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1.
Nature ; 568(7751): 259-263, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30944473

RESUMEN

The genetic compensation response (GCR) has recently been proposed as a possible explanation for the phenotypic discrepancies between gene-knockout and gene-knockdown1,2; however, the underlying molecular mechanism of the GCR remains uncharacterized. Here, using zebrafish knockdown and knockout models of the capn3a and nid1a genes, we show that mRNA bearing a premature termination codon (PTC) promptly triggers a GCR that involves Upf3a and components of the COMPASS complex. Unlike capn3a-knockdown embryos, which have small livers, and nid1a-knockdown embryos, which have short body lengths2, capn3a-null and nid1a-null mutants appear normal. These phenotypic differences have been attributed to the upregulation of other genes in the same families. By analysing six uniquely designed transgenes, we demonstrate that the GCR is dependent on both the presence of a PTC and the nucleotide sequence of the transgene mRNA, which is homologous to the compensatory endogenous genes. We show that upf3a (a member of the nonsense-mediated mRNA decay pathway) and components of the COMPASS complex including wdr5 function in GCR. Furthermore, we demonstrate that the GCR is accompanied by an enhancement of histone H3 Lys4 trimethylation (H3K4me3) at the transcription start site regions of the compensatory genes. These findings provide a potential mechanistic basis for the GCR, and may help lead to the development of therapeutic strategies that treat missense mutations associated with genetic disorders by either creating a PTC in the mutated gene or introducing a transgene containing a PTC to trigger a GCR.


Asunto(s)
Codón sin Sentido/genética , Prueba de Complementación Genética , Complejos Multiproteicos/metabolismo , ARN Mensajero/genética , Pez Cebra/genética , Animales , Proteínas de Unión al Calcio/deficiencia , Proteínas de Unión al Calcio/genética , Eliminación de Gen , Células HCT116 , Histonas/metabolismo , Humanos , Complejos Multiproteicos/química , Degradación de ARNm Mediada por Codón sin Sentido , Organismos Modificados Genéticamente , Proteínas de Pez Cebra/deficiencia , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo
2.
Histopathology ; 84(4): 661-670, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38084644

RESUMEN

AIMS: Nuclear receptor subfamily 1 group D member 1 (NR1D1)-rearranged soft tissue tumour is a newly described entity with an epithelioid morphology and a potential for aggressive behaviour. Largely due to under-recognition, this tumour type has not yet been widely acknowledged. Herein, we report four additional cases to further expand its clinicopathological and molecular spectrum. METHODS AND RESULTS: Four mesenchymal tumours with NR1D1 rearrangement were identified from our consultation files. There were one male and three females with ages ranging from 19 to 47 years (median = 28.5 years). Tumour occurred in the tongue, neck, hip and index finger, respectively. Histologically, two tumours were composed predominantly of epithelioid cells; one tumour had admixed epithelioid-spindle cells and one tumour consisted of monomorphic small round to ovoid cells. By immunohistochemistry, none of the tumours expressed lineage-specific markers. Targeted RNA-sequencing identified NR1D1 fusions in all four tumours, the partner genes being MAML2, MAML3, KMT2A and NCOA2, respectively. The novel MAML3 and NCOA2 rearrangements were confirmed by fluorescence in-situ hybridisation analysis. On follow-up (2-23 months), one patient experienced local recurrence due to incomplete resection and one patient developed lung metastasis. The other two patients were alive without disease. CONCLUSIONS: This study adds more support for NR1D1-rearranged soft tissue tumour as an emerging entity. The occurrence of two additional tumours in the head and neck region, description of a small round cell variant and identification of novel MAML3, KMT2A and NCOA2 partners further expand its clinicopathological and molecular spectrum. More studies on larger series are necessary to validate the fully malignant potential of NR1D1-rearranged soft tissue tumour.


