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Horizontal gene transfer (HGT) is an important evolutionary force shaping prokaryotic and eukaryotic genomes. HGT-acquired genes have been sporadically reported in insects, a lineage containing >50% of animals. We systematically examined HGT in 218 high-quality genomes of diverse insects and found that they acquired 1,410 genes exhibiting diverse functions, including many not previously reported, via 741 distinct transfers from non-metazoan donors. Lepidopterans had the highest average number of HGT-acquired genes. HGT-acquired genes containing introns exhibited substantially higher expression levels than genes lacking introns, suggesting that intron gains were likely involved in HGT adaptation. Lastly, we used the CRISPR-Cas9 system to edit the prevalent unreported gene LOC105383139, which was transferred into the last common ancestor of moths and butterflies. In diamondback moths, males lacking LOC105383139 courted females significantly less. We conclude that HGT has been a major contributor to insect adaptation.
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Mariposas Diurnas , Transferencia de Gen Horizontal , Animales , Mariposas Diurnas/genética , Cortejo , Evolución Molecular , Masculino , FilogeniaRESUMEN
Large-scale genetic association studies have identified multiple susceptibility loci for nasopharyngeal carcinoma (NPC), but the underlying biological mechanisms remain to be explored. To gain insights into the genetic etiology of NPC, we conducted a follow-up study encompassing 6,907 cases and 10,472 controls and identified two additional NPC susceptibility loci, 9q22.33 (rs1867277; OR = 0.74, 95% CI = 0.68-0.81, p = 3.08 × 10-11) and 17q12 (rs226241; OR = 1.42, 95% CI = 1.26-1.60, p = 1.62 × 10-8). The two additional loci, together with two previously reported genome-wide significant loci, 5p15.33 and 9p21.3, were investigated by high-throughput sequencing for chromatin accessibility, histone modification, and promoter capture Hi-C (PCHi-C) profiling. Using luciferase reporter assays and CRISPR interference (CRISPRi) to validate the functional profiling, we identified PHF2 at locus 9q22.33 as a susceptibility gene. PHF2 encodes a histone demethylase and acts as a tumor suppressor. The risk alleles of the functional SNPs reduced the expression of the target gene PHF2 by inhibiting the enhancer activity of its long-range (4.3 Mb) cis-regulatory element, which promoted proliferation of NPC cells. In addition, we identified CDKN2B-AS1 as a susceptibility gene at locus 9p21.3, and the NPC risk allele of the functional SNP rs2069418 promoted the expression of CDKN2B-AS1 by increasing its enhancer activity. The overexpression of CDKN2B-AS1 facilitated proliferation of NPC cells. In summary, we identified functional SNPs and NPC susceptibility genes, which provides additional explanations for the genetic association signals and helps to uncover the underlying genetic etiology of NPC development.
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Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patología , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Estudios de Asociación Genética , Polimorfismo de Nucleótido Simple/genética , Proteínas de Homeodominio/genéticaRESUMEN
Atypical acute promyelocytic leukemia (aAPL) presents a complex landscape of retinoic acid receptor (RAR) fusion genes beyond the well-known PML::RARA fusion. Among these, 31 individually rare RARA and RARG fusion genes have been documented, often reported in the canonical X::RAR bipartite fusion form. Intriguingly, some artificially mimicked bipartite X::RAR fusions respond well to all-trans retinoic acid (ATRA) in vitro, contrasting with the ATRA resistance observed in patients. To unravel the underlying mechanisms, we conducted a comprehensive molecular investigation into the fusion transcripts in 27 RARA fusion gene-positive aAPL (RARA-aAPL) and 21 RARG-aAPL cases. Our analysis revealed an unexpected novel form of X::RAR::X or X::RAR::Y-type tripartite fusions in certain RARA- and all RARG-aAPL cases, with shared features and notable differences between these two disease subgroups. In RARA-aAPL cases, the occurrence of RARA 3' splices was associated with their 5' fusion partner genes, mapping across the coding region of helix 11_12 (H11_12) within the ligand-binding domain (LBD), resulting in LBD-H12 or H11_12 truncation. In RARG-aAPL cases, RARG 3' splices were consistently localized to the terminus of exon 9, leading to LBD-H11_12 truncation. Significant differences were also observed between RARA and RARG 5' splice patterns. Our analysis also revealed extensive involvement of transposable elements in constructing RARA and RARG 3' fusions, suggesting transposition mechanisms for fusion gene ontogeny. Both protein structural analysis and experimental results highlighted the pivotal role of LBD-H11_12/H12 truncation in driving ATRA unresponsiveness and leukemogenesis in tripartite fusion-positive aAPL, through a protein allosteric dysfunction mechanism.
