CFD Analysis of Bed Textural Characteristics on TBR Behavior: Kinetics, Scaling-up, Multiscale Analysis and Wall Effects

A simulation of a trickle bed reactor aided by computational fluid dynamics was implemented. With a Eulerian approach, geometrical characteristics were explicitly considered and two simultaneous heterogeneous reactions were included, hydrodesulphurization (HDS) and hydrodenitrogenation (HDN). This was performed in order to achieve the following: (1) attain further insight into a proper scaling‐up procedure to be able to obtain the same hydrodynamics and kinetics behavior in two reactors of different length and diameter scales; (2) develop a multiscale analysis regarding the communication of information between scales through the construction of a porous microstructure model from which the geometrical information of the microscale is captured by the effective transport coefficients (which affect the overall reactor behavior); (3) investigate the effect of operation conditions variations on hydrodynamics and kinetics; (4) and assess the deviations and further differences observed from average to punctual conversion values and the assumptions from kinetic literature models through a preliminary multiscale analysis. The CFD results were validated against experimental pressure drops data as well as HDS and HDN conversions theoretical data. An excellent agreement was found. The model produces a significant improvement in hydrodynamic parameters prediction, achieving 5 times better accuracy in predicting pressure drops and 50% improvement in holdup prediction. The fully coupled model predicts HDS conversion with 96% accuracy and HDN conversion with 94% accuracy. Results suggest that the best way to obtain similar kinetic and hydrodynamic behavior in TBRs with different length and diameter length scales is by equaling the liquid holdup (εγ) or the mass velocities (L‐G)

Synthesis and structure determination via ultra-fast electron diffraction of the new microporous zeolitic germanosilicate ITQ-62

