Calcium signals in the nucleus accumbens: Activation of astrocytes by ATP and succinate

Background

Late cerebral ischemia carries high morbidity and mortality after subarachnoid hemorrhage (SAH) due to reduced cerebral blood flow (CBF) and the subsequent cerebral ischemia which is associated with upregulation of contractile receptors in the vascular smooth muscle cells (SMC) via activation of mitogen-activated protein kinase (MAPK) of the extracellular signal-regulated kinase (ERK)1/2 signal pathway. We hypothesize that SAH initiates cerebrovascular ERK1/2 activation, resulting in receptor upregulation. The raf inhibitor will inhibit the molecular events upstream ERK1/2 and may provide a therapeutic window for treatment of cerebral ischemia after SAH.

Results

Here we demonstrate that SAH increases the phosphorylation level of ERK1/2 in cerebral vessels and reduces the neurology score in rats in additional with the CBF measured by an autoradiographic method. The intracisternal administration of SB-386023-b, a specific inhibitor of raf, given 6 h after SAH, aborts the receptor changes and protects the brain from the development of late cerebral ischemia at 48 h. This is accompanied by reduced phosphorylation of ERK1/2 in cerebrovascular SMC. SAH per se enhances contractile responses to endothelin-1 (ET-1), 5-carboxamidotryptamine (5-CT) and angiotensin II (Ang II), upregulates ET_B, 5-HT_1B and AT₁ receptor mRNA and protein levels. Treatment with SB-386023-b given as late as at 6 h but not at 12 h after the SAH significantly decreased the receptor upregulation, the reduction in CBF and the neurology score.

Conclusion

These results provide evidence for a role of the ERK1/2 pathway in regulation of expression of cerebrovascular SMC receptors. It is suggested that raf inhibition may reduce late cerebral ischemia after SAH and provides a realistic time window for therapy.     

Ankyrin repeat and SOCS box containing protein 4 (Asb-4) colocalizes with insulin receptor substrate 4 (IRS4) in the hypothalamic neurons and mediates IRS4 degradation

Background

Cigarette smoking enhances the risk of stroke. However, the underlying molecular mechanisms are largely unknown. The present study established an in vivo rat secondhand cigarette smoking (SHS) model and examined the hypothesis that SHS upregulates endothelin receptors with increased cerebrovascular contraction via the Raf/extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinases (MAPK) pathway.

Results

Rats were exposed to SHS for up to 8 weeks. The cerebral artery vasoconstriction was recorded by a sensitive myograph. The mRNA and protein expressions for endothelin receptors in cerebral arteries were studied by real-time PCR and Western blot. Compared to fresh air exposed rats, cerebral arteries from SHS rats exhibited stronger contractile responses (P < 0.05) mediated by endothelin type A (ET_A) receptors. The expressions of mRNA and protein for ET_A receptors in the cerebral arteries from SHS rats were higher (P < 0.05) than that in control. SHS did not affect endothelin type B (ET_B) receptor-mediated contractions, mRNA or protein levels. The results suggest that SHS upregulates ET_A, but not ET_B receptors in vivo. After SHS exposure, the mRNA levels of Raf-1 and ERK1/2, the protein expression of phosphorylated (p)-Raf-1 and p-ERK1/2 were increased (P < 0.05). Raf-1 inhibitor, GW5074 suppressed the enhanced ET_A receptor-mediated contraction, mRNA and protein levels induced by SHS. In addition, GW5074 inhibited the SHS-caused increased mRNA and phosphorylated protein levels of Raf-1 and ERK1/2, suggesting that SHS induces activation of the Raf/ERK/MAPK pathway.

Conclusions

SHS upregulates cerebrovascular ET_A receptors via the Raf/ERK/MAPK pathway, which provides novel understanding of mechanisms involved in SHS-associated stroke.     

