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1.
Addict Biol ; 28(10): e13332, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37753566

RESUMO

Substance use disorder (SUD) arises from the initiation to subsequent regular, irregular and harmful use of substances such as alcohol, tobacco/nicotine and cannabis. While thousands of genetic variants have been identified from recent large-scale genome-wide association studies (GWAS), understanding their functions in substance involvement and investigating the mechanisms by which they act in the addiction circuits remains challenging. In this study, we re-analysed the brain regional transcriptome data from the most comprehensive postmortem transcriptomic study, with a focus on up- or down-regulation of substance-associated protein-coding genes in the addiction circuit-related brain regions (AddictRegions), including six cortical and 11 subcortical regions. We found that substance-associated genes were overrepresented in AddictRegions. Interestingly, we observed a greater degree of genetic overlap between initiation and use and between use and SUD than between initiation and SUD. Moreover, substance initiation, use and SUD-associated genes tend to shift their enriched AddictRegions from the cortical for initiation and, to a lesser extent, substance use to subcortical regions for SUD (e.g., thalamus, substantia nigra and ventral tegmental area). We also uncovered a pattern of coordinated cortical up-regulation and subcortical down-regulation for the genes associated with tobacco initiation and alcohol use. Moreover, the Gene Ontology terms of glutamate receptor activity and neurotransmitter binding were most significantly overrepresented in AddictRegion-upregulated, substance-associated genes, with the strongest enrichment for those involved in common substance use behaviours. Overall, our analysis provides a resource of AddictRegion-related transcriptomes for studying substance-associated genes and generates intriguing insights into the genetic control of substance initiation, use and SUD.


Assuntos
Estudo de Associação Genômica Ampla , Transcriptoma , Encéfalo , Cognição , Perfilação da Expressão Gênica
2.
New Phytol ; 221(3): 1387-1397, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30368820

RESUMO

γ-Glutamylcyclotransferase initiates glutathione degradation to component amino acids l-glutamate, l-cysteine and l-glycine. The enzyme is encoded by three genes in Arabidopsis thaliana, one of which (GGCT2;1) is transcriptionally upregulated by starvation for the essential macronutrient sulfur (S). Regulation by S-starvation suggests that GGCT2;1 mobilizes l-cysteine from glutathione when there is insufficient sulfate for de novo l-cysteine synthesis. The response of wild-type seedlings to S-starvation was compared to ggct2;1 null mutants. S-starvation causes glutathione depletion in S-starved wild-type seedlings, but higher glutathione is maintained in the primary root tip than in other seedling tissues. Although GGCT2;1 is induced throughout seedlings, its expression is concentrated in the primary root tip where it activates the γ-glutamyl cycle. S-starved wild-type plants also produce longer primary roots, and lateral root growth is suppressed. While glutathione is also rapidly depleted in ggct2;1 null seedlings, much higher glutathione is maintained in the primary root tip compared to the wild-type. S-starved ggct2;1 primary roots grow longer than the wild-type, and lateral root growth is not suppressed. These results point to a role for GGCT2;1 in S-starvation-response changes to root system architecture through activity of the γ-glutamyl cycle in the primary root tip. l-Cysteine mobilization from glutathione is not solely a function of GGCT2;1.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimologia , Glutationa/metabolismo , Raízes de Plantas/metabolismo , Enxofre/deficiência , gama-Glutamilciclotransferase/metabolismo , Arabidopsis/efeitos dos fármacos , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/efeitos dos fármacos , Proteínas de Arabidopsis/genética , Butionina Sulfoximina/farmacologia , Cisteína/metabolismo , DNA Bacteriano/genética , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Ácido Glutâmico/metabolismo , Meristema/metabolismo , Modelos Biológicos , Mutação/genética , Fenótipo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Regiões Promotoras Genéticas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , gama-Glutamilciclotransferase/genética
3.
Alcohol Clin Exp Res ; 43(4): 628-639, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30830696

