Search

Your search keyword '"B, Barreiro"' showing total 369 results
Start Over Author "B, Barreiro"
369 results on '"B, Barreiro"'

1. A host-directed oxadiazole compound potentiates antituberculosis treatment via zinc poisoning in human macrophages and in a mouse model of infection.

Author

Alexandra Maure, Emeline Lawarée, Francesco Fiorentino, Alexandre Pawlik, Saideep Gona, Alexandre Giraud-Gatineau, Matthew J G Eldridge, Anne Danckaert, David Hardy, Wafa Frigui, Camille Keck, Claude Gutierrez, Olivier Neyrolles, Nathalie Aulner, Antonello Mai, Mélanie Hamon, Luis B Barreiro, Priscille Brodin, Roland Brosch, Dante Rotili, and Ludovic Tailleux

Subjects
Biology (General), QH301-705.5
Abstract

Antituberculosis drugs, mostly developed over 60 years ago, combined with a poorly effective vaccine, have failed to eradicate tuberculosis. More worryingly, multiresistant strains of Mycobacterium tuberculosis (MTB) are constantly emerging. Innovative strategies are thus urgently needed to improve tuberculosis treatment. Recently, host-directed therapy has emerged as a promising strategy to be used in adjunct with existing or future antibiotics, by improving innate immunity or limiting immunopathology. Here, using high-content imaging, we identified novel 1,2,4-oxadiazole-based compounds, which allow human macrophages to control MTB replication. Genome-wide gene expression analysis revealed that these molecules induced zinc remobilization inside cells, resulting in bacterial zinc intoxication. More importantly, we also demonstrated that, upon treatment with these novel compounds, MTB became even more sensitive to antituberculosis drugs, in vitro and in vivo, in a mouse model of tuberculosis. Manipulation of heavy metal homeostasis holds thus great promise to be exploited to develop host-directed therapeutic interventions.

Published
2024
Full Text
View/download PDF

3. DNA methylation-environment interactions in the human genome

Author

Rachel A Johnston, Katherine A Aracena, Luis B Barreiro, Amanda J Lea, and Jenny Tung

Subjects
epigenome, methylation, biological embedding, early life adversity, MPRA, IFNA, Medicine, Science, Biology (General), QH301-705.5
Abstract

Previously, we showed that a massively parallel reporter assay, mSTARR-seq, could be used to simultaneously test for both enhancer-like activity and DNA methylation-dependent enhancer activity for millions of loci in a single experiment (Lea et al., 2018). Here, we apply mSTARR-seq to query nearly the entire human genome, including almost all CpG sites profiled either on the commonly used Illumina Infinium MethylationEPIC array or via reduced representation bisulfite sequencing. We show that fragments containing these sites are enriched for regulatory capacity, and that methylation-dependent regulatory activity is in turn sensitive to the cellular environment. In particular, regulatory responses to interferon alpha (IFNA) stimulation are strongly attenuated by methyl marks, indicating widespread DNA methylation-environment interactions. In agreement, methylation-dependent responses to IFNA identified via mSTARR-seq predict methylation-dependent transcriptional responses to challenge with influenza virus in human macrophages. Our observations support the idea that pre-existing DNA methylation patterns can influence the response to subsequent environmental exposures—one of the tenets of biological embedding. However, we also find that, on average, sites previously associated with early life adversity are not more likely to functionally influence gene regulation than expected by chance.

Published
2024
Full Text
View/download PDF

4. QUIJOTE scientific results – VIII. Diffuse polarized foregrounds from component separation with QUIJOTE-MFI

Author

E de la Hoz, R B Barreiro, P Vielva, E Martínez-González, J A Rubiño-Martín, B Casaponsa, F Guidi, M Ashdown, R T Génova-Santos, E Artal, F J Casas, R Fernández-Cobos, M Fernández-Torreiro, D Herranz, R J Hoyland, A N Lasenby, M López-Caniego, C H López-Caraballo, M W Peel, L Piccirillo, F Poidevin, R Rebolo, B Ruiz-Granados, D Tramonte, F Vansyngel, and R A Watson

Published
2023
Full Text
View/download PDF

5. Universal gut microbial relationships in the gut microbiome of wild baboons

Author

Kimberly E Roche, Johannes R Bjork, Mauna R Dasari, Laura Grieneisen, David Jansen, Trevor J Gould, Laurence R Gesquiere, Luis B Barreiro, Susan C Alberts, Ran Blekhman, Jack A Gilbert, Jenny Tung, Sayan Mukherjee, and Elizabeth A Archie

Subjects
gut microbiota, microbiome community dynamics, correlations between bacteria, universality, personalization, longitudinal data analysis, Medicine, Science, Biology (General), QH301-705.5
Abstract

Ecological relationships between bacteria mediate the services that gut microbiomes provide to their hosts. Knowing the overall direction and strength of these relationships is essential to learn how ecology scales up to affect microbiome assembly, dynamics, and host health. However, whether bacterial relationships are generalizable across hosts or personalized to individual hosts is debated. Here, we apply a robust, multinomial logistic-normal modeling framework to extensive time series data (5534 samples from 56 baboon hosts over 13 years) to infer thousands of correlations in bacterial abundance in individual baboons and test the degree to which bacterial abundance correlations are ‘universal’. We also compare these patterns to two human data sets. We find that, most bacterial correlations are weak, negative, and universal across hosts, such that shared correlation patterns dominate over host-specific correlations by almost twofold. Further, taxon pairs that had inconsistent correlation signs (either positive or negative) in different hosts always had weak correlations within hosts. From the host perspective, host pairs with the most similar bacterial correlation patterns also had similar microbiome taxonomic compositions and tended to be genetic relatives. Compared to humans, universality in baboons was similar to that in human infants, and stronger than one data set from human adults. Bacterial families that showed universal correlations in human infants were often universal in baboons. Together, our work contributes new tools for analyzing the universality of bacterial associations across hosts, with implications for microbiome personalization, community assembly, and stability, and for designing microbiome interventions to improve host health.

Published
2023
Full Text
View/download PDF

6. Tensor-to-scalar ratio forecasts for extended LiteBIRD frequency configurations

Author

U. Fuskeland, J. Aumont, R. Aurlien, C. Baccigalupi, A. J. Banday, H. K. Eriksen, J. Errard, R. T. Génova-Santos, T. Hasebe, J. Hubmayr, H. Imada, N. Krachmalnicof, L. Lamagna, G. Pisano, D. Poletti, M. Remazeilles, K. L. Thompson, L. Vache, I. K. Wehus, S. Azzoni, M. Ballardini, R. B. Barreiro, N. Bartolo, A. Basyrov, D. Beck, M. Bersanelli, M. Bortolami, M. Brilenkov, E. Calabrese, A. Carones, F. J. Casas, K. Cheung, J. Chluba, S. E. Clark, L. Clermont, and E.J. Wollack

Subjects
Space Sciences (General)
Abstract

LiteBIRD is a planned JAXA-led cosmic microwave background (CMB) B-mode satellite experiment aiming for launch in the late 2020s, with a primary goal of detecting the imprint of primordial inflationary gravitational waves. Its current baseline focal-plane configuration includes 15 frequency bands between 40 and 402 GHz, fulfilling the mission requirements to detect the amplitude of gravitational waves with the total uncertainty on the tensor-to-scalar ratio, δr, down to δr < 0.001. A key aspect of this performance is accurate astrophysical component separation, and the ability to remove polarized thermal dust emission is particularly important. In this paper we note that the CMB frequency spectrum falls off nearly exponentially above 300 GHz relative to the thermal dust spectral energy distribution, and a relatively minor high frequency extension can therefore result in even lower uncertainties and better model reconstructions. Specifically, we compared the baseline design with five extended configurations, while varying the underlying dust modeling, in each of which the High-Frequency Telescope (HFT) frequency range was shifted logarithmically toward higher frequencies, with an upper cutoff ranging between 400 and 600 GHz. In each case, we measured the tensor-to-scalar ratio r uncertainty and bias using both parametric and minimum-variance component-separation algorithms. When the thermal dust sky model includes a spatially varying spectral index and temperature, we find that the statistical uncertainty on r after foreground cleaning may be reduced by as much as 30–50% by extending the upper limit of the frequency range from 400 to 600 GHz, with most of the improvement already gained at 500 GHz. We also note that a broader frequency range leads to higher residuals when fitting an incorrect dust model, but also it is easier to discriminate between models through higher χ2 sensitivity. Even in the case in which the fitting procedure does not correspond to the underlying dust model in the sky, and when the highest frequency data cannot be modeled with sufficient fidelity and must be excluded from the analysis, the uncertainty on r increases by only about 5% for a 500 GHz configuration compared to the baseline.

Published
2023
Full Text
View/download PDF

7. Transmission of stimulus-induced epigenetic changes through cell division is coupled to continuous transcription factor activity

Author

Sarah Sun, Raúl Aguirre-Gamboa, and Luis B. Barreiro

Subjects
innate immune memory, macrophages, histone modifications, immunogenomics, epigenetics, trained immunity, Immunologic diseases. Allergy, RC581-607
Abstract

Trained immunity, or innate immune memory, has been attributed to the long-term retention of stimulus-induced histone post-translational modifications (PTMs) following clearance of the initial stimulus. Yet, it remains unknown how this epigenetic memory can persist for months in dividing cells given the lack of any known mechanism for stimulus-induced histone PTMs to be directly copied from parent to daughter strand during DNA replication. Here, using time course RNA-seq, ChIP-seq, and infection assays, we find that trained macrophages are transcriptionally, epigenetically, and functionally re-programmed for at least 14 cell divisions after stimulus washout. However, the epigenetic changes observed after multiple rounds of cell division do not result from the self-sustained propagation of stimulus-induced epigenetic changes through cell division. Instead, long-lasting epigenetic differences between trained and non-trained cells are always coupled with changes in transcription factor (TF) activity, emphasizing the central role played by TFs, and gene expression changes more broadly, in driving the transmission of stimulus-induced epigenetic changes across cell divisions.

Published
2023
Full Text
View/download PDF

8. Human alveolar macrophage metabolism is compromised during Mycobacterium tuberculosis infection

Author

Laura E. Mendonca, Erwan Pernet, Nargis Khan, Joaquin Sanz, Eva Kaufmann, Jeffrey Downey, Alexandre Grant, Marianna Orlova, Erwin Schurr, Connie Krawczyk, Russell G. Jones, Luis B. Barreiro, and Maziar Divangahi

Subjects
tuberculosis, immunometabolism, immunity, pulmonary macrophages, metabolic reprograming, cell death programs, Immunologic diseases. Allergy, RC581-607
Abstract

Pulmonary macrophages have two distinct ontogenies: long-lived embryonically-seeded alveolar macrophages (AM) and bone marrow-derived macrophages (BMDM). Here, we show that after infection with a virulent strain of Mycobacterium tuberculosis (H37Rv), primary murine AM exhibit a unique transcriptomic signature characterized by metabolic reprogramming distinct from conventional BMDM. In contrast to BMDM, AM failed to shift from oxidative phosphorylation (OXPHOS) to glycolysis and consequently were unable to control infection with an avirulent strain (H37Ra). Importantly, healthy human AM infected with H37Ra equally demonstrated diminished energetics, recapitulating our observation in the murine model system. However, the results from seahorse showed that the shift towards glycolysis in both AM and BMDM was inhibited by H37Rv. We further demonstrated that pharmacological (e.g. metformin or the iron chelator desferrioxamine) reprogramming of AM towards glycolysis reduced necrosis and enhanced AM capacity to control H37Rv growth. Together, our results indicate that the unique bioenergetics of AM renders these cells a perfect target for Mtb survival and that metabolic reprogramming may be a viable host targeted therapy against TB.

Published
2023
Full Text
View/download PDF

9. Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity

Author

Sangman M. Kim, Jennifer R. DeFazio, Sanjiv K. Hyoju, Kishan Sangani, Robert Keskey, Monika A. Krezalek, Nikolai N. Khodarev, Naseer Sangwan, Scott Christley, Katharine G. Harris, Ankit Malik, Alexander Zaborin, Romain Bouziat, Diana R. Ranoa, Mara Wiegerinck, Jordan D. Ernest, Baddr A. Shakhsheer, Irma D. Fleming, Ralph R. Weichselbaum, Dionysios A. Antonopoulos, Jack A. Gilbert, Luis B. Barreiro, Olga Zaborina, Bana Jabri, and John C. Alverdy

Subjects
Science
Abstract

Sepsis due to multidrug resistant pathogens is the most common cause of death in intensive care units. Here, the authors report that fecal microbiota transplant (FMT) can rescue mice from lethal sepsis of pathogens isolated from stool of a critically ill patient and show that FMT reverses the immunosuppressive effect induced by the pathogen community.

Published
2020
Full Text
View/download PDF

11. Lung Epithelial Signaling Mediates Early Vaccine-Induced CD4+ T Cell Activation and Mycobacterium tuberculosis Control

Author

Shibali Das, Nancy D. Marin, Ekaterina Esaulova, Mushtaq Ahmed, Amanda Swain, Bruce A. Rosa, Makedonka Mitreva, Javier Rangel-Moreno, Mihai G. Netea, Luis B. Barreiro, Maziar Divangahi, Maxim N. Artyomov, Deepak Kaushal, and Shabaana A. Khader

Subjects
tuberculosis, vaccine-induced response, clonality, parenchyma, epithelial cells, cytokines, Microbiology, QR1-502
Abstract

ABSTRACT Tuberculosis (TB) is one of the leading causes of death due to a single infectious agent. The development of a TB vaccine that induces durable and effective immunity to Mycobacterium tuberculosis (Mtb) infection is urgently needed. Early and superior Mtb control can be induced in M. bovis Bacillus Calmette-Guérin (BCG)-vaccinated hosts when the innate immune response is targeted to generate effective vaccine-induced immunity. In the present study, we show that innate activation of DCs is critical for mucosal localization of clonally activated vaccine-induced CD4+ T cells in the lung and superior early Mtb control. In addition, our study reveals that Th1/Th17 cytokine axis play an important role in superior vaccine-induced immunity. Our studies also show that activation of the nuclear factor kappa-light-chain enhancer of activated B cell (NF-κβ) pathway in lung epithelial cells is critical for the mucosal localization of activated vaccine-induced CD4+ T cells for rapid Mtb control. Thus, our study provides novel insights into the immune mechanisms that can overcome TB vaccine bottlenecks and provide early rapid Mtb control. IMPORTANCE Tuberculosis is a leading cause of death due to single infectious agent accounting 1.4 million deaths each year. The only licensed vaccine, BCG, is not effective due to variable efficacy. In our study, we determined the early immune events necessary for achieving complete protection in a BCG-vaccinated host. Our study reveals that innate activation of DCs can mediate superior and early Mtb control in BCG-vaccinated mice through lung epithelial cell signaling and localization of clonal activated, Mtb antigen-specific, cytokine-producing CD4+ T cells within the lung parenchyma and airways. Thus, our study provides novel insights into the immune mechanisms that can overcome TB vaccine bottlenecks and provide early rapid Mtb control.

