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1.
Adv Sci (Weinh) ; 11(14): e2308496, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38308190

RESUMEN

During maternal-to-zygotic transition (MZT) in the embryo, mRNA undergoes complex post-transcriptional regulatory processes. However, it is unclear whether and how alternative splicing plays a functional role in MZT. By analyzing transcriptome changes in mouse and human early embryos, dynamic changes in alternative splicing during MZT are observed and a previously unnoticed process of zygotic splicing activation (ZSA) following embryonic transcriptional activation is described. As the underlying mechanism of RNA splicing, splicing factors undergo dramatic maternal-to-zygotic conversion. This conversion relies on the key maternal factors BTG4 and PABPN1L and is zygotic-transcription-dependent. CDK11-dependent phosphorylation of the key splicing factor, SF3B1, and its aggregation with SRSF2 in the subnuclear domains of 2-cell embryos are prerequisites for ZSA. Isoforms generated by erroneous splicing, such as full-length Dppa4, hinder normal embryonic development. Moreover, alternative splicing regulates the conversion of early embryonic blastomeres from totipotency to pluripotency, thereby affecting embryonic lineage differentiation. ZSA is an essential post-transcriptional process of MZT and has physiological significance in generating new life. In addition to transcriptional activation, appropriate expression of transcript isoforms is also necessary for preimplantation embryonic development.


Asunto(s)
Transcriptoma , Cigoto , Humanos , Animales , Ratones , Transcriptoma/genética , Cigoto/metabolismo , Desarrollo Embrionario/genética , Empalme del ARN , Isoformas de Proteínas/genética , Proteínas de Unión a Poli(A)/genética , Proteínas de Unión a Poli(A)/metabolismo , Proteínas Nucleares/genética
2.
Artículo en Chino | MEDLINE | ID: mdl-36987962

RESUMEN

Objective:To investigate the changes of inflammation and immune function in children with chronic tonsillitis after tonsillotomy. Methods:Prospectively collected 60 children with obstructive sleep apnea (OSA) diagnosed as chronic tonsillitis with adenoids and tonsillar hypertrophy from January to June 2021. Two groups were divided, the experimental group (n=30) underwent bilateral partial tonsillectomy + adenoidectomy by hypothermia plasma ablation, and the control group (n=30) underwent adenoidectomy by using the same hypothermia plasma ablation method. The number of tonsillitis attacks before surgery and within one year after surgery was recorded, and the serum immunoglobulin IgM, IgG, IgA, complement C3 and complement C4 levels before operation, one month and three months after operation were measured. Results:The number of tonsillitis attacks in the experimental group and the control group at one year after surgery was lower than that before surgery(P<0.05); The number of inflammatory attacks in the experimental group was (0.50±0.63) times/year, which was lower than that of (1.33±0.80) times/year in the control group. There was no significant difference in the five immunization results of the two groups at one month and three months after operation compared with before operation, and there was also no significant difference between the experimental and the control groups. Conclusion:Partial tonsillectomy can be applied to children with chronic tonsillitis, which can effectively reduce the number of tonsillitis attacks and has no effect on the immune function of children.


Asunto(s)
Hipotermia , Tonsilectomía , Tonsilitis , Niño , Humanos , Tonsilectomía/métodos , Tonsilitis/cirugía , Adenoidectomía , Tonsila Palatina/cirugía , Inflamación , Enfermedad Crónica , Inmunidad
3.
RSC Adv ; 13(4): 2372-2378, 2023 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-36741139

RESUMEN

Copper is an important interconnect material in integrated circuits (IC) due to its outstanding electrical and thermal properties. However, the development of the IC industry requires novel interconnect materials with higher conductivity. Here, uniform graphene oxide (GO) is deposited on copper by electrophoretic deposition (EPD) to obtain a GO-Cu bilayer structure at room temperature. (3-Mercaptopropyl) trimethoxysilane (MPTS) is self-assembled on the Cu anode surface, which protects the anode from oxidation during the EPD process. We find that the in situ hydrolysis of methoxy under the promotion of EPD voltage can facilitate the uniform deposition of GO and enhance the interface bonding force. In order to achieve better electrical performance, different reduction methods are conducted to reduce the structural disorder of GO. ERGO-Cu reduced by the electrochemical reduction method at -0.75 V for 1 min shows the lowest square resistance with a 16% resistance decrease compared with the GO-Cu structure and a 4.5% decrease compared with Cu substrate, due to the proper adjustment of the GO crystal structure. The room temperature fabricated ERGO-Cu bilayer structure provides a possibility for future interconnects with improved conductivity.

