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     

Micromorphology of epicuticular wax structures of the garden strawberry leaves by electron microscopy: Syntopism and polymorphism

Ultrastructural aspects of leaf epicuticular wax structures were investigated in the garden strawberry Fragaria × ananassa by scanning and transmission electron microscopy. Both the adaxial and abaxial surfaces of two cultivars (Maehyang and Red Pearl) were collected and subjected to surface observations and ultrathin sections. The most prominent leaf epicuticular wax structures included membraneous platelets and angular rodlets. Most wax platelets were membraneous, and appeared to protrude from the surface at an acute angle. Angular rodlets were usually bent and had rather distinct facets in the abaxial surface of the two cultivars. Membraneous platelets were predominant on the adaxial surface of Maehyang, whereas the adaxial surface of Red Pearl was characterized by angular rodlets. However, both cultivars possessed angular rodlets on the abaxial surface, simultaneously. The combination of air-drying without vacuum and in-lens imaging of secondary electron signals with a field emission gun could impart the superb resolution at low electron dose with minimal specimen shrinkage. In vertical profiles of the leaf epidermis, epicuticular waxes were observed above the cuticle layer, and measured approximately as 50 nm in thickness. The natural epicuticular waxes were seemingly mixtures of electron-dense microfibrils, and heterogeneous in shape on ultrathin sections. Distinct crystal-like strata could be hardly discernable in the wax structures. These results suggest that the garden strawberry has the nature of syntopism within one plant and polymorphism within the same species in the formation and occurrence of leaf epicuticular waxes.     

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.     

Bistable stochastic biochemical networks: highly specific systems with few chemicals

In this paper we describe a class of stochastic biochemical systems exhibiting bistable behavior, in the sense that the invariant measure associated to the system is concentrated near two different classes of states of the system. We develop methods that allow us to describe the behavior of the invariant measure in some suitable asymptotic limits, as well as the switching times for the transitions between the states close to each of the states with high probability. Due to the discrete character of the problem, switching times cannot be computed using the classical Kramers’ formula, and alternative methods are required.     

Orientational and electro-optical properties of liquid crystal aligned with a directly spinnable carbon nanotube web

We investigated the orientational and electro-optical properties of a nematic liquid crystal (LC) aligned with a directly spinnable carbon nanotube (CNT) web functioning both as an electrode and as an alignment layer. The LC molecules were uniformly oriented along the drawing direction of the CNT web and the spatially averaged birefringence was comparable to a rubbed polyimide sample. The CNT web sample also showed smaller residual DC and hysteresis compared to the polyimide sample.     

Investigation on ion movement in the fringe-field switching mode depending on resistivity of alignment layer and dielectric anisotropic sign of liquid crystal

Adsorption and desorption of ions at interface between liquid crystal and alignment layer in liquid crystal displays play a crucial role in residual direct current voltage associated with image sticking. In this article, the dependency of such adsorption and desorption of ions on resistivity of alignment layer and sign of liquid crystal dielectric anisotropy in the fringe-field liquid crystal cell has been investigated. Our studies show that the time constant of ions during adsorption and desorption depends upon resistivity and dielectric constant of liquid crystal and alignment layer, and most strongly influenced by the resistivity of alignment layer such that the one with lower resistivity in two orders shows much faster adsorption and desorption at the interface than that of the one with higher resistivity.     

