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We employ kinetic Monte-Carlo simulations to study the growth process of metal-oxide nanocomposites obtained via sequential pulsed laser deposition. Using Ni-SrTiO3 (Ni-STO) as a model system, we reduce the complexity of the computational problem by choosing a coarse-grained approach mapping Sr, Ti and O atoms onto a single effective STO pseudo-atom species. With this ansatz, we scrutinize the kinetics of the sequential synthesis process, governed by alternating deposition and relaxation steps, and analyze the self-organization propensity of Ni atoms into straight vertically aligned nanowires embedded in the surrounding STO matrix. We finally compare the predictions of our binary toy model with experiments and demonstrate that our computational approach captures fundamental aspects of self-assembled nanowire synthesis. Despite its simplicity, our modeling strategy successfully describes the impact of relevant parameters like the concentration or laser frequency on the final nanoarchitecture of metal-oxide thin films grown via pulsed laser deposition.
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Antiferromagnets offer a unique combination of properties including the radiation and magnetic field hardness, the absence of stray magnetic fields, and the spin-dynamics frequency scale in terahertz. Recent experiments have demonstrated that relativistic spin-orbit torques can provide the means for an efficient electric control of antiferromagnetic moments. Here we show that elementary-shape memory cells fabricated from a single-layer antiferromagnet CuMnAs deposited on a III-V or Si substrate have deterministic multi-level switching characteristics. They allow for counting and recording thousands of input pulses and responding to pulses of lengths downscaled to hundreds of picoseconds. To demonstrate the compatibility with common microelectronic circuitry, we implemented the antiferromagnetic bit cell in a standard printed circuit board managed and powered at ambient conditions by a computer via a USB interface. Our results open a path towards specialized embedded memory-logic applications and ultra-fast components based on antiferromagnets.
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The growth by pulsed laser deposition of fully epitaxial nanocomposites made of Co x Ni1-x nanowires (NW) vertically self-assembled in Sr0.5Ba0.5TiO3/SrTiO3(001) layers is reported. The diameter of the wires can be tuned in the 1.8-6 nm range. The composition of the wires can be controlled, with the growth sequence and the fcc crystallographic structure of the wires preserved for Co content up to 78%. The nanocomposite systems obtained display a uniaxial magnetic anisotropy with out-of-plane easy axis as shown through analysis of ferromagnetic resonance measurements. It is shown that the magnitude of the magnetic anisotropy depends sensitively on the structural quality of the nanocomposites.The energy barrier for magnetization reversal scales as the square of the diameter of the NW and reaches 60 [Formula: see text] for 6 nm diameter, with T amb = 300 K.
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AIMS: A broad spectrum of synthetic agents is available for the treatment of overactive bladder. Anti-cholinergic drugs show a poor compliance due to side effects. There is an increasing use of plant extracts in medicine. We have therefore investigated the inhibitory effects of leaf press juice from Bryophyllum pinnatum (Lam.) Oken (Kalanchoe pinnata L.) on bladder strips and compared the effects to that of oxybutynin. METHODS: Strips of porcine detrusor were prepared in Krebs solution and contractility was measured in a myograph system chamber aired with O2/CO2 at 37 °C. To induce contractions, electrical field stimulation (32 Hz, 40 V) was used for the inhibitory effect measurements, and carbachol (50 µM) for the relaxant effect measurements. Recordings were obtained in the absence and presence of increasing concentrations of Bryophyllum pinnatum leaf press juice (BPJ, 0.1-10%), and oxybutynin (10â»7-10⻳ M) as a reference substance. RESULTS: In inhibition experiments, BPJ as well as oxybutynin inhibited electrically induced contractions of porcine detrusor. BPJ at concentrations of 5% inhibited the contraction compared to a time matched control significantly by 74.6±10.2% (p<0.001). BPJ as well as oxybutynin relaxed carbachol pre-contracted porcine detrusor strips. The maximum relaxant effect of BPJ compared to a time matched control was 18.7±3.7 (p<0.05) at a concentration of 10% BPJ. CONCLUSIONS: Our investigations show that BPJ inhibits contractions induced by electrical field stimulation and relaxes carbachol-induced contractions. However, the effect was lower than that of the reference substance oxybutynin. It is important to continue in vitro experiments as well as clinical studies with BPJ that might offer a new treatment option for patients with OAB.
