Toward Antifragility: Social Defeat Stress Enhances Learning and Memory in Young Mice Via Hippocampal Synaptosome Associated Protein 25.

Social adversity not only causes severe psychological diseases but also may improve people's ability to learn and grow. However, the beneficial effects of social adversity are often ignored. In this study, we investigated whether and how social adversity affects learning and memory in a mouse social defeat stress (SDS) model. A total of 652 mice were placed in experimental groups of six to 23 mice each. SDS enhanced spatial, novelty, and fear memory with increased synaptosome associated protein 25 (SNAP-25) level and dendritic spine density in hippocampal neurons among young but not middle-aged mice. Chemogenetic inhibition of hippocampal CaMK2A+ neurons blocked SDS-induced enhancement of learning or memory. Knockdown of SNAP-25 or blockade of N-methyl-D-aspartate (NMDA) receptor subunit GluN2B in the hippocampus prevented SDS-induced learning memory enhancement in an emotion-independent manner. These findings suggest that social adversity promotes learning and memory ability in youths and provide a neurobiological foundation for biopsychological antifragility.

Elucidating the Reactivity of O2 (a 1Δg): A Study with Amino Acid Anions and Related Sulfur and Oxygen Anionic Species.

Rate constants and product ions were determined for a series of anions reacting with singlet molecular oxygen O2 (a 1Δg) at thermal energy using an electrospray ionization-selected ion flow tube. The 20 naturally occurring amino acids were used to produce corresponding deprotonated anions; only [Cys-H]- and [Pro-H]- were found to be reactive with O2 (a 1Δg), generating OSCH2CH(NH2)CO2- + HO and C5H6NO2- + H2O2, respectively. The reaction of O2 (a 1Δg) with [Cys-H]- has a rate constant more than ten times larger than the reaction of O2 (a 1Δg) with [Pro-H]-. Furthermore, reactions of O2 (a 1Δg) with carboxylic acid and thiol anions were carried out to elucidate the reactivity of the sulfur-containing functional groups. Potential energy surfaces and overall reaction exothermicities were calculated for representative reactions using density functional theory. Reactions in which attack occurs at the sulfur produce HCSO- as an ionic product. Reactions of several carboxylic acid anions likely proceed through a hydroperoxide intermediate that is analogous to that calculated for reactions with amino acid anions at a higher collision energy. Overall, rate constants for reactions of carboxylic acid anions RC(O)O- were found to be smaller for larger R groups.

The HNO- radical anion: A proposed intermediate in diazeniumdiolate synthesis using nitric oxide and alkoxides.

The strategy of synthesizing diazeniumdiolates (X-N(O)=NO-) through the coexistence of nitric oxide and alkoxides (RO-) was introduced by Wilhelm Traube 120 years ago. Today, despite the wide use of diazeniumdiolate derivatives to release nitric oxide in the treatment of cancer, the first step of the reaction mechanism for diazeniumdiolate synthesis remains a mystery and is thought to be complex. We have studied the gas-phase reactions of nitric oxide with alkoxides at room temperature. An electron-coupled hydrogen transfer is observed, and the radical anion HNO- is the only ionic product in these reactions. HNO- can further react with nitric oxide to form N2O and HO-.

Reactivity of amino acid anions with nitrogen and oxygen atoms.

For many decades, astronomers have searched for biological molecules, including amino acids, in the interstellar medium; this endeavor is important for investigating the hypothesis of the origin of life from space. The space environment is complex and atomic species, such as nitrogen and oxygen atoms, are widely distributed. In this work, the reactions of eight typical deprotonated amino acids (glycine, alanine, cysteine, proline, aspartic acid, histidine, tyrosine, and tryptophan) with ground state nitrogen and oxygen atoms are studied by experiment and theory. These amino acid anions do not react with nitrogen atoms. However, the reactions of these ions with oxygen atoms show an intriguing variety of ionic products and the reaction rate constants are of the order of 10-10 cm3 s-1. Density functional calculations provide detailed mechanisms of the reactions, and demonstrate that spin conversion is essential for some processes. Our study provides important data and insights for understanding the kinetic and dynamic behavior of amino acids in space environments.

Experimental and Computational Studies of the Reactions of N and O Atoms with Small Heterocyclic Anions.

