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Abstract Neurovascular coupling is a precise mechanism that induces increased blood flow to activated brain regions, thereby providing oxygen and glucose. In this study, we hypothesized that N-methyl-D-aspartate (NMDA) receptor signaling, the most well characterized neurotransmitter signaling system which regulates delivery of essential molecules through the blood–brain barrier (BBB). Upon application of NMDA in both in vitro and in vivo models, increased delivery of bioactive molecules that was mediated through modulation of molecules involved in molecular delivery, including clathrin and caveolin were observed. Also, NMDA activation induced structural changes in the BBB and increased transcellular permeability that showed regional heterogeneity in its responses. Moreover, NMDA receptor activation increased endosomal trafficking and facilitated inactivation of lysosomal pathways and consequently increased molecular delivery mediated by activation of calmodulin-dependent protein kinase II (CaMKII) and RhoA/protein kinase C (PKC). Subsequent in vivo experiments using mice specifically lacking NMDA receptor subunit 1 in endothelial cells showed decreased neuronal density in the brain cortex, suggesting that a deficiency in NMDA receptor signaling in brain endothelial cells induces neuronal losses. Together, these results highlight the importance of NMDA-receptor-mediated signaling in the regulation of BBB permeability that surprisingly also affected CD31 staining.

Cytoplasmic accumulation of TDP-43 in motor neurons is the most prominent pathological feature in amyotrophic lateral sclerosis (ALS). A feedback cycle between nucleocytoplasmic transport (NCT) defect and TDP-43 aggregation was shown to contribute to accumulation of TDP-43 in the cytoplasm. However, little is known about cellular factors that can control the activity of NCT, thereby affecting TDP-43 accumulation in the cytoplasm. Here, we identified via FRAP and optogenetics cytosolic calcium as a key cellular factor controlling NCT of TDP-43. Dynamic and reversible changes in TDP-43 localization were observed in Drosophila sensory neurons during development. Genetic and immunohistochemical analyses identified the cytosolic calcium-Calpain-A-Importin α3 pathway as a regulatory mechanism underlying NCT of TDP-43. In C9orf72 ALS fly models, upregulation of the pathway activity by increasing cytosolic calcium reduced cytoplasmic accumulation of TDP-43 and mitigated behavioral defects. Together, these results suggest the calcium-Calpain-A-Importin α3 pathway as a potential therapeutic target of ALS.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease (COVID-19), is currently infecting millions of people worldwide and is causing drastic changes in people’s lives. Recent studies have shown that neurological symptoms are a major issue for people infected with SARS-CoV-2. However, the mechanism through which the pathological effects emerge is still unclear. Brain endothelial cells (ECs), one of the components of the blood–brain barrier, are a major hurdle for the entry of pathogenic or infectious agents into the brain. They strongly express angiotensin converting enzyme 2 (ACE2) for its normal physiological function, which is also well-known to be an opportunistic receptor for SARS-CoV-2 spike protein, facilitating their entry into host cells. First, we identified rapid internalization of the receptor-binding domain (RBD) S1 domain (S1) and active trimer (Trimer) of SARS-CoV-2 spike protein through ACE2 in brain ECs. Moreover, internalized S1 increased Rab5, an early endosomal marker while Trimer decreased Rab5 in the brain ECs. Similarly, the permeability of transferrin and dextran was increased in S1 treatment but decreased in Trimer, respectively. Furthermore, S1 and Trimer both induced mitochondrial damage including functional deficits in mitochondrial respiration. Overall, this study shows that SARS-CoV-2 itself has toxic effects on the brain ECs including defective molecular delivery and metabolic function, suggesting a potential pathological mechanism to induce neurological signs in the brain.

