Discovery of conjoined charge density waves in the kagome superconductor CsV3Sb5.

The electronic instabilities in CsV3Sb5 are believed to originate from the V 3d-electrons on the kagome plane, however the role of Sb 5p-electrons for 3-dimensional orders is largely unexplored. Here, using resonant tender X-ray scattering and high-pressure X-ray scattering, we report a rare realization of conjoined charge density waves (CDWs) in CsV3Sb5, where a 2 × 2 × 1 CDW in the kagome sublattice and a Sb 5p-electron assisted 2 × 2 × 2 CDW coexist. At ambient pressure, we discover a resonant enhancement on Sb L1-edge (2s→5p) at the 2 × 2 × 2 CDW wavevectors. The resonance, however, is absent at the 2 × 2 × 1 CDW wavevectors. Applying hydrostatic pressure, CDW transition temperatures are separated, where the 2 × 2 × 2 CDW emerges 4 K above the 2 × 2 × 1 CDW at 1 GPa. These observations demonstrate that symmetry-breaking phases in CsV3Sb5 go beyond the minimal framework of kagome electronic bands near van Hove filling.

Structural features associated with multiferroic behavior in the RX3(BO3)4 system.

The magnetoelectric effect in the RX3(BO3)4 system (R = Ho, Eu, Sm, Nd, Gd; X = Fe, Al) varies significantly with the cation R despite very similar structural arrangements. Our structural studies reveal a symmetry reducing tilting of the BO3 planes and of the FeO6 polyhedra in the systems exhibiting low magnetic field induced electric polarization. Neutron scattering measurements reveal a lack of magnetic ordering indicating the primary importance of the atomic structure in the multiferroic behavior of this system.

Elastic and viscoelastic characterization of agar.

Agar is a biological polymer, frequently used in tissue engineering research; due to its consistency, controllable size, and concentration-based properties, it often serves as a representative material for actual biological tissues. In this study, nanoindentation was used to characterize both the time-independent and time-dependent response of agar samples having various concentrations (0.5%-5.0% by weight). Quasi-static indentation was performed at different loads and depths using both open- and closed-loop controls. Reduced modulus (Er) values change with agar concentration, ranging from ∼30 kPa for 0.5% samples to ∼700 kPa for 5.0% samples, which is the same modulus range as usually encountered in soft biological materials. Dynamic indentation was performed to assess the effects of load, dynamic frequency and amplitude. Storage modulus values ranged from approximately 30 to 2300 kPa depending on agar concentration. Loss modulus remained consistently less than 30 kPa at all conditions, indicating a diminished damping response in agar.

Fragile magnetic ground state in half-doped LaSr2Mn2O7.

We investigated the orbital and antiferromagnetic ordering behaviors of the half-doped bilayer manganite La(2-2x)Sr(1+2x)Mn2O7 (x ≃ 0.5) by using Mn L(2,3)-edge resonant soft x-ray scattering. Resonant soft x-ray scattering reveals the CE-type orbital order below T(oo) ≃ 220 K, which shows partial melting behavior below T(m) ≃ 165 K. We also found coexistence CE- and A-type antiferromagnetic orders. Both orders involve the CE-type orbital order with nearly the same orbital character and are coupled with each other. These results manifest that the ground state with the CE-type antiferromagnetic order is easily susceptible to destabilization into the A-type one even with a small fluctuation of the doping level, as suggested by the extremely narrow magnetic phase boundaries at x ≃ 0.5±0.005.

Hidden magnetic configuration in epitaxial La(1-x) Sr(x) MnO3 films.

We present an unreported magnetic configuration in epitaxial La(1-x) Sr(x) MnO3 (x ∼ 0.3) (LSMO) films grown on strontium titanate (STO). X-ray magnetic circular dichroism indicates that the remanent magnetic state of thick LSMO films is opposite to the direction of the applied magnetic field. Spectroscopic and scattering measurements reveal that the average Mn valence varies from mixed Mn(3+)/Mn(4+) to an enriched Mn3+ region near the STO interface, resulting in a compressive lattice along the a, b axis and a possible electronic reconstruction in the Mn e(g) orbital (d(3)z(2)-r(2). This reconstruction may provide a mechanism for coupling the Mn3+ moments antiferromagnetically along the surface normal direction, and in turn may lead to the observed reversed magnetic configuration.

