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Photocatalytic carbon dioxide (CO2) reduction to value-added chemicals is a multielectron transfer process, and the crucial step is the synthesis of photocatalysts. The introduction of small conjugated organic ligands can make the catalytic active site of the compound easier to be exposed in the reaction system and fully contact with the substrate, accelerating the photocatalytic reaction process. In this paper, we synthesized two isomorphic compounds, namely, {[Co(mtrz)3·(H2O)2]2·[SiW12O40]}·6H2O (1) and {[Ni(mtrz)3·(H2O)2]2·[SiW12O40]}·6H2O (2) (mtrz = 1-methyl-1,2,4-triazole). We found that compound 1 has a great photocatalytic performance through a series of experiments, with a CO reduction yield of 7364.92 µmol g-1 h-1 and a CO selectivity of 82.5%. Furthermore, the high catalytic activity can be maintained over four cycle experiments. The catalytic mechanism of its photocatalytic system is also elucidated, which provides an idea for realizing efficient catalytic reduction of CO2 to CO.
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In the field of recycling CO2, the photocatalytic CO2 reduction reaction (CO2RR) is a typical example, and researchers have designed a variety of photocatalysts to improve the conversion rate of CO2 over the years. In this paper, two metal-oxygen clusters are designed and formulated as [Co3Zn(OH)6(SO4)]·4H2O (1) and [Ni3Zn(OH)6(SO4)]·4H2O (2). As for compound 1, the main structure is composed of {CoO6} octahedra connected by edge-sharing to form a two-dimensional layer, on which {ZnO4} and {SO4} tetrahedra are supported. More interestingly, compound 1 has outstanding photocatalytic activity, which is mainly attributed to the open-framework structure and the cobalt ions as active sites. Upon catalysis for eight hours, its maximum CO generation rate is 9982.13 µmol g-1 h-1, with a selectivity of 81.8%. Additionally, compound 1 takes on weak antiferromagnetic coupling due to Co(II) ions.
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BACKGROUND: The benefit of routine lymphadenectomy (LD) in improving outcomes for patients with primary intrahepatic cholangiocarcinoma (ICC) undergoing curative hepatectomy remains unclear. MATERIALS AND METHODS: This study enrolled 269 consecutive patients who underwent liver resection for primary ICC from January 2009 to July 2020 in West China Hospital. The association of the nodal status with disease-free survival (DFS) and overall survival (OS) was analyzed using the Cox proportional hazards model and 1:1 propensity score matching (PSM) analysis. RESULTS: Seventy-five (27.9%) patients underwent curative liver resection combined with LD (LD+ group), while 194 (72.1%) patients received curative liver resection without LD (LD- group and Nx group). Among the LD+ group, metastatic disease was present in 36 patients (48%, N1 group) and absent in 39 patients (N0 group). During the follow-up period, 116 patients (43.1%) experienced tumor recurrence and 101 patients (37.5%) died due to recurrence. Multivariate analysis revealed that lymph node metastasis (N1, HR 3.682, 95% CI 1.949-6.957, p < 0.001) was associated with worse OS, while LD+ status (HR 0.504, 95% CI 0.298-0.853, p = 0.011) was associated with improved OS. Adjuvant therapy was a protective factor for both DFS (HR 0.602, 95% CI, 0.447-0.810, p = 0.001) and OS (HR 0.683, 95% CI 0.484-0.963, p = 0.030). After 1:1 PSM, the LD+ patients (n = 74) displayed similar 1-, 3- and 5-year DFS rates (40.0, 7.9 and 7.9% vs. 29.0, 13.7 and 13.7%, p = 0.741) and OS rates (56.0, 26.6 and 22.2% vs. 58.9, 25.6, and 16.4%, p = 0.644) to the LD- patients (n = 74). Additionally, among the 75 LD+ patients, 48 patients underwent hepatic hilar lymphadenectomy (HHL), and 27 patients underwent extended hepatic hilar lymphadenectomy (EHL). Both DFS (p = 0.504) and OS (p = 0.215) were similar between the HHL and EHL groups. CONCLUSION: Routine LD and adjuvant therapy may contribute to improved OS according to the crude analysis. LD could provide accurate staging without excessive risk and guide adjuvant therapy based on the tumor stage, potentially resulting in better survival. These results suggest that a routine LD should be considered during curative hepatectomy for ICC.