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  1. Article: Progressive heterogeneity of enlarged and irregularly shaped apicoplasts in

    Micchelli, Chiara E / Percopo, Caroline / Traver, Maria / Brzostowski, Joseph / Amin, Shuchi N / Prigge, Sean T / Sá, Juliana M / Wellems, Thomas E

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Morphological modifications and shifts in organelle relationships are hallmarks of dormancy in eukaryotic cells. Communications between altered mitochondria and nuclei are associated with metabolic quiescence of cancer cells that can survive chemotherapy. ...

    Abstract Morphological modifications and shifts in organelle relationships are hallmarks of dormancy in eukaryotic cells. Communications between altered mitochondria and nuclei are associated with metabolic quiescence of cancer cells that can survive chemotherapy. In plants, changes in the pathways between nuclei, mitochondria, and chloroplasts are associated with cold stress and bud dormancy.
    Language English
    Publishing date 2024-01-04
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.01.03.574077
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Sensitive Immunoassay Detection of

    Mu, Jianbing / Yu, Lee L / Wellems, Thomas E

    Frontiers in cellular and infection microbiology

    2021  Volume 10, Page(s) 620419

    Abstract: Rapid, reliable, and sensitive detection ... ...

    Abstract Rapid, reliable, and sensitive detection of
    MeSH term(s) Antigens, Protozoan ; Gold ; Humans ; Immunoassay ; L-Lactate Dehydrogenase ; Malaria, Falciparum/diagnosis ; Mass Spectrometry ; Metal Nanoparticles ; Plasmodium ; Plasmodium falciparum ; Sensitivity and Specificity
    Chemical Substances Antigens, Protozoan ; Gold (7440-57-5) ; L-Lactate Dehydrogenase (EC 1.1.1.27)
    Language English
    Publishing date 2021-01-11
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 2619676-1
    ISSN 2235-2988 ; 2235-2988
    ISSN (online) 2235-2988
    ISSN 2235-2988
    DOI 10.3389/fcimb.2020.620419
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  3. Article: Single-cell analyses of polyclonal

    Hazzard, Brittany / Sá, Juliana M / Bogale, Haikel N / Pascini, Tales V / Ellis, Angela C / Amin, Shuchi / Armistead, Jennifer S / Adams, John H / Wellems, Thomas E / Serre, David

    Research square

    2024  

    Abstract: ... ...

    Abstract Most
    Language English
    Publishing date 2024-02-13
    Publishing country United States
    Document type Preprint
    DOI 10.21203/rs.3.rs-3888175/v1
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  4. Article ; Online: Structure of complex III with bound antimalarial agent CK-2-68 provides insights into selective inhibition of Plasmodium cytochrome bc

    Esser, Lothar / Zhou, Fei / Zeher, Allison / Wu, Weimin / Huang, Rick / Yu, Chang-An / Lane, Kristin D / Wellems, Thomas E / Xia, Di

    The Journal of biological chemistry

    2023  Volume 299, Issue 7, Page(s) 104860

    Abstract: Among the various components of the protozoan Plasmodium mitochondrial respiratory chain, only Complex III is a validated cellular target for antimalarial drugs. The compound CK-2-68 was developed to specifically target the alternate NADH dehydrogenase ... ...

    Abstract Among the various components of the protozoan Plasmodium mitochondrial respiratory chain, only Complex III is a validated cellular target for antimalarial drugs. The compound CK-2-68 was developed to specifically target the alternate NADH dehydrogenase of the malaria parasite respiratory chain, but the true target for its antimalarial activity has been controversial. Here, we report the cryo-EM structure of mammalian mitochondrial Complex III bound with CK-2-68 and examine the structure-function relationships of the inhibitor's selective action on Plasmodium. We show that CK-2-68 binds specifically to the quinol oxidation site of Complex III, arresting the motion of the iron-sulfur protein subunit, which suggests an inhibition mechanism similar to that of P
    MeSH term(s) Animals ; Antimalarials/chemistry ; Electron Transport Complex III/metabolism ; Plasmodium falciparum/metabolism ; Plasmodium/metabolism ; Cytochromes/metabolism ; Mammals/metabolism
    Chemical Substances Antimalarials ; 7-chloro-3-methyl-2-(4-(4-(trifluoromethoxy)benzyl)phenyl)quinolin-4(1H)-one ; Electron Transport Complex III (EC 7.1.1.8) ; Cytochromes
    Language English
    Publishing date 2023-05-24
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1016/j.jbc.2023.104860
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    Uc I Zs.108: Show issues Location:
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  5. Article ; Online: Optimism, persistence, and our collective crystal ball.

