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  1. Article ; Online: In-Distribution and Out-of-Distribution Self-Supervised ECG Representation Learning for Arrhythmia Detection.

    Soltanieh, Sahar / Hashemi, Javad / Etemad, Ali

    IEEE journal of biomedical and health informatics

    2024  Volume 28, Issue 2, Page(s) 789–800

    Abstract: This paper presents a systematic investigation into the effectiveness of Self-Supervised Learning (SSL) methods for Electrocardiogram (ECG) arrhythmia detection. We begin by conducting a novel analysis of the data distributions on three popular ECG-based ...

    Abstract This paper presents a systematic investigation into the effectiveness of Self-Supervised Learning (SSL) methods for Electrocardiogram (ECG) arrhythmia detection. We begin by conducting a novel analysis of the data distributions on three popular ECG-based arrhythmia datasets: PTB-XL, Chapman, and Ribeiro. To the best of our knowledge, our study is the first to quantitatively explore and characterize these distributions in the area. We then perform a comprehensive set of experiments using different augmentations and parameters to evaluate the effectiveness of various SSL methods, namely SimCRL, BYOL, and SwAV, for ECG representation learning, where we observe the best performance achieved by SwAV. Furthermore, our analysis shows that SSL methods achieve highly competitive results to those achieved by supervised state-of-the-art methods. To further assess the performance of these methods on both In-Distribution (ID) and Out-of-Distribution (OOD) ECG data, we conduct cross-dataset training and testing experiments. Our comprehensive experiments show almost identical results when comparing ID and OOD schemes, indicating that SSL techniques can learn highly effective representations that generalize well across different OOD datasets. This finding can have major implications for ECG-based arrhythmia detection. Lastly, to further analyze our results, we perform detailed per-disease studies on the performance of the SSL methods on the three datasets.
    MeSH term(s) Humans ; Electrocardiography ; Arrhythmias, Cardiac/diagnosis ; Knowledge ; Self-Management
    Language English
    Publishing date 2024-02-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2695320-1
    ISSN 2168-2208 ; 2168-2194
    ISSN (online) 2168-2208
    ISSN 2168-2194
    DOI 10.1109/JBHI.2023.3331626
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Book ; Online: In-Distribution and Out-of-Distribution Self-supervised ECG Representation Learning for Arrhythmia Detection

    Soltanieh, Sahar / Hashemi, Javad / Etemad, Ali

    2023  

    Abstract: This paper presents a systematic investigation into the effectiveness of Self-Supervised Learning (SSL) methods for Electrocardiogram (ECG) arrhythmia detection. We begin by conducting a novel distribution analysis on three popular ECG-based arrhythmia ... ...

    Abstract This paper presents a systematic investigation into the effectiveness of Self-Supervised Learning (SSL) methods for Electrocardiogram (ECG) arrhythmia detection. We begin by conducting a novel distribution analysis on three popular ECG-based arrhythmia datasets: PTB-XL, Chapman, and Ribeiro. To the best of our knowledge, our study is the first to quantify these distributions in this area. We then perform a comprehensive set of experiments using different augmentations and parameters to evaluate the effectiveness of various SSL methods, namely SimCRL, BYOL, and SwAV, for ECG representation learning, where we observe the best performance achieved by SwAV. Furthermore, our analysis shows that SSL methods achieve highly competitive results to those achieved by supervised state-of-the-art methods. To further assess the performance of these methods on both In-Distribution (ID) and Out-of-Distribution (OOD) ECG data, we conduct cross-dataset training and testing experiments. Our comprehensive experiments show almost identical results when comparing ID and OOD schemes, indicating that SSL techniques can learn highly effective representations that generalize well across different OOD datasets. This finding can have major implications for ECG-based arrhythmia detection. Lastly, to further analyze our results, we perform detailed per-disease studies on the performance of the SSL methods on the three datasets.
    Keywords Computer Science - Machine Learning ; Computer Science - Artificial Intelligence ; Electrical Engineering and Systems Science - Signal Processing
    Subject code 006
    Publishing date 2023-04-13
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Book ; Online: Analysis of Augmentations for Contrastive ECG Representation Learning

    Soltanieh, Sahar / Etemad, Ali / Hashemi, Javad

    2022  

    Abstract: This paper systematically investigates the effectiveness of various augmentations for contrastive self-supervised learning of electrocardiogram (ECG) signals and identifies the best parameters. The baseline of our proposed self-supervised framework ... ...

