Background and Purpose
Phytocannabinoids in Cannabis sativa have diverse pharmacological targets extending beyond cannabinoid receptors and several exert notable anticonvulsant effects. For the first ...time, we investigated the anticonvulsant profile of the phytocannabinoid cannabidivarin (CBDV) in vitro and in in vivo seizure models.
Experimental Approach
The effect of CBDV (1–100 μM) on epileptiform local field potentials (LFPs) induced in rat hippocampal brain slices by 4‐aminopyridine (4‐AP) application or Mg2+‐free conditions was assessed by in vitro multi‐electrode array recordings. Additionally, the anticonvulsant profile of CBDV (50–200 mg·kg−1) in vivo was investigated in four rodent seizure models: maximal electroshock (mES) and audiogenic seizures in mice, and pentylenetetrazole (PTZ) and pilocarpine‐induced seizures in rats. The effects of CBDV in combination with commonly used antiepileptic drugs on rat seizures were investigated. Finally, the motor side effect profile of CBDV was investigated using static beam and grip strength assays.
Key Results
CBDV significantly attenuated status epilepticus‐like epileptiform LFPs induced by 4‐AP and Mg2+‐free conditions. CBDV had significant anticonvulsant effects on the mES (≥100 mg·kg−1), audiogenic (≥50 mg·kg−1) and PTZ‐induced seizures (≥100 mg·kg−1). CBDV (200 mg·kg−1) alone had no effect against pilocarpine‐induced seizures, but significantly attenuated these seizures when administered with valproate or phenobarbital at this dose. CBDV had no effect on motor function.
Conclusions and Implications
These results indicate that CBDV is an effective anticonvulsant in a broad range of seizure models. Also it did not significantly affect normal motor function and, therefore, merits further investigation as a novel anti‐epileptic in chronic epilepsy models.
Linked Articles
This article is part of a themed section on Cannabinoids. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.167.issue‐8
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The chronic mild (or unpredictable/variable) stress (CMS) model was developed as an animal model of depression more than 20 years ago. The foundation of this model was that following long-term ...exposure to a series of mild, but unpredictable stressors, animals would develop a state of impaired reward salience that was akin to the anhedonia observed in major depressive disorder. In the time since its inception, this model has also been used for a variety of studies examining neurobiological variables that are associated with depression, despite the fact that this model has never been critically examined to validate that the neurobiological changes induced by CMS are parallel to those documented in depressive disorder. The aim of the current review is to summarize the current state of knowledge regarding the effects of chronic mild stress on neurobiological variables, such as neurochemistry, neurochemical receptor expression and functionality, neurotrophin expression and cellular plasticity. These findings are then compared to those of clinical research examining common variables in populations with depressive disorders to determine if the changes observed following chronic mild stress are in fact consistent with those observed in major depression. We conclude that the chronic mild stress paradigm: (1) evokes an array of neurobiological changes that mirror those seen in depressive disorders and (2) may be a suitable tool to investigate novel systems that could be disturbed in depression, and thus aid in the development of novel targets for the treatment of depression.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The Energetic Particle Detector (EPD) Investigation is one of 5 fields-and-particles investigations on the Magnetospheric Multiscale (MMS) mission. MMS comprises 4 spacecraft flying in close ...formation in highly elliptical, near-Earth-equatorial orbits targeting understanding of the fundamental physics of the important physical process called magnetic reconnection using Earth’s magnetosphere as a plasma laboratory. EPD comprises two sensor types, the Energetic Ion Spectrometer (EIS) with one instrument on each of the 4 spacecraft, and the Fly’s Eye Energetic Particle Spectrometer (FEEPS) with 2 instruments on each of the 4 spacecraft. EIS measures energetic ion energy, angle and elemental compositional distributions from a required low energy limit of 20 keV for protons and 45 keV for oxygen ions, up to >0.5 MeV (with capabilities to measure up to >1 MeV). FEEPS measures instantaneous all sky images of energetic electrons from 25 keV to >0.5 MeV, and also measures total ion energy distributions from 45 keV to >0.5 MeV to be used in conjunction with EIS to measure all sky ion distributions. In this report we describe the EPD investigation and the details of the EIS sensor. Specifically we describe EPD-level science objectives, the science and measurement requirements, and the challenges that the EPD team had in meeting these requirements. Here we also describe the design and operation of the EIS instruments, their calibrated performances, and the EIS in-flight and ground operations. Blake et al. (The Flys Eye Energetic Particle Spectrometer (FEEPS) contribution to the Energetic Particle Detector (EPD) investigation of the Magnetospheric Magnetoscale (MMS) Mission,
this issue