[EN] Here, we present the synthesis and structure determination of the new zeolite ITQ-62. Its structure was determined via ultra-fast electron diffraction tomography and refined using powder XRD data of the calcined material. This new zeolite contains a tridirectional channel system of highly distorted 8-rings, as well as a monodirectional 12-ring channel system.The authors gratefully acknowledge financial support from the Spanish Government (MAT2015-71842-P and MAT2015-71261-R MINECO/FEDER and Severo Ochoa SEV-2016-0683). The authors thank ALBA Light Source for beam allocation at the beamline MSPD, and specially thank the Electron Microscopy Service of the Universitat Politecnica de Valencia. Finally, the authors thank Dr Alejandro Vidal and Dr Teresa Blasco for helping in the NMR data discussion.Bieseki, L.; Simancas Coloma, R.; Jorda Moret, JL.; Bereciartua-Pérez, PJ.; Cantin Sanz, A.; Simancas-Coloma, J.; Pergher, SB.... (2018). Synthesis and structure determination via ultra-fast electron diffraction of the new microporous zeolitic germanosilicate ITQ-62. Chemical Communications. 54(17):2122-2125. https://doi.org/10.1039/c7cc09240gS212221255417Barrer, R. M., & Denny, P. J. (1961). 201. Hydrothermal chemistry of the silicates. Part IX. Nitrogenous aluminosilicates. Journal of the Chemical Society (Resumed), 971. doi:10.1039/jr9610000971Kerr, G. T. (1966). Chemistry of Crystalline Aluminosilicates. II. The Synthesis and Properties of Zeolite ZK-4. Inorganic Chemistry, 5(9), 1537-1539. doi:10.1021/ic50043a015Burton, A. W., & Zones, S. I. (2007). Organic Molecules in Zeolite Synthesis: Their Preparation and Structure-Directing Effects. Introduction to Zeolite Science and Practice, 137-179. doi:10.1016/s0167-2991(07)80793-2Zones, S. I., Nakagawa, Y., Lee, G. S., Chen, C. Y., & Yuen, L. T. (1998). Searching for new high silica zeolites through a synergy of organic templates and novel inorganic conditions. Microporous and Mesoporous Materials, 21(4-6), 199-211. doi:10.1016/s1387-1811(98)00011-0Burton, A. W., Zones, S. I., & Elomari, S. (2005). The chemistry of phase selectivity in the synthesis of high-silica zeolites. Current Opinion in Colloid & Interface Science, 10(5-6), 211-219. doi:10.1016/j.cocis.2005.08.005Moliner, M., Rey, F., & Corma, A. (2013). Towards the Rational Design of Efficient Organic Structure-Directing Agents for Zeolite Synthesis. Angewandte Chemie International Edition, 52(52), 13880-13889. doi:10.1002/anie.201304713Park, G. T., Jo, D., Ahn, N. H., Cho, J., & Hong, S. B. (2017). Synthesis and Structural Characterization of a CHA-type AlPO4 Molecular Sieve with Penta-Coordinated Framework Aluminum Atoms. Inorganic Chemistry, 56(14), 8504-8512. doi:10.1021/acs.inorgchem.7b01194Dorset, D. L., Strohmaier, K. G., Kliewer, C. E., Corma, A., Díaz-Cabañas, M. J., Rey, F., & Gilmore, C. J. (2008). Crystal Structure of ITQ-26, a 3D Framework with Extra-Large Pores. Chemistry of Materials, 20(16), 5325-5331. doi:10.1021/cm801126tDorset, D. L., Kennedy, G. J., Strohmaier, K. G., Diaz-Cabañas, M. J., Rey, F., & Corma, A. (2006). P-Derived Organic Cations as Structure-Directing Agents:  Synthesis of a High-Silica Zeolite (ITQ-27) with a Two-Dimensional 12-Ring Channel System. Journal of the American Chemical Society, 128(27), 8862-8867. doi:10.1021/ja061206oJo, D., Ryu, T., Park, G. T., Kim, P. S., Kim, C. H., Nam, I.-S., & Hong, S. B. (2016). Synthesis of High-Silica LTA and UFI Zeolites and NH3–SCR Performance of Their Copper-Exchanged Form. ACS Catalysis, 6(4), 2443-2447. doi:10.1021/acscatal.6b00489Miller, M. A., Moscoso, J. G., Koster, S. C., Gatter, M. G., & Lewis, G. J. (2007). Synthesis and characterization of the 12-ring zeolites UZM-4 (BPH) and UZM-22 (MEI) via the charge density mismatch approach in the Choline-Li2O-SrO-Al2O3-SiO2 system. Studies in Surface Science and Catalysis, 347-354. doi:10.1016/s0167-2991(07)80859-7Simancas, R., Jordá, J. L., Rey, F., Corma, A., Cantín, A., Peral, I., & Popescu, C. (2014). A New Microporous Zeolitic Silicoborate (ITQ-52) with Interconnected Small and Medium Pores. Journal of the American Chemical Society, 136(9), 3342-3345. doi:10.1021/ja411915cSimancas, R., Dari, D., Velamazan, N., Navarro, M. T., Cantin, A., Jorda, J. L., … Rey, F. (2010). Modular Organic Structure-Directing Agents for the Synthesis of Zeolites. Science, 330(6008), 1219-1222. doi:10.1126/science.1196240Martinez-Franco, R., Moliner, M., Yun, Y., Sun, J., Wan, W., Zou, X., & Corma, A. (2013). Synthesis of an extra-large molecular sieve using proton sponges as organic structure-directing agents. Proceedings of the National Academy of Sciences, 110(10), 3749-3754. doi:10.1073/pnas.1220733110Choi, M., Na, K., Kim, J., Sakamoto, Y., Terasaki, O., & Ryoo, R. (2009). Stable single-unit-cell nanosheets of zeolite MFI as active and long-lived catalysts. Nature, 461(7261), 246-249. doi:10.1038/nature08288Zones, S. I., & Davis, M. E. (1996). Zeolite materials: recent discoveries and future prospects. Current Opinion in Solid State and Materials Science, 1(1), 107-117. doi:10.1016/s1359-0286(96)80018-0Bellussi, G., Carati, A., & Millini, R. (2010). Industrial Potential of Zeolites. Zeolites and Catalysis, 449-491. doi:10.1002/9783527630295.ch16Zones, S. I. (2011). Translating new materials discoveries in zeolite research to commercial manufacture. Microporous and Mesoporous Materials, 144(1-3), 1-8. doi:10.1016/j.micromeso.2011.03.039Olsbye, U., Svelle, S., Bjørgen, M., Beato, P., Janssens, T. V. W., Joensen, F., … Lillerud, K. P. (2012). Conversion of Methanol to Hydrocarbons: How Zeolite Cavity and Pore Size Controls Product Selectivity. Angewandte Chemie International Edition, 51(24), 5810-5831. doi:10.1002/anie.201103657Korhonen, S. T., Fickel, D. W., Lobo, R. F., Weckhuysen, B. M., & Beale, A. M. (2011). Isolated Cu2+ions: active sites for selective catalytic reduction of NO. Chem. Commun., 47(2), 800-802. doi:10.1039/c0cc04218hMoliner, M., Franch, C., Palomares, E., Grill, M., & Corma, A. (2012). Cu–SSZ-39, an active and hydrothermally stable catalyst for the selective catalytic reduction of NOx. Chemical Communications, 48(66), 8264. doi:10.1039/c2cc33992gBereciartua, P. J., Cantín, Á., Corma, A., Jordá, J. L., Palomino, M., Rey, F., … Casty, G. L. (2017). Control of zeolite framework flexibility and pore topology for separation of ethane and ethylene. Science, 358(6366), 1068-1071. doi:10.1126/science.aao0092Dodin, M., Paillaud, J.