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1.
Clin Neurophysiol ; 162: 165-173, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38642482

RESUMO

OBJECTIVE: The current study examined the efficacy of the facial corticobulbar motor evoked potentials (FCoMEPs) and blink reflex (BR) on predicting postoperative facial nerve function during cerebellopontine angle (CPA) tumor surgery. METHODS: Data from 110 patients who underwent CPA tumor resection with intraoperative FCoMEPs and BR monitoring were retrospectively reviewed. The association between the amplitude reduction ratios of FCoMEPs and BR at the end of surgery and postoperative facial nerve function was determined. Subsequently, the optimal threshold of FCoMEPs and BR for predicting postoperative facial nerve dysfunction were determined by receiver operating characteristic curve analysis. RESULTS: Valid BR was record in 103 of 110 patients, whereas only 43 patients successfully recorded FCoMEP in orbicularis oculi muscle. A reduction over 50.3% in FCoMEP (O. oris) amplitude was identified as a predictor of postoperative facial nerve dysfunction (sensitivity, 77.1%; specificity, 83.6%). BR was another independent predictor of postoperative facial nerve deficit with excellent predictive performance, especially eyelid closure function. Its optimal cut-off value for predicting long-term postoperative eyelid closure dysfunction was was 51.0% (sensitivity, 94.4%; specificity, 94.4%). CONCLUSIONS: BR can compensate for the deficiencies of the FCoMEPs. The combination of BR and FCoMEPs can be used in CPA tumor surgery. SIGNIFICANCE: The study first proposed an optimal cut-off value of BR amplitude deterioration (50.0%) for predicting postoperative eyelid closure deficits in patients undergoing CPA tumor surgery.


Assuntos
Piscadela , Potencial Evocado Motor , Humanos , Masculino , Feminino , Piscadela/fisiologia , Pessoa de Meia-Idade , Adulto , Potencial Evocado Motor/fisiologia , Idoso , Estudos Retrospectivos , Nervo Facial/fisiopatologia , Valor Preditivo dos Testes , Ângulo Cerebelopontino/cirurgia , Ângulo Cerebelopontino/fisiopatologia , Adulto Jovem , Neuroma Acústico/cirurgia , Neuroma Acústico/fisiopatologia , Monitorização Neurofisiológica Intraoperatória/métodos , Adolescente , Neoplasias Cerebelares/cirurgia , Neoplasias Cerebelares/fisiopatologia , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/diagnóstico
2.
Spine J ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38679075

RESUMO

BACKGROUND CONTEXT: The primary treatment method for intramedullary spinal cord tumor (IMSCT) is surgical resection, but this procedure carries a significant risk of neurological damage. Intraoperative neurophysiological monitoring (IONM) has become a necessary adjunctive tool for IMSCT resection. PURPOSE: The current study aimed to explore the application value of D-wave monitoring in IMSCT surgery, and tried to investigate a tailored criterion for its early warning. STUDY DESIGN: A retrospective clinical study. PATIENT SAMPLE: A retrospective analysis was conducted based on the data of patients who underwent IMSCT surgeries performed by the same neurosurgical team at our hospital. IONM was applied in all surgeries. According to inclusion and exclusion criteria, ultimately 90 patients were enrolled in the study. OUTCOME MEASURES: The McCormick Scale (MMS) was applied to assess the functional outcome through outpatient visits or telephone follow-up at one month and six months postoperatively. Patients with an MMS grade over II one month after surgery were considered to have newly developed postoperative motor dysfunction (PMD). If the MMS grade could be restored to I or II six months after surgery, it was defined as a short-term PMD. Otherwise, it was defined as a long-term PMD. METHODS: The predictive value of different IONM modalities, including somatosensory evoked potential (SEP), muscle motor evoked potential (MEP), and D-wave for PMD, was assessed with sensitivity, specificity, positive predictive value, negative predictive value, and subsequent logistic regression analysis. At last, the cut-off value of the D-wave amplitude reduction ratio for predicting PMD was obtained through the receiver operating characteristic (ROC) curve analysis. RESULTS: SEP showed the worst performance in predicting short-term and long-term PMD. Significant MEP changes were indicated as an independent predictive factor for short-term PMD (OR 5.062, 95% CI 1.947-13.166, p=.001), while D-wave changes were demonstrated as an independent predictor for long-term PMD (OR 339.433, 95% CI 11.337-10770.311, p=.001). The optimum cut-off value of the D-wave amplitude reduction ratio for predicting long-term PMD was 42.18%, with a sensitivity of 100% and a specificity of 93.8% (AUC=0.981, p<.001). CONCLUSIONS: D-wave monitoring showed extremely high specificity in predicting PMD compared to SEP and MEP monitoring. Moreover, the authors suggested that a D-wave amplitude reduction of over 40% during IMSCT surgery generally indicates long-term PMD for patients.