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Hepatectomía/efectos adversos , Puntaje de Propensión , Estudios Retrospectivos , Recurrencia Local de Neoplasia/cirugía , Colangiocarcinoma/cirugía , Colangiocarcinoma/patología , Escisión del Ganglio Linfático , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/cirugía , PronósticoRESUMEN
It has been reported that abnormal epigenetic modification is associated with the occurrence of Parkinson's disease (PD). Here, we found that a ten-eleven translocation 2 (TET2), a staff of the DNA hydroxylases family, was increased in dopaminergic neurons in vitro and in vivo. Genome-wide mapping of DNA 5-hydroxymethylcytosine (5-hmC)-sequencing has revealed an aberrant epigenome 5-hmC landscape in 1-methyl-4-phenylpyridinium iodide (MPP+)-induced SH-SY5Y cells. The TET family of DNA hydroxylases could reverse DNA methylation by oxidization of 5-methylcytosine (5-mC) to 5-hmC. However, the relationship between modification of DNA hydroxymethylation and the pathogenesis of PD is not clear. According to the results of 5-hmC-sequencing studies, 5-hmC was associated with gene-rich regions in the genomes related to cell cycle, especially gene-cyclin-dependent kinase inhibitor 2A (Cdkn2A). Downregulation of TET2 expression could significantly rescue MPP+-stimulated SH-SY5Y cell damage and cell cycle arrest. Meanwhile, knockdown of Tet2 expression in the substantia nigra pars compacta of MPTP-induced PD mice resulted in attenuated MPTP-induced motor deficits and dopaminergic neuronal injury via p16 suppression. In this study, we demonstrated a critical function of TET2 in PD development via the CDKN2A activity-dependent epigenetic pathway, suggesting a potential new strategy for epigenetic therapy.
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Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Proteínas de Unión al ADN/genética , Neuronas Dopaminérgicas/metabolismo , Enfermedad de Parkinson/genética , Proteínas Proto-Oncogénicas/genética , 5-Metilcitosina/análogos & derivados , 5-Metilcitosina/metabolismo , Animales , Metilación de ADN/genética , Dioxigenasas , Modelos Animales de Enfermedad , Epigénesis Genética , Humanos , Masculino , Mesencéfalo/lesiones , Mesencéfalo/metabolismo , Ratones , Enfermedad de Parkinson/patologíaRESUMEN
Nanoparticles with unique properties have potential applications in food, medicine, pharmacology, and agriculture industries. Accordingly, many significant researches have been conducted to develop novel nanoparticles using chemical and biological techniques. This review focuses on the synthesis of selenium nanoparticles (SeNPs) using polysaccharides as templates. Various instrumental techniques being used to confirm the formation of polysaccharide-SeNPs conjugates and characterize the properties of nanoparticles are also introduced. Finally, the biological activities of the synthesized SeNPs and the influence of structural factors of polysaccharides on the property of synthetic nanocomposites are highlighted. In general, the polysaccharides functionalized SeNPs can be easily obtained using sodium selenite as precursor and ascorbic acid as reductant. The final products having different particle size, morphology, and selenium content exhibit abundant physiological activities. Structural factors of polysacchairdes involving molecular weights, substitution of functional groups, and chain conformation play determinant roles on the properties of nanocomposites, resulting in different biological performances. The review on the achievements and current status of polysaccharides conjugated SeNPs provides insights into this exciting research topic for further studies in the future.
