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  1. Article ; Online: The choice of the objective function in flux balance analysis is crucial for predicting replicative lifespans in yeast.

    Schnitzer, Barbara / Österberg, Linnea / Cvijovic, Marija

    PloS one

    2022  Volume 17, Issue 10, Page(s) e0276112

    Abstract: Flux balance analysis (FBA) is a powerful tool to study genome-scale models of the cellular metabolism, based on finding the optimal flux distributions over the network. While the objective function is crucial for the outcome, its choice, even though ... ...

    Abstract Flux balance analysis (FBA) is a powerful tool to study genome-scale models of the cellular metabolism, based on finding the optimal flux distributions over the network. While the objective function is crucial for the outcome, its choice, even though motivated by evolutionary arguments, has not been directly connected to related measures. Here, we used an available multi-scale mathematical model of yeast replicative ageing, integrating cellular metabolism, nutrient sensing and damage accumulation, to systematically test the effect of commonly used objective functions on features of replicative ageing in budding yeast, such as the number of cell divisions and the corresponding time between divisions. The simulations confirmed that assuming maximal growth is essential for reaching realistic lifespans. The usage of the parsimonious solution or the additional maximisation of a growth-independent energy cost can improve lifespan predictions, explained by either increased respiratory activity using resources otherwise allocated to cellular growth or by enhancing antioxidative activity, specifically in early life. Our work provides a new perspective on choosing the objective function in FBA by connecting it to replicative ageing.
    MeSH term(s) Cell Cycle ; DNA Replication ; Longevity ; Models, Biological ; Saccharomyces cerevisiae/metabolism
    Language English
    Publishing date 2022-10-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0276112
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Multi-scale model suggests the trade-off between protein and ATP demand as a driver of metabolic changes during yeast replicative ageing.

    Schnitzer, Barbara / Österberg, Linnea / Skopa, Iro / Cvijovic, Marija

    PLoS computational biology

    2022  Volume 18, Issue 7, Page(s) e1010261

    Abstract: The accumulation of protein damage is one of the major drivers of replicative ageing, describing a cell's reduced ability to reproduce over time even under optimal conditions. Reactive oxygen and nitrogen species are precursors of protein damage and ... ...

    Abstract The accumulation of protein damage is one of the major drivers of replicative ageing, describing a cell's reduced ability to reproduce over time even under optimal conditions. Reactive oxygen and nitrogen species are precursors of protein damage and therefore tightly linked to ageing. At the same time, they are an inevitable by-product of the cell's metabolism. Cells are able to sense high levels of reactive oxygen and nitrogen species and can subsequently adapt their metabolism through gene regulation to slow down damage accumulation. However, the older or damaged a cell is the less flexibility it has to allocate enzymes across the metabolic network, forcing further adaptions in the metabolism. To investigate changes in the metabolism during replicative ageing, we developed an multi-scale mathematical model using budding yeast as a model organism. The model consists of three interconnected modules: a Boolean model of the signalling network, an enzyme-constrained flux balance model of the central carbon metabolism and a dynamic model of growth and protein damage accumulation with discrete cell divisions. The model can explain known features of replicative ageing, like average lifespan and increase in generation time during successive division, in yeast wildtype cells by a decreasing pool of functional enzymes and an increasing energy demand for maintenance. We further used the model to identify three consecutive metabolic phases, that a cell can undergo during its life, and their influence on the replicative potential, and proposed an intervention span for lifespan control.
    MeSH term(s) Adenosine Triphosphate/metabolism ; Nitrogen/metabolism ; Oxygen/metabolism ; Saccharomyces cerevisiae/metabolism
    Chemical Substances Adenosine Triphosphate (8L70Q75FXE) ; Nitrogen (N762921K75) ; Oxygen (S88TT14065)
    Language English
    Publishing date 2022-07-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2193340-6
    ISSN 1553-7358 ; 1553-734X
    ISSN (online) 1553-7358
    ISSN 1553-734X
    DOI 10.1371/journal.pcbi.1010261
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The synergy of damage repair and retention promotes rejuvenation and prolongs healthy lifespans in cell lineages.

    Schnitzer, Barbara / Borgqvist, Johannes / Cvijovic, Marija

    PLoS computational biology

    2020  Volume 16, Issue 10, Page(s) e1008314

    Abstract: Damaged proteins are inherited asymmetrically during cell division in the yeast Saccharomyces cerevisiae, such that most damage is retained within the mother cell. The consequence is an ageing mother and a rejuvenated daughter cell with full replicative ... ...

