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28 Publications

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    Zuker Lab
    08/10/01 | Mammalian sweet taste receptors.
    Nelson G, Hoon MA, Chandrashekar J, Zhang Y, Ryba NJ, Zuker CS
    Cell. 2001 Aug 10;106(3):381-90

    The sense of taste provides animals with valuable information about the quality and nutritional value of food. Previously, we identified a large family of mammalian taste receptors involved in bitter taste perception (the T2Rs). We now report the characterization of mammalian sweet taste receptors. First, transgenic rescue experiments prove that the Sac locus encodes T1R3, a member of the T1R family of candidate taste receptors. Second, using a heterologous expression system, we demonstrate that T1R2 and T1R3 combine to function as a sweet receptor, recognizing sweet-tasting molecules as diverse as sucrose, saccharin, dulcin, and acesulfame-K. Finally, we present a detailed analysis of the patterns of expression of T1Rs and T2Rs, thus providing a view of the representation of sweet and bitter taste at the periphery.

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    06/15/01 | Drosophila fasciclinII is required for the formation of odor memories and for normal sensitivity to alcohol.
    Cheng Y, Endo K, Wu K, Rodan AR, Heberlein U, Davis RL
    Cell. 2001 Jun 15;105(6):757-68

    Drosophila fasciclinII (fasII) mutants perform poorly after olfactory conditioning due to a defect in encoding, stabilizing, or retrieving short-term memories. Performance was rescued by inducing the expression of a normal transgene just before training and immediate testing. Induction after training but before testing failed to rescue performance, showing that Fas II does not have an exclusive role in memory retrieval processes. The stability of odor memories in fasII mutants are indistinguishable from control animals when initial performance is normalized. Like several other mutants deficient in odor learning, fasII mutants exhibit a heightened sensitivity to ethanol vapors. A combination of behavioral and genetic strategies have therefore revealed a role for Fas II in the molecular operations of encoding short-term odor memories and conferring alcohol sensitivity. The preferential expression of Fas II in the axons of mushroom body neurons furthermore suggests that short-term odor memories are formed in these neurites.

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    06/01/01 | Rapid atomic density methods for molecular shape characterization.
    Mitchell JC, Kerr R, Ten Eyck LF
    Journal of Molecular Graphics & Modelling. 2001 Jun;19(3-4):325-30, 388-90

    Two methods for rapid characterization of molecular shape are presented. Both techniques are based on the density of atoms near the molecular surface. The Fast Atomic Density Evaluation (FADE) algorithm uses fast Fourier transforms to quickly estimate densities. The Pairwise Atomic Density Reverse Engineering (PADRE) method derives modified density measures from the relationship between atomic density and total potentials. While many shape-characterization techniques define shape relative to a surface, the descriptors returned by FADE and PADRE can measure local geometry from points within the three-dimensional space surrounding a molecule. The methods can be used to find crevices and protrusions near the surface of a molecule and to test shape complementarity at the interface between docking molecules.

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    05/17/01 | Action potential bursting in subicular pyramidal neurons is driven by a calcium tail current.
    Jung HY, Staff NP, Spruston N
    J Neurosci. 2001 May 15;21(10):3312-21

    Subiculum is the primary output area of the hippocampus and serves as a key relay center in the process of memory formation and retrieval. A majority of subicular pyramidal neurons communicate via bursts of action potentials, a mode of signaling that may enhance the fidelity of information transfer and synaptic plasticity or contribute to epilepsy when unchecked. In the present study, we show that a Ca(2+) tail current drives bursting in subicular pyramidal neurons. An action potential activates voltage-activated Ca(2+) channels, which deactivate slowly enough during action potential repolarization to produce an afterdepolarization that triggers subsequent action potentials in the burst. The Ca(2+) channels underlying bursting are located primarily near the soma, and the amplitude of Ca(2+) tail currents correlates with the strength of bursting across cells. Multiple channel subtypes contribute to Ca(2+) tail current, but the need for an action potential to produce the slow depolarization suggests a central role for high-voltage-activated Ca(2+) channels in subicular neuron bursting.

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    05/07/01 | Ionic liquids based on FeCl(3) and FeCl(2). Raman scattering and ab initio calculations.
    Sitze MS, Schreiter ER, Patterson EV, Freeman RG
    Inorganic Chemistry. 2001 May 7;40(10):2298-304

    We have prepared ionic liquids by mixing either iron(II) chloride or iron(III) chloride with 1-butyl-3-methylimidazolium chloride (BMIC). Iron(II) chloride forms ionic liquids from a mole ratio of 1 FeCl(2)/3 BMIC to almost 1 FeCl(2)/1 BMIC. Both Raman scattering and ab initio calculations indicate that FeCl(4)(2-) is the predominant iron-containing species in these liquids. Iron(III) chloride forms ionic liquids from a mole ratio of 1 FeCl(3)/1.9 BMIC to 1.7 FeCl(3)/1 BMIC. When BMIC is in excess, Raman scattering indicates the presence of FeCl(4-). When FeCl(3) is in excess, Fe(2)Cl(7-) begins to appear and the amount of Fe(2)Cl(7-) increases with increasing amounts of FeCl(3). Ionic liquids were also prepared from a mixture of FeCl(2) and FeCl(3) and are discussed. Finally, we have used both Hartree-Fock and density functional theory methods to compute the optimized structures and vibrational spectra for these species. An analysis of the results using an all-electron basis set, 6-31G, as well as two different effective core potential basis sets, LANL2DZ and CEP-31G is presented.

