Experimental realization of entangled coherent states in two-dimensional harmonic oscillators of a trapped ion.

Entangled coherent states play pivotal roles in various fields such as quantum computation, quantum communication, and quantum sensing. We experimentally demonstrate the generation of entangled coherent states with the two-dimensional motion of a trapped ion system. Using Raman transitions with appropriate detunings, we simultaneously drive the red and blue sidebands of the two transverse axes of a single trapped ion and observe multi-periodic entanglement and disentanglement of its spin and two-dimensional motion. Then, by measuring the spin state, we herald entangled coherent states of the transverse motions of the trapped ion and observe the corresponding modulation in the parity of the phonon distribution of one of the harmonic oscillators. Lastly, we trap two ions in a linear chain and realize Mølmer-Sørensen gate using two-dimensional motion.

Micromotion compensation of trapped ions by qubit transition and direct scanning of dc voltages.

Excess micromotion is detrimental to accurate qubit control of trapped ions, thus measuring and minimizing it is crucial. In this paper, we present a simple approach for measuring and suppressing excess micromotion of trapped ions by leveraging the existing laser-driven qubit transition scheme combined with direct scanning of dc voltages. The compensation voltage is deduced by analyzing the Bessel expansion of a scanned qubit transition rate. The method provides a fair level of sensitivity for practical quantum computing applications, while demanding minimal deviation of trap condition. By accomplishing compensation of excess micromotion in the qubit momentum-excitation direction, the scheme offers an additional avenue for excess micromotion compensation, complementing existing compensation schemes.

Genetically Encoding Unnatural Amino Acids in Neurons In Vitro and in the Embryonic Mouse Brain for Optical Control of Neuronal Proteins.

Deciphering neuronal networks governing specific brain functions is a longstanding mission in neuroscience, yet global manipulation of protein functions pharmacologically or genetically lacks sufficient specificity to reveal a neuronal protein's function in a particular neuron or a circuitry. Photostimulation presents a great venue for researchers to control neuronal proteins with high temporal and spatial resolution. Recently, an approach to optically control the function of a neuronal protein directly in neurons has been demonstrated using genetically encoded light-sensitive Unnatural amino acids (Uaas). Here, we describe procedures for genetically incorporating Uaas into target neuronal proteins in neurons in vitro and in embryonic mouse brain. As an example, a photocaged Uaa was incorporated into an inwardly rectifying potassium channel Kir2.1 to render Kir2.1 photo-activatable. This method has the potential to be generally applied to many neuronal proteins to achieve optical regulation of different processes in brains. Uaas with other properties can be similarly incorporated into neuronal proteins in neurons for various applications.

Deficits in the activity of presynaptic γ-aminobutyric acid type B receptors contribute to altered neuronal excitability in fragile X syndrome.

The behavioral and anatomical deficits seen in fragile X syndrome (FXS) are widely believed to result from imbalances in the relative strengths of excitatory and inhibitory neurotransmission. Although modified neuronal excitability is thought to be of significance, the contribution that alterations in GABAergic inhibition play in the pathophysiology of FXS are ill defined. Slow sustained neuronal inhibition is mediated by γ-aminobutyric acid type B (GABAB) receptors, which are heterodimeric G-protein-coupled receptors constructed from R1a and R2 or R1b and R2 subunits. Via the activation of Gi/o, they limit cAMP accumulation, diminish neurotransmitter release, and induce neuronal hyperpolarization. Here we reveal that selective deficits in R1a subunit expression are seen in Fmr1 knock-out mice (KO) mice, a widely used animal model of FXS, but the levels of the respective mRNAs were unaffected. Similar trends of R1a expression were seen in a subset of FXS patients. GABAB receptors (GABABRs) exert powerful pre- and postsynaptic inhibitory effects on neurotransmission. R1a-containing GABABRs are believed to mediate presynaptic inhibition in principal neurons. In accordance with this result, deficits in the ability of GABABRs to suppress glutamate release were seen in Fmr1-KO mice. In contrast, the ability of GABABRs to suppress GABA release and induce postsynaptic hyperpolarization was unaffected. Significantly, this deficit contributes to the pathophysiology of FXS as the GABABR agonist (R)-baclofen rescued the imbalances between excitatory and inhibitory neurotransmission evident in Fmr1-KO mice. Collectively, our results provided evidence that selective deficits in the activity of presynaptic GABABRs contribute to the pathophysiology of FXS.

Optical Control of a Neuronal Protein Using a Genetically Encoded Unnatural Amino Acid in Neurons.