The existence of heterocyclic aromatic anions in extraterrestrial environments, such as the upper atmosphere of Titan, has been recently confirmed by data from the Cassini spacecraft. Nitrogen and oxygen atoms are also common species in the ionospheres of planets and moons and in the interstellar medium. In the current work, we extend previous studies to explore the reactivity of five-membered ring aromatic anions that contain nitrogen, oxygen, or sulfur (deprotonated pyrrole, furan, and thiophene) with N and O atoms both experimentally and computationally. Furanide and thiophenide anions react with the N atom by associative electron detachment (AED). All three anions react with the O atom both by AED and by processes that form ionic products. The reaction of pyrrolide anion with the O atom generates only one ionic product C4H3NO-, corresponding to an O addition and H loss process. The corresponding process is observed as the major channel for the reaction of furanide anion with the O atom while other ionic products HCOO- and C2H- are also formed. The reaction of thiophenide with the O atom is more complex, and four ionic products are generated, of which three are sulfur-containing ions. The reaction mechanisms are studied theoretically by employing density functional theory calculations, and spin conversion is found to be critical for understanding some product distributions. This work provides insight into the rich gas-phase chemistry of aromatic ion-atom reactions, which are relevant to ionospheric and interstellar chemistry.

Experimental and Theoretical Studies of the Reactivity and Thermochemistry of Dicyanamide: N(CN)(2)(-).

Dicyanamide [N(CN)2(-)] is a common anionic component of ionic liquids, several of which have shown hypergolic reactivity upon mixing with white-fuming nitric acid. In this study, we explore the thermochemistry of dicyanamide and its reactivity with nitric acid and other molecules to gain insight into the initial stages of the hypergolic phenomenon. We have developed and utilized an electrospray ion source for our selected ion flow tube (SIFT) to generate the dicyanamide anion. We have explored the general reactivity of this ion with several neutral molecules and atoms. Dicyanamide does not show reactivity with O2, H2SO4, H2O2, DBr, HCl, NH3, N2O, SO2, COS, CO2, CH3OH, H2O, CH4, N2, CF4, or SF6 (k < 1 × 10(-12) cm(3)/s); moreover, dicyanamide does not react with N atom, O atom, or electronically excited molecular oxygen (k < 5 × 10(-12) cm(3)/s), and our previous studies showed no reactivity with H atom. However, at 0.45 Torr helium, we observe the adduct of dicyanamide with nitric acid with an effective bimolecular rate constant of 2.7 × 10(-10) cm(3)/s. Intrinsically, dicyanamide is a very stable anion in the gas phase, as illustrated by its lack of reactivity, high electron-binding energy, and low proton affinity. The lack of reactivity of dicyanamide with H2SO4 gives an upper limit for the gas-phase deprotonation enthalpy of the parent compound (HNCNCN; <310 ± 3 kcal/mol). This limit is in agreement with theoretical calculations at the MP2/6-311++G(d,p) level of theory, finding that ΔH298 K(HNCNCN) = 308.5 kcal/mol. Dicyanamide has two different proton acceptor sites. Experimental and computational results indicate that it is lower in energy to protonate the terminal nitrile nitrogen than the central nitrogen. Although proton transfer to dicyanamide was not observed for any of the acidic molecules investigated here, the calculations on dicyanamide with one to three nitric acid molecules reveal that higher-order solvation can favor exothermic proton transfer. Furthermore, the formation of 1,5-dinitrobiuret, proposed to be the key intermediate during the hypergolic ignition of dicyanamide ionic liquids with nitric acid, is investigated by calculation of the reaction coordinate. Our results suggest that solvation dynamics of dicyanamide with nitric acid play an important role in hypergolic ignition and the interactions at the droplet/condensed-phase surface between the two hypergolic liquids are very important. Moreover, dicyanamide exists in the atmosphere of Saturn's moon, Titan; the intrinsic stability of dicyanamide strongly suggests that it may exist in molecular clouds of the interstellar medium, especially in regions where other stable carbon-nitrogen anions have been detected.

Reactions of substituted benzene anions with N and O atoms: Chemistry in Titan's upper atmosphere and the interstellar medium.