Published
2021
Full Text
View/download PDF

13. QUIJOTE scientific results – V. The microwave intensity and polarization spectra of the Galactic regions W49, W51 and IC443

Author

D Tramonte, R T Génova-Santos, J A Rubiño-Martín, P Vielva, F Poidevin, C H López-Caraballo, M W Peel, M Ashdown, E Artal, R B Barreiro, F J Casas, E de la Hoz, M Fernández-Torreiro, F Guidi, D Herranz, R J Hoyland, A N Lasenby, E Martinez-Gonzalez, L Piccirillo, R Rebolo, B Ruiz-Granados, F Vansyngel, and R A Watson

Subjects
Cosmology and Nongalactic Astrophysics (astro-ph.CO), Space and Planetary Science, Astrophysics of Galaxies (astro-ph.GA), FOS: Physical sciences, Astronomy and Astrophysics, Astrophysics - Astrophysics of Galaxies, Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

We present new intensity and polarisation maps obtained with the QUIJOTE experiment towards the Galactic regions W49, W51 and IC443, covering the frequency range from 10 to 20 GHz at $\sim$ 1 deg angular resolution, with a sensitivity in the range 35-79 ${\mu}$K/beam for total intensity and 13-23 ${\mu}$K/beam for polarisation. For each region, we combine QUIJOTE maps with ancillary data at frequencies ranging from 0.4 to 3000 GHz, reconstruct the spectral energy distribution and model it with a combination of known foregrounds. We detect anomalous microwave emission (AME) in total intensity towards W49 at 4.7${\sigma}$ and W51 at 4.0${\sigma}$ with peak frequencies ${\nu}_{AME}$ = (20.0 $\pm$ 1.4) GHz and ${\nu}_{AME}$ = (17.7 $\pm$ 3.6) GHz respectively; this is the first detection of AME towards W51. The contamination from ultra-compact HII regions to the residual AME flux density is estimated at 10% in W49 and 5% in W51, and does not rule out the AME detection. The polarised SEDs reveal a synchrotron contribution with spectral indices ${\alpha}_s$ = -0.67 $\pm$ 0.10 in W49 and ${\alpha}_s$ = -0.51 $\pm$ 0.07 in W51, ascribed to the diffuse Galactic emission and to the local supernova remnant respectively. Towards IC443 in total intensity we measure a broken power-law synchrotron spectrum with cut-off frequency ${\nu}_{0,s}$ = (114 $\pm$ 73) GHz, in agreement with previous studies; our analysis, however, rules out any AME contribution which had been previously claimed towards IC443. No evidence of polarised AME emission is detected in this study., Comment: 29 pages, 11 figures. Accepted for publication in MNRAS

Published
2023
Full Text
View/download PDF

14. Evolution of immune genes is associated with the Black Death

Author

Jennifer Klunk, Tauras P. Vilgalys, Christian E. Demeure, Xiaoheng Cheng, Mari Shiratori, Julien Madej, Rémi Beau, Derek Elli, Maria I. Patino, Rebecca Redfern, Sharon N. DeWitte, Julia A. Gamble, Jesper L. Boldsen, Ann Carmichael, Nükhet Varlik, Katherine Eaton, Jean-Christophe Grenier, G. Brian Golding, Alison Devault, Jean-Marie Rouillard, Vania Yotova, Renata Sindeaux, Chun Jimmie Ye, Matin Bikaran, Anne Dumaine, Jessica F. Brinkworth, Dominique Missiakas, Guy A. Rouleau, Matthias Steinrücken, Javier Pizarro-Cerdá, Hendrik N. Poinar, Luis B. Barreiro, McMaster Ancient DNA Center [Hamilton, Ontario], McMaster University [Hamilton, Ontario], Daicel Arbor Biosciences [Ann Arbor, MI], University of Chicago, Yersinia, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Museum of London, University of South Carolina [Columbia], University of Manitoba [Winnipeg], University of Southern Denmark (SDU), Indiana University [Bloomington], Indiana University System, Rutgers University [Newark], Rutgers University System (Rutgers), Université de Montréal (UdeM), University of Michigan [Ann Arbor], University of Michigan System, Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada], Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], University of California [San Francisco] (UC San Francisco), University of California (UC), University of Illinois at Urbana-Champaign [Urbana], University of Illinois System, McGill University = Université McGill [Montréal, Canada], and This work was supported by grant R01-GM134376 to L.B.B., H.P. and J.P.-C., a grant from the Wenner-Gren Foundation to J.F.B. (8702), and the UChicago DDRCC, Center for Interdisciplinary Study of Inflammatory Intestinal Disorders (C-IID) (NIDDK P30 DK042086). The SSHRC Insight Development Grant supported the collection of the Danish samples (430-2017-01193). H.N.P. was supported by an Insight Grant no. 20008499 from the Social Sciences and Humanities Research Council of Canada (SSHRC) and The Canadian Institute for Advanced Research under the Humans and the Microbiome programme. T.P.V. was supported by NIH F32GM140568. X.C. and M. Steinrücken were supported by grant R01GM146051. We also thank the University of Chicago Genomics Facility (RRID:SCR_019196), especially P. Faber, for their assistance with RNA sequencing. H.P. thanks D. Poinar for continued support and manuscript suggestions and editing.

Subjects
Yersinia pestis, General Science & Technology, Denmark, Datasets as Topic, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Aminopeptidases, Ancient, Genetic, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, London, Genetics, Humans, Genetic Predisposition to Disease, DNA, Ancient, Selection, Genetic, Selection, Plague, Multidisciplinary, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Prevention, Immunity, DNA, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Europe, Vector-Borne Diseases, Emerging Infectious Diseases, Infectious Diseases, Good Health and Well Being, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Infection
Abstract

International audience; Infectious diseases are among the strongest selective pressures driving human evolution1,2. This includes the single greatest mortality event in recorded history, the first outbreak of the second pandemic of plague, commonly called the Black Death, which was caused by the bacterium Yersinia pestis3. This pandemic devastated Afro-Eurasia, killing up to 30-50% of the population4. To identify loci that may have been under selection during the Black Death, we characterized genetic variation around immune-related genes from 206 ancient DNA extracts, stemming from two different European populations before, during and after the Black Death. Immune loci are strongly enriched for highly differentiated sites relative to a set of non-immune loci, suggesting positive selection. We identify 245 variants that are highly differentiated within the London dataset, four of which were replicated in an independent cohort from Denmark, and represent the strongest candidates for positive selection. The selected allele for one of these variants, rs2549794, is associated with the production of a full-length (versus truncated) ERAP2 transcript, variation in cytokine response to Y. pestis and increased ability to control intracellular Y. pestis in macrophages. Finally, we show that protective variants overlap with alleles that are today associated with increased susceptibility to autoimmune diseases, providing empirical evidence for the role played by past pandemics in shaping present-day susceptibility to disease.

Published
2022
Full Text
View/download PDF

15. Overview of the Medium and High Frequency Telescopes of the LiteBIRD Satellite Mission

Author

L. Montier, B. Mot, P. de Bernardis, B. Maffei, G. Pisano, F. Columbro, J. E. Gudmundsson, S. Henrot-Versillé, L. Lamagna, J. Montgomery, T. Prouvé, M. Russell, G. Savini, S. Stever, K. L. Thompson, M. Tsujimoto, C. Tucker, B. Westbrook, P. A.R. Ade, A. Adler, E. Allys, K. Arnold, D. Auguste, J. Aumont, R. Aurlien, J. Austermann, C. Baccigalupi, A. J. Banda, R. Banerji, R. B. Barreiro, S. Basak, J. Beall, D. Beck, S. Beckman, J. Bermejo, M. Bersanelli, J. Bonis, J. Borrill, F. Boulanger, S. Bounissou, M. Brilenkov, M. Brown, M. Bucher, E. Calabrese, P. Campeti, A. Carones, F. J. Casas, A. Challinor, V. Chan, K. Cheung, Y. Chinone, J. F. Cliché, L. Colombo, J. Cubas, A. Cukierman, D. Curtis, G. D’Alessandro, N. Dachlythra, M. De Petris, C. Dickinson, P. Diego-Palazuelos, M. Dobbs, T. Dotani, L. Duband, S. Duff, J. M. Duval, K. Ebisawa, T. Elleflot, H. K. Eriksen, J. Errard, T. Essinger-Hileman, F. Finelli, R. Flauger, C. Franceschet, U. Fuskeland, M. Galloway, K. Ganga, J. R. Gao, R. Genova-Santos, M. Gerbino, M. Gervasi, T. Ghigna, E. Gjerløw, M. L. Gradziel, J. Grain, F. Grupp, A. Gruppuso, T. de Haan, N. W. Halverson, P. Hargrave, T. Hasebe, M. Hasegawa, M. Hattori, M. Hazumi, D. Herman, D. Herranz, C. A. Hill, G. Hilton, Y. Hirota, E. Hivon, R. A. Hlozek, Y. Hoshino, E. de la Hoz, J. Hubmayr, K. Ichiki, T. Iida, H. Imada, K. Ishimura, H. Ishino, G. Jaehnig, T. Kaga, S. Kashima, N. Katayama, A. Kato, T. Kawasaki, R. Keskitalo, T. Kisner, Y. Kobayashi, N. Kogiso, A. Kogut, K. Kohri, E. Komatsu, K. Komatsu, K. Konishi, N. Krachmalnicoff, I. Kreykenbohm, C. L. Kuo, A. Kushino, J. V. Lanen, M. Lattanzi, A.T. Lee, C. Leloup, F. Levrier, E. Linder, T. Louis, G. Luzzi, T. Maciaszek, D. Maino, M. Maki, S. Mandelli, E. Martinez-Gonzalez, S. Masi, T. Matsumura, A. Mennella, M. Migliaccio, Y. Minami, K. Mitsuda, G. Morgante, Y. Murata, J. A. Murphy, M. Nagai, Y. Nagano, T. Nagasaki, R. Nagata, S. Nakamura, T. Namikawa, P. Natoli, S. Nerval, T. Nishibori, H. Nishino, C. O’Sullivan, H. Ogawa, S. Oguri, H. Ohsaki, I. S. Ohta, N. Okada, L. Pagano, A. Paiella, D. Paoletti, G. Patanchon, J. Peloton, F. Piacentini, G. Polenta, D. Poletti, G. Puglisi, D. Rambaud, C. Raum, S. Realini, M. Reinecke, M. Remazeilles, A. Ritacco, G. Roudil, J. A. Rubino-Martin, H. Sakurai, Y. Sakurai, M. Sandri, M. Sasaki, D. Scott, J. Seibert, Y. Sekimoto, B. Sherwin, K. Shinozaki, M. Shiraishi, P. J. Shirron, G. Signorelli, G. Smecher, R. Stompor, H. Sugai, S. Sugiyama, A. Suzuki, J. Suzuki, T. L. Svalheim, E. Switzer, R. Takaku, H. Takakura, S. Takakura, Y. Takase, Y. Takeda, A. Tartari, E. Taylor, Y. Terao, H. Thommesen, B. Thorne, T. Toda, M. Tomasi, M. Tominaga, N. Trappe, M. Tristram, M. Tsuji, J. Ullom, G. Vermeulen, P. Vielva, F. Villa, M. Vissers, N. Vittorio, I. Wehus, J. Weller, J. Wilms, B. Winter, E. J. Wollack, N. Y. Yamasaki, T. Yoshida, J. Yumoto, M. Zannoni, and A. Zonca

Subjects
Instrumentation And Photography, Astrophysics
Abstract

LiteBIRD is a JAXA-led Strategic Large-Class mission designed to search for the existence of the primordial gravitational waves produced during the inflationary phase of the Universe, through the measurements of their imprint onto the polarization of the cosmic microwave background (CMB). These measurements, requiring unprecedented sensitivity, will be performed over the full sky, at large angular scales, and over 15 frequency bands from 34 GHz to 448 GHz. The LiteBIRD instruments consist of three telescopes, namely the Low-, Medium- and High-Frequency Telescope (respectively LFT, MFT and HFT). We present in this paper an overview of the design of the Medium-Frequency Telescope (89–224 GHz) and the High-Frequency Telescope (166–448 GHz), the so-called MHFT, under European responsibility, which are two cryogenic refractive telescopes cooled down to 5 K. They include a continuous rotating half-wave plate as the first optical element, two high-density polyethylene (HDPE) lenses and more than three thousand transition-edge sensor (TES) detectors cooled to 100 mK. We provide an overview of the concept design and the remaining specific challenges that we have to face in order to achieve the scientific goals of LiteBIRD.

Published
2020
Full Text
View/download PDF

16. Genetic regulatory effects modified by immune activation contribute to autoimmune disease associations

Author

Sarah Kim-Hellmuth, Matthias Bechheim, Benno Pütz, Pejman Mohammadi, Yohann Nédélec, Nicholas Giangreco, Jessica Becker, Vera Kaiser, Nadine Fricker, Esther Beier, Peter Boor, Stephane E. Castel, Markus M. Nöthen, Luis B. Barreiro, Joseph K. Pickrell, Bertram Müller-Myhsok, Tuuli Lappalainen, Johannes Schumacher, and Veit Hornung

Subjects
Science
Abstract

Insight into the genetic influence on the immune response is important for the understanding of interindividual variability in human pathologies. Here, the authors generate transcriptome data from human blood monocytes stimulated with various immune stimuli and provide a time-resolved response eQTL map.

Published
2017
Full Text
View/download PDF

17. Predicting susceptibility to tuberculosis based on gene expression profiling in dendritic cells

Author

John D. Blischak, Ludovic Tailleux, Marsha Myrthil, Cécile Charlois, Emmanuel Bergot, Aurélien Dinh, Gloria Morizot, Olivia Chény, Cassandre Von Platen, Jean-Louis Herrmann, Roland Brosch, Luis B. Barreiro, and Yoav Gilad

Subjects
Medicine, Science
Abstract

Abstract Tuberculosis (TB) is a deadly infectious disease, which kills millions of people every year. The causative pathogen, Mycobacterium tuberculosis (MTB), is estimated to have infected up to a third of the world’s population; however, only approximately 10% of infected healthy individuals progress to active TB. Despite evidence for heritability, it is not currently possible to predict who may develop TB. To explore approaches to classify susceptibility to TB, we infected with MTB dendritic cells (DCs) from putatively resistant individuals diagnosed with latent TB, and from susceptible individuals that had recovered from active TB. We measured gene expression levels in infected and non-infected cells and found hundreds of differentially expressed genes between susceptible and resistant individuals in the non-infected cells. We further found that genetic polymorphisms nearby the differentially expressed genes between susceptible and resistant individuals are more likely to be associated with TB susceptibility in published GWAS data. Lastly, we trained a classifier based on the gene expression levels in the non-infected cells, and demonstrated reasonable performance on our data and an independent data set. Overall, our promising results from this small study suggest that training a classifier on a larger cohort may enable us to accurately predict TB susceptibility.

