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1.
Mol Cell ; 42(3): 356-66, 2011 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-21549312

RESUMEN

Argonaute (AGO) proteins are critical components of RNA silencing pathways that bind small RNAs and mediate gene silencing at their target sites. We found that Arabidopsis AGO2 is highly induced by the bacterial pathogen Pseudomonas syringae pv. tomato (Pst). Further genetic analysis demonstrated that AGO2 functions in antibacterial immunity. One abundant species of AGO2-bound small RNA is miR393b(∗), which targets a Golgi-localized SNARE gene, MEMB12. Pst infection downregulates MEMB12 in a miR393b(∗)-dependent manner. Loss of function of MEMB12, but not SYP61, another intracellular SNARE, leads to increased exocytosis of an antimicrobial pathogenesis-related protein, PR1. Overexpression of miR393b(∗) resembles memb12 mutant in resistance responses. Thus, AGO2 functions in antibacterial immunity by binding miR393b(∗) to modulate exocytosis of antimicrobial PR proteins via MEMB12. Since miR393 also contributes to antibacterial responses, miR393(∗)/miR393 represent an example of a miRNA(∗)/miRNA pair that functions in immunity through two distinct AGOs: miR393(∗) through AGO2 and miR393 through AGO1.


Asunto(s)
Proteínas de Arabidopsis/genética , Arabidopsis/genética , MicroARNs/genética , Proteínas de Unión al ARN/genética , Proteínas SNARE/genética , Arabidopsis/metabolismo , Arabidopsis/microbiología , Proteínas de Arabidopsis/metabolismo , Proteínas Argonautas , Secuencia de Bases , Northern Blotting , Electroforesis en Gel de Poliacrilamida , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Aparato de Golgi/metabolismo , Interacciones Huésped-Patógeno/genética , Interacciones Huésped-Patógeno/inmunología , Inmunidad Innata/genética , Inmunidad Innata/inmunología , MicroARNs/metabolismo , Mutación , Unión Proteica , Pseudomonas syringae/inmunología , Pseudomonas syringae/fisiología , Interferencia de ARN , Proteínas de Unión al ARN/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteínas SNARE/metabolismo , Homología de Secuencia de Ácido Nucleico
2.
Molecules ; 24(2)2019 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-30646587

RESUMEN

Kinesin-1, kinesin-2 and kinesin-5 are three families of a superfamily of motor proteins; which can walk processively on microtubule filaments by hydrolyzing ATP. It was experimentally shown that while the three kinesin dimers show similar feature on the force dependence of velocity, they show rather different features on the force dependence of run length. However, why the three families of kinesins show these rather different features is unclear. Here, we computationally studied the movement dynamics of the three dimers based on our proposed model. The simulated results reproduce well the available experimental data on the force dependence of velocity and run length. Moreover, the simulated results on the velocity and run length for the three dimers with altered neck linker lengths are also in quantitative agreement with the available experimental data. The studies indicate that the three families of kinesins show much similar movement mechanism and the rather different features on the force dependence of run length arise mainly from the difference in rate constants of the ATPase activity and neck linker docking. Additionally, the asymmetric (limping) movement dynamics of the three families of homodimers with and without altered neck linker lengths are studied, providing predicted results.


Asunto(s)
Cinesinas/química , Modelos Teóricos , Proteínas Motoras Moleculares/química , Adenosina Trifosfato/química , Adenosina Trifosfato/metabolismo , Cinesinas/genética , Proteínas Motoras Moleculares/genética , Familia de Multigenes , Multimerización de Proteína
3.
BMC Genomics ; 18(Suppl 1): 932, 2017 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-28198673

