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  1. Article ; Online: Atroposelective Synthesis of Axially Chiral Naphthylpyrroles by a Catalytic Asymmetric 1,3-Dipolar Cycloaddition/Aromatization Sequence.

    Maclean, Ian / Gallent, Enrique / Orozco, Oscar / Molina, Alba / Rodríguez, Nuria / Adrio, Javier / Carretero, Juan C

    Organic letters

    2024  Volume 26, Issue 4, Page(s) 922–927

    Abstract: A straightforward methodology for the enantioselective preparation of axially chiral 2-naphthylpyrroles has been developed. This protocol is based on a ... ...

    Abstract A straightforward methodology for the enantioselective preparation of axially chiral 2-naphthylpyrroles has been developed. This protocol is based on a Cu
    Language English
    Publishing date 2024-01-24
    Publishing country United States
    Document type Journal Article
    ISSN 1523-7052
    ISSN (online) 1523-7052
    DOI 10.1021/acs.orglett.3c04261
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Plasmid-mediated phenotypic noise leads to transient antibiotic resistance in bacteria.

    Hernandez-Beltran, J Carlos R / Rodríguez-Beltrán, Jerónimo / Aguilar-Luviano, Oscar Bruno / Velez-Santiago, Jesús / Mondragón-Palomino, Octavio / MacLean, R Craig / Fuentes-Hernández, Ayari / San Millán, Alvaro / Peña-Miller, Rafael

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 2610

    Abstract: The rise of antibiotic resistance is a critical public health concern, requiring an understanding of mechanisms that enable bacteria to tolerate antimicrobial agents. Bacteria use diverse strategies, including the amplification of drug-resistance genes. ... ...

    Abstract The rise of antibiotic resistance is a critical public health concern, requiring an understanding of mechanisms that enable bacteria to tolerate antimicrobial agents. Bacteria use diverse strategies, including the amplification of drug-resistance genes. In this paper, we showed that multicopy plasmids, often carrying antibiotic resistance genes in clinical bacteria, can rapidly amplify genes, leading to plasmid-mediated phenotypic noise and transient antibiotic resistance. By combining stochastic simulations of a computational model with high-throughput single-cell measurements of bla
    MeSH term(s) Plasmids/genetics ; Anti-Bacterial Agents/pharmacology ; Drug Resistance, Microbial/genetics ; Escherichia coli/genetics ; Gene Dosage ; Drug Resistance, Bacterial/genetics
    Chemical Substances Anti-Bacterial Agents
    Language English
    Publishing date 2024-03-23
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-45045-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: No evidence for distinct types in the evolution of SARS-CoV-2.

    MacLean, Oscar A / Orton, Richard J / Singer, Joshua B / Robertson, David L

    Virus evolution

    2020  Volume 6, Issue 1, Page(s) veaa034

    Abstract: A recent study by Tang et al. claimed that two major types of severe acute respiratory syndrome-coronavirus-2 (CoV-2) had evolved in the ongoing CoV disease-2019 pandemic and that one of these types was more 'aggressive' than the other. Given the ... ...

    Abstract A recent study by Tang et al. claimed that two major types of severe acute respiratory syndrome-coronavirus-2 (CoV-2) had evolved in the ongoing CoV disease-2019 pandemic and that one of these types was more 'aggressive' than the other. Given the repercussions of these claims and the intense media coverage of these types of articles, we have examined in detail the data presented by Tang et al., and show that the major conclusions of that paper cannot be substantiated. Using examples from other viral outbreaks, we discuss the difficulty in demonstrating the existence or nature of a functional effect of a viral mutation, and we advise against overinterpretation of genomic data during the pandemic.
    Keywords covid19
    Language English
    Publishing date 2020-05-14
    Publishing country England
    Document type Journal Article
    ZDB-ID 2818949-8
    ISSN 2057-1577
    ISSN 2057-1577
    DOI 10.1093/ve/veaa034
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  4. Article ; Online: No evidence for distinct types in the evolution of SARS-CoV-2

    MacLean, Oscar A / Orton, Richard J / Singer, Joshua B / Robertson, David L

    Virus Evolution

    2020  Volume 6, Issue 1

    Abstract: Abstract A recent study by Tang et al. claimed that two major types of severe acute respiratory syndrome-coronavirus-2 (CoV-2) had evolved in the ongoing CoV disease-2019 pandemic and that one of these types was more ‘aggressive’ than the other. Given ... ...

