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1.
Mol Cell ; 84(18): 3438-3454.e8, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39232583

RESUMEN

Spreading of H3K27me3 is crucial for the maintenance of mitotically inheritable Polycomb-mediated chromatin silencing in animals and plants. However, how Polycomb repressive complex 2 (PRC2) accesses unmodified nucleosomes in spreading regions for spreading H3K27me3 remains unclear. Here, we show in Arabidopsis thaliana that the chromatin remodeler PICKLE (PKL) plays a specialized role in H3K27me3 spreading to safeguard cell identity during differentiation. PKL specifically localizes to H3K27me3 spreading regions but not to nucleation sites and physically associates with PRC2. Loss of PKL disrupts the occupancy of the PRC2 catalytic subunit CLF in spreading regions and leads to aberrant dedifferentiation. Nucleosome density increase endowed by the ATPase function of PKL ensures that unmodified nucleosomes are accessible to PRC2 catalytic activity for H3K27me3 spreading. Our findings demonstrate that PKL-dependent nucleosome compaction is critical for PRC2-mediated H3K27me3 read-and-write function in H3K27me3 spreading, thus revealing a mechanism by which repressive chromatin domains are established and propagated.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Diferenciación Celular , Ensamble y Desensamble de Cromatina , Histonas , Nucleosomas , Complejo Represivo Polycomb 2 , Nucleosomas/metabolismo , Nucleosomas/genética , Arabidopsis/genética , Arabidopsis/metabolismo , Histonas/metabolismo , Histonas/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Complejo Represivo Polycomb 2/metabolismo , Complejo Represivo Polycomb 2/genética , Regulación de la Expresión Génica de las Plantas , Cromatina/metabolismo , Cromatina/genética
2.
Plant Cell ; 35(7): 2464-2483, 2023 06 26.
Artículo en Inglés | MEDLINE | ID: mdl-37062961

RESUMEN

Switch defective/sucrose nonfermentable (SWI/SNF) complexes are evolutionarily conserved multisubunit machines that play vital roles in chromatin architecture regulation for modulating gene expression via sliding or ejection of nucleosomes in eukaryotes. In plants, perturbations of SWI/SNF subunits often result in severe developmental disorders. However, the subunit composition, pathways of assembly, and genomic targeting of the plant SWI/SNF complexes are poorly understood. Here, we report the organization, genomic targeting, and assembly of 3 distinct SWI/SNF complexes in Arabidopsis thaliana: BRAHMA-Associated SWI/SNF complexes (BAS), SPLAYED-Associated SWI/SNF complexes (SAS), and MINUSCULE-Associated SWI/SNF complexes (MAS). We show that BAS complexes are equivalent to human ncBAF, whereas SAS and MAS complexes evolve in multiple subunits unique to plants, suggesting plant-specific functional evolution of SWI/SNF complexes. We further show overlapping and specific genomic targeting of the 3 plant SWI/SNF complexes on chromatin and reveal that SAS complexes are necessary for the correct genomic localization of the BAS complexes. Finally, we define the role of the core module subunit in the assembly of plant SWI/SNF complexes and highlight that ATPase module subunit is required for global complex stability and the interaction of core module subunits in Arabidopsis SAS and BAS complexes. Together, our work highlights the divergence of SWI/SNF chromatin remodelers during eukaryote evolution and provides a comprehensive landscape for understanding plant SWI/SNF complex organization, assembly, genomic targeting, and function.


Asunto(s)
Arabidopsis , Humanos , Arabidopsis/genética , Arabidopsis/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Ensamble y Desensamble de Cromatina/genética , Proteínas Cromosómicas no Histona/genética , Proteínas Cromosómicas no Histona/metabolismo , Cromatina/genética , Cromatina/metabolismo , Genómica
3.
Plant Cell ; 34(10): 3915-3935, 2022 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-35866997

