Epigenetic mechanisms play important roles in the neurobiology of substance use disorder. In particular, bromodomain and extra-terminal domain (BET) proteins, a class of histone acetylation readers, ...have been found to regulate cocaine conditioned behaviors, but their role in the behavioral response to other drugs of abuse remains unclear. To address this knowledge gap, we examined the effects of the BET inhibitor, JQ1, on nicotine, amphetamine, morphine, and oxycodone conditioned place preference (CPP). Similar to previous cocaine studies, systemic administration of JQ1 caused a dose-dependent reduction in the acquisition of amphetamine and nicotine CPP in male mice. However, in opioid studies, JQ1 did not alter morphine or oxycodone CPP. Investigating the effects of JQ1 on other types of learning and memory, we found that JQ1 did not alter the acquisition of contextual fear conditioning. Together, these results indicate that BET proteins play an important role in the acquisition of psychostimulant-induced CPP but not the acquisition of opioid-induced CPP nor contextual fear conditioning.
Molecular catalysts for hydrogenation of CO2 are widely studied as a means of chemical hydrogen storage. Catalysts are traditionally designed from the perspective of controlling the ligands bound to ...the metal. In recent years, studies have shown that the solvent can also play a key role in the mechanism of CO2 hydrogenation. A prominent example is the impact of the solvent on the thermodynamic hydride donor ability, or hydricity, of metal hydride complexes relative to the hydride acceptor ability of CO2. In some cases, simply changing from an organic solvent to water can reverse the direction of hydride transfer between a metal hydride and CO2. Additionally, the solvent can impact catalysis by converting CO2 into carbonate species, as well as activate intermediate products for hydrogenation to more reduced products. By understanding the substrate and product speciation, as well as the reactivity of the catalyst towards the substrate, the solvent can be used as a central design component for the rational development of new catalytic systems.
Solvent matters: Despite being a necessary component of homogeneous catalysis, explicit solvent interactions are frequently unaccounted for in mechanistic analyses. For hydrogenation of CO2, the solvent plays a central role in determining the reactivity of metal hydride complexes towards CO2, the speciation of CO2, and conversion of CO2 to highly reduced products such as methanol.
Infrared pumping and its effect on the excitation of HCN molecules can be important when using rotational lines of HCN to probe dense molecular gas in galaxy nuclei. We report the first extragalactic ...detection of (sub)millimeter rotational lines of vibrationally excited HCN, in the dust-enshrouded nucleus of the luminous infrared galaxy NGC 4418. We estimate the excitation temperature of Tvib 230 K between the vibrational ground and excited (v 2 = 1) states. This excitation is most likely due to infrared radiation. At this high vibrational temperature the path through the v 2 = 1 state must have a strong impact on the rotational excitation in the vibrational ground level, although it may not be dominant for all rotational levels. Our observations also revealed nearly confusion-limited lines of CO, HCN, HCO+, H13CN, HC15N, CS, N2H+, and HC3N at Delta *l ~ 1 mm. Their relative intensities may also be affected by the infrared pumping.
The Co(−I) dihydrogen complexes, (η2-H2)CoML−, where ML is the group 13 metalloligand, N(o-(NCH2PiPr2)C6H4)3M, and M is Al, Ga, or In, were previously reported ( J. Am. Chem. Soc. 2017, 139, ...6570−6573 ). In this work, the related Co(−I) end-on dinitrogen adducts, (N2)CoML−, were isolated and investigated as precatalysts for CO2 hydrogenation. The Co–Ga catalyst was highly active, achieving 19,200 formate turnovers with an initial turnover frequency of 27,000 h–1 under 34 atm of 1:1 CO2/H2 and using Verkade’s proazaphosphatrane as a base at ambient temperature. The Co–Al catalyst was moderately active, while the Co–In complex was inactive. Hence, tuning the group 13 ion greatly influences the catalytic activity at the Co site. To elucidate the role of the group 13 support, experimental and theoretical mechanistic studies of the Co–Ga and Co–Al catalysts were conducted. The Co(−I) H2 species are potent hydride donors with estimated thermodynamic hydricities (ΔG° H–) of 32.0(1) and 37.4(1) kcal/mol in CH3CN for M = Al and Ga, respectively. By acting as masked Co(I) dihydrides, the Co(−I) H2 species operate via an unusual Co(−I)/Co(I) redox cycle. After hydride transfer to CO2, the resulting intermediate is the Co(I) hydride complex, HCoML, which was independently synthesized and structurally characterized for M = Al and Ga. The Gibbs free energy for H2 binding, ΔG° bind (1 atm), to generate (η2-H2)HCoML was slightly more favorable for HCoGaL (−4.2(1) kcal/mol) than for HCoAlL (−2.7(1) kcal/mol). In the subsequent step, the deprotonation reaction to regenerate the initial catalyst was much more favorable for (η2-H2)HCoGaL (pK a of 31.4, CH3CN) than for (η2-H2)HCoAlL (pK a of 34.3). The straightforward substitution of Al with Ga perturbs the energy profile of the catalytic reaction (|ΔΔG° H–| = 5.4 kcal/mol, |ΔΔG° bind| = 1.5 kcal/mol, and |ΔΔG° K a | = 4.0 kcal/mol) and thus provides a thermodynamic rationale for the higher catalytic efficiency of Co–Ga over Co–Al.
