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1.
Artigo em Inglês | MEDLINE | ID: mdl-38607712

RESUMO

Generating realistic 3D human motion has been a fundamental goal of the game/animation industry. This work presents a novel transition generation technique that can bridge the actions of people in the foreground by generating 3D poses and shapes in-between photos, allowing 3D animators/novice users to easily create/edit 3D motions. To achieve this, we propose an adaptive motion network (ADAM-Net) that effectively learns human motion from masked action sequences to generate kinematically compliant 3D poses and shapes in-between given temporally-sparse photos. Three core learning designs underpin ADAM-Net. First, we introduce a random masking process that randomly masks images from an action sequence and fills masked regions in latent space by interpolation of unmasked images to simulate various transitions under given temporally-sparse photos. Second, we propose a long-range adaptive motion (L-ADAM) attention module that leverages visual cues observed from human motion to adaptively recalibrate the range that needs attention in a sequence, along with a multi-head cross-attention. Third, we develop a short-range adaptive motion (S-ADAM) attention module that weightedly selects and integrates adjacent feature representations at different levels to strengthen temporal correlation. By coupling these designs, the results demonstrate that ADAM-Net excels not only in generating 3D poses and shapes in-between photos, but also in classic 3D human pose and shape estimation.

2.
Anal Methods ; 15(35): 4533-4540, 2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37641926

RESUMO

Surface-enhanced Raman scattering (SERS) has been widely used as a sensitive molecular spectroscopy technology in food safety detection. Precise morphology control of plasmonic nanoparticles for high sensitivity and high uniformity SERS substrates remains challenging. Herein, silver decahedral nanoparticles (AgDeNPs) with uniform and adjustable sizes were synthesized by a photochemical seed-mediated method and utilized as SERS substrates for pesticide residue detection. The SERS sensitivity was demonstrated by using 4-mercaptobenzoic acid (4-MBA) as a typical model molecule, and the limit of detection (LOD) reached 1.0 × 10-13 M. The pesticide residue detection of thiram in aqueous solution and on fruit peels was successfully realized; the LODs were 1.0 × 10-11 M and 0.96 ng cm-2, respectively, and SERS repeatability was also proved. Overall, size-tunable AgDeNPs show attractive SERS performances and are expected to hold potential application in sensitive food and environmental safety detection.

3.
Artigo em Inglês | MEDLINE | ID: mdl-36012030

RESUMO

University library spaces play an important role in the learning experience of students. However, the traditional designs for these learning spaces no longer meet the needs of users, and researchers have been turning their attention to university library space renovation. By combing existing theories and practices, this study determined a framework of six university library space renovation design principles and subsequently conducted a survey to examine university library space user learning experience in two university libraries in Wuhan, China. Data analysis was conducted using SPSS. From the questionnaire-based survey results, this study determined seven design elements that affect the learning experience of university library users. The results of binary logistic regression showed that two elements, indoor physical space comfort and indoor acoustic environment comfort, have positive effects on the frequency and length of visits to the library. Key spatial elements that can promote library space users' learning experience were also identified, thus providing data that can reliably inform future design strategies for the space renovation of university libraries.


Assuntos
Arquitetura de Instituições de Saúde , Bibliotecas Médicas , China , Humanos , Estudantes , Universidades
4.
Food Res Int ; 149: 110667, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34600669

RESUMO

Sichuan industrial paocai and traditional home-made paocai have different aroma profiles due to different manufacturing techniques, but detailed information about the aroma profiles and aroma-producing microorganism of Sichuan industrial paocai remain largely elusive. For this reason, we established and validated an external standard method of headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) combined with gas chromatography-olfactometry (GC-O) for identification and accurate quantitation of aroma-active compounds in Sichuan industrial paocai. This method was combined with 16S rRNA amplicon sequencing to comprehensively analyze the aroma and bacteria profiles of Sichuan industrial paocai. A total of 121 volatile compounds were identified, among which 36 odorants were identified as aroma-active compounds with aroma intensities (AIs) ranging from 0.67 to 5.00 by GC-O. The types of aroma-active compounds in Sichuan industrial paocai were variety-specific to some extent, but the aroma-active compounds shared by different varieties of Sichuan industrial paocai (i.e., skeleton aroma-active compounds) were phenylethyl alcohol, acetic acid, butanoic acid, 2-methylbutanoic acid, ethyl hexanoate, 4-ethylphenol and 4-ethylguaiacol. Moreover, 17 key aroma-active compounds of AI > 1 in radish paocai were quantitated by external standard method, and their odor activity values (OAVs) were calculated based on the odor thresholds. Further, 12 aroma-active compounds with OAV ≥ 1 in one of the radish paocai were selected to construct the recombination model, which revealed good agreement with the original sample. Furthermore, Lactobacillus, Pediococcus, Pseudomonas and Sphingomonas were the dominant bacteria in Sichuan industrial paocai. Correlation analysis between 16 dominant bacteria and 36 aroma-active compounds showed that Pediococcus, Arcobacter and Lactobacillus could be the core aroma-producing bacteria of Sichuan industrial paocai.