RESUMEN

PICKLE (PKL) is a chromodomain helicase DNA-binding domain 3 (CHD3) chromatin remodeler that plays essential roles in controlling the gene expression patterns that determine developmental identity in plants, but the molecular mechanisms through which PKL is recruited to its target genes remain elusive. Here, we define a cis-motif and trans-acting factors mechanism that governs the genomic occupancy profile of PKL in Arabidopsis thaliana. We show that two homologous trans-factors VIVIPAROUS1/ABI3-LIKE1 (VAL1) and VAL2 physically interact with PKL in vivo, localize extensively to PKL-occupied regions in the genome, and promote efficient PKL recruitment at thousands of target genes, including those involved in seed maturation. Transcriptome analysis and genetic interaction studies reveal a close cooperation of VAL1/VAL2 and PKL in regulating gene expression and developmental fate. We demonstrate that this recruitment operates at two master regulatory genes, ABSCISIC ACID INSENSITIVE3 and AGAMOUS-LIKE 15, to repress the seed maturation program and ensure the seed-to-seedling transition. Together, our work unveils a general rule through which the CHD3 chromatin remodeler PKL binds to its target chromatin in plants.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Ácido Abscísico/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Cromatina/genética , Cromatina/metabolismo , ADN/metabolismo , ADN Helicasas/genética , ADN Helicasas/metabolismo , Regulación de la Expresión Génica de las Plantas/genética , Semillas/genética , Transactivadores/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
4.
Exp Cell Res ; 442(1): 114199, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39103070

RESUMEN

Brain metastases account for more than 50 % of intracranial central nervous system tumors. The blood-brain barrier (BBB) is mainly composed of endothelial cells, which exhibit low endocytosis and high efflux pumps. Although they are connected by continuous tight junctions and serve as a protective insulation, the BBB does not prevent the development of brain metastases from non-small cell lung cancer (NSCLC). Improving understanding on the mechanisms underlying the development of brain metastasis and the differential molecular characteristics relative to the primary tumor are therefore key in the treatment of brain metastases. This study evaluated the differential expression of miR-522-3p in NSCLC and brain metastases using the Gene Expression Omnibus database. NSCLC brain metastasis model was constructed to screen for cell lines that demonstrated high potential for brain metastasis; We also observed differential expression of miRNA-522-3p in the paraffin-embedded specimens of non-small cell lung cancer and brain metastases from our hospital. The molecular biological functions of miRNA-522-3p were verified using 5-ethynyl-2'-deoxyuridine (EdU) proliferation assay and Transwell invasion assays. RNA-seq was employed to identify downstream target proteins, and the dual-luciferase reporter assay confirmed Tensin 1 (TNS1), a protein that links the actin cytoskeleton to the extracellular matrix, as the downstream regulatory target protein. In vitro blood-brain barrier models and co-culture models were constructed to further identify the role of miRNA-522-3p and TNS1; the expression of BBB-related proteins (ZO-1 and OLCN) was also identified. In vivo experiments were performed to verify the effects of miRNA-522-3p on the time and incidence of NSCLC brain metastasis. The results showed significantly high expression in GSE51666; consistent results were obtained in brain metastasis cells and paraffin samples. RNA-seq combined with miRNA target protein prediction demonstrated TNS1 to be directly downstream of miR-522-3p and to be associated with cell proliferation and invasion. By regulating ZO-1 and OCLN expression, mi-522-3p/TNS1 may increase tumor cell penetration through the BBB while decreasing its permeability. In vivo, miR-522-3p was further demonstrated to significantly promote the formation of brain metastases. miR-522-3p/TNS1 can affect BBB permeability and encourage the growth of brain metastases by modifying the BBB TJ proteins. This axis offers new therapeutic targets for the prevention of brain metastasis.


Asunto(s)
Barrera Hematoencefálica , Neoplasias Encefálicas , Carcinoma de Pulmón de Células no Pequeñas , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares , MicroARNs , Tensinas , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/patología , MicroARNs/genética , MicroARNs/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/metabolismo , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Animales , Regulación Neoplásica de la Expresión Génica/genética , Ratones , Tensinas/metabolismo , Tensinas/genética , Proliferación Celular/genética , Ratones Desnudos , Línea Celular Tumoral , Permeabilidad , Ratones Endogámicos BALB C , Movimiento Celular/genética
5.
Plant Cell ; 33(4): 1196-1211, 2021 05 31.
Artículo en Inglés | MEDLINE | ID: mdl-33604650