-L., Lorgouilloux, Y., Caullet, P., Elkaïm, E., & Bats, N. (2010). A Zeolitic Material with a Three-Dimensional Pore System Formed by Straight 12- and 10-Ring Channels Synthesized with an Imidazolium Derivative as Structure-Directing Agent. Journal of the American Chemical Society, 132(30), 10221-10223. doi:10.1021/ja103648kPaillaud, J.-L. (2004). Extra-Large-Pore Zeolites with Two-Dimensional Channels Formed by 14 and 12 Rings. Science, 304(5673), 990-992. doi:10.1126/science.1098242Lorgouilloux, Y., Dodin, M., Paillaud, J.-L., Caullet, P., Michelin, L., Josien, L., … Bats, N. (2009). IM-16: A new microporous germanosilicate with a novel framework topology containing d4r and mtw composite building units. Journal of Solid State Chemistry, 182(3), 622-629. doi:10.1016/j.jssc.2008.12.002Earl, D. J., Burton, A. W., Rea, T., Ong, K., Deem, M. W., Hwang, S.-J., & Zones, S. I. (2008). Synthesis and Monte Carlo Structure Determination of SSZ-77: A New Zeolite Topology. The Journal of Physical Chemistry C, 112(24), 9099-9105. doi:10.1021/jp7116856Tang, L., Shi, L., Bonneau, C., Sun, J., Yue, H., Ojuva, A., … Zou, X. (2008). A zeolite family with chiral and achiral structures built from the same building layer. Nature Materials, 7(5), 381-385. doi:10.1038/nmat2169Corma, A., Navarro, M. T., Rey, F., Rius, J., & Valencia, S. (2001). Pure Polymorph C of Zeolite Beta Synthesized by Using Framework Isomorphous Substitution as a Structure-Directing Mechanism. Angewandte Chemie International Edition, 40(12), 2277-2280. doi:10.1002/1521-3773(20010618)40:123.0.co;2-oYun, Y., Hernández, M., Wan, W., Zou, X., Jordá, J. L., Cantín, A., … Corma, A. (2015). The first zeolite with a tri-directional extra-large 14-ring pore system derived using a phosphonium-based organic molecule. Chemical Communications, 51(36), 7602-7605. doi:10.1039/c4cc10317cJiang, J., Yun, Y., Zou, X., Jorda, J. L., & Corma, A. (2015). ITQ-54: a multi-dimensional extra-large pore zeolite with 20 × 14 × 12-ring channels. Chemical Science, 6(1), 480-485. doi:10.1039/c4sc02577fHernández-Rodríguez, M., Jordá, J. L., Rey, F., & Corma, A. (2012). Synthesis and Structure Determination of a New Microporous Zeolite with Large Cavities Connected by Small Pores. Journal of the American Chemical Society, 134(32), 13232-13235. doi:10.1021/ja306013kJiang, J., Jorda, J. L., Diaz-Cabanas, M. J., Yu, J., & Corma, A. (2010). The Synthesis of an Extra-Large-Pore Zeolite with Double Three-Ring Building Units and a Low Framework Density. Angewandte Chemie International Edition, 49(29), 4986-4988. doi:10.1002/anie.201001506Blasco, T., Corma, A., Díaz-Cabañas, M. J., Rey, F., Vidal-Moya, J. A., & Zicovich-Wilson, C. M. (2002). Preferential Location of Ge in the Double Four-Membered Ring Units of ITQ-7 Zeolite. The Journal of Physical Chemistry B, 106(10), 2634-2642. doi:10.1021/jp013302bMoliner, M., Willhammar, T., Wan, W., González, J., Rey, F., Jorda, J. L., … Corma, A. (2012). Synthesis Design and Structure of a Multipore Zeolite with Interconnected 12- and 10-MR Channels. Journal of the American Chemical Society, 134(14), 6473-6478. doi:10.1021/ja301082nCorma, A., Diaz-Cabanas, M. J., Jorda, J. L., Rey, F., Sastre, G., & Strohmaier, K. G. (2008). A Zeolitic Structure (ITQ-34) with Connected 9- and 10-Ring Channels Obtained with Phosphonium Cations as Structure Directing Agents. Journal of the American Chemical Society, 130(49), 16482-16483. doi:10.1021/ja806903cCorma, A., Díaz-Cabañas, M. J., Jordá, J. L., Martínez, C., & Moliner, M. (2006). High-throughput synthesis and catalytic properties of a molecular sieve with 18- and 10-member rings. Nature, 443(7113), 842-845. doi:10.1038/nature05238Sun, J., Bonneau, C., Cantín, Á., Corma, A., Díaz-Cabañas, M. J., Moliner, M., … Zou, X. (2009). The ITQ-37 mesoporous chiral zeolite. Nature, 458(7242), 1154-1157. doi:10.1038/nature07957Corma, A., Rey, F., Valencia, S., Jordá, J. L., & Rius, J. (2003). A zeolite with interconnected 8-, 10- and 12-ring pores and its unique catalytic selectivity. Nature Materials, 2(7), 493-497. doi:10.1038/nmat921Werner, P. E., Eriksson, L., & Westdahl, M. (1985). TREOR, a semi-exhaustive trial-and-error powder indexing program for all symmetries. Journal of Applied Crystallography, 18(5), 367-370. doi:10.1107/s0021889885010512Simancas, J., Simancas, R., Bereciartua, P. J., Jorda, J. L., Rey, F., Corma, A., … Mugnaioli, E. (2016). Ultrafast Electron Diffraction Tomography for Structure Determination of the New Zeolite ITQ-58. Journal of the American Chemical Society, 138(32), 10116-10119. doi:10.1021/jacs.6b06394Kolb, U., Mugnaioli, E., & Gorelik, T. E. (2011). Automated electron diffraction tomography - a new tool for nano crystal structure analysis. Crystal Research and Technology, 46(6), 542-554. doi:10.1002/crat.201100036Grosse-Kunstleve, R. W., McCusker, L. B., & Baerlocher, C. (1999). Zeolite structure determination from powder diffraction data: applications of theFOCUSmethod. Journal of Applied Crystallography, 32(3), 536-542. doi:10.1107/s0021889899003453R. Bialek , KRIBER. Crystallographic computation program , ETH Zurich Institut fur Kristallographie , Zurich, Switzerland , 1991Ch. Baerlocher , A.Hepp and W. M.Meier , DLS-76. Distance least squares refinement program , ETH Zurich Institut fur Kristallographie , Zurich, Switzerland , 1977Fauth, F., Peral, I., Popescu, C., & Knapp, M. (2013). The new Material Science Powder Diffraction beamline at ALBA Synchrotron. Powder Diffraction, 28(S2), S360-S370. doi:10.1017/s0885715613000900Peral, I., McKinlay, J., Knapp, M., & Ferrer, S. (2011). Design and construction of multicrystal analyser detectors using Rowland circles: application to MAD26 at ALBA. Journal of Synchrotron Radiation, 18(6), 842-850. doi:10.1107/s090904951103152

