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Anxiety is a remarkably common condition among patients with pharyngitis, but the relationship between these disorders has received little research attention, and the underlying neural mechanisms remain unknown. Here, we show that the densely innervated pharynx transmits signals induced by pharyngeal inflammation to glossopharyngeal and vagal sensory neurons of the nodose/jugular/petrosal (NJP) superganglia in mice. Specifically, the NJP superganglia project to norepinephrinergic neurons in the nucleus of the solitary tract (NTSNE). These NTSNE neurons project to the ventral bed nucleus of the stria terminalis (vBNST) that induces anxiety-like behaviors in a murine model of pharyngeal inflammation. Inhibiting this pharynxâNJPâNTSNEâvBNST circuit can alleviate anxiety-like behaviors associated with pharyngeal inflammation. This study thus defines a pharynx-to-brain axis that mechanistically links pharyngeal inflammation and emotional response.
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Faringitis , Faringe , Humanos , Animales , Ratones , Ansiedad , Encéfalo , Células Receptoras Sensoriales , InflamaciónRESUMEN
The Q transcription factor plays important roles in improving multiple wheat domestication traits such as spike architecture, threshability and rachis fragility. However, whether and how it regulates abiotic stress adaptation remain unclear. We found that the transcriptional expression of Q can be induced by NaCl and abscisic acid treatments. Using the q mutants generated by CRISPR/Cas9 and Q overexpression transgenic lines, we showed that the domesticated Q gene causes a penalty in wheat salt tolerance. Then, we demonstrated that Q directly represses the transcription of TaSOS1-3B and reactive oxygen species (ROS) scavenging genes to regulate Na+ and ROS homeostasis in wheat. Furthermore, we showed that wheat salt tolerance protein TaWD40 interacts with Q to competitively interfere with the interaction between Q and the transcriptional co-repressor TaTPL. Taken together, our findings reveal that Q directly represses the expression of TaSOS1 and some ROS scavenging genes, thus causing a harmful effect on wheat salt tolerance.
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Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Plantas Modificadas Genéticamente , Especies Reactivas de Oxígeno , Tolerancia a la Sal , Triticum , Triticum/genética , Triticum/fisiología , Triticum/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Tolerancia a la Sal/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Ácido Abscísico/metabolismo , Ácido Abscísico/farmacologíaRESUMEN
Leaf senescence is a complex process strictly regulated by various external and endogenous factors. However, the key signaling pathway mediating leaf senescence remains unknown. Here, we show that Arabidopsis SPX1/2 negatively regulate leaf senescence genetically downstream of the strigolactone (SL) pathway. We demonstrate that the SL receptor AtD14 and MAX2 mediate the age-dependent degradation of SPX1/2. Intriguingly, we uncover an age-dependent accumulation of SLs in leaves via transcriptional activation of SL biosynthetic genes by the transcription factors (TFs) SPL9/15. Furthermore, we reveal that SPX1/2 interact with the WRKY75 subclade TFs to inhibit their DNA-binding ability and thus repress transcriptional activation of salicylic acid (SA) biosynthetic gene SA Induction-Deficient 2, gating the age-dependent SA accumulation in leaves at the leaf senescence onset stage. Collectively, our new findings reveal a signaling pathway mediating sequential activation of SL and salicylate biosynthesis for the onset of leaf senescence in Arabidopsis.
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Proteínas de Arabidopsis , Arabidopsis , Regulación de la Expresión Génica de las Plantas , Lactonas , Hojas de la Planta , Senescencia de la Planta , Factores de Transcripción , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/efectos de los fármacos , Hojas de la Planta/metabolismo , Hojas de la Planta/efectos de los fármacos , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Lactonas/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Ácido Salicílico/metabolismo , Salicilatos/metabolismo , Transducción de Señal , Unión Proteica/efectos de los fármacos , Proteolisis/efectos de los fármacos , Vías Biosintéticas/efectos de los fármacos , Vías Biosintéticas/genéticaRESUMEN
Salt stress is one of the major factors that limits rice production. Therefore, identification of salt-tolerant alleles from wild rice is important for rice breeding. In this study, we constructed a set of chromosome segment substitution lines (CSSLs) using wild rice as the donor parent and cultivated rice Nipponbare (Nip) as the recurrent parent. Salt tolerance germinability (STG) was evaluated, and its association with genotypes was determined using this CSSL population. We identified 17 QTLs related to STG. By integrating the transcriptome and genome data, four candidate genes were identified, including the previously reported AGO2 and WRKY53. Compared with Nip, wild rice AGO2 has a structure variation in its promoter region and the expression levels were upregulated under salt treatments; wild rice WRKY53 also has natural variation in its promoter region, and the expression levels were downregulated under salt treatments. Wild rice AGO2 and WRKY53 alleles have combined effects for improving salt tolerance at the germination stage. One CSSL line, CSSL118 that harbors these two alleles was selected. Compared with the background parent Nip, CSSL118 showed comprehensive salt tolerance and higher yield, with improved transcript levels of reactive oxygen species scavenging genes. Our results provided promising genes and germplasm resources for future rice salt tolerance breeding.
