Growth of large SbSI crystals

In this paper a novel method of SbSI single crystals fabrication is presented. In this method a sonochemically prepared SbSI gel is used as an intermediate product in a vapour growth process. The main advantages of the presented technique are as follows. First, the SbSI gel source material has lower temperature of sublimation and allows to avoid explosions during SbSI synthesis (the sonochemical synthesis is free of any explosion hazard). Second, but not least, the grown SbSI single crystals have smaller ratio of longitudinal and lateral dimensions. The cross sections of the presented crystals are relatively large (they are up to 9 mm2). The crystals have been characterized by X-ray diffraction, angle-resolved optical spectroscopy, and diffusive reflectivity

A novel α-conotoxin, PeIA, cloned from Conus pergrandis, discriminates between Rat α9α10 and α7 nicotinic cholinergic receptors

The α9 and α10 nicotinic cholinergic subunits assemble to form the receptor believed to mediate synaptic transmission between efferent olivocochlear fibers and hair cells of the cochlea, one of the few examples of postsynaptic function for a non-muscle nicotinic acetylcholine receptor (nAChR). However, it has been suggested that the expression profile of α9 and α10 overlaps with that of α7 in the cochlea and in sites such as dorsal root ganglion neurons, peripheral blood lymphocytes, developing thymocytes, and skin. We now report the cloning, total synthesis, and characterization of a novel toxin α-conotoxin PeIA that discriminates between α9α10 and α7 nAChRs. This is the first toxin to be identified from Conus pergrandis, a species found in deep waters of the Western Pacific. α-Conotoxin PeIA displayed a 260-fold higher selectivity for α-bungarotoxin-sensitive α9α10 nAChRs compared with α-bungarotoxin-sensitive α7 receptors. The IC50 of the toxin was 6.9 ± 0.5 nM and 4.4 ± 0.5 nM for recombinant α9α10 and wild-type hair cell nAChRs, respectively. α-Conotoxin PeIA bears high resemblance to α-conotoxins MII and GIC isolated from Conus magus and Conus geographus, respectively. However, neither α-conotoxin MII nor α-conotoxin GIC at concentrations of 10 μM blocked acetylcholine responses elicited in Xenopus oocytes injected with the α9 and α10 subunits. Among neuronal non-α-bungarotoxin- sensitive receptors, α-conotoxin PeIA was also active at α3β2 receptors and chimeric α6/α3β2β3 receptors. α-Conotoxin PeIA represents a novel probe to differentiate responses mediated either through α9α10 or α7 nAChRs in those tissues where both receptors are expressed.Fil: McIntosh, J. Michael. University of Utah; Estados UnidosFil: Plazas, Paola Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Watkins, Maren. University of Utah; Estados UnidosFil: Gomez Casati, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Olivera, Baldomero M.. University of Utah; Estados UnidosFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentin

Sulfonylurea Receptor 1, Transient Receptor Potential Cation Channel Subfamily M Member 4, and KIR6.2:Role in Hemorrhagic Progression of Contusion

Contusió cerebral; Glibenclamida; Progressió hemorràgica de contusióBrain contusion; Glibenclamide; Hemorrhagic progression of contusionContusión cerebral; Glibenclamida; Progresión hemorrágica de contusiónIn severe traumatic brain injury (TBI), contusions often are worsened by contusion expansion or hemorrhagic progression of contusion (HPC), which may double the original contusion volume and worsen outcome. In humans and rodents with contusion-TBI, sulfonylurea receptor 1 (SUR1) is upregulated in microvessels and astrocytes, and in rodent models, blockade of SUR1 with glibenclamide reduces HPC. SUR1 does not function by itself, but must co-assemble with either KIR6.2 or transient receptor potential cation channel subfamily M member 4 (TRPM4) to form KATP (SUR1-KIR6.2) or SUR1-TRPM4 channels, with the two having opposite effects on membrane potential. Both KIR6.2 and TRPM4 are reportedly upregulated in TBI, especially in astrocytes, but the identity and function of SUR1-regulated channels post-TBI is unknown. Here, we analyzed human and rat brain tissues after contusion-TBI to characterize SUR1, TRPM4, and KIR6.2 expression, and in the rat model, to examine the effects on HPC of inhibiting expression of the three subunits using intravenous antisense oligodeoxynucleotides (AS-ODN). Glial fibrillary acidic protein (GFAP) immunoreactivity was used to operationally define core versus penumbral tissues. In humans and rats, GFAP-negative core tissues contained microvessels that expressed SUR1 and TRPM4, whereas GFAP-positive penumbral tissues contained astrocytes that expressed all three subunits. Förster resonance energy transfer imaging demonstrated SUR1-TRPM4 heteromers in endothelium, and SUR1-TRPM4 and SUR1-KIR6.2 heteromers in astrocytes. In rats, glibenclamide as well as AS-ODN targeting SUR1 and TRPM4, but not KIR6.2, reduced HPC at 24 h post-TBI. Our findings demonstrate upregulation of SUR1-TRPM4 and KATP after contusion-TBI, identify SUR1-TRPM4 as the primary molecular mechanism that accounts for HPC, and indicate that SUR1-TRPM4 is a crucial target of glibenclamide.J.M.S is supported by grants from the Department of Veterans Affairs (I01BX002889), the Department of Defense (SCI170199), the National Heart, Lung and Blood Institute (R01HL082517) and the National Institute of Neurological Disorders and Stroke (NINDS) (R01NS060801; R01NS102589; R01NS105633); V.G. is supported by a grant from NINDS (NS061934)

