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1.
Nanotechnology ; 35(5)2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37879325

RESUMO

Ternary GaAsSb nanowires (NW) are key materials for integrated high-speed photonic applications on silicon (Si), where homogeneous, high aspect-ratio dimensions and high-quality properties for controlled absorption, mode confinement and waveguiding are much desired. Here, we demonstrate a unique high-temperature (high-T >650 °C) molecular beam epitaxial (MBE) approach to realize self-catalyzed GaAsSb NWs site-selectively on Si with high aspect-ratio and non-tapered morphologies under antimony (Sb)-saturated conditions. While hitherto reported low-moderate temperature growth processes result in early growth termination and inhomogeneous morphologies, the non-tapered nature of NWs under high-T growth is independent of the supply rates of relevant growth species. Analysis of dedicated Ga-flux and growth time series, allows us to pinpoint the microscopic mechanisms responsible for the elimination of tapering, namely concurrent vapor-solid, step-flow growth along NW side-facets enabled by enhanced Ga diffusion under the high-T growth. Performing growth in an Sb-saturated regime, leads to high Sb-content in VLS-GaAsSb NW close to 30% that is independent of Ga-flux. This independence enables multi-step growth via sequentially increased Ga-flux to realize uniform and very long (>7µm) GaAsSb NWs. The excellent properties of these NWs are confirmed by a completely phase-pure, twin-free zincblende (ZB) crystal structure, a homogeneous Sb-content along the VLS-GaAsSb NW growth axis, along with remarkably narrow, single-peak low-temperature photoluminescence linewidth (<15 meV) at wavelengths of ∼1100-1200 nm.

2.
Sex Health ; 17(3): 279-287, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32571477

RESUMO

Background The kissing practices of heterosexual men are not well understood, despite the potential of kissing to be a significant risk factor for gonorrhoea transmission. This study aimed to explore kissing and sex practices among heterosexual men. METHODS: A cross-sectional survey among heterosexual men attending the Melbourne Sexual Health Centre in 2016-2017 was conducted. Men were asked to report their number of kissing-only (in the absence of sex), sex-only (in the absence of kissing) and kissing-with-sex partners in the last 3 months. The mean number of each partner type was calculated, and multivariable negative binomial regression was used to investigate associations between the number of different types of partners and demographic characteristics. RESULTS: Of the 2351 heterosexual men, men reported a mean of 2.98 kissing-only, 0.54 sex-only and 2.64 kissing-with-sex partners in the last 3 months. Younger men had a mean higher number of kissing-only partners than older men (4.52 partners among men aged ≤24 years compared with 1.75 partners among men ≥35 years, P < 0.001). Men born in Europe had the most kissing-only partners (mean: 5.16 partners) and men born in Asia had the fewest kissing-only partners (mean: 1.61 partners). Men recently arrived in Australia, including travellers from overseas, had significantly more kissing-only partners (adjusted incidence rate ratio (aIRR): 1.53; 95% CI: 1.31-1.80) than local men. CONCLUSIONS: This study provides novel data about kissing practices of heterosexual men. Studies assessing oropharyngeal gonorrhoea should include measurements of kissing until studies can clarify its contribution to transmission risk.


Assuntos
Heterossexualidade , Comportamento Sexual , Saúde Sexual , Adolescente , Adulto , Fatores Etários , Austrália/epidemiologia , Estudos Transversais , Etnicidade , Humanos , Masculino , Pessoa de Meia-Idade , Viagem
3.
Nanotechnology ; 30(49): 495703, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31469097

