov, S., Kachanov, V., Kalinin, A., Konstantinov, D., Krychkine, V., Petrov, V., Ryutin, R., Sobol, A., Tourtchanovitch, L., Troshin, S., Tyurin, N., Uzunian, A., Volkov, A., Adzic, P., Ekmedzic, M., Milosevic, J., Rekovic, V., Alcaraz Maestre, J., Battilana, C., Calvo, E., Cerrada, M., Chamizo Llatas, M., Colino, N., De La Cruz, B., Delgado Peris, A., Domínguez Vázquez, D., Escalante Del Valle, A., Fernandez Bedoya, C., Fernández Ramos, J. P., Flix, J., Fouz, M. C., Garcia-Abia, P., Gonzalez Lopez, O., Goy Lopez, S., Hernandez, J. M., Josa, M. I., Navarro De Martino, E., Pérez-Calero Yzquierdo, A., Puerta Pelayo, J., Quintario Olmeda, A., Redondo, I., Romero, L., Soares, M. S., Albajar, C., de Trocóniz, J. 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V., Polyakov, I., Savrina, D., Semennikov, A., Zhokhov, A., Berezhnoy, A., Korolev, M., Leflat, A., Nikitin, N., Filippov, S., Gushchin, E., Kravchuk, L., Bondar, A., Eidelman, S., Krokovny, P., Kudryavtsev, V., Shekhtman, L., Vorobyev, V., Artamonov, A., Belous, K., Dzhelyadin, R., Guz, Yu., Novoselov, A., Obraztsov, V., Romanovsky, V., Shapkin, M., Stenyakin, O., Yushchenko, O., Badalov, A., Calvo Gomez, M., Garrido, L., Gascon, D., Graciani Diaz, R., Graugés, E., Marin Benito, C., Picatoste Olloqui, E., Rives Molina, V., Ruiz, H., Vilasis-Cardona, X., Adeva, B., Alvarez Cartelle, P., Dosil Suárez, A., Fernandez Albor, V., Gallas Torreira, A., García Pardiñas, J., Hernando Morata, J. A., Plo Casasus, M., Romero Vidal, A., Saborido Silva, J. J., Sanmartin Sedes, B., Santamarina Rios, C., Vazquez Regueiro, P., Vázquez Sierra, C., Vieites Diaz, M., Alessio, F., Archilli, F., Barschel, C., Benson, S., Buytaert, J., Campora Perez, D., Castillo Garcia, L., Cattaneo, M., Charpentier, Ph., Cid Vidal, X., Clemencic, M., Closier, J., Coco, V., Collins, P., Corti, G., Couturier, B., DʼAmbrosio, C., Dettori, F., Di Canto, A., Dijkstra, H., Durante, P., Ferro-Luzzi, M., Forty, R., Frank, M., Frei, C., Gaspar, C., Gligorov, V. V., Granado Cardoso, L. A., Gys, T., Haen, C., He, J., Head, T., van Herwijnen, E., Jacobsson, R., Johnson, D., Joram, C., Jost, B., Karacson, M., Karbach, T. M., Lacarrere, D., Langhans, B., Lindner, R., Linn, C., Lohn, S., Mapelli, A., Matev, R., Mathe, Z., Neubert, S., Neufeld, N., Otto, A., Panman, J., Pepe Altarelli, M., Rauschmayr, N., Rihl, M., Roiser, S., Ruf, T., Schindler, H., Schmidt, B., Schopper, A., Schwemmer, R., Sridharan, S., Stagni, F., Subbiah, V. K., Teubert, F., Thomas, E., Tonelli, D., Trisovic, A., Ubeda Garcia, M., Wicht, J., Wyllie, K., Battista, V., Bay, A., Blanc, F., Dorigo, M., Dupertuis, F., Fitzpatrick, C., Gianì, S., Haefeli, G., Jaton, P., Khurewathanakul, C., Komarov, I., La Thi, V. N., Lopez-March, N., Märki, R., Martinelli, M., Muster, B., Nakada, T., Nguyen, A. D., Nguyen, T. D., Nguyen-Mau, C., Prisciandaro, J., Puig Navarro, A., Rakotomiaramanana, B., Rouvinet, J., Schneider, O., Soomro, F., Szczypka, P., Tobin, M., Tourneur, S., Tran, M. T., Veneziano, G., Bernet, R., Bowen, E., Bursche, A., Chiapolini, N., Chrzaszcz, M., Elsasser, Ch., Graverini, E., Lionetto, F., Lowdon, P., Müller, K., Serra, N., Steinkamp, O., Storaci, B., Straumann, U., Tresch, M., Vollhardt, A., Aaij, R., Ali, S., van Beuzekom, M., David, P. N.Y., De