RESUMEN

Arabidopsis thaliana CONSTANS (CO) is an essential transcription factor that promotes flowering by activating the expression of the floral integrator FLOWERING LOCUS T (FT). A number of histone modification enzymes involved in the regulation of flowering have been identified, but the involvement of epigenetic mechanisms in the regulation of the core flowering regulator CO remains unclear. Previous studies have indicated that the transcription factors, FLOWERING BHLH1 (FBH1), FBH2, FBH3, and FBH4, function redundantly to activate the expression of CO. In this study, we found that the KDM3 group H3K9 demethylase JMJ28 interacts with the FBH transcription factors to activate CO by removing the repressive mark H3K9me2. The occupancy of JMJ28 on the CO locus is decreased in the fbh quadruple mutant, suggesting that the binding of JMJ28 is dependent on FBHs. Furthermore, genome-wide occupancy profile analyses indicate that the binding of JMJ28 to the genome overlaps with that of FBH3, indicating a functional association of JMJ28 and FBH3. Together, these results indicate that Arabidopsis JMJ28 functions as a CO activator by interacting with the FBH transcription factors to remove H3K9me2 from the CO locus.


Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiología , Proteínas de Unión al ADN/metabolismo , Flores/fisiología , Histona Demetilasas/metabolismo , Factores de Transcripción/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Proteínas de Unión al ADN/genética , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Genoma de Planta , Histona Demetilasas/genética , Histonas/metabolismo , Lisina/metabolismo , Plantas Modificadas Genéticamente/genética , Factores de Transcripción/genética
6.
J Org Chem ; 89(13): 9381-9388, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38885147

RESUMEN

A Pd(II)/N,N'-disulfonyl bisimidazoline-catalyzed asymmetric 1,4-conjugate addition reaction of low-cost arylboronic acids with readily available ß-substituted cyclic enones is described, providing a straightforward way of constructing cyclic all-carbon quaternary stereocenters with high enantioselectivity, in which ≥96% ee was obtained in most cases. The reaction proceeded without the protection of inert gas, making the operation process simple. Theoretical calculations have been applied to understand the origins of enantioselectivity.

7.
Environ Res ; 258: 119411, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38876423

RESUMEN

Epidemiological evidence on the impact of airborne organic pollutants on lung function among the elderly is limited, and their underlying biological mechanisms remain largely unexplored. Herein, a longitudinal panel study was conducted in Jinan, Shandong Province, China, involving 76 healthy older adults monitored over a span of five months repetitively. We systematically evaluated personal exposure to a diverse range of airborne organic pollutants using a wearable passive sampler and their effects on lung function. Participants' pulmonary function indicators were assessed, complemented by comprehensive multi-omics analyses of blood and urine samples. Leveraging the power of interaction analysis, causal inference test (CIT), and integrative pathway analysis (IPA), we explored intricate relationships between specific organic pollutants, biomolecules, and lung function deterioration, elucidating the biological mechanisms underpinning the adverse impacts of these pollutants. We observed that bis (2-chloro-1-methylethyl) ether (BCIE) was significantly associated with negative changes in the forced vital capacity (FVC), with glycerolipids mitigating this adverse effect. Additionally, 31 canonical pathways [e.g., high mobility group box 1 (HMGB1) signaling, phosphatidylinositol 3-kinase (PI3K)/AKT pathway, epithelial mesenchymal transition, and heme and nicotinamide adenine dinucleotide (NAD) biosynthesis] were identified as potential mechanisms. These findings may hold significant implications for developing effective strategies to prevent and mitigate respiratory health risks arising from exposure to such airborne pollutants. However, due to certain limitations of the study, our results should be interpreted with caution.


Asunto(s)
Contaminantes Atmosféricos , Humanos , Anciano , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/toxicidad , Masculino , Femenino , China , Estudios Longitudinales , Persona de Mediana Edad , Pulmón/efectos de los fármacos , Exposición a Riesgos Ambientales/efectos adversos , Pruebas de Función Respiratoria , Capacidad Vital/efectos de los fármacos
8.
Nucleic Acids Res ; 50(6): 3565-3580, 2022 04 08.
Artículo en Inglés | MEDLINE | ID: mdl-35286371