3.
Transl Oncol ; 44: 101947, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38555740

RESUMO

BACKGROUND: The KCa3.1 channel (KCNN4) is extensively investigated as an oncogene in human cancers. The current study aimed to explore the clinicopathological significance of KCNN4 expression in patients with primary adult-type diffuse gliomas. METHODS: Demographic, RNA-seq, and follow-up data of 477 patients were retrospectively reviewed. Patients were divided into the experimental and validation groups (278 and 199). KCNN4-related genes were determined by Pearson correlation analysis, and enrichment analyses and tumor-infiltrating immune cell assessments were applied to explore the potential mechanisms of KCNN4 involving glioma progression. The Kaplan-Meier method and the Cox regression analysis were used to evaluate the prognostic value of KCNN4 expression. RESULTS: KCNN4 showed significantly higher expression level in glioblastoma, IDH-wildtype, followed by astrocytoma, IDH-mutant and oligodendroglioma, IDH-mutant and 1p/19q-codeleted (p < 0.001). Enrichment analyses and tumor-infiltrating immune cell assessments suggested that KCNN4 could involve glioma progression through extracellular regulation, affecting immune response, and modulating subcellular trafficking. At last, the Kaplan-Meier analysis showed that high KCNN4 expression was significantly correlated with poor progression-free and overall survival (p < 0.001 for both). While multivariate Cox regression analysis obtained an insignificant result. CONCLUSIONS: KCNN4 was identified to be overexpressed in glioma cells and its expression level is positively related to tumor malignancy. It potentially participates in glioma biology by affecting extracellular regulation, subcellular trafficking, and immune escape. Additionally, high KCNN4 expression was correlated with poor survival outcomes of patients. The results can shed new light on the mechanisms of glioma progression, and provide a potential therapeutic target for treating gliomas.

4.
J Neurosurg ; : 1-6, 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37948695

RESUMO

OBJECTIVE: Postoperative visual outcome is a major concern of neurosurgeons for patients with craniopharyngiomas. The current study aimed to investigate the value of visual evoked potential (VEP) amplitude reduction (N75-P100 and P100-N145) for predicting postoperative visual dysfunction (POVD) and refining current warning criteria for VEP monitoring. METHODS: Data from 96 patients who underwent the extended endoscopic endonasal approach for craniopharyngiomas between October 2020 and November 2021 were retrospectively reviewed. VEP amplitude reduction ratios were calculated and compared between patients with POVD and those without. Subsequently, the critical threshold values of VEP amplitude reduction ratios for predicting POVD were obtained through receiver operating characteristic curve analysis. Finally, multivariate binary logistic regression analysis was applied to evaluate the effect of potential factors on the probability of experiencing POVD. RESULTS: Both N75-P100 and P100-N145 amplitude reduction ratios were significantly higher in patients with POVD (p < 0.001 for both). The threshold value of the N75-P100 amplitude reduction ratio for predicting POVD was 51.76% with an area under the curve (AUC) of 0.816 (p < 0.001), while the threshold value of the P100-N145 amplitude reduction ratio was 38.80% with an AUC of 0.738 (p < 0.001). Both N75-P100 and P100-N145 amplitude reduction ratios were identified as independent predictors for POVD via multivariate analysis (p < 0.001 and p = 0.018, respectively). CONCLUSIONS: Both N75-P100 and P100-N145 amplitude reduction ratios showed great potential to be indicators for POVD in patients with craniopharyngiomas. Regarding warning criteria for VEP monitoring, the authors recommend that both N75-P100 and P100-N145 amplitude reduction should be considered, with early warning criteria of a 50% reduction for N75-P100 amplitude and/or a 40% reduction for P100-N145 amplitude.

5.
J Clin Neurophysiol ; 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37797240

RESUMO

PURPOSE: Motor evoked potential (MEP) monitoring has been widely applied in various neurosurgical operations. This study aimed to assess the predictive value of MEP monitoring for postoperative motor deficit (PMD) in patients with insular gliomas. METHODS: Demographic and clinical data, MEP monitoring data, and follow-up data of 42 insular glioma patients were retrospectively reviewed, and 40 patients were finally enrolled. The value of MEP monitoring for predicting PMD was assessed with sensitivity, specificity, and false-positive/false-negative rates. Binary multivariate logistic regression analysis was performed to further identify the predictive value of MEP monitoring. RESULTS: Statistical analysis showed that irreversible MEP changes, but not all MEP changes, were more effective in predicting PMD. The sensitivity and specificity of irreversible MEP changes for predicting long-term PMD were 85.71 and 93.94%, whereas the false-positive and -negative rates were 25.00 and 3.12% respectively. In addition, irreversible MEP changes were identified as the only independent predictor for long-term PMD (odds ratio, 101.714; 95% confidence interval, 6.001-1724.122; p = 0.001). CONCLUSIONS: MEP monitoring has been proven to be feasible in insular glioma surgery. Irreversible MEP changes showed good performance in predicting PMD. Their absence can offer an optimistic expectation for the long-term motor outcome. The findings can provide the surgical team with a more effective interpretation of MEP changes and contribute to exploring tailored MEP warning criteria.