Assuntos
Odorantes , Compostos Orgânicos Voláteis , Bactérias/genética , Cromatografia Gasosa-Espectrometria de Massas , Odorantes/análise , RNA Ribossômico 16S/genética , Microextração em Fase Sólida , Compostos Orgânicos Voláteis/análise
5.
Chem Commun (Camb) ; 57(60): 7390-7393, 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34223840

RESUMO

Remarkable chiral amplification in plasmon-coupled circular dichroism spectroscopy (CD) is demonstrated by using discrete Ag nanorods as amplifiers. An unprecedented CD enhancement factor of over 3000 times is achieved without resonant or near-resonant exciton-plasmon couplings.

6.
ACS Appl Mater Interfaces ; 12(5): 6362-6370, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31913593

RESUMO

Conductive supports could improve the electrical conductivity of the electrode in lithium-sulfur (Li-S) batteries but suffer from the shuttle effect originated from the polysulfide dissolution, while the hydrophilic metal oxides could avoid the shuttle effect but with poor conductivity. Herein, a facile approach was developed to fabricate hierarchically porous tin oxide (SnO2) nanoparticle-anchored tubular polypyrrole (T-PPy) as a sulfur host, in order to integrate the advantages of conductive supports and metal oxides but overcome their shortcomings. In the unique structure, the T-PPy nanotubes acted as a conductive network to not only improve the electrical conductivity of cathodes but also accommodate the volume expansion of the sulfur cathode during cycling as well as relatively confine the polysulfide diffusion, while the SnO2 nanoparticles served as a high-efficient polysulfide trap to mitigate the shuttle effect due to the chemical bond between SnO2 and polysulfides. Moreover, the hierarchically porous structure and therefore large surface area of the proposed S/(T-PPy)@SnO2 cathode were favorable for the accommodation of sulfur and lithium sulfides. Consequently, S/(T-PPy)@SnO2 with 64.7% sulfur mass content exhibited excellent cyclic stability with a decay rate of only 0.05% per cycle along with 500 cycles at 1 C, rate capability of 383.7 mA h/g at 5 C, and Coulombic efficiency above 90%, outstanding among most of the reported PPy-based sulfur cathodes and PPy-based ternary sulfur cathodes.

7.
Nanoscale ; 11(20): 10097-10105, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31089610

RESUMO

Rechargeable lithium-sulfur batteries have emerged as a viable technology for next generation electrochemical energy storage, and the sulfur cathode plays a critical role in determining the device performance. In this study, we prepared functional composites based on polypyrrole-coated MnO2 nanotubes as a highly efficient sulfur host (sulfur mass loading 63.5%). The hollow interior of the MnO2 nanotubes not only allowed for accommodation of volumetric changes of sulfur particles during the cycling process, but also confined the diffusion of lithium polysulfides by physical restriction and chemical adsorption, which minimized the loss of polysulfide species. In addition, the polypyrrole outer layer effectively enhanced the electrical conductivity of the cathode to facilitate ion and electron transport. The as-prepared MnO2-PPy-S composite delivered an initial specific capacity of 1469 mA h g-1 and maintained an extremely stable cycling performance, with a small capacity decay of merely 0.07% per cycle at 0.2C within 500 cycles, a high average coulombic efficiency of 95.7% and an excellent rate capability at 470 mA h g-1 at the current density of 3C.