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The detection of microbial infections by plants induces the rapid formation of immune receptor complexes at the plasma membrane. However, how this process is controlled to ensure proper immune signaling remains largely unknown. Here, we found that the Nicotiana benthamiana membrane-localized leucine-rich repeat receptor-like kinase BAK1-INTERACTING RLK 2 (NbBIR2) constitutively associates with BRI1-ASSOCIATED RECEPTOR KINASE 1 (NbBAK1) in vivo and in vitro and promotes complex formation with pattern recognition receptors. In addition, NbBIR2 is targeted by 2 RING-type ubiquitin E3 ligases, SNC1-INFLUENCING PLANT E3 LIGASE REVERSE 2a (NbSNIPER2a) and NbSNIPER2b, for ubiquitination and subsequent degradation in planta. NbSNIPER2a and NbSNIPER2b interact with NbBIR2 in vivo and in vitro and are released from NbBIR2 upon treatment with different microbial patterns. Furthermore, accumulation of NbBIR2 in response to microbial patterns is tightly associated with NbBAK1 abundance in N. benthamiana. NbBAK1 acts as a modular protein that stabilizes NbBIR2 by competing with NbSNIPER2a or NbSNIPER2b for association with NbBIR2. Similar to NbBAK1, NbBIR2 positively regulates pattern-triggered immunity and resistance to bacterial and oomycete pathogens in N. benthamiana, whereas NbSNIPER2a and NbSNIPER2b have the opposite effect. Together, these results reveal a feedback regulatory mechanism employed by plants to tailor pattern-triggered immune signaling.
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Proteínas de Arabidopsis , Nicotiana , Nicotiana/metabolismo , Reconocimiento de Inmunidad Innata , Proteínas , Transducción de Señal , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Inmunidad de la Planta/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Enfermedades de las Plantas/microbiologíaRESUMEN
Protein arginine methyltransferase CARM1 has been shown to methylate a large number of non-histone proteins, and play important roles in gene transcriptional activation, cell cycle progress, and tumorigenesis. However, the critical substrates through which CARM1 exerts its functions remain to be fully characterized. Here, we reported that CARM1 directly interacts with the GATAD2A/2B subunit in the nucleosome remodeling and deacetylase (NuRD) complex, expanding the activities of NuRD to include protein arginine methylation. CARM1 and NuRD bind and activate a large cohort of genes with implications in cell cycle control to facilitate the G1 to S phase transition. This gene activation process requires CARM1 to hypermethylate GATAD2A/2B at a cluster of arginines, which is critical for the recruitment of the NuRD complex. The clinical significance of this gene activation mechanism is underscored by the high expression of CARM1 and NuRD in breast cancers, and the fact that knockdown CARM1 and NuRD inhibits cancer cell growth in vitro and tumorigenesis in vivo. Targeting CARM1-mediated GATAD2A/2B methylation with CARM1 specific inhibitors potently inhibit breast cancer cell growth in vitro and tumorigenesis in vivo. These findings reveal a gene activation program that requires arginine methylation established by CARM1 on a key chromatin remodeler, and targeting such methylation might represent a promising therapeutic avenue in the clinic.
