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  1. AU="Moussavi-Baygi, Ruhollah"
  2. AU=Joffe Russell T
  3. AU="Szerencsés, Viktória"
  4. AU="Venkatesan, Vettriselvi"
  5. AU="Houzé, Sandrine"
  6. AU="Cox, Caitlin"
  7. AU="Sheng, Xin-Qing"
  8. AU="Marrink, Siewert J"
  9. AU="Boland, Fiona"
  10. AU="Semcesen, Liana N"
  11. AU="Beah, Peter Y"
  12. AU="Zakzuk, Josefina"
  13. AU="Buchner, Denise"
  14. AU="Xueting Feng"
  15. AU="Chen, Si-Rui"
  16. AU="Hoffmann, Sven"
  17. AU="Kang, Kyung Jun"
  18. AU="Brinks, Henriette L"

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  1. Artikel: Integrative identification of non-coding regulatory regions driving metastatic prostate cancer.

    Woo, Brian J / Moussavi-Baygi, Ruhollah / Karner, Heather / Karimzadeh, Mehran / Garcia, Kristle / Joshi, Tanvi / Yin, Keyi / Navickas, Albertas / Gilbert, Luke A / Wang, Bo / Asgharian, Hosseinali / Feng, Felix Y / Goodarzi, Hani

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Large-scale sequencing efforts of thousands of tumor samples have been undertaken to understand the mutational landscape of the coding genome. However, the vast majority of germline and somatic variants occur within non-coding portions of the genome. ... ...

    Abstract Large-scale sequencing efforts of thousands of tumor samples have been undertaken to understand the mutational landscape of the coding genome. However, the vast majority of germline and somatic variants occur within non-coding portions of the genome. These genomic regions do not directly encode for specific proteins, but can play key roles in cancer progression, for example by driving aberrant gene expression control. Here, we designed an integrative computational and experimental framework to identify recurrently mutated non-coding regulatory regions that drive tumor progression. Application of this approach to whole-genome sequencing (WGS) data from a large cohort of metastatic castration-resistant prostate cancer (mCRPC) revealed a large set of recurrently mutated regions. We used (i)
    Sprache Englisch
    Erscheinungsdatum 2023-06-02
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2023.04.14.535921
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Looking "Under the Hood" of Cellular Mechanotransduction with Computational Tools: A Systems Biomechanics Approach across Multiple Scales.

    Shams, Hengameh / Soheilypour, Mohammad / Peyro, Mohaddeseh / Moussavi-Baygi, Ruhollah / Mofrad, Mohammad R K

    ACS biomaterials science & engineering

    2017  Band 3, Heft 11, Seite(n) 2712–2726

    Abstract: Signal modulation has been developed in living cells throughout evolution to promote utilizing the same machinery for multiple cellular functions. Chemical and mechanical modules of signal transmission and transduction are interconnected and necessary ... ...

    Abstract Signal modulation has been developed in living cells throughout evolution to promote utilizing the same machinery for multiple cellular functions. Chemical and mechanical modules of signal transmission and transduction are interconnected and necessary for organ development and growth. However, due to the high complexity of the intercommunication of physical intracellular connections with biochemical pathways, there are many missing details in our overall understanding of mechanotransduction processes, i.e., the process by which mechanical signals are converted to biochemical cascades. Cell-matrix adhesions are mechanically coupled to the nucleus through the cytoskeleton. This modulated and tightly integrated network mediates the transmission of mechanochemical signals from the extracellular matrix to the nucleus. Various experimental and computational techniques have been utilized to understand the basic mechanisms of mechanotransduction, yet many aspects have remained elusive. Recently,
    Sprache Englisch
    Erscheinungsdatum 2017-06-29
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ISSN 2373-9878
    ISSN (online) 2373-9878
    DOI 10.1021/acsbiomaterials.7b00117
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: The interaction of CRM1 and the nuclear pore protein Tpr.

    Zhao, Charles L / Mahboobi, Seyed Hanif / Moussavi-Baygi, Ruhollah / Mofrad, Mohammad R K

    PloS one

    2014  Band 9, Heft 4, Seite(n) e93709

    Abstract: While much has been devoted to the study of transport mechanisms through the nuclear pore complex (NPC), the specifics of interactions and binding between export transport receptors and the NPC periphery have remained elusive. Recent work has ... ...

