Main Menu (Mobile)- Block

Main Menu - Block

janelia7_blocks-janelia7_fake_breadcrumb | block
Koyama Lab / Publications
custom | custom

Filter

facetapi-Q2b17qCsTdECvJIqZJgYMaGsr8vANl1n | block

Associated Lab

facetapi-W9JlIB1X0bjs93n1Alu3wHJQTTgDCBGe | block
facetapi-PV5lg7xuz68EAY8eakJzrcmwtdGEnxR0 | block
facetapi-021SKYQnqXW6ODq5W5dPAFEDBaEJubhN | block

Type of Publication

general_search_page-panel_pane_1 | views_panes

2508 Publications

Showing 2191-2200 of 2508 results
Your Criteria:
    Sternson LabLooger LabLavis Lab
    03/27/12 | Selective esterase-ester pair for targeting small molecules with cellular specificity.
    Tian L, Yang Y, Wysocki LM, Arnold AC, Hu A, Ravichandran B, Sternson SM, Looger LL, Lavis LD
    Proceedings of the National Academy of Sciences of the United States of America. 2012 Mar 27;109:4756-61. doi: 10.1073/pnas.1111943109

    Small molecules are important tools to measure and modulate intracellular signaling pathways. A longstanding limitation for using chemical compounds in complex tissues has been the inability to target bioactive small molecules to a specific cell class. Here, we describe a generalizable esterase-ester pair capable of targeted delivery of small molecules to living cells and tissue with cellular specificity. We used fluorogenic molecules to rapidly identify a small ester masking motif that is stable to endogenous esterases, but is efficiently removed by an exogenous esterase. This strategy allows facile targeting of dyes and drugs in complex biological environments to label specific cell types, illuminate gap junction connectivity, and pharmacologically perturb distinct subsets of cells. We expect this approach to have general utility for the specific delivery of many small molecules to defined cellular populations.

    View Publication Page
    03/16/12 | Sexual deprivation increases ethanol intake in Drosophila.
    Shohat-Ophir G, Kaun K, Azanchi R, Mohammed H, Heberlein U
    Science. 2012 Mar 16;335(6074):1351-5. doi: 10.1126/science.1215932

    The brain’s reward systems reinforce behaviors required for species survival, including sex, food consumption, and social interaction. Drugs of abuse co-opt these neural pathways, which can lead to addiction. Here, we used Drosophila melanogaster to investigate the relationship between natural and drug rewards. In males, mating increased, whereas sexual deprivation reduced, neuropeptide F (NPF) levels. Activation or inhibition of the NPF system in turn reduced or enhanced ethanol preference. These results thus link sexual experience, NPF system activity, and ethanol consumption. Artificial activation of NPF neurons was in itself rewarding and precluded the ability of ethanol to act as a reward. We propose that activity of the NPF-NPF receptor axis represents the state of the fly reward system and modifies behavior accordingly.

    View Publication Page
    03/15/12 | Cutting edge: the role of IFN-α receptor and MyD88 signaling in induction of IL-15 expression in vivo.
    Colpitts SL, Stoklasek TA, Plumlee CR, Obar JJ, Guo C, Lefran\c cois L
    Journal of Immunology. 2012 Mar 15;188(6):2483-7. doi: 10.4049/jimmunol.1103609

    IL-15 plays a multifaceted role in immune homeostasis, but the unreliability of IL-15 detection has stymied exploration of IL-15 regulation in vivo. To visualize IL-15 expression, we created a transgenic mouse expressing emerald-GFP (EmGFP) under IL-15 promoter control. EmGFP/IL-15 was prevalent in innate cells including dendritic cells (DCs), macrophages, and monocytes. However, DC subsets expressed varying levels of EmGFP/IL-15 with CD8(+) DCs constitutively expressing EmGFP/IL-15 and CD8(-) DCs expressing low EmGFP/IL-15 levels. Virus infection resulted in IL-15 upregulation in both subsets. By crossing the transgenic mice to mice deficient in specific elements of innate signaling, we found a cell-intrinsic dependency of DCs and Ly6C(+) monocytes on IFN-α receptor expression for EmGFP/IL-15 upregulation after vesicular stomatitis virus infection. In contrast, myeloid cells did not require the expression of MyD88 to upregulate EmGFP/IL-15 expression. These findings provide evidence of previously unappreciated regulation of IL-15 expression in myeloid lineages during homeostasis and following infection.