    Abstract This paper systematically investigates the effectiveness of various augmentations for contrastive self-supervised learning of electrocardiogram (ECG) signals and identifies the best parameters. The baseline of our proposed self-supervised framework consists of two main parts: the contrastive learning and the downstream task. In the first stage, we train an encoder using a number of augmentations to extract generalizable ECG signal representations. We then freeze the encoder and finetune a few linear layers with different amounts of labelled data for downstream arrhythmia detection. We then experiment with various augmentations techniques and explore a range of parameters. Our experiments are done on PTB-XL, a large and publicly available 12-lead ECG dataset. The results show that applying augmentations in a specific range of complexities works better for self-supervised contrastive learning. For instance, when adding Gaussian noise, a sigma in the range of 0.1 to 0.2 achieves better results, while poor training occurs when the added noise is too small or too large (outside of the specified range). A similar trend is observed with other augmentations, demonstrating the importance of selecting the optimum level of difficulty for the added augmentations, as augmentations that are too simple will not result in effective training, while augmentations that are too difficult will also prevent the model from effective learning of generalized representations. Our work can influence future research on self-supervised contrastive learning on bio-signals and aid in selecting optimum parameters for different augmentations.

    Comment: This paper has been accepted to IJCNN 2022 conference
    Keywords Electrical Engineering and Systems Science - Signal Processing ; Computer Science - Artificial Intelligence ; Computer Science - Machine Learning
    Subject code 006
    Publishing date 2022-05-30
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Ischemia-Reperfusion Injury in a Simulated Lung Transplant Setting Differentially Regulates Transcriptomic Profiles between Human Lung Endothelial and Epithelial Cells.

    Saren, Gaowa / Wong, Aaron / Lu, Yun-Bi / Baciu, Cristina / Zhou, Wenyong / Zamel, Ricardo / Soltanieh, Sahar / Sugihara, Junichi / Liu, Mingyao

    Cells

    2021  Volume 10, Issue 10

    Abstract: Current understanding of mechanisms of ischemia-reperfusion-induced lung injury during lung preservation and transplantation is mainly based on clinical observations and animal studies. Herein, we used cell and systems biology approaches to explore these ...

    Abstract Current understanding of mechanisms of ischemia-reperfusion-induced lung injury during lung preservation and transplantation is mainly based on clinical observations and animal studies. Herein, we used cell and systems biology approaches to explore these mechanisms at transcriptomics levels, especially by focusing on the differences between human lung endothelial and epithelial cells, which are crucial for maintaining essential lung structure and function. Human pulmonary microvascular endothelial cells and human lung epithelial cells were cultured to confluent, subjected to different cold ischemic times (CIT) to mimic static cold storage with preservation solution, and then subjected to warm reperfusion with a serum containing culture medium to simulate lung transplantation. Cell morphology, viability, and transcriptomic profiles were studied. Ischemia-reperfusion injury induced a CIT time-dependent cell death, which was associated with dramatic changes in gene expression. Under normal control conditions, endothelial cells showed gene clusters enriched in the vascular process and inflammation, while epithelial cells showed gene clusters enriched in protein biosynthesis and metabolism. CIT 6 h alone or after reperfusion had little effect on these phenotypic characteristics. After CIT 18 h, protein-biosynthesis-related gene clusters disappeared in epithelial cells; after reperfusion, metabolism-related gene clusters in epithelial cells and multiple gene clusters in the endothelial cells also disappeared. Human pulmonary endothelial and epithelial cells have distinct phenotypic transcriptomic signatures. Severe cellular injury reduces these gene expression signatures in a cell-type-dependent manner. Therapeutics that preserve these transcriptomic signatures may represent new treatment to prevent acute lung injury during lung transplantation.
    MeSH term(s) Cell Line ; Cryopreservation ; Endothelial Cells/metabolism ; Epithelial Cells/metabolism ; Gene Expression Profiling ; Gene Expression Regulation ; Humans ; Lung/blood supply ; Lung Transplantation ; Microvessels/pathology ; Multigene Family ; Phenotype ; Reperfusion Injury/genetics ; Reperfusion Injury/pathology ; Transcriptome/genetics
    Language English
    Publishing date 2021-10-10
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells10102713
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Ischemia-Reperfusion Injury in a Simulated Lung Transplant Setting Differentially Regulates Transcriptomic Profiles between Human Lung Endothelial and Epithelial Cells