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    Murphy Lab
    05/01/01 | Postnatal development of spike generation in rat medial vestibular nucleus neurons.
    Murphy GJ, Du Lac S
    Journal of Neurophysiology. 2001 May;85(5):1899-906

    Image stability during self motion depends on the combined actions of the vestibuloocular and optokinetic reflexes (VOR and OKR, respectively). Neurons in the medial vestibular nucleus (MVN) participate in the VOR and OKR by firing in response to both head and image motion. Their intrinsic spike-generating properties enable MVN neurons to modulate firing rates linearly over a broad range of input amplitudes and frequencies such as those that occur during natural head and image motion. This study examines the postnatal development of the intrinsic spike-generating properties of rat MVN neurons with respect to maturation of peripheral vestibular and visual function. Spike generation was studied in a brain stem slice preparation by recording firing responses to current injected intracellularly through whole cell patch electrodes. MVN neurons fired spontaneously and modulated their firing rate in response to injected current at all postnatal ages. However, the input-output properties of the spike generator changed dramatically during the first two postnatal weeks. Neurons younger than postnatal day 10 could not fire faster than 80 spikes/s, modulated their firing rates over a limited range of input amplitudes, and tended to exhibit a nonlinear relationship between input current and mean evoked firing rate. In response to sustained depolarization, firing rates declined significantly in young neurons. Response gains tended to be highest in the first few postnatal days but varied widely across neurons and were not correlated with age. By about the beginning of the third postnatal week, MVN neurons could fire faster than 100 spikes/s in response to a broad range of input amplitudes, exhibited predominantly linear current-firing rate relationships, and adapted little in response to sustained depolarization. Concomitant decreases in action potential width and the time course of the afterhyperpolarization suggest that changes in potassium currents contribute to the maturation of the MVN neuronal spike generator. The results demonstrate that developmental changes in intrinsic membrane properties enable MVN neurons to fire linearly in response to a broad range of stimuli in time for the onset of visual function at the beginning of the third postnatal week.

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    Simpson Lab
    04/27/01 | Switching repulsion to attraction: changing responses to slit during transition in mesoderm migration.
    Kramer SG, Kidd T, Simpson JH, Goodman CS
    Science. 2001 Apr 27;292(5517):737-40. doi: 10.1126/science.1058766

    Slit is secreted by cells at the midline of the central nervous system, where it binds to Roundabout (Robo) receptors and functions as a potent repellent. We found that migrating mesodermal cells in vivo respond to Slit as both an attractant and a repellent and that Robo receptors are required for both functions. Mesoderm cells expressing Robo receptors initially migrate away from Slit at the midline. A few hours after migration, these same cells change their behavior and require Robo to extend toward Slit-expressing muscle attachment sites. Thus, Slit functions as a chemoattractant to provide specificity for muscle patterning.

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    04/24/01 | Conversion of a maltose receptor into a zinc biosensor by computational design.
    Marvin JS, Hellinga HW
    Proceedings of the National Academy of Sciences of the United States of America. 2001 Apr 24;98(9):4955-60. doi: 10.1073/pnas.091083898

    We have demonstrated that it is possible to radically change the specificity of maltose binding protein by converting it into a zinc sensor using a rational design approach. In this new molecular sensor, zinc binding is transduced into a readily detected fluorescence signal by use of an engineered conformational coupling mechanism linking ligand binding to reporter group response. An iterative progressive design strategy led to the construction of variants with increased zinc affinity by combining binding sites, optimizing the primary coordination sphere, and exploiting conformational equilibria. Intermediates in the design series show that the adaptive process involves both introduction and optimization of new functions and removal of adverse vestigial interactions. The latter demonstrates the importance of the rational design approach in uncovering cryptic phenomena in protein function, which cannot be revealed by the study of naturally evolved systems.

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    04/19/01 | The concepts of ’sameness’ and ’difference’ in an insect.
    Giurfa M, Zhang S, Jenett A, Menzel R, Srinivasan MV
    Nature. 2001 Apr 19;410(6831):930-3. doi: 10.1038/35073582

    Insects process and learn information flexibly to adapt to their environment. The honeybee Apis mellifera constitutes a traditional model for studying learning and memory at behavioural, cellular and molecular levels. Earlier studies focused on elementary associative and non-associative forms of learning determined by either olfactory conditioning of the proboscis extension reflex or the learning of visual stimuli in an operant context. However, research has indicated that bees are capable of cognitive performances that were thought to occur only in some vertebrate species. For example, honeybees can interpolate visual information, exhibit associative recall, categorize visual information and learn contextual information. Here we show that honeybees can form ’sameness’ and ’difference’ concepts. They learn to solve ’delayed matching-to-sample’ tasks, in which they are required to respond to a matching stimulus, and ’delayed non-matching-to-sample’ tasks, in which they are required to respond to a different stimulus; they can also transfer the learned rules to new stimuli of the same or a different sensory modality. Thus, not only can bees learn specific objects and their physical parameters, but they can also master abstract inter-relationships, such as sameness and difference.

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    Baker Lab
    04/06/01 | Are complex behaviors specified by dedicated regularoty genes? Reasoning from Drosophila.
    Baker B, Taylor B, Hall JC
    Cell. 2001 Apr 6;105(1):13-24