RESUMO

BACKGROUND: Alcohol use disorder (AUD) is a wide-spread, heritable brain disease, but few studies have linked genetic variants or epigenetic factors to brain structures related to AUD in humans, due to many factors including the high-dimensional nature of imaging and genomic data. METHODS: To provide potential insights into the links among epigenetic regulation, brain structure, and AUD, we have performed an integrative analysis of brain structural imaging and blood DNA methylome data from 52 AUD and 58 healthy control (HC) subjects collected in the Nathan Kline Institute-Rockland Sample. RESULTS: We first found that AUD subjects had significantly larger insular surface area than HC in both left and right hemispheres. We then found that 7,827 DNA methylation probes on the HumanMethylation450K BeadChip had significant correlations with the right insular surface area (false discovery rate [FDR] < 0.05). Furthermore, we showed that 44 of the insular surface area-correlated methylation probes were also strongly correlated with AUD status (FDR < 0.05). These AUD-correlated probes are annotated to 36 protein-coding genes, with 16 genes (44%) having been reported by others to be related to AUD or alcohol response, including TAS2R16 and PER2. The remaining 20 genes, in particular ARHGAP22, might represent novel genes involved in AUD or responsive to alcohol. CONCLUSIONS: We have identified 36 insular surface area- and AUD-correlated protein-coding genes that are either known to be AUD- or alcohol-related or not yet reported by prior studies. Therefore, our study suggests that the brain imaging-guided epigenetic analysis has a potential of identifying possible epigenetic mechanisms involved in AUD.


Assuntos
Transtornos Relacionados ao Uso de Álcool/genética , Transtornos Relacionados ao Uso de Álcool/metabolismo , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Metilação de DNA/genética , Epigenoma/genética , Adulto , Estudos de Casos e Controles , Biologia Computacional , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Mapas de Interação de Proteínas
4.
Proc Natl Acad Sci U S A ; 113(50): E8197-E8206, 2016 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-27911772

RESUMO

Rho GTPases, including the Rho, Cdc42, Rac, and ROP subfamilies, act as pivotal signaling switches in various growth and developmental processes. Compared with the well-defined role of cytoskeletal organization in Rho signaling, much less is known regarding transcriptional regulation. In a mutant screen for phenotypic enhancers of transgenic Arabidopsis plants expressing a constitutively active form of ROP2 (designated CA1-1), we identified RNA polymerase II (Pol II) C-terminal domain (CTD) phosphatase-like 1 (CPL1) as a transcriptional regulator of ROP2 signaling. We show that ROP2 activation inhibits CPL1 activity by promoting its degradation, leading to an increase in CTD Ser5 and Ser2 phosphorylation. We also observed similar modulation of CTD phosphorylation by yeast Cdc42 GTPase and enhanced degradation of the yeast CTD phosphatase Fcp1 by activated ROP2 signaling. Taken together, our results suggest that modulation of the Pol II CTD code by Rho GTPase signaling represents an evolutionarily conserved mechanism in both unicellular and multicellular eukaryotes.


Assuntos
Arabidopsis/metabolismo , Fosfoproteínas Fosfatases/metabolismo , RNA Polimerase II/metabolismo , Saccharomycetales/metabolismo , Schizosaccharomyces/metabolismo , Proteínas rho de Ligação ao GTP/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Genes de Plantas , Modelos Biológicos , Mutação , Fosfoproteínas Fosfatases/química , Fosfoproteínas Fosfatases/genética , Fosforilação , Plantas Geneticamente Modificadas , Proteólise , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Saccharomycetales/genética , Schizosaccharomyces/genética , Proteínas de Schizosaccharomyces pombe/genética , Proteínas de Schizosaccharomyces pombe/metabolismo , Serina/química , Transdução de Sinais , Fatores de Transcrição/química , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteína cdc42 de Ligação ao GTP/metabolismo
5.
BMC Plant Biol ; 17(1): 186, 2017 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-29084509