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Neoplasias de la Mama , Ensamble y Desensamble de Cromatina , Regulación Neoplásica de la Expresión Génica , Complejo Desacetilasa y Remodelación del Nucleosoma Mi-2 , Proteína-Arginina N-Metiltransferasas , Complejo Desacetilasa y Remodelación del Nucleosoma Mi-2/metabolismo , Complejo Desacetilasa y Remodelación del Nucleosoma Mi-2/genética , Proteína-Arginina N-Metiltransferasas/genética , Proteína-Arginina N-Metiltransferasas/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Humanos , Femenino , Animales , Línea Celular Tumoral , Ciclo Celular/genética , Ratones , Metilación , Arginina/metabolismo , Carcinogénesis/genética , Activación TranscripcionalRESUMEN
Microsomal glutathione transferase 3 (MGST3) regulates eicosanoid and glutathione metabolism. These processes are associated with oxidative stress and apoptosis, suggesting that MGST3 might play a role in the pathophysiology of Alzheimer's disease. Here, we report that knockdown (KD) of MGST3 in cell lines reduced the protein level of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) and the resulting amyloidogenesis. Interestingly, MGST3 KD did not alter intracellular reactive oxygen species level but selectively reduced the expression of apoptosis indicators which could be associated with the receptor of cysteinyl leukotrienes, the downstream metabolites of MGST3 in arachidonic acid pathway. We then showed that the effect of MGST3 on BACE1 was independent of cysteinyl leukotrienes but involved a translational mechanism. Further RNA-seq analysis identified that regulator of G-protein signaling 4 (RGS4) was a target gene of MGST3. Silencing of RGS4 inhibited BACE1 translation and prevented MGST3 KD-mediated reduction of BACE1. The potential mechanism was related to AKT activity, as the protein level of phosphorylated AKT was significantly reduced by silencing of MGST3 and RGS4, and the AKT inhibitor abolished the effect of MGST3/RGS4 on phosphorylated AKT and BACE1. Together, MGST3 regulated amyloidogenesis by controlling BACE1 protein expression, which was mediated by RGS4 and downstream AKT signaling pathway.
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OBJECTIVE: Although accumulating evidence implicating altered gut microbiota in human immunodeficiency virus (HIV) infection and neurodegenerative disorders; however, the association between dysbiosis of the gut microbiota and metabolites in the pathogenesis of HIV-associated neurocognitive disorder (HAND) remains unclear. METHODS: Fecal and plasma samples were obtained from 3 cohorts (HAND, HIV-non-HAND, and healthy controls), metagenomic analysis and metabolomic profiling were performed to investigate alterations in the gut microbial composition and circulating metabolites in HAND. RESULTS: The gut microbiota of people living with HIV (PLWH) had an increased relative abundance of Prevotella and a decreased relative abundance of Bacteroides. In contrast, Prevotella and Megamonas were substantially decreased, and Bacteroides and Phocaeicola were increased in HAND patients. Moreover, untargeted metabolomics identified several neurotransmitters and certain amino acids associated with neuromodulation, and the differential metabolic pathways of amino acids associated with neurocognition were depleted in HAND patients. Notably, most neuromodulatory metabolites are associated with an altered abundance of specific gut bacteria. INTERPRETATION: Our findings provide new insights into the intricate interplay between the gut and microbiome-brain axis in the pathogenesis of HAND, highlighting the potential for developing novel therapeutic strategies that specifically target the gut microbiota. ANN NEUROL 2024;96:306-320.
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Aminoácidos , Microbioma Gastrointestinal , Metabolómica , Metagenómica , Humanos , Microbioma Gastrointestinal/fisiología , Masculino , Persona de Mediana Edad , Femenino , Metabolómica/métodos , Aminoácidos/metabolismo , Aminoácidos/sangre , Adulto , Infecciones por VIH/complicaciones , Complejo SIDA Demencia/metabolismo , Complejo SIDA Demencia/microbiología , Heces/microbiología , DisbiosisRESUMEN
Maximum likelihood (ML) phylogenetic inference is widely used in phylogenomics. As heuristic searches most likely find suboptimal trees, it is recommended to conduct multiple (e.g., ten) tree searches in phylogenetic analyses. However, beyond its positive role, how and to what extent multiple tree searches aid ML phylogenetic inference remains poorly explored. Here, we found that a random starting tree was not as effective as the BioNJ and parsimony starting trees in inferring ML gene tree and that RAxML-NG and PhyML were less sensitive to different starting trees than IQ-TREE. We then examined the effect of the number of tree searches on ML tree inference with IQ-TREE and RAxML-NG, by running 100 tree searches on 19,414 gene alignments from 15 animal, plant, and fungal phylogenomic datasets. We found that the number of tree searches substantially impacted the recovery of the best-of-100 ML gene tree topology among 100 searches for a given ML program. In addition, all of the concatenation-based trees were topologically identical if the number of tree searches was ≥ 10. Quartet-based ASTRAL trees inferred from 1 to 80 tree searches differed topologically from those inferred from 100 tree searches for 6 /15 phylogenomic datasets. Lastly, our simulations showed that gene alignments with lower difficulty scores had a higher chance of finding the best-of-100 gene tree topology and were more likely to yield the correct trees.
