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1.
Sci Rep ; 11(1): 6237, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33737577

RESUMO

This study investigates the effect of strain on the compensation temperature of ferrimagnetic Tb-Fe films formed on a flexible substrate. The compensation temperature is determined by the anomalous Hall measurement, and an application of 1.2% tensile strain reduces the compensation temperature by 12 K. X-ray magnetic circular dichroism reveals that approximately 5% of Fe magnetic moment and approximately 1% of Tb magnetic moment are reduced by an application of 0.9% tensile strain at the room temperature. To understand the greater reduction in Fe magnetization compared with that in Tb and the compensation temperature reduction simultaneously, a model applying molecular field theory is analyzed. Changes in three types of exchange coupling between Fe and Tb atoms are speculated to be caused by the strain.

2.
Sci Adv ; 4(12): eaav0265, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30588494

RESUMO

We show that the electric field (EF) can control the domain wall (DW) velocity in a Pt/Co/Pd asymmetric structure. With the application of a gate voltage, a substantial change in DW velocity up to 50 m/s is observed, which is much greater than that observed in previous studies. Moreover, modulation of a DW velocity exceeding 100 m/s is demonstrated in this study. An EF-induced change in the interfacial Dzyaloshinskii-Moriya interaction (DMI) up to several percent is found to be the origin of the velocity modulation. The DMI-mediated velocity change shown here is a fundamentally different mechanism from that caused by EF-induced anisotropy modulation. Our results will pave the way for the electrical manipulation of spin structures and dynamics via DMI control, which can enhance the performance of spintronic devices.

3.
Sci Rep ; 8(1): 7195, 2018 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-29739954

RESUMO

A vertical spin metal-oxide-semiconductor field-effect transistor (spin MOSFET) is a promising low-power device for the post scaling era. Here, using a ferromagnetic-semiconductor GaMnAs-based vertical spin MOSFET with a GaAs channel layer, we demonstrate a large drain-source current IDS modulation by a gate-source voltage VGS with a modulation ratio up to 130%, which is the largest value that has ever been reported for vertical spin field-effect transistors thus far. We find that the electric field effect on indirect tunneling via defect states in the GaAs channel layer is responsible for the large IDS modulation. This device shows a tunneling magnetoresistance (TMR) ratio up to ~7%, which is larger than that of the planar-type spin MOSFETs, indicating that IDS can be controlled by the magnetization configuration. Furthermore, we find that the TMR ratio can be modulated by VGS. This result mainly originates from the electric field modulation of the magnetic anisotropy of the GaMnAs ferromagnetic electrodes as well as the potential modulation of the nonmagnetic semiconductor GaAs channel layer. Our findings provide important progress towards high-performance vertical spin MOSFETs.

4.
Nat Commun ; 9(1): 1648, 2018 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-29695776

RESUMO

Chiral spin textures of a ferromagnetic layer in contact to a heavy non-magnetic metal, such as Néel-type domain walls and skyrmions, have been studied intensively because of their potential for future nanomagnetic devices. The Dyzaloshinskii-Moriya interaction (DMI) is an essential phenomenon for the formation of such chiral spin textures. In spite of recent theoretical progress aiming at understanding the microscopic origin of the DMI, an experimental investigation unravelling the physics at stake is still required. Here we experimentally demonstrate the close correlation of the DMI with the anisotropy of the orbital magnetic moment and with the magnetic dipole moment of the ferromagnetic metal in addition to Heisenberg exchange. The density functional theory and the tight-binding model calculations reveal that inversion symmetry breaking with spin-orbit coupling gives rise to the orbital-related correlation. Our study provides the experimental connection between the orbital physics and the spin-orbit-related phenomena, such as DMI.

