RESUMEN
We reported the upconversion luminescence (UCL) properties of Er3+-Yb3+ co-doped BiOCl semiconductor nanosheets synthesized by hydrothermal method. Under 980nm excitation, the red and green UCL of Er3+ ions were observed to be populated by a four and three-photon process in the case of absent or low concentration Yb3+ dopant. However, an increase of Yb3+ dopants show a completely opposite effect on the emission intensity of red and green one, accompanying with the change of upconverting process. It indicates that the red-shifting absorption edge of semiconductor and the super saturation UC processes involved with Yb3+ and Er3+ doping in BiOCl semiconductor nanosheets, respectively, are mainly responsible for the above UC phenomena.
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Ovarian cancer is the most lethal disease among the malignant tumors of female reproductive organs. Few successful therapeutic options exist for patients with ovarian cancer. The common therapeutic methods are surgical operation, chemotherapy, radiotherapy, and combination of these treatments. In recent years, studies have indicated that Pinellia pedatisecta Schott (PPS), a traditional Chinese medicine, could inhibit tumor growth. In this study, we demonstrated that PPS extract could induce apoptosis in SKOV3 cells in a dose- and time-dependent manner. We further conducted transcriptome sequencing on PPS extract-treated SKOV3 cells along with controls, and identified 1,754 transcripts whose expression differs at least 3-fold over the controls. These differentially expressed transcripts include the apoptosis-related genes such as the caspase family members, and were significantly enriched in steroid biosynthesis in the KEGG pathway database compared with the transcriptome background. Most of the differentially expressed transcripts from this pathway were upregulated in PPS extract-treated cell line, indicating that PPS extract-induced apoptosis was accompanied by increased steroid biosynthesis (e.g. zymosterol). These results suggest that PPS extract could be a new cytostatic therapeutic agent for ovarian cancer.
Asunto(s)
Redes Reguladoras de Genes/efectos de los fármacos , Neoplasias Ováricas/genética , Pinellia/química , Extractos Vegetales/farmacología , Apoptosis/efectos de los fármacos , Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/genética , Caspasas/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Femenino , Redes Reguladoras de Genes/genética , Humanos , Medicina Tradicional China/métodos , Transcriptoma/efectos de los fármacos , Transcriptoma/genéticaRESUMEN
The endoplasmic reticulum (ER) serves virtually all aspects of cell physiology and, by pathways that are incompletely understood, is dynamically remodeled to meet changing cell needs. Inositol-requiring enzyme 1 (Ire1), a conserved core protein of the unfolded protein response (UPR), participates in ER remodeling and is particularly required during the differentiation of cells devoted to intense secretory activity, so-called 'professional' secretory cells. Here, we characterize the role of Ire1 in ER differentiation in the developing Drosophila compound eye photoreceptors (R cells). As part of normal development, R cells take a turn as professional secretory cells with a massive secretory effort that builds the photosensitive membrane organelle, the rhabdomere. We find rough ER sheets proliferate as rhabdomere biogenesis culminates, and Ire1 is required for normal ER differentiation. Ire1 is active early in R cell development and is required in anticipation of peak biosynthesis. Without Ire1, the amount of rough ER sheets is strongly reduced and the extensive cortical ER network at the rhabdomere base, the subrhabdomere cisterna (SRC), fails. Instead, ER proliferates in persistent and ribosome-poor tubular tangles. A phase of Ire1 activity early in R cell development thus shapes dynamic ER.