4.
J Adv Res ; 51: 45-57, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-36396044

RESUMEN

INTRODUCTION: The R-loop is a naturally formed three-strand nucleic acid structure that recently has been reported to participate in multiple biological processes and helped answer some previously unexplained scientific questions. Meiosis process involves multiple chromatin-related events such as DNA double-stranded breaks (DSB) formation, repairing and transcriptional dynamics. OBJECTIVES: Explore the regulatory roles and physiological functions of R-loops in the mammalian meiosis process. METHODS: In our study, using genome-wide S9.6 CUT & Tag seq, we first mapped the genomic distribution and dynamic changes of R-loop during the meiotic process in mice, from spermatogonia to secondary spermatocytes. And we further explore the role of R-loop in physiological conditions by constructing conditional knockout mice of Rnaseh1, which deleted the R-loop endonuclease before meiosis entry. RESULTS: R-loop predominantly distributes at promoter-related regions and varies across different meiotic stages. By joint analysis with the corresponding transcriptome, we found that the R-loop was closely related to transcription during the meiotic process. The high frequency of promoter-related R-loop in meiotic cells is usually accompanied by high transcription activity, and we further verified this in the leptotene/zygotene to the pachytene transition process. Moreover, the lack of RNase H1 caused sterility in male mice with R-loop accumulation and abnormal DSB repair in spermatocytes. Further analysis showed that abnormal R-loop accumulation in the leptotene/zygotene stages influenced transcriptional regulation in the pachytene stage. CONCLUSION: The mutual regulation of the R-loop and transcription plays an essential role in spermatogenesis. And R-loop is also important for the normal repair process of DSB during meiosis.


Asunto(s)
Roturas del ADN de Doble Cadena , Estructuras R-Loop , Masculino , Ratones , Animales , Meiosis/genética , Espermatogénesis/genética , Espermatocitos , Ratones Noqueados , Mamíferos/genética
5.
Front Pediatr ; 10: 1051993, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36507143

RESUMEN

Allergic rhinitis (AR) is one of the popular childhood diseases, bringing physical and metal burdens to the children and their families. The study was performed to detect common allergens eliciting AR in children, to investigate the prevalence of allergens in different age and gender cohorts, and to provide a reliable basis for clinical prevention and treatment of AR during childhood. We measured serum-specific IgE and performed inhalant and ingestion allergen examinations in 2,316 children with AR, in collaboration with BioSciTec GmbH. The prevalence of different allergens was determined according to gender, age, severity, and season. Among the 2,316 AR cases, the top five inhalant allergens were Dermatophagoides pteronyssinus (1,674 cases, 72.3%), Dermatophagoides farinae (1,520 cases, 65.6%), Blomia tropicalis (1,477 cases, 63.8%), Cockroach (602 cases, 26.0%), and Dog hair (602 cases, 26.0%). The top five ingestive allergens were Milk (1,111 cases, 48.0%), Egg white (543 cases, 23.4%), Shrimp/Crab (425 cases, 18.4%), Beef/Mutton (422 cases, 18.2%), and Egg yold (329 cases, 14.2%). AR severity analyses showed that 50.9% (1,180 cases) of D. pteronyssinus allergies were above level three, 47.9% (1,109 cases) of D. farinae allergies were above level three, only 23.3% (539 cases) of B. tropicalis allergies were level three, and B. tropicalis allergies were mainly of level 2. Other AR-inducing allergens mainly produced level one or two reactions. Regarding ingestion allergens, 7.9% (183 cases) of milk allergies and 4.7% (108 cases) of Shrimp/Crab allergies were above level three, and other allergens induced AR mainly of level one or two. The study investigated the major allergens eliciting AR in children from Guangdong, China, assessed the prevalence and severity among cohorts regarding age, gender, and season, and produced essential information on childhood AR, laying important references for AR prevention and treatment in the future.