Bruyn, K., Farinelli, C., Heijne, V., Hulsbergen, W., Jans, E., Koppenburg, P., Kozlinskiy, A., van Leerdam, J., Merk, M., Oggero, S., Pellegrino, A., Snoek, H., van Tilburg, J., Tsopelas, P., Tuning, N., de Vries, J. A., Ketel, T., Koopman, R. F., Lambert, R. W., Martinez Santos, D., Raven, G., Schiller, M., Syropoulos, V., Tolk, S., Dovbnya, A., Kandybei, S., Raniuk, I., Okhrimenko, O., Pugatch, V., Bifani, S., Farley, N., Griffith, P., Kenyon, I. R., Lazzeroni, C., Mazurov, A., McCarthy, J., Pescatore, L., Watson, N. K., Williams, M. P., Adinolfi, M., Benton, J., Brook, N. H., Cook, A., Coombes, M., Dalseno, J., Hampson, T., Harnew, S. T., Naik, P., Price, E., Prouve, C., Rademacker, J. H., Richards, S., Saunders, D. M., Skidmore, N., Souza, D., Velthuis, J. J., Voong, D., Barter, W., Bettler, M.-O., Cliff, H. V., Evans, H.-M., Garra Tico, J., Gibson, V., Gregson, S., Haines, S. C., Jones, C. R., Sirendi, M., Ward, D. R., Wotton, S. A., Wright, S., Back, J. J., Blake, T., Craik, D. C., Crocombe, A. C., Dossett, D., Gershon, T., Kreps, M., Langenbruch, C., Latham, T., OʼHanlon, D. P., Pilař, T., Poluektov, A., Reid, M. M., Silva Coutinho, R., Wallace, C., Whitehead, M., Easo, S., Nandakumar, R., Papanestis, A., Ricciardi, S., Wilson, F. F., Carson, L., Clarke, P. E.L., Cowan, G. A., Eisenhardt, S., Ferguson, D., Lambert, D., Luo, H., Morris, A.-B., Muheim, F., Needham, M., Playfer, S., Alexander, M., Beddow, J., Dean, C.-T., Eklund, L., Hynds, D., Karodia, S., Longstaff, I., Ogilvy, S., Pappagallo, M., Sail, P., Skillicorn, I., Soler, F. J.P., Spradlin, P., Affolder, A., Bowcock, T. J.V., Brown, H., Casse, G., Donleavy, S., Dreimanis, K., Farry, S., Fay, R., Hennessy, K., Hutchcroft, D., Liles, M., McSkelly, B., Patel, G. D., Price, J. D., Pritchard, A., Rinnert, K., Shears, T., Smith, N. A., Ciezarek, G., Cunliffe, S., Currie, R., Egede, U., Fol, P., Golutvin, A., Hall, S., McCann, M., Owen, P., Patel, M., Redi, F., Sepp, I., Smith, E., Sutcliffe, W., Websdale, D., Appleby, R. B., Barlow, R. J., Bird, T., Bjørnstad, P. M., Borghi, S., Brett, D., Brodzicka, J., Capriotti, L., Chen, S., De Capua, S., Dujany, G., Gersabeck, M., Harrison, J., Hombach, C., Klaver, S., Lafferty, G., McNab, A., Parkes, C., Pearce, A., Reichert, S., Rodrigues, E., Rodriguez Perez, P., Smith, M., Cheung, S.-F., Derkach, D., Evans, T., Gauld, R., Greening, E., Harnew, N., Hill, D., Hunt, P., Hussain, N., Jalocha, J., John, M., Lupton, O., Malde, S., Stevenson, S., Thomas, C., Topp-Joergensen, S., Torr, N., Wilkinson, G., Counts, I., Ilten, P., Williams, M., Andreassen, R., Davis, A., De Silva, W., Meadows, B., Sokoloff, M. D., Sun, L., Todd, J., Andrews, J. E., Hamilton, B., Jawahery, A., Wimberley, J., Artuso, M., Blusk, S., Borgia, A., Britton, T., Ely, S., Gandini, P., Garofoli, J., Gui, B., Hadjivasiliou, C., Jurik, N., Kelsey, M., Mountain, R., Pal, B. K., Skwarnicki, T., Stone, S., Xing, Z., Zhang, L., Baesso, C., Cruz Torres, M., Göbel, C., Molina Rodriguez, J., Xie, Y., Milanes, D. A., Grünberg, O., He, M., Vo, C., Waldi, R., Likhomanenko, T., Malinin, A., Shevchenko, V., Ustyuzhanin, A., Martinez Vidal, F., Oyanguren, A., Ruiz Valls, P., Sanchez Mayordomo, C., Onderwater, C. J.G., Wilschut, H. W., and Pesen, E.
Published: 2015
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