2,266 research outputs found

    Medial Ganglionic Eminence Progenitors Transplanted into Hippocampus Integrate in a Functional and Subtype-Appropriate Manner.

    Get PDF
    Medial ganglionic eminence (MGE) transplantation rescues disease phenotypes in various preclinical models with interneuron deficiency or dysfunction, including epilepsy. While underlying mechanism(s) remains unclear to date, a simple explanation is that appropriate synaptic integration of MGE-derived interneurons elevates GABA-mediated inhibition and modifies the firing activity of excitatory neurons in the host brain. However, given the complexity of interneurons and potential for transplant-derived interneurons to integrate or alter the host network in unexpected ways, it remains unexplored whether synaptic connections formed by transplant-derived interneurons safely mirror those associated with endogenous interneurons. Here, we combined optogenetics, interneuron-specific Cre driver mouse lines, and electrophysiology to study synaptic integration of MGE progenitors. We demonstrated that MGE-derived interneurons, when transplanted into the hippocampus of neonatal mice, migrate in the host brain, differentiate to mature inhibitory interneurons, and form appropriate synaptic connections with native pyramidal neurons. Endogenous and transplant-derived MGE progenitors preferentially formed inhibitory synaptic connections onto pyramidal neurons but not endogenous interneurons. These findings demonstrate that transplanted MGE progenitors functionally integrate into the postnatal hippocampal network

    Drug diffusion from polymeric delivery devices: a problem with two moving boundaries

    Get PDF
    An existing model for solvent penetration and drug release from a spherically-shaped polymeric drug delivery device is revisited. The model has two moving boundaries, one that describes the interface between the glassy and rubbery states of polymer, and another that defines the interface between the polymer ball and the pool of solvent. The model is extended so that the nonlinear diffusion coefficient of drug explicitly depends on the concentration of solvent, and the resulting equations are solved numerically using a front-fixing transformation together with a finite difference spatial discretisation and the method of lines. We present evidence that our scheme is much more accurate than a previous scheme. Asymptotic results in the small-time limit are presented, which show how the use of a kinetic law as a boundary condition on the innermost moving boundary dictates qualitative behaviour, the scalings being very different to the similar moving boundary problem that arises from modelling the melting of an ice ball. The implication is that the model considered here exhibits what is referred to as ``non-Fickian'' or Case II diffusion which, together with the initially constant rate of drug release, has certain appeal from a pharmaceutical perspective

    Integrated-light Two Micron All Sky Survey infrared photometry of Galactic globular clusters

    Get PDF
    We have mosaicked Two Micron All Sky Survey (2MASS) images to derive surface brightness profiles in J, H, and K_s for 104 Galactic globular clusters. We fit these with King profiles and show that the core radii are identical to within the errors for each of these IR colors and are identical to the core radii at V in essentially all cases. We derive integrated-light colors V-J, V-H, V-K_s, J-H, and J-Ks for these globular clusters. Each color shows a reasonably tight relation between the dereddened colors and metallicity. Fits to these are given for each color. The IR-IR colors have very small errors, due largely to the all-sky photometric calibration of the 2MASS survey, while the V-IR colors have substantially larger uncertainties. We find fairly good agreement with measurements of integrated-light colors for a smaller sample of Galactic globular clusters by M. Aaronson, M. Malkan, and D. Kleinmann from 1977. Our results provide a calibration for the integrated light of distant single-burst old stellar populations from very low to solar metallicities. A comparison of our dereddened measured colors with predictions from several models of the integrated light of single-burst old populations shows good agreement in the low-metallicity domain for V-K_s colors but also shows an offset at a fixed [Fe/H] of ~0.1 mag in J-K_s, which we ascribe to photometric system transformation issues. Some of the models fail to reproduce the behavior of the integrated-light colors of the Galactic globular clusters near solar metallicity

    Integrated Light 2MASS IR Photometry of Galactic Globular Clusters

    Full text link
    We have mosaiced 2MASS images to derive surface brightness profiles in JHK for 104 Galactic globular clusters. We fit these with King profiles, and show that the core radii are identical to within the errors for each of these IR colors, and are identical to the core radii at V in essentially all cases. We derive integrated light colors V-J, V-H, V-K_s, J-H and J-K_s for these globular clusters. Each color shows a reasonably tight relation between the dereddened colors and metallicity. Fits to these are given for each color. The IR--IR colors have very small errors due largely to the all-sky photometric calibration of the 2MASS survey, while the V-IR colors have substantially larger uncertainties. We find fairly good agreement with measurements of integrated light colors for a smaller sample of Galactic globular clusters by Aaronson, Malkan & Kleinmann from 1977. Our results provide a calibration for the integrated light of distant single burst old stellar populations from very low to Solar metallicities. A comparison of our dereddened measured colors with predictions from several models of the integrated light of single burst old populations shows good agreement in the low metallicity domain for V-K_s colors, but an offset at a fixed [Fe/H] of ~0.1 mag in J-K_s, which we ascribe to photometric system transformation issues. Some of the models fail to reproduce the behavior of the integrated light colors of the Galactic globular clusters near Solar metallicity.Comment: Accepted for publication in the A

    Gate Voltage Controllable Non-Equilibrium and Non-Ohmic Behavior in Suspended Carbon Nanotubes

