Adenosine receptor signaling: a key to opening the blood–brain door

International audienceAbstractThe aim of this review is to outline evidence that adenosine receptor (AR) activation can modulate blood–brain barrier (BBB) permeability and the implications for disease states and drug delivery. Barriers of the central nervous system (CNS) constitute a protective and regulatory interface between the CNS and the rest of the organism. Such barriers allow for the maintenance of the homeostasis of the CNS milieu. Among them, the BBB is a highly efficient permeability barrier that separates the brain micro-environment from the circulating blood. It is made up of tight junction-connected endothelial cells with specialized transporters to selectively control the passage of nutrients required for neural homeostasis and function, while preventing the entry of neurotoxic factors. The identification of cellular and molecular mechanisms involved in the development and function of CNS barriers is required for a better understanding of CNS homeostasis in both physiological and pathological settings. It has long been recognized that the endogenous purine nucleoside adenosine is a potent modulator of a large number of neurological functions. More recently, experimental studies conducted with human/mouse brain primary endothelial cells as well as with mouse models, indicate that adenosine markedly regulates BBB permeability. Extracellular adenosine, which is efficiently generated through the catabolism of ATP via the CD39/CD73 ecto-nucleotidase axis, promotes BBB permeability by signaling through A1 and A2A ARs expressed on BBB cells. In line with this hypothesis, induction of AR signaling by selective agonists efficiently augments BBB permeability in a transient manner and promotes the entry of macromolecules into the CNS. Conversely, antagonism of AR signaling blocks the entry of inflammatory cells and soluble factors into the brain. Thus, AR modulation of the BBB appears as a system susceptible to tighten as well as to permeabilize the BBB. Collectively, these findings point to AR manipulation as a pertinent avenue of research for novel strategies aiming at efficiently delivering therapeutic drugs/cells into the CNS, or at restricting the entry of inflammatory immune cells into the brain in some diseases such as multiple sclerosis

Non-Alcoholic Fatty Liver Disease Induces Signs of Alzheimer’s Disease (AD) in Wild-Type Mice and Accelerates Pathological Signs of AD in an AD Model

Background: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease afflicting about one third of the world\u27s population and 30 % of the US population. It is induced by consumption of high-lipid diets and is characterized by liver inflammation and subsequent liver pathology. Obesity and consumption of a high-fat diet are known to increase the risk of Alzheimer\u27s disease (AD). Here, we investigated NAFLD-induced liver inflammation in the pathogenesis of AD. Methods: WT and APP-Tg mice were fed with a standard diet (SD) or a high-fat diet (HFD) for 2, 5 months, or 1 year to induce NAFLD. Another set of APP-Tg mice were removed from HFD after 2 months and put back on SD for 3 months. Results: During acute phase NAFLD, WT and APP-Tg mice developed significant liver inflammation and pathology that coincided with increased numbers of activated microglial cells in the brain, increased inflammatory cytokine profile, and increased expression of toll-like receptors. Chronic NAFLD induced advanced pathological signs of AD in both WT and APP-Tg mice, and also induced neuronal apoptosis. We observed decreased brain expression of low-density lipoprotein receptor-related protein-1 (LRP-1) which is involved in β-amyloid clearance, in both WT and APP-Tg mice after ongoing administration of the HFD. LRP-1 expression correlated with advanced signs of AD over the course of chronic NAFLD. Removal of mice from HFD during acute NAFLD reversed liver pathology, decreased signs of activated microglial cells and neuro-inflammation, and decreased β-amyloid plaque load. Conclusions: Our findings indicate that chronic inflammation induced outside the brain is sufficient to induce neurodegeneration in the absence of genetic predisposition

Flora of Vascular Plants in Ridgelines in the Palgongsa Procincial Park, Korea

AbstractWe investigated and analyzed the flora of vascular plants around ridgelines in the Palgongsan Provincial Park to suggest fundamental data for establishing preservation plans of them. The flora of vascular plants around ridgelines was a total of 587 taxa including 102 familiies, 314 genera, 518 species, 58 varieties, 7 forma, and 4 subspecies. Rare plants designated by Korea Forest Service were 27 taxa including Semiquilegia mandshurica and Aristolochia manshuriensis. Endemic plants were 15 taxa including Clematis trichotoma and Carex okamotoi. Floristic special plants were a total of 100 taxa including all five classes. Naturalized plants were 13 taxa including Phytolacca Americana, ambrosia, and Taraxacum officinale