Asunto(s)
Neoplasias de los Tejidos Blandos , Factores de Transcripción , Femenino , Humanos , Masculino , Biomarcadores de Tumor/genética , Hibridación Fluorescente in Situ , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares/genética , Neoplasias de los Tejidos Blandos/genética , Neoplasias de los Tejidos Blandos/patología , Factores de Transcripción/genética , Adulto Joven , Adulto , Persona de Mediana Edad
3.
Reproduction ; 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-39042724

RESUMEN

MiR-122-5p, high expression in follicular fluid exosomes of patients with endometriosis, impairs the glucose metabolism function of cumulus cells and may further impair oocyte quality. Endometriosis (EMs) affects fertility in women of childbearing age in many ways. However, the mechanisms are complex, including the decrease in oocyte quality, which still needs to be studied. Exosomes, small vesicles responsible for intercellular information exchange, have been found to be involved in many biological events, such as follicle development and oocyte meiosis recovery. From the perspective of follicular fluid exosomes, this study aims to elucidate the mechanism of EMs-related oocyte quality decline. Follicular fluid was collected from three groups of women: the untreated EMs group (EMs_UT), the satisfactorily treated EMs group (EMs_ST) and the control group (Ctrl). Mouse cumulus oocyte complexes (COCs) were cocultured with exosomes extracted from follicular fluid during in vitro maturation. Oocyte quality and cumulus cell function were assessed. High-throughput sequencing of miRNA in exosomes was conducted. The function of differentially expressed miRNAs was studied by using SVOG cells (human ovarian granulosa cell line) transfected with miRNA mimic and inhibitor. Our date suggest that follicular fluid exosomes from patients with untreated EMs reduce the maturation rate and damage the quality of mouse oocytes. MiR-122-5p, overexpressed in untreated EMs, inhibits the translation of key aldolase enzymes related to glucose metabolism and partially impairs cumulus cells of endometriosis patients.

4.
J Minim Invasive Gynecol ; 31(3): 227-236, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38147937

RESUMEN

STUDY OBJECTIVE: To develop a noninvasive predictive model based on patients with infertility for identifying minimal or mild endometriosis. DESIGN: A retrospective cohort study. SETTING: This study was conducted at a tertiary referral center. PATIENTS: A total of consecutive 1365 patients with infertility who underwent laparoscopy between January 2013 and August 2020 were divided into a training set (n = 910) for developing the predictive model and a validation set (n = 455) to confirm the model's prediction efficiency. The patients were randomly assigned in a 2:1 ratio. INTERVENTIONS: Sensitivities, specificities, area under the curve, the Hosmer-Lemeshow goodness of fit test, Net Reclassification Improvement index, and Integrated Discrimination Improvement index were evaluated in the training set to select the optimum model. In the validation set, the model's discriminations, calibrations, and clinical use were tested for validation. MEASUREMENTS AND MAIN RESULTS: In the training set, there were 587 patients with minimal or mild endometriosis and 323 patients without endometriosis. The combination of clinical parameters in the model was evaluated for both statistical and clinical significance. The best-performing model ultimately included body mass index, dysmenorrhea, dyspareunia, uterosacral tenderness, and serum cancer antigen 125 (CA-125). The nomogram based on this model demonstrated sensitivities of 87.7% and 93.3%, specificities of 68.6% and 66.4%, and area under the curve of 0.84 (95% confidence interval 0.81-0.87) and 0.85 (95% confidence interval 0.80-0.89) for the training and validation sets, respectively. Calibration curves and decision curve analyses also indicated that the model had good calibration and clinical value. Uterosacral tenderness emerged as the most valuable predictor. CONCLUSION: This study successfully developed a predictive model with high accuracy in identifying infertile women with minimal or mild endometriosis based on clinical characteristics, signs, and cost-effective blood tests. This model would assist clinicians in screening infertile women for minimal or mild endometriosis, thereby facilitating early diagnosis and treatment.