RESUMO

BACKGROUND: The ratio of sugars to organic acids, two of the major metabolites in fleshy fruits, has been considered the most important contributor to fruit sweetness. Although accumulation of sugars and acids have been extensively studied, whether plants evolve a mechanism to maintain, sense or respond to the fruit sugar/acid ratio remains a mystery. In a prior study, we used an integrated systems biology tool to identify a group of 39 acid-associated genes from the fruit transcriptomes in four sweet orange varieties (Citrus sinensis L. Osbeck) with varying fruit acidity, Succari (acidless), Bingtang (low acid), and Newhall and Xinhui (normal acid). RESULTS: We reanalyzed the prior sweet orange fruit transcriptome data, leading to the identification of 72 genes highly correlated with the fruit sugar/acid ratio. The majority of these sugar/acid ratio-related genes are predicted to be involved in regulatory functions such as transport, signaling and transcription or encode enzymes involved in metabolism. Surprisingly, only three of these sugar/acid ratio-correlated genes are weakly correlated with sugar level and none of them overlaps with the acid-associated genes. Weighted Gene Coexpression Network Analysis (WGCNA) has revealed that these genes belong to four modules, Blue, Grey, Brown and Turquoise, with the former two modules being unique to the sugar/acid ratio control. CONCLUSION: Our results indicate that orange fruits contain a possible mechanistically distinct class of genes that may potentially be involved in maintaining fruit sugar/acid ratios and/or responding to the cellular sugar/acid ratio status. Therefore, our analysis of orange transcriptomes provides an intriguing insight into the potentially novel genetic or molecular mechanisms controlling the sugar/acid ratio in fruits.


Assuntos
Citrus sinensis/genética , Frutas/metabolismo , Redes Reguladoras de Genes/genética , Genes de Plantas/genética , Ácidos/metabolismo , Citrus sinensis/metabolismo , Perfilação da Expressão Gênica , Genes de Plantas/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Açúcares/metabolismo , Transcriptoma/genética
6.
Plant J ; 77(2): 185-97, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24308460

RESUMO

Sulfur is required for the biosynthesis of cysteine, methionine and numerous other metabolites, and thus is critical for cellular metabolism and various growth and developmental processes. Plants are able to sense their physiological state with respect to sulfur availability, but the sensor remains to be identified. Here we report the isolation and characterization of two novel allelic mutants of Arabidopsis thaliana, sel1-15 and sel1-16, which show increased expression of a sulfur deficiency-activated gene ß-glucosidase 28 (BGLU28). The mutants, which represent two different missense alleles of SULTR1;2, which encodes a high-affinity sulfate transporter, are defective in sulfate transport and as a result have a lower cellular sulfate level. However, when treated with a very high dose of sulfate, sel1-15 and sel1-16 accumulated similar amounts of internal sulfate and its metabolite glutathione (GSH) to wild-type, but showed higher expression of BGLU28 and other sulfur deficiency-activated genes than wild-type. Reduced sensitivity to inhibition of gene expression was also observed in the sel1 mutants when fed with the sulfate metabolites Cys and GSH. In addition, a SULTR1;2 knockout allele also exhibits reduced inhibition in response to sulfate, Cys and GSH, consistent with the phenotype of sel1-15 and sel1-16. Taken together, the genetic evidence suggests that, in addition to its known function as a high-affinity sulfate transporter, SULTR1;2 may have a regulatory role in response to sulfur nutrient status. The possibility that SULTR1;2 may function as a sensor of sulfur status or a component of a sulfur sensory mechanism is discussed.


Assuntos
Proteínas de Transporte de Ânions/genética , Proteínas de Arabidopsis/genética , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Mutação , Enxofre/metabolismo , Sequência de Aminoácidos , Proteínas de Transporte de Ânions/química , Proteínas de Transporte de Ânions/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/metabolismo , Cisteína/administração & dosagem , Glutationa/administração & dosagem , Dados de Sequência Molecular , Homologia de Sequência de Aminoácidos
7.
Anal Biochem ; 460: 22-8, 2014 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-24857786

RESUMO

A luciferase-based method was developed for measurement of 5'-adenylylsulfate (APS) reductase (APR), an enzyme of the reductive sulfate assimilation pathway in prokaryotes and plants. APR catalyzes the two-electron reduction of APS and forms sulfite and adenosine 5'-monophospahate (AMP). The luciferase-based assay measures AMP production using an enzyme-coupled system that generates luminescence. The method is shown to provide an accurate measurement of APR kinetic properties and can be used for both endpoint and continuous assays. APR activity can be measured from pure enzyme preparations as well as from crude protein extracts of tissues. In addition, the assay is ideally suited to high-throughput sample analysis of APR activity in a microtiter dish format. The method adds new capability to the study of the biochemistry and physiology of APR.


