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1.
Hereditas ; 161(1): 26, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39192352

RESUMO

OBJECTIVE: Non-small cell lung cancer (NSCLC) patients undergoing chemotherapy and immunotherapy experience disturbances in the gut microbiota. This study intends to find out the correlation between gut microbiota and clinical indices before and after radiotherapy for NSCLC. METHODS: Ten patients with primary NSCLC were screened, and plasma and fecal samples were collected before and after radiotherapy, respectively. Inflammatory indices in plasma were detected. Genomic DNA was extracted from fecal specimens and sequenced on on Illumina HiSeq2000 sequencing platform. Thee sequenced data were subjected to Metagenome assembly, gene prediction, species annotation, and gene function analysis to study and analyze gut microbiota and metabolic functions. The correlation between the diversity of gut microbiota and the clinical indicators of NSCLC patients was evaluated, and the changes of gut microbiota before and after radiotherapy were observed. RESULTS: The diversity of gut microbiota in NSCLC patients did not correlate with smoking, pathology, and inflammatory markers. The abundance of phylum (p)_Bacteroidetes increased; p_Firmicutes and p_Bacteroidetes accounted for the highest proportion in NSCLC patients, and the abundance of both was dominantly exchanged after radiotherapy. There was a decrease in genus (g)_Bifidobacterium after radiotherapy in NSCLC patients. There was no significant correlation between the diversity of gut microbiota after radiotherapy and radiotherapy sensitivity, and the structural composition and abundance of gut microbiota remained stable. CONCLUSION: The diversity of gut microbiota is altered after radiotherapy in NSCLC patients, showing an increase in harmful bacteria and a decrease in beneficial bacteria.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Microbioma Gastrointestinal , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/microbiologia , Masculino , Pessoa de Meia-Idade , Feminino , Fezes/microbiologia , Idoso , Metagenoma , Metagenômica/métodos , Bactérias/genética , Bactérias/classificação
2.
Cancer Sci ; 114(2): 619-629, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36221784

RESUMO

Vimentin expression in tumor tissues and the tumor-stroma ratio (TSR) have been demonstrated as strong prognostic factors for cancer patients, but whether they are predictive markers of neoadjuvant chemoradiotherapy (nCRT) outcome in locally advanced rectal cancer (LARC) patients is poorly understood. This study aimed to explore the predictive significance of vimentin and TSR combined for nCRT response in LARC patients. Imaging mass cytometry (IMC) was performed to determine the association of vimentin and TSR with nCRT response in six LARC patients [three achieved pathological complete response (pCR), three did not]. Immunohistochemistry (IHC) for vimentin and TSR on biopsy tissues before nCRT and logistic regression analysis were performed to further evaluate their predictive value for treatment responses in a larger patient cohort. A trend of decreased vimentin expression and increased TSR in the pCR group was revealed by IMC. In the validation group, vimentin [odds ratio (OR) 0.260, 95% confidence interval (CI) 0.102-0.602, p = 0.002] and TSR (OR 4.971, 95% CI 1.933-15.431, p = 0.002) were associated with pCR by univariate analysis. Patients in the vimentin-low/TSR-low or vimentin-high/TSR-high (OR 5.211, 95% CI 1.248-35.582, p = 0.042) and vimentin-low/TSR-high groups (OR 11.846, 95% CI 3.197-77.079, p = 0.001) had significantly higher odds of pCR. By multivariate analysis, only the combination of vimentin and TSR was an independent predictor for nCRT response (OR 9.324, 95% CI 2.290-63.623, p = 0.006). Our study suggested that the combined assessment of vimentin and TSR can provide additive significance and may be a promising indicator of nCRT response in LARC patients.


Assuntos
Segunda Neoplasia Primária , Neoplasias Retais , Humanos , Neoplasias Retais/patologia , Terapia Neoadjuvante , Vimentina , Quimiorradioterapia/métodos , Reto/patologia , Estudos Retrospectivos
3.
Int J Mol Sci ; 24(7)2023 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-37047211

RESUMO

E3 ubiquitin ligases play important roles in plant immunity, but their role in soybean has not been investigated previously. Here, we used Bean pod mottle virus (BPMV)-mediated virus-induced gene silencing (VIGS) to investigate the function of GmSAUL1 (Senescence-Associated E3 Ubiquitin Ligase 1) homologs in soybean. When two closely related SAUL1 homologs were silenced simultaneously, the soybean plants displayed autoimmune phenotypes, which were significantly alleviated by high temperature, suggesting that GmSAUL1a/1b might be guarded by an R protein. Interestingly, silencing GmSAUL1a/1b resulted in the decreased activation of GmMPK6, but increased activation of GmMPK3 in response to flg22, suggesting that the activation of GmMPK3 is most likely responsible for the activated immunity observed in the GmSAUL1a/1b-silenced plants. Furthermore, we provided evidence that GmSAUL1a is a bona fide E3 ligase. Collectively, our results indicated that GmSAUL1 plays a negative role in regulating cell death and immunity in soybean.