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Nanopartículas , Selenio , Tamaño de la Partícula , PolisacáridosRESUMEN
OBJECTIVE: To explore the procedure of selective internal pudendal arteriography (IPA) and its application in the diagnosis of arteriogenic erectile dysfunction (AED). METHODS: We performed selective IPA for 62 patients highly suspected of AED with abnormal nocturnal penile tumescence (NPT) and peak systolic velocity (PSV) of the penile cavernosal artery < 25 ml/s. Using digital subtraction angiography, we assessed the stenosis of the main internal pudendal artery and measured the lengths of the dorsal penile arteries and cavernosal arteries. RESULTS: Of the total number of patients, 21 were found with normal internal pudendal arteries, dorsal penile arteries and cavernosal arteries, 7 with abnormal pudendal arteries and atherosclerotic lesions, 37 with inadequately visualized dorsal penile arteries and/or cavernosal arteries, and 3 with both abnormal pundendal and dorsal penile arteries or inadequately visualized cavernosal arteries. No complications were observed except for 3 cases of subcutaneous hematoma at the puncture site. CONCLUSIONS: Selective IPA can display the morphological features of internal pudendal, dorsal penile and cavernosal arteries and help to localize arterial lesions and evaluate blood supply in the penile artery. Therefore, it is a safe and reliable method for the diagnosis of AED.
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Angiografía , Disfunción Eréctil/diagnóstico , Impotencia Vasculogénica/diagnóstico , Pene/irrigación sanguínea , Arterias , Humanos , Masculino , Erección Peniana , Pene/fisiopatologíaRESUMEN
BACKGROUND: The adoption of laparoscopic techniques for living donor major hepatectomy has been controversial issue. The aim of this study is to present the preliminary experience of laparoscopic right hepatectomy in China. METHODS: All the donors receiving right hepatectomy for adult-to-adult living donor liver transplantation (LDLT) were divided into three groups: pure laparoscopic right hepatectomy (PLRH) group, hand-assisted right hepatectomy (HARH) group and open right hepatectomy (ORH) group. We compared the perioperative data and surgical outcomes of donors and recipients among three groups. RESULTS: From November 2001 to May 2017, 295 donors have received right hepatectomy for LDLT in our center. Among them, 7 donors received PLRH, 26 donors received HARH and 262 donors received ORH. The operation time of PLRH group (509.3 ± 98.9 min) was longer than that of the HARH group (451.6 ± 89.7 min) and the ORH group (418.4 ± 81.1 min, p = 0.003). The blood loss was the least in the PLRH group (378.6 ± 177.1 mL), compared with that in the HARH group (617.3 ± 240.4 mL) and that in the ORH group (798.6 ± 483.7 mL, p = 0.0013). The postoperative hospital stay was shorter in the PLRH group (7, 7-10 days) than that in the HATH group (8.5, 7.5-12 days) and ORH group (11, 9-14 days; p = 0.001). Only one donor had pleural effusion (Grade I) and another one experienced pulmonary infection (Grade II). One recipient (14.3%) in the PLRH group occurred hepatic venous stenosis. CONCLUSIONS: Laparoscopic approaches for right hepatectomy contribute to less blood loss, better cosmetic satisfaction, less severe complications, and faster rehabilitation. PLRH is a safe and feasible procedure, which must be performed in highly specialized centers with expertise of both LDLT and laparoscopic hepatectomy, and requires a hybrid-to-pure stepwise development.
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Hepatectomía , Laparoscopía , Trasplante de Hígado/métodos , Donadores Vivos , Recolección de Tejidos y Órganos/métodos , Adulto , China , Estudios de Factibilidad , Femenino , Hepatectomía/efectos adversos , Hepatectomía/métodos , Humanos , Laparoscopía/efectos adversos , Laparoscopía/métodos , Tiempo de Internación , Masculino , Tempo Operativo , Evaluación de Procesos y Resultados en Atención de SaludRESUMEN
OBJECTIVE: To investigate the clinical effects of circumcision by surgical plane positioning with a disposable circumcision suture device in the treatment of phimosis and redundant prepuce. METHODS: From September 2016 to June 2017, we treated 250 patients with phimosis or redundant prepuce, 127 by conventional circumcision (the control group) and the other 123 by surgical plane positioning with a disposable circumcision suture device (the observation group). We compared the operation time, intra-operative bleeding, preputial frenulum alignment, postoperative ecchymosis, and postoperative penile appearance between the two groups of patients. RESULTS: Compared with the controls, the patients in the observation group showed significantly longer operation time (ï¼»4.48 ± 1.18ï¼½ vs ï¼»7.17 ± 1.42ï¼½ min, P<0.05), lower rates of intra-operative frenulum bleeding (15.0% ï¼»19/127ï¼½ vs 4.1% ï¼»5/123ï¼½, P<0.05) and frenulum misalignment (26.8% ï¼»34/127ï¼½ vs 0.8% ï¼»1/123ï¼½, P<0.05), higher incidence of postoperative ecchymosis (41.7% ï¼»53/127ï¼½ vs 21.1% ï¼»26/123ï¼½, P<0.05), and higher satisfaction of the patients with the postoperative penile appearance (92.9% ï¼»18/127ï¼½ vs 98.4% ï¼»121/123ï¼½, P<0.05). However, no statistically significant difference was found between the control and observation groups in intra-operative non-frenulum bleeding (4.7% ï¼»6/127ï¼½ vs 1.6% ï¼»2/123ï¼½, P = 0.164). CONCLUSIONS: Circumcision by surgical plane positioning with a disposable circumcision suture device can effectively avoid preputial frenulum misalignment, reduce intra-operative bleeding, and improve postoperative penile appearance.
