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

Cytotoxicity and reactive oxygen species production induced by different co-monomer eluted from nanohybrid dental composites

Background Safety issues for dental restorative composites are critical to material selection, but, limited information is available to dental practitioners. This study aimed to compare the chemical and biological characteristics of three nanohybrid dental composites by assessing filler particle analysis, monomer degree of conversion (DC), the composition of eluates, and cytotoxicity and reactive oxygen species (ROS) production in fibroblasts. Methods Three nanohybrid composites (TN, Tetric N-Ceram; CX, Ceram X Sphere Tec One; and DN, DenFil NX) were used. The size distribution and morphology of the filler particles were analysed using scanning electron microscopy (n = 5). The DC was measured via micro-Raman spectroscopy (n = 5). For the component analysis, methanol eluates from the light-polymerised composites were evaluated by gas chromatography/mass spectrometry (n = 3). The eluates were prepared from the polymerised composites after 24h in a cell culture medium. A live/dead assay (n = 9) and Water-Soluble Tetrazolium-1 assay (n = 9) were performed and compared with negative and positive controls. The ROS in composites were compared with NC. Statistical significance in differences was assessed using a t-test and ANOVA (α = 0.05). Results Morphological variations in different-sized fillers were observed in the composites. The DC values were not significantly different among the composites. The amounts of 2-hydroxyethyl methacrylate (HEMA) were higher in TN than DN (p = 0.0022) and triethylene glycol dimethacrylate (TEGDMA) in CX was higher than in others (p < 0.0001). The lowest cell viability was shown in CX (p < 0.0001) and the highest ROS formation was detected in TN (p < 0.0001). Conclusions Three nanohybrid dental composites exhibited various compositions of filler sizes and resin components, resulting in different levels of cytotoxicity and ROS production. Chemical compositions of dental composites can be considered with their biological impact on safety issues in the intraoral use of dental restorative composites. CX with the highest TEGDMA showed the highest cytotoxicity induced by ROS accumulation. DN with lower TEGDMA and HEMA presented the highest cell viability.This work was supported by the Korea Medical Device Development Fund grant funded by the Korea government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health & Wel‑fare, the Ministry of Food and Drug Safety) (Project Number: 9991006717, KMDF_PR_20200901_0044)

Jets in a Gamma-Ray Burst During its Prompt Emission: Evolution of Lorentz Factor

Knowledge about the Lorentz factor and its evolution of relativistic jets in gamma-ray bursts (GRBs) is crucial to understand their physics. An exact value of bulk Lorentz factor can be estimated based on a high-energy spectral cutoff, which may appear in GRBs' prompt emission owing to the absorption of photon-photon pair production. In this work, we focus on the investigation of the bulk Lorentz factor evolution of jets in an individual burst. Based on \textsl{Fermi} observations, we search for the bursts with multiple $\gamma$-ray pulses characterized by a high-energy spectral cutoff, and nine GRBs are obtained. Together with the estimation of the pulse duration and radiation spectrum, the Lorentz factor of jets corresponding to different pulses in an individual GRB are estimated. It is shown that the Lorentz factor of jets in an individual GRB fluctuates within a certain range and without a general trend in these nine GRBs. In addition, the Lorentz factors of the jets in GRBs~130821A, 160509A and 160625B seem to increase with time. We also study the relations among $L_{\rm iso }$, $E_{\rm p,z}$, and $\Gamma$ for the pulses in our sample, which is found to be consistent with that found in previous works.Comment: Accepted for publication in Ap

Plasmoid ejection and secondary current sheet generation from magnetic reconnection in laser-plasma interaction

Reconnection of the self-generated magnetic fields in laser-plasma interaction was first investigated experimentally by Nilson {\it et al.} [Phys. Rev. Lett. 97, 255001 (2006)] by shining two laser pulses a distance apart on a solid target layer. An elongated current sheet (CS) was observed in the plasma between the two laser spots. In order to more closely model magnetotail reconnection, here two side-by-side thin target layers, instead of a single one, are used. It is found that at one end of the elongated CS a fan-like electron outflow region including three well-collimated electron jets appears. The ($>1$ MeV) tail of the jet energy distribution exhibits a power-law scaling. The enhanced electron acceleration is attributed to the intense inductive electric field in the narrow electron dominated reconnection region, as well as additional acceleration as they are trapped inside the rapidly moving plasmoid formed in and ejected from the CS. The ejection also induces a secondary CS