COVID-19 Flow-Maps an open geographic information system on COVID-19 and human mobility for Spain

COVID-19 is an infectious disease caused by the SARS-CoV-2 virus, which has spread all over the world leading to a global pandemic. The fast progression of COVID-19 has been mainly related to the high contagion rate of the virus and the worldwide mobility of humans. In the absence of pharmacological therapies, governments from different countries have introduced several non-pharmaceutical interventions to reduce human mobility and social contact. Several studies based on Anonymized Mobile Phone Data have been published analysing the relationship between human mobility and the spread of coronavirus. However, to our knowledge, none of these data-sets integrates cross-referenced geo-localised data on human mobility and COVID-19 cases into one all-inclusive open resource. Herein we present COVID-19 Flow-Maps, a cross-referenced Geographic Information System that integrates regularly updated time-series accounting for population mobility and daily reports of COVID-19 cases in Spain at different scales of time spatial resolution. This integrated and up-to-date data-set can be used to analyse the human dynamics to guide and support the design of more effective non-pharmaceutical interventions.This work was supported by the Generalitat de Catalunya through the project PDAD14/20/00001, and by the H2020 programme under Grant Agreement 825070 (INFORE) and the INB Grant (PT17/0009/0001 - ISCIII-SGEFI/ERDF).Peer ReviewedPostprint (published version

