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1.
Front Microbiol ; 15: 1371849, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38486701

RESUMO

Bovine herpes virus 1 (BoHV-1) causes a wide variety of diseases in wild and domestic cattle. The most widely used method for viral identification is real-time PCR, which can only be performed in laboratories using sophisticated instruments by expert personnel. Herein, we developed an ultrasensitive time-resolved fluorescence lateral flow immunochromatographic strip (ICS) assay for detecting BoHV-1 in bovine samples using a monoclonal antibody against BoHV-1 labelled with fluorescent microspheres, which can be applied in any setting. The intact process from sample collection to final result can be achieved in 15 min. The limit of detection of the assay for BoHV-1 was 102 TCID50/100 µL. The coincidence rate of the ICS method and real-time PCR recommended by the World Organization for Animal Health (WOAH) was 100% for negative, 92.30% for positive, and 95.42% for total, as evaluated by the detection of 131 clinical samples. This detection method was specifically targeted to BoHV-1, not exhibiting cross-reactivity with other bovine pathogens including BoHV-5. We developed an ICS assay equipped with a portable instrument that offers a sensitive and specific platform for the rapid and reliable detection of BoHV-1 in the field. The Point-of-Care test of BoHV-1 is suitable for the screening and surveillance of BoHV-1 in dairy herds.

2.
Brief Bioinform ; 24(6)2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37930025

RESUMO

Drug combination therapy has gradually become a promising treatment strategy for complex or co-existing diseases. As drug-drug interactions (DDIs) may cause unexpected adverse drug reactions, DDI prediction is an important task in pharmacology and clinical applications. Recently, researchers have proposed several deep learning methods to predict DDIs. However, these methods mainly exploit the chemical or biological features of drugs, which is insufficient and limits the performances of DDI prediction. Here, we propose a new deep multimodal feature fusion framework for DDI prediction, DMFDDI, which fuses drug molecular graph, DDI network and the biochemical similarity features of drugs to predict DDIs. To fully extract drug molecular structure, we introduce an attention-gated graph neural network for capturing the global features of the molecular graph and the local features of each atom. A sparse graph convolution network is introduced to learn the topological structure information of the DDI network. In the multimodal feature fusion module, an attention mechanism is used to efficiently fuse different features. To validate the performance of DMFDDI, we compare it with 10 state-of-the-art methods. The comparison results demonstrate that DMFDDI achieves better performance in DDI prediction. Our method DMFDDI is implemented in Python using the Pytorch machine-learning library, and it is freely available at https://github.com/DHUDEBLab/DMFDDI.git.


Assuntos
Aprendizado de Máquina , Redes Neurais de Computação , Interações Medicamentosas , Estrutura Molecular , Biblioteca Gênica
3.
Neuroimage ; 283: 120418, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37866757

RESUMO

BACKGROUND AND AIMS: Minimal hepatic encephalopathy (MHE) is a mild form of hepatic encephalopathy that lacks observable signs and symptoms. Nevertheless, MHE can cause neurocognitive dysfunction, although the neurobiological mechanisms are not fully understood. Here, the effects of hippocampal iron deposition on cognitive function and its role in MHE were investigated. MATERIALS AND METHODS: Eighteen rats were assigned to experimental and control groups. MHE was induced by thioacetamide. Spatial memory and exploratory behavior were assessed by the Morris water and elevated plus mazes. Hippocampal susceptibility was measured by quantitative susceptibility mapping, iron deposition in the hippocampus and liver by Prussian blue staining, and inflammatory cytokine and ferritin levels in the hippocampus were measured by ELISA. RESULTS: MHE rats showed impaired spatial memory and exploratory behavior (P < 0.05 for all parameters). The bilateral hippocampal susceptibility values were significantly raised in MHE rats, together with evidence of neuroinflammation (increased pro-inflammatory and reduced anti-inflammatory cytokine levels (all P < 0.05). Further analysis indicated good correlations between hippocampal susceptibility values with latency time and inflammatory cytokine levels in MHE but not in control rats. CONCLUSION: MHE induced by thioacetamide was associated with hippocampal iron deposition and inflammation, suggesting that iron overload may be an important driver of neuroinflammatory responses.


