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Rice is sensitive to cold and can be grown only in certain climate zones. Human selection of japonica rice has extended its growth zone to regions with lower temperature, while the molecular basis of this adaptation remains unknown. Here, we identify the quantitative trait locus COLD1 that confers chilling tolerance in japonica rice. Overexpression of COLD1(jap) significantly enhances chilling tolerance, whereas rice lines with deficiency or downregulation of COLD1(jap) are sensitive to cold. COLD1 encodes a regulator of G-protein signaling that localizes on plasma membrane and endoplasmic reticulum (ER). It interacts with the G-protein α subunit to activate the Ca(2+) channel for sensing low temperature and to accelerate G-protein GTPase activity. We further identify that a SNP in COLD1, SNP2, originated from Chinese Oryza rufipogon, is responsible for the ability of COLD(jap/ind) to confer chilling tolerance, supporting the importance of COLD1 in plant adaptation.
Assuntos
Proteínas e Peptídeos de Choque Frio/metabolismo , Oryza/fisiologia , Proteínas de Plantas/metabolismo , Sequência de Aminoácidos , Cruzamento , Proteínas e Peptídeos de Choque Frio/genética , Temperatura Baixa , Retículo Endoplasmático , Proteínas de Ligação ao GTP/química , Proteínas de Ligação ao GTP/genética , Proteínas de Ligação ao GTP/metabolismo , Regulação da Expressão Gênica de Plantas , Dados de Sequência Molecular , Mutação , Oryza/citologia , Oryza/genética , Proteínas de Plantas/química , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Alinhamento de SequênciaRESUMO
Expression quantitative trait loci (eQTLs) are used to inform the mechanisms of transcriptional regulation in eukaryotic cells. However, the specificity of genome-wide eQTL identification is limited by stringent control for false discoveries. Here, we described a method based on the non-homogeneous Poisson process to identify 125 489 regions with highly frequent, multiple eQTL associations, or 'eQTL-hotspots', from the public database of 59 human tissues or cell types. We stratified the eQTL-hotspots into two classes with their distinct sequence and epigenomic characteristics. Based on these classifications, we developed a machine-learning model, E-SpotFinder, for augmented discovery of tissue- or cell-type-specific eQTL-hotspots. We applied this model to 36 tissues or cell types. Using augmented eQTL-hotspots, we recovered 655 402 eSNPs and reconstructed a comprehensive regulatory network of 2 725 380 cis-interactions among eQTL-hotspots. We further identified 52 012 modules representing transcriptional programs with unique functional backgrounds. In summary, our study provided a framework of epigenome-augmented eQTL analysis and thereby constructed comprehensive genome-wide networks of cis-regulations across diverse human tissues or cell types.
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Epigenoma , Epigenômica , Humanos , Bases de Dados Factuais , Células Eucarióticas , Aprendizado de MáquinaRESUMO
Heat stress is an environmental factor that significantly threatens crop production worldwide. Nevertheless, the molecular mechanisms governing plant responses to heat stress are not fully understood. Plant zinc finger CCCH proteins have roles in stress responses as well as growth and development through protein-RNA, protein-DNA, and protein-protein interactions. Here, we reveal an integrated multi-level regulation of plant thermotolerance that is mediated by the CCCH protein C3H15 in Arabidopsis. Heat stress rapidly suppressed C3H15 transcription, which attenuated C3H15-inhibited expression of its target gene HEAT SHOCK TRANSCRIPTION FACTOR A2 (HSFA2), a central regulator of heat stress response (HSR), thereby activating HEAT SHOCK COGNATE 70 (HSC70.3) expression. The RING-type E3 ligase MED25-BINDING RING-H2 PROTEIN 2 (MBR2) was identified as an interacting partner of C3H15. The mbr2 mutant was susceptible to heat stress compared to wild-type plants, whereas plants overexpressing MBR2 showed increased heat tolerance. MBR2-dependent ubiquitination mediated the degradation of phosphorylated C3H15 protein in the cytoplasm, which was enhanced by heat stress. Consistently, heat sensitivities of C3H15 overexpression lines increased in MBR2 loss-of-function and decreased in MBR2 overexpression backgrounds. Heat stress-induced accumulation of HSC70.3 promoted MBR2-mediated degradation of C3H15 protein, implying that an auto-regulatory loop involving C3H15, HSFA2, and HSC70.3 regulates HSR. Heat stress also led to the accumulation of C3H15 in stress granules (SGs), a kind of cytoplasmic RNA granule. This study advances our understanding of the mechanisms plants use to respond to heat stress, which will facilitate technologies to improve thermotolerance in crops.