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Genes de Plantas , Oryza , Fitomejoramiento , Tolerancia a la Sal , Oryza/anatomía & histología , Oryza/genética , Oryza/crecimiento & desarrollo , Tolerancia a la Sal/genética , Cromosomas de las Plantas/genética , Alelos , Fitomejoramiento/métodos , Sitios de Carácter Cuantitativo/genética , Genotipo , Transcriptoma , Genoma de Planta/genética , Regiones Promotoras Genéticas , Regulación de la Expresión Génica de las Plantas , Germinación , Brotes de la Planta , Raíces de Plantas , Técnicas de Genotipaje , Polimorfismo Genético , FenotipoRESUMEN
Cochlear implants can directly activate the auditory system's primary sensory neurons, the spiral ganglion neurons (SGNs), via circumvention of defective cochlear hair cells. This bypass restores auditory input to the brainstem. SGN loss etiologies are complex, with limited mammalian regeneration. Protecting and revitalizing SGN is critical. Tissue engineering offers a novel therapeutic strategy, utilizing seed cells, biomolecules, and scaffold materials to create a cellular environment and regulate molecular cues. This review encapsulates the spectrum of both human and animal research, collating the factors contributing to SGN loss, the latest advancements in the utilization of exogenous stem cells for auditory nerve repair and preservation, the taxonomy and mechanism of action of standard biomolecules, and the architectural components of scaffold materials tailored for the inner ear. Furthermore, we delineate the potential and benefits of the biohybrid neural interface, an incipient technology in the realm of implantable devices. Nonetheless, tissue engineering requires refined cell selection and differentiation protocols for consistent SGN quality. In addition, strategies to improve stem cell survival, scaffold biocompatibility, and molecular cue timing are essential for biohybrid neural interface integration.
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Regeneración Nerviosa , Ganglio Espiral de la Cóclea , Ingeniería de Tejidos , Andamios del Tejido , Ganglio Espiral de la Cóclea/citología , Humanos , Ingeniería de Tejidos/métodos , Animales , Andamios del Tejido/química , Neuronas , Implantes Cocleares , Células Madre/citología , Diferenciación CelularRESUMEN
Plant organ size is an important agronomic trait that makes a significant contribution to plant yield. Despite its central importance, the genetic and molecular mechanisms underlying organ size control remain to be fully clarified. Here, we report that the trithorax group protein ULTRAPETALA1 (ULT1) interacts with the TEOSINTE BRANCHED1/CYCLOIDEA/PCF14/15 (TCP14/15) transcription factors by antagonizing the LIN-11, ISL-1, and MEC-3 (LIM) peptidase DA1, thereby regulating organ size in Arabidopsis. Loss of ULT1 function significantly increases rosette leaf, petal, silique, and seed size, whereas overexpression of ULT1 results in reduced organ size. ULT1 associates with TCP14 and TCP15 to co-regulate cell size by affecting cellular endoreduplication. Transcriptome analysis revealed that ULT1 and TCP14/15 regulate common target genes involved in endoreduplication and leaf development. ULT1 can be recruited by TCP14/15 to promote lysine 4 of histone H3 trimethylation at target genes, activating their expression to determine final cell size. Furthermore, we found that ULT1 influences the interaction of DA1 and TCP14/15 and antagonizes the effect of DA1 on TCP14/15 degradation. Collectively, our findings reveal a novel epigenetic mechanism underlying the regulation of organ size in Arabidopsis.