Asunto(s)
Endometriosis , Infertilidad Femenina , Laparoscopía , Femenino , Humanos , Infertilidad Femenina/diagnóstico , Infertilidad Femenina/etiología , Endometriosis/complicaciones , Endometriosis/diagnóstico , Endometriosis/cirugía , Estudios Retrospectivos , Dismenorrea
5.
Angew Chem Int Ed Engl ; 63(11): e202318595, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38224211

RESUMEN

Achieving a more balanced charge transport by morphological control is crucial in reducing bimolecular and trap-assisted recombination and enhancing the critical parameters for efficient organic solar cells (OSCs). Hence, a facile strategy is proposed to reduce the crystallinity difference between donor and acceptor by incorporating a novel multifunctional liquid crystal small molecule (LCSM) BDTPF4-C6 into the binary blend. BDTPF4-C6 is the first LCSM based on a tetrafluorobenzene unit and features a low liquid crystal phase transition temperature and strong self-assembly ability, conducive to regulating the active layer morphology. When BDTPF4-C6 is introduced as a guest molecule into the PM6 : Y6 binary, it exhibits better compatibility with the donor PM6 and primarily resides within the PM6 phase because of the similarity-intermiscibility principle. Moreover, systematic studies revealed that BDTPF4-C6 could be used as a seeding agent for PM6 to enhance its crystallinity, thereby forming a more balanced and favourable charge transport with suppressed charge recombination. Intriguingly, dual Förster resonance energy transfer was observed between the guest molecule and the host donor and acceptor, resulting in an improved current density. This study demonstrates a facile approach to balance the charge mobilities and offers new insights into boosting the efficiency of single-junction OSCs beyond 20 %.

6.
Arch Insect Biochem Physiol ; 114(3): e22043, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37545053

RESUMEN

Superoxide dismutase (SOD) is an important enzyme that acts as the first line of protection in the mite antioxidant defense system, involved in eliminating reactive oxygen species (ROS) under harsh environmental conditions. Nevertheless, the SOD gene family was yet to be reported in stored grain pest mite (Aleuroglyphus ovatus). In this study, A. ovatus was used to evaluate the response of SOD gene during lead stress. A. ovatus were separately exposed to different concentration lead (12.5, 25, 50, and 100 mg/kg), which induce the dynamic trend of SOD enzyme activity initially increased and then reduced with an increase in lead concentration, whereas they were still substantially higher than the control group. Moreover, after lead stress, it was found that all of the three SOD genes showed enhanced relative messenger RNA expression at high concentrations and decreased relative expression at low concentrations, which indicated that lead stress induces the expression of AoSODs. The present work implies that AoSODs play an important role in resisting oxidative damage caused by lead stress.

7.
Proc Natl Acad Sci U S A ; 117(6): 3270-3280, 2020 02 11.
Artículo en Inglés | MEDLINE | ID: mdl-31992638

RESUMEN

Protein kinases are major regulatory components in almost all cellular processes in eukaryotic cells. By adding phosphate groups, protein kinases regulate the activity, localization, protein-protein interactions, and other features of their target proteins. It is known that protein kinases are central components in plant responses to environmental stresses such as drought, high salinity, cold, and pathogen attack. However, only a few targets of these protein kinases have been identified. Moreover, how these protein kinases regulate downstream biological processes and mediate stress responses is still largely unknown. In this study, we introduce a strategy based on isotope-labeled in vitro phosphorylation reactions using in vivo phosphorylated peptides as substrate pools and apply this strategy to identify putative substrates of nine protein kinases that function in plant abiotic and biotic stress responses. As a result, we identified more than 5,000 putative target sites of osmotic stress-activated SnRK2.4 and SnRK2.6, abscisic acid-activated protein kinases SnRK2.6 and casein kinase 1-like 2 (CKL2), elicitor-activated protein kinase CDPK11 and MPK6, cold-activated protein kinase MPK6, H2O2-activated protein kinase OXI1 and MPK6, and salt-induced protein kinase SOS1 and MPK6, as well as the low-potassium-activated protein kinase CIPK23. These results provide comprehensive information on the role of these protein kinases in the control of cellular activities and could be a valuable resource for further studies on the mechanisms underlying plant responses to environmental stresses.