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Kalanchoe , Ácidos Mandélicos/uso terapéutico , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Parasimpatolíticos/uso terapéutico , Vejiga Urinaria Hiperactiva , Vejiga Urinaria/efectos de los fármacos , Animales , Carbacol/farmacología , Agonistas Colinérgicos/farmacología , Estimulación Eléctrica , Ácidos Mandélicos/farmacología , Antagonistas Muscarínicos/farmacología , Antagonistas Muscarínicos/uso terapéutico , Músculo Liso/fisiología , Parasimpatolíticos/farmacología , Fitoterapia , Hojas de la Planta , Preparaciones de Plantas/farmacología , Preparaciones de Plantas/uso terapéutico , Porcinos , Vejiga Urinaria/fisiología , Vejiga Urinaria Hiperactiva/tratamiento farmacológicoRESUMEN
GABA(B) (gamma-aminobutyric acid type B) receptors are important for keeping neuronal excitability under control. Cloned GABA(B) receptors do not show the expected pharmacological diversity of native receptors and it is unknown whether they contribute to pre- as well as postsynaptic functions. Here, we demonstrate that Balb/c mice lacking the GABA(B(1)) subunit are viable, exhibit spontaneous seizures, hyperalgesia, hyperlocomotor activity, and memory impairment. Upon GABA(B) agonist application, null mutant mice show neither the typical muscle relaxation, hypothermia, or delta EEG waves. These behavioral findings are paralleled by a loss of all biochemical and electrophysiological GABA(B) responses in null mutant mice. This demonstrates that GABA(B(1)) is an essential component of pre- and postsynaptic GABA(B) receptors and casts doubt on the existence of proposed receptor subtypes.
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Epilepsia/genética , Hiperalgesia/genética , Trastornos de la Memoria/genética , Memoria/fisiología , Neuronas/fisiología , Receptores de GABA-B/fisiología , Animales , Animales Recién Nacidos , Reacción de Prevención/fisiología , Baclofeno/farmacología , Regulación de la Temperatura Corporal , Ritmo Delta/efectos de los fármacos , Epilepsia/fisiopatología , Agonistas del GABA/farmacología , Hipocampo/fisiología , Hipocampo/fisiopatología , Hiperalgesia/fisiopatología , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Trastornos de la Memoria/fisiopatología , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Actividad Motora/efectos de los fármacos , Actividad Motora/fisiología , Relajación Muscular/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/fisiología , Músculo Esquelético/fisiopatología , Dolor/fisiopatología , Técnicas de Placa-Clamp , Subunidades de Proteína , Receptores de GABA-B/deficiencia , Receptores de GABA-B/genéticaRESUMEN
Assembly of fully functional GABA(B) receptors requires heteromerization of the GABA(B(1)) and GABA(B(2)) subunits. It is thought that GABA(B(1)) and GABA(B(2)) undergo coiled-coil dimerization in their cytoplasmic C termini and that assembly is necessary to overcome GABA(B(1)) retention in the endoplasmatic reticulum (ER). We investigated the mechanism underlying GABA(B(1)) trafficking to the cell surface. We identified a signal, RSRR, proximal to the coiled-coil domain of GABA(B(1)) that when deleted or mutagenized allows for surface delivery in the absence of GABA(B(2)). A similar motif, RXR, was recently shown to function as an ER retention/retrieval (ERR/R) signal in K(ATP) channels, demonstrating that G-protein-coupled receptors (GPCRs) and ion channels use common mechanisms to control surface trafficking. A C-terminal fragment of GABA(B(2)) is able to mask the RSRR signal and to direct the GABA(B(1)) monomer to the cell surface, where it is functionally inert. This indicates that in the heteromer, GABA(B(2)) participates in coupling to the G-protein. Mutagenesis of the C-terminal coiled-coil domains in GABA(B(1)) and GABA(B(2)) supports the possibility that their interaction is involved in shielding the ERR/R signal. However, assembly of heteromeric GABA(B) receptors is possible in the absence of the C-terminal domains, indicating that coiled-coil interaction is not necessary for function. Rather than guaranteeing heterodimerization, as previously assumed, the coiled-coil structure appears to be important for export of the receptor complex from the secretory apparatus.
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Membrana Celular/metabolismo , Riñón/metabolismo , Neuronas/metabolismo , Transporte de Proteínas/fisiología , Receptores de GABA-B/metabolismo , Secuencias de Aminoácidos/fisiología , Calcio/metabolismo , Línea Celular , Dimerización , Retículo Endoplásmico/metabolismo , Proteínas de Unión al GTP/metabolismo , Humanos , Inmunohistoquímica , Riñón/citología , Mutagénesis Sitio-Dirigida , Neuronas/citología , Etiquetas de Fotoafinidad/metabolismo , Unión Proteica/fisiología , Estructura Terciaria de Proteína/fisiología , Subunidades de Proteína , Receptores de GABA-B/genética , Receptores de Glutamato Metabotrópico/metabolismo , Transducción de Señal/fisiologíaRESUMEN
A gamma-aminobutyric acid (GABA)(B) receptor (named GABA(B)R1) has been recently cloned in the rat and human brain and two variants generated by alternative RNA splicing were identified. In the present study, we addressed the question as to whether these variants contribute to the diversity of GABA(B) receptor-mediated physiological responses and constitute real receptor subtypes with distinct functions. To this aim, we have mapped the GABA(B)R1 (R1a) and GABA(B)R1b (R1b) transcript distribution in the rat brain using in situ hybridization. We have compared the mRNA distribution with the distribution of [(3)H]CGP54626-labeled binding GABA(B)R1 receptor sites as assessed in adjacent cryosections by quantitative autoradiography. We found that GABA(B) receptor transcripts and binding sites are expressed in the brain in almost all neuronal cell populations. Expression in glial cells, if any, is marginal. We observed a good parallelism between GABA(B)R1 mRNA transcripts and binding sites in broad neuroanatomical entities with highest densities in hippocampus, thalamic nuclei, and cerebellum. By contrast, R1a and R1b transcripts exhibit marked differences in their regional and cellular distribution pattern. A typical example is the cerebellum with an almost exclusive expression of R1b in the Purkinje cells and of R1a in the granule, stellate, and basket cells. Data pointing at a pre- versus postsynaptic localization for R1a and R1b, respectively, at some neuronal sites are presented.