    Abstract Damaged proteins are inherited asymmetrically during cell division in the yeast Saccharomyces cerevisiae, such that most damage is retained within the mother cell. The consequence is an ageing mother and a rejuvenated daughter cell with full replicative potential. Daughters of old and damaged mothers are however born with increasing levels of damage resulting in lowered replicative lifespans. Remarkably, these prematurely old daughters can give rise to rejuvenated cells with low damage levels and recovered lifespans, called second-degree rejuvenation. We aimed to investigate how damage repair and retention together can promote rejuvenation and at the same time ensure low damage levels in mother cells, reflected in longer health spans. We developed a dynamic model for damage accumulation over successive divisions in individual cells as part of a dynamically growing cell lineage. With detailed knowledge about single-cell dynamics and relationships between all cells in the lineage, we can infer how individual damage repair and retention strategies affect the propagation of damage in the population. We show that damage retention lowers damage levels in the population by reducing the variability across the lineage, and results in larger population sizes. Repairing damage efficiently in early life, as opposed to investing in repair when damage has already accumulated, counteracts accelerated ageing caused by damage retention. It prolongs the health span of individual cells which are moreover less prone to stress. In combination, damage retention and early investment in repair are beneficial for healthy ageing in yeast cell populations.
    MeSH term(s) Cell Division/physiology ; Cell Survival/physiology ; Cellular Senescence/physiology ; Computational Biology ; Computer Simulation ; Models, Biological ; Saccharomyces cerevisiae/cytology ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/metabolism ; Single-Cell Analysis
    Chemical Substances Saccharomyces cerevisiae Proteins
    Language English
    Publishing date 2020-10-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2193340-6
    ISSN 1553-7358 ; 1553-734X
    ISSN (online) 1553-7358
    ISSN 1553-734X
    DOI 10.1371/journal.pcbi.1008314
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The effect of stress on biophysical characteristics of misfolded protein aggregates in living Saccharomyces cerevisiae cells.

    Schnitzer, Barbara / Welkenhuysen, Niek / Leake, Mark C / Shashkova, Sviatlana / Cvijovic, Marija

    Experimental gerontology

    2022  Volume 162, Page(s) 111755

    Abstract: Aggregation of misfolded or damaged proteins is often attributed to numerous metabolic and neurodegenerative disorders. To reveal underlying mechanisms and cellular responses, it is crucial to investigate protein aggregate dynamics in cells. Here, we ... ...

    Abstract Aggregation of misfolded or damaged proteins is often attributed to numerous metabolic and neurodegenerative disorders. To reveal underlying mechanisms and cellular responses, it is crucial to investigate protein aggregate dynamics in cells. Here, we used super-resolution single-molecule microscopy to obtain biophysical characteristics of individual aggregates of a model misfolded protein ∆ssCPY* labelled with GFP. We demonstrated that oxidative and hyperosmotic stress lead to increased aggregate stoichiometries but not necessarily the total number of aggregates. Moreover, our data suggest the importance of the thioredoxin peroxidase Tsa1 for the controlled sequestering and clearance of aggregates upon both conditions. Our work provides novel insights into the understanding of the cellular response to stress via revealing the dynamical properties of stress-induced protein aggregates.
    MeSH term(s) Oxidation-Reduction ; Protein Aggregates ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins
    Chemical Substances Protein Aggregates ; Saccharomyces cerevisiae Proteins
    Language English
    Publishing date 2022-02-28
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 390992-x
    ISSN 1873-6815 ; 0531-5565
    ISSN (online) 1873-6815
    ISSN 0531-5565
    DOI 10.1016/j.exger.2022.111755
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 579: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
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  5. Article: Robustness of Nutrient Signaling Is Maintained by Interconnectivity Between Signal Transduction Pathways.

    Welkenhuysen, Niek / Schnitzer, Barbara / Österberg, Linnea / Cvijovic, Marija

    Frontiers in physiology

    2019  Volume 9, Page(s) 1964

    Abstract: Systems biology approaches provide means to study the interplay between biological processes leading to the mechanistic understanding of the properties of complex biological systems. Here, we developed a vector format rule-based Boolean logic model of ... ...

    Abstract Systems biology approaches provide means to study the interplay between biological processes leading to the mechanistic understanding of the properties of complex biological systems. Here, we developed a vector format rule-based Boolean logic model of the yeast
    Language English
    Publishing date 2019-01-21
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2018.01964
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: ''Problemorientiertes Lernen, mehr als Strukturänderung?''

    Clénin, Brigitte / Elfrich, Ursula / Gnädinger-Schnitzer, Barbara

    Pflegepädagogik

    1995  , Issue 6, Page(s) 11

    Keywords Pflegeausbildung ; problemorientiertes Lernen
    Language German
    Document type Article
    ZDB-ID 1092747-5
    ISSN 1019-0651
    ISSN 1019-0651
    Database bibnet.org

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3496: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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