RESUMEN

BACKGROUND: Gastrointestinal microbiota, particularly gut microbiota, is associated with human health. The biodiversity of gut microbiota is affected by ethnicities and environmental factors such as dietary habits or medicine intake, and three enterotypes of the human gut microbiome were announced in 2011. These enterotypes are not significantly correlated with gender, age, or body weight but are influenced by long-term dietary habits. However, to date, only two enterotypes (predominantly consisting of Bacteroides and Prevotella) have shown these characteristics in previous research; the third enterotype remains ambiguous. Understanding the enterotypes can improve the knowledge of the relationship between microbiota and human health. RESULTS: We obtained 181 human fecal samples from adults in Taiwan. Microbiota compositions were analyzed using next-generation sequencing (NGS) technology, which is a culture-independent method of constructing microbial community profiles by sequencing 16S ribosomal DNA (rDNA). In these samples, 17,675,898 sequencing reads were sequenced, and on average, 215 operational taxonomic units (OTUs) were identified for each sample. In this study, the major bacteria in the enterotypes identified from the fecal samples were Bacteroides, Prevotella, and Enterobacteriaceae, and their correlation with dietary habits was confirmed. A microbial interaction network in the gut was observed on the basis of the amount of short-chain fatty acids, pH value of the intestine, and composition of the bacterial community (enterotypes). Finally, a decision tree was derived to provide a predictive model for the three enterotypes. The accuracies of this model in training and independent testing sets were 97.2 and 84.0%, respectively. CONCLUSIONS: We used NGS technology to characterize the microbiota and constructed a predictive model. The most significant finding was that Enterobacteriaceae, the predominant subtype, could be a new subtype of enterotypes in the Asian population.


Asunto(s)
Biodiversidad , Microbioma Gastrointestinal , Metagenoma , Metagenómica , Adulto , Análisis por Conglomerados , Árboles de Decisión , Heces/microbiología , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Metagenómica/métodos , Fenotipo , ARN Ribosómico 16S/genética , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
4.
J Am Chem Soc ; 137(1): 436-44, 2015 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-25535941

RESUMEN

The crowded intracellular environment influences the diffusion-mediated cellular processes, such as metabolism, signaling, and transport. The hindered diffusion of macromolecules in heterogeneous cytoplasm has been studied over years, but the detailed diffusion distribution and its origin still remain unclear. Here, we introduce a novel method to map rapidly the diffusion distribution in single cells based on single-particle tracking (SPT) of quantum dots (QDs). The diffusion map reveals the heterogeneous intracellular environment and, more importantly, an unreported compartmentalization of QD diffusions in cytoplasm. Simultaneous observations of QD motion and green fluorescent protein-tagged endoplasmic reticulum (ER) dynamics provide direct evidence that the compartmentalization results from micron-scale domains defined by ER tubules, and ER cisternae form perinuclear areas that restrict QDs to enter. The same phenomenon was observed using fluorescein isothiocyanate-dextrans, further confirming the compartmentalized diffusion. These results shed new light on the diffusive movements of macromolecules in the cell, and the mapping of intracellular diffusion distribution may be used to develop strategies for nanoparticle-based drug deliveries and therapeutics.


Asunto(s)
Difusión , Retículo Endoplásmico/metabolismo , Puntos Cuánticos , Línea Celular Tumoral , Humanos
5.
Circulation ; 128(6): 632-42, 2013 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-23838163

RESUMEN

BACKGROUND: The molecular basis for the focal nature of atherosclerotic lesions is poorly understood. Here, we explored whether disturbed flow patterns activate an innate immune response to form the NLRP3 inflammasome scaffold in vascular endothelial cells via sterol regulatory element binding protein 2 (SREBP2). METHODS AND RESULTS: Oscillatory flow activates SREBP2 and induces NLRP3 inflammasome in endothelial cells. The underlying mechanisms involve SREBP2 transactivating NADPH oxidase 2 and NLRP3. Consistently, SREBP2, NADPH oxidase 2, and NLRP3 levels were elevated in atheroprone areas of mouse aortas, suggesting that the SREBP2-activated NLRP3 inflammasome causes functionally disturbed endothelium with increased inflammation. Mimicking the effect of atheroprone flow, endothelial cell-specific overexpression of the activated form of SREBP2 synergized with hyperlipidemia to increase atherosclerosis in the atheroresistant areas of mouse aortas. CONCLUSIONS: Atheroprone flow induces NLRP3 inflammasome in endothelium through SREBP2 activation. This increased innate immunity in endothelium synergizes with hyperlipidemia to cause topographical distribution of atherosclerotic lesions.