8.
Nanoscale ; 10(27): 13037-13044, 2018 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-29952387

RESUMO

Well-defined core-shell structured coaxial sulfur/polypyrrole tubular nanocomposites, polypyrrole nanotubes wrapped by uniform rough sulfur layers, were fabricated as Li-S battery cathodes via a facile one-pot method. In the designed structure, the polypyrrole backbone can facilitate the charge transport and also restrain the soluble polysulfide diffusion, while the active sulfur layer can efficiently react with Li+ assisted by the PPy nanotubes, and the lithium polysulfides can be massively trapped by the PPy nanotubes during charge-discharge processes. The as-prepared coaxial sulfur/polypyrrole tubular nanocomposites with a sulfur loading of 53.3% exhibited a high initial discharge specific capacity of 1117 mA h g-1 with a remarkable cycling stability, retaining 692 mA h g-1 and 525 mA h g-1 after 200 cycles at a current density of 0.2C and 1C, respectively. Moreover, they expressed an excellent rate capability performance, maintaining 470 mA h g-1 at a high current density of 2C.

9.
J Colloid Interface Sci ; 518: 57-68, 2018 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-29438865

RESUMO

Hierarchical porous nickel based metal-organic framework (Ni-MOF) constructed with nanosheets is fabricated by a facile hydrothermal process with the existence of trimesic acid and nickel ions. Various structures of Ni-MOFs can be obtained through adjusting the molar ratio of trimesic acid and nickel ion, the obtained hierarchical porous Ni-MOF exhibits optimal porous structure, which also possesses largest specific surface area. The hierarchical porous structure constructed with nanosheets can supply more active sites for electrochemical reactions to realize the excellent electrochemical properties, thus the hierarchical porous Ni-MOF reveals an outstanding specific capacitance of 1057 F/g at current density of 1 A/g, and delivers high specific capacitance of 649 F/g at current density of 30 A/g, indicating that it exhibits good rate capability of 63.4% even up to 30 A/g. The hierarchical porous Ni-MOF keeps 70% of its original value up to 2 500 charge-discharge cycles at the current density of 10 A/g. Furthermore, asymmetric supercapacitors (ASCs) were assembled based on hierarchical porous Ni-MOF and activated carbon (AC), the ASCs reveal specific capacitance of 87 F/g at current density of 0.5 A/g, and exhibit high energy density of 21.05 Wh/kg and power density of 6.03 kW/kg. Additionally, the tandem ASCs can light up a red LED. The hierarchical porous Ni-MOF exhibits promising applications in high performance supercapacitors.

10.
J Colloid Interface Sci ; 513: 295-303, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29156237

RESUMO

Polyaniline coated reduced graphene oxide/carbon nanotube composite fibers ((RGO/CNTs)@PANI, RCP) with skeleton/skin structure are designed as fiber-shaped electrodes for high performance all-solid-state symmetric supercapacitor. The one-dimensional reduced graphene oxide/carbon nanotube composite fibers (RGO/CNTs, RC) are prepared via a simple in-situ reduction of graphene oxide in presence of carbon nanotubes in quartz glass pipes, which exhibit excellent mechanical performance of >193.4 MPa of tensile strength. Then polyaniline is coated onto the RC fibers by electrodepositing technique. The electrochemical properties of the RCP fiber-shaped electrodes are optimized by adjusting the feeding ratio of carbon nanotubes. The optimized one exhibits good electrochemical characteristic such as highest volumetric specific capacitance of 193.1 F cm-3 at 1 A cm-3, as well as excellent cyclic retention of 92.60% after 2000 cyclic voltammetry cycles. Furthermore, the all-solid-state symmetric supercapacitor, fabricated by using the final composite fiber as both positive and negative electrodes pre-coated with the poly(vinyl alcohol)/H2SO4 gel polyelectrolyte, possesses volumetric capacitance of 36.7 F cm-3 at 0.2 A cm-3 and could light up a red light-emitting diode easily. The excellent mechanical and electrochemical performances make the designed supercapacitor as promising high performance wearable energy storage device.

11.
J Colloid Interface Sci ; 506: 572-581, 2017 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-28759857

RESUMO

The free-standing polyaniline (PANI)-based composite film electrodes were prepared with polyvinyl chloride (PVC) and the aniline modified PVC (PVC-An) films as flexible substrates for supercapacitors, via facile in-situ chemical oxidative polymerization of aniline, with conventional chemical oxidative polymerization or rapid-mixing chemical oxidative polymerization technique. Owing to the grafting of PANI from the PVC-An film as substrate and the suppression of the secondary growth of the primary PANI particles in the rapid-mixing chemical oxidative polymerization, the PVC-g-PANI-2 composite film with loose surface possessed better comprehensive performance, accompanying the high specific capacitance (645.3F/g at a current density of 1A/g), good rate capacitance (retaining 63.2% of original value at a current density of 10A/g and 52.0% at a scan rate of 100mV/s), good cycle stability (retaining 83.1% after 1000 cycles) and the improved internal resistance. Besides its excellent flexibility, it could retain 61.2% of its original specific capacitance under the stress of 8.66MPa for 1h, demonstrating a good tensile-resistance.

