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1.
J Am Chem Soc ; 146(20): 14357-14367, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38726589

RESUMEN

Introducing dynamic behavior into periodic frameworks has borne fruit in the form of flexible porous crystals. The detailed molecular design of frameworks in order to control their collective dynamics is of particular interest, for example, to achieve stimulus-induced behavior. Herein, by varying the degree of rigidity of ditopic pillar linkers, two isostructural flexible metal-organic frameworks (MOFs) with common rigid supermolecular building bilayers were constructed. The subtle substitution of single (in bibenzyl-4,4'-dicarboxylic acid; H2BBDC) with double (in 4,4'-stilbenedicarboxylic acid; H2SDC) C-C bonds in pillared linkers led to markedly different flexible behavior of these two MOFs. Upon the removal of guest molecules, both frameworks clearly show reversible single-crystal-to-single-crystal transformations involving the cis-trans conformation change and a resulting swing of the corresponding pillar linkers, which gives rise to Flex-Cd-MOF-1a and Flex-Cd-MOF-2a, respectively. Strikingly, a more favorable gas-induced dynamic behavior in Flex-Cd-MOF-2a was verified in detail by stepwise C3H6/C3H8 sorption isotherms and the corresponding in situ powder X-ray diffraction experiments. These insights are strongly supported by molecular modeling studies on the sorption mechanism that explores the sorption landscape. Furthermore, a consistency between the macroscopic elasticity and microscopic flexibility of Flex-Cd-MOF-2 was observed. This work fuels a growing interest in developing MOFs with desired chemomechanical functions and presents detailed insights into the origins of flexible MOFs.

2.
Microb Biotechnol ; 17(5): e14472, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38683679

RESUMEN

The availability of an alternative and efficient genetic editing technology is critical for fundamental research and strain improvement engineering of Streptomyces species, which are prolific producers of complex secondary metabolites with significant pharmaceutical activities. The mobile group II introns are retrotransposons that employ activities of catalytic intron RNAs and intron-encoded reverse transcriptase to precisely insert into DNA target sites through a mechanism known as retrohoming. We here developed a group II intron-based gene editing tool to achieve precise chromosomal gene insertion in Streptomyces. Moreover, by repressing the potential competition of RecA-dependent homologous recombination, we enhanced site-specific insertion efficiency of this tool to 2.38%. Subsequently, we demonstrated the application of this tool by screening and characterizing the secondary metabolite biosynthetic gene cluster (BGC) responsible for synthesizing the red pigment in Streptomyces roseosporus. Accompanied with identifying and inactivating this BGC, we observed that the impair of this cluster promoted cell growth and daptomycin production. Additionally, we applied this tool to activate silent jadomycin BGC in Streptomyces venezuelae. Overall, this work demonstrates the potential of this method as an alternative tool for genetic engineering and cryptic natural product mining in Streptomyces species.


Asunto(s)
Intrones , Familia de Multigenes , Streptomyces , Streptomyces/genética , Streptomyces/metabolismo , Intrones/genética , Edición Génica/métodos , Mutagénesis Insercional/métodos , Metabolismo Secundario/genética , Vías Biosintéticas/genética , Recombinación Homóloga
3.
Plants (Basel) ; 13(8)2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38674540

