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7 Publications

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    04/01/05 | Ataxin-3 suppresses polyglutamine neurodegeneration in Drosophila by a ubiquitin-associated mechanism.
    Warrick JM, Morabito LM, Bilen J, Gordesky-Gold B, Faust LZ, Paulson HL, Bonini NM
    Molecular Cell. 2005 Apr 1;18(1):37-48. doi: 10.1016/j.molcel.2005.02.030

    Two central issues in polyglutamine-induced neurodegeneration are the influence of the normal function of the disease protein and modulation by protein quality control pathways. By using Drosophila, we now directly link host protein function and disease pathogenesis to ubiquitin pathways in the polyglutamine disease spinocerebellar ataxia type 3 (SCA3). Normal human ataxin-3–a polyubiquitin binding protein with ubiquitin protease activity–is a striking suppressor of polyglutamine neurodegeneration in vivo. This suppressor activity requires ubiquitin-associated activities of the protein and is dependent upon proteasome function. Our results highlight the critical importance of host protein function in SCA3 disease and a potential therapeutic role of ataxin-3 activity for polyglutamine disorders.

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    04/01/05 | Genetic mapping of aphicarus -- a sex-linked locus controlling a wing polymorphism in the pea aphid (Acyrthosiphon pisum).
    Braendle C, Caillaud MC, Stern DL
    Heredity (Edinb). 2005 Apr;94(4):435-42. doi: 10.1038/sj.hdy.6800633

    We have initiated research to determine the genetic basis of a male wing polymorphism in the pea aphid Acyrthosiphon pisum (Hemiptera: Aphididae). Previous studies showed that this polymorphism is controlled by a single biallelic locus, which we name aphicarus (api), on the X chromosome. Our objectives were to confirm that api segregates as a polymorphism of a single gene on the X chromosome, and to obtain molecular markers flanking api that can be used as a starting point for high-resolution genetic and physical mapping of the target region, which will ultimately allow the cloning of api. We have established an F2 population segregating for api and have generated X-linked AFLP markers. The segregation pattern of api in the F2 population shows that the male wing polymorphism segregates as a polymorphism of a single gene, or set of closely linked genes on the X chromosome. Using a subset of 78 F2 males, we have constructed a linkage map of the chromosomal region encompassing api using seven AFLP markers. The map spans 74.1 cM and we have mapped api to an interval of 10 cM. In addition, we confirmed X linkage of our AFLP markers and api by using one X-linked marker developed in an earlier study. Our study presents the first mapping of a gene with known function in aphids, and the results indicate that target gene mapping in aphids is feasible.

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    Tjian Lab
    04/01/05 | Maintenance of spermatogenesis requires TAF4b, a gonad-specific subunit of TFIID.
    Falender AE, Freiman RN, Geles KG, Lo KC, Hwang K, Lamb DJ, Morris PL, Tjian R, Richards JS
    Genes & Development. 2005 Apr 1;19(7):794-803. doi: 10.1073/pnas.1100640108

    The establishment and maintenance of spermatogenesis in mammals requires specialized networks of gene expression programs in the testis. The gonad-specific TAF4b component of TFIID (formerly TAF(II)105) is a transcriptional regulator enriched in the mouse testis. Herein we show that TAF4b is required for maintenance of spermatogenesis in the mouse. While young Taf4b-null males are initially fertile, Taf4b-null males become infertile by 3 mo of age and eventually exhibit seminiferous tubules devoid of germ cells. At birth, testes of Taf4b-null males appear histologically normal; however, at post-natal day 3 gonocyte proliferation is impaired and expression of spermatogonial stem cell markers c-Ret, Plzf, and Stra8 is reduced. Together, these data indicate that TAF4b is required for the precise expression of gene products essential for germ cell proliferation and suggest that TAF4b may be required for the regulation of spermatogonial stem cell specification and proliferation that is obligatory for normal spermatogenic maintenance in the adult.

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    04/01/05 | Minimum redundancy feature selection from microarray gene expression data.
    Ding C, Peng H
    Journal of Bioinformatics and Computational Biology. 2005 Apr;3(2):185-205. doi: 10.1007/s12021-010-9090-x

    How to selecting a small subset out of the thousands of genes in microarray data is important for accurate classification of phenotypes. Widely used methods typically rank genes according to their differential expressions among phenotypes and pick the top-ranked genes. We observe that feature sets so obtained have certain redundancy and study methods to minimize it. We propose a minimum redundancy - maximum relevance (MRMR) feature selection framework. Genes selected via MRMR provide a more balanced coverage of the space and capture broader characteristics of phenotypes. They lead to significantly improved class predictions in extensive experiments on 6 gene expression data sets: NCI, Lymphoma, Lung, Child Leukemia, Leukemia, and Colon. Improvements are observed consistently among 4 classification methods: Naive Bayes, Linear discriminant analysis, Logistic regression, and Support vector machines. SUPPLIMENTARY: The top 60 MRMR genes for each of the datasets are listed in http://crd.lbl.gov/ cding/MRMR/. More information related to MRMR methods can be found at http://www.hpeng.net/.

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    04/01/05 | Properties of dopamine release and uptake in the songbird basal ganglia.
    Gale SD, Perkel DJ
    Journal of Neurophysiology. 2005 Apr;93:1871-9. doi: 10.1152/jn.01053.2004

    Vocal learning in songbirds requires a basal ganglia circuit termed the anterior forebrain pathway (AFP). The AFP is not required for song production, and its role in song learning is not well understood. Like the mammalian striatum, the striatal component of the AFP, Area X, receives dense dopaminergic innervation from the midbrain. Since dopamine (DA) clearly plays a crucial role in basal ganglia-mediated motor control and learning in mammals, it seems likely that DA signaling contributes importantly to the functions of Area X as well. In this study, we used voltammetric methods to detect subsecond changes in extracellular DA concentration to gain better understanding of the properties and regulation of DA release and uptake in Area X. We electrically stimulated Ca(2+)- and action potential-dependent release of an electroactive substance in Area X brain slices and identified the substance as DA by the voltammetric waveform, electrode selectivity, and neurochemical and pharmacological evidence. As in the mammalian striatum, DA release in Area X is depressed by autoinhibition, and the lifetime of extracellular DA is strongly constrained by monoamine transporters. These results add to the known physiological similarities of the mammalian and songbird striatum and support further use of voltammetry in songbirds to investigate the role of basal ganglia DA in motor learning.

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    04/15/05 | Template-dependent morphogenesis of oriented calcite crystals in the presence of magnesium ions.
    Han Y, Wysocki LM, Thanawala MS, Siegrist T, Aizenberg J
    Angewandte Chemie (International ed. in English). 2005 Apr 15;44(16):2386-90. doi: 10.1002/anie.200462296
    04/01/05 | The origin of a mutualism: a morphological trait promoting the evolution of ant-aphid mutualisms.
    Shingleton AW, Stern DL, Foster WA
    Evolution. 2005 Apr;59(4):921-6

    Mutualisms are mutually beneficial interactions between species and are fundamentally important at all levels of biological organization. It is not clear, however, why one species participates in a particular mutualism whereas another does not. Here we show that pre-existing traits can dispose particular species to evolve a mutualistic interaction. Combining morphological, ecological, and behavioral data in a comparative analysis, we show that resource use in Chaitophorus aphids (Hemiptera: Aphididae) modulates the origin of their mutualism with ants. We demonstrate that aphid species that feed on deeper phloem elements have longer mouthparts, that this inhibits their ability to withdraw their mouthparts and escape predators and that, consequently, this increases their need for protection by mutualist ants.

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