Assuntos
Glycine max , Ubiquitina-Proteína Ligases , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Glycine max/fisiologia , Fenótipo , Imunidade Vegetal/genética , Regulação da Expressão Gênica de Plantas
4.
Plant Cell ; 30(2): 481-494, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29437988

RESUMO

MAC3A and MAC3B are conserved U-box-containing proteins in eukaryotes. They are subunits of the MOS4-associated complex (MAC) that plays essential roles in plant immunity and development in Arabidopsis thaliana However, their functional mechanisms remain elusive. Here, we show that Arabidopsis MAC3A and MAC3B act redundantly in microRNA (miRNA) biogenesis. Lack of both MAC3A and MAC3B in the mac3b mac3b double mutant reduces the accumulation of miRNAs, causing elevated transcript levels of miRNA targets. mac3a mac3b also decreases the levels of primary miRNA transcripts (pri-miRNAs). However, MAC3A and MAC3B do not affect the promoter activity of genes encoding miRNAs (MIR genes), suggesting that they may not affect MIR transcription. This result, together with the fact that MAC3A associates with pri-miRNAs in vivo, indicates that MAC3A and MAC3B may stabilize pri-miRNAs. Furthermore, we find that MAC3A and MAC3B interact with the DCL1 complex that catalyzes miRNA maturation, promote DCL1 activity, and are required for the localization of HYL1, a component of the DCL1 complex. Besides MAC3A and MAC3B, two other MAC subunits, CDC5 and PRL1, also function in miRNA biogenesis. Based on these results, we propose that MAC functions as a complex to control miRNA levels through modulating pri-miRNA transcription, processing, and stability.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , MicroRNAs/genética , Ubiquitina-Proteína Ligases/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Regulação da Expressão Gênica de Plantas , Complexos Multiproteicos , Regiões Promotoras Genéticas/genética , Processamento Pós-Transcricional do RNA , Estabilidade de RNA , RNA de Plantas/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Ribonuclease III/genética , Ribonuclease III/metabolismo , Ubiquitina-Proteína Ligases/genética
5.
Future Oncol ; 17(23): 3061-3076, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34156282

RESUMO

Aims: The aim of this study was to identify the immune- and locus-associated genes in pancreatic ductal adenocarcinoma and evaluate their value in prognosis. Methods: The pancreatic ductal adenocarcinoma stromal and immune scores were calculated with the estimation of stromal and immune cells in malignant tumor tissues using expression data algorithm. The authors screened the differentially expressed genes to generate immune- and stromal-related differentially expressed genes. Next, the authors conducted weighted correlation network analysis to find the gene sets related to tumor sites. Results: IL1R1 and LAMA2 were identified as the site- and immune-related genes in pancreatic ductal adenocarcinoma, and their high expression in pancreatic head cancer exhibited high immune scores and predicted unfavorable prognosis. Conclusion: The authors identified IL1R1 and LAMA2 as immune- and locus-associated genes, and their high expression predicted a poor prognosis.


Lay abstract The prognosis of pancreatic cancer is poor, and pancreatic head carcinoma is different from pancreatic body/tail carcinoma in many respects. In recent years, the role of the immune microenvironment in tumors has been increasingly revealed. The authors wanted to find ways to improve the diagnosis and treatment of patients with pancreatic cancer by analyzing the key genes associated with different immune scores and pancreatic cancer sites. In the authors' study, IL1R1 and LAMA2 were identified as immune- and locus-associated genes, and their high expression predicted a poor prognosis, especially in pancreatic body/tail cancer. Early identification of high IL1R1 expression in pancreatic body/tail carcinoma may improve tumor prognosis.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/genética , Laminina/genética , Neoplasias Pancreáticas/genética , Receptores Tipo I de Interleucina-1/genética , Adulto , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/mortalidade , Conjuntos de Dados como Assunto , Feminino , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Pâncreas/imunologia , Pâncreas/patologia , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/mortalidade , Prognóstico , Mapas de Interação de Proteínas , RNA-Seq , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
6.
J Cell Biochem ; 120(6): 9117-9124, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30582205