5.
Rev. argent. microbiol ; 50(1): 12-22, mar. 2018. ilus, tab
Artigo em Inglês | LILACS | ID: biblio-958025

RESUMO

The objectives of this study were to determine the serovar of a collection of Actinobacillus pleuropneumoniae strains within the 3-6-8-15 cross-reacting group and to analyze their phenotypic and genetic properties. Based on the serological tests, forty-seven field strains of Actinobacillus pleuropneumoniae isolated from lungs with pleuropneumonia lesions in Japan and Argentina were found to be serovars belonging to the 3-6-8-15 cross-reacting group. By using a capsule loci-based PCR, twenty-nine (96.7%) and one (3.3%) from Japan were identified as serovars 15 and 8, respectively, whereas seventeen (100%) from Argentina were identified as serovar 8. The findings suggested that serovars 8 and 15 were prevalent within the 3-6-8-15 cross-reacting group, in Argentina and Japan, respectively. Phenotypic analyses revealed that the protein patterns observed on SDS-PAGE and the lipopolysaccharide antigen detected by immunoblotting of the reference and field strains of serovars 8 and 15 were similar to each other. Genetic (16S rDNA, apxIIA, apxIIIA, cps, cpx genes, apx and omlA patterns) analyses revealed that the apxIIA and apxIIIA genes of the field strains of serovars 8 and 15 were similar to those of the reference strains of serovars 3, 4, 6, 8 and 15. The results obtained in the present study may be useful for the development of more effective vaccines against disease caused by A. pleuropneumoniae by including the homologous antigens to the most prevalent serovars in specific geographical areas.


Los objetivos del presente estudio fueron determinar el serovar de una colección de cepas de Actinobacillus pleuropneumoniae pertenecientes al grupo 3, 6, 8, 15 de reacciones cruzadas y analizar sus propiedades fenotípicas y genéticas. En base a técnicas serológicas se determinó que cuarenta y siete cepas de A. pleuropneumoniae aisladas a partir de pulmones con lesiones de pleuroneumonía en Japón y Argentina pertenecen al grupo 3, 6, 8, 15. Mediante el uso de PCR basado en locus capsulares, veintinueve (96.7%) y una (3.3%) de los aislados japoneses fueron identificados como serovar 15 y 8 respectivamente, mientras que diecisiete (100%) de los aislados argentinos resultaron pertenecer al serotipo 8. Este hallazgo sugirió que los serovares 8 y 15 fueron los prevalentes dentro del grupo 3, 6, 8, 15 en Japón y Argentina, respectivamente. El análisis fenotípico reveló que los perfiles proteicos determinados por SDS-PAGE, y de antígenos lipopolisacáridos estudiados por inmunoblot, de las cepas de referencia y de campo de los serovares 8 y 15 fueron similares entre sí. El análisis genético (Í6S rDNA, apxIIA, apxIIA, cps, genes cpx, apx y los perfiles omlA) reveló que los genes apxIIA y apxIIIA de las cepas de campo de los serovares 8 y 15 fueron similares a sus homólogos de las cepas de referencia de los serovares 3, 4, 6, 8 y 15. Los resultados obtenidos en el presente estudio pueden ser útiles para el desarrollo de vacunas más efectivas contra la enfermedad causada por A. pleuropneumoniae, al posibilitar incluir antígenos homólogos a los serovares prevalentes en las áreas geográficas de interés.


Assuntos
Animais , Doenças dos Suínos , Infecções por Actinobacillus , Actinobacillus pleuropneumoniae , Argentina , Suínos , Doenças dos Suínos/genética , Infecções por Actinobacillus/genética , Infecções por Actinobacillus/veterinária , Actinobacillus pleuropneumoniae/genética , Japão
6.
Rev Argent Microbiol ; 50(1): 12-22, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28886933

