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1.
J Integr Plant Biol ; 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31965735

RESUMO

Large scale production of male sterile seeds can be achieved by introducing a fertility-restoration gene linked with a pollen-killer gene into a recessive male sterile mutant. We attempted to construct this system in rice by using a late-stage pollen-specific (LSP) promoter driving the expression of maize α-amylase gene ZM-AA1. To obtain such promoters in rice, we conducted comparative RNA-seq analysis of mature pollen with premeiosis anther, and compared with the transcriptomic data of various tissues in Rice Expression Database, resulting in 269 candidate LSP genes. Initial test of 9 LSP genes showed that only the most active OsLSP3 promoter could drive ZM-AA1 to disrupt pollen. We then analyzed additional 22 LSP genes and found 12 genes stronger than OsLSP3 in late stage anthers. The promoters of OsLSP5 and OsLSP6 showing higher expression than OsLSP3 at stages 11 and 12 could drive ZM-AA1 to inactivate pollen, while the promoter of OsLSP4 showing higher expression at stage 12 only could not drive ZM-AA1 to disrupt pollen, suggesting strong promoter activity at stage 11 was critical for pollen inactivation. The strong pollen-specific promoters identified in this study provided valuable tools for genetic engineering of rice male sterile system for hybrid rice production. This article is protected by copyright. All rights reserved.

2.
J Biomed Nanotechnol ; 16(1): 65-75, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31996286

RESUMO

Objective: To investigate the innovative application of gold nanorods combined with a laser in posttraumatic osteoarthritis (PTOA) modeling and to discuss the possible mechanisms. Methods: Electron microscopy was used to characterize the gold nanorods. Cell counting kit-8 assay and enzyme-linked immunosorbent assay were used to evaluate cell proliferation and cytotoxicity. An infrared spectroscopy (IR) thermal camera was used to monitor the temperature changes of gold nanorods with or without the laser treatment. Furthermore, western blotting was used to evaluate the expression of related proteins in response to the indicated treatments. Finally, microcomputed tomography (micro-CT) was used to determine the structural changes in knee joints. Changes in the cartilage and various other tissues were assessed by histological examination. Results: The characteristics and biosafety of the gold nanorods were confirmed. Our study showed that gold nanorods combined with the laser inhibited cell viability, but the gold nanorods or laser alone did not affect cell viability. Moreover, the effect on cell viability was time dependent. Similarly, only gold nanorods with the laser caused the apoptosis of cartilage cells and the upregulation of IL-1ß, MMP-13 and Comp. We injected gold nanorods and used laser irradiation to develop an osteoarthritis (OA) model. The temperature of the knees in the OA model increased to 60 °C and then remained at approximately 60 °C. As the time increased, gold nanorods combined with the laser caused more injuries and degeneration in the knee joints. Conclusion: OA models that were established using gold nanorods and a laser were precise, controllable, observable and stable and could be an excellent premise for investigating the exact mechanisms underlying OA and exploring new treatment strategies.


Assuntos
Nanotubos , Osteoartrite , Cartilagem , Ouro , Humanos , Microtomografia por Raio-X
3.
J Exp Bot ; 71(1): 204-218, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31587067

RESUMO

Meiotic recombination plays a central role in maintaining genome stability and increasing genetic diversity. Although meiotic progression and core components are widely conserved across kingdoms, significant differences remain among species. Here we identify a rice gene ABERRANT GAMETOGENESIS 1 (AGG1) that controls both male and female gametogenesis. Cytological and immunostaining analysis showed that in the osagg1 mutant the early recombination processes and synapsis occurred normally, but the chiasma number was dramatically reduced. Moreover, OsAGG1 was found to interact with ZMM proteins OsHEI10, OsZIP4, and OsMSH5. These results suggested that OsAGG1 plays an important role in crossover formation. Phylogenetic analysis showed that OsAGG1 is a plant-specific protein with a highly conserved N-terminal region. Further genetic and protein interaction analyses revealed that the conserved N-terminus was essential for the function of the OsAGG1 protein. Overall, our work demonstrates that OsAGG1 is a novel and critical component in rice meiotic crossover formation, expanding our understanding of meiotic progression. This study identified a plant-specific gene ABERRANT GAMETOGENESIS 1 that is required for meiotic crossover formation in rice. The conserved N-terminus of the AGG1 protein was found to be essential for its function.