Asunto(s)
Proteínas de Arabidopsis/metabolismo , Mapas de Interacción de Proteínas/fisiología , Proteínas Quinasas/metabolismo , Proteoma/metabolismo , Estrés Fisiológico/fisiología , Arabidopsis/metabolismo , Arabidopsis/fisiología , Fosforilación , Mapeo de Interacción de Proteínas
8.
Pestic Biochem Physiol ; 193: 105431, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37248009

RESUMEN

The entomopathogenic fungus is recognized as an ideal alternative to chemical pesticides, nonetheless, its efficacy is often limited by insect's innate immune system. The suppression of the host immunity may overcome the obstacle and promote the toxicity of the fungi. Here, by using an entomopathogenic fungus Beauveria bassiana and immune genes dsRNA-expressing bacteria, we explored the potentially synergistic toxicity of the two agents on a leaf beetle Plagiodera versicolora (Coleoptera: Chrysomelidae). We first determined the susceptibilities of P. versicolora to a B. bassiana 476 strain (hereafter referred to Bb476). And the immune genes were identified based on the transcriptome of Bb476 challenged beetles. Subsequently, five immune genes (PGRP1, Toll1, Domeless,SPN1,and Lysozyme) were targeted by feeding dsRNA-expressing bacteria, which produced a 71.4, 39.0, 72.0, 49.0, and 68.7% gene silencing effect, respectively. Furthermore, we found a significantly increased mortality of P. versicolora when combined the Bb476 and the immune suppressive dsRNAs. Taking together, this study highlights the importance of insect immunity in the defense of entomopathogens and also paves the way toward the development of a more efficient pest management strategy that integrates both entomopathogens and immune suppressive dsRNAs.


Asunto(s)
Beauveria , Escarabajos , Control Biológico de Vectores , Animales , Bacterias , Beauveria/genética , Escarabajos/microbiología , Insecticidas
9.
Ann Diagn Pathol ; 67: 152203, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37634346

RESUMEN

In this study, we present six cases of epithelioid dedifferentiated liposarcoma to further characterize its clinical and pathological features. The patients are all adult men with age at presentation ranging from 46 to 64 years (median 58.5 years). The patients presented with nonspecific symptoms of retroperitoneal mass, intermittent dull pain or discomfort. None of the patients had any prior history of a primary tumor. Radiological examinations revealed the presence of ill-demarcated heterogenous mass located in the deep soft tissue, including retroperitoneum (4 cases), pelvis and trunk (1 case each). Grossly, they appeared as solid tumors with focal areas of necrosis being presented in 2 cases. Histologically, all tumors were characterized by sheets of epithelioid cells that displayed marked cellular atypia and brisk mitotic activity. Variable portion of atypical lipomatous tumor/well-differentiated liposarcoma was present in 3 cases. By immunohistochemistry, the high-grade epithelioid component in all 6 cases showed strong and diffuse nuclear staining of MDM2, CDK4 and P16, with partial expression of AE1/AE3 in 3 cases. Fluorescence in situ hybridization analysis revealed high-level amplification of MDM2 in all 6 cases, with co-amplification of CDK4 in 3 cases. Follow up information showed that two patients died of the disease within one year despite multidisciplinary treatment. Due to the striking epithelioid appearance, this rare variant of dedifferentiated liposarcoma may be confused with undifferentiated epithelioid sarcoma, poorly differentiated carcinoma, mesothelioma or other malignancies with epithelioid phenotype. The study presented herein further highlights the aggressive clinical behavior of this unique tumor type. For patients with advanced disease, CDK4 inhibitor may provide an optional targeted treatment.


Asunto(s)
Lipoma , Liposarcoma , Sarcoma , Masculino , Adulto , Humanos , Persona de Mediana Edad , Liposarcoma/diagnóstico , Liposarcoma/genética , Liposarcoma/patología , Hibridación Fluorescente in Situ , Proteínas Proto-Oncogénicas c-mdm2/genética , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/análisis
10.
Angew Chem Int Ed Engl ; 62(35): e202304931, 2023 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-37431837

RESUMEN

Reducing non-radiative recombination energy loss (ΔE3 ) is one key to boosting the efficiency of organic solar cells. Although the recent studies have indicated that the Y-series asymmetric acceptors-based devices featured relatively low ΔE3 , the understanding of the energy loss mechanism derived from molecular structure change is still lagging behind. Herein, two asymmetric acceptors named BTP-Cl and BTP-2Cl with different terminals were synthesized to make a clear comparative study with the symmetric acceptor BTP-0Cl. Our results suggest that asymmetric acceptors exhibit a larger difference of electrostatic potential (ESP) in terminals and semi-molecular dipole moment, which contributes to form a stronger π-π interaction. Besides, the experimental and theoretical studies reveal that a lower ESP-induced intermolecular interaction can reduce the distribution of PM6 near the interface to enhance the built-in potential and decrease the charge transfer state ratio for asymmetric acceptors. Therefore, the devices achieve a higher exciton dissociation efficiency and lower ΔE3 . This work establishes a structure-performance relationship and provides a new perspective to understand the state-of-the-art asymmetric acceptors.

