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

10 Publications

Showing 1-10 of 10 results
Your Criteria:
    07/22/11 | An evolutionary conserved role for anaplastic lymphoma kinase in behavioral responses to ethanol.
    Lasek AW, Lim J, Kliethermes CL, Berger KH, Joslyn G, Brush G, Xue L, Robertson M, Moore MS, Vranizan K, Morris SW, Schuckit MA, White RL, Heberlein U
    PLoS One. 2011 Jul 22;6(7):e22636. doi: 10.1371/journal.pone.0022636

    Anaplastic lymphoma kinase (Alk) is a gene expressed in the nervous system that encodes a receptor tyrosine kinase commonly known for its oncogenic function in various human cancers. We have determined that Alk is associated with altered behavioral responses to ethanol in the fruit fly Drosophila melanogaster, in mice, and in humans. Mutant flies containing transposon insertions in dAlk demonstrate increased resistance to the sedating effect of ethanol. Database analyses revealed that Alk expression levels in the brains of recombinant inbred mice are negatively correlated with ethanol-induced ataxia and ethanol consumption. We therefore tested Alk gene knockout mice and found that they sedate longer in response to high doses of ethanol and consume more ethanol than wild-type mice. Finally, sequencing of human ALK led to the discovery of four polymorphisms associated with a low level of response to ethanol, an intermediate phenotype that is predictive of future alcohol use disorders (AUDs). These results suggest that Alk plays an evolutionary conserved role in ethanol-related behaviors. Moreover, ALK may be a novel candidate gene conferring risk for AUDs as well as a potential target for pharmacological intervention.

    View Publication Page
    07/21/11 | Tubular network formation protects mitochondria from autophagosomal degradation during nutrient starvation.
    Rambold AS, Kostelecky B, Elia N, Lippincott-Schwartz J
    Proceedings of the National Academy of Sciences of the United States of America. 2011 Jun 21;108(25):10190-5. doi: 10.1073/pnas.1107402108

    Mitochondria are highly dynamic organelles that mediate essential cell functions such as apoptosis and cell-cycle control in addition to their role as efficient ATP generators. Mitochondrial morphology changes are tightly regulated, and their shape can shift between small, fragmented units and larger networks of elongated mitochondria. We demonstrate that mitochondrial elements become significantly elongated and interconnected shortly after nutrient depletion. This mitochondrial morphological shift depends on the type of starvation, with an additive effect observed when multiple nutrients are depleted simultaneously. We further show that starvation-induced mitochondrial elongation is mediated by down-regulation of dynamin-related protein 1 (Drp1) through modulation of two Drp1 phosphorylation sites, leading to unopposed mitochondrial fusion. Finally, we establish that mitochondrial tubulation upon nutrient deprivation protects mitochondria from autophagosomal degradation, which could permit mitochondria to maximize energy production and supply autophagosomal membranes during starvation.

    View Publication Page
    07/19/11 | Bridging structure and process in developmental biology through new imaging technologies.
    Lippincott-Schwartz J
    Developmental cell. 2011 Jul 19;21(1):5-10. doi: 10.1016/j.devcel.2011.06.030

    Many unexpected discoveries in developmental biology have depended on advancement of imaging technologies to visualize developmental processes as they unfold across multiple spatial and temporal scales. This essay surveys the recent advances in imaging, highlighting emerging capabilities with an eye toward those poised to have the greatest impact on developmental biology.