5.
Nanomaterials (Basel) ; 9(12)2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31818009

RESUMO

Graphene (GR) was used to blend with eugenol polysiloxane-polycarbonate (Si-PC) copolymer to prepare a Si-PC/GR nanocomposite via a solution blending method and the impact of graphene on the properties of Si-PC/GR nanocomposite was investigated. The morphology and structure of the Si-PC/GR nanocomposite were characterized. Combining morphology and property analysis, the result showed that when the graphene dispersed uniformly in the Si-PC matrix, the mechanical properties, thermostability and barrier property of Si-PC/GR nanocomposite were enhanced. Compared with Si-PC copolymer, the pyrolytic temperature of Si-PC/2.5%GR nanocomposite at 5% weight loss was 434.3 °C, which was 20.6 °C higher than Si-PC copolymer; and the oxygen barrier value of Si-PC/1.5%GR nanocomposite decreased to 160.2 cm3/m2 24 h 0.1 MPa, which was 53.2 less than pure Si-PC. The mechanical properties of Si-PC/GR nanocomposite were enhanced with an appropriate additive amount of graphene. The hydrophobicity also had been enhanced at the meantime.

6.
J Integr Plant Biol ; 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31833176

RESUMO

Pollen grains are covered by exine that protects the pollen from stress and facilitates pollination. Here we isolated a male sterile mutant s13283 in rice exhibiting aborted pollen with abnormal exine and defective aperture. The mutant gene encodes a novel plasma membrane-localized legume-lectin receptor kinase that we named OsLecRK-S.7. OsLecRK-S.7 was expressed at different levels in all tested tissues and throughout anther development. In vitro kinase assay showed OsLecRK-S.7 capable of autophosporylation. Mutation in s13283 (E560K) and mutation of the conserved ATP binding site (K418E) both knocked out the kinase activity. Mass spectrometry showed Thr376 , Ser378 , Thr386 , Thr403 , and Thr657 to be the autophosphorylation sites. Mutation of individual autophosphorylation site affected the in vitro kinase activity to different degrees, but did not abolish the gene function in fertility complementation. oslecrk-s.7 mutant plant overexpressing OsLecRK-S.7 recovered male fertility but showed severe growth retardation with reduced number of tillers, and these phenotypes were abolished by E560K or K418E mutation. The results indicated that OsLecRK-S.7 was a key regulator of pollen development. This article is protected by copyright. All rights reserved.

7.
Epigenetics Chromatin ; 12(1): 76, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31856916

RESUMO

BACKGROUND: Neural tube defects (NTDs) are severe, common birth defects that result from failure of normal neural tube closure during early embryogenesis. Accumulating strong evidence indicates that genetic factors contribute to NTDs etiology, among them, HOX genes play a key role in neural tube closure. Although abnormal HOX gene expression can lead to NTDs, the underlying pathological mechanisms have not fully been understood. METHOD: We detected that H3K27me3 and expression of the Hox genes in a retinoic acid (RA) induced mouse NTDs model on E8.5, E9.5 and E10.5 using RNA-sequencing and chromatin immunoprecipitation sequencing assays. Furthermore, we quantified 10 Hox genes using NanoString nCounter in brain tissue of fetuses with 39 NTDs patients including anencephaly, spina bifida, hydrocephaly and encephalocele. RESULTS: Here, our results showed differential expression in 26 genes with a > 20-fold change in the level of expression, including 10 upregulated Hox genes. RT-qPCR revealed that these 10 Hox genes were all upregulated in RA-induced mouse NTDs as well as RA-treated embryonic stem cells (ESCs). Using ChIP-seq assays, we demonstrate that a decrease in H3K27me3 level upregulates the expression of Hox cluster A-D in RA-induced mouse NTDs model on E10.5. Interestingly, RA treatment led to attenuation of H3K27me3 due to cooperate between UTX and Suz12, affecting Hox gene regulation. Further analysis, in human anencephaly cases, upregulation of 10 HOX genes was observed, along with aberrant levels of H3K27me3. Notably, HOXB4, HOXC4 and HOXD1 expression was negatively correlated with H3K27me3 levels. CONCLUSION: Our results indicate that abnormal HOX gene expression induced by aberrant H3K27me3 levels may be a risk factor for NTDs and highlight the need for further analysis of genome-wide epigenetic modification in NTDs.