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Circuncisión Masculina/instrumentación , Pene/anomalías , Pene/cirugía , Fimosis/cirugía , Técnicas de Sutura/instrumentación , Equipos Desechables , Equimosis/etiología , Prepucio , Humanos , Incidencia , Masculino , Tempo Operativo , Satisfacción Personal , Complicaciones Posoperatorias/etiología , Periodo PosoperatorioAsunto(s)
Carcinoma Hepatocelular , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Neoplasias Hepáticas , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/prevención & control , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/prevención & controlRESUMEN
The habenula (Hb) is an evolutionarily conserved diencephalic structure in vertebrates. It is considered as an emotion center and plays critical roles in regulating diverse types of emotion-related behaviors, including anxiety, fear, reward, depression, and nicotine withdrawal. On the one hand, action selection- and emotion-relevant inputs are transferred to the Hb through the basal ganglia and limbic system, respectively. At the same time, sensory inputs of multiple modalities also converge on the Hb. Among them, the visual input of the Hb from the retina ganglion cells â thalamus pathway has been found to play a critical role in light-preference behavior of zebrafish. On the other hand, the Hb projects to two main neuromodulatory systems, the dopaminergic system and the serotoninergic system. As the Hb receives both internal emotion inputs and external sensory inputs and regulates the function of neuromodulatory systems, its functions are quite diverse and complex. In this review, we summarize the progress in both the structure and connection of the Hb and propose future study direction.
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Habénula/anatomía & histología , Habénula/fisiología , Animales , Ansiedad/fisiopatología , Miedo/fisiología , Humanos , Dolor/fisiopatología , Recompensa , Trastornos Relacionados con Sustancias/fisiopatologíaRESUMEN
Dopamine plays crucial roles in a broad spectrum of brain functions, and neural circuit mechanisms underlying dopaminergic regulation have been intensively studied in the past decade. As larval zebrafish have relatively simple and highly conserved dopaminergic systems, it can serve as an ideal vertebrate animal model to tackle this issue at a whole-brain scale. For this purpose, it is important to develop methods for monitoring endogenous dopamine release in intact larval zebrafish. Here, we developed a real-time method to monitor dopamine release at high spatiotemporal resolution in the brain of awake larval zebrafish using carbon fiber microelectrodes. As an example for application, we combined this method with genetic tools and in vivo calcium imaging and found that food extract can activate pretectal dopaminergic neurons, which in turn release dopamine at the visual center through their projection, providing a dopaminergic circuit mechanism for olfactory modulation of visual functions. Thus, our study demonstrates, for the first time, the utility of carbon fiber microelectrodes for monitoring sensory-evoked dopamine release in the brain of an awake small organism. SIGNIFICANCE STATEMENT: With carbon fiber microelectrodes, we have succeeded in monitoring sensory-evoked dopamine release in the brain of an awake small organism for the first time. By elucidating the circuitry origin of the dopamine release, we illustrated the potential application of this method in dissection of the neural circuitry mechanisms underlying dopaminergic neuromodulation.
