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  1. Article ; Online: Dynamic Changes in Heparan Sulfate Nanostructure in Human Pluripotent Stem Cell Differentiation.

    Al Mahbuba, Deena / Masuko, Sayaka / Wang, Shiwei / Syangtan, Deepsing / Kang, Jeong Seuk / Song, Yuefan / Shin, Tay Won / Xia, Ke / Zhang, Fuming / Linhardt, Robert J / Boyden, Edward S / Kiessling, Laura L

    ACS nano

    2023  Volume 17, Issue 8, Page(s) 7207–7218

    Abstract: Heparan sulfate (HS) is a heterogeneous, cell-surface polysaccharide critical for transducing signals essential for mammalian development. Imaging of signaling proteins has revealed how their localization influences their information transfer. In ... ...

    Abstract Heparan sulfate (HS) is a heterogeneous, cell-surface polysaccharide critical for transducing signals essential for mammalian development. Imaging of signaling proteins has revealed how their localization influences their information transfer. In contrast, the contribution of the spatial distribution and nanostructure of information-rich, signaling polysaccharides like HS is not known. Using expansion microscopy (ExM), we found striking changes in HS nanostructure occur as human pluripotent stem (hPS) cells differentiate, and these changes correlate with growth factor signaling. Our imaging studies show that undifferentiated hPS cells are densely coated with HS displayed as hair-like protrusions. This ultrastructure can recruit fibroblast growth factor for signaling. When the hPS cells differentiate into the ectoderm lineage, HS is localized into dispersed puncta. This striking change in HS distribution coincides with a decrease in fibroblast growth factor binding to neural cells. While developmental variations in HS sequence were thought to be the primary driver of alterations in HS-mediated growth factor signaling, our high-resolution images indicate a role for the HS nanostructure. Our study highlights the utility of high-resolution glycan imaging using ExM. In the case of HS, we found that changes in how the polysaccharide is displayed link to profound differences in growth factor binding.
    MeSH term(s) Animals ; Humans ; Heparitin Sulfate/chemistry ; Heparitin Sulfate/metabolism ; Cell Differentiation ; Pluripotent Stem Cells/metabolism ; Signal Transduction ; Fibroblast Growth Factors ; Mammals/metabolism
    Chemical Substances Heparitin Sulfate (9050-30-0) ; Fibroblast Growth Factors (62031-54-3)
    Language English
    Publishing date 2023-04-12
    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.
    ISSN 1936-086X
    ISSN (online) 1936-086X
    DOI 10.1021/acsnano.2c10072
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Transcript decay mediated by RNase III in Borrelia burgdorferi

    Snow, Santina / Bacon, Emily / Bergeron, Jennifer / Katzman, David / Wilhelm, Amelia / Lewis, Owen / Syangtan, Deepsing / Calkins, Andrew / Archambault, Linda / Anacker, Melissa L / Schlax, Paula Jean

    Biochemical and biophysical research communications. 2020 Aug. 20, v. 529, no. 2

    2020  

    Abstract: The causative agent of Lyme disease, Borrelia burgdorferi, requires shifts in gene expression to undergo its natural enzootic cycle between tick and vertebrate hosts. mRNA decay mechanisms play significant roles in governing gene expression in other ... ...

    Abstract The causative agent of Lyme disease, Borrelia burgdorferi, requires shifts in gene expression to undergo its natural enzootic cycle between tick and vertebrate hosts. mRNA decay mechanisms play significant roles in governing gene expression in other bacteria, but are not yet characterized in B. burgdorferi. RNase III is an important enzyme in processing ribosomal RNA, but it also plays a role in mRNA decay in many bacteria. We compared RNA decay profiles and steady-state abundances of transcripts in wild-type Borrelia burgdorferi strain B31 and in an RNase III null (rnc⁻) mutant. Transcripts encoding RNA polymerase subunits (rpoA and rpoS), ribosomal proteins (rpsD, rpsK, rpsM, rplQ, and rpsO), a nuclease (pnp), a flagellar protein (flaB), and a translational regulator (bpuR) decayed more rapidly in the wild-type strain than in the slow growing rnc⁻ mutant indicating that RNA turnover is mediated by RNase III in the bacterium that causes Lyme disease. Additionally, in wild type bacteria, RNA decay rates of rpoS, rpoN, ospA, ospC, bpuR and dbpA transcripts are only modestly affected by changes in the osmolarity.
    Keywords Borrelia burgdorferi ; DNA-directed RNA polymerase ; Lyme disease ; bacteria ; enzootic diseases ; etiological agents ; gene expression ; mutants ; osmolarity ; research ; ribonucleases ; ribosomal RNA ; ticks ; vertebrates
    Language English
    Dates of publication 2020-0820
    Size p. 386-391.
    Publishing place Elsevier Inc.
    Document type Article
    Note NAL-AP-2-clean
    ZDB-ID 205723-2
    ISSN 0006-291X ; 0006-291X
    ISSN (online) 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2020.05.201
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Bonn / Germany

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  3. Article ; Online: Transcript decay mediated by RNase III in Borrelia burgdorferi.