RESUMO

OBJECTIVE: To develop an independent prognostic signature for patients with hepatocellular carcinoma (HCC). METHODS: HCC gene expression profile the cancer genome atlas-liver hepatocellular carcinoma and GSE14520 were used as discovery and test set, respectively. Differentially expressed genes (DEGs) were identified between HCC tissues and adjacent normal liver tissues. Univariate Cox proportional hazards regression analysis was performed to identify DEGs correlated with survival of HCC patients. A 4-gene-based signature was constructed based on a least absolute shrinkage and selection operator Cox penalized regression model. The predictive value of the signature was analyzed and validated. RESULTS: Two hundred sixty-three DEGs were identified between HCC and adjacent liver tissues. After univariate survival analysis, 90 DEGs were found to be significantly correlated with the overall survival (OS) of HCC patients, of which 4 genes (KPNA2, CDC20, SPP1, and TOP2A) with non-zero coefficient were used to construct a prognostic signature. The 4-gene signature was significantly associated with the age (P = 0.046), grade ( P = 0.022), and T stage ( P = 0.023) of HCC patients in the discovery set and it also significantly associated with TNM stage ( P = 0.033), and serum alpha-fetoprotein lever ( P = 0.034). Patients in the 4-gene low-risk group were associated with better OS and recurrence-free survival (RFS) than those in the high-risk group in the discovery and test set. Meanwhile, the 4-gene signature is an independent prognostic factor regarding OS and RFS in the discovery and test set. CONCLUSION: We developed a 4-gene-based signature, which could be a candidate prognostic factor for patients with HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Fígado/metabolismo , Fígado/patologia , Biomarcadores Tumorais/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Técnicas In Vitro , Estimativa de Kaplan-Meier , Masculino , Prognóstico , RNA Longo não Codificante/metabolismo
7.
Med Sci Monit ; 25: 4082-4093, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31152645

RESUMO

BACKGROUND Alzheimer's disease (AD) is an age-associated neurodegenerative disorder. This study aimed to investigate effects of acupuncture administration on cognitive function and associated mechanisms. MATERIAL AND METHODS Senescence-accelerated prone 8 (SAM-P8) mice were randomly divided into 3 groups: the SAM-P8 group (P8-CN), the SAM-P8 administrating with acupuncture (P8-Acup) group, and the SAM-P8 administrating without acupuncture (P8-Sham) group. Morris water maze test was conducted to evaluate cognitive functions (memory and learning ability). PDK1, nPKC, and Rac1 inhibitors were used to treat SAM-P8 mice. Transmission electron microscope analysis was used to examine nuclear damage hippocampal tissues. Hematoxylin and eosin (H&E) staining was employed to evaluate inflammation. Western blot was used to detect PI3K, PDK1, nPKC, and Rac 1 expression in hippocampal tissues. RESULTS Acupuncture administration significantly reduced PI3K, PDK1, nPKC, and Rac 1 levels compared to P8-CN group (P<0.05). Both acupuncture and enzyme inhibitors (NSC23766, Rottlerin, OSU03012) significantly improved cognitive functions, reduced inflammation, and alleviated nuclear damages of SAM-P8 mice compared to P8-CN group (P<0.05). Acupuncture significantly enhanced effects of inhibitors on inflammation and nuclear damages compared to inhibitor treatment single (P<0.05). Acupuncture significantly enhanced down-regulative effects of OSU03012 on PI3K and PDK1 levels, increased down-regulative effects of Rottlerin on nPKC and Rac 1 levels and enhanced effects of Rottlerin on Rac 1 compared to P8-CN group (P<0.05). CONCLUSIONS Acupuncture administration improved cognitive functions and alleviated inflammatory response and nuclear damage of SAM-P8 mice, by downregulating PI3K/PDK1/nPKC/Rac 1 signaling pathway. This study could provide potential insight for treating cognitive dysfunction and aging of AD patients.


Assuntos
Terapia por Acupuntura/métodos , Doença de Alzheimer/terapia , Cognição/fisiologia , Proteínas Quinases Dependentes de 3-Fosfoinositídeo/metabolismo , Terapia por Acupuntura/veterinária , Envelhecimento/metabolismo , Doença de Alzheimer/fisiopatologia , Animais , China , Modelos Animais de Doenças , Hipocampo/metabolismo , Aprendizagem , Masculino , Medicina Tradicional Chinesa/métodos , Memória , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Proteína Quinase C/metabolismo , Transdução de Sinais/fisiologia
8.
BMC Plant Biol ; 18(1): 149, 2018 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-30021519