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Diferenciación Celular , Proteínas de Drosophila/fisiología , Drosophila melanogaster/citología , Retículo Endoplásmico/fisiología , Endorribonucleasas/fisiología , Células Fotorreceptoras de Invertebrados/fisiología , Animales , Ojo Compuesto de los Artrópodos/citología , Ojo Compuesto de los Artrópodos/metabolismo , Drosophila melanogaster/crecimiento & desarrollo , Drosophila melanogaster/metabolismo , Retículo Endoplásmico/ultraestructura , Femenino , Masculino , Morfogénesis , Células Fotorreceptoras de Invertebrados/ultraestructuraRESUMEN
The aim of this study was to analyze the molecular epidemiologic characteristics of Acinetobacter baumannii. A total of 398 isolates were collected in 7 regions of South China from January to June of 2012. Drug sensitivity was tested toward 15 commonly used antibiotics; thus, 146 multi-drug-resistant strains (resistant to more than 7 drugs) were identified, representing 36.7% of all isolates. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were used for molecular subtyping. According to the PFGE results (with a cutoff of 70% similarity for the DNA electrophoretic bands), 146 strains were subdivided into 15 clusters, with cluster A being the largest (33.6%, distributed in all districts except Jiaxing). Cluster B was also widespread and included 14.4% of all strains. In addition, MLST results revealed 11 sequence types (ST), with ST208 being the most prevalent, followed by ST191 and ST729. Furthermore, 4 novel alleles and 6 novel STs were identified. Our results showed that multi-drug-resistant A. baumannii in South China shares the origin with other widespread strains in other countries. The nosocomial infections caused by A. baumannii have been severe in South China. Continuous monitoring and judicious antibiotic use are required.
Asunto(s)
Infecciones por Acinetobacter/epidemiología , Acinetobacter baumannii/genética , Infección Hospitalaria/epidemiología , Farmacorresistencia Bacteriana Múltiple/genética , Genotipo , Filogenia , Infecciones por Acinetobacter/diagnóstico , Infecciones por Acinetobacter/tratamiento farmacológico , Infecciones por Acinetobacter/microbiología , Acinetobacter baumannii/clasificación , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/aislamiento & purificación , Alelos , Antibacterianos/farmacología , Técnicas de Tipificación Bacteriana , China/epidemiología , Infección Hospitalaria/diagnóstico , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/microbiología , Electroforesis en Gel de Campo Pulsado , Humanos , Epidemiología Molecular , Familia de Multigenes , Tipificación de Secuencias MultilocusRESUMEN
The present study was designed to determine the effects of phycocyanin (PC) on Human ovarian cancer SKOV-3 cells and the underlying molecular mechanisms of action. The inhibitory effects of PC on the cell proliferation were detected by MTT assay. The IC50 values of PC were 182.0µM and 133.6µM for 24h and 48h exposure, respectively. PC induced apoptosis in SKOV-3 cells was observed by electron microscopy and flow cytometry. The apoptosis rate was increased from 1.6% to 19.8% after PC exposure. The fluorescence intensity of ROS and the activities of Caspase-3, Caspase-8, and Caspase-9 were increased. Differentiated expression protein spots were selected and identified using proteomic techniques. There were 698±73 and 683±79 protein spots resolved in untreated and PC-treated cells, respectively. Forty five differential protein spots were analyzed by MALDI-TOF-MS, including mtSSB, PSME3, and nucleolin. The mRNA expression profiles determined by RT-PCR were consistent with that of the two-dimensional electrophoresis. The decreased proteins such as HSP60, nucleolin, PPase, peroxiredoxin-4 and the increased protein (mtSSB) were identified in SKOV-3 cells after PC treatment, indicating that the effects of PC on tumor cell apoptosis may be relate to multiple target proteins. And the mitochondrial pathway may be the main pathway for PC-induced apoptosis.
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Apoptosis/efectos de los fármacos , Proteínas de Neoplasias/metabolismo , Ficocianina/farmacología , Spirulina/química , Apoptosis/genética , Caspasas/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Electroforesis en Gel Bidimensional , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Proteínas de Neoplasias/genética , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Neoplasias Ováricas/ultraestructura , ARN Mensajero/genética , ARN Mensajero/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
In order to get insights into plasmid evolution and the dissemination of multidrug resistance, we performed extensive comparative genomics analyses of the Klebsiella pneumoniae plasmid pKF3-94 and some of its related plasmids. pKF3-94 is one of three plasmids isolated from the K. pneumoniae strain KF3. Of the 144 putative genes it harbors, 69 can be functionally assigned to be involved in transfer conjugation, transfer leading, antimicrobial resistance, transposon function, and plasmid replication. Comparison of plasmid replicon sequence types revealed that pKF3-94 carries two replicons that are distinct from those carried on the two sibling K. pneumonia plasmids pKF3-70 and pKF3-140, thereby allowing pKF3-94 to coexist with these latter plasmids in the same host cell. Comparative genomics analyses further showed that pKF3-94 is more similar to plasmids pK1HV and pC15-k, which were isolated from different K. pneumonia strains, than to pKF3-70 and pKF3-140. Interestingly, pK1HV contains a unique 49 kb region rich in mobile genetic elements and drug resistance genes, while pKF3-94 and pC15-k share a 15 kb homology region partitioned into a region rich in drug resistance genes and one containing a replicon. It is conceivable, therefore, that pK1HV and pC15-k have both arisen from a common pKF3-94-like plasmid. The comparisons lend further support for the role horizontal gene transfer plays in genome evolution and in the dissemination of genetic elements including drug resistance genes.