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Colloidal quantum dots (QDs) are excellent luminescent nanomaterials for many optoelectronic applications. However, photoluminescence blinking has limited their practical use. Coupling QDs to plasmonic nanostructures shows potential in suppressing blinking. However, the underlying mechanism remains unclear and debated, hampering the development of bright nonblinking dots. Here, by deterministically coupling a QD to a plasmonic nanocavity, we clarify the mechanism and demonstrate unprecedented single-QD brightness. In particular, we report for the first time that a blinking QD could obtain nonblinking photoluminescence with a blinking lifetime through coupling to the nanocavity. We show that the plasmon-enhanced radiative decay outcompetes the nonradiative Auger process, enabling similar quantum yields for charged and neutral excitons in the same dot. Meanwhile, we demonstrate a record photon detection rate of 17 MHz from a colloidal QD, indicating an experimental photon generation rate of more than 500 MHz. These findings pave the way for ultrabright nonblinking QDs, benefiting diverse QD-based applications.
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Psychedelic indolethylamines have emerged as potential medicines to treat several psychiatric pathologies. Natural sources of these compounds include 'magic mushrooms' (Psilocybe spp.), plants used to prepare ayahuasca, and toads. The skin and parotid glands of certain toads accumulate a variety of specialized metabolites including toxic guanidine alkaloids, lipophilic alkaloids, poisonous steroids, and hallucinogenic indolethylamines such as DMT, 5-methoxy-DMT, and bufotenin. The occurrence of psychedelics has contributed to the ceremonial use of toads, particularly among Mesoamerican peoples. Yet, the biosynthesis of psychedelic alkaloids has not been elucidated. Herein, we report a novel indolethylamine N-methyltransferase (RmNMT) from cane toad (Rhinella marina). The RmNMT sequence was used to identify a related NMT from the common toad, Bufo bufo. Close homologs from various frog species were inactive, suggesting a role for psychedelic indolethylamine biosynthesis in toads. Enzyme kinetic analyses and comparison with functionally similar enzymes showed that recombinant RmNMT was an effective catalyst and not product inhibited. The substrate promiscuity of RmNMT enabled the bioproduction of a variety of substituted indolethylamines at levels sufficient for purification, pharmacological screening, and metabolic stability assays. Since the therapeutic potential of psychedelics has been linked to activity at serotonergic receptors, we evaluated binding of derivatives at 5-HT1A and 5-HT2A receptors. Primary amines exhibited enhanced affinity at the 5-HT1A receptor compared with tertiary amines. With the exception of 6-substituted derivatives, N,N-dimethylation also protected against catabolism by liver microsomes.
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Follicular cysts are a common reproductive disorder in domestic animals that cause considerable economic losses to the farming industry. Effective prevention and treatment methods are lacking because neither the pathogenesis nor formation mechanisms of follicular cysts are well-understood. In this study, we first investigated the granulosa cells (GCs) of cystic follicles isolated from pigs. We observed a significant reduction in the expression of methyltransferase-like 3 (METTL3). Subsequent experiments revealed that METTL3 downregulation in GCs caused a decrease in m6A modification of pri-miR-21. This reduction further inhibited DGCR8 recognition and binding to pri-miR-21, dampening the synthesis of mature miR-21-5p. Additionally, the decrease in miR-21-5p promotes IL-1ß expression in GCs. Elevated IL-1ß activates the NFκB pathway, in turn upregulating apoptotic genes TNFa and BAX/BCL2. The subsequent apoptosis of GCs and inhibition of autophagy causes downregulation of CYP19A1 expression. These processes lower oestrogen secretion and contribute to follicular cyst formation. In conclusion, our findings provide a foundation for understanding and further exploring the mechanisms of follicular-cyst development in farm animals. This work has important implications for treating ovarian disorders in livestock and could potentially be extended to humans.