6.
Clin Neurol Neurosurg ; 232: 107865, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37480785

RESUMO

OBJECTIVE: To analyze the associated factors with stimulation-induced seizures (SIS) and the relevant factors in predicting surgical outcomes. METHODS: We analyzed 80 consecutive epilepsy patients explored by stereo-electroencephalography with routine electrical stimulation mapping (ESM). If seizures induced by ESM, patients were classified as SIS-positive (SIS-P); otherwise, SIS-negative (SIS-N). Patients received radical surgery were further classified as favorable (Engel I) and unfavorable (Engel II-IV) groups. RESULTS: Of the 80 patients included, we identified 44 (55.0%) and 36(45.0%) patients in the SIS-P and SIS-N groups, respectively. Multivariate analysis revealed that the seizure onset pattern (SOP) of preceding repetitive epileptiform discharges following LVFA (PRED→LVFA) (OR 3.319, 95% CI 1.200-9.183, P = 0.021) and pathology of focal cortical dysplasia (FCD) type II (OR 3.943, 95% CI 1.093-14.226, P = 0.036) were independent factors influencing whether the electrical stimulation can induce a seizure. Among the patients received radical surgery, there were 55 and 15 patients in the favorable and unfavorable groups separately. Multivariate analysis revealed that the SOP of PRED→LVFA induced seizures by stimulation (OR 11.409, 95% CI 1.182-110.161, P = 0.035) and bilateral implantation (OR 0.048, 95% CI 0.005-0.497, P = 0.011) were independent factors affecting surgical outcomes. The previous epilepsy surgery had a trend to be a negative factor with SIS (OR 0.156, 95% CI 0.028-0.880, P = 0.035) and surgical outcomes (OR 0.253, 95% CI 0.053-1.219, P = 0.087). CONCLUSION: ESM is a highly valuable method for localizing the seizure onset zone. The SOP of PRED→LVFA and FCD type II were associated with elicitation of SIS by ESM, whereas a previous epilepsy surgery showed a negative association. Furthermore, the SOP of PRED→LVFA together with SIS in the same patient predicted favorable surgical outcomes, whereas bilateral electrode implantation predicted unfavorable outcomes.


Assuntos
Líquidos Corporais , Convulsões , Humanos , Convulsões/cirurgia , Estimulação Elétrica , Resultado do Tratamento
7.
PLoS Pathog ; 19(4): e1011301, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37011127

RESUMO

Cereal yellow dwarf virus (CYDV-RPV) encodes a P0 protein that functions as a viral suppressor of RNA silencing (VSR). The strength of silencing suppression is highly variable among CYDV-RPV isolates. In this study, comparison of the P0 sequences of CYDV-RPV isolates and mutational analysis identified a single C-terminal amino acid that influenced P0 RNA-silencing suppressor activity. A serine at position 247 was associated with strong suppressor activity, whereas a proline at position 247 was associated with weak suppressor activity. Amino acid changes at position 247 did not affect the interaction of P0 with SKP1 proteins from Hordeum vulgare (barley) or Nicotiana benthamiana. Subsequent studies found P0 proteins containing a P247 residue were less stable than the P0 proteins containing an S247 residue. Higher temperatures contributed to the lower stability and in planta and the P247 P0 proteins were subject to degradation via the autophagy-mediated pathway. A P247S amino acid residue substitution in P0 increased CYDV-RPV replication after expression in agroinfiltrated plant leaves and increased viral pathogenicity of P0 generated from the heterologous Potato virus X expression vector system. Moreover, an S247 CYDV-RPV could outcompete the P247 CYDV-RPV in a mixed infection in natural host at higher temperature. These traits contributed to increased transmission by aphid vectors and could play a significant role in virus competition in warming climates. Our findings underscore the capacity of a plant RNA virus to adapt to climate warming through minor genetic changes in gene-silencing suppressor, resulting in the potential for disease persistence and prevalence.