RESUMO

The objectives of this study were to determine the serovar of a collection of Actinobacillus pleuropneumoniae strains within the 3-6-8-15 cross-reacting group and to analyze their phenotypic and genetic properties. Based on the serological tests, forty-seven field strains of Actinobacillus pleuropneumoniae isolated from lungs with pleuropneumonia lesions in Japan and Argentina were found to be serovars belonging to the 3-6-8-15 cross-reacting group. By using a capsule loci-based PCR, twenty-nine (96.7%) and one (3.3%) from Japan were identified as serovars 15 and 8, respectively, whereas seventeen (100%) from Argentina were identified as serovar 8. The findings suggested that serovars 8 and 15 were prevalent within the 3-6-8-15 cross-reacting group, in Argentina and Japan, respectively. Phenotypic analyses revealed that the protein patterns observed on SDS-PAGE and the lipopolysaccharide antigen detected by immunoblotting of the reference and field strains of serovars 8 and 15 were similar to each other. Genetic (16S rDNA, apxIIA, apxIIIA, cps, cpx genes, apx and omlA patterns) analyses revealed that the apxIIA and apxIIIA genes of the field strains of serovars 8 and 15 were similar to those of the reference strains of serovars 3, 4, 6, 8 and 15. The results obtained in the present study may be useful for the development of more effective vaccines against disease caused by A. pleuropneumoniae by including the homologous antigens to the most prevalent serovars in specific geographical areas.


Assuntos
Infecções por Actinobacillus , Actinobacillus pleuropneumoniae , Doenças dos Suínos , Infecções por Actinobacillus/genética , Infecções por Actinobacillus/veterinária , Actinobacillus pleuropneumoniae/genética , Animais , Argentina , Japão , Suínos , Doenças dos Suínos/genética
7.
Sci Rep ; 7(1): 790, 2017 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-28400565

RESUMO

Manipulation of magnetization using current-induced torque is crucial for magnetic recording devices. Recently, the spin-orbit torque (SOT) that emerges in a ferromagnetic thin film on a heavy metal is focused as a new scheme for magnetization switching in perpendicularly magnetized systems. Since the SOT provides a perpendicular effective field to the system, the formation of a magnetic multiple domain state because of Joule heating is supressed in the magnetization reversal process. This means that high reliable switching is possible using the SOT. Here, by utilizing the SOT induced domain stability, we show that an electrical current directly injected to a perpendicularly magnetized Pt/Co/Pd system can magnetize itself, that is, current-induced magnetization process from multi to single domain state. A quantitative determination of the SOT is performed using the current-induced magnetization curve. The present results are of great importance as another approach to evaluate the SOT effect, as well as a demonstration of domain state switching caused by the SOT.

8.
Sci Rep ; 7: 46132, 2017 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-28406236

RESUMO

We used x-ray absorption spectroscopy and x-ray magnetic circular dichroism to investigate the effects of inserting Cu into Co/Pt interfaces, and found that a 0.4-nm-thick inserted Cu layer showed perpendicularly magnetized properties induced by the proximity effect through the Co and Pt layers. The dependence of the magnetic properties on the thickness of the Cu layers showed that the proximity effects between Co and Pt with perpendicular magnetic anisotropy can be prevented by the insertion of a Cu layer with a nominal threshold thickness of 0.7 nm. Element-specific magnetization curves were also obtained, demonstrating that the out-of-plane magnetization is induced in the Cu layers of the Co/Cu/Pt structures.

9.
Microbiol Immunol ; 60(7): 447-58, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27211905

RESUMO

Apx toxins produced by Actinobacillus pleuropneumoniae are essential components of new generation vaccines. In this study, apxIIA and apxIIIA genes of serovars 2, 3, 4, 6, 8 and 15 were cloned and sequenced. Amino acid sequences of ApxIIA proteins of serovars 2, 3, 4, 6, 8 and 15 were almost identical to those of serovars 1, 5, 7, 9 and 11-13. Immunoblot analysis showed that rApxIIA from serovars 2 and 15 reacts strongly with sera from animals infected with various serovars. Sequence analysis revealed that ApxIIIA proteins has two variants, one in strains of serovar 2 and the other in strains of serovars 3, 4, 6, 8 and 15. A mouse cross-protection study showed that mice actively immunized with rApxIIIA/2 or rApxIIIA/15 are protected against challenge with A. pleuropneumoniae strains of serovars 3, 4, 6, 8, 15, and 2 expressing ApxIII/15 and ApxIII/2, respectively. Similarly, mice passively immunized with rabbit anti-rApxIIIA/2 or anti-rApxIIIA/15 sera were found to be protected against challenge with strains of serovars 2 and 15. Our study revealed antigenic and sequence similarities within ApxIIA and ApxIIIA proteins, which may help in the development of effective vaccines against disease caused by A. pleuropneumoniae.