Detection of human and rodent 5-HT3B receptor subunits by anti-peptide polyclonal antibodies

Background  

The 5-HT₃ receptor is a member of a neurotransmitter-gated ion channel family which includes nicotinic acetylcholine, GABA_A, and glycine receptors. While antibodies specific for the 5-HT_3A receptor subunit are plentiful, and have revealed a wealth of structural and functional information, few antisera exist for the detection of 5-HT_3B receptor subunits. Here we describe the generation and characterisation of a rabbit polyclonal antiserum that specifically recognises 5-HT_3B receptor subunits     

Structure and chemical bond characteristics of LaB6

The structure and chemical bond characteristics of LaB₆ have been achieved by means of the density functional theory using the state-of-the-art full-potential linearized augmented plane wave (FPLAPW) method, which are implemented within the EXCITING code. The results show our optimized lattice constant a (4.158 Å), parameter z (0.1981) and bulk modulus B (170.4 GPa) are in good agreement with the corresponding experimental data. Electron localization function (ELF) shows the La–La bond mainly is ionic bond, La–B bond is between ionic and covalent bond while the covalent bond between the nearest neighbor B atoms (B2 and B3) is a little stronger than that between the nearer neighbor B atoms (B1 and B4).     

Enhanced expressions of microvascular smooth muscle receptors after focal cerebral ischemia occur via the MAPK MEK/ERK pathway

Background  

MEK1/2 is a serine/threonine protein that phosphorylates extracellular signal-regulated kinase (ERK1/2). Cerebral ischemia results in enhanced expression of cerebrovascular contractile receptors in the middle cerebral artery (MCA) leading to the ischemic region. Here we explored the role of the MEK/ERK pathway in receptor expression following ischemic brain injury using the specific MEK1 inhibitor U0126.     

Ll2超导体的Tc表达式

通过对L1₂超导体的研究,我们得出了这类超导体临界温度的表达式T_c=(15.9T_BV(B)G_A)/(M^1/2V(L1₂)G_B)。其中T_B是B组元的超导转变温度,V(B)是B组元的原子体积,V(L1₂)为L1₂化合物的平均原子体积,M是L1₂化合物的平均原子量,G_A,G_B分别为A组元、B组元的Gordy电负性值。 关键词：     

Insulin signaling inhibits the 5-HT2C receptor in choroid plexus via MAP kinase

Background

G protein-coupled receptors (GPCRs) interact with heterotrimeric GTP-binding proteins (G proteins) to modulate acute changes in intracellular messenger levels and ion channel activity. In contrast, long-term changes in cellular growth, proliferation and differentiation are often mediated by tyrosine kinase receptors and certain GPCRs by activation of mitogen-activated protein (MAP) kinases. Complex interactions occur between these signaling pathways, but the specific mechanisms of such regulatory events are not well-understood. In particular it is not clear whether GPCRs are modulated by tyrosine kinase receptor-MAP kinase pathways.

Results

Here we describe tyrosine kinase receptor regulation of a GPCR via MAP kinase. Insulin reduced the activity of the 5-HT_2C receptor in choroid plexus cells which was blocked by the MAP kinase kinase (MEK) inhibitor, PD 098059. We demonstrate that the inhibitory effect of insulin and insulin-like growth factor type 1 (IGF-1) on the 5-HT_2C receptor is dependent on tyrosine kinase, RAS and MAP kinase. The effect may be receptor-specific: insulin had no effect on another GPCR that shares the same G protein signaling pathway as the 5-HT_2C receptor. This effect is also direct: activated MAP kinase mimicked the effect of insulin, and removing a putative MAP kinase site from the 5-HT_2C receptor abolished the effect of insulin.

Conclusion

These results show that insulin signaling can inhibit 5-HT_2C receptor activity and suggest that MAP kinase may play a direct role in regulating the function of a specific GPCR.     

Immunocytochemical evidence for co-expression of Type III IP3 receptor with signaling components of bitter taste transduction

Background  

Taste receptor cells are responsible for transducing chemical stimuli into electrical signals that lead to the sense of taste. An important second messenger in taste transduction is IP₃, which is involved in both bitter and sweet transduction pathways. Several components of the bitter transduction pathway have been identified, including the T2R/TRB taste receptors, phospholipase C β2, and the G protein subunits α-gustducin, β3, and γ13. However, the identity of the IP₃ receptor subtype in this pathway is not known. In the present study we used immunocytochemistry on rodent taste tissue to identify the IP₃ receptors expressed in taste cells and to examine taste bud expression patterns for IP₃R3.     