    Wellems, Thomas E

    The American journal of tropical medicine and hygiene

    2010  Volume 83, Issue 1, Page(s) 1–6

    MeSH term(s) Humans ; Medication Adherence/psychology ; Motivation/physiology ; Psychology, Clinical/trends ; Visual Perception/physiology
    Language English
    Publishing date 2010-07-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2942-7
    ISSN 1476-1645 ; 0002-9637
    ISSN (online) 1476-1645
    ISSN 0002-9637
    DOI 10.4269/ajtmh.2010.10-0107
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    Ud II Zs.61: Show issues Location:
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  6. Article ; Online: Long read single cell RNA sequencing reveals the isoform diversity of Plasmodium vivax transcripts.

    Hazzard, Brittany / Sá, Juliana M / Ellis, Angela C / Pascini, Tales V / Amin, Shuchi / Wellems, Thomas E / Serre, David

    PLoS neglected tropical diseases

    2022  Volume 16, Issue 12, Page(s) e0010991

    Abstract: Plasmodium vivax infections often consist of heterogenous populations of parasites at different developmental stages and with distinct transcriptional profiles, which complicates gene expression analyses. The advent of single cell RNA sequencing (scRNA- ... ...

    Abstract Plasmodium vivax infections often consist of heterogenous populations of parasites at different developmental stages and with distinct transcriptional profiles, which complicates gene expression analyses. The advent of single cell RNA sequencing (scRNA-seq) enabled disentangling this complexity and has provided robust and stage-specific characterization of Plasmodium gene expression. However, scRNA-seq information is typically derived from the end of each mRNA molecule (usually the 3'-end) and therefore fails to capture the diversity in transcript isoforms documented in bulk RNA-seq data. Here, we describe the sequencing of scRNA-seq libraries using Pacific Biosciences (PacBio) chemistry to characterize full-length Plasmodium vivax transcripts from single cell parasites. Our results show that many P. vivax genes are transcribed into multiple isoforms, primarily through variations in untranslated region (UTR) length or splicing, and that the expression of many isoforms is developmentally regulated. Our findings demonstrate that long read sequencing can be used to characterize mRNA molecules at the single cell level and provides an additional resource to better understand the regulation of gene expression throughout the Plasmodium life cycle.
    MeSH term(s) Humans ; Plasmodium vivax/genetics ; Protein Isoforms/genetics ; Gene Expression Profiling ; RNA-Seq ; Malaria, Vivax ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Transcriptome ; Sequence Analysis, RNA/methods ; High-Throughput Nucleotide Sequencing
    Chemical Substances Protein Isoforms ; RNA, Messenger
    Language English
    Publishing date 2022-12-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
    ZDB-ID 2429704-5
    ISSN 1935-2735 ; 1935-2735
    ISSN (online) 1935-2735
    ISSN 1935-2735
    DOI 10.1371/journal.pntd.0010991
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  7. Article ; Online: A Plasmodium falciparum RING Finger E3 Ubiquitin Ligase Modifies the Roles of PfMDR1 and PfCRT in Parasite Drug Responses.

    Singh, Brajesh K / Zhang, Cui / Wu, Jian / Peng, Yu-Chih / He, Xiao / Tumas, Keyla C / Sá, Juliana M / Lane, Kristin D / Eastman, Richard T / Narum, David L / Wellems, Thomas E / Su, Xin-Zhuan

    Antimicrobial agents and chemotherapy

    2023  Volume 67, Issue 2, Page(s) e0082122

    Abstract: Protein ubiquitination is an important posttranslational regulation mechanism that ... ...

    Abstract Protein ubiquitination is an important posttranslational regulation mechanism that mediates
    MeSH term(s) Humans ; Antimalarials/pharmacology ; Chloroquine/pharmacology ; Drug Resistance/genetics ; Malaria, Falciparum/drug therapy ; Membrane Transport Proteins/genetics ; Multidrug Resistance-Associated Proteins/genetics ; Plasmodium falciparum/drug effects ; Plasmodium falciparum/genetics ; Protozoan Proteins/genetics ; Protozoan Proteins/metabolism ; Ubiquitin-Protein Ligases/genetics ; Ubiquitin-Protein Ligases/metabolism
    Chemical Substances Antimalarials ; Chloroquine (886U3H6UFF) ; Membrane Transport Proteins ; Multidrug Resistance-Associated Proteins ; Protozoan Proteins ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
    Language English
    Publishing date 2023-01-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 217602-6
    ISSN 1098-6596 ; 0066-4804
    ISSN (online) 1098-6596
    ISSN 0066-4804
    DOI 10.1128/aac.00821-22
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    Zs.A 809: Show issues Location:
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    Einzelsignatur: Show issues

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  8. Article ; Online: 'Artemisinin Resistance': Something New or Old? Something of a Misnomer?

    Wellems, Thomas E / Sá, Juliana M / Su, Xin-Zhuan / Connelly, Sean V / Ellis, Angela C

    Trends in parasitology

    2020  Volume 36, Issue 9, Page(s) 735–744

    Abstract: Artemisinin and its derivatives (ART) are crucial first-line antimalarial drugs that rapidly clear parasitemia, but recrudescences of the infection frequently follow ART monotherapy. For this reason, ART must be used in combination with one or more ... ...

    Abstract Artemisinin and its derivatives (ART) are crucial first-line antimalarial drugs that rapidly clear parasitemia, but recrudescences of the infection frequently follow ART monotherapy. For this reason, ART must be used in combination with one or more partner drugs that ensure complete cure. The ability of malaria parasites to survive ART monotherapy may relate to an innate growth bistability phenomenon whereby a fraction of the drug-exposed population enters into metabolic quiescence (dormancy) as persister forms. Characterization of the events that underlie entry and waking from persistence may lead to lasting breakthroughs in malaria chemotherapy that can prevent recrudescences and protect the future of ART-based combination therapies.
    MeSH term(s) Antimalarials/pharmacology ; Artemisinins/pharmacology ; Drug Resistance ; Humans ; Plasmodium/drug effects ; Recurrence
    Chemical Substances Antimalarials ; Artemisinins ; artemisinin (9RMU91N5K2)
    Language English
    Publishing date 2020-06-22
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Intramural ; Review
    ZDB-ID 2036227-4
    ISSN 1471-5007 ; 1471-4922
    ISSN (online) 1471-5007
    ISSN 1471-4922
    DOI 10.1016/j.pt.2020.05.013
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    Zs.B 2898: Show issues Location:
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  9. Article ; Online: Single-cell transcription analysis of Plasmodium vivax blood-stage parasites identifies stage- and species-specific profiles of expression.

    Sà, Juliana M / Cannon, Matthew V / Caleon, Ramoncito L / Wellems, Thomas E / Serre, David

    PLoS biology

    2020  Volume 18, Issue 5, Page(s) e3000711

    Abstract: Plasmodium vivax and P. falciparum, the parasites responsible for most human malaria worldwide, exhibit striking biological differences, which have important clinical consequences. Unfortunately, P. vivax, unlike P. falciparum, cannot be cultivated ... ...

    Abstract Plasmodium vivax and P. falciparum, the parasites responsible for most human malaria worldwide, exhibit striking biological differences, which have important clinical consequences. Unfortunately, P. vivax, unlike P. falciparum, cannot be cultivated continuously in vitro, which limits our understanding of its biology and, consequently, our ability to effectively control vivax malaria. Here, we describe single-cell gene expression profiles of 9,215 P. vivax parasites from bloodstream infections of Aotus and Saimiri monkeys. Our results show that transcription of most P. vivax genes occurs during short periods of the intraerythrocytic cycle and that this pattern of gene expression is conserved in other Plasmodium species. However, we also identify a strikingly high proportion of species-specific transcripts in late schizonts, possibly associated with the specificity of erythrocyte invasion. Our findings provide new and robust markers of blood-stage parasites, including some that are specific to the elusive P. vivax male gametocytes, and will be useful for analyzing gene expression data from laboratory and field samples.
    MeSH term(s) Animals ; Aotidae ; Chloroquine ; Female ; Gene Expression ; Male ; Multigene Family ; Plasmodium vivax/growth & development ; Plasmodium vivax/metabolism ; Saimiri ; Schizonts/metabolism ; Sequence Analysis, RNA ; Single-Cell Analysis ; Species Specificity ; Transcriptome
    Chemical Substances Chloroquine (886U3H6UFF)
    Language English
    Publishing date 2020-05-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
    ZDB-ID 2126776-5
    ISSN 1545-7885 ; 1544-9173
    ISSN (online) 1545-7885
    ISSN 1544-9173
    DOI 10.1371/journal.pbio.3000711
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  10. Article ; Online: Transcriptional heterogeneity and tightly regulated changes in gene expression during

    Bogale, Haikel N / Pascini, Tales V / Kanatani, Sachie / Sá, Juliana M / Wellems, Thomas E / Sinnis, Photini / Vega-Rodríguez, Joel / Serre, David

    Proceedings of the National Academy of Sciences of the United States of America

    2021  Volume 118, Issue 10

    Abstract: Despite the critical role ... ...

    Abstract Despite the critical role of
    MeSH term(s) Animals ; Anopheles/parasitology ; Gene Expression Regulation ; Mice ; Plasmodium berghei/metabolism ; Salivary Glands/parasitology ; Sporozoites/metabolism ; Transcription, Genetic
    Language English
    Publishing date 2021-03-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2023438118
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    Zs.A 1148: Show issues Location:
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