The role of TDP-43 propagation in neurodegenerative diseases: integrating insights from clinical and experimental studies

TAR DNA-binding protein 43 (TDP-43) is a highly conserved nuclear RNA/DNA-binding protein involved in the regulation of RNA processing. The accumulation of TDP-43 aggregates in the central nervous system is a common feature of many neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer’s disease (AD), and limbic predominant age-related TDP-43 encephalopathy (LATE). Accumulating evidence suggests that prion-like spreading of aberrant protein aggregates composed of tau, amyloid-β, and α-synuclein is involved in the progression of neurodegenerative diseases such as AD and PD. Similar to those of prion-like proteins, pathological aggregates of TDP-43 can be transferred from cell-to-cell in a seed-dependent and self-templating manner. Here, we review clinical and experimental studies supporting the prion-like spreading of misfolded TDP-43 and discuss the molecular mechanisms underlying the propagation of these pathological aggregated proteins. The idea that misfolded TDP-43 spreads in a prion-like manner between cells may guide novel therapeutic strategies for TDP-43-associated neurodegenerative diseases.Subject terms: Neurodegenerative diseases, Neurodegeneration     

Reoxidation of uranium in electrolytically reduced simulated oxide fuel during residual salt distillation

Apoptosis is one of the fundamental phenomena behind successful radiation and chemotherapy treatments. Non-invasive imaging of apoptosis can offer an early diagnosis of disease and the true efficiency of an ongoing treatment procedure. The present study describes an attempt to develop ^99mTc-labeled 2-methyl-2-pentylmalonic acid ([^99mTc] 8) as a new SPECT based apoptosis imaging agent. An optimized chemical and radiosynthesis procedure provided desired product [^99mTc] 8 with high radiochemical yield (84%, n = 3) and radiochemical purity (>99%) as determined by radio HPLC. Biodistribution data indicated that the radiotracer has a rapid clearance from blood and other background tissues. High testes accumulation confirmed the ability of the radiotracer to detect testicular apoptosis in mice.

     

Dual-path handheld system for cornea and retina imaging using optical coherence tomography

Optical Review - A dual-path handheld system is proposed for cornea and retina imaging using spectral domain optical coherence tomography. The handheld sample arm is designed to acquire two images...     

High‐Performance Transition Metal Dichalcogenide Photodetectors Enhanced by Self‐Assembled Monolayer Doping

Most doping research into transition metal dichalcogenides (TMDs) has been mainly focused on the improvement of electronic device performance. Here, the effect of self‐assembled monolayer (SAM)‐based doping on the performance of WSe₂‐ and MoS₂‐based transistors and photodetectors is investigated. The achieved doping concentrations are ≈1.4 × 10¹¹ for octadecyltrichlorosilane (OTS) p‐doping and ≈10¹¹ for aminopropyltriethoxysilane (APTES) n‐doping (nondegenerate). Using this SAM doping technique, the field‐effect mobility is increased from 32.58 to 168.9 cm² V^?1 s in OTS/WSe₂ transistors and from 28.75 to 142.2 cm² V^?1 s in APTES/MoS₂ transistors. For the photodetectors, the responsivity is improved by a factor of ≈28.2 (from 517.2 to 1.45 × 10⁴ A W^?1) in the OTS/WSe₂ devices and by a factor of ≈26.4 (from 219 to 5.75 × 10³ A W^?1) in the APTES/MoS₂ devices. The enhanced photoresponsivity values are much higher than that of the previously reported TMD photodetectors. The detectivity enhancement is ≈26.6‐fold in the OTS/WSe₂ devices and ≈24.5‐fold in the APTES/MoS₂ devices and is caused by the increased photocurrent and maintained dark current after doping. The optoelectronic performance is also investigated with different optical powers and the air‐exposure times. This doping study performed on TMD devices will play a significant role for optimizing the performance of future TMD‐based electronic/optoelectronic applications.     

