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Liquid-liquid phase separation promotes the formation of membraneless condensates that mediate diverse cellular functions, including autophagy of misfolded proteins. However, how phase separation participates in autophagy of dysfunctional mitochondria (mitophagy) remains obscure. We previously discovered that nuclear receptor Nur77 (also called TR3, NGFI-B, or NR4A1) translocates from the nucleus to mitochondria to mediate celastrol-induced mitophagy through interaction with p62/SQSTM1. Here, we show that the ubiquitinated mitochondrial Nur77 forms membraneless condensates capable of sequestrating damaged mitochondria by interacting with the UBA domain of p62/SQSTM1. However, tethering clustered mitochondria to the autophagy machinery requires an additional interaction mediated by the N-terminal intrinsically disordered region (IDR) of Nur77 and the N-terminal PB1 domain of p62/SQSTM1, which confers Nur77-p62/SQSTM1 condensates with the magnitude and liquidity. Our results demonstrate how composite multivalent interaction between Nur77 and p62/SQSTM1 coordinates to sequester damaged mitochondria and to connect targeted cargo mitochondria for autophagy, providing mechanistic insight into mitophagy.
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Mitocondrias/efectos de los fármacos , Mitofagia/efectos de los fármacos , Miembro 1 del Grupo A de la Subfamilia 4 de Receptores Nucleares/genética , Triterpenos Pentacíclicos/farmacología , Proteína Sequestosoma-1/genética , Animales , Complejo IV de Transporte de Electrones , Femenino , Regulación de la Expresión Génica , Genes Reporteros , Proteínas Fluorescentes Verdes , Células HeLa , Humanos , Proteínas Luminiscentes , Ratones , Ratones Endogámicos C57BL , Mitocondrias/genética , Mitocondrias/metabolismo , Mitofagia/genética , Miembro 1 del Grupo A de la Subfamilia 4 de Receptores Nucleares/metabolismo , Unión Proteica , Transporte de Proteínas , Proteínas Recombinantes de Fusión , Reología , Proteína Sequestosoma-1/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Proteína Fluorescente RojaRESUMEN
Apostasia ramifera S. C. Chen & K. Y. Lang 1986 is a Chinese endemic and endangered orchid. Here, we report the complete chloroplast (cp) genome sequence and the cp genome features of A. ramifera. The cp genome was 157,518 bp in length with a typical quadripartite structure, which was comprised of one large single-copy region (LSC, 86,353 bp) and one small single-copy region (SSC, 16,445 bp) separated by two inverted repeat regions (IRs, 27,360 bp). The cp genome encoded 133 genes, which included 87 protein-coding genes, 38 tRNAs and eight rRNAs. The average GC content of the genome is 35.8%. The phylogenetic analysis showed that A. ramifera was sister with A. wallichii and then nested in the other Apostasia species.
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Geodorum eulophioides Schltr., is a critically Endangered orchid (IUCN). In this study, we report the first complete chloroplast (cp) genome of G. eulophioides to provide the underlying information for genetic breeding and conservation studies of this species. The cp genome sequence of G. eulophioides is 149,466 bp in length, which contains one large single-copy region (LSC, 85,436 bp), one small single-copy region (SSC, 14,086 bp), and two inverted repeat regions (IRs, 24,972 bp). The cp genome encoded 177 genes, of which 106 were unique genes (78 protein-coding genes, 24 tRNAs, and 4 rRNAs). Phylogenetic analysis showed that G. eulophioides is closely related to the genera Eulophia.
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OBJECTIVE: To investigate the age distribution characteristics of intestinal segmented filamentous bacteria (SFB) in children and their relationship with intestinal mucosal immunity. METHODS: The fresh feces of 177 children and the ileocecal fluid of 47 children during colonoscopy were collected. The SFB was determined by real-time PCR. The concentration of secretory immunoglobulin A (sIgA) was determined by enzyme-linked immunosorbent assay. The numbers of interleukin 17A (IL-17A) cells and intraepithelial lymphocytes in the terminal ileum mucosa and the expression of transcription factors associated with the differentiation of T helper (Th) cells, T-box transcription factor (T-bet), forkhead box P3 (FOXP3), and retinoid-related orphan receptor gamma t (ROR-γt), were determined by immunohistochemistry. RESULTS: The positive rate of intestinal SFB in these children was 19.2% (34/177). Trend analysis showed that the positive rate of SFB was correlated with age: the rates for children aged 0-, 1-, 2-, 3-, 4-, 5-, 6-, and 7-15 years were 40%, 47%, 32%, 15%, 12%, 13%, 15% and 4% respectively (P<0.001). The concentration of sIgA in intestinal fluid was significantly higher in SFB-positive children (n=24) than in SFB-negative children (n=23) (P<0.01). The number of intraepithelial lymphocytes in the terminal ileum mucosa and the expression of T-bet, FOXP3, and ROR-γt were not significantly different between the SFB-positive group (n=12) and the SFB-negative group (n=11), but the number of IL-17A cells in the terminal ileum mucosa was significantly lower in the SFB-positive group than in the SFB-negative group (P<0.05). CONCLUSIONS: Intestinal SFB colonization in children is age-related, and the colonization rate is relatively high in children under 3 years old. In SFB-positive children, the secretion of intestinal sIgA is increased, while the number of IL-17A cells in the terminal ileum is reduced.