Magnetic structure of RuSr2GdCu2O8 determined by resonant x-ray diffraction.

X-ray diffraction with photon energies near the Ru L2-absorption edge was used to detect resonant reflections characteristic of a G-type superstructure in RuSr2GdCu2O8 single crystals. A polarization analysis confirms that these reflections are due to magnetic order of Ru moments, and the azimuthal-angle dependence of the scattering amplitude reveals that the moments lie along a low-symmetry axis with substantial components parallel and perpendicular to the RuO2 layers. Complemented by susceptibility data and a symmetry analysis of the magnetic structure, these results reconcile many of the apparently contradictory findings reported in the literature.

Surface effects on the orbital order in the single-layered manganite La0.5Sr1.5MnO4.

The question of how bulk electronic order is terminated at a surface is an intriguing one, and one with possible practical implications--for example in nanoscaled systems that may be characterized by their surface behaviour. One example of such order is orbital order, and in principle it should be possible to probe the termination of this order with surface X-ray scattering. Here, we report the first observation of the scattering arising from the termination of bulk orbital order at the surface of a crystal--so-called 'orbital truncation rods'. The measurements, carried out on a cleaved perovskite, La(0.5)Sr(1.5)MnO(4), reveal that whereas the crystallographic surface is atomically smooth, the orbital 'surface', which is observed through the atomic displacements caused by the orbital order, is much rougher, with a typical scale of the surface roughness of approximately 7 degrees A. Interestingly, the temperature dependence of this scattering shows evidence of a surface-induced second-order transition.

Orbital ordering transition in Ca2RuO4 observed with resonant X-ray diffraction.

Resonant x-ray diffraction performed at the L(II) and L(III) absorption edges of Ru has been used to investigate the magnetic and orbital ordering in Ca2RuO4 single crystals. A large resonant enhancement due to electric dipole 2p-->4d transitions is observed at the wave-vector characteristic of antiferromagnetic ordering. Besides the previously known antiferromagnetic phase transition at T(N)=110 K, an additional phase transition, between two paramagnetic phases, is observed around 260 K. Based on the polarization and azimuthal angle dependence of the diffraction signal, this transition can be attributed to orbital ordering of the Ru t(2g) electrons. The propagation vector of the orbital order is inconsistent with some theoretical predictions for the orbital state of Ca2RuO4.

Enhanced interfacial magnetic coupling of Gd /Fe multilayers.

The spatial extent zeta(AFM) and strength J(AFM) of the antiferromagnetic (AFM) exchange coupling at buried Gd /Fe interfaces in ferrimagnetic [Gd(50 A)Fe(15,35 A)](15) sputtered multilayers is obtained from combined x-ray resonance magnetic reflectivity and magnetic circular dichroism measurements. zeta(AFM) is 4.1(7) A or approximately 1-2 interatomic distances in bulk Gd and Fe; J(AFM) is 1050(90) K, comparable to the ferromagnetic exchange in bulk Fe.

Regulation of melatonin 1a receptor signaling and trafficking by asparagine-124.

Melatonin is a pineal hormone that regulates seasonal reproduction and has been used to treat circadian rhythm disorders. The melatonin 1a receptor is a seven- transmembrane domain receptor that signals predominately via pertussis toxin-sensitive G-proteins. Point mutations were created at residue N124 in cytoplasmic domain II of the receptor and the mutant receptors were expressed in a neurohormonal cell line. The acidic N124D- and E-substituted receptors had high-affinity (125)I-melatonin binding and a subcellular localization similar to the neutral N124N wild-type receptor. Melatonin efficacy for the inhibition of cAMP by N124D and E mutations was significantly decreased. N124D and E mutations strongly compromised melatonin efficacy and potency for inhibition of K(+)-induced intracellular Ca(++) fluxes and eliminated control of spontaneous calcium fluxes. However, these substitutions did not appear to affect activation of Kir3 potassium channels. The hydrophobic N124L and N124A or basic N124K mutations failed to bind (125)I-melatonin and appeared to aggregate or traffic improperly. N124A and N124K receptors were retained in the Golgi. Therefore, mutants at N124 separated into two sets: the first bound (125)I-melatonin with high affinity and trafficked normally, but with reduced inhibitory coupling to adenylyl cyclase and Ca(++) channels. The second set lacked melatonin binding and exhibited severe trafficking defects. In summary, asparagine-124 controls melatonin receptor function as evidenced by changes in melatonin binding, control of cAMP levels, and regulation of ion channel activity. Asparagine-124 also has a unique structural effect controlling receptor distribution within the cell.