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Regulação da Expressão Gênica de Plantas , Fatores de Transcrição de Choque Térmico , Resposta ao Choque Térmico , Termotolerância , Arabidopsis/genética , Arabidopsis/fisiologia , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Termotolerância/genética , Resposta ao Choque Térmico/genética , Resposta ao Choque Térmico/fisiologia , Fatores de Transcrição de Choque Térmico/genética , Fatores de Transcrição de Choque Térmico/metabolismo , Plantas Geneticamente Modificadas , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Companionship refers to one's being in the presence of another individual. For adults, acquiring a new language is a highly social activity that often involves learning in the context of companionship. However, the effects of companionship on new language learning have gone relatively underexplored, particularly with respect to word learning. Using a within-subject design, the current study employs electroencephalography to examine how two types of companionship (monitored and co-learning) affect word learning (semantic and lexical) in a new language. Dyads of Chinese speakers of English as a second language participated in a pseudo-word-learning task during which they were placed in monitored and co-learning companionship contexts. The results showed that exposure to co-learning companionship affected the early attention stage of word learning. Moreover, in this early stage, evidence of a higher representation similarity between co-learners showed additional support that co-learning companionship influenced attention. Observed increases in delta and theta interbrain synchronization further revealed that co-learning companionship facilitated semantic access. In all, the similar neural representations and interbrain synchronization between co-learners suggest that co-learning companionship offers important benefits for learning words in a new language.
Assuntos
Encéfalo , Eletroencefalografia , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Encéfalo/fisiologia , Aprendizagem/fisiologia , Semântica , Multilinguismo , Idioma , Atenção/fisiologia , Aprendizagem Verbal/fisiologiaRESUMO
BACKGROUND: Most of the important biological mechanisms and functions of transmembrane proteins (TMPs) are realized through their interactions with non-transmembrane proteins(nonTMPs). The interactions between TMPs and nonTMPs in cells play vital roles in intracellular signaling, energy metabolism, investigating membrane-crossing mechanisms, correlations between disease and drugs. RESULTS: Despite the importance of TMP-nonTMP interactions, the study of them remains in the wet experimental stage, lacking specific and comprehensive studies in the field of bioinformatics. To fill this gap, we performed a comprehensive statistical analysis of known TMP-nonTMP interactions and constructed a deep learning-based predictor to identify potential interactions. The statistical analysis describes known TMP-nonTMP interactions from various perspectives, such as distributions of species and protein families, enrichment of GO and KEGG pathways, as well as hub proteins and subnetwork modules in the PPI network. The predictor implemented by an end-to-end deep learning model can identify potential interactions from protein primary sequence information. The experimental results over the independent validation demonstrated considerable prediction performance with an MCC of 0.541. CONCLUSIONS: To our knowledge, we were the first to focus on TMP-nonTMP interactions. We comprehensively analyzed them using bioinformatics methods and predicted them via deep learning-based solely on their sequence. This research completes a key link in the protein network, benefits the understanding of protein functions, and helps in pathogenesis studies of diseases and associated drug development.