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Apoptosis , Células de la Granulosa , Metiltransferasas , MicroARNs , Animales , Femenino , Apoptosis/genética , Células Cultivadas , Regulación hacia Abajo , Quiste Folicular/genética , Quiste Folicular/patología , Quiste Folicular/metabolismo , Células de la Granulosa/metabolismo , Interleucina-1beta/metabolismo , Interleucina-1beta/genética , Metiltransferasas/metabolismo , Metiltransferasas/genética , MicroARNs/genética , MicroARNs/metabolismo , FN-kappa B/metabolismo , FN-kappa B/genética , Transducción de Señal , Porcinos , Proteínas de Unión al ARN/metabolismoRESUMEN
PURPOSE: Chronic stress is a significant risk factor for mood disorders such as depression, where synaptic plasticity plays a central role in pathogenesis. Transient Receptor Potential Vanilloid Type-2 (TRPV2) Ion Channels are implicated in hypothalamic-pituitary-adrenal axis disorders. Previous proteomic analysis indicated a reduction in TRPV2 levels in the chronic unpredictable mild stress (CUMS) rat model, yet its role in synaptic plasticity during depression remains to be elucidated. This study aims to investigate TRPV2's role in depression and its underlying mechanisms. METHODS: In vivo and in vitro experiments were conducted using the TRPV2-specific agonist probenecid and ERK1/2 inhibitors SCH772984. In vivo, rats underwent six weeks of CUMS before probenecid administration. Depressive-like behaviors were assessed through behavioral tests. ELISA kits measured 5-HT, DA, NE levels in rat hippocampal tissues. Hippocampal morphology was examined via Nissl staining. In vitro, rat hippocampal neuron cell lines were treated with ERK1/2 inhibitors SCH772984 and probenecid. Western blot, immunofluorescence, immunohistochemical staining, and RT-qPCR assessed TRPV2 expression, neurogenesis-related proteins, synaptic markers, and ERK1/2-CREB-BDNF signaling proteins. RESULTS: Decreased hippocampal TRPV2 levels were observed in CUMS rats. Probenecid treatment mitigated depressive-like behavior and enhanced hippocampal 5-HT, NE, and DA levels in CUMS rats. TRPV2 activation countered CUMS-induced synaptic plasticity inhibition. Probenecid activated the ERK1/2-CREB-BDNF pathway, suggesting TRPV2's involvement in this pathway via ERK1/2. CONCLUSION: These findings indicate that TRPV2 activation offers protective effects against depressive-like behaviors and enhances hippocampal synaptic plasticity in CUMS rats via the ERK1/2-CREB-BDNF pathway. TRPV2 emerges as a potential therapeutic target for depression.
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Factor Neurotrófico Derivado del Encéfalo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico , Hipocampo , Sistema de Señalización de MAP Quinasas , Plasticidad Neuronal , Ratas Sprague-Dawley , Estrés Psicológico , Canales Catiónicos TRPV , Animales , Canales Catiónicos TRPV/metabolismo , Canales Catiónicos TRPV/antagonistas & inhibidores , Plasticidad Neuronal/efectos de los fármacos , Masculino , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Estrés Psicológico/complicaciones , Estrés Psicológico/metabolismo , Estrés Psicológico/fisiopatología , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Ratas , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Depresión/metabolismo , Depresión/tratamiento farmacológico , Enfermedad Crónica , Probenecid/farmacologíaRESUMEN
BACKGROUND: Pembrolizumab has been indicated in the treatment of solid tumors with high frequency microsatellite instability (MSI-H) or high tumor mutational burden (TMB-H); however, real-world data on the effectiveness of pembrolizumab with or without chemotherapy in this molecular subset remain limited. Our retrospective study evaluated the clinical efficacy and safety of pembrolizumab in treating advanced solid tumors with either MSI-H or TMB-H. METHODS: This retrospective study analyzed data from 116 patients with MSI-H or TMB-H advanced solid cancers who received pembrolizumab with or without chemotherapy regardless of treatment setting. We analyzed objective response rate (ORR) and progression-free survival (PFS). RESULTS: The top three cancer types were colorectal (48.6% MSI-H, 6.5% TMB-H), lung (15.4% MSI-H, 84.4% TMB-H), and gastric (15.4% MSI-H, 5.1% TMB-H). The ORR with pembrolizumab was 52.6%, including complete response (CR) observed in 8.6% (n = 10) of cases and partial responses (PR) in 43.9% (n = 51). Of the 93 patients who received first-line pembrolizumab, 52 patients achieved objective response (10 CR, 42 PR), with a median PFS of 14.0 months (95% confidence intervals [CI] 6.6-21.4). Of the 23 who received subsequent-line pembrolizumab, the ORR was 39.1%, disease control rate was 91.3%, and median PFS was 5.7 months (95% CI 3.9-7.5). Treatment-related adverse events were observed in 32 patients (27.6%), with no reported treatment-related fatal adverse events. CONCLUSION: Our study provides real-world evidence on the clinical effectiveness of pembrolizumab with or without chemotherapy in the treatment of patients with MSI-H and TMB-H advanced solid cancers.