    View Publication Page
    03/09/12 | Triggering a cell shape change by exploiting preexisting actomyosin contractions.
    Roh-Johnson M, Shemer G, Higgins CD, McClellan JH, Werts AD, Tulu US, Gao L, Betzig E, Kiehart DP, Goldstein B
    Science. 2012 Mar 9;335(6073):1232-5. doi: 10.1126/science.1217869

    Apical constriction changes cell shapes, driving critical morphogenetic events, including gastrulation in diverse organisms and neural tube closure in vertebrates. Apical constriction is thought to be triggered by contraction of apical actomyosin networks. We found that apical actomyosin contractions began before cell shape changes in both Caenorhabitis elegans and Drosophila. In C. elegans, actomyosin networks were initially dynamic, contracting and generating cortical tension without substantial shrinking of apical surfaces. Apical cell-cell contact zones and actomyosin only later moved increasingly in concert, with no detectable change in actomyosin dynamics or cortical tension. Thus, apical constriction appears to be triggered not by a change in cortical tension, but by dynamic linking of apical cell-cell contact zones to an already contractile apical cortex.

    View Publication Page
    03/01/12 | An improved Greengenes taxonomy with explicit ranks for ecological and evolutionary analyses of bacteria and archaea.
    McDonald D, Price MN, Goodrich J, Nawrocki EP, Desantis TZ, Probst A, Andersen GL, Knight R, Hugenholtz P
    The ISME Journal. 2012 Mar;6(3):610-8. doi: 10.1038/ismej.2011.139

    Reference phylogenies are crucial for providing a taxonomic framework for interpretation of marker gene and metagenomic surveys, which continue to reveal novel species at a remarkable rate. Greengenes is a dedicated full-length 16S rRNA gene database that provides users with a curated taxonomy based on de novo tree inference. We developed a ’taxonomy to tree’ approach for transferring group names from an existing taxonomy to a tree topology, and used it to apply the Greengenes, National Center for Biotechnology Information (NCBI) and cyanoDB (Cyanobacteria only) taxonomies to a de novo tree comprising 408 315 sequences. We also incorporated explicit rank information provided by the NCBI taxonomy to group names (by prefixing rank designations) for better user orientation and classification consistency. The resulting merged taxonomy improved the classification of 75% of the sequences by one or more ranks relative to the original NCBI taxonomy with the most pronounced improvements occurring in under-classified environmental sequences. We also assessed candidate phyla (divisions) currently defined by NCBI and present recommendations for consolidation of 34 redundantly named groups. All intermediate results from the pipeline, which includes tree inference, jackknifing and transfer of a donor taxonomy to a recipient tree (tax2tree) are available for download. The improved Greengenes taxonomy should provide important infrastructure for a wide range of megasequencing projects studying ecosystems on scales ranging from our own bodies (the Human Microbiome Project) to the entire planet (the Earth Microbiome Project). The implementation of the software can be obtained from http://sourceforge.net/projects/tax2tree/.

    View Publication Page
    Pastalkova Lab
    03/01/12 | Implantable blood pressure monitoring cuff for small laboratory animal.
    Pais R, Duttaroy A, Wolever J, Dobbs M, Pastalkova E
    Microsystems for Measurement and Instrumentation (MAMNA), 2012. 2012 Mar:. doi: 10.1109/MAMNA.2012.6195099

    Continuous monitoring of blood pressure in laboratory animals is necessary to understand the effect of treatments for cardiovascular related conditions, such as hypertension. Current methods to measure laboratory rat blood pressure require the animal to be constrained. Our proposed method is a small implantable device which fits around the carotid artery of the rat. Initial data from a mock rat artery setup, with equivalent artery pressure as found in the rat, show that the cuff design effectively detects the pressure change inside the mock artery.

    View Publication Page
    Looger LabSvoboda LabLeonardo LabGENIE
    02/29/12 | A Cre-dependent GCaMP3 reporter mouse for neuronal imaging in vivo.
    Zariwala HA, Borghuis BG, Hoogland TM, Madisen L, Tian L, De Zeeuw CI, Zeng H, Looger LL, Svoboda K, Chen T
    The Journal of Neuroscience. 2012 Feb 29;32:3131-41. doi: 10.1523/JNEUROSCI.4469-11.2012

    Fluorescent calcium indicator proteins, such as GCaMP3, allow imaging of activity in genetically defined neuronal populations. GCaMP3 can be expressed using various gene delivery methods, such as viral infection or electroporation. However, these methods are invasive and provide inhomogeneous and nonstationary expression. Here, we developed a genetic reporter mouse, Ai38, which expresses GCaMP3 in a Cre-dependent manner from the ROSA26 locus, driven by a strong CAG promoter. Crossing Ai38 with appropriate Cre mice produced robust GCaMP3 expression in defined cell populations in the retina, cortex, and cerebellum. In the primary visual cortex, visually evoked GCaMP3 signals showed normal orientation and direction selectivity. GCaMP3 signals were rapid, compared with virally expressed GCaMP3 and synthetic calcium indicators. In the retina, Ai38 allowed imaging spontaneous calcium waves in starburst amacrine cells during development, and light-evoked responses in ganglion cells in adult tissue. Our results show that the Ai38 reporter mouse provides a flexible method for targeted expression of GCaMP3.