    Snow, Santina / Bacon, Emily / Bergeron, Jennifer / Katzman, David / Wilhelm, Amelia / Lewis, Owen / Syangtan, Deepsing / Calkins, Andrew / Archambault, Linda / Anacker, Melissa L / Schlax, Paula Jean

    Biochemical and biophysical research communications

    2020  Volume 529, Issue 2, Page(s) 386–391

    Abstract: The causative agent of Lyme disease, Borrelia burgdorferi, requires shifts in gene expression to undergo its natural enzootic cycle between tick and vertebrate hosts. mRNA decay mechanisms play significant roles in governing gene expression in other ... ...

    Abstract The causative agent of Lyme disease, Borrelia burgdorferi, requires shifts in gene expression to undergo its natural enzootic cycle between tick and vertebrate hosts. mRNA decay mechanisms play significant roles in governing gene expression in other bacteria, but are not yet characterized in B. burgdorferi. RNase III is an important enzyme in processing ribosomal RNA, but it also plays a role in mRNA decay in many bacteria. We compared RNA decay profiles and steady-state abundances of transcripts in wild-type Borrelia burgdorferi strain B31 and in an RNase III null (rnc
    MeSH term(s) Animals ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Borrelia burgdorferi/genetics ; Borrelia burgdorferi/metabolism ; Gene Deletion ; Gene Expression Regulation, Bacterial ; Humans ; Lyme Disease/microbiology ; RNA Stability ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Ribonuclease III/genetics ; Ribonuclease III/metabolism
    Chemical Substances Bacterial Proteins ; RNA, Messenger ; Ribonuclease III (EC 3.1.26.3)
    Language English
    Publishing date 2020-07-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 205723-2
    ISSN 1090-2104 ; 0006-291X ; 0006-291X
    ISSN (online) 1090-2104 ; 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2020.05.201
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
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  4. Article ; Online: Virtual screening for small-molecule pathway regulators by image-profile matching.

    Rohban, Mohammad H / Fuller, Ashley M / Tan, Ceryl / Goldstein, Jonathan T / Syangtan, Deepsing / Gutnick, Amos / DeVine, Ann / Nijsure, Madhura P / Rigby, Megan / Sacher, Joshua R / Corsello, Steven M / Peppler, Grace B / Bogaczynska, Marta / Boghossian, Andrew / Ciotti, Gabrielle E / Hands, Allison T / Mekareeya, Aroonroj / Doan, Minh / Gale, Jennifer P /
    Derynck, Rik / Turbyville, Thomas / Boerckel, Joel D / Singh, Shantanu / Kiessling, Laura L / Schwarz, Thomas L / Varelas, Xaralabos / Wagner, Florence F / Kafri, Ran / Eisinger-Mathason, T S Karin / Carpenter, Anne E

    Cell systems

    2022  Volume 13, Issue 9, Page(s) 724–736.e9

    Abstract: Identifying the chemical regulators of biological pathways is a time-consuming bottleneck in developing therapeutics and research compounds. Typically, thousands to millions of candidate small molecules are tested in target-based biochemical screens or ... ...

    Abstract Identifying the chemical regulators of biological pathways is a time-consuming bottleneck in developing therapeutics and research compounds. Typically, thousands to millions of candidate small molecules are tested in target-based biochemical screens or phenotypic cell-based screens, both expensive experiments customized to each disease. Here, our uncustomized, virtual, profile-based screening approach instead identifies compounds that match to pathways based on the phenotypic information in public cell image data, created using the Cell Painting assay. Our straightforward correlation-based computational strategy retrospectively uncovered the expected, known small-molecule regulators for 32% of positive-control gene queries. In prospective, discovery mode, we efficiently identified new compounds related to three query genes and validated them in subsequent gene-relevant assays, including compounds that phenocopy or pheno-oppose YAP1 overexpression and kill a Yap1-dependent sarcoma cell line. This image-profile-based approach could replace many customized labor- and resource-intensive screens and accelerate the discovery of biologically and therapeutically useful compounds.
    MeSH term(s) Cell Line ; Prospective Studies ; Retrospective Studies
    Language English
    Publishing date 2022-09-02
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2854138-8
    ISSN 2405-4720 ; 2405-4712
    ISSN (online) 2405-4720
    ISSN 2405-4712
    DOI 10.1016/j.cels.2022.08.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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