The likely existence of aromatic anions in many important extraterrestrial environments, from the atmosphere of Titan to the interstellar medium (ISM), is attracting increasing attention. Nitrogen and oxygen atoms are also widely observed in the ISM and in the ionospheres of planets and moons. In the current work, we extend previous studies to explore the reactivity of prototypical aromatic anions (deprotonated toluene, aniline, and phenol) with N and O atoms both experimentally and computationally. The benzyl and anilinide anions both exhibit slow associative electron detachment (AED) processes with N atom, and moderate reactivity with O atom in which AED dominates but ionic products are also formed. The reactivity of phenoxide is dramatically different; there is no measurable reaction with N atom, and the moderate reactivity with O atom produces almost exclusively ionic products. The reaction mechanisms are studied theoretically by employing density functional theory calculations, and spin conversion is found to be critical for understanding some product distributions. This work provides insight into the rich gas-phase chemistry of aromatic ion-atom reactions and their relevance to ionospheric and interstellar chemistry.

Reactions of Azine Anions with Nitrogen and Oxygen Atoms: Implications for Titan's Upper Atmosphere and Interstellar Chemistry.

Azines are important in many extraterrestrial environments, from the atmosphere of Titan to the interstellar medium. They have been implicated as possible carriers of the diffuse interstellar bands in astronomy, indicating their persistence in interstellar space. Most importantly, they constitute the basic building blocks of DNA and RNA, so their chemical reactivity in these environments has significant astrobiological implications. In addition, N and O atoms are widely observed in the ISM and in the ionospheres of planets and moons. However, the chemical reactions of molecular anions with abundant interstellar and atmospheric atomic species are largely unexplored. In this paper, gas-phase reactions of deprotonated anions of benzene, pyridine, pyridazine, pyrimidine, pyrazine, and s-triazine with N and O atoms are studied both experimentally and computationally. In all cases, the major reaction channel is associative electron detachment; these reactions are particularly important since they control the balance between negative ions and free electron densities. The reactions of the azine anions with N atoms exhibit larger rate constants than reactions of corresponding chain anions. The reactions of azine anions with O atoms are even more rapid, with complex product patterns for different reactants. The mechanisms are studied theoretically by employing density functional theory; spin conversion is found to be important in determining some product distributions. The rich gas-phase chemistry observed in this work provides a better understanding of ion-atom reactions and their contributions to ionospheric chemistry as well as the chemical processing that occurs in the boundary layers between diffuse and dense interstellar clouds.

Gas-phase reactions of CF(+) with molecules of interstellar relevance.

We have studied the gas-phase reactions of CF(+) with 24 neutral species. Reaction rate constants and product branching fractions are measured at 298 K using a flowing afterglow-selected ion flow tube. Experimental work is supported by computational chemistry calculations to provide insight into the reactivity of classes of neutral molecules. Reactions of CF(+) with small triatomic species and oxygen-containing organic molecules produce the stable molecule CO. The product branching fractions are discussed, and the potential energy surfaces for a few representative reactions are examined. CF(+) is highly reactive with complex molecules and will likely be destroyed in dense environments in the interstellar medium. However, the lack of reactivity with small diatomic molecules will likely enable its survival in diffuse regions.

Deprotonated purine dissociation: experiments, computations, and astrobiological implications.

A central focus of astrobiology is the determination of abiotic formation routes to important biomolecules. The dissociation mechanisms of these molecules lend valuable insights into their synthesis pathways. Because of the detection of organic anions in the interstellar medium (ISM), it is imperative to study their role in these syntheses. This work aims to experimentally and computationally examine deprotonated adenine and guanine dissociation in an effort to illuminate potential anionic precursors to purine formation. Collision-induced dissociation (CID) products and their branching fractions are experimentally measured using an ion trap mass spectrometer. Deprotonated guanine dissociates primarily by deammoniation (97%) with minor losses of carbodiimide (HNCNH) and/or cyanamide (NH2CN), and isocyanic acid (HNCO). Deprotonated adenine fragments by loss of hydrogen cyanide and/or isocyanide (HCN/HNC; 90%) and carbodiimide (HNCNH) and/or cyanamide (NH2CN; 10%). Tandem mass spectrometry (MS(n)) experiments reveal that deprotonated guanine fragments lose additional HCN and CO, while deprotonated adenine fragments successively lose HNC and HCN. Every neutral fragment observed in this study has been detected in the ISM, highlighting the potential for nucleobases such as these to form in such environments. Lastly, the acidity of abundant fragment ions is experimentally bracketed. Theoretical calculations at the B3LYP/6-311++G(d,p) level of theory are performed to delineate the mechanisms of dissociation and analyze the energies of reactants, intermediates, transition states, and products of these CID processes.