8.
Anal Bioanal Chem ; 411(30): 8073-8080, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31761955

RESUMO

Vitamin A deficiency (VAD) is a major micronutrient deficiency in children. Although plasma and serum retinol levels are proposed as the key indicators of VAD, collecting and transporting plasma and serum are difficult and inconvenient in field studies. Dried blood spot (DBS) retinol has been used as an alternative to plasma retinol in several epidemiological and clinical studies. A limitation of methods that use DBS retinol is the instability and apparent loss of retinol in DBSs. Therefore, an accurate, reliable method for stabilizing retinol in DBSs and quantifying and comparing DBS retinol concentrations with equivalent plasma retinol levels is required. In this study, antioxidants on paper combined with vacuum treatment were found to greatly increase the stability of DBS retinol during 120 min of air drying and 30 days of room-temperature storage. A surrogate matrix of whole blood prepared using a mixture of human erythrocytes and 2% BSA in PBS was firstly used in DBS retinol determination based on the fact that retinol is excluded from erythrocytes. The method was linear in the concentration range of 0.04-300 µg/mL. Both the between-run (n = 5) and within-run (n = 6) precision (relative standard deviations, RSD%) were below 8.42%. The spiked recoveries at 3 concentrations ranged from 86.48 to 98.13%. The internal standard (IS)-normalized matrix factor (MF) was 99.72% with a RSD% of 10.50% (n = 3). The accuracy was calibrated using two National Institute of Standards and Technology (NIST) serum-generated calibrants at concentrations of 0.1962 and 0.3948 g/mL, and relative errors (RE% values) of 0.07% and 4.95% were found, respectively. A simple calibration model was first developed to convert DBS retinol concentration to the equivalent plasma retinol concentration, thereby enabling comparisons with clinical reference ranges and with studies using serum or plasma samples. Graphical abstract.


Assuntos
Cromatografia Líquida/métodos , Teste em Amostras de Sangue Seco , Espectrometria de Massas em Tandem/métodos , Vitamina A/sangue , Calibragem , Humanos , Reprodutibilidade dos Testes
9.
Epigenetics Chromatin ; 12(1): 69, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31722724

RESUMO

BACKGROUND: Neural tube defects (NTDs) are common congenital malformations resulting in failure of the neural tube closure during early embryonic development. Although it is known that maternal folate deficiency increases the risk of NTDs, the mechanism remains elusive. RESULTS: Herein, we report that histone H2A monoubiquitination (H2AK119ub1) plays a role in neural tube closure. We found that the folate antagonist methotrexate induced H2AK119ub1 in mouse embryonic stem cells. We demonstrated that an increase in H2AK119ub1 downregulated expression of the neural tube closure-related genes Cdx2, Nes, Pax6, and Gata4 in mouse embryonic stem cells under folate deficiency conditions. We also determined that the E3 ligase Mdm2 was responsible for the methotrexate-induced increase in H2AK119ub1 and downregulation of neural tube closure-related genes. Surprisingly, we found that Mdm2 is required for MTX-induced H2A ubiquitination and is recruited to the sites of DSB, which is dependent on DNA damage signaling kinase ATM. Furthermore, folic acid supplementation restored H2AK119ub1 binding to neural tube closure-related genes. Downregulation of these genes was also observed in both brain tissue of mouse and human NTD cases, and high levels of H2AK119ub1 were found in the corresponding NTDs samples with their maternal serum folate under low levels. Pearson correlation analysis showed a significant negative correlation between expression of the neural precursor genes and H2AK119ub1. CONCLUSION: Our results indicate that folate deficiency contributes to the onset of NTDs by altering H2AK119ub1 and subsequently affecting expression of neural tube closure-related genes. This may be a potential risk factor for NTDs in response to folate deficiency.