p, T, E-diagram of Sn₂P₂S₆ ferroelectric with high-pressure incommensurate phase

The investigations on the temperature change in dielectric permeability of Sn₂P₂S₆ crystal at different misaligning electric fields and hydrostatic pressures have been carried out to establish the form of p, T, E-diagram for this crystal. Based on the investigations on dielectric permeability anomalies, the E, T -diagrams at different magnitudes of hydrostatic pressure and p, T, E-diagram of Sn₂P₂S₆ crystal have been constructed. The magnitudes of coefficients in the thermodynamic potential expansion have been estimated and coordinates of critical points in E, T -diagrams have been defined.Проведено дослідження температурної зміни діелектричної проникності кристала Sn₂P₂S₆ при різних зміщуючих електричних полях та гідростатичних тисках з метою встановлення виду p, T, E-діаграми цього кристала. На основі досліджень аномалій діелектричної проникності побудовано E, T -діаграми при різних величинах гідростатичного тиску та p, T, E-діаграму кристала Sn₂P₂S₆. Проведено оцінку величин коефіцієнтів у розкладі термодинамічного потенціалу та визначено координати критичних точок на E, T -діаграмах

The effect of hydrostatic pressure on transverse dielectric permeability of KH₂PO₄ crystals

Temperature dependences of transverse dielectric permeability of KH₂PO₄ crystals under different values of hydrostatic pressure have been investigated. Within the framework of a tunnelling mode model, the dipole interaction energy and the tunnelling energy are suggested to be determined using the temperature position of the dielectric permeability kinking point. From the temperature dependences of the dielectric permeability εa(T) under various pressures, the pressure dependences of these values are derived.Досліджено температурні залежності поперечної діелектричної проникності кристала КН₂Р0₄ при різних величинах гідростатичного тиску. В рамках моделі тунельної моди запропоновано спосіб визначення енергії дипольної взаємодії та енергії тунелювання з використанням температурного положення точки перегину діелектричної проникності. За результатами експериментальних досліджень залежностей ε(Т) при різних тисках отримано баричні залежності вказаних величин

Heparin Reduces Neuroinflammation and Transsynaptic Neuronal Apoptosis in a Model of Subarachnoid Hemorrhage

Subarachnoid hemorrhage (SAH) can lead to disabling motor, cognitive, and neuropsychological abnormalities. Part of the secondary injury to cerebral tissues associated with SAH is attributable to the neuroinflammatory response induced by blood. Heparin is a pleiotropic compound that reduces inflammatory responses in conditions outside the central nervous system. Using a model of SAH devoid of global insult, we evaluated the effect of delayed intravenous (IV) infusion of heparin, at a dose that does not produce therapeutic anticoagulation, on neuroinflammation, myelin preservation, and apoptosis. Adult male rats underwent bilateral stereotactic injections of autologous blood (50 μL) into the subarachnoid space of the entorhinal cortex. The rats were implanted with mini-osmotic pumps that delivered either vehicle or unfractionated heparin (10 U/kg/h IV) beginning 12 h after SAH. No mechanical or hemorrhagic injury was observed in the hippocampus. In vehicle controls assessed at 48 h, SAH was associated with robust neuroinflammation in the adjacent cortex [neutrophils, activated phagocytic microglia, nuclear factor-kappa B, tumor necrosis factor-alpha, and interleukin-1beta] and neurodegeneration (Fluoro-Jade C staining and loss of NeuN). In the hippocampus, a muted neuroinflammatory response was indicated by Iba1-positive, ED1-negative microglia exhibiting an activated morphology. The perforant pathway showed Fluoro-Jade C staining and demyelination, and granule cells of the dentate gyrus had pyknotic nuclei, labeled with Fluoro-Jade C and showed upregulation of cleaved caspase-3, consistent with transsynaptic apoptosis. Administration of heparin significantly reduced neuroinflammation, demyelination, and transsynaptic apoptosis. We conclude that delayed IV infusion of low-dose unfractionated heparin may attenuate adverse neuroinflammatory effects of SAH

Endogenous cholinergic inputs and local circuit mechanisms govern the phasic mesolimbic dopamine response to nicotine