Carbonate-type macrodiols synthesized by base-catalyzed polycondensation of co-diols and dimethyl carbonate as an environmentally-friendly route were subsequently utilized for the preparation of transparent and self-healable thermoplastic polyurethanes (TPUs) containing a carbonate-type soft segment. Three types of macrodiols, obtained from mono, dual and triple diol-monomers for target molecular weights of 1 and 1.5 kg mol−1, were analyzed by 1H NMR integration and the OH titration value. Colorless transparent macrodiols in a liquid state at a room temperature of 20 °C were obtained, except the macrodiol from mono 1,6-hexanediol. Before TPU synthesis, macrodiols require pH neutralization to prevent gelation. TPUs synthesized by a solution pre-polymer method with 4,4′-methylene(bisphenyl isocyanate) and 1,4-butanediol as a chain extender exhibited moderate molecular weights, good transparencies and robust mechanical properties. Especially, the incorporation of 3-methyl-1,5-pentanediol within carbonate-type macrodiols enhanced the transparency of the resultant TPUs by decreasing the degree of microphase separation evidenced by ATR-FTIR and DSC. Interestingly, packing density of hard segments and the degree of microphase separation determined the self-healing efficiency of TPUs, which showed good performances in the case of sourced macrodiols from triple diol-monomers.

Lipoxygenases (LOXs) catalyze the formation of fatty acid hydroperoxides involved in responses to stresses. This study examines the expression of a non-traditional dual positional specific maize LOX in response to wounding or methyl jasmonate (MeJA). Full-length maize LOX cDNA was expressed in Escherichia coli, and recombinant LOX was purified and characterized enzymatically. RP-HPLC and GC-MS analysis showed that the purified LOX converts &agr;-linolenic acid into 13-hydroperoxylinolenic acid and 9-hydroperoxylinolenic acid in a 6:4 ratio. LOX mRNA accumulated rapidly and transiently in response to wounding reaching a peak of expression about 3 h after wounding. This increase followed an initial increase in endogenous jasmonic acid (JA) 1 h after wounding (JA burst). However, the expression of LOX induced by MeJA lasted longer than the expression induced by wounding, and the MeJA-induced expression seemed to be biphasic pattern composed of early and late phases. The expression of LOX in the presence of inhibitors of JA biosynthesis was not completely inhibited, but delayed in wound response and the expression period was shortened in MeJA response. These results suggest that wound-responsive JA burst may trigger the early phase of LOX expression which facilitates biosynthesis of endogenous JA through its 13-LOX activity, and subsequently leads to the activation of the late phase LOX expression in MeJA-treated maize seedlings. Implications of dual positional specificity of maize LOX in the observed expression kinetics are discussed. [ABSTRACT FROM AUTHOR]

Neurovascular coupling is a precise mechanism that induces increased blood flow to activated brain regions, thereby providing oxygen and glucose. In this study, we hypothesized that N-methyl-D-aspartate (NMDA) receptor signaling, the most well characterized neurotransmitter signaling system which regulates delivery of essential molecules through the blood–brain barrier (BBB). Upon application of NMDA in both in vitro and in vivo models, increased delivery of bioactive molecules that was mediated through modulation of molecules involved in molecular delivery, including clathrin and caveolin were observed. Also, NMDA activation induced structural changes in the BBB and increased transcellular permeability that showed regional heterogeneity in its responses. Moreover, NMDA receptor activation increased endosomal trafficking and facilitated inactivation of lysosomal pathways and consequently increased molecular delivery mediated by activation of calmodulin-dependent protein kinase II (CaMKII) and RhoA/protein kinase C (PKC). Subsequent in vivo experiments using mice specifically lacking NMDA receptor subunit 1 in endothelial cells showed decreased neuronal density in the brain cortex, suggesting that a deficiency in NMDA receptor signaling in brain endothelial cells induces neuronal losses. Together, these results highlight the importance of NMDA-receptor-mediated signaling in the regulation of BBB permeability that surprisingly also affected CD31 staining. [ABSTRACT FROM AUTHOR]

