Latent N-methyl-D-aspartate receptors in the recurrent excitatory pathway between hippocampal CA1 pyramidal neurons: Ca(2+)-dependent activation by blocking A1 adenosine receptors.

When performed at increased external [Ca2+]/[Mg2+] ratio (2.5 mM/0.5 mM), temporary block of A1 adenosine receptors in hippocampus [by 8-cyclopentyltheophylline (CPT)] leads to a dramatic and irreversible change in the excitatory postsynaptic current (EPSC) evoked by Schaffer collateral/commissural (SCC) stimulation and recorded by in situ patch clamp in CA1 pyramidal neurons. The duration of the EPSC becomes stimulus dependent, increasing with increase in stimulus strength. The later occurring component of the EPSC is carried through N-methyl-D-aspartate (NMDA) receptor-operated channels but disappears under either the NMDA antagonist 2-amino-5-phosphonovaleric acid (APV) or the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). These findings indicate that the late component of the SCC-evoked EPSC is polysynaptic: predominantly non-NMDA receptor-mediated SCC inputs excite CA1 neurons that recurrently excite each other by predominantly NDMA receptor-mediated synapses. These recurrent connections are normally silent but become active after CPT treatment, leading to enhancement of the late component of the EPSC. The activity of these connections is maintained for at least 2 hr after CPT removal. When all functional NMDA receptors are blocked by dizocilpine maleate (MK-801), subsequent application of CPT leads to a partial reappearance of NMDA receptor-mediated EPSCs evoked by SCC stimulation, indicating that latent NMDA receptors are recruited. Altogether, these findings indicate the existence of a powerful system of NMDA receptor-mediated synaptic contacts in SCC input to hippocampal CA1 pyramidal neurons and probably also in reciprocal connections between these neurons, which in the usual preparation are kept latent by activity of A1 receptors.

Blocking effects of polyunsaturated fatty acids on Na+ channels of neonatal rat ventricular myocytes.

Recent evidence indicates that polyunsaturated long-chain fatty acids (PUFAs) prevent lethal ischemia-induced cardiac arrhythmias in animals and probably in humans. To increase understanding of the mechanism(s) of this phenomenon, the effects of PUFAs on Na+ currents were assessed by the whole-cell patch-clamp technique in cultured neonatal rat ventricular myocytes. Extracellular application of the free 5,8,11,14,17-eicosapentaenoic acid (EPA) produced a concentration-dependent suppression of ventricular, voltage-activated Na+ currents (INa). After cardiac myocytes were treated with 5 or 10 microM EPA, the peak INa (elicited by a single-step voltage change with pulses from -80 to -30 mV) was decreased by 51% +/- 8% (P < 0.01; n = 10) and 64% +/- 5% (P < 0.001; n = 21), respectively, within 2 min. Likewise, the same concentrations of 4,7,10,16,19-docosahexaenoic acid produced the same inhibition of INa. By contrast, 5 and 10 microM arachidonic acid (AA) caused less inhibition of INa, but both n - 6 and n - 3 PUFAs inhibited INa significantly. A monounsaturated fatty acid and a saturated fatty acid did not. After washing out EPA, INa returned to the control level. Raising the concentration of EPA to 40 microM completely blocked INa. The IC50 of EPA was 4.8 microM. The inhibition of this Na+ channel was found to be dose and time, but not use dependent. Also, the EPA-induced inhibition of INa was voltage dependent, since 10 microM EPA produced 83% +/- 7% and 29% +/- 5% inhibition of INa elicited by pulses from -80 to -30 mV and from -150 to -30 mV, respectively, in single-step voltage changes. A concentration of 10 microM EPA shifted the steady-state inactivation curve of INa by -19 +/- 3 mV (n = 7; P < 0.01). These effects of PUFAs on INa may be important for their antiarrhythmic effect in vivo.

Daidzin suppresses ethanol consumption by Syrian golden hamsters without blocking acetaldehyde metabolism.

