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18 Publications

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    12/29/95 | Drosophila homologs of baculovirus inhibitor of apoptosis proteins function to block cell death.
    Hay BA, Wassarman DA, Rubin GM
    Cell. 1995 Dec 29;83(7):1253-62. doi: 10.1186/gb-2007-8-7-r145

    Apoptotic cell death is a mechanism by which organisms eliminate superfluous or harmful cells. Expression of the cell death regulatory protein REAPER (RPR) in the developing Drosophila eye results in a small eye owing to excess cell death. We show that mutations in thread (th) are dominant enhancers of RPR-induced cell death and that th encodes a protein homologous to baculovirus inhibitors of apoptosis (IAPs), which we call Drosophila IAP1 (DIAP1). Overexpression of DIAP1 or a related protein, DIAP2, in the eye suppresses normally occurring cell death as well as death due to overexpression of rpr or head involution defective. IAP death-preventing activity localizes to the N-terminal baculovirus IAP repeats, a motif found in both viral and cellular proteins associated with death prevention.

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    12/01/95 | Regulation of nuclear genes encoding mitochondrial proteins in Saccharomyces cerevisiae.
    Brown TA, Evangelista C, Trumpower BL
    Journal of Bacteriology. 1995 Dec;177(23):6836-43

    Selection for mutants which release glucose repression of the CYB2 gene was used to identify genes which regulate repression of mitochondrial biogenesis. We have identified two of these as the previously described GRR1/CAT80 and ROX3 genes. Mutations in these genes not only release glucose repression of CYB2 but also generally release respiration of the mutants from glucose repression. In addition, both mutants are partially defective in CYB2 expression when grown on nonfermentable carbon sources, indicating a positive regulatory role as well. ROX3 was cloned by complementation of a glucose-inducible flocculating phenotype of an amber mutant and has been mapped as a new leftmost marker on chromosome 2. The ROX3 mutant has only a modest defect in glucose repression of GAL1 but is substantially compromised in galactose induction of GAL1 expression. This mutant also has increased SUC2 expression on nonrepressing carbon sources. We have also characterized the regulation of CYB2 in strains carrying null mutation in two other glucose repression genes, HXK2 and SSN6, and show that HXK2 is a negative regulator of CYB2, whereas SSN6 appears to be a positive effector of CYB2 expression.

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    12/01/95 | Role of the morphogenetic furrow in establishing polarity in the Drosophila eye.
    Chanut F, Heberlein U
    Development. 1995 Dec;121(12):4085-94

    The Drosophila retina is a crystalline array of 800 ommatidia whose organization and assembly suggest polarization of the retinal epithelium along anteroposterior and dorsoventral axes. The retina develops by a stepwise process following the posterior-to-anterior progression of the morphogenetic furrow across the eye disc. Ectopic expression of hedgehog or local removal of patched function generates ectopic furrows that can progress in any direction across the disc leaving in their wake differentiating fields of ectopic ommatidia. We have studied the effect of these ectopic furrows on the polarity of ommatidial assembly and rotation. We find that the anteroposterior asymmetry of ommatidial assembly parallels the progression of ectopic furrows, regardless of their direction. In addition, ommatidia developing behind ectopic furrows rotate coordinately, forming equators in various regions of the disc. Interestingly, the expression of a marker normally restricted to the equator is induced in ectopic ommatidial fields. Ectopic equators are stable as they persist to adulthood, where they can coexist with the normal equator. Our results suggest that ectopic furrows can impart polarity to the disc epithelium, regarding the direction of both assembly and rotation of ommatidia. We propose that these processes are polarized as a consequence of furrow propagation, while more global determinants of dorsoventral and anteroposterior polarity may act less directly by determining the site of furrow initiation.

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    Egnor Lab
    12/01/95 | The uncertain response in the bottlenosed dolphin (Tursiops truncatus).
    Smith JD, Schull J, Strote J, McGee K, Egnor R, Erb L
    Journal of Experimental Psychology. 1995 Dec;124(4):391-408

    Humans respond adaptively to uncertainty by escaping or seeking additional information. To foster a comparative study of uncertainty processes, we asked whether humans and a bottlenosed dolphin (Tursiops truncatus) would use similarly a psychophysical uncertain response. Human observers and the dolphin were given 2 primary discrimination responses and a way to escape chosen trials into easier ones. Humans escaped sparingly from the most difficult trials near threshold that left them demonstrably uncertain of the stimulus. The dolphin performed nearly identically. The behavior of both species is considered from the perspectives of signal detection theory and optimality theory, and its appropriate interpretation is discussed. Human and dolphin uncertain responses seem to be interesting cognitive analogs and may depend on cognitive or controlled decisional mechanisms. The capacity to monitor ongoing cognition, and use uncertainty appropriately, would be a valuable adaptation for animal minds. This recommends uncertainty processes as an important but neglected area for future comparative research.