RESUMEN
The homocysteine methyltransferase encoded by mmuM is widely distributed among microbial organisms. It is the key enzyme that catalyzes the last step in methionine biosynthesis and plays an important role in the metabolism process. It also enables the microbial organisms to tolerate high concentrations of selenium in the environment. In this research, 533 mmuM gene sequences covering 70 genera of the bacteria were selected from GenBank database. The distribution frequency of mmuM is different in the investigated genera of bacteria. The mapping results of 160 mmuM reference sequences showed that the mmuM genes were found in 7 species of pathogen genomes sequenced in this work. The polymerase chain reaction products of one mmuM genotype (NC_013951 as the reference) were sequenced and the sequencing results confirmed the mapping results. Furthermore, 144 representative sequences were chosen for phylogenetic analysis and some mmuM genes from totally different genera (such as the genes between Escherichia and Klebsiella and between Enterobacter and Kosakonia) shared closer phylogenetic relationship than those from the same genus. Comparative genomic analysis of the mmuM encoding regions on plasmids and bacterial chromosomes showed that pKF3-140 and pIP1206 plasmids shared a 21 kb homology region and a 4.9 kb fragment in this region was in fact originated from the Escherichia coli chromosome. These results further suggested that mmuM gene did go through the gene horizontal transfer among different species or genera of bacteria. High-throughput sequencing combined with comparative genomics analysis would explore distribution and dissemination of the mmuM gene among bacteria and its evolution at a molecular level.
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Bacterias/enzimología , Transferencia de Gen Horizontal/genética , Variación Genética/genética , Homocisteína S-Metiltransferasa/genética , Filogenia , Secuencia de Bases , Mapeo Cromosómico , Análisis por Conglomerados , Cartilla de ADN/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Datos de Secuencia Molecular , ARN Ribosómico 16S/genética , Especificidad de la EspecieRESUMEN
The post-translational modification of protein by acetylation has been emerging as a prevalent modification in enzymes that catalyze intermediary metabolism. However, the dynamics of protein acetylation during adipocyte differentiation that involves a major shift in cellular metabolism is not known. In this study, we investigated the temporal changes in acetylation during adipocyte differentiation. Almost all acetylated proteins identified showed a sequential change in acetylation during the differentiation process. While the majority of the acetylated proteins showed a sequential upregulation during adipocyte differentiation, in a few proteins a sequential downregulation of protein acetylation was also observed. Our findings suggest that a wide-ranging temporal change in protein acetylation occurs during adipocyte differentiation including differentially expressed proteins signifying an important role in adipocyte differentiation.