Assuntos
Disfunção Cognitiva , Encefalopatia Hepática , Sobrecarga de Ferro , Ratos , Animais , Encefalopatia Hepática/complicações , Doenças Neuroinflamatórias , Tioacetamida , Disfunção Cognitiva/etiologia , Inflamação/induzido quimicamente , Inflamação/complicações , Citocinas , Sobrecarga de Ferro/complicações , Ferro
4.
Accid Anal Prev ; 191: 107204, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37454562

RESUMO

Conveying supporting information by an in-vehicle human-machine interface (HMI) overtaking assistance system represents a promising approach to facilitate safe overtaking maneuvers. Although various researchers have attempted to examine the safety of systems, numerous HMI concepts are not validated and the impacts of systems on driver behavior following exposure to a connected environment remain unclear. Thus, the objective of this study is to assess the effectiveness of various HMI concepts and their effects on drivers' gaze behavior and driving performance in the connected environment. Three types of supporting information, namely distance, advice and guidance, were designed based on implicit and explicit concepts and displayed on the HMI. The guidance information provides more detailed maneuver instructions. A driving simulator experiment was conducted to imitate a connected environment and included an overtaking scenario on a two-lane highway under three distance gaps (short, middle and long) of oncoming vehicles and four HMI conditions including baseline (3*4). 39 participants (mean = 28.3 years, SD = 8.2 years) drove the simulator. Visual attention, driving maneuver, and subjective evaluation data were collected. The results indicated that the supporting information was valid in facilitating overtaking behavior compared without HMI, particularly under the middle distance gap scenario. Advice information was the most effective, required the least attention, exhibited the best performance, and was accepted by drivers. Detailed maneuver instructions were perceived as helpful, although no effect on acceptance was found. The findings of the study provide valuable insights into the development of user-friendly overtaking assistance systems.


Assuntos
Acidentes de Trânsito , Condução de Veículo , Humanos , Adulto Jovem , Adulto
5.
J Immunol ; 210(9): 1408-1418, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36971659

RESUMO

Complement receptor type 2 (CR2) is an important membrane molecule expressed on B cells and follicular dendritic cells. Human CR2 has been shown to play a critical role in bridging the innate complement-mediated immune response with adaptive immunity by binding complement component 3d (C3d). However, the chicken CR2 (chCR2) gene has not been identified or characterized. In this study, unannotated genes that contain short consensus repeat (SCR) domains were analyzed based on RNA sequencing data for chicken bursa lymphocytes, and a gene with >80% homology to CR2 from other bird species was obtained. The gene consisted of 370 aa and was much smaller than the human CR2 gene because 10-11 SCRs were missing. The gene was then demonstrated as a chCR2 that exhibited high binding activity to chicken C3d. Further studies revealed that chCR2 interacts with chicken C3d through a binding site in its SCR1-4 region. An anti-chCR2 mAb that recognizes the epitope 258CKEISCVFPEVQ269 was prepared. Based on the anti-chCR2 mAb, the flow cytometry and confocal laser scanning microscopy experiments confirmed that chCR2 was expressed on the surface of bursal B lymphocytes and DT40 cells. Immunohistochemistry and quantitative PCR analyses further indicated that chCR2 is predominantly expressed in the spleen, bursa, and thymus, as well as in PBLs. Additionally, the expression of chCR2 varied according to the infectious bursal disease virus infection status. Collectively, this study identified and characterized chCR2 as a distinct immunological marker in chicken B cells.