Assuntos
Ensaios Enzimáticos/métodos , Luciferases/metabolismo , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/metabolismo , Monofosfato de Adenosina/biossíntese , Animais , Luciferases/química , Medições Luminescentes , Ulva/enzimologia , Zea mays/enzimologia
8.
BMC Genomics ; 14: 27, 2013 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-23324561

RESUMO

BACKGROUND: Huanglongbing (HLB) is arguably the most destructive disease for the citrus industry. HLB is caused by infection of the bacterium, Candidatus Liberibacter spp. Several citrus GeneChip studies have revealed thousands of genes that are up- or down-regulated by infection with Ca. Liberibacter asiaticus. However, whether and how these host genes act to protect against HLB remains poorly understood. RESULTS: As a first step towards a mechanistic view of citrus in response to the HLB bacterial infection, we performed a comparative transcriptome analysis and found that a total of 21 Probesets are commonly up-regulated by the HLB bacterial infection. In addition, a number of genes are likely regulated specifically at early, late or very late stages of the infection. Furthermore, using Pearson correlation coefficient-based gene coexpression analysis, we constructed a citrus HLB response network consisting of 3,507 Probesets and 56,287 interactions. Genes involved in carbohydrate and nitrogen metabolic processes, transport, defense, signaling and hormone response were overrepresented in the HLB response network and the subnetworks for these processes were constructed. Analysis of the defense and hormone response subnetworks indicates that hormone response is interconnected with defense response. In addition, mapping the commonly up-regulated HLB responsive genes into the HLB response network resulted in a core subnetwork where transport plays a key role in the citrus response to the HLB bacterial infection. Moreover, analysis of a phloem protein subnetwork indicates a role for this protein and zinc transporters or zinc-binding proteins in the citrus HLB defense response. CONCLUSION: Through integrating transcriptome comparison and gene coexpression network analysis, we have provided for the first time a systems view of citrus in response to the Ca. Liberibacter spp. infection causing HLB.


Assuntos
Citrus sinensis/genética , Citrus sinensis/microbiologia , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Doenças das Plantas/microbiologia , Rhizobiaceae/fisiologia , Transporte Biológico/genética , Citrus sinensis/citologia , Citrus sinensis/metabolismo , Genes de Plantas/genética , Doenças das Plantas/imunologia , Reguladores de Crescimento de Plantas/metabolismo , Transdução de Sinais/genética , Fatores de Tempo , Regulação para Cima , Zinco/metabolismo
9.
Food Chem ; 417: 135769, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-36917902

RESUMO

This study evaluated the effects of Maillard reaction products of pea protein hydrolyzates (MRPs-PPH) as salt-reducing and umami-enhancing components on the flavor and physicochemical properties of beef flavors. The addition of MRPs-PPH reduced the brightness of beef flavors, increased the redness and yellowness, as well as changed the texture characteristics of beef flavors. With the addition of MRPs-PPH, the apparent viscosity, storage modulus and loss modulus of beef flavors decreased. Finally, the relationship between taste attributes and flavor compounds of the samples was analyzed by Partial Least Squares Regression (PLSR), and flavor compounds with significant positive contributions to different taste attributes were found. This study showed that MRPs-PPH could be used as a flavor enhancer derived from biomacromolecules with salt reduction and freshness enhancement.