    Abstract While much has been devoted to the study of transport mechanisms through the nuclear pore complex (NPC), the specifics of interactions and binding between export transport receptors and the NPC periphery have remained elusive. Recent work has demonstrated a binding interaction between the exportin CRM1 and the unstructured carboxylic tail of Tpr, on the nuclear basket. Strong evidence suggests that this interaction is vital to the functions of CRM1. Using molecular dynamics simulations and a newly refined method for determining binding regions, we have identified nine candidate binding sites on CRM1 for C-Tpr. These include two adjacent to RanGTP--from which one is blocked in the absence of RanGTP--and three next to the binding region of the cargo Snurportin. We report two additional interaction sites between C-Tpr and Snurportin, suggesting a possible role for Tpr import into the nucleus. Using bioinformatics tools we have conducted conservation analysis and functional residue prediction investigations to identify which parts of the obtained binding sites are inherently more important and should be highlighted. Also, a novel measure based on the ratio of available solvent accessible surface (RASAS) is proposed for monitoring the ligand/receptor binding process.
    Mesh-Begriff(e) Binding Sites ; Humans ; Karyopherins/chemistry ; Ligands ; Molecular Conformation ; Molecular Dynamics Simulation ; Nuclear Pore/chemistry ; Nuclear Pore/physiology ; Nuclear Pore Complex Proteins/chemistry ; Protein Binding ; Proto-Oncogene Proteins/chemistry ; RNA Cap-Binding Proteins/chemistry ; RNA, Messenger/metabolism ; Receptors, Cytoplasmic and Nuclear/chemistry ; Software ; ran GTP-Binding Protein/chemistry ; Exportin 1 Protein
    Chemische Substanzen Karyopherins ; Ligands ; Nuclear Pore Complex Proteins ; Proto-Oncogene Proteins ; RNA Cap-Binding Proteins ; RNA, Messenger ; Receptors, Cytoplasmic and Nuclear ; SNUPN protein, human ; TPR protein, human ; ran GTP-Binding Protein (EC 3.6.5.2)
    Sprache Englisch
    Erscheinungsdatum 2014-04-10
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0093709
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Brownian dynamics simulation of nucleocytoplasmic transport: a coarse-grained model for the functional state of the nuclear pore complex.

    Moussavi-Baygi, Ruhollah / Jamali, Yousef / Karimi, Reza / Mofrad, Mohammad R K

    PLoS computational biology

    2011  Band 7, Heft 6, Seite(n) e1002049

    Abstract: The nuclear pore complex (NPC) regulates molecular traffic across the nuclear envelope (NE). Selective transport happens on the order of milliseconds and the length scale of tens of nanometers; however, the transport mechanism remains elusive. Central to ...

    Abstract The nuclear pore complex (NPC) regulates molecular traffic across the nuclear envelope (NE). Selective transport happens on the order of milliseconds and the length scale of tens of nanometers; however, the transport mechanism remains elusive. Central to the transport process is the hydrophobic interactions between karyopherins (kaps) and Phe-Gly (FG) repeat domains. Taking into account the polymeric nature of FG-repeats grafted on the elastic structure of the NPC, and the kap-FG hydrophobic affinity, we have established a coarse-grained model of the NPC structure that mimics nucleocytoplasmic transport. To establish a foundation for future works, the methodology and biophysical rationale behind the model is explained in details. The model predicts that the first-passage time of a 15 nm cargo-complex is about 2.6±0.13 ms with an inverse Gaussian distribution for statistically adequate number of independent Brownian dynamics simulations. Moreover, the cargo-complex is primarily attached to the channel wall where it interacts with the FG-layer as it passes through the central channel. The kap-FG hydrophobic interaction is highly dynamic and fast, which ensures an efficient translocation through the NPC. Further, almost all eight hydrophobic binding spots on kap-β are occupied simultaneously during transport. Finally, as opposed to intact NPCs, cytoplasmic filaments-deficient NPCs show a high degree of permeability to inert cargos, implying the defining role of cytoplasmic filaments in the selectivity barrier.
    Mesh-Begriff(e) Active Transport, Cell Nucleus ; Animals ; Cytoskeleton/metabolism ; Elastic Modulus ; Hydrophobic and Hydrophilic Interactions ; Models, Biological ; Molecular Dynamics Simulation ; Nuclear Pore/chemistry ; Nuclear Pore/metabolism ; Nucleocytoplasmic Transport Proteins/chemistry ; Nucleocytoplasmic Transport Proteins/metabolism ; Oocytes ; Protein Structure, Tertiary ; Viscosity ; Xenopus
    Chemische Substanzen Nucleocytoplasmic Transport Proteins
    Sprache Englisch
    Erscheinungsdatum 2011-06-02
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2193340-6
    ISSN 1553-7358 ; 1553-734X
    ISSN (online) 1553-7358
    ISSN 1553-734X
    DOI 10.1371/journal.pcbi.1002049
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: The DNA methylation landscape of advanced prostate cancer.

