RESUMO
Complex oxide heterointerfaces contain a rich playground of novel physical properties and functionalities, which give rise to emerging technologies. Among designing and controlling the functional properties of complex oxide film heterostructures, vertically aligned nanostructure (VAN) films using a self-assembling bottom-up deposition method presents great promise in terms of structural flexibility and property tunability. Here, the bottom-up self-assembly is extended to a new approach using a mixture containing a 2Dlayer-by-layer film growth, followed by a 3D VAN film growth. In this work, the two-phase nanocomposite thin films are based on LaAlO3 :LaBO3 , grown on a lattice-mismatched SrTiO3001 (001) single crystal. The 2D-to-3D transient structural assembly is primarily controlled by the composition ratio, leading to the coexistence of multiple interfacial properties, 2D electron gas, and magnetic anisotropy. This approach provides multidimensional film heterostructures which enrich the emergent phenomena for multifunctional applications.
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Precise intracellular calcium signaling is crucial to numerous cellular functions. In non-excitable cells, store-operated calcium entry (SOCE) is a key step in the generation of intracellular calcium signals. Tight regulation of SOCE is important, and dysregulation is involved in several pathophysiological cellular malfunctions. The current underlying SOCE, calcium release-activated calcium current (ICRAC), was first discovered almost three decades ago. Since its discovery, the molecular components of ICRAC, Orai1 and stromal interaction molecule 1 (STIM1), have been extensively investigated. Several regulatory mechanisms and proteins contribute to alterations in SOCE and cellular malfunctions in cancer, immune and neurodegenerative diseases, inflammation, and neuronal disorders. This review summarizes these regulatory mechanisms, including glycosylation, pH sensing, and the regulatory proteins golli, α-SNAP, SARAF, ORMDL3, CRACR2A, and TRPM4 channels.
Assuntos
Cálcio/metabolismo , Inflamação/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Doenças Neurodegenerativas/metabolismo , Proteína ORAI1/metabolismo , Molécula 1 de Interação Estromal/metabolismo , Animais , Sinalização do Cálcio , Humanos , Inflamação/patologia , Neoplasias/patologia , Doenças Neurodegenerativas/patologiaRESUMO
A surge in interest of oxide-based materials is testimony for their potential utility in a wide array of device applications and offers a fascinating landscape for tuning the functional properties through a variety of physical and chemical parameters. In particular, selective electronic/defect doping has been demonstrated to be vital in tailoring novel functionalities, not existing in the bulk host oxides. Here, an extraordinary interstitial doping effect is demonstrated centered around a light element, boron (B). The host matrix is a novel composite system, made from discrete bulk LaAlO3 :LaBO3 compounds. The findings show a spontaneous ordering of the interstitial B cations within the host LaAlO3 lattices, and subsequent spin-polarized charge injection into the neighboring cations. This leads to a series of remarkable cation-dominated electrical switching and high-temperature ferromagnetism. Hence, the induced interstitial doping serves to transform a nonmagnetic insulating bulk oxide into a ferromagnetic ionic-electronic conductor. This unique interstitial B doping effect upon its control is proposed to be as a general route for extracting/modifying multifunctional properties in bulk oxides utilized in energy and spin-based applications.
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Store-operated Ca(2+) entry mediated by STIM1-gated Orai1 channels is essential to activate immune cells and its inhibition or gain-of-function can lead to immune dysfunction and other pathologies. Reactive oxygen species interacting with cysteine residues can alter protein function. Pretreatment of the Ca(2+) selective Orai1 with the oxidant H2O2 reduces ICRAC with C195, distant to the pore, being its major redox sensor. However, the mechanism of inhibition remained elusive. Here we combine experimental and theoretical approaches and show that oxidation of Orai1 leads to reduced subunit interaction, slows diffusion and that either oxidized C195 or its oxidomimetic mutation C195D located at the exit of transmembrane helix 3 virtually eliminates channel activation by intramolecular interaction with S239 of transmembrane helix 4, thereby locking the channel in a closed conformation. Our results demonstrate a novel mechanistic model for ROS-mediated inhibition of Orai1 and identify a candidate residue for pharmaceutical intervention.