10.
J Transl Med ; 17(1): 335, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31585536

RESUMO

BACKGROUND: The P38 mitogen-activated protein kinase (MAPK) pathway plays an essential role in CVB3-induced diseases. We previously demonstrated microRNA-21 has potential inhibitory effect on the MAP2K3 which locates upstream of P38 MAPK and was upregulated in mouse hearts upon CVB3 infection. However, the effect and underlying mechanism of miRNA-21 on CVB3 infection remain unclear. METHODS: We detected continuous changes of cellular miRNA-21 and P38 MAPK proteins expression profiling post CVB3 infection in vitro within 12 h. P38 MAPK signaling was inhibited by the specific inhibitor, small interfering RNA and miRNA-21 mimic in vitro, CVB3 replication, cell apoptosis rate and proliferation were detected. Viral load in the mice heart, cardiomyocyte apoptosis rate and histological of the heart were also detected in the mice model of viral myocarditis pretreated with miRNA-21-lentivirus. RESULTS: We observed significant upregulation of miRNA-21 expression followed by suppression of the MAP2K3/P38 MAPK signaling in CVB3-infected Hela cells. The inactivation of the MAP2K3/P38 MAPK signaling by P38 MAPK specific inhibitor, small interfering RNA against MAP2K3, or miRNA-21 overexpression significantly inhibited viral progeny release from CVB3-infected cells. Mechanistically, when compared with control miRNA, miRNA-21 showed no effect on capsid protein VP1 expression and viral load within host cells, while significantly reversing CVB3-induced caspase-3 activation and cell apoptosis rate, further promoting proliferation of infected cells, which indicates the inhibitory effect of miRNA-21 on CVB3 progeny release. In the in vivo study, when compared with control miRNA, miRNA-21 pretreatment remarkably inactivated the MAP2K3/P38 MAPK signaling in mice and protected them against CVB3 infection as evidenced by significantly alleviated cell apoptosis rate, reduced viral titers, necrosis in the heart as well as by remarkably prolonged survival time. CONCLUSIONS: miRNA-21 were reverse correlated with P38 MAPK activation post CVB3 infection, miRNA-21 overexpression significantly inhibited viral progeny release and decreased myocytes apoptosis rate in vitro and in vivo, suggesting that miRNA-21 may serve as a potential therapeutic agent against CVB3 infection through targeting the MAP2K3/P38 MAPK signaling.

11.
Cell Metab ; 30(4): 675-688.e7, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31543403

RESUMO

The underlying etiology of nonalcoholic fatty liver disease (NAFLD) is believed to be quite varied. Changes in the gut microbiota have been investigated and are believed to contribute to at least some cases of the disease, though a causal relationship remains unclear. Here, we show that high-alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) is associated with up to 60% of individuals with NAFLD in a Chinese cohort. Transfer of clinical isolates of HiAlc Kpn by oral gavage into mice induced NAFLD. Likewise, fecal microbiota transplant (FMT) into mice using a HiAlc-Kpn-strain-containing microbiota isolated from an individual with NASH induced NAFLD. However, selective elimination of the HiAlc Kpn strain before FMT prevented NAFLD in the recipient mice. These results suggest that at least in some cases of NAFLD an alteration in the gut microbiome drives the condition due to excess endogenous alcohol production.

12.
Int J Endocrinol ; 2019: 9145452, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31467530

RESUMO

Background: Genome-wide association studies have found an obesity-related single-nucleotide polymorphism rs10938397 near the glucosamine-6-phosphate deaminase 2 gene (GNPDA2) encoding, an enzyme that catalyzes the deamination of the glucosamine-6-phosphate involved in the hexosamine signaling pathway, but the molecular mechanisms underlying the missing link between GNPDA2 and obesity remain elusive. Methods: As obesity is accompanied by an increase in the size and the number of adipocytes, the present study investigates the possible mechanism of the GNPDA2 in adipogenesis using GeneChip® Human Transcriptome Array 2.0 in human adipose-derived mesenchymal stem cells. Results: We found that overexpression of GNPDA2 enhanced accumulation of lipid droplets, and knocking down the gene decreased accumulation of lipid droplets. GO term enrichment analysis indicated that most differentially expressed genes (DEGs) affected by deficiency of GNPDA2 have functions to lipid and glucose metabolism. Further KEGG enrichment analysis showed that the greatest proportion of DEGs are involved in thermogenesis, peroxisome proliferator-activated receptor (PPAR) signaling pathway, carbon metabolism, and fatty acid metabolism including fatty acid degradation, elongation, and biosynthesis. Conclusion: These findings suggest that GNPDA2 may be a critical gene for lipid and glucose metabolism, and the expression level of GNPDA2 alters the transcriptome profile of human adipose-derived mesenchymal stem cells.