    Gaowa Saren / Aaron Wong / Yun-Bi Lu / Cristina Baciu / Wenyong Zhou / Ricardo Zamel / Sahar Soltanieh / Junichi Sugihara / Mingyao Liu

    Cells, Vol 10, Iss 2713, p

    2021  Volume 2713

    Abstract: Current understanding of mechanisms of ischemia-reperfusion-induced lung injury during lung preservation and transplantation is mainly based on clinical observations and animal studies. Herein, we used cell and systems biology approaches to explore these ...

    Abstract Current understanding of mechanisms of ischemia-reperfusion-induced lung injury during lung preservation and transplantation is mainly based on clinical observations and animal studies. Herein, we used cell and systems biology approaches to explore these mechanisms at transcriptomics levels, especially by focusing on the differences between human lung endothelial and epithelial cells, which are crucial for maintaining essential lung structure and function. Human pulmonary microvascular endothelial cells and human lung epithelial cells were cultured to confluent, subjected to different cold ischemic times (CIT) to mimic static cold storage with preservation solution, and then subjected to warm reperfusion with a serum containing culture medium to simulate lung transplantation. Cell morphology, viability, and transcriptomic profiles were studied. Ischemia-reperfusion injury induced a CIT time-dependent cell death, which was associated with dramatic changes in gene expression. Under normal control conditions, endothelial cells showed gene clusters enriched in the vascular process and inflammation, while epithelial cells showed gene clusters enriched in protein biosynthesis and metabolism. CIT 6 h alone or after reperfusion had little effect on these phenotypic characteristics. After CIT 18 h, protein-biosynthesis-related gene clusters disappeared in epithelial cells; after reperfusion, metabolism-related gene clusters in epithelial cells and multiple gene clusters in the endothelial cells also disappeared. Human pulmonary endothelial and epithelial cells have distinct phenotypic transcriptomic signatures. Severe cellular injury reduces these gene expression signatures in a cell-type-dependent manner. Therapeutics that preserve these transcriptomic signatures may represent new treatment to prevent acute lung injury during lung transplantation.
    Keywords ischemia-reperfusion injury ; cell culture model for lung transplantation ; transcriptomics and bioinformatics ; functional genomics ; translational research ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2021-10-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: L-alanyl-L-glutamine modified perfusate improves human lung cell functions and extend porcine ex vivo lung perfusion.

    Huang, Lei / Hough, Olivia / Vellanki, Ravi N / Takahashi, Mamoru / Zhu, Zhiyuan / Xiang, Yun-Yan / Chen, Manyin / Gokhale, Hemant / Shan, Hongchao / Soltanieh, Sahar / Jing, Lei / Gao, Xinliang / Wouters, Bradly G / Cypel, Marcelo / Keshavjee, Shaf / Liu, Mingyao

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation

    2022  Volume 42, Issue 2, Page(s) 183–195

    Abstract: Background: The clinical application of normothermic ex vivo lung perfusion (EVLP) has increased donor lung utilization for transplantation through functional assessment. To develop it as a platform for donor lung repair, reconditioning and regeneration, ...