RESUMEN

Anther length is the critical floral trait determining hybrid rice seed production and is controlled by many quantitative trait loci (QTL). However, the cloning of genes specifically controlling anther size has yet to be reported. Here, we report the fine mapping of qAL5.2 for anther size using backcross inbred lines (BILs) in the genetic background of Oryza sativa indica Huazhan (HZ). Gene chip analysis on the BC4F2 and BC5F1 population identified effective loci on Chr1, Chr5, and Chr8 and two genomic regions on Chr5, named qAL5.1 and qAL5.2. qAL5.2 was identified in both populations with LOD values of 17.54 and 10.19, which explained 35.73% and 25.1% of the phenotypic variances, respectively. Ultimately qAL5.2 was localized to a 73 kb region between HK139 and HK140 on chromosome 5. And we constructed two near-isogenic lines (NILs) for RNA-seq analysis, named NIL-qAL5.2HZ and NIL-qAL5.2KLY, respectively. The result of the GO enrichment analysis revealed that differential genes were significantly enriched in the carbohydrate metabolic process, extracellular region, and nucleic acid binding transcription, and KEGG enrichment analysis revealed that alpha-linolenic acid metabolism was significantly enriched. Meanwhile, candidate genes of qAL5.2 were analyzed in RNA-seq, and it was found that ORF8 is differentially expressed between NIL-qAL5.2HZ and NIL-qAL5.2KLY. The fine mapping of qAL5.2 conferring anther length will promote the breed improvement of the restorer line and understanding of the mechanisms driving crop mating patterns.

4.
Chemosphere ; 356: 141902, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38582158

RESUMEN

Sediment siltation has been regarded as the serious challenge in sewer system, which dominantly root in the gelatinous extracellular polymeric substance (EPS) structure and cohesive ability. Considering the crucial roles of divalent cation bridging and macromolecular biopolymer winding in sediment EPS formation and adhesive behavior, an innovative combination strategy of sodium pyrophosphate (SP)-mediated divalent cation chelation and alkaline biopolymer hydrolysis was developed to degenerate sediment adhesion. At the SP dosage of 0.25 g/g TS and the alkaline pH 12, the SP + pH 12 treatment triggered structural transformation of aromatic proteins (α-helix to ß-turn) and functional group shifts of macromolecular biopolymers. In this case, the deconstruction and outward dissolution of gelatinous biopolymers were achievable, including proteins (tyrosine-like proteins, tryptophan-like proteins), humic acids, fulvic acids, polysaccharides and various soluble microbial products. These were identified as the major driving forces for sediment EPS matrix disintegration and bio-aggregation deflocculation. The extraction EPS content was obviously increased by 18.88 mg COD/g TS. The sediment adhesion was sensitive to EPS matrix damage and gelatinous biopolymer deconstruction, leading to considerable average adhesion degeneration to 0.98 nN with reduction rate of 78.32%. As such, the sediments could be disrupted into dispersive fragments with increased surface electronegativity and electric repulsion (up to -45.6 mV), thereby the sediment resistance to hydraulic erosion was impaired, providing feasibility for in-situ sediment floating and removal by gravity sewage flow in sewer.


Asunto(s)
Aguas del Alcantarillado , Biopolímeros/química , Hidrólisis , Aguas del Alcantarillado/química , Quelantes/química , Eliminación de Residuos Líquidos/métodos , Cationes/química , Concentración de Iones de Hidrógeno , Matriz Extracelular de Sustancias Poliméricas/química
6.
Microb Biotechnol ; 17(1): e14319, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37986689

RESUMEN

Streptomyces species have a complex life cycle and are the producers of ~70% of commercial antibiotics. Global regulators AfsR and AfsS are widespread among Streptomyces and have been identified as key activators of antibiotic production in several species. However, their roles as repressors of antibiotic production are unclear; in particular, nothing is known regarding the regulatory mechanism of AfsS, despite many decades of research, because it has no DNA-binding domain. Here, we demonstrate that AfsR and AfsS negatively regulate avermectin production and morphological development in the industrially important species S. avermitilis. AfsR directly represses ave structural genes (aveA1, aveA4), cluster-situated activator gene aveR, and eight key developmental genes, whereas it directly activates afsS, aco (for autoregulator avenolide biosynthesis), and avaR1 (encoding avenolide receptor). GST pull-down, microscale thermophoresis, co-immunoprecipitation, and chromatin immunoprecipitation-quantitative PCR assays demonstrated that AfsS interacts with AfsR to co-regulate target genes involved in avermectin production and development and that this interaction requires intact AfsS repeated sequences and enhances the binding affinity of AfsR to target promoters. AfsR/AfsS interaction also occurs in model species S. coelicolor and S. roseosporus (producer of daptomycin, a cyclic lipopeptide antibiotic widely used for the treatment of human infections), suggesting that such interaction is conserved in Streptomyces species. The master developmental repressor BldD acts as a direct activator of both afsR and afsS. Deletion of afsR or afsS strongly enhances avermectin production in wild-type and industrial S. avermitilis strains. Our findings demonstrate novel regulatory roles and mechanisms of AfsR and AfsS in Streptomyces and facilitate methods for antibiotic overproduction.