Published
2017
Full Text
View/download PDF

18. A Short-Term High-Fat Diet Alters Glutathione Levels and IL-6 Gene Expression in Oxidative Skeletal Muscles of Young Rats

Author

David E. Andrich, Lilya Melbouci, Ya Ou, Nickolas Auclair, Jocelyne Mercier, Jean-Christophe Grenier, Fábio Santos Lira, Luis B. Barreiro, Gawiyou Danialou, Alain-Steve Comtois, Jean-Claude Lavoie, and David H. St-Pierre

Subjects
high-fat diet, young rats, muscle glutathione, oxidative stress, inflammation, gene expression, Physiology, QP1-981
Abstract

Obesity and ensuing disorders are increasingly prevalent worldwide. High-fat diets (HFD) and diet-induced obesity have been shown to induce oxidative stress and inflammation while altering metabolic homeostasis in many organs, including the skeletal muscle. We previously observed that 14 days of HFD impairs contractile functions of the soleus (SOL) oxidative skeletal muscle. However, the mechanisms underlying these effects are not clarified. In order to determine the effects of a short-term HFD on skeletal muscle glutathione metabolism, young male Wistar rats (100–125 g) were fed HFD or a regular chow diet (RCD) for 14 days. Reduced (GSH) and disulfide (GSSG) glutathione levels were measured in the SOL. The expression of genes involved in the regulation of glutathione metabolism, oxidative stress, antioxidant defense and inflammation were measured by RNA-Seq. We observed a significant 25% decrease of GSH levels in the SOL muscle. Levels of GSSG and the GSH:GSSG ratio were similar in both groups. Further, we observed a 4.5 fold increase in the expression of pro-inflammatory cytokine interleukin 6 (IL-6) but not of other cytokines or markers of inflammation and oxidative stress. We hereby demonstrate that a short-term HFD significantly lowers SOL muscle GSH levels. This effect could be mediated through the increased expression of IL-6. Further, the skeletal muscle antioxidant defense could be impaired under cellular stress. We surmise that these early alterations could contribute to HFD-induced insulin resistance observed in longer protocols.

Published
2019
Full Text
View/download PDF

19. DNA methylation-environment interactions in the human genome

Author

Rachel A. Johnston, Katherine A. Aracena, Luis B. Barreiro, Amanda J. Lea, and Jenny Tung

Subjects
Article
Abstract

Previously we showed that a massively parallel reporter assay, mSTARR-seq, could be used to simultaneously test for both enhancer-like activity and DNA methylation-dependent enhancer activity for millions of loci in a single experiment (Leaet al., 2018). Here we apply mSTARR-seq to query nearly the entire human genome, including almost all CpG sites profiled either on the commonly used Illumina Infinium MethylationEPIC array or via reduced representation bisulfite sequencing. We show that fragments containing these sites are enriched for regulatory capacity, and that methylation-dependent regulatory activity is in turn sensitive to the cellular environment. In particular, regulatory responses to interferon alpha (IFNA) stimulation are strongly attenuated by methyl marks, indicating widespread DNA methylation-environment interactions. In agreement, methylation-dependent responses to IFNA identified via mSTARR-seq predict methylation-dependent transcriptional responses to challenge with influenza virus in human macrophages. Our observations support the idea that pre-existing DNA methylation patterns can influence the response to subsequent environmental exposures—one of the tenets of biological embedding. However, we also find that, on average, sites previously associated with early life adversity are not more likely to functionally influence gene regulation than expected by chance.

Published
2023
Full Text
View/download PDF

20. Reply to Barton et al: signatures of natural selection during the Black Death

Author

Tauras P. Vilgalys, Jennifer Klunk, Christian E. Demeure, Xiaoheng Cheng, Mari Shiratori, Julien Madej, Rémi Beau, Derek Elli, Maria I. Patino, Rebecca Redfern, Sharon N. DeWitte, Julia A. Gamble, Jesper L. Boldsen, Ann Carmichael, Nükhet Varlik, Katherine Eaton, Jean-Christophe Grenier, G. Brian Golding, Alison Devault, Jean-Marie Rouillard, Vania Yotova, Renata Sindeaux, Chun Jimmie Ye, Matin Bikaran, Anne Dumaine, Jessica F Brinkworth, Dominique Missiakas, Guy A. Rouleau, Matthias Steinrücken, Javier Pizarro-Cerdá, Hendrik N. Poinar, and Luis B. Barreiro

Abstract

Bartonet al.1raise several statistical concerns regarding our original analyses2that highlight the challenge of inferring natural selection using ancient genomic data. We show here that these concerns have limited impact on our original conclusions. Specifically, we recover the same signature of enrichment for high FSTvalues at the immune loci relative to putatively neutral sites after switching the allele frequency estimation method to a maximum likelihood approach, filtering to only consider known human variants, and down-sampling our data to the same mean coverage across sites. Furthermore, using permutations, we show that the rs2549794 variant nearERAP2continues to emerge as the strongest candidate for selection (p = 1.2×10−5), falling below the Bonferroni-corrected significance threshold recommended by Bartonet al. Importantly, the evidence for selection onERAP2is further supported by functional data demonstrating the impact of theERAP2genotype on the immune response toY. pestisand by epidemiological data from an independent group showing that the putatively selected allele during the Black Death protects against severe respiratory infection in contemporary populations.

Published
2023
Full Text
View/download PDF

21. L2-CalSat: A Calibration Satellite for Ultra-Sensitive CMB Polarization Space Missions

Author

Francisco J. Casas, Enrique Martínez-González, Juan Bermejo-Ballesteros, Sergio García, Javier Cubas, Patricio Vielva, Rita B. Barreiro, and Angel Sanz

Subjects
CMB polarization, formation flight, CubeSat, calibration, B-modes, Chemical technology, TP1-1185
Abstract

In this work, the use of a calibration satellite (L2-CalSat) flying in formation with a Cosmic Microwave Background (CMB) polarization mission in an orbit located at the second Lagrange point, is proposed. The new generation of CMB telescopes are expected to reach unprecedented levels of sensitivity to allow a very precise measurement of the B-mode of polarization, the curl-like polarization component expected from gravitational waves coming from Starobinski inflationary models. Due to the CMB polarized signal weakness, the instruments must be subjected to very precise calibration processes before and after launching. Celestial sources are often used as external references for calibration after launch, but these sources are not perfectly characterized. As a baseline option, L2-CalSat is based on the CubeSat standard and serves as a perfectly known source of a reference signal to reduce polarization measurements uncertainty. A preliminary design of L2-CalSat is described and, according to the scanning strategy followed by the telescope, the influence of the relative position between the spacecrafts in the calibration process is studied. This new calibration element will have a huge impact on the performance of CMB space missions, providing a significant improvement in the measurements accuracy without requiring new and costly technological developments.

Published
2021
Full Text
View/download PDF

22. High molecular weight DNA extraction strategies for long‐read sequencing of complex metagenomes

Author

Alon Shaiber, Luis B. Barreiro, Karen Lolans, Bana Jabri, Hilary G. Morrison, Emily Fogarty, A. Murat Eren, and Florian Trigodet

Subjects
Agarase, Extraction (chemistry), High-Throughput Nucleotide Sequencing, DNA, Sequence Analysis, DNA, Computational biology, Biology, DNA extraction, Genome, Molecular Weight, chemistry.chemical_compound, chemistry, biology.protein, Genetics, Humans, Metagenome, High molecular weight dna, Ecology, Evolution, Behavior and Systematics, Biotechnology
Abstract

By offering extremely long contiguous characterization of individual DNA molecules, rapidly emerging long-read sequencing strategies offer comprehensive insights into the organization of genetic information in genomes and metagenomes. However, successful long-read sequencing experiments demand high concentrations of highly purified DNA of high molecular weight (HMW), which limits the utility of established DNA extraction kits designed for short-read sequencing. The challenges associated with input DNA quality intensify further when working with complex environmental samples of low microbial biomass, which requires new protocols that are tailored to study metagenomes with long-read sequencing. Here, we use human tongue scrapings to benchmark six HMW DNA extraction strategies that are based on commercially available kits, phenol-chloroform (PC) extraction and agarose encasement followed by agarase digestion. A typical end goal of HMW DNA extractions is to obtain the longest possible reads during sequencing, which is often achieved by PC extractions, as demonstrated in sequencing of cultured cells. Yet our analyses that consider overall read-size distribution, assembly performance and the number of circularized elements found in sequencing results suggest that column-based kits with enzyme supplementation, rather than PC methods, may be more appropriate for long-read sequencing of metagenomes.

Published
2022
Full Text
View/download PDF

24. QUIJOTE scientific results -- IX. Radio sources in the QUIJOTE-MFI wide survey maps

Author

D Herranz, M López-Caniego, C H López-Caraballo, R T Génova-Santos, Y C Perrott, J A Rubiño-Martín, R Rebolo, E Artal, M Ashdown, R B Barreiro, F J Casas, E de la Hoz, M Fernández-Torreiro, F Guidi, R J Hoyland, A N Lasenby, E Martínez-González, M W Peel, L Piccirillo, F Poidevin, B Ruiz-Granados, D Tramonte, F Vansyngel, P Vielva, and R A Watson

Subjects
Cosmology and Nongalactic Astrophysics (astro-ph.CO), Space and Planetary Science, Astrophysics of Galaxies (astro-ph.GA), FOS: Physical sciences, Astronomy and Astrophysics, Astrophysics - Astrophysics of Galaxies, Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

We present the catalogue of Q-U-I JOint TEnerife (QUIJOTE) Wide Survey radio sources extracted from the maps of the Multi-Frequency Instrument compiled between 2012 and 2018. The catalogue contains 786 sources observed in intensity and polarization, and is divided into two separate sub-catalogues: one containing 47 bright sources previously studied by the \emph{Planck} collaboration and an extended catalogue of 739 sources either selected from the \emph{Planck} Second Catalogue of Compact Sources or found through a blind search carried out with a Mexican Hat 2 wavelet. A significant fraction of the sources in our catalogue (38.7 per cent) are within the $|b| \leq 20^\circ$ region of the Galactic plane. We determine statistical properties for those sources that are likely to be extragalactic. We find that these statistical properties are compatible with currently available models, with a $\sim$1.8 Jy completeness limit at 11 GHz. We provide the polarimetric properties of (38, 33, 31, 23) sources with P detected above the $99.99\%$ significance level at (11, 13, 17, 19) GHz, respectively. Median polarization fractions are in the $2.8$-$4.7$\% range in the 11-19 GHz frequency interval. We do not distinguish between Galactic and extragalactic sources here. The results presented here are consistent with those reported in the literature for flat- and steep-spectrum radio sources., 21 pages, 13 figures, 7 tables

Published
2023

25. QUIJOTE scientific results -- VI. The Haze as seen by QUIJOTE

Author

F Guidi, R T Génova-Santos, J A Rubiño-Martín, M W Peel, M Fernández-Torreiro, C H López-Caraballo, R Vignaga, E de la Hoz, P Vielva, R A Watson, M Ashdown, C Dickinson, E Artal, R B Barreiro, F J Casas, D Herranz, R J Hoyland, A N Lasenby, E Martinez-Gonzalez, L Piccirillo, F Poidevin, R Rebolo, B Ruiz-Granados, D Tramonte, and F Vansyngel

Subjects
High Energy Astrophysical Phenomena (astro-ph.HE), Space and Planetary Science, Astrophysics of Galaxies (astro-ph.GA), FOS: Physical sciences, Astronomy and Astrophysics, Astrophysics - High Energy Astrophysical Phenomena, Astrophysics - Astrophysics of Galaxies
Abstract

The Haze is an excess of microwave intensity emission surrounding the Galactic centre. It is spatially correlated with the $\gamma$-ray Fermi bubbles, and with the S-PASS radio polarization plumes, suggesting a possible common provenance. The models proposed to explain the origin of the Haze, including energetic events at the Galactic centre and dark matter decay in the Galactic halo, do not yet provide a clear physical interpretation. In this paper we present a re-analysis of the Haze including new observations from the Multi-Frequency Instrument (MFI) of the Q-U-I JOint TEnerife (QUIJOTE) experiment, at 11 and 13 GHz. We analyze the Haze in intensity and polarization, characterizing its spectrum. We detect an excess of diffuse intensity signal ascribed to the Haze. The spectrum at frequencies 11$\,\leq\nu\leq\,$70 GHz is a power-law with spectral index $\beta^{\rm H}=-2.79\pm0.08$, which is flatter than the Galactic synchrotron in the same region ($\beta^{\rm S}=-2.98\pm0.04$), but steeper than that obtained from previous works ($\beta^{\rm H}\sim-2.5$ at 23$\,\leq\,\nu\leq\,$70 GHz). We also observe an excess of polarized signal in the QUIJOTE-MFI maps in the Haze area. This is a first hint detection of polarized Haze, or a consequence of curvature of the synchrotron spectrum in that area. Finally, we show that the spectrum of polarized structures associated with Galactic centre activity is steep at low frequencies ($\beta \sim -3.2$ at 2.3 $\leq\nu\leq$ 23 GHz), and becomes flatter above 11 GHz., Comment: 31 pages. Accepted for publication in MNRAS

Published
2023

26. QUIJOTE scientific results -- IV. A northern sky survey in intensity and polarization at 10-20GHz with the Multi-Frequency Instrument

Author

J A Rubiño-Martín, F Guidi, R T Génova-Santos, S E Harper, D Herranz, R J Hoyland, A N Lasenby, F Poidevin, R Rebolo, B Ruiz-Granados, F Vansyngel, P Vielva, R A Watson, E Artal, M Ashdown, R B Barreiro, J D Bilbao-Ahedo, F J Casas, B Casaponsa, R Cepeda-Arroita, E de la Hoz, C Dickinson, R Fernández-Cobos, M Fernández-Torreiro, R González-González, C Hernández-Monteagudo, M López-Caniego, C López-Caraballo, E Martínez-González, M W Peel, A E Peláez-Santos, Y Perrott, L Piccirillo, N Razavi-Ghods, P Scott, D Titterington, D Tramonte, R Vignaga., and Universidad de Cantabria

Subjects
Methods: Data Analysis, Cosmology and Nongalactic Astrophysics (astro-ph.CO), Space and Planetary Science, Astrophysics of Galaxies (astro-ph.GA), Cosmic Background Radiation, Instrumentation: Polarimeters, FOS: Physical sciences, Astronomy and Astrophysics, Astrophysics - Astrophysics of Galaxies, Cosmology: Observations, Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

We present QUIJOTE intensity and polarization maps in four frequency bands centred around 11, 13, 17 and 19GHz, and covering approximately 29000 deg$^2$, including most of the Northern sky region. These maps result from 9000 h of observations taken between May 2013 and June 2018 with the first QUIJOTE instrument (MFI), and have angular resolutions of around $1^\circ$, and sensitivities in polarization within the range 35-40 $\mu$K per 1-degree beam, being a factor $\sim 2$-$4$ worse in intensity. We discuss the data processing pipeline employed, and the basic characteristics of the maps in terms of real space statistics and angular power spectra. A number of validation tests have been applied to characterise the accuracy of the calibration and the residual level of systematic effects, finding a conservative overall calibration uncertainty of 5%. We also discuss flux densities for four bright celestial sources (Tau A, Cas A, Cyg A and 3C274) which are often used as calibrators at microwave frequencies. The polarization signal in our maps is dominated by synchrotron emission. The distribution of spectral index values between the 11GHz and WMAP 23GHz map peaks at $\beta=-3.09$ with a standard deviation of 0.14. The measured BB/EE ratio at scales of $\ell=80$ is $0.26\pm 0.07$ for a Galactic cut $|b|>10^\circ$. We find a positive TE correlation for 11GHz at large angular scales ($\ell \lesssim 50$), while the EB and TB signals are consistent with zero in the multipole range $30 \lesssim \ell \lesssim 150$. The maps discussed in this paper are publicly available., Comment: 60 pages. Accepted for publication in MNRAS. Maps and derived data products available at https://research.iac.es/proyecto/quijote/

