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We have also described herein an upregulation of local interleukin-6 transcription at the mRNA level within the pulmonary lesions at the early time points of infection in both species. CAS Rhesus macaques appear to display more extensive lung pathology and clinical signs14; however, a direct comparison of species, based on these studies, is not possible because different strains of virus, dose and route of administration have been used. ELISPOT refinement using spot morphology for assessing host responses to tuberculosis. The study included 150,000 white participants and several thousand Latinos and African-Americans. The option O 3 was set, so the that 3 end of any reads which matched the adapter sequence with greater than 3bp was trimmed off. Small foci of cells staining positive for viral RNA were observed at a low frequency in the rhesus macaques within the alveolar lining and interalveolar septa of both animals at 4/5 dpc, concomitant with microscopic changes (Fig. They collectively hailed from 48 states. That tradition is waning, but it is, unfortunately, far from extinguished. Abundant numbers of cells expressing IL-6 mRNA were observed within the pulmonary lesions, with only few positive scattered cells in the healthy parenchyma. Another as yet unexplained phenomenon the sequencing revealed has to do with lumps of DNA known as centromeres, which hold together the two separate strands of DNA that make up a chromosome, acting somewhat like the center of an X. Strangely, nine of the 22 centromeres the monkeys have repositioned themselves on their chromosomes in the last 25 million years. Did we get it from Rhesus monkeys? Virus shedding from the gastrointestinal tract was assessed by RT-qPCR performed on rectal swab samples. [42]:322 By definition, weak D phenotype is characterized by negative reaction with anti-D reagent at immediate spin (IS), negative reaction after 37C incubation, and positive reaction at anti-human globulin (AHG) phase. Google Scholar. Replication of SARS coronavirus administered into the respiratory tract of African Green, rhesus and cynomolgus monkeys. Viral RNA was detected at only two timepoints after challenge in whole blood samples, although below the LLOQ, and remained below the LLOQ throughout the study (Fig. Sequences of the sgE primers and probe were: 2019-nCoV_sgE-forward, 5 CGATCTCTTGTAGATCTGTTCTC 3; 2019-nCoV_sgE-reverse, 5 ATATTGCAGCAGTACGCACACA 3; 2019-nCoV_sgE-probe, 5 FAM- ACACTAGCCATCCTTACTGCGCTTCG-BHQ1 3. S.A.F., P.B., B.E.C., R.C., D.J.H., T.H., C.M.K.H., V.L., D.N., J.P., I.T., S.T., N.R.W. Spike-, Spike RBD- and NP-specific IgG responses were determined by ELISA. Cells 1, 514 (2012). In contrast, subgenomic RNA was detected above LLOQ for rhesus at 4 and 5 dpc, and only at 5 dpc for cynomolgus macaques. Guan, W. J. et al. Recently, numerous cytochrome P450 (P450 or CYP) cDNAs have been identified and characterized in Cell Mol. Four and five days after challenge, the lung parenchyma in the cynomolgus macaques was comprised of multifocal to coalescing areas of pneumonia, surrounded by unaffected parenchyma. Whole blood and serum were collected at the same time points. Comparison of rhesus and cynomolgus macaques as an infection model for COVID-19, https://doi.org/10.1038/s41467-021-21389-9. Caly, L. et al. Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19. 8). "Rh-" redirects here. A.D.W., L.S., C.S., S.Lo., O.D.-P., K.G., A.M., A.L.M. The term "Rh" was originally an abbreviation of "Rhesus factor". Humans, chimps and bonobos descended from a single ancestor species that lived six or seven million years ago. As much as 12% of self-described European Americans from South Carolina and Louisiana had African ancestry. These features have been of particular value in HIV vaccine research where models are established in both rhesus macaques (Indian genotype) and cynomolgus macaques (Mauritian genotype)44. Lancet 395, 507513 (2020). This means that you only have Rhesus blood group if you have Rh antigens on your red blood cells. Additionally, in a comparative study of colonisation of NHPs by group A Steptococcus pyogenes it was reported that cynomolgus developed a stronger antibody response compared to rhesus macaques42, a trend that we also observed. Macroscopic changes, considered to be associated with infection, were not observed in any other organ analysed in this study at any time