11.
Angew Chem Int Ed Engl ; 62(22): e202303818, 2023 05 22.
Artículo en Inglés | MEDLINE | ID: mdl-36973833

RESUMEN

Protein tyrosine phosphatase 1B (PTP1B) and T-cell protein tyrosine phosphatase (TC-PTP) play non-redundant negative regulatory roles in T-cell activation, tumor antigen presentation, insulin and leptin signaling, and are potential targets for several therapeutic applications. Here, we report the development of a highly potent and selective small molecule degrader DU-14 for both PTP1B and TC-PTP. DU-14 mediated PTP1B and TC-PTP degradation requires both target protein(s) and VHL E3 ligase engagement and is also ubiquitination- and proteasome-dependent. DU-14 enhances IFN-γ induced JAK1/2-STAT1 pathway activation and promotes MHC-I expression in tumor cells. DU-14 also activates CD8+ T-cells and augments STAT1 and STAT5 phosphorylation. Importantly, DU-14 induces PTP1B and TC-PTP degradation in vivo and suppresses MC38 syngeneic tumor growth. The results indicate that DU-14, as the first PTP1B and TC-PTP dual degrader, merits further development for treating cancer and other indications.


Asunto(s)
Neoplasias , Proteína Tirosina Fosfatasa no Receptora Tipo 2 , Humanos , Proteína Tirosina Fosfatasa no Receptora Tipo 2/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 1/metabolismo , Linfocitos T CD8-positivos/metabolismo , Neoplasias/tratamiento farmacológico , Fosforilación , Inmunoterapia
12.
J Proteome Res ; 21(10): 2515-2525, 2022 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-36103635

RESUMEN

Protein phosphatases play an essential role in normal cell physiology and the development of diseases such as cancer. The innate challenges associated with studying protein phosphatases have limited our understanding of their substrates, molecular mechanisms, and unique functions within highly coordinated networks. Here, we introduce a novel strategy using substrate-trapping mutants coupled with quantitative proteomics methods to identify physiological substrates of Src homology 2 containing protein tyrosine phosphatase 2 (SHP2) in a high-throughput manner. The technique integrates three parallel mass spectrometry-based proteomics experiments, including affinity isolation of substrate-trapping mutant complex using wild-type and SHP2 KO cells, in vivo global quantitative phosphoproteomics, and in vitro phosphatase reaction. We confidently identified 18 direct substrates of SHP2 in the epidermal growth factor receptor signaling pathways, including both known and novel SHP2 substrates. Docking protein 1 was further validated using biochemical assays as a novel SHP2 substrate, providing a mechanism for SHP2-mediated Ras activation. This advanced workflow improves the systemic identification of direct substrates of protein phosphatases, facilitating our understanding of the equally important roles of protein phosphatases in cellular signaling.


Asunto(s)
Proteína Tirosina Fosfatasa no Receptora Tipo 11 , Proteómica , Receptores ErbB/metabolismo , Fosforilación , Proteína Tirosina Fosfatasa no Receptora Tipo 11/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 11/metabolismo , Transducción de Señal/fisiología
13.
Endoscopy ; 54(10): 972-979, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35391493