RESUMEN

CRISPR/Cas-derived base editing tools empower efficient alteration of genomic cytosines or adenines associated with essential genetic traits in plants and animals. Diversified target sequences and customized editing products call for base editors with distinct features regarding the editing window and target scope. Here we developed a toolkit of plant base editors containing AID10, an engineered human AID cytosine deaminase. When fused to the N-terminus or C-terminus of the conventional Cas9 nickase (nSpCas9), AID10 exhibited a broad or narrow activity window at the protospacer adjacent motif (PAM)-distal and -proximal protospacer, respectively, while AID10 fused to both termini conferred an additive activity window. We further replaced nSpCas9 with orthogonal or PAM-relaxed Cas9 variants to widen target scopes. Moreover, we devised dual base editors with AID10 located adjacently or distally to the adenine deaminase ABE8e, leading to juxtaposed or spaced cytosine and adenine co-editing at the same target sequence in plant cells. Furthermore, we expanded the application of this toolkit in plants for tunable knockdown of protein-coding genes via creating upstream open reading frame and for loss-of-function analysis of non-coding genes, such as microRNA sponges. Collectively, this toolkit increases the functional diversity and versatility of base editors in basic and applied plant research.


Asunto(s)
Proteína 9 Asociada a CRISPR , Edición Génica , Adenina , Animales , Proteína 9 Asociada a CRISPR/genética , Proteína 9 Asociada a CRISPR/metabolismo , Sistemas CRISPR-Cas/genética , Citosina
9.
Lasers Med Sci ; 39(1): 234, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39240409

RESUMEN

Although the technologies for auricular reconstruction in microtia have improved, issues such as low hairlines or excessive hair growth can still pose aesthetic problems for the reconstructed ear. Laser depilation has been reported as a solution for hair problems. However, few studies have discussed the appropriate region for hair removal. A retrospective analysis was performed on 276 patients with unilateral microtia who underwent the Nagata two-stage ear reconstruction. The gender ratio of male to female was 2.5 (198 males/78 females). Intense pulsed light depilation was used to remove hair. To determine the proper hair removal area, we measured the extent of hair removal. Before the first stage, the average vertical distance between the upper point (after localization) and hairline was 3.42 ± 4.75 mm (-10-20 mm). After the first stage, the average vertical distance between the upper point of the reconstructed ear and the hairline was 1.27 ± 2.41 mm (-10-15 mm). By using chi-square test to assess differences in hair removal success rates among various regions, we aimed to identify the suitable depilation region. Before the first stage, a depilation vertical distance ≥ 10 mm led to a 92.1% success rate. After the first stage surgery, among the patients needing additional hair removal, a vertical depilation distance ≥ 4 mm resulted in an 81.3% success rate. Based on our observation, we suggested that a depilation region of ≥ 10 mm (before the first surgery) or ≥ 4 mm (after the first surgery) would be the ideal range for laser hair removal.


Asunto(s)
Microtia Congénita , Remoción del Cabello , Procedimientos de Cirugía Plástica , Humanos , Femenino , Masculino , Estudios Retrospectivos , Microtia Congénita/cirugía , Remoción del Cabello/métodos , Procedimientos de Cirugía Plástica/métodos , Adolescente , Adulto Joven , Adulto , Niño , Terapia por Láser/métodos , Terapia por Láser/instrumentación
10.
J Am Chem Soc ; 145(9): 5496-5505, 2023 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-36812021

RESUMEN

Achieving transition-metal-catalyzed reactions of diene-ynes/diene-enes and carbon monoxide (CO) to deliver [4 + 2 + 1] cycloadducts, rather than the kinetically favored [2 + 2 + 1] products, is challenging. Here, we report that this can be solved by adding a cyclopropyl (CP) cap to the diene moiety of the original substrates. The resulting CP-capped diene-ynes/diene-enes can react with CO under Rh catalysis to give [4 + 2 + 1] cycloadducts exclusively without forming [2 + 2 + 1] products. This reaction has a broad scope and can be used to synthesize useful 5/7 bicycles with a CP moiety. Of the same importance, the CP moiety in the [4 + 2 + 1] cycloadducts can act as an intermediate group for further transformations so that other challenging bicyclic 5/7 and tricyclic 5/7/5, 5/7/6, and 5/7/7 skeletons, some of which are widely found in natural products, can be accessed. The mechanism of this [4 + 2 + 1] reaction has been investigated by quantum chemical calculations, and the role of the CP group in avoiding the possible side [2 + 2 + 1] reaction has been identified, showing that the [4 + 2 + 1] is controlled by releasing the ring strain in the methylenecyclopropyl (MCP) group (about 7 kcal/mol) in the CP-capped dienes.