Assuntos
Proteína ORAI1/metabolismo , Compostos de Sulfidrila/metabolismo , Células HEK293 , Humanos , Mesilatos/metabolismo , Mutação/genética , Proteínas de Neoplasias/metabolismo , Proteína ORAI1/antagonistas & inibidores , Oxirredução , Ligação Proteica , Subunidades Proteicas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Serina/metabolismo , Molécula 1 de Interação Estromal/metabolismoRESUMO
N-glycosylation of cell surface proteins affects protein function, stability, and interaction with other proteins. Orai channels, which mediate store-operated Ca(2+) entry (SOCE), are composed of N-glycosylated subunits. Upon activation by Ca(2+) sensor proteins (stromal interaction molecules STIM1 or STIM2) in the endoplasmic reticulum, Orai Ca(2+) channels in the plasma membrane mediate Ca(2+) influx. Lectins are carbohydrate-binding proteins, and Siglecs are a family of sialic acid-binding lectins with immunoglobulin-like repeats. Using Western blot analysis and lectin-binding assays from various primary human cells and cancer cell lines, we found that glycosylation of Orai1 is cell type-specific. Ca(2+) imaging experiments and patch-clamp experiments revealed that mutation of the only glycosylation site of Orai1 (Orai1N223A) enhanced SOCE in Jurkat T cells. Knockdown of the sialyltransferase ST6GAL1 reduced α-2,6-linked sialic acids in the glycan structure of Orai1 and was associated with increased Ca(2+) entry in Jurkat T cells. In human mast cells, inhibition of sialyl sulfation altered the N-glycan of Orai1 (and other proteins) and increased SOCE. These data suggest that cell type-specific glycosylation influences the interaction of Orai1 with specific lectins, such as Siglecs, which then attenuates SOCE. In summary, the glycosylation state of Orai1 influences SOCE-mediated Ca(2+) signaling and, thus, may contribute to pathophysiological Ca(2+) signaling observed in immune disease and cancer.
Assuntos
Sinalização do Cálcio/fisiologia , Cálcio/metabolismo , Proteína ORAI1/metabolismo , Antígenos CD/genética , Antígenos CD/metabolismo , Retículo Endoplasmático/genética , Retículo Endoplasmático/metabolismo , Técnicas de Silenciamento de Genes , Glicosilação , Humanos , Células Jurkat , Proteína ORAI1/genética , Sialiltransferases/genética , Sialiltransferases/metabolismoRESUMO
In prostate cancer, reactive oxygen species (ROS) are elevated and Ca(2+) signaling is impaired. Thus, several novel therapeutic strategies have been developed to target altered ROS and Ca(2+) signaling pathways in prostate cancer. Here, we investigate alterations of intracellular Ca(2+) and inhibition of cell viability caused by ROS in primary human prostate epithelial cells (hPECs) from healthy tissue and prostate cancer cell lines (LNCaP, DU145, and PC3). In hPECs, LNCaP and DU145 H2O2 induces an initial Ca(2+) increase, which in prostate cancer cells is blocked at high concentrations of H2O2. Upon depletion of intracellular Ca(2+) stores, store-operated Ca(2+) entry (SOCE) is activated. SOCE channels can be formed by hexameric Orai1 channels; however, Orai1 can form heteromultimers with its homolog, Orai3. Since the redox sensor of Orai1 (Cys-195) is absent in Orai3, the Orai1/Orai3 ratio in T cells determines the redox sensitivity of SOCE and cell viability. In prostate cancer cells, SOCE is blocked at lower concentrations of H2O2 compared with hPECs. An analysis of data from hPECs, LNCaP, DU145, and PC3, as well as previously published data from naive and effector TH cells, demonstrates a strong correlation between the Orai1/Orai3 ratio and the SOCE redox sensitivity and cell viability. Therefore, our data support the concept that store-operated Ca(2+) channels in hPECs and prostate cancer cells are heteromeric Orai1/Orai3 channels with an increased Orai1/Orai3 ratio in cells derived from prostate cancer tumors. In addition, ROS-induced alterations in Ca(2+) signaling in prostate cancer cells may contribute to the higher sensitivity of these cells to ROS.
Assuntos
Sinalização do Cálcio/fisiologia , Células Epiteliais/fisiologia , Peróxido de Hidrogênio/metabolismo , Próstata/fisiologia , Neoplasias da Próstata/fisiopatologia , Cálcio/metabolismo , Canais de Cálcio/genética , Canais de Cálcio/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/fisiologia , Técnicas de Silenciamento de Genes , Humanos , Peróxido de Hidrogênio/toxicidade , Espaço Intracelular/metabolismo , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteína ORAI1 , Oxirredução , Técnicas de Patch-Clamp , Interferência de RNA , Espécies Reativas de Oxigênio/metabolismo , Molécula 1 de Interação EstromalRESUMO
180° domain wall motion in a tetragonal ferroelectric oxide is accelerated by an order of magnitude using in situ strain in a force microscope. Single-domain PbZr0.2 Ti0.8 O3 films on piezoelectric (001)-oriented 0.72PbMg1/3 Nb2/3 O3 -0.28PbTiO3 substrates allow for direct investigation of strain-dependent domain dynamics. The strain effect depends on the sign of applied field through strain-dependent electrode built-in potentials and a suggested charging of tilted walls.