Among the components of the blood–brain barrier (BBB), endothelial cells (ECs) play an important role in supplying limited materials, especially glucose, to the brain. However, the mechanism by which glucose is metabolized in brain ECs is still elusive. To address this topic, we assessed the metabolic signature of glucose utilization using live-cell metabolic assays and liquid chromatography–tandem mass spectrometry metabolomic analysis. We found that brain ECs are highly dependent on aerobic glycolysis, generating lactate as its final product with minimal consumption of glucose. Glucose treatment decreased the oxygen consumption rate in a dose-dependent manner, indicating the Crabtree effect. Moreover, when glycolysis was inhibited, brain ECs showed impaired permeability to molecules utilizing transcellular pathway. In addition, we found that the blockade of glycolysis in mouse brain with 2-deoxyglucose administration resulted in decreased transcellular permeability of the BBB. In conclusion, utilizing glycolysis in brain ECs has critical roles in the maintenance and permeability of the BBB. Overall, we could conclude that brain ECs are highly glycolytic, and their energy can be used to maintain the transcellular permeability of the BBB. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease (COVID-19), is currently infecting millions of people worldwide and is causing drastic changes in people's lives. Recent studies have shown that neurological symptoms are a major issue for people infected with SARS-CoV-2. However, the mechanism through which the pathological effects emerge is still unclear. Brain endothelial cells (ECs), one of the components of the blood–brain barrier, are a major hurdle for the entry of pathogenic or infectious agents into the brain. They strongly express angiotensin converting enzyme 2 (ACE2) for its normal physiological function, which is also well-known to be an opportunistic receptor for SARS-CoV-2 spike protein, facilitating their entry into host cells. First, we identified rapid internalization of the receptor-binding domain (RBD) S1 domain (S1) and active trimer (Trimer) of SARS-CoV-2 spike protein through ACE2 in brain ECs. Moreover, internalized S1 increased Rab5, an early endosomal marker while Trimer decreased Rab5 in the brain ECs. Similarly, the permeability of transferrin and dextran was increased in S1 treatment but decreased in Trimer, respectively. Furthermore, S1 and Trimer both induced mitochondrial damage including functional deficits in mitochondrial respiration. Overall, this study shows that SARS-CoV-2 itself has toxic effects on the brain ECs including defective molecular delivery and metabolic function, suggesting a potential pathological mechanism to induce neurological signs in the brain. [ABSTRACT FROM AUTHOR]

Acrylic pressure sensitive adhesives (PSAs) were prepared by UV polymerization under varying curing conditions of both fast and slow curing, employing high- and low-intensity UV radiation, respectively. The influences of curing conditions and isobornyl acrylate (IBOA) content on PSA performance were comprehensively investigated by measurement of their rheological, thermal, and adhesive properties. In particular, rheological characterization was accomplished by several analytical methods, such as in situ UV rheology, frequency sweep, stress relaxation, and temperature ramp tests, to understand the effect of the UV curing process and IBOA content on the viscoelastic behavior of acrylic PSAs. The slow-cured samples were observed to form more tightly crosslinked networks compared to the fast-cured. On the other hand, at high loading levels of IBOA, in the case of slow curing, the sample exhibited a contrasting trend, having the shortest stress relaxation time and the highest energy dissipation; this was due to molecular chain scission occurring in the crosslinked polymer during UV polymerization. Consequently, we successfully demonstrated the influence of monomer composition of acrylic PSAs, and that of curing conditions employed in UV polymerization. This study provides valuable insights for the development of crosslinked polymer networks of acrylic PSAs for flexible display applications. [ABSTRACT FROM AUTHOR]

The hydrophobicity of film surfaces can be enhanced by introducing wrinkling and buckling, and the wrinkling method in this study is a facile way to induce various microstructures including wrinkles and buckles in film surfaces. When buckles formed, the water contact angle parallel to the wrinkled direction (θ//) changed dramatically with strain, but the contact angle perpendicular to the wrinkled direction did not change much. It was found that the buckle structural feature was the key characteristics affecting the change in contact angle, θ//. A dimensionless number, the ratio of buckle height to spacing (Hb/Sb) was introduced to determine the relationship between the structural feature and the contact angle, θ//. The contact angle, θ// strongly depended on Hb/Sb. The thickest film (hf = 605 nm) at the highest strain (ɛ = 30%) and the highest Hb/Sb formed many large buckles, and exhibited super-hydrophobicity (θ// = 169 ± 10°). [ABSTRACT FROM AUTHOR]