Published
2023
Full Text
View/download PDF

27. QUIJOTE Scientific Results -- VII. Galactic AME sources in the QUIJOTE-MFI Northern Hemisphere Wide-Survey

Author

F Poidevin, R T Génova-Santos, J A Rubiño-Martín, C H López-Caraballo, R A Watson, E Artal, M Ashdown, R B Barreiro, F J Casas, E de la Hoz, M Fernández-Torreiro, F Guidi, D Herranz, R J Hoyland, A N Lasenby, E Martinez-Gonzalez, M W Peel, L Piccirillo, R Rebolo, B Ruiz-Granados, D Tramonte, F Vansyngel, and P Vielva

Subjects
Space and Planetary Science, Astrophysics of Galaxies (astro-ph.GA), FOS: Physical sciences, Astronomy and Astrophysics, Astrophysics - Astrophysics of Galaxies
Abstract

The QUIJOTE-MFI Northern Hemisphere Wide-Survey has provided maps of the sky above declinations $-30^\circ$ at 11, 13, 17 and 19$\,$GHz. These data are combined with ancillary data to produce Spectral Energy Distributions in intensity in the frequency range 0.4--3\,000$\,$GHz on a sample of 52 candidate compact sources harbouring anomalous microwave emission (AME). We apply a component separation analysis at 1$^\circ$ scale on the full sample from which we identify 44 sources with high AME significance. We explore correlations between different fitted parameters on this last sample. QUIJOTE-MFI data contribute to notably improve the characterisation of the AME spectrum, and its separation from the other components. In particular, ignoring the 10--20\,GHz data produces on average an underestimation of the AME amplitude, and an overestimation of the free-free component. We find an average AME peak frequency of 23.6 $\pm$ 3.6$\,$GHz, about 4$\,$GHz lower than the value reported in previous studies. The strongest correlation is found between the peak flux density of the thermal dust and of the AME component. A mild correlation is found between the AME emissivity ($A_{\rm AME}/\tau_{250}$) and the interstellar radiation field. On the other hand no correlation is found between the AME emissivity and the free-free radiation Emission Measure. Our statistical results suggest that the interstellar radiation field could still be the main driver of the intensity of the AME as regards spinning dust excitation mechanisms. On the other hand, it is not clear whether spinning dust would be most likely associated with cold phases of the interstellar medium rather than with hot phases dominated by free-free radiation., Comment: 36 pages. Accepted for publication in MNRAS. Maps and derived data products available at https://research.iac.es/proyecto/quijote/

Published
2023
Full Text
View/download PDF

28. Genome-wide quantification of the effects of DNA methylation on human gene regulation

Author

Amanda J Lea, Christopher M Vockley, Rachel A Johnston, Christina A Del Carpio, Luis B Barreiro, Timothy E Reddy, and Jenny Tung

Subjects
DNA methylation, epigenomics, high-throughput reporter assay, Medicine, Science, Biology (General), QH301-705.5
Abstract

Changes in DNA methylation are involved in development, disease, and the response to environmental conditions. However, not all regulatory elements are functionally methylation-dependent (MD). Here, we report a method, mSTARR-seq, that assesses the causal effects of DNA methylation on regulatory activity at hundreds of thousands of fragments (millions of CpG sites) simultaneously. Using mSTARR-seq, we identify thousands of MD regulatory elements in the human genome. MD activity is partially predictable using sequence and chromatin state information, and distinct transcription factors are associated with higher activity in unmethylated versus methylated DNA. Further, pioneer TFs linked to higher activity in the methylated state appear to drive demethylation of experimentally methylated sites. MD regulatory elements also predict methylation-gene expression relationships across individuals, where they are 1.6x enriched among sites with strong negative correlations. mSTARR-seq thus provides a map of MD regulatory activity in the human genome and facilitates interpretation of differential methylation studies.

Published
2018
Full Text
View/download PDF

29. Genetic ancestry effects on the response to viral infection are pervasive but cell type specific

Author

Beth K Thielen, Jessica K. Fiege, Mari Shiratori, Clayton K. Mickelson, Ryan A. Langlois, Luis B. Barreiro, João Barroso-Batista, and Haley E. Randolph

Subjects
Genetics, Titer, Multidisciplinary, Immune system, Infectious disease (medical specialty), Interferon, Genetic genealogy, medicine, Quantitative trait locus, Biology, Gene, Peripheral blood mononuclear cell, medicine.drug
Abstract

Humans differ in their susceptibility to infectious disease, partly owing to variation in the immune response after infection. We used single-cell RNA sequencing to quantify variation in the response to influenza infection in peripheral blood mononuclear cells from European- and African-ancestry males. Genetic ancestry effects are common but highly cell type specific. Higher levels of European ancestry are associated with increased type I interferon pathway activity in early infection, which predicts reduced viral titers at later time points. Substantial population-associated variation is explained by cis-expression quantitative trait loci that are differentiated by genetic ancestry. Furthermore, genetic ancestryÐassociated genes are enriched among genes correlated with COVID-19 disease severity, suggesting that the early immune response contributes to ancestry-associated differences for multiple viral infection outcomes. [ FROM AUTHOR] Copyright of Science is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Published
2021
Full Text
View/download PDF

30. Planck 2018 results

Author

Antony Lewis, X. Dupac, James R. Fergusson, François R. Bouchet, Diego Molinari, E. Martínez-González, Jean-François Cardoso, L. Salvati, Jörg P. Rachen, Krzysztof M. Gorski, K. Ganga, A. Marcos-Caballero, C. Combet, Hannu Kurki-Suonio, E. Di Valentino, Jose M. Diego, L. Montier, Jan Hamann, J. F. Macías-Pérez, E. Franceschi, Charles R. Lawrence, M. Douspis, Erminia Calabrese, E. P. S. Shellard, Frederico Arroja, M. Le Jeune, P. Vielva, Andrea Zacchei, Graca Rocha, Martina Gerbino, Zhiqi Huang, Davide Maino, Adam Moss, Ricardo Genova-Santos, D. Tavagnacco, M. López-Caniego, A. A. Fraisse, M. Tenti, F. Piacentini, J.-P. Bernard, P. de Bernardis, Tiziana Trombetti, L. Toffolatti, Soumen Basak, F. Elsner, J.-L. Puget, Benjamin D. Wandelt, Julian Borrill, R. B. Barreiro, Gabriel Jung, Michele Liguori, S. Galeotta, Will Handley, F. Cuttaia, G. Polenta, R. C. Butler, K. Kiiveri, Anthony Lasenby, Alessandro Melchiorri, Reijo Keskitalo, A. J. Banday, M.-A. Miville-Deschênes, A. Renzi, P. Bielewicz, F. Oppizzi, Yashar Akrami, Anthony Challinor, B. Casaponsa, E. Keihänen, Gianmarco Maggio, B. P. Crill, Nicola Bartolo, B. Van Tent, Fabrizio Villa, Francesca Perrotta, F. K. Hansen, J. B. Kim, G. Sirri, Andrei V. Frolov, Michele Maris, J. A. Tauber, M. Savelainen, D. Herranz, A.-S. Suur-Uski, Yabebal Fantaye, Sabino Matarrese, M. Migliaccio, M. Tomasi, M. Bucher, Nicola Vittorio, J. Valiviita, V. Lindholm, W. C. Jones, Douglas Scott, R. Fernandez-Cobos, D. Paoletti, Marco Bersanelli, Torsten A. Enßlin, A. Moneti, M. Frailis, Carlo Baccigalupi, V. Pettorino, François Levrier, E. Hivon, J. Aumont, B. Racine, A. Mennella, G. Patanchon, Alessandro Gruppuso, Ingunn Kathrine Wehus, M. Reinecke, J.-M. Delouis, P. D. Meerburg, Massimiliano Lattanzi, Jose Alberto Rubino-Martin, N. Mandolesi, Chiara Sirignano, Kendrick M. Smith, Andrew H. Jaffe, Peter Meinhold, J.-M. Lamarre, A. de Rosa, G. de Zotti, B. Partridge, J. González-Nuevo, A. Ducout, Locke D. Spencer, M. Ashdown, H. K. Eriksen, Martin Kunz, Mathieu Remazeilles, Jon E. Gudmundsson, L. P. L. Colombo, Jason D. McEwen, Mario Ballardini, Peter G. Martin, George Efstathiou, Serge Gratton, Carlo Burigana, Nicoletta Krachmalnicoff, Yin-Zhe Ma, Jacques Delabrouille, Fabio Finelli, L. Pagano, N. Mauri, S. Dusini, Andrea Zonca, R. A. Sunyaev, P. B. Lilje, Luca Stanco, H. C. Chiang, K. Benabed, J. R. Bond, B. Ruiz-Granados, O. Doré, Paolo Natoli, Maresuke Shiraishi, Moritz Münchmeyer, S. Galli, Gianluca Morgante, Astrophysique, Laboratoire de physique de l'ENS - ENS Paris (LPENS (UMR_8023)), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut de recherche en astrophysique et planétologie (IRAP), Institut national des sciences de l'Univers (INSU - CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), Institut d'Astrophysique de Paris (IAP), Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University of Parma = Università degli studi di Parma [Parme, Italie], Canadian Institute for Theoretical Astrophysics (CITA), Lawrence Berkeley National Laboratory [Berkeley] (LBNL), Patrimoine, Littérature, Histoire (PLH), Université Toulouse - Jean Jaurès (UT2J), AstroParticule et Cosmologie (APC (UMR_7164)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Universidade Aberta [Lisboa], Laboratoire de Physique Subatomique et de Cosmologie (LPSC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Dipartimento di Fisica [Roma La Sapienza], Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), Institut d'astrophysique spatiale (IAS), Université Paris-Sud - Paris 11 (UP11)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Laboratory for Phytosanitary Diagnostics and Forecasts, All-Russian Institute for Plant Protection, Russian Academy of Sciences [Moscow] (RAS), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Department of Atmospheric, Oceanic, and Space Sciences [Ann Arbor] (AOSS), University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Laboratoire d'Etude du Rayonnement et de la Matière en Astrophysique (LERMA (UMR_8112)), Sorbonne Université (SU)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), ICRA and Physics Department, Dipartimento di Fisica 'G. Galilei', Universita degli Studi di Padova, University of Cambridge [UK] (CAM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire de Physique Nucléaire et de Hautes Énergies (LPNHE), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Pierre et Marie Curie - Paris 6 (UPMC), Astrophysique Interprétation Modélisation (AIM (UMR_7158 / UMR_E_9005 / UM_112)), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University of Manchester [Manchester], University of British Columbia (UBC), Laboratoire de neurobiologie cellulaire et moléculaire (NBCM), Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique des 2 Infinis Irène Joliot-Curie (IJCLab), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Planck Collaboration, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Université Paris Diderot - Paris 7 (UPD7), Centre National de la Recherche Scientifique (CNRS)-Observatoire Midi-Pyrénées (OMP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2020-....] (UGA [2020-....])-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2020-....] (Grenoble INP [2020-....]), Université Grenoble Alpes [2020-....] (UGA [2020-....]), Sorbonne Université (SU)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique Théorique d'Orsay [Orsay] (LPT), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Planck, Department of Physics, Helsinki Institute of Physics, Universidad de Cantabria, Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Observatoire de Paris, PSL Research University (PSL)-PSL Research University (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, PSL Research University (PSL)-PSL Research University (PSL)-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physique de l'ENS - ENS Paris (LPENS), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Sorbonne Université (SU)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Sorbonne Université (SU)-École normale supérieure - Paris (ENS Paris), High-Energy Frontier, Van Swinderen Institute for Particle Physics and G, Ministerio de Economía y Competitividad (España), Consejo Superior de Investigaciones Científicas (España), European Commission, European Research Council, European Space Agency, Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Département de Physique de l'ENS-PSL, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Département de Physique de l'ENS-PSL, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Università degli studi di Parma = University of Parma (UNIPR), Université de Toulouse (UT)-Université de Toulouse (UT), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Université Paris-Sud - Paris 11 (UP11)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National d’Études Spatiales [Paris] (CNES), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Padova = University of Padua (Unipd), Astrophysique Interprétation Modélisation (AIM (UMR7158 / UMR_E_9005 / UM_112)), Y. Akrami, F. Arroja, M. Ashdown, J. Aumont, C. Baccigalupi, M. Ballardini, A. J. Banday, R. B. Barreiro, N. Bartolo, S. Basak, K. Benabed, J. -P. Bernard, M. Bersanelli, P. Bielewicz, J. R. Bond, J. Borrill, F. R. Bouchet, M. Bucher, C. Burigana, R. C. Butler, E. Calabrese, J. -F. Cardoso, B. Casaponsa, A. Challinor, H. C. Chiang, L. P. L. Colombo, C. Combet, B. P. Crill, F. Cuttaia, P. de Bernardi, A. de Rosa, G. de Zotti, J. Delabrouille, J. -M. Deloui, E. Di Valentino, J. M. Diego, O. Doré, M. Douspi, A. Ducout, X. Dupac, S. Dusini, G. Efstathiou, F. Elsner, T. A. Enßlin, H. K. Eriksen, Y. Fantaye, J. Fergusson, R. Fernandez-Cobo, F. Finelli, M. Fraili, A. A. Fraisse, E. Franceschi, A. Frolov, S. Galeotta, K. Ganga, R. T. Génova-Santo, M. Gerbino, J. González-Nuevo, K. M. Górski, S. Gratton, A. Gruppuso, J. E. Gudmundsson, J. Hamann, W. Handley, F. K. Hansen, D. Herranz, E. Hivon, Z. Huang, A. H. Jaffe, W. C. Jone, G. Jung, E. Keihänen, R. Keskitalo, K. Kiiveri, J. Kim, N. Krachmalnicoff, M. Kunz, H. Kurki-Suonio, J. -M. Lamarre, A. Lasenby, M. Lattanzi, C. R. Lawrence, M. Le Jeune, F. Levrier, A. Lewi, M. Liguori, P. B. Lilje, V. Lindholm, M. López-Caniego, Y. -Z. Ma, J. F. Macías-Pérez, G. Maggio, D. Maino, N. Mandolesi, A. Marcos-Caballero, M. Mari, P. G. Martin, E. Martínez-González, S. Matarrese, N. Mauri, J. D. McEwen, P. D. Meerburg, P. R. Meinhold, A. Melchiorri, A. Mennella, M. Migliaccio, M. -A. Miville-Deschêne, D. Molinari, A. Moneti, L. Montier, G. Morgante, A. Mo, M. Münchmeyer, P. Natoli, F. Oppizzi, L. Pagano, D. Paoletti, B. Partridge, G. Patanchon, F. Perrotta, V. Pettorino, F. Piacentini, G. Polenta, J. -L. Puget, J. P. Rachen, B. Racine, M. Reinecke, M. Remazeille, A. Renzi, G. Rocha, J. A. Rubiño-Martín, B. Ruiz-Granado, L. Salvati, M. Savelainen, D. Scott, E. P. S. Shellard, M. Shiraishi, C. Sirignano, G. Sirri, K. Smith, L. D. Spencer, L. Stanco, R. Sunyaev, A. -S. Suur-Uski, J. A. Tauber, D. Tavagnacco, M. Tenti, L. Toffolatti, M. Tomasi, T. Trombetti, J. Valiviita, B. Van Tent, P. Vielva, F. Villa, N. Vittorio, B. D. Wandelt, I. K. Wehu, A. Zacchei, A. Zonca, Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Observatoire de Paris, and PSL Research University (PSL)-PSL Research University (PSL)-Université Paris Diderot - Paris 7 (UPD7)