6.
Langmuir ; 38(48): 14969-14980, 2022 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-36394474

RESUMEN

Covalent grafting of dielectric films containing polyhedral oligomeric silsesquioxane (POSS) on the surface of Cu(111) is performed by a one-step electrochemical reduction of diazonium salts. This method is efficient and economic and performs in a proton-polar solvent of deionized water and tetrahydrofuran (THF), where the monomer employs an octavinylsilsesquioxane (OVS) containing a POSS core. The eight vinyl bonds contained in OVS are used to participate in aryl radical-initiated polymerization reactions to form films. The formed film is dense and covers the copper surface completely and uniformly. The thickness of the film can be controlled by adjusting the reaction time. The components of the films are mainly polynitrophenyl (PNP) or polyaminophenyl (PAP) as well as poly(octavinylsilsesquioxane) (POVS), and the POVS content could be adjusted by the applied voltage. The introduction of POSS prevents the copper surface from being oxidized and often gives the film good properties such as good dielectric properties, mechanical properties, and thermal properties. In addition, the presence of Cu-O-C and Cu-C bonds between the film and copper interface is confirmed at different film thicknesses by X-ray photoelectron spectroscopy (XPS), which allowed the construction of covalent bonds between metal and nonmetal, further enhancing the bonding between the film and copper. Organic films prepared by electrochemical reduction of diazonium salts using OVS as a monomer will have potential significance for the future development of the electronics industry.

7.
Sci Adv ; 8(43): eabn9016, 2022 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-36306357

RESUMEN

Growing oocytes store a large amount of maternal mRNA to support the subsequent "maternal-zygotic transition" process. At present, it is not clear how the growing oocytes store and process the newly transcribed mRNA under physiological conditions. In this study, we report non-membrane-bound compartments, nuclear poly(A) domains (NPADs), as the hub for newly transcribed mRNA, in developing mouse oocytes. The RNA binding protein PABPN1 promotes the formation of NPAD through its N-terminal disordered domain and RNA-recognized motif by means of liquid phase separation. Pabpn1-null growing oocytes cannot form NPAD normally in vivo and have defects in stability of oocyte growing-related transcripts and formation of long 3' untranslated region isoform transcripts. Ultimately, Pabpn1fl/fl;Gdf9-Cre mice are completely sterile with primary ovarian insufficiency. These results demonstrate that NPAD formed by the phase separation properties of PABPN1-mRNA are the hub of the newly transcribed mRNA and essential for the development of oocytes and female reproduction.


Asunto(s)
Núcleo Celular , Poli A , Animales , Femenino , Ratones , Núcleo Celular/metabolismo , Oocitos/metabolismo , Poli A/genética , Poli A/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo
8.
Development ; 149(19)2022 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-36178098

RESUMEN

Recent large-scale mRNA sequencing has shown that introns are retained in 5-10% of mRNA, and these events are named intron retention (IR). IR has been recognized as a key mechanism in the regulation of gene expression. However, the role of this mechanism in female reproduction in mammals remains unclear. RNA terminal phosphate cyclase B (RTCB) is a RNA ligase; we found that RTCB conditional knockout mice have premature ovarian failure and that RTCB plays a crucial role in follicular development. RTCB regulated the splicing of transcripts related to DNA methylation and DNA damage repair. In addition, it regulated the resumption of oocyte meiosis by affecting CDK1 activation. Moreover, the loss of RTCB suppressed zygotic genome activation (ZGA) and decreased translation at the global level. In addition, Rtcb deletion resulted in the accumulation of maternal mRNAs containing unspliced introns and in a decline in the overall level of transcripts. As a result, the Rtcb-/- females were sterile. Our study highlights the important role of RTCB-regulated noncanonical alternative splicing in female reproduction.