Asunto(s)
Ivermectina/análogos & derivados , Streptomyces , Factores de Transcripción , Humanos , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Antibacterianos/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Streptomyces/genética , Streptomyces/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Regulación Bacteriana de la Expresión Génica
7.
Food Chem Toxicol ; 184: 114415, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38141941

RESUMEN

Chalcones from licorice and its related plants have many pharmacological effects. However, the effects of chalcones on the activity of human and rat 11ß-hydroxysteroid dehydrogenase 2 (11ß-HSD2), and associated side effects remain unclear. The inhibition of 11 chalcones on human and rat 11ß-HSD2 were evaluated in microsomes and a 3D-quantitative structure-activity relationship (3D-QSAR) was analyzed. Screening revealed that bavachalcone, echinatin, isobavachalcone, isobavachromene, isoliquiritigenin, licochalcone A, and licochalcone B significantly inhibited human 11ß-HSD2 with IC50 values ranging from 15.62 (licochalcone A) to 38.33 (echinatin) µM. Screening showed that the above chemicals and 4-hydroxychalcone significantly inhibited rat 11ß-HSD2 with IC50 values ranging from 6.82 (isobavachalcone) to 72.26 (4-hydroxychalcone) µM. These chalcones acted as noncompetitive/mixed inhibitors for both enzymes. Comparative analysis revealed that inhibition of 11ß-HSD2 depended on the species. Most chemicals bind to the NAD+ binding site or both the NAD+ and substrate binding sites. Bivariate correlation analysis showed that lipophilicity and molecular weight determine inhibitory strength. Through our 3D-QSAR models, we identified that the hydrophobic region, hydrophobic aliphatic groups, and hydrogen bond acceptors are pivotal factors in inhibiting 11ß-HSD2. In conclusion, many chalcones inhibit human and rat 11ß-HSD2, possibly causing side effects and there is structure-dependent and species-dependent inhibition on 11ß-HSD2.


Asunto(s)
Chalconas , Ratas , Humanos , Animales , Chalconas/farmacología , 11-beta-Hidroxiesteroide Deshidrogenasas/metabolismo , Relación Estructura-Actividad Cuantitativa , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 2/metabolismo , NAD/metabolismo
8.
Front Pediatr ; 11: 1132413, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38116578

RESUMEN

Purpose: The aim of this study was to explore parental preferences for the procedural sedation of children in dentistry through a discrete choice experiment (DCE) to inform clinical decisions and oral health management. Methods: Based on literature reviews, interviews with parents of pediatric dental patients, and expert consultation, six attributes, including fasting time, recovery time, sedative administration routes, adverse reactions, sedation depth and procedure cost, were incorporated into the DCE questionnaire. The DCE questionnaire collected data on parental preferences for pediatric dental sedation treatment from June to August 2022. A conditional logit model was used to analyze preference and willingness to pay (WTP) for each attribute and its level. Subgroup analyses assessing the impact of parents' dental anxiety on procedural sedation preferences were also conducted using conditional logit models. Results: A total of 186 valid questionnaires were gathered. Parents' preferences for fewer adverse reactions, a milder sedation depth, lower out-of-pocket cost, shorter fasting and recovery times and administration by inhalation were significantly associated with their choice of sedation model. The conditional logit model showed that parents were most interested in treatments with no adverse reactions (0% vs. 15%) (Coef, 1.033; 95% CI, 0.833-1.233), followed by those providing minimal sedation (vs. deep sedation) (Coef, 0.609; 95% CI, 0.448-0.769). Moreover, the relative importance of adverse reactions and fasting time was higher among anxious than nonanxious parents. The study found a WTP threshold of ¥1,538 for reducing adverse reactions (15% to 0%). The WTP threshold for the best sedation procedure scenario (no fasting requirement, 10 min recovery time, administration by inhalation, 0% adverse reaction incidence and minimal sedation) was ¥3,830. Conclusion: Reducing the adverse reactions and depth of sedation are predominant considerations for parents regarding procedural sedation in pediatric dentistry, followed by lower cost, shorter fasting and recovery times and inhalation sedation. Parents with dental anxiety had a stronger preference for options with a lower incidence of adverse reactions and shorter fasting time than parents without dental anxiety. This discovery is helpful for doctors and can promote collaborative decision-making among parents and doctors.