Daidzin is a potent, selective, and reversible inhibitor of human mitochondrial aldehyde dehydrogenase (ALDH) that suppresses free-choice ethanol intake by Syrian golden hamsters. Other ALDH inhibitors, such as disulfiram (Antabuse) and calcium citrate carbimide (Temposil), have also been shown to suppress ethanol intake of laboratory animals and are thought to act by inhibiting the metabolism of acetaldehyde produced from ingested ethanol. To determine whether or not daidzin inhibits acetaldehyde metabolism in vivo, plasma acetaldehyde in daidzin-treated hamsters was measured after the administration of a test dose of ethanol. Daidzin treatment (150 mg/kg per day i.p. for 6 days) significantly suppresses (> 70%) hamster ethanol intake but does not affect overall acetaldehyde metabolism. In contrast, after administration of the same ethanol dose, plasma acetaldehyde concentration in disulfiram-treated hamsters reaches 0.9 mM, 70 times higher than that of the control. In vitro, daidzin suppresses hamster liver mitochondria-catalyzed acetaldehyde oxidation very potently with an IC50 value of 0.4 microM, which is substantially lower than the daidzin concentration (70 microM) found in the liver mitochondria of daidzin-treated hamsters. These results indicate that (i) the action of daidzin differs from that proposed for the classic, broad-acting ALDH inhibitors (e.g., disulfiram), and (ii) the daidzin-sensitive mitochondrial ALDH is not the one and only enzyme that is essential for acetaldehyde metabolism in golden hamsters.

Ethanol inhibits luteinizing hormone-releasing hormone (LHRH) secretion by blocking the response of LHRH neuronal terminals to nitric oxide.

It has previously been shown that alcohol can suppress reproduction in humans, monkeys, and small rodents by inhibiting release of luteinizing hormone (LH). The principal action is via suppression of the release of LH-releasing hormone (LHRH) both in vivo and in vitro. The present experiments were designed to determine the mechanism by which alcohol inhibits LHRH release. Previous research has indicated that the release of LHRH is controlled by nitric oxide (NO). The proposed pathway is via norepinephrine-induced release of NO from NOergic neurons, which then activates LHRH release. In the present experiments, we further evaluated the details of this mechanism in male rats by incubating medial basal hypothalamic (MBH) explants in vitro and examining the release of NO, prostaglandin E2 (PGE2), conversion of arachidonic acid to prostanoids, and production of cGMP. The results have provided further support for our theory of LHRH control. Norepinephrine increased the release of NO as measured by conversion of [14C]arginine to [14C]citrulline, and this increase was blocked by the alpha 1 receptor blocker prazosin. Furthermore, the release of LHRH induced by nitroprusside (NP), a donor of NO, is related to the activation of soluble guanylate cyclase by NO since NP increased cGMP release from MBHs and cGMP also released LHRH. Ethanol had no effect on the production of NO by MBH explants or the increased release of NO induced by norepinephrine. Therefore, it does not act at that step in the pathway. Ethanol also failed to affect the increase in cGMP induced by NP. On the other hand, as might be expected from previous experiments indicating that LHRH release was brought about by PGE2, NP increased the conversion of [14C]arachidonic acid to its metabolites, particularly PGE2. Ethanol completely blocked the release of LHRH induced by NP and the increase in PGE2 induced by NP. Therefore, the results support the theory that norepinephrine acts to stimulate NO release from NOergic neurons. This NO diffuses to the LHRH terminals where it activates guanylate cyclase, leading to an increase in cGMP. At the same time, it also activates cyclooxygenase. The increase in cGMP increases intracellular free calcium, activating phospholipase A2 to provide arachidonic acid, the substrate for conversion by the activated cyclooxygenase to PGE2, which then activates the release of LHRH. Since alcohol inhibits the conversion of labeled arachidonic acid to PGE2, it must act either directly to inhibit cyclooxygenase or perhaps it may act by blocking the increase in intracellular free calcium induced by cGMP, which is crucial for activation of of both phospholipase A2 and cyclooxygenase.