RESUMO

InGaAs nanowire (NW) arrays have emerged as important active materials in future photovoltaic and photodetector applications, due to their excellent electronic properties and tunable band gap. Here, we report a systematic investigation of the optical absorption characteristics of composition-tunable vertical InGaAs NW arrays. Using finite-difference time-domain simulations we first study the effect of variable composition (Ga-molar fraction) and NW array geometry (NW diameter, period, fill factor) on the optical generation rate. NWs with typical diameters in the range of ∼100-250 nm lead to generation rates higher than the equivalent bulk case for moderate fill factors (NW period of ∼0.3-0.8 µm), while slightly smaller fill factors and increased diameters are required to maintain high generation rates at increased Ga-molar fraction. The optical absorption was further measured using spectrally resolved ultraviolet-visible-near-infrared (UV-vis-NIR) spectroscopy on NW arrays transferred to transparent substrates. Interestingly, large variations in Ga-molar fraction (0 < x(Ga) < 0.5) have a negligible influence, while minute changes in NW diameter of less than ±20 nm affect the absorption spectra very strongly, leading to pronounced shifts in the peak absorption energies by more than ∼700 meV. These results clearly highlight the much larger sensitivity of the optical absorption behavior to geometric parameters rather than to variations in the electronic band gap of the underlying NW array.

4.
Nano Lett ; 18(11): 6812-6819, 2018 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-30153417

RESUMO

We report the observation of the generation and routing of single plasmons generated by localized excitons in a WSe2 monolayer flake exfoliated onto lithographically defined Au-plasmonic waveguides. Statistical analysis of the position of different quantum emitters shows that they are (3.3 ± 0.7) times more likely to form close to the edges of the plasmonic waveguides. By characterizing individual emitters, we confirm their single-photon character via the observation of antibunching in the signal ( g(2)(0) = 0.42) and demonstrate that specific emitters couple to modes of the proximal plasmonic waveguide. Time-resolved measurements performed on emitters close to and far away from the plasmonic nanostructures indicate that Purcell factors up to 15 ± 3 occur, depending on the precise location of the quantum emitter relative to the tightly confined plasmonic mode. Measurement of the point spread function of five quantum emitters relative to the waveguide with <50 nm precision is compared with numerical simulations to demonstrate the potential for greater increases in the coupling efficiency for ideally positioned emitters. The integration of such strain-induced quantum emitters with deterministic plasmonic routing is a step toward deep-subwavelength on-chip single quantum light sources.

5.
Nano Lett ; 18(10): 6292-6300, 2018 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-30185051

RESUMO

Semiconductor nanowire (NW) lasers are attractive as integrated on-chip coherent light sources with strong potential for applications in optical communication and sensing. Realizing lasers from individual bulk-type NWs with emission tunable from the near-infrared to the telecommunications spectral region is, however, challenging and requires low-dimensional active gain regions with an adjustable band gap and quantum confinement. Here, we demonstrate lasing from GaAs-(InGaAs/AlGaAs) core-shell NWs with multiple InGaAs quantum wells (QW) and lasing wavelengths tunable from ∼0.8 to ∼1.1 µm. Our investigation emphasizes particularly the critical interplay between QW design, growth kinetics, and the control of InGaAs composition in the active region needed for effective tuning of the lasing wavelength. A low shell growth temperature and GaAs interlayers at the QW/barrier interfaces enable In molar fractions up to ∼25% without plastic strain relaxation or alloy intermixing in the QWs. Correlated scanning transmission electron microscopy, atom probe tomography, and confocal PL spectroscopy analyses illustrate the high sensitivity of the optically pumped lasing characteristics on microscopic properties, providing useful guidelines for other III-V-based NW laser systems.

6.
Nano Lett ; 17(1): 392-398, 2017 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-27959565

RESUMO

We demonstrate pronounced electric-field-induced second-harmonic generation in naturally inversion symmetric 2H stacked bilayer MoS2 embedded into microcapacitor devices. By applying strong external electric field perturbations (|F| = ±2.6 MV cm-1) perpendicular to the basal plane of the crystal, we control the inversion symmetry breaking and, hereby, tune the nonlinear conversion efficiency. Strong tunability of the nonlinear response is observed throughout the energy range (Eω ∼ 1.25-1.47 eV) probed by measuring the second-harmonic response at E2ω, spectrally detuned from both the A- and B-exciton resonances. A 60-fold enhancement of the second-order nonlinear signal is obtained for emission at E2ω = 2.49 eV, energetically detuned by ΔE = E2ω - EC = -0.26 eV from the C-resonance (EC = 2.75 eV). The pronounced spectral dependence of the electric-field-induced second-harmonic generation signal reflects the bandstructure and wave function admixture and exhibits particularly strong tunability below the C-resonance, in good agreement with density functional theory calculations. Moreover, we show that the field-induced second-harmonic generation relies on the interlayer coupling in the bilayer. Our findings strongly suggest that the strong tunability of the electric-field-induced second-harmonic generation signal in bilayer transition metal dichalcogenides may find applications in miniaturized electrically switchable nonlinear devices.