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Proteínas de Arabidopsis , Arabidopsis , Factores de Transcripción , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Histonas/metabolismo , Factores de Transcripción/metabolismoRESUMEN
BACKGROUND: Deaf children with cochlear nerve canal stenosis (CNCs) are always considered poor candidates for cochlear implantation. OBJECTIVES: To investigate the function of the peripheral auditory pathway in deaf children with CNCs, as revealed by the electrically evoked auditory brainstem response (EABR), and postoperative cochlear implants (CIs) outcomes. MATERIALS AND METHODS: Thirteen children with CNCs and 13 children with no inner ear malformations (IEMs) who received CIs were recruited. The EABR evoked by electrical stimulation from the CI electrode was recorded. Postoperative CI outcomes were assessed using Categories of Auditory Performance (CAP) and Speech Intelligibility Rate (SIR). RESULTS: Compared with children with no IEMs, children with CNCs showed lower EABR extraction rates, higher thresholds, a longer wave V (eV) latency and lower CAP and SIR scores. The auditory and speech performance was positively correlated with the diameter of the cochlear nerve canal and the number of channels showing wave III (eIII) and eV in children with CNCs. CONCLUSIONS AND SIGNIFICANCE: The physiological function of the peripheral auditory pathway in children with CNCs is poorer than that in children with no IEMs. Postoperative auditory and speech abilities may depend on the severity of cochlear nerve malformation and auditory conduction function.
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Nervio Coclear , Sordera , Potenciales Evocados Auditivos del Tronco Encefálico , Humanos , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Masculino , Femenino , Preescolar , Nervio Coclear/fisiopatología , Nervio Coclear/anomalías , Sordera/fisiopatología , Sordera/congénito , Sordera/cirugía , Niño , Constricción Patológica , Implantación Coclear/métodosRESUMEN
Laryngeal carcinoma (LC) is a common cancer of the respiratory tract. This study aims to investigate the role of RNA-binding motif protein 15 (RBM15) in the cisplatin (DDP) resistance of LC cells. LC-DDP-resistant cells were constructed. RBM15, lysine-specific demethylase 5B (KDM5B), lncRNA Fer-1 like family member 4 (FER1L4), lncRNA KCNQ1 overlapping transcript 1 (KCNQ1OT1), glutathione peroxidase 4 (GPX4), and Acyl-CoA synthetase long-chain family (ACSL4) was examined. Cell viability, IC50, and proliferation were assessed after RBM15 downregulation. The enrichment of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and N6-methyladenosine (m6A) on KDM5B was analyzed. KDM5B mRNA stability was measured after actinomycin D treatment. A tumor xenograft assay was conducted to verify the role of RBM15 in LC. Results showed that RBM15 was upregulated in LC and its knockdown decreased IC50, cell viability, proliferation, glutathione, and upregulated iron ion content, ROS, malondialdehyde, ACSL4, and ferroptosis. Mechanistically, RBM15 improved KDM5B stability in an IGF2BP3-dependent manner, resulting in FER1L4 downregulation and GPX4 upregulation. KDM5B increased KCNQ1OT1 and inhibited ACSL4. KDM5B/KCNQ1OT1 overexpression or FER1L4 knockdown promoted DDP resistance in LC by inhibiting ferroptosis. In conclusion, RBM15 promoted KDM5B expression, and KDM5B upregulation inhibited ferroptosis and promoted DDP resistance in LC by downregulating FER1L4 and upregulating GPX4, as well as by upregulating KCNQ1OT1 and inhibiting ACSL4. Silencing RBM15 inhibited tumor growth in vivo.
