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  • Sterol biosynthesis and sterol uptake in the fungal pathogen Pneumocsytis carinii

    Document thumbnail: Sterol biosynthesis and sterol uptake in the fungal pathogen Pneumocsytis carinii
    Type:
    Document
    Description/Abstract:
    Fungi in the genus Pneumocystis are the cause of a potentially life threatening pneumonia, Pneumocystis pneumonia (PCP). The understanding of the lifecycle, metabolism, and drug development has been hindered due to a lack of a long term in vitro culture system. Unlike most other fungi, members of the genus Pneumocystis do not appear to synthesize the major fungal sterol, ergosterol. However, genome scans and in vitro assays suggest the presence of functional genes involved in a sterol pathway. One of the goals of this work was to characterize the P. carinii sterol enzyme, lanosterol synthase (Erg7p), an essential enzyme of the sterol pathway. The activity of P. carinii Erg7p was assessed by heterologous expression of P. carinii Erg7p in a Saccharomyces cerevisiae Erg7p null mutant. Growth rates and lanosterol production were similar between S. cerevisiae expressing the P. carinii enzyme and S. cerevisiae expressing its own Erg7p under the same conditions, indicating that not only does P. carinii produce a functional Erg7p, but also that the enzyme functionally complements the S. cerevisiae enzyme. Western blotting and fluorescent localization studies revealed that P. carinii Erg7p localizes to lipid particles in S. cerevisiae as does S. cerevisiae Erg7p. A novel finding of these studies, was that P. carinii contains lipid particles, and that P. carinii Erg7p localizes to lipid particles in P. carinii. These studies indicate that P. carinii Erg7p functions similar to the S. cerevisiae enzyme, and may perform a similar function in P. carinii. Biochemical analyses of sterols within the membranes of P. carinii have shown that it utilizes cholesterol rather than ergosterol as its bulk sterol. However, P. carinii does not appear to synthesize cholesterol from a de novo pathway, but rather scavenges exogenous sterols from its mammalian host. S. cerevisiae is induced to undergo sterol scavenging under anaerobic conditions. Consequently, another goal of this work was to provide information on the effect of O2 on sterol biosynthesis and sterol scavenging by P. carinii. ATP measurements revealed that the viability of P. carinii is severely decreased when maintained under hypoxic conditions, and this decrease correlated with an increase in drug susceptibility. We show that uptake of exogenous cholesterol by P. carinii occurred under normal O2 tensions, indicating that sterol scavenging is not limited to anaerobic conditions. Microarray analysis indicated that hypoxic maintenance of P. carinii resulted in decreased transcription of several genes involved in sterol and lipid biosynthesis suggesting that while hypoxic conditions down-regulated genes involved in sterol biosynthesis, down-regulation of sterol biosynthesis is not a requirement for sterol scavenging in P. carinii. The ability of P. carinii to scavenge exogenous sterols under normal O2 tensions at which the sterol pathway is unaffected provides evidence that sterol scavenging may be the primary means that P. carinii utilizes to obtain its sterols.
    Creator/Author:
    Grant, Tiffany
    Submitter:
    Tiffany Grant
    Date Uploaded:
    04/14/2016
    Date Modified:
    08/09/2016
    License:
    All rights reserved

  • Ctenantedon kinziei 1a

    Image thumbnail: Ctenantedon kinziei 1a
    Type:
    Image
    Description/Abstract:
    Ctenantedon kinziei - discovery specimen, aboral side
    Creator/Author:
    Meyer, David L.
    Submitter:
    David L. Meyer
    Date Uploaded:
    04/13/2016
    Date Modified:
    08/01/2016
    Date Created:
    2016-04-13
    License:
    Attribution-NonCommercial 4.0 International

  • Ctenantedon kinziei 1

    Image thumbnail: Ctenantedon kinziei 1
    Type:
    Image
    Description/Abstract:
    Ctenantedon kinziei - discovery specimen, oral side
    Creator/Author:
    Meyer, David L.
    Submitter:
    David L. Meyer
    Date Uploaded:
    04/13/2016
    Date Modified:
    08/01/2016
    Date Created:
    2016-04-13
    License:
    Attribution-NonCommercial 4.0 International