Assuntos
Actinobacillus pleuropneumoniae/genética , Actinobacillus pleuropneumoniae/imunologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Proteínas Hemolisinas/genética , Proteínas Hemolisinas/imunologia , Sorogrupo , Infecções por Actinobacillus/imunologia , Infecções por Actinobacillus/prevenção & controle , Actinobacillus pleuropneumoniae/classificação , Sequência de Aminoácidos , Animais , Anticorpos Antibacterianos/imunologia , Proteínas de Bactérias/química , Proteínas de Bactérias/isolamento & purificação , Expressão Gênica , Proteínas Hemolisinas/química , Proteínas Hemolisinas/isolamento & purificação , Imunização , Camundongos , Modelos Moleculares , Conformação Proteica , Domínios Proteicos , Coelhos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/isolamento & purificação , Suínos
10.
J Anesth ; 30(2): 324-7, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26758074

RESUMO

Nonintubated video-assisted thoracoscopic surgery (VATS) has been reported to be safe and feasible for patients with various thoracic diseases, including those who have respiratory dysfunction. In nonintubated VATS, it is important to maintain spontaneous respiration and to obtain a satisfactory operating field through adequate collapse of the lung by surgical pneumothorax. Therefore, we need to minimize the patient's physical and psychological discomfort by using regional anesthesia and sedation. If analgesia and sedation are inadequate, conversion to intubated general anesthesia may be required. Dexmedetomidine (DEX) is a highly selective α2-adrenoceptor agonist that provides anxiolysis and cooperative sedation without respiratory depression. It seems to be a suitable sedative for nonintubated VATS, especially in high-risk patients for intubated general anesthesia, but there have been no report about its use combined with epidural anesthesia in nonintubated VATS for adult patients. Here, we report three patients with severe respiratory dysfunction who underwent nonintubated VATS for pneumothorax using epidural anesthesia and DEX. In all three patients, DEX infusion was started after placement of an epidural catheter and was titrated to achieve mild sedation, while maintaining communicability and cooperation. This seems to be a promising strategy for nonintubated VATS in patients with respiratory dysfunction, as well as patients with normal respiratory function.


Assuntos
Anestesia Epidural/métodos , Anestésicos/administração & dosagem , Cirurgia Torácica Vídeoassistida/métodos , Idoso , Idoso de 80 Anos ou mais , Anestesia Geral/métodos , Dexmedetomidina/administração & dosagem , Humanos , Hipnóticos e Sedativos/administração & dosagem , Masculino
12.
Sci Rep ; 5: 14303, 2015 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-26391306

RESUMO

Several magnetic properties have recently become tunable with an applied electric field. Particularly, electrically controlled magnetic phase transitions and/or magnetic moments have attracted attention because they are the most fundamental parameters in ferromagnetic materials. In this study, we showed that an electric field can be used to control the magnetic moment in films made of Pd, usually a non-magnetic element. Pd ultra-thin films were deposited on ferromagnetic Pt/Co layers. In the Pd layer, a ferromagnetically ordered magnetic moment was induced by the ferromagnetic proximity effect. By applying an electric field to the ferromagnetic surface of this Pd layer, a clear change was observed in the magnetic moment, which was measured directly using a superconducting quantum interference device magnetometer. The results indicate that magnetic moments extrinsically induced in non-magnetic elements by the proximity effect, as well as an intrinsically induced magnetic moments in ferromagnetic elements, as reported previously, are electrically tunable. The results of this study suggest a new avenue for answering the fundamental question of "can an electric field make naturally non-magnetic materials ferromagnetic?".