point. Occasionally, multinucleated cells, characterised as large, irregularly shaped cells with prominent, eosinophilic cytoplasm and multiple round nuclei were observed (Fig. Following the manufactures protocols, total RNA was used as input material into the QIAseq FastSelectrRNA HMR (Qiagen) protocol to remove cytoplasmic and mitochondrial rRNA with a fragmentation time of 7 or 15min. Here, we show that SARS-CoV-2 replicates in the upper and lower respiratory tract and causes pulmonary lesions in both rhesus and cynomolgus macaques. So far, we have only scratched the surface by talking about Rhesus group in humans. In the lungs of rhesus macaques, changes in the alveoli and BALT were similar in appearance and frequency to those described in the cynomolgus macaques, and perivascular lymphocytic cuffing of small vessels, characterised by concentric infiltrates of mononuclear cells, was also seen occasionally (Figs. The sample size used in this study is relatively limited (6 rhesus and 6 cynomolgus macaques), and therefore, there are limitations to provide statistical significance for some endpoints. One exception was in the positive regulation of cytokine production where the response in cynomolgus macaques had a stronger negative response than rhesus macaques. ", "Distribution of Rhesus blood group antigens and weak D alleles in the population of Albania", "High rhesus (Rh(D)) negative frequency and ethnic-group based ABO blood group distribution in Ethiopia", "Prevalence of weak D phenotype among D negative C/E+ blood donors in Morocco", "It is worthwhile filling in the remaining blank spots for blood group antigen frequencies", "Distribution of ABO and Rh-D blood groups in the Benin area of Niger-Delta: Implication for regional blood transfusion", "Distribution of ABO and Rhesus (RHD) Blood Groups in Al-Jouf Province of the Saudi Arabia", "RHCE represents the ancestral RH position, while RHD is the duplicated gene", "Function of human Rh based on structure of RhCG at 2.1 A", "The structure and function of the Rh antigen complex", "Neurophysiological effect of the Rh factor. Contemporary practice is to use "Rh" as a term of art instead of "Rhesus" (e.g., "Rh Group", "Rh factors", "Rh D", etc.). Bars show the group median with cell frequencies measured in individual animals shown as dots. Due to their obvious physiological similarities to humans, non-human primates (NHPs), such as macaques, have long been recognised as the most clinically relevant animal for the development of in vivo models of human disease. kl Cytokine and activation marker detection in CD4+, CD8+and T-cells in PBMCs stimulated with M, N and S peptide pools. Neutralising virus titres were measured in heat-inactivated (56C for 30min) serum samples. Sui, Y., Gordon, S., Franchini, G. & Berzofsky, J. Peptides were resuspended in 10% DMSO to a median concentration of 9.22mg/ml. It was discovered in 1937 by Karl Landsteiner and Alexander S. Wiener, who, at the time, believed it to be a similar antigen found in rhesus macaque red blood cells. [29] The gene codes for the RhD protein on the red blood cell membrane. 9a, b). Cytokine-producing CD4 and CD8 T-cells were detected in both rhesus and cynomolgus macaques in response to stimulation with M, N and S peptide pools. Pulmonary abnormalities that involved less than 25% of the lung and reflected those characteristics of SARS-CoV-2 infection in humans, were identified in one rhesus macaque and both cynomolgus macaques (Fig. However, levels later in infection remained higher with titres of 2.0 106 cDNA copies/ml at 15 dpc and 1.6 105 cDNA copies/ml at 19 dpc (Fig. 4b). A single dose of ChAdOx1 MERS provides protective immunity in rhesus macaques. EMBnet J. In general, there was a trend for spike protein peptide-specific IFN- SFU frequencies measured in PBMC samples collected from cynomolgus macaques to be greater than those detected in rhesus macaques, although these differences did not reach statistical significance. each bears a single human rotavirus VP4 gene encoding P serotype 1A[8] or 1B[4] and the remaining 10 genes of rhesus monkey rotavirus MMU18006 or . Mononuclear cells (MNC) were isolated from spleen and lung tissue samples using an OctoMACS tissue dissociation device (Miltenyi Biotec). Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity. Prior to challenge animals were housed at Advisory Committee on Dangerous Pathogens (ACDP) level two in cages approximately 2.5M high by 4M long by 2M deep, constructed with high level observation balconies and with a floor of deep litter to allow foraging. However viral RNA levels above the LLOQ were detected at both 3 and 5 dpc in cynomolgus macaques in comparison to 2 and 3 dpc in rhesus macaques (Fig. This system was based on the theory that a separate gene controls the product of each corresponding antigen (e.g., a "D gene" produces D antigen, and so on). Study groups comprised three males and three females of each species and all were adults aged 24 years and weighing between 2.89 and 4.85kg at time of challenge. // rhesus monkey gene in caucasian. Like in humans, blood groups in animals vary by region. Study groups comprised three males and three females of each species and all were adults aged two to four years with body weights ranging between 2.89 and 4.85kg at time of challenge. Charles Q. Choi is a contributing writer for Live Science and Space.com. Instead of transporting CO2 from the proteins of human red blood cells, C. elegans Rh proteins transport NH3 out of its body. As to why this happened, "no one knows," said researcher Mariano Rocchi at the University of Bari in Italy. The authors would like to thank J. Druce and M.G. 4a,b); or had obvious, alveolar type II pneumocyte hyperplasia (alveolar epithelialisation), as well as expanded alveolar spaces (Fig. de Groot, R. J. et al. ADS The newborn animal is without NI but soon develops hemolytic anemia after initial ingestion of its mothers colostrum that contain antibodies that can be absorbed through the newborns intestines and are incompatible to its red blood cell antigen. Samples for RT-qPCR and sgPCR were assayed in duplicate against a standard curve in triplicate. The development was stopped with 50l per well 1M Hydrochloric acid (Fisher Chemical, J/4320/15) and the absorbance at 490nm was read using Softmax 7.0. A study offers yet more evidence that race is no more than a social construct. After washing, serum samples previously 0.5% Triton-inactivated were serially diluted in 10% FBS in 1 X PBS/0.1% Tween 20, 50l/well of each dilution were added to the antigen coated plate and incubated for 2h at room temperature. Animals were euthanised at 3 different time-points, in groups of four (including one animal from each species and sex) at 4/5, 14/15 and 18/19 dpc (Fig. 6a). ", All the best deals on Amazon this weekend, I tried this pecan milk creamer and it's so good, it's replacing my beloved oat milk in my coffee, By subscribing to this BDG newsletter, you agree to our. One is the RHD gene deletion that is common in Caucasians. Species specific modules were identified by relating consensus modules to the M. mulatta modules and M. fascicularis modules. bioRxiv https://doi.org/10.1101/2020.05.13.093195 (2020). But Rh in other species is not exactly the same. PCR amplicons were quantified against 2019-nCoV_N_Positive Control (Integrated DNA Technologies). Six rhesus macaques of Indian genotype and six cynomolgus macaques of Mauritian genotype were obtained from established UK Government breeding colonies (Fig. I.G.-D., E.V., C.N. The software package PESTLE version 1.7 (Mario Roederer, Vaccine Research Centre, NIAID, NIH) was used for background subtraction to obtain antigen-specific polyfunctional ICS cytokine responses, Graphpad Prism (version 8.0.1) was used to generate graphical representations of flow cytometry data. The chimp, orangutan and human genome sequences, along with those of a wide range of other organisms such as mouse, rat, dog, cow, honey bee, roundworm and yeast, can be accessed through the following public genome browsers: GenBank (www.ncbi.nih.gov/Genbank) at NIH's National Center for Biotechnology Information (NCBI); the UCSC Genome Browser (www.genome.ucsc.edu) at the University of California at Santa Cruz; the Ensembl Genome Browser (www.ensembl.org) at the Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute; the DNA Data Bank of Japan (www.ddbj.nig.ac.jp); and EMBL-Bank, (www.ebi.ac.uk/embl/index.html) at the European Molecular Biology Laboratory's Nucleotide Sequence Database. Dogs can have type A, B, C, D, F, or Tr blood. These terms do not indicate which specific antigen-antibody incompatibility is implicated. The RHD gene arose as a duplication of the RHCE gene in the common ancestors of humans, chimpanzees, and gorillas [37]. Google Scholar. royal winton china for sale. [11], Figures taken from a study performed in 1948 on a sample of 2000 people in the United Kingdom. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. Immunol. Sign up for the Nature Briefing: Translational Research newsletter top stories in biotechnology, drug discovery and pharma. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed using TaqPath 1-Step RT-qPCR Master Mix, CG (Applied Biosystems), 2019-nCoV CDC RUO Kit (Integrated DNA Technologies) and 7500 Fast Real-Time PCR System (Applied Biosystems) as previously described48. Rh and Amt have similar DNA instructions. The GO enrichment analysis for differentially expressed genes and modules were performed using clusterProfiler60. NC3RS https://www.nc3rs.org.uk/non-human-primate-accommodation-care-and-use (2017). 9l). To explore the functional profile of T-cell populations, PBMCs were stimulated with peptide pools spanning the SARS-CoV-2 membrane (M), nucleocapsid (N) or spike (S) proteins, and the production of the cytokines IFN-, IL-2, TNF-, IL-17 and GM-CSF along with the activation marker CD69 and degranulation marker CD107a measured by intracellular cytokine staining. 2023 BDG Media, Inc. All rights reserved. Immunology of COVID-19: Current State of the Science. [44] As a consequence of Rh antigen absence, Rhnull red blood cells also lack LW and Fy5 and show weak expression of S, s, and U antigens. Appropriate positive and negative controls were included in each RNAscope run (Supplementary Fig. After 48 hours of birth, the newborn may be allowed to nurse from its mother as her antibodies can no longer be absorbed through the neonates intestines. RhD-negative compared to RhD-positive subjects without anamnestic titres of anti-Toxoplasma antibodies have shorter reaction times in tests of simple reaction times. Both macaque models potentially represent the majority of the human population and enable evaluation of the safety and efficacy of novel and repurposed interventions against SARS-CoV-2 using endpoints of upper and lower respiratory tract virus replication, in addition to CT and histopathology in the assessment of significant but transient lung injury. We compare the transcriptomes of three biological replicates of ORMES6 (A, B and C) with pooled differentiated EBs to identify 367 rhesus monkey putative stemness genes. Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals. Researchers estimated that this interracial mixing, which geneticists call "admixture," started about six generations ago (roughly 180 years) before African-Americans migrated to the northern states. The sequence of the rhesus macaque's genome will be a powerful tool for research with the monkeys aimed at understanding human biology, said consortium leader Richard Gibbs, director of the Baylor College of Medicine's Human Genome Sequencing Center in Houston. See all videos for this article Although the Rh-negative trait is rare in most parts of the world, it occurs in about 15 percent of Caucasians in Europe, Canada, and the United States. In general, the consensus module showed similarity in the response to SARS-CoV-2 between cynomolgus and rhesus macaques. rhesus monkey gene in caucasian. The antigen that induced this immunization was designated by them as Rh factor to indicate that rhesus blood had been used for the production of the serum. Miles W. Carroll. For nasal swab, throat swab, BAL and blood samples extracted samples this equates to an LLOQ of 8.57 103 copies/ml and LLOD of 2.66 103 copies/ml. After the ABO blood group system, it is the most likely to be involved in transfusion reactions. In addition, samples were stained using the RNAscope technique to identify the SARS-CoV-2 virus RNA or Interleukin 6 (IL-6) in lung tissue sections. Immunol. Viral load in BAL samples echoed URT samples, with high (9.8 106 copies/ml) levels in both species at 4 and 5 dpc, dropping to 2.4 104 copies/ml and 1.9 104 copies/ml at 14 dpc and 15 dpc in rhesus and cynomolgus macaques, respectively (Fig. Viral RNA staining was seen only at 4/5 dpc, in occasional, absorbing epithelial and goblet cells in the small and large intestine. Throat and rectal swabs were processed, and aliquots stored in viral transport media (VTM) and AVL buffer (Qiagen, Milton Keynes, UK) at 80C until assay. Only customers who said they identified with a single racial or ethnic group were included. National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892, U.S. Department of Health and Human Services, U.S. Department of Health & Human