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    Baker Lab

    In Drosophila dosage compensation increases the rate of transcription of the male's X chromosome and depends on four autosomal male-specific lethal genes. We have cloned the msl-2 gene and shown that MSL-2 protein is co-localized with the other three MSL proteins at hundreds of sites along the male polytene X chromosome and that this binding requires the other three MSL proteins. msl-2 encodes a protein with a putative DNA-binding domain: the RING finger. MSL-2 protein is not produced in females and sequences in both the 5' and 3' UTRs are important for this sex-specific regulation. Furthermore, msl-2 pre-mRNA is alternatively spliced in a Sex-lethal-dependent fashion in its 5' UTR.

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    07/01/95 | Toward simplifying and accurately formulating fragment assembly.
    Myers EW
    Journal of Computational Biology: A Journal of Computational Molecular Cell Biology. 1995 Summer;2(2):275-90

    The fragment assembly problem is that of reconstructing a DNA sequence from a collection of randomly sampled fragments. Traditionally, the objective of this problem has been to produce the shortest string that contains all the fragments as substrings, but in the case of repetitive target sequences this objective produces answers that are overcompressed. In this paper, the problem is reformulated as one of finding a maximum-likelihood reconstruction with respect to the two-sided Kolmogorov-Smirnov statistic, and it is argued that this is a better formulation of the problem. Next the fragment assembly problem is recast in graph-theoretic terms as one of finding a noncyclic subgraph with certain properties and the objectives of being shortest or maximally likely are also recast in this framework. Finally, a series of graph reduction transformations are given that dramatically reduce the size of the graph to be explored in practical instances of the problem. This reduction is very important as the underlying problems are NP-hard. In practice, the transformed problems are so small that simple branch-and-bound algorithms successfully solve them, thus permitting auxiliary experimental information to be taken into account in the form of overlap, orientation, and distance constraints.

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    06/30/95 | Mechanisms of Drosophila retinal morphogenesis: the virtues of being progressive.
    Heberlein U, Moses K
    Cell. 1995 Jun 30;81(7):987-90
    06/16/95 | Yan functions as a general inhibitor of differentiation and is negatively regulated by activation of the Ras1/MAPK pathway.
    Rebay I, Rubin GM
    Cell. 1995 Jun 16;81(6):857-66. doi: 10.1186/gb-2007-8-7-r145

    Drosophila yan has been postulated to act as an antagonist of the proneural signal mediated by the sevenless/Ras1/MAPK pathway. We have mutagenized the eight MAPK phosphorylation consensus sites of yan and examined the effects of overexpressing the mutant protein in transgenic flies and transfected S2 cultured cells. Our results suggest that phosphorylation by MAPK affects the stability and subcellular localization of yan, resulting in rapid down-regulation of yan activity. Furthermore, MAPK-mediated down-regulation of yan function appears to be critical for the proper differentiation of both neuronal and nonneuronal tissues throughout development, suggesting that yan is an essential component of a general timing mechanism controlling the competence of a cell to respond to inductive signals.

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    06/05/95 | Probing dendritic function with patch pipettes.
    Stuart G, Spruston N
    Curr Opin Neurobiol. 1995 Jun;5(3):389-94

    Most neurons in the CNS have complex, branching dendritic trees, which receive the majority of all synaptic input. As it is difficult to make electrical recordings from dendrites because of their small size, most of what is known about their electrical properties has been inferred from recordings made at the soma. By taking advantage of the higher resolution offered by improved optics, it is now possible to make patch-pipette recordings from the dendrites of neurons in brain slices under visual control. This new technique promises to provide valuable new information concerning dendritic function.

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    05/26/95 | Addition of a 29 residue carboxyl-terminal tail converts a simple HMG box-containing protein into a transcriptional activator.
    Dairaghi DJ, Shadel GS, Clayton DA
    Journal of Molecular Biology. 1995 May 26;249(1):11-28. doi: 10.1101/gad.1352105

    Human mitochondrial transcription factor A (h-mtTFA) is essential for initiation of transcription from the two promoters located in the displacement-loop region of human mitochondrial DNA. This 25 kDa protein contains two tandem, HMG box DNA-binding domains separated by a 27 amino acid residue linker region and followed by a 25 residue carboxyl-terminal tail; both the linker and tail are rich in basic amino acid residues. Mutational analysis of h-mtTFA revealed that the tail region is important for specific DNA recognition and essential for transcriptional activation. The critical role of the human tail in transcription was confirmed by constructing chimeric proteins that exchanged similar regions between h-mtTFA and its Saccharomyces cerevisiae homolog, sc-mtTFA. Wild-type sc-mtTFA is unable to activate transcription from the human mitochondrial light-strand promoter (LSP). Addition of the human tail region to sc-mtTFA conferred LSP-specific promoter activation. In all of the different h-mtTFA mutations tested, transcriptional activation was correlated with specific DNA-binding activity, suggesting that these two functions may be inseparable, a situation entirely consistent with previous mutational analyses of human mitochondrial promoters.

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