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  1. Article ; Online: The evolutionary tale of lactase persistence in humans.

    Barreiro, Luis B

    Nature reviews. Genetics

    2023  Volume 25, Issue 1, Page(s) 7

    MeSH term(s) Humans ; Lactase/genetics ; Selection, Genetic ; Biological Evolution ; Polymorphism, Single Nucleotide ; Gene Frequency
    Chemical Substances Lactase (EC 3.2.1.108)
    Language English
    Publishing date 2023-09-25
    Publishing country England
    Document type Journal Article
    ZDB-ID 2035157-4
    ISSN 1471-0064 ; 1471-0056
    ISSN (online) 1471-0064
    ISSN 1471-0056
    DOI 10.1038/s41576-023-00660-3
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    Zs.A 5474: Show issues Location:
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  2. Article ; Online: Transmission of stimulus-induced epigenetic changes through cell division is coupled to continuous transcription factor activity.

    Sun, Sarah / Aguirre-Gamboa, Raúl / Barreiro, Luis B

    Frontiers in immunology

    2023  Volume 14, Page(s) 1129577

    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 ... ...

    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.
    MeSH term(s) Histones/metabolism ; Epigenesis, Genetic ; Cell Division ; Gene Expression Regulation ; Transcription Factors/genetics ; Transcription Factors/metabolism
    Chemical Substances Histones ; Transcription Factors
    Language English
    Publishing date 2023-03-14
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1129577
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  3. Article ; Online: My Old World chap, this α-gal is not for you.

    Barreiro, Luis B / Chervonsky, Alexander

    Cell host & microbe

    2021  Volume 29, Issue 3, Page(s) 315–317

    Abstract: 30 million years ago, ancestors of Old World primates lost the ability to produce α-gal. In this issue of Cell Host & Microbe, Singh et al. (2021) show that the loss is associated with increased resistance to sepsis, but that this advantage comes ... ...

    Abstract 30 million years ago, ancestors of Old World primates lost the ability to produce α-gal. In this issue of Cell Host & Microbe, Singh et al. (2021) show that the loss is associated with increased resistance to sepsis, but that this advantage comes alongside a cost of accelerated reproductive senescence.
    MeSH term(s) Animals ; Antibodies ; Primates/immunology ; Sepsis
    Chemical Substances Antibodies
    Language English
    Publishing date 2021-03-08
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 2278004-X
    ISSN 1934-6069 ; 1931-3128
    ISSN (online) 1934-6069
    ISSN 1931-3128
    DOI 10.1016/j.chom.2021.02.013
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  4. Article ; Online: Shaping immunity: The influence of natural selection on population immune diversity.

    Randolph, Haley E / Aracena, Katherine A / Lin, Yen-Lung / Mu, Zepeng / Barreiro, Luis B

    Immunological reviews

    2024  

    Abstract: Humans exhibit considerable variability in their immune responses to the same immune challenges. Such variation is widespread and affects individual and population-level susceptibility to infectious diseases and immune disorders. Although the factors ... ...

    Abstract Humans exhibit considerable variability in their immune responses to the same immune challenges. Such variation is widespread and affects individual and population-level susceptibility to infectious diseases and immune disorders. Although the factors influencing immune response diversity are partially understood, what mechanisms lead to the wide range of immune traits in healthy individuals remain largely unexplained. Here, we discuss the role that natural selection has played in driving phenotypic differences in immune responses across populations and present-day susceptibility to immune-related disorders. Further, we touch on future directions in the field of immunogenomics, highlighting the value of expanding this work to human populations globally, the utility of modeling the immune response as a dynamic process, and the importance of considering the potential polygenic nature of natural selection. Identifying loci acted upon by evolution may further pinpoint variants critically involved in disease etiology, and designing studies to capture these effects will enrich our understanding of the genetic contributions to immunity and immune dysregulation.
    Language English
    Publishing date 2024-04-05
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 391796-4
    ISSN 1600-065X ; 0105-2896
    ISSN (online) 1600-065X
    ISSN 0105-2896
    DOI 10.1111/imr.13329
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  5. Article ; Online: DNA methylation-environment interactions in the human genome.

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

    eLife

    2024  Volume 12

    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) ...

    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.
    MeSH term(s) Humans ; DNA Methylation ; Gene-Environment Interaction ; Genome, Human ; Biological Assay ; Environmental Exposure ; Interferon-alpha
    Chemical Substances Interferon-alpha
    Language English
    Publishing date 2024-02-26
    Publishing country England
    Document type Journal Article
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.89371
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  6. Article ; Online: The epigenetically-encoded memory of the innate immune system.

    Sun, Sarah / Barreiro, Luis B

    Current opinion in immunology

    2020  Volume 65, Page(s) 7–13

    Abstract: Stimulation or infection of innate immune cells induces profound epigenetic changes, including the induction of histone modifications and alterations in DNA methylation levels. While some of these changes are rapidly reversible, others appear to be long- ... ...