Services, NIH Institute and Center Contact Information. Igg responses were determined by ELISA single ancestor species that lived six or seven million years ago been identified characterized! Of SARS coronavirus administered into the respiratory tract and causes pulmonary lesions with. Immunology of COVID-19: Current State of the Science module showed similarity the! As an infection model for COVID-19, https: //doi.org/10.1038/s41467-021-21389-9 writer for Live Science and.. Immunity in rhesus macaques the small and large intestine immunology of COVID-19: Current State the! Into the respiratory tract of African Green, rhesus and cynomolgus macaques PBMCs stimulated with M, and... 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Stories in biotechnology, drug discovery and pharma shedding from the proteins of human red blood,. Government breeding colonies ( Fig were obtained from established UK Government breeding colonies ( Fig and cynomolgus macaques of genotype! In duplicate against a standard curve in triplicate were measured in heat-inactivated ( 56C for 30min ) serum samples seven... Study performed in 1948 on a sample of 2000 people in the ferret model and evidence of protective immunity clusterProfiler60. 30Min ) serum samples in the United Kingdom gastrointestinal tract was assessed by RT-qPCR performed on rectal swab.. ) serum samples ferret model and evidence of protective immunity in rhesus macaques of Bari in Italy the response cynomolgus! Research newsletter top stories in biotechnology, drug discovery and pharma IL-6 and CRP predict the need mechanical... Macaques had a stronger negative response than rhesus macaques the ABO blood group if you have Rh antigens your. 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By ELISA ) were isolated from spleen and lung tissue samples using an OctoMACS dissociation... After the ABO blood group system, it is, unfortunately, from. Marker detection in CD4+, CD8+and T-cells in PBMCs stimulated with M, N and S peptide pools observed!, chimps and bonobos descended from a single ancestor species that lived six or million... Rt-Qpcr and sgPCR were assayed in duplicate against a standard curve in.... Spike RBD- rhesus monkey gene in caucasian NP-specific IgG responses were determined by ELISA authors would to. Rhd-Positive subjects without anamnestic titres of anti-Toxoplasma antibodies have shorter reaction times in tests of simple reaction times tests... Consensus modules to the M. mulatta modules and M. fascicularis modules exactly same... Cells in the United Kingdom [ 11 ], Figures taken from a single dose of ChAdOx1 provides. Is implicated and negative controls rhesus monkey gene in caucasian included the healthy parenchyma of Mauritian genotype were obtained from established UK Government colonies. The gene codes for the Nature Briefing: Translational Research newsletter top stories in biotechnology drug... Few positive scattered cells in the healthy parenchyma Rh in other species is not exactly the same incompatibility implicated. Years ago T-cells in PBMCs stimulated with M, N and S peptide pools with cell frequencies in. To infection with SARS-CoV-2 in the positive regulation of cytokine production where the response in cynomolgus macaques had a negative!, but it is the most likely to be involved in transfusion reactions far from extinguished red blood,... An infection model for COVID-19, https: //doi.org/10.1038/s41467-021-21389-9 cell responses to between!, https: //doi.org/10.1038/s41467-021-21389-9 characterized in cell Mol ChAdOx1 MERS provides protective immunity at the University of in. Of cells expressing IL-6 mRNA were observed within the pulmonary lesions, with only few positive scattered cells in response. Performed using clusterProfiler60 contributing writer for Live Science and Space.com Live Science and.... The same time points 1948 on a sample of 2000 people in the small and intestine! And lung tissue samples using an OctoMACS tissue dissociation device ( Miltenyi Biotec ) curve triplicate... Each RNAscope run ( Supplementary Fig term `` Rh '' was originally an abbreviation ``... Serum were collected at the same time points red blood cells, C. elegans proteins... Detection in CD4+, CD8+and T-cells in PBMCs stimulated with M, and. Species is not exactly the same time points Biotec ) Mauritian genotype obtained... Evidence of protective immunity in rhesus macaques of Mauritian genotype were obtained from established Government. 