Asunto(s)
Aterosclerosis/inmunología , Proteínas Portadoras/inmunología , Proteína 2 de Unión a Elementos Reguladores de Esteroles/inmunología , Vasculitis/inmunología , Animales , Apolipoproteínas E/genética , Aterosclerosis/metabolismo , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Células Endoteliales/inmunología , Células Endoteliales/metabolismo , Hemodinámica/inmunología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Inmunidad Innata/inmunología , Inflamasomas/inmunología , Inflamasomas/metabolismo , Masculino , Glicoproteínas de Membrana/inmunología , Glicoproteínas de Membrana/metabolismo , Ratones , Ratones Transgénicos , MicroARNs/inmunología , MicroARNs/metabolismo , NADPH Oxidasa 2 , NADPH Oxidasas/inmunología , NADPH Oxidasas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR , ARN Interferente Pequeño/genética , Proteína 2 de Unión a Elementos Reguladores de Esteroles/genética , Proteína 2 de Unión a Elementos Reguladores de Esteroles/metabolismo , Estrés Mecánico , Vasculitis/genética , Vasculitis/metabolismo
6.
PLoS Biol ; 9(6): e1000622, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21697975

RESUMEN

The genome-sequencing gold rush has facilitated the use of comparative genomics to uncover patterns of genome evolution, although their causal mechanisms remain elusive. One such trend, ubiquitous to prokarya and eukarya, is the association of insertion/deletion mutations (indels) with increases in the nucleotide substitution rate extending over hundreds of base pairs. The prevailing hypothesis is that indels are themselves mutagenic agents. Here, we employ population genomics data from Escherichia coli, Saccharomyces paradoxus, and Drosophila to provide evidence suggesting that it is not the indels per se but the sequence in which indels occur that causes the accumulation of nucleotide substitutions. We found that about two-thirds of indels are closely associated with repeat sequences and that repeat sequence abundance could be used to identify regions of elevated sequence diversity, independently of indels. Moreover, the mutational signature of indel-proximal nucleotide substitutions matches that of error-prone DNA polymerases. We propose that repeat sequences promote an increased probability of replication fork arrest, causing the persistent recruitment of error-prone DNA polymerases to specific sequence regions over evolutionary time scales. Experimental measures of the mutation rates of engineered DNA sequences and analyses of experimentally obtained collections of spontaneous mutations provide molecular evidence supporting our hypothesis. This study uncovers a new role for repeat sequences in genome evolution and provides an explanation of how fine-scale sequence contextual effects influence mutation rates and thereby evolution.


Asunto(s)
ADN Polimerasa Dirigida por ADN/metabolismo , Evolución Molecular , Mutación INDEL , Modelos Genéticos , Secuencias Repetitivas de Ácidos Nucleicos , Animales , Bacterias/genética , Enzimas Reparadoras del ADN/metabolismo , Drosophila , Escherichia coli , Eucariontes/genética , Variación Genética , Genoma , Haploidia , Haplotipos , Humanos , Saccharomyces , Proteínas de Saccharomyces cerevisiae/genética
7.
Arch Biochem Biophys ; 536(1): 12-24, 2013 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-23664917

RESUMEN

Cisplatin is the main platinum antitumor drug applied in clinical settings. However, its trans isomer, transplatin, is known to have an ineffective antitumor activity. Despite intensive studies in this field, the structural and biophysical properties of DNA molecules reacting with these two platinum complexes have not been fully elucidated. In the present study, we observed that transplatin made efficient cross-linking of DNA in the vicinity of cisplatin adducts. High-resolution atomic force microscopy studies revealed that the transplatin-induced cross-linkings of nucleotides flanking cisplatin adducts were characterized by kinked-loop structures with rod-like shapes of nanometer scales (∼10-60nm). The results were further confirmed by denaturing gel electrophoresis and single-molecule experiment using magnetic tweezers. In vivo studies revealed that transplatin and cisplatin co-treatment could induce a considerable amount of kinked loops with smaller sizes (∼15nm) in cellular DNA. Furthermore, compared with cisplatin treatment alone, the co-treatment resulted in enhanced cytotoxicity, increased amount of interstrand cross-links, and cell lesions more reluctant to cellular repair system. The results of the present study provide a new clue for understanding the stepwise reactions of DNA with platinum drugs and might serve as a basis for the development of a new antitumor strategy.