RESUMO

BACKGROUND: Ubiquitination is a major post-translational protein modification that regulates essentially all cellular and physiological pathways in eukaryotes. The ubiquitination process typically involves three distinct classes of enzymes, ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2) and ubiquitin ligase (E3). To date, a comprehensive identification and analysis of core components comprising of the whole soybean (Glycine max) ubiquitin system (UBS) has not been reported. RESULTS: We performed a systematic, genome-wide analysis of genes that encode core members of the soybean UBS in this study. A total of 1431 genes were identified with high confidence to encode putative soybean UBS components, including 4 genes encoding E1s, 71 genes that encode the E2s, and 1356 genes encoding the E3-related components. Among the E3-encoding genes, 760 encode RING-type E3s, 124 encode U-box domain-containing E3s, and 472 encode F-box proteins. To find out whether the identified soybean UBS genes encode active enzymes, a set of genes were randomly selected and the enzymatic activities of their recombinant proteins were tested. Thioester assays indicated proteins encoded by the soybean E1 gene GmUBA1 and the majority of selected E2 genes are active E1 or E2 enzymes, respectively. Meanwhile, most of the purified RING and U-box domain-containing proteins displayed E3 activity in the in vitro ubiquitination assay. In addition, 1034 of the identified soybean UBS genes were found to express in at least one of 14 soybean tissues examined and the transcript level of 338 soybean USB genes were significantly changed after abiotic or biotic (Fusarium oxysporum and Rhizobium strains) stress treatment. Finally, the expression level of a large number of the identified soybean UBS-related genes was found significantly altered after soybean cyst nematode (SCN) treatment, suggesting the soybean UBS potentially plays an important role in soybean immunity against SCN. CONCLUSIONS: Our findings indicate the presence of a large and diverse number of core UBS proteins in the soybean genome, which suggests that target-specific modification by ubiquitin is a complex and important part of cellular and physiological regulation in soybean. We also revealed certain members of the soybean UBS may be involved in immunity against soybean cyst nematode (SCN). This study sets up an essential foundation for further functional characterization of the soybean UBS in various physiological processes, such as host immunity against SCN.


Assuntos
Genes de Plantas/genética , Glycine max/genética , Nematoides , Doenças das Plantas/parasitologia , Ubiquitinas/fisiologia , Animais , Genes de Plantas/fisiologia , Genoma de Planta/genética , Estudo de Associação Genômica Ampla , Filogenia , Doenças das Plantas/imunologia , Alinhamento de Sequência , Glycine max/imunologia , Glycine max/metabolismo , Ubiquitinação , Ubiquitinas/genética
9.
Plant Physiol ; 173(2): 1371-1390, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27909045

RESUMO

Of the three classes of enzymes involved in ubiquitination, ubiquitin-conjugating enzymes (E2) have been often incorrectly considered to play merely an auxiliary role in the process, and few E2 enzymes have been investigated in plants. To reveal the role of E2 in plant innate immunity, we identified and cloned 40 tomato genes encoding ubiquitin E2 proteins. Thioester assays indicated that the majority of the genes encode enzymatically active E2. Phylogenetic analysis classified the 40 tomato E2 enzymes into 13 groups, of which members of group III were found to interact and act specifically with AvrPtoB, a Pseudomonas syringae pv tomato effector that uses its ubiquitin ligase (E3) activity to suppress host immunity. Knocking down the expression of group III E2 genes in Nicotiana benthamiana diminished the AvrPtoB-promoted degradation of the Fen kinase and the AvrPtoB suppression of host immunity-associated programmed cell death. Importantly, silencing group III E2 genes also resulted in reduced pattern-triggered immunity (PTI). By contrast, programmed cell death induced by several effector-triggered immunity elicitors was not affected on group III-silenced plants. Functional characterization suggested redundancy among group III members for their role in the suppression of plant immunity by AvrPtoB and in PTI and identified UBIQUITIN-CONJUGATING11 (UBC11), UBC28, UBC29, UBC39, and UBC40 as playing a more significant role in PTI than other group III members. Our work builds a foundation for the further characterization of E2s in plant immunity and reveals that AvrPtoB has evolved a strategy for suppressing host immunity that is difficult for the plant to thwart.


Assuntos
Imunidade Vegetal/fisiologia , Proteínas de Plantas/imunologia , Solanum lycopersicum/genética , Enzimas de Conjugação de Ubiquitina/imunologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Morte Celular , Inativação Gênica , Genoma de Planta , Interações Hospedeiro-Patógeno/imunologia , Solanum lycopersicum/citologia , Solanum lycopersicum/imunologia , Solanum lycopersicum/microbiologia , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Pseudomonas syringae/patogenicidade , Nicotiana/genética , Nicotiana/metabolismo , Enzimas de Conjugação de Ubiquitina/genética , Enzimas de Conjugação de Ubiquitina/metabolismo , Ubiquitinação
10.
Plant Cell Environ ; 41(3): 689-703, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29320607