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Plasmids are important antibiotic resistance determinant carriers that can disseminate various drug resistance genes among species or genera. By using a high throughput sequencing approach, two groups of plasmids of Escherichia coli (named E1 and E2, each consisting of 160 clinical E. coli strains isolated from different periods of time) were sequenced and analyzed. A total of 20 million reads were obtained and mapped onto the known resistance gene sequences. As a result, a total of 9 classes, including 36 types of antibiotic resistant genes, were identified. Among these genes, 25 and 27 single nucleotide polymorphisms (SNPs) appeared, of which 9 and 12 SNPs are nonsynonymous substitutions in the E1 and E2 samples. It is interesting to find that a novel genotype of bla(KLUC), whose close relatives, bla(KLUC-1) and bla(KLUC-2), have been previously reported as carried on the Kluyvera cryocrescens chromosome and Enterobacter cloacae plasmid, was identified. It shares 99% and 98% amino acid identities with Kluc-1 and Kluc-2, respectively. Further PCR screening of 608 Enterobacteriaceae family isolates yielded a second variant (named bla(KLUC-4)). It was interesting to find that Kluc-3 showed resistance to several cephalosporins including cefotaxime, whereas bla(KLUC-4) did not show any resistance to the antibiotics tested. This may be due to a positively charged residue, Arg, replaced by a neutral residue, Leu, at position 167, which is located within an omega-loop. This work represents large-scale studies on resistance gene distribution, diversification and genetic variation in pooled multi-drug resistance plasmids, and provides insight into the use of high throughput sequencing technology for microbial resistance gene detection.
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Farmacorresistencia Bacteriana/genética , Escherichia coli/genética , Plásmidos/genética , Secuencia de Bases , Enterobacteriaceae/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Proteínas de Escherichia coli/genética , Genotipo , Secuenciación de Nucleótidos de Alto Rendimiento , Kluyvera/efectos de los fármacos , Reacción en Cadena de la Polimerasa , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
BACKGROUND: The development of multidrug resistance is a major problem in the treatment of pathogenic microorganisms by distinct antimicrobial agents. Characterizing the genetic variation among plasmids from different bacterial species or strains is a key step towards understanding the mechanism of virulence and their evolution. RESULTS: We applied a deep sequencing approach to 206 clinical strains of Klebsiella pneumoniae collected from 2002 to 2008 to understand the genetic variation of multidrug resistance plasmids, and to reveal the dynamic change of drug resistance over time. First, we sequenced three plasmids (70 Kb, 94 Kb, and 147 Kb) from a clonal strain of K. pneumoniae using Sanger sequencing. Using the Illumina sequencing technology, we obtained more than 17 million of short reads from two pooled plasmid samples. We mapped these short reads to the three reference plasmid sequences, and identified a large number of single nucleotide polymorphisms (SNPs) in these pooled plasmids. Many of these SNPs are present in drug-resistance genes. We also found that a significant fraction of short reads could not be mapped to the reference sequences, indicating a high degree of genetic variation among the collection of K. pneumoniae isolates. Moreover, we identified that plasmid conjugative transfer genes and antibiotic resistance genes are more likely to suffer from positive selection, as indicated by the elevated rates of nonsynonymous substitution. CONCLUSION: These data represent the first large-scale study of genetic variation in multidrug resistance plasmids and provide insight into the mechanisms of plasmid diversification and the genetic basis of antibiotic resistance.
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Farmacorresistencia Bacteriana Múltiple/genética , Variación Genética , Klebsiella pneumoniae/fisiología , Plásmidos/genética , Secuencia de Bases , Conjugación Genética , Klebsiella pneumoniae/genética , Polimorfismo de Nucleótido Simple , Selección Genética , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: Klebsiella pneumoniae is a clinically significant species of bacterium which causes a variety of diseases. Clinical treatment of this bacterial infection is greatly hindered by the emergence of multidrug-resistant strains. The resistance is largely due to the acquisition of plasmids carrying drug-resistant as well as pathogenic genes, and its conjugal transfer facilitates the spread of resistant phenotypes. METHODOLOGY/PRINCIPAL FINDINGS: The 70,057 bp plasmid pKF3-70, commonly found in Klebsiella pneumoniae, is composed of five main functional modules, including regions involved in replication, partition, conjugation, transfer leading, and variable regions. This plasmid is more similar to several Escherichia coli plasmids than any previously reported K. pneumoniae plasmids and pKF3-70 like plasmids share a common and conserved backbone sequence. The replication system of the pKF3-70 is 100% identical to that of RepFII plasmid R100 from E. coli. A beta-lactamase gene ctx-m-14 with its surrounding insertion elements (ISEcp1, truncated IS903 and a 20 bp inverted repeat sequence) may compose an active transposon which is directly bordered by two putative target repeats "ATTAC." CONCLUSIONS/SIGNIFICANCE: The K. pneumoniae plasmid pKF3-70 carries an extended-spectrum beta-lactamase gene, ctx-m-14. The conjugative characteristic makes it a widespread plasmid among genetically relevant genera which poses significant threat to public health.