Charge-spin correlation in van der Waals antiferromagenet NiPS3

Strong charge-spin coupling is found in a layered transition-metal trichalcogenide NiPS3, a van derWaals antiferromagnet, from our study of the electronic structure using several experimental and theoretical tools: spectroscopic ellipsometry, x-ray absorption and photoemission spectroscopy, and density-functional calculations. NiPS3 displays an anomalous shift in the optical spectral weight at the magnetic ordering temperature, reflecting a strong coupling between the electronic and magnetic structures. X-ray absorption, photoemission and optical spectra support a self-doped ground state in NiPS3. Our work demonstrates that layered transition-metal trichalcogenide magnets are a useful candidate for the study of correlated-electron physics in two-dimensional magnetic material.Comment: 6 pages, 3 figur

C-ITS Environment Modeling and Attack Modeling

As technology advances, cities are evolving into smart cities, with the ability to process large amounts of data and the increasing complexity and diversification of various elements within urban areas. Among the core systems of a smart city is the Cooperative-Intelligent Transport Systems (C-ITS). C-ITS is a system where vehicles provide real-time information to drivers about surrounding traffic conditions, sudden stops, falling objects, and other accident risks through roadside base stations. It consists of road infrastructure, C-ITS centers, and vehicle terminals. However, as smart cities integrate many elements through networks and electronic control, they are susceptible to cybersecurity issues. In the case of cybersecurity problems in C-ITS, there is a significant risk of safety issues arising. This technical document aims to model the C-ITS environment and the services it provides, with the purpose of identifying the attack surface where security incidents could occur in a smart city environment. Subsequently, based on the identified attack surface, the document aims to construct attack scenarios and their respective stages. The document provides a description of the concept of C-ITS, followed by the description of the C-ITS environment model, service model, and attack scenario model defined by us.Comment: in Korean Language, 14 Figures, 15 Page

High-Performance Flexible Organic Light-Emitting Diodes Using Amorphous Indium Zinc Oxide Anode

We demonstrate a high-performance flexible organic light-emitting diode (OLED) employing amorphous indium zinc oxide (IZO) anode. The amorphous IZO on flexible polycarbonate (PC) substrate shows similar electrical conductivity and optical transmittance with commercial (ITO) glass, even though it was prepared at <50°C. Moreover, it exhibits little resistance change during 5000 bending cycles, demonstrating good mechanical robustness. A green phosphorescent OLED fabricated on amorphous IZO on flexible PC shows maximum external quantum efficiency of ext=13.7% and power efficiency of p=32.7 lm/W, which are higher than a device fabricated on a commercial ITO on glass (ext=12.4% and p=30.1 lm/W) and ITO on flexible PC (ext=8.5% and p =14.1 lm/W). The mechanical robustness and low-temperature deposition of IZO combined with high OLED performance clearly manifest that the amorphous IZO is a promising anode material for flexible displays.This work was supported by the Ministry of Commerce, Industry, and Energy through the OLED center and Samsung SDI. H.K.K. thanks the Korea Research Foundation (contract no. KRF-2006-331- D00243) for its support

Transparent Conducting Indium Zinc Tin Oxide Anode for Highly Efficient Phosphorescent Organic Light Emitting Diodes

The preparation and characteristics of a transparent conducting indium zinc tin oxide (IZTO) anode for highly efficient phosphorescent organic light emitting diodes (OLEDs) is described. The resistivity and transmittance of the IZTO anode are comparable to reference In2O3 (ITO) anode films even though it was prepared at room temperature. In addition, the work function of the ozone-treated amorphous IZTO anode (5.12±0.02 eV) is much higher than that of ozone-treated reference ITO anodes (4.94±0.02 eV). The current-voltage-luminance characteristics and efficiencies of OLEDs prepared on the IZTO anode are critically dependent on the sheet resistance of the IZTO anode. Furthermore, both the quantum efficiency and power efficiency of the OLED fabricated on the amorphous IZTO anode are much higher than those of an OLED with the reference ITO anode due to the higher work function of the IZTO anode than those of conventional ITO anode. This indicates that IZTO is an alternative material for conventional ITO anodes used in OLEDs and flexible displays.This work was supported by a Korea Research Foundation Grant funded by the Korea Government MOEHRD: Basic Research Promotion Fund grant no. KRF-2006-331-D00243 and the Ministry of Commerce, Industry, and Energy