The Endocannabinoid System and Oligodendrocytes in Health and Disease

Cannabinoid-based interventions are being explored for central nervous system (CNS) pathologies such as neurodegeneration, demyelination, epilepsy, stroke, and trauma. As these disease states involve dysregulation of myelin integrity and/or remyelination, it is important to consider effects of the endocannabinoid system on oligodendrocytes and their precursors. In this review, we examine research reports on the effects of the endocannabinoid system (ECS) components on oligodendrocytes and their precursors, with a focus on therapeutic implications. Cannabinoid ligands and modulators of the endocannabinoid system promote cell signaling in oligodendrocyte precursor survival, proliferation, migration and differentiation, and mature oligodendrocyte survival and myelination. Agonist stimulation of oligodendrocyte precursor cells (OPCs) at both CB1 and CB2 receptors counter apoptotic processes via Akt/PI3K, and promote proliferation via Akt/mTOR and ERK pathways. CB1 receptors in radial glia promote proliferation and conversion to progenitors fated to become oligodendroglia, whereas CB2 receptors promote OPC migration in neonatal development. OPCs produce 2-arachidonoylglycerol (2-AG), stimulating cannabinoid receptor-mediated ERK pathways responsible for differentiation to arborized, myelin basic protein (MBP)-producing oligodendrocytes. In cell culture models of excitotoxicity, increased reactive oxygen species, and depolarization-dependent calcium influx, CB1 agonists improved viability of oligodendrocytes. In transient and permanent middle cerebral artery occlusion models of anoxic stroke, WIN55212-2 increased OPC proliferation and maturation to oligodendroglia, thereby reducing cerebral tissue damage. In several models of rodent encephalomyelitis, chronic treatment with cannabinoid agonists ameliorated the damage by promoting OPC survival and oligodendrocyte function. Pharmacotherapeutic strategies based upon ECS and oligodendrocyte production and survival should be considered

SiPM-matrix readout of two-phase argon detectors using electroluminescence in the visible and near infrared range

Proportional electroluminescence (EL) in noble gases is used in two-phase detectors for dark matter searches to record (in the gas phase) the ionization signal induced by particle scattering in the liquid phase. The “standard” EL mechanism is considered to be due to noble gas excimer emission in the vacuum ultraviolet (VUV). In addition, there are two alternative mechanisms, producing light in the visible and near infrared (NIR) ranges. The first is due to bremsstrahlung of electrons scattered on neutral atoms (“neutral bremsstrahlung”, NBrS). The second, responsible for electron avalanche scintillation in the NIR at higher electric fields, is due to transitions between excited atomic states. In this work, we have for the first time demonstrated two alternative techniques of the optical readout of two-phase argon detectors, in the visible and NIR range, using a silicon photomultiplier matrix and electroluminescence due to either neutral bremsstrahlung or avalanche scintillation. The amplitude yield and position resolution were measured for these readout techniques, which allowed to assess the detection threshold for electron and nuclear recoils in two-phase argon detectors for dark matter searches. To the best of our knowledge, this is the first practical application of the NBrS effect in detection science

Design and construction of a new detector to measure ultra-low radioactive-isotope contamination of argon

Large liquid argon detectors offer one of the best avenues for the detection of galactic weakly interacting massive particles (WIMPs) via their scattering on atomic nuclei. The liquid argon target allows exquisite discrimination between nuclear and electron recoil signals via pulse-shape discrimination of the scintillation signals. Atmospheric argon (AAr), however, has a naturally occurring radioactive isotope, 39Ar, a β emitter of cosmogenic origin. For large detectors, the atmospheric 39Ar activity poses pile-up concerns. The use of argon extracted from underground wells, deprived of 39Ar, is key to the physics potential of these experiments. The DarkSide-20k dark matter search experiment will operate a dual-phase time projection chamber with 50 tonnes of radio-pure underground argon (UAr), that was shown to be depleted of 39Ar with respect to AAr by a factor larger than 1400. Assessing the 39Ar content of the UAr during extraction is crucial for the success of DarkSide-20k, as well as for future experiments of the Global Argon Dark Matter Collaboration (GADMC). This will be carried out by the DArT in ArDM experiment, a small chamber made with extremely radio-pure materials that will be placed at the centre of the ArDM detector, in the Canfranc Underground Laboratory (LSC) in Spain. The ArDM LAr volume acts as an active veto for background radioactivity, mostly γ-rays from the ArDM detector materials and the surrounding rock. This article describes the DArT in ArDM project, including the chamber design and construction, and reviews the background required to achieve the expected performance of the detector

Sparsely Cross-Linked Hydrogel with Starch Fragments as a Multifunctional Soil Conditioner

A sparsely cross-linked copolymer was synthesized, and was composed of acrylic acid, acrylamide, and starch. Swelling of the copolymer in an aqueous solution resulted in the formation of hydrogel particles; this formulation was used as a partially biodegradable soil conditioner. The hydrogel was characterized with the following main conclusions: (a) the degree of copolymer swelling increases from 300 to 550 when altering the pH of the solution from 3 to 9. (b) After mixing with sand and soil, the degree of swelling decreases because of restricted volumes of sand/soil-filled containers and a mechanical resistance from the sand/soil particles. (c) Initial sand and soil additions demonstrate unsatisfactory water-retaining properties; the addition of the hydrogel significantly increases the maximum water capacity, while a substantial part of the water in the hydrogel remains available to plants. (d) Upon deposition of the hydrogel formulation over sand/soil and drying out, a protective coating forms on the surface, composed of hydrogel and sand/soil particles, resistant to wind and water erosion. (e) The starch-containing hydrogel is non-toxic towards bacterial and fungal microorganisms; the latter can utilize the microgel in order to support their own development. The results of the work indicate that cross-linked anionic copolymers are promising for use as combined soil conditioners

Sparsely Cross-Linked Hydrogel with Starch Fragments as a Multifunctional Soil Conditioner

A sparsely cross-linked copolymer was synthesized, and was composed of acrylic acid, acrylamide, and starch. Swelling of the copolymer in an aqueous solution resulted in the formation of hydrogel particles; this formulation was used as a partially biodegradable soil conditioner. The hydrogel was characterized with the following main conclusions: (a) the degree of copolymer swelling increases from 300 to 550 when altering the pH of the solution from 3 to 9. (b) After mixing with sand and soil, the degree of swelling decreases because of restricted volumes of sand/soil-filled containers and a mechanical resistance from the sand/soil particles. (c) Initial sand and soil additions demonstrate unsatisfactory water-retaining properties; the addition of the hydrogel significantly increases the maximum water capacity, while a substantial part of the water in the hydrogel remains available to plants. (d) Upon deposition of the hydrogel formulation over sand/soil and drying out, a protective coating forms on the surface, composed of hydrogel and sand/soil particles, resistant to wind and water erosion. (e) The starch-containing hydrogel is non-toxic towards bacterial and fungal microorganisms; the latter can utilize the microgel in order to support their own development. The results of the work indicate that cross-linked anionic copolymers are promising for use as combined soil conditioners