Tet3 regulates synaptic transmission and homeostatic plasticity via DNA oxidation and repair.

Contrary to the long-held belief that DNA methylation of terminally differentiated cells is permanent and essentially immutable, post-mitotic neurons exhibit extensive DNA demethylation. The cellular function of active DNA demethylation in neurons, however, remains largely unknown. Tet family proteins oxidize 5-methylcytosine to initiate active DNA demethylation through the base-excision repair (BER) pathway. We found that synaptic activity bi-directionally regulates neuronal Tet3 expression. Functionally, knockdown of Tet or inhibition of BER in hippocampal neurons elevated excitatory glutamatergic synaptic transmission, whereas overexpressing Tet3 or Tet1 catalytic domain decreased it. Furthermore, dysregulation of Tet3 signaling prevented homeostatic synaptic plasticity. Mechanistically, Tet3 dictated neuronal surface GluR1 levels. RNA-seq analyses further revealed a pivotal role of Tet3 in regulating gene expression in response to global synaptic activity changes. Thus, Tet3 serves as a synaptic activity sensor to epigenetically regulate fundamental properties and meta-plasticity of neurons via active DNA demethylation

Hydrodynamic Description of Granular Convection

We present a hydrodynamic model that captures the essence of granular dynamics in a vibrating bed. We carry out the linear stability analysis and uncover the instability mechanism that leads to the appearance of the convective rolls via a supercritical bifurcation of a bouncing solution. We also explicitly determine the onset of convection as a function of control parameters and confirm our picture by numerical simulations of the continuum equations.Comment: 14 pages, RevTex 11pages + 3 pages figures (Type csh

Planetary Collisions outside the Solar System: Time Domain Characterization of Extreme Debris Disks

Luminous debris disks of warm dust in the terrestrial planet zones around solar-like stars are recently found to vary, indicative of ongoing large-scale collisions of rocky objects. We use Spitzer 3.6 and 4.5 {\mu}m time-series observations in 2012 and 2013 (extended to 2014 in one case) to monitor 5 more debris disks with unusually high fractional luminosities ("extreme debris disk"), including P1121 in the open cluster M47 (80 Myr), HD 15407A in the AB Dor moving group (80 Myr), HD 23514 in the Pleiades (120 Myr), HD 145263 in the Upper Sco Association (10 Myr), and the field star BD+20 307 (>1 Gyr). Together with the published results for ID8 in NGC 2547 (35 Myr), this makes the first systematic time-domain investigation of planetary impacts outside the solar system. Significant variations with timescales shorter than a year are detected in five out of the six extreme debris disks we have monitored. However, different systems show diverse sets of characteristics in the time domain, including long-term decay or growth, disk temperature variations, and possible periodicity.Comment: 50 pages, 14 figures, 9 tables; Accepted for publication in the Astrophysical Journa

Traffic Equations and Granular Convection

We investigate both numerically and analytically the convective instability of granular materials by two dimensional traffic equations. In the absence of vibrations the traffic equations assume two distinctive classes of fixed bed solutions with either a spatially uniform or nonuniform density profile. The former one exists only when the function V(\rho) that monitors the relaxation of grains assumes a cut off at the closed packed density, \rho_c, with V(\rho_c)=0, while the latter one exists for any form of V. Since there is little difference between the uniform and nonuniform solution deep inside the bed, the convective instability of the bulk may be studied by focusing on the stability of the uniform solution. In the presence of vibrations, we find that the uniform solution bifurcates into a bouncing solution, which then undergoes a supercritical bifurcation to the convective instability. We determine the onset of convection as a function of control parameters and confirm this picture by solving the traffic equations numerically, which reveals bouncing solutions, two convective rolls, and four convective rolls. Further, convective patterns change as the aspect ratio changes: in a vertically long container, the rolls move toward the surface, and in a horizontally long container, the rolls move toward the walls. We compare these results with those reported previously with a different continuum model by Hayakawa, Yue and Hong[Phys. Rev. Lett. 75,2328, 1995]. Finally, we also present a derivation of the traffic equations from Enskoq equation.Comment: 34 pages, 10 figure

A flavin-based extracellular electron transfer mechanism in diverse Gram-positive bacteria.

Extracellular electron transfer (EET) describes microbial bioelectrochemical processes in which electrons are transferred from the cytosol to the exterior of the cell1. Mineral-respiring bacteria use elaborate haem-based electron transfer mechanisms2-4 but the existence and mechanistic basis of other EETs remain largely unknown. Here we show that the food-borne pathogen Listeria monocytogenes uses a distinctive flavin-based EET mechanism to deliver electrons to iron or an electrode. By performing a forward genetic screen to identify L. monocytogenes mutants with diminished extracellular ferric iron reductase activity, we identified an eight-gene locus that is responsible for EET. This locus encodes a specialized NADH dehydrogenase that segregates EET from aerobic respiration by channelling electrons to a discrete membrane-localized quinone pool. Other proteins facilitate the assembly of an abundant extracellular flavoprotein that, in conjunction with free-molecule flavin shuttles, mediates electron transfer to extracellular acceptors. This system thus establishes a simple electron conduit that is compatible with the single-membrane structure of the Gram-positive cell. Activation of EET supports growth on non-fermentable carbon sources, and an EET mutant exhibited a competitive defect within the mouse gastrointestinal tract. Orthologues of the genes responsible for EET are present in hundreds of species across the Firmicutes phylum, including multiple pathogens and commensal members of the intestinal microbiota, and correlate with EET activity in assayed strains. These findings suggest a greater prevalence of EET-based growth capabilities and establish a previously underappreciated relevance for electrogenic bacteria across diverse environments, including host-associated microbial communities and infectious disease