12.
J Colloid Interface Sci ; 503: 205-213, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28527338

RESUMO

Facile one-step ultrasonic-assisted chemical precipitation strategy has been developed for the mass production of SnO2 nanomaterials with different morphologies. As anode material for lithium-ion batteries, the nanoporous SnO2 nanosheets exhibited an extremely high initial specific capacity of 2231mAh/g in comparison with 1242mAh/g of the SnO2 microcrystals and 1244mAh/g of the nanoporous SnO2 nanoflowers. Meanwhile the nanoporous SnO2 nanosheet electrode displayed a specific capacity of 688mAh/g after 60 cycles at 0.2 A/g current density and an extraordinary capacity retention of 224mAh/g at a current density of 8A/g (approximately 10 C) owing to a huge increase of Li+ diffusion coefficient.

13.
Water Sci Technol ; 73(7): 1608-18, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27054732

RESUMO

This paper is concerned with the simulation and experimental study of hydraulic characteristics in a pilot Carrousel oxidation ditch for the optimization of submerged depth ratio of surface aerators. The simulation was based on the large eddy simulation with the Smagorinsky model, and the velocity was monitored in the ditches with an acoustic Doppler velocimeter method. Comparisons of the simulated velocities and experimental ones show a good agreement, which validates that the accuracy of this simulation is good. The best submerged depth ratio of 2/3 for surface aerators was obtained according to the analysis of the flow field structure, the ratio of gas and liquid in the bottom layer of a ditch, the average velocity of mixture and the flow region with a velocity easily causing sludge deposition under the four operation conditions with submerged depth ratios of 1/3, 1/2, 2/3 and 3/4 for surface aerators. The research result can provide a reference for the design of Carrousel oxidation ditches.


Assuntos
Modelos Teóricos , Esgotos/química , Eliminação de Resíduos Líquidos/métodos , Simulação por Computador , Oxirredução
14.
Work ; 39(3): 283-90, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21709364

RESUMO

BACKGROUND: Consequences of traumatic brain injury underscore the need to study high-risk groups. Few studies have investigated work-related traumatic brain injuries (WrTBIs) in the construction industry. OBJECTIVE: To examine WrTBIs in Ontario for the construction industry compared to other industries. METHODS: A retrospective study of individuals who sustained a WrTBI and had a clinical assessment as an outpatient at a hospital-based referral centre. Data were collected for a number of factors including demographic, injury and occupation and were analyzed according to the Person-Environment-Occupation (PEO) model. PARTICIPANTS: 435 individuals who sustained a WrTBI. RESULTS: There were 19.1% in the construction industry, 80.9% in other industries. Compared to other industries, individuals in the construction industry were more likely to be male, to not have attained post-secondary education, and experience multiple traumas. WrTBIs in the construction industry were commonly due to elevated work. The construction occupations involved included skilled workers and general labourers, and compared to other industries, WrTBIs occurred most often for those employed for a short duration in the construction industry. CONCLUSIONS: Construction industry workers experience serious WrTBIs that are amenable to prevention. Use of the PEO model increased our understanding of WrTBIs in the construction industry.


Assuntos
Lesões Encefálicas/etiologia , Arquitetura de Instituições de Saúde , Indústrias , Exposição Ocupacional/efeitos adversos , Adulto , Lesões Encefálicas/epidemiologia , Lesões Encefálicas/prevenção & controle , Feminino , Humanos , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Saúde Ocupacional , Ontário/epidemiologia , Estudos Retrospectivos
15.
Brain Inj ; 24(11): 1358-63, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20715899