    Abstract Stimulation or infection of innate immune cells induces profound epigenetic changes, including the induction of histone modifications and alterations in DNA methylation levels. While some of these changes are rapidly reversible, others appear to be long-lasting, even in mitotic populations, with important functional consequences for the stimulus-experienced cell. Here we discuss the individual contributions of each of the plethora of known epigenetic modifications to the initial transcriptional response to immune activation, their dynamics as cells return to homeostasis, and their contribution to memory of the initial stimulus.
    MeSH term(s) Animals ; Epigenesis, Genetic/genetics ; Epigenesis, Genetic/immunology ; Humans ; Immune System/immunology ; Immunologic Memory/genetics ; Immunologic Memory/immunology
    Language English
    Publishing date 2020-03-25
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 1035767-1
    ISSN 1879-0372 ; 0952-7915
    ISSN (online) 1879-0372
    ISSN 0952-7915
    DOI 10.1016/j.coi.2020.02.002
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2773: Show issues Location:
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    Zs.MG 13: Show issues

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  7. Article ; Online: Herd Immunity: Understanding COVID-19.

    Randolph, Haley E / Barreiro, Luis B

    Immunity

    2020  Volume 52, Issue 5, Page(s) 737–741

    Abstract: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated disease, COVID-19, has demonstrated the devastating impact of a novel, infectious pathogen on a susceptible population. Here, we explain the basic concepts ... ...

    Abstract The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated disease, COVID-19, has demonstrated the devastating impact of a novel, infectious pathogen on a susceptible population. Here, we explain the basic concepts of herd immunity and discuss its implications in the context of COVID-19.
    MeSH term(s) Basic Reproduction Number ; Betacoronavirus/immunology ; COVID-19 ; Coronavirus Infections/epidemiology ; Coronavirus Infections/immunology ; Coronavirus Infections/transmission ; Global Health ; Humans ; Immunity, Herd ; Models, Immunological ; Pandemics ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/immunology ; Pneumonia, Viral/transmission ; SARS-CoV-2 ; Vaccination ; Vaccination Coverage
    Keywords covid19
    Language English
    Publishing date 2020-05-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2020.04.012
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    Zs.A 4227: Show issues Location:
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  8. Article: DNA methylation-environment interactions in the human genome.

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

    bioRxiv : the preprint server for biology

    2023  

    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 ( ... ...

    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
    Language English
    Publishing date 2023-12-15
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.05.19.541437
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  9. Article ; Online: Holy Immune Tolerance, Batman!

    Randolph, Haley E / Barreiro, Luis B

    Immunity

    2018  Volume 48, Issue 6, Page(s) 1074–1076

    Abstract: Bats are reservoir hosts of numerous viruses that cause severe pathology in humans. How bats cope with such pathogens remains elusive. In a recent issue of Cell, Pavlovich et al. (2018) describe several key adaptations in innate immune-related genes that ...

    Abstract Bats are reservoir hosts of numerous viruses that cause severe pathology in humans. How bats cope with such pathogens remains elusive. In a recent issue of Cell, Pavlovich et al. (2018) describe several key adaptations in innate immune-related genes that suggest that the Egyptian rousette fruit bat relies on immune tolerance mechanisms to manage viral infections.
    MeSH term(s) Animals ; Antiviral Agents ; Chiroptera ; Egypt ; Humans ; Immune Tolerance ; Immunity
    Chemical Substances Antiviral Agents
    Keywords covid19
    Language English
    Publishing date 2018-06-18
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2018.05.016
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  10. Article ; Online: Evolutionary and population (epi)genetics of immunity to infection.

    Barreiro, Luis B / Quintana-Murci, Lluis

    Human genetics

    2020  Volume 139, Issue 6-7, Page(s) 723–732

    Abstract: Immune response is one of the functions that have been more strongly targeted by natural selection during human evolution. The evolutionary genetic dissection of the immune system has greatly helped to distinguish genes and functions that are essential, ... ...

    Abstract Immune response is one of the functions that have been more strongly targeted by natural selection during human evolution. The evolutionary genetic dissection of the immune system has greatly helped to distinguish genes and functions that are essential, redundant or advantageous for human survival. It is also becoming increasingly clear that admixture between early Eurasians with now-extinct hominins such as Neanderthals or Denisovans, or admixture between modern human populations, can be beneficial for human adaptation to pathogen pressures. In this review, we discuss how the integration of population genetics with functional genomics in diverse human populations can inform about the changes in immune functions related to major lifestyle transitions (e.g., from hunting and gathering to farming), the action of natural selection to the evolution of the immune system, and the history of past epidemics. We also highlight the need of expanding the characterization of the immune system to a larger array of human populations-particularly neglected human groups historically exposed to different pathogen pressures-to fully capture the relative contribution of genetic, epigenetic, and environmental factors to immune response variation in humans.
    MeSH term(s) Animals ; Biological Evolution ; Epigenesis, Genetic ; Genetic Variation ; Genetics, Population ; Genome, Human ; Humans ; Infections/epidemiology ; Infections/genetics ; Infections/immunology ; Selection, Genetic
    Language English
    Publishing date 2020-04-13
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 223009-4
    ISSN 1432-1203 ; 0340-6717
    ISSN (online) 1432-1203
    ISSN 0340-6717
    DOI 10.1007/s00439-020-02167-x
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    Zs.A 256: Show issues Location:
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