20 - Putative Targets of the PP2A Serine/Threonine Phosphatase Complex In Regulating Dendritic Morphology

Proper dendritic development is essential for functional neuronal networks. Elucidating the molecular mechanisms that regulate dendritic diversification is therefore essential to understanding the formation and modulation of functional neural circuitry. PP2A is a serine/threonine phosphatase that is evolutionarily conserved from yeast to mammals. In Drosophila, the PP2A complex is composed of a catalytic subunit encoded by microtubule star (mts), a scaffolding subunit encoded by PP2A-29B and one of four alternate regulatory subunits encoded by widerborst (wdb), twins, PP2A-B’ and CG4733. Previous studies in the lab showed that specific RNAi-mediated knockdown of various PP2A subunits in CIV neurons severely impaired dendritic complexity. Knockdown of mts, PP2A-29B, and wdb led to a significant reduction in the total dendritic length and the number of branches compared to control. Knockdown of the other three PP2A regulatory subunits did not have an effect on CIV dendritic morphology, suggesting that wdb is the relevant regulatory subunit associated with this complex in this class of da neurons. In contrast, defects in mts and PP2A-29B in CI neurons leads to increased dendritic complexity via de novo filopodia formation. However, knockdown of only CG4733 leads to a decrease in total dendritic length suggesting that this subunit is required for modulating the activity of the complex in CI. The present study is aimed at identifying substrates of this complex and understanding how these putative targets regulate dendritic morphology in dendritic arborization neurons of D. melanogaster. Phenotypic analyses suggest that the Fragile X mental retardation protein (FMRP) and the transcription factor FoxO may function as targets of the PP2A complex in CIV neurons while FoxO may be a target of this complex in CI neurons. We study these targets using a combination of genetic perturbations and immunohistochemistry to observe whether mts and various proteins interact to promote dendritic morphology

Reply to ``Comment on `Insulating Behavior of λ\lambda-DNA on the Micron Scale' "

In our experiment, we found that the resistance of vacuum-dried $\lambda$-DNA exceeds $10^{14} \Omega$ at 295 K. Bechhoefer and Sen have raised a number of objections to our conclusion. We provide counter arguments to support our original conclusion.Comment: 1 page reply to comment, 1 figur

Cell-Type Specific Transcriptomic Profiling to Dissect Mechanisms of Differential Dendritogenesis

The establishment, maintenance and modulation of cell-type specific neural architectures are critically important to the formation of functional neural networks. At the neuroanatomical level, differential patterns of dendritic arborization directly impact neural function and connectivity, however the molecular mechanisms underlying the specification of distinct dendrite morphologies remain incompletely understood. To address this question, we analyzed global gene expression from purified populations of wild-type class I and class IV Drosophila melanogaster dendritic arborization (da) sensory neurons compared to wild-type whole larval RNA using oligo DNA microarray expression profiling. Herein we present detailed experimental methods and bioinformatic anal- yses to correspond with our data reported in the Gene Expression Omnibus under accession number GSE46154. We further provide R code to facilitate data accession, perform quality controls, and conduct bioinformatic analyses relevant to this dataset. Our cell-type specific gene expression datasets provide a valuable resource for guiding further investigations designed to explore the molecular mechanisms underlying differential patterns of neuronal patterning

Drosophila Insulin receptor regulates the persistence of injury-induced nociceptive sensitization

Diabetes-associated nociceptive hypersensitivity affects diabetic patients with hard-to-treat chronic pain. Because multiple tissues are affected by systemic alterations in insulin signaling, the functional locus of insulin signaling in diabetes-associated hypersensitivity remains obscure. Here, we used Drosophila nociception/nociceptive sensitization assays to investigate the role of Insulin receptor (Insulin-like receptor, InR) in nociceptive hypersensitivity. InR mutant larvae exhibited mostly normal baseline thermal nociception (absence of injury) and normal acute thermal hypersensitivity following UV-induced injury. However, their acute thermal hypersensitivity persists and fails to return to baseline, unlike in controls. Remarkably, injury-induced persistent hypersensitivity is also observed in larvae that exhibit either type 1 or type 2 diabetes. Cell type-specific genetic analysis indicates that InR function is required in multidendritic sensory neurons including nociceptive class IV neurons. In these same nociceptive sensory neurons, only modest changes in dendritic morphology were observed in the InRRNAi-expressing and diabetic larvae. At the cellular level, InR-deficient nociceptive sensory neurons show elevated calcium responses after injury. Sensory neuron-specific expression of InR rescues the persistent thermal hypersensitivity of InR mutants and constitutive activation of InR in sensory neurons ameliorates the hypersensitivity observed with a type 2-like diabetic state. Our results suggest that a sensory neuron-specific function of InR regulates the persistence of injury-associated hypersensitivity. It is likely that this new system will be an informative genetically tractable model of diabetes-associated hypersensitivity

