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  1. Article ; Online: AR activates YAP/TAZ differentially in prostate cancer.

    Salem, Omar / Jia, Siyang / Qian, Bin-Zhi / Hansen, Carsten Gram

    Life science alliance

    2023  Volume 6, Issue 9

    Abstract: The Hippo signalling pathway is a master regulator of cell growth, proliferation, and cancer. The transcriptional coregulators of the Hippo pathway, YAP and TAZ, are central in various cancers. However, how YAP and TAZ get activated in most types of ... ...

    Abstract The Hippo signalling pathway is a master regulator of cell growth, proliferation, and cancer. The transcriptional coregulators of the Hippo pathway, YAP and TAZ, are central in various cancers. However, how YAP and TAZ get activated in most types of cancers is not well understood. Here, we show that androgens activate YAP/TAZ via the androgen receptor (AR) in prostate cancer (PCa), and that this activation is differential. AR regulates YAP translation while inducing transcription of the TAZ encoding gene,
    MeSH term(s) Humans ; Male ; Androgens ; Carcinogenesis ; Prostate ; Prostatic Neoplasms/genetics ; Receptors, Androgen/genetics ; Transcriptional Coactivator with PDZ-Binding Motif Proteins/metabolism
    Chemical Substances Androgens ; Receptors, Androgen ; AR protein, human ; YAP1 protein, human ; Transcriptional Coactivator with PDZ-Binding Motif Proteins
    Language English
    Publishing date 2023-06-29
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2575-1077
    ISSN (online) 2575-1077
    DOI 10.26508/lsa.202201620
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: DNA and RNA Stability of Marine Microalgae in Cold-Stored Sediments and Its Implications in Metabarcoding Analyses.

    Chai, Zhaoyang / Liu, Yuyang / Jia, Siyang / Li, Fengting / Hu, Zhangxi / Deng, Yunyan / Yue, Caixia / Tang, Ying-Zhong

    International journal of molecular sciences

    2024  Volume 25, Issue 3

    Abstract: The ever-increasing applications of metabarcoding analyses for environmental samples demand a well-designed assessment of the stability of DNA and RNA contained in cells that are deposited or buried in marine sediments. We thus conducted a qPCR ... ...

    Abstract The ever-increasing applications of metabarcoding analyses for environmental samples demand a well-designed assessment of the stability of DNA and RNA contained in cells that are deposited or buried in marine sediments. We thus conducted a qPCR quantification of the DNA and RNA in the vegetative cells of three microalgae entrapped in facsimile marine sediments and found that >90% of DNA and up to 99% of RNA for all microalgal species were degraded within 60 days at 4 °C. A further examination of the potential interference of the relic DNA of the vegetative cells with resting cyst detection in sediments was performed via a metabarcoding analysis in artificial marine sediments spiked with the vegetative cells of two Kareniaceae dinoflagellates and the resting cysts of another three dinoflagellates. The results demonstrated a dramatic decrease in the relative abundances of the two Kareniaceae dinoflagellates in 120 days, while those of the three resting cysts increased dramatically. Together, our results suggest that a positive detection of microalgae via metabarcoding analysis in DNA or RNA extracted from marine sediments strongly indicates the presence of intact or viable cysts or spores due to the rapid decay of relic DNA/RNA. This study provides a solid basis for the data interpretation of metabarcoding surveys, particularly in resting cyst detection.
    MeSH term(s) Microalgae/genetics ; DNA ; Dinoflagellida/genetics ; DNA Barcoding, Taxonomic/methods ; RNA/genetics ; RNA Stability ; Geologic Sediments
    Chemical Substances DNA (9007-49-2) ; RNA (63231-63-0)
    Language English
    Publishing date 2024-01-31
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms25031724
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: PERCC1

    Sanchez-Pulido, Luis / Jia, Siyang / Hansen, Carsten Gram / Ponting, Chris P

    Bioinformatics advances

    2022  Volume 2, Issue 1, Page(s) vbac008

    Abstract: Motivation: Disrupted : Results: Our detailed evolutionary analysis of PERCC1 sequence reveals it to be a previously unappreciated member of the YAP/TAZ/FAM181 family of homologous transcriptional regulators. Like YAP and TAZ, PERCC1 likely interacts ...