DNA Methylation Profiles and Their Relationship with Cytogenetic Status in Adult Acute Myeloid Leukemia

Background: Aberrant promoter DNA methylation has been shown to play a role in acute myeloid leukemia (AML) pathophysiology. However, further studies to discuss the prognostic value and the relationship of the epigenetic signatures with defined genomic rearrangements in acute myeloid leukemia are required. Methodology/Principal Findings: We carried out high-throughput methylation profiling on 116 de novo AML cases and we validated the significant biomarkers in an independent cohort of 244 AML cases. Methylation signatures were associated with the presence of a specific cytogenetic status. In normal karyotype cases, aberrant methylation of the promoter of DBC1 was validated as a predictor of the disease-free and overall survival. Furthermore, DBC1 expression was significantly silenced in the aberrantly methylated samples. Patients with chromosome rearrangements showed distinct methylation signatures. To establish the role of fusion proteins in the epigenetic profiles, 20 additional samples of human hematopoietic stem/ progenitor cells (HSPC) transduced with common fusion genes were studied and compared with patient samples carrying the same rearrangements. The presence of MLL rearrangements in HSPC induced the methylation profile observed in the MLL-positive primary samples. In contrast, fusion genes such as AML1/ETO or CBFB/MYH11 failed to reproduce the epigenetic signature observed in the patients. Conclusions/Significance: Our study provides a comprehensive epigenetic profiling of AML, identifies new clinical markers for cases with a normal karyotype, and reveals relevant biological information related to the role of fusion proteins on the methylation signatur

DNA Methylation Profiles and Their Relationship with Cytogenetic Status in Adult Acute Myeloid Leukemia

Aberrant promoter DNA methylation has been shown to play a role in acute myeloid leukemia (AML) pathophysiology. However, further studies to discuss the prognostic value and the relationship of the epigenetic signatures with defined genomic rearrangements in acute myeloid leukemia are required.We carried out high-throughput methylation profiling on 116 de novo AML cases and we validated the significant biomarkers in an independent cohort of 244 AML cases. Methylation signatures were associated with the presence of a specific cytogenetic status. In normal karyotype cases, aberrant methylation of the promoter of DBC1 was validated as a predictor of the disease-free and overall survival. Furthermore, DBC1 expression was significantly silenced in the aberrantly methylated samples. Patients with chromosome rearrangements showed distinct methylation signatures. To establish the role of fusion proteins in the epigenetic profiles, 20 additional samples of human hematopoietic stem/progenitor cells (HSPC) transduced with common fusion genes were studied and compared with patient samples carrying the same rearrangements. The presence of MLL rearrangements in HSPC induced the methylation profile observed in the MLL-positive primary samples. In contrast, fusion genes such as AML1/ETO or CBFB/MYH11 failed to reproduce the epigenetic signature observed in the patients.Our study provides a comprehensive epigenetic profiling of AML, identifies new clinical markers for cases with a normal karyotype, and reveals relevant biological information related to the role of fusion proteins on the methylation signature