    Abstract Abstract A recent study by Tang et al. claimed that two major types of severe acute respiratory syndrome-coronavirus-2 (CoV-2) had evolved in the ongoing CoV disease-2019 pandemic and that one of these types was more ‘aggressive’ than the other. Given the repercussions of these claims and the intense media coverage of these types of articles, we have examined in detail the data presented by Tang et al., and show that the major conclusions of that paper cannot be substantiated. Using examples from other viral outbreaks, we discuss the difficulty in demonstrating the existence or nature of a functional effect of a viral mutation, and we advise against overinterpretation of genomic data during the pandemic.
    Keywords covid19
    Language English
    Publisher Oxford University Press (OUP)
    Publishing country uk
    Document type Article ; Online
    ZDB-ID 2818949-8
    ISSN 2057-1577
    ISSN 2057-1577
    DOI 10.1093/ve/veaa034
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article: No evidence for distinct types in the evolution of SARS-CoV-2

    MacLean, Oscar A. / Orton, Richard J. / Singer, Joshua B. / Robertson, David L.

    Virus Evol.

    Abstract: A recent study by Tang et al. claimed that two major types of severe acute respiratory syndrome-coronavirus-2 (CoV-2) had evolved in the ongoing CoV disease-2019 pandemic and that one of these types was more 'aggressive' than the other. Given the ... ...

    Abstract A recent study by Tang et al. claimed that two major types of severe acute respiratory syndrome-coronavirus-2 (CoV-2) had evolved in the ongoing CoV disease-2019 pandemic and that one of these types was more 'aggressive' than the other. Given the repercussions of these claims and the intense media coverage of these types of articles, we have examined in detail the data presented by Tang et al., and show that the major conclusions of that paper cannot be substantiated. Using examples from other viral outbreaks, we discuss the difficulty in demonstrating the existence or nature of a functional effect of a viral mutation, and we advise against overinterpretation of genomic data during the pandemic.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #143933
    Database COVID19

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  6. Article ; Online: No evidence for distinct types in the evolution of SARS-CoV-2

    MacLean, Oscar A. / Orton, Richard J. / Singer, Joshua B. / Robertson, David L.

    2020  

    Abstract: A recent study by Tang et al. claimed that two major types of severe acute respiratory syndrome-coronavirus-2 (CoV-2) had evolved in the ongoing CoV disease-2019 pandemic and that one of these types was more ‘aggressive’ than the other. Given the ... ...

    Abstract A recent study by Tang et al. claimed that two major types of severe acute respiratory syndrome-coronavirus-2 (CoV-2) had evolved in the ongoing CoV disease-2019 pandemic and that one of these types was more ‘aggressive’ than the other. Given the repercussions of these claims and the intense media coverage of these types of articles, we have examined in detail the data presented by Tang et al., and show that the major conclusions of that paper cannot be substantiated. Using examples from other viral outbreaks, we discuss the difficulty in demonstrating the existence or nature of a functional effect of a viral mutation, and we advise against overinterpretation of genomic data during the pandemic.
    Keywords covid19
    Language English
    Publisher Oxford University Press
    Publishing country uk
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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  7. Article ; Online: The Timing and Magnitude of the Type I Interferon Response Are Correlated with Disease Tolerance in Arbovirus Infection.

    Hardy, Alexandra / Bakshi, Siddharth / Furnon, Wilhelm / MacLean, Oscar / Gu, Quan / Varjak, Margus / Varela, Mariana / Aziz, Muhamad Afiq / Shaw, Andrew E / Pinto, Rute Maria / Cameron Ruiz, Natalia / Mullan, Catrina / Taggart, Aislynn E / Da Silva Filipe, Ana / Randall, Richard E / Wilson, Sam J / Stewart, Meredith E / Palmarini, Massimo

    mBio

    2023  Volume 14, Issue 3, Page(s) e0010123

    Abstract: Infected hosts possess two alternative strategies to protect themselves against the negative impact of virus infections: resistance, used to abrogate virus replication, and disease tolerance, used to avoid tissue damage without controlling viral burden. ... ...