    View Publication Page
    02/23/12 | Hierarchical deployment of factors regulating temporal fate in a diverse neuronal lineage of the Drosophila central brain.
    Kao C, Yu H, He Y, Kao J, Lee T
    Neuron. 2012 Feb 23;73(4):677-84. doi: 10.1016/j.neuron.2011.12.018

    The anterodorsal projection neuron lineage of Drosophila melanogaster produces 40 neuronal types in a stereotypic order. Here we take advantage of this complete lineage sequence to examine the role of known temporal fating factors, including Chinmo and the Hb/Kr/Pdm/Cas transcriptional cascade, within this diverse central brain lineage. Kr mutation affects the temporal fate of the neuroblast (NB) itself, causing a single fate to be skipped, whereas Chinmo null only elicits fate transformation of NB progeny without altering cell counts. Notably, Chinmo operates in two separate windows to prevent fate transformation (into the subsequent Chinmo-indenpendent fate) within each window. By contrast, Hb/Pdm/Cas play no detectable role, indicating that Kr either acts outside of the cascade identified in the ventral nerve cord or that redundancy exists at the level of fating factors. Therefore, hierarchical fating mechanisms operate within the lineage to generate neuronal diversity in an unprecedented fashion.

    View Publication Page
    02/22/12 | Excitation spectra and brightness optimization of two-photon excited probes.
    Mütze J, Iyer V, Macklin JJ, Colonell J, Karsh B, Petrá\v sek Ze, Schwille P, Looger LL, Lavis LD, Harris TD
    Biophysical Journal. 2012 Feb 22;102(4):934-44. doi: 10.1016/j.bpj.2011.12.056

    Two-photon probe excitation data are commonly presented as absorption cross section or molecular brightness (the detected fluorescence rate per molecule). We report two-photon molecular brightness spectra for a diverse set of organic and genetically encoded probes with an automated spectroscopic system based on fluorescence correlation spectroscopy. The two-photon action cross section can be extracted from molecular brightness measurements at low excitation intensities, while peak molecular brightness (the maximum molecular brightness with increasing excitation intensity) is measured at higher intensities at which probe photophysical effects become significant. The spectral shape of these two parameters was similar across all dye families tested. Peak molecular brightness spectra, which can be obtained rapidly and with reduced experimental complexity, can thus serve as a first-order approximation to cross-section spectra in determining optimal wavelengths for two-photon excitation, while providing additional information pertaining to probe photostability. The data shown should assist in probe choice and experimental design for multiphoton microscopy studies. Further, we show that, by the addition of a passive pulse splitter, nonlinear bleaching can be reduced-resulting in an enhancement of the fluorescence signal in fluorescence correlation spectroscopy by a factor of two. This increase in fluorescence signal, together with the observed resemblance of action cross section and peak brightness spectra, suggests higher-order photobleaching pathways for two-photon excitation.

    View Publication Page
    Looger Lab
    02/21/12 | Reduced release probability prevents vesicle depletion and transmission failure at dynamin mutant synapses.
    Lou X, Fan F, Messa M, Raimondi A, Wu Y, Looger LL, Ferguson SM, De Camilli P
    Proceedings of the National Academy of Sciences of the United States of America. 2012 Feb 21;109:E515-23. doi: 10.1073/pnas.1121626109

    Endocytic recycling of synaptic vesicles after exocytosis is critical for nervous system function. At synapses of cultured neurons that lack the two "neuronal" dynamins, dynamin 1 and 3, smaller excitatory postsynaptic currents are observed due to an impairment of the fission reaction of endocytosis that results in an accumulation of arrested clathrin-coated pits and a greatly reduced synaptic vesicle number. Surprisingly, despite a smaller readily releasable vesicle pool and fewer docked vesicles, a strong facilitation, which correlated with lower vesicle release probability, was observed upon action potential stimulation at such synapses. Furthermore, although network activity in mutant cultures was lower, Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activity was unexpectedly increased, consistent with the previous report of an enhanced state of synapsin 1 phosphorylation at CaMKII-dependent sites in such neurons. These changes were partially reversed by overnight silencing of synaptic activity with tetrodotoxin, a treatment that allows progression of arrested endocytic pits to synaptic vesicles. Facilitation was also counteracted by CaMKII inhibition. These findings reveal a mechanism aimed at preventing synaptic transmission failure due to vesicle depletion when recycling vesicle traffic is backed up by a defect in dynamin-dependent endocytosis and provide new insight into the coupling between endocytosis and exocytosis.

    View Publication Page