Asunto(s)
Antineoplásicos/farmacología , Cisplatino/farmacología , Reactivos de Enlaces Cruzados/farmacología , Aductos de ADN/metabolismo , Aductos de ADN/ultraestructura , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Sinergismo Farmacológico , Humanos , Neoplasias/tratamiento farmacológico , Conformación de Ácido Nucleico/efectos de los fármacos
8.
Circulation ; 124(5): 633-41, 2011 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-21768538

RESUMEN

BACKGROUND: Upregulated by atheroprotective flow, the transcription factor Krüppel-like factor 2 (KLF2) is crucial for maintaining endothelial function. MicroRNAs (miRNAs) are noncoding small RNAs that regulate gene expression at the posttranscriptional level. We examined the role of miRNAs, particularly miR-92a, in the atheroprotective flow-regulated KLF2. METHODS AND RESULTS: Dicer knockdown increased the level of KLF2 mRNA in human umbilical vein endothelial cells, suggesting that KLF2 is regulated by miRNA. In silico analysis predicted that miR-92a could bind to the 3' untranslated region of KLF2 mRNA. Overexpression of miR-92a decreased the expression of KLF2 and the KLF2-regulated endothelial nitric oxide synthase and thrombomodulin at mRNA and protein levels. A complementary finding is that miR-92a inhibitor increased the mRNA and protein expression of KLF2, endothelial nitric oxide synthase, and thrombomodulin. Subsequent studies revealed that atheroprotective laminar flow downregulated the level of miR-92a precursor to induce KLF2, and the level of this flow-induced KLF2 was reduced by miR-92a precursor. Furthermore, miR-92a level was lower in human umbilical vein endothelial cells exposed to the atheroprotective pulsatile shear flow than under atheroprone oscillatory shear flow. Anti-Ago1/2 immunoprecipitation coupled with real-time polymerase chain reaction revealed that pulsatile shear flow decreased the functional targeting of miR-92a precursor/KLF2 mRNA in human umbilical vein endothelial cells. Consistent with these findings, mouse carotid arteries receiving miR-92a precursor exhibited impaired vasodilatory response to flow. CONCLUSIONS: Atheroprotective flow patterns decrease the level of miR-92a, which in turn increases KLF2 expression to maintain endothelial homeostasis.


Asunto(s)
Aterosclerosis/fisiopatología , Células Endoteliales/fisiología , Factores de Transcripción de Tipo Kruppel/genética , MicroARNs/fisiología , Flujo Pulsátil/fisiología , Regiones no Traducidas 3'/genética , Aterosclerosis/genética , Aterosclerosis/patología , Células Cultivadas , Células Endoteliales/citología , Regulación de la Expresión Génica/fisiología , Técnicas de Silenciamiento del Gen , Homeostasis/fisiología , Humanos , Factores de Transcripción de Tipo Kruppel/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo III/genética , Óxido Nítrico Sintasa de Tipo III/metabolismo , ARN Mensajero/genética , Estrés Mecánico , Trombomodulina/genética , Trombomodulina/metabolismo , Venas Umbilicales/citología , Vasodilatación/fisiología
9.
Nucleic Acids Res ; 37(5): 1400-10, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19129234

RESUMEN

Structural properties of single lambda DNA treated with anti-cancer drug cisplatin were studied with magnetic tweezers and AFM. Under the effect of low-concentration cisplatin, the DNA became more flexible, with the persistence length decreased significantly from approximately 52 to 15 nm. At a high drug concentration, a DNA condensation phenomenon was observed. Based on experimental results from both single-molecule and AFM studies, we propose a model to explain this kind of DNA condensation by cisplatin: first, di-adducts induce local distortions of DNA. Next, micro-loops of approximately 20 nm appear through distant crosslinks. Then, large aggregates are formed through further crosslinks. Finally, DNA is condensed into a compact globule. Experiments with Pt(dach)Cl(2) indicate that oxaliplatin may modify the DNA structures in the same way as cisplatin. The observed loop structure formation of DNA may be an important feature of the effect of platinum anti-cancer drugs that are analogous to cisplatin in structure.


Asunto(s)
Antineoplásicos/farmacología , Cisplatino/farmacología , ADN/efectos de los fármacos , ADN/ultraestructura , Bacteriófago lambda/genética , ADN/química , ADN Viral/química , ADN Viral/efectos de los fármacos , ADN Viral/ultraestructura , Elasticidad , Microscopía de Fuerza Atómica , Conformación de Ácido Nucleico , Compuestos Organoplatinos/farmacología , Oxaliplatino
10.
PLoS One ; 15(8): e0237731, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32813752