Distinct DNA methylomes of newborns and centenarians

Human aging cannot be fully understood in terms of the constrained genetic setting. Epigenetic drift is an alternative means of explaining age-associated alterations. To address this issue, we performed whole-genome bisulfite sequencing (WGBS) of newborn and centenarian genomes. The centenarian DNA had a lower DNA methylation content and a reduced correlation in the methylation status of neighboring cytosine--phosphate--guanine (CpGs) throughout the genome in comparison with the more homogeneously methylated newborn DNA. The more hypomethylated CpGs observed in the centenarian DNA compared with the neonate covered all genomic compartments, such as promoters, exonic, intronic, and intergenic regions. For regulatory regions, the most hypomethylated sequences in the centenarian DNA were present mainly at CpG-poor promoters and in tissue-specific genes, whereas a greater level of DNA methylation was observed in CpG island promoters. We extended the study to a larger cohort of newborn and nonagenarian samples using a 450,000 CpG-site DNA methylation microarray that reinforced the observation of more hypomethylated DNA sequences in the advanced age group. WGBS and 450,000 analyses of middle-age individuals demonstrated DNA methylomes in the crossroad between the newborn and the nonagenarian/centenarian groups. Our study constitutes a unique DNA methylation analysis of the extreme points of human life at a single-nucleotide resolution level

Class III peroxidases PRX01, PRX44, and PRX73 potentially target extensins during root hair growth in Arabidopsis thaliana

Root hair cells are important sensors of soil conditions. Expanding several hundred times their original size, root hairs grow towards and absorb water-soluble nutrients. This rapid growth is oscillatory and is mediated by continuous remodelling of the cell wall. Root hair cell walls contain polysaccharides and hydroxyproline-rich glycoproteins including extensins (EXTs). Class-III peroxidases (PRXs) are secreted into the apoplastic space and are thought to trigger either cell wall loosening, mediated by oxygen radical species, or polymerization of cell wall components, including the Tyr-mediated assembly of EXT networks (EXT-PRXs). The precise role of these EXT-PRXs is unknown. Using genetic, biochemical, and modeling approaches, we identified and characterized three root hair-specific putative EXT-PRXs, PRX01, PRX44, and PRX73. The triple mutant prx01,44,73 and the PRX44 and PRX73 overexpressors had opposite phenotypes with respect to root hair growth, peroxidase activity and ROS production with a clear impact on cell wall thickness. Modeling and docking calculations suggested that these three putative EXT-PRXs may interact with non-O-glycosylated sections of EXT peptides that reduce the Tyr-to-Tyr intra-chain distances in EXT aggregates and thereby may enhance Tyr crosslinking. These results suggest that these three putative EXT-PRXs control cell wall properties during the polar expansion of root hair cells.Fil: Marzol, Eliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Borassi, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Ranocha, Philippe. Instituto National de Recherches Agronomiques. Centre de Recherches de Toulouse; FranciaFil: Aptekmann, Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Bringas, Mauro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Pennington, Janice. University of Wisconsin; Estados UnidosFil: Paez Valencia, Julio. University of Wisconsin; Estados UnidosFil: Martinez Pacheco, Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Rodriguez Garcia, Diana Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Rondon Guerrero, Yossmayer del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Carignani Sardoy, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Mangano, Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Fleming, Margaret. State University of Colorado - Fort Collins; Estados UnidosFil: Mishler Elmore, John W.. Ohio University; Estados UnidosFil: Blanco Herrera, Francisca. Universidad Andrés Bello and Millennium Institute for Integrative Biology (iBio). Facultad de Ciencias de la Vida. Centro de Biotecnología Vegeta; ChileFil: Bedinger, Patricia. State University of Colorado - Fort Collins; Estados UnidosFil: Dunand, Christophe. Instituto National de Recherches Agronomiques. Centre de Recherches de Toulouse; FranciaFil: Capece, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Nadra, Alejandro Daniel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Held, Michael. Ohio University; Estados UnidosFil: Otegui, Marisa S.. University of Wisconsin; Estados UnidosFil: Estevez, Jose Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad Andrés Bello; Chil

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality