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  1. Article: SARS-CoV2 Infection and the Importance of Potassium Balance.

    Causton, Helen C

    Frontiers in medicine

    2021  Volume 8, Page(s) 744697

    Abstract: SARS-CoV2 infection results in a range of symptoms from mild pneumonia to cardiac arrhythmias, hyperactivation of the immune response, systemic organ failure and death. However, the mechanism of action has been hard to establish. Analysis of symptoms ... ...

    Abstract SARS-CoV2 infection results in a range of symptoms from mild pneumonia to cardiac arrhythmias, hyperactivation of the immune response, systemic organ failure and death. However, the mechanism of action has been hard to establish. Analysis of symptoms associated with COVID-19, the activity of repurposed drugs associated with lower death rates or antiviral activity
    Language English
    Publishing date 2021-10-27
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2775999-4
    ISSN 2296-858X
    ISSN 2296-858X
    DOI 10.3389/fmed.2021.744697
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  2. Article ; Online: SARS-CoV2 Infection and the Importance of Potassium Balance

    Helen C. Causton

    Frontiers in Medicine, Vol

    2021  Volume 8

    Abstract: SARS-CoV2 infection results in a range of symptoms from mild pneumonia to cardiac arrhythmias, hyperactivation of the immune response, systemic organ failure and death. However, the mechanism of action has been hard to establish. Analysis of symptoms ... ...

    Abstract SARS-CoV2 infection results in a range of symptoms from mild pneumonia to cardiac arrhythmias, hyperactivation of the immune response, systemic organ failure and death. However, the mechanism of action has been hard to establish. Analysis of symptoms associated with COVID-19, the activity of repurposed drugs associated with lower death rates or antiviral activity in vitro and a small number of studies describing interventions, point to the importance of electrolyte, and particularly potassium, homeostasis at both the cellular, and systemic level. Elevated urinary loss of potassium is associated with disease severity, and the response to electrolyte replenishment correlates with progression toward recovery. These findings suggest possible diagnostic opportunities and therapeutic interventions. They provide insights into comorbidities and mechanisms associated with infection by SARS-CoV2 and other RNA viruses that target the ACE2 receptor, and/or activate cytokine-mediated immune responses in a potassium-dependent manner.
    Keywords electrolyte ; renin-angiotensin system ; drug repurposing ; SARS-CoV-2 infection ; potassium ; Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2021-10-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
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  3. Article ; Online: Metabolic rhythms: A framework for coordinating cellular function.

    Causton, Helen C

    The European journal of neuroscience

    2018  Volume 51, Issue 1, Page(s) 1–12

    Abstract: Circadian clocks are widespread among eukaryotes and generally involve feedback loops coupled with metabolic processes and redox balance. The organising power of these oscillations has not only allowed organisms to anticipate day-night cycles, but also ... ...

    Abstract Circadian clocks are widespread among eukaryotes and generally involve feedback loops coupled with metabolic processes and redox balance. The organising power of these oscillations has not only allowed organisms to anticipate day-night cycles, but also acts to temporally compartmentalise otherwise incompatible processes, enhance metabolic efficiency, make the system more robust to noise and propagate signals among cells. While daily rhythms and the function of the circadian transcription-translation loop have been the subject of extensive research over the past four decades, cycles of shorter period and respiratory oscillations, with which they are intertwined, have received less attention. Here, we describe features of yeast respiratory oscillations, which share many features with daily and 12 hr cellular oscillations in animal cells. This relatively simple system enables the analysis of dynamic rhythmic changes in metabolism, independent of cellular oscillations that are a product of the circadian transcription-translation feedback loop. Knowledge gained from studying ultradian oscillations in yeast will lead to a better understanding of the basic mechanistic principles and evolutionary origins of oscillatory behaviour among eukaryotes.
    MeSH term(s) Animals ; Circadian Clocks ; Circadian Rhythm ; Oxidation-Reduction
    Language English
    Publishing date 2018-12-27
    Publishing country France
    Document type Journal Article ; Review
    ZDB-ID 645180-9
    ISSN 1460-9568 ; 0953-816X
    ISSN (online) 1460-9568
    ISSN 0953-816X
    DOI 10.1111/ejn.14296
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  4. Article ; Online: Author Correction: Eukaryotic cell biology is temporally coordinated to support the energetic demands of protein homeostasis.

    O'Neill, John S / Hoyle, Nathaniel P / Robertson, J Brian / Edgar, Rachel S / Beale, Andrew D / Peak-Chew, Sew Y / Day, Jason / Costa, Ana S H / Frezza, Christian / Causton, Helen C

    Nature communications

    2021  Volume 12, Issue 1, Page(s) 7269

    Language English
    Publishing date 2021-12-08
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-021-27497-w
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  5. Article: Network-based approaches that exploit inferred transcription factor activity to analyze the impact of genetic variation on gene expression.

    Bussemaker, Harmen J / Causton, Helen C / Fazlollahi, Mina / Lee, Eunjee / Muroff, Ivor

    Current opinion in systems biology

    2017  Volume 2, Page(s) 98–102

    Abstract: Over the past decade, a number of methods have emerged for inferring protein-level transcription factor activities in individual samples based on prior information about the structure of the gene regulatory network. We discuss how this has enabled new ... ...

    Abstract Over the past decade, a number of methods have emerged for inferring protein-level transcription factor activities in individual samples based on prior information about the structure of the gene regulatory network. We discuss how this has enabled new methods for dissecting trans-acting mechanisms that underpin genetic variation in gene expression.
    Language English
    Publishing date 2017-04-17
    Publishing country England
    Document type Journal Article
    ISSN 2452-3100
    ISSN 2452-3100
    DOI 10.1016/j.coisb.2017.04.002
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  6. Article ; Online: Author Correction

    John S. O’Neill / Nathaniel P. Hoyle / J. Brian Robertson / Rachel S. Edgar / Andrew D. Beale / Sew Y. Peak-Chew / Jason Day / Ana S. H. Costa / Christian Frezza / Helen C. Causton

    Nature Communications, Vol 12, Iss 1, Pp 1-

    Eukaryotic cell biology is temporally coordinated to support the energetic demands of protein homeostasis

    2021  Volume 1

    Keywords Science ; Q
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
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  7. Article ; Online: Eukaryotic cell biology is temporally coordinated to support the energetic demands of protein homeostasis.

    O'Neill, John S / Hoyle, Nathaniel P / Robertson, J Brian / Edgar, Rachel S / Beale, Andrew D / Peak-Chew, Sew Y / Day, Jason / Costa, Ana S H / Frezza, Christian / Causton, Helen C

    Nature communications

    2020  Volume 11, Issue 1, Page(s) 4706

    Abstract: Yeast physiology is temporally regulated, this becomes apparent under nutrient-limited conditions and results in respiratory oscillations (YROs). YROs share features with circadian rhythms and interact with, but are independent of, the cell division ... ...

    Abstract Yeast physiology is temporally regulated, this becomes apparent under nutrient-limited conditions and results in respiratory oscillations (YROs). YROs share features with circadian rhythms and interact with, but are independent of, the cell division cycle. Here, we show that YROs minimise energy expenditure by restricting protein synthesis until sufficient resources are stored, while maintaining osmotic homeostasis and protein quality control. Although nutrient supply is constant, cells sequester and store metabolic resources via increased transport, autophagy and biomolecular condensation. Replete stores trigger increased H
    MeSH term(s) Autophagy/physiology ; Bioreactors ; Circadian Rhythm ; Energy Metabolism/physiology ; Eukaryotic Cells/physiology ; Glycogen/metabolism ; Heat-Shock Response ; Ionomycin ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Metabolomics ; Molecular Chaperones ; Osmolar Concentration ; Osmotic Pressure ; Oxygen/metabolism ; Protein Biosynthesis ; Protein Processing, Post-Translational ; Proteome ; Proteomics ; Proteostasis/physiology ; Ribosomes ; Yeasts/physiology
    Chemical Substances Molecular Chaperones ; Proteome ; Ionomycin (56092-81-0) ; Glycogen (9005-79-2) ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; Oxygen (S88TT14065)
    Language English
    Publishing date 2020-09-17
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-020-18330-x
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  8. Article ; Online: Identifying genetic modulators of the connectivity between transcription factors and their transcriptional targets.

    Fazlollahi, Mina / Muroff, Ivor / Lee, Eunjee / Causton, Helen C / Bussemaker, Harmen J

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

    2016  Volume 113, Issue 13, Page(s) E1835–43

    Abstract: Regulation of gene expression by transcription factors (TFs) is highly dependent on genetic background and interactions with cofactors. Identifying specific context factors is a major challenge that requires new approaches. Here we show that exploiting ... ...

    Abstract Regulation of gene expression by transcription factors (TFs) is highly dependent on genetic background and interactions with cofactors. Identifying specific context factors is a major challenge that requires new approaches. Here we show that exploiting natural variation is a potent strategy for probing functional interactions within gene regulatory networks. We developed an algorithm to identify genetic polymorphisms that modulate the regulatory connectivity between specific transcription factors and their target genes in vivo. As a proof of principle, we mapped connectivity quantitative trait loci (cQTLs) using parallel genotype and gene expression data for segregants from a cross between two strains of the yeast Saccharomyces cerevisiae We identified a nonsynonymous mutation in the DIG2 gene as a cQTL for the transcription factor Ste12p and confirmed this prediction empirically. We also identified three polymorphisms in TAF13 as putative modulators of regulation by Gcn4p. Our method has potential for revealing how genetic differences among individuals influence gene regulatory networks in any organism for which gene expression and genotype data are available along with information on binding preferences for transcription factors.
    MeSH term(s) Algorithms ; Basic-Leucine Zipper Transcription Factors/genetics ; Gene Expression Regulation, Fungal ; Gene Ontology ; Gene Regulatory Networks ; Genes, Mating Type, Fungal/genetics ; Models, Genetic ; Mutation ; Promoter Regions, Genetic ; Quantitative Trait Loci ; Reproducibility of Results ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae Proteins/genetics ; Transcription Factors/genetics
    Chemical Substances Basic-Leucine Zipper Transcription Factors ; DIG2 protein, S cerevisiae ; GCN4 protein, S cerevisiae ; STE12 protein, S cerevisiae ; Saccharomyces cerevisiae Proteins ; Transcription Factors
    Language English
    Publishing date 2016-03-29
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; 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.1517140113
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    Zs.A 1148: Show issues Location:
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  9. Article ; Online: Eukaryotic cell biology is temporally coordinated to support the energetic demands of protein homeostasis

    John S. O’ Neill / Nathaniel P. Hoyle / J. Brian Robertson / Rachel S. Edgar / Andrew D. Beale / Sew Y. Peak-Chew / Jason Day / Ana S. H. Costa / Christian Frezza / Helen C. Causton

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 11

    Abstract: Yeast exhibit oscillations that share features with circadian rhythms. The authors show that bioenergetic constraints promote oscillatory behaviour: resources are stored until supplies can support translational bursting, this is licensed by ion transport ...

    Abstract Yeast exhibit oscillations that share features with circadian rhythms. The authors show that bioenergetic constraints promote oscillatory behaviour: resources are stored until supplies can support translational bursting, this is licensed by ion transport and release from membrane-less compartments.
    Keywords Science ; Q
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
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  10. Article ; Online: Metabolic Cycles in Yeast Share Features Conserved among Circadian Rhythms.

    Causton, Helen C / Feeney, Kevin A / Ziegler, Christine A / O'Neill, John S

    Current biology : CB

    2015  Volume 25, Issue 8, Page(s) 1056–1062

    Abstract: Cell-autonomous circadian rhythms allow organisms to temporally orchestrate their internal state to anticipate and/or resonate with the external environment. Although ∼24-hr periodicity is observed across aerobic eukaryotes, the central mechanism has ... ...

    Abstract Cell-autonomous circadian rhythms allow organisms to temporally orchestrate their internal state to anticipate and/or resonate with the external environment. Although ∼24-hr periodicity is observed across aerobic eukaryotes, the central mechanism has been hard to dissect because few simple models exist, and known clock proteins are not conserved across phylogenetic kingdoms. In contrast, contributions to circadian rhythmicity made by a handful of post-translational mechanisms, such as phosphorylation of clock proteins by casein kinase 1 (CK1) and glycogen synthase kinase 3 (GSK3), appear conserved among phyla. These kinases have many other essential cellular functions and are better conserved in their contribution to timekeeping than any of the clock proteins they phosphorylate. Rhythmic oscillations in cellular redox state are another universal feature of circadian timekeeping, e.g., over-oxidation cycles of abundant peroxiredoxin proteins. Here, we use comparative chronobiology to distinguish fundamental clock mechanisms from species and/or tissue-specific adaptations and thereby identify features shared between circadian rhythms in mammalian cells and non-circadian temperature-compensated respiratory oscillations in budding yeast. We find that both types of oscillations are coupled with the cell division cycle, exhibit period determination by CK1 and GSK3, and have peroxiredoxin over-oxidation cycles. We also explore how peroxiredoxins contribute to YROs. Our data point to common mechanisms underlying both YROs and circadian rhythms and suggest two interpretations: either certain biochemical systems are simply permissive for cellular oscillations (with frequencies from hours to days) or this commonality arose via divergence from an ancestral cellular clock.
    MeSH term(s) Animals ; CLOCK Proteins/metabolism ; Casein Kinase I/genetics ; Casein Kinase I/metabolism ; Cell Division/genetics ; Circadian Clocks/physiology ; Circadian Rhythm/physiology ; Glycogen Synthase Kinase 3/genetics ; Glycogen Synthase Kinase 3/metabolism ; Oxidation-Reduction ; Peroxiredoxins/metabolism ; Phosphorylation ; Phylogeny ; Yeasts
    Chemical Substances Peroxiredoxins (EC 1.11.1.15) ; CLOCK Proteins (EC 2.3.1.48) ; Casein Kinase I (EC 2.7.11.1) ; Glycogen Synthase Kinase 3 (EC 2.7.11.26)
    Language English
    Publishing date 2015-04-20
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1071731-6
    ISSN 1879-0445 ; 0960-9822
    ISSN (online) 1879-0445
    ISSN 0960-9822
    DOI 10.1016/j.cub.2015.02.035
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