    Zhao, Shuang G / Chen, William S / Li, Haolong / Foye, Adam / Zhang, Meng / Sjöström, Martin / Aggarwal, Rahul / Playdle, Denise / Liao, Arnold / Alumkal, Joshi J / Das, Rajdeep / Chou, Jonathan / Hua, Junjie T / Barnard, Travis J / Bailey, Adina M / Chow, Eric D / Perry, Marc D / Dang, Ha X / Yang, Rendong /
    Moussavi-Baygi, Ruhollah / Zhang, Li / Alshalalfa, Mohammed / Laura Chang, S / Houlahan, Kathleen E / Shiah, Yu-Jia / Beer, Tomasz M / Thomas, George / Chi, Kim N / Gleave, Martin / Zoubeidi, Amina / Reiter, Robert E / Rettig, Matthew B / Witte, Owen / Yvonne Kim, M / Fong, Lawrence / Spratt, Daniel E / Morgan, Todd M / Bose, Rohit / Huang, Franklin W / Li, Hui / Chesner, Lisa / Shenoy, Tanushree / Goodarzi, Hani / Asangani, Irfan A / Sandhu, Shahneen / Lang, Joshua M / Mahajan, Nupam P / Lara, Primo N / Evans, Christopher P / Febbo, Phillip / Batzoglou, Serafim / Knudsen, Karen E / He, Housheng H / Huang, Jiaoti / Zwart, Wilbert / Costello, Joseph F / Luo, Jianhua / Tomlins, Scott A / Wyatt, Alexander W / Dehm, Scott M / Ashworth, Alan / Gilbert, Luke A / Boutros, Paul C / Farh, Kyle / Chinnaiyan, Arul M / Maher, Christopher A / Small, Eric J / Quigley, David A / Feng, Felix Y

    Nature genetics

    2020  Band 52, Heft 8, Seite(n) 778–789

    Abstract: Although DNA methylation is a key regulator of gene expression, the comprehensive methylation landscape of metastatic cancer has never been defined. Through whole-genome bisulfite sequencing paired with deep whole-genome and transcriptome sequencing of ... ...

    Abstract Although DNA methylation is a key regulator of gene expression, the comprehensive methylation landscape of metastatic cancer has never been defined. Through whole-genome bisulfite sequencing paired with deep whole-genome and transcriptome sequencing of 100 castration-resistant prostate metastases, we discovered alterations affecting driver genes that were detectable only with integrated whole-genome approaches. Notably, we observed that 22% of tumors exhibited a novel epigenomic subtype associated with hypermethylation and somatic mutations in TET2, DNMT3B, IDH1 and BRAF. We also identified intergenic regions where methylation is associated with RNA expression of the oncogenic driver genes AR, MYC and ERG. Finally, we showed that differential methylation during progression preferentially occurs at somatic mutational hotspots and putative regulatory regions. This study is a large integrated study of whole-genome, whole-methylome and whole-transcriptome sequencing in metastatic cancer that provides a comprehensive overview of the important regulatory role of methylation in metastatic castration-resistant prostate cancer.
    Mesh-Begriff(e) Aged ; Aged, 80 and over ; Carcinogenesis/genetics ; DNA Methylation/genetics ; Epigenomics/methods ; Gene Expression Regulation, Neoplastic/genetics ; Genome/genetics ; Humans ; Male ; Middle Aged ; Mutation/genetics ; Prospective Studies ; Prostatic Neoplasms/genetics ; Sequence Analysis, DNA/methods ; Whole Exome Sequencing/methods ; Whole Genome Sequencing/methods
    Sprache Englisch
    Erscheinungsdatum 2020-07-13
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Multicenter Study ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1108734-1
    ISSN 1546-1718 ; 1061-4036
    ISSN (online) 1546-1718
    ISSN 1061-4036
    DOI 10.1038/s41588-020-0648-8
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel: Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer

    Quigley, David A / Dang, Ha X / Zhao, Shuang G / Lloyd, Paul / Aggarwal, Rahul / Alumkal, Joshi J / Foye, Adam / Kothari, Vishal / Perry, Marc D / Bailey, Adina M / Playdle, Denise / Barnard, Travis J / Zhang, Li / Zhang, Jin / Youngren, Jack F / Cieslik, Marcin P / Parolia, Abhijit / Beer, Tomasz M / Thomas, George /
    Chi, Kim N / Gleave, Martin / Lack, Nathan A / Zoubeidi, Amina / Reiter, Robert E / Rettig, Matthew B / Witte, Owen / Ryan, Charles J / Fong, Lawrence / Kim, Won / Friedlander, Terence / Chou, Jonathan / Li, Haolong / Das, Rajdeep / Li, Hui / Moussavi-Baygi, Ruhollah / Goodarzi, Hani / Gilbert, Luke A / Lara, Primo N / Evans, Christopher P / Goldstein, Theodore C / Stuart, Joshua M / Tomlins, Scott A / Spratt, Daniel E / Cheetham, R. Keira / Cheng, Donavan T / Farh, Kyle / Gehring, Julian S / Hakenberg, Jörg / Liao, Arnold / Febbo, Philip G / Shon, John / Sickler, Brad / Batzoglou, Serafim / Knudsen, Karen E / He, Housheng H / Huang, Jiaoti / Wyatt, Alexander W / Dehm, Scott M / Ashworth, Alan / Chinnaiyan, Arul M / Maher, Christopher A / Small, Eric J / Feng, Felix Y

    Cell. 2018 July 26, v. 174, no. 3

    2018  

    Abstract: While mutations affecting protein-coding regions have been examined across many cancers, structural variants at the genome-wide level are still poorly defined. Through integrative deep whole-genome and -transcriptome analysis of 101 castration-resistant ... ...

    Abstract While mutations affecting protein-coding regions have been examined across many cancers, structural variants at the genome-wide level are still poorly defined. Through integrative deep whole-genome and -transcriptome analysis of 101 castration-resistant prostate cancer metastases (109X tumor/38X normal coverage), we identified structural variants altering critical regulators of tumorigenesis and progression not detectable by exome approaches. Notably, we observed amplification of an intergenic enhancer region 624 kb upstream of the androgen receptor (AR) in 81% of patients, correlating with increased AR expression. Tandem duplication hotspots also occur near MYC, in lncRNAs associated with post-translational MYC regulation. Classes of structural variations were linked to distinct DNA repair deficiencies, suggesting their etiology, including associations of CDK12 mutation with tandem duplications, TP53 inactivation with inverted rearrangements and chromothripsis, and BRCA2 inactivation with deletions. Together, these observations provide a comprehensive view of how structural variations affect critical regulators in metastatic prostate cancer.
    Schlagwörter DNA repair ; androgen receptors ; carcinogenesis ; etiology ; genomics ; metastasis ; mutation ; patients ; prostatic neoplasms ; tumor suppressor proteins
    Sprache Englisch
    Erscheinungsverlauf 2018-0726
    Umfang p. 758-769.e9.
    Erscheinungsort Elsevier Inc.
    Dokumenttyp Artikel
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2018.06.039
    Datenquelle NAL Katalog (AGRICOLA)

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  7. Artikel ; Online: Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer.

    Quigley, David A / Dang, Ha X / Zhao, Shuang G / Lloyd, Paul / Aggarwal, Rahul / Alumkal, Joshi J / Foye, Adam / Kothari, Vishal / Perry, Marc D / Bailey, Adina M / Playdle, Denise / Barnard, Travis J / Zhang, Li / Zhang, Jin / Youngren, Jack F / Cieslik, Marcin P / Parolia, Abhijit / Beer, Tomasz M / Thomas, George /
    Chi, Kim N / Gleave, Martin / Lack, Nathan A / Zoubeidi, Amina / Reiter, Robert E / Rettig, Matthew B / Witte, Owen / Ryan, Charles J / Fong, Lawrence / Kim, Won / Friedlander, Terence / Chou, Jonathan / Li, Haolong / Das, Rajdeep / Li, Hui / Moussavi-Baygi, Ruhollah / Goodarzi, Hani / Gilbert, Luke A / Lara, Primo N / Evans, Christopher P / Goldstein, Theodore C / Stuart, Joshua M / Tomlins, Scott A / Spratt, Daniel E / Cheetham, R Keira / Cheng, Donavan T / Farh, Kyle / Gehring, Julian S / Hakenberg, Jörg / Liao, Arnold / Febbo, Philip G / Shon, John / Sickler, Brad / Batzoglou, Serafim / Knudsen, Karen E / He, Housheng H / Huang, Jiaoti / Wyatt, Alexander W / Dehm, Scott M / Ashworth, Alan / Chinnaiyan, Arul M / Maher, Christopher A / Small, Eric J / Feng, Felix Y

    Cell

    2018  Band 175, Heft 3, Seite(n) 889

    Sprache Englisch
    Erscheinungsdatum 2018-10-18
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Published Erratum
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2018.10.019
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  8. Artikel ; Online: Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer.

