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15 Publications

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    Looger Lab
    10/29/10 | Filtering of visual information in the tectum by an identified neural circuit.
    Del Bene F, Wyart C, Robles E, Tran A, Looger L, Scott EK, Isacoff EY, Baier H
    Science. 2010 Oct 29;330(6004):669-73. doi: 10.1126/science.1192949

    The optic tectum of zebrafish is involved in behavioral responses that require the detection of small objects. The superficial layers of the tectal neuropil receive input from retinal axons, while its deeper layers convey the processed information to premotor areas. Imaging with a genetically encoded calcium indicator revealed that the deep layers, as well as the dendrites of single tectal neurons, are preferentially activated by small visual stimuli. This spatial filtering relies on GABAergic interneurons (using the neurotransmitter γ-aminobutyric acid) that are located in the superficial input layer and respond only to large visual stimuli. Photo-ablation of these cells with KillerRed, or silencing of their synaptic transmission, eliminates the size tuning of deeper layers and impairs the capture of prey.

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    10/27/12 | Into ImgLib—Generic image processing in Java
    Preibisch S, Tomancak P, Saalfeld S
    Proceedings of the ImageJ User and Developer Conference. 2012 Oct 27:

    The purpose of ImgLib, a Generic Java Image Processing Library, is to provide an abstract framework enabling Java developers to design and implement data processing algorithms without having to consider dimensionality, type of data (e. g. byte, float, complex float), or strategies for data access (e. g. linear arrays, cells, paged cells). This kind of programming has significant advantages over the classical way. An algorithm written once for a certain class of Type will potentially run on any compatible Type, even if it does not exist yet. Same applies for data access strategies and the number of dimensions.
    We achieve this abstraction by accessing data through Iterators and Type interfaces. Iterators guarantee e fficient traversal through pixels depending on whether random coordinate access is required or just all pixels have to be visited once, whether real or integer coordinates are accessed, whether coordinates outside of image boundaries are accessed or not. Type interfaces define the supported operators on pixel values (like basic algebra) and hide the underlying basic type from algorithm implementation.

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    Gonen Lab
    10/18/10 | An engineered DNA-binding protein self-assembles metallic nanostructures.
    Hall Sedlak R, Hnilova M, Gachelet E, Przybyla L, Dranow D, Gonen T, Sarikaya M, Tamerler C, Traxler B
    Chembiochem: A European Journal of Chemical Biology. 2010 Oct 18;11(15):2108-12. doi: 10.1002/cbic.201000407

    The golden age of DNA: We describe a strategy for engineering bifunctional proteins that simultaneously associate with metals and DNA to create self-assembled nanostructures. A DNA binding protein engineered with a gold binding peptide arranges colloidal gold particles along a DNA guide by virtue of its introduced peptide motif. These self-assembled complexes represent a step toward constructing nanoarchitectures with potential in nanoelectronic and photonic devices.

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    Grigorieff Lab
    10/14/10 | The Ndc80 kinetochore complex forms oligomeric arrays along microtubules.
    Alushin GM, Ramey VH, Pasqualato S, Ball DA, Grigorieff N, Musacchio A, Nogales E
    Nature. 2010 Oct 14;467(7317):805-10. doi: 10.1038/nature09423

    The Ndc80 complex is a key site of regulated kinetochore-microtubule attachment (a process required for cell division), but the molecular mechanism underlying its function remains unknown. Here we present a subnanometre-resolution cryo-electron microscopy reconstruction of the human Ndc80 complex bound to microtubules, sufficient for precise docking of crystal structures of the component proteins. We find that the Ndc80 complex binds the microtubule with a tubulin monomer repeat, recognizing α- and β-tubulin at both intra- and inter-tubulin dimer interfaces in a manner that is sensitive to tubulin conformation. Furthermore, Ndc80 complexes self-associate along protofilaments through interactions mediated by the amino-terminal tail of the NDC80 protein, which is the site of phospho-regulation by Aurora B kinase. The complex’s mode of interaction with the microtubule and its oligomerization suggest a mechanism by which Aurora B could regulate the stability of load-bearing kinetochore-microtubule attachments.

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    10/01/10 | Clarke’s column neurons as the focus of a corticospinal corollary circuit.
    Hantman AW, Jessell TM
    Nature Neuroscience. 2010 Oct;13(10):1233-9. doi: 10.1038/nn.2637

    Proprioceptive sensory signals inform the CNS of the consequences of motor acts, but effective motor planning involves internal neural systems capable of anticipating actual sensory feedback. Just where and how predictive systems exert their influence remains poorly understood. We explored the possibility that spinocerebellar neurons that convey proprioceptive sensory information also integrate information from cortical command systems. Analysis of the circuitry and physiology of identified dorsal spinocerebellar tract neurons in mouse spinal cord revealed distinct populations of Clarke’s column neurons that received direct excitatory and/or indirect inhibitory inputs from descending corticospinal axons. The convergence of these descending inhibitory and excitatory inputs to Clarke’s column neurons established local spinal circuits with the capacity to mark or modulate incoming proprioceptive input. Together, our genetic, anatomical and physiological results indicate that Clarke’s column spinocerebellar neurons nucleate local spinal corollary circuits that are relevant to motor planning and evaluation.

