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  1. Article ; Online: Stochastic pulsing of gene expression enables the generation of spatial patterns in Bacillus subtilis biofilms.

    Nadezhdin, Eugene / Murphy, Niall / Dalchau, Neil / Phillips, Andrew / Locke, James C W

    Nature communications

    2020  Volume 11, Issue 1, Page(s) 950

    Abstract: Stochastic pulsing of gene expression can generate phenotypic diversity in a genetically identical population of cells, but it is unclear whether it has a role in the development of multicellular systems. Here, we show how stochastic pulsing of gene ... ...

    Abstract Stochastic pulsing of gene expression can generate phenotypic diversity in a genetically identical population of cells, but it is unclear whether it has a role in the development of multicellular systems. Here, we show how stochastic pulsing of gene expression enables spatial patterns to form in a model multicellular system, Bacillus subtilis bacterial biofilms. We use quantitative microscopy and time-lapse imaging to observe pulses in the activity of the general stress response sigma factor σ
    MeSH term(s) Bacillus subtilis/genetics ; Bacillus subtilis/metabolism ; Bacillus subtilis/physiology ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Biofilms/growth & development ; Gene Expression Regulation, Bacterial ; Genetic Heterogeneity ; Microscopy, Fluorescence ; Models, Biological ; Sigma Factor/genetics ; Sigma Factor/metabolism ; Spores, Bacterial/genetics ; Spores, Bacterial/metabolism ; Spores, Bacterial/physiology ; Stochastic Processes ; Stress, Physiological ; Time-Lapse Imaging
    Chemical Substances Bacterial Proteins ; Sigma Factor
    Language English
    Publishing date 2020-02-19
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-020-14431-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: An α/β hydrolase and associated Per-ARNT-Sim domain comprise a bipartite sensing module coupled with diverse output domains.

    Nadezhdin, Eugene V / Brody, Margaret S / Price, Chester W

    PloS one

    2011  Volume 6, Issue 9, Page(s) e25418

    Abstract: The RsbQ α/β hydrolase and RsbP serine phosphatase form a signaling pair required to activate the general stress factor σ(B) of Bacillus subtilis in response to energy limitation. RsbP has a predicted N-terminal Per-ARNT-Sim (PAS) domain, a central ... ...

    Abstract The RsbQ α/β hydrolase and RsbP serine phosphatase form a signaling pair required to activate the general stress factor σ(B) of Bacillus subtilis in response to energy limitation. RsbP has a predicted N-terminal Per-ARNT-Sim (PAS) domain, a central coiled-coil, and a C-terminal protein phosphatase M (PPM) domain. Previous studies support a model in which RsbQ provides an activity needed for PAS to regulate the phosphatase domain via the coiled-coil. RsbQ and the PAS domain (RsbP-PAS) therefore appear to form a sensory module. Here we test this hypothesis using bioinformatic and genetic analysis. We found 45 RsbQ and RsbP-PAS homologues encoded by adjacent genes in diverse bacteria, with PAS and a predicted coiled-coil fused to one of three output domains: PPM phosphatase (Gram positive bacteria), histidine protein kinase (Gram negative bacteria), and diguanylate cyclase (both lineages). Multiple alignment of the RsbP-PAS homologues suggested nine residues that distinguish the class. Alanine substitutions at four of these conferred a null phenotype in B. subtilis, indicating their functional importance. The F55A null substitution lay in the Fα helix of an RsbP-PAS model. F55A inhibited interaction of RsbP with RsbQ in yeast two-hybrid and pull-down assays but did not significantly affect interaction of RsbP with itself. We propose that RsbQ directly contacts the PAS domains of an RsbP oligomer to provide the activating signal, which is propagated to the phosphatase domains via the coiled-coil. A similar mechanism would allow the RsbQ-PAS module to convey a common input signal to structurally diverse output domains, controlling a variety of physiological responses.
    MeSH term(s) Amino Acid Sequence ; Amino Acid Substitution ; Bacillus subtilis/cytology ; Bacillus subtilis/genetics ; Bacillus subtilis/metabolism ; Bacterial Proteins/chemistry ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Computational Biology ; Genetic Techniques ; Models, Molecular ; Molecular Sequence Data ; Phosphoproteins/chemistry ; Phosphoproteins/genetics ; Phosphoproteins/metabolism ; Protein Structure, Tertiary ; Sequence Alignment ; Sequence Homology, Nucleic Acid ; Signal Transduction
    Chemical Substances Bacterial Proteins ; Phosphoproteins ; RsbR protein, Bacillus subtilis
    Language English
    Publishing date 2011-09-29
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0025418
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Ruxolitinib Versus Best Available Therapy for Polycythemia Vera Intolerant or Resistant to Hydroxycarbamide in a Randomized Trial.