Cyclic AMP regulates the calcium transients released from IP(3)-sensitive stores by activation of rat kappa-opioid receptors expressed in CHO cells.

We analyzed intracellular Ca(2+)and cAMP levels in Chinese hamster ovary cells expressing a cloned rat kappa opioid receptor (CHO-kappa cells). Although expression of kappa(kappa)-opioid receptors was confirmed with a fluorescent dynorphin analog in almost all CHO-kappa cells, the kappa-specific agonists, U50488H or U69593, induced a Ca(2+) transient only in 35% of the cells. The Ca(2+) response occurred in all-or-none fashion and the half-maximal dosage of U50488H (812.1nM) was higher than that (3.2nM) to inhibit forskolin-stimulated cAMP. The kappa-receptors coupled to G(i/o)proteins since pertussis toxin significantly reduced the U50488H actions on intracellular Ca(2+) and cAMP. The Ca(2+) transient originates from IP(3)-sensitive internal stores since the Ca(2+) response was blocked by a PLC inhibitor (U73122) or by thapsigargin depletion of internal stores while removal of extracellular Ca(2+) had no effect. Interestingly, application of dibutyryl cAMP (+ 56.2%) or 8-bromo-cAMP (+ 174.7%) significantly increased the occurrence of U50488H-induced Ca(2+) mobilization while protein kinase A (PKA) inhibitors, Rp-cAMP (-32.3%) or myr-psi PKA (-73.9%) significantly reduced the response. Therefore, it was concluded that cAMP and PKA activity can regulate the Ca(2+) mobilization. These results suggest that the kappa receptor-linked cAMP cascade regulates the occurrence of kappa-opioid-mediated Ca(2+) mobilization.

Melatonin receptor potentiation of cyclic AMP and the cystic fibrosis transmembrane conductance regulator ion channel.

We have used the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel as a model system to study the cAMP signal transduction pathways coupled to the Xenopus melatonin receptor. During forskolin (Fsk) stimulation, melatonin reduced the amplitude of the CFTR currents in oocytes injected with in vitro transcribed cRNAs for the Xenopus melatonin receptor and CFTR. Pertussis toxin (Ptx) treatment eliminated melatonin inhibition of Fsk stimulated CFTR currents. In oocytes injected with cRNA for melatonin receptors, serotonin receptors (5-HT7), and CFTR Cl- channels, application of melatonin together with serotonin (5-HT) activated an additional inward current showing potentiation of adenylyl cyclases by melatonin receptors. Subthreshold activation of 5-HT7 receptors was sufficient and necessary to permit activation of CFTR channels by melatonin. Preexposure to melatonin desensitized the melatonin receptor mediated response. Therefore, based on this model system, the effects of melatonin in vivo could be either positive or negative modulation of other neuronal inputs, depending on the mode of adenylyl cyclase stimulation.

Orphanin-FQ/nociceptin (OFQ/N) modulates the activity of suprachiasmatic nucleus neurons.

