Lack of interleukin-1 type 1 receptor enhances the accumulation of mutant huntingtin in the striatum and exacerbates the neurological phenotypes of Huntington's disease mice

Huntington's disease results from expansion of a glutamine repeat (>36 glutamines) in the N-terminal region of huntingtin (htt) and is characterized by preferential neurodegeneration in the striatum of the brain. N171-82Q mice that express N-terminal 171 amino acids of htt with an 82-glutamine repeat show severe neurological phenotypes and die early, suggesting that N-terminal mutant htt is pathogenic. In addition, various cellular factors and genetic modifiers are found to modulate the cytotoxicity of mutant htt. Understanding the contribution of these factors to HD pathogenesis will help identify therapeutics for this disease. To investigate the role of interleukin type 1 (IL-1), a cytokine that has been implicated in various neurological diseases, in HD neurological symptoms, we crossed N171-82Q mice to type I IL-1 receptor (IL-1RI) knockout mice. Mice lacking IL-1RI and expressing N171-82Q show more severe neurological symptoms than N171-82Q or IL-1RI knockout mice, suggesting that lack of IL-1RI can promote the neuronal toxicity of mutant htt. Lack of IL-1RI also increases the accumulation of transgenic mutant htt in the striatum in N171-82Q mice. Since IL-1RI signaling mediates both toxic and protective effects on neurons, its basal function and protective effects may be important for preventing the neuropathology seen in HD

Design of a Low-Voltage Distribution Transformer Based on Inductive Filtering

Adopting the connection group structure of Dd0yn11, this paper designs a novel low-voltage (LV) distribution transformer (DT) based on inductive filtering (IF), and verifies the proposed transformer through a comprehensive innovation experiment. Firstly, the functional relationship between valve-side harmonic current and grid-side current was derived according to the winding model, and the filtering features were obtained to compute the impedance between the valve- and grid-side windings. Next, the design calculation was carried out by the engineering magnetic circuit (EMC) method. After that, a three-dimensional (3D) model was established for the proposed transformer on ANSYS Maxwell. The simulation results show that the proposed transformer meets the design requirements on the relevant parameters, and eliminates the harmonic pollution in the grid. Finally, the proposed transformer was proved correct and effective through experiments, and found to stimulate studentsꞌ interest in learning and innovation

Impaired ubiquitin–proteasome system activity in the synapses of Huntington's disease mice

Huntington's disease (HD) is caused by the expansion of a polyglutamine tract in the N-terminal region of huntingtin (htt) and is characterized by selective neurodegeneration. In addition to forming nuclear aggregates, mutant htt accumulates in neuronal processes as well as synapses and affects synaptic function. However, the mechanism for the synaptic toxicity of mutant htt remains to be investigated. We targeted fluorescent reporters for the ubiquitin–proteasome system (UPS) to presynaptic or postsynaptic terminals of neurons. Using these reporters and biochemical assays of isolated synaptosomes, we found that mutant htt decreases synaptic UPS activity in cultured neurons and in HD mouse brains that express N-terminal or full-length mutant htt. Given that the UPS is a key regulator of synaptic plasticity and function, our findings offer insight into the selective neuronal dysfunction seen in HD and also establish a method to measure synaptic UPS activity in other neurological disease models

β-Nd2Mo4O15

The title compound, dineodymium(III) tetra­molybdate(VI), has been prepared by a flux technique and is the second polymorph of composition Nd2Mo4O15. The crystal structure is isotypic with those of Ce2Mo4O15 and Pr2Mo4O15. It features a three-dimensional network composed of distorted edge- and corner-sharing NdO7 polyhedra, NdO8 polyhedra, MoO4 tetra­hedra and MoO6 octa­hedra

Features of the gamma-ray pulsar halo HESS J1831−-098

Gamma-ray pulsar halos are ideal indicators of cosmic-ray propagation in localized regions of the Galaxy and electron injection from pulsar wind nebulae. HESS~J1831$-$098 is a candidate pulsar halo observed by both H.E.S.S. and HAWC experiments. We adopt the flux map of the H.E.S.S. Galactic plane survey and the spectrum measurements of H.E.S.S. and \textit{Fermi}-LAT to study HESS~J1831$-$098. We find that HESS~J1831$-$098 meets all the criteria for a pulsar halo. The diffusion coefficient inside the halo and the conversion efficiency from the pulsar spin-down energy to the electron energy are both similar to the Geminga halo, a canonical pulsar halo. The injection spectrum can be well described by an exponentially-cutoff power law. However, the needed power-law term is very hard with $p\lesssim1$ if the diffusion coefficient is spatially and temporally independent. Considering the possible origins of the slow-diffusion environment, we adopt the two-zone diffusion model and the time-delayed slow-diffusion model. Both the models can interpret the H.E.S.S. and \textit{Fermi}-LAT results with a milder $p$. A modified injection time profile may have a similar effect.Comment: 15 pages (one column), 4 figures, 1 tabl