Assuntos
Galinhas , Complemento C3d , Animais , Humanos , Complemento C3d/metabolismo , Receptores de Complemento 3d/metabolismo , Sítios de Ligação , Fatores Imunológicos , Receptores de Complemento
6.
Opt Express ; 31(3): 4580-4598, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36785422

RESUMO

We propose a scheme consisting of coupled nanomechanical cantilever resonators and superconducting flux qubits to engineer a parity-time- (P T-) symmetric phononic system formed by active and passive modes. The effective gain (loss) of the phonon mode is achieved by the longitudinal coupling of the resonator and the fast dissipative superconducting qubit with a blue-sideband driving (red-sideband driving). A P T-symmetric to broken-P T-symmetric phase transition can be observed in both balanced gain-to-loss and unbalanced gain-to-loss cases. Applying a resonant weak probe field to the dissipative resonator, we find that (i) for balanced gain and loss, the acoustic signal absorption to amplification can be tuned by changing the coupling strength between resonators; (ii) for unbalanced gain and loss, both acoustically induced transparency and anomalous dispersion can be observed around Δ = 0, where the maximum group delay is also located at this point. Our work provides an experimentally feasible scheme to design P T-symmetric phononic systems and a powerful platform for controllable acoustic signal transmission in a hybrid quantum system.

7.
Appl Opt ; 62(1): 27-33, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36606845

RESUMO

A resistive switch effect-based optical memristive switch with an ultra-high extinction ratio and ultra-compact size working at 1550 nm is proposed. The device is composed of a metal-insulator-metal waveguide and a square resonator with active electrodes. The formation and rupture of conductive filaments in the resonant cavity can alter the resonant wavelength, which triggers the state of the optical switch ON or OFF. The numerical results demonstrate that the structure has an ultra-compact size (less than 1 µm) and ultra-high extinction ratio (37 dB). The proposed device is expected to address the problems of high-power consumption and large-scale optical switches and can be adopted in optical switches, optical modulation, optical storage and computing, and large-scale photonic integrated devices.

8.
Appl Microbiol Biotechnol ; 107(1): 379-390, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36456729

RESUMO

Infections caused by bovine herpesvirus 1 (BoHV-1) remain a serious global issue to the health and welfare of the bovine industry. Monitoring of neutralizing antibodies is essential not only for epidemic diagnosis, but also to assess vaccination efficacy. In this study, we generated a neutralizing monoclonal antibody, termed as 3F8, targeting glycoprotein D (gD) of BoHV-1. This monoclonal antibody could neutralize BoHV-1 with a 50% inhibitory concentration (IC50) of 37.82 ng/mL. Furthermore, 3F8 could inhibit BoHV-1 infection and cell-to-cell spread at the prebinding stage. A blocking enzyme-linked immunosorbent assay (ELISA) for detecting neutralizing antibodies against BoHV-1 was then developed based on 3F8 and protein gD generated using a baculovirus expression system. The sensitivity and specificity of the test were estimated to be 94.59% and 93.42%, respectively. A significant correlation (R2 = 0.9583, p < 0.01) was observed between the results obtained with the blocking ELISA and a virus neutralization test, which suggested that the blocking ELISA could detect neutralizing antibodies against BoHV-1. A serological survey was carried out in the dairy farms in Beijing district using 3F8-based blocking ELISA to monitor the annual neutralization antibody against BoHV-1 during 2012-2020. It revealed that the dairy farms in Beijing were at high risk of BoHV-1 infection during 2012-2017 but were protected since 2018 upon implementation of an immunization program. Our results demonstrated that this assay is suitable for BoHV-1 surveillance and vaccination efficacy in cattle as a replacement for the virus neutralization test. KEY POINTS: • Prevention of BoHV-1 infection requires the monitoring of neutralizing antibodies. • A blocking ELISA for the neutralizing antibody was developed based on mAb 3F8 against BoHV-1 gD. • It can replace the labor-intensive and time-consuming viral neutralizing tests.