    View Publication Page
    07/17/11 | Precise olfactory responses tile the sniff cycle.
    Shusterman R, Smear MC, Koulakov AA, Rinberg D
    Nature Neuroscience. 2011 Jul 17;14(8):1039-44. doi: 10.1038/nn.2877

    In terrestrial vertebrates, sniffing controls odorant access to receptors, and therefore sets the timescale of olfactory stimuli. We found that odorants evoked precisely sniff-locked activity in mitral/tufted cells in the olfactory bulb of awake mouse. The trial-to-trial response jitter averaged 12 ms, a precision comparable to other sensory systems. Individual cells expressed odor-specific temporal patterns of activity and, across the population, onset times tiled the duration of the sniff cycle. Responses were more tightly time-locked to the sniff phase than to the time after inhalation onset. The spikes of single neurons carried sufficient information to discriminate odors. In addition, precise locking to sniff phase may facilitate ensemble coding by making synchrony relationships across neurons robust to variation in sniff rate. The temporal specificity of mitral/tufted cell output provides a potentially rich source of information for downstream olfactory areas.

    View Publication Page
    Gonen Lab
    07/13/11 | Fragment-based phase extension for three-dimensional structure determination of membrane proteins by electron crystallography.
    Wisedchaisri G, Gonen T
    Structure. 2011 Jul 13;19:976-87. doi: 10.1016/j.str.2011.04.008

    In electron crystallography, membrane protein structure is determined from two-dimensional crystals where the protein is embedded in a membrane. Once large and well-ordered 2D crystals are grown, one of the bottlenecks in electron crystallography is the collection of image data to directly provide experimental phases to high resolution. Here, we describe an approach to bypass this bottleneck, eliminating the need for high-resolution imaging. We use the strengths of electron crystallography in rapidly obtaining accurate experimental phase information from low-resolution images and accurate high-resolution amplitude information from electron diffraction. The low-resolution experimental phases were used for the placement of α helix fragments and extended to high resolution using phases from the fragments. Phases were further improved by density modifications followed by fragment expansion and structure refinement against the high-resolution diffraction data. Using this approach, structures of three membrane proteins were determined rapidly and accurately to atomic resolution without high-resolution image data.

    View Publication Page
    Cui Lab
    07/04/11 | Phase resolved interferometric spectral modulation (PRISM) for ultrafast pulse measurement and compression.
    Wu T, Tang J, Hajj B, Cui M
    Optics Express. 2011 Jul 4;19(14):12961-8. doi: 10.1364/OE.19.012961

    We show through experiments and simulations that parallel phase modulation, a technique developed in the field of adaptive optics, can be employed to quickly determine the spectral phase profile of ultrafast laser pulses and to perform phase compensation as well as pulse shaping. Different from many existing ultrafast pulse measurement methods, the technique reported here requires no spectrum measurements of nonlinear signals. Instead, the power of nonlinear signals is used directly to quickly measure the spectral phase, a convenient feature for applications such as two-photon fluorescence microscopy. The method is found to work with both smooth and even completely random distortions. The experimental results are verified with MIIPS measurements.

    View Publication Page
    Baker Lab
    07/01/11 | Direct targets of the D. melanogaster DSXF protein and the evolution of sexual development.
    Luo SD, Shi GW, Baker BS
    Development. 2011 Jul;138(13):2761-71. doi: 10.1242/dev.065227

    Uncovering the direct regulatory targets of doublesex (dsx) and fruitless (fru) is crucial for an understanding of how they regulate sexual development, morphogenesis, differentiation and adult functions (including behavior) in Drosophila melanogaster. Using a modified DamID approach, we identified 650 DSX-binding regions in the genome from which we then extracted an optimal palindromic 13 bp DSX-binding sequence. This sequence is functional in vivo, and the base identity at each position is important for DSX binding in vitro. In addition, this sequence is enriched in the genomes of D. melanogaster (58 copies versus approximately the three expected from random) and in the 11 other sequenced Drosophila species, as well as in some other Dipterans. Twenty-three genes are associated with both an in vivo peak in DSX binding and an optimal DSX-binding sequence, and thus are almost certainly direct DSX targets. The association of these 23 genes with optimum DSX binding sites was used to examine the evolutionary changes occurring in DSX and its targets in insects.