Assuntos
Biologia Computacional , Proteínas de Membrana , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Biologia Computacional/métodos , Aprendizado Profundo , Humanos , Mapas de Interação de ProteínasRESUMO
To cope with flooding-induced hypoxia, plants have evolved different strategies. Molecular strategies, such as the N-degron pathway and transcriptional regulation, are known to be crucial for Arabidopsis thaliana's hypoxia response. Our study uncovered a novel molecular strategy that involves a single transcription factor interacting with two identical cis-elements, one located in the promoter region and the other within the intron. This unique double-element adjustment mechanism has seldom been reported in previous studies. In humid areas, WRKY70 plays a crucial role in A. thaliana's adaptation to submergence-induced hypoxia by binding to identical cis-elements in both the promoter and intron regions of WRKY33. This dual binding enhances WRKY33 expression and the activation of hypoxia-related genes. Conversely, in arid regions lacking the promoter cis-element, WRKY70 only binds to the intron cis-element, resulting in limited WRKY33 expression during submergence stress. The presence of a critical promoter cis-element in humid accessions, but not in dry accessions, indicates a coordinated regulation enabling A. thaliana to adapt and thrive in humid habitats.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regiões Promotoras Genéticas/genética , Hipóxia/genética , Regulação da Expressão Gênica de PlantasRESUMO
Anthracenylidene is an intriguing structural unit with potential in various fields. The study presents a novel approach to introducing axial chirality into this all-carbon core skeleton through a remotely controlled desymmetrization strategy. A palladium-catalyzed enantioselective Heck arylation of exocyclic double bond of anthracene with two distinct substituents at the C10 position is harnessed to realize such a transformation. The judicious identification of the P-centrally chiral ligand is pivotal to ensure the competitive competence in reactivity and stereocontrol when the heteroatom handle is absent from the anthracenylidene skeleton. Both C10 mono- and disubstituted substrates were compatible for the established catalytic system, and structurally diverse anthracenylidene-based frameworks were forged with good-to-high enantiocontrol. The subsequent derivatization of the obtained products yielded a valuable array of centrally and axially chiral molecules, thus emphasizing the practicality of this chemistry. DFT calculations shed light on the catalytic mechanism and provided insights into the origin of the experimentally observed enantioselectivity for this reaction.
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Modulating the electronic properties of transition metal sites in photocatalysts at the atomic level is essential for achieving high-activity carbon dioxide photoreduction (CO2PR). An electronic strategy is herein proposed to engineer In-d-band center of InVO4 by incorporating MnOx nanoparticles and oxygen vacancies (VO) into holey InVO4 nanobelts (MnOx/VO-InVO4), which synergistically modulates the In-d-band center to a moderate level and consequently leads to high-efficiency CO2PR. The MnOx/VO-InVO4 catalyst with optimized electronic property exhibits a single carbon evolution rate of up to 145.3 µmol g-1 h-1 and a carbon monoxide (CO) product selectivity of 92.6%, coming out in front of reported InVO4-based materials. It is discovered that the modulated electronic property favors the interaction between the In sites and their intermediates, which thereby improves the thermodynamics and kinetics of the CO2PR-to-CO reaction. This work not only demonstrates the effective engineering of the d orbital of the low-coordination In atoms to promote CO2PR, but also paves the way for the application of tuning d-band center to develop high-efficiency catalysts.
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The intricate processes that govern the interactions between peripatetic immune cells and distal renal injury in obesity are not fully understood. Employing transcriptomic analysis of circulating extracellular vesicles (EVs), a marked amplification of small RNA (miR-3960) is discerned within CD3-CD19+ B cells. This RNA is found to be preferentially augmented in kidney tissues, contrasting with its subdued expression in other organs. By synthesizing dual-luciferase reporter assay with co-immunoprecipitation analysis, it is pinpointed that miR-3960 specifically targets the nuclear gene TRMT5, a pivotal actor in the methylation of mitochondrial tRNA. This liaison instigates aberrations in the post-transcriptional modifications of mitochondrial tRNA, engendering deficiencies within the electron respiratory chain, primarily attributable to the diminution of the mitochondrial bioenergetic compound (NDUFA7) complex I. Such perturbations lead to a compromised mitochondrial respiratory capacity in renal tubular cells, thereby exacerbating tubular injury. In contrast, EV blockade or miR-3960 depletion markedly alleviates renal tubular injury in obesity. This investigation unveils a hitherto unexplored pathway by which obesity-induced circulating immune cells remotely manipulate mitochondrial metabolism in target organs. The strategic targeting of obese EVs or infiltrative immune cells and their specifically secreted RNAs emerges as a promising therapeutic avenue to forestall obesity-related renal afflictions.