    Harrison, Claire N / Nangalia, Jyoti / Boucher, Rebecca / Jackson, Aimee / Yap, Christina / O'Sullivan, Jennifer / Fox, Sonia / Ailts, Isaak / Dueck, Amylou C / Geyer, Holly L / Mesa, Ruben A / Dunn, William G / Nadezhdin, Eugene / Curto-Garcia, Natalia / Green, Anna / Wilkins, Bridget / Coppell, Jason / Laurie, John / Garg, Mamta /
    Ewing, Joanne / Knapper, Steven / Crowe, Josephine / Chen, Frederick / Koutsavlis, Ioannis / Godfrey, Anna / Arami, Siamak / Drummond, Mark / Byrne, Jennifer / Clark, Fiona / Mead-Harvey, Carolyn / Baxter, Elizabeth Joanna / McMullin, Mary Frances / Mead, Adam J

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology

    2023  Volume 41, Issue 19, Page(s) 3534–3544

    Abstract: Purpose: Polycythemia vera (PV) is characterized by JAK/STAT activation, thrombotic/hemorrhagic events, systemic symptoms, and disease transformation. In high-risk PV, ruxolitinib controls blood counts and improves symptoms.: Patients and methods: ... ...

    Abstract Purpose: Polycythemia vera (PV) is characterized by JAK/STAT activation, thrombotic/hemorrhagic events, systemic symptoms, and disease transformation. In high-risk PV, ruxolitinib controls blood counts and improves symptoms.
    Patients and methods: MAJIC-PV is a randomized phase II trial of ruxolitinib versus best available therapy (BAT) in patients resistant/intolerant to hydroxycarbamide (HC-INT/RES). Primary outcome was complete response (CR) within 1 year. Secondary outcomes included duration of response, event-free survival (EFS), symptom, and molecular response.
    Results: One hundred eighty patients were randomly assigned. CR was achieved in 40 (43%) patients on ruxolitinib versus 23 (26%) on BAT (odds ratio, 2.12; 90% CI, 1.25 to 3.60;
    Conclusion: The MAJIC-PV study demonstrates ruxolitinib treatment benefits HC-INT/RES PV patients with superior CR, and EFS as well as molecular response; importantly also demonstrating for the first time, to our knowledge, that molecular response is linked to EFS, PFS, and OS.
    MeSH term(s) Humans ; Polycythemia Vera/drug therapy ; Polycythemia Vera/genetics ; Polycythemia Vera/complications ; Treatment Outcome ; Hydroxyurea/adverse effects ; Nitriles/therapeutic use ; Hemorrhage/complications ; Hemorrhage/drug therapy
    Chemical Substances ruxolitinib (82S8X8XX8H) ; Hydroxyurea (X6Q56QN5QC) ; Nitriles
    Language English
    Publishing date 2023-05-01
    Publishing country United States
    Document type Randomized Controlled Trial ; Clinical Trial, Phase II ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 604914-x
    ISSN 1527-7755 ; 0732-183X
    ISSN (online) 1527-7755
    ISSN 0732-183X
    DOI 10.1200/JCO.22.01935
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  4. Article: Oil and gas industries in Central and Eastern Europe and in the USSR

    Nadezhdin, Eugene

    Energy systems and policy : an international interdisciplinary journal 15 ,2, S. 99-119

    status, problems, and prospects

    1991  

    Author's details Eugene Nadezhdin
    Keywords Mineralölwirtschaft ; Gaswirtschaft ; Energieprognose ; Osteuropa ; Sowjetunion
    Language English
    Publisher Crane, Russak & Co
    Publishing place New York, NY
    Document type Article
    ZDB-ID 191972-6
    ISSN 0090-8347
    Database ECONomics Information System

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