RESUMEN

Sudden cardiac death (SCD) is an important cause of mortality worldwide. It accounts for approximately half of all deaths from cardiovascular disease. While coronary artery disease and acute myocardial infarction account for the majority of SCD in the elderly population, inherited cardiac diseases (inherited CDs) comprise a substantial proportion of younger SCD victims with a significant genetic component. Currently, the use of next-generation sequencing enables the rapid analysis to investigate relationships between genetic variants and inherited CDs causing SCD. Genetic contribution to risk has been considered an alternate predictor of SCD. In the past years, large numbers of SCD susceptibility variants were reported, but these results are scattered in numerous publications. Here, we present the SCD-associated Variants Annotation Database (SVAD) to facilitate the interpretation of variants and to meet the needs of data integration. SVAD contains data from a broad screening of scientific literature. It was constructed to provide a comprehensive collection of genetic variants along with integrated information regarding their effects. At present, SVAD has accumulated 2,292 entries within 1,239 variants by manually surveying pertinent literature, and approximately one-third of the collected variants are pathogenic/likely-pathogenic following the ACMG guidelines. To the best of our knowledge, SVAD is the most comprehensive database that can provide integrated information on the associated variants in various types of inherited CDs. SVAD represents a valuable source of variant information based on scientific literature and benefits clinicians and researchers, and it is now available on http://svad.mbc.nctu.edu.tw/.


Asunto(s)
Bases de Datos Genéticas/estadística & datos numéricos , Muerte Súbita Cardíaca/etiología , Cardiopatías/genética , Modelos Genéticos , Simulación por Computador , Muerte Súbita Cardíaca/epidemiología , Cardiopatías/mortalidad , Humanos , Mutación , Polimorfismo de Nucleótido Simple , Medición de Riesgo/métodos
11.
BMC Bioinformatics ; 10: 328, 2009 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-19821977

RESUMEN

BACKGROUND: MicroRNAs (miRNAs), small non-coding RNAs of 19 to 25 nt, play important roles in gene regulation in both animals and plants. In the last few years, the oligonucleotide microarray is one high-throughput and robust method for detecting miRNA expression. However, the approach is restricted to detecting the expression of known miRNAs. Second-generation sequencing is an inexpensive and high-throughput sequencing method. This new method is a promising tool with high sensitivity and specificity and can be used to measure the abundance of small-RNA sequences in a sample. Hence, the expression profiling of miRNAs can involve use of sequencing rather than an oligonucleotide array. Additionally, this method can be adopted to discover novel miRNAs. RESULTS: This work presents a systematic approach, miRExpress, for extracting miRNA expression profiles from sequencing reads obtained by second-generation sequencing technology. A stand-alone software package is implemented for generating miRNA expression profiles from high-throughput sequencing of RNA without the need for sequenced genomes. The software is also a database-supported, efficient and flexible tool for investigating miRNA regulation. Moreover, we demonstrate the utility of miRExpress in extracting miRNA expression profiles from two Illumina data sets constructed for the human and a plant species. CONCLUSION: We develop miRExpress, which is a database-supported, efficient and flexible tool for detecting miRNA expression profile. The analysis of two Illumina data sets constructed from human and plant demonstrate the effectiveness of miRExpress to obtain miRNA expression profiles and show the usability in finding novel miRNAs.


Asunto(s)
Biología Computacional/métodos , MicroARNs/química , Análisis de Secuencia de ARN/métodos , Programas Informáticos , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica , Genoma Humano , Genoma de Planta , Humanos
12.
Phys Rev E Stat Nonlin Soft Matter Phys ; 79(5 Pt 1): 051912, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19518485

RESUMEN

We report observations of in vitro DNA compaction into toroids in the absence of any condensing agent. The DNA toroid formation is induced by geometry confinement from microdroplets on mica surfaces. With AFM imaging we show that the confined DNA molecules may take the form of random coils or semiordered folded loops with large microdroplets, while they readily take the form of compact and ordered toroids when the microdroplet sizes are small enough. To better understand these phenomena, we carried out coarse-grained Brownian dynamics simulation, obtaining results that were in good agreement with the experimental observations. The simulation reveals that the toroid formation is sensitive to not only the microdroplet size, but also the DNA stiffness.