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Herbivore-associated molecular patterns (HAMPs) enable plants to recognize herbivores and may help plants adjust their defense responses. Here, we report on herbivore-induced changes in a protein disulfide isomerase (PDI) widely distributed across arthropods. PDI from the spider mite Tetranychus evansi (TePDI), a mesophyll-feeding agricultural pest worldwide, triggered immunity in multiple Solanaceae plants. TePDI-mediated cell death in Nicotiana benthamiana required the plant signaling proteins SGT1 (suppressor of the G2 allele of skp1) and HSP90 (heat shock protein 90), but was suppressed by spider mite effectors Te28 and Te84. Moreover, PDIs from phylogenetically distinct herbivorous and nonherbivorous arthropods triggered plant immunity. Finally, although PDI-induced plant defenses impaired the performance of spider mites on plants, RNAi experiments revealed that PDI genes are essential for the survival of mites and whiteflies. Our findings indicate that plants recognize evolutionarily conserved HAMPs to activate plant defense and resist pest damage, pointing to opportunities for broad-spectrum pest management.
Assuntos
Herbivoria , Tetranychidae , Animais , Isomerases de Dissulfetos de Proteínas/genética , Plantas , Nicotiana/genética , Proteínas de Plantas/genética , Tetranychidae/fisiologiaRESUMO
Oxygen deprivation caused by flooding activates acclimation responses to stress and restricts plant growth. After experiencing flooding stress, plants must restore normal growth; however, which genes are dynamically and precisely controlled by flooding stress remains largely unknown. Here, we show that the Arabidopsis thaliana ubiquitin E3 ligase SUBMERGENCE RESISTANT1 (SR1) regulates the stability of the transcription factor WRKY33 to modulate the submergence response. SR1 physically interacts with WRKY33 in vivo and in vitro and controls its ubiquitination and proteasomal degradation. Both the sr1 mutant and WRKY33 overexpressors exhibited enhanced submergence tolerance and enhanced expression of hypoxia-responsive genes. Genetic experiments showed that WRKY33 functions downstream of SR1 during the submergence response. Submergence induced the phosphorylation of WRKY33, which enhanced the activation of RAP2.2, a positive regulator of hypoxia-response genes. Phosphorylated WRKY33 and RAP2.2 were degraded by SR1 and the N-degron pathway during reoxygenation, respectively. Taken together, our findings reveal that the on-and-off module SR1-WRKY33-RAP2.2 is connected to the well-known N-degron pathway to regulate acclimation to submergence in Arabidopsis. These two different but related modulation cascades precisely balance submergence acclimation with normal plant growth.
Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Proteólise , Fatores de Transcrição/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Escuridão , Epistasia Genética , Regulação da Expressão Gênica de Plantas , Modelos Biológicos , Fosforilação , Ligação Proteica , UbiquitinaçãoRESUMO
PURPOSE: Programmed cell death protein ligand 1 (PD-L1) is a crucial biomarker for immunotherapy. However, nearly 70% of patients do not respond to PD-L1 immune checkpoint therapy. Accurate monitoring of PD-L1 expression and quantification of target binding during treatment are essential. In this study, a series of small-molecule radiotracers were developed to assess PD-L1 expression and direct immunotherapy. METHODS: Radiotracers of [68Ga]Ga-D-PMED, [68Ga]Ga-D-PEG-PMED, and [68Ga]Ga-D-pep-PMED were designed based on a 2-methyl-3-biphenyl methanol scaffold and successfully synthesized. Cellular experiments and molecular docking assays were performed to determine their specificity for PD-L1. PD-L1 status was investigated via positron emission tomography (PET) imaging in MC38 tumor models. PET imaging of [68Ga]Ga-D-pep-PMED was performed to noninvasively quantify PD-L1 blocking using an anti-mouse PD-L1 antibody (PD-L1 mAb). RESULTS: The radiosyntheses of [68Ga]Ga-D-PMED, [68Ga]Ga-D-PEG-PMED, and [68Ga]Ga-D-pep-PMED were achieved with radiochemical yields of 87 ± 6%, 82 ± 4%, and 79 ± 9%, respectively. In vitro competition assays demonstrated their high affinities (the IC50 values of [68Ga]Ga-D-PMED, [68Ga]Ga-D-PEG-PMED, and [68Ga]Ga-D-pep-PMED were 90.66 ± 1.24, 160.8 ± 1.35, and 51.6 ± 1.32 nM, respectively). At 120 min postinjection (p.i.) of the radiotracers, MC38 tumors displayed optimized tumor-to-muscle ratios for all radioligands. Owing to its