    Abstract Infected hosts possess two alternative strategies to protect themselves against the negative impact of virus infections: resistance, used to abrogate virus replication, and disease tolerance, used to avoid tissue damage without controlling viral burden. The principles governing pathogen resistance are well understood, while less is known about those involved in disease tolerance. Here, we studied bluetongue virus (BTV), the cause of bluetongue disease of ruminants, as a model system to investigate the mechanisms of virus-host interactions correlating with disease tolerance. BTV induces clinical disease mainly in sheep, while cattle are considered reservoirs of infection, rarely exhibiting clinical symptoms despite sustained viremia. Using primary cells from multiple donors, we show that BTV consistently reaches higher titers in ovine cells than cells from cattle. The variable replication kinetics of BTV in sheep and cow cells were mostly abolished by abrogating the cell type I interferon (IFN) response. We identified restriction factors blocking BTV replication, but both the sheep and cow orthologues of these antiviral genes possess anti-BTV properties. Importantly, we demonstrate that BTV induces a faster host cell protein synthesis shutoff in primary sheep cells than cow cells, which results in an earlier downregulation of antiviral proteins. Moreover, by using RNA sequencing (RNA-seq), we also show a more pronounced expression of interferon-stimulated genes (ISGs) in BTV-infected cow cells than sheep cells. Our data provide a new perspective on how the type I IFN response in reservoir species can have overall positive effects on both virus and host evolution.
    MeSH term(s) Female ; Sheep ; Animals ; Cattle ; Interferon Type I/genetics ; Bluetongue/metabolism ; Viremia ; Antiviral Agents
    Chemical Substances Interferon Type I ; Antiviral Agents
    Language English
    Publishing date 2023-04-25
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mbio.00101-23
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Conserved recombination patterns across coronavirus subgenera.

    de Klerk, Arné / Swanepoel, Phillip / Lourens, Rentia / Zondo, Mpumelelo / Abodunran, Isaac / Lytras, Spyros / MacLean, Oscar A / Robertson, David / Kosakovsky Pond, Sergei L / Zehr, Jordan D / Kumar, Venkatesh / Stanhope, Michael J / Harkins, Gordon / Murrell, Ben / Martin, Darren P

    Virus evolution

    2022  Volume 8, Issue 2, Page(s) veac054

    Abstract: Recombination contributes to the genetic diversity found in coronaviruses and is known to be a prominent mechanism whereby they evolve. It is apparent, both from controlled experiments and in genome sequences sampled from nature, that patterns of ... ...

    Abstract Recombination contributes to the genetic diversity found in coronaviruses and is known to be a prominent mechanism whereby they evolve. It is apparent, both from controlled experiments and in genome sequences sampled from nature, that patterns of recombination in coronaviruses are non-random and that this is likely attributable to a combination of sequence features that favour the occurrence of recombination break points at specific genomic sites, and selection disfavouring the survival of recombinants within which favourable intra-genome interactions have been disrupted. Here we leverage available whole-genome sequence data for six coronavirus subgenera to identify specific patterns of recombination that are conserved between multiple subgenera and then identify the likely factors that underlie these conserved patterns. Specifically, we confirm the non-randomness of recombination break points across all six tested coronavirus subgenera, locate conserved recombination hot- and cold-spots, and determine that the locations of transcriptional regulatory sequences are likely major determinants of conserved recombination break-point hotspot locations. We find that while the locations of recombination break points are not uniformly associated with degrees of nucleotide sequence conservation, they display significant tendencies in multiple coronavirus subgenera to occur in low guanine-cytosine content genome regions, in non-coding regions, at the edges of genes, and at sites within the Spike gene that are predicted to be minimally disruptive of Spike protein folding. While it is apparent that sequence features such as transcriptional regulatory sequences are likely major determinants of where the template-switching events that yield recombination break points most commonly occur, it is evident that selection against misfolded recombinant proteins also strongly impacts observable recombination break-point distributions in coronavirus genomes sampled from nature.
    Language English
    Publishing date 2022-06-14
    Publishing country England
    Document type Journal Article
    ZDB-ID 2818949-8
    ISSN 2057-1577
    ISSN 2057-1577
    DOI 10.1093/ve/veac054
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Natural selection in the evolution of SARS-CoV-2 in bats created a generalist virus and highly capable human pathogen.