9.
BMC Biol ; 21(1): 241, 2023 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-37907908

RESUMEN

BACKGROUND: Epigenetic modifications that exhibit circadian oscillations also promote circadian oscillations of gene expression. Brassica napus is a heterozygous polyploid species that has undergone distant hybridization and genome doubling events and has a young and distinct species origin. Studies incorporating circadian rhythm analysis of epigenetic modifications can offer new insights into differences in diurnal oscillation behavior among subgenomes and the regulation of diverse expressions of homologous gene rhythms in biological clocks. RESULTS: In this study, we created a high-resolution and multioscillatory gene expression dataset, active histone modification (H3K4me3, H3K9ac), and RNAPII recruitment in Brassica napus. We also conducted the pioneering characterization of the diurnal rhythm of transcription and epigenetic modifications in an allopolyploid species. We compared the evolution of diurnal rhythms between subgenomes and observed that the Cn subgenome had higher diurnal oscillation activity in both transcription and active histone modifications than the An subgenome. Compared to the A subgenome in Brassica rapa, the An subgenome of Brassica napus displayed significant changes in diurnal oscillation characteristics of transcription. Homologous gene pairs exhibited a higher proportion of diurnal oscillation in transcription than subgenome-specific genes, attributed to higher chromatin accessibility and abundance of active epigenetic modification types. We found that the diurnal expression of homologous genes displayed diversity, and the redundancy of the circadian system resulted in extensive changes in the diurnal rhythm characteristics of clock genes after distant hybridization and genome duplication events. Epigenetic modifications influenced the differences in the diurnal rhythm of homologous gene expression, and the diurnal oscillation of homologous gene expression was affected by the combination of multiple histone modifications. CONCLUSIONS: Herein, we presented, for the first time, a characterization of the diurnal rhythm characteristics of gene expression and its epigenetic modifications in an allopolyploid species. Our discoveries shed light on the epigenetic factors responsible for the diurnal oscillation activity imbalance between subgenomes and homologous genes' rhythmic expression differences. The comprehensive time-series dataset we generated for gene expression and epigenetic modifications provides a valuable resource for future investigations into the regulatory mechanisms of protein-coding genes in Brassica napus.


Asunto(s)
Brassica napus , Brassica napus/genética , Poliploidía , Ritmo Circadiano/genética , Genoma de Planta
10.
Toxins (Basel) ; 15(9)2023 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-37756007

RESUMEN

Patulin is a mycotoxin with potential reproductive toxicity. We explored the impact of patulin on Leydig cell (LC) development in male rats. Male Sprague Dawley rats (21 days postpartum) were gavaged patulin at doses of 0.5, 1, and 2 mg/kg/day for 7 days. Patulin markedly lowered serum testosterone at ≥0.5 mg/kg and progesterone at 1 and 2 mg/kg, while increasing LH levels at 2 mg/kg. Patulin increased the CYP11A1+ (cholesterol side-chain cleavage, a progenitor LC biomarker) cell number and their proliferation at 1 and 2 mg/kg. Additionally, patulin downregulated Lhcgr (luteinizing hormone receptor), Scarb1 (high-density lipoprotein receptor), and Cyp17a1 (17α-hydroxylase/17,20-lyase) at 1 and 2 mg/kg. It increased the activation of pAKT1 (protein kinase B), pERK1/2 (extracellular signal-related kinases 1 and 2), pCREB (cyclic AMP response binding protein), and CCND1 (cyclin D1), associated with cell cycle regulation, in vivo. Patulin increased EdU incorporation into R2C LC and stimulated cell cycle progression in vitro. Furthermore, patulin showed a direct inhibitory effect on 11ß-HSD2 (11ß-hydroxysteroid dehydrogenase 2) activity, which eliminates the adverse effects of glucocorticoids. This study provides insights into the potential mechanisms via which patulin affects progenitor LC development in young male rats.