Subjects
High Energy Physics - Theory, cosmological model, Astronomy, Cosmic microwave background, POLARIZATION ANISOTROPIES, cosmic background radiation: polarization, Astrophysics, cosmic background radiation, Cosmic background radiation, Early Universe, 01 natural sciences, 7. Clean energy, expansion: multipole, General Relativity and Quantum Cosmology, High Energy Physics - Phenomenology (hep-ph), cosmology: theory, 3-POINT CORRELATION-FUNCTION, observations [Cosmology], data analysis [Methods], 010303 astronomy & astrophysics, TEMPERATURE, Physics, [PHYS.HTHE]Physics [physics]/High Energy Physics - Theory [hep-th], hep-th, formation, hep-ph, early Universe, CMB cold spot, inflation: model, High Energy Physics - Phenomenology, scale dependence, non-Gaussianity, symbols, Sunyaev-Zel'dovich effect, [PHYS.GRQC]Physics [physics]/General Relativity and Quantum Cosmology [gr-qc], astro-ph.CO, Trispectrum, Astrophysics - Cosmology and Nongalactic Astrophysics, Particle physics, data analysis method, Cosmology and Nongalactic Astrophysics (astro-ph.CO), satellite: Planck, gr-qc, FOS: Physical sciences, PREDICTIONS, General Relativity and Quantum Cosmology (gr-qc), Astrophysics::Cosmology and Extragalactic Astrophysics, Sunyaev–Zel'dovich effect, Separable space, NO, isocurvature, symbols.namesake, trispectrum, Settore FIS/05 - Astronomia e Astrofisica, parity: violation, gravitation: lens, statistical analysis, theory [Cosmology], Non-Gaussianity, 0103 physical sciences, BISPECTRUM, INFRARED BACKGROUND ANISOTROPIES, structure, bispectrum: scale dependence, Planck, cosmic background radiation: bispectrum, inflation, FAST ESTIMATOR, numerical calculations, non-Gaussianity: primordial, 010308 nuclear & particles physics, ISOCURVATURE PERTURBATIONS, Astronomy and Astrophysics, stability, 115 Astronomy, Space science, Inflation, methods: data analysis, boundary condition, cosmic background radiation: temperature, Cosmology: observations, Cosmology: theory, Methods: data analysis, High Energy Physics - Theory (hep-th), 13. Climate action, Space and Planetary Science, axion, [PHYS.HPHE]Physics [physics]/High Energy Physics - Phenomenology [hep-ph], cosmology: observations, Cosmic background radiation, Cosmology: observations, Cosmology: theory, Early Universe, Inflation, Methods: data analysis, [PHYS.ASTR]Physics [physics]/Astrophysics [astro-ph], Bispectrum
Abstract

Planck Collaboration: et al., arXiv:1905.05697v1, We analyse the Planck full-mission cosmic microwave background (CMB) temperature and E-mode polarization maps to obtain constraints on primordial non-Gaussianity (NG). We compare estimates obtained from separable template-fitting, binned, and optimal modal bispectrum estimators, finding consistent values for the local, equilateral, and orthogonal bispectrum amplitudes. Our combined temperature and polarization analysis produces the following final results: fNLlocal = −0.9 ± 5.1; fNLequil = −26 ± 47; and fNLortho = −38 ± 24 (68% CL, statistical). These results include low-multipole (4 ≤ ℓ < 40) polarization data that are not included in our previous analysis. The results also pass an extensive battery of tests (with additional tests regarding foreground residuals compared to 2015), and they are stable with respect to our 2015 measurements (with small fluctuations, at the level of a fraction of a standard deviation, which is consistent with changes in data processing). Polarization-only bispectra display a significant improvement in robustness; they can now be used independently to set primordial NG constraints with a sensitivity comparable to WMAP temperature-based results and they give excellent agreement. In addition to the analysis of the standard local, equilateral, and orthogonal bispectrum shapes, we consider a large number of additional cases, such as scale-dependent feature and resonance bispectra, isocurvature primordial NG, and parity-breaking models, where we also place tight constraints but do not detect any signal. The non-primordial lensing bispectrum is, however, detected with an improved significance compared to 2015, excluding the null hypothesis at 3.5σ. Beyond estimates of individual shape amplitudes, we also present model-independent reconstructions and analyses of the Planck CMB bispectrum. Our final constraint on the local primordial trispectrum shape is gNLlocal = (−5.8 ± 6.5) × 104 (68% CL, statistical), while constraints for other trispectrum shapes are also determined. Exploiting the tight limits on various bispectrum and trispectrum shapes, we constrain the parameter space of different early-Universe scenarios that generate primordial NG, including general single-field models of inflation, multi-field models (e.g. curvaton models), models of inflation with axion fields producing parity-violation bispectra in the tensor sector, and inflationary models involving vector-like fields with directionally-dependent bispectra. Our results provide a high-precision test for structure-formation scenarios, showing complete agreement with the basic picture of the ΛCDM cosmology regarding the statistics of the initial conditions, with cosmic structures arising from adiabatic, passive, Gaussian, and primordial seed perturbations., The Planck Collaboration acknowledges the support of: ESA; CNES and CNRS/INSU-IN2P3-INP (France); ASI, CNR, and INAF (Italy); NASA and DoE (USA); STFC and UKSA (UK); CSIC, MINECO, JA, and RES (Spain); Tekes, AoF, and CSC (Finland); DLR and MPG (Germany); CSA (Canada); DTU Space (Denmark); SER/SSO (Switzerland); RCN (Norway); SFI (Ireland); FCT/MCTES (Portugal); and ERC and PRACE (EU).

Published
2020
Full Text
View/download PDF

31. The <scp>picasso</scp> map-making code: application to a simulation of the QUIJOTE northern sky survey

Author

F Guidi, Ricardo Genova-Santos, Robert A. Watson, Simon Harper, R. B. Barreiro, J D Bilbao-Ahedo, A. Peláez-Santos, Jose Alberto Rubino-Martin, M. Ashdown, Ministerio de Ciencia, Innovación y Universidades (España), Ministerio de Economía y Competitividad (España), European Commission, and Agencia Estatal de Investigación (España)

Subjects
Physics, 010308 nuclear & particles physics, media_common.quotation_subject, Cosmic microwave background, Astrophysics::Instrumentation and Methods for Astrophysics, Cosmic background radiation, FOS: Physical sciences, Astronomy and Astrophysics, Astrophysics::Cosmology and Extragalactic Astrophysics, Function (mathematics), Polarization (waves), 01 natural sciences, High fidelity, Space and Planetary Science, Sky, 0103 physical sciences, Code (cryptography), Time domain, Astrophysics - Instrumentation and Methods for Astrophysics, Instrumentation and Methods for Astrophysics (astro-ph.IM), 010303 astronomy & astrophysics, Remote sensing, media_common
Abstract

Map-making is an important step for the data analysis of cosmic microwave background (CMB) experiments. It consists of converting the data, which are typically a long, complex, and noisy collection of measurements, into a map, which is an image of the observed sky. We present in this paper a new map-making code named PICASSO (Polarization and Intensity CArtographer for Scanned Sky Observations), which was implemented to construct intensity and polarization maps from the Multi Frequency Instrument (MFI) of the QUIJOTE (Q-U-I Joint TEnerife) CMB polarization experiment. PICASSO is based on the destriping algorithm, and is suited to address specific issues of ground-based microwave observations, with a technique that allows the fit of a template function in the time domain, during the map-making step. This paper describes the PICASSO code, validating it with simulations and assessing its performance. For this purpose, we produced realistic simulations of the QUIJOTE-MFI survey of the northern sky (approximately ∼20 000 deg2), and analysed the reconstructed maps with PICASSO, using real and harmonic space statistics. We show that, for this sky area, PICASSO is able to reconstruct, with high fidelity, the injected signal, recovering all the scales with ℓ > 10 in TT, EE, and BB. The signal error is better than 0.001 per cent at 20 < ℓ < 200. Finally, we validated some of the methods that will be applied to the real wide-survey data, like the detection of the CMB anisotropies via cross-correlation analyses. Despite that the implementation of PICASSO is specific for QUIJOTE-MFI data, it could be adapted to other experiments., Partial financial support is provided by the Spanish Ministry of Science, Innovation and Universities under the projects AYA2007-68058-C03-01, AYA2010-21766-C03-02, AYA2014-60438-P, AYA2017-84185-P, IACA13-3E-2336, IACA15-BE-3707, EQC2018-004918-P, the Severo Ochoa Program SEV-2015-0548, and also by the Consolider-Ingenio project CSD2010-00064 (EPI: Exploring the Physics of Inflation). This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement number 687312 (RADIOFOREGROUNDS). RBB and JDBA acknowledge the Spanish Agencia Estatal de Investigación (AEI, MICIU) for the financial support provided under the projects with references PID2019-110610RB-C21, ESP2017-83921-C2-1-R, and AYA2017-90675-REDC, co-funded with EU FEDER funds, and also acknowledge the funding from Unidad de Excelencia María de Maeztu (MDM-2017-0765).

Published
2021
Full Text
View/download PDF

32. A multilayered immune system through the lens of unconventional T cells

Author

Bana Jabri, Toufic Mayassi, Jamie Rossjohn, and Luis B. Barreiro

Subjects
Multidisciplinary, T cell, T-cell receptor, Receptors, Antigen, T-Cell, Adaptive Immunity, Biology, Ligands, Acquired immune system, Biological Evolution, Article, Immunity, Innate, Cell biology, medicine.anatomical_structure, Immune system, Antigen, T-Lymphocyte Subsets, medicine, Animals, Humans, Compartment (development), Tissue homeostasis, Function (biology)
Abstract

The unconventional T cell compartment encompasses a variety of cell subsets that straddle the line between innate and adaptive immunity, often reside at mucosal surfaces and can recognize a wide range of non-polymorphic ligands. Recent advances have highlighted the role of unconventional T cells in tissue homeostasis and disease. In this Review, we recast unconventional T cell subsets according to the class of ligand that they recognize; their expression of semi-invariant or diverse T cell receptors; the structural features that underlie ligand recognition; their acquisition of effector functions in the thymus or periphery; and their distinct functional properties. Unconventional T cells follow specific selection rules and are poised to recognize self or evolutionarily conserved microbial antigens. We discuss these features from an evolutionary perspective to provide insights into the development and function of unconventional T cells. Finally, we elaborate on the functional redundancy of unconventional T cells and their relationship to subsets of innate and adaptive lymphoid cells, and propose that the unconventional T cell compartment has a critical role in our survival by expanding and complementing the role of the conventional T cell compartment in protective immunity, tissue healing and barrier function.

Published
2021
Full Text
View/download PDF

33. Gut microbiome heritability is nearly universal but environmentally contingent

Author

Ran Blekhman, Tim L. Wango, Susan C. Alberts, Jean-Christophe Grenier, Luis B. Barreiro, Jacob B. Gordon, Trevor J. Gould, Niki H. Learn, Vania Yotova, Johannes R. Björk, Laura E. Grieneisen, David A. W. A. M. Jansen, R. S. Mututua, Jack A. Gilbert, Jenny Tung, J. Kinyua Warutere, Mauna Dasari, Laurence R. Gesquiere, Elizabeth A. Archie, Neil Gottel, and Long'ida Siodi

Subjects
Male, 0301 basic medicine, Aging, Genotype, Firmicutes, Environment, Biology, Feces, 03 medical and health sciences, 0302 clinical medicine, Animals, Humans, Microbiome, Social Behavior, Multidisciplinary, Bacteria, Bacteroidetes, Extramural, Host (biology), Heritability, Phenotype, Gut microbiome, Diet, Gastrointestinal Microbiome, Large sample, Actinobacteria, 030104 developmental biology, Evolutionary biology, Female, Seasons, 030217 neurology & neurosurgery, Papio
Abstract

Baboons inform on human gut microbiota Commensal bacteria are found throughout an organism, but it is not known whether associations between gut bacteria and their host are heritable. Grieneisen et al. examined changes in the microbiomes of 585 wild baboons from fecal samples collected over 14 years (see the Perspective by Cortes-Ortiz and Amato). Almost all microbiome traits tested demonstrated some level of statistically significant heritability. Most heritability values were low but varied over time correlating with the age of the host. Baboons live in an environment similar to that postulated for early humans and have a microbiome similar to that of humans. Thus, this heritability of the microbiome may reflect similar genetic determinants in humans, for which similar datasets are not available. Science , aba5483, this issue p. 181 ; see also abj5287, p. 159

Published
2021
Full Text
View/download PDF

34. Deciphering the genetic control of gene expression following Mycobacterium leprae antigen stimulation.

Author

Jérémy Manry, Yohann Nédélec, Vinicius M Fava, Aurélie Cobat, Marianna Orlova, Nguyen Van Thuc, Vu Hong Thai, Guillaume Laval, Luis B Barreiro, and Erwin Schurr

Subjects
Genetics, QH426-470
Abstract

Leprosy is a human infectious disease caused by Mycobacterium leprae. A strong host genetic contribution to leprosy susceptibility is well established. However, the modulation of the transcriptional response to infection and the mechanism(s) of disease control are poorly understood. To address this gap in knowledge of leprosy pathogenicity, we conducted a genome-wide search for expression quantitative trait loci (eQTL) that are associated with transcript variation before and after stimulation with M. leprae sonicate in whole blood cells. We show that M. leprae antigen stimulation mainly triggered the upregulation of immune related genes and that a substantial proportion of the differential gene expression is genetically controlled. Indeed, using stringent criteria, we identified 318 genes displaying cis-eQTL at an FDR of 0.01, including 66 genes displaying response-eQTL (reQTL), i.e. cis-eQTL that showed significant evidence for interaction with the M. leprae stimulus. Such reQTL correspond to regulatory variations that affect the interaction between human whole blood cells and M. leprae sonicate and, thus, likely between the human host and M. leprae bacilli. We found that reQTL were significantly enriched among binding sites of transcription factors that are activated in response to infection, and that they were enriched among single nucleotide polymorphisms (SNPs) associated with susceptibility to leprosy per se and Type-I Reaction, and seven of them have been targeted by recent positive selection. Our study suggested that natural selection shaped our genomic diversity to face pathogen exposure including M. leprae infection.

Published
2017
Full Text
View/download PDF

35. Hemispherical power asymmetry in intensity and polarization for Planck PR4 data

Author

C. Gimeno-Amo, R. B. Barreiro, and E. Martínez-González

Subjects
Hemispherical Power Asymmetry, Polarization, Cosmic Microwave Background, Inpainting, Planck Mission
Abstract

WMAP and Planck temperature data show evidence of several anomalies hinting that the large-scale anisotropies are not fully compatible with the statistical isotropy assumption, one of the fundamentals of the standard model of cosmology. In particular, a “hemispherical power asymmetry” has been found using different estimators with a significance close to 3σ. In this work we perform an analysis of this asymmetry using the local-variance estimator, and the Planck fourth release (PR4) data, which provides an improved data set with reduced systematics and noise, especially in polarization. Additionaly, we have implemented an alternative inpainting approach,which is necessary to reduce the E/B mixing.