13.
Cell Death Dis ; 10(8): 551, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31320612

RESUMO

Retinoic acid (RA), an active derivative of vitamin A, is critical for the neural system development. During the neural development, the RA/RA receptor (RAR) pathway suppresses BMP signaling-mediated proliferation and differentiation of neural progenitor cells. However, how the stability of RAR is regulated during neural system development and how BMP pathway genes expression in neural tissue from human fetuses affected with neural tube defects (NTDs) remain elusive. Here, we report that FBXO30 acts as an E3 ubiquitin ligase and targets RARγ for ubiquitination and proteasomal degradation. In this way, FBXO30 positively regulates BMP signaling in mammalian cells. Moreover, RA treatment leads to suppression of BMP signaling by reducing the level of FBXO30 in mammalian cells and in mouse embryos with NTDs. In samples from human NTDs with high levels of retinol, downregulation of BMP target genes was observed, along with aberrant FBXO30 levels. Collectively, our results demonstrate that RARγ levels are controlled by FBXO30-mediated ubiquitination and that FBXO30 is a key regulator of BMP signaling. Furthermore, we suggest a novel mechanism by which high-retinol levels affect the level of FBXO30, which antagonizes BMP signaling during early stage development.

14.
IEEE Trans Image Process ; 28(12): 6116-6125, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31265400

RESUMO

Humans are capable of learning a new fine-grained concept with very little supervision, e.g., few exemplary images for a species of bird, yet our best deep learning systems need hundreds or thousands of labeled examples. In this paper, we try to reduce this gap by studying the fine-grained image recognition problem in a challenging few-shot learning setting, termed few-shot fine-grained recognition (FSFG). The task of FSFG requires the learning systems to build classifiers for the novel fine-grained categories from few examples (only one or less than five). To solve this problem, we propose an end-to-end trainable deep network, which is inspired by the state-of-the-art fine-grained recognition model and is tailored for the FSFG task. Specifically, our network consists of a bilinear feature learning module and a classifier mapping module: while the former encodes the discriminative information of an exemplar image into a feature vector, the latter maps the intermediate feature into the decision boundary of the novel category. The key novelty of our model is a "piecewise mappings" function in the classifier mapping module, which generates the decision boundary via learning a set of more attainable sub-classifiers in a more parameter-economic way. We learn the exemplar-to-classifier mapping based on an auxiliary dataset in a meta-learning fashion, which is expected to be able to generalize to novel categories. By conducting comprehensive experiments on three fine-grained datasets, we demonstrate that the proposed method achieves superior performance over the competing baselines.

15.
BMC Cancer ; 19(1): 405, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31035970

RESUMO

BACKGROUND: Wilms' tumor is also called nephroblastoma and is the most common pediatric renal cancer. Several genetic and epigenetic factors have been found to account for the development of Wilms' tumor. MiRNAs play important roles in this tumorigenic process. In the present study, we aimed to investigate the role of miR-140-5p in nephroblastoma by identifying its targets, as well as its underlying molecular mechanism of action. METHODS: The miRNA expression profile of nephroblastoma samples was investigated and the targets of miR-140-5p were predicted and validated using the miRNA luciferase reporter method. Moreover, the roles of miR-140-5p in regulating nephroblastoma cell proliferation, migration and cell cycle were analyzed by the CCK8, migration and flow cytometry assays, respectively. The downstream protein of the direct target of miR-140-5p was also identified. RESULTS: miR-140-5p was downregulated in Wilms' tumor tissues, whereas in the nephroblastoma cell lines G401 and WT-CLS1 that exhibited high levels of miRNA-140-5p, inhibition of cellular proliferation and metastasis were noted as well as cell cycle arrest at the G1/S phase. TGFBRI and IGF1R were identified as direct target genes for miRNA-140-5p. In addition, SMAD2/3 and p-AKT were regulated by TGFBRI and IGF1R separately and participated in the miRNA-140-5p regulatory network. Ectopic expression of TGFBR1 and IGF-1R could abrogate the inhibitory effect of miR-140-5p. CONCLUSION: We demonstrated that miRNA-140-5p participates in the progression of Wilms' tumor by targeting the TGFBRI/SMAD2/3 and the IGF-1R/AKT signaling pathways.


