Divergent modulation of nociception by glutamatergic and GABAergic neuronal subpopulations in the periaqueductal gray

The ventrolateral periaqueductal gray (vlPAG) constitutes a major descending pain modulatory system and is a crucial site for opioid-induced analgesia. A number of previous studies have demonstrated that glutamate and GABA play critical opposing roles in nociceptive processing in the vlPAG. It has been suggested that glutamatergic neurotransmission exerts antinociceptive effects, whereas GABAergic neurotransmission exert pronociceptive effects on pain transmission, through descending pathways. The inability to exclusively manipulate subpopulations of neurons in the PAG has prevented direct testing of this hypothesis. Here, we demonstrate the different contributions of genetically defined glutamatergic and GABAergic vlPAG neurons in nociceptive processing by employing cell type-specific chemogenetic approaches in mice. Global chemogenetic manipulation of vlPAG neuronal activity suggests that vlPAG neural circuits exert tonic suppression of nociception, consistent with previous pharmacological and electrophysiological studies. However, selective modulation of GABAergic or glutamatergic neurons demonstrates an inverse regulation of nociceptive behaviors by these cell populations. Selective chemogenetic activation of glutamatergic neurons, or inhibition of GABAergic neurons, in vlPAG suppresses nociception. In contrast, inhibition of glutamatergic neurons, or activation of GABAergic neurons, in vlPAG facilitates nociception. Our findings provide direct experimental support for a model in which excitatory and inhibitory neurons in the PAG bidirectionally modulate nociception

On the mechanism of the digold(I) hydroxide-catalyzed hydrophenoxylation of alkynes

Herein we present a detailed investigation of the mechanistic aspects of the dual gold-catalysed hydrophenoxylation of alkynes, using both experimental and computational methods. The dissociation of [{Au(NHC)}2(µ-OH)][BF4] is essential to enter the catalytic cycle; this step is favored in the presence of bulky, non-coordinating counterions. Moreover, in silico studies confirmed that phenol does not only act as a reactant, but as a co-catalyst, lowering the energy barriers for several transition states. A gem-diaurated species might form during the reaction, but this lies deep within a potential energy well, and is likely to be an ‘off-cycle’ rather than an ‘in-cycle’ intermediate

Carbon Aerogel-Supported Nickel and Iron for Gasification Gas Cleaning. Part I: Ammonia Adsorption

Biomass gasification is a promising way to obtain green energy, but the gas composition makes it unsuitable for use in traditional technologies (i.e., IC engine). Gas purification over nickel and/or iron catalysts is an attractive alternative. Cellulose-based carbon aerogels (CAGs) have shown suitable physical chemical properties for use as catalyst supports. In this work, nickel and iron catalysts are supported on CAG made from cellulose microfibers. Microfibers were impregnated with (NH4)(2)SO4 to increase the mass yield. Carbonization was evaluated at different heating rates, maximum temperatures, and dwell times to generate CAGs. Resulting chars were characterized by N-2 adsorption, X-ray diffraction (XRD), and Raman spectroscopy. The CAG with better properties (specific surface, pore size, thermal resistance) was impregnated with the metal precursor salt via incipient wetness and treated with H-2. Catalysts were characterized by transmission electron microscopy (TEM), XRD, N-2 adsorption, and inductively coupled plasma optical emission spectrometry (ICP-OES). Ammonia adsorption was studied over CAG and catalysts to estimate the thermodynamic parameters. The impregnation with ((NH4)(2)SO4 improves thermal resistance of the char obtained from carbonization. The catalysts exhibit higher adsorption capacity than CAG (without metal), indicating chemical interaction between ammonia and metals. The metal-ammonia interaction is stronger on Fe than on Ni catalyst, which is consistent with reported theoretical calculations

Are intrinsic neural timescales related to sensory processing? Evidence from abnormal behavioral states

The brain exhibits a complex temporal structure which translates into a hierarchy of distinct neural timescales. An open question is how these intrinsic timescales are related to sensory or motor information processing and whether these dynamics have common patterns in different behavioral states. We address these questions by investigating the brain\u27s intrinsic timescales in healthy controls, motor (amyotrophic lateral sclerosis, locked-in syndrome), sensory (anesthesia, unresponsive wakefulness syndrome), and progressive reduction of sensory processing (from awake states over N1, N2, N3). We employed a combination of measures from EEG resting-state data: auto-correlation window (ACW), power spectral density (PSD), and power-law exponent (PLE). Prolonged neural timescales accompanied by a shift towards slower frequencies were observed in the conditions with sensory deficits, but not in conditions with motor deficits. Our results establish that the spontaneous activity\u27s intrinsic neural timescale is related to the neural capacity that specifically supports sensory rather than motor information processing in the healthy brain

Are intrinsic neural timescales related to sensory processing? Evidence from abnormal behavioral states