RESUMO

OBJECTIVE: Workplace falls are a common cause of head injuries; however, detailed study of this is limited. The objective of the study was to examine the person, environment and occupation factors associated with work-related traumatic brain injuries (WrTBI) due to falls from elevation (FFE) and falls from the same level (FFSL). METHODS: This study is a retrospective chart review. Data was extracted from consecutive medical records of workers who sustained a head injury at work and were referred to the Toronto Rehabilitation Institute for clinical assessment. RESULTS: FFE were more likely to occur in men and result in multiple traumas, compared to FFSL. FFSL occurred more equally among men and women. Slippery conditions and placement of objects were common for WrTBI due to FFSL. Change in elevation was common for WrTBI due to FFE. WrTBI due to FFE most often occurred in trades, transport occupations and the construction industry, whereas WrTBI due to FFSL most often occurred in professional, management, skilled positions and the manufacturing industry. CONCLUSIONS: Types of falls resulting in brain injury and their mechanisms of injury vary across industries and occupations. The study provides information for more tailored workplace safety strategies and primary prevention across industries.


Assuntos
Acidentes por Quedas/estatística & dados numéricos , Acidentes de Trabalho/estatística & dados numéricos , Lesões Encefálicas/epidemiologia , Doenças Profissionais/epidemiologia , Acidentes de Trabalho/legislação & jurisprudência , Acidentes de Trabalho/psicologia , Adulto , Lesões Encefálicas/fisiopatologia , Lesões Encefálicas/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/fisiopatologia , Doenças Profissionais/psicologia , Ontário/epidemiologia , Estudos Retrospectivos
16.
Proc Natl Acad Sci U S A ; 104(41): 16323-8, 2007 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-17913893

RESUMO

Exposure to low Ca(2+) and/or Mg(2+) is tolerated by cardiac myocytes, astrocytes, and neurons, but restoration to normal divalent cation levels paradoxically causes Ca(2+) overload and cell death. This phenomenon has been called the "Ca(2+) paradox" of ischemia-reperfusion. The mechanism by which a decrease in extracellular Ca(2+) and Mg(2+) is "detected" and triggers subsequent cell death is unknown. Transient periods of brain ischemia are characterized by substantial decreases in extracellular Ca(2+) and Mg(2+) that mimic the initial condition of the Ca(2+) paradox. In CA1 hippocampal neurons, lowering extracellular divalents stimulates a nonselective cation current. We show that this current resembles TRPM7 currents in several ways. Both (i) respond to transient decreases in extracellular divalents with inward currents and cell excitation, (ii) demonstrate outward rectification that depends on the presence of extracellular divalents, (iii) are inhibited by physiological concentrations of intracellular Mg(2+), (iv) are enhanced by intracellular phosphatidylinositol 4,5-bisphosphate (PIP(2)), and (v) can be inhibited by Galphaq-linked G protein-coupled receptors linked to phospholipase C beta1-induced hydrolysis of PIP(2). Furthermore, suppression of TRPM7 expression in hippocampal neurons strongly depressed the inward currents evoked by lowering extracellular divalents. Finally, we show that activation of TRPM7 channels by lowering divalents significantly contributes to cell death. Together, the results demonstrate that TRPM7 contributes to the mechanism by which hippocampal neurons "detect" reductions in extracellular divalents and provide a means by which TRPM7 contributes to neuronal death during transient brain ischemia.


Assuntos
Hipocampo/metabolismo , Neurônios/metabolismo , Canais de Cátion TRPM/metabolismo , Animais , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Cátions Bivalentes/metabolismo , Morte Celular/fisiologia , Células Cultivadas , Hipocampo/citologia , Humanos , Camundongos , Interferência de RNA , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Canais de Cátion TRPM/antagonistas & inibidores , Canais de Cátion TRPM/genética , Transfecção
17.
J Neurochem ; 98(5): 1657-63, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16879713

RESUMO

NMDA receptor function is modulated by both G-protein-coupled receptors and receptor tyrosine kinases. In acutely isolated rat hippocampal neurons, direct activation of the platelet-derived growth factor (PDGF) receptor or transactivation of the PDGF receptor by D4 dopamine receptors inhibits NMDA-evoked currents in a phospholipase C (PLC)-dependent manner. We have investigated further the ability of D2-class dopamine receptors to modulate NMDA-evoked currents in isolated rat prefrontal cortex (PFC). We have demonstrated that, similar to isolated hippocampal neurons, the application of PDGF-BB or quinpirole to isolated PFC neurons induces a slow-onset and long-lasting inhibition of NMDA-evoked currents. However, in contrast to hippocampal neurons, the inhibition of NMDA-evoked currents by quinpirole in PFC neurons is dependent upon D2/3, rather than D4, dopamine receptors. In PFC slices, application of both PDGF-BB and quinpirole induced a phosphorylation of the PDGF receptor at the PLCgamma binding and activation site, Tyr1021. The PDGF receptor kinase inhibitor, tyrphostin A9, and the D2/3 dopamine receptor antagonist, raclopride, inhibited quinpirole-induced Tyr1021 phosphorylation. These finding suggest that quinpirole treatment inhibits NMDAR signaling via PDGF receptor transactivation in both the hippocampus and the PFC, and that the effects of quinpirole in these regions are mediated by D4 and D2/3 dopamine receptors, respectively.