RESUMO

Seven in absentia (SINA) protein is one subgroup of ubiquitin ligases possessing an N-terminal cysteine-rich really interesting new gene (RING) domain, two zinc-finger motifs, and a C-terminal domain responsible for substrate-binding and dimerization. In tomato (Solanum lycopersicum), the SINA gene family has six members, and we characterize in this study all tomato SINA (SlSINA) genes and the gene products. Our results show that SlSINA genes are differentially regulated in leaf, bud, stem, flower, and root. All SlSINA proteins possess RING-dependent E3 ubiquitin ligase activity, exhibiting similar specificity towards the E2 ubiquitin-conjugating enzyme. SlSINA1/3/4/5/6 are localized in both cytoplasm and nucleus, whereas SlSINA2 is exclusively localized in the nucleus. Moreover, all SlSINAs can interact with each other for homo- or hetero-dimerization. The functionality of SlSINA proteins has been investigated. SlSINA4 plays a positive role in defense signalling, as manifested by elicitation of E3-dependent hypersensitive response-like cell death; the other SlSINAs are negative regulator and capable to suppress hypersensitive response cell death. Transgenic tomato plants overexpressing SlSINA2 exhibit pale-green leaf phenotype, suggesting SlSINA2 regulates chlorophyll level in plant cells, whereas transgenic tomato plants overexpressing SlSINA5 have altered floral structure with exserted stigma, implicating SlSINA5 plays a role in flower development.


Assuntos
Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas de Plantas/genética , Solanum lycopersicum/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Núcleo Celular/metabolismo , Flores/genética , Flores/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas , Solanum lycopersicum/metabolismo , Família Multigênica , Filogenia , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Domínios Proteicos , Nicotiana/genética , Nicotiana/metabolismo , Ubiquitinação
11.
Proteomics ; 16(14): 1949-51, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27273999

RESUMO

Similar to substrate-conjugated polyubiquitin, unanchored polyubiquitin chains are emerging as important regulators for diverse biological processes. The affinity purification of unanchored polyubiquitin from various organisms has been reported, however, tools able to distinguish unanchored polyubiquitin chains with different isopeptide linkages have not yet been described. Toward the goal of selectively identifying and purifying unanchored polyubiquitin chains linked through different Lysines, Scott et al. developed a novel strategy in their study [Proteomics 2016, 16, 1961-1969]. They designed a linker-optimized ubiquitin-binding domain hybrid (t-UBD) containing two UBDs, a ZnFCUBP domain, and a linkage-selective UBA domain, to specifically recognize unanchored Lys48-linked polyubiquitin chains. Subsequently, a series of assays has proved the feasibility of this novel strategy for the purification of endogenous substrate-free Lys48-linked polyubiquitin chains from mammalian cell extracts. Their research not only provides a tool for purifying unanchored polyubiquitin with different isopeptide linkages, but also paves the way for generating reagents to study the function of unanchored polyubiquitin chains of different linkages in the future. The design of UBD hybrids for defined unanchored polyubiquitin (Lys48-polyubiquitin) in this study also set an excellent example for future methodology studies regarding monitoring in vivo dynamic changes in the patterns of ubiquitination.


Assuntos
Lisina/metabolismo , Poliubiquitina/isolamento & purificação , Proteínas Recombinantes de Fusão/metabolismo , Sítios de Ligação , Misturas Complexas/química , Expressão Gênica , Células HEK293 , Humanos , Lisina/química , Poliubiquitina/química , Ligação Proteica , Domínios Proteicos , Engenharia de Proteínas , Proteínas Recombinantes de Fusão/genética , Ubiquitinação
12.
Plant Cell ; 25(9): 3615-31, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24076975

RESUMO

The activation of an immune response in tomato (Solanum lycopersicum) against Pseudomonas syringae relies on the recognition of E3 ligase-deficient forms of AvrPtoB by the host protein kinase, Fen. To investigate the mechanisms by which Fen-mediated immunity is regulated, we characterize in this study a Fen-interacting protein, Fni3, and its cofactor, S. lycoperiscum Uev (Suv). Fni3 encodes a homolog of the Ubc13-type ubiquitin-conjugating enzyme that catalyzes exclusively Lys-63-linked ubiquitination, whereas Suv is a ubiquitin-conjugating enzyme variant. The C-terminal region of Fen was necessary for interaction with Fni3, and this interaction was required for cell death triggered by overexpression of Fen in Nicotiana benthamiana leaves. Fni3 was shown to be an active E2 enzyme, but Suv displayed no ubiquitin-conjugating activity; Fni3 and Suv together directed Lys-63-linked ubiquitination. Decreased expression of Fni3, another tomato Ubc13 homolog, Sl-Ubc13-2, or Suv in N. benthamiana leaves diminished cell death associated with Fen-mediated immunity and cell death elicited by several other resistance (R) proteins and their cognate effectors. We also discovered that coexpression of Fen and other R proteins/effectors with a Fni3 mutant that is compromised for ubiquitin-conjugating activity diminished the cell death. These results suggest that Fni3/Sl-Ubc13-2 and Suv regulate the immune response mediated by Fen and other R proteins through Lys-63-linked ubiquitination.