Assuntos
Infecções por Herpesviridae , Herpesvirus Bovino 1 , Animais , Bovinos , Anticorpos Neutralizantes , Anticorpos Antivirais , Ensaio de Imunoadsorção Enzimática/métodos , Infecções por Herpesviridae/prevenção & controle , Infecções por Herpesviridae/veterinária , Anticorpos Monoclonais , Vacinação
9.
Macromol Rapid Commun ; 44(1): e2200301, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35748135

RESUMO

Polypeptoids, structural mimics of polypeptides, have attracted considerable attention due to their biocompatibility, proteolytic stability, thermal processability, good solubility, synthetic accessibility, and structural diversity. Polypeptoids have emerged as an interesting material in both polymer science and biological field. This review primarily discusses the research progress of polypeptoids prepared by controlled ring-opening polymerizations in the past decade, including synthetic strategies of monomers, polymerizations by different initiators, postfunctionalization, fundamental properties, crystallization-driven self-assembly, and potential biological applications.


Assuntos
Peptídeos , Polímeros , Polimerização , Peptídeos/química , Polímeros/química , Peptídeo Hidrolases , Cristalização
10.
Front Neurol ; 13: 900997, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36341087

RESUMO

Background and aims: Patients with cirrhosis commonly experience minimal hepatic encephalopathy (MHE), and alterations in neurotransmitters have been thought to be related to cognitive function. However, the relationship between alterations in peripheral and central butyrylcholinesterase (BuChE) with MHE disease progression remains unknown. As such, this study was designed to investigate potential changes in peripheral and central BuChE activity and their effects on cognitive function in the context of MHE. Materials and methods: We enrolled 43 patients with cirrhosis secondary to hepatitis B, 20 without MHE and 23 with MHE, and 25 with healthy controls (HC). All the selected subjects underwent resting-state functional MRI, and the original images were processed to obtain the regional homogeneity (ReHo) brain maps. Thereafter, the correlation of BuChE activity with ReHo, number connection test of type A (NCT-A), and digital symbol test (DST) scores with MHE patients were analyzed using Person correlation analysis. Meanwhile, we purchased 12 Sprague-Dawley (SD) rats and divided them into an experimental group (n = 6) and a control group (n = 6). The rats in the experimental group were intraperitoneally injected with thioacetamide (TAA) to prepare MHE model rats. After modeling, we used the Morris water maze (MWM) and elevated plus maze (EPM) to assess the cognition function and exploratory behavior of all rats. The activity of serum, hippocampus, and frontal lobe tissue BuChE was detected by ELISA. Results: BuChE activity gradually decreased among the HC, patients with cirrhosis, and MHE groups (all P < 0.01). We observed a linear correlation between serum BuChE and NCT-A and DST scores in MHE patients (all P < 0.01). We noted that BuChE activity can negatively correlate with ReHo values in the left middle temporal gyrus and left inferior temporal gyrus, and positively correlate with ReHo values in the right inferior frontal gyrus, and also found that the peripheral BuChE activity of MHE rats was significantly lower than their control counterparts, and the BuChE activity in frontal lobe extracts was significantly higher than the control rats (all P < 0.05). Conclusion: The altered activity of BuChE may contribute to cognitive impairment in MHE patients, which may be a potential biomarker of disease evolution in the context of MHE.

11.
J Am Chem Soc ; 144(46): 21046-21055, 2022 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-36316180

RESUMO

Chemical warfare agents (CWAs) are among the most lethal chemicals known to humans. Thus, developing multifunctional catalysts for highly efficient detoxification of various CWAs is of great importance. In this work, we developed a robust copper tetrazolate metal-organic framework (MOF) catalyst containing a dicopper unit similar to the coordination geometry of the active sites of natural phosphatase and tyrosinase enzymes. This catalyst aided in phosphate ester bond hydrolysis and hydrogen peroxide decomposition, ultimately achieving high detoxification efficiency against both a nerve agent simulant (diethoxy-phosphoryl cyanide (DECP)) with a half-life of 3.5 min and a sulfur mustard simulant (2-chloroethyl ethyl sulfide (CEES)) with a half-life of 4.5 min, making it competitive with other reported materials. The dicopper sites in ZZU-282 provide versatile binding modes with the substrates, thereby promoting the activation of substrates and enhancing the catalytic efficiency. A combination of postmodified metal exchange control experiments, density functional theory calculations, and catalytic evaluations confirmed that dual Cu sites are the active centers promoting the catalytic reaction. This study offers a new design perspective to achieve advanced catalysts for CWA detoxification.