Published
2022
Full Text
View/download PDF

36. Trained immunity, tolerance, priming and differentiation: distinct immunological processes

Author

Boris Novakovic, Andreas Schlitzer, Giuseppe Matarese, Zahi A. Fayad, Willem J. M. Mulder, Henk Stunnenberg, Andrew R. DiNardo, Niels P. Riksen, Joachim L. Schultze, Christine Stabell Benn, Joseph C. Sun, Eva Kaufmann, Shabaana A. Khader, Michael H. Sieweke, Siroon Bekkering, Stephanie Fanucchi, Luis B. Barreiro, Maziar Divangahi, Mihai G. Netea, Reinout van Crevel, Jordi Ochando, Peter Aaby, Shruti Naik, Leo A. B. Joosten, Triantafyllos Chavakis, Musa M. Mhlanga, Eicke Latz, David L. Williams, Jos W. M. van der Meer, Luke A. J. O'Neill, Ramnik J. Xavier, Nigel Curtis, Robert W. Sauerwein, Kate L. Jeffrey, Edward R. Sherwood, Elaine Fuchs, Sebastian Weis, Nargis Khan, Melanie Hamon, Raphael Duivenwoorden, Keiko Ozato, Simone J.C.F.M. Moorlag, Jorge Domínguez-Andrés, Frank L. van de Veerdonk, Precision Medicine, ICMS Core, McGill University Health Center [Montreal] (MUHC), Bandim Health Project, International Network for the Demographic Evaluation of Populations and Their Health (INDEPTH Network), Washington University in Saint Louis (WUSTL), The University of Chicago Medicine [Chicago], Radboud University Medical Center [Nijmegen], Technische Universität Dresden = Dresden University of Technology (TU Dresden), University of Melbourne, Baylor College of Medicine (BCM), Baylor University, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Eindhoven University of Technology [Eindhoven] (TU/e), University of Cape Town, Rockefeller University [New York], Chromatine et Infection - Chromatin and Infection, Institut Pasteur [Paris] (IP), Harvard Medical School [Boston] (HMS), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Trinity Biomedical Sciences Institute, School of Biochemistry & Immunology, National Institute of Child Health and Human Development [Bethesda], National Institutes of Health, Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Universität Bonn = University of Bonn, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biotechnology Center, and Center for Regenerative Therapies Dresden (CRTD), Max Delbrück Centrum für Molekulare Medizin (MDC), University of Southern Denmark (SDU), Radboud University [Nijmegen], Memorial Sloane Kettering Cancer Center [New York], Weill Medical College of Cornell University [New York], Jena University Hospital [Jena], East Tennessee State University (ETSU), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Massachusetts Institute of Technology (MIT), Divangahi, M., Aaby, P., Khader, S. A., Barreiro, L. B., Bekkering, S., Chavakis, T., van Crevel, R., Curtis, N., Dinardo, A. R., Dominguez-Andres, J., Duivenwoorden, R., Fanucchi, S., Fayad, Z., Fuchs, E., Hamon, M., Jeffrey, K. L., Khan, N., Joosten, L. A. B., Kaufmann, E., Latz, E., Matarese, G., van der Meer, J. W. M., Mhlanga, M., Moorlag, S. J. C. F. M., Mulder, W. J. M., Naik, S., Novakovic, B., O'Neill, L., Ochando, J., Ozato, K., Riksen, N. P., Sauerwein, R., Sherwood, E. R., Schlitzer, A., Schultze, J. L., Sieweke, M. H., Benn, C. S., Stunnenberg, H., Sun, J., van de Veerdonk, F. L., Weis, S., Williams, D. L., Xavier, R., Netea, M. G., Institut Pasteur [Paris], Consiglio Nazionale delle Ricerche (CNR), University of Bonn, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtzgemeinschaft, Radboud university [Nijmegen], Hamon, Melanie, and ACS - Atherosclerosis & ischemic syndromes

Subjects
0301 basic medicine, [SDV]Life Sciences [q-bio], animal diseases, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Priming (immunology), Adaptive Immunity, 0302 clinical medicine, Immunology and Allergy, MESH: Animals, ComputingMilieux_MISCELLANEOUS, immunology [BCG Vaccine], Vaccination, Vascular damage Radboud Institute for Molecular Life Sciences [Radboudumc 16], Cell Differentiation, Common framework, [SDV] Life Sciences [q-bio], MESH: BCG Vaccine, BCG Vaccine, MESH: Immunologic Memory, MESH: Immunity, Innate, MESH: Cell Differentiation, MESH: Immune Tolerance, Immunology, education, immunology [Adaptive Immunity], chemical and pharmacologic phenomena, Biology, Article, 03 medical and health sciences, Immune system, Immunity, Immune Tolerance, Animals, Humans, ddc:610, Molecular Biology, MESH: Humans, immunology [Immune Tolerance], Cell Biology, MESH: Vaccination, biochemical phenomena, metabolism, and nutrition, Immunity, Innate, immunology [Immunologic Memory], immunology [Immunity, Innate], Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], 030104 developmental biology, bacteria, Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19], Neuroscience, Immunologic Memory, MESH: Adaptive Immunity, 030215 immunology
Abstract

The similarities and differences between trained immunity and other immune processes are the subject of intense interrogation. Therefore, a consensus on the definition of trained immunity in both in vitro and in vivo settings, as well as in experimental models and human subjects, is necessary for advancing this field of research. Here we aim to establish a common framework that describes the experimental standards for defining trained immunity.

Published
2021
Full Text
View/download PDF

37. Epigenetic variation impacts ancestry-associated differences in the transcriptional response to influenza infection

Author

Katherine A Aracena, Yen-Lung Lin, Kaixuan Luo, Alain Pacis, Saideep Gona, Zepeng Mu, Vania Yotova, Renata Sindeaux, Albena Pramatarova, Marie-Michelle Simon, Xun Chen, Cristian Groza, David Lougheed, Romain Gregoire, David Brownlee, Yang Li, Xin He, David Bujold, Tomi Pastinen, Guillaume Bourque, and Luis B Barreiro

Abstract

SummaryHumans display remarkable inter-individual variation in immune response when exposed to identical immune challenges. Yet, our understanding of the genetic and epigenetic factors contributing to such variation remains limited. Here we carried out in-depth genetic, epigenetic, and transcriptional profiling on primary macrophages derived from a panel of European and African-ancestry individuals before and after infection with influenza A virus (IAV). We show that baseline epigenetic profiles are strongly predictive of the transcriptional response to IAV across individuals, and that ancestry-associated differences in gene expression are tightly coupled with variation in enhancer activity. Quantitative trait locus (QTL) mapping revealed highly coordinated genetic effects on gene regulation with many cis-acting genetic variants impacting concomitantly gene expression and multiple epigenetic marks. These data reveal that ancestry-associated differences in the epigenetic landscape are genetically controlled, even more so than variation in gene expression. Lastly, we show that among QTL variants that colocalized with immune-disease loci, only 7% were gene expression QTL, the remaining corresponding to genetic variants that impact one or more epigenetic marks, which stresses the importance of considering molecular phenotypes beyond gene expression in disease-focused studies.

Published
2022
Full Text
View/download PDF

38. Aberrant T-cell exhaustion in severe combined immunodeficiency survivors with poor T-cell reconstitution after transplantation

Author

Roxane Labrosse, Ines Boufaied, Benoîte Bourdin, Saideep Gona, Haley E. Randolph, Brent R. Logan, Sara Bourbonnais, Chloé Berthe, Wendy Chan, Rebecca H. Buckley, Roberta E. Parrott, Geoffrey D.E. Cuvelier, Neena Kapoor, Sharat Chandra, Blachy J. Dávila Saldaña, Hesham Eissa, Fred D. Goldman, Jennifer Heimall, Richard O’Reilly, Sonali Chaudhury, Edward A. Kolb, Shalini Shenoy, Linda M. Griffith, Michael Pulsipher, Donald B. Kohn, Luigi D. Notarangelo, Sung-Yun Pai, Morton J. Cowan, Christopher C. Dvorak, Élie Haddad, Jennifer M. Puck, Luis B. Barreiro, and Hélène Decaluwe

Subjects
Immunology, Immunology and Allergy
Abstract

Severe combined immunodeficiency (SCID) comprises rare inherited disorders of immunity that require definitive treatment through hematopoietic cell transplantation (HCT) or gene therapy for survival. Despite successes of allogeneic HCT, many SCID patients experience incomplete immune reconstitution, persistent T-cell lymphopenia, and poor long-term outcomes.We hypothesized that CD4We analyzed markers of exhaustion in blood samples from 61 SCID patients at a median of 10.4 years after HCT.Compared to post-HCT SCID patients with normal CD4Recipients of unconditioned HCT for SCID may develop late post-HCT T-cell exhaustion as a result of diminished production of T-lineage cells. Elevated expression of inhibitory receptors on their T cells may be a biomarker of poor long-term T-cell reconstitution.

Published
2022

39. Widespread Shortening of 3' Untranslated Regions and Increased Exon Inclusion Are Evolutionarily Conserved Features of Innate Immune Responses to Infection.

Author

Athma A Pai, Golshid Baharian, Ariane Pagé Sabourin, Jessica F Brinkworth, Yohann Nédélec, Joseph W Foley, Jean-Christophe Grenier, Katherine J Siddle, Anne Dumaine, Vania Yotova, Zachary P Johnson, Robert E Lanford, Christopher B Burge, and Luis B Barreiro

Subjects
Genetics, QH426-470
Abstract

The contribution of pre-mRNA processing mechanisms to the regulation of immune responses remains poorly studied despite emerging examples of their role as regulators of immune defenses. We sought to investigate the role of mRNA processing in the cellular responses of human macrophages to live bacterial infections. Here, we used mRNA sequencing to quantify gene expression and isoform abundances in primary macrophages from 60 individuals, before and after infection with Listeria monocytogenes and Salmonella typhimurium. In response to both bacteria we identified thousands of genes that significantly change isoform usage in response to infection, characterized by an overall increase in isoform diversity after infection. In response to both bacteria, we found global shifts towards (i) the inclusion of cassette exons and (ii) shorter 3' UTRs, with near-universal shifts towards usage of more upstream polyadenylation sites. Using complementary data collected in non-human primates, we show that these features are evolutionarily conserved among primates. Following infection, we identify candidate RNA processing factors whose expression is associated with individual-specific variation in isoform abundance. Finally, by profiling microRNA levels, we show that 3' UTRs with reduced abundance after infection are significantly enriched for target sites for particular miRNAs. These results suggest that the pervasive usage of shorter 3' UTRs is a mechanism for particular genes to evade repression by immune-activated miRNAs. Collectively, our results suggest that dynamic changes in RNA processing may play key roles in the regulation of innate immune responses.

Published
2016
Full Text
View/download PDF

40. Genetic and Transcriptional Analysis of Human Host Response to Healthy Gut Microbiota

Author

Allison L. Richards, Michael B. Burns, Adnan Alazizi, Luis B. Barreiro, Roger Pique-Regi, Ran Blekhman, and Francesca Luca

Subjects
complex traits, gene expression, genetics, host response, host-microbiota interaction, Microbiology, QR1-502
Abstract

ABSTRACT Many studies have demonstrated the importance of the gut microbiota in healthy and disease states. However, establishing the causality of host-microbiota interactions in humans is still challenging. Here, we describe a novel experimental system to define the transcriptional response induced by the microbiota for human cells and to shed light on the molecular mechanisms underlying host-gut microbiota interactions. In primary human colonic epithelial cells, we identified over 6,000 genes whose expression changed at various time points following coculturing with the gut microbiota of a healthy individual. Among the differentially expressed genes we found a 1.8-fold enrichment of genes associated with diseases that have been previously linked to the microbiome, such as obesity and colorectal cancer. In addition, our experimental system allowed us to identify 87 host single nucleotide polymorphisms (SNPs) that show allele-specific expression in 69 genes. Furthermore, for 12 SNPs in 12 different genes, allele-specific expression is conditional on the exposure to the microbiota. Of these 12 genes, 8 have been associated with diseases linked to the gut microbiota, specifically colorectal cancer, obesity, and type 2 diabetes. Our study demonstrates a scalable approach to study host-gut microbiota interactions and can be used to identify putative mechanisms for the interplay between host genetics and the microbiota in health and disease. IMPORTANCE The study of host-microbiota interactions in humans is largely limited to identifying associations between microbial communities and host phenotypes. While these studies have generated important insights on the links between the microbiota and human disease, the assessment of cause-and-effect relationships has been challenging. Although this relationship can be studied in germfree mice, this system is costly, and it is difficult to accurately account for the effects of host genotypic variation and environmental effects seen in humans. Here, we have developed a novel approach to directly investigate the transcriptional changes induced by live microbial communities on human colonic epithelial cells and how these changes are modulated by host genotype. This method is easily scalable to large numbers of host genetic backgrounds and diverse microbiota and can be utilized to elucidate the mechanisms of host-microbiota interactions. Future extensions may also include colonic organoid cultures.

Published
2016
Full Text
View/download PDF

41. IL-15, gluten and HLA-DQ8 drive tissue destruction in coeliac disease

Author

Romain Bouziat, Cezary Ciszewski, Joseph A. Murray, Chaitan Khosla, Thomas Lejeune, Eric V. Marietta, Jean-Christophe Grenier, Olivier Tastet, Brad A. Palanski, Vania Yotova, Luis B. Barreiro, Irina E. Horwath, Matthew A. Zurenski, Bana Jabri, Ian Lawrence, Jordan D. Ernest, Jordan Voisine, Sangman M. Kim, Kaushik Panigrahi, Mohamed B.F. Hawash, Valérie Abadie, Valentina Discepolo, Anne Dumaine, Abadie, V., Kim, S. M., Lejeune, T., Palanski, B. A., Ernest, J. D., Tastet, O., Voisine, J., Discepolo, V., Marietta, E. V., Hawash, M. B. F., Ciszewski, C., Bouziat, R., Panigrahi, K., Horwath, I., Zurenski, M. A., Lawrence, I., Dumaine, A., Yotova, V., Grenier, J. -C., Murray, J. A., Khosla, C., Barreiro, L. B., and Jabri, B.