The brain exhibits a complex temporal structure which translates into a hierarchy of distinct neural timescales. An open question is how these intrinsic timescales are related to sensory or motor information processing and whether these dynamics have common patterns in different behavioral states. We address these questions by investigating the brain\u27s intrinsic timescales in healthy controls, motor (amyotrophic lateral sclerosis, locked-in syndrome), sensory (anesthesia, unresponsive wakefulness syndrome), and progressive reduction of sensory processing (from awake states over N1, N2, N3). We employed a combination of measures from EEG resting-state data: auto-correlation window (ACW), power spectral density (PSD), and power-law exponent (PLE). Prolonged neural timescales accompanied by a shift towards slower frequencies were observed in the conditions with sensory deficits, but not in conditions with motor deficits. Our results establish that the spontaneous activity\u27s intrinsic neural timescale is related to the neural capacity that specifically supports sensory rather than motor information processing in the healthy brain

Are intrinsic neural timescales related to sensory processing? Evidence from abnormal behavioral states

The brain exhibits a complex temporal structure which translates into a hierarchy of distinct neural timescales. An open question is how these intrinsic timescales are related to sensory or motor information processing and whether these dynamics have common patterns in different behavioral states. We address these questions by investigating the brain\u27s intrinsic timescales in healthy controls, motor (amyotrophic lateral sclerosis, locked-in syndrome), sensory (anesthesia, unresponsive wakefulness syndrome), and progressive reduction of sensory processing (from awake states over N1, N2, N3). We employed a combination of measures from EEG resting-state data: auto-correlation window (ACW), power spectral density (PSD), and power-law exponent (PLE). Prolonged neural timescales accompanied by a shift towards slower frequencies were observed in the conditions with sensory deficits, but not in conditions with motor deficits. Our results establish that the spontaneous activity\u27s intrinsic neural timescale is related to the neural capacity that specifically supports sensory rather than motor information processing in the healthy brain

Lethal Interpersonal Violence in the Middle Pleistocene

Evidence of interpersonal violence has been documented previously in Pleistocene members of the genus Homo, but only very rarely has this been posited as the possible manner of death. Here we report the earliest evidence of lethal interpersonal violence in the hominin fossil record. Cranium 17 recovered from the Sima de los Huesos Middle Pleistocene site shows two clear perimortem depression fractures on the frontal bone, interpreted as being produced by two episodes of localized blunt force trauma. The type of injuries, their location, the strong similarity of the fractures in shape and size, and the different orientations and implied trajectories of the two fractures suggest they were produced with the same object in face-to-face interpersonal conflict. Given that either of the two traumatic events was likely lethal, the presence of multiple blows implies an intention to kill. This finding shows that the lethal interpersonal violence is an ancient human behavior and has important implications for the accumulation of bodies at the site, supporting an anthropic origin

Quantifying the impact of the Large Magellanic Cloud on the structure of the Milky Way's dark matter halo using Basis Function Expansions

Indications of disequilibrium throughout the Milky Way (MW) highlight the need for compact,flexible, non-parametric descriptions of phase--space distributions of galaxies. We present a new representation of the current Dark Matter (DM) distribution and potential derived from N-body simulations of the Milky Way and Large Magellanic Cloud (LMC) system using Basis Function Expansions (BFEs). We incorporate methods to maximize the physical signal in the representation. As a result, the simulations of $10^8$ DM particles representing the MW--LMC system can be described by 354 coefficients. We find that the LMC induces asymmetric perturbations (odd l, m) to the MW's halo, which are not well-described by oblate, prolate, or triaxial halos. Furthermore, the energy in high-order even modes (l,m $\geq$ 2) is similar to average triaxial halos found in cosmological simulations. As such, the response of the MW's halo to the LMC must be accounted for in order to recover the imprints of its assembly history. The LMC causes the outer halo ($\geq$ 30 kpc) to shift from the disk center of mass (COM) by $\sim$15-25 kpc at present day, manifesting as a dipole in the BFE and in the radial velocities of halo stars. The shift depends on the LMC's infall mass, the distortion of the LMC's halo and the MW halo response. Within 30 kpc, halo tracers are expected to orbit the COM of the MW's disk, regardless of LMC infall mass. The LMC's halo is also distorted by MW tides, we discuss the implications for its mass loss and the subsequent effects on current Magellanic satellites.Comment: 35 pages, 25 figures, Accepted for publication in ApJ. 3d movie can be found here: https://vimeo.com/54620711

Dispersion, solvent and metal effects in the binding of gold cations to alkynyl ligands: implications for Au(i) catalysis.

The coordination modes of the [Au(PPh3)](+) cation to metal alkynyl complexes have been investigated. On addition to ruthenium, a vinylidene complex, [Ru(η(5)-C5H5)(PPh3)2([double bond, length as m-dash]C[double bond, length as m-dash]CPh{AuPPh3})](+), is obtained while addition to a gold(iii) compound gives di- and trinuclear gold complexes depending on the conditions employed. In the trinuclear species, a gold(i) cation is sandwiched between two gold(iii) alkynyl complexes, suggesting that coordination of multiple C-C triple bonds to gold is facile