RESUMEN

BACKGROUND: This study aimed to develop an artificial intelligence (AI)-based system for measuring fold examination quality (FEQ) of colonoscopic withdrawal technique. We also examined the relationship between the system's evaluation of FEQ and FEQ scores from experts, and adenoma detection rate (ADR) and withdrawal time of colonoscopists, and evaluated the system's ability to improve FEQ during colonoscopy. METHODS: First, we developed an AI-based system for measuring FEQ. Next, 103 consecutive colonoscopies performed by 11 colonoscopists were collected for evaluation. Three experts graded FEQ of each colonoscopy, after which the recorded colonoscopies were evaluated by the system. We further assessed the system by correlating its evaluation of FEQ against expert scoring, historical ADR, and withdrawal time of each colonoscopist. We also conducted a prospective observational study to evaluate the system's performance in enhancing fold examination. RESULTS: The system's evaluations of FEQ of each endoscopist were significantly correlated with experts' scores (r = 0.871, P < 0.001), historical ADR (r = 0.852, P = 0.001), and withdrawal time (r = 0.727, P = 0.01). For colonoscopies performed by colonoscopists with previously low ADRs (< 25 %), AI assistance significantly improved the FEQ, evaluated by both the AI system (0.29 [interquartile range (IQR) 0.27-0.30] vs. 0.23 [0.17-0.26]) and experts (14.00 [14.00-15.00] vs. 11.67 [10.00-13.33]) (both P < 0.001). CONCLUSION: The system's evaluation of FEQ was strongly correlated with FEQ scores from experts, historical ADR, and withdrawal time of each colonoscopist. The system has the potential to enhance FEQ.


Asunto(s)
Adenoma , Neoplasias Colorrectales , Adenoma/diagnóstico por imagen , Inteligencia Artificial , Colonoscopios , Colonoscopía/métodos , Neoplasias Colorrectales/diagnóstico por imagen , Detección Precoz del Cáncer , Humanos
14.
Cell Immunol ; 359: 104255, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33316647

RESUMEN

BACKGROUND: Antibody-dependent cell-mediated cytotoxicity (ADCC) is one of the mechanisms connecting humoral immunity and cellular immunity and has been well-demonstrated in recent studies. Neutralizing antibodies and antibodies can mediate ADCC effects and both build a strong defense against H7N9 influenza virus infection. In our previous study, we found that H7N9 patients' plasma displayed low neutralizing activities that were not sufficient for host protection; however, the plasma of some patients can mediate strong ADCC effects. METHODS: Based on the plasma samples of H7N9 infected patients collected, we measured the ADCC activities of these samples and selected the best to locate the dominant epitopes on H7N9 hemagglutinin (HA) protein that can elicit antibodies and strong ADCC activities. We constructed a yeast surface-display H7N9 HA protein epitope library and screened this library against plasma samples with different potencies in mediating ADCC effects. RESULTS: Two dominant epitopes were selected from the screening. Plasma samples with depleted antibodies that were specific to the epitopes showed reduced ADCC activities. The serum of mice immunized with the epitopes elicited strong ADCC activities. Three monoclonal antibodies were isolated which showed high ADCC effects in vitro. Vaccination with isolated ADCC activating epitopes can provide partial protection from influenza infection in mouse model. And mice with vaccinated with combination of epitopes and extracellular domain can provide full protection from influenza infection in the same mouse model. CONCLUSIONS: In this study, the epitopes isolated on H7N9 HA were immunogenic and elicited antibodies and strong ADCC activities in mice. Although the protective effect of the epitopes is partial, the combination of epitopes and extracellular domain can provide 100% protection from influenza virus infection in the same mouse model. Our study provides information on the potential use of epitope vaccine design against H7N9 viral infection.


Asunto(s)
Hemaglutininas/inmunología , Subtipo H7N9 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Citotoxicidad Celular Dependiente de Anticuerpos/inmunología , Línea Celular , Reacciones Cruzadas/inmunología , Modelos Animales de Enfermedad , Epítopos/inmunología , Femenino , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Hemaglutininas/metabolismo , Humanos , Subtipo H1N1 del Virus de la Influenza A/inmunología , Gripe Humana/inmunología , Células Asesinas Naturales/inmunología , Ratones , Ratones Endogámicos BALB C , Infecciones por Orthomyxoviridae/inmunología , Vacunación/métodos
15.
Proc Natl Acad Sci U S A ; 115(51): 13123-13128, 2018 12 18.
Artículo en Inglés | MEDLINE | ID: mdl-30514814