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Anticuerpos Monoclonales Humanizados , Inestabilidad de Microsatélites , Neoplasias , Humanos , Estudios Retrospectivos , Neoplasias/tratamiento farmacológico , Neoplasias/genética , China , Respuesta Patológica CompletaRESUMEN
Salvia miltiorrhiza is commonly used as a Chinese herbal medicine to treat different cardiovascular and cerebrovascular illnesses due to its active ingredients. Environmental conditions, especially drought stress, can affect the yield and quality of S. miltiorrhiza. However, moderate drought stress could improve the quality of S. miltiorrhiza without significantly reducing the yield, and the mechanism of this initial drought resistance is still unclear. In our study, transcriptome and metabolome analyses of S. miltiorrhiza under different drought treatment groups (CK, A, B, and C groups) were conducted to reveal the basis for its drought tolerance. We discovered that the leaves of S. miltiorrhiza under different drought treatment groups had no obvious shrinkage, and the malondialdehyde (MDA) contents as well as superoxide dismutase (SOD) and peroxidase (POD) activities dramatically increased, indicating that our drought treatment methods were moderate, and the leaves of S. miltiorrhiza began to initiate drought resistance. The morphology of root tissue had no significant change under different drought treatment groups, and the contents of four tanshinones significantly enhanced. In all, 5213, 6611, and 5241 differentially expressed genes (DEGs) were shared in the A, B, and C groups compared with the CK group, respectively. The results of KEGG and co-expression analysis showed that the DEGs involved in plant-pathogen interactions, the MAPK signaling pathway, phenylpropanoid biosynthesis, flavonoid biosynthesis, and plant hormone signal transduction responded to drought stress and were strongly correlated with tanshinone biosynthesis. Furthermore, the results of metabolism analysis indicated that 67, 72, and 92 differentially accumulated metabolites (DAMs), including fumarate, ferulic acid, xanthohumol, and phytocassanes, which were primarily involved in phenylpropanoid biosynthesis, flavonoid biosynthesis, and diterpenoid biosynthesis pathways, were detected in these groups. These discoveries provide valuable information on the molecular mechanisms by which S. miltiorrhiza responds to drought stress and will facilitate the development of drought-resistant and high-quality S. miltiorrhiza production.
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Sequías , Metaboloma , Salvia miltiorrhiza , Transcriptoma , Salvia miltiorrhiza/genética , Salvia miltiorrhiza/metabolismo , Salvia miltiorrhiza/fisiología , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Estrés Fisiológico/genética , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Hojas de la Planta/fisiologíaRESUMEN
BACKGROUND: In agricultural production, fungal diseases significantly impact the yield and quality of cotton (Gossypium spp.) with Verticillium wilt posing a particularly severe threat. RESULTS: This study is focused on investigating the effectiveness of endophytic microbial communities present in the seeds of disease-resistant cotton genotypes in the control of cotton Verticillium wilt. The technique of 16S ribosomal RNA (16S rRNA) amplicon sequencing identified a significant enrichment of the Bacillus genus in the resistant genotype Xinluzao 78, which differed from the endophytic bacterial community structure in the susceptible genotype Xinluzao 63. Specific enriched strains were isolated and screened from the seeds of Xinluzao 78 to further explore the biological functions of seed endophytes. A synthetic microbial community (SynCom) was constructed using the broken-rod model, and seeds of the susceptible genotype Xinluzao 63 in this community that had been soaked with the SynCom were found to significantly control the occurrence of Verticillium wilt and regulate the growth of cotton plants. Antibiotic screening techniques were used to preliminarily identify the colonization of strains in the community. These techniques revealed that the strains can colonize plant tissues and occupy ecological niches in cotton tissues through a priority effect, which prevents infection by pathogens. CONCLUSION: This study highlights the key role of seed endophytes in driving plant disease defense and provides a theoretical basis for the future application of SynComs in agriculture.