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Dopamina/metabolismo , Olfato/fisiología , Vigilia/fisiología , Animales , Animales Modificados Genéticamente , Calcio/metabolismo , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/genética , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Neuronas Dopaminérgicas/fisiología , Electroquímica , Equidae , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Larva , Terapia por Láser , Microelectrodos , OptogenéticaRESUMEN
Plant breeding relies on creation of novel allelic combinations for desired traits. Identification and utilization of beneficial alleles, rare alleles and evolutionarily conserved genes in the germplasm (referred to as 'hidden' genes) provide an effective approach to achieve this goal. Here we show that a chemically induced null mutation in an evolutionarily conserved gene, FUWA, alters multiple important agronomic traits in rice, including panicle architecture, grain shape and grain weight. FUWA encodes an NHL domain-containing protein, with preferential expression in the root meristem, shoot apical meristem and inflorescences, where it restricts excessive cell division. Sequence analysis revealed that FUWA has undergone a bottleneck effect, and become fixed in landraces and modern cultivars during domestication and breeding. We further confirm a highly conserved role of FUWA homologs in determining panicle architecture and grain development in rice, maize and sorghum through genetic transformation. Strikingly, knockdown of the FUWA transcription level by RNA interference results in an erect panicle and increased grain size in both indica and japonica genetic backgrounds. This study illustrates an approach to create new germplasm with improved agronomic traits for crop breeding by tapping into evolutionary conserved genes.
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Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Mutación de Línea Germinal , Oryza/crecimiento & desarrollo , Oryza/genética , Proteínas de Plantas/genética , Datos de Secuencia Molecular , Sorghum/crecimiento & desarrollo , Zea mays/crecimiento & desarrolloRESUMEN
BACKGROUND: In living donor liver transplantation (LDLT), the hepatic hemodynamics plays important roles in graft regeneration, and the hepatic blood inflows are associated with graft size. However, the data of interplay between the hepatic arterial buffer response (HABR) and graft-to-recipient weight ratio (GRWR) in clinical LDLT are lacking. AIMS: To identify the effect of the HABR on the hepatic hemodynamics and recovery of graft function and to evaluate the safe lower limit of the GRWR in carefully selected recipients. METHODS: Portal venous and hepatic arterial blood flow was measured in recipients with ultrasonography, and the graft functional recovery, various complications, and survive states after LDLT were compared. RESULTS: In total, 246 consecutive patients underwent LDLT with right lobe grafts. In total, 26 had a GRWR < 0.7 % (A), 29 had a GRWR between 0.7 and 0.8 % (B), and 181 had a GRWR > 0.8 % (C). For small-for-size syndrome, there was no significant difference (P = 0.176). Graft survival rates at 1, 3, and 5 year were not different (P = 0.710). The portal vein flow and portal vein flow per 100 g graft weight peaks were significantly higher in the A. Hepatic arterial velocity and hepatic arterial flow decreased in all the three groups on postoperative day 1; however, the hepatic arterial flow per 100 g graft weight was close to healthy controls. CONCLUSIONS: HABR played important roles not only in the homeostasis of hepatic afferent blood supply but also in maintaining enough hepatic perfusion to the graft.
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Arteria Hepática/fisiología , Homeostasis/fisiología , Trasplante de Hígado , Hígado/irrigación sanguínea , Adulto , Anciano , Velocidad del Flujo Sanguíneo , Femenino , Supervivencia de Injerto , Hemodinámica , Humanos , Donadores Vivos , Masculino , Persona de Mediana Edad , Vena Porta/fisiología , Adulto JovenRESUMEN
Land plants have evolved increasingly complex regulatory modes of their flowering time (or heading date in crops). Rice (Oryza sativa L.) is a short-day plant that flowers more rapidly in short-day but delays under long-day conditions. Previous studies have shown that the CO-FT module initially identified in long-day plants (Arabidopsis) is evolutionary conserved in short-day plants (Hd1-Hd3a in rice). However, in rice, there is a unique Ehd1-dependent flowering pathway that is Hd1-independent. Here, we report isolation and characterization of a positive regulator of Ehd1, Early heading date 4 (Ehd4). ehd4 mutants showed a never flowering phenotype under natural long-day conditions. Map-based cloning revealed that Ehd4 encodes a novel CCCH-type zinc finger protein, which is localized to the nucleus and is able to bind to nucleic acids in vitro and transactivate transcription in yeast, suggesting that it likely functions as a transcriptional regulator. Ehd4 expression is most active in young leaves with a diurnal expression pattern similar to that of Ehd1 under both short-day and long-day conditions. We show that Ehd4 up-regulates the expression of the "florigen" genes Hd3a and RFT1 through Ehd1, but it acts independently of other known Ehd1 regulators. Strikingly, Ehd4 is highly conserved in the Oryza genus including wild and cultivated rice, but has no homologs in other species, suggesting that Ehd4 is originated along with the diversification of the Oryza genus from the grass family during evolution. We conclude that Ehd4 is a novel Oryza-genus-specific regulator of Ehd1, and it plays an essential role in photoperiodic control of flowering time in rice.