RESUMO
A drop of endoplasmic reticulum Ca(2+) concentration triggers its Ca(2+) ssensor protein stromal interaction molecule 1 (STIM1) to oligomerize and accumulate within endoplasmic reticulum-plasma membrane junctions where it activates Orai1 channels, providing store-operated Ca(2+) entry. To elucidate the functional significance of N-glycosylation sites of STIM1, we created different mutations of asparagine-131 and asparagine-171. STIM1 NN/DQ resulted in a strong gain of function. Patch clamp, Total Internal Reflection Fluorescent (TIRF) microscopy, and fluorescence recovery after photobleaching (FRAP) analyses revealed that expression of STIM1 DQ mutants increases the number of active Orai1 channels and the rate of STIM1 translocation to endoplasmic reticulum-plasma membrane junctions with a decrease in current latency. Surprisingly, co-expression of STIM1 DQ decreased Orai1 protein, altering the STIM1:Orai1 stoichiometry. We describe a novel mathematical tool to delineate the effects of altered STIM1 or Orai1 diffusion parameters from stoichiometrical changes. The mutant uncovers a novel mechanism whereby "superactive" STIM1 DQ leads to altered oligomerization rate constants and to degradation of Orai1 with a change in stoichiometry of activator (STIM1) to effector (Orai1) ratio leading to altered Ca(2+) homeostasis.
Assuntos
Canais de Cálcio/genética , Cálcio/metabolismo , Membrana Celular/metabolismo , Retículo Endoplasmático/metabolismo , Proteínas de Membrana/genética , Proteínas de Neoplasias/genética , Canais de Cálcio/química , Canais de Cálcio/metabolismo , Recuperação de Fluorescência Após Fotodegradação , Expressão Gênica , Glicosilação , Células HEK293 , Humanos , Transporte de Íons , Células Jurkat , Cinética , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Modelos Químicos , Mutação , Proteínas de Neoplasias/química , Proteínas de Neoplasias/metabolismo , Proteína ORAI1 , Técnicas de Patch-Clamp , Multimerização Proteica , Transporte Proteico , Molécula 1 de Interação Estromal , TransfecçãoRESUMO
Three-dimensional micro-objects are fabricated by the controlled release of inherently strained SrRuO3/Pr0.7Ca0.3MnO3/SrRuO3 nanometer-sized trilayers from SrTiO3(001) substrates. Freestanding cantilevers and rolled-up microtubes with a diameter of 6 to 8 µm are demonstrated. The etching behavior of the SrRuO3 film is investigated, and a selectivity of 1:9,100 with respect to the SrTiO3 substrate is found. The initial and final strain states of the rolled-up oxide layers are studied by X-ray diffraction on an ensemble of tubes. Relaxation of the sandwiched Pr0.7Ca0.3MnO3 layer towards its bulk lattice parameter is observed as the major driving force for the roll-up of the trilayers. Finally, µ-diffraction experiments reveal that a single object can represent the ensemble proving a good homogeneity of the rolled-up tubes.PACS: 81.07.-b; 68.60.-p; 68.37.Lp; 81.16.Dn.
RESUMO
Tunable biaxial stresses, both tensile and compressive, are applied to a single layer graphene by utilizing piezoelectric actuators. The Gruneisen parameters for the phonons responsible for the D, G, 2D and 2D' peaks are studied. The results show that the D peak is composed of two peaks, unambiguously revealing that the 2D peak frequency (omega(2D)) is not exactly twice that of the D peak (omega(D)). This finding is confirmed by varying the biaxial strain of the graphene, from which we observe that the shift of omega(2D)/2 and omega(D) are different. The employed technique allows a detailed study of the interplay between the graphene geometrical structures and its electronic properties.
RESUMO
This article presents a (scanning) transmission electron microscopy (TEM) study of Mn valency and its structural origin at La 0.7 Sr 0.3 MnO 3/SrTiO3(0 0 1) thin film interfaces. Mn valency deviations can lead to a breakdown of ferromagnetic order and thus lower the tunneling magnetoresistance of tunnel junctions. Here, at the interface, a Mn valency reduction of 0.16 +/- 0.10 compared to the film interior and an additional feature at the low energy-loss flank of the Mn-L3 line have been observed. The latter may be attributed to an elongation of the (0 0 1) plane spacing at the interface detected by geometrical phase analysis of high-resolution images. Regarding the interface geometry, high-resolution high-angle annular dark-field scanning TEM images reveal an atomically sharp interface in some regions whereas the transition appears broadened in others. This can be explained by the presence of steps. The performed measurements indicate that, among the various structure-related influences on the valency, the atomic layer termination and the local oxygen content are most important.
RESUMO
Arrays of GaAs microring optical resonators with embedded InGaAs quantum dots (QDs) are placed on top of Pb(Mg(1/3)Nb(2/3))O(3)-PbTiO(3) piezoelectric actuators, which allow the microcavities to be reversibly "stretched" or "squeezed" by applying relatively large biaxial stresses at low temperatures. The emission energy of both QDs and optical modes red- or blue- shift depending on the strain sign, with the QD emission shifting more rapidly than the optical mode with applied strain. The QD energy shifts are used to estimate the strain in the structures based on linear deformation potential theory and the finite element method. The shift of the modes is attributed to both the physical deformation and the change in refractive index due to the photoelastic effect. Remarkably, excitonic emissions from different QDs are observed to shift at different rates, implying that this technique can be used to bring spatially separated excitons into resonance.