Assuntos
Luteoviridae , Vírus de Plantas , Luteoviridae/genética , Luteoviridae/metabolismo , Aminoácidos/metabolismo , Inativação Gênica , Vírus de Plantas/genética , Vírus de Plantas/metabolismo , Interferência de RNA , Doenças das Plantas/genética , Nicotiana
8.
Viruses ; 14(8)2022 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-36016426

RESUMO

The selection of resistant crops is an effective method for controlling geminivirus diseases. ty-5 encodes a messenger RNA surveillance factor Pelota with a single amino acid mutation (PelotaV16G), which confers effective resistance to tomato yellow leaf curl virus (TYLCV). No studies have investigated whether ty-5 confers resistance to other geminiviruses. Here, we demonstrate that the tomato ty-5 line exhibits effective resistance to various geminiviruses. It confers resistance to two representative begomoviruses, tomato yellow leaf curl China virus/tomato yellow leaf curl China betasatellite complex and tomato leaf curl Yunnan virus. The ty-5 line also exhibits partial resistance to a curtovirus beet curly top virus. Importantly, ty-5 confers resistance to TYLCV with a betasatellite. Southern blotting and quantitative polymerase chain reaction analyses showed that significantly less DNA of these geminiviruses accumulated in the ty-5 line than in the susceptible line. Moreover, knockdown of Pelota expression converted a Nicotiana benthamiana plant from a geminivirus-susceptible host to a geminivirus-resistant host. Overall, our findings suggest that ty-5 is an important resistance gene resource for crop breeding to control geminiviruses.


Assuntos
Begomovirus , Geminiviridae , Solanum lycopersicum , Begomovirus/genética , China , Geminiviridae/genética , Melhoramento Vegetal , Doenças das Plantas/genética
9.
Int J Mol Sci ; 23(10)2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35628524

RESUMO

2-Amino-3-methylhexanoic acid (AMHA) was synthetized as a non-natural amino acid more than 70 years ago; however, its possible function as an inducer of plant resistance has not been reported. Plant resistance inducers, also known as plant elicitors, are becoming a novel and important development direction in crop protection and pest management. We found that free AMHA accumulated in the mycelia but not in fermentation broths of four fungal species, Magnaporthe oryzae and three Alternaria spp. We unequivocally confirmed that AMHA is a naturally occurring endogenous (2S, 3S)-α-amino acid, based on isolation, purification and structural analyses. Further experiments demonstrated that AMHA has potent activity-enhancing resistance against extreme temperature stresses in several plant species. It is also highly active against fungal, bacterial and viral diseases by inducing plant resistance. AMHA pretreatment strongly protected wheat against powdery mildew, Arabidopsis against Pseudomonas syringae DC3000 and tobacco against Tomato spotted wilt virus. AMHA exhibits a great potential to become a unique natural elicitor protecting plants against biotic and abiotic stresses.


Assuntos
Arabidopsis , Regulação da Expressão Gênica de Plantas , Aminoácidos/metabolismo , Arabidopsis/metabolismo , Norleucina/análogos & derivados , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Temperatura
10.
Mol Plant Pathol ; 23(5): 622-633, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34962031

RESUMO

Sw-5b is an effective resistance gene used widely in tomato to control tomato spotted wilt virus (TSWV), which causes severe losses in crops worldwide. Sw-5b confers resistance by recognizing a 21-amino-acid peptide region of the viral movement protein NSm (NSm21, amino acids 115-135). However, C118Y or T120N mutation within this peptide region of NSm has given rise to field resistance-breaking (RB) TSWV isolates. To investigate the potential ability of TSWV to break Sw-5b-mediated resistance, we mutagenized each amino acid on NSm21 and determined which amino acid mutations would evade Sw-5b recognition. Among all alanine-scan mutants, NSmP119A , NSmW121A , NSmD122A , NSmR124A , and NSmQ126A failed to induce a hypersensitive response (HR) when coexpressed with Sw-5b in Nicotiana benthamiana leaves. TSWV with the NSmP119A , NSmW121A , or NSmQ126A mutation was defective in viral cell-to-cell movement and systemic infection, while TSWV carrying the NSmD122A or NSmR124A mutation was not only able to infect wild-type N. benthamiana plants systemically but also able to break Sw-5b-mediated resistance and establish systemic infection on Sw-5b-transgenic N. benthamiana plants. Two improved mutants, Sw-5bL33P/K319E/R927A and Sw-5bL33P/K319E/R927Q , which we recently engineered and which provide effective resistance against field RB isolates carrying NSmC118Y or NSmT120N mutations, recognized all NSm21 alanine-substitution mutants and conferred effective resistance against new experimental RB TSWV with the NSmD122A or NSmR124A mutation. Collectively, we determined the key residues of NSm for Sw-5b recognition, investigated their potential RB ability, and demonstrated that the improved Sw-5b mutants could provide effective resistance to both field and potential RB TSWV isolates.