Nicotine exerts its reinforcing action by stimulating nicotinic acetylcholine receptors (nAChRs) and boosting dopamine (DA) output from the ventral tegmental area (VTA). Recent data have led to a debate about the principal pathway of nicotine action: direct stimulation of the DAergic cells through nAChR activation, or disinhibition mediated through desensitization of nAChRs on GABAergic interneurons. We use a computational model of the VTA circuitry and nAChR function to shed light on this issue. Our model illustrates that the α4β2-containing nAChRs either on DA or GABA cells can mediate the acute effects of nicotine. We account for in vitro as well as in vivo data, and predict the conditions necessary for either direct stimulation or disinhibition to be at the origin of DA activity increases. We propose key experiments to disentangle the contribution of both mechanisms. We show that the rate of endogenous acetylcholine input crucially determines the evoked DA response for both mechanisms. Together our results delineate the mechanisms by which the VTA mediates the acute rewarding properties of nicotine and suggest an acetylcholine dependence hypothesis for nicotine reinforcement.Peer reviewe

Sulfonylurea Receptor 1, Transient Receptor Potential Cation Channel Subfamily M Member 4, and KIR6.2:Role in Hemorrhagic Progression of Contusion

Altres ajuts: J.M.S is supported by grants from the Department of Veterans Affairs (I01BX002889), the Department of Defense (SCI170199), the National Heart, Lung and Blood Institute (R01HL082517) and the National Institute of Neurological Disorders and Stroke (NINDS) (R01NS060801; R01NS102589; R01NS105633); V.G. is supported by a grant from NINDS (NS061934).In severe traumatic brain injury (TBI), contusions often are worsened by contusion expansion or hemorrhagic progression of contusion (HPC), which may double the original contusion volume and worsen outcome. In humans and rodents with contusion-TBI, sulfonylurea receptor 1 (SUR1) is upregulated in microvessels and astrocytes, and in rodent models, blockade of SUR1 with glibenclamide reduces HPC. SUR1 does not function by itself, but must co-assemble with either KIR6.2 or transient receptor potential cation channel subfamily M member 4 (TRPM4) to form K (SUR1-KIR6.2) or SUR1-TRPM4 channels, with the two having opposite effects on membrane potential. Both KIR6.2 and TRPM4 are reportedly upregulated in TBI, especially in astrocytes, but the identity and function of SUR1-regulated channels post-TBI is unknown. Here, we analyzed human and rat brain tissues after contusion-TBI to characterize SUR1, TRPM4, and KIR6.2 expression, and in the rat model, to examine the effects on HPC of inhibiting expression of the three subunits using intravenous antisense oligodeoxynucleotides (AS-ODN). Glial fibrillary acidic protein (GFAP) immunoreactivity was used to operationally define core versus penumbral tissues. In humans and rats, GFAP-negative core tissues contained microvessels that expressed SUR1 and TRPM4, whereas GFAP-positive penumbral tissues contained astrocytes that expressed all three subunits. Förster resonance energy transfer imaging demonstrated SUR1-TRPM4 heteromers in endothelium, and SUR1-TRPM4 and SUR1-KIR6.2 heteromers in astrocytes. In rats, glibenclamide as well as AS-ODN targeting SUR1 and TRPM4, but not KIR6.2, reduced HPC at 24 h post-TBI. Our findings demonstrate upregulation of SUR1-TRPM4 and K after contusion-TBI, identify SUR1-TRPM4 as the primary molecular mechanism that accounts for HPC, and indicate that SUR1-TRPM4 is a crucial target of glibenclamide

Glibenclamide—10-h Treatment Window in a Clinically Relevant Model of Stroke

Glibenclamide improves outcomes in rat models of stroke, with treatment as late as 6 h after onset of ischemia shown to be beneficial. Because the molecular target of glibenclamide, the sulfonylurea receptor 1 (Sur1)-regulated NCCa-ATP channel, is upregulated de novo by a complex transcriptional mechanism, and the principal pathophysiological target, brain swelling, requires hours to develop, we hypothesized that the treatment window would exceed 6 h. We studied a clinically relevant rat model of stroke in which middle cerebral artery occlusion (75% < reduction in LDF signal ≤90%) was produced using an intra-arterial occluder. Recanalization was obtained 4.5 h later by removing the occluder. At that time, we administered recombinant tissue plasminogen activator (rtPA; 0.9 mg/kg IV over 30 min). Immunolabeling showed modest expression of Sur1 5 h after onset of ischemia, with expression increasing 7- to 11-fold (P < 0.01) by 24 h. Rats were administered either vehicle or glibenclamide (10 μg/kg IP loading dose plus 200 ng/h by constant subcutaneous infusion) beginning 4.5 or 10 h after onset of ischemia. In rats treated at 4.5 or 10 h, glibenclamide significantly reduced hemispheric swelling at 24 h from (mean ± SEM) 14.7 ± 1.5% to 8.1 ± 1.6% or 8.8 ± 1.1% (both P < 0.01), respectively, and significantly reduced 48-h mortality from 53% to 17% or 12% (both P < 0.01), and improved Garcia scores at 48 h from 3.8 ± 0.62 to 7.6 ± 0.70 or 8.4 ± 0.74 (both P < 0.01). We conclude that, in a clinically relevant model of stroke, the treatment window for glibenclamide extends to 10 h after onset of ischemia