Astrophysical parameters and orbital solution of the peculiar X-ray transient IGR J00370+6122

Context. BD + 60° 73 is the optical counterpart of the X-ray source IGR J00370+6122, a probable accretion-powered X-ray pulsar. The X-ray light curve of this binary system shows clear periodicity at 15.7 d, which has been interpreted as repeated outbursts around the periastron of an eccentric orbit. Aims. We aim to characterise the binary system IGR J00370+6122 by deriving its orbital and physical parameters. Methods. We obtained high-resolution spectra of BD + 60° 73 at different epochs. We used the fastwind code to generate a stellar atmosphere model to fit the observed spectrum and obtain physical magnitudes. The synthetic spectrum was used as a template for cross-correlation with the observed spectra to measure radial velocities. The radial velocity curve provided an orbital solution for the system. We also analysed the RXTE/ASM and Swift/BAT light curves to confirm the stability of the periodicity. Results. BD + 60° 73 is a BN0.7 Ib low-luminosity supergiant located at a distance ~3.1 kpc, in the Cas OB4 association. We derive Teff = 24 000 K and log gc = 3.0, and chemical abundances consistent with a moderately high level of evolution. The spectroscopic and evolutionary masses are consistent at the 1-σ level with a mass M∗ ≈ 15 M⊙. The recurrence time of the X-ray flares is the orbital period of the system. The neutron star is in a high-eccentricity (e = 0.56 ± 0.07) orbit, and the X-ray emission is strongly peaked around orbital phase φ = 0.2, though the observations are consistent with some level of X-ray activity happening at all orbital phases. Conclusions. The X-ray behaviour of IGR J00370+6122 is reminiscent of “intermediate” supergiant X-ray transients, though its peak luminosity is rather low. The orbit is somewhat wider than those of classical persistent supergiant X-ray binaries, which when combined with the low luminosity of the mass donor, explains the low X-ray luminosity. IGR J00370+6122 will very likely evolve towards a persistent supergiant system, highlighting the evolutionary connection between different classes of wind-accreting X-ray sources.

Orbital and Physical Properties of the σ Ori Aa, Ab, B Triple System

We provide a complete characterization of the astrophysical properties of the σ Ori Aa, Ab, B hierarchical triple system and an improved set of orbital parameters for the highly eccentric σ Ori Aa, Ab spectroscopic binary. We compiled a spectroscopic data set comprising 90 high-resolution spectra covering a total time span of 1963 days. We applied the Lehman-Filhés method for a detailed orbital analysis of the radial velocity curves and performed a combined quantitative spectroscopic analysis of the σ Ori Aa, Ab, B system by means of the stellar atmosphere code FASTWIND. We used our own plus other available information on photometry and distance to the system for measuring the radii, luminosities, and spectroscopic masses of the three components. We also inferred evolutionary masses and stellar ages using the Bayesian code BONNSAI. The orbital analysis of the new radial velocity curves led to a very accurate orbital solution of the σ Ori Aa, Ab pair. We provided indirect arguments indicating that σ Ori B is a fast-rotating early B dwarf. The FASTWIND+BONNSAI analysis showed that the Aa, Ab pair contains the hottest and most massive components of the triple system while σ Ori B is a bit cooler and less massive. The derived stellar ages of the inner pair are intriguingly younger than the one widely accepted for the σ Orionis cluster, at 3 ± 1 Ma. The outcome of this study will be of key importance for a precise determination of the distance to the σ Orionis cluster, the interpretation of the strong X-ray emission detected for σ Ori Aa, Ab, B, and the investigation of the formation and evolution of multiple massive stellar systems and substellar objects.

Orbital phase-resolved spectroscopy of 4U 1538−52 with MAXI

Context. 4U 1538−52, an absorbed high mass X-ray binary with an orbital period of ~3.73 days, shows moderate orbital intensity modulations with a low level of counts during the eclipse. Several models have been proposed to explain the accretion at different orbital phases by a spherically symmetric stellar wind from the companion. Aims. The aim of this work is to study both the light curve and orbital phase spectroscopy of this source in the long term. In particular, we study the folded light curve and the changes in the spectral parameters with orbital phase to analyse the stellar wind of QV Nor, the mass donor of this binary system. Methods. We used all the observations made from the Gas Slit Camera on board MAXI of 4U 1538−52 covering many orbits continuously. We obtained the good interval times for all orbital phase ranges, which were the input for extracting our data. We estimated the orbital period of the system and then folded the light curves, and we fitted the X-ray spectra with the same model for every orbital phase spectrum. We also extracted the averaged spectrum of all the MAXI data available. Results. The MAXI spectra in the 2–20 keV energy range were fitted with an absorbed Comptonisation of cool photons on hot electrons. We found a strong orbital dependence of the absorption column density but neither the fluorescence iron emission line nor low energy excess were needed to fit the MAXI spectra. The variation in the spectral parameters over the binary orbit were used to examine the mode of accretion onto the neutron star in 4U 1538−52. We deduce a best value of Ṁ/v∞ = 0.65 × 10-9M⊙ yr-1/ (km s-1) for QV Nor.