7.
Lab Invest ; 97(3): 256-267, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28165468

RESUMO

Thy-1-negative lung fibroblasts are resistant to apoptosis. The mechanisms governing this process and its relevance to fibrotic remodeling remain poorly understood. By using either sorted or transfected lung fibroblasts, we found that Thy-1 expression is associated with downregulation of anti-apoptotic molecules Bcl-2 and Bcl-xL, as well as increased levels of cleaved caspase-9. Addition of rhFasL and staurosporine, well-known apoptosis inducers, caused significantly increased cleaved caspase-3, -8, and PARP in Thy-1-transfected cells. Furthermore, rhFasL induced Fas translocation into lipid rafts and its colocalization with Thy-1. These in vitro results indicate that Thy-1, in a manner dependent upon its glycophosphatidylinositol anchor and lipid raft localization, regulates apoptosis in lung fibroblasts via Fas-, Bcl-, and caspase-dependent pathways. In vivo, Thy-1 deficient (Thy1-/-) mice displayed persistence of myofibroblasts in the resolution phase of bleomycin-induced fibrosis, associated with accumulation of collagen and failure of lung fibrosis resolution. Apoptosis of myofibroblasts is decreased in Thy1-/- mice in the resolution phase. Collectively, these findings provide new evidence regarding the role and mechanisms of Thy-1 in initiating myofibroblast apoptosis that heralds the termination of the reparative response to bleomycin-induced lung injury. Understanding the mechanisms regulating fibroblast survival/apoptosis should lead to novel therapeutic interventions for lung fibrosis.


Assuntos
Apoptose/fisiologia , Fibroblastos/metabolismo , Lesão Pulmonar/metabolismo , Microdomínios da Membrana/metabolismo , Antígenos Thy-1/metabolismo , Receptor fas/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Bleomicina , Caspase 9/metabolismo , Linhagem Celular , Embrião de Mamíferos/citologia , Proteína Ligante Fas/farmacologia , Fibroblastos/efeitos dos fármacos , Immunoblotting , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/prevenção & controle , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia Confocal , Miofibroblastos/efeitos dos fármacos , Miofibroblastos/metabolismo , Ligação Proteica , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fibrose Pulmonar/genética , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/prevenção & controle , Ratos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Estaurosporina/farmacologia , Antígenos Thy-1/genética , Proteína bcl-X/metabolismo
8.
Nano Lett ; 16(3): 1554-9, 2016 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-26845085

RESUMO

We demonstrate electrical control of the A-exciton interband transition in mono- and few-layer MoS2 crystals embedded into photocapacitor devices via the DC Stark effect. Electric field-dependent low-temperature photoluminescence spectroscopy reveals a significant tuneability of the A-exciton transition energy up to ∼ 16 meV from which we extract the mean DC exciton polarizability ⟨ß̅N⟩ = (0.58 ± 0.25) × 10(-8) Dm V(-1). The exciton polarizability is shown to be layer-independent, indicating a strong localization of both electron and hole wave functions in each individual layer.

9.
Nano Lett ; 16(1): 152-6, 2016 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-26618638

RESUMO

Reliable technologies for the monolithic integration of lasers onto silicon represent the holy grail for chip-level optical interconnects. In this context, nanowires (NWs) fabricated using III-V semiconductors are of strong interest since they can be grown site-selectively on silicon using conventional epitaxial approaches. Their unique one-dimensional structure and high refractive index naturally facilitate low loss optical waveguiding and optical recirculation in the active NW-core region. However, lasing from NWs on silicon has not been achieved to date, due to the poor modal reflectivity at the NW-silicon interface. We demonstrate how, by inserting a tailored dielectric interlayer at the NW-Si interface, low-threshold single mode lasing can be achieved in vertical-cavity GaAs-AlGaAs core-shell NW lasers on silicon as measured at low temperature. By exploring the output characteristics along a detection direction parallel to the NW-axis, we measure very high spontaneous emission factors comparable to nanocavity lasers (ß = 0.2) and achieve ultralow threshold pump energies ≤11 pJ/pulse. Analysis of the input-output characteristics of the NW lasers and the power dependence of the lasing emission line width demonstrate the potential for high pulsation rates ≥250 GHz. Such highly efficient nanolasers grown monolithically on silicon are highly promising for the realization of chip-level optical interconnects.