Simulated Cytoskeletal Collapse via Tau Degradation

We present a coarse-grained two dimensional mechanical model for the microtubule-tau bundles in neuronal axons in which we remove taus, as can happen in various neurodegenerative conditions such as Alzheimer's disease, tauopathies, and chronic traumatic encephalopathy. Our simplified model includes (i) taus modeled as entropic springs between microtubules, (ii) removal of taus from the bundles due to phosphorylation, and (iii) a possible depletion force between microtubules due to these dissociated phosphorylated taus. We equilibrate upon tau removal using steepest descent relaxation. In the absence of the depletion force, the transverse rigidity to radial compression of the bundle falls to zero at about 60% tau occupancy, in agreement with standard percolation theory results. However, with the attractive depletion force, spring removal leads to a first order collapse of the bundles over a wide range of tau occupancies for physiologically realizable conditions. While our simplest calculations assume a constant concentration of microtubule intercalants to mediate the depletion force, including a dependence that is linear in the detached taus yields the same collapse. Applying percolation theory to removal of taus at microtubule tips, which are likely to be the protective sites against dynamic instability, we argue that the microtubule instability can only obtain at low tau occupancy, from 0.06-0.30 depending upon the tau coordination at the microtubule tips. Hence, the collapse we discover is likely to be more robust over a wide range of tau occupancies than the dynamic instability. We suggest in vitro tests of our predicted collapse.Comment: 11 pages, 9 figure

Toward a systematic 1/d expansion: Two particle properties

We present a procedure to calculate 1/d corrections to the two-particle properties around the infinite dimensional dynamical mean field limit. Our method is based on a modified version of the scheme of Ref. onlinecite{SchillerIngersent}}. To test our method we study the Hubbard model at half filling within the fluctuation exchange approximation (FLEX), a selfconsistent generalization of iterative perturbation theory. Apart from the inherent unstabilities of FLEX, our method is stable and results in causal solutions. We find that 1/d corrections to the local approximation are relatively small in the Hubbard model.Comment: 4 pages, 4 eps figures, REVTe

KSU Chamber Singers and Men\u27s Ensemble

KSU School of Music presents Chamber Singers and Men\u27s Ensemble.https://digitalcommons.kennesaw.edu/musicprograms/1157/thumbnail.jp

Mixed-valent regime of the two-channel Anderson impurity as a model for UBe_13

We investigate the mixed-valent regime of a two-configuration Anderson impurity model for uranium ions, with separate quadrupolar and magnetic doublets. With a new Monte Carlo approach and the non-crossing approximation we find: (i) A non-Fermi-liquid fixed point with two-channel Kondo model critical behavior; (ii) Distinct energy scales for screening the low-lying and excited doublets; (iii) A semi-quantitative explanation of magnetic-susceptibility data for U$_{1-x}$Th$_x$Be$_{13}$ assuming 60-70% quadrupolar doublet ground-state weight, supporting the quadrupolar-Kondo interpretation.Comment: 4 Pages, 3 eps figures; submitted to Phys. Rev. Let

Three-Dimensional Simulations of Inflows Irradiated by a Precessing Accretion Disk in Active Galactic Nuclei: Formation of Outflows

We present three-dimensional (3-D) hydrodynamical simulations of gas flows in the vicinity of an active galactic nucleus (AGN) powered by a precessing accretion disk. We consider the effects of the radiation force from such a disk on its environment on a relatively large scale (up to ~10 pc. We implicitly include the precessing disk by forcing the disk radiation field to precess around a symmetry axis with a given period ($P$) and a tilt angle ($\Theta$). We study time evolution of the flows irradiated by the disk, and investigate basic dependencies of the flow morphology, mass flux, angular momentum on different combinations of $\Theta$ and $P$. We find the gas flow settles into a configuration with two components, (1) an equatorial inflow and (2) a bipolar inflow/outflow with the outflow leaving the system along the poles (the directions of disk normals). However, the flow does not always reach a steady state. We find that the maximum outflow velocity and the kinetic outflow power at the outer boundary can be reduced significantly with increasing $\Theta$. We also find that of the mass inflow rate across the inner boundary does not change significantly with increasing $\Theta$. (Abbreviated)Comment: Accepted for publication in ApJ. 15 pages, 7 figures. A version with full resolution figures can be downloaded from http://www.physics.unlv.edu/~rk/preprint/precess.pd

Design and implementation of multi-signal and time-varying neural reconstructions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Several efficient procedures exist to digitally trace neuronal structure from light microscopy, and mature community resources have emerged to store, share, and analyze these datasets. In contrast, the quantification of intracellular distributions and morphological dynamics is not yet standardized. Current widespread descriptions of neuron morphology are static and inadequate for subcellular characterizations. We introduce a new file format to represent multichannel information as well as an open-source Vaa3D plugin to acquire this type of data. Next we define a novel data structure to capture morphological dynamics, and demonstrate its application to different time-lapse experiments. Importantly, we designed both innovations as judicious extensions of the classic SWC format, thus ensuring full back-compatibility with popular visualization and modeling tools. We then deploy the combined multichannel/time-varying reconstruction system on developing neurons in live Drosophila larvae by digitally tracing fluorescently labeled cytoskeletal components along with overall dendritic morphology as they changed over time. This same design is also suitable for quantifying dendritic calcium dynamics and tracking arbor-wide movement of any subcellular substrate of interest.Peer reviewe