Assuntos
Solanum lycopersicum , Tospovirus , Alanina/genética , Alanina/metabolismo , Aminoácidos/metabolismo , Resistência à Doença/genética , Solanum lycopersicum/metabolismo , Peptídeos/metabolismo , Doenças das Plantas/genética , Proteínas do Movimento Viral em Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Tospovirus/fisiologia
11.
Front Neurol ; 12: 753902, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34925215

RESUMO

Background: The current study aimed to investigate the predictive value of visual-evoked potential (VEP) latency for post-operative visual deterioration in patients undergoing craniopharyngioma resection via extended endoscopic endonasal approach (EEEA). Methods: Data from 90 patients who underwent craniopharyngioma resection via EEEA with intraoperative VEP monitoring were retrospectively reviewed. P100 latency was compared between patients with and without post-operative visual deterioration, and the threshold value of P100 latency for predicting post-operative visual deterioration was calculated by the receiver operating characteristic curve analysis. In addition, other potential prognostic factors regarding post-operative visual outcomes were also analyzed by multivariate analysis. Results: Patients with post-operative visual deterioration showed a significantly longer VEP latency than those without (p < 0.001). An extension over 8.61% in VEP latency was identified as a predictor of post-operative visual deterioration (p < 0.001). By contrast, longer preoperative visual impairment duration and larger tumor volume were not significant predictors for post-operative visual deterioration. Conclusions: The current study revealed that intraoperative VEP monitoring in EEEA is effective for predicting post-operative visual deterioration, and an extension over 8.61% in VEP latency can be used as a critical cut-off value to predict post-operative visual deterioration.

12.
Viruses ; 13(8)2021 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-34452313

RESUMO

The tomato Sw-5b gene confers resistance to tomato spotted wilt virus (TSWV) and encodes a nucleotide-binding leucine-rich repeat (NLR) protein with an N-terminal Solanaceae-specific domain (SD). Although our understanding of how Sw-5b recognizes the viral NSm elicitor has increased significantly, the process by which Sw-5b activates downstream defense signaling remains to be elucidated. In this study, we used a tobacco rattle virus (TRV)-based virus-induced gene silencing (VIGS) system to investigate the roles of the SGT1/RAR1, EDS1/NDR1, NPR1, and NRC/ADR1/NRG1 genes in the Sw-5b-mediated signaling pathway. We found that chaperone SGT1 was required for Sw-5b function, but co-chaperone RAR1 was not. Sw-5b-mediated immune signaling was independent of both EDS1 and NDR1. Silencing NPR1, which is a central component in SA signaling, did not result in TSWV systemic infection in Sw-5b-transgenic N. benthamiana plants. Helper NLR NRCs (NLRs required for cell death) were required for Sw-5b-mediated systemic resistance to TSWV infection. Suppression of NRC2/3/4 compromised the Sw-5b resistance. However, the helper NLRs ADR1 and NRG1 may not participate in the Sw-5b signaling pathway. Silencing ADR1, NRG1, or both genes did not affect Sw-5b-mediated resistance to TSWV. Our findings provide new insight into the requirement for conserved key components in Sw-5b-mediated signaling pathways.


Assuntos
Resistência à Doença/genética , Proteínas de Plantas/genética , Transdução de Sinais/genética , Solanum lycopersicum/virologia , Tospovirus/genética , Inativação Gênica , Imunidade Inata , Solanum lycopersicum/imunologia , Doenças das Plantas/virologia , Imunidade Vegetal/genética , Proteínas de Plantas/classificação , Proteínas de Plantas/imunologia , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/virologia , Domínios Proteicos , Transdução de Sinais/imunologia , Tospovirus/metabolismo
13.
PLoS Pathog ; 17(7): e1009757, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34320034

RESUMO

Antiviral RNA silencing/interference (RNAi) of negative-strand (-) RNA plant viruses (NSVs) has been studied less than for single-stranded, positive-sense (+)RNA plant viruses. From the latter, genomic and subgenomic mRNA molecules are targeted by RNAi. However, genomic RNA strands from plant NSVs are generally wrapped tightly within viral nucleocapsid (N) protein to form ribonucleoproteins (RNPs), the core unit for viral replication, transcription and movement. In this study, the targeting of the NSV tospoviral genomic RNA and mRNA molecules by antiviral RNA-induced silencing complexes (RISC) was investigated, in vitro and in planta. RISC fractions isolated from tospovirus-infected N. benthamiana plants specifically cleaved naked, purified tospoviral genomic RNAs in vitro, but not genomic RNAs complexed with viral N protein. In planta RISC complexes, activated by a tobacco rattle virus (TRV) carrying tospovirus NSs or Gn gene fragments, mainly targeted the corresponding viral mRNAs and hardly genomic (viral and viral-complementary strands) RNA assembled into RNPs. In contrast, for the (+)ssRNA cucumber mosaic virus (CMV), RISC complexes, activated by TRV carrying CMV 2a or 2b gene fragments, targeted CMV genomic RNA. Altogether, the results indicated that antiviral RNAi primarily targets tospoviral mRNAs whilst their genomic RNA is well protected in RNPs against RISC-mediated cleavage. Considering the important role of RNPs in the replication cycle of all NSVs, the findings made in this study are likely applicable to all viruses belonging to this group.