Assuntos
Nicotiana/enzimologia , Doenças das Plantas/imunologia , Imunidade Vegetal , Proteínas de Plantas/metabolismo , Pseudomonas syringae/fisiologia , Solanum lycopersicum/enzimologia , Sequência de Bases , Inativação Gênica , Solanum lycopersicum/genética , Dados de Sequência Molecular , Filogenia , Doenças das Plantas/microbiologia , Proteínas de Plantas/genética , Ligação Proteica , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Estabilidade Proteica , Análise de Sequência de DNA , Nicotiana/genética , Nicotiana/imunologia , Nicotiana/microbiologia , Técnicas do Sistema de Duplo-Híbrido , Ubiquitina/metabolismo , Enzimas de Conjugação de Ubiquitina/genética , Enzimas de Conjugação de Ubiquitina/metabolismo , Ubiquitinação
13.
Psych J ; 13(3): 477-485, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38298167

RESUMO

Research has confirmed that individuals with social anxiety (SA) show an attentional bias towards threat-related stimuli. However, the extent to which this attentional bias depends on top-down cognitive control processes remains controversial. The present study investigated the effect of working memory (WM) load on selective attention to emotional faces in both high social anxiety (HSA) and low social anxiety (LSA) groups by manipulating WM load through the inclusion of forward counting in multiples of two (low load) or backward counting in multiples of seven (high load) within a modified flanker task. In the flanker task, emotional faces (angry, happy, or neutral faces) were used as targets and distractors. A total of 70 participants (34 HSA participants; 36 LSA participants) completed the flanker task in the laboratory. The results showed that the HSA individuals performed worse when responding to angry targets. Relative to LSA individuals, HSA individuals showed interference from angry distractors in the flanker task, resulting in significantly lower accuracy in identifying angry targets compared to happy targets. These results were unaffected by the manipulation of WM load. The findings imply HSA individuals have impaired attentional control, and that their threat-related attentional bias relies more on the bottom-up automatic attentional process.


Assuntos
Atenção , Expressão Facial , Memória de Curto Prazo , Humanos , Memória de Curto Prazo/fisiologia , Feminino , Masculino , Adulto , Adulto Jovem , Atenção/fisiologia , Emoções/fisiologia , Ansiedade , Viés de Atenção/fisiologia , Reconhecimento Facial/fisiologia , Fobia Social
14.
Clin Med (Lond) ; 24(2): 100033, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38513803

RESUMO

A 34-year-old woman was diagnosed with type 1 diabetes mellitus and treated with insulin for 24 years. The patient has a family history of diabetes in three consecutive generations. Her Whole exon sequencing showed a heterozygous mutation in the ABCC8 gene, and it also found some of her relatives to carry this mutation. She was diagnosed with MODY12 and received glimepiride therapy with the achievement of good glycaemic control.


Assuntos
Diabetes Mellitus Tipo 2 , Mutação , Receptores de Sulfonilureias , Humanos , Feminino , Adulto , Receptores de Sulfonilureias/genética , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico
15.
Adv Sci (Weinh) ; 11(21): e2309111, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38501909

RESUMO

Nickel oxide (NiOx)-based inverted perovskite solar cells stand as promising candidates for advancing perovskite photovoltaics towards commercialization, leveraging their remarkable stability, scalability, and cost-effectiveness. However, the interfacial redox reaction between high-valence Ni4+ and perovskite, alongside the facile conversion of iodide in perovskite into I2, significantly deteriorates the performance and reproducibility of NiOx-based perovskite photovoltaics. Here, potassium borohydride (KBH4) is introduced as a dual-action reductant, which effectively avoids the Ni4+/perovskite interface reaction and mitigates the iodide-to-I2 oxidation within perovskite film. This synergistic redox modulation significantly suppresses nonradiative recombination and increases the carrier lifetime. As a result, an impressive power conversion efficiency of 24.17% for NiOx-based perovskite solar cells is achieved, and a record efficiency of 20.2% for NiOx-based perovskite solar modules fabricated under ambient conditions. Notably, when evaluated using the ISOS-L-2 standard protocol, the module retains 94% of its initial efficiency after 2000 h of continuous illumination under maximum power point at 65 °C in ambient air.