Up-regulation of interleukin-23 induces persistent allodynia via CX3CL1 and interleukin-18 signaling in the rat spinal cord after tetanic sciatic stimulation.

Tetanic stimulation of the sciatic nerve (TSS) induces sciatic nerve injury and long-lasting pain hypersensitivity in rats, and spinal glial activation and proinflammatory cytokines releases are involved. In the present study, we showed that spinal interleukin (IL)-23 and its receptor, IL-23R, are crucial for the development of mechanical allodynia after TSS. In the spinal dorsal horn, both IL-23 and IL-23R are expressed in astrocytes, and this expression is substantially increased after TSS. Inhibition of IL-23 signaling attenuated TSS-induced allodynia and decreased the induction of glial fibrillary acidic protein (GFAP, an astrocytic marker). Conversely, intrathecally delivered IL-23 induced a persistent allodynia. Similar to IL-23 signaling, an increase in IL-18 and its receptor, IL-18R, as well as CX3CL1 and its receptor, CX3CR1, was simultaneously observed in the spinal dorsal horn after TSS. Interestingly, IL-18 and CX3CR1 were exclusively expressed in microglia, while IL-18R was mainly localized in astrocytes. In contrast, CX3CL1 was predominately expressed in neurons and secondarily in astrocytes. The functional inhibition of CX3CL1 and IL-18 signaling attenuated TSS-induced allodynia and suppressed IL-23 and IL-23R upregulation. Activation of CX3CR1 and IL-18R induced similar behavioral and biochemical changes to those observed after TSS. These results indicate that the interaction among CX3CL1, IL-18 and IL-23 signaling in the spinal cord plays a critical role in the development of allodynia. Thus, interrupting this chemokine-cytokine network might provide a novel therapeutic strategy for neuropathic pain.

Anionic derivatives of uracil: fragmentation and reactivity.

Uracil is an essential biomolecule for terrestrial life, yet its prebiotic formation mechanisms have proven elusive for decades. Meteorites have been shown to contain uracil and the interstellar abundance of aromatic species and nitrogen-containing molecules is well established, providing support for uracil's presence in the interstellar medium (ISM). The ion chemistry of uracil may provide clues to its prebiotic synthesis and role in the origin of life. The fragmentation of biomolecules provides valuable insights into their formation. Previous research focused primarily on the fragmentation and reactivity of cations derived from uracil. In this study, we explore deprotonated uracil-5-carboxylic acid and its anionic fragments to elucidate novel reagents of uracil formation and to characterize the reactivity of uracil's anionic derivatives. The structures of these fragments are identified through theoretical calculations, further fragmentation, experimental acidity bracketing, and reactivity with several detected and potential interstellar species (SO2, OCS, CS2, NO, N2O, CO, NH3, O2, and C2H4). Fragmentation is achieved through collision induced dissociation (CID) in a commercial ion trap mass spectrometer, and all reaction rate constants are measured using a modification of this instrument. Experimental data are supported by theoretical calculations at the B3LYP/6-311++G(d,p) level of theory. Lastly, the astrochemical implications of the observed fragmentation and reaction processes are discussed.

Near-UV Extinction of Submicron Thickness Ice Films in the 290-350 nm Range at 258 K.

Ice clouds affect the energy balance of the atmosphere through absorption, reflection, and scattering of solar radiation. We have developed a new experimental technique to simultaneously measure thin ice film extinction and its thickness (about 0.06-0.21 µm) by combining Brewster angle cavity ring-down spectroscopy and quartz crystal microbalance. The ice film serves as a proxy for ice clouds. Thin ice films were formed by water vapor deposition on a silica surface at 258 K. The average extinction cross sections of ice films were determined to be about 6.6 × 10-23, 8.1 × 10-23, 5.3 × 10-23, 5.6 × 10-23, 5.2 × 10-23, 5.1 × 10-23, and 3.9 × 10-23 cm2/molecule at wavelengths of 290, 300, 310, 320, 330, 340, and 350 nm at 258 K, respectively. Atmospheric implications of the results are discussed.