Assuntos
Nanotecnologia/métodos , Nanofios/química , Semicondutores , Silício/química , Lasers , Luz
10.
Phys Rev Lett ; 117(2): 027402, 2016 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-27447523

RESUMO

We measure time correlators of a spin qubit in an optically active quantum dot beyond the second order. Such higher-order correlators are shown to be directly sensitive to pure quantum effects that cannot be explained within the classical framework. They allow direct determination of ensemble and quantum dephasing times, T_{2}^{*} and T_{2}, using only repeated projective measurements and without the need for coherent spin control. Our method enables studies of purely quantum behavior in solid state systems, including tests of the Leggett-Garg type of inequalities that rule out local hidden variable interpretation of the quantum-dot spin dynamics.

11.
Phys Rev Lett ; 116(7): 077401, 2016 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-26943557

RESUMO

We report Coulomb mediated hybridization of excitonic states in optically active InGaAs quantum dot molecules. By probing the optical response of an individual quantum dot molecule as a function of the static electric field applied along the molecular axis, we observe unexpected avoided level crossings that do not arise from the dominant single-particle tunnel coupling. We identify a new few-particle coupling mechanism stemming from Coulomb interactions between different neutral exciton states. Such Coulomb resonances hybridize the exciton wave function over four different electron and hole single-particle orbitals. Comparisons of experimental observations with microscopic eight-band k·p calculations taking into account a realistic quantum dot geometry show good agreement and reveal that the Coulomb resonances arise from broken symmetry in the artificial semiconductor molecule.

12.
Proc Natl Acad Sci U S A ; 110(5): E387-96, 2013 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-23319652

RESUMO

cAMP-dependent protein kinase (PKA) regulates a myriad of functions in the heart, including cardiac contractility, myocardial metabolism,and gene expression. However, a molecular integrator of the PKA response in the heart is unknown. Here, we show that the PKA adaptor A-kinase interacting protein 1 (AKIP1) is up-regulated in cardiac myocytes in response to oxidant stress. Mice with cardiac gene transfer of AKIP1 have enhanced protection to ischemic stress. We hypothesized that this adaptation to stress was mitochondrial dependent. AKIP1 interacted with the mitochondrial localized apoptosis inducing factor (AIF) under both normal and oxidant stress. When cardiac myocytes or whole hearts are exposed to oxidant and ischemic stress, levels of both AKIP1 and AIF were enhanced. AKIP1 is preferentially localized to interfibrillary mitochondria and up-regulated in this cardiac mitochondrial subpopulation on ischemic injury. Mitochondria isolated from AKIP1 gene transferred hearts showed increased mitochondrial localization of AKIP1, decreased reactive oxygen species generation, enhanced calcium tolerance, decreased mitochondrial cytochrome C release,and enhance phosphorylation of mitochondrial PKA substrates on ischemic stress. These observations highlight AKIP1 as a critical molecular regulator and a therapeutic control point for stress adaptation in the heart.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Coração/fisiologia , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Fator de Indução de Apoptose/metabolismo , Western Blotting , Linhagem Celular Tumoral , Células Cultivadas , Células HEK293 , Células HeLa , Coração/fisiopatologia , Humanos , Peróxido de Hidrogênio/farmacologia , Técnicas In Vitro , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Confocal , Mitocôndrias Cardíacas/metabolismo , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/citologia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/efeitos dos fármacos , Proteínas Nucleares/genética , Oxidantes/farmacologia , Ligação Proteica , Ratos , Ratos Sprague-Dawley
13.
Nano Lett ; 15(10): 6869-74, 2015 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-26356189