16.
Sci Adv ; 10(32): eadl6398, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39110786

RESUMO

The growing interest in cost-effective and high-performing perovskite solar cells (PSCs) has driven extensive research. However, the challenge lies in upscaling PSCs while maintaining high performance. This study focuses on achieving uniform and compact perovskite films without pinholes and interfacial voids during upscaling from small PSCs to large-area modules. Competition in nucleation at concavities with various angles on rough-textured substrates during the gas-pumping drying process, coupled with different drying rates across the expansive film, aggravates these issues. Consequently, substrate roughness notably influences the deposition window of compact large-area perovskite films. We propose a supersaturation regulation approach aimed at achieving compact deposition of high-quality perovskite films over large areas. This involves introducing a rapid drying strategy to induce a high-supersaturation state, thereby equalizing nucleation across diverse concavities. This breakthrough enables the production of perovskite photovoltaics with high efficiencies of 25.58, 21.86, and 20.62% with aperture areas of 0.06, 29, and 1160 square centimeters, respectively.

17.
Plant J ; 69(1): 92-103, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21880077

RESUMO

Resistance in tomato (Solanum lycopersicum) to infection by Pseudomonas syringae involves both detection of pathogen-associated molecular patterns (PAMPs) and recognition by the host Pto kinase of pathogen effector AvrPtoB which is translocated into the host cell and interferes with PAMP-triggered immunity (PTI). The N-terminal portion of AvrPtoB is sufficient for its virulence activity and for recognition by Pto. An amino acid substitution in AvrPtoB, F173A, abolishes these activities. To investigate the mechanisms of AvrPtoB virulence, we screened for tomato proteins that interact with AvrPtoB and identified Bti9, a LysM receptor-like kinase. Bti9 has the highest amino acid similarity to Arabidopsis CERK1 among the tomato LysM receptor-like kinases (RLKs) and belongs to a clade containing three other tomato proteins, SlLyk11, SlLyk12, and SlLyk13, all of which interact with AvrPtoB. The F173A substitution disrupts the interaction of AvrPtoB with Bti9 and SlLyk13, suggesting that these LysM-RLKs are its virulence targets. Two independent tomato lines with RNAi-mediated reduced expression of Bti9 and SlLyk13 were more susceptible to P. syringae. Bti9 kinase activity was inhibited in vitro by the N-terminal domain of AvrPtoB in an F173-dependent manner. These results indicate Bti9 and/or SlLyk13 play a role in plant immunity and the N-terminal domain of AvrPtoB may have evolved to interfere with their kinase activity. Finally, we found that Bti9 and Pto interact with AvrPtoB in a structurally similar although not identical fashion, suggesting that Pto may have evolved as a molecular mimic of LysM-RLK kinase domains.


Assuntos
Proteínas de Bactérias/metabolismo , Proteínas de Plantas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Solanum lycopersicum/imunologia , Solanum lycopersicum/microbiologia , Motivos de Aminoácidos , Substituição de Aminoácidos , Proteínas de Arabidopsis/química , Interações Hospedeiro-Patógeno , Solanum lycopersicum/genética , Solanum lycopersicum/metabolismo , Mimetismo Molecular , Dados de Sequência Molecular , Proteínas de Plantas/química , Proteínas de Plantas/imunologia , Plantas Geneticamente Modificadas , Proteínas Serina-Treonina Quinases/química , Proteínas Serina-Treonina Quinases/imunologia , Pseudomonas syringae/patogenicidade , Técnicas do Sistema de Duplo-Híbrido
18.
Plant Physiol ; 159(1): 239-50, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22383540

RESUMO

The components in plant signal transduction pathways are intertwined and affect each other to coordinate plant growth, development, and defenses to stresses. The role of ubiquitination in connecting these pathways, particularly plant innate immunity and flowering, is largely unknown. Here, we report the dual roles for the Arabidopsis (Arabidopsis thaliana) Plant U-box protein13 (PUB13) in defense and flowering time control. In vitro ubiquitination assays indicated that PUB13 is an active E3 ubiquitin ligase and that the intact U-box domain is required for the E3 ligase activity. Disruption of the PUB13 gene by T-DNA insertion results in spontaneous cell death, the accumulation of hydrogen peroxide and salicylic acid (SA), and elevated resistance to biotrophic pathogens but increased susceptibility to necrotrophic pathogens. The cell death, hydrogen peroxide accumulation, and resistance to necrotrophic pathogens in pub13 are enhanced when plants are pretreated with high humidity. Importantly, pub13 also shows early flowering under middle- and long-day conditions, in which the expression of SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 and FLOWERING LOCUS T is induced while FLOWERING LOCUS C expression is suppressed. Finally, we found that two components involved in the SA-mediated signaling pathway, SID2 and PAD4, are required for the defense and flowering-time phenotypes caused by the loss of function of PUB13. Taken together, our data demonstrate that PUB13 acts as an important node connecting SA-dependent defense signaling and flowering time regulation in Arabidopsis.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Flores/fisiologia , Ubiquitina-Proteína Ligases/metabolismo , Arabidopsis/enzimologia , Arabidopsis/genética , Arabidopsis/microbiologia , Proteínas de Arabidopsis/genética , Botrytis/imunologia , Botrytis/patogenicidade , Hidrolases de Éster Carboxílico/genética , Hidrolases de Éster Carboxílico/metabolismo , Morte Celular , Clonagem Molecular , Ativação Enzimática , Ensaios Enzimáticos , Flores/metabolismo , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Umidade , Peróxido de Hidrogênio/metabolismo , Proteínas de Domínio MADS/genética , Proteínas de Domínio MADS/metabolismo , Doenças das Plantas/imunologia , Doenças das Plantas/microbiologia , Imunidade Vegetal , Plantas Geneticamente Modificadas/enzimologia , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/microbiologia , Plantas Geneticamente Modificadas/fisiologia , Estrutura Terciária de Proteína , Pseudomonas/patogenicidade , Salicilatos/metabolismo , Fatores de Tempo , Ubiquitina-Proteína Ligases/genética , Ubiquitinação
19.
Nature ; 448(7151): 370-4, 2007 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-17637671