Protein toxicity can be defined as all the pathological changes that ensue from accumulation, mis-localization, and/or multimerization of disease-specific proteins. Most neurodegenerative diseases manifest protein toxicity as one of their key pathogenic mechanisms, the details of which remain unclear. By systematically deconstructing the nature of toxic proteins, we aim to elucidate and illuminate some of the key mechanisms of protein toxicity from which therapeutic insights may be drawn. In this review, we focus specifically on protein toxicity from the point of view of various cellular compartments such as the nucleus and the mitochondria. We also discuss the cell-to-cell propagation of toxic disease proteins that complicates the mechanistic understanding of the disease progression as well as the spatiotemporal point at which to therapeutically intervene. Finally, we discuss selective neuronal vulnerability, which still remains largely enigmatic. [ABSTRACT FROM AUTHOR]

The article presents a study which examined the effects of pretreatment reagents on the hydrolysis and physical features of poly(ethylene terephthalate) (PET) fabrics. The fabrics were examined under different alkaline hydrolysis treatment and pretreatment conditions. The PET fabric used in the study was provided by the Korea Apparel Testing and Research Institute. The methods used included the differential scanning calorimetry (DCS) and field emission scanning electron microscopy (FESEM).

Bacterial and fungal pathogens have caused serious problems to the human health. This is particularly true for untreatable infectious diseases and clinical situations where there is no reliable treatment for infected patients. To increase the antimicrobial activity of materials, we introduce silver nanoparticle (NP) patches in which the NPs are incorporated to the surface of smooth and uniform poly(acrylic acid) (PAA) nanofibers. The PAA nanofibers were thermally crosslinked with ethylene glycol via heat treatment through a mild method. The characterization of the resulting PAA-silver NP patches was done using scanning electron microscopy (SEM), UV spectroscopy, X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). To demonstrate the antimicrobial activity of PAA, we incorporated the patches containing the silver NPs into strains of fungi such as Candida albicans (C. albican) and bacteria such as Methicillin-resistant Staphylococcus aureus (MRSA). The PAA-silver fibers achieved zones of inhibition against C. albicans and MRSA indicating their antimicrobial activity against both fungi and bacteria. We conclude that silver NP patches exhibited multiple inhibitory actions for the interruption and blockage of activity fungal and bacterial strains, which has the potential as an antimicrobial agent in infectious diseases. Moreover, the proposed material has the potential to be used in antimicrobial textile fabrics, food packaging films, and wound dressings. [ABSTRACT FROM AUTHOR]

We conducted a preliminary study on fiber structural development in the high-speed melt spinning of environmentally friendly polyethylene terephthalate (Ti-PET) synthesized with 25 ppm of titanium-based catalyst, which was compared with conventional PET (Sb-PET) synthesized with 260 ppm of antimony-based catalyst. Gel permeation chromatography of Ti- and Sb-PET resins of intrinsic viscosity 0.63 confirmed that both resins have similar molecular weights and distributions. However, differential scanning calorimetry revealed that the Ti-PET resin exhibited a lower melt–crystallization peak and isothermal melt-crystallization rate than the Sb-PET resin. High-speed melt spinning of the Ti- and Sb-PET was possible up to a spinning velocity of 6 km/min. Two-dimensional wide-angle X-ray diffraction analyses showed that the molecular orientation of the obtained as-spun Ti- and Sb-PET fibers increased with spinning velocity, and a highly oriented, crystalline structure by orientation-induced crystallization started to appear from 5 km/min. Notably, Ti-PET fibers showed a lower degree of crystalline structural development and lower tensile strength compared with Sb-PET fibers under the high-speed spinning conditions. Our results suggest that the catalyst in PET resins can act as nucleating agents in thermal- and orientation-induced crystallization, and that differences in catalyst content can influence PET fiber structure development under extreme conditions in high-speed melt spinning. [ABSTRACT FROM AUTHOR]