Asunto(s)
Silicatos de Aluminio/química , ADN/química , ADN/ultraestructura , Modelos Químicos , Modelos Moleculares , Simulación por Computador , Conformación de Ácido Nucleico , Soluciones , Propiedades de Superficie
13.
Biophys Chem ; 136(2-3): 87-95, 2008 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-18538916

RESUMEN

A mathematical model is proposed to illustrate the activation of STIM1 (stromal interaction molecule 1) protein, the assembly and activation of calcium-release activated calcium (CRAC) channels in T cells. In combination with De Young-Keizer-Li-Rinzel model, we successfully reproduce a sustained Ca(2+) oscillation in cytoplasm. Our results reveal that Ca(2+) oscillation dynamics in cytoplasm can be significantly affected by the way how the Orai1 CRAC channel are assembled and activated. A low sustained Ca(2+) influx is observed through the CRAC channels across the plasma membrane. In particular, our model shows that a tetrameric channel complex can effectively regulate the total quantity of the channels and the ratio of the active channels to the total channels, and a period of Ca(2+) oscillation about 29 s is in agreement with published experimental data. The bifurcation analyses illustrate the different dynamic properties between our mixed Ca(2+) feedback model and the single positive or negative feedback models.


Asunto(s)
Canales de Calcio/metabolismo , Calcio/metabolismo , Citoplasma/metabolismo , Simulación por Computador , Retículo Endoplásmico/metabolismo , Inositol 1,4,5-Trifosfato/metabolismo , Proteínas de Neoplasias/metabolismo , Unión Proteica
14.
J Air Waste Manag Assoc ; 58(12): 1579-89, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19189756

RESUMEN

Eleven ionic species and fine and coarse particle mass concentrations of fine (PM2.5) and coarse (PM10-2.5) particulate matter were investigated in Kaohsiung, southern Taiwan. The PM2.5 and PM10-2.5 particulate concentrations were 49-64 and 34-37 microg x m(-3), respectively. Fifty-five to 64% of the particulate matter less than 10 microm in aerodynamic diameter (PM10) mass was attributed to the PM2.5. PM2.5 concentrations at Daliao (a rural and industrial complex area) were higher than at Tzuoying (an urban and industrial complex area). Ionic species contributed 45-53% and 42-45% of PM2.5 and PM10, respectively. Potassium ions (K+), sulfate (SO4(2-)), and ammonium (NH4+) were predominant in PM2.5, whereas sodium, calcium, and magnesium ions were foremost in PM10-2.5. Nitrate (NO3-) existed in both the PM2.5 and PM10-2.5. Chloride (Cl-), NO3-, and NH4+ concentrations were higher at night than during the day, and they were easily transferred into the gas phase by photochemical reactions and temperature-induced volatilization. The NH4+/SO4(2-) ratios were 2.6 and 2.5 at Daliao and Tzuoying, respectively, which indicated that both sampling sites were rich in NH4+. Therefore, ammonium nitrate would be present in the area.


Asunto(s)
Tamaño de la Partícula , Material Particulado/química , Agua/química , Taiwán , Factores de Tiempo
15.
Environ Sci Pollut Res Int ; 23(16): 16722-37, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27184148

RESUMEN

Coarse and fine particulate matter (PM) were taken by a dichotomous sampler, and gas precursors were determined by a denuder sampler at two stations in central Taiwan. Water-soluble ionic constituents of PM and their precursor gases were analyzed by ionic chromatograph. In summer, the daytime/nighttime PM10 concentrations were 37 ± 10/41 ± 18 µg m(-3) and 36 ± 14/34 ± 18 µg m(-3) for Xitun and Jhushan, respectively. Average PM10 concentration in winter was 1.55 and 1.76 times that of summer for Xitun and Jhushan, respectively. PM mass concentrations were similar for both stations, although one station is located in the downtown area of Taichung, and the other is in a rural area with no heavy pollution sources. Water-soluble ionic species content was 38-53 % of PM2.5 and 43-48 % of PM10 mass concentration. HNO3, HCl, and SO2 were high in the daytime; the daytime-to-nighttime concentration ratio was 3.75-6.88 for HNO3,1.7-7.8 for HCl, and 1.45-2.77 for SO2. High NH3 levels were determined in the area, especially in winter, which could be a precursor of NH4 (+) to form particulate matter. In Xitun, motor vehicles downtown and in the industrial district could be sources of air pollution. In contrast, there are few industrial sources at Jhushan; therefore, the transport of air pollutants from upwind of other regions and the accumulation of pollutants could be important PM sources at Jhushan.