RESUMO

Many bacterial pathogens of plants and animals use a type III secretion system to deliver diverse virulence-associated 'effector' proteins into the host cell. The mechanisms by which these effectors act are mostly unknown; however, they often promote disease by suppressing host immunity. One type III effector, AvrPtoB, expressed by the plant pathogen Pseudomonas syringae pv. tomato, has a carboxy-terminal domain that is an E3 ubiquitin ligase. Deletion of this domain allows an amino-terminal region of AvrPtoB (AvrPtoB(1-387)) to be detected by certain tomato varieties leading to immunity-associated programmed cell death. Here we show that a host kinase, Fen, physically interacts with AvrPtoB(1-387 )and is responsible for activating the plant immune response. The AvrPtoB E3 ligase specifically ubiquitinates Fen and promotes its degradation in a proteasome-dependent manner. This degradation leads to disease susceptibility in Fen-expressing tomato lines. Various wild species of tomato were found to exhibit immunity in response to AvrPtoB(1-387 )and not to full-length AvrPtoB. Thus, by acquiring an E3 ligase domain, AvrPtoB has thwarted a highly conserved host resistance mechanism.


Assuntos
Doenças das Plantas/imunologia , Proteínas Quinases/metabolismo , Pseudomonas syringae/enzimologia , Solanum lycopersicum/imunologia , Solanum lycopersicum/microbiologia , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina/metabolismo , Solanum lycopersicum/classificação , Solanum lycopersicum/enzimologia , Fenótipo , Doenças das Plantas/microbiologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Ligação Proteica , Pseudomonas syringae/imunologia , Ubiquitina-Proteína Ligases/química
20.
Sci Rep ; 13(1): 328, 2023 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-36609585

RESUMO

The noise and redundant information are the main reasons for the performance bottleneck of medical image segmentation algorithms based on the deep learning. To this end, we propose a deep network embedded with rough fuzzy discretization (RFDDN) for OCT fundus image segmentation. Firstly, we establish the information decision table of OCT fundus image segmentation, and regard each category of segmentation region as a fuzzy set. Then, we use the fuzzy c-means clustering to get the membership degrees of pixels to each segmentation region. According to membership functions and the equivalence relation generated by the brightness attribute, we design the individual fitness function based on the rough fuzzy set, and use a genetic algorithm to search for the best breakpoints to discretize the features of OCT fundus images. Finally, we take the feature discretization based on the rough fuzzy set as the pre-module of the deep neural network, and introduce the deep supervised attention mechanism to obtain the important multi-scale information. We compare RFDDN with U-Net, ReLayNet, CE-Net, MultiResUNet, and ISCLNet on the two groups of 3D retinal OCT data. RFDDN is superior to the other five methods on all evaluation indicators. The results obtained by ISCLNet are the second only inferior to those obtained by RFDDN. DSC, sensitivity, and specificity of RFDDN are evenly 3.3%, 2.6%, and 7.1% higher than those of ISCLNet, respectively. HD95 and ASD of RFDDN are evenly 6.6% and 19.7% lower than those of ISCLNet, respectively. The experimental results show that our method can effectively eliminate the noise and redundant information in Oct fundus images, and greatly improve the accuracy of OCT fundus image segmentation while taking into account the interpretability and computational efficiency.


Assuntos
Algoritmos , Redes Neurais de Computação , Fundo de Olho , Análise por Conglomerados , Processamento de Imagem Assistida por Computador/métodos
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