RESUMEN

The perception and relay of cell-wall signals are critical for plants to regulate growth and stress responses, but the underlying mechanisms are poorly understood. We found that the cell-wall leucine-rich repeat extensins (LRX) 3/4/5 are critical for plant salt tolerance in Arabidopsis The LRXs physically associate with the RAPID ALKALINIZATION FACTOR (RALF) peptides RALF22/23, which in turn interact with the plasma membrane-localized receptor-like protein kinase FERONIA (FER). The lrx345 triple mutant as well as fer mutant plants display retarded growth and salt hypersensitivity, which are mimicked by overexpression of RALF22/23 Salt stress promotes S1P protease-dependent release of mature RALF22 peptides. Treatment of roots with mature RALF22/23 peptides or salt stress causes the internalization of FER. Our results suggest that the LRXs, RALFs, and FER function as a module to transduce cell-wall signals to regulate plant growth and salt stress tolerance.


Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiología , Desarrollo de la Planta , Plantas Modificadas Genéticamente/fisiología , Proteínas/metabolismo , Tolerancia a la Sal/genética , Estrés Fisiológico , Proteínas de Arabidopsis/genética , Pared Celular/metabolismo , Regulación de la Expresión Génica de las Plantas , Leucina/química , Proteínas Repetidas Ricas en Leucina , Proteínas/genética , Plantas Tolerantes a la Sal/fisiología , Transducción de Señal
16.
Inorg Chem ; 59(21): 15579-15582, 2020 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-33054195

RESUMEN

Four polyoxometalate (POM)-based Cu complexes with the hydroxylated pyridine analogue 3-(2-hydroxylpyrid-4-yl)-5-(1H-1,2,4-triazol-3-yl)-1,2,4-triazolyl (btpo), H3{[Cu2(btpo)2](PW12O40)}·2H2O (1), H3{[Cu2(btpo)2](PMo12O40)}·2H2O (2), H2{[Cu2(btpo)2](SiW12O40)·SO4 (3), and H4{[Cu4(btpo)4](SiW12O40)}·8H2O (4), were synthesized hydrothermally under acid conditions. Single-crystal X-ray structural analysis reveals that 3-(pyrid-4-yl)-5-(1H-1,2,4-triazol-3-yl)-1,2,4-triazolyl was hydroxylated into btpo in compounds 1-4, again providing structural evidence for the Gillard mechanism, in which H2O as a weak nucleophile can attack the α-C atom of N-heterocyclic molecules at a lower pH value (ca. 1.0) with the help of POMs.

17.
Mol Cell Proteomics ; 17(10): 2068-2080, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30006488

RESUMEN

Phosphorylation-mediated signaling transduction plays a crucial role in the regulation of plant defense mechanisms against environmental stresses. To address the high complexity and dynamic range of plant proteomes and phosphoproteomes, we present a universal sample preparation procedure that facilitates plant phosphoproteomic profiling. This advanced workflow significantly improves phosphopeptide identifications, enabling deep insight into plant phosphoproteomes. We then applied the workflow to study the phosphorylation events involved in tomato cold tolerance mechanisms. Phosphoproteomic changes of two tomato species (N135 Green Gage and Atacames) with distinct cold tolerance phenotypes were profiled under cold stress. In total, we identified more than 30,000 unique phosphopeptides from tomato leaves, representing about 5500 phosphoproteins, thereby creating the largest tomato phosphoproteomic resource to date. The data, along with the validation through in vitro kinase reactions, allowed us to identify kinases involved in cold tolerant signaling and discover distinctive kinase-substrate events in two tomato species in response to a cold environment. The activation of SnRK2s and their direct substrates may assist N135 Green Gage tomatoes in surviving long-term cold stress. Taken together, the streamlined approach and the resulting deep phosphoproteomic analyses revealed a global view of tomato cold-induced signaling mechanisms.