Asunto(s)
Patulina , Masculino , Femenino , Ratas , Animales , Patulina/toxicidad , Ratas Sprague-Dawley , Diferenciación Celular , Quinasas MAP Reguladas por Señal Extracelular , Proliferación Celular
11.
Methods Mol Biol ; 2698: 109-117, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37682472

RESUMEN

Histone post-translational modifications and transcription factors (TFs) play vital roles in regulating gene expression. A comprehensive understanding of transcriptional regulation requires genome-wide mapping of chromatin features such as histone modifications and TF binding sites. Here, we describe a detailed nucleus CUT&Tag (Cleavage Under Targets and Tagmentation) protocol, which is an antibody-guided in situ protein-DNA interaction mapping method using protein A/G fused Tn5 transposase. Compared with regular ChIP-seq in plants, nucleus CUT&Tag (nCUT&Tag) omits many steps such as sonication and immunoprecipitation, thus saving much time and making it possible to efficiently profile chromatin features from low-input and even single cells with higher signal-to-noise ratio.


Asunto(s)
Cromatina , ADN , Cromatina/genética , Núcleo Celular , Anticuerpos , Sitios de Unión
12.
Methods Mol Biol ; 2698: 183-194, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37682476

RESUMEN

Hierarchical chromatin structures are critical for transcriptional regulation and many biological processes. It has been widely known that the linear genome of many plants and animals is partitioned into various chromatin interacting domains or gene regulatory modules with specific chromatin features, such as H3K4me3-related active interacting domains, H3K27me3 or Polycomb-related repressive domains, and H3K9me2-related heterochromatin domains. ChIA-PET, which combines chromatin immunoprecipitation (ChIP) assay with proximity ligation, can detect gene contact networks that are connected by co-regulated genes by pulling down specific chromatin complexes using an antibody of interest. Here, we describe a detailed, long-read ChIA-PET protocol for mapping promoter-centered active gene modules in plants.


Asunto(s)
Cromatina , Oryza , Animales , Cromatina/genética , Oryza/genética , Secuenciación de Inmunoprecipitación de Cromatina , Heterocromatina , Inmunoprecipitación de Cromatina
13.
J Biomed Inform ; 146: 104496, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37704104

RESUMEN

Automatic radiology report generation has the potential to alert inexperienced radiologists to misdiagnoses or missed diagnoses and improve healthcare delivery efficiency by reducing the documentation workload of radiologists. Motivated by the continuous development of automatic image captioning, more and more deep learning methods have been proposed for automatic radiology report generation. However, the visual and textual data bias problem still face many challenges in the medical domain. Additionally, do not integrate medical knowledge, ignoring the mutual influences between medical findings, and abundant unlabeled medical images influence the accuracy of generating report. In this paper, we propose a Medical Knowledge with Contrastive Learning model (MKCL) to enhance radiology report generation. The proposed model MKCL uses IU Medical Knowledge Graph (IU-MKG) to mine the relationship among medical findings and improve the accuracy of identifying positive diseases findings from radiologic medical images. In particular, we design Knowledge Enhanced Attention (KEA), which integrates the IU-MKG and the extracted chest radiological visual features to alleviate textual data bias. Meanwhile, this paper leverages supervised contrastive learning to relieve radiographic medical images which have not been labeled, and identify abnormalities from images. Experimental results on the public dataset IU X-ray show that our proposed model MKCL outperforms other state-of-the-art report generation methods. Ablation studies also demonstrate that IU medical knowledge graph module and supervised contrastive learning module enhance the ability of the model to detect the abnormal parts and accurately describe the abnormal findings. The source code is available at: https://github.com/Eleanorhxd/MKCL.