11.
Int J Cancer ; 152(5): 998-1012, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36305649

RESUMEN

Increasing evidence indicates that glioma topographic location is linked to the cellular origin, molecular alterations and genetic profile. This research aims to (a) reveal the underlying mechanisms of tumor location predilection in glioblastoma multiforme (GBM) and lower-grade glioma (LGG) and (b) leverage glioma location features to predict prognosis. MRI images from 396 GBM and 190 LGG (115 astrocytoma and 75 oligodendroglioma) patients were standardized to construct frequency maps and analyzed by voxel-based lesion-symptom mapping. We then investigated the spatial correlation between glioma distribution with gene expression in healthy brains. We also evaluated transcriptomic differences in tumor tissue from predilection and nonpredilection sites. Furthermore, we quantitively characterized tumor anatomical localization and explored whether it was significantly related to overall survival. Finally, we employed a support vector machine to build a survival prediction model for GBM patients. GBMs exhibited a distinct location predilection from LGGs. GBMs were nearer to the subventricular zone and more likely to be localized to regions enriched with synaptic signaling, whereas astrocytoma and oligodendroglioma tended to occur in areas associated with the immune response. Synapse, neurotransmitters and calcium ion channel-related genes were all activated in GBM tissues coming from predilection regions. Furthermore, we characterized tumor location features in terms of a series of tumor-to-predilection distance metrics, which were able to predict GBM 1-year survival status with an accuracy of 0.71. These findings provide new perspectives on our understanding of tumor anatomic localization. The spatial features of glioma are of great value in individual therapy and prognosis prediction.


Asunto(s)
Astrocitoma , Neoplasias Encefálicas , Glioblastoma , Glioma , Oligodendroglioma , Humanos , Neoplasias Encefálicas/patología , Transcriptoma , Oligodendroglioma/genética , Glioma/patología , Glioblastoma/patología
12.
Planta ; 259(1): 8, 2023 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-38019301

RESUMEN

MAIN CONCLUSION: This study reveals that mutations in BRIP1/2 subunits of the BAS complex disrupt root meristem development by decreasing PIN genes expression, affecting auxin transport, and downregulating essential root genes PLT. Switch defective/sucrose non-fermentable (SWI/SNF) chromatin remodeling complexes play vital roles in plant development. BRAHMA-interacting proteins1 (BRIP1) and BRIP2 are subunits of BRAHMA (BRM)-associated SWI/SNF complex (BAS) in plants; however, their role and underlying regulatory mechanism in root development are still unknown. Here, we show that brip1 brip2 double mutants have a significantly shortened root meristem and an irregular arrangement in a portion of the root stem cell niche. The mutations in BRIP1 and BRIP2 cause decreased expression of the PIN-FORMED (PIN) genes, which in turn reduces the transport of auxin at the root tip, leading to the disruption of the accurate establishment of normal auxin concentration gradients in the stem cells. Chromatin immunoprecipitation (ChIP) experiments indicated that BRIP1 and BRIP2 directly bind to the PINs. Furthermore, we found a significant down-regulation in the expression of key root development genes, PLETHORA (PLT), in brip1 brip2. The brip1 brip2 plt1 plt2 quadruple mutations do not show further exacerbation in the short-root phenotype compared to plt1 plt2 double mutants. Using a dexamethasone (DEX)-inducible PLT2 transgenic line, we showed that acute overexpression of PLT2 partially rescues root meristem defects of brip1 brip2, suggesting that BRIP1 and BRIP2 act in part through the PLT1/2 pathway. Taken together, our results identify the critical role and the underlying mechanism of BRIP1/2 in maintaining the development of root meristem through the regulation of auxin output and expression of PLTs.