Assuntos
Imunidade Vegetal/imunologia , RNA Viral/imunologia , Complexo de Inativação Induzido por RNA/imunologia , Tospovirus/imunologia , RNA Mensageiro/imunologia , Nicotiana/virologia
14.
J Virol ; 95(14): e0058921, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-33952642

RESUMO

Negative-stranded RNA (NSR) viruses include both animal- and plant-infecting viruses that often cause serious diseases in humans and livestock and in agronomic crops. Rice stripe tenuivirus (RSV), a plant NSR virus with four negative-stranded/ambisense RNA segments, is one of the most destructive rice pathogens in many Asian countries. Due to the lack of a reliable reverse-genetics technology, molecular studies of RSV gene functions and its interaction with host plants are severely hampered. To overcome this obstacle, we developed a mini-replicon-based reverse-genetics system for RSV gene functional analysis in Nicotiana benthamiana. We first developed a mini-replicon system expressing an RSV genomic RNA3 enhanced green fluorescent protein (eGFP) reporter [MR3(-)eGFP], a nucleocapsid (NP), and a codon usage-optimized RNA-dependent RNA polymerase (RdRpopt). Using this mini-replicon system, we determined that RSV NP and RdRpopt are indispensable for the eGFP expression from MR3(-)eGFP. The expression of eGFP from MR3(-)eGFP can be significantly enhanced in the presence of four viral suppressors of RNA silencing (VSRs), NSs, and P19-HcPro-γb. In addition, NSvc4, the movement protein of RSV, facilitated eGFP trafficking between cells. We also developed an antigenomic RNA3-based replicon in N. benthamiana. However, we found that the RSV NS3 coding sequence acts as a cis element to regulate viral RNA expression. Finally, we made mini-replicons representing all four RSV genomic RNAs. This is the first mini-replicon-based reverse-genetics system for monocot-infecting tenuivirus. We believe that the mini-replicon system described here will allow studies of the RSV replication, transcription, cell-to-cell movement, and host machinery underpinning RSV infection in plants. IMPORTANCE Plant-infecting segmented negative-stranded RNA (NSR) viruses are grouped into three genera: Orthotospovirus, Tenuivirus, and Emaravirus. Reverse-genetics systems have been established for members of the genera Orthotospovirus and Emaravirus. However, there is still no reverse-genetics system available for Tenuivirus. Rice stripe virus (RSV) is a monocot-infecting tenuivirus with four negative-stranded/ambisense RNA segments. It is one of the most destructive rice pathogens and causes significant damage to the rice industry in Asian countries. Due to the lack of a reliable reverse-genetics system, molecular characterizations of RSV gene functions and the host machinery underpinning RSV infection in plants are extremely difficult. To overcome this obstacle, we developed a mini-replicon-based reverse-genetics system for RSV in Nicotiana benthamiana. This is the first mini-replicon-based reverse-genetics system for tenuivirus. We consider that this system will provide researchers a new working platform to elucidate the molecular mechanisms dictating segmented tenuivirus infections in plants.


Assuntos
Genes Fúngicos/fisiologia , Nicotiana/virologia , Replicon , Genética Reversa , Tenuivirus/genética , Regulação Viral da Expressão Gênica , Genes Reporter , Proteínas de Fluorescência Verde/genética , Movimento , Nucleocapsídeo/genética , Interferência de RNA , Proteínas não Estruturais Virais/genética
15.
Neurosurg Rev ; 44(1): 495-501, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31965363

RESUMO

To explore the relationship between postoperative motor deficits and the duration of reduced motor-evoked potentials (MEPs) in patients with middle cerebral artery (MCA) aneurysm. This study included 285 cases of MCA aneurysm treated with clipping surgery with MEP monitoring. The effects of MEP changes on postoperative motor function were assessed, and the key time point for minimizing the incidence of postoperative motor dysfunction was found through receiver operating characteristic (ROC) curve analysis. Motor dysfunction was significantly associated with the occurrence of MEP changes, and patients with irreversible changes were more likely to suffer motor dysfunction than were those with reversible changes. The critical duration of MEP changes that minimized the risk of postoperative motor dysfunction was 8.5 min. This study revealed that MEP monitoring is an effective method for preventing ischemic brain injury during surgical treatment of MCA aneurysm and proposes a critical cutoff for the duration of MEP deterioration of 8.5 min for predicting postoperative motor dysfunction.