    Abstract Motivation: Disrupted
    Results: Our detailed evolutionary analysis of PERCC1 sequence reveals it to be a previously unappreciated member of the YAP/TAZ/FAM181 family of homologous transcriptional regulators. Like YAP and TAZ, PERCC1 likely interacts with DNA via binding to TEA/ATTS domain transcription factors (TEADs) using its conserved interface-2 and -3 sequences. We compare the expression patterns of
    Availability and implementation: The data underlying this article are available in UniProt Database.
    Supplementary information: Supplementary data are available at
    Language English
    Publishing date 2022-02-03
    Publishing country England
    Document type Journal Article
    ISSN 2635-0041
    ISSN (online) 2635-0041
    DOI 10.1093/bioadv/vbac008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The Hippo pathway drives the cellular response to hydrostatic pressure.

    Park, Jiwon / Jia, Siyang / Salter, Donald / Bagnaninchi, Pierre / Hansen, Carsten G

    The EMBO journal

    2022  Volume 41, Issue 13, Page(s) e108719

    Abstract: Cells need to rapidly and precisely react to multiple mechanical and chemical stimuli in order to ensure precise context-dependent responses. This requires dynamic cellular signalling events that ensure homeostasis and plasticity when needed. A less well- ...

    Abstract Cells need to rapidly and precisely react to multiple mechanical and chemical stimuli in order to ensure precise context-dependent responses. This requires dynamic cellular signalling events that ensure homeostasis and plasticity when needed. A less well-understood process is cellular response to elevated interstitial fluid pressure, where the cell senses and responds to changes in extracellular hydrostatic pressure. Here, using quantitative label-free digital holographic imaging, combined with genome editing, biochemical assays and confocal imaging, we analyse the temporal cellular response to hydrostatic pressure. Upon elevated cyclic hydrostatic pressure, the cell responds by rapid, dramatic and reversible changes in cellular volume. We show that YAP and TAZ, the co-transcriptional regulators of the Hippo signalling pathway, control cell volume and that cells without YAP and TAZ have lower plasma membrane tension. We present direct evidence that YAP/TAZ drive the cellular response to hydrostatic pressure, a process that is at least partly mediated via clathrin-dependent endocytosis. Additionally, upon elevated oscillating hydrostatic pressure, YAP/TAZ are activated and induce TEAD-mediated transcription and expression of cellular components involved in dynamic regulation of cell volume and extracellular matrix. This cellular response confers a feedback loop that allows the cell to robustly respond to changes in interstitial fluid pressure.
    MeSH term(s) Hippo Signaling Pathway ; Homeostasis ; Hydrostatic Pressure ; Phosphoproteins/metabolism ; Protein Serine-Threonine Kinases/genetics ; Transcription Factors/genetics ; Transcription Factors/metabolism
    Chemical Substances Phosphoproteins ; Transcription Factors ; Protein Serine-Threonine Kinases (EC 2.7.11.1)
    Language English
    Publishing date 2022-06-15
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 586044-1
    ISSN 1460-2075 ; 0261-4189
    ISSN (online) 1460-2075
    ISSN 0261-4189
    DOI 10.15252/embj.2021108719
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1808: Show issues Location:
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  5. Article ; Online: YAP/TAZ activation predicts clinical outcomes in mesothelioma and is conserved in in vitro model of driver mutations.

    Cunningham, Richard / Jia, Siyang / Purohit, Krishna / Salem, Omar / Hui, Ning Sze / Lin, Yue / Carragher, Neil O / Hansen, Carsten Gram

    Clinical and translational medicine

    2023  Volume 13, Issue 2, Page(s) e1190

    Abstract: The Hippo signalling pathway is dysregulated across a wide range of cancer types and, although driver mutations that directly affect the core Hippo components are rare, a handful is found within pleural mesothelioma (PM). PM is a deadly disease of the ... ...