hydrophilic modification, [68Ga]Ga-D-pep-PMED had the highest target-to-nontarget (T/NT) ratio of approximately 6.2 ± 1.2. Interestingly, the tumor/liver ratio was hardly affected by different concentrations of the inhibitor BMS202. We then evaluated the impacts of dose and time on accessible PD-L1 levels in the tumor during anti-mouse PD-L1 antibody treatment. The tumor uptake of [68Ga]Ga-D-pep-PMED significantly decreased with increasing PD-L1 mAb dose. Moreover, after 8 days of treatment with a single antibody, the uptake of [68Ga]Ga-D-pep-PMED in the tumor significantly increased but remained lower than that in the saline group. CONCLUSION: PET imaging with [68Ga]Ga-D-pep-PMED, a small-molecule radiotracer, is a promising tool for evaluating PD-L1 expression and quantifying the target blockade of PD-L1 to assist in the development of effective therapeutic regimens.
Assuntos
Acetamidas , Antígeno B7-H1 , Tomografia por Emissão de Pósitrons , Piridinas , Imunoterapia , Antígeno B7-H1/análise , Antígeno B7-H1/antagonistas & inibidores , Humanos , Animais , Camundongos , Linhagem Celular Tumoral , Células A549 , Compostos Organometálicos , Radioisótopos de Gálio , Acetamidas/química , Piridinas/químicaRESUMO
Ventricular arrhythmias are the leading cause of sudden cardiac death in patients after myocardial infarction (MI). Connexin43 (Cx43) is the most important gap junction channel-forming protein in cardiomyocytes. Dysfunction of Cx43 contributes to impaired myocardial conduction and the development of ventricular arrhythmias. Following an MI, Cx43 undergoes structural remodeling, including expression abnormalities, and redistribution. These alterations detrimentally affect intercellular communication and electrical conduction within the myocardium, thereby increasing the susceptibility to post-infarction ventricular arrhythmias. Emerging evidence suggests that post-translational modifications play essential roles in Cx43 regulation after MI. Therefore, Cx43-targeted management has the potential to be a promising protective strategy for the prevention and treatment of post infarction ventricular arrhythmias. In this article, we primarily reviewed the regulatory mechanisms of Cx43 mediated post-translational modifications on post-infarction ventricular arrhythmias. Furthermore, Cx43-targeted therapy have also been discussed, providing insights into an innovative treatment strategy for ventricular arrhythmias after MI.
Assuntos
Conexina 43 , Infarto do Miocárdio , Humanos , Arritmias Cardíacas/metabolismo , Conexina 43/genética , Conexina 43/metabolismo , Infarto do Miocárdio/complicações , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Processamento de Proteína Pós-TraducionalRESUMO
Heavy metals pollution is a notable threat to environment and human health. This study evaluated the potential ecological and health risks of heavy metals (Cu, Cr, Cd, Pb, Zn, Ni, and As) and their accumulation in a peanut-soil system based on 34 soil and peanut kernel paired samples across China. Soil As and Cd posed the greatest pollution risk with 47.1% and 17.6% of soil samples exceeding the risk screen levels, respectively, with 26.5% and 20.6% of the soil sites at relatively strong potential ecological risk level, respectively, and with the geo-accumulation levels at several soil sites in the uncontaminated to moderately contaminated categories. About 35.29% and 2.94% of soil sites were moderately and severely polluted based on Nemerow comprehensive pollution index, respectively, and a total of 32.4% of samples were at moderate ecological hazard level based on comprehensive potential ecological risk index values. The Cd, Cr, Ni, and Cu contents exceeded the standard in 11.76, 8.82, 11.76 and 5.88% of the peanut kernel samples, respectively. Soil metals posed more health risks to children than adults in the order As > Ni > Cr > Cu > Pb > Zn > Cd for non-carcinogenic health risks and Ni > Cr â« Cd > As > Pb for carcinogenic health risks. The soil As non-cancer risk index for children was greater than the permitted limits at 14 sites, and soil Ni and Cr posed the greatest carcinogenic risk to adults and children at many soil sites. The metals in peanut did not pose a non-carcinogenic risk according to standard. Peanut kernels had strong enrichment ability for Cd with an average bio-concentration factor (BCF) of 1.62. Soil metals contents and significant soil properties accounted for 35-74% of the variation in the BCF values of metals based on empirical prediction models.