Assuntos
Aromatizantes , Paladar , Animais , Bovinos , Aromatizantes/química , Hidrolisados de Proteína , Pisum sativum/metabolismo , Reação de Maillard , Cloreto de Sódio na Dieta , Produtos Finais de Glicação Avançada
10.
Contrast Media Mol Imaging ; 2022: 3465556, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36082063

RESUMO

In order to provide theoretical support and ideas for the "dose" of high-stakes physical activity in athletics, the author has developed models for athletic competition based on nonlinear techniques together with ultrasound. Based on test data, average mean estimation method, and nonlinear regression model estimates, 52 points (46 test points, 6 point estimates) is enrolled in the highest voltage and maximum voltage measurement based on the BP neural network model. The estimation method was developed and the accuracy of the estimation of our estimation method was compared and evaluated using the estimation data. Experimental results show that the average relative error of the average estimate compared to the accuracy of the bench press was 25%, the standard estimate which is not linear regression is 31%, and BP neural network model estimation is 9%. Compared with the accuracy of the assumption of half squatting, the average relative error of the estimated velocity is 13%, the standard nonlinear regression estimate is 20%, and BP neural network model estimated method is 9%. The BP neural network predicts the method with the best performance and intelligence, but its actual functioning and application are complex. The average speed estimate is the most appropriate for use, but the equipment must be high. The process of estimating a linear regression model requires minimal equipment, but its prediction error is high.


Assuntos
Algoritmos , Redes Neurais de Computação , Atletas , Exercício Físico , Humanos , Modelos Lineares
11.
Cells ; 11(2)2022 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-35053398

RESUMO

Cell cycle control is vital for cell proliferation in all eukaryotic organisms. The entire cell cycle can be conceptually separated into four distinct phases, Gap 1 (G1), DNA synthesis (S), G2, and mitosis (M), which progress sequentially. The precise control of transcription, in particular, at the G1 to S and G2 to M transitions, is crucial for the synthesis of many phase-specific proteins, to ensure orderly progression throughout the cell cycle. This mini-review highlights highly conserved transcriptional regulators that are shared in budding yeast (Saccharomyces cerevisiae), Arabidopsis thaliana model plant, and humans, which have been separated for more than a billion years of evolution. These include structurally and/or functionally conserved regulators cyclin-dependent kinases (CDKs), RNA polymerase II C-terminal domain (CTD) phosphatases, and the classical versus shortcut models of Pol II transcriptional control. A few of CDKs and CTD phosphatases counteract to control the Pol II CTD Ser phosphorylation codes and are considered critical regulators of Pol II transcriptional process from initiation to elongation and termination. The functions of plant-unique CDKs and CTD phosphatases in relation to cell division are also briefly summarized. Future studies towards testing a cooperative transcriptional mechanism, which is proposed here and involves sequence-specific transcription factors and the shortcut model of Pol II CTD code modulation, across the three eukaryotic kingdoms will reveal how individual organisms achieve the most productive, large-scale transcription of phase-specific genes required for orderly progression throughout the entire cell cycle.


Assuntos
Ciclo Celular/genética , Quinases Ciclina-Dependentes/metabolismo , Regulação da Expressão Gênica , Monoéster Fosfórico Hidrolases/metabolismo , Plantas/genética , Sequência Conservada , Humanos , Filogenia
12.
Food Chem ; 377: 131902, 2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-34974407

RESUMO

The effects of beef tallow, phospholipid, microwave, and ultrasonic pretreatment (MUP) on the Maillard reaction process, the sensory characteristics of Maillard reaction products (MRPs), and the composition and content of volatile compounds were studied. Maillard reaction of the sample was more intense after MUP, but more hydrophobic amino acids were generated, resulting in relatively high sourness in MRPs. Beef tallow encapsulation has no significant effect on the sensory characteristics of MRPs. The content of volatile compounds in MRPs added with phospholipids increased significantly, and the content of sulfur compounds (especially furan and furanthiol) increased most significantly. Hexanal, Nonanal, 2-Hexylfuran, 2-Hexylthiophene, and 1-Octanol were positively correlated with the value of umami and saltiness of MRPs. The addition of phospholipids after MUP and beef tallow encapsulation helps to increase the saltiness and umami of MRPs, reduce astringency, and produce more sulfur and other flavor compounds.