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Inmunidad Mucosa , Mucosa Intestinal , Adolescente , Distribución por Edad , Bacterias , Niño , HumanosRESUMEN
In wireless rechargeable sensor networks (WRSNs), there is a way to use mobile vehicles to charge node and collect data. It is a rational pattern to use two types of vehicles, one is for energy charging, and the other is for data collecting. These two types of vehicles, data collection vehicles (DCVs) and wireless charging vehicles (WCVs), are employed to achieve high efficiency in both data gathering and energy consumption. To handle the complex scheduling problem of multiple vehicles in large-scale networks, a twice-partition algorithm based on center points is proposed to divide the network into several parts. In addition, an anchor selection algorithm based on the tradeoff between neighbor amount and residual energy, named AS-NAE, is proposed to collect the zonal data. It can reduce the data transmission delay and the energy consumption for DCVs' movement in the zonal. Besides, we design an optimization function to achieve maximum data throughput by adjusting data rate and link rate of each node. Finally, the effectiveness of proposed algorithm is validated by numerical simulation results in WRSNs.
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OBJECTIVE: To investigate the effect of atopy on the expression of glucocorticoid receptors in children with bronchiolitis. METHODS: ELISA was used to measure the changes in the serum levels of glucocorticoid receptor α (GRα) and glucocorticoid receptor ß (GRß) in the bronchiolitis group (77 children, including 34 children with atopy) and pneumonia group (68 children). Thirty-eight children who were prepared to undergo surgeries for non-infectious diseases and had no atopy or family history of allergic diseases were enrolled as the control group. RESULTS: The bronchiolitis group and the pneumonia group had significant increases in the serum levels of GRα and GRß compared with the control group (P<0.01), and the bronchiolitis group had significant increases in these levels compared with the pneumonia group (P<0.01). Compared with the control group and the pneumonia group, the bronchiolitis group had a significant increase in the GRα/GRß ratio (P<0.01). Compared with the control group, the children with or without atopy in the bronchiolitis group had significant increases in the serum levels of GRα and GRß (P<0.01). The non-atopic children in the bronchiolitis group had a significant increase in the serum level of GRß compared with the atopic children (P<0.01). The atopic children in the bronchiolitis group had a significant increase in the GRα/GRß ratio compared with the control group and non-atopic children in the bronchiolitis group (P<0.01). CONCLUSIONS: Children with bronchiolitis have increased serum levels of GRα and GRß. The children with atopy have an increased GRα/GRß ratio, suggesting that the atopic children with bronchiolitis are highly sensitive to glucocorticoids.
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Bronquiolitis/sangre , Hipersensibilidad/sangre , Receptores de Glucocorticoides/sangre , Femenino , Humanos , Lactante , MasculinoRESUMEN
Acoustic communication is an important behavior in frog courtship. Male and female frogs of most species, except the concave-eared torrent frog Odorrana tormota, have largely similar audiograms. The large odorous frogs (Odorrana graminea) are sympatric with O. tormota, but have no ear canals. The difference in hearing between two sexes of the frog is unknown. We recorded auditory evoked near-field potentials and single-unit responses from the auditory midbrain (the torus semicircularis) to determine auditory frequency sensitivity and threshold. The results show that males have the upper frequency limit at 24 kHz and females have the upper limit at 16 kHz. The more sensitive frequency range is 3-15 kHz for males and 1-8 kHz for females. Males have the minimum threshold at 11 kHz (58 dB SPL), higher about 5 dB than that at 3 kHz for females. The best excitatory frequencies of single units are mostly between 3 and 5 kHz in females and at 7-8 kHz in males. The underlying mechanism of auditory sexual differences is discussed.