14.
Nat Commun ; 4: 2011, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23771026

RESUMO

Energy barriers in magnetization reversal dynamics have long been of interest because the barrier height determines the thermal stability of devices as well as the threshold force triggering their dynamics. Especially in memory and logic applications, there is a dilemma between the thermal stability of bit data and the operation power of devices, because larger energy barriers for higher thermal stability inevitably lead to larger magnetic fields (or currents) for operation. Here we show that this is not the case for current-induced magnetic domain-wall motion induced by adiabatic spin-transfer torque. By quantifying domain-wall depinning energy barriers by magnetic field and current, we find that there exist two different pinning barriers, extrinsic and intrinsic energy barriers, which govern the thermal stability and threshold current, respectively. This unique two-barrier system allows low-power operation with high thermal stability, which is impossible in conventional single-barrier systems.

16.
J Anesth ; 27(6): 895-900, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23670803

RESUMO

PURPOSE: Early postoperative mobilization is crucial for early ambulation to reduce postoperative pulmonary complications after lung resection. However, orthostatic intolerance (OI) may delay patient recovery, leading to complications. It is therefore important to understand the prevalence of and predisposing factors for OI following video-assisted thoracic surgery (VATS), which have not been established. This study evaluated the incidence of OI, impact of OI on delayed ambulation, and predisposing factors associated with OI in patients after VATS. METHODS: This retrospective cohort study consecutively analyzed data from 236 patients who underwent VATS. The primary outcome was defined as OI with symptoms associated with ambulatory challenge on postoperative day 1 (POD1), including dizziness, nausea and vomiting, feeling hot, blurred vision, or transient syncope. Multivariate logistic regression was performed to identify independent factors associated with OI. RESULTS: Of the 236 patients, 35.2 % (83) experienced OI; 45.8 % of these could not ambulate at POD1, compared with 15.7 % of patients without OI (P < 0.001). Factors independently associated with OI included advanced age [odds ratio 2.83 (1.46-5.58); P = 0.002], female gender [odds ratio 2.40 (1.31-4.46); P = 0.004], and postoperative opioid use [odds ratio 2.61 (1.23-5.77); P = 0.012]. Use of thoracic epidural anesthesia was not independently associated with OI [odds ratio 0.72 (0.38-1.37); P = 0.318]. CONCLUSION: Postoperative OI was common in patients after VATS and significantly associated with delayed ambulation. Advanced age, female gender, and postoperative opioid use were identified as independent predisposing factors for OI.


Assuntos
Intolerância Ortostática/epidemiologia , Cirurgia Torácica Vídeoassistida/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/farmacologia , Deambulação Precoce/efeitos adversos , Deambulação Precoce/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento
17.
J Anesth ; 27(1): 93-7, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22926420

RESUMO

PURPOSE: Morphine is a powerful analgesic but its effect is often diminished owing to the development of tolerance. It has been suggested that morphine activates microglia through its action on the toll-like receptor 4 (TLR4) in the spinal cord, leading to suppression of the morphine effect. However, it has not been examined whether the development of morphine tolerance is affected by the deletion and mutation of the TLR4 gene. METHODS: Mice were treated with morphine (60 mg/kg) or vehicle once daily for five consecutive days to induce morphine tolerance, which was assessed by the tail-flick test before and after the treatment period. The effect of the microglial inhibitor minocycline, and the effect of TLR4 mutation (C3H/HeJ mouse) and deletion (TLR4-knockout mouse) on the development of morphine tolerance were tested. The expression of the microglial activation marker, CD11b, in the spinal cords of TLR4-knockout and wild-type mice after morphine treatment for 5 days was assessed by reverse-transcription polymerase chain reaction. RESULTS: Minocycline attenuated the development of morphine tolerance in mice. Mutation or deletion of the TLR4 gene did not significantly affect the development of morphine tolerance. CD11b mRNA expression was increased after morphine treatment both in TLR4-knockout and wild-type mice. CONCLUSION: Microglial activation caused by a mechanism independent of TLR4 is involved in the development of morphine tolerance. Further studies are necessary to clarify the cellular mechanisms of morphine-induced microglial activation.