Asunto(s)
Empalme Alternativo , Aminoacil-ARNt Sintetasas/metabolismo , Fosfatos , Empalme Alternativo/genética , Animales , Femenino , Ligasas/genética , Mamíferos/genética , Ratones , Oocitos , Empalme del ARN , ARN Mensajero/genética
9.
Nanotechnology ; 33(50)2022 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-36113353

RESUMEN

The rapid growth of information puts forward new requirements for computer including denser memory capacity and faster response beyond the traditional von Neumann architecture. One promising strategy is to employ novel computing devices such as artificial synapses (AS). Here, an Au/LPSE-SiO2/Si AS (LPSE-SiO2AS) with a simple sandwich structure was fabricated by UV curing. LPSE-SiO2AS emulated synaptic plasticity including excitatory postsynaptic current, paired-pulse facilitation, and spike-dependent plasticity. It also simulated the memory strengthening and forgetting analogue to biological system. The realization of synaptic plasticity is due to the homogeneously dispersed nano-silica in LPSE, which acts as lithium ions trapping center and conducts a reversible electrochemical conversion reaction with Li ions with pulse stimulation. These results indicate the potential for LPSE-SiO2AS in future large-scale integrated neuromorphic networks.

10.
Nucleic Acids Res ; 50(19): 10896-10913, 2022 10 28.
Artículo en Inglés | MEDLINE | ID: mdl-35801907

RESUMEN

Post-transcriptional RNA modifications critically regulate various biological processes. N4-acetylcytidine (ac4C) is an epi-transcriptome, which is highly conserved in all species. However, the in vivo physiological functions and regulatory mechanisms of ac4C remain poorly understood, particularly in mammals. In this study, we demonstrate that the only known ac4C writer, N-acetyltransferase 10 (NAT10), plays an essential role in male reproduction. We identified the occurrence of ac4C in the mRNAs of mouse tissues and showed that ac4C undergoes dynamic changes during spermatogenesis. Germ cell-specific ablation of Nat10 severely inhibits meiotic entry and leads to defects in homologous chromosome synapsis, meiotic recombination and repair of DNA double-strand breaks during meiosis. Transcriptomic profiling revealed dysregulation of functional genes in meiotic prophase I after Nat10 deletion. These findings highlight the crucial physiological functions of ac4C modifications in male spermatogenesis and expand our understanding of its role in the regulation of specific physiological processes in vivo.


Asunto(s)
Citidina , Meiosis , Masculino , Ratones , Animales , Meiosis/genética , Citidina/genética , Emparejamiento Cromosómico , Células Germinativas , Mamíferos
11.
Artículo en Chino | MEDLINE | ID: mdl-35822367

RESUMEN

Objective:To analyzed allergens and screen for common airborne allergens in patients with allergic rhinitis (AR) in Shenzhen, and identified the distribution pattern of allergens in this region. We aimed to provide scientific and feasible statistical and clinical basis for prevention and treatment of allergenic rhinitis. Methods:For 3351 suspected cases of allergenic rhinitis, 18 kinds of airborne allergen serum-specific IgE were determined using a detection system of BioSciTec GmbH company, and statistical analysis was carried out according to sex, age, severity and seasonal allergen. Results:A total of 3,351 cases with allergic rhinitis were positive for airborne allergens. The top five inhalation allergens were Blomia tropicalis (2231, 66.6%), Dermatophagoides pterronyssinus (2212, 66.0%), Dermatophagoides farinae (1986, 59.3%), Cockroach (967, 28.9%), and Short ragweed (844, 25.2%). For the severity of the allergen, Dermatophagoides pterronyssinus ≥ level 3 accounted for 41.3% (1385/3351 cases) and Dermatophagoides farinae ≥level 3 accounted for 40.6% (1360/3351 cases). Blomia tropicalis were classified as level 2, and other allergens were mainly classified as level 1 or 2. The detection rate among different age groups and gender is significantly different. Conclusion:The main airborne allergens in Shenzhen were Blomia tropicalis, Dermatophagoides pterronyssinus, Dermatophagoides farinae, Cockroach, as well as Short ragweed. The distribution of allergens was affected by sex, age and season.


Asunto(s)
Cucarachas , Rinitis Alérgica , Rinitis , Alérgenos/análisis , Animales , Humanos , Inmunoglobulina E , Pruebas Cutáneas
13.
Nat Commun ; 13(1): 3191, 2022 06 09.
Artículo en Inglés | MEDLINE | ID: mdl-35680896