Asunto(s)
Radiología , Humanos , Documentación , Conocimiento , Radiografía , Radiólogos , Aprendizaje
14.
J Comput Biol ; 30(8): 912-925, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37566468

RESUMEN

Clinical notes are comprehensive files containing explicit information about a patient's visit. However, accurately assigning medical codes from clinical documents can be a persistent challenge due to the complexity of clinical data and the vast range of medical codes. Moreover, the large volume of medical records, the noisy medical records, and the uneven quality of coders all negatively impact the quality of the final codes. Deep learning technology has recently been integrated into automatic International Classification of Diseases (ICD) coding tasks to improve accuracy. Nevertheless, the imbalanced class problem, the complexness of code associations, and the noise in lengthy records still restrict the advancement of ICD coding tasks in deep learning. Thus, we present the Note-code Interaction Denoising Network (NIDN) that employs the self-attention mechanism to pull critical semantic features in electronic medical records (EMRs). Our model utilizes the label attention mechanism for retaining code-specific text expression. We introduce Clinical Classifications Software coding for multitask learning, capturing the functional relationships of medical coding to oblige in model prediction. To minimize the impact of noise on model prediction and improve the label distribution imbalance, a denoising module is introduced to filter noise. Our practical consequences indicate that the model NIDN exceeds competitive models on a third version of Medical Information Mart for Intensive Care data set.


Asunto(s)
Registros Electrónicos de Salud , Clasificación Internacional de Enfermedades , Humanos , Automatización
15.
Plant Biotechnol J ; 21(11): 2333-2347, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37539491

RESUMEN

DNA methylation plays an important role in gene regulation and genomic stability. However, large DNA hypomethylated regions known as DNA methylation valleys (DMVs) or canyons have also been suggested to serve unique regulatory functions, largely unknown in rice (Oryza sativa). Here, we describe the DMVs in rice seedlings, which were highly enriched with developmental and transcription regulatory genes. Further detailed analysis indicated that grand DMVs (gDMVs) might be derived from nuclear integrants of organelle DNA (NORGs). Furthermore, Domains Rearranged Methylase 2 (OsDRM2) maintained DNA methylation at short DMV (sDMV) shores. Epigenetic maps indicated that sDMVs were marked with H3K4me3 and/or H3K27me3, although the loss of DNA methylation had a negligible effect on histone modification within these regions. In addition, we constructed H3K27me3-associated interaction maps for homozygous T-DNA insertion mutant of the gene (osdrm2) and wild type (WT). From a global perspective, most (90%) compartments were stable between osdrm2 and WT plants. At a high resolution, we observed a dramatic loss of long-range chromatin loops in osdrm2, which suffered an extensive loss of non-CG (CHG and CHH, H = A, T, or C) methylation. From another viewpoint, the loss of non-CG methylation at sDMV shores in osdrm2 could disrupt H3K27me3-mediated chromatin interaction networks. Overall, our results demonstrated that DMVs are a key genomic feature in rice and are precisely regulated by epigenetic modifications, including DNA methylation and histone modifications. OsDRM2 maintained DNA methylation at sDMV shores, while OsDRM2 deficiency strongly affected three-dimensional (3D) genome architectures.


