TDP-43 expression in mouse models of amyotrophic lateral sclerosis and spinal muscular atrophy

<p>Abstract</p> <p>Background</p> <p>Redistribution of nuclear TAR DNA binding protein 43 (TDP-43) to the cytoplasm and ubiquitinated inclusions of spinal motor neurons and glial cells is characteristic of amyotrophic lateral sclerosis (ALS) pathology. Recent evidence suggests that TDP-43 pathology is common to sporadic ALS and familial ALS without SOD1 mutation, but not SOD1-related fALS cases. Furthermore, it remains unclear whether TDP-43 abnormalities occur in non-ALS forms of motor neuron disease. Here, we characterise TDP-43 localisation, expression levels and post-translational modifications in mouse models of ALS and spinal muscular atrophy (SMA).</p> <p>Results</p> <p>TDP-43 mislocalisation to ubiquitinated inclusions or cytoplasm was notably lacking in anterior horn cells from transgenic mutant SOD1^G93Amice. In addition, abnormally phosphorylated or truncated TDP-43 species were not detected in fractionated ALS mouse spinal cord or brain. Despite partial colocalisation of TDP-43 with SMN, depletion of SMN- and coilin-positive Cajal bodies in motor neurons of affected SMA mice did not alter nuclear TDP-43 distribution, expression or biochemistry in spinal cords.</p> <p>Conclusion</p> <p>These results emphasise that TDP-43 pathology characteristic of human sporadic ALS is not a core component of the neurodegenerative mechanisms caused by SOD1 mutation or SMN deficiency in mouse models of ALS and SMA, respectively.</p

Oxygen-induced p(2x3) reconstruction on Mo(112) studied by LEED and STM

The open trough-and-row Mo(112) surface serves as substrate for the epitaxial growth of MoO2. In the early stage of oxygen exposure, oxygen chemisorption induces a p(2x3) surface reconstruction of the missing row type on Mo(112). The surface structure of this reconstructed surface has been studied in detail by low-energy electron diffraction and scanning tunneling microscope. The experimental findings can be explained based on the effective medium theory for oxygen adsorption on transition-metal surfaces, providing a structure model for the oxygen-modified Mo(112) surface. The structure model allows the discussion of the oxygen-chemisorbed surface phase as a possible precursor state fo

Transition from a molecular to a metallic adsorbate system: Core-hole creation and decay dynamics for CO coordinated to Pd

Two alternative methods to experimentally monitor the development of a CO-adsorption system that gradually changes from molecular to metallic are presented: firstly by adsorption of CO on Pd islands of increasing size deposited under UHV conditions, and secondly by growth of a Pd carbonyl-like species, formed by Pd deposition in CO atmosphere. The change in screening dynamics as a function of the number of metal atoms was investigated, using x-ray photoelectron spectroscopy, x-ray absorption spectroscopy, and core-hole-decay techniques. For CO adsorbed on UHV-deposited islands, the electronic properties of the whole CO-Pd complex is strongly dependent on island size and CO coverage: large amounts of CO result in a reduced screening ability, and small effects characteristic of molecular systems can be detected even for islands containing about 100 Pd atoms. If about half of the CO overlayer is desorbed, the CO-Pd complex exhibits a relaxation upon core ionization that is nearly as efficient as for metallic systems, even for the smallest islands (of the order of 10 Pd atoms). The growth of the carbonyl-like compound proceeds via formation of Pd-Pd bonds and has a relatively well-defined local structure. It is demonstrated that the properties of this compound approach those of an extended system for increasing coverages, and it may therefore also serve as an important link between a carbonyl and CO adsorbed on a metallic surface. A brief discussion is also given in which the results are discussed in terms of electronic properties of the thin alumina film versus bulk alumina and the applicability of the former to the construction of model catalysts

Interaction of CO with Pd clusters supported on a thin alumina film

The adsorption of CO on Pd particles supported on a thin alumina film has been studied employing high resolution x‐ray photoelectron spectroscopy (XPS) and x‐ray absorption spectroscopy (XAS), and of special interest was the CO–Pd interaction as a function of island size and CO coverage. CO saturation at 90 K leads to an overlayer characterized by a rather weak CO–Pd hybridization as manifested by the core ionized and core excited states. The interaction strength gradually increases with island size. Desorption of parts of the overlayer results in CO more strongly interacting with the Pd islands. A comparison between the XPS and XAS energies yields a behavior indistinguishable from metallic systems for islands larger than 15 Å, i.e., the XPS binding energy appears near the x‐ray absorption onset. For the smallest islands (5 Å), a CO coverage dependent reversal of the XPS–XAS energy relation was observed, indicating a drastic change in the screening ability of the CO–Pd complex

Polarization Correlations of 1S0 Proton Pairs as Tests of Bell and Wigner Inequalities

In an experiment designed to overcome the loophole of observer dependent reality and satisfying the counterfactuality condition, we measured polarization correlations of 1S0 proton pairs produced in 12C(d,2He) and 1H(d,He) reactions in one setting. The results of these measurements are used to test the Bell and Wigner inequalties against the predictions of quantum mechanics.Comment: 8 pages, 4 figure

Periostin Activation of Integrin Receptors on Sensory Neurons Induces Allergic Itch

Chronic allergic itch is a common symptom affecting millions of people and animals, but its pathogenesis is not fully explained. Herein, we show that periostin, abundantly expressed in the skin of patients with atopic dermatitis (AD), induces itch in mice, dogs, and monkeys. We identify the integrin αVβ3 expressed on a subset of sensory neurons as the periostin receptor. Using pharmacological and genetic approaches, we inhibited the function of neuronal integrin αVβ3, which significantly reduces periostin-induced itch in mice. Furthermore, we show that the cytokine TSLP, the application of AD-causing MC903 (calcipotriol), and house dust mites all induce periostin secretion. Finally, we establish that the JAK/STAT pathway is a key regulator of periostin secretion in keratinocytes. Altogether, our results identify a TSLP-periostin reciprocal activation loop that links the skin to the spinal cord via peripheral sensory neurons, and we characterize the non-canonical functional role of an integrin in itch

Tourette syndrome as a motor disorder revisited – Evidence from action coding

Because tics are the defining clinical feature of Tourette syndrome, it is conceptualized predominantly as a motor disorder. There is some evidence though suggesting that the neural basis of Tourette syndrome is related to perception–action processing and binding between perception and action. However, binding processes have not been examined in the motor domain in these patients. If it is particularly perception–action binding but not binding processes within the motor system, this would further corroborate that Tourette syndrome it is not predominantly, or solely, a motor disorder. Here, we studied N = 22 Tourette patients and N = 24 healthy controls using an established action coding paradigm derived from the Theory of Event Coding framework and concomitant EEG-recording addressing binding between a planned but postponed, and an interleaved immediate reaction with different levels of overlap of action elements. Behavioral performance during interleaved action coding was normal in Tourette syndrome. Response locked lateralized readiness potentials reflecting processes related to motor execution were larger in Tourette syndrome, but only in simple conditions. However, pre-motor processes including response preparation and configuration reflected by stimulus-locked lateralized readiness potentials were normal. This was supported by a Bayesian data analysis providing evidence for the null hypothesis. The finding that processes integrating different action-related elements prior to motor execution are normal in Tourette syndrome suggests that Tourette it is not solely a motor disorder. Considering other recent evidence, the data show that changes in “binding” in Tourette syndrome are specific for perception–action integration but not for action coding