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Flores , Proteínas Nucleares/genética , Oryza , Fotoperiodo , Proteínas de Plantas , Transactivadores/genética , Arabidopsis/genética , Arabidopsis/metabolismo , Flores/genética , Flores/crecimiento & desarrollo , Regulación de la Expresión Génica de las Plantas , Oryza/genética , Oryza/crecimiento & desarrollo , Fenotipo , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Flowering time (i.e., heading date in crops) is an important ecological trait that determines growing seasons and regional adaptability of plants to specific natural environments. Rice (Oryza sativa L.) is a short-day plant that originated in the tropics. Increasing evidence suggests that the northward expansion of cultivated rice was accompanied by human selection of the heading date under noninductive long-day (LD) conditions. We report here the molecular cloning and characterization of DTH2 (for Days to heading on chromosome 2), a minor-effect quantitative trait locus that promotes heading under LD conditions. We show that DTH2 encodes a CONSTANS-like protein that promotes heading by inducing the florigen genes Heading date 3a and RICE FLOWERING LOCUS T 1, and it acts independently of the known floral integrators Heading date 1 and Early heading date 1. Moreover, association analysis and transgenic experiments identified two functional nucleotide polymorphisms in DTH2 that correlated with early heading and increased reproductive fitness under natural LD conditions in northern Asia. Our combined population genetics and network analyses suggest that DTH2 likely represents a target of human selection for adaptation to LD conditions during rice domestication and/or improvement, demonstrating an important role of minor-effect quantitative trait loci in crop adaptation and breeding.
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Productos Agrícolas/genética , Genes de Plantas , Oryza/genética , Polimorfismo Genético , Asia , Ritmo Circadiano , Clonación Molecular , Datos de Secuencia Molecular , Proteínas de Plantas/genética , Proteínas de Plantas/fisiología , Activación Transcripcional , Regulación hacia ArribaRESUMEN
Despite the wide application of general anesthetic drugs in clinic, it is still unclear how these drugs induce the state of general anesthesia. Larval zebrafish has emerged as an ideal model for dissecting the mechanism of neural systems due to the conserved and simple brain structure. In the present study, we established an anesthesia model from behavioral to electrophysiological levels using larval zebrafish for the first time. Bath application of etomidate, as a kind of intravenous anesthetic drugs, suppressed the spontaneous locomotion of zebrafish in a concentration-dependent manner. Consistently, in vivo fictive motor patterns of spinal motoneurons recorded extracellularly were significantly inhibited as well. Furthermore, using in vivo extracellular recording and whole-cell recording, we found that etomidate application suppressed local field potentials (LFP) of the brain and blocked visually evoked responses of optic tectal neurons. The study indicates that larval zebrafish can serve as an ideal vertebrate animal model for studying neural mechanisms underlying general anesthesia.
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Anestesia , Anestésicos Intravenosos , Animales , Etomidato , Larva , Locomoción , Neuronas Motoras , Técnicas de Placa-Clamp , Pez CebraRESUMEN
Blood-brain barrier (BBB) precisely controls the material exchange between the blood and brain tissue, and plays a critical role in the maintenance of brain microenvironment homeostasis. Brain microvascular endothelial cells connect tightly with each other and intertwine with surrounding pericytes and astrocytes to form the BBB. These cells regulate the development and function of the BBB through expressing tight and adherens junction proteins, transporters, and relevant signal molecules. Neurons and microglia can also regulate the function of BBB in physiological and pathological conditions. Recent studies indicate that the occurrence and progress of various neurological diseases are accompanied with structural and functional impairment of the BBB. Therefore, elucidation of the mechanisms underlying BBB development and function will further benefit our understanding of neurovascular interaction and provide an important theoretical basis for the treatment of neurological diseases. In this review, we briefly summarize the progress of BBB research.