Assuntos
Reação de Maillard , Micro-Ondas , Animais , Bovinos , Gorduras , Fosfolipídeos , Ultrassom
13.
Sci Rep ; 11(1): 21128, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34702879

RESUMO

The mechanisms underlying retinal development have not been completely elucidated. Extracellular vesicles (EVs) are novel essential mediators of cell-to-cell communication with emerging roles in developmental processes. Nevertheless, the identification of EVs in human retinal tissue, characterization of their cargo, and analysis of their potential role in retina development has not been accomplished. Three-dimensional retinal tissue derived from human induced pluripotent stem cells (hiPSC) provide an ideal developmental system to achieve this goal. Here we report that hiPSC-derived retinal organoids release exosomes and microvesicles with small noncoding RNA cargo. EV miRNA cargo-predicted targetome correlates with Gene Ontology (GO) pathways involved in mechanisms of retinogenesis relevant to specific developmental stages corresponding to hallmarks of native human retina development. Furthermore, uptake of EVs by human retinal progenitor cells leads to changes in gene expression correlated with EV miRNA cargo predicted gene targets, and mechanisms involved in retinal development, ganglion cell and photoreceptor differentiation and function.


Assuntos
Comunicação Celular , Vesículas Extracelulares/metabolismo , Regulação da Expressão Gênica , Células-Tronco Pluripotentes Induzidas/metabolismo , Organoides/metabolismo , Retina/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Organoides/citologia , Retina/citologia
14.
Cells ; 9(3)2020 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-32143485

RESUMO

Rho GTPases, including Rho, Cdc42, Rac and ROP subfamilies, are key signaling molecules in RNA polymerase II (Pol II) transcriptional control. Our prior work has shown that plant ROP and yeast Cdc42 GTPases similarly modulate Ser2 and Ser5 phosphorylation status of the C-terminal domain (CTD) of the Pol II largest subunit by regulating CTD phosphatase degradation. Here, we present genetic and pharmacological evidence showing that Cdc42 and Rac1 GTPase signaling modulates a similar CTD Ser2 and Ser5 phosphorylation code in cultured human cancer cells. While siRNA knockdown of Cdc42 and Rac1, respectively, in HeLa cells increased the level of CTD Ser phosphatases RPAP2 and FCP1, they both decreased the level of CTD kinases CDK7 and CDK13. In addition, the protein degradation inhibitor MG132 reversed the effect of THZ1, a CDK7 inhibitor which could decrease the cell number and amount of CDK7 and CDK13, accompanied by a reduction in the level of CTD Ser2 and Ser5 phosphorylation and DOCK4 and DOCK9 (the activators for Rac1 and Cdc42, respectively). Conversely, treatments of Torin1 or serum deprivation, both of which promote protein degradation, could enhance the effect of THZ1, indicating the involvement of protein degradation in controlling CDK7 and CDK13. Our results support an evolutionarily conserved signaling shortcut model linking Rho GTPases to Pol II transcription across three kingdoms, Fungi, Plantae and Animalia, and could lead to the development of a potential synthetic-lethal strategy in controlling cancer cell proliferation or death.


Assuntos
Proteínas de Transporte/metabolismo , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Proteína cdc42 de Ligação ao GTP/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo , Humanos , Neoplasias/tratamento farmacológico , RNA Polimerase II/metabolismo , Saccharomyces cerevisiae/metabolismo , Transdução de Sinais/fisiologia , Proteínas rho de Ligação ao GTP/metabolismo
15.
Chin J Traumatol ; 11(6): 375-9, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19032855

RESUMO

OBJECTIVE: To explore a classification method which can provide the clinical guidance for internal fixation of tibial fracture. METHODS: The different fractures were fixed according to their mechanical classification. Totally, 71 cases of tibial plateau fracture, tibial proximal fracture, tibial distal fracture and Pilon fracture were analyzed to test this selective principle. RESULTS: All 71 patients were followed up for 6-32 months. The displacement was seldomly observed in cases treated acccording to the classification principle, while some cases against the principle had postoperative displacement. The difference was statistically significant (P less than 0.05). It was proved that there was remarkable correlation between tibial fracture classification, internal fixator and fixation methods. CONCLUSION: Types IIIa3, IIIb1 and IIIb2 fractures without eccentric moment should be fixed with double plates or angle-stable materials combined with locking structure, otherwise displacement may occur.