    Get PDF
    In this work, we measure the electrical conductance and temperature of individual, suspended quasi-metallic single-walled carbon nanotubes under high voltage biases using Raman spectroscopy, while varying the doping conditions with an applied gate voltage. By applying a gate voltage, the high-bias conductance can be switched dramatically between linear (Ohmic) behavior and nonlinear behavior exhibiting negative differential conductance (NDC). Phonon populations are observed to be in thermal equilibrium under Ohmic conditions but switch to nonequilibrium under NDC conditions. A typical Landauer transport model assuming zero bandgap is found to be inadequate to describe the experimental data. A more detailed model is presented, which incorporates the doping dependence in order to fit this data

    Identification of the Plasticity-Relevant Fucose-α(1−2)-Galactose Proteome from the Mouse Olfactory Bulb

    Get PDF
    Fucose-α(1−2)-galactose [Fucα(1−2)Gal] sugars have been implicated in the molecular mechanisms that underlie neuronal development, learning, and memory. However, an understanding of their precise roles has been hampered by a lack of information regarding Fucα(1−2)Gal glycoproteins. Here, we report the first proteomic studies of this plasticity-relevant epitope. We identify five classes of putative Fucα(1−2)Gal glycoproteins: cell adhesion molecules, ion channels and solute carriers/transporters, ATP-binding proteins, synaptic vesicle-associated proteins, and mitochondrial proteins. In addition, we show that Fucα(1−2)Gal glycoproteins are enriched in the developing mouse olfactory bulb (OB) and exhibit a distinct spatiotemporal expression that is consistent with the presence of a “glycocode” to help direct olfactory sensory neuron (OSN) axonal pathfinding. We find that expression of Fucα(1−2)Gal sugars in the OB is regulated by the α(1−2)fucosyltransferase FUT1. FUT1-deficient mice exhibit developmental defects, including fewer and smaller glomeruli and a thinner olfactory nerve layer, suggesting that fucosylation contributes to OB development. Our findings significantly expand the number of Fucα(1−2)Gal glycoproteins and provide new insights into the molecular mechanisms by which fucosyl sugars contribute to neuronal processes

    High-Oleic Ready-to-Use Therapeutic Food Maintains Docosahexaenoic Acid Status in Severe Malnutrition

    Get PDF
    Objectives:Ready-to-use therapeutic food (RUTF) is the preferred treatment for uncomplicated severe acute malnutrition. It contains large amounts of linoleic acid and little -linolenic acid, which may reduce the availability of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to the recovering child. A novel high-oleic RUTF (HO-RUTF) was developed with less linoleic acid to determine its effect on DHA and EPA status.Methods:We conducted a prospective, randomized, double-blind clinical effectiveness trial treating rural Malawian children with severe acute malnutrition. Children were treated with either HO-RUTF or standard RUTF. Plasma phospholipid fatty acid status was measured on enrollment and after 4 weeks and compared between the 2 intervention groups.Results:Among the 141 children enrolled, 48 of 71 receiving HO-RUTF and 50 of 70 receiving RUTF recovered. Plasma phospholipid samples were analyzed from 43 children consuming HO-RUTF and 35 children consuming RUTF. The change in DHA content during the first 4 weeks was +4% and -25% in the HO-RUTF and RUTF groups, respectively (P=0.04). For EPA, the change in content was 63% and -24% in the HO-RUTF and RUTF groups, respectively (P \u3c 0.001). For arachidonic acid, the change in content was -3% and 13% in the HO-RUTF and RUTF groups, respectively (P \u3c 0.009).Conclusions:The changes in DHA and EPA seen in the children treated with HO-RUTF warrant further investigation because they suggest that HO-RUTF support improved polyunsaturated fatty acid status, necessary for neural development and recovery

    The 2016 Reactivations of Main-Belt Comets 238P/Read and 288P/(300163) 2006 VW139

    Full text link
    We report observations of the reactivations of main-belt comets 238P/Read and 288P/(300163) 2006 VW139, that also track the evolution of each object's activity over several months in 2016 and 2017. We additionally identify and analyze archival SDSS data showing 288P to be active in 2000, meaning that both 238P and 288P have now each been confirmed to be active near perihelion on three separate occasions. From data obtained of 288P from 2012-2015 when it appeared inactive, we find best-fit R-band H,G phase function parameters of H_R=16.80+/-0.12 mag and G_R=0.18+/-0.11, corresponding to effective component radii of r_c=0.80+/-0.04 km, assuming a binary system with equally-sized components. Fitting linear functions to ejected dust masses inferred for 238P and 288P soon after their observed reactivations in 2016, we find an initial average net dust production rate of 0.7+/-0.3 kg/s and a best-fit start date of 2016 March 11 (when the object was at a true anomaly of -63 deg) for 238P, and an initial average net dust production rate of 5.6+/-0.7 kg/s and a best-fit start date of 2016 August 5 (when the object was at a true anomaly of -27 deg) for 288P. Applying similar analyses to archival data, we find similar start points for previous active episodes for both objects, suggesting that minimal mantle growth or ice recession occurred between the active episodes in question. Some changes in dust production rates between active episodes are detected, however. More detailed dust modeling is suggested to further clarify the process of activity evolution in main-belt comets.Comment: 21 pages, 9 figures, accepted by A
    corecore