) describe the design and operation of the FEEPS instruments, their calibrated performances, and the FEEPS in-flight and ground operations. The MMS spacecraft will launch in early 2015, and over its 2-year mission will provide comprehensive measurements of magnetic reconnection at Earth’s magnetopause during the 18 months that comprise orbital phase 1, and magnetic reconnection within Earth’s magnetotail during the about 6 months that comprise orbital phase 2.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Vibronic coupling, the interaction between molecular vibrations and electronic states, is a fundamental effect that profoundly affects chemical processes. In the case of molecular magnetic materials, ...vibronic, or spin-phonon, coupling leads to magnetic relaxation, which equates to loss of magnetic memory and loss of phase coherence in molecular magnets and qubits, respectively. The study of vibronic coupling is challenging, and most experimental evidence is indirect. Here we employ far-infrared magnetospectroscopy to directly probe vibronic transitions in Yb(trensal) (where H
trensal = 2,2,2-tris(salicylideneimino)trimethylamine). We find intense signals near electronic states, which we show arise due to an "envelope effect" in the vibronic coupling Hamiltonian, which we calculate fully ab initio to simulate the spectra. We subsequently show that vibronic coupling is strongest for vibrational modes that simultaneously distort the first coordination sphere and break the C
symmetry of the molecule. With this knowledge, vibrational modes could be identified and engineered to shift their energy towards or away from particular electronic states to alter their impact. Hence, these findings provide new insights towards developing general guidelines for the control of vibronic coupling in molecules.
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•A new Cr(VI) adsorbent, phosphonium-crosslinked chitosan (PCC), was synthesized.•PCC had over double the adsorption capacity of chitosan at < 120 mg L−1 Cr(VI) at pH 6.•PCC is an ...effective adsorbent for Cr(VI) species over a broad pH range (pH = 4–10).•MgSO4 solution partially regenerates PCC without damaging the structure.
Adsorption is a commonly used method for industrial wastewater treatment because of its low-cost, easy operation and high efficiency. In this work, chitosan was crosslinked and functionalized with a low-cost phosphonium salt, tetrakis(hydroxymethyl)phosphonium sulfate (THPS), to enhance its adsorption capacity for Cr(VI). The novel phosphonium-crosslinked chitosan (PCC) was characterized using elemental analysis, XRF, FTIR, NMR and SEM-EDX. At pH 6, PCC had a higher Langmuir equilibrium constant than the unmodified chitosan (0.19 ± 0.02 L mg−1 versus 0.0044 ± 0.0005 L mg−1) and PCC demonstrated higher adsorption capacity than chitosan at equilibrium Cr(VI) concentrations below 120 mg L−1. Additionally, magnesium sulfate or magnesium chloride was shown to desorb Cr(VI) and recycle PCC. When treated with THPS, chitosan is activated for Cr(VI) adsorption at pH 6; therefore, PCC can be used in wastewater treatment over a wider pH range than chitosan.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•HITRAN2016 molecular spectroscopic database is described.•Dynamic web interface at www.hitran.org is introduced.•HITRAN Application Programming Interface is introduced.•Substantial extent of the ...amount and quality of the data highlighted.•Many new spectroscopic parameters are now available in HITRAN.
This paper describes the contents of the 2016 edition of the HITRAN molecular spectroscopic compilation. The new edition replaces the previous HITRAN edition of 2012 and its updates during the intervening years. The HITRAN molecular absorption compilation is composed of five major components: the traditional line-by-line spectroscopic parameters required for high-resolution radiative-transfer codes, infrared absorption cross-sections for molecules not yet amenable to representation in a line-by-line form, collision-induced absorption data, aerosol indices of refraction, and general tables such as partition sums that apply globally to the data. The new HITRAN is greatly extended in terms of accuracy, spectral coverage, additional absorption phenomena, added line-shape formalisms, and validity. Moreover, molecules, isotopologues, and perturbing gases have been added that address the issues of atmospheres beyond the Earth. Of considerable note, experimental IR cross-sections for almost 300 additional molecules important in different areas of atmospheric science have been added to the database. The compilation can be accessed through www.hitran.org. Most of the HITRAN data have now been cast into an underlying relational database structure that offers many advantages over the long-standing sequential text-based structure. The new structure empowers the user in many ways. It enables the incorporation of an extended set of fundamental parameters per transition, sophisticated line-shape formalisms, easy user-defined output formats, and very convenient searching, filtering, and plotting of data. A powerful application programming interface making use of structured query language (SQL) features for higher-level applications of HITRAN is also provided.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
We present radio and gamma -ray observations, which, along with concurrent X-ray observations, reveal that the binary millisecond pulsar (MSP)/low-mass X-ray binary transition system PSR J1023+0038 ...has undergone a transformation in state. Whereas until recently the system harbored a bright millisecond radio pulsar, the radio pulsations at frequencies between 300 to 5000 MHz have now become undetectable. Concurrent with this radio disappearance, the gamma -ray flux of the system has quintupled. We conclude that, though the radio pulsar is currently not detectable, the pulsar mechanism is still active and the pulsar wind, as well as a newly formed accretion disk, are together providing the necessary conditions to create the gamma -ray increase. This system is the first example of a compact, low-mass binary which has shown significant state changes accompanied by large changes in gamma -ray flux; it will continue to provide an exceptional test bed for better understanding the formation of MSPs as well as accretion onto neutron stars in general.