Asunto(s)
Metilación de ADN , Oryza , Metilación de ADN/genética , Cromatina/genética , Histonas/genética , Histonas/metabolismo , Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Metiltransferasas/genética , ADN , Regulación de la Expresión Génica de las Plantas/genética
16.
Nucleic Acids Res ; 51(17): 9001-9018, 2023 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-37572350

RESUMEN

Photoperiods integrate with the circadian clock to coordinate gene expression rhythms and thus ensure plant fitness to the environment. Genome-wide characterization and comparison of rhythmic genes under different light conditions revealed delayed phase under constant darkness (DD) and reduced amplitude under constant light (LL) in rice. Interestingly, ChIP-seq and RNA-seq profiling of rhythmic genes exhibit synchronous circadian oscillation in H3K9ac modifications at their loci and long non-coding RNAs (lncRNAs) expression at proximal loci. To investigate how gene expression rhythm is regulated in rice, we profiled the open chromatin regions and transcription factor (TF) footprints by time-series ATAC-seq. Although open chromatin regions did not show circadian change, a significant number of TFs were identified to rhythmically associate with chromatin and drive gene expression in a time-dependent manner. Further transcriptional regulatory networks mapping uncovered significant correlation between core clock genes and transcription factors involved in light/temperature signaling. In situ Hi-C of ZT8-specific expressed genes displayed highly connected chromatin association at the same time, whereas this ZT8 chromatin connection network dissociates at ZT20, suggesting the circadian control of gene expression by dynamic spatial chromatin conformation. These findings together implicate the existence of a synchronization mechanism between circadian H3K9ac modifications, chromatin association of TF and gene expression, and provides insights into circadian dynamics of spatial chromatin conformation that associate with gene expression rhythms.


Asunto(s)
Ritmo Circadiano , Oryza , Cromatina/genética , Relojes Circadianos/genética , Ritmo Circadiano/genética , Epigenoma , Perfilación de la Expresión Génica , Oryza/genética , Oryza/fisiología , Factores de Transcripción/genética
17.
CNS Neurosci Ther ; 2023 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-37650344

RESUMEN

BACKGROUND: TUB-like protein 4 (TULP4) is one of the distant members of tubby family proteins, whose function remains largely unknown. In the present study, we intend to identify the role of TULP4 in schizophrenia from human samples and animal models. METHODS: Whole-exome sequencing was used to detect the four schizophrenia families collected. In different cell lines, the effects of identified variants in TULP4 gene on its expression and localization were analyzed. Knockdown models in utero and adult mice were employed to investigate the role of Tulp4 on neuronal migration and schizophrenia-related behavior. Subsequently, co-IP assays were used to search for proteins that interact with TULP4 and the effects of mutants on the molecular function of TULP4. RESULTS: For the first time, we identified five rare variants in TULP4 from schizophrenia families, of which three significantly reduced TULP4 protein expression. Knockdown the expression of Tulp4 delayed neuronal migration during embryological development and consequently triggered abnormal behaviors in adult mice, including impaired sensorimotor gating and cognitive dysfunction. Furthermore, we confirmed that TULP4 is involved in the formation of a novel E3 ligase through interaction with CUL5-ELOB/C-RNF7 and the three deleterious variants affected the binding amount of TULP4 and CUL5 to a certain extent. CONCLUSIONS: Together, we believe TULP4 plays an important role in neurodevelopment and subsequent schizophrenic-related phenotypes through its E3 ubiquitin ligase function.