Assuntos
Agonistas de Aminoácidos Excitatórios/farmacologia , N-Metilaspartato/farmacologia , Inibição Neural/fisiologia , Neurônios/efeitos dos fármacos , Córtex Pré-Frontal/citologia , Receptores de Dopamina D2/fisiologia , Receptores do Fator de Crescimento Derivado de Plaquetas/fisiologia , Animais , Animais Recém-Nascidos , Benzamidas/farmacologia , Biotinilação/métodos , Western Blotting/métodos , Agonistas de Dopamina/farmacologia , Antagonistas de Dopamina/farmacologia , Interações Medicamentosas , Hipocampo/citologia , Técnicas In Vitro , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Inibição Neural/efeitos dos fármacos , Neurônios/fisiologia , Técnicas de Patch-Clamp/métodos , Piperazinas/farmacologia , Fator de Crescimento Derivado de Plaquetas/farmacologia , Quimpirol/farmacologia , Racloprida/farmacologia , Ratos , Ratos Wistar
18.
Cell ; 118(6): 687-98, 2004 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-15369669

RESUMO

Ca2+ toxicity remains the central focus of ischemic brain injury. The mechanism by which toxic Ca2+ loading of cells occurs in the ischemic brain has become less clear as multiple human trials of glutamate antagonists have failed to show effective neuroprotection in stroke. Acidosis is a common feature of ischemia and is assumed to play a critical role in brain injury; however, the mechanism(s) remain ill defined. Here, we show that acidosis activates Ca2+ -permeable acid-sensing ion channels (ASICs), inducing glutamate receptor-independent, Ca2+ -dependent, neuronal injury inhibited by ASIC blockers. Cells lacking endogenous ASICs are resistant to acid injury, while transfection of Ca2+ -permeable ASIC1a establishes sensitivity. In focal ischemia, intracerebroventricular injection of ASIC1a blockers or knockout of the ASIC1a gene protects the brain from ischemic injury and does so more potently than glutamate antagonism. Thus, acidosis injures the brain via membrane receptor-based mechanisms with resultant toxicity of [Ca2+]i, disclosing new potential therapeutic targets for stroke.


Assuntos
Acidose/metabolismo , Isquemia Encefálica/metabolismo , Cálcio/metabolismo , Ácido Glutâmico/metabolismo , Proteínas de Membrana/metabolismo , Degeneração Neural/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Canais de Sódio/metabolismo , Canais Iônicos Sensíveis a Ácido , Acidose/complicações , Acidose/tratamento farmacológico , Animais , Isquemia Encefálica/tratamento farmacológico , Células COS , Cálcio/toxicidade , Bloqueadores dos Canais de Cálcio/farmacologia , Sinalização do Cálcio/efeitos dos fármacos , Sinalização do Cálcio/genética , Células Cultivadas , Modelos Animais de Doenças , Desenho de Fármacos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Ácido Glutâmico/toxicidade , Masculino , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Degeneração Neural/tratamento farmacológico , Degeneração Neural/etiologia , Proteínas do Tecido Nervoso/antagonistas & inibidores , Proteínas do Tecido Nervoso/genética , Fármacos Neuroprotetores/farmacologia , Ratos , Receptores de Glutamato/efeitos dos fármacos , Receptores de Glutamato/metabolismo , Bloqueadores dos Canais de Sódio/farmacologia , Canais de Sódio/genética
19.
Cell ; 115(7): 863-77, 2003 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-14697204