RESUMEN

A decrease in oocyte developmental potential is a major obstacle for successful pregnancy in women of advanced age. However, the age-related epigenetic modifications associated with dynamic transcriptome changes, particularly meiotic maturation-coupled mRNA clearance, have not been adequately characterized in human oocytes. This study demonstrates a decreased storage of transcripts encoding key factors regulating the maternal mRNA degradome in fully grown oocytes of women of advanced age. A similar defect in meiotic maturation-triggered mRNA clearance is also detected in aged mouse oocytes. Mechanistically, the epigenetic and cytoplasmic aspects of oocyte maturation are synchronized in both the normal development and aging processes. The level of histone H3K4 trimethylation (H3K4me3) is high in fully grown mouse and human oocytes derived from young females but decreased during aging due to the decreased expression of epigenetic factors responsible for H3K4me3 accumulation. Oocyte-specific knockout of the gene encoding CxxC-finger protein 1 (CXXC1), a DNA-binding subunit of SETD1 methyltransferase, causes ooplasm changes associated with accelerated aging and impaired maternal mRNA translation and degradation. These results suggest that a network of CXXC1-maintained H3K4me3, in association with mRNA decay competence, sets a timer for oocyte deterioration and plays a role in oocyte aging in both mouse and human oocytes.


Asunto(s)
Histonas , Oocitos , Animales , Femenino , Histonas/genética , Histonas/metabolismo , Humanos , Meiosis/genética , Ratones , Oocitos/metabolismo , Embarazo , Estabilidad del ARN/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Mensajero Almacenado/metabolismo , Transactivadores/metabolismo
14.
Nucleic Acids Res ; 50(10): 5599-5616, 2022 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-35640597

RESUMEN

Maternal-to-zygotic transition (MZT) is the first and key step in the control of animal development and intimately related to changes in chromatin structure and histone modifications. H2AK119ub1, an important epigenetic modification in regulating chromatin configuration and function, is primarily catalyzed by PRC1 and contributes to resistance to transcriptional reprogramming in mouse embryos. In this study, the genome-wide dynamic distribution of H2AK119ub1 during MZT in mice was investigated using chromosome immunoprecipitation and sequencing. The results indicated that H2AK119ub1 accumulated in fully grown oocytes and was enriched at the TSSs of maternal genes, but was promptly declined after meiotic resumption at genome-wide including the TSSs of early zygotic genes, by a previously unidentified mechanism. Genetic evidences indicated that ubiquitin-specific peptidase 16 (USP16) is the major deubiquitinase for H2AK119ub1 in mouse oocytes. Conditional knockout of Usp16 in oocytes did not impair their survival, growth, or meiotic maturation. However, oocytes lacking USP16 have defects when undergoing zygotic genome activation or gaining developmental competence after fertilization, potentially associated with high levels of maternal H2AK119ub1 deposition on the zygotic genomes. Taken together, H2AK119ub1 level is declined during oocyte maturation by an USP16-dependent mechanism, which ensures zygotic genome reprogramming and transcriptional activation of essential early zygotic genes.


Asunto(s)
Histonas , Lisina , Animales , Cromatina/genética , Regulación del Desarrollo de la Expresión Génica , Histonas/genética , Histonas/metabolismo , Lisina/metabolismo , Ratones , Oocitos/metabolismo , Oogénesis/genética , Ubiquitina Tiolesterasa/genética , Ubiquitina Tiolesterasa/metabolismo , Cigoto
15.
Nanotechnology ; 33(24)2022 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-35255485

RESUMEN

Since uncontrolled lithium (Li) dendrite growth and dendrite-induced dead Li severely limit the development of Li metal batteries, 3D Cu current collectors can effectively alleviate these problems during Li plating/stripping. Herein, one-step galvanostatic electrodeposition method is employed to fabricate a new current collector on Cu foam decorated with large-scale and uniform 3D porous Cu-based nanoflake (NF) structures (abbreviated as 3D Cu NF@Cu foam). This 3D structure with large internal surface areas not only generates lithophilic surface copper oxides and hydroxides as charge centers and nucleation sites for Li insertion/extraction, but also endows abundant space with interlinked NFs for buffering the cell volume expansion and increasing battery performance. As a result, Li-deposited 3D Cu NF@Cu foam current collector can realize stable cycling over 455 cycles with an average Coulombic efficiency of 98.8% at a current density of 1.0 mA cm-2, as well as a prolonged lifespan of >380 cycles in symmetrical cell without short-circuit, which are superior to those of blank Cu foam current collector. This work realizes Li metal anode stabilization by constructing 3D porous Cu NFs current collectors, which can advance the development of Li metal anode for battery industries.