Asunto(s)
Ácidos Indolacéticos , Meristema , Proteínas de Plantas , Transporte Biológico , Regulación hacia Abajo , Expresión Génica , Meristema/genética , Proteínas de Plantas/genética
13.
Plant Physiol ; 190(1): 532-547, 2022 08 29.
Artículo en Inglés | MEDLINE | ID: mdl-35708655

RESUMEN

Arabidopsis (Arabidopsis thaliana) FLOWERING LOCUS C (FLC) acts as a key flowering regulator by repressing the expression of the floral integrator FLOWERING LOCUS T (FT). Prolonged exposure to cold (vernalization) induces flowering by reducing FLC expression. The long noncoding RNAs (lncRNAs) COOLAIR and COLDAIR, which are transcribed from the 3' end and the first intron of FLC, respectively, are important for FLC repression under vernalization. However, the molecular mechanism of how COOLAIR and COLDAIR are transcriptionally activated remains elusive. In this study, we found that the group-III WRKY transcription factor WRKY63 can directly activate FLC. wrky63 mutant plants display an early flowering phenotype and are insensitive to vernalization. Interestingly, we found that WRKY63 can activate the expression of COOLAIR and COLDAIR by binding to their promoters.WRKY63 therefore acts as a dual regulator that activates FLC directly under non-vernalization conditions but represses FLC indirectly during vernalization through inducing COOLAIR and COLDAIR. Furthermore, genome-wide occupancy profile analyses indicated that the binding of WRKY63 to vernalization-induced genes increases after vernalization. In addition, WRKY63 binding is associated with decreased levels of the repressive marker Histone H3 Lysine 27 trimethylation (H3K27me3). Collectively, our results indicate that WRKY63 is an important flowering regulator involved in vernalization-induced transcriptional regulation.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Frío , Flores/fisiología , Regulación de la Expresión Génica de las Plantas , Proteínas de Dominio MADS/genética , Proteínas de Dominio MADS/metabolismo , Activación Transcripcional/genética
14.
Opt Lett ; 48(5): 1244-1247, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36857258

RESUMEN

Quantum network applications such as distributed quantum computing and quantum secret sharing represent a promising future network equipped with quantum resources. Entanglement generation and distribution over long distances are critical and unavoidable when utilizing quantum technology in a fully connected network. The distribution of bipartite entanglement over long distances has seen some progress, while the distribution of multipartite entanglement over long distances remains unsolved. Here we report a two-dimensional quantum repeater protocol for the generation of multipartite entanglement over long distances with an all-photonic framework to fill this gap. The entanglement generation yield remains proportional to the transmission efficiency regardless of the number of network users and shows long transmission distance under various numbers of network users. With the improved efficiency and flexibility of extending the number of users, we anticipate that our protocol can work as a significant building block for quantum networks in the future.

15.
FASEB J ; 36(3): e22183, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35202487

RESUMEN

Glioblastoma multiforme (GBM) is the most common and aggressive type of tumor of the primary nervous system. Treatment options for GBM include surgery, chemotherapy, and radiation therapy; however, the clinical outcomes are poor, with a high rate of recurrence. An increasing number of studies have shown that circular RNAs (circRNAs) serve important roles in several types of cancer. Gene Expression Omnibus (GEO) database was utilized to identify the differentially expressed circRNAs and their biological functions. Then, we detected the circular RNA bifunctional apoptosis regulator (circBFAR) was significantly increased in three GEO datasets. However, the role of circBFAR has not been reported in GBM. In this study, the expression of circBFAR was significantly increased both in GBM tissues or cell lines and was negatively correlated with overall survival in patients with GBM. Knockdown of circBFAR inhibited proliferation and invasion both in vitro and in vivo. Increased expression of circBFAR resulted in a reduction of miR-548b expression in glioma cells. A luciferase reporter and RIP assay indicated that miR-548b was a direct target of circBFAR, and miR-548b may negatively regulate the expression of FoxM1. Rescue experiments showed that overexpression of FoxM1 could counter the effect of circBFAR silencing on the proliferation and invasion of glioma cell lines. Moreover, we identified that circBFAR regulates FoxM1 by interacting with miR-548b in glioma cells. In conclusion, the present study demonstrated that a circBFAR/miR-548b/FoxM1 axis regulates the development of GBM and highlights potentially novel therapeutic targets for the treatment of GBM.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Reguladoras de la Apoptosis/genética , Biomarcadores de Tumor/metabolismo , Proteína Forkhead Box M1/metabolismo , Regulación Neoplásica de la Expresión Génica , Glioblastoma/patología , Proteínas de la Membrana/genética , MicroARNs/genética , ARN Circular/genética , Adulto , Anciano , Animales , Apoptosis , Biomarcadores de Tumor/genética , Proliferación Celular , Femenino , Proteína Forkhead Box M1/genética , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto , Adulto Joven
16.
Biomacromolecules ; 24(6): 2918-2927, 2023 06 12.
Artículo en Inglés | MEDLINE | ID: mdl-37235210