Thermal methane activation by a binary V-Nb transition-metal oxide cluster cation: a further example for the crucial role of oxygen-centered radicals.

The heteronuclear transition-metal oxide cluster activates methane: VNbO5(+) reacts with CH4 under ambient conditions via hydrogen-atom transfer (HAT), thus providing an interesting prototype example of room-temperature methane activation by a binary transition-metal oxide cluster.

Catalytic oxidation of CO by N2O conducted via the neutral oxide cluster couple VO2/VO3.

Neutral vanadium and cobalt oxide clusters are generated at the same time employing a V-Co mixed target. Experimental results indicate that the reaction VO2 + N2O → VO3 + N2 occurs in a fast flow reactor. This interpretation is further supported for a gas mixture of CO and N2O in the flow cell: regeneration of VO2 is observed for this case via the reaction VO3 + CO → VO2 + CO2. A full catalytic cycle for the reaction N2O + CO → N2 + CO2 is thus complete at room temperature enabled by the VO2/VO3 cluster couple. DFT calculations demonstrate that the entire catalytic process is overall barrierless and reproduce the experimental results quite well.

Double C-H bond activation of hydrocarbons by a gas phase neutral oxide cluster: the importance of spin state.

The neutral cluster V2O5 is generated and detected in the gas phase. Its reactivity toward butane is studied both experimentally and theoretically. Experimental results show clearly that neutral V2O5 can react with n-butane (C4H10) to generate V2O5H2, indicating double hydrogen atom transfer from C4H10 to V2O5 to produce C4H8. Further experimental evidence indicates that V2O5 is only partially reacted even at very high concentrations of C4H10. Density functional theory (DFT) studies show that the lowest energy triplet state of V2O5 is reactive toward C4H10, whereas the ground state singlet V2O5 is inert. Calculated results are in agreement with experimental findings, and a detailed reaction mechanism is provided. Reactions of V2O5H2 with several oxidants are also studied theoretically to find a path to regenerate V2O5. Neutral (3)V2O5 can also react with C2H6 to form V2O5H2 and C2H4, but only as a minor reaction channel; the major product is the adsorption product V2O5(C2H6).

Generation and reactivity of putative support systems, Ce-Al neutral binary oxide nanoclusters: CO oxidation and C-H bond activation.

Both ceria (CeO2) and alumina (Al2O3) are very important catalyst support materials. Neutral binary oxide nanoclusters (NBONCs), CexAlyOz, are generated and detected in the gas phase and their reactivity with carbon monoxide (CO) and butane (C4H10) is studied. The very active species CeAlO4 (●) can react with CO and butane via O atom transfer (OAT) and H atom transfer (HAT), respectively. Other CexAlyOz NBONCs do not show reactivities toward CO and C4H10. The structures, as well as the reactivities, of CexAlyOz NBONCs are studied theoretically employing density functional theory (DFT) calculations. The ground state CeAlO4 (●) NBONC possesses a kite-shaped structure with an OtCeObObAlOt configuration (Ot, terminal oxygen; Ob, bridging oxygen). An unpaired electron is localized on the Ot atom of the AlOt moiety rather than the CeOt moiety: this Ot centered radical moiety plays a very important role for the reactivity of the CeAlO4 (●) NBONC. The reactivities of Ce2O4, CeAlO4 (●), and Al2O4 toward CO are compared, emphasizing the importance of a spin-localized terminal oxygen for these reactions. Intramolecular charge distributions do not appear to play a role in the reactivities of these neutral clusters, but could be important for charged isoelectronic BONCs. DFT studies show that the reaction of CeAlO4 (●) with C4H10 to form the CeAlO4H●C4H9 (●) encounter complex is barrierless. While HAT processes have been previously characterized for cationic and anionic oxide clusters, the reported study is the first observation of a HAT process supported by a ground state neutral oxide cluster. Mechanisms for catalytic oxidation of CO over surfaces of AlxOy∕MmOn or MmOn∕AlxOy materials are proposed consistent with the presented experimental and theoretical results.