18.
Micromachines (Basel) ; 14(8)2023 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-37630075

RESUMEN

The performance of supercapacitors is directly influenced by the conductivity of polypyrrole, which serves as the electrode material. In order to balance considerations of cost-effectiveness and conductivity, this study employs magnetron sputtering to fabricate a copper-tin alloy layer as the conductive layer for polypyrrole. The deposition of a copper-tin alloy film through magnetron sputtering has a significant impact on the polymerization effect of pyrrole as well as being a crucial factor influencing the performance of supercapacitors. Various parameters, including working pressure, sputtering time, and sputtering power, affect the conductivity of the copper-tin alloy film. Furthermore, the degree of influence of each parameter on the conductivity of the copper-tin alloy film varies. This study utilizes an orthogonal experimental design to investigate the impact of various factors and levels on the conductivity and uniformity of a metal film. The objective is to optimize the process parameters for the creation of a copper-tin alloy film with desirable characteristics. Experimental results indicate that the working voltage, sputtering time, and sputtering power significantly influence the coefficient of variation, deposition rate, target current, and operating voltage of the film. Furthermore, FT-IR, XRD, and SEM tests are conducted on samples prepared using the identified optimal process parameters. In addition, we demonstrate various approaches to enhance the experiment's reliability. The findings indicate that the most favorable process parameters for achieving optimal results are a working pressure of 0.065 Pa, a sputtering time of 20 min, and a sputtering power of 70 W. It was observed that the sputtering time significantly influences the uniformity of the copper-tin alloy film, whereas the sputtering power has a minimal impact on its uniformity. The deposition rate is primarily influenced by the working pressure, with the greatest effect observed. Conversely, the sputtering time has the least impact on the deposition rate. Similarly, the target current is predominantly affected by the sputtering power, exhibiting the greatest influence, while the sputtering time has the least effect. Furthermore, the working voltage is most significantly influenced by the working pressure, whereas the sputtering time has the least impact on the working voltage.

19.
Nat Genet ; 55(8): 1381-1389, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37500729

RESUMEN

One-step and two-step pathways are proposed to synthesize cytokinin in plants. The one-step pathway is mediated by LONELY GUY (LOG) proteins. However, the enzyme for the two-step pathway remains to be identified. Here, we show that quantitative trait locus GY3 may boost grain yield by more than 20% through manipulating a two-step pathway. Locus GY3 encodes a LOG protein that acts as a 5'-ribonucleotide phosphohydrolase by excessively consuming the cytokinin precursors, which contrasts with the activity of canonical LOG members as phosphoribohydrolases in a one-step pathway. The residue S41 of GY3 is crucial for the dephosphorylation of iPRMP to produce iPR. A solo-LTR insertion within the promoter of GY3 suppressed its expression and resulted in a higher content of active cytokinins in young panicles. Introgression of GY302428 increased grain yield per plot by 7.4% to 16.3% in all investigated indica backgrounds, which demonstrates the great value of GY302428 in indica rice production.


Asunto(s)
Citocininas , Oryza , Citocininas/genética , Citocininas/metabolismo , Monoéster Fosfórico Hidrolasas/metabolismo , Grano Comestible/genética , Grano Comestible/metabolismo , Sitios de Carácter Cuantitativo/genética , Regulación de la Expresión Génica de las Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
20.
Sci Total Environ ; 893: 164896, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37329905

RESUMEN

Deposition of sediment in sewers decreased flow capacity, with harmful gases and pipe erosion. Sediment floating and removal remained challenges due to its gelatinous structure, which induced strong erosion resistance. This study proposed an innovative alkaline treatment for destructuring gelatinous organic matters and improving hydraulic flushing capacity of sediments. At the optimal pH 11.0 condition, the gelatinous extracellular polymeric substance (EPS) and microbial cells were disrupted, with numerous outward migration and solubilization of proteins, polysaccharides and humus. The aromatic protein solubilization (tryptophan-like and tyrosine-like proteins) and humic acid-like substance deconstruction were the major driving factors for sediment cohesion reduction, which disintegrated the bio-aggregation and increased the surface electronegativity. Meanwhile, the variations of functional groups (CC, CO, COO-, CN, NH, C-O-C, C-OH, OH) also contributed to the interaction breakage and glutinous structure disruption of sediment particles. It was found that the rising pH conditions reduced sediment adhesion and promoted particle floating. Solubilizations of total suspended solids and volatile suspended solids were increased by 12.8 and 9.4 times, respectively, while the sediment adhesion was reduced by 3.8 fold. The alkaline treatment greatly improved sediment erosion and flushing capacities under shear stress of gravity sewage flow. Such sustainable strategy only cost 36.4 CNY per sewer meter length, which was 29.5-55.0 % of the high-pressure water jet flushing and perforated tube flushing approaches.


Asunto(s)
Matriz Extracelular de Sustancias Poliméricas , Aguas del Alcantarillado , Aguas del Alcantarillado/química , Gases , Sedimentos Geológicos/química
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