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Escherichia coli/genética , Klebsiella pneumoniae/genética , Plásmidos , Secuencia de Bases , Conjugación Genética , Datos de Secuencia Molecular , Homología de Secuencia de Ácido NucleicoRESUMEN
Epidemiological studies have suggested that intake of whole grains is inversely associated with coronary artery disease. The mechanisms, however, are not completely clear. We tested the hypothesis that intake of wheat bran or corn bran would (1) increase the plasma concentration of phenolic antioxidants and (2) reduce atherosclerosis in apo E-knockout mice. Apo E-knockout (E-KO) mice were fed for 18 weeks with a 0.1% cholesterol-supplemented diet in the absence of grain brans or the presence of 1.7% yellow dent corn bran or 3.3% hard red spring wheat bran. The concentration of antioxidant ferulic acid in plasma and urine was measured by HPLC to monitor the bioavailability of grain phenolics. Plasma lipoprotein profiles were determined by a combination of HPLC and online enzymatic methods. Urinary 15-isoprostane F(2t), an in vivo LDL oxidation biomarker, and atherosclerotic lesions were analyzed by ELISA and histological methods, respectively. Dietary supplementation with corn or wheat bran resulted in a 4- and 24-fold increase, respectively, in urinary excretion of ferulic acid. The urinary recovery rate of ferulic acid from the two brans in apo E-KO mice was approximately 1.9-2.9%. Dietary corn bran but not wheat bran also significantly increased the concentration of total ferulic acid in plasma. Nevertheless, the supplementation with either bran product for 18 weeks did not significantly alter the urinary excretion of 15-isoprostane F(2t), change the lipoprotein profiles, nor reduce the atherosclerotic lesion development in this animal model. The results suggest that phenolic antioxidants from the two types of bran may not be sufficient to reduce atherosclerosis in this animal model.
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Apolipoproteínas E/deficiencia , Aterosclerosis/prevención & control , Fibras de la Dieta/administración & dosificación , Zea mays/química , Animales , Antioxidantes/administración & dosificación , Antioxidantes/análisis , Aterosclerosis/metabolismo , Aterosclerosis/patología , Ácidos Cumáricos/administración & dosificación , Ácidos Cumáricos/sangre , Ácidos Cumáricos/orina , Dieta , Lípidos/sangre , Lipoproteínas/sangre , Masculino , Ratones , Ratones NoqueadosRESUMEN
OBJECTIVE: To establish underlying molecular mechanisms of pro-atherogenic effects of probucol in apo E-KO mice. METHODS: Affymetrix Gene Chip System, GenMAPP/MAPPFinder software and real-time PCR techniques were used to identify alterations in gene expression and biological pathways in the liver and aorta of both male apo E-KO and male wild-type mice treated with or without probucol (1%, w/w) for 18 weeks. Plasma levels of lipids, cytokines, liver function test, and the extent of atherosclerosis and liver histology were examined. RESULTS AND CONCLUSIONS: Probucol treatment paradoxically reduced plasma cholesterol levels, increased plasma cytokine levels and atherogenesis in apo E-KO mice. Three hundred and sixty genes/transcripts and 110 biological processes were significantly differentially expressed in the liver of probucol-treated apo E-KO mice. The response to biotic stimulus, immune response and inflammatory response were the most prominent processes expressed in the liver. The expression of 60 of these genes involved in immune response including inflammatory responses, antigen presentation, humoral immune response, immune cell activation, innate immune response, and regulation of immune response was over-expressed. Many of these genes were also over-expressed in the aorta of probucol-treated apo E-KO mice. Such effects of probucol were not observed in the liver and aorta of wild-type mice. A significant interaction between apo E deficiency and probucol treatment was observed. Histological examinations showed a significant infiltration of inflammatory cells in the liver of probucol-treated apo E-KO mice, but not in C57BL/6 mice. These findings suggest that probucol-induced atherogenesis may be mediated through a pro-inflammatory state.