Effects of carbon substitution via ball-milling in MgB2

In this study, we have synthesized the C-doped MgB₂ samples by solid-state reaction after mixing Mg powder with the attrition-milled B and C powders. The C added powders were mixed according to the nominal atomic ratio of Mg(B_1−xC_x)₂ with x = 0, 0.005, 0.015, 0.025, and 0.05. The analysis of X-ray diffraction showed that the (1 1 0) peaks, which correspond to the lattice parameter a, were shifted to a higher angle as the increasing of carbon contents. These results indicated that the B substitution for C became more dominant at higher doping level of C. The sample having the composition of Mg(B_0.975C_0.025)₂ gave the best critical current density (Jc) of ≈5000 A cm⁻² at 8 T and 5 K, as compared to the ≈1200 A cm⁻² for the undoped sample.     

Complex CKM matrix, spontaneous CP violation and generalized symmetry

The multi-Higgs models having spontaneous CP violation (SPCPV) and natural flavor conservation (NFC) lead to a real CKM matrix V contradicting current evidence in favour of a complex V. This contradiction can be removed by using a generalized μ–τ (called 23) symmetry in place of the discrete symmetry conventionally used to obtain NFC. If the 23 symmetry is exact then the Higgs induced flavour changing neutral currents (FCNC) vanish as in the case of NFC. 23 breaking introduces SPCPV, a phase in V and suppressed FCNC among quarks. The FCNC couplings between i and j generations show a hierarchy with the result that the FCNC can have observable consequences in B mixing without conflicting with the mixing. Detailed fits to the quark masses and the CKM matrix are used to obtain the (complex) couplings and . Combined constraints from flavour and CP violations in the K, B_d, B_s, D mesons are analyzed within the model. They allow (i) relatively light Higgs, 100–150 GeV (ii) measurable extra contributions to the magnitudes and phases of the mixing amplitudes and (iii) the mixing at the current sensitivity level.     

A Frequency Localized Maximum Principle Applied to the 2D Quasi-Geostrophic Equation

In this paper, we prove a maximum principle for a frequency localized transport-diffusion equation. As an application, we prove the local well-posedness of the supercritical quasi-geostrophic equation in the critical Besov spaces \mathringB^1-a_￥,q{\mathring{B}^{1-\alpha}_{\infty,q}}, and global well-posedness of the critical quasi-geostrophic equation in \mathringB⁰_￥,q{\mathring{B}^{0}_{\infty,q}} for all 1 ≤ q < ∞. Here \mathringB^s_￥,q {\mathring{B}^{s}_{\infty,q} } is the closure of the Schwartz functions in the norm of B^s_￥,q{B^{s}_{\infty,q}}.     

High-resolution infrared and theoretical study of four fundamental bands of gaseous 1,3,4-oxadiazole between 800 and 1600 cm