Asunto(s)
Respuesta al Choque por Frío , Fosfoproteínas/metabolismo , Proteínas de Plantas/metabolismo , Proteómica/métodos , Transducción de Señal , Solanum lycopersicum/metabolismo , Estrés Fisiológico , Secuencia de Aminoácidos , Marcaje Isotópico , Fenotipo , Fosfoproteínas/química , Proteínas de Plantas/química , Proteínas Quinasas/metabolismo , Especificidad por Sustrato , Flujo de Trabajo
18.
New Phytol ; 224(1): 274-290, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31009077

RESUMEN

The capability to maintain cell wall integrity is critical for plants to adapt to unfavourable conditions. l-Arabinose (Ara) is a constituent of several cell wall polysaccharides and many cell wall-localised glycoproteins, but so far the contribution of Ara metabolism to abiotic stress tolerance is still poorly understood. Here, we report that mutations in the MUR4 (also known as HSR8) gene, which is required for the biosynthesis of UDP-Arap in Arabidopsis, led to reduced root elongation under high concentrations of NaCl, KCl, NaNO3 , or KNO3 . The short root phenotype of the mur4/hsr8 mutants under high salinity is rescued by exogenous Ara or gum arabic, a commercial product of arabinogalactan proteins (AGPs) from Acacia senegal. Mutation of the MUR4 gene led to abnormal cell-cell adhesion under salt stress. MUR4 forms either a homodimer or heterodimers with its isoforms. Analysis of the higher order mutants of MUR4 with its three paralogues, MURL, DUR, MEE25, reveals that the paralogues of MUR4 also contribute to the biosynthesis of UDP-Ara and are critical for root elongation. Taken together, our work revealed the importance of the Ara metabolism in salt stress tolerance and also provides new insights into the enzymes involved in the UDP-Ara biosynthesis in plants.


Asunto(s)
Arabidopsis/fisiología , Arabinosa/biosíntesis , Tolerancia a la Sal/fisiología , Estrés Fisiológico , Ácido Abscísico/farmacología , Arabidopsis/efectos de los fármacos , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arabinosa/farmacología , Adhesión Celular/efectos de los fármacos , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Mucoproteínas/metabolismo , Mutación/genética , Fenotipo , Proteínas de Plantas/metabolismo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/crecimiento & desarrollo , Isoformas de Proteínas/metabolismo , Multimerización de Proteína/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Cloruro de Sodio/farmacología , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/genética
19.
Inorg Chem ; 56(19): 11998-12002, 2017 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-28925694

RESUMEN

A POMs templated 3D Ag-carbene framework with lvt-a topology was hydrothermally synthesized. The POMs templated MCF combining the advantages of POMs, MOFs, and carbene not only shows excellent thermal and chemical stabilities but also possesses a good discharge capacity of 481 mAh·g-1 after 100 cycles applied as anode material in LIBs.

20.
Inorg Chem ; 56(14): 8311-8318, 2017 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-28648059

RESUMEN

A series of remarkable crystalline compounds containing metallapillararene/metallacalixarene metal-organic frameworks (MOFs), [Ag5(pyttz)3·Cl·(H2O)][H3SiMo12O40]·3H2O (1), [Ag5(trz)6][H5SiMo12O40] (2), [Ag5(trz)6][H5GeMo12O40] (3), and [Ag5(trz)6][H4PW12O40] (4) (pyttz = 3-(pyrid-4-yl)-5-(1H-1,2,4-triazol-3-yl)-1,2,4-triazolyl, trz = 1,2,4-triazole), have been obtained by using a simple one-step hydrothermal reaction of silver nitrate, pyttz for 1 and trz for 2-4, and Keggin type polyoxometalates (POMs). Crystal analysis reveals that Keggin POMs have been successfully incorporated in the windows of the metallapillararene/metallacalixarene MOFs in compounds 1-4. In addition, the Keggin silicomolybdenate-based hybrid compounds 1 and 2 were used as anode materials in lithium ion batteries (LIBs), which exhibited promising electrochemical performance with the first discharge capacities of 1344 mAh g-1 for 1 and 1452 mAh g-1 for 2, and this stabilized at 520 mAh g-1 for 1 and 570 mAh g-1 for 2 after 100 cycles at a current density of 100 mA g-1. The performances are better than that of (NBu4)4[SiMo12O40] matrix and commercial graphite anodes.

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