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Apolipoproteínas E/deficiencia , Aterosclerosis/etiología , Probucol/farmacología , Animales , Aorta/metabolismo , Colesterol/sangre , Citocinas/biosíntesis , Perfilación de la Expresión Génica , Inmunidad/efectos de los fármacos , Inmunidad/genética , Hígado/metabolismo , Hígado/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Análisis de Secuencia por Matrices de OligonucleótidosRESUMEN
We investigated the effects of a high-fructose (HF) diet on cardiovascular risks in Sprague-Dawley rats. Twelve rats were randomly assigned to standard chow or HF diet for 20 weeks. Systolic blood pressure and circulating insulin, total cholesterol, and triacylglycerol levels were significantly higher in the HF group. Aortic sections appeared normal, but liver sections from the HF group showed lipid accretion, mild inflammation, and bile pigmentation. Liver samples from the HF group showed significantly higher total lipid levels and changes in fatty acid profile. Levels of 16:0, cis-9-18:2, cis-11-20:1, cis-13-20:1, cis-11-20:2 and 24:0 were significantly raised in the phospholipid fraction. Lower levels of cis-11-18:1, cis-9-18:2, and cis-11-20:1 and increased levels of 16:1, cis-9-18:1, and cis-13-20:1 were found in the non-esterified fatty acid fraction. HF-feeding resulted in significant reductions in plasma levels of certain inflammatory biomarkers. HF intake over time may negatively impact cardiovascular health and liver function in rats.
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Carbohidratos de la Dieta/administración & dosificación , Fructosa/administración & dosificación , Animales , Glucemia/metabolismo , Presión Sanguínea , Peso Corporal , Enfermedades Cardiovasculares/epidemiología , Citocinas/sangre , Carbohidratos de la Dieta/farmacología , Ingestión de Alimentos , Fructosa/farmacología , Prueba de Tolerancia a la Glucosa , Insulina/sangre , Grasa Intraabdominal/metabolismo , Lípidos/sangre , Masculino , Ratas , Ratas Sprague-Dawley , Factores de RiesgoRESUMEN
Dietary phytosterols significantly reduce plasma cholesterol concentrations and atherosclerosis in apolipoprotein E-knockout (apo E-KO) mice. We investigated the long-term effects of phytosterol treatment on gene expression in the liver of these mice. Male apo E-KO mice were fed an atherogenic diet supplemented with (n=6) or without (n=6) 2% (wt/wt) phytosterol mixtures for 14 weeks. Liver specimens were collected and stored in RNAlater immediately. mRNA was extracted and subjected to microarray analyses and real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay for confirmation. Oligonuleotide microarray analysis of pooled samples (n=3) revealed that the expression of 132 genes/transcripts was significantly altered in treated animals, considering the false discovery rate (FDR) of 0.23. Real-time RT-PCR techniques confirmed these alterations in the expression of several of these genes, including Hmgcr (2.16-fold; P=.0002), Hmgcs1 (1.79-fold; P=.001), Hsd17b7 (2.11-fold; P=.028), Sqle (2.03-fold; P=.01), Cyp51 (1.8-fold; P=.001), Fads1 (1.55-fold; P=.031), Fads2 (2.17-fold; P=.047), Lpin1 (3.67-fold; P=.001), Ppargc1b (PGC-1beta; a coactivator of sterol-regulatory element-binding proteins; 1.66-fold; P=.007) and Cyp7B1 (1.81-fold; P=.025). In summary, our data suggest that long-term dietary phytosterols can alter the expression of a number of hepatic genes that regulate sterol metabolism in apo E-KO mice. It is possible that these changes are due to inhibition of cholesterol absorption, but are not a direct effect of plant sterols. Further multivariate correlation or association analysis is needed to establish the relations between changes in the expression of these genes and prevention of atherosclerosis by phytosterols.