We present a catalogue of 2135 galaxy redshifts from the VLT LBG Redshift Survey (VLRS), a spectroscopic survey of z 3 galaxies in wide fields centred on background quasi-stellar objects. We have ...used deep optical imaging to select galaxies via the Lyman-break technique. Spectroscopy of the Lyman-break galaxies (LBGs) was then made using the Very Large Telescope (VLT) Visible Multi-Object Spectrograph (VIMOS) instrument, giving a mean redshift of z = 2.79. We analyse the clustering properties of the VLRS sample and also of the VLRS sample combined with the smaller area Keck-based survey of Steidel et al. From the semiprojected correlation function, w
p(σ), for the VLRS and combined surveys, we find that the results are well fit with a single power-law model, with clustering scale lengths of r
0 = 3.46 ± 0.41 and 3.83 ± 0.24 h
−1 Mpc, respectively. We note that the corresponding combined ξ(r) slope is flatter than for local galaxies at γ = 1.5-1.6 rather than γ = 1.8. This flat slope is confirmed by the z-space correlation function, ξ(s), and in the range 10 < s < 100 h
−1 Mpc the VLRS shows an 2.5σ excess over the Λ cold dark matter (ΛCDM) linear prediction. This excess may be consistent with recent evidence for non-Gaussianity in clustering results at z 1. We then analyse the LBG z-space distortions using the 2D correlation function, ξ(σ, π), finding for the combined sample a large-scale infall parameter of β = 0.38 ± 0.19 and a velocity dispersion of
. Based on our measured β, we are able to determine the gravitational growth rate, finding a value of f(z = 3) = 0.99 ± 0.50 (or fσ8 = 0.26 ± 0.13), which is the highest redshift measurement of the growth rate via galaxy clustering and is consistent with ΛCDM. Finally, we constrain the mean halo mass for the LBG population, finding that the VLRS and combined sample suggest mean halo masses of log(M
DM/M) = 11.57 ± 0.15 and 11.73 ± 0.07, respectively.
Several fast solar wind streams and stream interaction regions (SIRs) were observed by the Parker Solar Probe (PSP) during its first orbit (2018 September-2019 January). During this time, several ...recurring SIRs were also seen at 1 au at both L1 (Advanced Composition Explorer (ACE) and Wind) and the location of the Solar Terrestrial Relations Observatory-Ahead (STEREO-A). In this paper, we compare four fast streams observed by PSP at different radial distances during its first orbit. For three of these fast stream events, measurements from L1 (ACE and Wind) and STEREO-A indicated that the fast streams were observed by both PSP and at least one of the 1 au monitors. Our associations are supported by simulations made by the ENLIL model driven by GONG-(ADAPT-)WSA, which allows us to contextualize the inner heliospheric conditions during the first orbit of PSP. Additionally, we determine which of these fast streams are associated with an SIR and characterize the SIR properties for these events. From these comparisons, we find that the compression region associated with the fast-speed streams overtaking the preceding solar wind can form at various radial distances from the Sun in the inner heliosphere inside 0.5 au, with the suprathermal ion population (energies between 30 and 586 keV) observed as isolated enhancements suggesting localized acceleration near the SIR stream interface at ∼0.3 au, which is unlike those seen at 1 au, where the suprathermal enhancements extend throughout and behind the SIR. This suprathermal enhancement extends further into the fast stream with increasing distance from the Sun.
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