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Arachis , Metais Pesados , Poluentes do Solo , Metais Pesados/análise , Arachis/química , Medição de Risco , Poluentes do Solo/análise , Humanos , China , Monitoramento Ambiental , Solo/química , CriançaRESUMO
BACKGROUND: Radiotheranostics differs from the vast majority of other cancer therapies in its capacity for simultaneous imaging and therapy, and it is becoming more widely implemented. A balance between diagnostic and treatment requirements is essential for achieving effective radiotheranostics. Herein, we propose a proof-of-concept strategy aiming to address the profound differences in the specific requirements of the diagnosis and treatment of radiotheranostics. RESULTS: To validate the concept, we designed an s-tetrazine (Tz) conjugated prostate-specific membrane antigen (PSMA) ligand (DOTA-PSMA-Tz) for 68Ga or 177Lu radiolabeling and tumor radiotheranostics, a trans-cyclooctene (TCO) modified Pd@Au nanoplates (Pd@Au-PEG-TCO) for signal amplification, respectively. We then demonstrated this radiotheranostic strategy in the tumor-bearing mice with the following three-step procedures: (1) i.v. injection of the [68Ga]Ga-PSMA-Tz for diagnosis; (2) i.v. injection of the signal amplification module Pd@Au-PEG-TCO; (3) i.v. injection of the [177Lu]Lu-PSMA-Tz for therapy. Firstly, this strategy was demonstrated in 22Rv1 tumor-bearing mice via positron emission tomography (PET) imaging with [68Ga]Ga-PSMA-Tz. We observed significantly higher tumor uptake (11.5 ± 0.8%ID/g) with the injection of Pd@Au-PEG-TCO than with the injection [68Ga]Ga-PSMA-Tz alone (5.5 ± 0.9%ID/g). Furthermore, we validated this strategy through biodistribution studies of [177Lu]Lu-PSMA-Tz, with the injection of the signal amplification module, approximately five-fold higher tumor uptake of [177Lu]Lu-PSMA-Tz (24.33 ± 2.53% ID/g) was obtained when compared to [177Lu]Lu-PSMA-Tz alone (5.19 ± 0.26%ID/g) at 48 h post-injection. CONCLUSION: In summary, the proposed strategy has the potential to expand the toolbox of pretargeted radiotherapy in the field of theranostics.
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Neoplasias Colorretais , Compostos Radiofarmacêuticos , Masculino , Animais , Camundongos , Radioisótopos de Gálio , Distribuição Tecidual , Linhagem Celular Tumoral , Neoplasias Colorretais/patologiaRESUMO
This clinical report describes a digital workflow for the rehabilitation of an 8-year-old patient diagnosed with ectodermal dysplasia. Based on the patient's digital primary casts, small custom trays and an arch tracer were designed and 3-dimensionally printed. The mandibular custom tray and retention plate with a tracing screw were assembled with tracing plate, forming an individual assembled mini-arch tracer system to record the jaw relationship together with a conventional facebow and a digital articulator. In addition, composite resin injection guides were designed and fabricated to form the predesigned targeted shape of the abutment teeth and provide a buffer. By following this workflow, complete overdentures with good fit, occlusion, and acceptable esthetics were delivered.