    Abstract Background: The clinical application of normothermic ex vivo lung perfusion (EVLP) has increased donor lung utilization for transplantation through functional assessment. To develop it as a platform for donor lung repair, reconditioning and regeneration, the perfusate should be modified to support the lung during extended EVLP.
    Methods: Human lung epithelial cells and pulmonary microvascular endothelial cells were cultured, and the effects of Steen solution (commonly used EVLP perfusate) on basic cellular function were tested. Steen solution was modified based on screening tests in cell culture, and further tested with an EVLP cell culture model, on apoptosis, GSH, HSP70, and IL-8 expression. Finally, a modified formula was tested on porcine EVLP. Physiological parameters of lung function, histology of lung tissue, and amino acid concentrations in EVLP perfusate were measured.
    Results: Steen solution reduced cell confluence, induced apoptosis, and inhibited cell migration, compared to regular cell culture media. Adding L-alanyl-L-glutamine to Steen solution improved cell migration and decreased apoptosis. It also reduced cold preservation and warm perfusion-induced apoptosis, enhanced GSH and HSP70 production, and inhibited IL-8 expression on an EVLP cell culture model. L-alanyl-L-glutamine modified Steen solution supported porcine lungs on EVLP with significantly improved lung function, well-preserved histological structure, and significantly higher levels of multiple amino acids in EVLP perfusate.
    Conclusions: Adding L-alanyl-L-glutamine to perfusate may provide additional energy support, antioxidant, and cytoprotective effects to lung tissue. The pipeline developed herein, with cell culture, cell EVLP, and porcine EVLP models, can be used to further optimize perfusates to improve EVLP outcomes.
    MeSH term(s) Animals ; Humans ; Endothelial Cells ; Interleukin-8/pharmacology ; Lung/blood supply ; Lung/physiology ; Lung Transplantation ; Organ Preservation ; Perfusion ; Swine
    Chemical Substances Interleukin-8 ; alanylglutamine (U5JDO2770Z)
    Language English
    Publishing date 2022-11-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1062522-7
    ISSN 1557-3117 ; 1053-2498
    ISSN (online) 1557-3117
    ISSN 1053-2498
    DOI 10.1016/j.healun.2022.10.022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Nucleolar proteins Bfr2 and Enp2 interact with DEAD-box RNA helicase Dbp4 in two different complexes.

    Soltanieh, Sahar / Lapensée, Martin / Dragon, François

    Nucleic acids research

    2013  Volume 42, Issue 5, Page(s) 3194–3206

    Abstract: Different pre-ribosomal complexes are formed during ribosome biogenesis, and the composition of these complexes is highly dynamic. Dbp4, a conserved DEAD-box RNA helicase implicated in ribosome biogenesis, interacts with nucleolar proteins Bfr2 and Enp2. ...

    Abstract Different pre-ribosomal complexes are formed during ribosome biogenesis, and the composition of these complexes is highly dynamic. Dbp4, a conserved DEAD-box RNA helicase implicated in ribosome biogenesis, interacts with nucleolar proteins Bfr2 and Enp2. We show that, like Dbp4, Bfr2 and Enp2 are required for the early processing steps leading to the production of 18S ribosomal RNA. We also found that Bfr2 and Enp2 associate with the U3 small nucleolar RNA (snoRNA), the U3-specific protein Mpp10 and various pre-18S ribosomal RNA species. Thus, we propose that Bfr2, Dbp4 and Enp2 are components of the small subunit (SSU) processome, a large complex of ∼80S. Sucrose gradient sedimentation analyses indicated that Dbp4, Bfr2 and Enp2 sediment in a peak of ∼50S and in a peak of ∼80S. Bfr2, Dbp4 and Enp2 associate together in the 50S complex, which does not include the U3 snoRNA; however, they associate with U3 snoRNA in the 80S complex (SSU processome). Immunoprecipitation experiments revealed that U14 snoRNA associates with Dbp4 in the 50S complex, but not with Bfr2 or Enp2. The assembly factor Tsr1 is not part of the '50S' complex, indicating this complex is not a pre-40S ribosome. A combination of experiments leads us to propose that Bfr2, Enp2 and Dbp4 are recruited at late steps during assembly of the SSU processome.
    MeSH term(s) DEAD-box RNA Helicases/metabolism ; Nuclear Proteins/metabolism ; Phosphoproteins/metabolism ; RNA Nucleotidyltransferases/metabolism ; RNA Precursors/metabolism ; RNA Processing, Post-Transcriptional ; RNA, Ribosomal, 18S/metabolism ; RNA, Small Nucleolar/metabolism ; Ribonucleoproteins/metabolism ; Saccharomyces cerevisiae Proteins/metabolism
    Chemical Substances BFR2 protein, S cerevisiae ; MPP10 protein, S cerevisiae ; Nuclear Proteins ; Phosphoproteins ; RNA Precursors ; RNA, Ribosomal, 18S ; RNA, Small Nucleolar ; RNA, U3 small nucleolar ; Ribonucleoproteins ; Saccharomyces cerevisiae Proteins ; RNA Nucleotidyltransferases (EC 2.7.7.-) ; HCA4 protein, S cerevisiae (EC 3.6.1.-) ; DEAD-box RNA Helicases (EC 3.6.4.13)
    Language English
    Publishing date 2013-12-18
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkt1293
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: DEAD-Box RNA Helicase Dbp4 Is Required for Small-Subunit Processome Formation and Function