一种基于多传感器的红外图像正则化超分辨率算法

提出一种红外图像多传感器超分辨率重建算法。 算法存在两个关键点:一是有效利用两类图像的相关性;二是针对红外图像的特点利用其自 身信息 构造正则化模型。采用相位一致性算法提取可见光图像边缘,利用此边缘信息对正则化模型 加权,以 充分利用可见光和红外图像的相关性;将一阶梯度锐化算子引入总广义变分模型,构成针对 红外 图像特点的正则化模型;最后采用一阶主-对偶优化算法求得加权后模型的最优解。实验表 明,本文算法可获得边缘清晰的重建结果,并且有效抑制噪声,在主观视觉效果和客观评价 指标方面均优于其他算法。     

Contralaterally transplanted human embryonic stem cell-derived neural precursor cells (ENStem-A) migrate and improve brain functions in stroke-damaged rats

The transplantation of neural precursor cells (NPCs) is known to be a promising approach to ameliorating behavioral deficits after stroke in a rodent model of middle cerebral artery occlusion (MCAo). Previous studies have shown that transplanted NPCs migrate toward the infarct region, survive and differentiate into mature neurons to some extent. However, the spatiotemporal dynamics of NPC migration following transplantation into stroke animals have yet to be elucidated. In this study, we investigated the fates of human embryonic stem cell (hESC)-derived NPCs (ENStem-A) for 8 weeks following transplantation into the side contralateral to the infarct region using 7.0T animal magnetic resonance imaging (MRI). T2- and T2*-weighted MRI analyses indicated that the migrating cells were clearly detectable at the infarct boundary zone by 1 week, and the intensity of the MRI signals robustly increased within 4 weeks after transplantation. Afterwards, the signals were slightly increased or unchanged. At 8 weeks, we performed Prussian blue staining and immunohistochemical staining using human-specific markers, and found that high percentages of transplanted cells migrated to the infarct boundary. Most of these cells were CXCR4-positive. We also observed that the migrating cells expressed markers for various stages of neural differentiation, including Nestin, Tuj1, NeuN, TH, DARPP-32 and SV38, indicating that the transplanted cells may partially contribute to the reconstruction of the damaged neural tissues after stroke. Interestingly, we found that the extent of gliosis (glial fibrillary acidic protein-positive cells) and apoptosis (TUNEL-positive cells) were significantly decreased in the cell-transplanted group, suggesting that hESC-NPCs have a positive role in reducing glia scar formation and cell death after stroke. No tumors formed in our study. We also performed various behavioral tests, including rotarod, stepping and modified neurological severity score tests, and found that the transplanted animals exhibited significant improvements in sensorimotor functions during the 8 weeks after transplantation. Taken together, these results strongly suggest that hESC-NPCs have the capacity to migrate to the infarct region, form neural tissues efficiently and contribute to behavioral recovery in a rodent model of ischemic stroke.     

Radical Addition Reactions of α-Substituted β,β-Difluorovinyl Sulfones

The radical addition reactions of α-substituted β,β-difluorovinyl sulfones 1 with α-oxy and acyl radical species, such as 1,3-dioxolane, tetrahydrofuran, 1,4-dioxane, butanal and hexanal, afforded radical addition products 2--16 in good yields.     

Electrophoretic separation of gold nanoparticles according to bifunctional molecules‐induced charge and size

Gold nanospheres modified with bifunctional molecules have been separated and characterized by using agarose gel electrophoresis as well as optical spectroscopy and electron microscopy. The electrophoretic mobility of a gold nanosphere capped with 11‐mercaptoundecanoic acid (MUA) has been found to depend on the number of MUA molecules per gold nanosphere, indicating that it increases with the surface charge of the nanoparticle. The extinction spectrum of gold nanospheres capped with MUA at an MUA molecules per gold nanosphere value of 1000 and connected via 1,6‐hexanedithiol (HDT) decreases by 33% in magnitude and shifts to the red as largely as 22 nm with the increase of the molar ratio of HDT to MUA (R_HM). Gold nanospheres capped with MUA and connected via HDT have been separated successfully using gel electrophoresis and characterized by measuring reflectance spectra of discrete electrophoretic bands directly in the gel and by monitoring transmission electron microscope images of gold nanoparticles collected from the discrete bands. Electrophoretic mobility has been found to decrease substantially with the increment of HDT to MUA, indicating that the size of aggregated gold nanoparticles increases with the concentration of HDT.