Assuntos
Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Transdução de Sinais/genética , Tumor de Wilms/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Criança , Progressão da Doença , Regulação para Baixo , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes/genética , Humanos , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I/genética , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Receptores de Somatomedina/genética , Receptores de Somatomedina/metabolismo , Proteína Smad2/genética , Proteína Smad2/metabolismo , Proteína Smad3/genética , Proteína Smad3/metabolismo , Tumor de Wilms/metabolismo , Tumor de Wilms/patologia
16.
Epigenetics Chromatin ; 12(1): 22, 2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30992047

RESUMO

BACKGROUND: Neural tube defects (NTDs) are common birth defects involving the central nervous system. Recent studies on the etiology of human NTDs have raised the possibility that epigenetic regulation could be involved in determining susceptibility to them. RESULTS: Here, we show that the H2AK119ub1 E3 ligase CUL4B is required for the activation of retinoic acid (RA)-inducible developmentally critical homeobox (HOX) genes in NT2/D1 embryonal carcinoma cells. RA treatment led to attenuation of H2AK119ub1 due to decrease in CUL4B, further affecting HOX gene regulation. Furthermore, we found that CUL4B interacted directly with RORγ and negatively regulated its transcriptional activity. Interestingly, knockdown of RORγ decreased the expression of HOX genes along with increased H2AK119ub1 occupancy levels, at HOX gene sites in N2/D1 cells. In addition, upregulation of HOX genes was observed along with lower levels of CUL4B-mediated H2AK119ub1 in both mouse and human anencephaly NTD cases. Notably, the expression of HOXA10 genes was negatively correlated with CUL4B levels in human anencephaly NTD cases. CONCLUSIONS: Our results indicate that abnormal HOX gene expression induced by aberrant CUL4B-mediated H2AK119ub1 levels may be a risk factor for NTDs, and highlight the need for further analysis of genome-wide epigenetic modifications in NTDs.


Assuntos
Anencefalia/genética , Proteínas Culina/genética , Código das Histonas , Histonas/metabolismo , Proteínas de Homeodomínio/genética , Ubiquitinação , Animais , Linhagem Celular , Linhagem Celular Tumoral , Proteínas Culina/metabolismo , Histonas/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Ligação Proteica
17.
Biochem Biophys Res Commun ; 511(4): 855-861, 2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30850164

RESUMO

Adipogenesis is one of the key processes during obesity development. Better understanding of this process could advance our knowledge on obesity and its treatment. Transcription factors (TFs) are master regulators during adipogenesis, however, a system-wide analysis of TFs dynamic proteome during adipogenesis is lacking. Here, we profiled 472 TFs and systematically elucidated their roles during the first 7 days of adipogenesis of human adipose-derived stem cells (hADSCs) on proteome scale. We identified two main and four sub-phases during adipogenesis. The commitment phase (0 h-8 h) mainly mediated stem cell proliferation, differentiation and chromatin remodeling, in which proteins of SWI/SNF family are the key centroid nodes. The determination phase (1D-7D) predominately regulated fat cell differentiation and response to lipid and oxygen, which could be associated with terminal differentiation of adipocyte and responsible for maturation. PPARγ, CREB1 and MYC are the centroid nodes of this phase. Remarkably, we identified and verified three TFs (BATF3, MAFF and MXD4) as novel regulators of adipogenesis, whose over-expression could inhibit adipogenesis of hADSCs in vitro. Overall, our study provided a valuable TFs resource to understand the complex process of adipogenesis.