    Soltanieh, Sahar / Osheim, Yvonne N. / Spasov, Krasimir / Trahan, Christian / Beyer, Ann L. / Dragon, François

    Molecular and Cellular Biology. 2015 Mar. 1, v. 35, no. 5 p.816-830

    2015  

    Abstract: DEAD-box RNA helicase Dbp4 is required for 18S rRNA synthesis: cellular depletion of Dbp4 impairs the early cleavage reactions of the pre-rRNA and causes U14 small nucleolar RNA (snoRNA) to remain associated with pre-rRNA. Immunoprecipitation experiments ...

    Abstract DEAD-box RNA helicase Dbp4 is required for 18S rRNA synthesis: cellular depletion of Dbp4 impairs the early cleavage reactions of the pre-rRNA and causes U14 small nucleolar RNA (snoRNA) to remain associated with pre-rRNA. Immunoprecipitation experiments (IPs) carried out with whole-cell extracts (WCEs) revealed that hemagglutinin (HA)-tagged Dbp4 is associated with U3 snoRNA but not with U14 snoRNA. IPs with WCEs also showed association with the U3-specific protein Mpp10, which suggests that Dbp4 interacts with the functionally active U3 RNP; this particle, called the small-subunit (SSU) processome, can be observed at the 5′ end of nascent pre-rRNA. Electron microscopy analyses indicated that depletion of Dbp4 compromised SSU processome formation and cotranscriptional cleavage of the pre-rRNA. Sucrose density gradient analyses revealed that depletion of U3 snoRNA or the Mpp10 protein inhibited the release of U14 snoRNA from pre-rRNA, just as was seen with Dbp4-depleted cells, indicating that alteration of SSU processome components has significant consequences for U14 snoRNA dynamics. We also found that the C-terminal extension flanking the catalytic core of Dbp4 plays an important role in the release of U14 snoRNA from pre-rRNA.
    Keywords DEAD-box RNA helicases ; RNA ; cell biology ; electron microscopy ; hemagglutinins ; precipitin tests ; sucrose
    Language English
    Dates of publication 2015-0301
    Size p. 816-830.
    Publishing place Taylor & Francis
    Document type Article ; Online
    ZDB-ID 779397-2
    ISSN 1098-5549 ; 0270-7306
    ISSN (online) 1098-5549
    ISSN 0270-7306
    DOI 10.1128/MCB.01348-14
    Database NAL-Catalogue (AGRICOLA)

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  9. Article ; Online: DEAD-box RNA helicase Dbp4 is required for small-subunit processome formation and function.

    Soltanieh, Sahar / Osheim, Yvonne N / Spasov, Krasimir / Trahan, Christian / Beyer, Ann L / Dragon, François

    Molecular and cellular biology

    2015  Volume 35, Issue 5, Page(s) 816–830

    Abstract: DEAD-box RNA helicase Dbp4 is required for 18S rRNA synthesis: cellular depletion of Dbp4 impairs the early cleavage reactions of the pre-rRNA and causes U14 small nucleolar RNA (snoRNA) to remain associated with pre-rRNA. Immunoprecipitation experiments ...