RESUMEN

Fluorine-19 magnetic resonance imaging (19F MRI) probes have received considerable research interest as imaging contrast agents (CAs), but they remain neglected and underutilized due to the limited fluorine content or poor performance of fluorinated tracers. Here, we present polymeric nanoparticles (NPs) as 19F MRI CAs with a simple synthesis method and promising imaging performance. First, hydrophilic random copolymers were synthesized from oligo(ethylene glycol) methyl ether acrylate and perfluoropolyether methacrylate by reversible addition-fragmentation chain transfer (RAFT) polymerization. The optimal fluorine content, polymer concentration, and cytotoxicity as 19F MRI CAs were investigated in detail. Then, the optimal copolymer was selected as the macromolecular chain transfer agent, and the chain extension was performed with 2-(perfluorooctyl ethyl methacrylate). Subsequently, the NPs with different morphologies, such as ellipsoidal, spherical nanoparticles and vesicles, were prepared in situ by the RAFT-mediated polymerization-induced self-assembly method. In addition, the 19F MRI signal and cytotoxicity studies further confirmed that these polymeric NPs are nontoxic and have great potential as promising 19F MRI CAs for biological applications.


Asunto(s)
Medios de Contraste , Nanopartículas , Medios de Contraste/farmacología , Polimerizacion , Flúor , Polímeros , Imagen por Resonancia Magnética , Metacrilatos
17.
Biomacromolecules ; 24(6): 2777-2789, 2023 06 12.
Artículo en Inglés | MEDLINE | ID: mdl-37212788

RESUMEN

19F magnetic resonance imaging (MRI)-assisted drug delivery provides the possibility to monitor and track drug transportation details in situ. A series of photo-responsive amphiphilic block copolymers consisting of hydrophilic poly(ethylene glycol) and 19F-containing hydrophobic segments, poly(2,2,2-trifluoroethyl acrylate) (PTFEA), with different chain lengths were synthesized by reversible addition-fragmentation chain-transfer polymerization. In particular, the photo-sensitive functional group of o-nitrobenzyl oxygen was introduced to control the photolysis behavior of the copolymers under ultraviolet irradiation. With the extension of the hydrophobic chain length, the drug loading capacity and photoresponsivity were both enhanced, while the chain mobility of PTFEA was suppressed, and the 19F MRI signal was attenuated. When the polymerization degree of PTFEA was about 10, the nanoparticles exhibit detectable 19F MRI signals and sufficient drug loading capacity (loading efficiency = 10%, cumulative release = 49%). These results offer a promising "smart" theranostic platform for 19F MRI.


Asunto(s)
Nanopartículas , Medicina de Precisión , Polímeros/química , Nanopartículas/uso terapéutico , Nanopartículas/química , Polietilenglicoles/química , Micelas , Imagen por Resonancia Magnética , Portadores de Fármacos/química
18.
Nucleic Acids Res ; 49(1): 98-113, 2021 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-33270882