Assuntos
Adipócitos/citologia , Adipogenia , Tecido Adiposo/citologia , Células-Tronco/citologia , Fatores de Transcrição/genética , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Proliferação de Células , Células Cultivadas , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Obesidade/genética , Proteômica , Células-Tronco/metabolismo
18.
Pediatr Res ; 85(6): 816-821, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30712057

RESUMO

BACKGROUND: Approximately 10-20% of children with idiopathic nephrotic syndrome (NS) fail to respond to steroid therapy. NS is divided into steroid-sensitive NS (SSNS) and steroid-resistant NS (SRNS). Over 45 recessive and dominant genes have been found to be associated with SRNS and/or focal segmental glomerulosclerosis (FSGS). METHODS: Targeted sequencing of 339 candidate genes, expressed in glomerular filtration barrier or located in the signaling pathway of podocyte function, were sequenced by NGS in a cohort of total 89 Chinese Han children (29 sporadic SRNS, 33 sporadic SSNS, and 27 healthy). RESULTS: Two variants (WT1 p.R441X and NPHS2 p.G149V) were screened out as pathogenic mutations and 14 variants were likely pathogenic. Mutations of KIRREL2 (SRNS vs SSNS: 24.1% vs 3.0%, adjusted OR = 10.11, 95% CI: 1.56-198.66, P = 0.039) were significantly associated with the risk of pediatric sporadic SRNS. Besides, three pathogenic or likely pathogenic variants were identified in HP gene. CONCLUSION: Two pathogenic mutations and 14 likely pathogenic mutations were discovered through targeted sequencing of 339 candidate genes. Two genes, HP and KIRREL2, as candidate genes, were first proposed to be associated with the risk of pediatric sporadic SRNS.

19.
J Cell Physiol ; 234(6): 9475-9485, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30362570

RESUMO

Macrophages and many chemokines are closely associated with the adipogenic differentiation of bone marrow mesenchymal stem cells (MSCs), but their roles in adipogenesis and the underlying mechanisms are not fully understood. Here, we first investigated the influence of macrophages on the differentiation of MSCs in vitro. We found that RAW246.7 macrophages cocultured with MSCs strongly blocked the differentiation progress and inhibited the expression of C-X-C motif chemokine ligand 1 (CXCL1) during adipogenesis. Coculture with MSCs mainly induced macrophages toward M2 polarization. In addition, the expression of CXCL1 and its receptor, C-X-C chemokine receptor type 2, CXCR2 are high during adipogenic differentiation of MSCs and not in mature adipocytes. Although CXCL1 had no effect on adipogenesis, treatment with a specific CXCR2 inhibitor, SB225002, hampered the adipogenic differentiation of MSCs. Blocking CXCR2 decreased p38 and Elk1 phosphorylation but increased the extracellular signal-regulated kinase (ERK) phosphorylation at the initial stage of adipogenesis, which suppressed the phosphorylation of p38/ERK-Elk1 at the late stage. Inhibition of ERK had similar effects on adipogenesis and Elk1 phosphorylation. Our data suggest that MSCs interact with macrophages during adipogenic differentiation. CXCR2 regulates the adipogenic differentiation of MSCs by altering the activation of the p38/ERK-Elk1 signaling pathway.

20.
IEEE Trans Pattern Anal Mach Intell ; 41(10): 2525-2538, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30040622

RESUMO

This paper aims at accelerating and compressing deep neural networks to deploy CNN models into small devices like mobile phones or embedded gadgets. We focus on filter level pruning, i.e., the whole filter will be discarded if it is less important. An effective and unified framework, ThiNet (stands for "Thin Net"), is proposed in this paper. We formally establish filter pruning as an optimization problem, and reveal that we need to prune filters based on statistics computed from its next layer, not the current layer, which differentiates ThiNet from existing methods. We also propose "gcos" (Group COnvolution with Shuffling), a more accurate group convolution scheme, to further reduce the pruned model size. Experimental results demonstrate the effectiveness of our method, which has advanced the state-of-the-art. Moreover, we show that the original VGG-16 model can be compressed into a very small model (ThiNet-Tiny) with only 2.66 MB model size, but still preserve AlexNet level accuracy. This small model is evaluated on several benchmarks with different vision tasks (e.g., classification, detection, segmentation), and shows excellent generalization ability.

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