16.
Nucleic Acids Res ; 50(1): 458-472, 2022 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-34904664

RESUMEN

An embryo starts its life with maternal mRNA clearance, which is crucial for embryonic development. The elimination of maternal transcripts occurs by the joint action of two pathways: the maternally encoded mRNA decay pathway (M-decay) and the zygotic genome activation (ZGA)-dependent pathway (Z-decay). However, zygotic factors triggering maternal mRNA decay in early mammalian embryos remain largely unknown. In this study, we identified the zygotically encoded nuclear poly(A) binding protein 1 (PABPN1) as a factor required for maternal mRNA turnover, with a previously undescribed cytoplasmic function. Cytoplasmic PABPN1 docks on 3'-uridylated transcripts, downstream of terminal uridylyl transferases TUT4 and TUT7, and recruits 3'-5' exoribonuclease DIS3L2 to its targets, facilitating maternal mRNA decay. Pabpn1-knockout in mice resulted in preimplantation stage mortality due to early developmental arrest at the morula stage. Maternal mRNAs to be eliminated via the Z-decay pathway failed to be removed from Pabpn1-depleted embryos. Furthermore, PABPN1-mediated Z-decay is essential for major ZGA and regulates the expression of cell fate-determining factors in mouse preimplantation embryos. This study revealed an unforeseen cytoplasmic function of PABPN1 coupled with early embryonic development, characterized the presence of a zygotic destabilizer of maternal mRNA, and elucidated the Z-decay process mechanisms, which potentially contribute to human fertility.


Asunto(s)
Regulación del Desarrollo de la Expresión Génica , Proteína I de Unión a Poli(A)/metabolismo , ARN Mensajero/metabolismo , Cigoto/metabolismo , Animales , Embrión de Mamíferos , Femenino , Células HeLa , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Oocitos , Estabilidad del ARN
17.
Cell Rep ; 37(7): 110007, 2021 11 16.
Artículo en Inglés | MEDLINE | ID: mdl-34788619

RESUMEN

CCR4-NOT deadenylase is a major regulator of mRNA turnover. It contains two heterogeneous catalytic subunits CNOT7/8 and CNOT6/6L in vertebrates. The physiological function of each catalytic subunit is unclear due to the gene redundancy. In this study, Cnot6/6l double knockout mice are generated. Cnot6l-/- female mice are infertile, with poor ovarian responses to gonadotropins. Follicle-stimulating hormone (FSH) stimulates the transcription and translation of Cnot6 and Cnot6l in ovarian granulosa cells. CNOT6/6L function as key effectors of FSH in granulosa cells and trigger the clearance of specific transcripts in granulosa cells during preantral to antral follicle transition. These results demonstrate that FSH modulates granulosa cell function by stimulating selective translational activation and degradation of existing mRNAs, in addition to inducing de novo gene transcription. Meanwhile, this study provides in vivo evidence that CNOT6/6L-mediated mRNA deadenylation is dispensable in most somatic cell types, but is essential for female reproductive endocrine regulation.


Asunto(s)
Folículo Ovárico/fisiología , Ribonucleasas/metabolismo , Animales , Exorribonucleasas/metabolismo , Femenino , Hormona Folículo Estimulante/metabolismo , Gonadotropinas/metabolismo , Células de la Granulosa/metabolismo , Células de la Granulosa/patología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Folículo Ovárico/metabolismo , Ovario/metabolismo , Estabilidad del ARN/genética , ARN Mensajero/metabolismo , Proteínas Represoras/metabolismo , Ribonucleasas/fisiología , Diferenciación Sexual
18.
Adv Sci (Weinh) ; 8(10): 2003636, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-34026442