Assuntos
Fixação Interna de Fraturas/métodos , Fraturas da Tíbia/classificação , Fraturas da Tíbia/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Fenômenos Biomecânicos , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Fraturas da Tíbia/diagnóstico por imagem , Fraturas da Tíbia/fisiopatologia
16.
Transcription ; 8(4): 268-274, 2017 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-28548879

RESUMO

Transcriptional control is critical in relaying signals mediated by Ras and Rho family small GTPases to effect gene expression. In the classical model, signaling components such as MAP kinase target sequence-specific transcription factors, which in turn recruit RNA polymerase (Pol) II holoenzyme to the promoter and activate transcription. Findings in recent years have led to the proposal of a shortcut model in which the Mediator components of the Pol II holoenzyme are regulated by signaling pathways. A very recent finding shows that an evolutionarily conserved Rho GTPase signaling pathway can directly modulate the Pol II C-terminal domain (CTD) phosphorylation by inhibiting the CTD phosphatase in yeast and Arabidopsis. This shortcut model allows direct targeting of the Pol II CTD code and thus has an advantage over the classical model in bringing about rapid, large-scale changes in gene expression.


Assuntos
RNA Polimerase II/metabolismo , Transcrição Gênica , Proteínas ras/metabolismo , Proteínas rho de Ligação ao GTP/metabolismo , Regulação da Expressão Gênica , Holoenzimas , Modelos Genéticos , Fosforilação , Domínios Proteicos , RNA Polimerase II/química , Transdução de Sinais
17.
Drug Alcohol Depend ; 170: 66-73, 2017 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-27875803

RESUMO

BACKGROUND: Although differences in both neuroanatomical measures and personality traits, in particular neuroticism, have been associated with alcohol use disorders (AUD), whether lifetime AUD diagnosis alters the relationship between neuroticism and neuroanatomical structures remains to be determined. METHODS: Data from 65 patients with lifetime AUD diagnoses and 65 healthy comparisons (HC) group-matched on age, sex and race were extracted from the Nathan Kline Institute - Rockland Sample data set. Each subject completed personality trait measures and underwent MRI scanning. Cortical thickness measures at 68 Desikan-Killiany Atlas regions were obtained using FreeSurfer 5.3.0. Regression analyses were performed to identify brain regions at which the neuroticism-cortical thickness relationship was altered by lifetime AUD status. RESULTS: As expected, AUDs had higher neuroticism scores than HCs. Correlations between neuroticism and cortical thickness in the left insula and right fusiform differed significantly across groups. Higher neuroticism score in AUD and the interaction between the insular cortical thickness-neuroticism correlation and AUD status were confirmed in a replication study using the Human Connectome Project data set. CONCLUSIONS: Results confirmed the relationship between neuroticism and AUD and suggests that specific cortical regions, particularly the left insula, represent anatomic substrates underlying this association in AUD.


Assuntos
Transtornos Relacionados ao Uso de Álcool/diagnóstico por imagem , Transtornos Relacionados ao Uso de Álcool/psicologia , Transtornos de Ansiedade , Córtex Cerebral/diagnóstico por imagem , Adulto , Conectoma , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Neuroticismo , Tamanho do Órgão
18.
Front Plant Sci ; 7: 486, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27092171

RESUMO

Organic acids, such as citrate and malate, are important contributors for the sensory traits of fleshy fruits. Although their biosynthesis has been illustrated, regulatory mechanisms of acid accumulation remain to be dissected. To provide transcriptional architecture and identify candidate genes for citrate accumulation in fruits, we have selected for transcriptome analysis four varieties of sweet orange (Citrus sinensis L. Osbeck) with varying fruit acidity, Succari (acidless), Bingtang (low acid), and Newhall and Xinhui (normal acid). Fruits of these varieties at 45 days post anthesis (DPA), which corresponds to Stage I (cell division), had similar acidity, but they displayed differential acid accumulation at 142 DPA (Stage II, cell expansion). Transcriptomes of fruits at 45 and 142 DPA were profiled using RNA sequencing and analyzed with three different algorithms (Pearson correlation, gene coexpression network and surrogate variable analysis). Our network analysis shows that the acid-correlated genes belong to three distinct network modules. Several of these candidate fruit acidity genes encode regulatory proteins involved in transport (such as AHA10), degradation (such as APD2) and transcription (such as AIL6) and act as hubs in the citrate accumulation gene networks. Taken together, our integrated systems biology analysis has provided new insights into the fruit citrate accumulation gene network and led to the identification of candidate genes likely associated with the fruit acidity control.