Asunto(s)
Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente , Material Particulado/análisis , Contaminación del Aire/estadística & datos numéricos , Gases/análisis , Tamaño de la Partícula , Estaciones del Año , Taiwán , Agua/química
16.
J Invest Dermatol ; 135(9): 2237-2248, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25946710

RESUMEN

Allopurinol, a first-line drug for treating gout and hyperuricemia, is one of the leading causes of severe cutaneous adverse reactions (SCARs). To investigate the molecular mechanism of allopurinol-induced SCAR, we enrolled 21 patients (13 Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and 8 drug reaction with eosinophilia and systemic symptoms (DRESS)), 11 tolerant controls, and 23 healthy donors. We performed in vitro T-cell activation assays by culturing peripheral blood mononuclear cells (PBMCs) with allopurinol, oxypurinol, or febuxostat and measuring the expression of granulysin and IFN-γ in the supernatants of cultures. TCR repertoire was investigated by next-generation sequencing. Oxypurinol stimulation resulted in a significant increase in granulysin in the cultures of blood samples from SCAR patients (n=14) but not tolerant controls (n=11) or healthy donors (n=23). Oxypurinol induced T-cell response in a concentration- and time-dependent manner, whereas allopurinol or febuxostat did not. T cells from patients with allopurinol-SCAR showed no crossreactivity with febuxostat. Preferential TCR-V-ß usage and clonal expansion of specific CDR3 (third complementarity-determining region) were found in the blister cells from skin lesions (n=8) and oxypurinol-activated T-cell cultures (n=4) from patients with allopurinol-SCAR. These data suggest that, in addition to HLA-B*58:01, clonotype-specific T cells expressing granulysin upon oxypurinol induction participate in the pathogenesis of allopurinol-induced SCAR.


Asunto(s)
Alopurinol/efectos adversos , Antígenos de Diferenciación de Linfocitos T/metabolismo , Leucocitos Mononucleares/efectos de los fármacos , Activación de Linfocitos/efectos de los fármacos , Oxipurinol/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Alopurinol/farmacología , Estudios de Casos y Controles , Células Cultivadas/inmunología , Reacciones Cruzadas , Erupciones por Medicamentos/etiología , Erupciones por Medicamentos/inmunología , Ensayo de Inmunoadsorción Enzimática , Febuxostat , Femenino , Humanos , Interferón gamma/efectos de los fármacos , Interferón gamma/inmunología , Leucocitos Mononucleares/metabolismo , Masculino , Persona de Mediana Edad , Oxipurinol/farmacología , Valores de Referencia , Síndrome de Stevens-Johnson/etiología , Síndrome de Stevens-Johnson/inmunología , Tiazoles/efectos adversos , Tiazoles/farmacología
17.
Zhonghua Yi Xue Za Zhi ; 83(4): 285-8, 2003 Feb 25.
Artículo en Zh | MEDLINE | ID: mdl-12812643

RESUMEN

OBJECTIVE: To investigate the morbidity of congenital hearing impairment among high-risk newborns and the relevant pathogenic factors. METHODS: Initial screening of hearing by otoacoustic emission (OAE) was conducted among 208 high-risk newborns, 130 males and 78 females after they were born and the second screening was conducted by OAE was conducted 42 days after those with positive results were examined by auditary brainstem response (ABR). RESULTS: All of the 208 newborns received the initial screening with a screening rate of 100%, and 130 newborns received the second screening with a screening rate of 62.5%. The positive rates in the initial screening and second screening were 34.61% and 7.14% respectively. Six newborns were examined by ABR and 2 of them were diagnoses as with hearing impairment with a prevalence rate of 1.78%. The factors, such as sex, age, and Apgar score affected the initial screening results. CONCLUSION: The most proper time for initial hearing screening is around the 42nd day after birth. High-risk newborns should receive regular test even though they pass the initial screening. A special follow-up system should be constructed for the high-risk newborns.


Asunto(s)
Trastornos de la Audición/diagnóstico , Potenciales Evocados Auditivos del Tronco Encefálico , Femenino , Estudios de Seguimiento , Humanos , Recién Nacido , Masculino , Tamizaje Neonatal , Emisiones Otoacústicas Espontáneas , Riesgo
18.
Biomed Res Int ; 2014: 906168, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25202708