RESUMEN

The CCR4-NOT complex is a major mRNA deadenylase in eukaryotes, comprising the catalytic subunits CNOT6/6L and CNOT7/8, as well as CNOT4, a regulatory subunit with previously undetermined functions. These subunits have been hypothesized to play synergistic biochemical functions during development. Cnot7 knockout male mice have been reported to be infertile. In this study, viable Cnot6/6l double knockout mice are constructed, and the males are fertile. These results indicate that CNOT7 has CNOT6/6L-independent functions in vivo. It is also demonstrated that CNOT4 is required for post-implantation embryo development and meiosis progression during spermatogenesis. Conditional knockout of Cnot4 in male germ cells leads to defective DNA damage repair and homologous crossover between X and Y chromosomes. CNOT4 functions as a previously unrecognized mRNA adaptor of CCR4-NOT by targeting mRNAs to CNOT7 for deadenylation of poly(A) tails, thereby mediating the degradation of a subset of transcripts from the zygotene to pachytene stage. The mRNA removal promoted by the CNOT4-regulated CCR4-NOT complex during the zygotene-to-pachytene transition is crucial for the appropriate expression of genes involved in the subsequent events of spermatogenesis, normal DNA double-strand break repair during meiosis, efficient crossover between X and Y chromosomes, and ultimately, male fertility.


Asunto(s)
Cromosomas/metabolismo , Reparación del ADN , Células Germinativas/fisiología , Meiosis , Estabilidad del ARN , Ribonucleasas/metabolismo , Espermatogénesis , Factores de Transcripción/metabolismo , Animales , Daño del ADN , Desarrollo Embrionario/fisiología , Exorribonucleasas/genética , Exorribonucleasas/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Factores de Transcripción/genética
19.
Nucleic Acids Res ; 49(5): 2569-2582, 2021 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-33621320

RESUMEN

During oogenesis, oocytes gain competence and subsequently undergo meiotic maturation and prepare for embryonic development; trimethylated histone H3 on lysine-4 (H3K4me3) mediates a wide range of nuclear events during these processes. Oocyte-specific knockout of CxxC-finger protein 1 (CXXC1, also known as CFP1) impairs H3K4me3 accumulation and causes changes in chromatin configurations. This study investigated the changes in genomic H3K4me3 landscapes in oocytes with Cxxc1 knockout and the effects on other epigenetic factors such as the DNA methylation, H3K27me3, H2AK119ub1 and H3K36me3. H3K4me3 is overall decreased after knocking out Cxxc1, including both the promoter region and the gene body. CXXC1 and MLL2, which is another histone H3 methyltransferase, have nonoverlapping roles in mediating H3K4 trimethylation during oogenesis. Cxxc1 deletion caused a decrease in DNA methylation levels and affected H3K27me3 and H2AK119ub1 distributions, particularly at regions with high DNA methylation levels. The changes in epigenetic networks implicated by Cxxc1 deletion were correlated with the transcriptional changes in genes in the corresponding genomic regions. This study elucidates the epigenetic changes underlying the phenotypes and molecular defects in oocytes with deleted Cxxc1 and highlights the role of CXXC1 in orchestrating multiple factors that are involved in establishing the appropriate epigenetic states of maternal genome.


Asunto(s)
Epigénesis Genética , Oocitos/metabolismo , Transactivadores/fisiología , Animales , Células Cultivadas , Metilación de ADN , Femenino , Eliminación de Gen , Genoma , Código de Histonas , Histonas/metabolismo , Ratones , Ratones Endogámicos C57BL , Regiones Promotoras Genéticas , Transactivadores/genética , Transcripción Genética
20.
ACS Appl Mater Interfaces ; 13(3): 4294-4304, 2021 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-33440933

RESUMEN

Effective nonprecious metal catalysts are urgently needed for hydrogen evolution reaction (HER). The hybridization of N-doped graphene and a cost-effective metal is expected to be a promising approach for enhanced HER performance but faces bottlenecks in controllable fabrication. Herein, a silica medium-assisted method is developed for the high-efficient synthesis of single-layer N-doped graphene encapsulating nickel nanoparticles (Ni@SNG), where silica nanosheets molecule sieves tactfully assist the self-limiting growth of single-layer graphene over Ni nanoparticles by depressing the diffusion of gaseous carbon radical reactants. The Ni@SNG sample synthesized at 800 °C shows excellent activity for HER in alkaline medium with a low overpotential of 99.8 mV at 10 mA cm-2, which is close to that of the state-of-the-art Pt/C catalyst. Significantly, the Ni@SNG catalyst is also developed as a binder-free electrode in magnetic field, exhibiting much improved performance than the common Nafion binder-based electrode. Therefore, the magnetism adsorption technique will be a greatly promising approach to overcome the high electron resistance and poor adhesive stability of polymer binder-based electrodes in practical applications.

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