Neurons in the suprachiasmatic nucleus (SCN) constitute the principal circadian pacemaker of mammals. In situ hybridization studies revealed expression of orphanin-FQ/nociceptin (OFQ/N) receptor (NOR) mRNA in the SCN, whereas no expression of mRNA for preproOFQ/N (ppOFQ/N) was detected. The presence of OFQ/N peptide in the SCN was demonstrated by radioimmunoassay. SCN neurons (88%) responded dose-dependently to OFQ/N with an outward current (EC50 = 22.3 nM) that was reduced in amplitude by membrane hyperpolarization and reversed polarity near the theoretical potassium equilibrium potential. [Phe1psi(Ch2-NH)Gly2]OFQ/N(1-13)NH2 (3 microM), a putative NOR antagonist, activated a small outward current and significantly reduced the amplitude of the OFQ/N-stimulated current. OFQ/N reduced the NMDA receptor-mediated increase in intracellular Ca2+. When injected unilaterally into the SCN of Syrian hamsters housed in constant darkness, OFQ/N (1-50 pmol) failed to alter the timing of the hamsters' wheel-running activity. However, injection of OFQ/N (0.1-50 pmol) before a brief exposure to light during the midsubjective night significantly attenuated the light-induced phase advances of the activity rhythm. These data are consistent with the interpretation that OFQ/N acting at specific receptors modulates the activity of SCN neurons and, thereby, the response of the circadian clock to light.

Cyclic AMP analogs induce synthesis, processing, and secretion of prepro nociceptin/orphanin FQ-derived peptides by NS20Y neuroblastoma cells.

Recent studies have shown that cAMP analogs can induce expression of prepro (pp) orphanin FA (OFQ)/nociceptin-related gene products in NS20Y mouse neuroblastoma cells (Saito et al. [1996]. J Biol Chem 271, 15615-15622). Additionally, exposure of NS20Y cells to cAMP analogs promoted neurite outgrowth and large dense-core vesicle formation. Even though an OFQ-like precursor (called 27K) was identified in NS20Y cell extracts, no secretion of OFQ-related peptides was detected. We have used reversed-phase high-performance liquid chromatography combined with a specific radioimmunoassay for OFQ(1-17) to determine if NS20Y cells secrete ppOFQ-derived peptides when stimulated by the cAMP analog ctp-cAMP. We found that NS20Y cells secreted abundant amounts of OFQ-derived products when stimulated by cAMP analogs. We also have determined that secretion of OFQ peptides was both time and concentration dependent and reversible on removal of cAMP analogs from the culture medium. In addition, the opioid agonist D-Pen2-D-Pen5-enkephalin inhibited forskolin-stimulated OFQ peptide secretion. Further, the synthetic glucocorticoid dexamethasone virtually abolished ctp-cAMP-stimulated OFQ peptide secretion. These results suggest that the biosynthesis, processing, and secretion of the OFQ neuropeptide transmitter system can be modulated through intracellular cAMP levels and that these functions are regulated by opioids and molecules involved in mediating the stress response. The NS20Y cell system will be extremely valuable for studying the regulation of OFQ-derived peptides by a variety of intra-cellular and extracellular signaling pathways.

Contribution of serine residues to constitutive and agonist-induced signaling via the D2S dopamine receptor: evidence for multiple, agonist-specific active conformations.

Dopamine D2 receptors contain a cluster of serine residues in the fifth transmembrane domain that contribute to activation of the receptor as well as to the binding of agonists. We used rat D2S dopamine receptor mutants, each containing a serine-to-alanine substitution (S193A, S194A, S197A), to investigate the mechanism through which these residues affect activation of the receptor. Activation of the mutant receptor S194A was abolished in an agonist-dependent manner, such that dopamine no longer inhibited cAMP accumulation in C6 glioma cells or activated G protein-regulated K+ channels in Xenopus laevis oocytes, whereas the efficacy of several other agonists was unaffected. Dihydrexidine did not inhibit cAMP accumulation at either S193A or S194A. The decreased efficacy of dihydrexidine at S193A and S194A and dopamine at S194A was associated with a decreased ability to detect a GTP-sensitive high affinity binding state for these agonists. The ability of dopamine to stimulate [35S]guanosine-5'-O-(3-thio)triphosphate binding via S194A also was decreased by approximately 50%. Finally, constitutive stimulation of [35S]guanosine-5'-O-(3-thio)triphosphate binding and inhibition of adenylate cyclase by the D2S receptor was reduced by mutation of either S193 or S194. These data support the existence of multiple active receptor conformations that are differentially sensitive to mutation of serine residues in the fifth-transmembrane domain.