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Cisplatino , Resistencia a Antineoplásicos , Epigénesis Genética , Ferroptosis , Neoplasias Laríngeas , Proteínas de Unión al ARN , Ferroptosis/genética , Cisplatino/farmacología , Resistencia a Antineoplásicos/genética , Humanos , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Línea Celular Tumoral , Ratones , Animales , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/metabolismo , Ratones Desnudos , Regulación Neoplásica de la Expresión Génica , Proliferación Celular/efectos de los fármacos , Antineoplásicos/farmacología , Coenzima A Ligasas/genética , Coenzima A Ligasas/metabolismoRESUMEN
OBJECTIVE: Sensory intelligence in the brain helps listeners automatically extract abstract auditory rules formed by invariant acoustic features from complex speech sound streams, presumably serving as the neural basis for speech comprehension. However, whether this intelligence is deficient in children with cochlear implants (CIs) remains unclear. METHODS: Mandarin Chinese monosyllables shared a flat lexical tone contour to form an abstract auditory rule but differed in other acoustic features to construct a complex speech sound stream. The abstract rule was occasionally violated by monosyllables with a rising or falling lexical tone. RESULTS: In normal hearing (NH) children, the abstract auditory rule could be extracted, as revealed by a mismatch negativity (MMN) and a late discriminative negativity (LDN). However, the MMN and LDN were only evoked in CI children with good hearing and speech performance. NH children with a higher speech perception or spatial hearing score had a greater MMN. The LDN was attenuated with increasing age in NH children. CONCLUSIONS: The sensory intelligence for extraction of auditory abstract rules, associated with speech perception, is deficient in CI children. This intelligence may gradually develop during childhood and adolescence. SIGNIFICANCE: Deficient sensory intelligence in CI children may aid in understanding poor speech comprehension in complex environments.
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Powdery mildew (PM) is one of the most destructive diseases that threaten cucumber production globally. Efficient breeding of novel PM-resistant cultivars will require a robust understanding of the molecular mechanisms of cucumber resistance against PM. Using a genome-wide association study, we detected a locus significantly correlated with PM resistance in cucumber stem, pm-s5.1. A 1449-bp insertion in the CsMLO8 coding region at the pm-s5.1 locus resulted in enhanced stem PM resistance. Knockout mutants of CsMLO8 and CsMLO11 generated by CRISPR/Cas9 both showed improved PM resistance in the stem, hypocotyl, and leaves, and the double mutant mlo8mlo11 displayed even stronger resistance. We found that reactive oxygen species (ROS) accumulation was higher in the stem of these mutants. Protein interaction assays suggested that CsMLO8 and CsMLO11 could physically interact with CsRbohD and CsCRK2, respectively. Further, we showed that CsMLO8 and CsCRK2 competitively interact with the C-terminus of CsRbohD to affect CsCRK2-CsRbohD module-mediated ROS production during PM defense. These findings provide new insights into the understanding of CsMLO proteins during PM defense responses.
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Hair cell (HC) damage is a leading cause of sensorineural hearing loss, and in mammals supporting cells (SCs) are unable to divide and regenerate HCs after birth spontaneously. Procollagen C-endopeptidase enhancer 2 (Pcolce2), which encodes a glycoprotein that acts as a functional procollagen C protease enhancer, was screened as a candidate regulator of SC plasticity in our previous study. In the current study, we used adeno-associated virus (AAV)-ie (a newly developed adeno-associated virus that targets SCs) to overexpress Pcolce2 in SCs. AAV-Pcolce2 facilitated SC re-entry into the cell cycle both in cultured cochlear organoids and in the postnatal cochlea. In the neomycin-damaged model, regenerated HCs were detected after overexpression of Pcolce2, and these were derived from SCs that had re-entered the cell cycle. These findings reveal that Pcolce2 may serve as a therapeutic target for the regeneration of HCs to treat hearing loss.
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Animales Recién Nacidos , Reprogramación Celular , Cóclea , Animales , Ratones , Cóclea/metabolismo , Cóclea/citología , Células Ciliadas Auditivas/metabolismo , Células Ciliadas Auditivas/citología , Dependovirus/genética , Ciclo Celular , Ratones Endogámicos C57BL , Regeneración , Células Laberínticas de Soporte/metabolismo , Neomicina/farmacologíaRESUMEN
Peripheral nerve injury (PNI) can cause partial or total motor and sensory nerve function, leading to physical disability and nerve pain that severely affects patients' quality of life. Autologous nerve transplantation is currently the clinically recognized gold standard, but due to its inherent limitations, researchers have been searching for alternative treatments. Nerve guidance conduits (NGCs) have attracted much attention as a favorable alternative to promote the repair and regeneration of damaged peripheral nerves. In this review, we provide an overview of the anatomy of peripheral nerves, peripheral nerve injury and repair, and current treatment methods. Importantly, different design strategies of NGCs used for the treatment of PNI and their applications in PNI repair are highlighted. Finally, an outlook on the future development and challenges of NGCs is presented.