Subjects
CD4-Positive T-Lymphocytes, Male, Glutens, Tissue transglutaminase, Mice, Transgenic, Human leukocyte antigen, Biology, Coeliac disease, Article, Interferon-gamma, Mice, HLA-DQ Antigens, medicine, Cytotoxic T cell, Humans, Animals, Villous atrophy, Interleukin-15, Lamina propria, Multidisciplinary, Innate immune system, Animal, Microfilament Proteins, HLA-DQ Antigen, nutritional and metabolic diseases, medicine.disease, digestive system diseases, Celiac Disease, medicine.anatomical_structure, CD4-Positive T-Lymphocyte, Interleukin 15, Immunology, biology.protein, Female, Gluten, Human
Abstract

Coeliac disease is a complex, polygenic inflammatory enteropathy caused by exposure to dietary gluten that occurs in a subset of genetically susceptible individuals who express either the HLA-DQ8 or HLA-DQ2 haplotypes1,2. The need to develop non-dietary treatments is now widely recognized3, but no pathophysiologically relevant gluten- and HLA-dependent preclinical model exists. Furthermore, although studies in humans have led to major advances in our understanding of the pathogenesis of coeliac disease4, the respective roles of disease-predisposing HLA molecules, and of adaptive and innate immunity in the development of tissue damage, have not been directly demonstrated. Here we describe a mouse model that reproduces the overexpression of interleukin-15 (IL-15) in the gut epithelium and lamina propria that is characteristic of active coeliac disease, expresses the predisposing HLA-DQ8 molecule, and develops villous atrophy after ingestion of gluten. Overexpression of IL-15 in both the epithelium and the lamina propria is required for the development of villous atrophy, which demonstrates the location-dependent central role of IL-15 in the pathogenesis of coeliac disease. In addition, CD4+ T cells and HLA-DQ8 have a crucial role in the licensing of cytotoxic T cells to mediate intestinal epithelial cell lysis. We also demonstrate a role for the cytokine interferon-γ (IFNγ) and the enzyme transglutaminase 2 (TG2) in tissue destruction. By reflecting the complex interaction between gluten, genetics and IL-15-driven tissue inflammation, this mouse model provides the opportunity to both increase our understanding of coeliac disease, and develop new therapeutic strategies. An HLA- and gluten-dependent mouse model of coeliac disease with villous atrophy provides evidence for the cooperative role of IL-15 and gluten-specific CD4+ T cells in licensing the full activation of cytotoxic T cells that are necessary for inducing epithelial damage.

Published
2020

42. Cosmic Birefringence from Planck Data Release 4

Author

P. Diego-Palazuelos, J. R. Eskilt, Y. Minami, M. Tristram, R. M. Sullivan, A. J. Banday, R. B. Barreiro, H. K. Eriksen, K. M. Górski, R. Keskitalo, E. Komatsu, E. Martínez-González, D. Scott, P. Vielva, I. K. Wehus, Max Planck Society, European Space Agency, National Aeronautics and Space Administration (US), Department of Energy (US), European Commission, European Research Council, Ministerio de Ciencia, Innovación y Universidades (España), Japan Society for the Promotion of Science, Agencia Estatal de Investigación (España), German Research Foundation, Gobierno de Cantabria, Universidad de Cantabria, Laboratoire de Physique des 2 Infinis Irène Joliot-Curie (IJCLab), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de recherche en astrophysique et planétologie (IRAP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)

Subjects
polarization, cosmological model, Cosmology and Nongalactic Astrophysics (astro-ph.CO), satellite: Planck, birefringence, Astrophysics::Instrumentation and Methods for Astrophysics, FOS: Physical sciences, General Physics and Astronomy, cosmic background radiation, Astrophysics::Cosmology and Extragalactic Astrophysics, parity: violation, galaxy, [PHYS.ASTR]Physics [physics]/Astrophysics [astro-ph], signature, Astrophysics::Galaxy Astrophysics, Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

We search for the signature of parity-violating physics in the cosmic microwave background, called cosmic birefringence, using the Planck data release 4. We initially find a birefringence angle of β=0.30°±0.11° (68% C.L.) for nearly full-sky data. The values of β decrease as we enlarge the Galactic mask, which can be interpreted as the effect of polarized foreground emission. Two independent ways to model this effect are used to mitigate the systematic impact on β for different sky fractions. We choose not to assign cosmological significance to the measured value of β until we improve our knowledge of the foreground polarization., Open access publication funded by the Max Planck Society., Planck is a project of the European Space Agency (ESA) with instruments provided by two scientific consortia funded by ESA member states and led by Principal Investigators from France and Italy, telescope reflectors provided through a collaboration between ESA and a scientific consortium led and funded by Denmark, and additional contributions from NASA (USA). Some of the results in this Letter have been derived using the HEALPix package. This research used resources of the National Energy Research Scientific Computing Center (NERSC), a U.S. Department of Energy Office of Science User Facility operated under Contract No. DE-AC02-05CH11231. Part of the research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration (80NM0018D0004). J. R. E., H. K. E., and I.W. acknowledge funding from the European Research Council (ERC) under the Horizon 2020 Research and Innovation Programme (Grant Agreement No. 819478). The work of Y. M. was supported in part by the Japan Society for the Promotion of Science (JSPS) KAKENHI, Grants No. JP20K14497. R. S. and D. S. acknowledge the support of the Natural Sciences and Engineering Research Council of Canada. P. D.-P. acknowledges financial support from the Formación del Profesorado Universitario (FPU) Programme of the Spanish Ministerio de Ciencia, Innovación y Universidades, and thanks the Max Planck Institute for Astrophysics for hospitality when this work was being finalized. P. D.-P., B. B., E.M.-G., and P. V. thank the Spanish Agencia Estatal de Investigación (AEI, MICIU) for the financial support provided under the projects with references PID2019-110610RB-C21, ESP2017-83921-C2-1-R and AYA2017-90675-REDC, co-funded with EU FEDER funds, and acknowledge supports from Universidad de Cantabria and Consejería de Universidades, Igualdad, Cultura y Deporte del Gobierno de Cantabria via the “Instrumentación y ciencia de datos para sondear la naturaleza del universo” project, as well as from Unidad de Excelencia María de Maeztu (MDM-2017-0765). The work of E. K. was supported in part by JSPS KAKENHI Grants No. JP20H05850 and No. JP20H05859, and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy—EXC-2094–390783311. The Kavli I. P. M. U. is supported by World Premier International Research Center Initiative (WPI), MEXT, Japan.

Published
2022
Full Text
View/download PDF

43. Optical Characterization of OMT-Coupled TES Bolometers for LiteBIRD

Author

J. Hubmayr, P. A. R. Ade, A. Adler, E. Allys, D. Alonso, K. Arnold, D. Auguste, J. Aumont, R. Aurlien, J. E. Austermann, S. Azzoni, C. Baccigalupi, A. J. Banday, R. Banerji, R. B. Barreiro, N. Bartolo, S. Basak, E. Battistelli, L. Bautista, J. A. Beall, D. Beck, S. Beckman, K. Benabed, J. Bermejo-Ballesteros, M. Bersanelli, J. Bonis, J. Borrill, F. Bouchet, F. Boulanger, S. Bounissou, M. Brilenkov, M. L. Brown, M. Bucher, E. Calabrese, M. Calvo, P. Campeti, A. Carones, F. J. Casas, A. Catalano, A. Challinor, V. Chan, K. Cheung, Y. Chinone, C. Chiocchetta, S. E. Clark, L. Clermont, S. Clesse, J. Cliche, F. Columbro, J. A. Connors, A. Coppolecchia, W. Coulton, J. Cubas, A. Cukierman, D. Curtis, F. Cuttaia, G. D’Alessandro, K. Dachlythra, P. de Bernardis, T. de Haan, E. de la Hoz, M. De Petris, S. Della Torre, J. J. Daz Garca, C. Dickinson, P. Diego-Palazuelos, M. Dobbs, T. Dotani, D. Douillet, E. Doumayrou, L. Duband, A. Ducout, S. M. Duff, J. M. Duval, K. Ebisawa, T. Elleflot, H. K. Eriksen, J. Errard, T. Essinger-Hileman, S. Farrens, F. Finelli, R. Flauger, K. Fleury-Frenette, C. Franceschet, U. Fuskeland, L. Galli, S. Galli, M. Galloway, K. Ganga, J. R. Gao, R. T. Genova-Santos, M. Georges, M. Gerbino, M. Gervasi, T. Ghigna, S. Giardiello, E. Gjerlw, R. Gonzlez Gonzles, M. L. Gradziel, J. Grain, L. Grandsire, F. Grupp, A. Gruppuso, J. E. Gudmundsson, N. W. Halverson, J. Hamilton, P. Hargrave, T. Hasebe, M. Hasegawa, M. Hattori, M. Hazumi, S. Henrot-Versill, B. Hensley, D. Herman, D. Herranz, G. C. Hilton, E. Hivon, R. A. Hlozek, D. Hoang, A. L. Hornsby, Y. Hoshino, K. Ichiki, T. Iida, T. Ikemoto, H. Imada, K. Ishimura, H. Ishino, G. Jaehnig, M. Jones, T. Kaga, S. Kashima, N. Katayama, A. Kato, T. Kawasaki, R. Keskitalo, C. Kintziger, T. Kisner, Y. Kobayashi, N. Kogiso, A. Kogut, K. Kohri, E. Komatsu, K. Komatsu, K. Konishi, N. Krachmalnicoff, I. Kreykenbohm, C. L. Kuo, A. Kushino, L. Lamagna, J. V. Lanen, G. Laquaniello, M. Lattanzi, A. T. Lee, C. Leloup, F. Levrier, E. Linder, M. J. Link, A. I. Lonappan, T. Louis, G. Luzzi, J. Macias-Perez, T. Maciaszek, B. Maffei, D. Maino, M. Maki, S. Mandelli, M. Maris, B. Marquet, E. Martnez-Gonzlez, F. A. Martire, S. Masi, M. Massa, M. Masuzawa, S. Matarrese, F. T. Matsuda, T. Matsumura, L. Mele, A. Mennella, M. Migliaccio, Y. Minami, K. Mitsuda, A. Moggi, M. Monelli, A. Monfardini, J. Montgomery, L. Montier, G. Morgante, B. Mot, Y. Murata, J. A. Murphy, M. Nagai, Y. Nagano, T. Nagasaki, R. Nagata, S. Nakamura, R. Nakano, T. Namikawa, F. Nati, P. Natoli, S. Nerval, N. Neto Godry Farias, T. Nishibori, H. Nishino, F. Noviello, G. C. O’Neil, C. O’Sullivan, K. Odagiri, H. Ochi, H. Ogawa, S. Oguri, H. Ohsaki, I. S. Ohta, N. Okada, L. Pagano, A. Paiella, D. Paoletti, G. Pascual Cisneros, A. Passerini, G. Patanchon, V. Pelgrim, J. Peloton, V. Pettorino, F. Piacentini, M. Piat, G. Piccirilli, F. Pinsard, G. Pisano, J. Plesseria, G. Polenta, D. Poletti, T. Prouv, G. Puglisi, D. Rambaud, C. Raum, S. Realini, M. Reinecke, C. D. Reintsema, M. Remazeilles, A. Ritacco, P. Rosier, G. Roudil, J. Rubino-Martin, M. Russell, H. Sakurai, Y. Sakurai, M. Sandri, M. Sasaki, G. Savini, D. Scott, J. Seibert, Y. Sekimoto, B. Sherwin, K. Shinozaki, M. Shiraishi, P. Shirron, A. Shitvov, G. Signorelli, G. Smecher, F. Spinella, J. Starck, S. Stever, R. Stompor, R. Sudiwala, S. Sugiyama, R. Sullivan, A. Suzuki, J. Suzuki, T. Suzuki, T. L. Svalheim, E. Switzer, R. Takaku, H. Takakura, S. Takakura, Y. Takase, Y. Takeda, A. Tartari, D. Tavagnacco, A. Taylor, E. Taylor, Y. Terao, L. Terenzi, J. Thermeau, H. Thommesen, K. L. Thompson, B. Thorne, T. Toda, M. Tomasi, M. Tominaga, N. Trappe, M. Tristram, M. Tsuji, M. Tsujimoto, C. Tucker, R. Ueki, J. N. Ullom, K. Umemori, L. Vacher, J. Van Lanen, G. Vermeulen, P. Vielva, F. Villa, M. R. Vissers, N. Vittorio, B. Wandelt, W. Wang, I. K. Wehus, J. Weller, B. Westbrook, G. Weymann-Despres, J. Wilms, B. Winter, E. J. Wollack, N. Y. Yamasaki, T. Yoshida, J. Yumoto, K. Watanuki, A. Zacchei, M. Zannoni, A. Zonca, Hubmayr, J, Ade, P, Adler, A, Allys, E, Alonso, D, Arnold, K, Auguste, D, Aumont, J, Aurlien, R, Austermann, J, Azzoni, S, Baccigalupi, C, Banday, A, Banerji, R, Barreiro, R, Bartolo, N, Basak, S, Battistelli, E, Bautista, L, Beall, J, Beck, D, Beckman, S, Benabed, K, Bermejo-Ballesteros, J, Bersanelli, M, Bonis, J, Borrill, J, Bouchet, F, Boulanger, F, Bounissou, S, Brilenkov, M, Brown, M, Bucher, M, Calabrese, E, Calvo, M, Campeti, P, Carones, A, Casas, F, Catalano, A, Challinor, A, Chan, V, Cheung, K, Chinone, Y, Chiocchetta, C, Clark, S, Clermont, L, Clesse, S, Cliche, J, Columbro, F, Connors, J, Coppolecchia, A, Coulton, W, Cubas, J, Cukierman, A, Curtis, D, Cuttaia, F, D’Alessandro, G, Dachlythra, K, de Bernardis, P, de Haan, T, de la Hoz, E, De Petris, M, Della Torre, S, Daz Garca, J, Dickinson, C, Diego-Palazuelos, P, Dobbs, M, Dotani, T, Douillet, D, Doumayrou, E, Duband, L, Ducout, A, Duff, S, Duval, J, Ebisawa, K, Elleflot, T, Eriksen, H, Errard, J, Essinger-Hileman, T, Farrens, S, Finelli, F, Flauger, R, Fleury-Frenette, K, Franceschet, C, Fuskeland, U, Galli, L, Galli, S, Galloway, M, Ganga, K, Gao, J, Genova-Santos, R, Georges, M, Gerbino, M, Gervasi, M, Ghigna, T, Giardiello, S, Gjerlw, E, Gonzles, R, Gradziel, M, Grain, J, Grandsire, L, Grupp, F, Gruppuso, A, Gudmundsson, J, Halverson, N, Hamilton, J, Hargrave, P, Hasebe, T, Hasegawa, M, Hattori, M, Hazumi, M, Henrot-Versill, S, Hensley, B, Herman, D, Herranz, D, Hilton, G, Hivon, E, Hlozek, R, Hoang, D, Hornsby, A, Hoshino, Y, Ichiki, K, Iida, T, Ikemoto, T, Imada, H, Ishimura, K, Ishino, H, Jaehnig, G, Jones, M, Kaga, T, Kashima, S, Katayama, N, Kato, A, Kawasaki, T, Keskitalo, R, Kintziger, C, Kisner, T, Kobayashi, Y, Kogiso, N, Kogut, A, Kohri, K, Komatsu, E, Komatsu, K, Konishi, K, Krachmalnicoff, N, Kreykenbohm, I, Kuo, C, Kushino, A, Lamagna, L, Lanen, J, Laquaniello, G, Lattanzi, M, Lee, A, Leloup, C, Levrier, F, Linder, E, Link, M, Lonappan, A, Louis, T, Luzzi, G, Macias-Perez, J, Maciaszek, T, Maffei, B, Maino, D, Maki, M, Mandelli, S, Maris, M, Marquet, B, Martnez-Gonzlez, E, Martire, F, Masi, S, Massa, M, Masuzawa, M, Matarrese, S, Matsuda, F, Matsumura, T, Mele, L, Mennella, A, Migliaccio, M, Minami, Y, Mitsuda, K, Moggi, A, Monelli, M, Monfardini, A, Montgomery, J, Montier, L, Morgante, G, Mot, B, Murata, Y, Murphy, J, Nagai, M, Nagano, Y, Nagasaki, T, Nagata, R, Nakamura, S, Nakano, R, Namikawa, T, Nati, F, Natoli, P, Nerval, S, Neto Godry Farias, N, Nishibori, T, Nishino, H, Noviello, F, O’Neil, G, O’Sullivan, C, Odagiri, K, Ochi, H, Ogawa, H, Oguri, S, Ohsaki, H, Ohta, I, Okada, N, Pagano, L, Paiella, A, Paoletti, D, Pascual Cisneros, G, Passerini, A, Patanchon, G, Pelgrim, V, Peloton, J, Pettorino, V, Piacentini, F, Piat, M, Piccirilli, G, Pinsard, F, Pisano, G, Plesseria, J, Polenta, G, Poletti, D, Prouv, T, Puglisi, G, Rambaud, D, Raum, C, Realini, S, Reinecke, M, Reintsema, C, Remazeilles, M, Ritacco, A, Rosier, P, Roudil, G, Rubino-Martin, J, Russell, M, Sakurai, H, Sakurai, Y, Sandri, M, Sasaki, M, Savini, G, Scott, D, Seibert, J, Sekimoto, Y, Sherwin, B, Shinozaki, K, Shiraishi, M, Shirron, P, Shitvov, A, Signorelli, G, Smecher, G, Spinella, F, Starck, J, Stever, S, Stompor, R, Sudiwala, R, Sugiyama, S, Sullivan, R, Suzuki, A, Suzuki, J, Suzuki, T, Svalheim, T, Switzer, E, Takaku, R, Takakura, H, Takakura, S, Takase, Y, Takeda, Y, Tartari, A, Tavagnacco, D, Taylor, A, Taylor, E, Terao, Y, Terenzi, L, Thermeau, J, Thommesen, H, Thompson, K, Thorne, B, Toda, T, Tomasi, M, Tominaga, M, Trappe, N, Tristram, M, Tsuji, M, Tsujimoto, M, Tucker, C, Ueki, R, Ullom, J, Umemori, K, Vacher, L, Van Lanen, J, Vermeulen, G, Vielva, P, Villa, F, Vissers, M, Vittorio, N, Wandelt, B, Wang, W, Wehus, I, Weller, J, Westbrook, B, Weymann-Despres, G, Wilms, J, Winter, B, Wollack, E, Yamasaki, N, Yoshida, T, Yumoto, J, Watanuki, K, Zacchei, A, Zannoni, M, Zonca, A, and National Aeronautics and Space Administration (US)