19.
Infect Dis Poverty ; 5: 32, 2016 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-27109419

RESUMO

BACKGROUND: From 2007 to 2013, intensive control measures reduced malaria burden by 90 % along the China-Myanmar border. However, despite these measures a P. falciparum malaria outbreak was reported in the Shan Special Region II of Myanmar in June of 2014. METHODS: Epidemiological, parasitological and entomological investigations were performed. Dihydroartemisinin piperaquine (DAPQ) was immediately administered to treat parasite positive individuals. Long lasting insecticidal nets (LLIN), indoor residual spraying (IRS) with insecticides and behavior change communication (BCC) were also provided for outbreak control. An embedded efficacy study was conducted evaluating DP. Molecular genotyping via polymerase chain reaction (PCR) was performed on the Kelch gene on chromosome 13. RESULTS: All infections were identified as Plasmodium falciparum by RDT and microscopy. Two fatalities resulted from the outbreak. The attack rate was 72.8 % (67/92) and the incidence density rate was 14.2 per 100 person-weeks. The positive rate of rapid diagnostic test (RDT) was 72.2 % (65/90) and microscopically-determine parasite rate 42.2 % (38/90). Adjusted odds ratio (OR) of multivariate logistic regression analysis for aged <15 years, 15-45 years, inappropriate treatment from a private healer and lack of bed nets were 13.51 (95 % confidence interval, 2.21-105.89), 7.75 (1.48-44.97), 3.78 (1.30-46.18) and 3.21(1.21-15.19) respectively. In the six surrounding communities of the outbreak site, positive RDT rate was 1.2 % (4/328) and microscopically-determine parasite rate 0.6 % (2/328). Two light traps collected a total of 110 anopheline mosquitoes including local vectors, An. minimus, An. sinensis and An. maculates. After intensive control, the detection of malaria attacks, parasites and antigen were reduced to zero between July 1 and December 1, 2014. The cure rate of P. falciparum patients at day 42 was 94.3 % (95 % CI, 80.8-99.3 %). The PCR did not detect K13-propeller mutations. CONCLUSION: Imported P. falciparum caused the outbreak. Age, seeking inappropriate treatment and lack of bed nets were risk factors for infection during the outbreak. P. falciparum was sensitive to treatment with DAPQ. The integrated measures controlled the outbreak and prevented the spread of P. falciparum effectively. The results of this study indicate that malaria control on the China-Myanmar border, especially among special populations, needs further collaboration between China, Myanmar and international societies.


Assuntos
Malária Falciparum/parasitologia , Plasmodium falciparum/isolamento & purificação , Adolescente , Adulto , Idoso , Animais , Antimaláricos/uso terapêutico , Criança , Pré-Escolar , China/epidemiologia , Culicidae/parasitologia , Surtos de Doenças , Feminino , Genótipo , Humanos , Lactente , Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Malária Falciparum/prevenção & controle , Masculino , Pessoa de Meia-Idade , Mianmar/epidemiologia , Plasmodium falciparum/classificação , Plasmodium falciparum/genética , Viagem , Adulto Jovem
20.
Front Plant Sci ; 5: 710, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25566284

RESUMO

Plants have evolved a sophisticated mechanism to sense the extracellular sulfur (S) status so that sulfate transport and S assimilation/metabolism can be coordinated. Genetic, biochemical, and molecular studies in Arabidopsis over the past 10 years have started to shed some light on the regulatory mechanism of the S response. Key advances in transcriptional regulation (SLIM1, MYB, and miR395), involvement of hormones (auxin, cytokinin, and abscisic acid) and identification of putative sensors (OASTL and SULTR1;2) are highlighted here. Although our current view of S nutrient sensing and signaling remains fragmented, it is anticipated that through further studies a sensing and signaling network will be revealed in the near future.

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