    View Publication Page
    Sternson Lab
    07/01/11 | Flip-flop memory circuit uses a synaptic AMPK-dependent positive feedback loop and is switched by hunger state.
    Y.Yang , D.Atasoy , S.Sternson
    Appetite. 2011 Jul 01;57(1):47. doi: 10.1016/j.appet.2011.05.296

    Synaptic plasticity in response to changes in physiologic state is coordinated by hormonal signals across multiple neuronal cell types, but the significance and underlying mechanisms are unclear. Here, we combine cell type-specific electrophysiological, pharmacological, and optogenetic techniques to dissect neural circuits and molecular pathways controlling synaptic plasticity onto AGRP neurons, a population that regulates feeding. We find that food deprivation elevates excitatory synaptic input, which is mediated by a presynaptic positive feedback loop involving AMP-activated protein kinase. Potentiation of glutamate release was triggered by the orexigenic hormone ghrelin and exhibited hysteresis, persisting for hours after ghrelin removal. Persistent activity was reversed by the anorexigenic hormone leptin, and optogenetic photostimulation demonstrated involvement of opioid release from POMC neurons. Based on these experiments, we propose a memory storage device for physiological state constructed from bistable synapses that are flipped between two sustained activity states by transient exposure to hormones signaling energy levels. Supported by: Howard Hughes Medical Institute.

    View Publication Page
    Eddy/Rivas Lab
    07/01/11 | HMMER web server: interactive sequence similarity searching.
    Finn RD, Clements J, Eddy SR
    Nucleic Acids Research. 2011 Jul;39:W29-37. doi: 10.1093/nar/gkr367

    HMMER is a software suite for protein sequence similarity searches using probabilistic methods. Previously, HMMER has mainly been available only as a computationally intensive UNIX command-line tool, restricting its use. Recent advances in the software, HMMER3, have resulted in a 100-fold speed gain relative to previous versions. It is now feasible to make efficient profile hidden Markov model (profile HMM) searches via the web. A HMMER web server (http://hmmer.janelia.org) has been designed and implemented such that most protein database searches return within a few seconds. Methods are available for searching either a single protein sequence, multiple protein sequence alignment or profile HMM against a target sequence database, and for searching a protein sequence against Pfam. The web server is designed to cater to a range of different user expertise and accepts batch uploading of multiple queries at once. All search methods are also available as RESTful web services, thereby allowing them to be readily integrated as remotely executed tasks in locally scripted workflows. We have focused on minimizing search times and the ability to rapidly display tabular results, regardless of the number of matches found, developing graphical summaries of the search results to provide quick, intuitive appraisement of them.

    View Publication Page
    07/01/11 | The genetic relationships between ethanol preference, acute ethanol sensitivity, and ethanol tolerance in Drosophila melanogaster.
    Devineni AV, McClure KD, Guarnieri DJ, Corl AB, Wolf FW, Eddison M, Heberlein U
    Fly (Austin). 2011 Jul-Sep;5(3):191-9

    The relationship between alcohol consumption, sensitivity, and tolerance is an important question that has been addressed in humans and rodent models. Studies have shown that alcohol consumption and risk of abuse may correlate with (1) increased sensitivity to the stimulant effects of alcohol, (2) decreased sensitivity to the depressant effects of alcohol, and (3) increased alcohol tolerance. However, many conflicting results have been observed. To complement these studies, we utilized a different organism and approach to analyze the relationship between ethanol consumption and other ethanol responses. Using a set of 20 Drosophila melanogaster mutants that were isolated for altered ethanol sensitivity, we measured ethanol-induced hyperactivity, ethanol sedation, sedation tolerance, and ethanol consumption preference. Ethanol preference showed a strong positive correlation with ethanol tolerance, consistent with some rodent and human studies, but not with ethanol hyperactivity or sedation. No pairwise correlations were observed between ethanol hyperactivity, sedation, and tolerance. The evolutionary conservation of the relationship between tolerance and ethanol consumption in flies, rodents, and humans indicates that there are fundamental biological mechanisms linking specific ethanol responses.

    View Publication Page