Lead inhibition of N-methyl-D-aspartate receptors containing NR2A, NR2C and NR2D subunits.

The potency of Pb2+ inhibition of glutamate-activated currents mediated by N-methyl-D-aspartate (NMDA) receptors was dependent on the subunits composing the receptors when functionally expressed in Xenopus laevis oocytes. Pb2+ reduced the amplitudes of glutamate-activated currents and shifted the agonist EC50 values of NMDA receptors consisting of different subunit compositions. The IC50 values for Pb2+ ranged from 1.52 to 8.19 microM, with a rank order of potency of NR1b-2A > NR1b-2C > NR1b-2D > NR1b-2AC. For NR1b-2AC NMDA receptors, the IC50 value was dependent on the agonist concentration; at saturating agonist concentrations (300 microM), the IC50 value was 8.19 microM, whereas at 3 microM glutamate, the IC50 value was 3.39 microM. Pb2+ was a noncompetitive inhibitor of NR1b-2A, NR1b-2C and NR1b-2D NMDA receptors. At low concentrations (<1 microM) Pb2+ potentiated NR1b-2AC NMDA receptors. These data provide further evidence to support the hypothesis that the actions of Pb2+ on NMDA receptors are determined by the receptor subunit composition.

Cloning and characterization of Kir3.1 (GIRK1) C-terminal alternative splice variants.

Southern blot analysis of RT-PCR products from brain and heart revealed multiple products for a C-terminal region of Kir3.1. Sequencing yielded clones for wild-type Kir3.1 and three Kir3.1 C-terminal alternative splice variants, including a unique alternative exon. Two of these variants encoded truncated Kir3.1 molecules. Tissue distribution and electrophysiological characterization of a single truncated variant, Kir3.1(00) were then examined. Kir3.1 channels are gated by G-protein beta gamma-subunits binding to the C-terminal domain, thus, the truncation of Kir3.1(00) removes a major functional domain. When incorporated into heteromeric channels with other family members (Kir3.1, 3.2 or 3.4) several functional changes were observed: (1) Kir3.1(00) changes G-protein activation of Kir3 channels; (2) Kir3.1(00) is restricted in its ability to assemble with other channel subunits as heteromers; and (3) incorporation of Kir3.1(00) into heteromeric channel complexes alters the kinetics of channel re-activation.

The sensitivity of N-methyl-D-aspartate receptors to lead inhibition is dependent on the receptor subunit composition.

Pb+2 is a potent inhibitor of N-methyl-D-aspartate (NMDA) receptors and its action is dependent on neuronal maturation. Developmentally regulated expression of NMDA receptor subunits may underlie the changing sensitivity to Pb+2. In oocytes expressing in vitro transcribed cRNAs for zeta 1 epsilon 1 or zeta 1 epsilon 2 NMDA receptor subunits, Pb+2 inhibited glutamate-activated currents with IC50 values of 0.87 +/- 0.25 and 1.21 +/- 0.22 microM, respectively, and NMDA-activated currents with IC50 values of 1.37 +/- 0.47 and 1.11 +/- 0.33 microM, respectively. In oocytes expressing zeta 1 epsilon 1 epsilon 2 subunits, the IC50 values for Pb+2 blockade of NMDA- or glutamate-activated currents were significantly larger when compared to zeta 1 epsilon 1 or zeta 1 epsilon 2 combinations. Pb+2 concentrations greater than 1 microM inhibited glutamate-activated currents with an IC50 of 6.1 +/- 1.22 microM and NMDA-activated currents with an IC50 of 6.64 +/- 3.34 microM. Pb+2 reduced the maximal current amplitude consistent with a noncompetitive block. zeta 1 epsilon 1 epsilon 2 NMDA receptors were potentiated by low concentrations of Pb+2 ( < 1.0 microM). These data suggest that brain regions with zeta 1 epsilon 1 or zeta 1 epsilon 2 NMDA receptors subunits would be more vulnerable to Pb+2 toxicity than those with zeta 1 epsilon 1 epsilon 2 NMDA-receptors, which are expressed later in development. These data provide a mechanism for the reported changes in the efficacy of block of NMDA receptors by Pb+2 during development.