RESUMO

Excitotoxicity in brain ischemia triggers neuronal death and neurological disability, and yet these are not prevented by antiexcitotoxic therapy (AET) in humans. Here, we show that in neurons subjected to prolonged oxygen glucose deprivation (OGD), AET unmasks a dominant death mechanism perpetuated by a Ca2+-permeable nonselective cation conductance (IOGD). IOGD was activated by reactive oxygen/nitrogen species (ROS), and permitted neuronal Ca2+ overload and further ROS production despite AET. IOGD currents corresponded to those evoked in HEK-293 cells expressing the nonselective cation conductance TRPM7. In cortical neurons, blocking IOGD or suppressing TRPM7 expression blocked TRPM7 currents, anoxic 45Ca2+ uptake, ROS production, and anoxic death. TRPM7 suppression eliminated the need for AET to rescue anoxic neurons and permitted the survival of neurons previously destined to die from prolonged anoxia. Thus, excitotoxicity is a subset of a greater overall anoxic cell death mechanism, in which TRPM7 channels play a key role.


Assuntos
Hipóxia-Isquemia Encefálica/metabolismo , Ativação do Canal Iônico/fisiologia , Canais Iônicos/deficiência , Proteínas de Membrana , Degeneração Neural/metabolismo , Neurotoxinas/antagonistas & inibidores , Proteínas Quinases/deficiência , Animais , Ácido Araquidônico/metabolismo , Cálcio/metabolismo , Sinalização do Cálcio/fisiologia , Cátions/metabolismo , Morte Celular/fisiologia , Linhagem Celular , Sobrevivência Celular/fisiologia , Glucose/deficiência , Humanos , Hipóxia-Isquemia Encefálica/fisiopatologia , Ativação do Canal Iônico/efeitos dos fármacos , Canais Iônicos/antagonistas & inibidores , Canais Iônicos/genética , Ferro/metabolismo , Camundongos , Degeneração Neural/fisiopatologia , Neurotoxinas/metabolismo , Inibidores de Proteínas Quinases , Proteínas Quinases/genética , Proteínas Serina-Treonina Quinases , Interferência de RNA , RNA Interferente Pequeno , Espécies Reativas de Oxigênio/metabolismo , Canais de Cátion TRPM
20.
J Physiol ; 550(Pt 2): 385-99, 2003 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-12777448

RESUMO

The effects of extracellular pH (pHo) on calcium-sensing non-selective cation (csNSC) channels in cultured mouse hippocampal neurons were investigated using whole-cell voltage-clamp and current-clamp recordings. Decreasing extracellular Ca2+ concentrations ([Ca2+]o) activated slow and sustained inward currents through the csNSC channels. Decreasing pHo activated amiloride-sensitive transient proton-gated currents which decayed to baseline in several seconds. With proton-gated channels inactivated by pre-perfusion with low pH solution or blocked by amiloride, decreasing pHo to 6.5 inhibited the csNSC currents with a leftward shift of the Ca2+ dose-inhibition curve. Increasing pH to 8.5, on the other hand, caused a rightward shift of the Ca2+ dose-inhibition curve and potentiated the csNSC currents. Intracellular alkalinization following bath perfusion of quinine mimicked the potentiation of the csNSC currents by increasing pHo, while intracellular acidification by addition and subsequent withdrawal of NH4Cl mimicked the inhibition of the csNSC currents by decreasing pHo. Intracellular pH (pHi) imaging demonstrated that decreasing pHo induced a corresponding decrease in pHi. Including 30 mM Hepes in the pipette solution eliminated the effects of quinine and NH4Cl on the csNSC currents, but only partially reduced the effect of lowering pHo. In current-clamp recordings, decreasing [Ca2+]o induced sustained membrane depolarization and excitation of hippocampal neurons. Decreasing pHo to 6.5 inhibited the low [Ca2+]o-induced csNSC channel-mediated membrane depolarization and the excitation of neurons. Our results indicate that acidosis may inhibit low [Ca2+]o-induced neuronal excitation by inhibiting the activity of the csNSC channels. Both the extracellular and the intracellular sites are involved in the proton modulation of the csNSC channels.


Assuntos
Acidose/fisiopatologia , Cálcio/farmacologia , Hipocampo/metabolismo , Neurônios/metabolismo , Receptores de Detecção de Cálcio/antagonistas & inibidores , Amilorida/farmacologia , Animais , Células Cultivadas , Diuréticos/farmacologia , Estimulação Elétrica , Eletrofisiologia , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Potenciais da Membrana/fisiologia , Camundongos , Neurônios/efeitos dos fármacos , Técnicas de Patch-Clamp
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