RESUMO

We investigate the ultrafast optoelectronic properties of single Al0.3Ga0.7As/GaAs core-shell nanowires. The nanowires contain GaAs-based quantum wells. For a resonant excitation of the quantum wells, we find a picosecond photocurrent which is consistent with an ultrafast lateral expansion of the photogenerated charge carriers. This Dember-effect does not occur for an excitation of the GaAs-based core of the nanowires. Instead, the core exhibits an ultrafast displacement current and a photothermoelectric current at the metal Schottky contacts. Our results uncover the optoelectronic dynamics in semiconductor core-shell nanowires comprising quantum wells, and they demonstrate the possibility to use the low-dimensional quantum well states therein for ultrafast photoswitches and photodetectors.

14.
Nano Lett ; 15(8): 5208-13, 2015 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-26102603

RESUMO

Quantum optical circuits can be used to generate, manipulate, and exploit nonclassical states of light to push semiconductor based photonic information technologies to the quantum limit. Here, we report the on-chip generation of quantum light from individual, resonantly excited self-assembled InGaAs quantum dots, efficient routing over length scales ≥1 mm via GaAs ridge waveguides, and in situ detection using evanescently coupled integrated NbN superconducting single photon detectors fabricated on the same chip. By temporally filtering the time-resolved luminescence signal stemming from single quantum dots we use the quantum optical circuit to perform time-resolved excitation spectroscopy on single dots and demonstrate resonance fluorescence with a line-width of 10 ± 1 µeV; key elements needed for the use of single photons in prototypical quantum photonic circuits.

15.
Nano Lett ; 15(5): 3295-302, 2015 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-25923841

RESUMO

Strong surface and impurity scattering in III-V semiconductor-based nanowires (NW) degrade the performance of electronic devices, requiring refined concepts for controlling charge carrier conductivity. Here, we demonstrate remote Si delta (δ)-doping of radial GaAs-AlGaAs core-shell NWs that unambiguously exhibit a strongly confined electron gas with enhanced low-temperature field-effect mobilities up to 5 × 10(3) cm(2) V(-1) s(-1). The spatial separation between the high-mobility free electron gas at the NW core-shell interface and the Si dopants in the shell is directly verified by atom probe tomographic (APT) analysis, band-profile calculations, and transport characterization in advanced field-effect transistor (FET) geometries, demonstrating powerful control over the free electron gas density and conductivity. Multigated NW-FETs allow us to spatially resolve channel width- and crystal phase-dependent variations in electron gas density and mobility along single NW-FETs. Notably, dc output and transfer characteristics of these n-type depletion mode NW-FETs reveal excellent drain current saturation and record low subthreshold slopes of 70 mV/dec at on/off ratios >10(4)-10(5) at room temperature.


Assuntos
Alumínio/química , Arsenicais/química , Gálio/química , Nanotecnologia , Nanofios/química , Elétrons , Semicondutores , Silício/química
16.
Anesthesiology ; 121(3): 538-48, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24821070