Orbital Magnetization of Quantum Spin Hall Insulator Nanoparticles

Both spin and orbital degrees of freedom contribute to the magnetic moment of isolated atoms. However, when inserted in crystals, atomic orbital moments are quenched because of the lack of rotational symmetry that protects them when isolated. Thus, the dominant contribution to the magnetization of magnetic materials comes from electronic spin. Here we show that nanoislands of quantum spin Hall insulators can host robust orbital edge magnetism whenever their highest occupied Kramers doublet is singly occupied, upgrading the spin edge current into a charge current. The resulting orbital magnetization scales linearly with size, outweighing the spin contribution for islands of a few nm in size. This linear scaling is specific of the Dirac edge states and very different from Schrodinger electrons in quantum rings. By modeling Bi(111) flakes, whose edge states have been recently observed, we show that orbital magnetization is robust with respect to disorder, thermal agitation, shape of the island, and crystallographic direction of the edges, reflecting its topological protection.

Controlled Complete Suppression of Single-Atom Inelastic Spin and Orbital Cotunneling

The inelastic portion of the tunnel current through an individual magnetic atom grants unique access to read out and change the atom’s spin state, but it also provides a path for spontaneous relaxation and decoherence. Controlled closure of the inelastic channel would allow for the latter to be switched off at will, paving the way to coherent spin manipulation in single atoms. Here, we demonstrate complete closure of the inelastic channels for both spin and orbital transitions due to a controlled geometric modification of the atom’s environment, using scanning tunneling microscopy (STM). The observed suppression of the excitation signal, which occurs for Co atoms assembled into chains on a Cu2N substrate, indicates a structural transition affecting the dz2 orbital, effectively cutting off the STM tip from the spin-flip cotunneling path.

Phase relationships between orbital forcing and the composition of air trapped in Antarctic ice cores

Orbital tuning is central for ice core chronologies beyond annual layer counting, available back to 60 ka (i.e. thousands of years before 1950) for Greenland ice cores. While several complementary orbital tuning tools have recently been developed using δ¹⁸Oatm, δO₂⁄N₂ and air content with different orbital targets, quantifying their uncertainties remains a challenge. Indeed, the exact processes linking variations of these parameters, measured in the air trapped in ice, to their orbital targets are not yet fully understood. Here, we provide new series of δO₂∕N₂ and δ¹⁸Oatm data encompassing Marine Isotopic Stage (MIS) 5 (between 100 and 160 ka) and the oldest part (340–800 ka) of the East Antarctic EPICA Dome C (EDC) ice core. For the first time, the measurements over MIS 5 allow an inter-comparison of δO₂∕N₂ and δ¹⁸Oatm records from three East Antarctic ice core sites (EDC, Vostok and Dome F). This comparison highlights some site-specific δO₂∕N₂ variations. Such an observation, the evidence of a 100 ka periodicity in the δO₂∕N₂ signal and the difficulty to identify extrema and mid-slopes in δO2∕N2 increase the uncertainty associated with the use of δO₂∕N₂ as an orbital tuning tool, now calculated to be 3–4 ka. When combining records of δ¹⁸Oatm and δO₂∕N₂ from Vostok and EDC, we find a loss of orbital signature for these two parameters during periods of minimum eccentricity (∼ 400 ka, ∼ 720–800 ka). Our data set reveals a time-varying offset between δO₂∕N₂ and δ¹⁸Oatm records over the last 800 ka that we interpret as variations in the lagged response of δ¹⁸Oatm to precession. The largest offsets are identified during Terminations II, MIS 8 and MIS 16, corresponding to periods of destabilization of the Northern polar ice sheets. We therefore suggest that the occurrence of Heinrich–like events influences the response of δ¹⁸Oatm to precession.