RESUMEN

The Polycomb repressive complex 2 (PRC2) catalyzes histone H3 Lys27 trimethylation (H3K27me3) to repress gene transcription in multicellular eukaryotes. Despite its importance in gene silencing and cellular differentiation, how PRC2 is recruited to target loci is still not fully understood. Here, we report genome-wide evidence for the recruitment of PRC2 by the transcriptional repressors VIVIPAROUS1/ABI3-LIKE1 (VAL1) and VAL2 in Arabidopsis thaliana. We show that the val1 val2 double mutant possesses somatic embryonic phenotypes and a transcriptome strikingly similar to those of the swn clf double mutant, which lacks the PRC2 catalytic subunits SWINGER (SWN) and CURLY LEAF (CLF). We further show that VAL1 and VAL2 physically interact with SWN and CLF in vivo. Genome-wide binding profiling demonstrated that they colocalize with SWN and CLF at PRC2 target loci. Loss of VAL1/2 significantly reduces SWN and CLF enrichment at PRC2 target loci and leads to a genome-wide redistribution of H3K27me3 that strongly affects transcription. Finally, we provide evidence that the VAL1/VAL2-RY regulatory system is largely independent of previously identified modules for Polycomb silencing in plants. Together, our work demonstrates an extensive genome-wide interaction between VAL1/2 and PRC2 and provides mechanistic insights into the establishment of Polycomb silencing in plants.


Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Regulación de la Expresión Génica de las Plantas , Silenciador del Gen , Complejo Represivo Polycomb 2/metabolismo , Proteínas Represoras/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Represión Epigenética , Ontología de Genes , Histonas/metabolismo , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Complejo Represivo Polycomb 2/genética , Unión Proteica , Mapeo de Interacción de Proteínas , Proteínas Represoras/deficiencia , Proteínas Represoras/genética , Elementos de Respuesta/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Transcripción Genética
19.
Entropy (Basel) ; 25(7)2023 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-37509958

RESUMEN

Rampant terrorism poses a serious threat to the national security of many countries worldwide, particularly due to separatism and extreme nationalism. This paper focuses on the development and application of a temporal self-exciting point process model to the terror data of three countries: the US, Turkey, and the Philippines. To account for occurrences with the same time-stamp, this paper introduces the order mark and reward term in parameter selection. The reward term considers the triggering effect between events in the same time-stamp but different order. Additionally, this paper provides comparisons between the self-exciting models generated by day-based and month-based arrival times. Another highlight of this paper is the development of a model to predict the number of terror events using a combination of simulation and machine learning, specifically the random forest method, to achieve better predictions. This research offers an insightful approach to discover terror event patterns and forecast future occurrences of terror events, which may have practical application towards national security strategies.

20.
Plant J ; 106(1): 200-213, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33432631

RESUMEN

SPLAYED (SYD) is a SWItch/Sucrose Non-Fermentable (SWI/SNF)-type chromatin remodeler identified in Arabidopsis thaliana (Arabidopsis). It is believed to play both redundant and differential roles with its closest homolog BRAHMA (BRM) in diverse plant growth and development processes. To better understand how SYD functions, we profiled the genome-wide occupancy of SYD and its impact on the global transcriptome and trimethylation of histone H3 on lysine 27 (H3K27me3). To map the global occupancy of SYD, we generated a GFP-tagged transgenic line and used it for chromatin immunoprecipitation experiments followed by next-generation sequencing, by which more than 6000 SYD target genes were identified. Through integrating SYD occupancy and transcriptome profiles, we found that SYD preferentially targets to nucleosome-free regions of expressed genes. Further analysis revealed that SYD occupancy peaks exhibit five distinct patterns, which were also shared by BRM and BAF60, a conserved SWI/SNF complex component, indicating the common target sites of these SWI/SNF chromatin remodelers and the functional relevance of such distinct patterns. To investigate the interplay between SYD and Polycomb-group (PcG) proteins, we performed a genome-wide analysis of H3K27me3 in syd-5. We observed both increases and decreases in H3K27me3 levels at a few hundred genes in syd-5 compared to wild type. Our results imply that SYD can act antagonistically or synergistically with PcG at specific genes. Together, our SYD genome-wide occupancy data and the transcriptome and H3K27me3 profiles provide a much-needed resource for dissecting SYD's crucial roles in the regulation of plant growth and development.


Asunto(s)
Adenosina Trifosfatasas/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , Histonas/metabolismo , Proteínas del Grupo Polycomb/metabolismo , Factores de Transcripción/metabolismo , Adenosina Trifosfatasas/genética , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Ensamble y Desensamble de Cromatina , Proteínas Cromosómicas no Histona/genética , Regulación de la Expresión Génica de las Plantas , Metilación , Proteínas del Grupo Polycomb/genética , Factores de Transcripción/genética
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