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Apolipoproteínas E/deficiencia , Expresión Génica/genética , Hígado/química , Fitosteroles/farmacología , Adipogénesis/genética , Animales , Apolipoproteínas E/genética , Apoptosis/genética , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/patología , Colesterol/sangre , delta-5 Desaturasa de Ácido Graso , Dieta Aterogénica , Masculino , Ratones , Ratones Noqueados , Análisis de Secuencia por Matrices de Oligonucleótidos , Fitosteroles/administración & dosificación , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Esteroles/metabolismoRESUMEN
Identification of all the transcription factors (TFs) encoded in a given genome is a prerequisite for understanding transcriptional regulatory networks. Archaea are prokaryotes that constitute one of the three main branches of organisms with an astounding diversity of habitats. In this report, we establish the ArchaeaTF database to provide an integrated information resource about TFs in Archaea, such as basic characteristics, domain architectures, and sequence similarities against the linked databases. Through its Web interface, ArchaeaTF provides three different ways for users to retrieve the data: simple browse, keyword search, and BLAST search. Moreover, ArchaeaTF can serve as a useful platform for comparative genomics analysis of archaeal TFs since it implements a series of tools, including MUSCLE for multiple sequence alignments of the DNA-binding domains, QuickTree for phylogenetic tree construction, and OrthoMCL for ortholog identification. The released ArchaeaTF 1.0 contains 2135 putative TFs from 37 completed archaeal genomes. In conclusion, we believe that ArchaeaTF will be a useful resource and convenient platform for researchers working on TFs and transcriptional regulatory networks to retrieve information from TFs in Archaea rapidly. ArchaeaTF is accessible at http://bioinformatics.zj.cn/archaeatf.
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Archaea/genética , Proteínas Arqueales/genética , Proteínas de Unión al ADN/genética , Bases de Datos de Proteínas , Filogenia , Factores de Transcripción/genética , Internet , Estructura Terciaria de Proteína/genéticaRESUMEN
Dietary conjugated linoleic acid (CLA) and the antihypertensive drug, telmisartan, have both been shown to modify cardiovascular risks. The effects of a combination of these two agents have, however, not been investigated. This 20 week study sought to assess the therapeutic potential of a CLA/telmisartan co-administration in rats fed a high-fructose high-fat diet. Thirty-three male Sprague-Dawley rats were randomly assigned to five experimental groups, including control, losartan, telmisartan, CLA, and CLA + telmisartan-treated animals. Body weight, blood pressure, and blood levels of lipids, glucose, insulin, and inflammatory markers were measured. Co-administration of CLA and telmisartan resulted in significant (P < 0.05) reductions in body weight, visceral fat, serum total cholesterol, triglycerides, glucose, plasma insulin concentrations, and systolic blood pressure compared with those in the control group. Moreover, plasma levels of IL1-alpha and IFN-gamma were reduced and levels of IL1-beta, IL-4, IL-6, and IL-10, plus TNF-alpha were increased in the co-therapy group, compared with controls. In conclusion, this study suggests that a combination of CLA with telmisartan may modify several risk factors of cardiovascular disease commonly seen in metabolic syndrome. This combination of nutraceuticals and pharmaceuticals may be a safe and cost-effective strategy in a number of high-risk subjects. Future studies will further document clinical benefits of such combination therapy.