    Abstract The Hippo signalling pathway is dysregulated across a wide range of cancer types and, although driver mutations that directly affect the core Hippo components are rare, a handful is found within pleural mesothelioma (PM). PM is a deadly disease of the lining of the lung caused by asbestos exposure. By pooling the largest-scale clinical datasets publicly available, we here interrogate associations between the most prevalent driver mutations within PM and Hippo pathway disruption in patients, while assessing correlations with a variety of clinical markers. This analysis reveals a consistent worse outcome in patients exhibiting transcriptional markers of YAP/TAZ activation, pointing to the potential of leveraging Hippo pathway transcriptional activation status as a metric by which patients may be meaningfully stratified. Preclinical models recapitulating disease are transformative in order to develop new therapeutic strategies. We here establish an isogenic cell-line model of PM, which represents the most frequently mutated genes and which faithfully recapitulates the molecular features of clinical PM. This preclinical model is developed to probe the molecular basis by which the Hippo pathway and key driver mutations affect cancer initiation and progression. Implementing this approach, we reveal the role of NF2 as a mechanosensory component of the Hippo pathway in mesothelial cells. Cellular NF2 loss upon physiological stiffnesses analogous to the tumour niche drive YAP/TAZ-dependent anchorage-independent growth. Consequently, the development and characterisation of this cellular model provide a unique resource to obtain molecular insights into the disease and progress new drug discovery programs together with future stratification of PM patients.
    MeSH term(s) Humans ; Hippo Signaling Pathway ; Mesothelioma/genetics ; Mesothelioma/metabolism ; Mesothelioma/pathology ; Mutation/genetics ; Protein Serine-Threonine Kinases/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transcriptional Coactivator with PDZ-Binding Motif Proteins ; YAP-Signaling Proteins
    Chemical Substances Protein Serine-Threonine Kinases (EC 2.7.11.1) ; Transcription Factors ; Transcriptional Coactivator with PDZ-Binding Motif Proteins ; WWTR1 protein, human ; YAP-Signaling Proteins ; YAP1 protein, human
    Language English
    Publishing date 2023-01-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2697013-2
    ISSN 2001-1326 ; 2001-1326
    ISSN (online) 2001-1326
    ISSN 2001-1326
    DOI 10.1002/ctm2.1190
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  6. Article ; Online: Indian Hedgehog release from TNF-activated renal epithelia drives local and remote organ fibrosis.

    O'Sullivan, Eoin D / Mylonas, Katie J / Xin, Cuiyan / Baird, David P / Carvalho, Cyril / Docherty, Marie-Helena / Campbell, Ross / Matchett, Kylie P / Waddell, Scott H / Walker, Alexander D / Gallagher, Kevin M / Jia, Siyang / Leung, Steve / Laird, Alexander / Wilflingseder, Julia / Willi, Michaela / Reck, Maximilian / Finnie, Sarah / Pisco, Angela /
    Gordon-Keylock, Sabrina / Medvinsky, Alexander / Boulter, Luke / Henderson, Neil C / Kirschner, Kristina / Chandra, Tamir / Conway, Bryan R / Hughes, Jeremy / Denby, Laura / Bonventre, Joseph V / Ferenbach, David A

    Science translational medicine

    2023  Volume 15, Issue 698, Page(s) eabn0736

    Abstract: Progressive fibrosis is a feature of aging and chronic tissue injury in multiple organs, including the kidney and heart. Glioma-associated oncogene 1 expressing ( ... ...

    Abstract Progressive fibrosis is a feature of aging and chronic tissue injury in multiple organs, including the kidney and heart. Glioma-associated oncogene 1 expressing (Gli1
    MeSH term(s) Animals ; Humans ; Mice ; Fibrosis ; Hedgehog Proteins/metabolism ; Inflammation ; NF-kappa B ; Renal Insufficiency, Chronic ; Tumor Necrosis Factors ; Zinc Finger Protein GLI1
    Chemical Substances Hedgehog Proteins ; NF-kappa B ; Tumor Necrosis Factors ; Zinc Finger Protein GLI1 ; IHH protein, human ; ihh protein, mouse
    Language English
    Publishing date 2023-05-31
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2518854-9
    ISSN 1946-6242 ; 1946-6234
    ISSN (online) 1946-6242
    ISSN 1946-6234
    DOI 10.1126/scitranslmed.abn0736
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6941: Show issues Location:
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