Assuntos
Substâncias para a Guerra Química , Estruturas Metalorgânicas , Humanos , Substâncias para a Guerra Química/química , Cobre , Catálise , Organofosfatos
12.
Brain Res ; 1793: 148041, 2022 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-35944657

RESUMO

BACKGROUND AND AIMS: Minimal hepatic encephalopathy (MHE) is a common neuropsychiatric complication in patients with cirrhosis. Alterations in monoamine neurotransmitters have been associated with the pathogenesis of MHE. We investigated the levels of hippocampal noradrenergic neurotransmitter in a rat model of thioacetamide-induced chronic liver failure-related MHE, and their role in cognitive impairment. MATERIALS: 18 male Sprague-Dawley (SD) rats were equally divided in MHE and control groups. A rat model of MHE was established by intraperitoneal injection of thioacetamide (TAA) for 12 weeks. Cognitive function was assessed using the Morris water maze (MWM) test and locomotor activity and exploratory behavior assessed with open field test. The concentration of hippocampal noradrenaline (NE) was detected by ELISA, and the magnetic susceptibility value in the hippocampus was detected by quantitative susceptibility mapping. Hippocampal iron content was quantified by Prussian blue staining. RESULTS: MHE rats performed significantly poorer than their control counterparts in the MWM test, as seen by decreased number of platform crossings and time in the target quadrant, and increased path length to reach the target zone (P < 0.05 for all parameters). In the open field test, the MHE group exhibited lower locomotor activity and exploratory behavior than the control group (P < 0.05 for all parameters). We detected pronounced iron staining in the hippocampus of MHE rats, whereas no iron-stained particles were found in control rats. We observed an imbalance of inflammatory (increased pro- and decreased anti-) cytokines in the hippocampus of MHE rats. Further analysis of the data showed that the level of hippocampal noradrenaline in MHE rats was significantly lower than that of control rats (P < 0.05). We observed a correlation between the level of inflammatory cytokine and noradrenaline land susceptibility value in the rat hippocampus of the MHE group. CONCLUSION: Our results suggest that MHE associated with TAA-induced chronic liver failure is associated with alterations in noradrenergic neurotransmission. We propose that iron imbalance in the brain might lead to reduction in the levels of noradrenaline, and cognitive impairment.


Assuntos
Disfunção Cognitiva , Doença Hepática Terminal , Encefalopatia Hepática , Animais , Encéfalo/metabolismo , Disfunção Cognitiva/patologia , Citocinas/metabolismo , Doença Hepática Terminal/complicações , Doença Hepática Terminal/patologia , Encefalopatia Hepática/complicações , Encefalopatia Hepática/patologia , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Masculino , Norepinefrina , Ratos , Ratos Sprague-Dawley , Tioacetamida/toxicidade
13.
Front Microbiol ; 13: 973278, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36016774