Photostimulation is a noninvasive way to control biological events with excellent spatial and temporal resolution. New methods are desired to photo-regulate endogenous proteins expressed in their native environment. Here, we present an approach to optically control the function of a neuronal protein directly in neurons using a genetically encoded unnatural amino acid (Uaa). By using an orthogonal tRNA/aminoacyl-tRNA synthetase pair to suppress the amber codon, a photo-reactive Uaa 4,5-dimethoxy-2-nitrobenzyl-cysteine (Cmn) is site-specifically incorporated in the pore of a neuronal protein Kir2.1, an inwardly rectifying potassium channel. The bulky Cmn physically blocks the channel pore, rendering Kir2.1 non-conducting. Light illumination instantaneously converts Cmn into a smaller natural amino acid Cys, activating Kir2.1 channel function. We express these photo-inducible inwardly rectifying potassium (PIRK) channels in rat hippocampal primary neurons, and demonstrate that light-activation of PIRK ceases the neuronal firing due to the outflux of K(+) current through the activated Kir2.1 channels. Using in utero electroporation, we also express PIRK in the embryonic mouse neocortex in vivo, showing the light-activation of PIRK in neocortical neurons. Genetically encoding Uaa imposes no restrictions on target protein type or cellular location, and a family of photoreactive Uaas is available for modulating different natural amino acid residues. This technique thus has the potential to be generally applied to many neuronal proteins to achieve optical regulation of different processes in brains. The current protocol presents an accessible procedure for intricate Uaa incorporation in neurons in vitro and in vivo to achieve photo control of neuronal protein activity on the molecular level.

In vivo expression of a light-activatable potassium channel using unnatural amino acids.

Optical control of protein function provides excellent spatial-temporal resolution for studying proteins in situ. Although light-sensitive exogenous proteins and ligands have been used to manipulate neuronal activity, a method for optical control of neuronal proteins using unnatural amino acids (Uaa) in vivo is lacking. Here, we describe the genetic incorporation of a photoreactive Uaa into the pore of an inwardly rectifying potassium channel Kir2.1. The Uaa occluded the pore, rendering the channel nonconducting, and, on brief light illumination, was released to permit outward K(+) current. Expression of this photoinducible inwardly rectifying potassium (PIRK) channel in rat hippocampal neurons created a light-activatable PIRK switch for suppressing neuronal firing. We also expanded the genetic code of mammals to express PIRK channels in embryonic mouse neocortex in vivo and demonstrated a light-activated PIRK current in cortical neurons. These principles could be generally expanded to other proteins expressed in the brain to enable optical regulation.

Sasa quelpaertensis phenylpropanoid derivative suppresses lipopolysaccharide-induced nitric oxide synthase and cyclo-oxygenase-2 expressions in RAW 264.7 cells.

3-O-p-Coumaroyl-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-O-ß-D-gulcopyranosylpropanol (ESQ10) is a naturally occurring phenylpropanoid derivative isolated from Sasa quelpaertensis (Gramineae). In the present study, we discovered that ESQ10 inhibits nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. ESQ10 attenuated LPS-induced synthesis of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in parallel and inhibited LPS-induced interleukin-6 production, as determined by an enzyme-linked immunosorbent assay in the macrophages. The mechanism of the antiinflammatory action of ESQ10, i.e., suppression of nuclear factor (NF)-κB and mitogen-activated protein kinase activation, has been documented. However, ESQ10 could not influence LPS-mediated IκB-α degradation and extracellular signal-regulated kinase/c-Jun amino-terminal kinase phosphorylation at concentrations of up to 373 µM. To test the potential application of ESQ10 as a topical material, we also conducted a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on human HaCaT keratinocytes as well as human dermal fibroblast cells. In this assay, ESQ10 did not induce cytotoxicity. Taken together, the results suggest that ESQ10 may be considered an antiinflammatory candidate for treating inflammatory and skin diseases.

Neolitsea sericea essential oil attenuates LPS-induced inflammation in RAW 264.7 macrophages by suppressing NF-kappaB and MAPK activation.

The chemical composition and anti-inflammatory activities of hydrodistilled essential oil from Neolitsea sericea leaves (NSE) have been investigated for the first time. The chemical constituents of NSE were analysed by GC-MS and found to include sericenine (32.3%), sabinene (21.0%), trans-beta-ocimene (13.3%), beta-caryophyllene (4.8%), and 4-terpineol (4.2%). The effects of NSE on nitric oxide (NO), prostaglandin E2 (PGE2), tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages were also examined. Pro-inflammatory cytokine and mediator tests indicated that NSE has excellent dose-dependent inhibitory activities. To further examine the mechanism responsible for the inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression by NSE, we examined the effect of NSE on nuclear factor-kappaB (NF-kappaB) activation and the phosphorylation of mitogen-activated protein kinases (MAPK). NSE inhibited NF-kappaB activation by LPS, and this was associated with the abrogation of IkappaB-alpha phosphorylation and subsequent decreases in nuclear p50 and p65 protein levels. Further, the phosphorylation of p38, ERK and JNK was suppressed by NSE in a concentration-dependent manner. These results suggest that NSE exerts anti-inflammatory effects in LPS-stimulated RAW 264.7 macrophages by inhibition of NF-kappaB activation and MAPK phosphorylation, and, therefore, may be useful for treatment of inflammatory diseases.