Assuntos
Analgésicos Opioides/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Microglia/efeitos dos fármacos , Morfina/farmacologia , Receptor 4 Toll-Like/efeitos dos fármacos , Animais , Antígeno CD11b/metabolismo , Tolerância a Medicamentos , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Knockout , Minociclina/farmacologia , Mutação de Sentido Incorreto/genética , Mutação de Sentido Incorreto/fisiologia , Medição da Dor/efeitos dos fármacos , RNA/genética , RNA/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Receptor 4 Toll-Like/genética
18.
J Anesth ; 26(4): 503-8, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22526434

RESUMO

PURPOSE: Early ambulation is essential for rapid functional recovery after surgery; however, orthostatic intolerance may delay recovery and cause syncope, leading to potential serious complications such as falls. Opioids may contribute to orthostatic intolerance because of reduced arterial pressure and associated reduction in cerebral blood flow and oxygenation. This study aimed to examine the effect of postoperative continuous infusion of fentanyl on orthostatic intolerance and delayed ambulation in patients after gynecologic laparoscopic surgery. METHODS: In this retrospective cohort study, data from 195 consecutive patients who underwent gynecologic laparoscopic surgery were analyzed to evaluate the association between postoperative continuous infusion of fentanyl and the incidence of orthostatic intolerance or delayed ambulation. The primary outcome was defined as delayed ambulation, an inability to ambulate on postoperative day 1. The secondary outcome was defined as orthostatic intolerance and symptoms associated with ambulatory challenge, including dizziness, nausea and vomiting, feeling hot, blurred vision, and eventual syncope. Multivariate logistic regression was used to determine the independent predictors of delayed ambulation and orthostatic intolerance. RESULTS: There were 24 cases with documented orthostatic intolerance and 5 with delayed ambulation. After multivariate logistic regression modeling, postoperative continuous infusion of fentanyl was found to be significantly associated with both orthostatic intolerance [adjusted odds ratio (95% confidence interval), 34.78 (11.12-131.72)] and delayed ambulation [adjusted odds ratio (95% confidence interval), 8.37 (1.23-72.15)]. CONCLUSION: Postoperative continuous infusion of fentanyl is associated with increased orthostatic intolerance and delayed ambulation in patients after gynecologic laparoscopic surgery.


Assuntos
Analgésicos Opioides/efeitos adversos , Deambulação Precoce , Fentanila/efeitos adversos , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Laparoscopia/efeitos adversos , Intolerância Ortostática/induzido quimicamente , Cuidados Pós-Operatórios/efeitos adversos , Complicações Pós-Operatórias/induzido quimicamente , Adolescente , Adulto , Idoso , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Anestesia Intravenosa , Índice de Massa Corporal , Estudos de Coortes , Feminino , Fentanila/administração & dosagem , Fentanila/uso terapêutico , Humanos , Infusões Intravenosas , Pessoa de Meia-Idade , Intolerância Ortostática/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
19.
Nature ; 483(7391): 623-6, 2012 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-22407319