Assuntos
Potencial Evocado Motor/fisiologia , Aneurisma Intracraniano/fisiopatologia , Aneurisma Intracraniano/cirurgia , Monitorização Neurofisiológica Intraoperatória , Transtornos Motores/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Fatores de Tempo , Adulto Jovem
16.
Front Hum Neurosci ; 14: 186, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32581741

RESUMO

BACKGROUND: High-frequency oscillation (HFO) represents a promising biomarker of epileptogenicity. However, the significant interindividual differences among patients limit its application in clinical practice. Here, we applied and evaluated an individualized, frequency-based approach of HFO analysis in stereoelectroencephalography (SEEG) data for localizing the epileptogenic zones (EZs). METHODS: Clinical and SEEG data of 19 patients with drug-resistant focal epilepsy were retrospectively analyzed. The individualized spectral power of all signals recorded by electrode array, i.e., the relative strength of HFO, was computed with a wavelet method for each patient. Subsequently, the clinical value of the relative strength of HFO for identifying the EZ was evaluated. RESULTS: Focal increase in the relative strength of HFO in SEEG recordings were identified in all 19 patients. HFOs identified inside the clinically identified seizure onset zone had more spectral power than those identified outside (p < 0.001), and HFOs in 250-500 Hz band (fast ripples) seemed to be more specific identifying the EZ than in those in 80-250 Hz band (ripples) (p < 0.01). The resection of brain regions generating HFOs resulted in a favorable seizure outcome in 17 patients (17/19; 89.5%), while in the cases of other patients with poor outcomes, the brain regions generating HFOs were not removed completely. CONCLUSION: The relative strength of HFO, especially fast ripples, is a promising effective biomarker for identifying the EZ and can lead to a favorable seizure outcome if used to guide epilepsy surgery.

17.
Neurosurg Rev ; 43(1): 293-299, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30635746

RESUMO

Although the application of somatosensory evoked potential (SSEP) in intracranial aneurysm surgery has been well demonstrated, the relationship between the duration of SSEP deterioration and postoperative neurological deficits (PNDs) is still not clear. The objectives of this study were (1) to detect the relationship between the SSEP deterioration duration and PND; and (2) detect the relationship between SSEP deterioration duration and postoperative computed tomography (CT) findings. Data from 587 patients were reviewed and 40 patients with SSEP deterioration were enrolled. Four patients presented irreversible disappearance and 36 patients presented reversible deterioration (including 9 [25%] patients with reversible reduction and 27 [75%] patients with reversible disappearance). In the patients with reversible SSEP deterioration, 17 patients had PNDs, and the SSEP deterioration duration was 42 ± 46 min, ranging from 5 to 180 min. Nineteen patients did not have PNDs, and their duration of SSEP deterioration was 11 ± 9 min (range 2-40 min). The SSEP deterioration duration significantly differed between patients with or without PND (P < 0.01). Eleven minutes is the optimal cut-off value of motor evoked potential change duration avoiding PND (area under the curve = 0.84). Patients with a SSEP deteriorating duration > 11 min had a significant higher incidence rate of abnormal CT finding postoperatively (p < 0.05). According to these results, we conclude that the duration of SSEP deterioration is extremely important to postoperative neurological function, and in order to avoid PND, the SSEP deterioration duration must not exceed 10 min. The SSEP deterioration duration is also associated with postoperative CT findings.


Assuntos
Potencial Evocado Motor/fisiologia , Potenciais Somatossensoriais Evocados/fisiologia , Aneurisma Intracraniano/fisiopatologia , Aneurisma Intracraniano/cirurgia , Complicações Pós-Operatórias/etiologia , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Adolescente , Adulto , Idoso , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico , Monitorização Neurofisiológica Intraoperatória , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto Jovem
18.
Proc Natl Acad Sci U S A ; 117(2): 1181-1190, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31879355

RESUMO

Negative-stranded/ambisense RNA viruses (NSVs) include not only dangerous pathogens of medical importance but also serious plant pathogens of agronomic importance. Tomato spotted wilt virus (TSWV) is one of the most important plant NSVs, infecting more than 1,000 plant species, and poses major threats to global food security. The segmented negative-stranded/ambisense RNA genomes of TSWV, however, have been a major obstacle to molecular genetic manipulation. In this study, we report the complete recovery of infectious TSWV entirely from complementary DNA (cDNA) clones. First, a replication- and transcription-competent minigenome replication system was established based on 35S-driven constructs of the S(-)-genomic (g) or S(+)-antigenomic (ag) RNA template, flanked by the 5' hammerhead and 3' ribozyme sequence of hepatitis delta virus, a nucleocapsid (N) protein gene and codon-optimized viral RNA-dependent RNA polymerase (RdRp) gene. Next, a movement-competent minigenome replication system was developed based on M(-)-gRNA, which was able to complement cell-to-cell and systemic movement of reconstituted ribonucleoprotein complexes (RNPs) of S RNA replicon. Finally, infectious TSWV and derivatives carrying eGFP reporters were rescued in planta via simultaneous expression of full-length cDNA constructs coding for S(+)-agRNA, M(-)-gRNA, and L(+)-agRNA in which the glycoprotein gene sequence of M(-)-gRNA was optimized. Viral rescue occurred with the addition of various RNAi suppressors including P19, HcPro, and γb, but TSWV NSs interfered with the rescue of genomic RNA. This reverse genetics system for TSWV now allows detailed molecular genetic analysis of all aspects of viral infection cycle and pathogenicity.