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Antihipertensivos/administración & dosificación , Bencimidazoles/administración & dosificación , Benzoatos/administración & dosificación , Enfermedades Cardiovasculares/prevención & control , Ácidos Linoleicos Conjugados/administración & dosificación , Animales , Antihipertensivos/uso terapéutico , Bencimidazoles/uso terapéutico , Benzoatos/uso terapéutico , Glucemia/metabolismo , Presión Sanguínea , Peso Corporal , Citocinas/sangre , Suplementos Dietéticos , Fructosa/metabolismo , Insulina/sangre , Grasa Intraabdominal/metabolismo , Ácidos Linoleicos Conjugados/uso terapéutico , Lípidos/sangre , Masculino , Ratas , Ratas Sprague-Dawley , Factores de Riesgo , Telmisartán , Factores de TiempoRESUMEN
BACKGROUND: Consumption of fish oil and n-3 fatty acids is associated with beneficial modifications in plasma lipid levels. The impact of these modifications on development of atherosclerotic lesions merits further investigation. AIM OF THE STUDY: The aim of this study was to investigate the impact of fish oil consumption on quality and quantity of lipoprotein fatty acids and its influence on atherosclerosis in apolipoprotein E-knockout (apo E-KO) mice. METHODS: Male apo E-KO mice were treated with 1% dietary fish oil for 14 weeks. Plasma triglycerides (TG), phospholipids, (PL) and cholesteryl ester (CE) fractions were separated using thin layer chromatography. Plasma-free fatty acids (FFA) plus fatty acid contents of TG, PL, CE were determined using gas chromatography. Aortic atherosclerosis was assessed by histological and morphometrical techniques. RESULTS: Twenty-eight fatty acids were identified in each of the four lipid compartments. High amounts of n-3 fatty acids (eicosapentaenoic (EPA), docosahexaenoic (DHA)) were found in all of these fractions. The levels of EPA and DHA increased by 400 and 150%, respectively, in FFA, TG and PL compartments; higher increases (>500 and 200%) in EPA and DHA were found in CE. This markedly decreased the n-6/n-3 ratios in FFA, TG, PL, and CE by 60, 72, 53, and 61%, respectively. These changes were accompanied by a significant increase in plasma triglyceride levels. Surprisingly, these changes did not affect atherogenesis. CONCLUSIONS: Elevated levels of EPA and DHA do not appear to prevent development of atherosclerotic plaques in this model. Longer studies warrant investigation of the direct benefits of these fatty acids against myocardial damage as clinical consequences of advanced atherosclerosis.
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Aterosclerosis/metabolismo , Ácidos Grasos Omega-3/metabolismo , Ácidos Grasos/metabolismo , Aceites de Pescado , Animales , Apolipoproteínas E/genética , Aterosclerosis/prevención & control , Ésteres del Colesterol/química , Ésteres del Colesterol/metabolismo , Cromatografía de Gases/métodos , Cromatografía en Capa Delgada/métodos , Ácidos Docosahexaenoicos/análisis , Ácidos Docosahexaenoicos/metabolismo , Ácido Eicosapentaenoico/análisis , Ácido Eicosapentaenoico/metabolismo , Ácidos Grasos/análisis , Ácidos Grasos Omega-3/análisis , Ácidos Grasos Volátiles/sangre , Aceites de Pescado/administración & dosificación , Aceites de Pescado/química , Masculino , Ratones , Ratones Noqueados , Fosfolípidos/química , Fosfolípidos/metabolismo , Distribución Aleatoria , Triglicéridos/química , Triglicéridos/metabolismoRESUMEN
Most proterminal regions of human chromosomes are GC-rich and gene-rich. Chromosome 3p is an exception. Its proterminal region is GC-poor, and likely to lose heterozygosity, thus causing a number of fatal diseases. Except one gap left in the telomeric position, the proterminal region of human chromosome 3p has been completely sequenced. The detailed sequence analysis showed: (i) the GC content of this region was 38.5%, being the lowest among all the human proterminal regions; (ii) this region contained 20 known genes and 22 predicted genes, with an average gene size of 97.5 kb. The previously mapped gene Cntn3 was not found in this region, but instead located in the 74 Mb position of human chromosome 3p; (iii) the interspersed repeats of this region were more active than the average level of the whole human genome, especially (TA)n, the content of which was twice the genome average; (iv) this region had a conserved synteny extending from 104.1 Mb to 112.4 Mb on the mouse chromosome 6, which was 8% larger in size, not in accordance with the whole genome comparison, probably because the 3pter-p26 region was more likely to lose nucleotides and its mouse synteny had more active interspersed repeats.
Asunto(s)
Genoma Humano , Análisis de Secuencia de ADN/métodos , Animales , Mapeo Cromosómico , Cromosomas Humanos Par 3 , Islas de CpG , ADN/metabolismo , ADN Complementario/metabolismo , Etiquetas de Secuencia Expresada , Genoma , Heterocigoto , Humanos , Pérdida de Heterocigocidad , Ratones , Modelos GenéticosRESUMEN
We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000-40,000. Only 2%-3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family.