Subjects
CMB, TES, OMT, Low temperature detector, Bolometer, FIS/05 - ASTRONOMIA E ASTROFISICA, Settore FIS/05 - Astronomia e Astrofisica, General Materials Science, Condensed Matter Physics, CMB, TES, OMT, Low temperature detector, Bolometer, Atomic and Molecular Physics, and Optics
Abstract

et al., Feedhorn- and orthomode transducer- (OMT) coupled transition edge sensor (TES) bolometers have been designed and micro-fabricated to meet the optical specifications of the LiteBIRD high frequency telescope (HFT) focal plane. We discuss the design and optical characterization of two LiteBIRD HFT detector types: dual-polarization, dual-frequency-band pixels with 195/280 GHz and 235/337 GHz band centers. Results show well-matched passbands between orthogonal polarization channels and frequency centers within 3% of the design values. The optical efficiency of each frequency channel is conservatively reported to be within the range 0.64−0.72, determined from the response to a cryogenic, temperature-controlled thermal source. These values are in good agreement with expectations and either exceed or are within 10% of the values used in the LiteBIRD sensitivity forecast. Lastly, we report a measurement of loss in Nb/SiNx/Nb microstrip at 100 mK and over the frequency range 200–350 GHz, which is comparable to values previously reported in the literature., This work is supported by NASA under grant no. 80NSSC18K0132.

Published
2022

45. GATA4 controls regionalization of tissue immunity and commensal-driven immunopathology

Author

Zachary M. Earley, Wioletta Lisicka, Joseph J. Sifakis, Raúl Aguirre-Gamboa, Anita Kowalczyk, Jacob T. Barlow, Dustin G. Shaw, Valentina Discepolo, Ineke L. Tan, Saideep Gona, Jordan D. Ernest, Polly Matzinger, Luis B. Barreiro, Andrey Morgun, Albert Bendelac, Rustem F. Ismagilov, Natalia Shulzhenko, Samantha J. Riesenfeld, and Bana Jabri

Subjects
Infectious Diseases, Immunology, Immunology and Allergy
Published
2023
Full Text
View/download PDF

46. Improved limits on the tensor-to-scalar ratio using BICEP and Planck

Author

M. Tristram, A. J. Banday, K. M. Górski, R. Keskitalo, C. R. Lawrence, K. J. Andersen, R. B. Barreiro, J. Borrill, L. P. L. Colombo, H. K. Eriksen, R. Fernandez-Cobos, T. S. Kisner, E. Martínez-González, B. Partridge, D. Scott, T. L. Svalheim, I. K. Wehus, Laboratoire de Physique des 2 Infinis Irène Joliot-Curie (IJCLab), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de recherche en astrophysique et planétologie (IRAP), Institut national des sciences de l'Univers (INSU - CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), Universidad de Cantabria, Centre National de la Recherche Scientifique (France), Department of Energy (US), National Energy Research Scientific Computing Center (US), California Institute of Technology, National Aeronautics and Space Administration (US), and European Space Agency

Subjects
Quantum Physics, Cosmology and Nongalactic Astrophysics (astro-ph.CO), satellite: Planck, FOS: Physical sciences, Molecular, Astrophysics::Cosmology and Extragalactic Astrophysics, baryon: oscillation: acoustic, BICEP, sensitivity, Atomic, Nuclear & Particles Physics, Particle and Plasma Physics, cosmological model: parameter space, ionization, path length: optical, Nuclear, [PHYS.ASTR]Physics [physics]/Astrophysics [astro-ph], Astronomical and Space Sciences, Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

We present constraints on the tensor-to-scalar ratio r using a combination of BICEP/Keck 2018 (BK18) and Planck PR4 data allowing us to fit for r consistently with the six parameters of the Λ CDM model. We discuss the sensitivity of constraints on r to uncertainties in the Λ CDM parameters as defined by the Planck data. In particular, we are able to derive a constraint on the reionization optical depth τ and thus propagate its uncertainty into the posterior distribution for r. While Planck sensitivity to r is slightly lower than the current ground-based measurements, the combination of Planck with BK18 and baryon-acoustic-oscillation data yields results consistent with r=0 and tightens the constraint to r, We gratefully acknowledge support from the CNRS/IN2P3 Computing Center for providing computing and data-processing resources needed for this work. This research used resources of the National Energy Research Scientific Computing Center, which is supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC0205CH11231. Part of the research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration (Grant No. 80NM0018D0004). Planck is a project of the European Space Agency (ESA).

Published
2021

47. Synchrony and idiosyncrasy in the gut microbiome of wild baboons

Author

Jean-Christophe Grenier, David J Jansen, Sayan Mukherjee, L.I. Siodi, K. Roche, Vania Yotova, Laurence R. Gesquiere, Luis B. Barreiro, Jenny Tung, Laura E. Grieneisen, Jack A. Gilbert, Ran Blekhman, Neil Gottel, Jacob B. Gordon, R. S. Mututua, Johannes R. Björk, Niki H. Learn, Susan C. Alberts, Mauna Dasari, J.K. Warutere, Trevor J. Gould, Elizabeth A. Archie, and Tim L. Wango

Subjects
Idiosyncrasy, Ecology, biology, Bacteria, Microbiota, Gut flora, biology.organism_classification, Gut microbiome, Diet, Gastrointestinal Microbiome, Human gut, Evolutionary biology, Animals, Humans, Microbiome, Ecology, Evolution, Behavior and Systematics, Papio
Abstract

Human gut microbial dynamics are highly individualized, making it challenging to link microbiota to health and to design universal microbiome therapies. This individuality is typically attributed to variation in host genetics, diets, environments and medications but it could also emerge from fundamental ecological forces that shape microbiota more generally. Here, we leverage extensive gut microbial time series from wild baboons-hosts who experience little interindividual dietary and environmental heterogeneity-to test whether gut microbial dynamics are synchronized across hosts or largely idiosyncratic. Despite their shared lifestyles, baboon microbiota were only weakly synchronized. The strongest synchrony occurred among baboons living in the same social group, probably because group members range over the same habitat and simultaneously encounter the same sources of food and water. However, this synchrony was modest compared to each host's personalized dynamics. In support, host-specific factors, especially host identity, explained, on average, more than three times the deviance in longitudinal dynamics compared to factors shared with social group members and ten times the deviance of factors shared across the host population. These results contribute to mounting evidence that highly idiosyncratic gut microbiomes are not an artefact of modern human environments and that synchronizing forces in the gut microbiome (for example, shared environments, diets and microbial dispersal) are not strong enough to overwhelm key drivers of microbiome personalization, such as host genetics, priority effects, horizontal gene transfer and functional redundancy.

Published
2021

48. Alveolar macrophages from persons living with HIV show impaired epigenetic response to Mycobacterium tuberculosis

Author

Ron Olivenstein, Christoph Lange, Alain Pacis, Renata H.M. Sindeaux, Jean-Pierre Routy, Vania Yotova, Marianna Orlova, Pauline Cassart, Wilian Correa-Macedo, Vinicius M. Fava, Anne Dumaine, Erwin Schurr, Barbara Kalsdorf, Joaquín Sanz, Luis B. Barreiro, Yong Zhong Xu, and Josée Girouard

Subjects
Adult, Male, Tuberculosis, HIV Infections, Disease, Epigenesis, Genetic, Mycobacterium tuberculosis, Macrophages, Alveolar, Humans, Medicine, Epigenetics, Infectious disease (athletes), Adverse effect, Aged, Innate immune system, biology, medicine.diagnostic_test, Coinfection, business.industry, General Medicine, Middle Aged, biology.organism_classification, medicine.disease, Bronchoalveolar lavage, Anti-Retroviral Agents, Immunology, Commentary, Female, Pre-Exposure Prophylaxis, Transcriptome, business, Research Article
Abstract

Persons living with HIV (PLWH) are at increased risk of tuberculosis (TB). HIV-associated TB is often the result of recent infection with Mycobacterium tuberculosis (M. tuberculosis) followed by rapid progression to disease. Alveolar macrophages (AMs) are the first cells of the innate immune system that engage M. tuberculosis, but how HIV and antiretroviral therapy (ART) affect the anti-mycobacterial response of AMs is not known. To investigate the impact of HIV and ART on the transcriptomic and epigenetic response of AMs to M. tuberculosis, we obtained AMs by bronchoalveolar lavage from 20 PLWH receiving ART, 16 control subjects who were HIV-free (HC), and 14 subjects who received ART as preexposure prophylaxis (PrEP) to prevent HIV infection. Following in vitro challenge with M. tuberculosis, AMs from each group displayed overlapping but distinct profiles of significantly up- and downregulated genes in response to M. tuberculosis. Comparatively, AMs isolated from both PLWH and PrEP subjects presented a substantially weaker transcriptional response. In addition, AMs from HC subjects challenged with M. tuberculosis responded with pronounced chromatin accessibility changes while AMs obtained from PLWH and PrEP subjects displayed no significant changes in their chromatin state. Collectively, these results revealed a stronger adverse effect of ART than HIV on the epigenetic landscape and transcriptional responsiveness of AMs.

Published
2021
Full Text
View/download PDF

49. GATA4 regionalizes intestinal metabolism and barrier function to prevent immunopathology

Author

Jacob T. Barlow, Dustin G. Shaw, Joseph J. Sifakis, Natalia Shulzhenko, Albert Bendelac, Andriy Morgun, Zachary M. Earley, Jordan D. Ernest, Valentina Discepolo, Polly Matzinger, Raúl Aguirre-Gamboa, Wioletta Lisicka, Bana Jabri, Saideep Gona, Ineke L. Tan, Anita Kowalczyk, Samantha J. Riesenfeld, Luis B. Barreiro, and Rustem F. Ismagilov

Subjects
Autoimmune disease, Gastrointestinal tract, Inflammation, Biology, medicine.disease, Small intestine, medicine.anatomical_structure, Immunity, Immunopathology, Immunology, Citrobacter rodentium, medicine, medicine.symptom, Barrier function
Abstract

SummaryDifferent regions of the gastrointestinal tract have distinct digestive and absorptive functions, which may be locally disrupted by infection or autoimmune disease. Yet, the mechanisms underlying intestinal regionalization and its dysregulation in disease are not well understood. Here, we used mouse models, transcriptomics, and immune profiling to show that regional epithelial expression of the transcription factor GATA4 prevented adherent bacterial colonization and inflammation in the proximal small intestine by regulating retinol metabolism and luminal IgA. Loss of epithelial GATA4 expression increased mortality in mice infected with Citrobacter rodentium. In active celiac patients with villous atrophy, low GATA4 expression was associated with metabolic alterations, mucosal Actinobacillus, and increased IL-17 immunity. This study reveals broad impacts of GATA4-regulated intestinal regionalization and highlights an elaborate interdependence of intestinal metabolism, immunity, and microbiota in homeostasis and disease.One-sentence summaryEpithelial GATA4 regulates intestinal regionalization of bacterial colonization, metabolic pathways, and tissue immunity.

Published
2021
Full Text
View/download PDF

50. Genome graphs detect human polymorphisms in active epigenomic state during influenza infection

Author

Aracena Ka, Albena Pramatarova, Marie-Michelle Simon, Luis B. Barreiro, Tomi Pastinen, Alain Pacis, Cristian Groza, Xun Chen, and Guillaume Bourque

Subjects
Whole genome sequencing, education.field_of_study, Population, Epigenome, Computational biology, Biology, Biochemistry, Genetics and Molecular Biology (miscellaneous), Genome, Genetics, Human genome, education, Gene, Epigenomics, Reference genome
Abstract

Background Epigenomic experiments can be used to survey the chromatin state of the human genome and find functionally relevant sequences in given cells. However, the reference genome that is typically used to interpret these data does not account for SNPs, indels, and other structural variants present in the individual being profiled. Fortunately, population studies and whole genome sequencing can assemble tens of thousands of sequences that are not in the reference, including mobile element insertions (MEIs), which are known to influence the epigenome. We hypothesized that the use of a genome graph, which can capture this genetic diversity, could help identify more peaks and reveal notable regulatory sequences hidden by the use of a biased reference. Results Given the contributions of MEIs to the evolution of human innate immunity, we wanted to test this hypothesis in macrophages derived from 35 individuals of African and European ancestry before and after in-vitro Influenza infection. We used local assembly to resolve non-reference MEIs based on linked reads obtained from these individuals and reconstructed over five thousand Alu, over three hundred L1, and tens of SVA and ERV insertions. Next, we built a genome graph representing SNPs, indels and MEIs in these genomes and demonstrated improved read mapping sensitivity and specificity. Aligning H3K27ac and H3K4me1 ChIP-seq and ATAC-seq data on this genome graph revealed between 2 to 6 thousand novel peaks per sample. Notably, we observed hundreds of polymorphic MEIs that were marked by active histone modifications or accessible chromatin, of which 12 were associated with differential gene expression. Lastly, we found a MEI polymorphism in an active epigenomic state that is associated with the expression of TRIM25, a gene that restricts influenza RNA synthesis. Conclusion Our results demonstrate that the use of graph genomes capturing genetic variability can reveal notable regulatory regions that would have been missed by standard analytical approaches.

Published
2021
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results