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Microbiota , Verticillium , Verticillium/fisiología , Gossypium/genética , Gossypium/microbiología , ARN Ribosómico 16S/genética , Bacterias/genética , Semillas/genética , Enfermedades de las Plantas/microbiología , Resistencia a la Enfermedad/genéticaRESUMEN
The development of highly efficient electrocatalysts for the sluggish anodic oxygen evolution reaction (OER) is crucial to meet the practical demand for water splitting. In this study, an effective approach is proposed that simultaneously enhances interfacial interaction and catalytic activity by modifying Fe2O3/CoS heterojunction using Ru doping strategy to construct an efficient electrocatalytic oxygen evolution catalyst. The unique morphology of Ru doped Fe2O3 (Ru-Fe2O3) nanoring decorated by CoS nanoparticles ensures a large active surface area and a high number of active sites. The designed Ru-Fe2O3/CoS catalyst achieves a low OER overpotential (264 mV) at 10 mA cm-2 and demonstrates exceptional stability even at high current density of 100 mA cm-2, maintaining its performance for an impressive duration of 90 h. The catalytic performance of this Ru-Fe2O3/CoS catalyst surpasses that of other iron-based oxide catalysts and even outperforms the state-of-the-art RuO2. Density functional theory (DFT) calculation as well as experimental in situ characterization confirm that the introduction of Ru atoms can enhance the interfacial electron interaction, accelerating the electron transfer, and serve as highly active sites reducing the energy barrier for rate determination step. This work provides an efficient strategy to reveal the enhancement of electrocatalytic oxygen evolution activity of heterojunction catalysts by doping engineering.
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Ovarian theca cells produce testosterone, which acts as a vital precursor substance for synthesizing estrogens during follicular development. Nerve growth factor (NGF) has been shown to participate in reproductive physiology, specifically to follicular development and ovulation. There is currently no available data on the impact of NGF on testosterone synthesis in porcine theca cells. Furthermore, m6A modification is the most common internal modification in eukaryotic mRNAs that are closely associated with female gametogenesis, follicle development, ovulation, and other related processes. It is also uncertain whether the three main enzymes associated with m6A, such as Writers, Erasers and Readers, play a role in this process. The present study, with an in vitro culture model, investigated the effect of NGF on testosterone synthesis in porcine theca cells and the role of Writers-METTL14 in this process. It was found that NGF activates the PI3K/AKT signaling pathway through METTL14, which regulates testosterone synthesis in porcine theca cells. This study will help to further elucidate the mechanisms by which NGF regulates follicular development and provide new therapeutic targets for ovary-related diseases in female animals.
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The plant rapid alkalinization factor (RALF) peptides function as key regulators in cell growth and immune responses through the receptor kinase FERONIA (FER). In this study, we report that the transcription factor FgPacC binds directly to the promoter of FgRALF gene, which encodes a functional homologue of the plant RALF peptides from the wheat head blight fungus Fusarium graminearum (FgRALF). More importantly, FgPacC promotes fungal infection via host immune suppression by activating the expression of FgRALF. The FgRALF peptide also exhibited typical activities of plant RALF functions, such as inducing plant alkalinization and inhibiting cell growth, including wheat (Triticum aestivum), tomato (Solanum lycopersicum) and Arabidopsis thaliana. We further identified the wheat receptor kinase FERONIA (TaFER), which is capable of restoring the defects of the A. thaliana FER mutant. In addition, we found that FgRALF peptide binds to the extracellular malectin-like domain (ECD) of TaFER (TaFERECD) to suppress the PAMP-triggered immunity (PTI) and cell growth. Overexpression of TaFERECD in A. thaliana confers plant resistance to F. graminearum and protects from FgRALF-induced cell growth inhibition. Collectively, our results demonstrate that the fungal pathogen-secreted RALF mimic suppresses host immunity and inhibits cell growth via plant FER receptor. This establishes a novel pathway for the development of disease-resistant crops in the future without compromising their yield potential.