  • Davidaster "yellow-tip" 5

    Image thumbnail: Davidaster "yellow-tip" 5
    Type:
    Image
    Description/Abstract:
    D. "yellow-tip"
    Creator/Author:
    Meyer, David L.
    Submitter:
    David L. Meyer
    Date Uploaded:
    04/13/2016
    Date Modified:
    08/01/2016
    Date Created:
    2016-04-13
    License:
    Attribution-NonCommercial 4.0 International

  • Davidaster "yellow-tip" 4

    Image thumbnail: Davidaster "yellow-tip" 4
    Type:
    Image
    Description/Abstract:
    D. "yellow-tip"
    Creator/Author:
    Sacco, William K. (photographer) and Meyer, David L.
    Submitter:
    David L. Meyer
    Date Uploaded:
    04/13/2016
    Date Modified:
    08/01/2016
    Date Created:
    2016-04-13
    License:
    Attribution-NonCommercial 4.0 International

  • Davidaster "yellow-tip" 3

    Image thumbnail: Davidaster "yellow-tip" 3
    Type:
    Image
    Description/Abstract:
    D. "yellow-tip"
    Creator/Author:
    Sacco, William K. (photographer) and Meyer, David L.
    Submitter:
    David L. Meyer
    Date Uploaded:
    04/13/2016
    Date Modified:
    08/01/2016
    Date Created:
    2016-04-13
    License:
    Attribution-NonCommercial 4.0 International

  • Davidaster "yellow tip" 2

    Image thumbnail: Davidaster "yellow tip" 2
    Type:
    Image
    Description/Abstract:
    D. " yellow tip"
    Creator/Author:
    Sacco, William K. (photographer) and Meyer, David L.
    Submitter:
    David L. Meyer
    Date Uploaded:
    04/12/2016
    Date Modified:
    08/02/2016
    Date Created:
    2016-04-12
    License:
    Attribution-NonCommercial 4.0 International

  • Davidaster "yellow tip" 1

    Image thumbnail: Davidaster "yellow tip" 1
    Type:
    Image
    Description/Abstract:
    D. "yellow tip"
    Creator/Author:
    Meyer, David L.
    Submitter:
    David L. Meyer
    Date Uploaded:
    04/12/2016
    Date Modified:
    08/02/2016
    Date Created:
    2016-04-12
    License:
    Attribution-NonCommercial 4.0 International

  • Davidaster discoidea 8

    Image thumbnail: Davidaster discoidea 8
    Type:
    Image
    Description/Abstract:
    D. discoidea
    Creator/Author:
    Meyer, David L.
    Submitter:
    David L. Meyer
    Date Uploaded:
    04/12/2016
    Date Modified:
    08/02/2016
    Date Created:
    2016-04-12
    License:
    Attribution-NonCommercial 4.0 International

  • Sound & Music Part 4 of 5 Digital Recording, Signal Processing, Movie, Television, and Live Sound iBook Version

    Document thumbnail: Sound & Music Part 4 of 5 Digital Recording, Signal Processing, Movie, Television, and Live Sound iBook Version
    Type:
    Document
    Description/Abstract:
    This is the iBook version of chapter four of five. It requires the iBooks app to read. The media is embedded so no internet connection is necessary after the book has been downloaded. It contains many interactive widgets and videos that are not found in the epub, pdf, and mobi versions. However, the file size for this format is much larger and requires the book to be broken into individual chapters. All the text can be read by clicking the Closed Caption (CC) button on each video. There are keywords on the right side of each page to enable word searches.
    Creator/Author:
    Petach, Jay
    Submitter:
    Jay Petach
    Date Uploaded:
    12/06/2016
    Date Modified:
    12/06/2016
    Date Created:
    2016-12-05
    License:
    All rights reserved