RESUMO

BACKGROUND: Caveolae are a nexus for protective signaling. Trafficking of caveolin to mitochondria is essential for adaptation to cellular stress though the trafficking mechanisms remain unknown. The authors hypothesized that G protein-coupled receptor/inhibitory G protein (Gi) activation leads to caveolin trafficking to mitochondria. METHODS: Mice were exposed to isoflurane or oxygen vehicle (30 min, ± 36 h pertussis toxin pretreatment, an irreversible Gi inhibitor). Caveolin trafficking, cardioprotective "survival kinase" signaling, mitochondrial function, and ultrastructure were assessed. RESULTS: Isoflurane increased cardiac caveolae (n = 8 per group; data presented as mean ± SD for Ctrl versus isoflurane; [caveolin-1: 1.78 ± 0.12 vs. 3.53 ± 0.77; P < 0.05]; [caveolin-3: 1.68 ± 0.29 vs. 2.67 ± 0.46; P < 0.05]) and mitochondrial caveolin levels (n = 16 per group; [caveolin-1: 0.87 ± 0.18 vs. 1.89 ± .19; P < 0.05]; [caveolin-3: 1.10 ± 0.29 vs. 2.26 ± 0.28; P < 0.05]), and caveolin-enriched mitochondria exhibited improved respiratory function (n = 4 per group; [state 3/complex I: 10.67 ± 1.54 vs. 37.6 ± 7.34; P < 0.05]; [state 3/complex II: 37.19 ± 4.61 vs. 71.48 ± 15.28; P < 0.05]). Isoflurane increased phosphorylation of survival kinases (n = 8 per group; [protein kinase B: 0.63 ± 0.20 vs. 1.47 ± 0.18; P < 0.05]; [glycogen synthase kinase 3ß: 1.23 ± 0.20 vs. 2.35 ± 0.20; P < 0.05]). The beneficial effects were blocked by pertussis toxin. CONCLUSIONS: Gi proteins are involved in trafficking caveolin to mitochondria to enhance stress resistance. Agents that target Gi activation and caveolin trafficking may be viable cardioprotective agents.


Assuntos
Caveolinas/metabolismo , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/fisiologia , Mitocôndrias/metabolismo , Animais , Cavéolas/efeitos dos fármacos , Cavéolas/fisiologia , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Isoflurano/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/ultraestrutura , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Toxina Pertussis/farmacologia , Transporte Proteico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/fisiologia
17.
Nanotechnology ; 25(7): 075203, 2014 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-24452056

RESUMO

We present an optical investigation of surface plasmon polaritons propagating along nanoscale Au-wires, lithographically defined on GaAs substrates. A two-axis confocal microscope was used to perform spatially and polarization resolved measurements in order to confirm the guiding of surface plasmon polaritons over lengths ranging from 5 to 20 µm along nanowires with a lateral dimension of only ≈ 100 nm. Finite difference time domain simulations are used to corroborate our experimental observations, and highlight the potential to couple proximal quantum emitters to propagating plasmon modes in such extreme subwavelength devices. Our findings are of strong relevance for the development of semiconductor based integrated plasmonic and active quantum plasmonic nanosystems that merge quantum emitters with nanoscale plasmonic elements.

18.
Mol Cell Neurosci ; 56: 283-97, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23851187

RESUMO

Microglia are ramified cells that serve as central nervous system (CNS) guardians, capable of proliferation, migration, and generation of inflammatory cytokines. In non-pathological states, these cells exhibit ramified morphology with processes intermingling with neurons and astrocytes. Under pathological conditions, they acquire a rounded amoeboid morphology and proliferative and migratory capabilities. Such morphological changes require cytoskeleton rearrangements. The molecular control points for polymerization states of microtubules and actin are still under investigation. Caveolins (Cavs), membrane/lipid raft proteins, are expressed in inflammatory cells, yet the role of caveolin isoforms in microglia physiology is debatable. We propose that caveolins provide a necessary control point in the regulation of cytoskeletal dynamics, and thus investigated a role for caveolins in microglia biology. We detected mRNA and protein for both Cav-1 and Cav-3. Cav-1 protein was significantly less and localized to plasmalemma (PM) and cytoplasmic vesicles (CVs) in the microglial inactive state, while the active (amoeboid-shaped) microglia exhibited increased Cav-1 expression. In contrast, Cav-3 was highly expressed in the inactive state and localized with cellular processes and perinuclear regions and was detected in active amoeboid microglia. Pharmacological manipulation of the cytoskeleton in the active or non-active state altered caveolin expression. Additionally, increased Cav-1 expression also increased mitochondrial respiration, suggesting possible regulatory roles in cell metabolism necessary to facilitate the morphological changes. The present findings strongly suggest that regulation of microglial morphology and activity are in part due to caveolin isoforms, providing promising novel therapeutic targets in CNS injury or disease.