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Barrera Hematoencefálica , Astrocitos , Encéfalo , Células Endoteliales , Homeostasis , Microglía , Neuronas , PericitosRESUMEN
DNA methylation and histone H3 Lys 9 dimethylation (H3K9me2) are important epigenetic repression marks for silencing transposons in heterochromatin and for regulating gene expression. However, the mechanistic relationship to other repressive marks, such as histone H3 Lys 27 trimethylation (H3K27me3) is unclear. FERTILIZATION-INDEPENDENT ENDOSPERM1 (FIE1) encodes an Esc-like core component of the Polycomb repressive complex 2, which is involved in H3K27me3-mediated gene repression. Here, we identify a gain-of-function epi-allele (Epi-df) of rice (Oryza sativa) FIE1; this allele causes a dwarf stature and various floral defects that are inherited in a dominant fashion. We found that Epi-df has no changes in nucleotide sequence but is hypomethylated in the 5' region of FIE1 and has reduced H3K9me2 and increased H3K4me3. In Epi-df, FIE1 was ectopically expressed and its imprinting was disrupted. FIE1 interacted with rice Enhancer of Zeste homologs, consistent with its role in H3K27me3 repression. Ectopic expression of FIE1 in Epi-df resulted in alteration of H3K27me3 levels in hundreds of genes. In summary, this work identifies an epi-allele involved in H3K27me3-mediated gene repression that itself is highly regulated by DNA methylation and histone H3K9me2, thereby shedding light on the link between DNA methylation and histone methylation, the two important epigenetic marks regulating rice development.
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Represión Epigenética/genética , Regulación de la Expresión Génica de las Plantas , Impresión Genómica/genética , Histonas/genética , Oryza/genética , Complejo Represivo Polycomb 2/genética , Alelos , Metilación de ADN , Flores/genética , Flores/crecimiento & desarrollo , Flores/metabolismo , Expresión Génica , Genes Dominantes , Heterocromatina/genética , Histonas/metabolismo , Lisina/metabolismo , Metilación , Mutación , Oryza/crecimiento & desarrollo , Oryza/metabolismo , Fenotipo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Complejo Represivo Polycomb 2/metabolismo , Plantones/genética , Plantones/crecimiento & desarrollo , Plantones/metabolismo , Técnicas del Sistema de Dos HíbridosRESUMEN
The brain blood vasculature consists of a highly ramified vessel network that is tailored to meet its physiological functions. How the brain vasculature is formed has long been fascinating biologists. Here we report that the developing vasculature in the zebrafish midbrain undergoes not only angiogenesis but also extensive vessel pruning, which is driven by changes in blood flow. This pruning process shapes the initial exuberant interconnected meshwork into a simplified architecture. Using in vivo long-term serial confocal imaging of the same zebrafish larvae during 1.5-7.5 d post-fertilization, we found that the early formed midbrain vasculature consisted of many vessel loops and higher order segments. Vessel pruning occurred preferentially at loop-forming segments via a process mainly involving lateral migration of endothelial cells (ECs) from pruned to unpruned segments rather than EC apoptosis, leading to gradual reduction in the vasculature complexity with development. Compared to unpruned ones, pruned segments exhibited a low and variable blood flow, which further decreased irreversibly prior to the onset of pruning. Local blockade of blood flow with micro-bead obstruction led to vessel pruning, whereas increasing blood flow by noradrenergic elevation of heartbeat impeded the pruning process. Furthermore, the occurrence of vessel pruning could be largely predicted by haemodynamics-based numerical simulation of vasculature refinement. Thus, changes of blood flow drive vessel pruning via lateral migration of ECs, leading to the simplification of the vasculature and possibly efficient routing of blood flow in the developing brain.