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    Riddiford Lab
    10/01/10 | Developmental expression of mRNAs for epidermal and fat body proteins and hormonally regulated transcription factors in the tobacco hornworm, Manduca sexta.
    Hiruma K, Riddiford LM
    Journal of Insect Physiology. 2010 Oct;56(10):1390-5. doi: 10.1016/j.jinsphys.2010.03.029

    This paper provides a compilation of diagrammatic representations of the expression profiles of epidermal and fat body mRNAs during the last two larval instars and metamorphosis of the tobacco hornworm, Manduca sexta. Included are those encoding insecticyanin, three larval cuticular proteins, dopa decarboxylase, moling, and the juvenile hormone-binding protein JP29 produced by the dorsal abdominal epidermis, and arylphorin and the methionine-rich storage proteins made by the fat body. The mRNA profiles of the ecdysteroid-regulated cascade of transcription factors in the epidermis during the larval molt and the onset of metamorphosis and in the pupal wing during the onset of adult development are also shown. These profiles are accompanied by a brief summary of the current knowledge about the regulation of these mRNAs by ecdysteroids and juvenile hormone based on experimental manipulations, both in vivo and in vitro.

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    10/01/10 | Error tolerant indexing and alignment of short reads with covering template families.
    Giladi E, Healy J, Myers G, Hart C, Kapranov P, Lipson D, Roels S, Thayer E, Letovsky S
    Journal of Computational Biology: A Journal of Computational Molecular Cell Biology. 2010 Oct;17(10):1397-1411. doi: 10.1089/cmb.2010.0005

    The rapid adoption of high-throughput next generation sequence data in biological research is presenting a major challenge for sequence alignment tools—specifically, the efficient alignment of vast amounts of short reads to large references in the presence of differences arising from sequencing errors and biological sequence variations. To address this challenge, we developed a short read aligner for high-throughput sequencer data that is tolerant of errors or mutations of all types—namely, substitutions, deletions, and insertions. The aligner utilizes a multi-stage approach in which template-based indexing is used to identify candidate regions for alignment with dynamic programming. A template is a pair of gapped seeds, with one used with the read and one used with the reference. In this article, we focus on the development of template families that yield error-tolerant indexing up to a given error-budget. A general algorithm for finding those families is presented, and a recursive construction that creates families with higher error tolerance from ones with a lower error tolerance is developed.

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    10/01/10 | Evolutionary divergence of the paralogs Methoprene tolerant (Met) and germ cell expressed (gce) within the genus Drosophila.
    Baumann A, Fujiwara Y, Wilson TG
    Journal of Insect Physiology. 2010 Oct;56(10):1445-55. doi: 10.1016/j.jinsphys.2010.05.001

    Juvenile hormone (JH) signaling underpins both regulatory and developmental pathways in insects. However, the JH receptor is poorly understood. Methoprene tolerant (Met) and germ cell expressed (gce) have been implicated in JH signaling in Drosophila. We investigated the evolution of Met and gce across 12 Drosophila species and found that these paralogs are conserved across at least 63 million years of dipteran evolution. Distinct patterns of selection found using estimates of dN/dS ratios across Drosophila Met and gce coding sequences, along with their incongruent temporal expression profiles in embryonic Drosophila melanogaster, illustrate avenues through which these genes have diverged within the Diptera. Additionally, we demonstrate that the annotated gene CG15032 is the 5’ terminus of gce. In mosquitoes and beetles, a single Met-like homolog displays structural similarity to both Met and gce, and the intron locations are conserved with those of gce. We found that Tribolium and mosquito Met orthologs are assembled from Met- and gce-specific domains in a modular fashion. Our results suggest that Drosophila Met and gce experienced divergent evolutionary pressures following the duplication of an ancestral gce-like gene found in less derived holometabolous insects.

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    10/01/10 | Lmo4 in the nucleus accumbens regulates cocaine sensitivity.
    Lasek AW, Kapfhamer D, Kharazia V, Gesch J, Giorgetti F, Heberlein U
    Genes, Brain, and Behavior. 2010 Oct;9(7):817-24. doi: 10.1111/j.1601-183X.2010.00620.x

    An estimated 2 million Americans use cocaine, resulting in large personal and societal costs. Discovery of the genetic factors that contribute to cocaine abuse is important for understanding this complex disease. Previously, mutations in the Drosophila LIM-only (dLmo) gene were identified because of their increased behavioral sensitivity to cocaine. Here we show that the mammalian homolog Lmo4, which is highly expressed in brain regions implicated in drug addiction, plays a similar role in cocaine-induced behaviors. Mice with a global reduction in Lmo4 levels show increased sensitivity to the locomotor stimulatory effects of cocaine upon chronic cocaine administration. This effect is reproduced with downregulation of Lmo4 in the nucleus accumbens by RNA interference. Thus, Lmo genes play conserved roles in regulating the behavioral effects of cocaine in invertebrate and mammalian models of drug addiction.

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    10/01/10 | Machines that learn to segment images: a crucial technology for connectomics.
    Jain V, Seung HS, Turaga SC
    Current Opinion in Neurobiology. 2010 Oct;20(5):653-66. doi: 10.1016/j.conb.2010.07.004

    Connections between neurons can be found by checking whether synapses exist at points of contact, which in turn are determined by neural shapes. Finding these shapes is a special case of image segmentation, which is laborious for humans and would ideally be performed by computers. New metrics properly quantify the performance of a computer algorithm using its disagreement with ’true’ segmentations of example images. New machine learning methods search for segmentation algorithms that minimize such metrics. These advances have reduced computer errors dramatically. It should now be faster for a human to correct the remaining errors than to segment an image manually. Further reductions in human effort are expected, and crucial for finding connectomes more complex than that of Caenorhabditis elegans.

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