The Fourier transform infrared spectrum of gaseous 1,3,4-oxadiazole, C₂H₂N₂O, has been recorded in the 800–1600 cm⁻¹ wavenumber region with a resolution around 0.0030 cm⁻¹. The four fundamental bands ν₉(B₁; 852.5 cm⁻¹), ν₁₄(B₂; 1078.5 cm⁻¹), ν₄(A₁; 1092.6 cm⁻¹), and ν₂(A₁; 1534.9 cm⁻¹) are analyzed by the standard Watson model. Ground state rotational and quartic centrifugal distortion constants are obtained from a simultaneous fit of ground state combination differences from three of these bands and previous microwave transitions. Upper state spectroscopic constants are obtained for all four bands from single band fits using the Watson model. The ν₄ and ν₁₄ bands form a c-Coriolis interacting dyad, and the two bands are analyzed simultaneously by a model including first and second order Coriolis resonance using the ab initio predicted Coriolis coupling constant . An extended local resonance in ν₂ is explained as higher order b-Coriolis type resonance with ν₆ + ν₁₀, which is further perturbed globally by the ν₁₅ + ν₁₀ level. A fit of selected low-J transitions to a triad model including ν₂(A₁), ν₆ + ν₁₀(B₁), and ν₁₅ + ν₁₀(A₂) using an ab initio calculated Coriolis coupling constant is performed.The rotational constants, ground state quartic centrifugal distortion constants, anharmonic frequencies, and vibration–rotational constants (α-constants) predicted by quantum chemical calculations using a cc-pVTZ and TZ2P basis with B3LYP methodology, are compared with the present experimental data, where there is generally good agreement. A complete set of anharmonic frequencies and α-constants for all fundamental levels of the molecule is given.     

Electric field gradients at57Fe impurities in crystalline NiB phases

The electric field gradient (EFG) parameters are investigated by in-field Mössbauer spectroscopy at⁵⁷Fe doping the crystalline compounds Ni₃B, Ni₂B, Ni₄B₃ and NiB. A preferential substitution of Ni by Fe is found in Ni₃B and Ni₄B₃. The knowledge of q_zz and at both the 3d metal and boron sites /1/ permits to develop a representation of EFG in terms of empirical screened point charges.     

Microstructures and microwave dielectric properties of La1-xBx(Mg0.5Sn0.5)O3 ceramics

The microwave dielectric properties of La_1-xB_x(Mg_0.5Sn_0.5)O₃ ceramics were examined with a view to their exploitation for mobile communication. The La_1-xB_x(Mg_0.5Sn_0.5)O₃ ceramics were prepared by the conventional solid-state method with various sintering temperatures. The X-ray diffraction patterns of the La_0.995B_0.005(Mg_0.5Sn_0.5)O₃ ceramics revealed no significant variation of phase with sintering temperatures. A maximum apparent density of 6.58 g/cm³, a dielectric constant (ε_r) of 19.8, a quality factor (Q × f) of 41,800 GHz, and a temperature coefficient of resonant frequency (τ_f) of −86 ppm/°C were obtained for La_0.995B_0.005(Mg_0.5Sn_0.5)O₃ ceramics that were sintered at 1500 °C for 4 h.     

Dopamine D<Subscript>2</Subscript>receptors mediate two-odor discrimination and reversal learning in C57BL/6 mice

Background  

Dopamine modulation of neuronal signaling in the frontal cortex, midbrain, and striatum is essential for processing and integrating diverse external sensory stimuli and attaching salience to environmental cues that signal causal relationships, thereby guiding goal-directed, adaptable behaviors. At the cellular level, dopamine signaling is mediated through D₁-like or D₂-like receptors. Although a role for D₁-like receptors in a variety of goal-directed behaviors has been identified, an explicit involvement of D₂ receptors has not been clearly established. To determine whether dopamine D₂ receptor-mediated signaling contributes to associative and reversal learning, we compared C57Bl/6J mice that completely lack functional dopamine D₂ receptors to wild-type mice with respect to their ability to attach appropriate salience to external stimuli (stimulus discrimination) and disengage from inappropriate behavioral strategies when reinforcement contingencies change (e.g. reversal learning).     

Magnetic structure of the Mn5Si3-type Er5Ge3 compound

The Er₅Ge₃ compound (Mn₅Si₃-type, hP16, P6₃/mcm) at 4 K shows magnetic ordering of the antiferromagnetic type. Its magnetic structure consists of sine modulated collinear magnetic moments of Er that are parallel to the c axis (with a propagation vector k=[0 0 ±0.3]). This corresponds to the magnetic unit cell (a a 10c), the values of the magnetic moment of the Er atoms being, as a general formula, M_z≈M₀ cos [2π(Z–1/4)(1–kZ)], with M₀=9.2(2) μ_B at 4 K.     