    Quigley, David A / Dang, Ha X / Zhao, Shuang G / Lloyd, Paul / Aggarwal, Rahul / Alumkal, Joshi J / Foye, Adam / Kothari, Vishal / Perry, Marc D / Bailey, Adina M / Playdle, Denise / Barnard, Travis J / Zhang, Li / Zhang, Jin / Youngren, Jack F / Cieslik, Marcin P / Parolia, Abhijit / Beer, Tomasz M / Thomas, George /
    Chi, Kim N / Gleave, Martin / Lack, Nathan A / Zoubeidi, Amina / Reiter, Robert E / Rettig, Matthew B / Witte, Owen / Ryan, Charles J / Fong, Lawrence / Kim, Won / Friedlander, Terence / Chou, Jonathan / Li, Haolong / Das, Rajdeep / Li, Hui / Moussavi-Baygi, Ruhollah / Goodarzi, Hani / Gilbert, Luke A / Lara, Primo N / Evans, Christopher P / Goldstein, Theodore C / Stuart, Joshua M / Tomlins, Scott A / Spratt, Daniel E / Cheetham, R Keira / Cheng, Donavan T / Farh, Kyle / Gehring, Julian S / Hakenberg, Jörg / Liao, Arnold / Febbo, Philip G / Shon, John / Sickler, Brad / Batzoglou, Serafim / Knudsen, Karen E / He, Housheng H / Huang, Jiaoti / Wyatt, Alexander W / Dehm, Scott M / Ashworth, Alan / Chinnaiyan, Arul M / Maher, Christopher A / Small, Eric J / Feng, Felix Y

    Cell

    2018  Band 174, Heft 3, Seite(n) 758–769.e9

    Abstract: While mutations affecting protein-coding regions have been examined across many cancers, structural variants at the genome-wide level are still poorly defined. Through integrative deep whole-genome and -transcriptome analysis of 101 castration-resistant ... ...

    Abstract While mutations affecting protein-coding regions have been examined across many cancers, structural variants at the genome-wide level are still poorly defined. Through integrative deep whole-genome and -transcriptome analysis of 101 castration-resistant prostate cancer metastases (109X tumor/38X normal coverage), we identified structural variants altering critical regulators of tumorigenesis and progression not detectable by exome approaches. Notably, we observed amplification of an intergenic enhancer region 624 kb upstream of the androgen receptor (AR) in 81% of patients, correlating with increased AR expression. Tandem duplication hotspots also occur near MYC, in lncRNAs associated with post-translational MYC regulation. Classes of structural variations were linked to distinct DNA repair deficiencies, suggesting their etiology, including associations of CDK12 mutation with tandem duplications, TP53 inactivation with inverted rearrangements and chromothripsis, and BRCA2 inactivation with deletions. Together, these observations provide a comprehensive view of how structural variations affect critical regulators in metastatic prostate cancer.
    Mesh-Begriff(e) Aged ; Aged, 80 and over ; BRCA2 Protein/metabolism ; Cyclin-Dependent Kinases/metabolism ; DNA Copy Number Variations ; Exome ; Gene Expression Profiling/methods ; Genomic Structural Variation/genetics ; Genomics/methods ; Humans ; Male ; Middle Aged ; Mutation ; Neoplasm Metastasis/genetics ; Prostatic Neoplasms/genetics ; Proto-Oncogene Proteins c-myc/genetics ; Proto-Oncogene Proteins c-myc/metabolism ; Receptors, Androgen/genetics ; Receptors, Androgen/metabolism ; Tandem Repeat Sequences/genetics ; Tumor Suppressor Protein p53/metabolism ; Whole Genome Sequencing/methods
    Chemische Substanzen AR protein, human ; BRCA2 Protein ; BRCA2 protein, human ; MYC protein, human ; Proto-Oncogene Proteins c-myc ; Receptors, Androgen ; TP53 protein, human ; Tumor Suppressor Protein p53 ; CDK12 protein, human (EC 2.7.11.22) ; Cyclin-Dependent Kinases (EC 2.7.11.22)
    Sprache Englisch
    Erscheinungsdatum 2018-07-19
    Erscheinungsland United States
    Dokumenttyp 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 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2018.06.039
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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