Assuntos
DNA Complementar/genética , Tospovirus/genética , Tospovirus/fisiologia , Tospovirus/patogenicidade , RNA Polimerases Dirigidas por DNA/genética , Vírus Delta da Hepatite/genética , Proteínas do Nucleocapsídeo/genética , Doenças das Plantas/virologia , RNA Catalítico/genética , RNA Viral/genética , Replicon , Nicotiana/virologia , Proteínas Virais/genética , Vírion/genética , Vírion/metabolismo , Replicação Viral
19.
Clin Neurophysiol ; 130(5): 707-713, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30878764

RESUMO

OBJECTIVE: The study aimed to investigate the predictive value of motor evoked potential (MEP) deterioration duration for postoperative motor deficits in patients undergoing intracranial aneurysm surgery. METHODS: Data from 587 patients were reviewed and 92 patients with MEP deterioration were enrolled. MEP deterioration duration was compared between patients with and without postoperative motor deficits. Receiver operating characteristic (ROC) curve analysis was performed to define the threshold value for predicting postoperative motor deficit risk. Additionally, the association between MEP deterioration duration and postoperative CT findings was explored. RESULTS: Patients with postoperative motor deficits had a significantly longer MEP deterioration duration (p < 0.01). An MEP deterioration duration greater than or equal to 13 min was identified as an independent predictor of immediate (p < 0.01), short-term (p < 0.01), and long-term postoperative motor deficits (p < 0.05). There was no significant association between MEP deterioration duration and new CT abnormalities. CONCLUSION: MEP deterioration duration could be used for predicting intracranial aneurysm surgical outcome. SIGNIFICANCE: The study first proposed a threshold value of MEP deterioration duration (13 min) for predicting the risk of postoperative motor deficits in patients undergoing intracranial aneurysm surgery.


Assuntos
Potencial Evocado Motor/fisiologia , Aneurisma Intracraniano/cirurgia , Procedimentos Neurocirúrgicos/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Adolescente , Adulto , Idoso , Feminino , Humanos , Aneurisma Intracraniano/fisiopatologia , Monitorização Neurofisiológica Intraoperatória , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/fisiopatologia , Período Pós-Operatório , Valor Preditivo dos Testes , Adulto Jovem
20.
Viruses ; 10(11)2018 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-30469406

RESUMO

Tomato spotted wilt virus (TSWV) is one of the most destructive viral pathogens of plants. Recently, a single dominant gene conferring complete resistance to TSWV (RTSW) was identified in Nicotina alata and introgressed into cultivated tobacco (N. tabacum). However, whether the TSWV carries an avirulence (Avr) factor directed against RTSW remains obscure. In the present study, we identified the non-structural protein (NSm), the movement protein of TSWV, which is an RTSW-specific Avr factor, by using two different transient expression systems. Using amino acid (aa) substitution mutants, we demonstrated the ability to induce RTSW-mediated hypersensitive response (HR) of NSm is independent of its movement function. Moreover, key substitutions (C118Y and T120N), a 21-aa viral effector epitope, and different truncated versions of NSm, which are responsible for the recognition of the Sw-5b resistance gene of tomato, were tested for their ability to trigger HR to TSWV in tobacco. Together, our results demonstrated that RTSW-mediated resistance is triggered by NSm in the same way as by Sw-5b, however, via different elicitor active sites. Finally, an Avr gene-based diagnostic approach was established and used to determine the presence and effectiveness of resistance genes in tobacco.


Assuntos
Nicotiana/virologia , Proteínas do Movimento Viral em Plantas/metabolismo , Solanum lycopersicum/virologia , Tospovirus/imunologia , Proteínas não Estruturais Virais/metabolismo , Fatores de Virulência/metabolismo , Substituição de Aminoácidos , Análise Mutacional de DNA , Resistência à Doença , Solanum lycopersicum/imunologia , Proteínas do Movimento Viral em Plantas/genética , Nicotiana/imunologia , Tospovirus/crescimento & desenvolvimento , Proteínas não Estruturais Virais/genética , Fatores de Virulência/genética
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