[Involvement of peripheral NFκB in tetanic sciatic stimulation-induced neuropathic pain].

Tetanic stimulation of the sciatic nerve (TSS) induces long-term potentiation (LTP) of both C- and A-fiber-evoked field potentials in the spinal dorsal horn and long-lasting mechanical allodynia in rats. Though central mechanisms underlying those phenomena have been well studied, peripheral mechanisms still remain poorly known. Nuclear factor kappa B (NFκB) is an important transcription factor. In the spinal cord, NFκB plays a key role in regulating the expression of numerous pro-inflammation factors and contributes to glial activation in central nervous system, suggesting the involvement of spinal NFκB in central sensitization. To address whether NFκB in the dorsal root ganglion (DRG) participates in peripheral sensitization, we examined NFκB expression in the DRG and the effect of inhibiting NFκB activation on neuropathic pain using behavior test, Western blot analysis and immunohistochemical approaches. The results showed that TSS induced long-lasting mechanical allodynia in bilateral hind paws and increased phospho-NFκB expression in the bilateral DRG. The activated NFκB mainly expressed in nuclei not only of neurons, but also of Schwann cells and satellite glial cells. Moreover, NFκB inhibitor pyrrolidine dithiocarbamate (PDTC) significantly alleviated TSS-induced allodynia. Our results suggest that peripheral NFκB may be involved in TSS-induced neuropathic pain, and provide new evidence for the peripheral mechanism of 'mirror pain'.

Ovariectomy induces hyperalgesia accompanied by upregulated estrogen receptor α and protein kinase B in the rat spinal cord.

Hormone supplementation is one of the common therapies for menopause-related disorders. Among different tools, the ovariectomy (OVX) rodents are widely accepted as an appropriate menopausal pain model. Our previous study has showed that OVX produces a significant pain facilitation in both acute pain and tonic pain, however, the underlying mechanisms remain unclear. In this study, we examined the effects of OVX treatment and estradiol (E2) supplementation on formalin-induced nociceptive responses, and explored the associated spinal mechanisms. Female Sprague-Dawley rats underwent bilateral OVX, and E2 supplementation was given subcutaneously from the 5th week after surgery (30 µg/day for 7 days). Our results showed that formalin-induced nociceptive behaviors did not differ between diestrus and proestrus stages of the estrous in intact rats. However, OVX exacerbated formalin-evoked inflammatory pain, especially in the late phase at 4-5 weeks but not 2 weeks post-surgery. E2 supplementation significantly reversed the OVX-triggered hyperalgesia. Double immunofluorescence staining revealed that both ERα and ERß in the spinal dorsal horn were co-labeled with the neuronal markers, but not with markers of astrocytes or microglia. The spinal ERα (but not ERß) expression significantly increased in the OVX group, which was reversed by E2 supplementation. Moreover, the OVX individuals showed an increased protein kinase B (AKT) level in lumbar spinal cord, and E2 supplementation diminished the AKT expression in OVX rats. Finally, intrathecal injection Wortmannin, an inhibitor for AKT signaling, effectively reduced the nociceptive behaviors in the late phase and the number of c-fos positive cells. Together, our findings indicate that E2 supplementation alleviates the OVX-induced hyperalgesia, which might be involved in spinal ERα and AKT mechanisms.

Structure of the oxygen-rich cluster cation Al2O7+ and its reactivity toward methane and water.

The oxygen-rich cluster Al(2)O(7)(+) is generated in the gas phase and investigated with respect to both its structure and its reactivity toward small, inert molecules using Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometry and DFT-based calculations. Al(2)O(7)(+) reacts with CH(4) under ambient conditions via hydrogen atom transfer (HAT), and with H(2)O a ligand exchange occurs which gives rise to the evaporation of two O(2) molecules. The resulting product ion Al(2)O(4)H(2)(+) is also capable of abstracting a hydrogen atom from both H(2)O and CH(4). As indicated in the H(2)O/2O(2) ligand exchange and supported by collision-induced dissociation (CID) experiments, two O(2) units constitute structural elements of Al(2)O(7)(+). Further insight is provided by DFT calculations, performed at the unrestricted B3LYP/TZVP level, and reaction mechanisms are suggested on the basis of both the experimental and theoretical results.