    MacLean, Oscar A / Lytras, Spyros / Weaver, Steven / Singer, Joshua B / Boni, Maciej F / Lemey, Philippe / Kosakovsky Pond, Sergei L / Robertson, David L

    PLoS biology

    2021  Volume 19, Issue 3, Page(s) e3001115

    Abstract: Virus host shifts are generally associated with novel adaptations to exploit the cells of the new host species optimally. Surprisingly, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has apparently required little to no significant ... ...

    Abstract Virus host shifts are generally associated with novel adaptations to exploit the cells of the new host species optimally. Surprisingly, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has apparently required little to no significant adaptation to humans since the start of the Coronavirus Disease 2019 (COVID-19) pandemic and to October 2020. Here we assess the types of natural selection taking place in Sarbecoviruses in horseshoe bats versus the early SARS-CoV-2 evolution in humans. While there is moderate evidence of diversifying positive selection in SARS-CoV-2 in humans, it is limited to the early phase of the pandemic, and purifying selection is much weaker in SARS-CoV-2 than in related bat Sarbecoviruses. In contrast, our analysis detects evidence for significant positive episodic diversifying selection acting at the base of the bat virus lineage SARS-CoV-2 emerged from, accompanied by an adaptive depletion in CpG composition presumed to be linked to the action of antiviral mechanisms in these ancestral bat hosts. The closest bat virus to SARS-CoV-2, RmYN02 (sharing an ancestor about 1976), is a recombinant with a structure that includes differential CpG content in Spike; clear evidence of coinfection and evolution in bats without involvement of other species. While an undiscovered "facilitating" intermediate species cannot be discounted, collectively, our results support the progenitor of SARS-CoV-2 being capable of efficient human-human transmission as a consequence of its adaptive evolutionary history in bats, not humans, which created a relatively generalist virus.
    MeSH term(s) Animals ; COVID-19/epidemiology ; COVID-19/transmission ; COVID-19/virology ; Chiroptera/virology ; Evolution, Molecular ; Genome, Viral ; Host Specificity ; Humans ; Pandemics ; Phylogeny ; Receptors, Virus/genetics ; SARS-CoV-2/genetics ; SARS-CoV-2/pathogenicity ; Selection, Genetic ; Viral Zoonoses/genetics ; Viral Zoonoses/transmission ; Viral Zoonoses/virology
    Chemical Substances Receptors, Virus
    Language English
    Publishing date 2021-03-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2126776-5
    ISSN 1545-7885 ; 1544-9173
    ISSN (online) 1545-7885
    ISSN 1544-9173
    DOI 10.1371/journal.pbio.3001115
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Natural selection in the evolution of SARS-CoV-2 in bats, not humans, created a highly capable human pathogen.

    MacLean, Oscar A / Lytras, Spyros / Weaver, Steven / Singer, Joshua B / Boni, Maciej F / Lemey, Philippe / Kosakovsky Pond, Sergei L / Robertson, David L

    bioRxiv : the preprint server for biology

    2020  

    Abstract: RNA viruses are proficient at switching host species, and evolving adaptations to exploit the new host's cells efficiently. Surprisingly, SARS-CoV-2 has apparently required no significant adaptation to humans since the start of the COVID-19 pandemic, ... ...

    Abstract RNA viruses are proficient at switching host species, and evolving adaptations to exploit the new host's cells efficiently. Surprisingly, SARS-CoV-2 has apparently required no significant adaptation to humans since the start of the COVID-19 pandemic, with no observed selective sweeps since genome sampling began. Here we assess the types of natural selection taking place in
    Keywords covid19
    Language English
    Publishing date 2020-07-30
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2020.05.28.122366
    Database MEDical Literature Analysis and Retrieval System OnLINE

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