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Arabidopsis , Fusarium , Inmunidad de la Planta , Arabidopsis/inmunología , Arabidopsis/genética , Arabidopsis/microbiología , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/inmunología , Triticum/microbiología , Triticum/genética , Triticum/inmunología , Triticum/metabolismo , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Regulación de la Expresión Génica de las Plantas , Fosfotransferasas/metabolismo , Fosfotransferasas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Solanum lycopersicum/microbiología , Solanum lycopersicum/genética , Solanum lycopersicum/inmunología , Solanum lycopersicum/metabolismo , Proteínas Serina-Treonina QuinasasRESUMEN
Volatile esters in apple (Malus domestica) fruit are the critical aroma components determining apple flavor quality. While the exact molecular regulatory mechanism remains unknown, jasmonic acid (JA) plays a crucial role in stimulating the synthesis of ester aromas in apples. In our study, we investigated the effects of methyl jasmonate (MeJA) on the production of ester aroma in apples. MeJA treatment significantly increased ester aroma synthesis, accompanied by the upregulation of several genes involved in the jasmonate pathway transduction. Specifically, expression of the gene MdMYC2, which encodes a transcription factor associated with the jasmonate pathway, and the R2R3-MYB transcription factor gene MdMYB85 increased upon MeJA treatment. Furthermore, the essential gene ALCOHOL ACYLTRANSFERASE 1 (MdAAT1), encoding an enzyme responsible for ester aroma synthesis, showed increased expression levels as well. Our investigation revealed that MdMYC2 and MdMYB85 directly interacted with the promoter region of MdAAT1, thereby enhancing its transcriptional activity. In addition, MdMYC2 and MdMYB85 directly bind their promoters and activate transcription. Notably, the interaction between MdMYC2 and MdMYB85 proteins further amplified the regulatory effect of MdMYB85 on MdMYC2 and MdAAT1, as well as that of MdMYC2 on MdMYB85 and MdAAT1. Collectively, our findings elucidate the role of the gene module consisting of MdMYC2, MdMYB85, and MdAAT1 in mediating the effects of JA and promoting ester aroma synthesis in apples.
Asunto(s)
Malus , Malus/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Odorantes , Proteínas de Plantas/metabolismo , Ésteres/metabolismo , Frutas/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
PURPOSE: Esophageal squamous carcinoma (ESCC) is a gastrointestinal malignancy with a high mortality, but the tumorigenesis is still unclear, restricting the target therapy development of ESCC. We explored the role of COL8A1 in ESCC development. METHODS: Tissue microarrays were used to investigate the expression level of COL8A1 in ESCC tissues. The association between COL8A1 and the overall survival of ESCC patients was assessed. The effect of differential COL8A1 expression on tumor growth was investigated by the xenograft model. The regulation of COL8A1 on tumor growth, migration, and invasion was studied by using ESCC cell lines. The signal transduction pathways involved in COL8A1 were bioinformatically profiled and validated. RESULTS: The COL8A1 was significantly expressed in cancerous tissues and was associated with poor prognosis in patients with ESCC. In vivo, the tumor growth obviously declined after inhibition of the COL8A1 expression. The abilities of cell proliferation and invasion were both decreased when the expression of COL8A1 was knockdown in ESCC cell line. Furthermore, we found the inactivation of the PI3K/AKT pathway that was mediated by knockdown of COL8A1 in ESCC cells, which was reversed with COL8A1 overexpression, whereas the cell proliferation and invasion ability were restored. CONCLUSIONS: This is the first report that COL8A1 promote ESCC progression, which hopefully will provide a theoretical basis for clinical targeting of ESCC.