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ACYL-CoA-BINDING PROTEINs (ACBPs) play crucial regulatory roles during plant response to hypoxia, but their molecular mechanisms remain poorly understood. Our study reveals that ACBP4 serves as a positive regulator of the plant hypoxia response by interacting with WRKY70, influencing its nucleocytoplasmic shuttling in Arabidopsis thaliana. Furthermore, we demonstrate the direct binding of WRKY70 to the ACBP4 promoter, resulting in its upregulation and suggesting a positive feedback loop. Additionally, we pinpointed a phosphorylation site at Ser638 of ACBP4, which enhances submergence tolerance, potentially by facilitating WRKY70's nuclear shuttling. Surprisingly, a natural variation in this phosphorylation site of ACBP4 allowed A. thaliana to adapt to humid conditions during its historical demographic expansion. We further observed that both phosphorylated ACBP4 and oleoyl-CoA can impede the interaction between ACBP4 and WRKY70, thus promoting WRKY70's nuclear translocation. Finally, we found that the overexpression of orthologous BnaC5.ACBP4 and BnaA7.WRKY70 in Brassica napus increases submergence tolerance, indicating their functional similarity across genera. In summary, our research not only sheds light on the functional significance of the ACBP4 gene in hypoxia response, but also underscores its potential utility in breeding flooding-tolerant oilseed rape varieties.
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Proteínas de Arabidopsis , Arabidopsis , Regulação da Expressão Gênica de Plantas , Fatores de Transcrição , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Ligação a DNA , Fosforilação , Regiões Promotoras Genéticas/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genéticaRESUMO
A digital workflow is presented for multiple transfers of targeted jaw relation and restorative spaces from interim to definitive restorations in patients with severe tooth wear. Following analysis of the targeted restorative space, segmented arch stereolithographic templates were digitally created and fabricated for precise control of reduction depth. Then, the jaw relation was transferred from the initially determined stabilization splint to the temporary fixed restoration and definitive restoration by using a digital articulator. This digital approach yielded a stabilized jaw relationship and restorative spaces transferring effect throughout successive stages of occlusal reconstruction resulting in satisfactory prosthetic outcomes.
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In real-life communication, individuals use language that carries evident rewarding and punishing elements, such as praise and criticism. A common trend is to seek more praise while avoiding criticism. Furthermore, semantics is crucial for conveying information, but such semantic access to native and foreign languages is subtly distinct. To investigate how rule learning occurs in different languages and to highlight the importance of semantics in this process, we investigated both verbal and non-verbal rule learning in first (L1) and second (L2) languages using a reinforcement learning framework, including a semantic rule and a color rule. Our computational modeling on behavioral and brain imaging data revealed that individuals may be more motivated to learn and adhere to rules in an L1 compared to L2, with greater striatum activation during the outcome phase in the L1. Additionally, results on the learning rates and inverse temperature in the two rule learning tasks showed that individuals tend to be conservative and are reluctant to change their judgments regarding rule learning of semantic information. Moreover, the greater the prediction errors, the greater activation of the right superior temporal gyrus in the semantic-rule learning condition, demonstrating that such learning has differential neural correlates than symbolic rule learning. Overall, the findings provide insight into the neural mechanisms underlying rule learning in different languages, and indicate that rule learning involving verbal semantics is not a general symbolic learning that resembles a conditioned stimulus-response, but rather has its own specific characteristics.
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Aprendizagem , Semântica , Humanos , Idioma , Encéfalo/fisiologia , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/fisiologia , Mapeamento Encefálico , Imageamento por Ressonância MagnéticaRESUMO
Chiral cyclobutene units are commonly found in natural products and biologically active molecules. Transition-metal-catalysis has been extensively used in asymmetric synthesis of such structures, while organocatalytic approaches remain elusive. In this study, bicyclo[1.1.0]butanes are involved in enantioselective transformation for the first time to offer a highly efficient route toward cyclobutenes with good regio- and enantiocontrol. The utilization of N-triflyl phosphoramide as a chiral Brønsted acid promoter enables this isomerization process to proceed under mild conditions with low catalyst loading as well as good functional group compatibility. The resulting chiral cyclobutenes could serve as platform molecules for downstream manipulations with excellent reservation of stereochemical integrity, demonstrating the synthetic practicality of the developed method. Control experiments have also been performed to verify the formation of a key carbocation intermediate at the benzylic position.