Main Menu (Mobile)- Block

Main Menu - Block

janelia7_blocks-janelia7_fake_breadcrumb | block
Lee Tzumin Lab / Publications
general_search_page-panel_pane_1 | views_panes

6 Publications

Showing 1-6 of 6 results
Your Criteria:

    Axon pruning is widely used for the refinement of neural circuits in both vertebrates and invertebrates, and may also contribute to the pathogenesis of neurodegenerative diseases. However, little is known about the cellular and molecular mechanisms of axon pruning. We use the stereotyped pruning of gamma neurons of the Drosophila mushroom bodies (MB) during metamorphosis to investigate these mechanisms. Detailed time course analyses indicate that MB axon pruning is mediated by local degeneration rather than retraction and that the disruption of the microtubule cytoskeleton precedes axon pruning. In addition, multiple lines of genetic evidence demonstrate an intrinsic role of the ubiquitin-proteasome system in axon pruning; for example, loss-of-function mutations of the ubiquitin activating enzyme (E1) or proteasome subunits in MB neurons block axon pruning. Our findings suggest that some forms of axon pruning during development may share similarities with degeneration of axons in response to injury.

    View Publication Page
    06/17/03 | Redesigning an antibody fragment for faster association with its antigen.
    Marvin JS, Lowman HB
    Biochemistry. 2003 Jun 17;42(23):7077-83. doi: 10.1021/bi026947q

    Traditional approaches for increasing the affinity of protein-protein complexes focus on constructing highly complementary binding surfaces. Recent theoretical simulations and experimental results suggest that electrostatic steering forces can also be manipulated to increase association rates while leaving dissociation rates unchanged, thus increasing affinity. Here we demonstrate that electrostatic attraction can be enhanced between an antibody fragment and its cognate antigen through application of a few simple rules to identify potential on-rate amplification sites that lie at the periphery of the antigen-antibody interface.

    View Publication Page
    06/09/03 | Spike sorting in the frequency domain with overlap detection.
    Rinberg D, Bialek W, Davidowitz H, Tishby N

    This paper deals with the problem of extracting the activity of individual neurons from multi-electrode recordings. Important aspects of this work are: 1) the sorting is done in two stages - a statistical model of the spikes from different cells is built and only then are occurrences of these spikes in the data detected by scanning through the original data, 2) the spike sorting is done in the frequency domain, 3) strict statistical tests are applied to determine if and how a spike should be classiffed, 4) the statistical model for detecting overlaping spike events is proposed, 5) slow dynamics of spike shapes are tracked during long experiments. Results from the application of these techniques to data collected from the escape response system of the American cockroach, Periplaneta americana, are presented.

    View Publication Page
    Tjian Lab
    06/01/03 | Diversified transcription initiation complexes expand promoter selectivity and tissue-specific gene expression.
    Hochheimer A, Tjian R
    Genes & Development. 2003 Jun 1;17(11):1309-20. doi: 10.1073/pnas.1100640108
    Truman LabRiddiford Lab
    06/01/03 | E74 exhibits stage-specific hormonal regulation in the epidermis of the tobacco hornworm, manduca sexta.
    Stilwell GE, Nelson CA, Weller J, Cui H, Hiruma K, Truman JW, Riddiford LM
    Developmental Biology. 2003 Jun 1;258(1):76-90

    The transcription factor E74 is one of the early genes induced by ecdysteroids during metamorphosis of Drosophila melanogaster. Here, we report the cloning and hormonal regulation of E74 from the tobacco hornworm, Manduca sexta (MsE74). MsE74 is 98% identical to that of D. melanogaster within the DNA-binding ETS domain of the protein. The 5’-isoform-specific regions of MsE74A and MsE74B share significantly lower sequence similarity (30-40%). Developmental expression by Northern blot analysis reveals that, during the 5th larval instar, MsE74B expression correlates with pupal commitment on day 3 and is induced to maximal levels within 12h by low levels of 20-hydroxyecdysone (20E) and repressed by physiologically relevant levels of juvenile hormone I (JH I). Immunocytochemical analysis shows that MsE74B appears in the epidermis before the 20E-induced Broad transcription factor that is correlated with pupal commitment (Zhou and Riddiford, 2001). In contrast, MsE74A is expressed late in the larval and the pupal molts when the ecdysteroid titer has declined to low levels and in the adult molt just as the ecdysteroid titer begins to decline. This change in timing during the adult molt appears not to be due to the absence of JH as there was no change during the pupal molt of allatectomized animals. When either 4th or 5th instar larval epidermis was explanted and subjected to hormonal manipulations, MsE74A induction occurred only after exposure to 20E followed by its removal. Thus, MsE74B appears to have a similar role at the onset of metamorphosis in Manduca as it does in Drosophila, whereas MsE74A is regulated differently at pupation in Manduca than at pupariation in Drosophila.

    View Publication Page
    Tjian Lab
    06/01/03 | Targeting genes and transcription factors to segregated nuclear compartments.
    Isogai Y, Tjian R
    Current Opinion in Cell Biology. 2003 Jun;15(3):296-303. doi: 10.1073/pnas.1100640108

    With increasingly detailed images of nuclear structures revealed by advanced microscopy, a remarkably compartmentalized cell nucleus has come into focus. Although this complex nuclear organization remains largely unexplored, some progress has been made in deciphering the functional aspects of various subnuclear structures, revealing how this elaborate framework can influence gene activation. Several recent studies have helped illustrate how cells might utilize the nuclear architecture as an additional level of transcriptional control, perhaps by targeting genes and regulatory factors to specific sites within the nucleus that are designated for active RNA synthesis.

    View Publication Page