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Química Encefálica/fisiología , Encéfalo/fisiología , ARN Mensajero/biosíntesis , Receptores de GABA-B/biosíntesis , Animales , Autorradiografía , Encéfalo/citología , Mapeo Encefálico , Agonistas del GABA/metabolismo , Hibridación in Situ , Masculino , Neuronas/metabolismo , Compuestos Organofosforados/metabolismo , Células de Purkinje/metabolismo , RatasAsunto(s)
Proteínas de Unión al GTP/metabolismo , Receptores de GABA-B/metabolismo , Animales , Línea Celular , Clonación Molecular , Proteínas Fluorescentes Verdes , Humanos , Inmunohistoquímica , Proteínas Luminiscentes , Canales de Potasio/metabolismo , Ratas , Receptores de GABA-B/genética , Proteínas Recombinantes de FusiónRESUMEN
gamma-Aminobutyric acid type B receptors (GABABRs) are involved in the fine tuning of inhibitory synaptic transmission. Presynaptic GABABRs inhibit neurotransmitter release by down-regulating high-voltage activated Ca2+ channels, whereas postsynaptic GABABRs decrease neuronal excitability by activating a prominent inwardly rectifying K+ (Kir) conductance that underlies the late inhibitory postsynaptic potentials. Here we report the cloning and functional characterization of two human GABABRs, hGABABR1a (hR1a) and hGABABR1b (hR1b). These receptors closely match the pharmacological properties and molecular weights of the most abundant native GABABRs. We show that in transfected mammalian cells hR1a and hR1b can modulate heteromeric Kir3.1/3.2 and Kir3.1/3.4 channels. Heterologous expression therefore supports the notion that Kir3 channels are the postsynaptic effectors of GABABRs. Our data further demonstrate that in principle either of the cloned receptors could mediate inhibitory postsynaptic potentials. We find that in the cerebellum hR1a and hR1b transcripts are largely confined to granule and Purkinje cells, respectively. This finding supports a selective association of hR1b, and not hR1a, with postsynaptic Kir3 channels. The mapping of the GABABR1 gene to human chromosome 6p21.3, in the vicinity of a susceptibility locus (EJM1) for idiopathic generalized epilepsies, identifies a candidate gene for inherited forms of epilepsy.
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Canales de Potasio/fisiología , Receptores de GABA-B/fisiología , Secuencia de Aminoácidos , Animales , Células CHO , Células COS , Cricetinae , Electrofisiología , Humanos , Activación del Canal Iónico , Datos de Secuencia Molecular , TransfecciónRESUMEN
B-type receptors for the neurotransmitter GABA (gamma-aminobutyric acid) inhibit neuronal activity through G-protein-coupled second-messenger systems, which regulate the release of neurotransmitters and the activity of ion channels and adenylyl cyclase. Physiological and biochemical studies show that there are differences in drug efficiencies at different GABA(B) receptors, so it is expected that GABA(B)-receptor (GABA(B)R) subtypes exist. Two GABA(B)-receptor splice variants have been cloned (GABA(B)R1a and GABA(B)R1b), but native GABA(B) receptors and recombinant receptors showed unexplained differences in agonist-binding potencies. Moreover, the activation of presumed effector ion channels in heterologous cells expressing the recombinant receptors proved difficult. Here we describe a new GABA(B) receptor subtype, GABA(B)R2, which does not bind available GABA(B) antagonists with measurable potency. GABA(B)R1a, GABA(B)R1b and GABA(B)R2 alone do not activate Kir3-type potassium channels efficiently, but co-expression of these receptors yields a robust coupling to activation of Kir3 channels. We provide evidence for the assembly of heteromeric GABA(B) receptors in vivo and show that GABA(B)R2 and GABA(B)R1a/b proteins immunoprecipitate and localize together at dendritic spines. The heteromeric receptor complexes exhibit a significant increase in agonist- and partial-agonist-binding potencies as compared with individual receptors and probably represent the predominant native GABA(B) receptor. Heteromeric assembly among G-protein-coupled receptors has not, to our knowledge, been described before.