    Abstract DEAD-box RNA helicase Dbp4 is required for 18S rRNA synthesis: cellular depletion of Dbp4 impairs the early cleavage reactions of the pre-rRNA and causes U14 small nucleolar RNA (snoRNA) to remain associated with pre-rRNA. Immunoprecipitation experiments (IPs) carried out with whole-cell extracts (WCEs) revealed that hemagglutinin (HA)-tagged Dbp4 is associated with U3 snoRNA but not with U14 snoRNA. IPs with WCEs also showed association with the U3-specific protein Mpp10, which suggests that Dbp4 interacts with the functionally active U3 RNP; this particle, called the small-subunit (SSU) processome, can be observed at the 5' end of nascent pre-rRNA. Electron microscopy analyses indicated that depletion of Dbp4 compromised SSU processome formation and cotranscriptional cleavage of the pre-rRNA. Sucrose density gradient analyses revealed that depletion of U3 snoRNA or the Mpp10 protein inhibited the release of U14 snoRNA from pre-rRNA, just as was seen with Dbp4-depleted cells, indicating that alteration of SSU processome components has significant consequences for U14 snoRNA dynamics. We also found that the C-terminal extension flanking the catalytic core of Dbp4 plays an important role in the release of U14 snoRNA from pre-rRNA.
    MeSH term(s) Centrifugation, Density Gradient ; Chromatin/chemistry ; DEAD-box RNA Helicases/metabolism ; Genotype ; Microscopy, Electron ; Phosphoproteins/metabolism ; Protein Structure, Tertiary ; RNA Helicases/metabolism ; RNA Nucleotidyltransferases/metabolism ; RNA, Ribosomal, 18S/metabolism ; RNA, Small Nucleolar/metabolism ; Ribonucleoproteins/metabolism ; Ribosomes/chemistry ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae Proteins/metabolism
    Chemical Substances Chromatin ; MPP10 protein, S cerevisiae ; Phosphoproteins ; RNA, Ribosomal, 18S ; RNA, Small Nucleolar ; RNA, U3 small nucleolar ; Ribonucleoproteins ; Saccharomyces cerevisiae Proteins ; RNA Nucleotidyltransferases (EC 2.7.7.-) ; HCA4 protein, S cerevisiae (EC 3.6.1.-) ; DEAD-box RNA Helicases (EC 3.6.4.13) ; RNA Helicases (EC 3.6.4.13)
    Language English
    Publishing date 2015-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 779397-2
    ISSN 1098-5549 ; 0270-7306
    ISSN (online) 1098-5549
    ISSN 0270-7306
    DOI 10.1128/MCB.01348-14
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Context-Dependent and Disease-Specific Diversity in Protein Interactions within Stress Granules.

    Markmiller, Sebastian / Soltanieh, Sahar / Server, Kari L / Mak, Raymond / Jin, Wenhao / Fang, Mark Y / Luo, En-Ching / Krach, Florian / Yang, Dejun / Sen, Anindya / Fulzele, Amit / Wozniak, Jacob M / Gonzalez, David J / Kankel, Mark W / Gao, Fen-Biao / Bennett, Eric J / Lécuyer, Eric / Yeo, Gene W

    Cell

    2018  Volume 172, Issue 3, Page(s) 590–604.e13

    Abstract: Stress granules (SGs) are transient ribonucleoprotein (RNP) aggregates that form during cellular stress and are increasingly implicated in human neurodegeneration. To study the proteome and compositional diversity of SGs in different cell types and in ... ...

    Abstract Stress granules (SGs) are transient ribonucleoprotein (RNP) aggregates that form during cellular stress and are increasingly implicated in human neurodegeneration. To study the proteome and compositional diversity of SGs in different cell types and in the context of neurodegeneration-linked mutations, we used ascorbate peroxidase (APEX) proximity labeling, mass spectrometry, and immunofluorescence to identify ∼150 previously unknown human SG components. A highly integrated, pre-existing SG protein interaction network in unstressed cells facilitates rapid coalescence into larger SGs. Approximately 20% of SG diversity is stress or cell-type dependent, with neuronal SGs displaying a particularly complex repertoire of proteins enriched in chaperones and autophagy factors. Strengthening the link between SGs and neurodegeneration, we demonstrate aberrant dynamics, composition, and subcellular distribution of SGs in cells from amyotrophic lateral sclerosis (ALS) patients. Using three Drosophila ALS/FTD models, we identify SG-associated modifiers of neurotoxicity in vivo. Altogether, our results highlight SG proteins as central to understanding and ultimately targeting neurodegeneration.
    MeSH term(s) Amyotrophic Lateral Sclerosis/metabolism ; Animals ; Cytoplasmic Granules/metabolism ; Drosophila melanogaster ; HEK293 Cells ; HeLa Cells ; Humans ; Neurons/metabolism ; Protein Interaction Maps ; Protein Transport ; Ribonucleoproteins/metabolism ; Stress, Physiological
    Chemical Substances Ribonucleoproteins
    Language English
    Publishing date 2018-01-18
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2017.12.032
    Database MEDical Literature Analysis and Retrieval System OnLINE

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