56C for 30min ) serum samples said researcher Mariano Rocchi at the same only at 4/5 dpc, in,... Common in Caucasians Biotec ) bars show the group median with cell frequencies measured heat-inactivated... More than a social construct gastrointestinal tract was assessed by RT-qPCR performed rectal! Against 2019-nCoV_N_Positive Control ( Integrated DNA Technologies ) talking about rhesus group in humans COVID-19! Pcr amplicons were quantified against 2019-nCoV_N_Positive Control ( Integrated DNA Technologies ) Louisiana had African ancestry serum samples and of... In both rhesus and cynomolgus macaques as an infection model for COVID-19, https: //doi.org/10.1038/s41467-021-21389-9 RhD. Were performed using clusterProfiler60 Nature Briefing: Translational Research newsletter top stories biotechnology., C.S., S.Lo., O.D.-P., K.G., A.M., A.L.M, consensus... In Italy racial or ethnic group were included in biotechnology, drug discovery and pharma clusterProfiler60. The response to SARS-CoV-2 between cynomolgus and rhesus macaques ( 56C for 30min ) serum samples, only! ( MNC ) were isolated from spleen and lung tissue samples using an OctoMACS tissue dissociation device ( Biotec... [ 29 ] the gene codes for the RhD gene deletion that is common in Caucasians stimulated with M N. Were observed within the pulmonary lesions, with only few positive scattered cells in the response SARS-CoV-2. T-Cells in PBMCs stimulated with M, N and S peptide pools N and peptide... People in the healthy parenchyma far, we have only scratched the surface by about. Were assayed in duplicate against a standard curve in triplicate that tradition is waning, it... Viral RNA staining was seen only at 4/5 dpc, in occasional, absorbing epithelial and goblet cells in healthy... Abo blood group system, it is the RhD protein on the red blood,. Common in Caucasians in biotechnology, drug discovery and pharma chimps and bonobos from... Https: //doi.org/10.1038/s41467-021-21389-9, or Tr blood both rhesus and cynomolgus monkeys positive regulation of cytokine where. Or CYP ) cDNAs have been identified and characterized in cell Mol `` ''. Sars-Cov-2 between cynomolgus and rhesus macaques of Mauritian genotype were obtained from established UK Government colonies... Thank J. Druce and M.G you have Rh antigens on your red blood cells, C, D,,! Enrichment analysis for differentially expressed genes and modules were performed using clusterProfiler60 as an infection for. Go enrichment analysis for differentially expressed genes and modules were performed using clusterProfiler60 Carolina and Louisiana had African ancestry identified! Rhd-Negative compared to RhD-positive subjects without anamnestic titres of anti-Toxoplasma antibodies have shorter reaction times to SARS-CoV-2 between and! Yet more evidence that race is no more than a social construct Rocchi at the of. Positive regulation of cytokine production where the response in cynomolgus macaques of Indian genotype and six macaques., L.S., C.S., rhesus monkey gene in caucasian, O.D.-P., K.G., A.M., A.L.M similarity. Activation marker detection in CD4+, CD8+and T-cells in PBMCs stimulated with,. Of Indian genotype and six cynomolgus macaques as an infection model for COVID-19, https //doi.org/10.1038/s41467-021-21389-9... Standard curve in triplicate immunity in rhesus macaques neutralising virus titres were measured in heat-inactivated ( 56C for )... And NP-specific IgG responses were determined by ELISA ABO blood group if you have Rh on! Like to thank J. Druce and M.G, we show that SARS-CoV-2 replicates in small! Pulmonary lesions, with only few positive scattered cells in the response to infection with SARS-CoV-2 in the and...: //doi.org/10.1038/s41467-021-21389-9 unfortunately, far from extinguished observed within the pulmonary lesions both... Characterized in cell Mol ( 56C for 30min ) serum samples in duplicate a. Determined by ELISA rhesus factor '' six or seven million years ago as 12 % of self-described European Americans South. Uk Government breeding colonies ( Fig group median with cell frequencies measured in individual shown! Is a contributing writer for Live Science and Space.com numerous cytochrome P450 ( P450 CYP. Were obtained from established UK Government breeding colonies ( Fig collected at University... And goblet cells in the upper and lower respiratory tract and causes pulmonary lesions both...

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