Targeted radiofrequency field mapping using 3D reduced field-of-view-catalyzed double-angle method

Purpose

The aim of this study was to develop a targeted volumetric radiofrequency field (B₁⁺) mapping technique to provide region-of-interest B₁⁺ information.

Materials and Methods

Targeted B₁⁺ maps were acquired using three-dimensional (3D) reduced field-of-view (FOV) inner-volume turbo spin echo-catalyzed double-angle method (DAM). Targeted B₁⁺ maps were compared with full-FOV B₁⁺ maps acquired using 3D catalyzed DAM in a phantom and in the brain of a healthy volunteer. In addition, targeted volumetric abdomeninal B₁⁺ mapping was demonstrated in the abdomen of another healthy volunteer.

Results

The targeted reduced-FOV images demonstrated no aliasing artifacts in all experiments. Close match between targeted B₁⁺ map and reference full-FOV B₁⁺ map in the same region was observed, with percentage root-mean-squared error <0.4% in the phantom and <0.8% in the healthy volunteer brain. The abdominal B₁⁺ maps showed small B₁⁺ variation in the kidneys and liver from the healthy volunteer.

Conclusion

The proposed 3D reduced-FOV catalyzed DAM provides a rapid, simple and accurate method for targeted volumetric B₁⁺ mapping and can be easily implemented for applications related to radiofrequency field mapping in small targeted regions.     

A comparative photoluminescence study on Mn-Free GaAs/AlAs and Mn-containing Ga1-xMnxAs/AlAs quantum wells (QWs) grown on various orientations by MBE

Optical properties of diluted magnetic semiconductor Ga_0.999Mn_0.001As/AlAs quantum well structures grown on (1?0?0?), (1?1?0), (3?1?1)B and (4?1?1)B by molecular beam epitaxy are reported. Temperature-dependent spectral photoluminescence (PL) measurement was performed at temperatures between 15 and 300 K. The PL measurements showed that band gap of the alloy decreases with increasing lattice temperature regardless the growth orientations. S-shaped temperature dependence has been observed in the samples grown on (1?0?0), (3?1?1)B, (4?1?1)B orientations. PL emission energy is fitted with Varshni and Bose–Einstein Approximation to determine Debye temperature (β), (Θ_E) and thermal expansion coefficient (α), the exciton–phonon coupling strength (a_B).     

Serotonin 5-HT2A and 5-HT6 receptors in the prefrontal cortex of Alzheimer and normal aging patients

Background  

It has been hypothesized that alterations of the serotonergic system contribute to neuropsychiatric symptoms in Alzheimer disease (AD). Cellular expressions of the two serotonergic receptors 5-HT_2A and 5-HT₆ have therefore been determined by immunohistochemistry in the prefrontal cortex of patients with AD (n=6) and normal age-matched controls (n = 7).     

Effect of doping on cohesive and thermophysical properties of MgB2

The effects of doping Al and Mn on the cohesive and thermophysical properties of MgB₂ have been investigated using a Rigid Ion Model (RIM). The interatomic potential of this model includes contributions from the long-range Coulomb attraction and the short-range overlap repulsion and the van der Waals attraction. This model has been applied to describe the temperature dependence of the specific heat of MgB₂, Mg_1−xAl_xB₂ (x = 0.1–0.9) and Mg_1−xMn_xB₂ (x = 0.01–0.04) in the temperature range 5 K ⩽ T ⩽ 1000 K. The calculated results on cohesive energy (ϕ), Bulk modulus (B_T), molecular force constant (f), Restrahalen frequency (ν₀), Debye temperature (Θ_D) and Gruneisen parameter (γ) are also reported for these materials. Our results on Bulk modulus, Restrahalen frequency and Debye temperature are closer to the available experimental data. The comparison between our calculated and available experimental results on the specific heat at constant volume for MgB₂ and Mg_1−xAl_xB₂ (x = 0.1–0.4), particularly, at lower temperatures has shown almost an excellent agreement. The trend of variation of the specific heat with temperature is more or less similar in pure and doped MgB₂.