RESUMO

Many bacterial pathogens can enter various host cells and then survive intracellularly, transiently evade humoral immunity, and further disseminate to other cells and tissues. When bacteria enter host cells and replicate intracellularly, the host cells sense the invading bacteria as damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) by way of various pattern recognition receptors. As a result, the host cells induce alarm signals that activate the innate immune system. Therefore, bacteria must modulate host inflammatory signalling and dampen these alarm signals. How pathogens do this after invading epithelial cells remains unclear, however. Here we show that OspI, a Shigella flexneri effector encoded by ORF169b on the large plasmid and delivered by the type ΙΙΙ secretion system, dampens acute inflammatory responses during bacterial invasion by suppressing the tumour-necrosis factor (TNF)-receptor-associated factor 6 (TRAF6)-mediated signalling pathway. OspI is a glutamine deamidase that selectively deamidates the glutamine residue at position 100 in UBC13 to a glutamic acid residue. Consequently, the E2 ubiquitin-conjugating activity required for TRAF6 activation is inhibited, allowing S. flexneri OspI to modulate the diacylglycerol-CBM (CARD-BCL10-MALT1) complex-TRAF6-nuclear-factor-κB signalling pathway. We determined the 2.0 Å crystal structure of OspI, which contains a putative cysteine-histidine-aspartic acid catalytic triad. A mutational analysis showed this catalytic triad to be essential for the deamidation of UBC13. Our results suggest that S. flexneri inhibits acute inflammatory responses in the initial stage of infection by targeting the UBC13-TRAF6 complex.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Amidoidrolases/química , Amidoidrolases/metabolismo , Inflamação/imunologia , Inflamação/metabolismo , Shigella flexneri/enzimologia , Shigella flexneri/imunologia , Enzimas de Conjugação de Ubiquitina/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Amidoidrolases/genética , Sequência de Aminoácidos , Animais , Ácido Aspártico/metabolismo , Proteína 10 de Linfoma CCL de Células B , Biocatálise , Caspases/metabolismo , Domínio Catalítico/genética , Cristalografia por Raios X , Cisteína/metabolismo , Análise Mutacional de DNA , Diglicerídeos/antagonistas & inibidores , Diglicerídeos/metabolismo , Disenteria Bacilar/microbiologia , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Células HEK293 , Células HeLa , Histidina/metabolismo , Humanos , Imunidade Inata , Inflamação/enzimologia , Camundongos , Modelos Moleculares , Dados de Sequência Molecular , Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa , NF-kappa B/metabolismo , Proteínas de Neoplasias/metabolismo , Shigella flexneri/genética , Shigella flexneri/patogenicidade , Fator 6 Associado a Receptor de TNF/deficiência , Fator 6 Associado a Receptor de TNF/genética , Fator 6 Associado a Receptor de TNF/metabolismo , Enzimas de Conjugação de Ubiquitina/química , Enzimas de Conjugação de Ubiquitina/genética , Fatores de Virulência/metabolismo
20.
Cell Host Microbe ; 9(5): 376-89, 2011 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-21575909

RESUMO

Selective autophagy of bacterial pathogens represents a host innate immune mechanism. Selective autophagy has been characterized on the basis of distinct cargo receptors but the mechanisms by which different cargo receptors are targeted for autophagic degradation remain unclear. In this study we identified a highly conserved Tectonin domain-containing protein, Tecpr1, as an Atg5 binding partner that colocalized with Atg5 at Shigella-containing phagophores. Tecpr1 activity is necessary for efficient autophagic targeting of bacteria, but has no effect on rapamycin- or starvation-induced canonical autophagy. Tecpr1 interacts with WIPI-2, a yeast Atg18 homolog and PI(3)P-interacting protein required for phagophore formation, and they colocalize to phagophores. Although Tecpr1-deficient mice appear normal, Tecpr1-deficient MEFs were defective for selective autophagy and supported increased intracellular multiplication of Shigella. Further, depolarized mitochondria and misfolded protein aggregates accumulated in the Tecpr1-knockout MEFs. Thus, we identify a Tecpr1-dependent pathway as important in targeting bacterial pathogens for selective autophagy.


Assuntos
Autofagia , Proteínas de Membrana/metabolismo , Shigella/imunologia , Animais , Proteína 5 Relacionada à Autofagia , Células Cultivadas , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Modelos Biológicos , Fagossomos/imunologia , Mapeamento de Interação de Proteínas , Técnicas do Sistema de Duplo-Híbrido
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