We report ~100 pc (03) resolution observations of (sub)millimeter HCO+ and CO lines in the ultraluminous infrared galaxy Arp 220. The lines peak at two merger nuclei, with HCO+ being more spatially ...concentrated than CO. Asymmetric line profiles with blueshifted absorption and redshifted emission are discovered in HCO+(3-2) and (4-3) toward the two nuclei and in CO(3-2) toward one nucleus. We suggest that these P Cygni profiles are due to ~100 km s-1 outward motion of molecular gas from the nuclei. This gas is most likely outflowing from the inner regions of the two nuclear disks rotating around individual nuclei, clearing the shroud around the luminosity sources there.
We have observed the nucleus of the nearby luminous infrared galaxy NGC 4418 with subarcsec resolution at 860 and 450 mu m for the first time to characterize its hidden power source. A ~20 pc (0".1) ...hot dusty core was found inside a 100 pc scale concentration of molecular gas at the galactic center. The 860 mu m continuum core has a deconvolved (peak) brightness temperature of 120-210 K. The CO(3-2) peak brightness temperature there is as high as 90 K at 50 pc resolution. The core has a bolometric luminosity of about 10 super(11) L sub(middot in circle), which accounts for most of the galaxy luminosity. It is Compton thick (N sub(H) gap 10 super(25) cm super(-2)) and has a high luminosity-to-mass ratio (L/M) ~ 500 L sub(middot in circle) M sub(middot in circle) super(-1) as well as a high luminosity surface density 10 super(8.5+ or -0.5) L sub(middot in circle) pc super(-2). These parameters are consistent with an active galactic nucleus to be the main luminosity source (with an Eddington ratio about 0.3), while they can be also due to a young starburst near its maximum L/M. We also found an optical color (reddening) feature that we attribute to an outflow cone emanating from the nucleus. The hidden hot nucleus thus shows evidence of both an inflow, previously seen with absorption lines, and the new outflow reported here in a different direction. The nucleus must be rapidly evolving with these gas flows.
Abstract Growing evidence indicates that targeting nociceptin receptor (NOP) signaling may have therapeutic efficacy in treating alcohol and opioid addiction. However, little is known about the ...therapeutic value of selective NOP agonists for the treatment of cocaine dependence. Recently, we identified a highly selective, brain-penetrant NOP small molecule agonist (SR-8993), and using this compound, we previously showed that nociceptin receptor activation attenuated consolidation o f fear-related memories. Here, we sought to determine whether SR-8993 also affects the rewarding properties of cocaine. Using a conditioned place preference (CPP) procedure, we show that SR-8993 (3 or 10 mg/kg) failed to disrupt acquisition or expression of cocaine CPP (7.5 or 15 mg/kg) in C57BL/6 mice. Additionally, SR-8993 did not affect rate of extinction or reinstatement (yohimbine- and cocaine-induced) of cocaine CPP. These studies indicate that selective activation of NOP may not be sufficient in reducing behavioral responses to cocaine.
Abstract
A partial wave analysis of antiproton–proton annihilation data in flight at 900
$$\mathrm {MeV/}c$$
MeV
/
c
into
$${\pi ^0\pi ^0\eta }$$
π
0
π
0
η
,
$${\pi ^0\eta \eta }$$
π
0
η
η
and
...$${K^+K^-\pi ^0}$$
K
+
K
-
π
0
is presented. The data were taken at LEAR by the Crystal Barrel experiment in 1996. The three channels have been coupled together with
$$\pi \pi $$
π
π
-scattering isospin I = 0 S- and D-wave as well as I = 1 P-wave data utilizing the K-matrix approach. Analyticity is treated using Chew–Mandelstam functions. In the fit all ingredients of the K-matrix, including resonance masses and widths, were treated as free parameters. In spite of the large number of parameters, the fit results are in the ballpark of the values published by the Particle Data Group. In the channel
$${\pi ^0\pi ^0\eta }$$
π
0
π
0
η
a significant contribution of the spin exotic
$$I^G=1^-$$
I
G
=
1
-
$$J^{PC}=1^{-+}$$
J
PC
=
1
-
+
$$\pi _1$$
π
1
-wave with a coupling to
$$\pi ^0 \eta $$
π
0
η
is observed. Furthermore the contributions of
$$\phi (1020) \pi ^0$$
ϕ
(
1020
)
π
0
and
$$K^*(892)^\pm K^\mp $$
K
∗
(
892
)
±
K
∓
in the channel
$${K^+K^-\pi ^0}$$
K
+
K
-
π
0
have been studied in detail. The differential production cross section for the two reactions and the spin-density-matrix elements for the
$$\phi (1020)$$
ϕ
(
1020
)
and
$$K^*(892)^\pm $$
K
∗
(
892
)
±
have been extracted. No spin-alignment is observed for both vector mesons. The spin density matrix elements have been also determined for the spin exotic wave.
A partial wave analysis of antiproton–proton annihilation data in flight at 900 MeV/c into π0π0η, π0ηη and K+K-π0 is presented. The data were taken at LEAR by the Crystal Barrel experiment in 1996. ...The three channels have been coupled together with ππ-scattering isospin I = 0 S- and D-wave as well as I = 1 P-wave data utilizing the K-matrix approach. Analyticity is treated using Chew–Mandelstam functions. In the fit all ingredients of the K-matrix, including resonance masses and widths, were treated as free parameters. In spite of the large number of parameters, the fit results are in the ballpark of the values published by the Particle Data Group. In the channel π0π0η a significant contribution of the spin exotic IG=1-JPC=1-+π1-wave with a coupling to π0η is observed. Furthermore the contributions of ϕ(1020)π0 and K∗(892)±K∓ in the channel K+K-π0 have been studied in detail. The differential production cross section for the two reactions and the spin-density-matrix elements for the ϕ(1020) and K∗(892)± have been extracted. No spin-alignment is observed for both vector mesons. The spin density matrix elements have been also determined for the spin exotic wave.