Designed Synthesis of Well‐Defined Pd@Pt Core–Shell Nanoparticles with Controlled Shell Thickness as Efficient Oxygen Reduction Electrocatalysts

Improving the electrocatalytic activity and durability of Pt‐based catalysts with low Pt content toward the oxygen reduction reaction (ORR) is one of the main challenges in advancing the performance of polymer electrolyte membrane fuel cells (PEMFCs). Herein, a designed synthesis of well‐defined Pd@Pt core–shell nanoparticles (NPs) with a controlled Pt shell thickness of 0.4–1.2 nm by a facile wet chemical method and their electrocatalytic performances for ORR as a function of shell thickness are reported. Pd@Pt NPs with predetermined structural parameters were prepared by in situ heteroepitaxial growth of Pt on as‐synthesized 6 nm Pd NPs without any sacrificial layers and intermediate workup processes, and thus the synthetic procedure for the production of Pd@Pt NPs with well‐defined sizes and shell thicknesses is greatly simplified. The Pt shell thickness could be precisely controlled by adjusting the molar ratio of Pt to Pd. The ORR performance of the Pd@Pt NPs strongly depended on the thickness of their Pt shells. The Pd@Pt NPs with 0.94 nm Pt shells exhibited enhanced specific activity and higher durability compared to other Pd@Pt NPs and commercial Pt/C catalysts. Testing Pd@Pt NPs with 0.94 nm Pt shells in a membrane electrode assembly revealed a single‐cell performance comparable with that of the Pt/C catalyst despite their lower Pt content, that is the present NP catalysts can facilitate low‐cost and high‐efficient applications of PEMFCs.     

Recyclable N-heterocyclic carbene/palladium catalyst on graphene oxide for the aqueous-phase Suzuki reaction

Graphene oxide (GO) was functionalized with a N-heterocyclic carbene (NHC) precursor, 3-(3-aminopropyl)-1-methylimidazolium bromide ([APMIm][Br]) for the immobilization of palladium catalyst. The GO-supported NHC precursor (IMGO) formed a stable complex with Pd(OAc)₂ (GO–NHC–Pd), which showed excellent catalytic activity and fast reaction kinetics in the aqueous-phase Suzuki reaction of aryl bromides and chlorides at relatively mild conditions (1 h at 50 °C). The GO–NHC–Pd catalyst was reused several times without any loss of its catalytic activity in the Suzuki reaction of aryl bromide.     

Precise characterization method of antibody‐conjugated magnetic nanoparticles for pathogen detection using stuffer‐free multiplex ligation‐dependent probe amplification

Antibody‐conjugated magnetic nanoparticles (Ab‐MNPs) have potential in pathogen detection because they allow target cells to be easily separated from complex sample matrices. However, the sensitivity and specificity of pathogen capture by Ab‐MNPs generally vary according to the types of MNPs, antibodies, and sample matrices, as well as preparation methods, including immobilization. Therefore, achieving a reproducible analysis utilizing Ab‐MNPs as a pathogen detection method requires accurate characterization of Ab‐MNP capture ability and standardization of all handling processes. In this study, we used high‐resolution CE‐single strand conformational polymorphism coupled with a stuffer‐free multiplex ligation‐dependent probe amplification system to characterize Ab‐MNPs. The capture ability of Ab‐MNPs targeting Salmonella enteritidis and nine pathogens, including S. enteritidis, was analyzed in phosphate buffer and milk. The effect of storage conditions on the stability of Ab‐MNPs was also assessed. The results showed that the stuffer‐free multiplex ligation‐dependent probe amplification system has the potential to serve as a standard characterization method for Ab‐MNPs. Moreover, the precise characterization of Ab‐MNPs facilitated robust pathogen detection in various applications.     

Preparation of 2,2-difluoro-1-trialkylsilylethenylstannanes and their cross-coupling reactions

Reaction of 2 with bis(tributyltin) in the presence of 3 mol % Pd₂(dba)₃, 6 mol % XPhos, and 30 equiv of LiBr in wet and air bubbled THF at reflux for 8 h afforded the desired products 3 in 73–74% yields. The cross-coupling reaction of 3a with aryl iodides in the presence of 10 mol % Pd(PPh₃)₄ and 10 mol % CuI afforded the coupled products 4a–p in 47–90% yields. The coupling reaction of 3b with various alkynyl bromides having aryl-, alkyl, or trialkylsilyl group also afforded the corresponding 1,3-enynes 5a–g in 61–77% yields.