RESUMEN

Eighty-one stool samples from Taiwanese were collected for analysis of the association between the gut flora and obesity. The supervised analysis showed that the most, abundant genera of bacteria in normal samples (from people with a body mass index (BMI) ≤ 24) were Bacteroides (27.7%), Prevotella (19.4%), Escherichia (12%), Phascolarctobacterium (3.9%), and Eubacterium (3.5%). The most abundant genera of bacteria in case samples (with a BMI ≥ 27) were Bacteroides (29%), Prevotella (21%), Escherichia (7.4%), Megamonas (5.1%), and Phascolarctobacterium (3.8%). A principal coordinate analysis (PCoA) demonstrated that normal samples were clustered more compactly than case samples. An unsupervised analysis demonstrated that bacterial communities in the gut were clustered into two main groups: N-like and OB-like groups. Remarkably, most normal samples (78%) were clustered in the N-like group, and most case samples (81%) were clustered in the OB-like group (Fisher's P value = 1.61E - 07). The results showed that bacterial communities in the gut were highly associated with obesity. This is the first study in Taiwan to investigate the association between human gut flora and obesity, and the results provide new insights into the correlation of bacteria with the rising trend in obesity.


Asunto(s)
Bacterias/genética , Biología Computacional/métodos , Tracto Gastrointestinal/microbiología , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Obesidad/microbiología , Adulto , Anciano , Anciano de 80 o más Años , Biodiversidad , Biomarcadores/metabolismo , Peso Corporal , Estudios de Casos y Controles , Análisis por Conglomerados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis de Componente Principal , Adulto Joven
19.
PLoS One ; 8(8): e71556, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23951187

RESUMEN

The interactions of DNA with oxaliplatin (Pt(R,R-DACH)) or its enantiomer (Pt(S,S-DACH)) were investigated using magnetic tweezers and atomic force microscope. In the process of DNA condensation induced by Pt-DACH, only diadducts and micro-loops are formed at low Pt-DACH concentrations, while at high Pt-DACH concentrations, besides the diadducts and micro-loops, long-range cross-links are also formed. The diadduct formation rate of Pt(R,R-DACH) is higher than that of Pt(S,S-DACH). However, the proportions of micro-loops and long-range cross-links for Pt(S,S-DACH) are higher than those for Pt(R,R-DACH). We propose a model to explain these differences between the effect of Pt(R,R-DACH) and that of Pt(S,S-DACH) on DNA condensation. The study has strong implications for the understanding of the effect of chirality on the interaction between Pt-DACH and DNA and the kinetics of DNA condensation induced by platinum complexes.


Asunto(s)
ADN/química , Compuestos Organoplatinos/química , ADN/efectos de los fármacos , Modelos Químicos , Estructura Molecular , Compuestos Organoplatinos/farmacología , Oxaliplatino
20.
J Clin Invest ; 123(3): 1057-67, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23426184

RESUMEN

Despite a general repression of translation under hypoxia, cells selectively upregulate a set of hypoxia-inducible genes. Results from deep sequencing revealed that Let-7 and miR-103/107 are hypoxia-responsive microRNAs (HRMs) that are strongly induced in vascular endothelial cells. In silico bioinformatics and in vitro validation showed that these HRMs are induced by HIF1α and target argonaute 1 (AGO1), which anchors the microRNA-induced silencing complex (miRISC). HRM targeting of AGO1 resulted in the translational desuppression of VEGF mRNA. Inhibition of HRM or overexpression of AGO1 without the 3' untranslated region decreased hypoxia-induced angiogenesis. Conversely, AGO1 knockdown increased angiogenesis under normoxia in vivo. In addition, data from tumor xenografts and human cancer specimens indicate that AGO1-mediated translational desuppression of VEGF may be associated with tumor angiogenesis and poor prognosis. These findings provide evidence for an angiogenic pathway involving HRMs that target AGO1 and suggest that this pathway may be a suitable target for anti- or proangiogenesis strategies.


Asunto(s)
Proteínas Argonautas/genética , Factores Eucarióticos de Iniciación/genética , MicroARNs/genética , Neovascularización Patológica/metabolismo , Regiones no Traducidas 3' , Animales , Proteínas Argonautas/metabolismo , Proteínas Argonautas/fisiología , Secuencia de Bases , Sitios de Unión , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidad , Hipoxia de la Célula , Línea Celular Tumoral , Factores Eucarióticos de Iniciación/metabolismo , Factores Eucarióticos de Iniciación/fisiología , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidad , Masculino , Neoplasias Mamarias Experimentales/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones SCID , MicroARNs/metabolismo , Trasplante de Neoplasias , Especificidad de Órganos , Interferencia de ARN , Activación Transcripcional , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo
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