RESUMO

Bovine herpesvirus 1 (BoHV-1) is an alphaherpesvirus that causes infectious bovine rhinotracheitis and infectious pustular vulvovaginitis in cattle. Ιnterferon-gamma (IFN-γ) is a pleiotropic cytokine with antiviral activity that modulates the innate and adaptive immune responses. In this study, we prepared high-purity bovine interferon gamma (BoIFN-γ) dimer protein using prokaryotic expression system and affinity chromatography. We subsequently investigated the effect of BoIFN-γ on BoHV-1 infection in Madin-Darby bovine kidney (MDBK) cells. The results showed that BoIFN-γ pre-treament not only decreased the production of BoHV-1 but also reduced the cytopathic effect of the virus. Differential gene expression profiles of BoHV-1 infected MDBK cells were then analysed through high-throughput RNA sequencing. The data showed that BoIFN-γ pre-treatment reduced lipid metabolism disorder and DNA damage caused by BoHV-1 infection. Furthermore, BoIFN-γ treatment upregulated the transcription of interferon regulatory transcription factors (IRF1 and GBP5) and interferon-stimulated genes (ISGs) of MDBK cells. Additionally, BoIFN-γ promotes expression of cellular protein involved in complement activation and coagulation cascades response as well as antigen processing and presentation process, while BoHV-1 infection dramatically downregulates transcription of these immune components including C3, C1r, C1s, PLAT, ITGB2, PROCR, BoLA, CD74, B2M, PA28, BoLA-DRA, and TAPBP. Collectively, our findings revealed that BoIFN-γ pre-treatment can improve host resistance to BoHV-1 infection and regulate transcription or expression of host protein associated with cellular metabolism and innate immune response. This provides insights into the development of prophylactic agents for prevention and control of BoHV-1 infection.

15.
Magn Reson Imaging ; 86: 20-27, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34808303

RESUMO

BACKGROUND: To investigate the performance of synthetic relaxometry, three-dimensional pseudo-continuous arterial spin labelling (pCASL) and diffusion-weighted imaging (DWI) in differentiating high-grade gliomas (HGGs) from low-grade gliomas (LGGs) and to compare with the conventional MRI. METHODS: Seventy-two patients with gliomas (including 27 LGGs and 45 HGGs) were studied using synthetic magnetic resonance imaging (sy-MRI), pCASL, and DWI with a 3.0 T MR scanner. T1 relaxometry (T1), T2 relaxometry (T2), as well as proton density (PD) from sy-MRI, cerebral blood flow (CBF) from pCASL, apparent diffusion coefficient (ADC) from DWI and enhancement quality (EQ), proportion enhancing (PE) from conventional contrast enhanced image based Visually-Accessible-Rembrandt-Images (VASARI) scoring system, were all analyzed by two radiologists. The Student's t-test, Mann-Whitney U test or Fisher's exact test was used to compare the parameters between LGGs and HGGs. The diagnostic performance of each parameter and their combination for glioma grading were analyzed. RESULTS: Significant statistical differences in T1, PD, CBF, ADC, EQ and PE are observed between LGGs and HGGs (all P < 0.001). The ADC values have higher discrimination abilities compared with other univariable parameters, with the AUC of 0.905. AUC values for conventional contrast-enhanced method, EQ and PE from VASARI, and conventional contrast-free method, CBF + ADC, are 0.873 and 0.912 respectively. The combined T1, PD, CBF and ADC model had the best performance for differentiating LGGs and HGGs with AUC, sensitivity and specificity of 0.993, 95.5%, 100%, respectively. CONCLUSIONS: Relaxometry parameters derived from synthetic MRI contributed to the discrimination of low-grade gliomas from high-grade gliomas. Proposed contrast-free approach combining T1, PD, CBF and ADC showed a strong discriminative power, and outperformed conventional approaches.


Assuntos
Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Glioma/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Gradação de Tumores , Estudos Retrospectivos , Sensibilidade e Especificidade , Marcadores de Spin
16.
Viruses ; 15(1)2022 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-36680047