Assuntos
Caveolina 1/metabolismo , Caveolina 3/metabolismo , Microglia/metabolismo , Animais , Caveolina 1/genética , Caveolina 3/genética , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Respiração Celular , Células Cultivadas , Vesículas Citoplasmáticas/metabolismo , Citoesqueleto/metabolismo , Camundongos , Microglia/ultraestrutura , Mitocôndrias/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
19.
FASEB J ; 26(11): 4637-49, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22859372

RESUMO

We show here that the apposition of plasma membrane caveolae and mitochondria (first noted in electron micrographs >50 yr ago) and caveolae-mitochondria interaction regulates adaptation to cellular stress by modulating the structure and function of mitochondria. In C57Bl/6 mice engineered to overexpress caveolin specifically in cardiac myocytes (Cav-3 OE), localization of caveolin to mitochondria increases membrane rigidity (4.2%; P<0.05), tolerance to calcium, and respiratory function (72% increase in state 3 and 23% increase in complex IV activity; P<0.05), while reducing stress-induced generation of reactive oxygen species (by 20% in cellular superoxide and 41 and 28% in mitochondrial superoxide under states 4 and 3, respectively; P<0.05) in Cav-3 OE vs. TGneg. By contrast, mitochondrial function is abnormal in caveolin-knockout mice and Caenorhabditis elegans with null mutations in caveolin (60% increase free radical in Cav-2 C. elegans mutants; P<0.05). In human colon cancer cells, mitochondria with increased caveolin have a 30% decrease in apoptotic stress (P<0.05), but cells with disrupted mitochondria-caveolin interaction have a 30% increase in stress response (P<0.05). Targeted gene transfer of caveolin to mitochondria in C57Bl/6 mice increases cardiac mitochondria tolerance to calcium, enhances respiratory function (increases of 90% state 4, 220% state 3, 88% complex IV activity; P<0.05), and decreases (by 33%) cardiac damage (P<0.05). Physical association and apparently the transfer of caveolin between caveolae and mitochondria is thus a conserved cellular response that confers protection from cellular damage in a variety of tissues and settings.


Assuntos
Caveolinas/metabolismo , Mitocôndrias Cardíacas/metabolismo , Miócitos Cardíacos/metabolismo , Estresse Fisiológico/fisiologia , Adaptação Fisiológica , Animais , Cálcio/metabolismo , Cálcio/toxicidade , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Mitocôndrias Cardíacas/efeitos dos fármacos , Transporte Proteico , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/análise
20.
J Biol Chem ; 286(38): 33310-21, 2011 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-21799010

RESUMO

Decreased expression of prosurvival and progrowth-stimulatory pathways, in addition to an environment that inhibits neuronal growth, contribute to the limited regenerative capacity in the central nervous system following injury or neurodegeneration. Membrane/lipid rafts, plasmalemmal microdomains enriched in cholesterol, sphingolipids, and the protein caveolin (Cav) are essential for synaptic development/stabilization and neuronal signaling. Cav-1 concentrates glutamate and neurotrophin receptors and prosurvival kinases and regulates cAMP formation. Here, we show that primary neurons that express a synapsin-driven Cav-1 vector (SynCav1) have increased raft formation, neurotransmitter and neurotrophin receptor expression, NMDA- and BDNF-mediated prosurvival kinase activation, agonist-stimulated cAMP formation, and dendritic growth. Moreover, expression of SynCav1 in Cav-1 KO neurons restores NMDA- and BDNF-mediated signaling and enhances dendritic growth. The enhanced dendritic growth occurred even in the presence of inhibitory cytokines (TNFα, IL-1ß) and myelin-associated glycoproteins (MAG, Nogo). Targeting of Cav-1 to neurons thus enhances prosurvival and progrowth signaling and may be a novel means to repair the injured and neurodegenerative brain.


Assuntos
Caveolina 1/metabolismo , Neurônios/metabolismo , Transdução de Sinais , Animais , Axônios/efeitos dos fármacos , Axônios/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Colesterol/metabolismo , Citocinas/farmacologia , Dendritos/efeitos dos fármacos , Dendritos/metabolismo , Microdomínios da Membrana/efeitos dos fármacos , Microdomínios da Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Glicoproteína Associada a Mielina/farmacologia , Neurônios/citologia , Neurônios/efeitos dos fármacos , Especificidade de Órgãos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Sinapsinas/metabolismo
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