Construction of a precise early Eocene orbital cyclostratigraphy for DSDP Site 80-550 from the Goban Spur, North Atlantic

We constructed a precise early Eocene orbital cyclostratigraphy for DSDP Site 550 (Leg 80, Goban Spur, North Atlantic) utilizing precession related cycles as represented in a high resolution X-Ray Fluorescence based Barium core log. Based on counting of those cycles, we constrain the exact timing of two volcanic ash layers in Site 550 which correlate to ashes +19 and -17 of the Fur Formation in Denmark. The ashes, relative to the onset of the Paleocene/Eocene Thermal Maximum (PETM), are offset by 862 kyr and 672 kyr, respectively. When combined with published absolute ages for ash -17, the absolute age for the onset of the PETM is consistent with astronomically calibrated ages. Using the current absolute age of 28.02 Ma for the Fish Canyon Tuff (FCT) standard for calibrating the absolute age of ash -17 is consistent with tuning option 2 in the astronomically calibrated Paleocene time scale of Westerhold et al. (2008) [Westerhold, T., Röhl, U., Raffi, I., Fornaciari, E., Monechi, S., Reale, V., Bowles, J., and Evans, H.F., 2008, Astronomical calibration of the Paleocene time: Palaeogeography, Palaeoclimatology, Palaeoecology, v. 257, p. 377-403]. Using the recently recalibrated absolute age of 28.201 Ma for the FCT standard is consistent with tuning option 3 in the astronomically calibrated Paleocene time scale. The new results do not support the existence of any additional 405-kyr cycle in the early Paleocene astronomically tuned time scale.

Calcareous plankton response to orbital and millennial-scale climate changes from ODP Leg 161-975

The paleoenvironmental conditions through MIS 15-9 at the Mediterranean Ocean Drilling Program (ODP) Site 975 were interpreted by high resolution study of calcareous plankton assemblages compared with available d18O and d13C records and high resolution paleoclimate proxies from the Atlantic Ocean. Sea Surface Temperatures (SSTs) have been estimated from planktonic foraminiferal assemblages using the artificial neural networks method. Calcareous plankton varied dominantly on a glacial-interglacial scale as testified by the SST record, foraminiferal diversity, total coccolith abundance and changes in warm-water calcareous nannofossil taxa. A general increase in foraminiferal diversity and of total coccolith abundance is observed during interglacials. Warmest SSTs are reached during MIS 11, while MIS 12 and MIS 10 represent the coldest intervals of the studied record. During MIS 12, one of the most extreme glacials of the last million years, occurrence of Globorotalia inflata and of neogloboquadrinids indicates a shoaling of the interface between Atlantic inflowing and Mediterranean outflowing waters. Among calcareous nannofossils the distribution of Gephyrocapsa margereli-G. muellerae > 4 µm also supports a reduced Atlantic-Mediterranean exchange during MIS 12. Superimposed on glacial-interglacial variability, six short-terms coolings are recognized during MIS 12 and 10, which appear comparable in their distribution and amplitude to the Heinrich - type events documented in the Atlantic Ocean in the same interval. During these H-type events, N. pachyderma (s) and G. margereli-G. muellerae > 4 µm increase as a response to the enhanced inflow of cold Atlantic water into the Mediterranean via the Strait of Gibraltar. Mediterranean surface water hydrography appears to have been most severely affected at Termination V during the H-type event Ht4, possibly as a response to a large volume of Atlantic meltwater inflow via the Strait of Gibraltar and/or to freshwater/terrigenous input deriving from local mountain glaciers. Three additional SST coolings are recorded through MIS 14-16, but these are not well correlated with Heinrich - type events documented in the Atlantic Ocean in the same interval; during these cooling episodes only the subpolar Turborotalita quinqueloba increases. These results highlight the sensitive response of the Mediterranean basin to millennial-scale climate variations related to Northern Hemisphere ice-sheet instability and support the hypothesis that the tight connection between high latitude climate dynamics and Mediterranean sea surface water features can be traced through the Middle Pleistocene.