RESUMO

Marek's disease virus (MDV) infection results in Marek's disease (MD) in chickens, a lymphoproliferative and oncogenic deadly disease, leading to severe economic losses. The spleen and bursa are the most important lymphoid and major target organs for MDV replication. The immune response elicited by MDV replication in the spleen and bursa is critical for the formation of latent MDV infection and reactivation. However, the mechanism of the host immune response induced by MDV in these key lymphoid organs during the latent and reactivation infection phases is not well understood. In the study, we focused on the replication dynamics of a vaccine MDV strain MDV/CVI988 and a very virulent MDV strain MDV/RB1B in the spleen and bursa in the latent and reactivation infection phases (7-28 days post-inoculation [dpi]), as well as the expression of some previously characterized immune-related molecules. The results showed that the replication ability of MDV/RB1B was significantly stronger than that of MDV/CVI988 within 28 days post-infection, and the replication levels of both MDV strains in the spleen were significantly higher than those in the bursa. During the latent and reactivation phase of MDV infection (7-28 dpi), the transcriptional upregulation of chicken IL-1ß, IL6, IL-8L1 IFN-γ and PML in the spleen and bursa induced by MDV/RB1B infection was overall stronger than that of MDV/CVI988. However, compared to MDV/RB1Binfection, MDV/CVI988 infection resulted in a more effective transcriptional activation of CCL4 in the latent infection phase (7-14 dpi), which may be a characteristic distinguishing MDV vaccine strain from the very virulent strain.


Assuntos
Herpesvirus Galináceo 2 , Infecção Latente , Vacinas contra Doença de Marek , Doença de Marek , Animais , Citocinas , Baço , Galinhas , Vacinas contra Doença de Marek/genética
17.
PLoS Pathog ; 17(4): e1009530, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33909701

RESUMO

Multi-functional DEAD-box helicase 5 (DDX5), which is important in transcriptional regulation, is hijacked by diverse viruses to facilitate viral replication. However, its regulatory effect in antiviral innate immunity remains unclear. We found that DDX5 interacts with the N6-methyladenosine (m6A) writer METTL3 to regulate methylation of mRNA through affecting the m6A writer METTL3-METTL14 heterodimer complex. Meanwhile, DDX5 promoted the m6A modification and nuclear export of transcripts DHX58, p65, and IKKγ by binding conserved UGCUGCAG element in innate response after viral infection. Stable IKKγ and p65 transcripts underwent YTHDF2-dependent mRNA decay, whereas DHX58 translation was promoted, resulting in inhibited antiviral innate response by DDX5 via blocking the p65 pathway and activating the DHX58-TBK1 pathway after infection with RNA virus. Furthermore, we found that DDX5 suppresses antiviral innate immunity in vivo. Our findings reveal that DDX5 serves as a negative regulator of innate immunity by promoting RNA methylation of antiviral transcripts and consequently facilitating viral propagation.


Assuntos
Adenosina/análogos & derivados , RNA Helicases DEAD-box/fisiologia , Evasão da Resposta Imune/genética , Estabilidade de RNA/genética , Viroses , Adenosina/metabolismo , Animais , Células Cultivadas , Embrião de Galinha , Cricetinae , RNA Helicases DEAD-box/genética , Células HEK293 , Humanos , Imunidade Inata/genética , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/genética , NF-kappa B/metabolismo , RNA Helicases/genética , RNA Helicases/metabolismo , RNA Mensageiro/metabolismo , Viroses/genética , Viroses/imunologia , Viroses/metabolismo , Replicação Viral/genética
18.
Dev Comp Immunol ; 119: 104048, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33609615

RESUMO

DEAD-box helicase 5 (DDX5) plays a significant role in tumorigenesis and regulates viral replication of several viruses. An avian oncogenic herpesvirus, Marek's disease virus (MDV), is widely known to cause immunosuppression and lymphoma in chickens. However, the underlying mechanisms of how DDX5 plays a role in viral replication remain unclear. In this study, we show that MDV inhibits the production of interferon beta (IFN-ß) in chicken embryo fibroblasts (CEFs) by increasing the expression level and promoting the nuclear aggregation of DDX5. We further reveal how DDX5 down-regulates melanoma differentiation-associated gene 5/toll-like receptor 3 signaling through the fundamental transcription factor, interferon regulatory factor 1. MDV replication is suppressed, and the production of IFN-ß is promoted in the DDX5 absented CEFs. Taken together, our investigations demonstrate that MDV inhibits IFN-ß production by targeting DDX5-mediated signaling to facilitate viral replication, which offers a novel insight into the mechanism by which an avian oncogenic herpesvirus replicates in chicken cells.


Assuntos
Proteínas Aviárias/imunologia , RNA Helicases DEAD-box/imunologia , Fibroblastos/imunologia , Herpesvirus Galináceo 2/imunologia , Interferon beta/imunologia , Replicação Viral/imunologia , Animais , Proteínas Aviárias/genética , Proteínas Aviárias/metabolismo , Western Blotting , Células Cultivadas , Embrião de Galinha , Galinhas/genética , Galinhas/imunologia , Galinhas/virologia , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Fibroblastos/metabolismo , Fibroblastos/virologia , Regulação da Expressão Gênica/imunologia , Herpesvirus Galináceo 2/fisiologia , Interações Hospedeiro-Patógeno/imunologia , Imunidade Inata/genética , Imunidade Inata/imunologia , Interferon beta/genética , Interferon beta/metabolismo , Doença de Marek/genética , Doença de Marek/imunologia , Doença de Marek/virologia , RNA-Seq/métodos , Transcriptoma/imunologia
19.
J Phys Condens Matter ; 33(1): 015701, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33034303

RESUMO

Chiral interfaces provide a new platform to execute quantum control of light-matter interactions. One phenomenon which has emerged from engineering such nanophotonic interfaces is spin-momentum locking akin to similar reports in electronic topological materials and phases. While there are reports of spin-momentum locking with combination of chiral emitters and/or chiral metamaterials with directional far field excitation it is not readily observable with both achiral emitters and metamaterials. Here, we report the observation of photonic spin-momentum locking in the form of directional and chiral emission from achiral quantum dots (QDs) evanescently coupled to achiral hyperbolic metamaterials (HMM). Efficient coupling between QDs and the metamaterial leads to emergence of these photonic topological modes which can be detected in the far field. We provide theoretical explanation for the emergence of spin-momentum locking through rigorous modeling based on photon Green's function where pseudo spin of light arises from coupling of QDs to evanescent modes of HMM.

20.
PLoS Negl Trop Dis ; 14(12): e0008888, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33373362

RESUMO

Brucella spp. are facultative intracellular pathogens that can persistently colonize host cells and cause the zoonosis- brucellosis. The WHO recommended a treatment for brucellosis that involves a combination of doxycycline, rifampicin, or streptomycin. The aim of this study was to screen rifampicin-resistance related genes by transcriptomic analysis and gene recombination method at low rifampicin concentrations and to predict the major rifampicin- resistance pathways in Brucella spp. The results showed that the MIC value of rifampicin for B. melitensis bv.3 Ether was 0.5 µg / mL. Meanwhile, B. melitensis had an adaptive response to the resistance of low rifampicin in the early stages of growth, while the SNPs changed in the rpoB gene in the late stages of growth when incubated at 37°C with shaking. The transcriptome results of rifampicin induction showed that the functions of significant differentially expressed genes were focused on metabolic process, catalytic activity and membrane and membrane part. The VirB operon, ß-resistance genes, ABC transporters, quorum-sensing genes, DNA repair- and replication -related genes were associated with rifampicin resistance when no variations of the in rpoB were detected. Among the VirB operons, VirB7-11 may play a central role in rifampicin resistance. This study provided new insights for screening rifampicin resistance-related genes and also provided basic data for the prevention and control of rifampicin-resistant Brucella isolates.


Assuntos
Antibióticos Antituberculose/farmacologia , Brucella melitensis/efeitos dos fármacos , Rifampina/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Membrana Celular , RNA Polimerases Dirigidas por DNA/genética , RNA Polimerases Dirigidas por DNA/metabolismo , Farmacorresistência Bacteriana , Regulação Bacteriana da Expressão Gênica , Genoma Bacteriano , Testes de Sensibilidade Microbiana , Rifampina/administração & dosagem
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